@article {pmid39936988, year = {2025}, author = {González-Martínez, S and Palacios, J and Carretero-Barrio, I and Lanza, VF and García-Cosío Piqueras, M and Caniego-Casas, T and Hardisson, D and Esteban-Rodríguez, I and Cortés, J and Pérez-Mies, B}, title = {Single-Cell RNA Sequencing on Formalin-Fixed and Paraffin-Embedded (FFPE) Tissue Identified Multi-Ciliary Cells in Breast Cancer.}, journal = {Cells}, volume = {14}, number = {3}, pages = {}, pmid = {39936988}, issn = {2073-4409}, support = {PI22/01892, PMP22/00054, PMP21/00107//Instituto de Salud Carlos III/ ; }, mesh = {Humans ; *Breast Neoplasms/genetics/pathology ; *Paraffin Embedding ; Female ; *Single-Cell Analysis/methods ; *Formaldehyde ; *Tissue Fixation ; *Sequence Analysis, RNA/methods ; Tumor Microenvironment ; }, abstract = {The purpose of this study was to evaluate the suitability of formalin-fixed and paraffin-embedded (FFPE) samples and fixed fresh (FF) samples for single-cell RNA sequencing (scRNAseq). To this end, we compared single-cell profiles from FFPE and matched FF tissue samples of one invasive carcinoma of no special type carcinoma (invasive ductal carcinoma-IDC) and one invasive lobular carcinoma (ILC) to assess consistency in cell type distribution and molecular profiles. The results were validated using immunohistochemistry (IHC), fluorescence in situ hybridization (FISH), and electron microscopy. Additionally, immune cell proportions identified by IHC were quantified using QuPath and compared to the scRNAseq results. FFPE- and FF-derived libraries demonstrated high-quality sequencing metrics, and cellular heterogeneity was similar. No exclusive cell populations were identified by either approach. The four samples analysis identified six types of epithelial cells, as well as tumoral microenvironment populations. The scRNAseq results from epithelial neoplastic cells were concordant with common IHC markers. The proportion of immune cells identified by IHC in FFPE sections were similar to those obtained by scRNAseq. We identified and validated a previously poorly recognized subpopulation of neoplastic multi-ciliated cells (MCCs) (FOXJ1, ROPN1L). Analysis of FOXJ1 in 214 ER-positive invasive carcinomas demonstrated protein expression in one third of tumors, suggesting frequent focal MCC differentiation. Our results support the suitability of scRNAseq analysis using FFPE tissue, and identified a subpopulation of neoplastic MCC in breast cancer.}, } @article {pmid39925473, year = {2025}, author = {Maxey, J and Harvey, D}, title = {Neisseria weaveri: Atypical Infection in Breast Implant-Based Reconstruction.}, journal = {Plastic and reconstructive surgery. Global open}, volume = {13}, number = {2}, pages = {e6505}, pmid = {39925473}, issn = {2169-7574}, abstract = {Surgical site infection (SSI) following breast implant surgery can have devastating complications. Infection is most commonly from coagulase-negative Staphylococcus bacteria. Neisseria weaveri is a gram-negative bacterium that is associated with animal bites. We present the first known case of N. weaveri causing SSI following breast implant reconstruction. We report the case of a 61-year-old woman with invasive ductal carcinoma who underwent bilateral skin-sparing mastectomy with immediate implant-based reconstruction. She presented on postoperative day 24 with malodorous drainage from her Jackson-Pratt drain. The patient explained that she has a shih tzu at home that frequently licked her. Cultures from the drain grew N. weaveri. The patient's antibiotic regimen was transitioned, and she completed her course without complications. Practitioners should counsel their patients on adequate postsurgery hygiene and take into consideration rare causes of SSI and how this may affect patient care.}, } @article {pmid39906646, year = {2025}, author = {Shi, J and Qi, X and Ran, Y and Zhou, Q and Ding, Y and Li, L and Zeng, Y and Qiu, D and Cai, Z and Cai, X and Pan, Y}, title = {Saliva-acquired pellicle inspired multifunctional gargle with wet adhesion, photodynamic antimicrobial, and In situ remineralization properties for dental caries prevention.}, journal = {Bioactive materials}, volume = {47}, number = {}, pages = {212-228}, pmid = {39906646}, issn = {2452-199X}, abstract = {Dental caries is primarily caused by cariogenic bacteria metabolizing carbohydrates to produce acidic substances that erode the dental hard tissues. Traditional remineralization treatments often have limited efficacy due to their lack of antibacterial activity. According to the Interrupting Dental Caries (IDC) theory, ideal caries-preventive materials should possess both antibacterial and remineralizing properties. Furthermore, effective adhesion to dental surfaces is crucial. Inspired by the wet adhesion properties of the salivary acquired pellicle, we developed a multifunctional gargle named Ce6@PDN-SAP (CP-SAP). This formulation employed peptide dendrimer nanogels (PDN) as a carrier for the photosensitizer Ce6, further functionalized with saliva-acquired peptide (SAP) to confer wet adhesion properties. CP-SAP rapidly adhered to the dental surface and remained effective for extended periods. Upon laser irradiation, Ce6 generated reactive oxygen species (ROS), disrupting bacterial outer membrane integrity, causing protein leakage, and reducing ATP levels, thereby achieving potent antibacterial effects. Following this, PDN and SAP acted as nucleation templates to promote in situ remineralization of demineralized dental hard tissues. In vivo studies using rat models demonstrated that CP-SAP provided significantly superior caries-preventive effects compared to chlorhexidine gargle. In conclusion, CP-SAP, as an innovative approach grounded in the IDC theory, holds great promise for the prevention and treatment of dental caries.}, } @article {pmid39879501, year = {2025}, author = {Uppal, R and Saeed, U and Khattak, ME and Khan, AA and Uppal, MR and Piracha, ZZ and Khan, MN and Shaikh, D and Tariq, U and Mahmood, AR and Ali, SS and Muhammad, B and Tariq, MN and Gilani, SS and Ozsahin, DU and Uzun, B and Ozsahin, I}, title = {Epidemiological analysis of Leishmaniasis prevalence in Pakistan during 2016-2023.}, journal = {Brazilian journal of biology = Revista brasleira de biologia}, volume = {84}, number = {}, pages = {e284742}, doi = {10.1590/1519-6984.284742}, pmid = {39879501}, issn = {1678-4375}, mesh = {Humans ; Pakistan/epidemiology ; Prevalence ; Male ; Female ; Child ; Retrospective Studies ; Adult ; Adolescent ; Child, Preschool ; *Leishmaniasis/epidemiology ; Young Adult ; Middle Aged ; Infant ; }, abstract = {Leishmaniasis, caused by the Leishmania parasite, remains a persistent public health challenge in Pakistan. Despite control efforts, the disease prevalence continues to rise, particularly among pediatric populations. Understanding prevalence patterns and transmission dynamics is critical for effective control strategies. This study aims to analyze leishmaniasis prevalence data from January 2016 to July 2023 in Pakistan. Specific objectives include assessing temporal trends, demographic patterns, and geographical hotspots of transmission, while emphasizing the need for enhanced surveillance and research for targeted interventions. Retrospective analysis was conducted on leishmaniasis prevalence data collected from multiple healthcare facilities across Pakistan. Data included results from diagnostic tests on suspected cases, encompassing both pediatric and adult patients. Descriptive statistical analysis was employed to evaluate prevalence rates, demographic characteristics, and geographical distribution of positive cases. Analysis revealed an increasing trend in leishmaniasis prevalence over the study period. Initially, from 2016 to 2020, a positivity rate of 27% was observed exclusively among pediatric patients in Islamabad, with no adult cases. Subsequently, from 2017 to 2022, the positivity rate increased to 42%, affecting both pediatric and adult populations in Islamabad, Rawalpindi, and Swat. Notably, between July 2022 and July 2023, the positivity rate surged to 56%, primarily impacting adult males in the identified hotspots. The study provides evidence of rising leishmaniasis prevalence in Pakistan, particularly among pediatric patients. Identified hotspots suggest localized transmission, warranting targeted interventions. Enhanced surveillance and research efforts are crucial for understanding disease dynamics and implementing effective control measures. Priority should be given to vulnerable populations and high-burden regions to mitigate leishmaniasis impact in Pakistan.}, } @article {pmid39879500, year = {2025}, author = {Piracha, ZZ and Saeed, U and Uppal, R and Uppal, MR and Khan, AA and Abdullah, M and Mari, K and Basra, A and Gilani, SS and Tariq, MN and Ozsahin, DU and Uzun, B and Ozsahin, I}, title = {Prevalence and clinical profile of hepatitis C virus infections in multitransfused thalassemic patients in the capital twin cities of Pakistan.}, journal = {Brazilian journal of biology = Revista brasleira de biologia}, volume = {84}, number = {}, pages = {e284453}, doi = {10.1590/1519-6984.284453}, pmid = {39879500}, issn = {1678-4375}, mesh = {Humans ; Pakistan/epidemiology ; *Hepatitis C/epidemiology ; Male ; Female ; Prevalence ; Adult ; Young Adult ; *Alanine Transaminase/blood ; Adolescent ; Child ; Middle Aged ; beta-Thalassemia/epidemiology/complications ; Hepacivirus/isolation & purification ; Splenomegaly/epidemiology/etiology ; Creatinine/blood ; Child, Preschool ; Transfusion Reaction/epidemiology ; Hepatomegaly/epidemiology/etiology ; }, abstract = {Hepatitis C virus (HCV) presents a significant global health concern, affecting 3.3% of the world's population. The primary mode of HCV transmission is through blood and blood products. Patients with beta thalassemia, who rely on lifelong blood transfusions, are particularly vulnerable to HCV infections. This study aimed to assess the prevalence of hepatitis C virus infections among multitransfused thalassemic patients in the twin cities of Pakistan's capital. The clinical research, involving the enrollment of 262 multitransfused beta thalassemic patients residing in the capital twin cities of Pakistan. The investigation encompassed the evaluation of hepatitis C virus presence, alanine aminotransferase (ALT) levels, serum creatinine, hepatomegaly, splenomegaly, and the occurrence of splenectomy. The overall prevalence of Hepatitis C virus infections was notably high at 55.73%. This was particularly pronounced among patients aged 20 years and older, with a 100% infection rate. In HCV-positive thalassemic patients, the average ALT level was observed to be 98 U/L, while average creatinine values stood at 0.39 mg/dL. Additionally, hepatomegaly was prevalent in 82.20% of HCV-positive thalassemic patients, featuring an average liver size increase of 4.33 cm. Splenomegaly was evident in 67.12% of HCV-positive thalassemic patients, with an average spleen size augmentation of 4.46 cm. Splenectomy was identified in 15.75% of cases. The incidence of HCV infections in the thalassemic population of Pakistan is alarmingly high. Furthermore, the risk of contracting HCV infections escalates with the advancing age of thalassemic patients. Elevated ALT levels and hepatomegaly were pervasive among the majority of HCV-positive thalassemic patients. Consequently, there is a compelling need for rigorous screening of blood products prior to transfusion to mitigate the future burden of HCV in Pakistan.}, } @article {pmid39864363, year = {2025}, author = {Metzger Filho, O and Cardoso, F and Poncet, C and Desmedt, C and Linn, S and Wesseling, J and Hilbers, F and Delaloge, S and Pierga, JY and Brain, E and Vrijaldenhoven, S and Neijenhuis, PA and Rutgers, EJT and Piccart, M and van 't Veer, LJ and Viale, G}, title = {Survival outcomes for patients with invasive lobular cancer by MammaPrint: Results from the MINDACT phase III trial.}, journal = {European journal of cancer (Oxford, England : 1990)}, volume = {217}, number = {}, pages = {115222}, doi = {10.1016/j.ejca.2025.115222}, pmid = {39864363}, issn = {1879-0852}, mesh = {Humans ; Female ; *Breast Neoplasms/genetics/mortality/pathology/therapy ; *Carcinoma, Lobular/genetics/mortality/pathology/therapy ; Middle Aged ; Aged ; Prognosis ; Adult ; Biomarkers, Tumor/genetics ; Gene Expression Profiling ; Neoplasm Invasiveness ; Disease-Free Survival ; }, abstract = {BACKGROUND: Evaluation of the prognostic performance and clinical utility of the MammaPrint 70-gene signature in early-stage invasive lobular carcinoma (ILC) for whom such analyses in a randomized trial is awaited.

PATIENTS AND METHODS: Exploratory subgroup analysis of MINDACT trial patients with centrally assessed histology (n = 5929) with invasive breast cancer of no-special-type (NST), or pure ILC. In the trial patients were categorized based on the 70-gene signature for genomic risk and modified Adjuvant!Online for clinical risk. Survival outcomes at 8.7 years median follow-up by 70-gene signature were compared between NST and ILC for Distant Metastasis-Free Survival (DMFS), Disease-Free Survival (DFS) and Overall Survival (OS).

RESULTS: 5313 patients were ILC (n = 487) or NST (n = 4826). ILC was further classified into classic ILC (n = 255) or ILC variants (n = 232). The 70-gene signature classified 16.2 % of ILC and 39.1 % of NST as genomic high-risk (gH). Survival outcomes for ILC vs. NST revealed similar estimates according to genomic risk overall and across subsets. The 70-gene signature classified 10.2 % of classic ILC and 22.8 % of ILC variants as gH. 5-yr DFS estimates for ILC variants 88.4 % (95 %CI: 83.1-92.1) was inferior to classic ILC 93.0 % (95 %CI: 88.7-95.7).

CONCLUSIONS: Sixteen percent of ILC were classified high genomic risk by the 70-gene signature, with unfavorable survival outcomes. Survival estimates were similar for patients with ILC and NST classified as either low- or high-genomic risk, suggesting that the 70-gene signature also has prognostic value in ILC and may be a clinically useful tool for adjuvant treatment decision-making in ILC.}, } @article {pmid39805165, year = {2025}, author = {Michelon, I and Castro, CER and Madeira, T and Dacoregio, MI and Stecca, C and Soares, LR and Saeed, A and Vilbert, M and Cavalcante, L}, title = {Trastuzumab deruxtecan in human epidermal growth factor receptor 2-positive breast cancer brain metastases: A systematic review and updated meta-analysis.}, journal = {Cancer treatment reviews}, volume = {133}, number = {}, pages = {102882}, doi = {10.1016/j.ctrv.2025.102882}, pmid = {39805165}, issn = {1532-1967}, mesh = {Humans ; *Trastuzumab/therapeutic use ; *Breast Neoplasms/drug therapy/pathology/metabolism ; *Receptor, ErbB-2/metabolism ; *Brain Neoplasms/secondary/drug therapy ; Female ; Camptothecin/analogs & derivatives/therapeutic use ; Antineoplastic Agents, Immunological/therapeutic use ; Immunoconjugates/therapeutic use ; }, abstract = {BACKGROUND: Trastuzumab deruxtecan (T-DXd) has shown promising activity in patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer (BC) and central nervous system (CNS) involvement. In this updated meta-analysis, we explore the effectiveness of T-DXd in a large subset of patients with HER2-positive BC and CNS disease.

METHODS: A systematic search was made on September 16th, 2024, for studies investigating T-DXd in the scenario of HER2-positive BC and brain metastases (BMs) and/or leptomeningeal disease (LMD). We used random effects models for all statistical analyses.

RESULTS: We included 18 studies with 786 HER2-positive BC patients with CNS involvement (16 studies with 750 BMs patients and three studies with 36 LMD patients). We observed high overall antitumor responses (objective response rate [ORR], 60.4 %; disease control rate [DCR], 94.4 %; and clinical benefit rate [CBR], 79.3 %) and a 12-month PFS of 64.7 % and OS of 82.7 %. Intracranial ORR, DCR, and CBR were seen in 62.2 %, 88.6 %, and 68.6 % of patients, respectively, and 67.4 % achieved intracranial PFS at 12 months. Both stable and active BMs subgroups derived similar benefit from T-DXd. Better intracranial responses were seen for 33 patients with untreated BMs compared to 56 patients with previously treated or progressing lesions (odds ratio 3.82, 95 % confidence interval 1.3-10.8, p = 0.01). For the LMD group, T-DXd elicited intracranial ORR and CBR in 59.4 % and 94.1 % of patients, respectively.

CONCLUSIONS: This updated meta-analysis continues to support the overall and intracranial activity of T-DXd in patients with HER2-positive BC and CNS involvement, including those with LMD.}, } @article {pmid39822422, year = {2024}, author = {Aleksiev, T and Popov, V and Dobrev, H}, title = {Radiation-Associated Herpes Zoster: A Clinical Case.}, journal = {Cureus}, volume = {16}, number = {12}, pages = {e75857}, pmid = {39822422}, issn = {2168-8184}, abstract = {Herpes zoster (HZ) is a viral infection caused by the reactivation of endogenous and latent varicella-zoster virus that remains dormant in the cranial nerve or dorsal root ganglia. HZ occurs in a portion of the general population, with a higher incidence observed in high-risk individuals. Patients with impaired immunity, including human immunodeficiency virus infection, organ transplantation, old age, and cancer-related treatments such as chemotherapy (CT) and radiotherapy (RT) were found more prone to HZ infection. We present a case of a 50-year-old patient who underwent a surgical excision of an invasive ductal carcinoma of the right breast. Following 15 fractions of RT, the patient presented with HZ appearing in the radiation field. The patient was treated successfully with Acyclovir, and RT was continued while on maintenance therapy with antiviral drugs. This case presents the importance of early diagnosis and the right choice of treatment in cancer patients and HZ due to the higher risk of complications and further development of the primary condition.}, } @article {pmid39788307, year = {2025}, author = {Doan, VTH and Imai, T and Kawazoe, N and Chen, G and Yoshitomi, T}, title = {Regulation of antigen presentation and interleukin 10 production in murine dendritic cells via the oxidative stimulation of cell membrane using a polycation-porphyrin-conjugate-immobilized cell culture dish.}, journal = {Acta biomaterialia}, volume = {193}, number = {}, pages = {231-241}, doi = {10.1016/j.actbio.2025.01.004}, pmid = {39788307}, issn = {1878-7568}, mesh = {Animals ; *Dendritic Cells/cytology/metabolism/immunology ; *Interleukin-10/metabolism/biosynthesis ; *Porphyrins/chemistry/pharmacology ; Mice ; *Cell Membrane/metabolism ; *Antigen Presentation ; Polyelectrolytes/chemistry/pharmacology ; Oxidation-Reduction ; Mice, Inbred C57BL ; Cell Culture Techniques/methods ; Reactive Oxygen Species/metabolism ; }, abstract = {Tolerogenic dendritic cells with professional antigen presentation via major histocompatibility complex molecules, co-stimulatory molecules (CD80/86), and interleukin 10 production have attracted significant attention as cellular therapies for autoimmune, allergic, and graft-versus-host diseases. In this study, we developed a cell culture dish equipped with polycation-porphyrin-conjugate-immobilized glass (PA-HP-G) to stimulate immature murine dendritic cell (iDCs). Upon irradiation with a red light at 635 nm toward the PA-HP-G surface, singlet oxygen was generated by the immobilized porphyrins on the PA-HP-G surface. When iDCs were cultured on the PA-HP-G surface, moderate light irradiation generated lipid radicals without excessive generation of reactive oxygen species in the cytoplasm and nucleus, which led to the oxidative stimulation of the iDC cell membrane without cell death. Light irradiation changed the morphology of dendritic cells on the PA-HP-G surface to a tree-like structure with dendrites, accelerated their maturation, and enhanced the antigen-presenting ability for the ovalbumin peptide via major histocompatibility complex class I molecules. Additionally, the antigen-presenting dendritic cells on the PA-HP-G surface produced the anti-inflammatory cytokine interleukin 10 upon light irradiation. These results indicated that upon moderate light irradiation, the PA-HP-G surface regulated the maturation of iDCs into tolerogenic dendritic cells. STATEMENT OF SIGNIFICANCE: • Cell culture dish is developed for selective oxidative stimulus of cell membrane. • [1]O2 is generated from polycation/porphyrin-immobilized glass by light irradiation. • Lipid radicals are generated without generation of ROS in cytoplasm and nuclei. • Immature dendritic cells are maturated by oxidative stimulation of cell membrane. • Oxidative membrane stimulus enhances antigen-presentation and IL-10 secretion.}, } @article {pmid38746984, year = {2025}, author = {Rampal, R and Jones, S and Hogg, W and Rengabashyam, B and Hogan, B and Achuthan, R and Kim, B}, title = {Evaluation of long-term outcome following therapeutic mammaplasty: the effect of wound complication on initiation of adjuvant therapy and subsequent oncological outcome.}, journal = {Annals of the Royal College of Surgeons of England}, volume = {107}, number = {2}, pages = {112-118}, pmid = {38746984}, issn = {1478-7083}, mesh = {Humans ; Middle Aged ; Female ; *Mammaplasty/adverse effects ; *Breast Neoplasms/surgery/pathology ; Aged ; Adult ; *Neoplasm Recurrence, Local/epidemiology ; Chemotherapy, Adjuvant ; Disease-Free Survival ; Postoperative Complications/etiology/epidemiology ; Treatment Outcome ; Retrospective Studies ; Carcinoma, Ductal, Breast/surgery/pathology/mortality ; Time-to-Treatment/statistics & numerical data ; }, abstract = {INTRODUCTION: Therapeutic mammaplasty (TM) facilitates large tumour resection while maintaining optimal aesthetic outcome. It carries higher wound complication risks, which may delay adjuvant therapy initiation. Whether this delay affects oncological outcome requires evaluation.

METHODS: Data were collected for consecutive patients receiving TM at the Leeds breast unit (2009-2017). A prospectively maintained database was used to determine tumour characteristics, wound complication rates, receipt of adjuvant therapy and breast cancer recurrence or death.

RESULTS: In total 112 patients (median age of 54 years) underwent 114 TM procedures. The most common histological subtypes were invasive ductal carcinoma (61.4%), invasive lobular carcinoma (13.2%) and ductal carcinoma in situ (13.2%). Of the patients, 88.2% had oestrogen receptor-positive cancer and 14% had human epidermal growth factor receptor-positive cancer; 26.3% had multifocal cancer. The median tumour size was 30mm. The median Nottingham Prognostic Index was 4.2. The local recurrence rate was 3.5% (median follow-up of 8.6 years). The 5- and 10-year disease-free survival (DFS) was 88.5% and 83.5%, and the equivalent overall survival (OS) rates were 94% and 83.5%. Wound complication rate was 23.6% (n=27), the commonest being wound infection (11.4%; n=13) and T-junction wound breakdown (10.5%; n=12). The median time to adjuvant therapy was 72 days (interquartile range [IQR] 56-90) for patients with wound complications, and 51 days (IQR 42-58) for those without. However, this delay did not affect DFS or OS (log-rank test; p=0.58 and p=0.94, respectively). This was confirmed on Cox regression analysis.

CONCLUSION: Our study finding demonstrates that although wound complications after TM leads to a modest delay to adjuvant therapy, the long-term oncological outcomes were comparable with those in patients without wound complications.}, } @article {pmid39821030, year = {2025}, author = {Bullock, E and Brunton, VG}, title = {E-Cadherin-Mediated Cell-Cell Adhesion and Invasive Lobular Breast Cancer.}, journal = {Advances in experimental medicine and biology}, volume = {1464}, number = {}, pages = {259-275}, pmid = {39821030}, issn = {0065-2598}, mesh = {Humans ; *Cadherins/metabolism/genetics ; *Breast Neoplasms/pathology/genetics/metabolism ; Female ; *Carcinoma, Lobular/pathology/genetics/metabolism ; *Cell Adhesion/genetics ; Epithelial-Mesenchymal Transition/genetics ; Neoplasm Invasiveness ; Antigens, CD/genetics/metabolism ; Adherens Junctions/metabolism ; }, abstract = {E-cadherin is a transmembrane protein and central component of adherens junctions (AJs). The extracellular domain of E-cadherin forms homotypic interactions with E-cadherin on adjacent cells, facilitating the formation of cell-cell adhesions, known as AJs, between neighbouring cells. The intracellular domain of E-cadherin interacts with α-, β- and p120-catenins, linking the AJs to the actin cytoskeleton. Functional AJs maintain epithelial tissue identity and integrity. Transcriptional downregulation of E-cadherin is the first step in epithelial-to-mesenchymal transition (EMT), a process essential in development and tissue repair, which, in breast cancer, can contribute to tumour progression and metastasis. In addition, loss-of-function mutations in E-cadherin are a defining feature of invasive lobular breast cancer (also known as invasive lobular carcinoma (ILC)), the second most common histological subtype of breast cancer. ILC displays a discohesive, single-file invasive growth pattern due to the loss of functional AJs. Despite being so prevalent, until recently there has been limited ILC-focused research and historically ILC patients have often been excluded from clinical trials. Despite displaying a number of good prognostic indicators, such as low grade and high rates of estrogen receptor positivity, ILC patients tend to have similar or poorer outcomes relative to the most common subtype of breast cancer, invasive ductal carcinoma (IDC). In ILC, E-cadherin loss promotes hyperactivation of growth factor receptors, in particular insulin-like growth factor 1 receptor, anoikis resistance and synthetic lethality with ROS1 inhibition. These features introduce clinical vulnerabilities that could potentially be exploited to improve outcomes for ILC patients, for whom there are currently limited tailored treatments available.}, } @article {pmid39806949, year = {2025}, author = {Gallas, AE and Morenikeji, GO and King, RE and Adegbaju, MS and Ayoola, A and Taiwo, G and Morenikeji, OB}, title = {An Overview of Invasive Ductal Carcinoma (IDC) in Women's Breast Cancer.}, journal = {Current molecular medicine}, volume = {}, number = {}, pages = {}, doi = {10.2174/0115665240349468241113065031}, pmid = {39806949}, issn = {1875-5666}, abstract = {Invasive ductal carcinoma (IDC) is the most common type of breast cancer, primarily affecting women in the United States and across the world. This review summarizes key concepts related to IDC causes, treatment approaches, and the identification of biological markers for specific prognoses. Furthermore, we reviewed many studies, including those involving patients with IDC and ductal carcinoma in situ (DCIS) that progressed to IDC. We reported various studies on the causes of IDC, including mutations on BRCA1 and BRCA2, different levels of expression of specific genes in signaling pathways, menopause status, alcohol consumption, aging, and hormone imbalances that cause IDC while p-SMAD4 expressions, DNA methylation, regulations of hub genes, and underestimation of IDC affecting prognoses. Prompt IDC diagnosis and early intervention have been reported to demonstrate a greater probability of eradicating IDC and preventing further recurrence in the future. It is crucial for physicians and researchers to equip patients with the best information possible to proactively manage their health, whether it be for IDC prevention or treatment. Overall, our review provided a comprehensive understanding of IDC that enables patients to grasp the nature of the disease with the hope of mitigating IDC risk, decrease the anxiety of a cancer diagnosis, and encourage patients to become more involved in making informed decisions for their healthcare.}, } @article {pmid38839260, year = {2025}, author = {Sun, T and Golestani, R and Zhan, H and Krishnamurti, U and Harigopal, M and Zhong, M and Liang, Y}, title = {Clinicopathologic Characteristics of MYC Copy Number Amplification in Breast Cancer.}, journal = {International journal of surgical pathology}, volume = {33}, number = {1}, pages = {59-64}, doi = {10.1177/10668969241256109}, pmid = {38839260}, issn = {1940-2465}, mesh = {Humans ; Female ; Middle Aged ; *Gene Amplification ; *Breast Neoplasms/pathology/genetics/mortality/diagnosis ; Aged ; Adult ; *Proto-Oncogene Proteins c-myc/genetics/metabolism ; Biomarkers, Tumor/genetics/metabolism/analysis ; Gene Dosage ; Carcinoma, Ductal, Breast/genetics/pathology/diagnosis/mortality ; Aged, 80 and over ; Immunohistochemistry ; High-Throughput Nucleotide Sequencing ; Disease-Free Survival ; }, abstract = {INTRODUCTION: MYC overexpression is a known phenomenon in breast cancer. This study investigates the correlation of MYC gene copy number amplification and MYC protein overexpression with coexisting genetic abnormalities and associated clinicopathologic features in breast cancer patients.

METHODS: The study analyzed data from 81 patients with localized or metastatic breast cancers using targeted next-generation sequencing and MYC immunohistochemical studies, along with pathological and clinical data.

RESULTS: Applying the criteria of MYC/chromosome 8 ratio ≥5, MYC copy number amplified tumors (n = 11, 14%) were associated with invasive ductal carcinoma (91% vs 68%, P = .048), poorly differentiated (grade 3, 64% vs 30%, P = .032), mitotically active (Nottingham mitotic score 3, 71% vs 20%, P = .004), estrogen receptor (ER)-negative (45% vs 12%, P = .008), and triple-negative (56% vs 12%, P = .013) compared to MYC non-amplified tumors. Among MYC-amplified breast cancer patients, those with triple-negative status showed significantly shorter disease-free survival time than non-triple negative MYC-amplified patients (median survival month: 25.5 vs 127.6, P = .049). MYC amplification is significantly associated with TP53 mutation (P = .007). The majority (10 of 11; 91%) of MYC-amplified tumors showed positive c-MYC immunostaining.

CONCLUSION: Breast cancers with MYC copy number amplication display distinct clinicopathologic characteristics indicative of more aggressive behavior.}, } @article {pmid39804847, year = {2025}, author = {Wang, K and Fischer, A and Maccio, U and Zitzmann, K and Robledo, M and Lauseker, M and Bauer, J and Bechmann, N and Gahr, S and Maurer, J and Peischer, L and Reul, A and Nieß, H and Zimmermann, P and Ilmer, M and Schilbach, K and Knösel, T and Kroiss, M and Fassnacht, M and Müller, SA and Morand, GB and Huber, A and Vetter, D and Lehmann, K and Kulcsar, Z and Mohr, H and Pellegata, NS and Hantel, C and Reincke, M and Beuschlein, F and Pacak, K and Grossman, AB and Auernhammer, CJ and Nölting, S}, title = {Impact of sex hormones on pheochromocytomas, paragangliomas, and gastroenteropancreatic neuroendocrine tumors.}, journal = {European journal of endocrinology}, volume = {192}, number = {1}, pages = {46-60}, doi = {10.1093/ejendo/lvae163}, pmid = {39804847}, issn = {1479-683X}, support = {314061271 - TRR 205//German Research Foundation/ ; }, mesh = {Humans ; *Pheochromocytoma/metabolism/pathology/drug therapy ; Female ; *Adrenal Gland Neoplasms/metabolism/pathology/drug therapy ; *Neuroendocrine Tumors/metabolism/pathology/drug therapy ; Male ; *Gonadal Steroid Hormones/pharmacology ; *Pancreatic Neoplasms/metabolism/pathology/drug therapy ; *Paraganglioma/metabolism/genetics/pathology/drug therapy ; *Intestinal Neoplasms/pathology/metabolism ; *Stomach Neoplasms/metabolism/pathology/drug therapy ; Middle Aged ; Estradiol/pharmacology ; Testosterone/pharmacology/metabolism ; Adult ; Progesterone/pharmacology/metabolism ; Dehydroepiandrosterone Sulfate/metabolism ; Cell Survival/drug effects ; Tumor Cells, Cultured ; Estrogen Receptor alpha/metabolism/genetics ; }, abstract = {OBJECTIVE: The effects of sex hormones remain largely unexplored in pheochromocytomas and paragangliomas (PPGLs) and gastroenteropancreatic neuroendocrine tumors (GEP-NETs).

METHODS: We evaluated the effects of estradiol, progesterone, Dehydroepiandrosterone sulfate (DHEAS), and testosterone on human patient-derived PPGL/GEP-NET primary culture cell viability (n = 38/n = 12), performed next-generation sequencing and immunohistochemical hormone receptor analysis in patient-derived PPGL tumor tissues (n = 36).

RESULTS: In PPGLs, estradiol and progesterone (1 µm) demonstrated overall significant antitumor effects with the strongest efficacy in PPGLs with NF1 (cluster 2) pathogenic variants. Estrogen receptor alpha (ERα) positivity was detected in 11/36 PPGLs, including 4/4 head-and-neck paragangliomas (HNPGLs). ERα-positive tumors responded with a significant cell viability decrease to estradiol. DHEAS and testosterone (1 µm) displayed no effects, but higher doses of testosterone (10 µm) demonstrated significant antitumor effects, including a pheochromocytoma lung metastasis with strong androgen receptor positivity (30%). Driven by the antitumor effects of estrogen, we evaluated G-protein-coupled estrogen receptor (GPER) agonist G-1 as a potential therapeutic option for PPGLs and found strong significant antitumor potential, with the strongest efficacy in tumors with NF1 pathogenic variants. Moreover, we detected sex-related differences-tumors from male patients showed significantly stronger responsivity to G-1 compared with tumors from female patients. In GEP-NETs, sex hormones showed overall no effects, especially no tumor growth-promoting effects.

CONCLUSION: We provide novel data on the effects of elevated sex hormone levels, potentially seen during pregnancy or hormone replacement therapy, on PPGL/GEP-NET tumor growth. G-1 might offer a novel therapeutic approach for some PPGLs depending on patient's sex and the individual tumor's genetic/molecular background. All HNPGLs showed ERα positivity.}, } @article {pmid39799921, year = {2025}, author = {Fu, J and Wang, J and Ma, Z and Yuan, D and Zhang, Y and Wang, L and Luo, Y}, title = {CaCO3-coated indoxacarb deep eutectic solvent complexed with diatomaceous earth improves insecticidal activity against the red imported fire ants.}, journal = {Ecotoxicology and environmental safety}, volume = {289}, number = {}, pages = {117709}, doi = {10.1016/j.ecoenv.2025.117709}, pmid = {39799921}, issn = {1090-2414}, abstract = {The red imported fire ants (RIFAs) are a globally important invasive pest that severely affects the ecosystem and human health, and its current control is primarily through chemical pesticides. However, the extensive use of chemical pesticides causes environmental problems, and alternative strategies for controlling this pest are being explored. In our study, we aimed to design a deep eutectic solvent (DES)-CaCO3 system in which RIFAs were used as target insects to increase the lethal activity and behavioural regulation effects on RIFAs via contact and feeding. Indoxacarb (IDC) was made into DESs with three fatty acids, oleic acid (OA), linoleic acid (LA), and linolenic acid (LNA), which showed a significant increase in lethal activity against worker ants compared with IDC. OA@IDC@CaCO3, LA@IDC@CaCO3, and LNA@IDC@CaCO3 nanoparticles were prepared via interfacial precipitation. Characterization of the structures of the three pesticide-carrying nanoparticles revealed that all three fatty acid eutectic solvents formed spherical CaCO3 nanoparticles, with average particle sizes between 0.59 and 0.90 μm, which increased with increasing degree of fatty acid unsaturation. The pesticide loading ranged from 2.13 %⁓3.43 %, and the surfaces were all positively charged and well dispersed. OA@IDC@CaCO3 was relatively more effective and was able to dramatically inhibit the abandonment and foraging behaviours of RIFAs, prolong the time required for these behaviours, and decrease the number of feeding worker ants and the amount of food consumed. OA@IDC@CaCO3 was subsequently compounded with diatomaceous earth (DA), and spiked into baits, which significantly increased the contact and feeding activity of worker ants, inhibited the feeding, digging, and corpse-discarding behaviours of RIFAs. In the field trial, the combined control effect of the DA + OA@IDC@CaCO3 group was 83.38 %, which was greater than the 69.65 % of the commercial agent control group. In this study, IDC bait was co-prepared by using acid as a comelting solvent, CaCO3 as a coating, and DA as a pesticide adjuvant, which improved the activity against RIFAs, prolonged the holding period of IDC, and improved the prevention and control of RIFAs. Therefore, our research provides a simple and feasible approach for designing and constructing novel nanopesticides for RIFAs control.}, } @article {pmid39724992, year = {2025}, author = {Wang, Y and Zhang, J and Wang, Y and Liu, Y and Shi, B and Li, X and He, J and Zhang, H}, title = {Lower expression of MMP2, FLNA, and CFL1 is correlated with favorable prognosis in invasive micropapillary breast cancer.}, journal = {Gene}, volume = {940}, number = {}, pages = {149192}, doi = {10.1016/j.gene.2024.149192}, pmid = {39724992}, issn = {1879-0038}, mesh = {Humans ; Female ; *Breast Neoplasms/genetics/pathology/mortality ; *Filamins/genetics/metabolism ; Prognosis ; Middle Aged ; *Matrix Metalloproteinase 2/genetics/metabolism ; *Cofilin 1/genetics/metabolism ; Retrospective Studies ; *Gene Expression Regulation, Neoplastic ; Aged ; Carcinoma, Ductal, Breast/genetics/pathology/mortality/metabolism ; Biomarkers, Tumor/genetics/metabolism ; Nomograms ; Carcinoma, Papillary/genetics/pathology ; Adult ; }, abstract = {PURPOSE: Despite its recognized aggressive clinical manifestations, invasive micropapillary carcinoma has a controversial prognosis in comparison to invasive ductal carcinoma of the breast. This retrospective study aimed to explore the prognosis and underlying molecular mechanisms of invasive micropapillary carcinoma.

METHODS: Through the SEER database, we compared patients survival outcomes with invasive micropapillary carcinoma versus invasive ductal carcinoma, and developed a nomogram to predict the overall survival of the former group. We explored gene profiles of invasive micropapillary carcinoma in the GEO database. Hub genes were identified as the top ten genes in the PPI network with the highest degrees of connectivity, and three of them were selected for validation by immunohistochemistry.

RESULTS: Invasive micropapillary carcinoma patients had better overall survival and breast cancer-specific survival than invasive ductal carcinoma patients did. Multivariate analysis revealed age, marital status, TN stage, ER status, and chemotherapy as independent prognostic factors for invasive micropapillary carcinoma patients, which were used to construct a nomogram with good performance. A total of 294 DEGs were identified, with ten hub genes, including MMP2, FLNA and CFL1, which were expressed at lower levels in invasive micropapillary carcinoma patients than in invasive ductal carcinoma patients, indicating favorable outcomes.

CONCLUSIONS: Patients with invasive micropapillary carcinoma generally have a better prognosis than those with invasive ductal carcinoma does, which could be attributed to the lower expression of pro-oncogenic genes in the former group; however, the underlying mechanism needs further investigation.}, } @article {pmid39795975, year = {2024}, author = {Caca, J and Bartelt, A and Egea, V}, title = {Hypoxia Regulates Brown Adipocyte Differentiation and Stimulates miR-210 by HIF-1α.}, journal = {International journal of molecular sciences}, volume = {26}, number = {1}, pages = {}, pmid = {39795975}, issn = {1422-0067}, mesh = {*MicroRNAs/genetics/metabolism ; *Hypoxia-Inducible Factor 1, alpha Subunit/metabolism/genetics ; Animals ; *Adipocytes, Brown/metabolism ; *Cell Differentiation/genetics ; Mice ; Thermogenesis/genetics ; Cell Hypoxia ; }, abstract = {MicroRNAs (miRNAs) are short sequences of single-stranded non-coding RNAs that target messenger RNAs, leading to their repression or decay. Interestingly, miRNAs play a role in the cellular response to low oxygen levels, known as hypoxia, which is associated with reactive oxygen species and oxidative stress. However, the physiological implications of hypoxia-induced miRNAs ("hypoxamiRs") remain largely unclear. Here, we investigate the role of miR-210 in brown adipocyte differentiation and thermogenesis. We treated the cells under sympathetic stimulation with hypoxia, CoCl2, or IOX2. To manipulate miR-210, we performed reverse transfection with antagomiRs. Adipocyte markers expression, lipid accumulation, lipolysis, and oxygen consumption were measured. Hypoxia hindered BAT differentiation and suppressed sympathetic stimulation. Hypoxia-induced HIF-1α stabilization increased miR-210 in brown adipocytes. Interestingly, miR-210-5p enhanced differentiation under normoxic conditions but was insufficient to rescue the inhibition of brown adipocyte differentiation under hypoxic conditions. Although adrenergic stimulation activated HIF-1α signaling and upregulated miR-210 expression, inhibition of miR-210-5p did not significantly influence UCP1 expression or oxygen consumption. In summary, hypoxia and adrenergic stimulation upregulated miR-210, which impacted brown adipocyte differentiation and thermogenesis. These findings offer new insights for the physiological role of hypoxamiRs in brown adipose tissue, which could aid in understanding oxidative stress and treatment of metabolic disorders.}, } @article {pmid39721789, year = {2024}, author = {Nagahara, M and Tezuka, K}, title = {[Invasive Ductal Carcinoma with Total Infarction and Necrosis-Case Report and Literature Review].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {51}, number = {12}, pages = {1255-1258}, pmid = {39721789}, issn = {0385-0684}, mesh = {Humans ; Female ; Aged ; *Necrosis ; *Breast Neoplasms/pathology/complications/surgery ; *Infarction/etiology/pathology ; *Carcinoma, Ductal, Breast/complications/pathology/surgery ; Mastectomy ; }, abstract = {A 71-year-old woman visited our hospital with pain and itching in her left breast which had commenced the day before admission. On palpation, we detected a 2.0 cm nodule, indicative of an elastic and hard tumor located centrally in the left breast. Mammography revealed an oval, microlobulated mass in the central quadrant of the left breast. Ultrasonography indicated a 1.5×1.3 cm hypoechoic lesion at the 12 o'clock position near the left nipple. Core needle biopsy revealed an invasive ductal carcinoma. Therefore, we mastectomized the left breast. Histologically, the tumor mass exhibited total necrosis, with viable carcinoma cells detected in a paramammary lymph node at the resected breast edge. Consequently, the tumor was diagnosed as a solid tubular carcinoma with total infarction and necrosis. Here, we present a rare case of breast cancer associated with infarction and necrosis.}, } @article {pmid39708123, year = {2024}, author = {Xie, T and Fan, G and Tang, L and Xing, P and Shi, Y}, title = {Artificial neural network systems to predict the response to sintilimab in squamous-cell non-small-cell lung cancer based on data of ORIENT-3 study.}, journal = {Cancer immunology, immunotherapy : CII}, volume = {74}, number = {1}, pages = {29}, pmid = {39708123}, issn = {1432-0851}, mesh = {Humans ; *Carcinoma, Non-Small-Cell Lung/drug therapy/immunology ; *Neural Networks, Computer ; *Lung Neoplasms/drug therapy/immunology ; *Antibodies, Monoclonal, Humanized/therapeutic use ; Male ; Female ; Biomarkers, Tumor ; Prognosis ; Middle Aged ; Carcinoma, Squamous Cell/drug therapy/immunology ; Aged ; }, abstract = {BACKGROUND: Existing biomarkers and models for predicting response to programmed cell death protein 1 monoclonal antibody in advanced squamous-cell non-small cell lung cancer (sqNSCLC) did not have enough accuracy. We used data from the ORIENT-3 study to construct artificial neural network (ANN) systems to predict the response to sintilimab for sqNSCLC.

METHODS: Four ANN systems based on bulk RNA data to predict disease control (DC), immune DC (iDC), objective response (OR) and immune OR (iOR) were constructed and tested for patients with sqNSCLC treated with sintilimab. The mechanism exploration on the bulk and the spatial level were performed in patients from the ORIENT-3 study and the real world, respectively.

FINDINGS: sqNSCLC patients with different responses to sintilimab showed each unique transcriptomic spectrum. Four ANN systems showed high accuracy in the test cohort (AUC of DC, iDC, OR and iOR were 0.83, 0.89, 0.93 and 0.94, respectively). The performance of ANN systems was better than that of linear model systems and showed high stability. The mechanism exploration on the bulk level suggested that patients with lower ANN system scores (worse response) had a higher ratio of immune-related pathways enrichment. The mechanism exploration on the spatial level indicated that patients with better response to immunotherapy had fewer clusters of both tumor and cytotoxicity T cell spots.

INTERPRETATION: The four ANN systems showed high accuracy, robustness and stability in predicting the response to sintilimab for patients with sqNSCLC.}, } @article {pmid39684874, year = {2024}, author = {Galappaththi, SPL and Smith, KR and Alsatari, ES and Hunter, R and Dyess, DL and Turbat-Herrera, EA and Dasgupta, S}, title = {The Genomic and Biologic Landscapes of Breast Cancer and Racial Differences.}, journal = {International journal of molecular sciences}, volume = {25}, number = {23}, pages = {}, pmid = {39684874}, issn = {1422-0067}, support = {1R21MD019400-01/MD/NIMHD NIH HHS/United States ; }, mesh = {Humans ; *Breast Neoplasms/genetics/pathology/epidemiology ; Female ; *Genomics/methods ; Dysbiosis ; Racial Groups/genetics ; }, abstract = {Breast cancer is a significant health challenge worldwide and is the most frequently diagnosed cancer among women globally. This review provides a comprehensive overview of breast cancer biology, genomics, and microbial dysbiosis, focusing on its various subtypes and racial differences. Breast cancer is primarily classified into carcinomas and sarcomas, with carcinomas constituting most cases. Epidemiology and breast cancer risk factors are important for public health intervention. Staging and grading, based on the TNM and Nottingham grading systems, respectively, are crucial to determining the clinical outcome and treatment decisions. Histopathological subtypes include in situ and invasive carcinomas, such as invasive ductal carcinoma (IDC) and invasive lobular carcinoma (ILC). The review explores molecular subtypes, including Luminal A, Luminal B, Basal-like (Triple Negative), and HER2-enriched, and delves into breast cancer's histological and molecular progression patterns. Recent research findings related to nuclear and mitochondrial genetic alterations, epigenetic reprogramming, and the role of microbiome dysbiosis in breast cancer and racial differences are also reported. The review also provides an update on breast cancer's current diagnostics and treatment modalities.}, } @article {pmid39513960, year = {2025}, author = {Huang, H and Couch, RE and Karam, R and Hu, C and Boddicker, N and Polley, EC and Na, J and Ambrosone, CB and Yao, S and Trentham-Dietz, A and Eliassen, AH and Penney, K and Brantley, K and Bodelon, C and Teras, LR and Hodge, J and Patel, A and Haiman, CA and John, EM and Neuhausen, SL and Martinez, E and Lacey, JV and O'Brien, KM and Sandler, DP and Weinberg, CR and Palmer, JR and Bertrand, KA and Vachon, CM and Olson, JE and Ruddy, KE and Anton-Culver, H and Ziogas, A and Goldgar, DE and Nathanson, KL and Domchek, SM and Weitzel, JN and Kraft, P and Dolinsky, JS and Pesaran, T and Richardson, ME and Yadav, S and Couch, FJ}, title = {Pathogenic Variants in Cancer Susceptibility Genes Predispose to Ductal Carcinoma In Situ of the Breast.}, journal = {Clinical cancer research : an official journal of the American Association for Cancer Research}, volume = {31}, number = {1}, pages = {130-138}, doi = {10.1158/1078-0432.CCR-24-1884}, pmid = {39513960}, issn = {1557-3265}, support = {R35CA253187//National Cancer Institute (NCI)/ ; R01CA225662//National Cancer Institute (NCI)/ ; P50CA116201//National Cancer Institute (NCI)/ ; K12CA090628//National Cancer Institute (NCI)/ ; //Breast Cancer Research Foundation (BCRF)/ ; //Breast Cancer Research Foundation (BCRF)/ ; //Breast Cancer Research Foundation (BCRF)/ ; //Breast Cancer Research Foundation (BCRF)/ ; }, mesh = {Humans ; Female ; *Genetic Predisposition to Disease ; *Breast Neoplasms/genetics/pathology/epidemiology ; *Carcinoma, Intraductal, Noninfiltrating/genetics/pathology/epidemiology ; Middle Aged ; Adult ; *Germ-Line Mutation ; Aged ; Carcinoma, Ductal, Breast/genetics/pathology/epidemiology ; }, abstract = {PURPOSE: To determine the relationship between germline pathogenic variants (PV) in cancer predisposition genes and the risk of ductal carcinoma in situ (DCIS).

EXPERIMENTAL DESIGN: Germline PV frequencies in breast cancer predisposition genes (ATM, BARD1, BRCA1, BRCA2, CDH1, CHEK2, PALB2, RAD51C, and RAD51D) were compared between DCIS cases and unaffected controls and between DCIS and invasive ductal breast cancer (IDC) cases from a clinical testing cohort (n = 9,887), a population-based cohort (n = 3,876), and the UK Biobank (n = 2,421). The risk of contralateral breast cancer (CBC) for DCIS cases with PV was estimated in the population-based cohort.

RESULTS: Germline PV were observed in 6.5% and 4.6% of women with DCIS in the clinical testing and population-based cohorts, respectively. BRCA1, BRCA2, and PALB2 PV frequencies were significantly lower among women with DCIS than those with IDC (clinical cohort: 2.8% vs. 5.7%; population-based cohort: 1.7% vs. 3.7%), whereas the PV frequencies for ATM and CHEK2 were similar. ATM, BRCA1, BRCA2, CHEK2, and PALB2 PV were significantly associated with an increased risk of DCIS (OR > 2.0), but only BRCA2 PV were associated with high risk (OR > 4) in both cohorts. The cumulative incidence of CBC among carriers of PV in high-penetrance genes with DCIS was 23% over 15 years.

CONCLUSIONS: The enrichment of PV in ATM, BRCA1, BRCA2, CHEK2, and PALB2 among women with DCIS suggests that multigene panel testing may be appropriate for women with DCIS. Elevated risks of CBC in carriers of PV in high-penetrance genes with DCIS confirmed the utility of testing for surgical decision-making.}, } @article {pmid39684409, year = {2024}, author = {Feng, M and Cui, H and Li, S and Li, L and Zhou, C and Chen, L and Cao, Y and Gao, Y and Li, D}, title = {Ubiquitin-Activating Enzyme E1 (UBA1) as a Prognostic Biomarker and Therapeutic Target in Breast Cancer: Insights into Immune Infiltration and Functional Implications.}, journal = {International journal of molecular sciences}, volume = {25}, number = {23}, pages = {}, pmid = {39684409}, issn = {1422-0067}, support = {22YF1407800//Shanghai Municipal Commission of Science and Technology/ ; No.82103429//National Natural Science Foundation of China/ ; No.82303311//National Natural Science Foundation of China/ ; }, mesh = {Humans ; *Breast Neoplasms/genetics/immunology/pathology/metabolism ; Female ; *Ubiquitin-Activating Enzymes/genetics/metabolism ; *Biomarkers, Tumor/genetics/metabolism ; Prognosis ; *Gene Expression Regulation, Neoplastic ; Cell Line, Tumor ; }, abstract = {Ubiquitin-Activating Enzyme E1 (UBA1), an E1 enzyme involved in the activation of ubiquitin enzymes, has been involved in the onset and progression of different cancers in humans. Nevertheless, the precise contribution of UBA1 in breast cancer (BC) is still poorly characterized. In this study, a thorough investigation was carried out to elucidate the significance of UBA1 and validate its functionality in BC. Through the analysis of mRNA sequencing data of BC patients, the mRNA expression of UBA1 was observed to be notably enhanced in cancer tissues relative to controls, and high UBA1 expression was linked to worse overall survival (OS), disease-specific survival (DSS), and progress-free survival (PFS). Moreover, UBA1 exhibited potential as an independent prognostic and diagnostic biomarker for individuals with BC. Additionally, functional enrichment analysis revealed the involvement of UBA1 in inflammation-linked pathways, like the TNF-α signaling pathway, the IL-6 signaling pathway, and various immune-related biological processes. Notably, single-sample gene set enrichment analysis (ssGSEA) aided in the identification of a negative link between UBA1 expression and the levels of infiltrating mast cells, Th1 cells, iDC cells, B cells, DC cells, Tem cells, Cytotoxic cells, T cells, CD8T cells, and pDC cells. Finally, this study demonstrated that silencing UBA1 significantly impeded the growth and development of BC cell lines. These findings highlight UBA1 as a potential prognostic biomarker linked to immune infiltration in BC, thereby depicting its potential as a new therapeutic target for individuals with BC.}, } @article {pmid39654135, year = {2024}, author = {Rasheed, U and Khalid, M and Noor, A and Saeed, U and Uppal, R and Zafar, S}, title = {Genetic assessment of apolipoprotein E polymorphism and PRNP genotypes in rapidly progressive dementias in Pakistan.}, journal = {Prion}, volume = {18}, number = {1}, pages = {1-7}, doi = {10.1080/19336896.2024.2439598}, pmid = {39654135}, issn = {1933-690X}, mesh = {Humans ; Pakistan ; *Prion Proteins/genetics ; *Genotype ; *Apolipoproteins E/genetics ; Female ; Male ; Polymorphism, Genetic/genetics ; Creutzfeldt-Jakob Syndrome/genetics ; Dementia/genetics ; Mutation/genetics ; Alleles ; Gene Frequency/genetics ; Middle Aged ; Alzheimer Disease/genetics ; Aged ; }, abstract = {Rapidly progressive dementias (RPDs) are a type of fatal dementias that cause rapid progression of neuronal dysfunction. This study aimed to assess the prevalence of APOE genotypes (ε2, ε3, ε4) and PRNP mutations (E200K, M129V) in the general population of Pakistan because of their association with RPDs, including Rapidly Progressive Alzheimer's Disease (rpAD) and Creutzfeldt-Jakob Disease (CJD). Blood samples (n = 100) were collected from healthy Pakistani population and the stated mutations were assessed using polymerase chain reaction. In the analysis of the APOE genotype, ε3/ε3 genotype was the most common (95%), followed by ε3/ε4 (5%) and ε2 allele was completely absent. A low frequency of ε4 allele and the absence of a protective ε2 allele is associated with an increased risk of rpAD. In the case of PRNP mutations, the most common genotype was M129-Ε200 (71%) and V129-Ε200 (29%). E200K mutation was completely absent from the given population. It is noteworthy that the MM homozygous genotype was present in 71 samples, VV genotype was present in 29. Homozygosity on codon 129, as observed in most of our samples, has been associated with more efficient production of PrP[Sc] and disease pathology. This study provides preliminary data indicating that rpAD and CJD pose a significant threat to the Pakistani population.}, } @article {pmid39578650, year = {2024}, author = {Berriel Diaz, M and Rohm, M and Herzig, S}, title = {Cancer cachexia: multilevel metabolic dysfunction.}, journal = {Nature metabolism}, volume = {6}, number = {12}, pages = {2222-2245}, pmid = {39578650}, issn = {2522-5812}, support = {949017//EC | EU Framework Programme for Research and Innovation H2020 | H2020 Priority Excellent Science | H2020 European Research Council (H2020 Excellent Science - European Research Council)/ ; }, mesh = {*Cachexia/metabolism/etiology ; Humans ; *Neoplasms/complications/metabolism ; *Energy Metabolism ; Animals ; Metabolic Diseases/metabolism/complications/etiology ; }, abstract = {Cancer cachexia is a complex metabolic disorder marked by unintentional body weight loss or 'wasting' of body mass, driven by multiple aetiological factors operating at various levels. It is associated with many malignancies and significantly contributes to cancer-related morbidity and mortality. With emerging recognition of cancer as a systemic disease, there is increasing awareness that understanding and treatment of cancer cachexia may represent a crucial cornerstone for improved management of cancer. Here, we describe the metabolic changes contributing to body wasting in cachexia and explain how the entangled action of both tumour-derived and host-amplified processes induces these metabolic changes. We discuss energy homeostasis and possible ways that the presence of a tumour interferes with or hijacks physiological energy conservation pathways. In that context, we highlight the role played by metabolic cross-talk mechanisms in cachexia pathogenesis. Lastly, we elaborate on the challenges and opportunities in the treatment of this devastating paraneoplastic phenomenon that arise from the complex and multifaceted metabolic cross-talk mechanisms and provide a status on current and emerging therapeutic approaches.}, } @article {pmid39418320, year = {2025}, author = {Schwarz, D and Le Marois, M and Sturm, V and Peters, AS and Longuespée, R and Helm, D and Schneider, M and Eichmüller, B and Hidmark, AS and Fischer, M and Kender, Z and Schwab, C and Hausser, I and Weis, J and Dihlmann, S and Böckler, D and Bendszus, M and Heiland, S and Herzig, S and Nawroth, PP and Szendroedi, J and Fleming, T}, title = {Exploring Structural and Molecular Features of Sciatic Nerve Lesions in Diabetic Neuropathy: Unveiling Pathogenic Pathways and Targets.}, journal = {Diabetes}, volume = {74}, number = {1}, pages = {65-74}, doi = {10.2337/db24-0493}, pmid = {39418320}, issn = {1939-327X}, support = {GRK 1874/2//DFG/ ; //Deutsche Forschungsgemeinschaft/ ; //German Centre for Diabetes Research/ ; }, mesh = {*Diabetic Neuropathies/metabolism/pathology ; Humans ; *Sciatic Nerve/metabolism/pathology ; Male ; *Diabetes Mellitus, Type 2/metabolism/complications ; Middle Aged ; *Proteomics ; Female ; Aged ; Blood-Nerve Barrier/metabolism ; Magnetic Resonance Imaging ; Adult ; }, abstract = {Lesioned fascicles (LFs) in the sciatic nerves of individuals with diabetic neuropathy (DN) correlate with clinical symptom severity. This study aimed to characterize the structural and molecular composition of these lesions to better understand DN pathogenesis. Sciatic nerves from amputees with and without type 2 diabetes (T2D) were examined using ex vivo magnetic resonance neurography, in vitro imaging, and proteomic analysis. Lesions were only found in T2D donors and exhibited significant structural abnormalities, including axonal degeneration, demyelination, and impaired blood-nerve barrier (BNB). Although non-LFs from T2D donors showed activation of neuroprotective pathways, LFs lacked this response and instead displayed increased complement activation via the classical pathway. The detection of liver-derived acute-phase proteins suggests that BNB disruption facilitates harmful interorgan communication between the liver and nerves. These findings reveal key molecular mechanisms contributing to DN and highlight potential targets for therapeutic intervention.}, } @article {pmid39645755, year = {2024}, author = {Parmar, DS and Thakur, MN and Agarwal, I and Ganesh, SR and Vogel, G}, title = {Report of stray sightings of Dendrelaphis proarchos (Wall, 1909) (Serpentes: Colubridae) in Surat, Gujarat, western India.}, journal = {Zootaxa}, volume = {5433}, number = {2}, pages = {231-248}, doi = {10.11646/zootaxa.5433.2.4}, pmid = {39645755}, issn = {1175-5334}, mesh = {Animals ; India ; Male ; *Animal Distribution ; Female ; *Colubridae/anatomy & histology/classification/growth & development ; Animal Structures/anatomy & histology/growth & development ; Body Size ; Ecosystem ; Organ Size ; Humans ; }, abstract = {We here report on likely human-mediated, stray sightings of Dendrelaphis proarchos (Wall, 1909) in an unnatural range-Surat, Gujarat in western India. This population shows the following characters: (1) vertebral scales distinctly enlarged, larger than the dorsals of the first row; (2) 185-194 ventrals; (3) 139-142 divided subcaudals in complete tails; (4) 15 dorsal scale rows at midbody; (5) cloacal shield undivided; (6) one loreal scale; (7) three supralabials touching the eye; (8) a moderate first sublabial that touches two infralabials; (9) 11-12 temporal scales; (10) preoculars 1 or 2; (11) two or three postoculars; (12) maximum total length 1150 mm; (13) interparietal spot absent; (14) a black temporal stripe that does not starts on the postnasal or loreal but starts on the center of the eye follows postoculars (middle or second postocular) covers the majority of the temporal region and extends onto the neck; (15) a distinct, bright ventrolateral stripe bordered by one black line at the bottom; (16) dorsal interstitial color blue and (17) tongue color red with black tip. Data from a partial fragment of the mitochondrial 16S gene also reveal genetic congruence with published sequences from Sagaing and Ayeyarwady in Myanmar and Mizoram, India, further attesting the morphological conclusions. Absence of any sighting of this form in the wild despite long-term (> 15 years) studies in south Gujarat by us, the lack of previous reports of this population especially in natural habitats in Gujarat by colleagues, and reports of many such stray populations of non-native herpetofauna in the coastal port city of Surat together, indicate an unnatural, probably human-mediated, transportation of D. proarchos to Surat. Such likely human-mediated introductions of species outside their native range are a cause for concern and require awareness campaigns among snake rescuers not to 'release' such snakes in the Gujarat forests, but to keep them in zoos or return to the actual point of wild origin, if known or feasible.}, } @article {pmid39639228, year = {2024}, author = {Hu, J and Ke, J and Xu, S and Pei, L and Cao, L and Zhou, H and Zhu, X}, title = {The combination of focal breast edema and adjacent vessel sign to assess the behavior of mass-type invasive ductal carcinoma.}, journal = {BMC medical imaging}, volume = {24}, number = {1}, pages = {332}, pmid = {39639228}, issn = {1471-2342}, mesh = {Humans ; Female ; *Breast Neoplasms/diagnostic imaging/pathology/complications ; Middle Aged ; Retrospective Studies ; *Carcinoma, Ductal, Breast/diagnostic imaging/pathology/complications ; *Magnetic Resonance Imaging/methods ; *Edema/diagnostic imaging/pathology ; Adult ; Aged ; Breast/diagnostic imaging/pathology/blood supply ; Lymphatic Metastasis/diagnostic imaging ; Neoplasm Invasiveness ; Neoplasm Grading ; }, abstract = {BACKGROUND: The objective of this study was to investigate the association between focal breast edema (FBE) and adjacent vessel sign (AVS) with tumor size, histologic grade, lymphovascular invasion, axillary lymph node status, Ki-67 index, and molecular subtype in breast cancer. These findings have provided valuable insights into the biological characteristics and prognosis of mass-type invasive ductal carcinoma (M-IDC).

METHODS: We retrospectively included patients with M-IDC between January 2016 and December 2021. FBE was evaluated using T2-weighted sequence. AVS was assessed using maximum-intensity projection images obtained using early dynamic contrast-enhanced magnetic resonance imaging. The breast peritumor score (BPS) was defined as follows: BPS 1, absence of both edema and AVS; BPS 2, AVS without edema; BPS 3, AVS with peritumoral edema; BPS 4, AVS with prepectoral edema; and BPS 5, AVS with subcutaneous edema. The correlation between different BPS scores and clinicopathological variables was examined using Kendall's tau-b correlation coefficient. The DeLong test was used to compare the performances of three clinicopathological models combined with peritumoral features (FBE, AVS, and BPS) in predicting luminal A-like M-IDC.

RESULTS: In 228 patients with M-IDC, BPS was positively correlated with tumor size, histologic grade, lymphovascular invasion, axillary lymph node status, Ki-67 index, and negatively correlated with estrogen receptor expression (all P < 0.05). Furthermore, BPS 1 was more likely to be present in patients with luminal A-like breast cancer (P < 0.001). Among the three prediction models, the clinicopathological model combined with the BPS model demonstrated superior diagnostic performance for luminal A-like breast cancer.

CONCLUSIONS: The BPS is a valuable, non-invasive biomarker for assessing the aggressiveness of M-IDC and can facilitate treatment planning.}, } @article {pmid39612651, year = {2024}, author = {Shrestha, LB and Tungatt, K and Aggarwal, A and Stubis, A and Fewings, NL and Fichter, C and Akerman, A and Rodrigo, C and Tedla, N and Lee, S and Lloyd, AR and Brilot, F and Britton, WJ and Kelleher, A and Caterson, ID and Douglas, MW and Rockett, R and Tangye, SG and Triccas, JA and Turville, SG and Sandgren, KJ and Bull, RA and Cunningham, AL and , }, title = {Bivalent Omicron BA.1 vaccine booster increases memory B cell breadth and neutralising antibodies against emerging SARS-CoV-2 variants.}, journal = {EBioMedicine}, volume = {110}, number = {}, pages = {105461}, doi = {10.1016/j.ebiom.2024.105461}, pmid = {39612651}, issn = {2352-3964}, mesh = {Humans ; *COVID-19 Vaccines/immunology/administration & dosage ; *SARS-CoV-2/immunology ; *Memory B Cells/immunology ; *COVID-19/immunology/prevention & control ; *Antibodies, Viral/immunology ; *Antibodies, Neutralizing/immunology ; *Immunization, Secondary ; *Spike Glycoprotein, Coronavirus/immunology ; Adult ; Female ; Male ; Middle Aged ; Immunologic Memory ; B-Lymphocytes/immunology ; }, abstract = {BACKGROUND: Current literature informs us that bivalent vaccines will generate a broader serum neutralizing antibody response to multiple SARS-CoV-2 variants, but studies on how this breadth relates to the memory B cell (MBC) and T cell responses are sparse. This study compared breadth of neutralising antibody, and memory B and T cell responses to monovalent or a bivalent ancestral/Omicron BA.1 COVID-19 booster vaccine.

METHODS: At baseline and 1-month post-booster, neutralisation activity and frequencies of receptor binding domain (RBD)-specific MBCs and Spike-specific memory T cells were measured against a panel of variants.

FINDINGS: Both vaccines boosted neutralising antibodies to 5 variants - Wuhan-Hu-1, Delta, BA.1, BA.5 and JN.1, the latter of which had not yet emerged at the time of sample collection. The bivalent vaccine induced a significantly larger increase in nAb against BA.1 and JN.1. Both vaccines boosted RBD-specific MBC responses to Wuhan-Hu-1, Delta, BA.1 and BA.5 variants with a significantly greater increase for BA.1 in the bivalent group. The breadth of MBCs was significantly higher in those who received the bivalent boost and correlated with nAb breadth. Both vaccines significantly boosted Spike-specific T cell responses to the Wuhan-Hu-1 and BA.5 variants, but only the bivalent vaccine boosted BA.1 responses.

INTERPRETATION: These results suggest that the bivalent vaccine confers an advantage against future novel variants due to increased frequency of broadly reactive RBD-specific B cells.

FUNDING: Work supported by NSW Health for the NSW Vaccine, Infection and Immunology Collaborative (VIIM).}, } @article {pmid38833720, year = {2025}, author = {Wang, L and Vasudevaraja, V and Tran, I and Sukhadia, P and Reuter, VE and Abu-Rustum, NR and Rubinstein, MM and Gopalan, A and Ross, D and Snuderl, M and Chiang, S}, title = {Novel Androgen Receptor Splice Variant 7 in Gynecologic Tumors.}, journal = {International journal of gynecological pathology : official journal of the International Society of Gynecological Pathologists}, volume = {44}, number = {1}, pages = {88-93}, doi = {10.1097/PGP.0000000000001029}, pmid = {38833720}, issn = {1538-7151}, mesh = {Humans ; Female ; *Receptors, Androgen/genetics ; Ovarian Neoplasms/pathology/genetics ; Biomarkers, Tumor/genetics ; Middle Aged ; Uterine Neoplasms/genetics/pathology ; Genital Neoplasms, Female/genetics/pathology ; DNA Methylation ; Aged ; }, abstract = {Androgen receptor splicing variant 7 (AR-V7) is a truncated variant of the AR mRNA that may be a predictive biomarker for AR-targeted therapy. AR-V7 has been described in prostate, breast, salivary duct, and hepatocellular carcinomas as well as mammary and extra-mammary Paget disease. We report 2 gynecologic cancers occurring in the lower uterine segment and ovary and both harboring AR-V7 by targeted RNA sequencing. The uterine tumor was an undifferentiated carcinoma consisting of epithelioid cells and focally spindled cells arranged in sheets, nests, and cords associated with brisk mitotic activity and tumor necrosis. The ovarian tumor consisted of glands with cribriform and solid architecture and uniform cytologic atypia. ER and PR were positive in the ovarian tumor and negative in the uterine tumor. Both were positive for AR and negative for HER2, GATA3, and NKX3.1. DNA methylation profiling showed epigenetic similarity of the AR-V7-positive gynecologic cancers to AR-V7-positive breast cancers rather than to prostate cancers. AR-V7 may underpin rare gynecologic carcinomas with undifferentiated histology or cribriform growth reminiscent of prostatic adenocarcinoma and breast invasive ductal carcinoma.}, } @article {pmid39639029, year = {2024}, author = {Nayak, S and Peto, TJ and Kucharski, M and Tripura, R and Callery, JJ and Quang Huy, DT and Gendrot, M and Lek, D and Nghia, HDT and van der Pluijm, RW and Dong, N and Long, LT and Vongpromek, R and Rekol, H and Hoang Chau, N and Miotto, O and Mukaka, M and Dhorda, M and von Seidlein, L and Imwong, M and Roca, X and Day, NPJ and White, NJ and Dondorp, AM and Bozdech, Z}, title = {Population genomics and transcriptomics of Plasmodium falciparum in Cambodia and Vietnam uncover key components of the artemisinin resistance genetic background.}, journal = {Nature communications}, volume = {15}, number = {1}, pages = {10625}, pmid = {39639029}, issn = {2041-1723}, mesh = {*Artemisinins/pharmacology/therapeutic use ; *Plasmodium falciparum/genetics/drug effects ; Cambodia ; *Drug Resistance/genetics ; Humans ; *Malaria, Falciparum/parasitology/drug therapy ; *Antimalarials/pharmacology/therapeutic use ; *Polymorphism, Single Nucleotide ; Vietnam ; Protozoan Proteins/genetics/metabolism ; Transcriptome ; Genomics ; Gene Expression Profiling ; }, abstract = {The emergence of Plasmodium falciparum parasites resistant to artemisinins compromises the efficacy of Artemisinin Combination Therapies (ACTs), the global first-line malaria treatment. Artemisinin resistance is a complex genetic trait in which nonsynonymous SNPs in PfK13 cooperate with other genetic variations. Here, we present population genomic/transcriptomic analyses of P. falciparum collected from patients with uncomplicated malaria in Cambodia and Vietnam between 2018 and 2020. Besides the PfK13 SNPs, several polymorphisms, including nonsynonymous SNPs (N1131I and N821K) in PfRad5 and an intronic SNP in PfWD11 (WD40 repeat-containing protein on chromosome 11), appear to be associated with artemisinin resistance, possibly as new markers. There is also a defined set of genes whose steady-state levels of mRNA and/or splice variants or antisense transcripts correlate with artemisinin resistance at the base level. In vivo transcriptional responses to artemisinins indicate the resistant parasite's capacity to decelerate its intraerythrocytic developmental cycle (IDC), which can contribute to the resistant phenotype. During this response, PfRAD5 and PfWD11 upregulate their respective alternatively/aberrantly spliced isoforms, suggesting their contribution to the protective response to artemisinins. PfRAD5 and PfWD11 appear under selective pressure in the Greater Mekong Sub-region over the last decade, suggesting their role in the genetic background of the artemisinin resistance.}, } @article {pmid38348593, year = {2024}, author = {Schweiger, M and Arredondo-Lasso, MN and Friano, ME and Gil-Lozano, M and Herzig, S and Uhlenhaut, NH}, title = {Lipid sensing nuclear receptors involved in the pathogenesis of fatty liver disease.}, journal = {FEBS letters}, volume = {598}, number = {23}, pages = {2854-2855}, doi = {10.1002/1873-3468.14818}, pmid = {38348593}, issn = {1873-3468}, support = {UH 275/6-1-ID 457050056//German Research Foundation DFG/ ; TRR333 BATEnergy ID 450149205//German Research Foundation DFG/ ; TRR205 Adrenal Gland ID 314061271//German Research Foundation DFG/ ; CRC1064 Chromatin Dynamics ID 213249687//German Research Foundation DFG/ ; 457050056//German Research Foundation/ ; 450149205//TRR333 BAT-Energy/ ; }, mesh = {Humans ; *Receptors, Cytoplasmic and Nuclear/metabolism/genetics ; Animals ; *Lipid Metabolism ; *Non-alcoholic Fatty Liver Disease/metabolism/pathology/genetics ; Fatty Liver/metabolism/pathology/genetics ; }, abstract = {Non-alcoholic fatty liver disease (NAFLD) begins with lipid accumulation and progresses toward inflammation and fibrosis. Nuclear receptors (NRs), like the Peroxisome Proliferator-Activated Receptors alpha and gamma (PPARα and PPARy), the Farnesoid X Receptor (FXR), and the Liver X receptor (LXR), regulate genes by heterodimerizing with Retinoid X receptor (RXR). These receptors are emerging targets for pharmaceutical intervention for metabolic diseases.}, } @article {pmid39637037, year = {2024}, author = {Jha, A and Chaudhary, RK and Shrivastav, S and Khanal, U}, title = {Ultrasonographic and pathological correlation of asymmetric retroareolar density on mammogram.}, journal = {PloS one}, volume = {19}, number = {12}, pages = {e0301180}, pmid = {39637037}, issn = {1932-6203}, mesh = {Humans ; Female ; Middle Aged ; *Mammography/methods ; Adult ; *Breast Neoplasms/diagnostic imaging/pathology ; Aged ; Nipples/diagnostic imaging/pathology ; Mastitis/diagnostic imaging/pathology ; Ultrasonography/methods ; Breast Density ; Carcinoma, Ductal, Breast/diagnostic imaging/pathology ; Ultrasonography, Mammary/methods ; }, abstract = {BACKGROUND: Retroareolar region refers to the region within two centimeters from the nipple and/or involves the nipple-areolar complex on mammogram. In this study, we graded asymmetric retroareolar density on mammography and determined the underlying cause.

OBJECTIVES: To identify and grade retroareolar densities and evaluate characteristics of lesion using ultrasonography and histopathology.

METHODS: Mammograms with asymmetric retroareolar density done in our tertiary care hospital were included. Retroareolar density was categorized into three grades based on morphological appearance in mammography. Sonography was performed in all patients and tissue diagnosis was obtained for suspicious lesions.

RESULTS: Of the 100 patients included in the study, most of the patients with mammographic grade 1, grade 2 and 3 retroareolar asymmetry had normal sonography, pathologically proven mastitis and invasive ductal carcinoma, respectively. Presenting indication usually was diagnostic (n = 87), lump being most common. Benign (58%) diagnosis was more often present, with equal number of normal studies and malignancies (21%). Frequently pathologically proven malignant lesions (n = 17) had grade 3 asymmetry and none were grade 1. Invasive ductal carcinoma was the most common malignancy while mastitis the most common benign disease.

CONCLUSIONS: Grade I retroareolar asymmetric density on mammography was normal or had a benign etiology while grade 2 or 3 asymmetric density had underlying pathology, often malignancy.

CONTRIBUTION: Grading retroareolar density in mammogram may improve the evaluation of retroareolar region and increase emphasis on higher grades.}, } @article {pmid39621168, year = {2024}, author = {Im, YJ and Yoon, YC and Sung, DH}, title = {Brachial plexopathy due to perineural tumor spread: a retrospective single-center experience of clinical manifestations, diagnosis, treatments, and outcomes.}, journal = {Acta neurochirurgica}, volume = {166}, number = {1}, pages = {490}, pmid = {39621168}, issn = {0942-0940}, mesh = {Humans ; Middle Aged ; Female ; Retrospective Studies ; *Brachial Plexus Neuropathies/diagnosis/etiology ; Male ; Adult ; *Positron Emission Tomography Computed Tomography/methods ; Aged ; *Breast Neoplasms/pathology/diagnostic imaging ; *Peripheral Nervous System Neoplasms/diagnostic imaging/pathology/diagnosis ; Lung Neoplasms/pathology/diagnostic imaging/diagnosis ; Treatment Outcome ; Magnetic Resonance Imaging ; Carcinoma, Ductal, Breast/pathology/diagnostic imaging/diagnosis ; Thyroid Cancer, Papillary/pathology/diagnostic imaging/diagnosis/surgery/therapy ; Fluorodeoxyglucose F18 ; Brachial Plexus/pathology/diagnostic imaging ; Adenocarcinoma of Lung/pathology/diagnostic imaging/diagnosis ; }, abstract = {BACKGROUND: Perineural tumor spread (PNTS) to the brachial plexus (BP) is a rare and challenging condition. This study aimed to elucidate the clinical presentations, diagnostic challenges, and outcomes of patients with PNTS to the BP.

METHODS: We retrospectively reviewed patients diagnosed with PNTS to the BP at our institution between January 2009 and June 2024. Clinical characteristics, magnetic resonance imaging (MRI), [18]F-fluorodeoxyglucose ([18]F-FDG) positron emission tomography/computed tomography (PET/CT) findings, and treatment outcomes were analyzed.

RESULTS: Seven patients (mean age, 50.3 years) were identified. The primary cancer diagnoses included invasive ductal carcinoma of the breast (n = 3), metaplastic carcinoma of the breast (n = 1), lung adenocarcinoma (n = 2), and papillary thyroid carcinoma (n = 1). The median time from the initial cancer diagnosis to PNTS symptom onset was 71.0 months. All patients initially presented with progressive unilateral pain or paresthesia, followed by motor weakness. Lower trunk plexopathy was the most common electrodiagnostic finding (n = 5). In most patients, BP MRI showed diffuse tubular enlargement and T2 hyperintensity throughout the BP (n = 6), with gadolinium enhancement primarily in the proximal regions (n = 7). [18]F-FDG PET/CT demonstrated increased uptake in the BP, most prominently at the cervical spinal root or trunk levels (n = 6). Despite treatment, neurological outcomes were generally poor. Six of the seven patients died after a median follow-up of 19 months post-PNTS diagnosis.

CONCLUSIONS: PNTS to the BP can occur years after initial cancer diagnosis and may signify cancer progression. A high index of suspicion is crucial for timely diagnosis, particularly in patients with cancer and progressive upper extremity symptoms. Comprehensive imaging, including BP MRI and PET/CT, is essential for diagnosis. Despite treatment, prognosis remains poor, highlighting the need for improved diagnostic and therapeutic strategies.}, } @article {pmid39616738, year = {2024}, author = {Rivera, A and Plumber, N and Louis, M and Grabill, N and Strom, P}, title = {Surgical stress as a potential trigger for spontaneous coronary artery dissection: A case report.}, journal = {International journal of surgery case reports}, volume = {126}, number = {}, pages = {110644}, doi = {10.1016/j.ijscr.2024.110644}, pmid = {39616738}, issn = {2210-2612}, abstract = {INTRODUCTION AND IMPORTANCE: Spontaneous coronary artery dissection (SCAD) is a rare cause of acute coronary syndrome, predominantly affecting women without traditional cardiovascular risk factors. It is often underdiagnosed, especially in postoperative patients, due to its atypical presentation and the challenges in distinguishing it from other causes of chest pain.

CASE PRESENTATION: We report the case of a 62-year-old woman with type 2 diabetes mellitus, hypertension, hyperlipidemia, and recent bilateral mastectomy for invasive ductal carcinoma, who presented three days post-surgery with sudden onset of chest pain radiating to her left arm. Electrocardiography revealed ST-segment depression suggestive of anterior ischemia, and cardiac biomarkers were significantly elevated. Imaging studies were limited due to recent surgery, but urgent coronary angiography identified spontaneous coronary artery dissections.

CLINICAL DISCUSSION: This case highlights the potential role of surgical stress as a precipitating factor for SCAD in patients without traditional cardiovascular risk factors. The physiological stress of major surgery may contribute to arterial wall vulnerability and dissection. Diagnostic challenges in the postoperative setting necessitate a high index of suspicion for timely identification. Conservative management was pursued, aligning with current guidelines that favor non-invasive treatment in stable SCAD cases to prevent further dissection or complications.

CONCLUSION: SCAD should be considered in the differential diagnosis of acute coronary syndrome in postoperative patients presenting with chest pain, even in the absence of significant cardiovascular risk factors. Early recognition and appropriate management are crucial for improving patient outcomes.}, } @article {pmid39610583, year = {2024}, author = {Yasin, R and Zafar, G and Rooman Ali Syed, F and Afzal, S and Fatima, M and Rathore, Z and Chughtai, A and Chughtai, A}, title = {CK5/6 Expression in Molecular Subtypes of Invasive Ductal Carcinoma.}, journal = {Cureus}, volume = {16}, number = {10}, pages = {e72608}, pmid = {39610583}, issn = {2168-8184}, abstract = {Background Breast cancer (BC) is the leading cause of cancer-related deaths in women worldwide. There has been a significant increase in the incidence of BC in Pakistan. Family history, older age, obesity, tobacco use, oral contraceptive use, early menarche, and hormonal replacement therapy are among the major risk factors. The most common histological subtype of BC is invasive ductal carcinoma (IDC). Molecular subtypes of BC include mainly Luminal A, Luminal B, human epidermal growth factor receptor 2 (HER-2) enriched, and triple-negative BC subtypes, with the triple-negative subtype having the worst prognosis. CK5/6 serves as a basal keratin biomarker. This aimed to assess the expression of CK5/6 in IDC of the breast belonging to different molecular classes and to compare its expression with traditionally defined prognostic factors for different molecular subtypes. Methodology A cross-sectional, observational study was conducted at the Chughtai Institute of Pathology after approval from the Institutional Review Board (approval number: 1198/IRB/CIP). All cases during a period of six months (April 2023 to September 2023) were sampled using non-probability convenient sampling. All mastectomy samples diagnosed as IDC were included in the study. After standard tissue processing, paraffin tissue blocks and slides were prepared followed by hematoxylin & eosin staining. Hormonal receptors (estrogen receptor, progesterone receptor, HER-2) were assessed for cases to segregate them into molecular subtypes. CK5/6 antibody was then applied and the data were collected on a pre-designed proforma. SPSS version 25.0 (IBM Corp., Armonk, NY, USA) was used for data analysis. Results Of a total of 85 cases, 19 (22.3%) were positive for CK5/6. Of these 19 cases, the majority (68%, p = 0.001) belonged to the triple-negative class of tumors, comprising 13 cases. No case from the Luminal A class showed expression for CK5/6 stain (p = 0.028). Overall, four cases of the Luminal B subtype showed CK5/6 positivity (10.8%, p = 0.022) while two cases of the HER-2-enriched subtype were positive for the stain (33.3%, p > 0.05). These results were analyzed in relation to different prognostic factors. The majority of CK5/6-positive cases showed lymphovascular invasion (42%) and belonged to grade 3 tumors (57.8%). Conclusions The expression of CK5/6 in IDC of the breast is associated with poor prognostic factors such as triple-negative molecular subtypes, high histological grade, lymphovascular invasion, positive nodal status, and high pathological stage.}, } @article {pmid39605123, year = {2024}, author = {Noroozpoor, M and Mozdarani, H and Rahbar Parvaneh, R and Lashkari, M}, title = {Evaluation of TP53TG1 and PANDA lncRNAs expression in association with adjuvant chemotherapy response in the peripheral blood of invasive ductal carcinoma patients.}, journal = {Cellular and molecular biology (Noisy-le-Grand, France)}, volume = {70}, number = {10}, pages = {58-63}, doi = {10.14715/cmb/2024.70.10.9}, pmid = {39605123}, issn = {1165-158X}, mesh = {Humans ; Female ; Chemotherapy, Adjuvant ; *RNA, Long Noncoding/genetics/blood ; *Breast Neoplasms/drug therapy/genetics/blood ; Middle Aged ; *Gene Expression Regulation, Neoplastic/drug effects ; Carcinoma, Ductal, Breast/drug therapy/genetics/blood ; Adult ; Biomarkers, Tumor/genetics/blood ; }, abstract = {Breast cancer is the most common malignancy in women. Breast cancer, the second leading cause of cancer deaths, affects 2.1 million women each year and is estimated to have killed 627,000 women worldwide in 2018. Unfortunately, the age of onset of this cancer in our country IRAN is about 10 years lower than the global average and is close to 45 years. Chemotherapy is one of the basic treatments for cancer. Predicting the benefits of chemotherapy is challenging. Studies are now underway to use gene expression tests to pinpoint patients who are most likely to benefit from adjuvant chemotherapy. In the present study, the expression of two long non-coding RNAs TP53TG1 and PANDA in the blood of breast cancer patients before and after receiving chemotherapy compared with this amount in the blood of normal people using Real-Time RT PCR technique to find a meaningful relationship ¬ Compared statistically. Compared to normal samples, the expression level of TP53TG1 in the blood of patients was reduced. Although it was not statistically significant. Its expression also increased after receiving chemotherapy. Compared to normal samples, the expression of PANDA in the blood of patients was increased, which was statistically significant. Also, its expression decreased after receiving chemotherapy. These findings suggest that PANDA and TP53TG1 expression levels may be possible markers associated with tumorigenesis and may also be considered as possible indicators of response to chemotherapy.}, } @article {pmid39593081, year = {2024}, author = {Trippler, L and Ali, SM and Masoud, MO and Mohammed, ZH and Amour, AK and Suleiman, KR and Ame, SM and Kabole, F and Hattendorf, J and Knopp, S}, title = {Impact of chemical snail control on intermediate host snail populations for urogenital schistosomiasis elimination in Pemba, Tanzania: findings of a 3-year intervention study.}, journal = {Parasites & vectors}, volume = {17}, number = {1}, pages = {489}, pmid = {39593081}, issn = {1756-3305}, support = {PR00P3_179753 / 1//Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung/ ; }, mesh = {Animals ; Tanzania/epidemiology ; *Schistosomiasis haematobia/prevention & control/epidemiology/drug therapy/transmission ; *Schistosoma haematobium/drug effects/physiology ; *Bulinus/parasitology ; Humans ; *Niclosamide/pharmacology ; Snails/parasitology ; Disease Eradication ; Fresh Water/parasitology ; }, abstract = {BACKGROUND: The World Health Organization (WHO) has set the goal of eliminating schistosomiasis as a public health problem globally by 2030 and to interrupt transmission in selected areas. Chemical snail control is one important measure to reduce transmission and achieve local elimination. We aimed to assess the impact of several rounds of chemical snail control on the presence and number of the Schistosoma haematobium intermediate snail host (Bulinus spp.) in water bodies (WBs) on Pemba Island, Tanzania, a setting targeted for elimination of urogenital schistosomiasis.

METHODS: During the three annual intervention periods of the SchistoBreak study implemented in the north of Pemba from 2020 to 2024, malacological surveys were conducted up to four times per period in WBs of hotspot implementation units (IUs). Present freshwater snail species, vegetation, and WB characteristics were recorded. If Bulinus were found, the snails were inspected for Schistosoma infection and snail control with niclosamide was conducted.

RESULTS: Across the three intervention periods, a total of 112 WBs were identified in 8 hotspots IUs. The spatial distribution of WBs with Bulinus per IU was heterogeneous, ranging from 0.0% (0/15) of WBs infested in one IU in 2022 to 80.0% (8/10) of WBs infested in one IU in 2021. Bulinus presence was significantly associated with lower pH values in WBs (odds ratio: 0.2, 95% confidence interval 0.1-0.4). A total of 0.2% (6/2360) of collected Bulinus were shedding Schistosoma cercariae. Following snail control, the number of Bulinus decreased or remained absent in 56.7% (38/67) of visits at WBs when compared with the previous visit in 2021, 54.9% (28/51) in 2022, and 33.3% (32/96) in 2023. In a total of 43.1% (22/55) of initially infested WBs, no Bulinus were found in the survey round conducted a few weeks after the first application of niclosamide. However, 25.4% (14/55) of WBs showed a pattern of recurring Bulinus presence.

CONCLUSIONS: The distribution of WBs containing Bulinus was very heterogeneous. The percentage of Bulinus with patent Schistosoma infection in our study area was extremely low. Repeated niclosamide application reduced the number of Bulinus in WBs, but snails often recurred after one or multiple treatments. While chemical mollusciciding can reduce snail numbers, to fully break the S. haematobium transmission cycle, timely diagnosis and treatment of infected humans, access to clean water, sanitation, and health communication remain of prime importance.

TRIAL REGISTRATION: ISRCTN, ISRCTN91431493. Registered 11 February. 2020, https://www.isrctn.com/ISRCTN91431493.}, } @article {pmid39341603, year = {2024}, author = {Pereira, LHS and Alves, ADC and Lopes, GFM and da Silva, BF and Vieira, MS and Lopes, DO and Ferreira, JMS and Lara Dos Santos, L}, title = {Soluble isoforms of the DC-SIGN receptor can increase the dengue virus infection in immature dendritic cells.}, journal = {The Brazilian journal of infectious diseases : an official publication of the Brazilian Society of Infectious Diseases}, volume = {28}, number = {6}, pages = {103873}, pmid = {39341603}, issn = {1678-4391}, mesh = {*Cell Adhesion Molecules/metabolism ; *Receptors, Cell Surface/metabolism ; *Lectins, C-Type/metabolism ; *Dengue Virus/immunology ; *Dendritic Cells/virology/immunology ; Humans ; Animals ; *Protein Isoforms ; Viral Load ; Dengue/immunology ; Aedes/virology ; }, abstract = {Dengue is a disease with a high-impact on public health worldwide. Many researches have focused on the cell receptors involved in its pathogenesis. The role of soluble isoforms of DC-SIGN (Dendritic Cell-Specific ICAM-3 Grabbing Non-integrin) receptor in the process of Dengue Virus (DENV) infection is not well understood. This work proposes to evaluate changes in the infection process of Immature Dendritic Cells (iDCs) by DENV in the presence of DC-SIGN recombinant soluble isoforms 8, 10, and 12. The recombinant isoforms were built by heterologous expression, the DENV-2 was multiplied in the Aedes albopictus C6/36 cells and quantified in BHK-21 cells, and the iDCs were produced from the THP-1 strain. Infection assays were performed in the presence of iDCs, DENV-2, and isoforms 8, 10, and 12 separately at 25, 50 and 100 ng/mL. The final viral load was estimated by qPCR and statistical analysis was performed by Kruskal-Wallis and ANOVA tests. The iDC profile was confirmed by increasing expression of CD11c, CD86, and CD209 surface markers and maintaining CD14 expression. Infection assays demonstrated a 23-fold increase in DENV viral load in the presence of isoforms 8 and 10 at 100 ng/mL compared to the viral control (p < 0.05), while isoform 12 did not alter the viral load. It was possible to conclude that at 100 ng/mL isoforms (8 and 10) can interact with DENV, increasing viral infection, and potentially acting as opsonins.}, } @article {pmid39567714, year = {2024}, author = {Khan, B and Qahwaji, R and Alfaifi, MS and Athar, T and Khan, A and Mobashir, M and Ashankyty, I and Imtiyaz, K and Alahmadi, A and Rizvi, MMA}, title = {Deciphering molecular landscape of breast cancer progression and insights from functional genomics and therapeutic explorations followed by in vitro validation.}, journal = {Scientific reports}, volume = {14}, number = {1}, pages = {28794}, pmid = {39567714}, issn = {2045-2322}, mesh = {Humans ; *Breast Neoplasms/genetics/pathology/drug therapy ; Female ; *Gene Expression Regulation, Neoplastic ; Genomics/methods ; Gene Regulatory Networks ; Disease Progression ; Biomarkers, Tumor/genetics/metabolism ; Carcinoma, Ductal, Breast/genetics/pathology/drug therapy ; Carcinoma, Intraductal, Noninfiltrating/genetics/pathology/drug therapy ; Molecular Docking Simulation ; Gene Expression Profiling ; Prognosis ; Cell Line, Tumor ; }, abstract = {Breast cancer is caused by aberrant breast cells that proliferate and develop into tumors. Tumors have the potential to spread throughout the body and become lethal if ignored. Metastasis is the process by which invasive tumors move to neighboring lymph nodes or other organs. Metastasis can be lethal and perhaps fatal. The objective of our study was to elucidate the molecular mechanisms underlying the transition of Ductal Carcinoma In Situ (DCIS) to Invasive Ductal Carcinoma (IDC), with a particular focus on hub genes and potential therapeutic agents. Using Weighted Gene Co-expression Network Analysis (WGCNA), we built a comprehensive network combining clinical and phenotypic data from both DCIS and IDC. Modules within this network, correlated with specific phenotypic traits, were identified, and hub genes were identified as critical markers. Receiver Operating Characteristic (ROC) analysis assessed their potential as biomarkers, while survival curve analysis gauged their prognostic value. Furthermore, molecular docking predicted interactions with potential therapeutic agents. Ten hub genes-CDK1, KIF11, NUF2, ASPM, CDCA8, CENPF, DTL, EXO1, KIF2C, and ZWINT-emerged as pivotal fibroblast-specific genes potentially involved in the DCIS to IDC transition. These genes exhibited pronounced positive correlations with key pathways like the cell cycle and DNA repair, Molecular docking revealed Fisetin, an anti-inflammatory compound, effectively binding to both CDK1 and DTL underscoring their role in orchestrating cellular transformation. CDK1 and DTL were selected for molecular docking with CDK1 inhibitors, revealing effective binding of Fisetin, an anti-inflammatory compound, to both. Of the identified hub genes, DTL-an E3 ubiquitin ligase linked to the CRL4 complex-plays a central role in cancer progression, impacting tumor growth, invasion, and metastasis, as well as cell cycle regulation and epithelial-mesenchymal transition (EMT). CDK1, another hub gene, is pivotal in cell cycle progression and associated with various biological processes. In conclusion, our study offers insights into the complex mechanisms driving the transition from DCIS to IDC. It underscores the importance of hub genes and their potential interactions with therapeutic agents, particularly Fisetin. By shedding light on the interplay between CDK1 and DTL expression, our findings contribute to understanding the regulatory landscape of invasive ductal carcinoma and pave the way for future investigations and novel therapeutic avenues.}, } @article {pmid39560723, year = {2024}, author = {Cendrowski, J and Wrobel, M and Mazur, M and Jary, B and Maurya, R and Wang, S and Korostynski, M and Dziewulska, A and Rohm, M and Kuropka, P and Pudelko-Malik, N and Mlynarz, P and Dobrzyn, A and Zeigerer, A and Miaczynska, M}, title = {NFκB and JNK pathways mediate metabolic adaptation upon ESCRT-I deficiency.}, journal = {Cellular and molecular life sciences : CMLS}, volume = {81}, number = {1}, pages = {458}, pmid = {39560723}, issn = {1420-9071}, support = {POIR.04.04.00-00-1C54/16-00//Fundacja na rzecz Nauki Polskiej/ ; POIR.04.04.00-00-20CE/16-00//Fundacja na rzecz Nauki Polskiej/ ; }, mesh = {*Endosomal Sorting Complexes Required for Transport/metabolism/genetics ; Humans ; *NF-kappa B/metabolism ; *Glycolysis/genetics ; Lysosomes/metabolism ; MAP Kinase Signaling System ; Mitochondria/metabolism ; Adaptation, Physiological/genetics ; Transcription Factors/metabolism/genetics ; Glucose/metabolism ; DNA-Binding Proteins ; }, abstract = {Endosomal Sorting Complexes Required for Transport (ESCRTs) are crucial for delivering membrane receptors or intracellular organelles for lysosomal degradation which provides the cell with lysosome-derived nutrients. Yet, how ESCRT dysfunction affects cell metabolism remained elusive. To address this, we analyzed transcriptomes of cells lacking TSG101 or VPS28 proteins, components of ESCRT-I subcomplex. ESCRT-I deficiency reduced the expression of genes encoding enzymes involved in oxidation of fatty acids and amino acids, such as branched-chain amino acids, and increased the expression of genes encoding glycolytic enzymes. The changes in metabolic gene expression were associated with Warburg effect-like metabolic reprogramming that included intracellular accumulation of lipids, increased glucose/glutamine consumption and lactate production. Moreover, depletion of ESCRT-I components led to expansion of the ER and accumulation of small mitochondria, most of which retained proper potential and performed ATP-linked respiration. Mechanistically, the observed transcriptional reprogramming towards glycolysis in the absence of ESCRT-I occurred due to activation of the canonical NFκB and JNK signaling pathways and at least in part by perturbed lysosomal degradation. We propose that by activating the stress signaling pathways ESCRT-I deficiency leads to preferential usage of extracellular nutrients, like glucose and glutamine, for energy production instead of lysosome-derived nutrients, such as fatty acids and branched-chain amino acids.}, } @article {pmid39557919, year = {2024}, author = {Rusak, A and Kątnik, E and Górnicki, T and Schmuttermaier, C and Kujawa, K and Piotrowska, A and Ratajczak-Wielgomas, K and Kmiecik, A and Wojnar, A and Dzięgiel, P and Kzhyshkowska, J}, title = {New insights into the role of the CHI3L2 protein in invasive ductal breast carcinoma.}, journal = {Scientific reports}, volume = {14}, number = {1}, pages = {28529}, pmid = {39557919}, issn = {2045-2322}, support = {2021/05/X/NZ2/01698//National Science Center, Poland (NCN)/ ; }, mesh = {Humans ; Female ; *Carcinoma, Ductal, Breast/metabolism/pathology/genetics ; *Breast Neoplasms/metabolism/pathology/genetics ; Middle Aged ; STAT3 Transcription Factor/metabolism ; Cell Line, Tumor ; Phosphorylation ; Chitinase-3-Like Protein 1/metabolism/genetics ; Gene Expression Regulation, Neoplastic ; Adult ; Macrophages/metabolism ; Aged ; MAP Kinase Signaling System ; Chitinases ; }, abstract = {Chitinase-like proteins have multiple biological functions that promote tumor growth, angiogenesis and metastasis. Expression of CHI3L2, which is similar in structure to CHI3L1, is detected in glioma cells and tumor-associated macrophages (TAMs) in glioma and breast cancer. However, its exact role remains unclear. We analyzed the expression of CHI3L2 in 74 invasive ductal breast carcinoma (IDC) tumors, breast cancer and macrophages cell cultures using immunohistochemistry, immunofluorescence, Western blot and PCR methods. Clinicopathologic data were included in the analysis. The results obtained show that CHI3L2 expression decreases with increasing degree of tumor grade and negative status of estrogen (ER) and progesterone receptors (PR). Furthermore, CHI3L2 is significantly and positively correlated with phosphorylation of STAT-3 and ERK1/2 signaling pathways, but negatively correlated with macrophage infiltration. CHI3L2 is expressed both in the cytoplasm of cancer cells and in macrophages and may regulate STAT-3 and ERK1/2 phosphorylation in breast cancer cell lines. Analysis of the clinicopathologic data revealed that CHI3L2 levels had no effect on patient survival. CHI3L2 expression may be specific for cancer cells in IDC and involved in cross-talk with the tumor microenvironment. Our study has shown that IDC cancer cells express the CHI3L2 protein, possibly indicating a novel function of this protein.}, } @article {pmid39382167, year = {2024}, author = {Koumantou, D and Adiko, AC and Bourdely, P and Nugue, M and Boedec, E and El-Benna, J and Monteiro, R and Saveanu, C and Laffargue, M and Wymann, MP and Dalod, M and Guermonprez, P and Saveanu, L}, title = {Specific Requirement of the p84/p110γ Complex of PI3Kγ for Antibody-Activated, Inducible Cross-Presentation in Murine Type 2 DCs.}, journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)}, volume = {11}, number = {44}, pages = {e2401179}, doi = {10.1002/advs.202401179}, pmid = {39382167}, issn = {2198-3844}, support = {ANR-11-IDEX-0005-02//Agence Nationale de la Recherche/ ; ANR-15-CE15-0005//Agence Nationale de la Recherche/ ; ANR-17-CE11-0001//Agence Nationale de la Recherche/ ; //Fondation pour la Recherche Medicale/ ; ANR-10-EQPX-03//ICGex NGS platform of the Institut Curie/ ; ANR-10-INBS-09-08//ICGex NGS platform of the Institut Curie/ ; INCa-DGOS-465//SiRIC-Curie program/ ; INCa-DGOS- Inserm_12554//SiRIC-Curie program/ ; SNF-310030-189065/SNSF_/Swiss National Science Foundation/Switzerland ; }, mesh = {Animals ; Mice ; *Dendritic Cells/immunology/metabolism ; *Cross-Priming/immunology ; *Mice, Inbred C57BL ; Class Ib Phosphatidylinositol 3-Kinase/metabolism/immunology/genetics ; Antigen Presentation/immunology ; }, abstract = {Cross-presentation by MHCI is optimally efficient in type 1 dendritic cells (DC) due to their high capacity for antigen processing. However, through specific pathways, other DCs, such as type 2 DCs and inflammatory DCs (iDCs) can also cross-present antigens. FcγR-mediated uptake by type 2 DC and iDC subsets mediates antibody-dependent cross-presentation and activation of CD8[+] T cell responses. Here, an important role for the p84 regulatory subunit of PI3Kγ in mediating efficient cross-presentation of exogenous antigens in otherwise inefficient cross-presenting cells, such as type 2 DCs and GM-CSF-derived iDCs is identified. FcγR-mediated cross-presentation is shown in type 2 and iDCs depend on the enzymatic activity of the p84/p110γ complex of PI3Kγ, which controls the activity of the NADPH oxidase NOX2 and ROS production in murine spleen type 2 DCs and GM-CSF-derived iDCs. In contrast, p84/p110γ is largely dispensable for cross-presentation by type 1 DCs. These findings suggest that PI3Kγ-targeted therapies, currently considered for oncological practice, may interfere with the ability of type 2 DCs and iDCs to cross-present antigens contained in immune complexes.}, } @article {pmid39541956, year = {2024}, author = {Abdelwahab, RM and Aghazadeh Mohandesi, N and Sturgis, CD and Alavi, A}, title = {Squamous Metaplasia of Lactiferous Ducts (Zuska's disease) of the Breast: Clinical and Histopathologic Manifestations.}, journal = {Dermatology (Basel, Switzerland)}, volume = {}, number = {}, pages = {1-9}, doi = {10.1159/000542622}, pmid = {39541956}, issn = {1421-9832}, abstract = {Squamous metaplasia of lactiferous ducts (SMOLD), also known as Zuska's disease, is an uncommon, recurrent inflammatory fistulizing disease of the breast that strongly correlates with smoking in premenopausal patients .1 Clinical and imaging findings may overlap with other breast conditions/ SMOLD is well-recognized by breast pathologists, however, the dermatology literature on this condition remains scarce. In this retrospective study, we reviewed 29 patients with SMOLD diagnosed at Mayo Clinic. The mean age of the patient cohort is 50.3 with a range of 30 to 81 years. One patient (3.7%) had hidradenitis suppurativa of the retro-areolar area. Patient smoking history demonstrated prior/current smokers 37.9% (11/29), lifetime nonsmokers with significant secondhand exposure 6.9% (2/29), and unknown smoking status 3.4% (1/29). One patient had a personal history of invasive ductal carcinoma and 10.3% (3/29) had a history of breast cancer in a first-degree relative. The clinical presentation of the patient cohort includes areolar papules, nodules and draining tract/fistula 13.7% (4/29), pustular cyst/abscess on the breast 13.7% (4/29), breast mass 3.4% (1/29), pain breast discomfort/pain 13.7% (4/29), nipple retraction 3.4% (1/29), and asymptomatic with nipple calcifications on mammogram 3.4% (1/29). 77.8% (7/9) patients with bacterial cultures demonstrated polymicrobial growth. 37.9% (11/29) patients received at least one round of antibiotic therapy. 27.6% (8/29) patients underwent invasive intervention. Staphylococcus, Streptococcus, and Cutibacterium species were the most frequent causes of infection in our patient cohort. We confirm previous findings of strong association between SMOLD & current/former smoking status and a potential, novel correlation between extensive secondhand exposure and SMOLD development. While both medical and surgical interventions are employed in patient management, many patients ultimately require complete excision of the involved duct(s). Dermatologists should consider SMOLD in the differential diagnosis of patients presenting with breast abscess, fistulizing tracts with mass, and breast pain.}, } @article {pmid39520846, year = {2024}, author = {Turk, A and Metin, TO and Kuloglu, T and Yilmaz, M and Artas, G and Ozercan, IH and Hancer, S}, title = {Isthmin-1 and spexin as promising novel biomarker candidates for invasive ductal breast carcinoma.}, journal = {Tissue & cell}, volume = {91}, number = {}, pages = {102601}, doi = {10.1016/j.tice.2024.102601}, pmid = {39520846}, issn = {1532-3072}, abstract = {INTRODUCTION: Breast cancer is one of the most common malignant tumors and a leading cause of cancer-related death in women. Research is focusing on biomarkers linked to breast cancer, particularly two novel proteins: isthmin-1 (ISM-1) and spexin (SPX), which require further investigation.

MATERIAL AND METHODS: The study involved 20 healthy controls and 60 patients with invasive ductal carcinoma, categorized into three groups: Grade I (n=20), Grade II (n=20), and Grade III (n=20). Levels of ISM-1 and SPX in tissue were analyzed using immunohistochemistry alongside the clinicopathologic data of patients.

RESULTS: There were no statistically significant differences in age, menopausal status, ER, PR, and Cerb-B2 values across grades (p>0.05). Tumor diameters showed a significant increase in Grade I compared to Grade II (p<0.05), while no significant difference was noted between Grade II and Grade III, although diameters were larger in Grade III compared to Grade I (p<0.05). Notably, ISM-1 immunoreactivity decreased, and SPX immunoreactivity increased significantly across all grades compared to normal tissue (p<0.05), with no significant differences between tumor grades for these markers (p>0.05).

CONCLUSIONS: This study presents new findings on ISM-1 and SPX expression in invasive ductal breast carcinoma. The decrease in ISM-1 and increase in SPX suggest a need for further research into the relationship between adipokines and tumor development in breast cancer.}, } @article {pmid39519098, year = {2024}, author = {Kim, YJ and Nanda, SS and Jiang, F and Pyo, SY and Han, JY and Koh, SS and Kang, TH}, title = {Pancreatic Adenocarcinoma Up-Regulated Factor (PAUF) Transforms Human Monocytes into Alternative M2 Macrophages with Immunosuppressive Action.}, journal = {International journal of molecular sciences}, volume = {25}, number = {21}, pages = {}, pmid = {39519098}, issn = {1422-0067}, mesh = {Humans ; *Pancreatic Neoplasms/pathology/metabolism/immunology ; *Monocytes/metabolism/immunology ; *Cell Differentiation ; *Macrophages/metabolism/immunology ; *Tumor Microenvironment/immunology ; Toll-Like Receptor 2/metabolism ; Tumor-Associated Macrophages/metabolism/immunology ; Cell Proliferation ; Adenocarcinoma/pathology/metabolism/immunology ; Cell Line, Tumor ; Intercellular Signaling Peptides and Proteins ; }, abstract = {Tumor-associated macrophages (TAMs) in the tumor microenvironment (TME) promote immune evasion, cancer cell proliferation, and metastasis. Ongoing research is focused on finding ways to prevent tumor growth by inhibiting TAM polarization, which has shown a correlation with unfavorable prognosis in clinical studies. Pancreatic adenocarcinoma up-regulated factor (PAUF) is a protein secreted from pancreatic cancer (PC) and acts as a TME modulator that affects the TME by acting on not only cancer cells but also stromal cells and immune cells. Tumor cells can evade the immune system by PAUF binding to Toll-like receptor (TLR) in monocytes, as this research shows. In this study, the examination centered around the recruitment of human monocytes by PAUF and the subsequent differentiation into macrophages. In an in vitro chemotaxis assay, PAUF induced chemotactic migration of TLR2-mediated monocytes. In addition, PAUF induced differentiation of monocytes into M2 macrophages, which was verified based on expressing surface markers and cytokines and morphological analysis. The inhibition of T cell proliferation and function was observed in differentiated M2 macrophages. To conclude, these findings indicate that PAUF functions as a promoter of cancer progression by regulating the recruitment and differentiation of macrophages within TMEs, ultimately causing immunosuppression.}, } @article {pmid39519012, year = {2024}, author = {Newman, NA and Burke, MA}, title = {Dilated Cardiomyopathy: A Genetic Journey from Past to Future.}, journal = {International journal of molecular sciences}, volume = {25}, number = {21}, pages = {}, pmid = {39519012}, issn = {1422-0067}, mesh = {Humans ; *Cardiomyopathy, Dilated/genetics ; *Genetic Predisposition to Disease ; Genetic Testing ; }, abstract = {Dilated cardiomyopathy (DCM) is characterized by reduced systolic function and cardiac dilation. Cases without an identified secondary cause are classified as idiopathic dilated cardiomyopathy (IDC). Over the last 35 years, many cases of IDC have increasingly been recognized to be genetic in etiology with a core set of definitively causal genes in up to 40% of cases. While over 200 genes have been associated with DCM, the evidence supporting pathogenicity for most remains limited. Further, rapid advances in sequencing and bioinformatics have recently revealed a complex genetic spectrum ranging from monogenic to polygenic in DCM. These advances have also led to the discovery of causal and modifier genetic variants in secondary forms of DCM (e.g., alcohol-induced cardiomyopathy). Current guidelines recommend genetic counseling and screening, as well as endorsing a handful of genotype-specific therapies (e.g., device placement in LMNA cardiomyopathy). The future of genetics in DCM will likely involve polygenic risk scores, direct-to-consumer testing, and pharmacogenetics, requiring providers to have a thorough understanding of this rapidly developing field. Herein we outline three decades of genetics in DCM, summarize recent advances, and project possible future avenues for the field.}, } @article {pmid39506855, year = {2024}, author = {Kook, Y and Lee, YJ and Chu, C and Jang, JS and Baek, SH and Bae, SJ and Cha, YJ and Gong, G and Jeong, J and Lee, SB and Ahn, SG}, title = {Differentiating HER2-low and HER2-zero tumors with 21-gene multigene assay in 2,295 h + HER2- breast cancer: a retrospective analysis.}, journal = {Breast cancer research : BCR}, volume = {26}, number = {1}, pages = {154}, pmid = {39506855}, issn = {1465-542X}, support = {2021M3H9A2096954//National Research Foundation of Korea/ ; RS-2024-00343001//Korean government/ ; }, mesh = {Humans ; Female ; *Breast Neoplasms/genetics/pathology/mortality/drug therapy ; *Receptor, ErbB-2/genetics/metabolism ; Retrospective Studies ; Middle Aged ; *Biomarkers, Tumor/genetics ; Adult ; Aged ; Gene Expression Profiling ; Immunohistochemistry ; Prognosis ; }, abstract = {BACKGROUND: HER2-positivity is an essential marker for therapeutic decisions, while HER2 expression is heterogenous. In recent years, there has been increasing recognition of a subgroup of breast cancer patients who have low levels of HER2 expression, also known as HER2-low because trastuzumab deruxtecan offers clinical benefit for patients with HER2-low metastatic breast cancer. Despite the growing interest in HER2-low breast cancer, there is limited research on how multigene assays can help differentiate between HER2-low and HER2-negative breast cancer. Among HR + HER2- breast cancer, we compared genomic characteristics between HER2-low and HER2-zero using the 21-gene assay.

METHODS: A retrospective review of clinical records was performed in 2,295 patients who underwent Oncotype DX[®] test in two hospitals between 2013 and 2020. Patients were classified into two groups as the HER2-zero and HER2-low based on HER2 immunohistochemistry. In cases with HER2 2+, no amplification of HER2 gene was confirmed by silver in situ hybridization. High genomic risk was defined as cases with 21-gene recurrence score (RS) > 25. Multivariable binary logistic-regression analysis was performed.

RESULTS: Of these, 944 (41.1%) patients were assigned to the HER2-zero group, while 1351 (58.9%) patients were assigned to the HER2-low group. The average Recurrence Score (RS) was found to be 17.802 in the HER2-zero breast cancer group and 18.503 in the HER2-low group, respectively (p-value < 0.005). When comparing the proportion of high RS between the two groups, the HER2-zero group had a high RS rate of 12.4% (117 out of 944), while the HER2-low group had a high RS rate of 17.0% (230 out of 1351) (p = 0.002). The HER2 score identified by qRT-PCR was 8.912 in the HER2-zero group and 9.337 in the HER2-low group (p < 0.005). In multivariable analysis, HER2-low status was found to be an independent factor for high RS, with an odds ratio of 1.517 (1.172-1.964), independent of ER, PR, and Ki67. Within the subgroup of patients with invasive ductal carcinoma, the high RS rates were 19% in the HER2-low group and 14% in the HER2-zero group. However, when considering all patients, there were no significant differences observed in recurrence-free survival and overall survival between the HER2-low and HER2-zero groups.

CONCLUSION: Within HR + HER2- breast cancer, HER2-low tumors are associated with high RS, especially for histologically invasive ductal carcinoma. A prognostic influence of HER2-low expression among HR + HER2- breast cancer remains as an area that requires further study.}, } @article {pmid39512981, year = {2024}, author = {Eshaqi, MJ and Al Shamsi, SA and Al Saidi, AM and Mahesh, S}, title = {Clinical Insights Into Ductal Carcinoma In Situ in Males: A Report of Two Cases From the Sultanate of Oman.}, journal = {Cureus}, volume = {16}, number = {10}, pages = {e71071}, doi = {10.7759/cureus.71071}, pmid = {39512981}, issn = {2168-8184}, abstract = {Breast cancer is a disease that predominantly affects the female population; however, rarely it can manifest in males, yet its etiology remains poorly elucidated. The scarcity of literature reviews and case reports done on male breast cancer in comparison to the female counterpart makes it difficult to understand the risk factors, treatment options, and extension of the disease. Moreover, high-grade ductal carcinoma in situ (DCIS) is exceptionally uncommon among male patients. The prognosis for male patients diagnosed with DCIS is similar to that of females at the same disease stage making early recognition and diagnosis significant. However, more efforts are being made to understand the clinical presentation, increase awareness, and acknowledge the etiology of this disease. This study addresses this gap by presenting two distinctive cases of invasive ductal carcinoma in males from the Sultanate of Oman. The aim of this study is to contribute to the growing efforts in comprehending the unclear landscape of male breast cancer, fostering awareness, and advancing knowledge of its etiology.}, } @article {pmid39505971, year = {2024}, author = {Olbromski, M and Mrozowska, M and Smolarz, B and Romanowicz, H and Rusak, A and Piotrowska, A}, title = {ERα status of invasive ductal breast carcinoma as a result of regulatory interactions between lysine deacetylases KAT6A and KAT6B.}, journal = {Scientific reports}, volume = {14}, number = {1}, pages = {26935}, pmid = {39505971}, issn = {2045-2322}, mesh = {Humans ; Female ; *Estrogen Receptor alpha/metabolism/genetics ; *Breast Neoplasms/pathology/metabolism/genetics ; *Histone Acetyltransferases/metabolism/genetics ; *Carcinoma, Ductal, Breast/genetics/metabolism/pathology ; Cell Line, Tumor ; Middle Aged ; Gene Expression Regulation, Neoplastic ; Adult ; Histone Deacetylases/metabolism/genetics ; MCF-7 Cells ; Aged ; Lysine/metabolism ; }, abstract = {Breast cancer (BC) is the leading cause of death among cancer patients worldwide. In 2020, almost 12% of all cancers were diagnosed with BC. Therefore, it is important to search for new potential markers of cancer progression that could be helpful in cancer diagnostics and successful anti-cancer therapies. In this study, we investigated the potential role of the lysine acetyltransferases KAT6A and KAT6B in the outcome of patients with invasive breast carcinoma. The expression profiles of KAT6A/B in 495 cases of IDC and 38 cases of mastopathy (FBD) were examined by immunohistochemistry. KAT6A/B expression was also determined in the breast cancer cell lines MCF-7, BT-474, SK-BR-3, T47D, MDA-MB-231, and MDA-MB-231/BO2, as well as in the human epithelial mammary gland cell line hTERT-HME1 - ME16C, both at the mRNA and protein level. Statistical analysis of the results showed that the nuclear expression of KAT6A/B correlates with the estrogen receptor status: KAT6ANUC vs. ER r = 0.2373 and KAT6BNUC vs. ER r = 0.1496. Statistical analysis clearly showed that KAT6A cytoplasmic and nuclear expression levels were significantly higher in IDC samples than in FBD samples (IRS 5.297 ± 2.884 vs. 2.004 ± 1.072, p < 0.0001; IRS 5.133 ± 4.221 vs. 0.1665 ± 0.4024, p < 0.0001, respectively). Moreover, we noticed strong correlations between ER and PR status and the nuclear expression of KAT6A and KAT6B (nucKAT6A vs. ER, p = 0.0048; nucKAT6A vs. PR p = 0.0416; nucKAT6B vs. ER p = 0.0306; nucKAT6B vs. PR p = 0.0213). Significantly higher KAT6A and KAT6B expression was found in the ER-positive cell lines T-47D and BT-474, whereas significantly lower expression was observed in the triple-negative cell lines MDA-MB-231 and MDA-MB-231/BO2. The outcomes of small interfering RNA (siRNA)-mediated suppression of KAT6A/B genes revealed that within estrogen receptor (ER) positive and negative cell lines, MCF-7 and MDA-MB-231, attenuation of KAT6A led to concurrent attenuation of KAT6A, whereas suppression of KAT6B resulted in simultaneous attenuation of KAT6A. Furthermore, inhibition of KAT6A/B genes resulted in a reduction in estrogen receptor (ER) mRNA and protein expression levels in MCF-7 and MDA-MMB-231 cell lines. Based on our findings, the lysine acetyltransferases KAT6A and KAT6B may be involved in the progression of invasive ductal breast cancer. Further research on other types of cancer may show that KAT6A and KAT6B could serve as diagnostic and prognostic markers for these types of malignancies.}, } @article {pmid39500528, year = {2024}, author = {Degavre, C and Lepez, A and Ibanez, S and François, C and Głowacka, K and Guilbaud, C and Laloux-Morris, F and Esfahani, H and Brusa, D and Bouzin, C and Feron, O}, title = {In situ endoscopic photodynamic therapy combined with immature DC vaccination induces a robust T cell response against peritoneal carcinomatosis.}, journal = {Journal for immunotherapy of cancer}, volume = {12}, number = {11}, pages = {}, pmid = {39500528}, issn = {2051-1426}, mesh = {*Photochemotherapy/methods ; Animals ; Mice ; *Peritoneal Neoplasms/immunology/therapy/secondary ; *Dendritic Cells/immunology ; Humans ; Female ; Cancer Vaccines/therapeutic use/pharmacology/immunology ; Photosensitizing Agents/pharmacology/therapeutic use ; Cell Line, Tumor ; Vaccination/methods ; }, abstract = {BACKGROUND: Immunogenic cell death (ICD) and ferroptosis have recently emerged as key factors in the anticancer immune response. Among the treatments able to induce ICD and the associated release of danger signals is photodynamic therapy (PDT). Ferroptosis for its part results from lipid peroxidation and is induced by CD8[+] T cells to kill nearby cancer cells on IFN-γ production. We aimed to combine the two concepts, that is, to evaluate whether the strong pro-oxidant effects of PDT may promote ferroptosis and antigen release and to develop a procedure for in situ PDT to prepare the soil for highly endocytotic immature dendritic cell (iDC) adoptive transfer. This approach was implemented for managing peritoneal carcinomatosis, a lesion often associated with poor outcomes.

METHODS: We used three-dimensional (3D) heterotypic spheroids made of cancer cells, exposed them to a white light-activated OR141 photosensitizer (PS), and subsequently complexified them by adding iDC and naive lymphocytes. We next used a model of mouse peritoneal carcinomatosis and administered PDT using laparoscopy to locally induce photoactivation using the endoscope light. The immune response following adoptive transfer of iDC was tracked both in vivo and ex vivo using isolated immune cells from in situ vaccinated mice.

RESULTS: Cancer cells undergoing PDT-induced cell death significantly increased ICD markers and the infiltration of iDCs in spheroids, relying on ferroptosis. These actions induced the sequential activation of CD8[+] and CD4[+] T cells as revealed by a significant spheroid 3D structure deterioration and, remarkably, were not recapitulated by conventional ferroptosis inducer RSL3. Using LED light from an endoscope for in situ photoactivation of PS enabled us to apply the vaccination modality in mice with peritoneal tumors. Consecutive intraperitoneal injection of iDCs resulted in delayed tumor growth, increased survival rates, and prevented tumor relapse on rechallenge. CD8[+] T cell response was supported by depletion experiments, nodal detection of early activated T cells, and ex vivo T cell-induced cytotoxicity toward spheroids.

CONCLUSIONS: The combination of in situ PDT locally delivered by an endoscope light and iDC administration induces a durable memory immune response against peritoneal carcinomatosis thereby opening new perspectives for the treatment of a life-threatening condition.}, } @article {pmid39331289, year = {2024}, author = {Vasigh, M and Mohamed, A and Jacobs, L and Lange, J and Camp, M and Sun, B and Wright, P and O'Donnell, M and Tran, HT and Sogunro, O and Habibi, M and Johnston, F and Euhus, D}, title = {The Association Between Breast Cancer Predisposing Genetic Variants and Multifocal, Multicentric Breast Cancer.}, journal = {Annals of surgical oncology}, volume = {31}, number = {13}, pages = {8891-8899}, pmid = {39331289}, issn = {1534-4681}, mesh = {Humans ; Female ; *Breast Neoplasms/genetics/pathology ; Retrospective Studies ; Middle Aged ; *Genetic Predisposition to Disease ; Adult ; Prognosis ; Follow-Up Studies ; Carcinoma, Ductal, Breast/genetics/pathology ; Aged ; Biomarkers, Tumor/genetics ; Genetic Variation ; }, abstract = {BACKGROUND: Breast-conserving surgery is often discouraged in BRCA gene carriers with early onset breast cancer. The genetic variant carrier breast cancers are more likely to be multifocal or multicentric (MFMC).

PATIENTS AND METHOD: This retrospective study includes newly diagnosed patients with breast cancer undergoing genetic testing between 2010 and 2021 within the Johns Hopkins Regional Health System. After excluding patients who received neoadjuvant chemotherapy or stage IV breast cancers, patients were divided into two groups: those who tested positive for a variant recognized by the National Comprehensive Cancer Network as predisposing the patient to breast cancer (ATM, BRCA1, BRCA2, CHEK2, NF1, PALB2, RAD51C, RAD51D, and TP53) and those who tested negative. Pathologic features of the tumors were compared, focusing on evidence for MFMC disease, defined as more than one malignant foci more than 5 mm apart.

RESULTS: Among the 282 eligible cases, 69 (24%) were positive for a genetic variant. The variant carriers were younger at diagnosis (p < 0.001), more likely to have invasive ductal carcinoma (p = 0.03), more likely to have undergone mastectomy (p = 0.03), and more likely to have a grade 3 cancer (p = 0.003). Variant carriers were not more likely to have MFMC disease (28% vs. 22%, p = 0.4). A positive genetic variant was not a predictor of MFMC within the entire cohort [odds ratio (OR):1.3, 95% confidence interval (CI) 0.6-2.6, p = 0.5).

CONCLUSION: Genetic variant carrier cancers are not more likely to be MCMF than sporadic cancers.}, } @article {pmid38195987, year = {2024}, author = {Knödlseder, N and Fábrega, MJ and Santos-Moreno, J and Manils, J and Toloza, L and Marín Vilar, M and Fernández, C and Broadbent, K and Maruotti, J and Lemenager, H and Carolis, C and Zouboulis, CC and Soler, C and Lood, R and Brüggemann, H and Güell, M}, title = {Delivery of a sebum modulator by an engineered skin microbe in mice.}, journal = {Nature biotechnology}, volume = {42}, number = {11}, pages = {1661-1666}, pmid = {38195987}, issn = {1546-1696}, support = {Marie Skłodowska-Curie Grant Agreement 882387//EC | Horizon 2020 Framework Programme (EU Framework Programme for Research and Innovation H2020)/ ; Award N62909-18-1-2155//United States Department of Defense | United States Navy | Office of Naval Research (ONR)/ ; - IdC 2019 PROD 00057//Government of Catalonia | Agència de Gestió d'Ajuts Universitaris i de Recerca (Agency for Management of University and Research Grants)/ ; Fellowship number 8240//European Molecular Biology Organization (EMBO)/ ; Award Juan de la Cierva FJC 2018-037096-I//Ministerio de Economía y Competitividad (Ministry of Economy and Competitiveness)/ ; Grant Agreement 882387//EC | EU Framework Programme for Research and Innovation H2020 | H2020 Priority Excellent Science | H2020 Marie Skłodowska-Curie Actions (H2020 Excellent Science - Marie Skłodowska-Curie Actions)/ ; }, mesh = {*Sebum/metabolism ; Animals ; Mice ; *Skin/microbiology/metabolism ; Humans ; Propionibacteriaceae/genetics ; }, abstract = {Microorganisms can be equipped with synthetic genetic programs for the production of targeted therapeutic molecules. Cutibacterium acnes is the most abundant commensal of the human skin, making it an attractive chassis to create skin-delivered therapeutics. Here, we report the engineering of this bacterium to produce and secrete the therapeutic molecule neutrophil gelatinase-associated lipocalin, in vivo, for the modulation of cutaneous sebum production.}, } @article {pmid39445528, year = {2024}, author = {Zhao, Z and Li, L and He, M and Li, Y and Ma, X and Zhao, B}, title = {Prognostic and Predictive Markers for Early Stage Triple-Negative Breast Cancer Treated With Platinum-Based Neoadjuvant Chemotherapy.}, journal = {Cancer medicine}, volume = {13}, number = {20}, pages = {e70336}, pmid = {39445528}, issn = {2045-7634}, support = {2019D01C258//The Natural Science Foundation of Xinjiang Uygur Autonomous Region/ ; }, mesh = {Humans ; *Triple Negative Breast Neoplasms/drug therapy/genetics/mortality/pathology ; Female ; *Neoadjuvant Therapy/methods ; Middle Aged ; *Polymorphism, Single Nucleotide ; Prognosis ; *BRCA1 Protein/genetics ; *Biomarkers, Tumor/genetics ; Adult ; *Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Neoplasm Staging ; BRCA2 Protein/genetics ; Aged ; X-ray Repair Cross Complementing Protein 1/genetics ; Prospective Studies ; Treatment Outcome ; }, abstract = {BACKGROUND: Emerging evidence has indicated possible efficacy benefit of platinum-based chemotherapy as neoadjuvant treatment for invasive ductal carcinoma triple-negative breast cancer (TNBC). However, it has not been endorsed by current guidelines due to highly controversial results.

MATERIALS AND METHODS: Present study aims to investigate predictive and prognostic roles concerning single nucleotide polymorphisms (SNPs) in XRCC1 and BRCA1, BRCA2 genes for early stage TNBC patients that received platinum-based neoadjuvant treatment. We prospectively enrolled women with stage IIB-IIIB TNBC that had progressed on neoadjuvant taxane and anthracycline-based chemotherapy at Xinjiang Medical University Affiliated Cancer Hospital. Tumor response and pathological complete response (pCR) rate were assessed. Invasive disease-free survival (iDFS) and overall survival (OS) were analyzed. Patients' blood samples were subject to Sanger sequencing to genotype XRCC1 Arg194Trp and Arg399Gln, BRCA1 s1799949, and BRCA2 rs206115. Univariate and multivariate logistic regressions were employed to investigate associations between SNPs and clinical characteristics with treatment response and pCR. A total of 45 patients were enrolled.

RESULTS: The cohort showcased ORR of 44.4%, pCR of 28.9%, median iDFS of 22 months, and a 3-year OS of 73.3%. The A/G and G/G genotypes of BRCA1 rs1799949, and the T/T genotype of BRCA2 rs206115 were associated with higher responsive rate. Histologic grade of III and Ki67 expression > 65% were associated with low responsive rate. Moreover, the A/G genotype of BRCA1 rs1799949 and T/T genotype of BRCA2 rs206115 correlated to high pCR. The histologic III and T4 stage correlated to inferior iDFS. Carrier of BRCA1 rs1799949 G/G had the most favorable OS, carriers of A/A showed the poorest OS, and those with A/G genotype showed an intermediate OS.

CONCLUSIONS: Platinum-based chemotherapy might serve as a therapeutic option for TNBC patients who were resistant to anthracycline- and taxane-based neoadjuvant therapy. Our study identified several genetic and clinical features that might function as prognostic and predictive markers.}, } @article {pmid39435217, year = {2024}, author = {Kumaravel, A and Esakki, M}, title = {Comparing CD10 Expression With the Clinicopathological Features and Hormone Status of Invasive Breast Cancer.}, journal = {Cureus}, volume = {16}, number = {9}, pages = {e69836}, pmid = {39435217}, issn = {2168-8184}, abstract = {Background Worldwide, female breast cancer is the most common cancer (11.7%), followed by lung (11.4%), colorectal, prostate, and stomach. Breast cancer is the fifth most common cause of cancer-related mortality, with lung cancer being the leading cause. In India, breast and cervical cancers are the two most common cancers among women. This study was undertaken to analyse the expression of CD10 in invasive duct cancer (IDC) and its correlation with the various clinicopathological features and hormone status. Materials and methods This study was conducted in the Department of Pathology, Saveetha Medical College and Hospital on 42 cases of invasive ductal carcinoma - no special type (IDC NST). The clinical and histopathologic parameters such as age, tumor site, tumor size, histologic type, histologic grade, lymph node metastases, lymphovascular invasion, and perineural invasion were assessed in hematoxylin and eosin-stained sections of the tumor tissue along with the hormone status of positivity for ER, PR and Her2Neu. These parameters were subsequently compared with the expression of CD10 in the corresponding slides and statsitical correlation was done using the chi square test. Results The most common age group was more than 40 years, with 41-50 years, and 51-60 years in particular. CD10 was positive in 93% of cases. There was a positive correlation between CD 10 expression and lymphovascular invasion in the study (p-0.006). There was no significant relationship between hormone status and CD10 expression. Conclusion A significant association was seen between CD10 expression and lymphovascular invasion. No relation was found between CD10 and the other parameters such as tumour grade, lymph node metastases, lymphovascular invasion, perineural invasion and hormone status. Further studies are required to explore the potential of CD10 as a prognostic marker for IDC.}, } @article {pmid39392173, year = {2024}, author = {Huang, YJ and Lin, JA and Chen, WM and Shia, BC and Wu, SY}, title = {Statin Therapy Reduces Radiation-Induced Cardiotoxicity in Patients With Breast Cancer Receiving Adjuvant Radiotherapy.}, journal = {Journal of the American Heart Association}, volume = {13}, number = {20}, pages = {e036411}, doi = {10.1161/JAHA.124.036411}, pmid = {39392173}, issn = {2047-9980}, mesh = {Humans ; Female ; *Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use ; Middle Aged ; Retrospective Studies ; *Cardiotoxicity ; Radiotherapy, Adjuvant/adverse effects ; Taiwan/epidemiology ; Aged ; Breast Neoplasms/radiotherapy ; Incidence ; Mastectomy, Segmental ; Registries ; Risk Assessment ; Radiation Injuries/epidemiology/prevention & control/etiology ; Adult ; Carcinoma, Ductal, Breast/radiotherapy ; Risk Factors ; Treatment Outcome ; }, abstract = {BACKGROUND: To evaluate the efficacy of statin therapy in reducing major adverse cardiovascular event (MACE) risk among patients with breast cancer undergoing breast-conserving surgery and adjuvant whole breast radiotherapy.

METHODS AND RESULTS: A retrospective cohort study was conducted using data from the Taiwan Cancer Registry Database linked to the National Health Insurance Research Database. Patients diagnosed with left-sided early breast invasive ductal carcinoma between 2016 and 2019 were included. Propensity score matching was employed to compare MACE risk between statin users and nonusers. Cox regression models were used to estimate adjusted hazard ratios (aHRs) for MACE, considering cumulative defined daily doses and daily defined doses of statins. Among 1481 patients undergoing breast-conserving surgery and adjuvant whole breast radiotherapy, statin use significantly reduced MACE risk (aHR, 0.34 [95% CI, 0.25-0.44]). Hydrophilic statins, particularly rosuvastatin and pravastatin, demonstrated the greatest risk reduction. Higher cumulative defined daily doses and daily intensity doses of statins were associated with lower MACE risk, indicating a dose-response relationship. The 5-year cumulative incidence of MACE was significantly lower in statin users compared with nonusers (12.24% versus 31.70%).

CONCLUSIONS: Statin therapy is associated with a reduced risk of MACE in patients with breast cancer undergoing breast-conserving surgery and adjuvant whole breast radiotherapy. Hydrophilic statins rosuvastatin and pravastatin exhibit the most pronounced cardioprotective effects. These findings suggest a potential role for statins in mitigating cardiovascular complications in this population and highlight the need for further research to optimize statin therapy in survivors of breast cancer undergoing radiotherapy.}, } @article {pmid39284909, year = {2024}, author = {Brunetta, HS and Jung, AS and Valdivieso-Rivera, F and de Campos Zani, SC and Guerra, J and Furino, VO and Francisco, A and Berçot, M and Moraes-Vieira, PM and Keipert, S and Jastroch, M and Martinez, LO and Sponton, CH and Castilho, RF and Mori, MA and Bartelt, A}, title = {IF1 is a cold-regulated switch of ATP synthase hydrolytic activity to support thermogenesis in brown fat.}, journal = {The EMBO journal}, volume = {43}, number = {21}, pages = {4870-4891}, pmid = {39284909}, issn = {1460-2075}, support = {2022/00358-1//Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)/ ; 852742//EC | European Research Council (ERC)/ ; BA4925/2-1//Deutsche Forschungsgemeinschaft (DFG)/ ; 81X3600212//Deutsches Zentrum für Herz-Kreislaufforschung (DZHK)/ ; 310287/2018-9//Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)/ ; 88881.143924/2017-01//Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)/ ; }, mesh = {Animals ; *Thermogenesis/genetics ; Mice ; *Adipose Tissue, Brown/metabolism ; *Cold Temperature ; *ATPase Inhibitory Protein ; *Mitochondrial Proton-Translocating ATPases/metabolism/genetics ; Hydrolysis ; Mitochondria/metabolism ; Mice, Inbred C57BL ; Male ; Adipocytes, Brown/metabolism ; Membrane Potential, Mitochondrial ; Energy Metabolism ; }, abstract = {While mechanisms controlling uncoupling protein-1 (UCP1) in thermogenic adipocytes play a pivotal role in non-shivering thermogenesis, it remains unclear whether F1Fo-ATP synthase function is also regulated in brown adipose tissue (BAT). Here, we show that inhibitory factor 1 (IF1, encoded by Atp5if1), an inhibitor of ATP synthase hydrolytic activity, is a critical negative regulator of brown adipocyte energy metabolism. In vivo, IF1 levels are diminished in BAT of cold-adapted mice compared to controls. Additionally, the capacity of ATP synthase to generate mitochondrial membrane potential (MMP) through ATP hydrolysis (the so-called "reverse mode" of ATP synthase) is increased in brown fat. In cultured brown adipocytes, IF1 overexpression results in an inability of mitochondria to sustain the MMP upon adrenergic stimulation, leading to a quiescent-like phenotype in brown adipocytes. In mice, adeno-associated virus-mediated IF1 overexpression in BAT suppresses adrenergic-stimulated thermogenesis and decreases mitochondrial respiration in BAT. Taken together, our work identifies downregulation of IF1 upon cold as a critical event for the facilitation of the reverse mode of ATP synthase as well as to enable energetic adaptation of BAT to effectively support non-shivering thermogenesis.}, } @article {pmid38621672, year = {2024}, author = {Sánchez-Dávila, JN and Verástegui, EL and Peña-Nieves, A and Allende-Pérez, SR}, title = {Integration of the geriatric palliative care in oncological care of elderly patient with cancer.}, journal = {Palliative & supportive care}, volume = {22}, number = {4}, pages = {792-800}, doi = {10.1017/S1478951524000294}, pmid = {38621672}, issn = {1478-9523}, mesh = {Humans ; Aged ; *Palliative Care/methods/standards ; Aged, 80 and over ; Female ; Male ; *Neoplasms/complications/therapy ; *Geriatrics/methods ; Geriatric Assessment/methods ; }, abstract = {OBJECTIVES: The objective of this article is to describe the profile of the population attended to by the palliative geriatrics clinic and to evaluate the symptomatic control derived from the care provided.

METHODS: During 2017 a model based on a holistic approach was implemented, in this model the team geriatric palliative care plays a fundamental role by being part of the palliative care team and functioning as a liaison with the oncology team and other required services. We outlined the profile of 100 patients aged 70 and older seen between 2017 and 2019 at our geriatric palliative care clinic. Descriptive statistics were used. In addition, the symptoms and the care clinic model effect on the symptomatic control were analyzed, as well as the complexity of patients in palliative care with IDC-Pal.

RESULTS: The patients median age was 83.5 years. Patients were classified by type of management: 47% within the supportive care group and 53% with palliative care only; 58% had metastatic disease and 84% presented at least 1 comorbidity. Frailty was observed in 78% and a Karnofsky scale of 60 or less was observed in 59% of the overall population.

SIGNIFICANCE OF RESULTS: Elderly cancer patients have a complex profile and may have multiple needs. Integrating geriatric palliative care can help to provide better and personalized care along with symptomatic control. Further studies are required to establish the ideal care model for these patients. Importantly, a personalized treatment with a geriatric palliative care specialist is a key element.}, } @article {pmid39315404, year = {2024}, author = {Liu, Y and Lin, D and Najam, SS and Huang, S and Song, M and Sirakawin, C and Zhao, C and Jiang, H and Konopka, W and Herzig, S and Vinnikov, IA}, title = {Functional redundancy between glucocorticoid and mineralocorticoid receptors in mature corticotropin-releasing hormone neurons protects from obesity.}, journal = {Obesity (Silver Spring, Md.)}, volume = {32}, number = {10}, pages = {1885-1896}, doi = {10.1002/oby.24116}, pmid = {39315404}, issn = {1930-739X}, support = {31771433//National Natural Science Foundation of China/ ; 32241020//National Natural Science Foundation of China/ ; 32350610254//National Natural Science Foundation of China/ ; }, mesh = {Animals ; Male ; Mice ; *Corticosterone/blood/metabolism ; *Corticotropin-Releasing Hormone/metabolism ; *Energy Metabolism ; Insulin Resistance ; Mice, Inbred C57BL ; *Mice, Knockout ; *Neurons/metabolism ; *Obesity/metabolism ; Paraventricular Hypothalamic Nucleus/metabolism ; *Receptors, Glucocorticoid/metabolism/genetics ; *Receptors, Mineralocorticoid/metabolism/genetics ; Female ; }, abstract = {OBJECTIVE: Here, we aimed to investigate the role of glucocorticoid and mineralocorticoid receptors (GRs and MRs, respectively) in the regulation of energy homeostasis.

METHODS: We used three mouse models with simultaneous deletion of GRs and MRs in either forebrain neurons, the paraventricular nucleus, or corticotropin-releasing hormone (CRH) neurons and compared them with wild-type controls or isolated knockout groups. In addition to body weight, food intake, energy expenditure, insulin sensitivity, fat/lean mass distribution, and plasma corticosterone levels, we also performed transcriptomic analysis of CRH neurons and assessed their response to melanocortinergic stimulation.

RESULTS: Similar to global double-knockout models, deletion of GRs and MRs specifically in mature CRH neurons resulted in obesity. Importantly, the latter was accompanied by insulin resistance, but not increased plasma corticosterone levels. Transcriptomic analysis of these neurons revealed upregulation of several genes involved in postsynaptic signal transduction, including the Ptk2b gene, which encodes proline-rich tyrosine kinase 2. Knockout of both nuclear receptors leads to upregulation of Ptk2b in CRH neurons, which results in their diminished responsiveness to melanocortinergic stimulation.

CONCLUSIONS: Our data demonstrate the functional redundancy of GRs and MRs in CRH neurons to maintain energy homeostasis and prevent obesity. Simultaneous targeting of both receptors might represent an unprecedented approach to counteract obesity.}, } @article {pmid39296436, year = {2024}, author = {Mihai, AM and Ianculescu, LM and Suciu, N}, title = {MiRNAs as potential biomarkers in early breast cancer detection: a systematic review.}, journal = {Journal of medicine and life}, volume = {17}, number = {6}, pages = {549-554}, pmid = {39296436}, issn = {1844-3117}, mesh = {Female ; Humans ; *Biomarkers, Tumor/blood/genetics ; *Breast Neoplasms/blood/diagnosis/genetics ; *Early Detection of Cancer/methods ; *Circulating MicroRNA/blood/genetics ; }, abstract = {Breast cancer remains a significant global health challenge, with high incidence and mortality rates. While mammography has contributed to declining mortality, its limitations in sensitivity and specificity for early detection, particularly in distinguishing between pure atypical ductal hyperplasia (ADH), ductal carcinoma in situ (DCIS), and invasive ductal carcinoma (IDC), highlight the need for more precise tools. Even with core needle biopsy (CNB), conclusive diagnoses often require surgical excision. This underscores the urgency for non-invasive biomarkers to improve early detection and differentiation, potentially reducing invasive procedures. Recent research has shifted focus from mRNA to microRNAs (miRNAs) as promising biomarkers for breast cancer screening. These small non-coding RNAs, which exhibit abnormal expression patterns in breast cancer patients' tissue and serum/plasma, play crucial roles in early breast cancer development by modulating proto-oncogenes or tumor suppressor genes at the post-transcriptional level. Notably, miRNAs such as miR-21, miR-155, and miR-200c are key regulators of cell proliferation and apoptosis, with the potential to distinguish between normal tissue and various stages of breast lesions, including ADH, DCIS, and IDC. Additionally, miRNAs in serum and plasma offer a non-invasive method to differentiate breast cancer stages. This review aims to consolidate current knowledge on early breast lesions and explore the potential of miRNAs as biomarkers for early breast cancer detection, which could enhance risk prediction and reduce reliance on invasive diagnostic procedures.}, } @article {pmid39283254, year = {2024}, author = {Cai, F and Li, Y and Liu, H and Luo, J}, title = {Single-cell and Spatial Transcriptomic Analyses Implicate Formation of the Immunosuppressive Microenvironment during Breast Tumor Progression.}, journal = {Journal of immunology (Baltimore, Md. : 1950)}, volume = {213}, number = {9}, pages = {1392-1401}, doi = {10.4049/jimmunol.2400025}, pmid = {39283254}, issn = {1550-6606}, support = {62072058//MOST | National Natural Science Foundation of China (NSFC)/ ; 82073339//MOST | National Natural Science Foundation of China (NSFC)/ ; BK20231271//JST | Natural Science Foundation of Jiangsu Province (Jiangsu Natural Science Foundation)/ ; }, mesh = {Humans ; *Tumor Microenvironment/immunology/genetics ; *Breast Neoplasms/immunology/genetics/pathology ; Female ; *Single-Cell Analysis ; *Disease Progression ; *Transcriptome ; Gene Expression Profiling ; Carcinoma, Intraductal, Noninfiltrating/immunology/genetics/pathology ; Carcinoma, Ductal, Breast/immunology/genetics/pathology ; Gene Expression Regulation, Neoplastic/immunology ; }, abstract = {Ductal carcinoma in situ and invasive ductal carcinoma represent two stages of breast cancer progression. A multitude of studies have shown that genomic instability increases during tumor development, as manifested by higher mutation and copy number variation rates. The advent of single-cell and spatial transcriptomics has enabled the investigation of the subtle differences in cellular states during the tumor progression at single-cell level, thereby providing more nuanced understanding of the intercellular interactions within the solid tumor. However, the evolutionary trajectory of tumor cells and the establishment of the immunosuppressive microenvironment during breast cancer progression remain unclear. In this study, we performed an exploratory analysis of the single-cell sequencing dataset of 13 ductal carcinoma in situ and invasive ductal carcinoma samples. We revealed that tumor cells became more malignant and aggressive during their progression, and T cells transited to an exhausted state. The tumor cells expressed various coinhibitory ligands that interacted with the receptors of immune cells to create an immunosuppressive tumor microenvironment. Furthermore, spatial transcriptomics data confirmed the spatial colocalization of tumor and immune cells, as well as the expression of the coinhibitory ligand-receptor pairs. Our analysis provides insights into the cellular and molecular mechanism underlying the formation of the immunosuppressive landscape during two typical stages of breast cancer progression.}, } @article {pmid39226766, year = {2024}, author = {Madrigal, JM and Pruitt, CN and Fisher, JA and Liao, LM and Graubard, BI and Gierach, GL and Silverman, DT and Ward, MH and Jones, RR}, title = {Carcinogenic industrial air pollution and postmenopausal breast cancer risk in the National Institutes of Health AARP Diet and Health Study.}, journal = {Environment international}, volume = {191}, number = {}, pages = {108985}, pmid = {39226766}, issn = {1873-6750}, support = {Z99 CA999999/ImNIH/Intramural NIH HHS/United States ; ZIA CP010125/ImNIH/Intramural NIH HHS/United States ; }, mesh = {Humans ; Female ; *Breast Neoplasms/epidemiology/chemically induced ; *Postmenopause ; Middle Aged ; United States/epidemiology ; Aged ; *Air Pollution/statistics & numerical data ; Air Pollutants/analysis ; Prospective Studies ; Carcinogens/analysis ; Risk Factors ; National Institutes of Health (U.S.) ; Environmental Exposure/statistics & numerical data ; Benzene/analysis ; }, abstract = {BACKGROUND: Chemicals emitted from industrial facilities include known or suspected mammary carcinogens and endocrine disruptors, but epidemiologic studies are limited. We evaluated associations between air emissions of multiple carcinogenic chemicals and postmenopausal breast cancer risk in a large prospective U.S.

METHODS: We used the U.S. Environmental Protection Agency's Toxics Release Inventory to estimate historical airborne emissions (1987-1995) of 19 known and probable carcinogens for participants enrolled (1995-1996) in the NIH-AARP Diet and Health Study. Among 170,402 women, 15,124 breast cancers were diagnosed through 2018. We constructed inverse distance- and wind-weighted average emissions metrics within 1, 2, 5, and 10 km of the enrollment address for each chemical. We estimated multivariable adjusted HRs and 95 % CIs for categories (quartiles, tertiles, medians) of each chemical in association with breast cancer overall and separately by type (invasive, ductal carcinoma in situ) and estrogen receptor (ER) status.

RESULTS: We observed an association between benzene emissions and breast cancer risk that was strongest at 1 km (HRQ4 vs. non-exposed = 2.06, 95 %CI: 1.34-3.17; p-trend = 0.001). The magnitude of the association weakened with increasing distance (2 km HRQ4 vs. non-exposed = 1.17, 95 %CI=0.92-1.49; p-trend = 0.19; 5 km HRQ4 vs. non-exposed = 1.05, 95 %CI=0.94-1.16; p-trend = 0.37; 10 km HRQ4 vs. non-exposed = 0.95, 95 %CI=0.89-1.02; p-trend = 0.19) and appeared to be most relevant for invasive rather than intraductal disease. Overall risk was also elevated for vinyl chloride at 5 km (HR≥median vs. non-exposed = 1.20, 95 %CI=1.01-1.43; p-trend = 0.04), but not 2 km or 10 km. We observed suggestive associations for asbestos, trichloroethylene, and styrene in different subgroup analyses, but risk patterns were not clear across distances. Associations with other chemicals were generally null, with limited evidence of heterogeneity by disease type or ER status.

CONCLUSIONS: An increased risk of breast cancer associated with relatively high levels of industrial benzene emissions warrants additional study, particularly among participants with diverse sociodemographic characteristics that live in areas with higher density of industrial facilities.}, } @article {pmid39031014, year = {2024}, author = {Chen, C and Tseng, J and Amersi, F and Silberman, AW}, title = {Second primary malignancies in women with breast cancer.}, journal = {Journal of surgical oncology}, volume = {130}, number = {3}, pages = {355-359}, doi = {10.1002/jso.27785}, pmid = {39031014}, issn = {1096-9098}, support = {//Gottlieb, Buss, and Snyder Endowments in Surgical Oncology/ ; }, mesh = {Humans ; Female ; *Neoplasms, Second Primary/epidemiology/pathology ; Middle Aged ; *Breast Neoplasms/pathology/therapy/genetics ; Adult ; Aged ; Aged, 80 and over ; Retrospective Studies ; Young Adult ; Carcinoma, Ductal, Breast/pathology/therapy/epidemiology/genetics ; Prospective Studies ; Follow-Up Studies ; Risk Factors ; }, abstract = {BACKGROUND: Increased screening and treatment advancements have resulted in improved survival rates in women with breast cancer (BC). However, recent data suggests these women have elevated risk of developing a second primary malignancy (SPM) compared to the general population. Limited data exists on factors associated with BC patients developing a SPM.

METHOD: A retrospective review of a prospective single institution database (1990-2016) identified 782 patients with a history of BC. One hundred and ninety-four BC patients developed a SPM. Clinicopathologic and treatment characteristics were analyzed.

RESULTS: Of the 194 patients (24.8%) who developed a SPM, 56 (28.9%) BC patients were <50 years old (range: 24-87 years). Two-thirds (64.9%) had at least one first or second degree relative with a malignancy (no relatives-35.1%; ≥1 relative-62.9%). Most patients had invasive ductal carcinoma (n = 117, 60.3%) or ductal carcinoma in situ (n = 39, 20.1%). Twenty-two patients (11.3%) had pathogenic genetic mutations. Mean time to developing a SPM was 8.9 years (range: 4 months-50 years). Eighty (47.6%) patients received chemotherapy with 91 (54.5%) completing radiation. The most common SPMs were breast (22%), melanoma (17.8%), gynecologic (14.1%), colorectal (12.6%), hematologic (8.9%), and sarcoma (6.5%). Most breast tumors were estrogen receptor (ER) (n = 99, 78.0%) or progesterone receptor (PR) positive (n = 87, 73.1%) but not HER2-neu positive (n = 13, 14.0%).

CONCLUSION: Most BC patients who developed a SPM had ER/PR positive tumors and a family history of malignancy, with most <50 years old. Although chemotherapy and radiation increase cancer risk, there were an equal number of patients with SPMs who did or did not receive either treatment. Most SPMs were breast, soft tissue, gynecologic, hematologic, or colorectal. BC patients should be followed closely given an elevated propensity for developing SPMs.}, } @article {pmid38215056, year = {2024}, author = {Schimpfle, L and Tsilingiris, D and Mooshage, CM and Kender, Z and Sulaj, A and von Rauchhaupt, E and Szendroedi, J and Herzig, S and Goepfert, J and Groener, J and Nawroth, PP and Bendszus, M and Heiland, S and Kurz, FT and Jende, JME and Kopf, S}, title = {Phase Angle of Bioelectrical Impedance Analysis as an Indicator for Diabetic Polyneuropathy in Type 2 Diabetes Mellitus.}, journal = {The Journal of clinical endocrinology and metabolism}, volume = {109}, number = {11}, pages = {e2110-e2119}, doi = {10.1210/clinem/dgad737}, pmid = {38215056}, issn = {1945-7197}, support = {B05//Collaborative Research Council 1118/ ; A03//Collaborative Research Council 1158/ ; //Deutsches Zentrum für Diabetesforschung (DZD e.V.)/ ; }, mesh = {Humans ; *Diabetes Mellitus, Type 2/complications/physiopathology ; *Diabetic Neuropathies/diagnosis/physiopathology ; Female ; Male ; *Electric Impedance ; Middle Aged ; Cross-Sectional Studies ; Aged ; Neural Conduction/physiology ; Adult ; }, abstract = {CONTEXT: Due to the heterogenous clinical symptoms and deficits, the diagnosis of diabetic polyneuropathy (DPN) is still difficult in clinical routines, leading to increased morbidity and mortality.

OBJECTIVE: We studied the correlation of phase angle (PhA) of bioelectrical impedance analysis (BIA) with clinical, laboratory, and physical markers of DPN to evaluate PhA as a possible diagnostic method for DPN.

MATERIALS AND METHODS: In this cross-sectional observational study as part of the Heidelberg Study on Diabetes and Complications, we examined 104 healthy individuals and 205 patients with type 2 diabetes mellitus (T2D), among which 63 had DPN. The PhA was calculated from multifrequency BIA. Nerve conduction studies, quantitative sensory testing (QST) and diffusion-weighted magnetic resonance neurography to determine fractional anisotropy (FA) reflecting peripheral nerve integrity were performed.

RESULTS: T2D patients with DPN had lower PhA values (5.71 ± 0.10) compared to T2D patients without DPN (6.07 ± 0.08, P = .007, + 6.1%) and healthy controls (6.18 ± 0.08, P < .001, + 7.9%). Confounder-adjusted analyses showed correlations of the PhA with conduction velocities and amplitudes of the peroneal (β=.28; β=.31, P < .001) and tibial nerves (β=.28; β=.32, P < .001), Z-scores of QST (thermal detection β=.30, P < .05) and the FA (β=.60, P < .001). Receiver-operating characteristic analysis showed similar performance of PhA in comparison to the mentioned diagnostic methods.

CONCLUSION: The study shows that PhA is, in comparison to other test systems used, at least an equally good and much easier to handle investigator-independent marker for detection of DPN.}, } @article {pmid38838211, year = {2024}, author = {Wang, Y and Li, G and Chen, B and Shakir, G and Volz, M and van der Vorst, EPC and Maas, SL and Geiger, M and Jethwa, C and Bartelt, A and Li, Z and Wettich, J and Sachs, N and Maegdefessel, L and Nazari Jahantigh, M and Hristov, M and Lacy, M and Lutz, B and Weber, C and Herzig, S and Guillamat Prats, R and Steffens, S}, title = {Myeloid cannabinoid CB1 receptor deletion confers atheroprotection in male mice by reducing macrophage proliferation in a sex-dependent manner.}, journal = {Cardiovascular research}, volume = {120}, number = {12}, pages = {1411-1426}, doi = {10.1093/cvr/cvae125}, pmid = {38838211}, issn = {1755-3245}, support = {STE1053/6-1//Deutsche Forschungsgemeinschaft/ ; 81Z0600205//German Ministry of Research and Education/ ; 1061//LMU Medical Faculty FöFoLe program/ ; //Interdisciplinary Center for Clinical Research/ ; //RWTH Aachen University/ ; 10.20.2.043MN//Fritz Thyssen Stiftung/ ; 201908080123//Chinese Scholar Council/ ; }, mesh = {Animals ; Male ; Female ; *Cell Proliferation ; *Macrophages/metabolism/pathology ; *Receptor, Cannabinoid, CB1/metabolism/genetics ; *Signal Transduction ; *Disease Models, Animal ; *Atherosclerosis/genetics/pathology/metabolism/prevention & control/enzymology ; Sex Factors ; *Plaque, Atherosclerotic ; Humans ; *Mice, Knockout ; *Phenotype ; Estrogen Receptor alpha/metabolism/genetics/deficiency ; Mice, Inbred C57BL ; Carotid Artery Diseases/genetics/pathology/metabolism/prevention & control ; Tumor Suppressor Protein p53/metabolism/genetics/deficiency ; Estradiol/pharmacology ; Aortic Diseases/genetics/pathology/prevention & control/metabolism/enzymology ; }, abstract = {AIMS: Although the cannabinoid CB1 receptor has been implicated in atherosclerosis, its cell-specific effects in this disease are not well understood. To address this, we generated a transgenic mouse model to study the role of myeloid CB1 signalling in atherosclerosis.

METHODS AND RESULTS: Here, we report that male mice with myeloid-specific Cnr1 deficiency on atherogenic background developed smaller lesions and necrotic cores than controls, while only minor genotype differences were observed in females. Male Cnr1-deficient mice showed reduced arterial monocyte recruitment and macrophage proliferation with less inflammatory phenotype. The sex-specific differences in proliferation were dependent on oestrogen receptor (ER)α-oestradiol signalling. Kinase activity profiling identified a CB1-dependent regulation of p53 and cyclin-dependent kinases. Transcriptomic profiling further revealed chromatin modifications, mRNA processing, and mitochondrial respiration among the key processes affected by CB1 signalling, which was supported by metabolic flux assays. Chronic administration of the peripherally restricted CB1 antagonist JD5037 inhibited plaque progression and macrophage proliferation, but only in male mice. Finally, CNR1 expression was detectable in human carotid endarterectomy plaques and inversely correlated with proliferation, oxidative metabolism, and inflammatory markers, suggesting a possible implication of CB1-dependent regulation in human pathophysiology.

CONCLUSION: Impaired macrophage CB1 signalling is atheroprotective by limiting their arterial recruitment, proliferation, and inflammatory reprogramming in male mice. The importance of macrophage CB1 signalling appears to be sex-dependent.}, } @article {pmid38837365, year = {2024}, author = {Voloch, L and Icht, M and Ben-David, BM and Carmel Neiderman, NN and Levenberg, G and Manor, Y and Shpunt, D and Oestreicher-Kedem, Y}, title = {Seven Days of Voice Rest Post-phonosurgery Is Not Better than 3 days: A Prospective Randomized Short-term Outcome Study.}, journal = {The Laryngoscope}, volume = {134}, number = {11}, pages = {4661-4666}, doi = {10.1002/lary.31556}, pmid = {38837365}, issn = {1531-4995}, mesh = {Humans ; Female ; Male ; Prospective Studies ; Adult ; *Vocal Cords/surgery/physiopathology ; *Voice Quality ; Time Factors ; Treatment Outcome ; Middle Aged ; *Laryngeal Diseases/surgery/physiopathology ; Rest/physiology ; Voice Disorders/etiology/surgery/physiopathology ; Phonation/physiology ; Postoperative Period ; Postoperative Care/methods ; }, abstract = {OBJECTIVE: The aim of the study is to compare the short-term effect of 7 versus 3 days of voice rest (VR) on objective vocal (acoustic) parameters following phonosurgery.

METHODS: A prospective randomized study conducted at a tertiary referral medical center. Patients with vocal fold nodules, polyps, or cysts and scheduled for phonosurgery were recruited from the Voice Clinic. They were randomized into groups of 7- or 3-day postoperative VR periods and their voices were recorded preoperatively and at 4-week postoperatively. A mixed linear model statistical analysis (MLMSA) was used to compare pre- and postoperative jitter, shimmer, harmonic-to-noise ratio, and maximum phonation time between the two groups.

RESULTS: Sixty-five patients were recruited, but only 34 fully complied with the study protocol, and their data were included in the final analysis (19 males, 20 females; mean age: 40.6 years; 17 patients in the 7-day VR group and 16 in the 3-day VR group). The groups were comparable in age, sex, and type of vocal lesion distribution. The preoperative MLMSA showed no significant group differences in the tested vocal parameters. Both groups exhibited significant (p < 0.05) and comparable improvement in all vocal parameters at postoperative week 4.

CONCLUSIONS: A VR duration of 7 days showed no greater benefit on the examined vocal parameters than the 3-day protocol 4-week postoperatively. Our results suggest that a 3-day VR regimen can be followed by patients who undergo phonosurgery without compromising the vocal results. Larger-scale and longer-duration studies are needed to confirm our findings.

LEVEL OF EVIDENCE: 2 Laryngoscope, 134:4661-4666, 2024.}, } @article {pmid38414161, year = {2024}, author = {Geppert, J and Rohm, M}, title = {Cancer cachexia: biomarkers and the influence of age.}, journal = {Molecular oncology}, volume = {18}, number = {9}, pages = {2070-2086}, doi = {10.1002/1878-0261.13590}, pmid = {38414161}, issn = {1878-0261}, support = {//Helmholtz-Gemeinschaft/ ; 949017//European Commission/ ; }, mesh = {*Cachexia/metabolism/diagnosis ; Humans ; *Neoplasms/complications/metabolism ; *Aging/metabolism ; Animals ; Biomarkers/metabolism ; Biomarkers, Tumor/metabolism ; Inflammation/metabolism ; }, abstract = {Cancer cachexia (Ccx) is a complex metabolic condition characterized by pronounced muscle and fat wasting, systemic inflammation, weakness and fatigue. Up to 30% of cancer patients succumb directly to Ccx, yet therapies that effectively address this perturbed metabolic state are rare. In recent decades, several characteristics of Ccx have been established in mice and humans, of which we here highlight adipose tissue dysfunction, muscle wasting and systemic inflammation, as they are directly linked to biomarker discovery. To counteract cachexia pathogenesis as early as possible and mitigate its detrimental impact on anti-cancer treatments, identification and validation of clinically endorsed biomarkers assume paramount importance. Ageing was recently shown to affect both the validity of Ccx biomarkers and Ccx development, but the underlying mechanisms are still unknown. Thus, unravelling the intricate interplay between ageing and Ccx can help to counteract Ccx pathogenesis and tailor diagnostic and treatment strategies to individual needs.}, } @article {pmid38795111, year = {2024}, author = {Voß, F and Zweck, E and Ipek, R and Schultheiss, HP and Roden, M and Kelm, M and Szendroedi, J and Polzin, A and Westenfeld, R and Scheiber, D}, title = {Myocardial Mitochondrial Function Is Impaired in Cardiac Light-Chain Amyloidosis Compared to Transthyretin Amyloidosis.}, journal = {JACC. Heart failure}, volume = {12}, number = {10}, pages = {1778-1780}, doi = {10.1016/j.jchf.2024.03.012}, pmid = {38795111}, issn = {2213-1787}, mesh = {Humans ; *Amyloid Neuropathies, Familial/metabolism/physiopathology/complications ; *Cardiomyopathies/etiology/physiopathology/metabolism ; Mitochondria, Heart/metabolism ; Male ; Female ; Immunoglobulin Light-chain Amyloidosis ; Aged ; Middle Aged ; Myocardium/pathology/metabolism ; }, } @article {pmid39187318, year = {2024}, author = {Kolia, A and Frountzas, M and Liatsou, E and Samelis, G and Zagouri, F and Zografos, GC and Gazouli, M and Michalopoulos, NV}, title = {The Role of Serum Nestin in Diagnosis and Prognosis of Breast Cancer: A Prospective Observational Study.}, journal = {In vivo (Athens, Greece)}, volume = {38}, number = {5}, pages = {2399-2403}, pmid = {39187318}, issn = {1791-7549}, mesh = {Humans ; *Breast Neoplasms/blood/diagnosis/pathology/metabolism ; Female ; *Nestin/metabolism/blood ; Middle Aged ; Prognosis ; *Biomarkers, Tumor/blood ; Aged ; Adult ; Prospective Studies ; Neoplasm Staging ; Receptor, ErbB-2/metabolism/genetics ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; Aged, 80 and over ; }, abstract = {BACKGROUND/AIM: The molecular classification of breast cancer has enabled targeted therapy for specific molecular subtypes. Nestin, which has been studied for its role in oncogenesis, could contribute to this direction. This study aimed to investigate the differences between serum nestin levels and molecular profiling, as well as histopathological tumor types, in women who underwent surgery for breast cancer.

PATIENTS AND METHODS: Women who underwent surgery for breast cancer at the Breast Unit of the 1[st] Propaedeutic Department of Surgery, Hippocration General Hospital, National and Kapodistrian University of Athens were prospectively included. Patients' demographic data were recorded and serum nestin levels were measured. Molecular biomarker analysis was performed, as well as histopathologic assessment.

RESULTS: Seventy patients were included in the analysis. Among patients with breast cancer, 93% were estrogen receptor (ER) positive, 91% were progesterone receptor (PR) positive, and 43% were human epidermal growth factor receptor 2 (HER2) positive. Ki67 was expressed in 16% of patients and p53 was expressed in 32% of patients. Invasive ductal carcinoma was diagnosed in 80% of patients, with 44% of tumors classified as T1 and 46% as T2. Additionally, 43% were G1 and 56% were N0, while 34% were N1. No statistically significant difference was observed between serum nestin levels and ER, PR, HER2, Ki67, and p53 expression. Furthermore, no difference was observed between serum nestin levels and breast cancer histological type, size, N-stage, and grading.

CONCLUSION: The diagnostic and prognostic role of circulating nestin for breast cancer was not confirmed and no correlation with immunohistochemistry results was observed. Thus, the necessity of larger prospective studies is enhanced.}, } @article {pmid39148033, year = {2024}, author = {Chen, JH and Addanki, S and Roy, D and Bassett, R and Kalashnikova, E and Spickard, E and Kuerer, HM and Meas, S and Sarli, VN and Korkut, A and White, JB and Rauch, GM and Tripathy, D and Arun, BK and Barcenas, CH and Yam, C and Sethi, H and Rodriguez, AA and Liu, MC and Moulder, SL and Lucci, A}, title = {Monitoring response to neoadjuvant chemotherapy in triple negative breast cancer using circulating tumor DNA.}, journal = {BMC cancer}, volume = {24}, number = {1}, pages = {1016}, pmid = {39148033}, issn = {1471-2407}, mesh = {Humans ; *Triple Negative Breast Neoplasms/drug therapy/blood/mortality/genetics/pathology ; *Circulating Tumor DNA/blood/genetics ; Female ; *Neoadjuvant Therapy/methods ; Middle Aged ; Adult ; *Neoplastic Cells, Circulating/pathology/metabolism ; Biomarkers, Tumor/blood ; Aged ; Prognosis ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Treatment Outcome ; }, abstract = {BACKGROUND: Triple negative breast cancer (TNBC) is an aggressive subtype with poor prognosis. We aimed to determine whether circulating tumor DNA (ctDNA) and circulating tumor cell (CTC) could predict response and long-term outcomes to neoadjuvant chemotherapy (NAC).

METHODS: Patients with TNBC were enrolled between 2017-2021 at The University of Texas MD Anderson Cancer Center (Houston, TX). Serial plasma samples were collected at four timepoints: pre-NAC (baseline), 12-weeks after NAC (mid-NAC), after NAC/prior to surgery (post-NAC), and one-year after surgery. ctDNA was quantified using a tumor-informed ctDNA assay (Signatera[TM], Natera, Inc.) and CTC enumeration using CellSearch. Wilcoxon and Fisher's exact tests were used for comparisons between groups and Kaplan-Meier analysis used for survival outcomes.

RESULTS: In total, 37 patients were enrolled. The mean age was 50 and majority of patients had invasive ductal carcinoma (34, 91.9%) with clinical T2, (25, 67.6%) node-negative disease (21, 56.8%). Baseline ctDNA was detected in 90% (27/30) of patients, of whom 70.4% (19/27) achieved ctDNA clearance by mid-NAC. ctDNA clearance at mid-NAC was significantly associated with pathologic complete response (p = 0.02), whereas CTC clearance was not (p = 0.52). There were no differences in overall survival (OS) and recurrence-free survival (RFS) with positive baseline ctDNA and CTC. However, positive ctDNA at mid-NAC was significantly associated with worse OS and RFS (p = 0.0002 and p = 0.0034, respectively).

CONCLUSIONS: Early clearance of ctDNA served as a predictive and prognostic marker in TNBC. Personalized ctDNA monitoring during NAC may help predict response and guide treatment.}, } @article {pmid39138514, year = {2024}, author = {Moragas, N and Fernandez-Nogueira, P and Recalde-Percaz, L and Inman, JL and López-Plana, A and Bergholtz, H and Noguera-Castells, A and Del Burgo, PJ and Chen, X and Sorlie, T and Gascón, P and Bragado, P and Bissell, M and Carbó, N and Fuster, G}, title = {The SEMA3F-NRP1/NRP2 axis is a key factor in the acquisition of invasive traits in in situ breast ductal carcinoma.}, journal = {Breast cancer research : BCR}, volume = {26}, number = {1}, pages = {122}, pmid = {39138514}, issn = {1465-542X}, support = {Juan de la Cierva//Agencia Estatal de Investigación,Spain/ ; Postdoctoral grant//Asociación Española contra el cáncer (AECC)/ ; 201915-30-31//La Marató TV3/ ; FPU//Spanish Ministry of Education/ ; PREDOCS-UB fellowship//Universitat de Barcelona (UB)/ ; PID2019-104991RB-I00//Spanish Ministry of Economy and Competitiveness/ ; BBM-TRA-0041//Becas Leonardo 2018/ ; }, mesh = {Humans ; *Neuropilin-1/metabolism/genetics ; Female ; *Breast Neoplasms/pathology/metabolism/genetics ; *Neuropilin-2/metabolism/genetics ; *Neoplasm Invasiveness ; *Carcinoma, Intraductal, Noninfiltrating/metabolism/pathology/genetics ; Cell Line, Tumor ; *Nerve Tissue Proteins/metabolism/genetics ; Epithelial-Mesenchymal Transition/genetics ; Animals ; Membrane Proteins/metabolism/genetics ; Mice ; Carcinoma, Ductal, Breast/pathology/metabolism/genetics ; Gene Expression Regulation, Neoplastic ; Signal Transduction ; }, abstract = {BACKGROUND: A better understanding of ductal carcinoma in situ (DCIS) is urgently needed to identify these preinvasive lesions as distinct clinical entities. Semaphorin 3F (SEMA3F) is a soluble axonal guidance molecule, and its coreceptors Neuropilin 1 (NRP1) and NRP2 are strongly expressed in invasive epithelial BC cells.

METHODS: We utilized two cell line models to represent the progression from a healthy state to the mild-aggressive or ductal carcinoma in situ (DCIS) stage and, ultimately, to invasive cell lines. Additionally, we employed in vivo models and conducted analyses on patient databases to ensure the translational relevance of our results.

RESULTS: We revealed SEMA3F as a promoter of invasion during the DCIS-to-invasive ductal carcinoma transition in breast cancer (BC) through the action of NRP1 and NRP2. In epithelial cells, SEMA3F activates epithelialmesenchymal transition, whereas it promotes extracellular matrix degradation and basal membrane and myoepithelial cell layer breakdown.

CONCLUSIONS: Together with our patient database data, these proof-of-concept results reveal new SEMA3F-mediated mechanisms occurring in the most common preinvasive BC lesion, DCIS, and represent potent and direct activation of its transition to invasion. Moreover, and of clinical and therapeutic relevance, the effects of SEMA3F can be blocked directly through its coreceptors, thus preventing invasion and keeping DCIS lesions in the preinvasive state.}, } @article {pmid39103259, year = {2024}, author = {Wang, DH and Yin, WL and Pan, XY and Zhang, MN and Nie, L and Chen, XQ and Zeng, H and Zhou, Q and Chen, N}, title = {[Prostate cancer with BRCA2 pathogenic mutation: a clinicopathological analysis].}, journal = {Zhonghua bing li xue za zhi = Chinese journal of pathology}, volume = {53}, number = {8}, pages = {789-796}, doi = {10.3760/cma.j.cn112151-20240402-00216}, pmid = {39103259}, issn = {0529-5807}, support = {82273047, 82273073, 82203280//National Natural Science Foundation of China/ ; 24SYSX0223, 2022YFS0305//Foundation of Science and Technology Department of Sichuan Province/ ; }, mesh = {Humans ; Male ; *Prostatic Neoplasms/genetics/pathology ; *BRCA2 Protein/genetics ; Aged ; Retrospective Studies ; Middle Aged ; *Mutation ; Prognosis ; Aged, 80 and over ; Bone Neoplasms/genetics/secondary/pathology ; }, abstract = {Objective: To analyze the clinicopathological features of prostate cancers with BRCA2 pathogenic mutations, and the association between BRCA2 pathogenic mutation and clinicopathological characteristics. Patient survivals were also examined. Methods: Clinicopathological data of 249 prostate cancer patients who underwent genetic testing in West China Hospital of Sichuan University, Chengdu, China from June 2014 to August 2021 were collected. A retrospective analysis of histopathological morphology, clinicopathological characteristics, and patient survivals was conducted. Results: The genetic testing in the 249 prostate cancer patients showed a pathogenic mutation of DNA damage repair gene (DRG) in 73 cases (73/249, 29.3%), including 22 cases (8.8%) with BRCA2 pathogenic mutation and 51 cases with pathogenic mutations of other DRG. Among the 22 patients with BRCA2 pathogenic mutation, 14 patients (5.6%) harbored germline mutations and 8 patients (3.2%) somatic mutations. Their ages ranged from 48 to 91 years, with a median of 67 years. Seventeen patients (77.3%) had distant metastasis, including 16 cases with bone metastasis and 1 case with multiple metastases. Thirteen patients (59.1%) were castration-resistant prostate cancer. The histological type was mainly classical prostatic acinar adenocarcinoma, including 16 cases (72.7%) with intraductal carcinoma of the prostate (IDC-P). Six cases (27.3%) showed focal neuroendocrine differentiation. Perineural/vascular invasion and extraprostatic extension were seen in 11 cases (50.0%) and 8 cases (36.4%), respectively. The Gleason scores of 19 patients (86.4%) were≥8. IDC-P was more commonly found in patients with BRCA2 germline pathogenic mutation than those with BRCA2 somatic pathogenic mutation, other DRG pathogenic mutation or no-DRG pathogenic mutation (P=0.002). With a total follow-up time of 189 months, the median overall survival (OS) was 132.3 months. Patients with DRG pathogenic mutation had shorter OS than those with no-DRG pathogenic mutation (P=0.040). The OS of patients with BRCA2 germline pathogenic mutation did not significantly differ from that of patients with BRCA2 somatic pathogenic mutation, other DRG pathogenic mutation or no-DRG pathogenic mutation (P=0.216). Conclusions: The presence of BRCA2 gene pathogenic mutation is common in the prostate cancers with high Gleason grade, advanced clinical stage, and castration resistance. IDC-P is more commonly noted in cases with BRCA2 germline pathogenic mutation than those without. Patients with DRG pathogenic mutation have shorter OS than those with no-DRG pathogenic mutation, but there is no significant association between BRCA2 pathogenic mutations and OS.}, } @article {pmid39069624, year = {2024}, author = {Imamura, T and Komatsu, S and Nishibeppu, K and Kiuchi, J and Ohashi, T and Konishi, H and Shiozaki, A and Yamamoto, Y and Moriumura, R and Ikoma, H and Ochiai, T and Otsuji, E}, title = {Urinary microRNA-210-3p as a novel and non-invasive biomarker for the detection of pancreatic cancer, including intraductal papillary mucinous carcinoma.}, journal = {BMC cancer}, volume = {24}, number = {1}, pages = {907}, pmid = {39069624}, issn = {1471-2407}, mesh = {Humans ; *MicroRNAs/urine/blood/genetics ; Female ; Male ; *Biomarkers, Tumor/urine/genetics/blood ; *Pancreatic Neoplasms/urine/genetics/diagnosis/blood ; Middle Aged ; Aged ; Adenocarcinoma, Mucinous/urine/genetics/diagnosis ; ROC Curve ; Case-Control Studies ; Gene Expression Regulation, Neoplastic ; Adult ; Carcinoma, Pancreatic Ductal/urine/genetics/diagnosis/blood ; }, abstract = {BACKGROUND: This study aims to explore novel microRNAs in urine for screening and predicting clinical characteristics in pancreatic cancer (PC) patients using a microRNA array-based approach.

METHODS: We used the Toray[®] 3D-Gene microRNA array-based approach to compare urinary levels between PC patients and healthy volunteers.

RESULTS: (1) Four oncogenic microRNAs (miR-744-5p, miR-572, miR-210-3p, and miR-575) that were highly upregulated in the urine of PC patients compared to healthy individuals were identified by comprehensive microRNA array analysis. (2) Test-scale analysis by quantitative RT-PCR for each group of 20 cases showed that miR-210-3p was significantly upregulated in the urine of PC patients compared to healthy individuals (P = 0.009). (3) Validation analysis (58 PC patients and 35 healthy individuals) confirmed that miR-210-3p was significantly upregulated in the urine of PC patients compared to healthy individuals (P < 0.001, area under the receiver operating characteristic curve = 0.79, sensitivity: 0.828, specificity: 0.743). We differentiated PC patients into invasive ductal carcinoma (IDCa) and intraductal papillary mucinous carcinoma (IPMC) groups. In addition to urinary miR-210-3p levels being upregulated in IDCa over healthy individuals (P = 0.009), urinary miR-210-3p levels were also elevated in IPMC over healthy individuals (P = 0.0018). Urinary miR-210-3p can differentiate IPMC from healthy individuals by a cutoff of 8.02 with an AUC value of 0.762, sensitivity of 94%, and specificity of 63%. (4) To test whether urinary miR210-3p levels reflected plasma miR-210-3p levels, we examined the correlation between urinary and plasma levels. Spearman's correlation analysis showed a moderate positive correlation (ρ = 0.64, P = 0.005) between miR-210-3p expression in plasma and urine.

CONCLUSIONS: Urinary miR-210-3p is a promising, non-invasive diagnostic biomarker of PC, including IPMC.

TRIAL REGISTRATION: Not applicable.}, } @article {pmid39062707, year = {2024}, author = {Corrêa, TS and Asprino, PF and de Oliveira, ESC and Leite, ACR and Weis, L and Achatz, MI and de Oliveira, CP and Sandoval, RL and Barroso-Sousa, R}, title = {TP53 p.R337H Germline Variant among Women at Risk of Hereditary Breast Cancer in a Public Health System of Midwest Brazil.}, journal = {Genes}, volume = {15}, number = {7}, pages = {}, pmid = {39062707}, issn = {2073-4425}, mesh = {Humans ; Female ; *Breast Neoplasms/genetics/epidemiology ; Brazil/epidemiology ; *Germ-Line Mutation ; Adult ; *Tumor Suppressor Protein p53/genetics ; Middle Aged ; *Genetic Predisposition to Disease ; Genetic Testing/methods ; Public Health ; Li-Fraumeni Syndrome/genetics/epidemiology ; Aged ; }, abstract = {Despite the high prevalence of TP53 pathogenic variants (PV) carriers in the South and Southeast regions of Brazil, germline genetic testing for hereditary breast cancer (HBC) is not available in the Brazilian public health system, and the prevalence of Li-Fraumeni syndrome (LFS) is not well established in other regions of Brazil. We assessed the occurrence of TP53 p.R337H carriers among women treated for breast cancer (BC) between January 2021 and January 2022 at public hospitals of Brasilia, DF, Brazil. A total of 180 patients who met at least one of the NCCN criteria for HBC underwent germline testing; 44.4% performed out-of-pocket germline multigene panel testing, and 55.6% were tested for the p.R337H variant by allelic discrimination PCR. The median age at BC diagnosis was 43.5 years, 93% had invasive ductal carcinoma, 50% had estrogen receptor-positive/HER2 negative tumors, and 41% and 11% were diagnosed respectively at stage III and IV. Two patients (1.11%) harbored the p.R337H variant, and cascade family testing identified 20 additional carriers. The TP53 p.R337H detection rate was lower than that reported in other studies from south/southeast Brazil. Nonetheless, identifying TP53 PV carriers through genetic testing in the Brazilian public health system could guide cancer treatment and prevention.}, } @article {pmid39039278, year = {2024}, author = {Das, M and Semple, JI and Haemmerli, A and Volodkina, V and Scotton, J and Gitchev, T and Annan, A and Campos, J and Statzer, C and Dakhovnik, A and Ewald, CY and Mozziconacci, J and Meister, P}, title = {Condensin I folds the Caenorhabditis elegans genome.}, journal = {Nature genetics}, volume = {56}, number = {8}, pages = {1737-1749}, pmid = {39039278}, issn = {1546-1718}, support = {31003A_176226/PP00P3_159320//Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (Swiss National Science Foundation)/ ; }, mesh = {Animals ; *Caenorhabditis elegans/genetics ; *Adenosine Triphosphatases/genetics/metabolism ; *Multiprotein Complexes/genetics/metabolism ; *DNA-Binding Proteins/genetics/metabolism ; *Caenorhabditis elegans Proteins/genetics/metabolism ; *X Chromosome/genetics ; Chromosomal Proteins, Non-Histone/metabolism/genetics ; Cohesins ; Cell Cycle Proteins/metabolism/genetics ; Interphase/genetics ; Genome, Helminth ; Genes, X-Linked ; Chromosomes/genetics ; }, abstract = {The structural maintenance of chromosome (SMC) complexes-cohesin and condensins-are crucial for chromosome separation and compaction during cell division. During the interphase, mammalian cohesins additionally fold the genome into loops and domains. Here we show that, in Caenorhabditis elegans, a species with holocentric chromosomes, condensin I is the primary, long-range loop extruder. The loss of condensin I and its X-specific variant, condensin I[DC], leads to genome-wide decompaction, chromosome mixing and disappearance of X-specific topologically associating domains, while reinforcing fine-scale epigenomic compartments. In addition, condensin I/I[DC] inactivation led to the upregulation of X-linked genes and unveiled nuclear bodies grouping together binding sites for the X-targeting loading complex of condensin I[DC]. C. elegans condensin I/I[DC] thus uniquely organizes holocentric interphase chromosomes, akin to cohesin in mammals, as well as regulates X-chromosome gene expression.}, } @article {pmid39038425, year = {2024}, author = {Bar, Y and Bar, K and Feldman, D and Dror, JB and Shahoha, M and Lerner, S and Shachar, SS and Weiss-Meilik, A and Dershowitz, N and Wolf, I and Sonnenblick, A}, title = {The impact of extensive intraductal component (EIC) on the genomic risk of recurrence in early hormone receptor positive breast cancer.}, journal = {Breast (Edinburgh, Scotland)}, volume = {77}, number = {}, pages = {103777}, pmid = {39038425}, issn = {1532-3080}, mesh = {Humans ; Female ; *Breast Neoplasms/genetics/pathology/surgery ; Middle Aged ; *Neoplasm Recurrence, Local/genetics ; *Carcinoma, Intraductal, Noninfiltrating/genetics/pathology ; *Carcinoma, Ductal, Breast/genetics/pathology/surgery ; Aged ; Adult ; Receptor, ErbB-2/genetics/metabolism ; Receptors, Estrogen/metabolism/analysis ; Receptors, Progesterone/metabolism ; Risk Assessment ; Retrospective Studies ; Genomics ; Risk Factors ; }, abstract = {BACKGROUND: Early invasive ductal carcinoma (IDC) breast cancer often presents with a coexisting ductal carcinoma in situ (DCIS) component, while about 5 % of cases present with an extensive (>25 %) intraductal component (EIC). The impact of EIC on the genomic risk of recurrence is unclear.

METHODS: Patients with early hormone receptor-positive HER2neu-negative (HR + HER2-) IDC breast cancer and a known OncotypeDX Breast Recurrence Score® (RS) who underwent breast surgery at our institute were included. Using a rule-based text-analysis algorithm, we analyzed pathological reports and categorized patients into three groups: EIC, non-extensive DCIS (DCIS-L), and pure-IDC (NO-DCIS). Genomic risk was determined using OncotypeDX RS.

RESULTS: A total of 33 (4.6 %) EIC cases, 377 (57.2 %) DCIS-L cases and 307 (42.8 %) NO-DCIS cases were identified. Patients in the EIC group were younger and had lower tumor grades than other groups. The distribution of genomic risk varied between the groups, with EIC tumors significantly less likely to have a high RS (>25) compared to DCIS-L and No-DCIS tumors (3 % vs 20 % and 20 %, respectively; p = 0.03). When adjusted to age, tumor size, grade and LNs involvement, both DCIS-L and NO-DCIS groups were significantly correlated with a higher probability of high RS compared to the EIC group (OR 12.3 and OR 13.1, respectively; p < 0.02). Moreover, patients with EIC had a lower likelihood for adjuvant chemotherapy recommendation.

CONCLUSIONS: In early HR + HER2- IDC, an EIC correlates with a reduced genomic recurrence risk. The impact on genomic risk seems to be influenced by the extent, not merely the presence, of DCIS.}, } @article {pmid39012819, year = {2024}, author = {Zin, I and China, A and Khan, K and Nag, JK and Vasu, K and Deshpande, GM and Ghosh, PK and Khan, D and Ramachandiran, I and Ganguly, S and Tamagno, I and Willard, B and Gogonea, V and Fox, PL}, title = {AKT-dependent nuclear localization of EPRS1 activates PARP1 in breast cancer cells.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {121}, number = {30}, pages = {e2303642121}, pmid = {39012819}, issn = {1091-6490}, support = {R01 AG067146/AG/NIA NIH HHS/United States ; R01 NS124547/NS/NINDS NIH HHS/United States ; R01 DK123236/DK/NIDDK NIH HHS/United States ; R01 DK124203/DK/NIDDK NIH HHS/United States ; R01 NS124581/NS/NINDS NIH HHS/United States ; }, mesh = {Humans ; *Breast Neoplasms/metabolism/genetics/pathology ; Female ; *Poly (ADP-Ribose) Polymerase-1/metabolism/genetics ; *Cell Nucleus/metabolism ; *Proto-Oncogene Proteins c-akt/metabolism/genetics ; Cell Line, Tumor ; PTEN Phosphohydrolase/metabolism/genetics ; Amino Acyl-tRNA Synthetases/metabolism/genetics ; Active Transport, Cell Nucleus ; Nuclear Localization Signals/metabolism ; }, abstract = {Glutamyl-prolyl-tRNA synthetase (EPRS1) is a bifunctional aminoacyl-tRNA-synthetase (aaRS) essential for decoding the genetic code. EPRS1 resides, with seven other aaRSs and three noncatalytic proteins, in the cytoplasmic multi-tRNA synthetase complex (MSC). Multiple MSC-resident aaRSs, including EPRS1, exhibit stimulus-dependent release from the MSC to perform noncanonical activities distinct from their primary function in protein synthesis. Here, we show EPRS1 is present in both cytoplasm and nucleus of breast cancer cells with constitutively low phosphatase and tensin homolog (PTEN) expression. EPRS1 is primarily cytosolic in PTEN-expressing cells, but chemical or genetic inhibition of PTEN, or chemical or stress-mediated activation of its target, AKT, induces EPRS1 nuclear localization. Likewise, preferential nuclear localization of EPRS1 was observed in invasive ductal carcinoma that were also P-Ser[473]-AKT[+]. EPRS1 nuclear transport requires a nuclear localization signal (NLS) within the linker region that joins the catalytic glutamyl-tRNA synthetase and prolyl-tRNA synthetase domains. Nuclear EPRS1 interacts with poly(ADP-ribose) polymerase 1 (PARP1), a DNA-damage sensor that directs poly(ADP-ribosyl)ation (PARylation) of proteins. EPRS1 is a critical regulator of PARP1 activity as shown by markedly reduced ADP-ribosylation in EPRS1 knockdown cells. Moreover, EPRS1 and PARP1 knockdown comparably alter the expression of multiple tumor-related genes, inhibit DNA-damage repair, reduce tumor cell survival, and diminish tumor sphere formation by breast cancer cells. EPRS1-mediated regulation of PARP1 activity provides a mechanistic link between PTEN loss in breast cancer cells, PARP1 activation, and cell survival and tumor growth. Targeting the noncanonical activity of EPRS1, without inhibiting canonical tRNA ligase activity, provides a therapeutic approach potentially supplementing existing PARP1 inhibitors.}, } @article {pmid38994984, year = {2024}, author = {Nascimento, KCG and São Marcos, BF and Fontes, PHB and Isídio, BEO and Leão, SL and da Silva, GRP and Lussón, DB and Dos Santos, DL and Leal, LRS and Espinoza, BCF and de Macêdo, LS and de França Neto, PL and Silva, AJD and Silva Neto, JC and Santos, VEP and de Freitas, AC}, title = {HPV Detection in Breast Tumors and Associated Risk Factors in Northeastern Brazil.}, journal = {Cells}, volume = {13}, number = {13}, pages = {}, pmid = {38994984}, issn = {2073-4409}, support = {444606/2023-8//National Council for Scientific and Technological Development/ ; 444156/2023-2//National Council for Scientific and Technological Development/ ; 308684/2023-0//National Council for Scientific and Technological Development/ ; }, mesh = {Humans ; Brazil/epidemiology ; Female ; Middle Aged ; Risk Factors ; *Breast Neoplasms/virology ; *Papillomavirus Infections/virology/complications/epidemiology ; Adult ; Aged ; Papillomaviridae ; Viral Load ; }, abstract = {Breast cancer risk factors include lifestyle, genetic-hormonal influences, and viral infections. Human papillomavirus (HPV), known primarily as the etiological agent of cervical cancer, also appears active in breast carcinogenesis, as evidenced in our study of 56 patients from northeastern Brazil. We assessed the clinical and sociodemographic characteristics, correlating them with various breast cancer tumor types. HPV detection involved amplifying the L1 region, with viral load measured using the E2/E6 ratio and viral activity indicated by E5 oncogene expression. Predominantly, patients over 56 years of age with healthy lifestyles showed a high incidence of invasive ductal carcinoma and triple-negative breast cancer. HPV was detected in 35.7% of cases, mostly HPV16, which is associated with high viral loads (80 copies per cell) and significant E5 expression. These results hint at a possible link between HPV and breast carcinogenesis, necessitating further studies to explore this association and the underlying viral mechanisms.}, } @article {pmid38968480, year = {2024}, author = {Zhang, Z and Huang, C and Wu, J and Cheng, Q and Wang, S}, title = {TICRR as a potential prognostic biomarker for lung adenocarcinoma: A comprehensive analysis using TCGA database.}, journal = {Medicine}, volume = {103}, number = {27}, pages = {e38660}, pmid = {38968480}, issn = {1536-5964}, mesh = {Humans ; *Adenocarcinoma of Lung/genetics/mortality/pathology ; Male ; *Biomarkers, Tumor/genetics/metabolism ; Female ; Prognosis ; *Lung Neoplasms/genetics/mortality/pathology ; Middle Aged ; Nomograms ; Kaplan-Meier Estimate ; Aged ; ROC Curve ; Neoplasm Staging ; Databases, Genetic ; }, abstract = {To investigate the role of TopBP1-interacting checkpoint and replication regulator (TICRR) in the tumorigenesis and prognosis of lung adenocarcinoma (LUAD) patients. Wilcoxon signed-rank test and logistic regression were utilized to analyze the relationship between clinical characteristics and TICRR expression in LUAD from TCGA dataset. Kaplan-Meier plots and Cox regressions were used to assess the impact of TICRR impact on prognosis. ROC curves and nomograms were generated to further evaluate the relationship between TICRR expression and the risk of LUAD. Gene set enrichment analysis (GSEA) was conducted on TCGA dataset, and ssGSEA was employed to investigate the association between TICRR and immune infiltrates. The results showed that high TICRR expression was significantly associated with various clinical factors including gender, age, pathological stage, T stage, N stage, M stage, outcome of primary therapy and smoking status. ROC curves also demonstrated that TICRR was a promising biomarker for molecular pathology diagnosis in LUAD patients (AUC = 0.952). Further analysis using gene ontology (GO) term enrichment and GSEA revealed an abnormal correlation between TICRR expression and cell division. Interestingly, ssGSEA analysis showed that TICRR expression correlated with multiple immune cell types, such as Th2 cell, TFH cell, mast cell, iDC, eosinophils, and dendritic cell. Lastly, the KM-plotters indicated that LUAD patients with high TICRR expression obtained worse life expectancy (P < .001). TICRR has proven to be a valuable tool in predicting disease progression and prognosis in patients with LUAD, thereby establishing itself as a fitting biomarker for forecasting overall survival (OS) of LUAD patients.}, } @article {pmid38944914, year = {2024}, author = {Bogaard, M and Strømme, JM and Kidd, SG and Johannessen, B and Bakken, AC and Lothe, RA and Axcrona, K and Skotheim, RI and Axcrona, U}, title = {GRIN3A: A biomarker associated with a cribriform pattern and poor prognosis in prostate cancer.}, journal = {Neoplasia (New York, N.Y.)}, volume = {55}, number = {}, pages = {101023}, pmid = {38944914}, issn = {1476-5586}, mesh = {Humans ; Male ; *Prostatic Neoplasms/genetics/pathology/metabolism/surgery ; *Biomarkers, Tumor/genetics/metabolism ; Prognosis ; *Neoplasm Grading ; Middle Aged ; Aged ; Gene Expression Regulation, Neoplastic ; Prostatectomy ; Gene Expression Profiling ; }, abstract = {Prostate cancer with a cribriform pattern, including invasive cribriform carcinoma (ICC) and/or intraductal carcinoma (IDC) is associated with a poor prognosis, and the underlying mechanisms are unclear. Therefore, we aimed to identify biomarkers for this feature. Using a radical prostatectomy cohort, we performed within-patient differential expression analyses with RNA sequencing data to compare samples with a cribriform pattern to those with non-cribriform Gleason pattern 4 (NcGP4; n=13). ACSM1, GRIN3A, PCDHB2, and REG4 were identified as differentially expressed, and validation was performed using real-time reverse transcription polymerase chain reaction (n=99; 321 RNA samples) and RNA in situ hybridization on tissue microarrays (n=479; 2047 tissue cores). GRIN3A was significantly higher expressed in cribriform pattern vs. NcGP4, when assessed within the same patient (n=27; p=0.005) and between different patients (n=83; p=0.001). Tissue cores with IDC more often expressed GRIN3A compared to ICC, NcGP4, and benign tissue (52 % vs. ≤ 32 %). When IDC and NcGP4 was compared within the same patient (173 pairs of tissue cores; 54 patients), 38 (22 %) of the tissue microarray core pairs had GRIN3A expression in only IDC, 33 (19 %) had expression in both IDC and NcGP4, 14 (8 %) in only NcGP4 and 88 (51 %) were negative in both entities (p=0.001). GRIN3A was as well associated with biochemical recurrence (log-rank, p=0.002). In conclusion, ectopic GRIN3A expression is an RNA-based biomarker for the presence of cribriform prostate cancer, particularly for IDC.}, } @article {pmid38935197, year = {2024}, author = {Delfin, L and Doff, JJ and Gagan, J and Flack, A and Krane, JF and Jo, VY and Torell, AG and Palsgrove, D and Bishop, JA}, title = {Pure Apocrine Intraductal Carcinoma of Salivary Glands: Reassessment of Molecular Underpinnings and Behavior.}, journal = {Head and neck pathology}, volume = {18}, number = {1}, pages = {58}, pmid = {38935197}, issn = {1936-0568}, mesh = {Humans ; Male ; Middle Aged ; Aged ; Female ; *Salivary Gland Neoplasms/pathology/genetics ; Aged, 80 and over ; Carcinoma, Intraductal, Noninfiltrating/pathology/genetics ; Biomarkers, Tumor/analysis/genetics ; Adult ; Carcinoma, Ductal/pathology/genetics ; }, abstract = {BACKGROUND: Intraductal carcinoma (IDC) of the salivary glands is a confounding entity, our understanding of which continues to evolve. At least four forms have been elucidated based on histomorphology, immunophenotype, and molecular profile: (1) intercalated duct-like, S100/SOX10+ with frequent NCOA4::RET fusions; (2) oncocytic, S100/SOX10+ with TRIM33::RET, NCOA4::RET, and BRAF V600E; (3) apocrine, AR+ with PI3 kinase pathway mutations; and (4) mixed/hybrid intercalated duct-like/apocrine, with S100/SOX10+ and AR+ areas and frequent TRIM27::RET. The revelation that myoepithelial cells harbor the same fusion as luminal cells suggested that fusion-positive cases are not in situ carcinomas as previously believed. To this point, purely apocrine IDC with entirely intraductal growth has not been found to harbor fusions, but very few cases have been tested.

METHODS: IDCs with pure apocrine morphology, entirely intraductal growth, and no precursor lesion (pleomorphic adenoma or sclerosing polycystic adenoma) were retrieved from the authors' archives. Several immunostains (S100, SOX10, GCDFP-15, AR, p40/SMA) and targeted next generation sequencing (NGS) panel including 1425 cancer-related genes were performed.

RESULTS: Seven entirely IDC with pure apocrine type were collected. The cases arose in the parotid glands (mean, 1.9 cm) of 5 men and 2 women ranging from 51 to 84 years (mean, 69.7 years). Histologically, tumors consisted of rounded to angulated ductal cysts lined by epithelial cells with abundant finely granular eosinophilic cytoplasm and large nuclei with prominent nucleoli. Pleomorphism was mild to moderate, the mitotic rate was low, and necrosis was absent. Conventionally invasive foci or areas of intercalated duct-like morphology were not identified. In all cases, luminal cells were diffusely positive for AR and GCDFP-15 while negative for S100/SOX10, and the ducts were completely surrounded by myoepithelial cells highlighted by p40 and SMA. Molecular analysis was successful in 6 cases. Three harbored fusions: one with NCOA4::RET, another with STRN::ALK and one with both CDKN2A::CNTRL and TANC1::YY1AP1. The three fusion-negative cases all harbored HRAS mutations; additional mutations (PIK3CA, SPEN, ATM) were found in 2 of 3 cases. All patients were treated by surgery alone. Six of them are currently free of disease (follow up 12-190 months), but the case harboring NCOA4::RET developed lymph nodes metastasis in the form of a fusion-positive invasive salivary duct carcinoma.

CONCLUSIONS: Purely apocrine IDC is a heterogeneous disease. A subset seems to be genetically similar to salivary duct carcinoma and may indeed represent carcinoma in situ. The other group harbors fusions, similar to other forms of IDC. Moreover, the occurrence of lymph node metastasis discredits the idea that any fusion-positive IDC with a complete myoepithelial cell layer has no metastatic potential. With the wide use of RET-and ALK-based targeted therapies, our findings further underscore the importance of fusion analysis for IDC.}, } @article {pmid38927753, year = {2024}, author = {Markalunas, EG and Arnold, DH and Funkhouser, AT and Martin, JC and Shtutman, M and Edenfield, WJ and Blenda, AV}, title = {Correlation Analysis of Genetic Mutations and Galectin Levels in Breast Cancer Patients.}, journal = {Genes}, volume = {15}, number = {6}, pages = {}, pmid = {38927753}, issn = {2073-4425}, mesh = {Humans ; *Breast Neoplasms/genetics/blood/pathology ; Female ; *Galectins/genetics/blood ; *Mutation ; *Biomarkers, Tumor/genetics/blood ; Galectin 1/genetics/blood ; Middle Aged ; Galectin 3/genetics/blood ; Adult ; Blood Proteins ; }, abstract = {Galectins are innate immune system regulators associated with disease progression in cancer. This paper aims to investigate the correlation between mutated cancer-critical genes and galectin levels in breast cancer patients to determine whether galectins and genetic profiles can be used as biomarkers for disease and potential therapy targets. Prisma Health Cancer Institute's Biorepository provided seventy-one breast cancer samples, including all four stages spanning the major molecular subtypes and histologies. Hotspot mutation statuses of cancer-critical genes were determined using multiplex PCR in tumor samples from the same patients by Precision Genetics and the University of South Carolina Functional Genomics Core Facility. The galectin-1, -3, and -9 levels in patients' sera were analyzed using Enzyme-linked Immunosorbent Assay (ELISA). An analysis was performed using JMP software to compare mean and median serum galectin levels between samples with and without specific cancer-critical genes, including pooled t-test, Wilcoxon Rank Sum Test, ANOVA, and Steel Dwass Test (α=0.05). Our analysis indicates that KIT mutations correlate with elevated serum levels of galectin-9 in patients with breast cancer. In patients with Luminal A subtype, FLT3 mutation correlates with lower serum galectin-1 and -9 levels and TP53 mutations correlate with higher serum galectin-3 levels. Patients with invasive ductal carcinoma had significantly higher serum galectin-3 levels than patients with ductal carcinoma in situ. Patients with both TP53 and PIK3CA mutations exhibit elevated serum galectin-3 levels, while patients with one or neither mutation show no significant difference in serum galectin-3 levels. In addition, metastatic breast cancer samples were more likely to have a KIT or PIK3CA mutation compared to primary breast cancer samples. The relationship between genetic mutations and galectin levels has the potential to identify appropriate candidates for combined therapy, targeting genetic mutations and galectins. Further understanding of the effect of genetic mutations and galectin levels on cancer progression and metastasis could aid in the search for biomarkers for breast cancer diagnosis, disease progression, and prognosis.}, } @article {pmid38926485, year = {2024}, author = {Baranová, I and Samec, M and Dvorská, D and Šťastný, I and Janíková, K and Kašubová, I and Hornáková, A and Lukáčová, E and Kapinová, A and Biringer, K and Halašová, E and Danková, Z}, title = {Droplet digital PCR analysis of CDH13 methylation status in Slovak women with invasive ductal breast cancer.}, journal = {Scientific reports}, volume = {14}, number = {1}, pages = {14700}, pmid = {38926485}, issn = {2045-2322}, support = {1/0286/22//Ministry of Education, Science, Research and Sport of the Slovak Republic and Slovak Academy of Sciences/ ; }, mesh = {Humans ; *Cadherins/genetics ; Female ; *DNA Methylation ; *Breast Neoplasms/genetics/pathology ; Middle Aged ; *Carcinoma, Ductal, Breast/genetics/pathology/metabolism ; Aged ; *Promoter Regions, Genetic ; Slovakia ; Biomarkers, Tumor/genetics ; Adult ; Polymerase Chain Reaction/methods ; }, abstract = {Identifying novel epigenetic biomarkers is a promising way to improve the clinical management of patients with breast cancer. Our study aimed to determine the methylation pattern of 25 tumor suppressor genes (TSG) and select the best methylation biomarker associated with clinicopathological features in the cohort of Slovak patients diagnosed with invasive ductal carcinoma (IDC). Overall, 166 formalin-fixed, paraffin-embedded (FFPE) tissues obtained from patients with IDC were included in the study. The methylation status of the promoter regions of 25 TSG was analyzed using semiquantitative methylation-specific MLPA (MS-MLPA). We identified CDH13 as the most frequently methylated gene in our cohort of patients. Further analysis by ddPCR confirmed an increased level of methylation in the promoter region of CDH13. A significant difference in CDH13 methylation levels was observed between IDC molecular subtypes LUM A versus HER2 (P = 0.0116) and HER2 versus TNBC (P = 0.0234). In addition, significantly higher methylation was detected in HER2+ versus HER2- tumors (P = 0.0004) and PR- versus PR+ tumors (P = 0.0421). Our results provide evidence that alteration in CDH13 methylation is associated with clinicopathological features in the cohort of Slovak patients with IDC. In addition, using ddPCR as a methylation-sensitive method represents a promising approach characterized by higher precision and technical simplicity to measure the methylation of target CpGs in CDH13 compared to other conventional methods such as MS-MLPA.}, } @article {pmid38897820, year = {2024}, author = {Corso, G and Fusco, N and Guerini-Rocco, E and Leonardi, MC and Criscitiello, C and Zagami, P and Nicolò, E and Mazzarol, G and La Vecchia, C and Pesapane, F and Zanzottera, C and Tarantino, P and Petitto, S and Bianchi, B and Massari, G and Boato, A and Sibilio, A and Polizzi, A and Curigliano, G and De Scalzi, AM and Lauria, F and Bonanni, B and Marabelli, M and Rotili, A and Nicosia, L and Albini, A and Calvello, M and Mukhtar, RA and Robson, ME and Sacchini, V and Rennert, G and Galimberti, V and Veronesi, P and Magnoni, F}, title = {Invasive lobular breast cancer: Focus on prevention, genetics, diagnosis, and treatment.}, journal = {Seminars in oncology}, volume = {51}, number = {3-4}, pages = {106-122}, doi = {10.1053/j.seminoncol.2024.05.001}, pmid = {38897820}, issn = {1532-8708}, mesh = {Humans ; *Breast Neoplasms/diagnosis/genetics/therapy/pathology/prevention & control ; Female ; *Carcinoma, Lobular/diagnosis/therapy/genetics/pathology ; }, abstract = {Invasive lobular cancer (ILC) is the most common of the breast cancer special types, accounting for up to 15% of all breast malignancies. The distinctive biological features of ILC include the loss of the cell adhesion molecule E-cadherin, which drives the tumor's peculiar discohesive growth pattern, with cells arranged in single file and dispersed throughout the stroma. Typically, such tumors originate in the lobules, are more commonly bilateral compared to invasive ductal cancer (IDC) and require a more accurate diagnostic examination through imaging. They are luminal in molecular subtype, and exhibit estrogen and progesterone receptor positivity and HER2 negativity, thus presenting a more unpredictable response to neoadjuvant therapies. There has been a significant increase in research focused on this distinctive breast cancer subtype, including studies on its pathology, its clinical and surgical management, and the high-resolution definition of its genomic profile, as well as the development of new therapeutic perspectives. This review will summarize the heterogeneous pattern of this unique disease, focusing on challenges in its comprehensive clinical management and on future insights and research objectives.}, } @article {pmid38830849, year = {2024}, author = {Wearn, A and Tremblay, SA and Tardif, CL and Leppert, IR and Gauthier, CJ and Baracchini, G and Hughes, C and Hewan, P and Tremblay-Mercier, J and Rosa-Neto, P and Poirier, J and Villeneuve, S and Schmitz, TW and Turner, GR and Spreng, RN and , }, title = {Neuromodulatory subcortical nucleus integrity is associated with white matter microstructure, tauopathy and APOE status.}, journal = {Nature communications}, volume = {15}, number = {1}, pages = {4706}, pmid = {38830849}, issn = {2041-1723}, support = {AARG-22-927100/ALZ/Alzheimer's Association/United States ; NIA R01 AG068563//U.S. Department of Health & Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging)/ ; }, mesh = {Humans ; *White Matter/diagnostic imaging/pathology/metabolism ; Female ; Male ; Aged ; Middle Aged ; *Alzheimer Disease/genetics/pathology/cerebrospinal fluid/metabolism/diagnostic imaging ; *Tauopathies/diagnostic imaging/metabolism/pathology/genetics/cerebrospinal fluid ; *tau Proteins/metabolism/cerebrospinal fluid ; *Magnetic Resonance Imaging ; Brain/pathology/diagnostic imaging/metabolism ; Apolipoproteins E/genetics/metabolism ; Apolipoprotein E4/genetics/metabolism ; Neurites/metabolism/pathology ; }, abstract = {The neuromodulatory subcortical nuclei within the isodendritic core (IdC) are the earliest sites of tauopathy in Alzheimer's disease (AD). They project broadly throughout the brain's white matter. We investigated the relationship between IdC microstructure and whole-brain white matter microstructure to better understand early neuropathological changes in AD. Using multiparametric quantitative magnetic resonance imaging we observed two covariance patterns between IdC and white matter microstructure in 133 cognitively unimpaired older adults (age 67.9 ± 5.3 years) with familial risk for AD. IdC integrity related to 1) whole-brain neurite density, and 2) neurite orientation dispersion in white matter tracts known to be affected early in AD. Pattern 2 was associated with CSF concentration of phosphorylated-tau, indicating AD specificity. Apolipoprotein-E4 carriers expressed both patterns more strongly than non-carriers. IdC microstructure variation is reflected in white matter, particularly in AD-affected tracts, highlighting an early mechanism of pathological development.}, } @article {pmid38747597, year = {2024}, author = {Stindt, KR and McClean, MN}, title = {Tuning interdomain conjugation to enable in situ population modification in yeasts.}, journal = {mSystems}, volume = {9}, number = {6}, pages = {e0005024}, pmid = {38747597}, issn = {2379-5077}, support = {R01 AI154940/AI/NIAID NIH HHS/United States ; P30CA014520//University of Wisconsin Carbone Cancer Center (UWCCC)/ ; P30 CA014520/CA/NCI NIH HHS/United States ; R35 GM128873/GM/NIGMS NIH HHS/United States ; 135AAI9593//Wisconsin Alumni Research Foundation (WARF)/ ; R35GM128873//HHS | NIH | National Institute of General Medical Sciences (NIGMS)/ ; T32 GM130550/GM/NIGMS NIH HHS/United States ; T32GM130550//Molecular Biophysics Training Grant/ ; R01AI154940//HHS | NIH | National Institute of Allergy and Infectious Diseases (NIAID)/ ; }, mesh = {*Saccharomyces cerevisiae/genetics ; *Escherichia coli/genetics/metabolism ; Conjugation, Genetic ; }, abstract = {The ability to modify and control natural and engineered microbiomes is essential for biotechnology and biomedicine. Fungi are critical members of most microbiomes, yet technology for modifying the fungal members of a microbiome has lagged far behind that for bacteria. Interdomain conjugation (IDC) is a promising approach, as DNA transfer from bacterial cells to yeast enables in situ modification. While such genetic transfers have been known to naturally occur in a wide range of eukaryotes and are thought to contribute to their evolution, IDC has been understudied as a technique to control fungal or fungal-bacterial consortia. One major obstacle to the widespread use of IDC is its limited efficiency. In this work, we manipulated metabolic and physical interactions between genetically tractable Escherichia coli and Saccharomyces cerevisiae to control the incidence of IDC. We test the landscape of population interactions between the bacterial donors and yeast recipients to find that bacterial commensalism leads to maximized IDC, both in culture and in mixed colonies. We demonstrate the capacity of cell-to-cell binding via mannoproteins to assist both IDC incidence and bacterial commensalism in culture and model how these tunable controls can predictably yield a range of IDC outcomes. Furthermore, we demonstrate that these controls can be utilized to irreversibly alter a recipient yeast population, by both "rescuing" a poor-growing recipient population and collapsing a stable population via a novel IDC-mediated CRISPR/Cas9 system.IMPORTANCEFungi are important but often unaddressed members of most natural and synthetic microbial communities. This work highlights opportunities for modifying yeast microbiome populations through bacterial conjugation. While conjugation has been recognized for its capacity to deliver engineerable DNA to a range of cells, its dependence on cell contact has limited its efficiency. Here, we find "knobs" to control DNA transfer, by engineering the metabolic dependence between bacterial donors and yeast recipients and by changing their ability to physically adhere to each other. Importantly, we functionally validate these "knobs" by irreversibly altering yeast populations. We use these controls to "rescue" a failing yeast population, demonstrate the capacity of conjugated CRISPR/Cas9 to depress or collapse populations, and show that conjugation can be easily interrupted by disrupting cell-to-cell binding. These results offer building blocks toward in situ mycobiome editing, with significant implications for clinical treatments of fungal pathogens and other fungal system engineering.}, } @article {pmid38734990, year = {2024}, author = {Greenland, NY and Cooperberg, MR and Carroll, PR and Cowan, JE and Simko, JP and Stohr, BA and Chan, E}, title = {Morphologic patterns observed in prostate biopsy cases with discrepant grade group and molecular risk classification.}, journal = {The Prostate}, volume = {84}, number = {11}, pages = {1076-1085}, doi = {10.1002/pros.24725}, pmid = {38734990}, issn = {1097-0045}, mesh = {Humans ; Male ; *Prostatic Neoplasms/pathology/genetics ; *Neoplasm Grading ; *Prostate/pathology ; Biopsy ; Middle Aged ; Aged ; Biomarkers, Tumor/genetics ; Risk Assessment ; Prostatectomy ; }, abstract = {BACKGROUND: Molecular-based risk classifier tests are increasingly being utilized by urologists and radiation oncologists to guide clinical decision making. The Decipher prostate biopsy test is a 22-gene RNA biomarker assay designed to predict likelihood of high-grade disease at radical prostatectomy and risk of metastasis and mortality. The test provides a risk category of low, intermediate, or high. We investigated histologic features of biopsies in which the Grade Group (GG) and Decipher risk category (molecular risk) were discrepant.

METHODS: Our institutional urologic outcomes database was searched for men who underwent prostate biopsies with subsequent Decipher testing from 2016 to 2020. We defined discrepant GG and molecular risk as either GG1-2 with high Decipher risk category or GG ≥ 3 with low Decipher risk category. The biopsy slide on which Decipher testing was performed was re-reviewed for GG and various histologic features, including % Gleason pattern 4, types of Gleason pattern 4 and 5, other "high risk" features (e.g., complex papillary, ductal carcinoma, intraductal carcinoma [IDC]), and other unusual and often "difficult to grade" patterns (e.g., atrophic carcinoma, mucin rupture, pseudohyperplastic carcinoma, collagenous fibroplasia, foamy gland carcinoma, carcinoma with basal cell marker expression, carcinoma with prominent vacuoles, and stromal reaction). Follow-up data was also obtained from the electronic medical record.

RESULTS: Of 178 men who underwent prostate biopsies and had Decipher testing performed, 41 (23%) had discrepant GG and molecular risk. Slides were available for review for 33/41 (80%). Of these 33 patients, 23 (70%) had GG1-2 (GG1 n = 5, GG2 n = 18) with high Decipher risk, and 10 (30%) had GG ≥ 3 with low Decipher risk. Of the 5 GG1 cases, one case was considered GG2 on re-review; no other high risk features were identified but each case showed at least one of the following "difficult to grade" patterns: 3 atrophic carcinoma, 1 collagenous fibroplasia, 1 carcinoma with mucin rupture, and 1 carcinoma with basal cell marker expression. Of the 18 GG2 high Decipher risk cases, 2 showed GG3 on re-review, 5 showed large cribriform and/or other high risk features, and 10 showed a "difficult to grade" pattern. Of the 10 GG ≥ 3 low Decipher risk cases, 5 had known high risk features including 2 with large cribriform, 1 with IDC, and 1 with Gleason pattern 5.

CONCLUSIONS: In GG1-2 high Decipher risk cases, difficult to grade patterns were frequently seen in the absence of other known high risk morphologic features; whether these constitute true high risk cases requires further study. In the GG ≥ 3 low Decipher risk cases, aggressive histologic patterns such as large cribriform and IDC were observed in half (50%) of cases; therefore, the molecular classifier may not capture all high risk histologic patterns.}, } @article {pmid38684889, year = {2024}, author = {Khani, S and Topel, H and Kardinal, R and Tavanez, AR and Josephrajan, A and Larsen, BDM and Gaudry, MJ and Leyendecker, P and Egedal, NM and Güller, AS and Stanic, N and Ruppert, PMM and Gaziano, I and Hansmeier, NR and Schmidt, E and Klemm, P and Vagliano, LM and Stahl, R and Duthie, F and Krause, JH and Bici, A and Engelhard, CA and Gohlke, S and Frommolt, P and Gnad, T and Rada-Iglesias, A and Pradas-Juni, M and Schulz, TJ and Wunderlich, FT and Pfeifer, A and Bartelt, A and Jastroch, M and Wachten, D and Kornfeld, JW}, title = {Cold-induced expression of a truncated adenylyl cyclase 3 acts as rheostat to brown fat function.}, journal = {Nature metabolism}, volume = {6}, number = {6}, pages = {1053-1075}, pmid = {38684889}, issn = {2522-5812}, support = {675014//EC | EC Seventh Framework Programm | FP7 Ideas: European Research Council (FP7-IDEAS-ERC - Specific Programme: "Ideas" Implementing the Seventh Framework Programme of the European Community for Research, Technological Development and Demonstration Activities (2007 to 2013))/ ; PROTEOFIT//EC | EC Seventh Framework Programm | FP7 Ideas: European Research Council (FP7-IDEAS-ERC - Specific Programme: "Ideas" Implementing the Seventh Framework Programme of the European Community for Research, Technological Development and Demonstration Activities (2007 to 2013))/ ; 33444//Novo Nordisk Fonden (Novo Nordisk Foundation)/ ; 28416//Novo Nordisk Fonden (Novo Nordisk Foundation)/ ; A/12/97620//Deutscher Akademischer Austauschdienst (German Academic Exchange Service)/ ; TRR333/1 (450149205)//Deutsche Forschungsgemeinschaft (German Research Foundation)/ ; SFB 1454 (432325352)//Deutsche Forschungsgemeinschaft (German Research Foundation)/ ; TRR83//Deutsche Forschungsgemeinschaft (German Research Foundation)/ ; SPP1926//Deutsche Forschungsgemeinschaft (German Research Foundation)/ ; SPP1726//Deutsche Forschungsgemeinschaft (German Research Foundation)/ ; FOR2743//Deutsche Forschungsgemeinschaft (German Research Foundation)/ ; SFB1123-B10//Deutsche Forschungsgemeinschaft (German Research Foundation)/ ; 676-2021//European Molecular Biology Organization (EMBO)/ ; }, mesh = {*Adenylyl Cyclases/metabolism/genetics ; *Adipose Tissue, Brown/metabolism ; Animals ; Mice ; *Cold Temperature ; Male ; Humans ; Thermogenesis/genetics ; Energy Metabolism ; Cyclic AMP/metabolism ; Mice, Knockout ; }, abstract = {Promoting brown adipose tissue (BAT) activity innovatively targets obesity and metabolic disease. While thermogenic activation of BAT is well understood, the rheostatic regulation of BAT to avoid excessive energy dissipation remains ill-defined. Here, we demonstrate that adenylyl cyclase 3 (AC3) is key for BAT function. We identified a cold-inducible promoter that generates a 5' truncated AC3 mRNA isoform (Adcy3-at), whose expression is driven by a cold-induced, truncated isoform of PPARGC1A (PPARGC1A-AT). Male mice lacking Adcy3-at display increased energy expenditure and are resistant to obesity and ensuing metabolic imbalances. Mouse and human AC3-AT are retained in the endoplasmic reticulum, unable to translocate to the plasma membrane and lack enzymatic activity. AC3-AT interacts with AC3 and sequesters it in the endoplasmic reticulum, reducing the pool of adenylyl cyclases available for G-protein-mediated cAMP synthesis. Thus, AC3-AT acts as a cold-induced rheostat in BAT, limiting adverse consequences of cAMP activity during chronic BAT activation.}, } @article {pmid38678597, year = {2024}, author = {Rostami, B and Kahrizi, S and Ghorbani Yekta, B and Ghadyani, R and Keramatinia, A and Hoseini, SJ and Karima, S and Nikzamir, AR and Mansouri, N and Chen, M and Movafagh, A}, title = {Correlation of IDH1 gene expression error in breast tumor biopsy in patients with invasive ductal carcinoma.}, journal = {Cellular and molecular biology (Noisy-le-Grand, France)}, volume = {70}, number = {4}, pages = {242-247}, doi = {10.14715/cmb/2024.70.4.38}, pmid = {38678597}, issn = {1165-158X}, mesh = {Humans ; *Isocitrate Dehydrogenase/genetics ; Female ; *Breast Neoplasms/genetics/pathology ; Middle Aged ; *Carcinoma, Ductal, Breast/genetics/pathology ; *Gene Expression Regulation, Neoplastic ; Adult ; Biopsy ; RNA, Messenger/genetics/metabolism ; Aged ; }, abstract = {One of the most important cancers in terms of worldwide prevalence is breast tumors, which have been less investigated in correlation with the enzyme Isocitrate Dehydrogenase 1 (IDH1) gene. The aim of this study was that expression of this gene could have significant effects on the progression of metastasis and invasive disease in breast cancer patients. We used the molecular method of RT-PCR with SYBR-Green to analyze breast tumor tissue from patients with metastasis and non-metastasis, the latter confirmed by the pathology department of Shohada-e Tajrish Hospital (serving as a control group). Also, patients population and its relationship with the degree of tumor in the IDH1 gene was investigated. The IDH1 gene has shown high expression in patients with metastatic breast cancer rather than in patients with non-metastatic breast cancer. The metastatic samples were compared with non-metastatic samples for IDH1 mRNA expression. In this research work, 72.5% (29 samples) were up-regulated in comparison to 27.5% of samples (11 samples) that did not exhibit high expression (P=0.000). This study examined the IDH1 gene expression, suggesting that changes in this gene's expression could impact the prognosis of breast cancer. However, further research is needed to draw definitive conclusions.}, } @article {pmid38592540, year = {2024}, author = {Rukhsana, and Supty, AT and Hussain, M and Lee, Y}, title = {STK3 higher expression association with clinical characteristics in intrinsic subtypes of breast cancer invasive ductal carcinoma patients.}, journal = {Breast cancer research and treatment}, volume = {206}, number = {1}, pages = {119-129}, pmid = {38592540}, issn = {1573-7217}, support = {2022R1F1A1069631//National Research Foundation of Korea/ ; }, mesh = {Aged ; Female ; Humans ; Middle Aged ; *Biomarkers, Tumor/genetics ; *Breast Neoplasms/genetics/pathology/mortality/metabolism ; *Carcinoma, Ductal, Breast/genetics/pathology/mortality/metabolism ; Gene Expression Profiling ; *Gene Expression Regulation, Neoplastic ; Kaplan-Meier Estimate ; Neoplasm Staging ; Prognosis ; Protein Serine-Threonine Kinases/genetics/metabolism ; *Serine-Threonine Kinase 3/analysis/genetics ; }, abstract = {PURPOSE: STK3 has a central role in maintaining cell homeostasis, proliferation, growth, and apoptosis. Previously, we investigated the functional link between STK3/MST2, and estrogen receptor in MCF-7 breast cancer cells. To expand the investigation, this study evaluated STK3's higher expression and associated genes in breast cancer intrinsic subtypes using publicly available data.

METHODS: The relationship between clinical pathologic features and STK3 high expression was analyzed using descriptive and multivariate analysis.

RESULTS: Increased STK3 expression in breast cancer was significantly associated with higher pathological cancer stages, and a different expression level was observed in the intrinsic subtypes of breast cancer. Kaplan-Meier analysis showed that breast cancer with high STK3 had a lower survival rate in IDC patients than that with low STK3 expression (p < 0.05). The multivariate analysis unveiled a strong correlation between STK3 expression and the survival rate among IDC patients, demonstrating hazard ratios for lower expression. In the TCGA dataset, the hazard ratio was 0.56 (95% CI 0.34-0.94, p = 0.029) for patients deceased with tumor, and 0.62 (95% CI 0.42-0.92, p = 0.017) for all deceased patients. Additionally, in the METABRIC dataset, the hazard ratio was 0.76 (95% CI 0.64-0.91, p = 0.003) for those deceased with tumor. From GSEA outcomes 7 gene sets were selected based on statistical significance (FDR < 0.25 and p < 0.05). Weighted Sum model (WSM) derived top 5% genes also have higher expression in basal and lower in luminal A in association with STK3.

CONCLUSION: By introducing a novel bioinformatics approach that combines GSEA and WSM, the study successfully identified the top 5% of genes associated with higher expression of STK3.}, } @article {pmid38578876, year = {2024}, author = {Rodriguez, GF and Shah, A and Maderal, AD}, title = {Telangiectasias induced by combination tucatinib and ado-trastuzumab emtansine in a patient with metastatic breast cancer.}, journal = {Breast disease}, volume = {43}, number = {1}, pages = {61-64}, pmid = {38578876}, issn = {1558-1551}, mesh = {Female ; Humans ; Aged ; Ado-Trastuzumab Emtansine/therapeutic use ; *Breast Neoplasms/pathology ; Trastuzumab/adverse effects ; Quinazolines/therapeutic use ; Receptor, ErbB-2/genetics/metabolism ; Antineoplastic Combined Chemotherapy Protocols/adverse effects ; *Oxazoles ; *Pyridines ; }, abstract = {BACKGROUND: Tucatinib is a tyrosine kinase inhibitor currently used in salvage therapy for human epidermal growth factor receptor 2 (HER2)-positive breast and colorectal cancer. The use of tucatinib alone or in combination with ado-trastuzumab emtansine (T-DM1) in the treatment of advanced HER2-positive cancers is rapidly expanding.

OBJECTIVE/METHODS: We report the case of a 66-year-old female who presented to the dermatology clinic with a one-year history of widespread telangiectasias that began after initiation of combination chemotherapy with tucatinib and T-DM1 for metastatic HER2-positive invasive ductal carcinoma.

RESULTS: The patient's lesions regressed upon cessation of combination therapy and reappeared in the setting of tucatinib re-initiation, with gradual improvement over the following four months following electrocautery to the affected regions.

CONCLUSIONS: We postulate that telangiectasias may be a previously unreported dermatologic side effect of combination treatment with tucatinib and T-DM1. Electrocautery is a safe and effective procedure to reduce the appearance of telangiectasias and improve patient satisfaction during chemotherapy.}, } @article {pmid38570490, year = {2024}, author = {Wang, J and Li, B and Luo, M and Huang, J and Zhang, K and Zheng, S and Zhang, S and Zhou, J}, title = {Progression from ductal carcinoma in situ to invasive breast cancer: molecular features and clinical significance.}, journal = {Signal transduction and targeted therapy}, volume = {9}, number = {1}, pages = {83}, pmid = {38570490}, issn = {2059-3635}, support = {82172344//National Natural Science Foundation of China (National Science Foundation of China)/ ; LY21H160039//Natural Science Foundation of Zhejiang Province (Zhejiang Provincial Natural Science Foundation)/ ; LGF21H030010//Natural Science Foundation of Zhejiang Province (Zhejiang Provincial Natural Science Foundation)/ ; }, mesh = {Humans ; Female ; *Carcinoma, Intraductal, Noninfiltrating/genetics/metabolism/pathology ; *Breast Neoplasms/pathology ; Clinical Relevance ; Artificial Intelligence ; Gene Expression Profiling ; Tumor Microenvironment/genetics ; }, abstract = {Ductal carcinoma in situ (DCIS) represents pre-invasive breast carcinoma. In untreated cases, 25-60% DCIS progress to invasive ductal carcinoma (IDC). The challenge lies in distinguishing between non-progressive and progressive DCIS, often resulting in over- or under-treatment in many cases. With increasing screen-detected DCIS in these years, the nature of DCIS has aroused worldwide attention. A deeper understanding of the biological nature of DCIS and the molecular journey of the DCIS-IDC transition is crucial for more effective clinical management. Here, we reviewed the key signaling pathways in breast cancer that may contribute to DCIS initiation and progression. We also explored the molecular features of DCIS and IDC, shedding light on the progression of DCIS through both inherent changes within tumor cells and alterations in the tumor microenvironment. In addition, valuable research tools utilized in studying DCIS including preclinical models and newer advanced technologies such as single-cell sequencing, spatial transcriptomics and artificial intelligence, have been systematically summarized. Further, we thoroughly discussed the clinical advancements in DCIS and IDC, including prognostic biomarkers and clinical managements, with the aim of facilitating more personalized treatment strategies in the future. Research on DCIS has already yielded significant insights into breast carcinogenesis and will continue to pave the way for practical clinical applications.}, } @article {pmid38554305, year = {2024}, author = {Dogan, I and Khanmammadov, N and Ozkurt, S and Aydiner, A and Saip, P}, title = {Outcomes of the patients with metastatic male breast cancer.}, journal = {Journal of cancer research and therapeutics}, volume = {20}, number = {1}, pages = {98-102}, doi = {10.4103/jcrt.jcrt_1829_22}, pmid = {38554305}, issn = {1998-4138}, mesh = {Humans ; Male ; Adult ; Middle Aged ; Aged ; Aged, 80 and over ; *Breast Neoplasms, Male/drug therapy ; Retrospective Studies ; Receptor, ErbB-2 ; Disease-Free Survival ; *Breast Neoplasms/pathology ; Trastuzumab/therapeutic use ; Prognosis ; *Brain Neoplasms/drug therapy/secondary ; Kaplan-Meier Estimate ; }, abstract = {BACKGROUND: The goal of this research is to investigate the clinical characteristics and prognosis of men with metastatic breast cancer (mMBC).

METHODS: A retrospective analysis of the data of 28 patients was conducted. Kaplan-Meier and Cox regression analyses were used to assess overall survival (OS) and prognostic variables.

RESULTS: At the time of diagnosis, the median age was 57 years (range 26-86). The most prevalent pathological subtype was invasive ductal carcinoma (92.6%). HER2 positivity was 21.6% in patients, with estrogen and progesterone receptor positivity at 96.4% and 71.4%, respectively. Bone-75%, lung-39.3%, brain-21.4%, and adrenal gland-10.7% were the most prevalent metastatic sites. Trastuzumab-based chemotherapy was given to six patients. During the study period, 14 patients (or half) died. All patients had a median OS of 42.6 months (range: 21.6-63.7). The OS rates after 1, 3, and 5 years were 95.7%, 54.2%, and 36.6%, respectively. The number of metastatic locations (P = 0.045), brain metastasis (P = 0.033), and a history of regular alcohol intake (P = 0.008) were all shown to be statistically significant factors affecting OS in univariate analysis. However, multivariate analysis did not support the findings. In addition, we discovered that trastuzumab-based therapy and de-novo metastatic disease had no effect on OS for mMBC.

CONCLUSIONS: The data on mMBC is restricted because of its rarity. The prognosis of mMBC was shown to be poor in this investigation. Despite the small number of patients, we discovered that in univariate analysis, having brain metastases, the number of metastatic locations, and a history of alcohol intake may be prognostic factors.}, } @article {pmid38451627, year = {2024}, author = {Saeed, U and Uppal, R and Khan, AA and Uppal, MR and Piracha, ZZ and Uppal, SR}, title = {Analytical assessment of clinical sensitivity and specificities of pharmaceutical rapid SARS-CoV-2 detection nasopharyngeal swab testing kits in Pakistan.}, journal = {Brazilian journal of biology = Revista brasleira de biologia}, volume = {84}, number = {}, pages = {e265550}, doi = {10.1590/1519-6984.265550}, pmid = {38451627}, issn = {1678-4375}, mesh = {Humans ; *COVID-19/diagnosis ; Cross-Sectional Studies ; Nasopharynx/virology ; Pakistan ; Pandemics ; *SARS-CoV-2/genetics ; *Reagent Kits, Diagnostic ; Sensitivity and Specificity ; }, abstract = {Despite of the global unity against COVID-19 pandemic, the threat of SARS-CoV-2 variants on the lives of human being is still not over. SARS-CoV-2 pandemic has urged the need of rapid viral detection at earliest. To cope with gradually expanding scenario of SARS-CoV-2, accurate diagnosis is extremely crucial factor which should be noticed by international health organizations. Limited research followed by sporadic marketing of SARS-CoV-2 rapid pharmaceutical detection kits raises critical questions against quality assurance and quality control measures. Herein we aimed to interrogate effectivity and specificity analysis of SARS-CoV-2 pharmaceutical rapid detection kits (nasopharyngeal swab based) using conventional gold standard triple target real-time polymerase chain reaction (USFDA approved). A cross-sectional study was conducted over 1500 suspected SARS-CoV-2 patients. 100 real time-PCR confirmed patients were evaluated for pharmaceutical RDT kits based upon nasopharyngeal swab based kits. The SARS-CoV-2 nasopharyngeal swab based rapid diagnostic kit (NSP RDTs) analysis showed 78% reactivity. Among real time PCR confirmed negative subjects, 49.3% represented false positivity. The positive predictive analysis revealed 67.82%, while negative predictive values were 64.40%. The NSP RDTs showed limited sensitivities and specificities as compared to gold standard real time PCR. Valid and authentic detection of SARS-CoV-2 is deemed necessary for accurate COVID-19 surveillance across the globe. Current study highlights the potential consequences of inadequate detection of SARS-CoV-2 and emerging novel mutants, compromising vaccine preventable diseases. Current study emphasizes need to wake higher authorities including strategic organizations for designing adequate measures to prevent future SARS-CoV-2 epidemics.}, } @article {pmid38417222, year = {2024}, author = {Hu, J and Chen, X and Sun, F and Liu, L and Liu, L and Yang, Z and Zhang, H and Yu, Z and Zhao, R and Wang, Y and Liu, H and Yang, X and Sun, F and Han, B}, title = {Identification of recurrent BRAF non-V600 mutations in intraductal carcinoma of the prostate in Chinese populations.}, journal = {Neoplasia (New York, N.Y.)}, volume = {50}, number = {}, pages = {100983}, pmid = {38417222}, issn = {1476-5586}, mesh = {Humans ; Male ; *Carcinoma, Intraductal, Noninfiltrating/genetics/pathology ; China ; Mutation ; Prostate/pathology ; *Prostatic Neoplasms/genetics/pathology ; *Proto-Oncogene Proteins B-raf/genetics ; }, abstract = {While BRAF alterations have been established as a driver in various solid malignancies, the characterization of BRAF alterations in prostate cancer (PCa) has not been thoroughly interrogated. By bioinformatics analysis, we first found that BRAF alterations were associated with advanced PCa and exhibited mutually exclusive pattern with ERG alteration across multiple cohorts. Of the most interest, recurrent non-V600 BRAF mutations were found in 3 of 21 (14.3 %) PCa patients demonstrating IDC-P morphology. Furthermore, experimental overexpression of BRAF[K601E] and BRAF[L597R] exhibited emergence of oncogenic phenotypes with intensified MAPK signaling in vitro, which could be targeted by MEK inhibitors. Comparison of the incidence of BRAF alterations in IDC-P between western and Chinese ancestry revealed an increased prevalence in the Chinese population. The BRAF mutation may represent important genetic alteration in a subset of IDC-P, highlighting the role of MAPK signaling pathway in this subtype of PCa. To the best of knowledge, this is the first description of non-V600 BRAF mutation in setting of IDC-P, which may in part explain the aggressive phenotype seen in IDC-P and could also bring more treatment options for PCa patients with IDC-P harboring such mutations.}, } @article {pmid38409747, year = {2024}, author = {Ruan, GJ and Zanwar, S and Ravindran, A and Schram, S and Abeykoon, JP and Hazim, A and Young, JR and Shah, MV and Bennani, NN and Jiang, L and Morlote, D and Rech, KL and Goyal, G and Go, RS and , }, title = {Clinical characteristics, molecular aberrations, treatments, and outcomes of malignant histiocytosis.}, journal = {American journal of hematology}, volume = {99}, number = {5}, pages = {871-879}, pmid = {38409747}, issn = {1096-8652}, support = {P50 CA097274/CA/NCI NIH HHS/United States ; R21 CA097422/CA/NCI NIH HHS/United States ; }, mesh = {Humans ; Child, Preschool ; Child ; Adolescent ; Young Adult ; Adult ; Middle Aged ; Aged ; Aged, 80 and over ; *Histiocytic Sarcoma/genetics/therapy/pathology ; Macrophages/pathology ; Bone Marrow/pathology ; Prognosis ; Liver/pathology ; }, abstract = {Malignant histiocytosis (MH) is an extremely rare neoplasm of the macrophage-dendritic cell lineage. We report the clinical characteristics, molecular aberrations, treatments, and outcomes of patients with MH seen at two referral centers from January 2000 to May 2023. We identified 43 patients with MH, of which 26 had histiocytic sarcoma (MH-H), 9 interdigitating dendritic cell sarcoma (MH-IDC), and 8 Langerhans cell sarcoma (MH-LC). The median age at diagnosis was 61 years (range, 3-83). Thirty-three patients (77%) had multifocal disease, while 10 had unifocal involvement. Tumor specimens from 22 patients (51%) underwent targeted next generation sequencing, and 19 of 22 (86%) had at least one pathogenic mutation, including mutations in MAPK pathway genes (73%). The median overall survival (OS) among the entire cohort was 16 months (95% CI: 8-50). The outcomes of those with multifocal disease were significantly shorter than their unifocal counterpart: median OS of 10 months versus 50 months (p = .07). Patients with risk organ involvement (bone marrow, spleen, or liver) had significantly inferior outcomes. Chemotherapy and surgery were the most common first-line treatments for multifocal and unifocal disease, respectively. While the outcome for patients with multifocal disease was poor, there was a subset of patients who had durable responses to treatment. Our study highlights that MH has heterogeneous clinical presentation, frequent oncogenic mutations, and prognosis, which is strongly tied to disease extent and type of organ involvement.}, } @article {pmid38379333, year = {2024}, author = {Zhu, S and Xu, N and Zeng, H}, title = {Molecular complexity of intraductal carcinoma of the prostate.}, journal = {Cancer medicine}, volume = {13}, number = {2}, pages = {e6939}, pmid = {38379333}, issn = {2045-7634}, support = {NSFC 82203110//National Natural Science Foundation of China/ ; 82172785//National Natural Science Foundation of China/ ; 81974398//National Natural Science Foundation of China/ ; 2022-I2M-C&T-B-098//Clinical and Translational Medicine Research Project, Chinese Academy of Medical Sciences/ ; 2021YFS0119//Science and Technology Support Program of Sichuan Province/ ; X-J-2020-016//Bethune Foundation, Oncology Basic Research Program/ ; ZYJC21020//West China Hospital, Sichuan University/ ; ZYGD22004//West China Hospital, Sichuan University/ ; mnzl202002//Bethune Foundation, Urological Oncology Special Research Fund/ ; mnzl202007//Bethune Foundation, Urological Oncology Special Research Fund/ ; }, mesh = {Male ; Humans ; *Carcinoma, Intraductal, Noninfiltrating/pathology ; Prostate/pathology ; *Prostatic Neoplasms/diagnosis/genetics/therapy ; Prognosis ; }, abstract = {Intraductal carcinoma of the prostate (IDC-P) is an aggressive subtype of prostate cancer characterized by the growth of tumor cells within the prostate ducts. It is often found alongside invasive carcinoma and is associated with poor prognosis. Understanding the molecular mechanisms driving IDC-P is crucial for improved diagnosis, prognosis, and treatment strategies. This review summarizes the molecular characteristics of IDC-P and their prognostic indications, comparing them to conventional prostate acinar adenocarcinoma, to gain insights into its unique behavior and identify potential therapeutic targets.}, } @article {pmid38379091, year = {2024}, author = {Bufman, H and Faermann, R and Halshtok-Neiman, O and Shalmon, A and Gotlieb, M and Samoocha, D and Yagil, Y and Feldman, DM and Friedman, E and Sklair-Levy, M}, title = {Breast cancer diagnosed after age 70 years in Israeli BRCA1/BRCA2 pathogenic sequence variant carriers: a single institution experience.}, journal = {Breast cancer research and treatment}, volume = {205}, number = {2}, pages = {281-285}, pmid = {38379091}, issn = {1573-7217}, mesh = {Humans ; Female ; *Breast Neoplasms/genetics/pathology/diagnosis/epidemiology ; Aged ; Israel/epidemiology ; Aged, 80 and over ; *BRCA1 Protein/genetics ; *BRCA2 Protein/genetics ; Heterozygote ; Genetic Predisposition to Disease ; Early Detection of Cancer/methods ; Mutation ; }, abstract = {PURPOSE: A semi-annual surveillance scheme from age 25 to 30 years is offered to BRCA1/BRCA2 pathogenic sequence variants (PSVs) carriers for early detection of breast cancer (BC). There is a paucity of data on the yield of adhering to this scheme beyond 70 years of age.

METHODS: Female BRCA1/BRCA2 PSV carriers followed at the Meirav high-risk clinic, Sheba Medical center, Israel were eligible. Type and frequencies if use of Imaging modalities, breast biopsies and histological outcomes for participants after age 70 years were retrieved and analyzed.

RESULTS: Overall, the study encompassed 88 consenting participants (46 BRCA1 carriers) mean age ± SD 73.7 ± 3.3 years (range 70-90 years), followed for an average of 3.8 years (range 1-11 years). Ten carriers (11.3%) were diagnosed with BC after age 70 years (mean age at diagnosis 72 ± 2 years) and an additional case was diagnosed with breast lymphoma. The imaging modality that has led to most diagnoses was MRI (8/11 cases). Eight of these ten cases were previously diagnosed with BC prior to age 70 and in six, BC past 70 years was in the contralateral breast. The lesions size averaged 1.29 ± 0.75 cm, with IDC and DCIS diagnosed in five cases each, and none had lymph node involvement.

CONCLUSION: In ~10% of BRCA1/BRCA2 PSV carriers BC is diagnosed by breast imaging after age 70 years. If these results are validated in a larger study, the guidelines for the maximum age for BC surveillance in high risk women should be revisited and set at 75 years.}, } @article {pmid38376291, year = {2023}, author = {Piracha, ZZ and Saeed, U}, title = {Leucine-rich repeats and immunoglobulin-like domains protein 1 (LRIG1) is downregulated in Invasive ductal carcinoma and potential prognostic marker of breast cancer.}, journal = {Journal of cancer research and therapeutics}, volume = {19}, number = {7}, pages = {1870-1879}, pmid = {38376291}, issn = {1998-4138}, mesh = {Female ; Humans ; beta Catenin ; *Breast Neoplasms/genetics ; *Carcinoma, Ductal ; *Fibroadenoma/genetics ; Glycogen Synthase Kinase 3 ; Immunoglobulin Domains ; Leucine ; *Membrane Glycoproteins/genetics ; Prognosis ; Proto-Oncogene Proteins c-akt ; }, abstract = {BACKGROUND: LRIG1 belongs to the family of transmembrane proteins containing leucine-rich repeats. LRIGs are considered as tumor suppressors as they negatively regulate receptor tyrosine kinases. The role of LRIG1 as an EGFR regulator makes it an important marker to be studied in various epithelial-derived cancers.

METHODS: LRIG1 expression was determined in Erbb2 + cell lines by western blotting, and cell motility was examined by cell migration assay. The AKT/GSK3-β/β-catenin pathway was determined in the presence of LRIG1 and Erbb2 by using western blotting.

RESULTS: So far, no study has reported the expression of LRIG1 in benign forms of tumor such as fibroadenoma. The current study aims to analyze LRIG1 expression in fibroadenoma and invasive ductal carcinoma (IDC) tissues. In this study, we compared the LRIG1 expression with different clinicopathological parameters of patients having IDC or fibroadenoma. LRIG1 expression was low in Erbb2+ cell lines, and more cell motility was observed. The AKT/GSK3-β/β-catenin pathway was activated when LRIG1 was downregulated; consequently, Erbb2 was upregulated. Our results indicated that LRIG1 expression can be significantly correlated with age, Nottingham index, and Her2/neu status of cancer. The expression of LRIG1 in IDC and fibroadenoma were found to be significantly different.

CONCLUSION: The fibroadenoma tissue sections were found to express LRIG1 more intensely as compared to the IDC sections, which are in line with the studies reporting reduced copy number of the gene either due to gene deletion or transcriptional inhibition. This further supports that the downregulation of LRIG1 may lead to malignant tumor acting as a tumor suppressor.}, } @article {pmid38369589, year = {2024}, author = {Liu, XS and Chen, YX and Wan, HB and Wang, YL and Wang, YY and Gao, Y and Wu, LB and Pei, ZJ}, title = {TRIP6 a potential diagnostic marker for colorectal cancer with glycolysis and immune infiltration association.}, journal = {Scientific reports}, volume = {14}, number = {1}, pages = {4042}, pmid = {38369589}, issn = {2045-2322}, mesh = {Humans ; *Adaptor Proteins, Signal Transducing/genetics/metabolism ; *Colorectal Neoplasms/diagnosis/genetics/pathology ; Glycolysis ; *LIM Domain Proteins/genetics/metabolism ; Proteasome Endopeptidase Complex/metabolism ; *Transcription Factors/genetics/metabolism ; }, abstract = {Thyroid hormone receptor interactor 6 (TRIP6) it is an adaptor protein belonging to the zyxin family of LIM proteins, participating in signaling events through interactions with various molecules. Despite this, TRIP6's role in colorectal cancer (CRC), particularly its correlation with glucose metabolism and immune cell infiltration, remains unclear. Through the TCGA and GEO databases, we obtained RNA sequencing data to facilitate our in-depth study and analysis of TRIP6 expression. To investigate the prognostic value of TRIP6 in CRC, we also used univariate Cox regression analysis. In addition, this study also covered a series of analyses, including clinicopathological analysis, functional enrichment analysis, glycolysis correlation analysis, immunoinfiltration analysis, immune checkpoint analysis, and angiogenesis correlation analysis, to gain a comprehensive and in-depth understanding of this biological phenomenon. It has been found that TRIP6 expression is significantly upregulated in CRC and correlates with the stage of the disease. Its overexpression portends a worse survival time. Functional enrichment analysis reveals that TRIP6 is associated with focal adhesion and glycolysis. Mechanistically, TRIP6 appears to exert its tumorigenic effect by regulating the glycolysis-related gene GPI. A higher level of expression of TRIP6 is associated with an increase in the number of iDC immune cells and a decrease in the number of Th1 immune cells. Also, TRIP6 may promote angiogenesis in tumor cells by promoting the expression of JAG2. Our study uncovers the upregulation of TRIP6 in CRC, illuminating its prognostic and diagnostic value within this context. Furthermore, we examine the relationship between TRIP6 expression levels, glycolysis, angiogenesis and immune cell infiltration. This underscores its potential as a biomarker for CRC treatment and as a therapeutic target.}, } @article {pmid38343885, year = {2023}, author = {Santos, MM and Baerga, CG and Lamsal, S and Engel, C and Ozdemir, S}, title = {Breast cancer in a Hispanic patient with Werner syndrome.}, journal = {Journal of radiology case reports}, volume = {17}, number = {10}, pages = {21-31}, pmid = {38343885}, issn = {1943-0922}, mesh = {Adult ; Female ; Humans ; *Breast Neoplasms/diagnostic imaging/genetics ; Hispanic or Latino ; Mastectomy ; Mutation ; *Werner Syndrome/complications/diagnostic imaging/genetics ; Werner Syndrome Helicase/genetics ; }, abstract = {Werner Syndrome is a rare autosomal recessive condition characterized by premature aging and increased risk of malignancies due to gene mutations associated with DNA stability. We present the first case report of a 29-year-old Hispanic female with WS diagnosed with breast cancer. Diagnostic mammography and ultrasound, breast MRI and PET examinations revealed two lesions biopsy proven as invasive ductal carcinoma. The patient underwent neoadjuvant chemotherapy and radical mastectomy. Recurrence occurred 10 months postoperatively with molecular analysis demonstrating TP53 mutations. The multifactorial assessment of breast cancer in this case study is crucial towards optimizing screening, diagnosis and management of this disease in patients with WS.}, } @article {pmid38326829, year = {2024}, author = {Verma, VK and Beevi, SS and Nair, RA and Kumar, A and Kiran, R and Alexander, LE and Dinesh Kumar, L}, title = {MicroRNA signatures differentiate types, grades, and stages of breast invasive ductal carcinoma (IDC): miRNA-target interacting signaling pathways.}, journal = {Cell communication and signaling : CCS}, volume = {22}, number = {1}, pages = {100}, pmid = {38326829}, issn = {1478-811X}, mesh = {Animals ; Female ; Mice ; Biomarkers ; Biomarkers, Tumor/genetics ; *Breast Neoplasms/pathology ; *Carcinoma, Ductal/genetics ; Gene Expression Profiling ; Gene Expression Regulation, Neoplastic ; *MicroRNAs/genetics/metabolism ; Signal Transduction ; }, abstract = {BACKGROUND: Invasive ductal carcinoma (IDC) is the most common form of breast cancer which accounts for 85% of all breast cancer diagnoses. Non-invasive and early stages have a better prognosis than late-stage invasive cancer that has spread to lymph nodes. The involvement of microRNAs (miRNAs) in the initiation and progression of breast cancer holds great promise for the development of molecular tools for early diagnosis and prognosis. Therefore, developing a cost effective, quick and robust early detection protocol using miRNAs for breast cancer diagnosis is an imminent need that could strengthen the health care system to tackle this disease around the world.

METHODS: We have analyzed putative miRNAs signatures in 100 breast cancer samples using two independent high fidelity array systems. Unique and common miRNA signatures from both array systems were validated using stringent double-blind individual TaqMan assays and their expression pattern was confirmed with tissue microarrays and northern analysis. In silico analysis were carried out to find miRNA targets and were validated with q-PCR and immunoblotting. In addition, functional validation using antibody arrays was also carried out to confirm the oncotargets and their networking in different pathways. Similar profiling was carried out in Brca2/p53 double knock out mice models using rodent miRNA microarrays that revealed common signatures with human arrays which could be used for future in vivo functional validation.

RESULTS: Expression profile revealed 85% downregulated and 15% upregulated microRNAs in the patient samples of IDC. Among them, 439 miRNAs were associated with breast cancer, out of which 107 miRNAs qualified to be potential biomarkers for the stratification of different types, grades and stages of IDC after stringent validation. Functional validation of their putative targets revealed extensive miRNA network in different oncogenic pathways thus contributing to epithelial-mesenchymal transition (EMT) and cellular plasticity.

CONCLUSION: This study revealed potential biomarkers for the robust classification as well as rapid, cost effective and early detection of IDC of breast cancer. It not only confirmed the role of these miRNAs in cancer development but also revealed the oncogenic pathways involved in different progressive grades and stages thus suggesting a role in EMT and cellular plasticity during breast tumorigenesis per se and IDC in particular. Thus, our findings have provided newer insights into the miRNA signatures for the classification and early detection of IDC.}, } @article {pmid38308423, year = {2024}, author = {Agaoglu, NB and Unal, B and Hayes, CP and Walker, M and Ng, OH and Doganay, L and Can, ND and Rana, HQ and Ghazani, AA}, title = {Genomic disparity impacts variant classification of cancer susceptibility genes in Turkish breast cancer patients.}, journal = {Cancer medicine}, volume = {13}, number = {3}, pages = {e6852}, pmid = {38308423}, issn = {2045-7634}, support = {Number YNY2016/144//The Istanbul Development Agency (ISTKA)/ ; }, mesh = {Humans ; Female ; *Breast Neoplasms/epidemiology/genetics ; *Carcinoma, Lobular ; Genomics ; *Carcinoma, Ductal, Breast ; Oncogenes ; }, abstract = {OBJECTIVE: Turkish genome is underrepresented in large genomic databases. This study aims to evaluate the effect of allele frequency in the Turkish population in determining the clinical utility of germline findings in breast cancer, including invasive lobular carcinoma (ILC), mixed invasive ductal and lobular carcinoma (IDC-L), and ductal carcinoma (DC).

METHODS: Two clinic-based cohorts from the Umraniye Research and Training Hospital (URTH) were used in this study: a cohort consisting of 132 women with breast cancer and a non-cancer cohort consisting of 492 participants. The evaluation of the germline landscape was performed by analysis of 27 cancer genes. The frequency and type of variants in the breast cancer cohort were compared to those in the non-cancer cohort to investigate the effect of population genetics. The variant allele frequencies in Turkish Variome and gnomAD were statistically evaluated.

RESULTS: The genetic analysis identified 121 variants in the breast cancer cohort (actionable = 32, VUS = 89) and 223 variants in the non-cancer cohort (actionable = 25, VUS = 188). The occurrence of 21 variants in both suggested a possible genetic population effect. Evaluation of allele frequency of 121 variants from the breast cancer cohort showed 22% had a significantly higher value in Turkish Variome compared to gnomAD (p < 0.0001, 95% CI) with a mean difference of 60 times (ranging from 1.37-354.4). After adjusting for variant allele frequency using the ancestry-appropriate database, 6.7% (5/75) of VUS was reclassified to likely benign.

CONCLUSION: To our knowledge, this is the first study of population genetic effects in breast cancer subtypes in Turkish women. Our findings underscore the need for a large genomic database representing Turkish population-specific variants. It further highlights the significance of the ancestry-appropriate population database for accurate variant assessment in clinical settings.}, } @article {pmid38307851, year = {2024}, author = {Coria, LM and Rodriguez, JM and Demaria, A and Bruno, LA and Medrano, MR and Castro, CP and Castro, EF and Del Priore, SA and Hernando Insua, AC and Kaufmann, IG and Saposnik, LM and Stone, WB and Prado, L and Notaro, US and Amweg, AN and Diaz, PU and Avaro, M and Ortega, H and Ceballos, A and Krum, V and Zurvarra, FM and Sidabra, JE and Drehe, I and Baqué, JA and Li Causi, M and De Nichilo, AV and Payes, CJ and Southard, T and Vega, JC and Auguste, AJ and Álvarez, DE and Flo, JM and Pasquevich, KA and Cassataro, J}, title = {A Gamma-adapted subunit vaccine induces broadly neutralizing antibodies against SARS-CoV-2 variants and protects mice from infection.}, journal = {Nature communications}, volume = {15}, number = {1}, pages = {997}, pmid = {38307851}, issn = {2041-1723}, support = {R01 AI153433/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; Mice ; Humans ; *SARS-CoV-2 ; Broadly Neutralizing Antibodies ; COVID-19 Vaccines ; *COVID-19/prevention & control ; Vaccines, Subunit ; Adjuvants, Immunologic ; Epitopes, B-Lymphocyte ; Antibodies, Viral ; Antibodies, Neutralizing ; Spike Glycoprotein, Coronavirus/genetics ; }, abstract = {In the context of continuous emergence of SARS-CoV-2 variants of concern (VOCs), one strategy to prevent the severe outcomes of COVID-19 is developing safe and effective broad-spectrum vaccines. Here, we present preclinical studies of a RBD vaccine derived from the Gamma SARS-CoV-2 variant adjuvanted with Alum. The Gamma-adapted RBD vaccine is more immunogenic than the Ancestral RBD vaccine in terms of inducing broader neutralizing antibodies. The Gamma RBD presents more immunogenic B-cell restricted epitopes and induces a higher proportion of specific-B cells and plasmablasts than the Ancestral RBD version. The Gamma-adapted vaccine induces antigen specific T cell immune responses and confers protection against Ancestral and Omicron BA.5 SARS-CoV-2 challenge in mice. Moreover, the Gamma RBD vaccine induces higher and broader neutralizing antibody activity than homologous booster vaccination in mice previously primed with different SARS-CoV-2 vaccine platforms. Our study indicates that the adjuvanted Gamma RBD vaccine is highly immunogenic and a broad-spectrum vaccine candidate.}, } @article {pmid38303308, year = {2023}, author = {Aoyagi, T and Namura, M and Sakata, H and Tamanuki, T and Iwai, M and Iwata, K and Takahashi, H and Matsuzaki, H}, title = {[A Case of Recurrent Breast Cancer That Was BRCA1 Pathogenic Variant-Positive Successfully Treated with PARP Inhibitor].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {50}, number = {13}, pages = {1462-1464}, pmid = {38303308}, issn = {0385-0684}, mesh = {Female ; Humans ; Aged ; Middle Aged ; *Breast Neoplasms/drug therapy/genetics/surgery ; Poly(ADP-ribose) Polymerase Inhibitors/therapeutic use ; Mastectomy ; Neoplasm Recurrence, Local/drug therapy/surgery ; *Antineoplastic Agents/therapeutic use ; BRCA1 Protein/genetics ; }, abstract = {The patient was a 51-year-old woman at the time of diagnosis of left breast cancer. She underwent a mastectomy and axillary dissection. Pathological findings were invasive ductal carcinoma of the breast, tumor diameter 25 mm, and metastasis in 2 of 16 removed axillary lymph nodes. The subtype was triple negative. Postoperative chemotherapy was administered, and the patient was followed by follow-up imaging. At the age of 63 years, ultrasonography showed local recurrence, and local mass excision was performed. Genetic abnormalities were suspected since she had a family history of breast cancer, and it was a recurrent case. After genetic counseling, she underwent genetic testing, which revealed a BRCA1 pathogenic variant, so we initiated imaging surveillance. At age 65, a chest CT scan was performed due to respiratory symptoms, and she was diagnosed with multiple lung metastases. Respiratory symptoms improved at the examination 1 month after administration of Poly ADP ribose polymerase(PARP)inhibitor, and the metastatic masses shrank at the CT scan 3 months later. She continues to maintain CR and has no respiratory symptoms at present.}, } @article {pmid38285770, year = {2024}, author = {Younas, H and Shahid, M and Khan, Z and Fatima, K and Tasadduq, R}, title = {Investigating the association of Angiotensin II Type I Receptor A1166C Polymorphism with Breast Cancer Risk in the Pakistani Population.}, journal = {Asian Pacific journal of cancer prevention : APJCP}, volume = {25}, number = {1}, pages = {79-85}, pmid = {38285770}, issn = {2476-762X}, mesh = {Humans ; Female ; *Breast Neoplasms/epidemiology/genetics ; Angiotensin II/genetics ; Pakistan/epidemiology ; Polymorphism, Genetic ; Renin-Angiotensin System/genetics ; Genotype ; Genetic Predisposition to Disease ; }, abstract = {The polymorphisms of the Renin-Angiotensin System are related to many disorders like diabetes, cardiovascular disease, and different types of cancer. Among all the polymorphisms related to AGTR1, A1166C has been associated with several disorders, including cardiovascular diseases and breast cancer. This study was conducted to discover the association of AGTR1 polymorphism (A1166C) Renin-Angiotensin and its effect on the development and progression of breast cancer in the Pakistani population. One hundred forty participants, including seventy diagnosed breast cancer patients and seventy healthy individuals, were included in this study and genotyped with an allele-specific polymerase chain reaction. The most frequent genotype in healthy participants and breast cancer patients was CC. An insignificant (p value>0.05) risk of breast cancer was found with A1166C polymorphism in codominant (CC vs. AA OR=1.200 [0.256-5.631] and AC vs. AA 0.941 [OR=0.223-3.976]), dominant (OR=1.00 [0.240-4.167]), recessive (OR=1.230 [0.593-2.552]) and additive models (OR=1.028 [0.533-1.983]) of general population genotypes. Nonetheless, when the AA genotype was considered a reference group, a significant association was found between AC and CC genotypes and invasive ductal and ductal carcinoma development in breast cancer patients. In conclusion, this study demonstrated no significant association between AGTR1 (A1166C) polymorphism and breast cancer risk.}, } @article {pmid38281565, year = {2024}, author = {Dimitrov, G and Shousha, S and Troianova, P}, title = {CD10 expression as a potential predictor of pathological complete response in ER-negative and triple-negative breast cancer patients treated with anthracycline-based neoadjuvant chemotherapy.}, journal = {Experimental and molecular pathology}, volume = {135}, number = {}, pages = {104885}, doi = {10.1016/j.yexmp.2024.104885}, pmid = {38281565}, issn = {1096-0945}, mesh = {Humans ; Female ; *Breast Neoplasms/drug therapy/genetics/metabolism ; *Triple Negative Breast Neoplasms/drug therapy/genetics ; Anthracyclines/therapeutic use ; Retrospective Studies ; Receptor, ErbB-2/metabolism ; Neoadjuvant Therapy ; Antibiotics, Antineoplastic ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Treatment Outcome ; Biomarkers, Tumor/metabolism ; }, abstract = {BACKGROUND: Neoadjuvant chemotherapy (NCT) can induce a pathological complete response (pCR) in breast cancer patients, leading to improved outcomes. However, predicting which patients will achieve pCR remains a challenge. CD10, a myoepithelial marker, has shown diagnostic and prognostic value in metastatic tumors. Its potential as a predictor of chemosensitivity to anthracycline-based NCT in breast cancer is unknown.

AIM: This retrospective study aimed to investigate the potential of CD10 cancer cell expression as a predictive marker of chemosensitivity in breast cancers treated with anthracycline-based neoadjuvant chemotherapy.

METHODS: We analyzed 130 patients with invasive ductal carcinoma who received anthracycline-based NCT. CD10 expression was assessed by immunohistochemistry on pre-treatment biopsies. Statistical analysis evaluated the association between CD10 expression and pCR rates.

RESULTS: Univariate analysis revealed that ER-positive and CD10-negative tumors had lower pCR rates [OR 7.4830 (95% CI 2.7762-20.1699); p = 0.0001]. Multivariate analysis confirmed ER status as a strong predictor of poor response [OR 0.085 (95% CI 0.024-0.30); p < 0.001] and CD10 expression as a predictor of a favourable response [OR 0.11 (0.8-0.19); p = 0.049]. CD10 expression significantly predicted pCR in ER-negative cases [OR 0.1098 (0.0268-0.4503); p = 0.0022] and triple-negative breast cancer [OR 0.0966 (95% CI 0.0270-0.3462); p = 0.0003]. Concordance was observed between core biopsies and excised samples.

CONCLUSION: Positive CD10 cancer cell expression may predict increased response to anthracycline-based neoadjuvant chemotherapy in ER-negative and triple-negative breast cancer cases. Further research is needed to validate these findings in larger cohorts and determine the clinical utility of CD10 as a predictive marker.}, } @article {pmid38278448, year = {2024}, author = {Mahlow, J and Barry, M and Albertson, DJ and Jo, YJ and Balatico, M and Seasor, T and Gebrael, G and Kumar, SA and Sayegh, N and Tripathi, N and Agarwal, N and Swami, U and Sirohi, D}, title = {Histologic patterns in prostatic adenocarcinoma are not predictive of mutations in the homologous recombination repair pathway.}, journal = {Human pathology}, volume = {144}, number = {}, pages = {28-33}, doi = {10.1016/j.humpath.2024.01.005}, pmid = {38278448}, issn = {1532-8392}, mesh = {Male ; Humans ; Recombinational DNA Repair ; BRCA1 Protein/genetics ; *Carcinoma, Lobular ; BRCA2 Protein/genetics ; Mutation ; *Breast Neoplasms ; *Prostatic Neoplasms/genetics ; }, abstract = {Somatic or germline homologous recombination repair (HRR) pathway gene mutations are commonly detected in prostate cancer, especially in advanced disease, and are associated with response to poly (ADP-ribose) polymerase (PARP) inhibitors. In this study, we evaluated whether histological patterns are predictive of HRR pathway gene mutations. The study population comprised 130 patients with advanced prostate carcinoma who underwent comprehensive genomic profiling (CGP) of tumor tissue at a CLIA-certified laboratory. HRR genes in the study included BRCA1, BRCA2, ATM, BARD1, BRIP, CHEK2, MRE11A, NBN, PALB2, RAD51C, RAD51D, EMSY, ATR, CHEK1, and FAM175A. Overall, 38 patients had mutations in BRCA1/2, 36 in other HRR genes, and 56 were negative for HRR mutations. All cases were re-reviewed and quantified by two genitourinary pathologists blinded to mutational status for the following histological patterns of prostate carcinoma: cribriform, ductal, intraductal carcinoma (IDC), small cell carcinoma, signet ring-like pattern, and lobular carcinoma-like pattern. Discordances were resolved by consensus review. Histologic patterns were analyzed for any correlation with mutations in HRR pathway genes (grouped as BRCA1/2 mutated or non-BRCA1/2 mutated) compared to tumors without mutations in HRR genes by Chi-square testing. Patterns with >20 % and >30 % of tumor volume were additionally evaluated for correlation with mutational status. We found no significant association between HRR pathway mutations and cribriform pattern, IDC, ductal carcinoma, small cell carcinoma, signet ring-like pattern, or lobular carcinoma-like patterns. Tumors with >20 % or >30 % histologic patterns by volume also demonstrated no significant association with mutational status. This study suggests that histopathologic examination alone is insufficient to distinguish prostate cancer with germline or somatic mutations in HRR pathway genes, highlighting the continuing importance of ancillary molecular diagnostics in guiding therapy selection for prostate cancer patients who may benefit from PARP inhibitors.}, } @article {pmid38273267, year = {2024}, author = {Yang, ZJ and Xin, F and Chen, ZJ and Yu, Y and Wang, X and Cao, XC}, title = {Real-world data on neoadjuvant chemotherapy with dual-anti HER2 therapy in HER2 positive breast cancer.}, journal = {BMC cancer}, volume = {24}, number = {1}, pages = {134}, pmid = {38273267}, issn = {1471-2407}, mesh = {Humans ; Female ; *Breast Neoplasms/drug therapy/genetics/metabolism ; Neoadjuvant Therapy ; Treatment Outcome ; Receptor, ErbB-2/metabolism ; Ki-67 Antigen ; Retrospective Studies ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; }, abstract = {BACKGROUND: Neoadjuvant chemotherapy with dual-targeted therapy is the standard treatment for human epidermal growth factor 2 (HER2)-positive breast cancer. Although the dual-targeted therapy has significantly improved the pathological complete response (pCR) rate, further investigation is needed to identify biomarkers that predict the response to neoadjuvant therapy.

METHODS: This retrospective study analyzed 353 patients with HER2-positive breast invasive ductal carcinoma. The correlation between clinicopathological factors and pCR rate was evaluated. A nomogram was constructed based on the results of the multivariate logistic regression analysis to predict the probability of pCR.

RESULTS: The breast pCR (b-pCR) rate was 56.1% (198/353) and the total pCR (t-pCR) rate was 52.7% (186/353). Multivariate analysis identified ER status, PR status, HER2 status, Ki-67 index, and neoadjuvant chemotherapy regimens as independent indicators for both b-pCR and t-pCR. The nomogram had an area under the receiver operating characteristic curve (AUC) of 0.73 (95% CI: 0.68-0.78). According to the nomogram, the t- pCR rate was highest in the ER-PR- HER2-positive patients (131/208) and lowest in the ER + PR + HER2-positive patients (19/73). The subgroup analyses showed that there was no significant difference in pCR rate among the neoadjuvant chemotherapy regimens in ER positive, PR positive, HER2 IHC 2 + , Ki67 index < 30% population. However, for ER-PR-HER2-positive patients, the neoadjuvant chemotherapy regimen has a great influence on the pCR rates.

CONCLUSIONS: Patients with ER-negative, PR-negative, HER2 3 + and high KI-67 index were more likely to achieve pCR. THP may be used as an alternative to AC-THP or TCbHP in selected HER2-positive patients.}, } @article {pmid38229073, year = {2024}, author = {Ido, M and Fujii, K and Mishima, H and Kubo, A and Saito, M and Banno, H and Ito, Y and Goto, M and Ando, T and Mouri, Y and Kousaka, J and Imai, T and Nakano, S}, title = {Comprehensive genomic evaluation of advanced and recurrent breast cancer patients for tailored precision treatments.}, journal = {BMC cancer}, volume = {24}, number = {1}, pages = {85}, pmid = {38229073}, issn = {1471-2407}, mesh = {Humans ; Middle Aged ; Female ; *Breast Neoplasms/drug therapy/genetics/pathology ; Phosphatidylinositol 3-Kinases/genetics ; Neoplasm Recurrence, Local/drug therapy/genetics ; Genomics ; Mutation ; *Carcinoma ; High-Throughput Nucleotide Sequencing ; }, abstract = {AIM: The aim of this study was to investigate genetic alterations within breast cancer in the setting of recurrent or de novo stage IV disease.

PATIENTS AND METHODS: This study included 22 patients with recurrent breast cancer (n = 19) and inoperable de novo stage IV breast cancer (n = 3). For next generation sequencing, FoundationOneCDx (F1CDx) (Foundation Medicine Inc., Cambridge, MA, USA) was performed in 21 patients and FoundationOneLiquid CDx was performed in 1 patient.

RESULTS: Median age was 62.9 years (range, 33.4-82.1). Pathological diagnoses of specimens included invasive ductal carcinoma (n = 19), invasive lobular carcinoma (n = 2), and invasive micropapillary carcinoma (n = 1). F1CDx detected a median of 4.5 variants (range, 1-11). The most commonly altered gene were PIK3CA (n = 9), followed by TP53 (n = 7), MYC (n = 4), PTEN (n = 3), and CDH1 (n = 3). For hormone receptor-positive patients with PIK3CA mutations, hormonal treatment plus a phosphoinositide 3-kinase inhibitor was recommended as the treatment of choice. Patients in the hormone receptor-negative and no human epidermal growth factor receptor 2 expression group had significantly higher tumor mutational burden than patients in the hormone receptor-positive group. A BRCA2 reversion mutation was revealed by F1CDx in a patient with a deleterious germline BRCA2 mutation during poly ADP ribose polymerase inhibitor treatment.

CONCLUSION: Guidance on tailored precision therapy with consideration of genomic mutations was possible for some patients with information provided by F1CDx. Clinicians should consider using F1CDx at turning points in the course of the disease.}, } @article {pmid38180699, year = {2024}, author = {Nakagawa, S and Miyashita, M and Maeda, I and Goda, A and Tada, H and Amari, M and Kojima, Y and Tsugawa, K and Ohi, Y and Sagara, Y and Sato, M and Ebata, A and Harada-Shoji, N and Suzuki, T and Nakanishi, M and Ohta, T and Ishida, T}, title = {Potential role of Fbxo22 in resistance to endocrine therapy in breast cancer with invasive lobular carcinoma.}, journal = {Breast cancer research and treatment}, volume = {204}, number = {3}, pages = {453-463}, pmid = {38180699}, issn = {1573-7217}, mesh = {Female ; Humans ; *Breast Neoplasms/drug therapy/genetics/metabolism ; *Carcinoma, Lobular/pathology ; Selective Estrogen Receptor Modulators/therapeutic use ; *Carcinoma, Ductal, Breast/pathology ; Treatment Outcome ; Tumor Microenvironment ; }, abstract = {BACKGROUND: Invasive lobular carcinoma (ILC) is distinct from invasive ductal carcinoma (IDC) in terms of their hormonal microenvironments that may require different therapeutic strategies. We previously reported that selective estrogen receptor modulator (SERM) function requires F-box protein 22 (Fbxo22). Here, we investigated the role of Fbxo22 as a potential biomarker contributing to the resistance to endocrine therapy in ILC.

METHODS: A total of 302 breast cancer (BC) patients including 150 ILC were recruited in the study. Fbxo22 expression and clinical information were analyzed to elucidate whether Fbxo22 negativity could be a prognostic factor or there were any correlations among clinical variables and SERM efficacy.

RESULTS: Fbxo22 negativity was significantly higher in ILC compared with IDC (58.0% vs. 27.0%, P < 0.001) and higher in postmenopausal patients than premenopausal patients (64.1% vs. 48.2%, P = 0.041). In the ILC cohort, Fbxo22-negative patients had poorer overall survival (OS) than Fbxo22-positive patients, with 10-year OS rates of 77.4% vs. 93.6% (P = 0.055). All patients treated with SERMs, Fbxo22 negativity resulted in a poorer outcome, with 10-year OS rates of 81.3% vs. 92.3% (P = 0.032). In multivariate analysis regarding recurrence-free survival (RFS) in ILC patients, Fbxo22 status was independently predictive of survival as well as lymph node metastasis.

CONCLUSION: Fbxo22 negativity significantly impacts on survival in BC patients with IDC and ILC, and the disadvantage was enhanced among ILC postmenopausal women or patients treated with SERMs. The findings suggest that different therapeutic strategies might be needed according to the different histopathological types when considering adjuvant endocrine therapy.}, } @article {pmid38170222, year = {2024}, author = {Li, QY and Guo, Q and Luo, WM and Luo, XY and Ji, YM and Xu, LQ and Guo, JL and Shi, RS and Li, F and Lin, CY and Zhang, J and Ke, D}, title = {Overexpression of MTFR1 promotes cancer progression and drug-resistance on cisplatin and is related to the immune microenvironment in lung adenocarcinoma.}, journal = {Aging}, volume = {16}, number = {1}, pages = {66-88}, pmid = {38170222}, issn = {1945-4589}, mesh = {Humans ; Cisplatin/pharmacology/therapeutic use ; *Lung Neoplasms/drug therapy/genetics/pathology ; Proto-Oncogene Proteins c-akt/metabolism ; *Adenocarcinoma of Lung/drug therapy/genetics/pathology ; Drug Resistance, Neoplasm/genetics ; Cell Proliferation/genetics ; Gene Expression Regulation, Neoplastic ; Cell Line, Tumor ; Tumor Microenvironment/genetics ; }, abstract = {OBJECTIVE: The roles of MTFR1 in the drug resistance of lung adenocarcinoma (LAC) to cisplatin remain unexplored. In this study, the expression, clinical values and mechanisms of MTFR1 were explored, and the relationship between MTFR1 expression and immune microenvironment was investigated in LAC using bioinformatics analysis, cell experiments, and meta-analysis.

METHODS: MTFR1 expression and clinical values, and the relationship between MTFR1 expression and immunity were explored, through bioinformatics analysis. The effects of MTFR1 on the growth, migration and cisplatin sensitivity of LAC cells were identified using cell counting kit-8, wound healing and Transwell experiments. Additionally, the mechanisms of drug resistance of LAC cells involving MTFR1 were investigated using western blotting.

RESULTS: MTFR1 was elevated in LAC tissues. MTFR1 overexpression was associated with sex, age, primary therapy outcome, smoking, T stage, unfavourable prognosis and diagnostic value and considered an independent risk factor for an unfavourable prognosis in patients with LAC. MTFR1 co-expressed genes involved in the cell cycle, oocyte meiosis, DNA replication and others. Moreover, interfering with MTFR1 expression inhibited the proliferation, migration and invasion of A549 and A549/DDP cells and promoted cell sensitivity to cisplatin, which was related to the inhibition of p-AKT, p-P38 and p-ERK protein expression. MTFR1 overexpression was associated with stromal, immune and estimate scores along with natural killer cells, pDC, iDC and others in LAC.

CONCLUSIONS: MTFR1 overexpression was related to the unfavourable prognosis, diagnostic value and immunity in LAC. MTFR1 also participated in cell growth and migration and promoted the drug resistance of LAC cells to cisplatin via the p-AKT and p-ERK/P38 signalling pathways.}, } @article {pmid38151327, year = {2024}, author = {Kos, Z and Nielsen, TO and Laenkholm, AV}, title = {Breast Cancer Histopathology in the Age of Molecular Oncology.}, journal = {Cold Spring Harbor perspectives in medicine}, volume = {14}, number = {6}, pages = {}, pmid = {38151327}, issn = {2157-1422}, mesh = {Humans ; *Breast Neoplasms/pathology/genetics ; Female ; *Biomarkers, Tumor/genetics ; Prognosis ; Carcinoma, Ductal, Breast/pathology/genetics ; }, abstract = {For more than a century, microscopic histology has been the cornerstone for cancer diagnosis, and breast carcinoma is no exception. In recent years, clinical biomarkers, gene expression profiles, and other molecular tests have shown increasing utility for identifying the key biological features that guide prognosis and treatment of breast cancer. Indeed, the most common histologic pattern-invasive ductal carcinoma of no special type-provides relatively little guidance to management beyond triggering grading, biomarker testing, and clinical staging. However, many less common histologic patterns can be recognized by trained pathologists, which in many cases can be linked to characteristic biomarker and gene expression patterns, underlying mutations, prognosis, and therapy. Herein we describe more than a dozen such histomorphologic subtypes (including lobular, metaplastic, salivary analog, and several good prognosis special types of breast cancer) in the context of their molecular and clinical features.}, } @article {pmid38091153, year = {2024}, author = {Schwartz, CJ and Khorsandi, N and Blanco, A and Mukhtar, RA and Chen, YY and Krings, G}, title = {Clinicopathologic and genetic analysis of invasive breast carcinomas in women with germline CHEK2 variants.}, journal = {Breast cancer research and treatment}, volume = {204}, number = {1}, pages = {171-179}, pmid = {38091153}, issn = {1573-7217}, mesh = {Humans ; Female ; Adult ; Middle Aged ; Aged ; *Breast Neoplasms/genetics/pathology ; Checkpoint Kinase 2/genetics ; Genetic Predisposition to Disease ; Germ-Line Mutation ; Germ Cells ; Carrier Proteins/genetics ; }, abstract = {PURPOSE: Germline pathogenic variants in checkpoint kinase 2 (CHEK2) are associated with a moderately increased risk of breast cancer (BC). The spectrum of clinicopathologic features and genetics of these tumors has not been fully established.

METHODS: We characterized the histopathologic and clinicopathologic features of 44 CHEK2-associated BCs from 35 women, and assessed responses to neoadjuvant chemotherapy. A subset of cases (n = 23) was additionally analyzed using targeted next-generation DNA sequencing (NGS).

RESULTS: Most (94%, 33/35) patients were heterozygous carriers for germline CHEK2 variants, and 40% had the c.1100delC allele. Two patients were homozygous, and five had additional germline pathogenic variants in ATM (2), PALB2 (1), RAD50 (1), or MUTYH (1). CHEK2-associated BCs occurred in younger women (median age 45 years, range 25-75) and were often multifocal (20%) or bilateral (11%). Most (86%, 38/44) were invasive ductal carcinomas of no special type (IDC-NST). Almost all (95%, 41/43) BCs were ER + (79% ER + HER2-, 16% ER + HER2 + , 5% ER-HER2 +), and most (69%) were luminal B. Nottingham grade, proliferation index, and results of multiparametric molecular testing were heterogeneous. Biallelic CHEK2 alteration with loss of heterozygosity was identified in most BCs (57%, 13/23) by NGS. Additional recurrent alterations included GATA3 (26%), PIK3CA (226%), CCND1 (22%), FGFR1 (22%), ERBB2 (17%), ZNF703 (17%), TP53 (9%), and PPM1D (9%), among others. Responses to neoadjuvant chemotherapy were variable, but few patients (21%, 3/14) achieved pathologic complete response. Most patients (85%) were without evidence of disease at time of study (n = 34). Five patients (15%) developed distant metastasis, and one (3%) died (mean follow-up 50 months).

CONCLUSION: Almost all CHEK2-associated BCs were ER + IDC-NST, with most classified as luminal B with or without HER2 overexpression. NGS supported the luminal-like phenotype and confirmed CHEK2 as an oncogenic driver in the majority of cases. Responses to neoadjuvant chemotherapy were variable but mostly incomplete.}, } @article {pmid38090235, year = {2023}, author = {Adedokun, KA and Oluogun, WA and Oyenike, MA and Imodoye, SO and Yunus, LA and Lasisi, SA and Bello, IO and Kamorudeen, RT and Adekola, SA}, title = {Expression Patterns of ER, PR, HER-2/neu and p53 in Association with Nottingham Tumour Grade in Breast Cancer Patients.}, journal = {Sultan Qaboos University medical journal}, volume = {23}, number = {4}, pages = {526-533}, pmid = {38090235}, issn = {2075-0528}, mesh = {Humans ; Female ; *Breast Neoplasms/genetics/pathology ; Receptors, Progesterone/metabolism ; Tumor Suppressor Protein p53 ; Receptor, ErbB-2/genetics/metabolism ; Hormones ; }, abstract = {OBJECTIVES: Recent molecular studies show that breast cancer (BC) is a heterogeneous disease, and several molecular changes may accumulate over time to influence treatment response. As a result, employing reliable molecular biomarkers to monitor these modifications may help deliver personalised treatment. However, this may be unrealistic in the resource-limited parts of the world. Thus, this study aimed to investigate the expression pattern of hormone receptors and p53 tumour suppressor using immunohistochemistry (IHC) in BC compared to the traditional tumour grade.

METHODS: In total, 205 cases were investigated, and the Modified Bloom-Richardson score system was adopted in grading the tumours. The tissue sections of the cases were stained with specific primary antibodies at dilutions of 1:60 for oestrogen receptors (ER) and progesterone receptors (PR), 1:350 for the human epidermal growth factor (HER-2/neu) and 1:50 for p53.

RESULTS: Invasive ductal carcinoma of no-specific type (n = 190, 92.7%) was predominant and grade II tumour (n = 146, 71.2%) was the most frequent. Hormone receptors ER (n = 127) and PR (n = 145) had 62.0% and 70.7% positive cases, respectively; 34.1% (n = 70) were positive for HER-2/neu, while 76.1% (n = 156) were positive for p53. Significant associations between Nottingham grade and expression patterns of ER (P <0.01), PR (P <0.001), HER-2/neu (P <0.001) and p53 (P = 0.001) were observed.

CONCLUSION: Nottingham grade had a high degree of concordance with the patterns of expression of hormone receptors, HER-2/neu and p53, suggesting that it may play an important role in connection with the predictive and prognostic biomarkers for BC.}, } @article {pmid38070191, year = {2024}, author = {Mouabbi, JA and Qaio, W and Shen, Y and Raghavendra, AS and Tripathy, D and Layman, RM}, title = {Efficacy of Single-Agent Chemotherapy in Endocrine Therapy-Refractory Metastatic Invasive Lobular Carcinoma.}, journal = {The oncologist}, volume = {29}, number = {3}, pages = {213-218}, pmid = {38070191}, issn = {1549-490X}, support = {MIRA RP170067//Cancer Prevention and Research Institute of Texas/ ; //NIH/ ; //NCI/ ; }, mesh = {Humans ; Female ; *Carcinoma, Lobular/pathology ; Prospective Studies ; Receptor, ErbB-2/genetics/therapeutic use ; *Breast Neoplasms/pathology ; Capecitabine/therapeutic use ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; }, abstract = {BACKGROUND: Hormone receptor (HR)-positive, HER2-negative metastatic invasive lobular breast cancer (mILC) is distinct from invasive ductal cancer (IDC) in clinicopathologic and molecular characteristics, impacting its response to systemic therapy. While endocrine therapy (ET) combined with targeted therapies has shown efficacy in ET-sensitive mILC, data on chemotherapy in ET-refractory mILC remain limited. We investigated the efficacy of single-agent capecitabine (CAP) versus taxanes (TAX) in ET-refractory HR+ HER2-negative patients with mILC.

MATERIALS AND METHODS: Using data from the MD Anderson prospectively collected breast cancer database, we identified patients with HR+ HER2-negative mILC who received prior ET and first-time chemotherapy in the metastatic setting. We compared outcomes between 173 CAP-treated and 96 TAX-treated patients.

RESULTS: CAP-treated patients had significantly better median progression-free survival (PFS) than TAX-treated patients (8.8 vs 5.0 months, HR 0.63, P < .001). Overall survival (OS) did not differ significantly between the groups (42.7 vs 36.6 months for CAP vs TAX, respectively, HR 0.84, P = .241). Multivariate analyses for PFS and OS revealed better outcomes in subjects with fewer metastatic sites and those exposed to more lines of ET. Additionally, Black patients showed worse OS outcomes compared to White patients (HR 2.46; P = .001).

CONCLUSION: In ET-refractory HR+ HER2-negative mILC, single-agent CAP demonstrated superior PFS compared to TAX. Our findings highlight the potential benefit of CAP in this patient subset, warranting further investigation through prospective trials.}, } @article {pmid38047107, year = {2023}, author = {Zhang, W and Nowotny, H and Theodoropoulou, M and Simon, J and Hemmer, CM and Bidlingmaier, M and Auer, MK and Reincke, M and Uhlenhaut, H and Reisch, N}, title = {E47 as a novel glucocorticoid-dependent gene mediating lipid metabolism in patients with endogenous glucocorticoid excess.}, journal = {Frontiers in endocrinology}, volume = {14}, number = {}, pages = {1249863}, pmid = {38047107}, issn = {1664-2392}, mesh = {Animals ; Female ; Humans ; Mice ; Adrenocorticotropic Hormone/metabolism ; Cholesterol ; *Cushing Syndrome ; Dexamethasone/pharmacology ; *Glucocorticoids/pharmacology ; Hydrocortisone ; Lipid Metabolism/genetics ; Prospective Studies ; RNA, Messenger/metabolism ; }, abstract = {PURPOSE: E47 has been identified as a modulating transcription factor of glucocorticoid receptor target genes, its loss protecting mice from metabolic adverse effects of glucocorticoids. We aimed to analyze the role of E47 in patients with endogenous glucocorticoid excess [Cushing's syndrome (CS)] and its association with disorders of lipid and glucose metabolism.

METHODS: This is a prospective cohort study including 120 female patients with CS (ACTH-dependent = 79; ACTH-independent = 41) and 26 healthy female controls. Morning whole blood samples after an overnight fast were used to determine E47 mRNA expression levels in patients with overt CS before and 6-12 months after curative surgery. Expression levels were correlated with the clinical phenotype of the patients. Control subjects underwent ACTH stimulation tests and dexamethasone suppression tests to analyze short-term regulation of E47.

RESULTS: E47 gene expression showed significant differences in patient cohorts with overt CS vs. patients in remission (p = 0.0474) and in direct intraindividual comparisons pre- vs. post-surgery (p = 0.0353). ACTH stimulation of controls resulted in a significant decrease of E47 mRNA expression 30 min after i.v. injection compared to baseline measurements. Administration of 1 mg of dexamethasone overnight in controls did not change E47 mRNA expression. E47 gene expression showed a positive correlation with total serum cholesterol (p = 0.0036), low-density lipoprotein cholesterol (p = 0.0157), and waist-arm ratio (p = 0.0138) in patients with CS in remission.

CONCLUSION: E47 is a GC-dependent gene that is upregulated in GC excess potentially aiming at reducing metabolic glucocorticoid side effects such as dyslipidemia.}, } @article {pmid38046902, year = {2023}, author = {Naeimzadeh, Y and Ilbeigi, S and Dastsooz, H and Rafiee Monjezi, M and Mansoori, Y and Tabei, SMB}, title = {Protooncogenic Role of ARHGAP11A and ARHGAP11B in Invasive Ductal Carcinoma: Two Promising Breast Cancer Biomarkers.}, journal = {BioMed research international}, volume = {2023}, number = {}, pages = {8236853}, pmid = {38046902}, issn = {2314-6141}, mesh = {Female ; Humans ; *Breast Neoplasms/pathology ; Biomarkers, Tumor/genetics ; *Carcinoma, Ductal, Breast/pathology ; Breast/pathology ; GTPase-Activating Proteins/genetics/metabolism ; }, abstract = {Invasive duct carcinoma (IDC) is one of the most common types of breast cancer (BC) in women worldwide, with a high risk of malignancy, metastasis, recurrence, and death. So far, molecular patterns among IDC cases have not been fully defined. However, extensive evidence has shown that dysregulated Rho family small GTPases (Rho GTPases) including Rho GTPase activating proteins (RhoGAPs) have important roles in the invasive features of IDCs. In the current study, we analyzed the expression levels of two RhoGAP genes, ARHGAP11A and ARHGAP11B, in The Cancer Genome Atlas (TCGA) breast cancer (BRCA) and also our 51 IDC tumors compared to their matched normal tissues using quantitative polymerase chain reaction (qPCR). Our TCGA data analysis revealed higher expression of ARHGAP11A and ARHGAP11B in various cancers comprising BCs. Also, we found correlations between these genes and other genes in TCGA-BRCA. Moreover, our methylation analysis showed that their promotor methylation had a negative correlation with their overexpression. QPCR revealed their significant upregulation in our tumor samples. Furthermore, we found that the expression level of ARHGAP11A was considerably lower in women who were breastfeeding. Moreover, it had overexpression in cases who had regular menstrual cycles and early age (younger than 14) at menarche. However, ARHGAP11B had a higher expression in HER2-positive tumors versus HER2-positive and ER-positive tumors. Our study found possible protooncogenic roles for these genes and their involvement in IDC pathogenesis and malignancy. Therefore, they can be considered novel prognostic and diagnostic biomarkers for IDC.}, } @article {pmid38008819, year = {2023}, author = {Jalilian, E and Abolhasani-Zadeh, F and Afgar, A and Samoudi, A and Zeinalynezhad, H and Langroudi, L}, title = {Neutralizing tumor-related inflammation and reprogramming of cancer-associated fibroblasts by Curcumin in breast cancer therapy.}, journal = {Scientific reports}, volume = {13}, number = {1}, pages = {20770}, pmid = {38008819}, issn = {2045-2322}, support = {IR.KMU.REC.1398.326//Kerman University of Medical Sciences/ ; }, mesh = {Humans ; Female ; *Breast Neoplasms/genetics ; *Cancer-Associated Fibroblasts/metabolism ; *Curcumin/pharmacology/therapeutic use/metabolism ; Cyclooxygenase 2/metabolism ; Dinoprostone/metabolism ; Fibroblasts/metabolism ; Inflammation/pathology ; Cell Line, Tumor ; Tumor Microenvironment ; }, abstract = {Tumor-associated inflammation plays a vital role in cancer progression. Among the various stromal cells, cancer-associated fibroblasts are promising targets for cancer therapy. Several reports have indicated potent anti-inflammatory effects attributed to Curcumin. This study aimed to investigate whether inhibiting the inflammatory function of cancer-associated fibroblasts (CAFs) with Curcumin can restore anticancer immune responses. CAFs were isolated from breast cancer tissues, treated with Curcumin, and co-cultured with patients' PBMCs to evaluate gene expression and cytokine production alterations. Blood and breast tumor tissue samples were obtained from 12 breast cancer patients with stage II/III invasive ductal carcinoma. Fibroblast Activation Protein (FAP) + CAFs were extracted from tumor tissue, treated with 10 μM Curcumin, and co-cultured with corresponding PBMCs. The expression of smooth muscle actin-alpha (α-SMA), Cyclooxygenase-2(COX-2), production of PGE2, and immune cell cytokines were evaluated using Real-Time PCR and ELISA, respectively. Analyzes showed that treatment with Curcumin decreased the expression of genes α-SMA and COX-2 and the production of PGE2 in CAFs. In PBMCs co-cultured with Curcumin-treated CAFs, the expression of FoxP3 decreased along with the production of TGF-β, IL-10, and IL-4. An increase in IFN-γ production was observed that followed by increased T-bet expression. According to our results, Curcumin could reprogram the pro-tumor phenotype of CAFs and increase the anti-tumor phenotype in PBMCs. Thus, CAFs, as a component of the tumor microenvironment, are a suitable target for combination immunotherapies of breast cancer.}, } @article {pmid38000681, year = {2024}, author = {Boyraz, B and Ly, A}, title = {Spectrum of histopathologic findings in risk-reducing bilateral prophylactic mastectomy in patients with and without BRCA mutations.}, journal = {Human pathology}, volume = {151}, number = {}, pages = {105534}, doi = {10.1016/j.humpath.2023.11.010}, pmid = {38000681}, issn = {1532-8392}, mesh = {Adult ; Aged ; Female ; Humans ; Middle Aged ; Biomarkers, Tumor/genetics ; *BRCA1 Protein/genetics ; *BRCA2 Protein/genetics ; *Breast Neoplasms/genetics/pathology/prevention & control/surgery ; Carcinoma, Ductal, Breast/genetics/pathology/prevention & control/surgery ; Carcinoma, Intraductal, Noninfiltrating/genetics/pathology/surgery/prevention & control ; Genetic Predisposition to Disease ; *Germ-Line Mutation ; Phenotype ; *Prophylactic Mastectomy ; PTEN Phosphohydrolase/genetics ; Risk Factors ; }, abstract = {Many germline mutations have been implicated in breast cancer pathogenesis and despite several studies on occult atypical lesions in prophylactic mastectomy specimens from patients with BRCA1/2 mutations, there are very limited data on other genes associated with increased breast cancer risk and the distribution of lesions in patients with hereditary breast cancer. We identified 207 patients who underwent bilateral prophylactic mastectomy due to germline mutations in BRCA1/2, PALB2, CHEK2, ATM, CDH1, PTEN, BARD1, or strong family history between 2015 and 2023. Patients with biopsy-proven past or current invasive breast carcinoma or carcinoma in-situ preoperatively were excluded. In addition to multiple benign lesions, the following atypical lesions were identified: flat epithelial atypia (16.9%), atypical ductal hyperplasia (14.0%), lobular neoplasia (14.0%), ductal carcinoma in-situ (4.3%), invasive ductal carcinoma (0.4%). Both low-grade and high-grade pathway lesions were identified in this cohort, and in a subset of patients, they co-occurred. The frequency of atypical lesions identified in patients with strong family history were comparable to those with proven germline mutation. PTEN immunohistochemistry showed loss of expression in ductal carcinoma in-situ and tubular adenomas in PTEN-mutant patients. Overall, findings from this cohort support the benefit of prophylactic mastectomy in patients with germline mutations and/or strong family history. Additionally, this is the first demonstration that PTEN immunohistochemistry may be helpful in identifying germline mutations in patients with atypical or neoplastic proliferations.}, } @article {pmid37925055, year = {2024}, author = {Derakhshan, F and Da Cruz Paula, A and Selenica, P and da Silva, EM and Grabenstetter, A and Jalali, S and Gazzo, AM and Dopeso, H and Marra, A and Brown, DN and Ross, DS and Mandelker, D and Razavi, P and Chandarlapaty, S and Wen, HY and Brogi, E and Zhang, H and Weigelt, B and Pareja, F and Reis-Filho, JS}, title = {Nonlobular Invasive Breast Carcinomas with Biallelic Pathogenic CDH1 Somatic Alterations: A Histologic, Immunophenotypic, and Genomic Characterization.}, journal = {Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc}, volume = {37}, number = {2}, pages = {100375}, pmid = {37925055}, issn = {1530-0285}, support = {P30 CA008748/CA/NCI NIH HHS/United States ; P50 CA247749/CA/NCI NIH HHS/United States ; }, mesh = {Humans ; Female ; *Carcinoma, Lobular/pathology ; *Breast Neoplasms/pathology ; *Carcinoma, Ductal, Breast/pathology ; Cadherins/genetics ; Genomics ; Antigens, CD/genetics ; }, abstract = {CDH1 encodes for E-cadherin, and its loss of function is the hallmark of invasive lobular carcinoma (ILC). Albeit vanishingly rare, biallelic CDH1 alterations may be found in nonlobular breast carcinomas (NL-BCs). We sought to determine the clinicopathologic characteristics and repertoire of genetic alterations of NL-BCs harboring CDH1 biallelic genetic alterations. Analysis of 5842 breast cancers (BCs) subjected to clinical tumor-normal sequencing with an FDA-cleared multigene panel was conducted to identify BCs with biallelic CDH1 pathogenic/likely pathogenic somatic mutations lacking lobular features. The genomic profiles of NL-BCs with CDH1 biallelic genetic alterations were compared with those of ILCs and invasive ductal carcinomas (IDCs), matched by clinicopathologic characteristics. Of the 896 CDH1-altered BCs, 889 samples were excluded based on the diagnosis of invasive mixed ductal/lobular carcinoma or ILC or the detection of monoallelic CDH1 alterations. Only 7 of the 5842 (0.11%) BCs harbored biallelic CDH1 alterations and lacked lobular features. Of these, 4/7 (57%) cases were ER-positive/HER2-negative, 1/7 (14%) was ER-positive/HER2-positive, and 2/7 (29%) were ER-negative/HER2-negative. In total, 5/7 (71%) were of Nottingham grade 2, and 2/7 (29%) were of grade 3. The NL-BCs with CDH1 biallelic genetic alterations included a mucinous carcinoma (n = 1), IDCs with focal nested growth (n = 2), IDC with solid papillary (n = 1) or apocrine (n = 2) features, and an IDC of no special type (NST; n = 1). E-cadherin expression, as detected by immunohistochemistry, was absent (3/5) or aberrant (discontinuous membranous/cytoplasmic/granular; 2/5). However, NL-BCs with CDH1 biallelic genetic alterations displayed recurrent genetic alterations, including TP53, PIK3CA (57%, 4/7; each), FGFR1, and NCOR1 (28%, 2/7, each) alterations. Compared with CDH1 wild-type IDC-NSTs, NL-BCs less frequently harbored GATA3 mutations (0% vs 47%, P = .03), but no significant differences were detected when compared with matched ILCs. Therefore, NL-BCs with CDH1 biallelic genetic alterations are vanishingly rare, predominantly comprise IDCs with special histologic features, and have genomic features akin to luminal B ER-positive BCs.}, } @article {pmid37921670, year = {2023}, author = {Kalra, R and Lim, B and Ellis, MJ and Kavuri, SM}, title = {The uncharted role of HER2 mutant alleles in breast cancer.}, journal = {Oncotarget}, volume = {14}, number = {}, pages = {904-907}, pmid = {37921670}, issn = {1949-2553}, support = {P50 CA186784/CA/NCI NIH HHS/United States ; }, mesh = {Humans ; Female ; *Breast Neoplasms/drug therapy/genetics/pathology ; *Carcinoma, Ductal, Breast/pathology ; *Carcinoma, Lobular/genetics ; Alleles ; Receptor, ErbB-2/genetics ; }, abstract = {Somatic HER2 mutations are a novel class of therapeutic targets across different cancer types. Treatment with the tyrosine kinase inhibitor (TKI) neratinib as a single agent continues to be evaluated in HER2-mutant metastatic disease. However, responses are heterogeneous, with frequent early progression. Herein, we discuss the under-explored effects of individual HER2 mutant alleles on therapeutic response, a role for HER2 mutation in metastatic propensity, and differences in patient outcomes in ER+ invasive lobular carcinoma (ILC) versus invasive ductal carcinoma (IDC). The preclinical efficacy of additional agents is also discussed, particularly the pan-HER inhibitor poziotinib.}, } @article {pmid37910521, year = {2023}, author = {Imamichi, T and Chen, Q and Sowrirajan, B and Yang, J and Laverdure, S and Marquez, M and Mele, AR and Watkins, C and Adelsberger, JW and Higgins, J and Sui, H}, title = {Interleukin-27-induced HIV-resistant dendritic cells suppress reveres transcription following virus entry in an SPTBN1, autophagy, and YB-1 independent manner.}, journal = {PloS one}, volume = {18}, number = {11}, pages = {e0287829}, pmid = {37910521}, issn = {1932-6203}, support = {HHSN261200800001C/CA/NCI NIH HHS/United States ; HHSN261200800001E/CA/NCI NIH HHS/United States ; }, mesh = {Humans ; *Interleukin-27 ; *HIV Infections ; Virus Internalization ; *HIV-1 ; Interleukins/metabolism ; Monocytes ; Autophagy/genetics ; DNA/metabolism ; Dendritic Cells/metabolism ; Virus Replication ; Spectrin/metabolism ; }, abstract = {Interleukin (IL)-27, a member of the IL-12 family of cytokines, induces human immunodeficiency virus (HIV)-resistant monocyte-derived macrophages and T cells. This resistance is mediated via the downregulation of spectrin beta, non-erythrocytic 1 (SPTBN1), induction of autophagy, or suppression of the acetylation of Y-box binding protein-1 (YB-1); however, the role of IL-27 administration during the induction of immature monocyte-derived dendritic cells (iDC) is poorly investigated. In the current study, we investigated the function of IL-27-induced iDC (27DC) on HIV infection. 27DC inhibited HIV infection by 95 ± 3% without significant changes in the expression of CD4, CCR5, and SPTBN1 expression, autophagy induction and acetylation of YB-1 compared to iDC. An HIV proviral DNA copy number assay displayed that 27DC suppressed reverse transcriptase (RT) reaction without influencing the virus entry. A DNA microarray analysis was performed to identify the differentially expressed genes between 27DC and iDC. Compared to iDC, 51 genes were differentially expressed in 27DC, with more than 3-fold changes in four independent donors. Cross-reference analysis with the reported 2,214 HIV regulatory host genes identified nine genes as potential interests: Ankyrin repeat domain 22, Guanylate binding protein (GBP)-1, -2, -4, -5, Stabilin 1, Serpin family G member 1 (SERPING1), Interferon alpha inducible protein 6, and Interferon-induced protein with tetratricopeptide repeats 3. A knock-down study using si-RNA failed to determine a key factor associated with the anti-HIV activity due to the induction of robust amounts of off-target effects. Overexpression of each protein in cells had no impact on HIV infection. Thus, we could not define the mechanism of the anti-HIV effect in 27DC. However, our findings indicated that IL-27 differentiates monocytes into HIV-resistant DC, and the inhibitory mechanism differs from IL-27-induced HIV-resistant macrophages and T cells.}, } @article {pmid37897648, year = {2024}, author = {Zhao, YY and Ge, HJ and Yang, WT and Shao, ZM and Hao, S}, title = {Secretory breast carcinoma: clinicopathological features and prognosis of 52 patients.}, journal = {Breast cancer research and treatment}, volume = {203}, number = {3}, pages = {543-551}, pmid = {37897648}, issn = {1573-7217}, support = {82203789//National Natural Science Foundation of China/ ; 82102683//National Natural Science Foundation of China/ ; }, mesh = {Male ; Humans ; Female ; Middle Aged ; *Breast Neoplasms/diagnosis/genetics/therapy ; *Carcinoma, Ductal, Breast/pathology ; In Situ Hybridization, Fluorescence ; China ; Prognosis ; *Triple Negative Breast Neoplasms/pathology ; *Carcinoma ; }, abstract = {PURPOSE: Secretory breast carcinoma is a rare histological subtype of invasive breast cancer and considered with an indolent clinical behavior. This study was conducted to analyze the clinicopathological features of patients with secretory breast carcinoma (SBC), explore the outcome, and compare the prognostic difference with invasive ductal breast carcinoma (IDC). METHODS AND MATERIALS: Patients with SBC diagnosed between 2006 and 2017 from Fudan University Shanghai Cancer Center were included in the study, excluding patients with previous malignant tumor history and incomplete clinical data or follow-up records. Peculiar clinicopathological and immunohistochemical features of the cases were fully described. Clinical data of 4979 cases of IDC were also evaluated during this period. After propensity score matching, prognostic analysis of SBCs and IDCs was calculated by Kaplan-Meier method and landmark analysis method.

RESULTS: The data of 52 patients diagnosed with SBC were identified from the pathological files. Among them, 47 patients were women, and 5 were men. The median age of the 52 SBCs was 46 years (mean, 48.1 years; range, 10-80 years). The tumor sizes ranged from 0.3 to 6.8 cm, with a mean of 3.5 cm. Eight patients (15.4%) had positive axillary lymph node involvement. The molecular classification was mostly triple-negative breast cancer (65.4%). Fluorescence in situ hybridization confirmed the presence of ETV6::NTRK3 rearrangement in 16 of 18 cases (88.9%). Furthermore, Kaplan-Meier survival analysis and landmark analysis demonstrated that there were no statistically significant differences in DFS and OS between SBC and IDC patients.

CONCLUSION: Although SBCs are generally associated with a favorable prognosis, our work exhibited that the clinicopathological features of SBC were partly different from former understandings, indicating that therapeutic procedure should be prudent. Further studies are necessary to fully identify the clinical behavior and predictive markers to improve diagnosis and management in this unique subtype of breast cancer.}, } @article {pmid37890687, year = {2024}, author = {Liao, H and Wang, H and Zheng, R and Yu, Y and Zhang, Y and Lv, L and Zhang, B and Chen, J}, title = {LncRNA CARMN suppresses EMT through inhibiting transcription of MMP2 activated by DHX9 in breast cancer.}, journal = {Cellular signalling}, volume = {113}, number = {}, pages = {110943}, doi = {10.1016/j.cellsig.2023.110943}, pmid = {37890687}, issn = {1873-3913}, mesh = {Humans ; Female ; *Breast Neoplasms/pathology ; *RNA, Long Noncoding/genetics/metabolism ; Matrix Metalloproteinase 2/metabolism ; Epithelial-Mesenchymal Transition/genetics ; Epithelial Cells/metabolism ; Gene Expression Regulation, Neoplastic ; Cell Line, Tumor ; Cell Movement/genetics ; Cell Proliferation/genetics ; *MicroRNAs/genetics ; Neoplasm Proteins/genetics/metabolism ; DEAD-box RNA Helicases/genetics/metabolism ; }, abstract = {Long non-coding RNAs (lncRNAs) have been shown to drive cancer progression. However, the function of lncRNAs and the underlying mechanism in early-stage breast cancer(BC) have rarely been investigated. Datasets of pre-invasive ductal carcinoma in situ (DCIS), invasive ductal BC (IDC) and normal breast tissue from TCGA and GEO databases were used to conduct bioinformatics analysis. LncRNA CARMN was identified as a tumor suppressor in early-stage BC and related to a better prognosis. CARMN over-expression inhibited MMP2 mediated migration and EMT in BC. Further analysis showed that CARMN was located in the nucleus and functioned as an enhancer RNA (eRNA) in mammary epithelial cell. Mechanically, CARMN binding protein DHX9 was identified by RNA pull-down and mass spectrometry (MS) assays and it also bound to the MMP2 promoter to activate its transcription. As a decoy, CARMN competitively bound to DHX9 and blocked MMP2 transcriptional activation, thereby inhibiting metastasis and EMT of BC cells. These findings reveal the important role of CARMN as a tumor suppressor in the metastasis and a potential biomarker for progression in early-stage BC.}, } @article {pmid37879875, year = {2023}, author = {Wang, HY and Li, SJ and Zhang, AL and Ni, XC}, title = {[Identification of lymph node metastasis related genes in prostate cancer using weighted gene co-expression network analysis].}, journal = {Zhonghua yi xue za zhi}, volume = {103}, number = {40}, pages = {3204-3210}, doi = {10.3760/cma.j.cn112137-20230531-00902}, pmid = {37879875}, issn = {0376-2491}, mesh = {Male ; Humans ; Lymphatic Metastasis ; *Nomograms ; *Prostatic Neoplasms/genetics/pathology ; Neoplasm Grading ; Risk Factors ; }, abstract = {Objective: To explore the molecular markers related to lymph node metastasis of prostate cancer (PCa) based on bioinformatics technology and carry out clinical verification. Methods: The differentially expressed genes of PCa with lymph node metastasis were screened from geo data, and the hub genes of the gene co expression network were constructed. The hub genes were incorporated into the support vector machine model to evaluate its prediction efficiency. The hub genes were verified in the TCGA data set and analyzed for immune infiltration. The clinical data of 80 patients with prostate cancer in the Fourth Hospital of Hebei Medical University from January 2019 to December 2022 were collected. The logistic risk model was used to evaluate the prediction efficiency of hub gene metastasis. Results: Five hub genes (GSK3B, TP53, PSMC6, SUMO1, PIK3CA) were identified, and the support vector machine model constructed by them had good diagnostic value (the accuracy rate was 83.87%). TCGA validation results showed that only PSMC6 was significantly differentially expressed in PCa tissues with lymph node metastasis (P<0.001). The results of immune infiltration analysis showed that the expression of PSMC6 was significantly correlated with 9 kinds of immune cells (B cells, DC, IDC, etc.). Clinical information analysis showed that the expression of PSMC6 was significantly correlated with lymph node metastasis, PSA value, T stage and Gleason score (P<0.01). Univariate logistic results showed that T stage (OR=3.230, 95%CI:1.192-8.757, P=0.021), Gleason score (OR=4.627, 95%CI:2.212-9.677, P<0.001), PSMC6 (OR=25.235, 95%CI:5.326-119.560, P<0.001) could be used as predictors of lymph node metastasis. Multivariate logistic analysis showed that PSMC6 (OR=16.537, 95%CI:2.928-93.393, P=0.001) could be used as an independent risk factor for predicting lymph node metastasis. Conclusion: PSMC6 may be used as a potential molecular marker for judging lymph node metastasis in patients with PCa.}, } @article {pmid37874803, year = {2023}, author = {Coskunpinar, E and Tiryakioglu, DZ and Abaci, N and Tukenmez, M and Pence, S}, title = {Investigation of the miR-637 and miR-523-5p as candidate biomarkers in breast cancer.}, journal = {Bratislavske lekarske listy}, volume = {124}, number = {11}, pages = {814-820}, doi = {10.4149/BLL_2023_125}, pmid = {37874803}, issn = {0006-9248}, mesh = {Humans ; Female ; *Fibroadenoma/diagnosis/genetics ; *Breast Neoplasms/diagnosis/genetics/pathology ; *MicroRNAs/metabolism ; Biomarkers ; *Carcinoma, Ductal ; Biomarkers, Tumor/genetics ; Gene Expression Profiling ; }, abstract = {OBJECTIVES: The distinction of benign lesions from malign tumors is crucial for the diagnosis and treatment of breast cancers.

BACKGROUND: The aim of this study was to investigate the use of miRNAs as plasma biomarkers for the discrimination of malign and benign breast tumors.

METHODS: Whole blood samples obtained from 40 individuals in 3 groups designated as invasive ductal carcinoma group, fibroadenoma group and healthy controls were included in this study. The expression levels of 372 miRNAs were determined using RT-PCR.  Results: The comparison of fibroadenoma group with healthy controls revealed an upregulation of thirty miRNAs and downregulation of twenty-nine miRNAs. The comparison of invasive ductal carcinoma (IDC) group with controls has shown that eight miRNAs were upregulated while eleven miRNAs were downregulated. When comparing IDC and fibroadenoma groups, 15 miRNAs were found to be upregulated, while 10 miRNAs were downregulated. Further analysis of these miRNAs aimed to determine their power in distinguishing  IDCs from fibroadenomas. Among the miRNAs analyzed, seven miRNAs have shown sufficient discriminative power, of which three miRNAs, namely miR-637, miR-523-5p and miR-490-3p, have shown a significantly high discriminative power.

CONCLUSIONS: Circulating miR-637 and miR-523-5p combination maybe used to discriminate between invasive ductal carcinomas and fibroadenomas. (Tab. 9, Fig. 4, Ref. 30).}, } @article {pmid37847513, year = {2024}, author = {Zhao, J and Xu, N and Zhu, S and Nie, L and Zhang, M and Zheng, L and Cai, D and Sun, X and Chen, J and Dai, J and Ni, Y and Wang, Z and Zhang, X and Liang, J and Chen, Y and Hu, X and Pan, X and Yin, X and Liu, H and Zhao, F and Zhang, B and Chen, H and Miao, J and Qin, C and Zhao, X and Yao, J and Liu, Z and Liao, B and Wei, Q and Li, X and Liu, J and Gao, AC and Huang, H and Shen, P and Chen, N and Zeng, H and Sun, G}, title = {Genomic and Evolutionary Characterization of Concurrent Intraductal Carcinoma and Adenocarcinoma of the Prostate.}, journal = {Cancer research}, volume = {84}, number = {1}, pages = {154-167}, doi = {10.1158/0008-5472.CAN-23-1176}, pmid = {37847513}, issn = {1538-7445}, support = {82203110//National Natural Science Foundation of China/ ; 82172785//National Natural Science Foundation of China/ ; 81974398//National Natural Science Foundation of China/ ; ZYJC21020//1.3.5 project for disciplines of excellence, West China Hospital, Sichuan University/ ; 2021YFS0119//Science and Technology Support Program of Sichuan Province/ ; 2022-12M-C&T-B-098//Clinical and Translational Medicine Research Project, Chinese Academy of Mediccal Sciences/ ; mnzl202002//Beijing Bethune Charitable Foundation/ ; mnzl202007//Beijing Bethune Charitable Foundation/ ; 2023HXBH024//Postdoctoral Research and Development Fund of West China Hospital of Sichuan University/ ; }, mesh = {Male ; Humans ; *Carcinoma, Intraductal, Noninfiltrating/genetics/pathology ; Prostate/pathology ; *Adenocarcinoma/genetics/pathology ; *Prostatic Neoplasms/pathology ; Genomics ; Neoplasm Grading ; }, abstract = {UNLABELLED: Intraductal carcinoma of the prostate (IDC-P) is a lethal prostate cancer subtype that generally coexists with invasive high-grade prostate acinar adenocarcinoma (PAC) but exhibits distinct biological features compared with concomitant adenocarcinoma. In this study, we performed whole-exome, RNA, and DNA-methylation sequencing of IDC-P, concurrent invasive high-grade PAC lesions, and adjacent normal prostate tissues isolated from 22 radical prostatectomy specimens. Three evolutionary patterns of concurrent IDC-P and PAC were identified: early divergent, late divergent, and clonally distant. In contrast to those with a late divergent evolutionary pattern, tumors with clonally distant and early divergent evolutionary patterns showed higher genomic, epigenomic, transcriptional, and pathologic heterogeneity between IDC-P and PAC. Compared with coexisting PAC, IDC-P displayed increased expression of adverse prognosis-associated genes. Survival analysis based on an independent cohort of 505 patients with metastatic prostate cancer revealed that IDC-P carriers with lower risk International Society of Urological Pathology (ISUP) grade 1-4 adenocarcinoma displayed a castration-resistant free survival as poor as those with the highest risk ISUP grade 5 tumors that lacked concurrent IDC-P. Furthermore, IDC-P exhibited robust cell-cycle progression and androgen receptor activities, characterized by an enrichment of cellular proliferation-associated master regulators and genes involved in intratumoral androgen biosynthesis. Overall, this study provides a molecular groundwork for the aggressive behavior of IDC-P and could help identify potential strategies to improve treatment of IDC-P.

SIGNIFICANCE: The genomic, transcriptomic, and epigenomic characterization of concurrent intraductal carcinoma and adenocarcinoma of the prostate deepens the biological understanding of this lethal disease and provides a genetic basis for developing targeted therapies.}, } @article {pmid37828835, year = {2023}, author = {Yang, SY and Zhang, J and Yang, ZQ and Duan, JJ and Zhang, Y and Li, MK and Wang, L and Ye, CM and Nie, JY}, title = {Advanced hormone receptor-positive/human epidermal growth factor receptor 2-positive invasive ductal carcinoma with cecal metastasis: A case report.}, journal = {Science progress}, volume = {106}, number = {4}, pages = {368504231201043}, pmid = {37828835}, issn = {2047-7163}, mesh = {Humans ; Female ; *Carcinoma, Ductal, Breast/drug therapy/metabolism/pathology ; *Breast Neoplasms/metabolism ; Receptor, ErbB-2/genetics/metabolism ; }, abstract = {The incidence of gastrointestinal metastases from breast cancer (BC) is low. We report a special case of Luminal B (Hormone Receptor positive [HR+]/Human Epidermal Growth Factor receptor 2-positive [HER-2+]) BC. The patient presented with asymptomatic brain metastases two years after radical surgery for modified breast cancer and developed right lower abdominal pain during relief therapy. Electronic gastroenteroscopy revealed inflammatory changes in the cecal mucosa. These changes were confirmed on pathology to be cecal metastasis from BC. The patient's condition was stabilised after treatment with an antibody-drug conjugate (ADC). For patients with BC who develop appendicitis-like symptoms after treatment for invasive ductal carcinoma of the breast, clinicians should be fully aware that the possibility of cecal metastasis needs to be considered, despite the very low probability of occurrence.}, } @article {pmid37824772, year = {2023}, author = {Dieu Vuong, L and Ngoc Nguyen, Q}, title = {ABERRANT METHYLATION OF CANCER-RELATED GENES IN VIETNAMESE BREAST CANCER PATIENTS: ASSOCIATIONS WITH CLINICOPATHOLOGICAL FEATURES.}, journal = {Experimental oncology}, volume = {45}, number = {2}, pages = {195-202}, doi = {10.15407/exp-oncology.2023.02.195}, pmid = {37824772}, issn = {2312-8852}, mesh = {Aged ; Female ; Humans ; *Breast Neoplasms/genetics/pathology ; DNA Methylation ; ErbB Receptors/genetics ; Promoter Regions, Genetic ; Southeast Asian People ; Epigenomics ; Vietnam ; }, abstract = {BACKGROUND: Epigenetic alteration is one of the most common molecular changes identified in the progression of breast cancer (BC).

AIM: To study the frequency and relation between methylation of BRCA1, MLH1, MGMT, GSTP1, APC, RASSF1A, p16, WIF, and EGFR and the clinicopathological features in Vietnamese BC patients.

MATERIALS AND METHODS: Methylation-specific polymerase chain reaction (MS-PCR) and SPSS 20.0 software were utilized in order to identify methylated frequency as well as evaluate its relationship with the patient's clinical features.

RESULTS: In 162 BC cases, the methylation rates of the selected genes were 53.7%, 22.8%, 38.9%, 34.6%, 29.0%, 46.3%, 20.4%, 18.5%, and 28.4% respectively. In 32 cases of benign breast diseases (BBD) - 12.5%, 15.6%, 6.3%, 3.1%, 12.5%, 21.9%, 3.1%, 15.6% and 3.1%. BC samples displayed higher BRCA1, MGMT, GSTP1, APC, RASSF1A, WIF1, and p16 methylation levels than BBD samples (p < 0.001). Hypermethylation of BRCA1, GSTP1, and RASSF1A was predominant in the invasive ductal carcinoma, while hypermethylation of BRCA1, GSTP1, RASSF1A, WIF-1, and p16 was found to significantly correlate with lymph node metastasis (p < 0.05). Hypermethylation of BRCA1, MGMT, and GSTP1 was more common in stage III (p < 0.05) than in stages I/II, whereas MLH1 methylation was predominant in stage I and APC methylation was less common in stage III (p = 0.03). In addition, methylation of RASSF1A and EGFR was more frequent in younger patients (p < 0.01) than in elder patients.

CONCLUSION: These data suggest that a gene panel (BRCA1/MGMT/GSTP1) can be used to support the diagnosis and screening of Vietnamese patients' BC with a sensitivity of 70%, and a specificity of 85%.}, } @article {pmid37747019, year = {2023}, author = {Choi, JH and Yu, J and Jung, M and Jekal, J and Kim, KS and Jung, SU}, title = {Prognostic significance of TP53 and PIK3CA mutations analyzed by next-generation sequencing in breast cancer.}, journal = {Medicine}, volume = {102}, number = {38}, pages = {e35267}, pmid = {37747019}, issn = {1536-5964}, mesh = {Humans ; Female ; Adult ; Middle Aged ; *Breast Neoplasms/genetics ; Prognosis ; Mastectomy ; High-Throughput Nucleotide Sequencing ; Class I Phosphatidylinositol 3-Kinases/genetics ; Tumor Suppressor Protein p53/genetics ; }, abstract = {Breast cancer is one of the most prevalent malignant tumors affecting women globally. It is a heterogeneous disease characterized by mutations in several genes. Several gene panels have been applied to assess the risk of breast cancer and determine the appropriate treatment. As a powerful tool, Next-generation sequencing (NGS) has been widely utilized in cancer research due to its advantages, including high speed, high throughput, and high accuracy. In this study, we aim to analyze the correlation between somatic mutations in breast cancer, analyzed using NGS, and the prognosis of patients. Between May 2018 and May 2019, a total of 313 patients with breast cancer underwent surgical treatment, which included total mastectomy and breast-conserving surgery. Among these patients, 265 were diagnosed with invasive ductal carcinoma. In this study, we analyzed the NGS results, clinicopathological characteristics, and their correlation with prognosis. Using a gene panel, we examined 143 somatic mutations in solid cancers. Notably, the study population included patients who had received neoadjuvant chemotherapy. The mean age of the patients was 53.1 (±10.28) years, and the median follow-up time was 48 months (range, 8-54). Among the 265 patients, 68 had received prior systemic therapy. Of these, 203 underwent breast-conserving surgery, and 62 underwent a mastectomy. Various somatic mutations were observed in NGS, with the most frequent mutation being PIK3CA mutations, which accounted for 44% of all mutations. TP53 mutations were the second most frequent, and ERBB2 mutations were the third most frequent. TP53 mutations were associated with poor disease-free survival (P = .027), while PIK3CA mutations were associated with better disease-free survival (P = .035) than PIK3CA wild-type. In our study, we identified various somatic mutations in breast cancer. Particularly, we found that TP53 and PIK3CA mutations are potentially associated with the prognosis of breast cancer. These findings suggest that the presence of specific mutations may have implications for predicting the prognosis of breast cancer. Further research and validation are needed to gain a deeper understanding of the role of these mutations and their mechanisms in prognosis prediction.}, } @article {pmid37738898, year = {2023}, author = {Peng, L and He, X and Peng, X and Li, Z and Zhang, L}, title = {STGNNks: Identifying cell types in spatial transcriptomics data based on graph neural network, denoising auto-encoder, and k-sums clustering.}, journal = {Computers in biology and medicine}, volume = {166}, number = {}, pages = {107440}, doi = {10.1016/j.compbiomed.2023.107440}, pmid = {37738898}, issn = {1879-0534}, mesh = {Humans ; Cluster Analysis ; *Transcriptome/genetics ; *Neural Networks, Computer ; Algorithms ; Gene Expression Profiling/methods ; Breast Neoplasms/genetics/pathology/metabolism ; }, abstract = {BACKGROUND: Spatial transcriptomics technologies fully utilize spatial location information, tissue morphological features, and transcriptional profiles. Integrating these data can greatly advance our understanding about cell biology in the morphological background.

METHODS: We developed an innovative spatial clustering method called STGNNks by combining graph neural network, denoising auto-encoder, and k-sums clustering. First, spatial resolved transcriptomics data are preprocessed and a hybrid adjacency matrix is constructed. Next, gene expressions and spatial context are integrated to learn spots' embedding features by a deep graph infomax-based graph convolutional network. Third, the learned features are mapped to a low-dimensional space through a zero-inflated negative binomial (ZINB)-based denoising auto-encoder. Fourth, a k-sums clustering algorithm is developed to identify spatial domains by combining k-means clustering and the ratio-cut clustering algorithms. Finally, it implements spatial trajectory inference, spatially variable gene identification, and differentially expressed gene detection based on the pseudo-space-time method on six 10x Genomics Visium datasets.

RESULTS: We compared our proposed STGNNks method with five other spatial clustering methods, CCST, Seurat, stLearn, Scanpy and SEDR. For the first time, four internal indicators in the area of machine learning, that is, silhouette coefficient, the Davies-Bouldin index, the Caliniski-Harabasz index, and the S_Dbw index, were used to measure the clustering performance of STGNNks with CCST, Seurat, stLearn, Scanpy and SEDR on five spatial transcriptomics datasets without labels (i.e., Adult Mouse Brain (FFPE), Adult Mouse Kidney (FFPE), Human Breast Cancer (Block A Section 2), Human Breast Cancer (FFPE), and Human Lymph Node). And two external indicators including adjusted Rand index (ARI) and normalized mutual information (NMI) were applied to evaluate the performance of the above six methods on Human Breast Cancer (Block A Section 1) with real labels. The comparison experiments elucidated that STGNNks obtained the smallest Davies-Bouldin and S_Dbw values and the largest Silhouette Coefficient, Caliniski-Harabasz, ARI and NMI, significantly outperforming the above five spatial transcriptomics analysis algorithms. Furthermore, we detected the top six spatially variable genes and the top five differentially expressed genes in each cluster on the above five unlabeled datasets. And the pseudo-space-time tree plot with hierarchical layout demonstrated a flow of Human Breast Cancer (Block A Section 1) progress in three clades branching from three invasive ductal carcinoma regions to multiple ductal carcinoma in situ sub-clusters.

CONCLUSION: We anticipate that STGNNks can efficiently improve spatial transcriptomics data analysis and further boost the diagnosis and therapy of related diseases. The codes are publicly available at https://github.com/plhhnu/STGNNks.}, } @article {pmid37705411, year = {2023}, author = {McMurtry, V and Cleary, AS and Ruano, AL and Lomo, L and Gulbahce, HE}, title = {Metaplastic Breast Carcinoma: Clinicopathologic Features and Recurrence Score Results From a Population-based Database.}, journal = {American journal of clinical oncology}, volume = {46}, number = {12}, pages = {559-566}, doi = {10.1097/COC.0000000000001041}, pmid = {37705411}, issn = {1537-453X}, mesh = {Humans ; Female ; *Carcinoma, Ductal, Breast/genetics ; *Breast Neoplasms/genetics/epidemiology ; Proportional Hazards Models ; SEER Program ; Registries ; Prognosis ; }, abstract = {OBJECTIVES: Metaplastic breast carcinoma (MBC) is a rare, aggressive form of cancer comprising epithelial and mesenchymal elements. The purpose of this study was to use population-based data to review the clinicopathologic, molecular features, and outcomes of MBC.

METHODS: Surveillance, Epidemiology, and End Results Program (SEER) data were used to identify MBC and invasive ductal carcinoma (IDC), no special type (NOS) between 2004 and 2015. Results from Oncotype DX's 21-gene assay linked to SEER registries were included for hormone receptor (HR)-positive tumors. χ 2 analysis was performed to determine the differences between MBC and IDC. Kaplan-Meier curves and multivariate Cox proportional hazards models were used for breast cancer specific death (BCSD).

RESULTS: Compared with IDC, NOS (n=509,864), MBC (n=3876) were more likely to present at an older age, be black, have negative lymph nodes, be >2 cm, grade 3, and triple negative (TN). All subtypes [HR-positive/human epidermal growth receptor 2 (HER2)-negative, HR-positive/HER2-positive, HR-negative/HER2-positive, and TN] had higher BCSD than IDC, NOS. 22.3% of MBC cases were HR-positive. HR-positive MBCs tested for a recurrence score (RS) 65% were high-risk compared with 16.8% of IDC, NOS. Within the MBC cohort, no significant differences in BCSD were identified with respect to different molecular subtypes. In a fully adjusted model, TN or HER2-positive status did not adversely affect BCSD compared with HR-positive MBC.

CONCLUSIONS: All molecular subtypes of MBC had a poorer prognosis compared with IDC, NOS. The different molecular subtypes of MBC did not affect the BCSD. HR-positive MBC patients had a significantly higher high-risk RS than IDC, NOS patients.}, } @article {pmid37635979, year = {2023}, author = {Barlier, A and Romanet, P and Pellegata, NS}, title = {Editorial: New insights into multiple endocrine neoplasia type 1.}, journal = {Frontiers in endocrinology}, volume = {14}, number = {}, pages = {1266148}, pmid = {37635979}, issn = {1664-2392}, mesh = {Humans ; *Multiple Endocrine Neoplasia Type 1/genetics ; }, } @article {pmid37608749, year = {2023}, author = {Ito, T and Takahara, T and Taniguchi, N and Yamamoto, Y and Satou, A and Ohashi, A and Takahashi, E and Sassa, N and Tsuzuki, T}, title = {PTEN loss in intraductal carcinoma of the prostate has low incidence in Japanese patients.}, journal = {Pathology international}, volume = {73}, number = {11}, pages = {542-548}, doi = {10.1111/pin.13369}, pmid = {37608749}, issn = {1440-1827}, support = {21K06933//Japan Society for the Promotion of Science/ ; 21K15392//Japan Society for the Promotion of Science/ ; }, mesh = {Male ; Humans ; Prostate/pathology ; *Carcinoma, Intraductal, Noninfiltrating/pathology ; Incidence ; East Asian People ; *Prostatic Neoplasms/pathology ; PTEN Phosphohydrolase/genetics/metabolism ; }, abstract = {Clinical and genomic features of prostate cancer (PCa) vary considerably between Asian and Western populations. PTEN loss is the most frequent abnormality in intraductal carcinoma of the prostate (IDC-P) in Western populations. However, its prevalence and significance in Asian populations have not yet been well studied. In the present study, we evaluated PTEN expression in IDC-P in a Japanese population and its association with ERG expression. This study included 45 and 59 patients with PCa with and without IDC-P, respectively, who underwent radical prostatectomy. PTEN loss was observed in 10 patients with PCa with IDC-P (22%) and nine patients with PCa without IDC-P (17%). ERG expression was relatively frequent in patients with PCa with PTEN loss, although a significant difference was not observed. The co-occurrence of PTEN loss and ERG expression was observed in four patients with PCa with IDC-P and one without IDC-P. PTEN loss and ERG expression did not affect progression-free survival, regardless of the presence of IDC-P. The frequency of PTEN loss in IDC-P is lower in Asian patients than in Western patients. Our results indicate that mechanisms underlying IDC-P in Asian populations are different from those of Western populations.}, } @article {pmid37558640, year = {2023}, author = {Doi, K and Fujii, T and Hanamoto, M and Takamura, K and Nakada, T and Sato, Y and Ogura, K}, title = {[A Case of BRCA2 Mutation-Positive Intraductal Carcinoma of the Prostate].}, journal = {Hinyokika kiyo. Acta urologica Japonica}, volume = {69}, number = {7}, pages = {189-192}, doi = {10.14989/ActaUrolJap_69_7_189}, pmid = {37558640}, issn = {0018-1994}, mesh = {Male ; Humans ; Aged ; Prostate/pathology ; *Carcinoma, Intraductal, Noninfiltrating/pathology/surgery ; Prostate-Specific Antigen ; Hematuria ; *Prostatic Neoplasms/drug therapy/genetics/pathology ; Disease Progression ; Mutation ; *Prostatic Neoplasms, Castration-Resistant/drug therapy/genetics/pathology ; BRCA2 Protein/genetics ; }, abstract = {A 75-year-old man presented with macroscopic hematuria and a high serum prostate-specific antigen (PSA) level. Macroscopic hematuria had subsided by the time of consultation. The PSA level was 38.590 ng/ml, which, along with rectal examination and magnetic resonance imaging findings, led to the suspicion of prostate cancer. Transrectal needle biopsy of the prostate revealed intraductal carcinoma of the prostate (IDC-P). Computed tomography and bone scintigraphy were performed, and the prostate cancer was classified as cT2cN0M0. After 6 months of combined androgen blockade therapy, a radical prostatectomy was performed; however, PSA levels continued to increase, and the patient was diagnosed with castration resistant prostate cancer. Multiple bone metastases appeared 5 months after the initiation of abiraterone therapy. Three courses of docetaxel and two courses of cabazitaxel were administered, but the disease progression continued. The IDC-P was found to be positive for the BRCA2 mutation by BRACAnalysis® performed at the start of cabazitaxel therapy. To our knowledge, no other cases of BRCA2 mutation positive IDC-P have been reported in Japan. After we started administration of Olaparib, the patient's PSA level was lowered and the disease progression stopped.}, } @article {pmid37536436, year = {2023}, author = {Abdollahi, E and Mozdarani, H}, title = {Epigenetic regulation of circ-HIPK3, circ-PVT1, miR-25, and miR-149 in radiosensitivity of breast cancer.}, journal = {Experimental and molecular pathology}, volume = {132-133}, number = {}, pages = {104865}, doi = {10.1016/j.yexmp.2023.104865}, pmid = {37536436}, issn = {1096-0945}, mesh = {Humans ; Female ; Adult ; Middle Aged ; *Breast Neoplasms/genetics/radiotherapy ; Epigenesis, Genetic ; Leukocytes, Mononuclear ; Radiation Tolerance/genetics ; *MicroRNAs/genetics ; Cell Proliferation ; Protein Serine-Threonine Kinases ; Intracellular Signaling Peptides and Proteins ; }, abstract = {Assessing the radiosensitivity of cells before administering radiation therapy (RT) to individuals diagnosed with breast cancer (BC) can facilitate the selection of appropriate treatment regimens and minimize the incidence of adverse side effects in patients undergoing radiation exposure. In this research, blood samples were obtained from 60 women who had been diagnosed with Invasive Ductal Carcinoma (IDC) Breast Cancer. The average age of the patients was 47 ± 9.93. Additionally, the study incorporated 20 healthy women, with an average age of 44.43 ± 6.7. A standard G2 assay was conducted to predict the cellular response to radiation. Out of the 60 samples, the G2 assay identified 20 patients with breast cancer who exhibited radiosensitivity. Hence, molecular investigations were ultimately conducted on two equivalent cohorts comprising 20 subjects each, one with and the other without cellular radiosensitivity. The expression levels of miR-149, miR-25, circ-PVT1, and circ-HIPK3 in peripheral blood mononuclear cells (PBMCs) were evaluated using quantitative polymerase chain reaction (qPCR). Receiver Operating Characteristic (ROC) curves were used to evaluate the sensitivity and specificity of the RNAs. An analysis using binary logistic regression was performed to investigate the relationship between RNAs and both BC and cellular radiosensitivity (CR) in patients with BC. The findings revealed a significant upregulation of Circ-HIPK3 and circ-PVT1 in individuals diagnosed with BC. The levels of Circ-HIPK3 and Circ-PVT1 were found to be directly associated with CR in BC patients. The analysis of the ROC curve demonstrated that circ-HIPK3 and circ-PVT1 exhibit favorable specificity and sensitivity in accurately predicting both BC and CR in patients with BC. The findings from the binary logistic regression analysis demonstrated that circ-HIPK3 and circ-PVT1 were effective predictors of both BC and CR. The ROC curve and binary logistic regression analyses provide evidence that miR-25 is a reliable predictor for BC patients exclusively. Our research has demonstrated that circ-HIPK3, circ-PVT1, and miR-25 may be involved in BC regulatory processes. The circular RNAs Circ-HIPK3 and circ-PVT1, as well as miR-25, among other significant biomarkers, could potentially serve as promising biomarkers for predicting BC. Furthermore, Circ-HIPK3 and circ-PVT1 have the potential to serve as biomarkers for predicting CR in BC patients.}, } @article {pmid37530324, year = {2023}, author = {Cakir, Y and Talu, CK and Trabulus, DC and Mermut, O}, title = {The immunohistochemical Galectin-3 expression in tumor and cancer-associated fibroblasts in invasive ductal carcinomas of breast and their relationship with clinicopathological parameters.}, journal = {Indian journal of pathology & microbiology}, volume = {66}, number = {3}, pages = {456-464}, doi = {10.4103/ijpm.ijpm_284_21}, pmid = {37530324}, issn = {0974-5130}, mesh = {Humans ; Female ; *Cancer-Associated Fibroblasts/metabolism/pathology ; Galectin 3/genetics ; *Triple Negative Breast Neoplasms/pathology ; Retrospective Studies ; *Carcinoma, Ductal ; *Breast Neoplasms ; Biomarkers, Tumor/metabolism ; }, abstract = {BACKGROUND: Galectin-3 has an important role in metastasis, therefore, Galectin-3-focused therapies have attracted attention for various cancers.

AIM: We aimed to reveal the relationship between the expression of Galectin-3 within the tumor/cancer-associated fibroblasts (CAF) and clinicopathological parameters in patients with invasive ductal carcinomas.

MATERIALS AND METHODS: Hematoxylin and eosin-stained slides of breast excision materials diagnosed between 2010 and 2016 were re-examined retrospectively. Accordingly, 118 cases (luminal group = 58, Human epidermal growth factor receptor 2 (HER2) group = 27, and triple-negative breast carcinoma group [TNBC] =33 cases) were included. Galectin-3 levels were evaluated with a calculated H-score in tumor and semiquantitatively in CAFs.

STATISTICAL ANALYSIS: Data was analyzed with t-tests and Chi-square tests. Kaplan-Meier and Log-rank tests were used for survival analysis.

RESULTS: The presence of Galectin-3 expression in CAFs but not in the tumor was associated with the greater number of axillary metastatic nodes and advanced pN stage. The loss of Galectin-3 expression in CAFs was more frequent in TNBC. There was no significant relationship between the expression level of Galectin-3 and survival status. However, in most of the cases with distant metastasis or patients who died, Galectin-3 was negative in the tumor, whereas it was positive in CAFs.

CONCLUSIONS: The expression of Galectin-3 in tumors and CAFs may have a role in metastasis to axillary lymph nodes and distant sites. In terms of molecular subtype, TNBCs show a relationship with Galectin-3 negativity in CAFs.}, } @article {pmid37495452, year = {2023}, author = {Bódis, K and Bombrich, M and Schön, M and Knebel, B and Zaharia, OP and Bönhof, G and Karusheva, Y and Strassburger, K and Kupriyanova, Y and Kotzka, J and Guthoff, R and Schrauwen-Hinderling, V and Al-Hasani, H and Burkart, V and Szendroedi, J and Wagner, R and Markgraf, DF and Roden, M and , }, title = {Effects of TM6SF2 rs58542926 polymorphism on hepatocellular lipids and insulin resistance in early type 2 diabetes.}, journal = {Nutrition, metabolism, and cardiovascular diseases : NMCD}, volume = {33}, number = {9}, pages = {1785-1796}, doi = {10.1016/j.numecd.2023.06.004}, pmid = {37495452}, issn = {1590-3729}, mesh = {Humans ; Male ; Case-Control Studies ; *Diabetes Mellitus, Type 2/diagnosis/genetics/complications ; *Insulin Resistance/genetics ; Liver/metabolism ; *Liver Neoplasms ; Membrane Proteins/genetics/metabolism ; *Non-alcoholic Fatty Liver Disease/diagnosis/genetics/complications ; Polymorphism, Single Nucleotide ; Triglycerides/metabolism ; }, abstract = {BACKGROUND AND AIMS: Increased hepatocellular lipid content (HCL) is linked to insulin resistance, risk of type 2 diabetes and related complications. Conversely, a single-nucleotide polymorphism (TM6SF2[EK]; rs58542926) in the transmembrane 6 superfamily member 2-gene has been associated with nonalcoholic fatty liver disease (NAFLD), but lower cardiovascular risk. This case-control study tested the role of this polymorphism for tissue-specific insulin sensitivity during early course of diabetes.

METHODS AND RESULTS: Males with recent-onset type 2 diabetes with (TM6SF2[EK]: n = 16) or without (TM6SF2[EE]: n = 16) the heterozygous TM6SF2-polymorphism of similar age and body mass index, underwent Botnia-clamps with [6,6-[2]H2]glucose to measure whole-body-, hepatic- and adipose tissue-insulin sensitivity. HCL was assessed with [1]H-magnetic-resonance-spectroscopy. A subset of both groups (n = 24) was re-evaluated after 5 years. Despite doubled HCL, TM6SF2[EK] had similar hepatic- and adipose tissue-insulin sensitivity and 27% higher whole-body-insulin sensitivity than TM6SF2[EE]. After 5 years, whole-body-insulin sensitivity, HCL were similar between groups, while adipose tissue-insulin sensitivity decreased by 87% and 55% within both groups and circulating triacylglycerol increased in TM6SF2[EE] only.

CONCLUSIONS: The TM6SF2-polymorphism rs58542926 dissociates HCL from insulin resistance in recent-onset type 2 diabetes, which is attenuated by disease duration. This suggests that diabetes-related metabolic alterations dominate over effects of the TM6SF2-polymorphism during early course of diabetes and NAFLD.}, } @article {pmid37478120, year = {2023}, author = {Shi, K and Liu, XL and Guo, Q and Zhang, YQ and Fan, ST and Dai, L and Jiang, N and Li, D}, title = {TMEM41A overexpression correlates with poor prognosis and immune alterations in patients with endometrial carcinoma.}, journal = {PloS one}, volume = {18}, number = {7}, pages = {e0285817}, pmid = {37478120}, issn = {1932-6203}, mesh = {Female ; Humans ; Biomarkers, Tumor/genetics/metabolism ; *Endometrial Neoplasms/pathology ; Nomograms ; Prognosis ; RNA ; Tumor Microenvironment/genetics ; }, abstract = {BACKGROUND: Expression levels of transmembrane protein 41A (TMEM41A) are related to the progression of malignant tumors. However, the association between TMEM41A expression and endometrial carcinoma (EC) remains unclear. This study aims to identify the roles of TMEM41A expression in the prognosis of patients with EC and its correlation with EC progression.

METHODS: The TMEM41A expression and its correlation with the survival of patients with EC were assessed. Cox regression analysis was used to identify the prognostic factors, while nomograms were used to examine the association between the prognostic factors and the survival of patients with EC. Finally, the link between TMEM41A level and immune microenvironment and RNA modifications was investigated in EC.

RESULTS: TMEM41A was overexpressed in EC. TMEM41A overexpression could diagnose the EC and evaluate the poor prognosis of patients. Overexpression of TMEM41A was associated with clinical stage, age, weight, histological subtype, tumor grade, and survival status of patients with EC. Clinical stage, age, tumor grade, radiotherapy, and TMEM41A overexpression were factors of poor prognosis in patients with EC. The nomograms revealed the correlation between the TMEM41A level and survival time of patients with EC at 1, 3, and 5 years. Furthermore, TMEM41A overexpression was significantly correlated with the level of the stromal score, immune score, estimate score, NK CD56 bright cells, iDC, NK cells, eosinophils, pDC, T cells, TReg, cytotoxic cells, mast cells, Th17 cells, neutrophils, aDC, NK CD56 dim cells, TFH, Th2 cells, CD8 T cells, macrophages, immune cell markers, and RNA modifications.

CONCLUSIONS: TMEM41A is overexpressed in EC tissues and is associated with the prognosis, immune microenvironment, and RNA modification. Our preliminary studies indicate that overexpression of TMEM41A can potentially serve as a biomarker for EC treatment.}, } @article {pmid37474400, year = {2024}, author = {Chappidi, MR and Sjöström, M and Greenland, NY and Cowan, JE and Baskin, AS and Shee, K and Simko, JP and Chan, E and Stohr, BA and Washington, SL and Nguyen, HG and Quigley, DA and Davicioni, E and Feng, FY and Carroll, PR and Cooperberg, MR}, title = {Transcriptomic Heterogeneity of Expansile Cribriform and Other Gleason Pattern 4 Prostate Cancer Subtypes.}, journal = {European urology oncology}, volume = {7}, number = {2}, pages = {222-230}, doi = {10.1016/j.euo.2023.06.007}, pmid = {37474400}, issn = {2588-9311}, mesh = {Male ; Humans ; *Prostate-Specific Antigen ; Retrospective Studies ; Transcriptome ; *Prostatic Neoplasms/genetics/surgery/pathology ; Gene Expression Profiling ; }, abstract = {BACKGROUND: Prostate cancers featuring an expansile cribriform (EC) pattern are associated with worse clinical outcomes following radical prostatectomy (RP). However, studies of the genomic characteristics of Gleason pattern 4 subtypes are limited.

OBJECTIVE: To explore transcriptomic characteristics and heterogeneity within Gleason pattern 4 subtypes (fused/poorly formed, glomeruloid, small cribriform, EC/intraductal carcinoma [IDC]) and the association with biochemical recurrence (BCR)-free survival.

This was a retrospective cohort study including 165 men with grade group 2-4 prostate cancer who underwent RP at a single academic institution (2016-2020) and Decipher testing of the RP specimen. Patients with Gleason pattern 5 were excluded. IDC and EC patterns were grouped. Median follow-up was 2.5 yr after RP for patients without BCR.

Prompted by heterogeneity within pattern 4 subtypes identified via exploratory analyses, we investigated transcriptomic consensus clusters using partitioning around medoids and hallmark gene set scores. The primary clinical outcome was BCR, defined as two consecutive prostate-specific antigen measurements >0.2 ng/ml at least 8 wk after RP, or any additional treatment. Multivariable Cox proportional-hazards models were used to determine factors associated with BCR-free survival.

RESULTS AND LIMITATIONS: In this cohort, 99/165 patients (60%) had EC and 67 experienced BCR. Exploratory analyses and clustering demonstrated transcriptomic heterogeneity within each Gleason pattern 4 subtype. In the multivariable model controlled for pattern 4 subtype, margin status, Cancer of the Prostate Risk Assessment Post-Surgical score, and Decipher score, a newly identified steroid hormone-driven cluster (hazard ratio 2.35 95% confidence interval 1.01-5.47) was associated with worse BCR-free survival. The study is limited by intermediate follow-up, no validation cohort, and lack of accounting for intratumoral and intraprostatic heterogeneity.

CONCLUSIONS: Transcriptomic heterogeneity was present within and across each Gleason pattern 4 subtype, demonstrating there is additional biologic diversity not captured by histologic subtypes. This heterogeneity can be used to develop novel signatures and to classify transcriptomic subtypes, which may help in refining risk stratification following RP to further guide decision-making on adjuvant and salvage treatments.

PATIENT SUMMARY: We studied prostatectomy specimens and found that tumors with similar microscopic appearance can have genetic differences that may help to predict outcomes after prostatectomy for prostate cancer. Our results demonstrate that further gene expression analysis of prostate cancer subtypes may improve risk stratification after prostatectomy. Future studies are needed to develop novel gene expression signatures and validate these findings in independent sets of patients.}, } @article {pmid37470893, year = {2023}, author = {Chen, BF and Tsai, YF and Lien, PJ and Lin, YS and Feng, CJ and Chen, YJ and Cheng, HF and Tseng, LM and Huang, CC}, title = {Clinical characteristics and treatment outcomes of invasive ductal and lobular carcinoma: analyses of 54,832 taiwan cancer registry index cases.}, journal = {Breast cancer research and treatment}, volume = {201}, number = {3}, pages = {547-560}, pmid = {37470893}, issn = {1573-7217}, support = {V110E-005-3//Taipei Veterans General Hospital/ ; V111E-006-3//Taipei Veterans General Hospital/ ; V112E-004-3//Taipei Veterans General Hospital/ ; }, mesh = {Humans ; Female ; *Carcinoma, Lobular/pathology ; *Breast Neoplasms/epidemiology/genetics/therapy ; *Carcinoma, Ductal, Breast/therapy/drug therapy ; Taiwan/epidemiology ; Mastectomy ; Neoplasm Recurrence, Local/pathology ; Treatment Outcome ; Registries ; Retrospective Studies ; }, abstract = {PURPOSE: Invasive lobular cancer (ILC) is the second most common histology type of breast cancer followed by invasive ductal carcinoma (IDC). This study aimed to investigate the characteristic, treatment strategies, and clinical outcomes of ILC based on a national population-based cancer registry.

METHODS: This study recruited 2671 ILC and 52,215 IDC patients diagnosed between 2011 and 2017 using the Taiwan Cancer Registry (TCR). Correlations between ILC and IDC subgroups were assessed using 1:4 propensity score matching and compared using the χ2 test. Disease free survival(DFS) and overall survival(OS) were estimated using the Kaplan-Meier method with the log-rank test. The risk of disease relapse and mortality were assessed using Cox proportional hazards model.

RESULTS: ILC patients had larger tumor sizes, more positive axillary lymph node involvement, lower tumor grade, and higher cancer stage than IDC patients. After matching, ILC patients had a significantly higher rate of receiving mastectomy (58.93% and 53.85%) and positive surgical margin regardless of surgery type. ILC exhibited a significantly higher rate of distant metastasis than IDC(3.67% and 2.93%), but no difference in local recurrence rate, DFS or OS between the two groups. Higher cancer stage, higher grade, and mastectomy were risk factors for disease relapse and cancer-specific mortality. The hormone receptor-positive and HER2 over-expression subtypes were found to be associated with a reduced risk of disease relapse, while only PR positivity was associated with a decreased risk of mortality. (all P-values < 0.05).

CONCLUSION: ILC patients had a higher mastectomy rate, higher surgical margin rate and distant metastasis rate than IDC patients. There is no significant difference in DFS or OS between ILC and IDC patients. Mastectomy was associated with poor outcomes regardless of ILC or IDC.}, } @article {pmid37439959, year = {2023}, author = {Tsunokake, S and Iwabuchi, E and Miki, Y and Kanai, A and Onodera, Y and Sasano, H and Ishida, T and Suzuki, T}, title = {SGLT1 as an adverse prognostic factor in invasive ductal carcinoma of the breast.}, journal = {Breast cancer research and treatment}, volume = {201}, number = {3}, pages = {499-513}, pmid = {37439959}, issn = {1573-7217}, mesh = {Humans ; Female ; *Sodium-Glucose Transporter 2 Inhibitors/pharmacology/therapeutic use ; Sodium-Glucose Transporter 2/metabolism ; Prognosis ; Vascular Endothelial Growth Factor A/metabolism ; *Breast Neoplasms/drug therapy/genetics ; Glucose/metabolism ; *Carcinoma, Ductal ; }, abstract = {PURPOSE: Sodium/glucose cotransporter (SGLT) 1 and 2 expression in carcinoma cells was recently examined, but their association with the clinicopathological factors of the patients and their biological effects on breast carcinoma cells have remained remain virtually unknown. Therefore, in this study, we explored the expression status of SGLT1 and SGLT2 in breast cancer patients and examined the effects of SGLT1 inhibitors on breast carcinoma cells in vitro.

METHODS: SGLT1 and SGLT2 were immunolocalized and we first correlated the findings with clinicopathological factors of the patients. We then administered mizagliflozin and KGA-2727, SGLT1 specific inhibitors to MCF-7 and MDA-MB-468 breast carcinoma cell lines, and their growth-inhibitory effects were examined. Protein arrays were then used to further explore their effects on the growth factors.

RESULTS: The SGLT1 high group had significantly worse clinical outcome including both overall survival and disease-free survival than low group. SGLT2 status was not significantly correlated with clinical outcome of the patients. Both mizagliflozin and KGA-2727 inhibited the growth of breast cancer cell lines. Of particular interest, mizagliflozin inhibited the proliferation of MCF-7 cells, even under very low glucose conditions. Mizagliflozin downregulated vascular endothelial growth factor receptor 2 phosphorylation.

CONCLUSION: High SGLT1 expression turned out as an adverse clinical prognostic factor in breast cancer patient. This is the first study demonstrating that SGLT1 inhibitors suppressed breast carcinoma cell proliferation. These results indicated that SGLT1 inhibitors could be used as therapeutic agents for breast cancer patients with aggressive biological behaviors.}, } @article {pmid37385107, year = {2023}, author = {Chen, J and Gao, P and Xiao, W and Cheng, G and Krishna, S and Wang, J and Wong, YK and Wang, C and Gu, L and Yang, DH and Wang, J}, title = {Multi-omics dissection of stage-specific artemisinin tolerance mechanisms in Kelch13-mutant Plasmodium falciparum.}, journal = {Drug resistance updates : reviews and commentaries in antimicrobial and anticancer chemotherapy}, volume = {70}, number = {}, pages = {100978}, doi = {10.1016/j.drup.2023.100978}, pmid = {37385107}, issn = {1532-2084}, mesh = {Humans ; Plasmodium falciparum/genetics ; Multiomics ; Drug Resistance/genetics ; Protozoan Proteins/genetics/pharmacology/therapeutic use ; *Artemisinins/pharmacology/therapeutic use ; *Antimalarials/pharmacology/therapeutic use ; *Malaria, Falciparum/drug therapy/parasitology ; Mutation ; }, abstract = {AIMS: We investigated the stage-specific mechanisms of partial resistance to artemisinin (ART, an antimalarial drug) in Plasmodium falciparum (P. falciparum) carrying the Kelch13 C580Y mutation.

METHODS: Using fluorescence labeling and activity-based protein profiling, we systematically profile the ART activation levels in P. falciparum during the entire intra-erythrocytic developmental cycle (IDC), and determined the ART-targets profile of the ART-sensitive and -resistant strains at different stages. We retrieved and integrated datasets of single-cell transcriptomics and label-free proteomics across three IDC stages of wild-type P. falciparum. We also employed lipidomics to validate lipid metabolic reprogramming in the resistant strain.

RESULTS: The activation and expression patterns of genes and proteins of ART-targets in both ART-sensitive and resistant strains varied at different stages and periods of P. falciparum development, with the late trophozoite stage harboring the largest number of ART targets. We identified and validated 36 overlapping targets, such as GAPDH, EGF-1a, and SpdSyn, during the IDC stages in both strains. We revealed the ART-insensitivity of fatty acid-associated activities in the partially resistant strain at both the early ring and early trophozoite stages.

CONCLUSIONS: Our multi-omics strategies provide novel insights into the mechanisms of ART partial resistance in Kelch13 mutant P. falciparum, demonstrating the stage-specific interaction between ART and malaria parasites.}, } @article {pmid37301537, year = {2023}, author = {Wu, K and Li, W and Liu, H and Niu, C and Shi, Q and Zhang, J and Gao, G and Sun, H and Liu, F and Fu, L}, title = {Metabolome Sequencing Reveals that Protein Arginine-N-Methyltransferase 1 Promotes the Progression of Invasive Micropapillary Carcinoma of the Breast and Predicts a Poor Prognosis.}, journal = {The American journal of pathology}, volume = {193}, number = {9}, pages = {1267-1283}, doi = {10.1016/j.ajpath.2023.05.010}, pmid = {37301537}, issn = {1525-2191}, mesh = {Humans ; Female ; *Carcinoma, Ductal, Breast/metabolism ; Disease-Free Survival ; *Carcinoma, Papillary/pathology ; *Breast Neoplasms/metabolism ; Metabolome ; Methyltransferases/metabolism ; Prognosis ; Protein-Arginine N-Methyltransferases/genetics/metabolism ; Repressor Proteins/metabolism ; }, abstract = {Invasive micropapillary carcinoma (IMPC) of the breast is a special histopathologic type of cancer with a high recurrence rate and the biological features of invasion and metastasis. Previous spatial transcriptome studies indicated extensive metabolic reprogramming in IMPC, which contributes to tumor cell heterogeneity. However, the impact of metabolome alterations on IMPC biological behavior is unclear. Herein, endogenous metabolite-targeted metabolomic analysis was done on frozen tumor tissue samples from 25 patients with breast IMPC and 34 patients with invasive ductal carcinoma not otherwise specified (IDC-NOS) by liquid chromatography-mass spectrometry. An IMPC-like state, which is an intermediate transitional morphologic phenotype between IMPC and IDC-NOS, was observed. The metabolic type of IMPC and IDC-NOS was related to breast cancer molecular type. Arginine methylation modification and 4-hydroxy-phenylpyruvate metabolic changes play a major role in the metabolic reprogramming of IMPC. High protein arginine-N-methyltransferase (PRMT) 1 expression was an independent factor related to the poor prognosis of patients with IMPC in terms of disease-free survival. PRMT1 promoted H4R3me2a, which induced tumor cell proliferation via cell cycle regulation and facilitated tumor cell metastasis via the tumor necrosis factor signaling pathway. This study identified the metabolic type-related features and intermediate transition morphology of IMPC. The identification of potential targets of PRMT1 has the potential to provide a basis for the precise diagnosis and treatment of breast IMPC.}, } @article {pmid37283256, year = {2023}, author = {Bukamal, Z and AlRayes, A}, title = {Prevalence of BRCA1 and BRCA2 Mutations Among High-risk Bahraini Patients with Breast Cancer.}, journal = {The Gulf journal of oncology}, volume = {1}, number = {42}, pages = {22-25}, pmid = {37283256}, issn = {2078-2101}, mesh = {Humans ; Female ; Male ; *Breast Neoplasms/epidemiology/genetics/diagnosis ; Bahrain/epidemiology ; Retrospective Studies ; Prevalence ; Mutation ; *Carcinoma, Ductal ; BRCA1 Protein/genetics ; BRCA2 Protein/genetics ; }, abstract = {OBJECTIVE: The purpose is to study the prevalence of BRCA1 and BRCA2 mutations in high-risk Bahraini patients diagnosed with breast cancer, its relation to family history, and to determine the clinicopathologic features of breast cancer associated with these genetic mutations, over a period of 7 years.

BACKGROUND: Breast cancer is the most common type of cancer occurring in women and the second most common type generally. Approximately 12% of women worldwide will develop carcinoma of the breast sometime during their life. Additionally, 72% of women with an inherited BRCA1 mutation and 69% of those with a mutated BRCA2 will develop breast cancer by 80 years of age. The incidence of breast cancer in Bahraini women have increased over the last decade. Still, the data on BRCA1 & BRCA2 mutations in relation to breast cancer patients is limited in the Arab region, not omitting Bahrain as a country with deficient BRCA prevalence data.

METHODS: This retrospective study was carried out in Salmaniya Medical Complex, Bahrain, to determine the prevalence of BRCA1 and BRCA2 mutations and to observe the breast cancer's histopathologic features that are associated with these mutations.

RESULTS: 271 patients underwent the BRCA gene testing between 2013 and 2019. Out of 271 patients, 35 were excluded. Out of the 236 breast cancer patients, 219 (93%) did not have the mutation. The BRCA gene was carried by a total of 17 (7%) patients; 13 (5%) BRCA1 and 4 (2%) BRCA2. Thirteen BRCA carrier patients had invasive ductal carcinoma (IDC) (76%), 2 had ductal carcinoma in situ (DCIS) (12%), while 2 patients' histopathology was not available. Molecular subtypes showed 4 triple negative basal sub-type (TNBC), 10 positive ER and PR hormonal status, 1 positive HER-2, while 2 patients' hormonal receptor status was not available. Two BRCA1 carriers had both breast and ovarian cancers. A total of 5 (2%) breast cancer male patients were among the tested population, out of which, 1 (0.4% of the total and 20% of the male patients) was a BRCA2 carrier. Out of the 236 patients, 76 (32%) were younger than 40 years of age at the time of diagnosis. Then again, out of the 17 BRCA carrier patients, 7 (41%) were younger than 40 years.

CONCLUSION: The prevalence of BRCA mutation in high risk Bahraini breast cancer patients is 7%. Among those patients, BRCA1 mutation is the most prevalent (5%) and invasive ductal carcinoma (IDC) is the most common histopathological subtype. However, there was not enough data to conclude the most prevalent molecular subtype of breast cancer in BRCA carriers due to deficiency of overseas pathology reports for patients operated outside Bahrain. When developing treatment plans for younger patients with breast cancer, inherited syndromes and precisely BRCA mutations need to be considered. Bahrain is implementing genetic testing for breast cancer patients ≤ 50 years of age since 2018, according to NCCN guidelines. We will continue to build our database to better characterize breast cancer subtypes and determine their hereditary pattern for identification of high risk families in Bahrain and for future development of more specific therapeutic approaches.

KEY WORDS: Breast cancer, BRCA1, BRCA2, BRCA mutation, Bahrain, Arab region.}, } @article {pmid37246414, year = {2023}, author = {Lee, J and Park, S and Jung, HA and Lee, SH and Seo, S and Kim, SB and Kim, JW and Lee, KW and Kang, EJ and Kim, JW and Choi, YJ and Shim, BY and An, HJ and Park, LC and Shin, SH and Kim, JJ and Oh, SY and Kim, MK and Ahn, MJ}, title = {A phase 2 multicenter study of docetaxel-PM and trastuzumab-pkrb combination therapy in recurrent or metastatic salivary gland carcinomas.}, journal = {Cancer}, volume = {129}, number = {19}, pages = {2966-2974}, doi = {10.1002/cncr.34892}, pmid = {37246414}, issn = {1097-0142}, mesh = {Humans ; Female ; Docetaxel/therapeutic use ; Micelles ; Antibodies, Monoclonal, Humanized/therapeutic use ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Trastuzumab/therapeutic use ; Receptor, ErbB-2/genetics/metabolism ; *Carcinoma, Ductal ; Salivary Glands/metabolism ; *Breast Neoplasms/drug therapy ; }, abstract = {BACKGROUND: Salivary duct carcinoma (SDC) is uncommon but is the most aggressive subtype of salivary gland carcinomas. The high positivity rate for human epidermal growth factor receptor 2 (HER2) led to an investigation of the efficacy of HER2-targeted agents. Docetaxel-PM (polymeric micelle) is a low-molecular-weight, nontoxic, biodegradable, and docetaxel-loaded micellar formulation. Trastuzumab-pkrb is a biosimilar to trastuzumab.

METHODS: This was a multicenter, single-arm, open-label phase 2 study. Patients with HER2-positive (immunohistochemistry [IHC] score of ≥2+ and/or HER2/chromosome enumeration probe 17 [CEP17] ratio of ≥2.0) advanced SDCs were enrolled. Patients received docetaxel-PM (75 mg/m[2]) and trastuzumab-pkrb (8 mg/kg in the first cycle and 6 mg/kg in subsequent cycles) every 3 weeks. Primary end point was objective response rate (ORR).

RESULTS: A total of 43 patients were enrolled. The best objective responses were partial response in 30 (69.8%) patients and stable disease in 10 (23.3%) patients, leading to an ORR of 69.8% (95% confidence interval [CI], 53.9-82.8) and a disease control rate of 93.0% (80.9-98.5). Median progression-free survival, duration of response, and overall survival were 7.9 (6.3-9.5), 6.7 (5.1-8.4), and 23.3 (19.9-26.7) months, respectively. Patients with HER2 IHC score of 3+ or HER2/CEP17 ratio ≥2.0 demonstrated better efficacies compared to those with HER2 IHC score of 2+. Thirty-eight (88.4%) patients experienced treatment-related adverse events (TRAE). Because of TRAE, nine (20.9%), 14 (32.6%), and 19 (44.2%) patients required temporary discontinuation, permanent discontinuation, or dose reduction, respectively.

CONCLUSIONS: The combination of docetaxel-PM and trastuzumab-pkrb demonstrated promising antitumor activity with a manageable toxicity profile in HER2-positive advanced SDC.

PLAIN LANGUAGE SUMMARY: Salivary duct carcinoma (SDC) is uncommon but is the most aggressive subtype of salivary gland carcinomas. SDC shares morphological and histological similarities with invasive ductal carcinoma of breast, which led to an investigation of hormonal receptor and human epidermal growth factor receptor 2 (HER2)/neu expression status in SDC. In this study, patients with HER2-positive SDC were enrolled and treated with combination of docetaxel-polymeric micelle and trastuzumab-pkrb. Promising antitumor activities were shown with objective response rate of 69.8%, disease control rate of 93.0%, median progression-free survival of 7.9 months, median duration of response of 6.7 months, and median overall survival of 23.3 months.}, } @article {pmid37222952, year = {2023}, author = {Abdollahi, E and Mozdarani, H and Alizadeh, BZ}, title = {Role of circ-FOXO3 and miR-23a in radiosensitivity of breast cancer.}, journal = {Breast cancer (Tokyo, Japan)}, volume = {30}, number = {5}, pages = {714-726}, pmid = {37222952}, issn = {1880-4233}, support = {Grant Number: IG-39711//Tarbiat Modares University/ ; }, mesh = {Humans ; Female ; *Breast Neoplasms/genetics/radiotherapy ; Leukocytes, Mononuclear ; Apoptosis/genetics ; *Carcinoma ; *Drug-Related Side Effects and Adverse Reactions ; *MicroRNAs/genetics ; Cell Proliferation ; Cell Line, Tumor ; Gene Expression Regulation, Neoplastic ; Forkhead Box Protein O3/genetics ; }, abstract = {Identifying the radiosensitivity of cells before radiotherapy (RT) in breast cancer (BC) patients allows appropriate switching between routinely used treatment regimens and reduces adverse side effects in exposed patients. In this study, blood was collected from 60 women diagnosed with Invasive Ductal Carcinoma (IDC) BC and 20 healthy women. To predict cellular radiosensitivity, a standard G2-chromosomal assay was performed. From these 60 samples, 20 BC patients were found to be radiosensitive based on the G2 assay. Therefore, molecular studies were finally performed on two equal groups (20 samples each) of patients with and without cellular radiosensitivity. QPCR was performed to examine the expression levels of circ-FOXO3 and miR-23a in peripheral blood mononuclear cells (PBMCs) and RNA sensitivity and specificity were determined by plotting Receiver Operating Characteristic (ROC) curves. Binary logistic regression was performed to identify RNA involvement in BC and cellular radiosensitivity (CR) in BC patients. Meanwhile, qPCR was used to compare differential RNA expression in the radiosensitive MCF-7 and radioresistant MDA-MB-231 cell lines. An annexin -V FITC/PI binding assay was used to measure cell apoptosis 24 and 48 h after 2 Gy, 4 Gy, and 8 Gy gamma-irradiation. Results indicated that circ-FOXO3 was downregulated and miR-23a was upregulated in BC patients. RNA expression levels were directly associated with CR. Cell line results showed that circ-FOXO3 overexpression induced apoptosis in the MCF-7 cell line and miR-23a overexpression inhibited apoptosis in the MDA-MB-231 cell line. Evaluation of the ROC curves revealed that both RNAs had acceptable specificity and sensitivity in predicting CR in BC patients. Binary logistic regression showed that both RNAs were also successful in predicting breast cancer. Although only circ-FOXO3 has been shown to predict CR in BC patients, circ-FOXO3 may function as a tumor suppressor and miR-23a may function as oncomiR in BC. Circ-FOXO3 and miR-23a may be promising potential biomarkers for BC prediction. Furthermore, Circ-FOXO3 could be a potential biomarker for predicting CR in BC patients.}, } @article {pmid37201100, year = {2023}, author = {Koçberber, Z and Willemsen, N and Bartelt, A}, title = {The role of proteasome activators PA28αβ and PA200 in brown adipocyte differentiation and function.}, journal = {Frontiers in endocrinology}, volume = {14}, number = {}, pages = {1176733}, pmid = {37201100}, issn = {1664-2392}, mesh = {Animals ; Mice ; *Adipocytes, Brown/metabolism ; *Proteasome Endopeptidase Complex/metabolism ; Adipose Tissue, Brown/metabolism ; Adipogenesis/genetics ; Temperature ; Nuclear Proteins/metabolism ; }, abstract = {INTRODUCTION: Brown adipocytes produce heat through non shivering thermogenesis (NST). To adapt to temperature cues, they possess a remarkably dynamic metabolism and undergo substantial cellular remodeling. The proteasome plays a central role in proteostasis and adaptive proteasome activity is required for sustained NST. Proteasome activators (PAs) are a class of proteasome regulators but the role of PAs in brown adipocytes is unknown. Here, we studied the roles of PA28α (encoded by Psme1) and PA200 (encoded by Psme4) in brown adipocyte differentiation and function.

METHODS: We measured gene expression in mouse brown adipose tissue. In cultured brown adipocytes, we silenced Psme1 and/or Psme4 expression through siRNA transfection. We then assessed impact on the ubiquitin proteasome system, brown adipocyte differentiation and function.

RESULTS: We found that Psme1 and Psme4 are expressed in brown adipocytes in vivo and in vitro. Through silencing of Psme1 and/or Psme4 expression in cultured brown adipocytes, we found that loss of PAs did not impair proteasome assembly or activity, and that PAs were not required for proteostasis in this model. Loss of Psme1 and/or Psme4 did not impair brown adipocyte development or activation, suggesting that PAs are neither required for brown adipogenesis nor NST.

DISCUSSION: In summary, we found no role for Psme1 and Psme4 in brown adipocyte proteostasis, differentiation, or function. These findings contribute to our basic understanding of proteasome biology and the roles of proteasome activators in brown adipocytes.}, } @article {pmid37200388, year = {2023}, author = {Amer, NN and Khairat, R and Hammad, AM and Kamel, MM}, title = {DDX43 mRNA expression and protein levels in relation to clinicopathological profile of breast cancer.}, journal = {PloS one}, volume = {18}, number = {5}, pages = {e0284455}, pmid = {37200388}, issn = {1932-6203}, mesh = {Humans ; Female ; *Breast Neoplasms/genetics/pathology ; Neoplasm Proteins/genetics ; RNA, Messenger/genetics ; Prognosis ; Disease Progression ; Biomarkers, Tumor/genetics/analysis ; DEAD-box RNA Helicases/genetics/metabolism ; }, abstract = {BACKGROUND: Breast cancer (BC) is the most often diagnosed cancer in women globally. Cancer cells appear to rely heavily on RNA helicases. DDX43 is one of DEAD- box RNA helicase family members. But, the relationship between clinicopathological, prognostic significance in different BC subtypes and DDX43 expression remains unclear. Therefore, the purpose of this study was to assess the clinicopathological significance of DDX43 protein and mRNA expression in different BC subtypes.

MATERIALS AND METHODS: A total of 80 females newly diagnosed with BC and 20 control females that were age-matched were recruited for this study. DDX43 protein levels were measured by ELISA technique. We used a real-time polymerase chain reaction quantification (real-time PCR) to measure the levels of DDX43 mRNA expression. Levels of DDX43 protein and mRNA expression within BC patients had been compared to those of control subjects and correlated with clinicopathological data.

RESULTS: The mean normalized serum levels of DDX43 protein were slightly higher in control than in both benign and malignant groups, but this result was non-significant. The mean normalized level of DDX43 mRNA expression was higher in the control than in both benign and malignant cases, although the results were not statistically significant and marginally significant, respectively. Moreover, the mean normalized level of DDX43 mRNA expression was significantly higher in benign than in malignant cases. In malignant cases, low DDX43 protein expression was linked to higher nuclear grade and invasive duct carcinoma (IDC), whereas high mRNA expression was linked to the aggressive types of breast cancer such as TNBC, higher tumor and nuclear grades.

CONCLUSION: This study explored the potential of using blood DDX43 mRNA expression or protein levels, or both in clinical settings as a marker of disease progression in human breast cancer. DDX43 mRNA expression proposes a less invasive method for discriminating benign from malignant BC.}, } @article {pmid37186041, year = {2023}, author = {Wei, S and Bao, M and Zhu, Y and Zhang, W and Jiang, L}, title = {Identifying potential targets for lung cancer intervention by analyzing the crosstalk of cancer-associated fibroblasts and immune and metabolism microenvironment.}, journal = {Environmental toxicology}, volume = {38}, number = {8}, pages = {1951-1967}, doi = {10.1002/tox.23821}, pmid = {37186041}, issn = {1522-7278}, support = {82103309//Youth Found of National Natural Science Foundation of China/ ; }, mesh = {Humans ; *Cancer-Associated Fibroblasts/metabolism/pathology ; *Lung Neoplasms/pathology ; Lung/pathology ; Signal Transduction ; Glycerophospholipids/metabolism ; Tumor Microenvironment/genetics ; }, abstract = {BACKGROUND: Cancer-associated fibroblasts (CAFs) have been reported to play a crucial role in the tumor microenvironment and progression.

METHODS: The data used in this study were obtained from the Cancer Genome Atlas and Gene Expression Omnibus databases, and all analyses were performed using R software.

RESULTS: We first quantified the CAFs infiltration through single sample gene set enrichment analysis in the TCGA and combined GEO cohort (GSE30219, GSE37745, and GSE50081). Our result showed that patients with high levels of CAF infiltration were associated with worse clinical features and poor prognosis. Immune microenvironment analysis indicated that high CAF infiltration might result in increased infiltration of immune cells, including aDC, B cells, CD8+ T cells, cytotoxic cells, DC, eosinophils, iDC, macrophages, mast cells, neutrophils, NK CD56dim cells, NK cells, pDC, and T cells. Correlation analysis showed a significant positive correlation between CAFs and M2 macrophages, while a negative correlation was found between CAFs and glycerophospholipid metabolism. Kaplan-Meier survival curves indicated that glycerophospholipid metabolism was a protective factor against lung cancer. Biological enrichment analysis showed that pathways such as allograft rejection, epithelial-mesenchymal transition, KRAS signaling, TNF-α signaling, myogenesis, IL6/JAK/STAT3 signaling, IL2/STAT5 signaling were upregulated in the patients with high CAF infiltration. Moreover, patients with high CAF infiltration had a lower proportion of immunotherapy responders. Genome analysis showed that low CAFs infiltration was associated with high genome instability. We identified FGF5 and CELF3 as key genes involved in the interaction between CAFs, M2 macrophages, and glycerophospholipid metabolism, and further analyzed FGF5. In vitro experiments showed that FGF5 promoted the proliferation, invasion and migration of lung cancer cells and was primarily localized in the nucleoli fibrillar center.

CONCLUSIONS: Our study provides novel insights into the roles of CAFs in lung cancer progression and the underlying crosstalk of tumor metabolism and immune microenvironment.}, } @article {pmid37171457, year = {2023}, author = {Traberg, WC and Uribe, J and Druet, V and Hama, A and Moysidou, CM and Huerta, M and McCoy, R and Hayward, D and Savva, A and Genovese, AMR and Pavagada, S and Lu, Z and Koklu, A and Pappa, AM and Fitzgerald, R and Inal, S and Daniel, S and Owens, RM}, title = {Organic Electronic Platform for Real-Time Phenotypic Screening of Extracellular-Vesicle-Driven Breast Cancer Metastasis.}, journal = {Advanced healthcare materials}, volume = {12}, number = {27}, pages = {e2301194}, doi = {10.1002/adhm.202301194}, pmid = {37171457}, issn = {2192-2659}, mesh = {Humans ; Female ; *Breast Neoplasms/drug therapy/pathology ; Cell Line, Tumor ; Early Detection of Cancer ; *Triple Negative Breast Neoplasms/drug therapy/pathology ; *Extracellular Vesicles ; Epithelial-Mesenchymal Transition/genetics ; Cell Movement ; Melanoma, Cutaneous Malignant ; }, abstract = {Tumor-derived extracellular vesicles (TEVs) induce the epithelial-to-mesenchymal transition (EMT) in nonmalignant cells to promote invasion and cancer metastasis, representing a novel therapeutic target in a field severely lacking in efficacious antimetastasis treatments. However, scalable technologies that allow continuous, multiparametric monitoring for identifying metastasis inhibitors are absent. Here, the development of a functional phenotypic screening platform based on organic electrochemical transistors (OECTs) for real-time, noninvasive monitoring of TEV-induced EMT and screening of antimetastatic drugs is reported. TEVs derived from the triple-negative breast cancer cell line MDA-MB-231 induce EMT in nonmalignant breast epithelial cells (MCF10A) over a nine-day period, recapitulating a model of invasive ductal carcinoma metastasis. Immunoblot analysis and immunofluorescence imaging confirm the EMT status of TEV-treated cells, while dual optical and electrical readouts of cell phenotype are obtained using OECTs. Further, heparin, a competitive inhibitor of cell surface receptors, is identified as an effective blocker of TEV-induced EMT. Together, these results demonstrate the utility of the platform for TEV-targeted drug discovery, allowing for facile modeling of the transient drug response using electrical measurements, and provide proof of concept that inhibitors of TEV function have potential as antimetastatic drug candidates.}, } @article {pmid37143728, year = {2023}, author = {Cipolletti, M and Leone, S and Bartoloni, S and Acconcia, F}, title = {A functional genetic screen for metabolic proteins unveils GART and the de novo purine biosynthetic pathway as novel targets for the treatment of luminal A ERα expressing primary and metastatic invasive ductal carcinoma.}, journal = {Frontiers in endocrinology}, volume = {14}, number = {}, pages = {1129162}, pmid = {37143728}, issn = {1664-2392}, mesh = {Female ; Humans ; Estrogen Receptor alpha/genetics/metabolism ; Biosynthetic Pathways ; Neoplasm Recurrence, Local ; *Breast Neoplasms/drug therapy/genetics/pathology ; *Carcinoma, Ductal, Breast ; Purines ; *Carbon-Nitrogen Ligases/metabolism ; Phosphoribosylglycinamide Formyltransferase/metabolism ; }, abstract = {Targeting tumor cell metabolism is a new frontier in cancer management. Thus, metabolic pathway inhibitors could be used as anti-estrogen receptor α (ERα) breast cancer (BC) drugs. Here, the interplay among metabolic enzyme(s), the ERα levels and cell proliferation was studied. siRNA-based screen directed against different metabolic proteins in MCF10a, MCF-7 and MCF-7 cells genetically resistant to endocrine therapy (ET) drugs and metabolomic analyses in numerous BC cell lines unveil that the inhibition of GART, a key enzyme in the purine de novo biosynthetic pathway, induces ERα degradation and prevent BC cell proliferation. We report here that a reduced GART expression correlates with a longer relapse-free-survival (RFS) in women with ERα-positive BCs. ERα-expressing luminal A invasive ductal carcinomas (IDCs) are sensitive to GART inhibition and GART expression is increased in receptor-positive IDCs of high grade and stage and plays a role in the development of ET resistance. Accordingly, GART inhibition reduces ERα stability and cell proliferation in IDC luminal A cells where it deregulates 17β-estradiol (E2):ERα signaling to cell proliferation. Moreover, the GART inhibitor lometrexol (LMX) and drugs approved for clinical treatment of primary and metastatic BC (4OH-tamoxifen and the CDK4/CDK6 inhibitors) exert synergic antiproliferative effects in BC cells. In conclusion, GART inhibition by LMX or other inhibitors of the de novo purine biosynthetic pathway could be a novel effective strategy for the treatment of primary and metastatic BCs.}, } @article {pmid37121885, year = {2023}, author = {Ikegami, M}, title = {Prognostic benefit of comprehensive genomic profiling in clinical practice remains uncertain.}, journal = {Cancer science}, volume = {114}, number = {7}, pages = {3053-3055}, pmid = {37121885}, issn = {1349-7006}, support = {#22K15571//Japan Society for the Promotion of Science/ ; }, mesh = {Humans ; *Pancreatic Neoplasms/pathology ; Prognosis ; *Adenocarcinoma/genetics ; Retrospective Studies ; Genomics ; *Carcinoma, Pancreatic Ductal/genetics/therapy ; }, abstract = {The overall survival of patients who received genomically matched therapy was not significantly longer than that of patients receiving treatment only other than genomically matched therapy in the breast invasive ductal carcinoma (A), colorectal adenocarcinoma (B), and pancreatic adenocarcinoma (C) cohorts.}, } @article {pmid37083566, year = {2023}, author = {Bilici, A and Olmez, OF and Kaplan, MA and Oksuzoglu, B and Sezer, A and Karadurmus, N and Cubukcu, E and Sendur, MAN and Aksoy, S and Erdem, D and Basaran, G and Cakar, B and Shbair, ATM and Arslan, C and Sumbul, AT and Sezgin Goksu, S and Karadag, I and Cicin, I and Gumus, M and Selcukbiricik, F and Harputluoglu, H and Demirci, U}, title = {Impact of adding pertuzumab to trastuzumab plus chemotherapy in neoadjuvant treatment of HER2 positive breast cancer patients: a multicenter real-life HER2PATH study.}, journal = {Acta oncologica (Stockholm, Sweden)}, volume = {62}, number = {4}, pages = {381-390}, doi = {10.1080/0284186X.2023.2202330}, pmid = {37083566}, issn = {1651-226X}, mesh = {Humans ; Female ; Trastuzumab/therapeutic use ; *Breast Neoplasms/pathology ; Neoadjuvant Therapy/methods ; Docetaxel ; Retrospective Studies ; Receptor, ErbB-2 ; Neoplasm Recurrence, Local/drug therapy/genetics ; Paclitaxel ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; }, abstract = {AIM: To investigate the pathological complete response (pCR) achieved after neoadjuvant therapy with versus without adding pertuzumab (P) to trastuzumab (H) plus neoadjuvant chemotherapy (NCT) in HER2+ breast cancer (BC) patients in a real-life setting.

METHODS: A total of 1528 female HER2+ BC patients who received NCT plus H with or without P were included in this retrospective real-life study. Primary endpoint was pCR rate (ypT0/Tis ypN0). Clinicopathological characteristics, event-free survival (EFS) time, and relapse rates were evaluated with respect to HER2 blockade (NCT-H vs. NCT-HP) and pCR.

RESULTS: Overall, 62.2% of patients received NCT-H and 37.8% received NCT-HP. NCT-HP was associated with a significantly higher pCR rate (66.4 vs. 56.8%, p < 0.001) and lower relapse (4.5 vs. 12.2%, p < 0.001) in comparison to NCT-H. Patients with pCR had a significantly lower relapse (5.6 vs. 14.9%, p < 0.001) and longer EFS time (mean(SE) 111.2(1.9) vs. 93.9(2.7) months, p < 0.001) compared to patients with non-pCR. Patients in the NCT-HP group were more likely to receive docetaxel (75.0 vs. 40.6%, p < 0.001), while those with pCR were more likely to receive paclitaxel (50.2 vs. 40.7%, p < 0.001) and NCT-HP (41.5 vs. 32.1%, p < 0.001). Hormone receptor status and breast conservation rates were similar in NCT-HP vs. NCT-H groups and in patients with vs. without pCR. Invasive ductal carcinoma (OR, 2.669, 95% CI 1.596 to 4.464, p < 0.001), lower histological grade of the tumor (OR, 4.052, 95% CI 2.446 to 6.713, p < 0.001 for grade 2 and OR, 3.496, 95% CI 2.020 to 6.053, p < 0.001 for grade 3), lower T stage (OR, 1.959, 95% CI 1.411 to 2.720, p < 0.001) and paclitaxel (vs. docetaxel, OR, 1.571, 95% CI 1.127 to 2.190, p = 0.008) significantly predicted the pCR.

CONCLUSIONS: This real-life study indicates that adding P to NCT-H enables higher pCR than NCT-H in HER2+ BC, while pCR was associated with lower relapse and better EFS time.}, } @article {pmid37082801, year = {2023}, author = {Hacking, SM and Yakirevich, E and Wang, Y}, title = {Defining triple-negative breast cancer with neuroendocrine differentiation (TNBC-NED).}, journal = {The journal of pathology. Clinical research}, volume = {9}, number = {4}, pages = {313-321}, pmid = {37082801}, issn = {2056-4538}, mesh = {Humans ; *Triple Negative Breast Neoplasms/genetics/pathology ; Biomarkers, Tumor/analysis ; Tumor Suppressor Protein p53/genetics ; Retinoblastoma Protein/genetics/metabolism ; Retrospective Studies ; *Neuroendocrine Tumors/pathology ; *Carcinoma, Neuroendocrine/pathology ; *Carcinoma, Ductal, Breast ; Cell Differentiation ; RNA, Messenger ; Repressor Proteins ; }, abstract = {Primary breast neuroendocrine (NE) neoplasms are uncommon, and definitions harbor controversy. We retrospectively collected 73 triple-negative breast cancers (TNBC) and evaluated NE biomarker expression along with p53 aberrant staining (which correlates with TP53 gene mutation) and Rb protein loss by immunohistochemistry. In the study cohort, we found 11 (15%) cases of TNBC with neuroendocrine differentiation (TNBC-NED) showing positivity for one or more NE markers (synaptophysin/chromogranin/insulinoma-associated protein 1 [INSM1]). We also identified one separate small cell neuroendocrine carcinoma. Histologic types for these 11 TNBC-NED cases were as follows: 8 invasive ductal carcinoma (IDC) not otherwise specified (NOS), 2 IDC with apocrine features, 1 IDC with solid papillary features. INSM1 had the highest positivity and was seen in all 11 carcinomas. Seven (64%) cases showed p53 aberrant staining, 6 (55%) had Rb protein loss, while 6 (55%) had p53/Rb co-aberrant staining/protein loss. TNBC-NED was associated with Rb protein loss (p < 0.001), as well as p53/Rb co-aberrant staining/protein loss (p < 0.001). In 61 cases negative for NE markers, 37 (61%) showed p53 aberrant staining, while 5 (8%) had Rb protein loss. We also analyzed genomic and transcriptomic data from The Cancer Genome Atlas (TCGA) PanCancer Atlas of 171 basal/TNBC patients. Transcriptomic analysis revealed mRNA expression of RB1 to be correlated negatively with SYN1 mRNA expression (p = 0.0400) and INSM1 mRNA expression (p = 0.0106) in this cohort. We would like to highlight the importance of these findings. TNBC-NED is currently diagnosed as TNBC, and although it overlaps morphologically with TNBC without NED, the unique p53/Rb signature highlights a genetic overlap with NE carcinomas of the breast.}, } @article {pmid37061239, year = {2023}, author = {López-Janeiro, Á and Rodriguez, AM and Mendiola, M and Sabbagh, RN and Feliu, J and Villadóniga, A and Mendez, MDC}, title = {Pancreatic intraductal papillary mucinous neoplasm with sarcomatous transformation. A case report.}, journal = {Revista espanola de patologia : publicacion oficial de la Sociedad Espanola de Anatomia Patologica y de la Sociedad Espanola de Citologia}, volume = {56}, number = {2}, pages = {124-128}, doi = {10.1016/j.patol.2021.05.004}, pmid = {37061239}, issn = {1988-561X}, mesh = {Female ; Humans ; Aged ; *Pancreatic Intraductal Neoplasms ; *Carcinoma, Pancreatic Ductal/pathology ; *Adenocarcinoma, Mucinous/genetics/pathology ; Neoplasm Recurrence, Local ; *Pancreatic Neoplasms/pathology ; }, abstract = {Mixed pancreatic epithelial and mesenchymal tumors are rare, usually invasive, entities. Intraductal papillary mucinous neoplasm (IPMN) is a precursor of invasive ductal carcinoma and shares mutations with its invasive counterparts. We report the case of a 72-year-old female with a previously undescribed sarcomatous transformation of a residual IPMN with no evidence of an invasive component. The mesenchymal component showed no heterologous differentiation. Both the epithelial and the mesenchymal populations showed aberrant expression of p53 protein and the same point mutation in KRAS gene. After a 6 month follow up, there were no signs of local or distant relapse. The present case suggests that sarcomatous transformation is possible in non-invasive, intraductal pancreatic lesions.}, } @article {pmid37055018, year = {2023}, author = {De Angelis Rigotti, F and Wiedmann, L and Hubert, MO and Vacca, M and Hasan, SS and Moll, I and Carvajal, S and Jiménez, W and Starostecka, M and Billeter, AT and Müller-Stich, B and Wolff, G and Ekim-Üstünel, B and Herzig, S and Fandos-Ramo, C and Krätzner, R and Reich, M and Keitel-Anselmino, V and Heikenwälder, M and Mogler, C and Fischer, A and Rodriguez-Vita, J}, title = {Semaphorin 3C exacerbates liver fibrosis.}, journal = {Hepatology (Baltimore, Md.)}, volume = {78}, number = {4}, pages = {1092-1105}, doi = {10.1097/HEP.0000000000000407}, pmid = {37055018}, issn = {1527-3350}, mesh = {Animals ; Humans ; Mice ; *Hepatic Stellate Cells/metabolism ; Liver/pathology ; Liver Cirrhosis/pathology ; Phosphorylation ; *Semaphorins/genetics/metabolism ; Transforming Growth Factor beta/metabolism ; }, abstract = {BACKGROUND AND AIMS: Chronic liver disease is a growing epidemic, leading to fibrosis and cirrhosis. TGF-β is the pivotal profibrogenic cytokine that activates HSC, yet other molecules can modulate TGF-β signaling during liver fibrosis. Expression of the axon guidance molecules semaphorins (SEMAs), which signal through plexins and neuropilins (NRPs), have been associated with liver fibrosis in HBV-induced chronic hepatitis. This study aims at determining their function in the regulation of HSCs.

APPROACH AND RESULTS: We analyzed publicly available patient databases and liver biopsies. We used transgenic mice, in which genes are deleted only in activated HSCs to perform ex vivo analysis and animal models. SEMA3C is the most enriched member of the semaphorin family in liver samples from patients with cirrhosis. Higher expression of SEMA3C in patients with NASH, alcoholic hepatitis, or HBV-induced hepatitis discriminates those with a more profibrotic transcriptomic profile. SEMA3C expression is also elevated in different mouse models of liver fibrosis and in isolated HSCs on activation. In keeping with this, deletion of SEMA3C in activated HSCs reduces myofibroblast marker expression. Conversely, SEMA3C overexpression exacerbates TGF-β-mediated myofibroblast activation, as shown by increased SMAD2 phosphorylation and target gene expression. Among SEMA3C receptors, only NRP2 expression is maintained on activation of isolated HSCs. Interestingly, lack of NRP2 in those cells reduces myofibroblast marker expression. Finally, deletion of either SEMA3C or NRP2, specifically in activated HSCs, reduces liver fibrosis in mice.

CONCLUSION: SEMA3C is a novel marker for activated HSCs that plays a fundamental role in the acquisition of the myofibroblastic phenotype and liver fibrosis.}, } @article {pmid37017594, year = {2023}, author = {Zheng, L and Wu, H and Wen, N and Zhang, Y and Wang, Z and Peng, X and Tan, Y and Qiu, L and Qu, F and Tan, W}, title = {Aptamer-Functionalized Nanovaccines: Targeting In Vivo DC Subsets for Enhanced Antitumor Immunity.}, journal = {ACS applied materials & interfaces}, volume = {15}, number = {15}, pages = {18590-18597}, doi = {10.1021/acsami.2c20846}, pmid = {37017594}, issn = {1944-8252}, mesh = {Humans ; *Cancer Vaccines ; Immunotherapy/methods ; T-Lymphocytes ; Antigens, Neoplasm/genetics ; *Neoplasms/therapy ; Adjuvants, Immunologic ; Adjuvants, Pharmaceutic ; Dendritic Cells ; }, abstract = {Cancer vaccines, which directly pulsed in vivo dendritic cells (DCs) with specific antigens and immunostimulatory adjuvants, showed great potential for cancer immunoprevention. However, most of them were limited by suboptimal outcomes, mainly owing to overlooking the complex biology of DC phenotypes. Herein, based on adjuvant-induced antigen assembly, we developed aptamer-functionalized nanovaccines for in vivo DC subset-targeted codelivery of tumor-related antigens and immunostimulatory adjuvants. We chose two aptamers, iDC and CD209, and tested their performance on DC targeting. Our results verified that these aptamer-functionalized nanovaccines could specifically recognize circulating classical DCs (cDCs), a subset of DCs capable of priming naïve T cells, noting that iDC outperformed CD209 in this regard. With excellent cDC-targeting capability, the iDC-functionalized nanovaccine induced potent antitumor immunity, leading to effective inhibition of tumor occurrence and metastasis, thus providing a promising platform for cancer immunoprevention.}, } @article {pmid36973739, year = {2023}, author = {Cheng, X and Jia, X and Wang, C and Zhou, S and Chen, J and Chen, L and Chen, J}, title = {Hyperglycemia induces PFKFB3 overexpression and promotes malignant phenotype of breast cancer through RAS/MAPK activation.}, journal = {World journal of surgical oncology}, volume = {21}, number = {1}, pages = {112}, pmid = {36973739}, issn = {1477-7819}, support = {2021Y29//Medical science and technology program in Ningbo/ ; }, mesh = {Female ; Humans ; Phosphofructokinase-2/genetics/metabolism ; Cell Proliferation ; Cell Line, Tumor ; *MicroRNAs/genetics ; *Hyperglycemia/complications/genetics ; Phenotype ; *Carcinoma, Ductal/genetics ; Cell Movement ; Gene Expression Regulation, Neoplastic ; }, abstract = {BACKGROUND: Breast cancer is the most common tumor in women worldwide. Diabetes mellitus is a global chronic metabolic disease with increasing incidence. Diabetes mellitus has been reported to positively regulate the development of many tumors. However, the specific mechanism of hyperglycemic environment regulating breast cancer remains unclear. PFKFB3 (6-phosphofructose-2-kinase/fructose-2, 6-bisphosphatase 3) is a key regulatory factor of the glycolysis process in diabetes mellitus, as well as a promoter of breast cancer. So, we want to explore the potential link between PFKFB3 and the poor prognosis of breast cancer patients with hyperglycemia in this study.

METHODS: Cell culture was utilized to construct different-glucose breast cancer cell lines. Immunohistochemistry was adopted to analyze the protein level of PFKFB3 in benign breast tissues, invasive ductal carcinoma with diabetes and invasive ductal carcinoma without diabetes. The Kaplan-Meier plotter database and GEO database (GSE61304) was adopted to analyze the survival of breast cancer patients with different PFKFB3 expression. Western blot was adopted to analyze the protein level of PFKFB3, epithelial-mesenchymal transition (EMT)-related protein and extracellular regulated protein kinases (ERK) in breast cancer cells. Gene Set Cancer Analysis (GSCA) was utilized to investigate the potential downstream signaling pathways of PFKFB3. TargetScan and OncomiR were utilized to explore the potential mechanism of PFKFB3 overexpression by hyperglycemia. Transfections (including siRNAs and miRNA transfection premiers) was utilized to restrain or mimic the expression of the corresponding RNA. Cell functional assays (including cell counting, MTT, colony formation, wound-healing, and cell migration assays) were utilized to explore the proliferation and migration of breast cancer cells.

RESULTS: In this study, we demonstrated that the expression of PFKFB3 in breast cancer complicated with hyperglycemia was higher than that in breast cancer with euglycemia through cell experiment in vitro and histological experiment. PFKFB3 overexpression decreased the survival period of breast cancer patients and was correlated with a number of clinicopathological parameters of breast cancer complicated with diabetes. PFKFB3 promoted the proliferation and migration of breast cancer in a hyperglycemic environment and might be regulated by miR-26. In addition, PFKFB3 stimulated epithelial-mesenchymal transition of breast cancer in a hyperglycemic environment. In terms of downstream mechanism exploration, we predicted and verified the cancer-promoting effect of PFKFB3 in breast cancer complicated with hyperglycemia through RAS/MAPK pathway.

CONCLUSIONS: In conclusion, PFKFB3 could be overexpressed by hyperglycemia and might be a potential therapeutic target for breast cancer complicated with diabetes.}, } @article {pmid36973678, year = {2023}, author = {Tong, S and Jiang, N and Wan, JH and Chen, CR and Wang, SH and Wu, CY and Guo, Q and Xiao, XY and Huang, H and Zhou, T}, title = {The effects of the prognostic biomarker SAAL1 on cancer growth and its association with the immune microenvironment in lung adenocarcinoma.}, journal = {BMC cancer}, volume = {23}, number = {1}, pages = {275}, pmid = {36973678}, issn = {1471-2407}, mesh = {Humans ; Cyclin D1 ; Prognosis ; *Lung Neoplasms/pathology ; *Adenocarcinoma of Lung/genetics ; Biomarkers, Tumor/genetics ; Tumor Microenvironment ; }, abstract = {BACKGROUND: Inhibition of Serum Amyloid A-like 1 (SAAL1) expression could inhibit cancer progression and improve the prognosis of cancer patients. At present, the correlation between SAAL1 and lung adenocarcinoma (LAC) remains unclear. Therefore, this study surveyed the worth and pathway of SAAL1 in LAC progression and immunity.

METHODS: Bioinformatics and immunohistochemistry were used to identify the SAAL1 expression in LAC. The roles of SAAL1 expression in the existence values of LAC patients were explored, and the nomograms were constructed. Clinical values of SAAL1 co-expressed genes were evaluated by COX regression, survival, and Receiver operating characteristic (ROC) analysis. EDU and western blotting methods were used to inquiry the functions and pathways of the SAAL1 in cell growths. The correlation between the SAAL1 level and immune microenvironment was visualized using correlation research.

RESULTS: SAAL1 level was elevated in LAC tissues, and was observed in cancer tissues of dead patients. SAAL1 overexpression had something to do with shorter overall survival, progression-free interval, and disease-specific survival in LAC. The area under the curve of SAAL1 was 0.902 in normal tissues and cancer tissues. Inhibition of SAAL1 expression could inhibit cancer cell proliferation, which may be related to the decreased expression of cyclin D1 and Bcl-2 proteins. In LAC, SAAL1 level had something to do with stromal, immune, and estimate scores, and correlated with macrophages, T cells, Th2 cells, CD8 T cells, NK CD56dim cells, DC, eosinophils, NK CD56bright cells, pDC, iDC, cytotoxic cells, Tgd, aDC cells, B cells, Tcm, and TFH levels. SAAL1 overexpression had something to do with existence values and the immunity in LAC.

CONCLUSIONS: Inhibition of SAAL1 expression could regulate cancer growth via cyclin D1 and Bcl-2. SAAL1 is a promising prognostic biomarker in LAC patients.}, } @article {pmid36939123, year = {2023}, author = {Mareti, E and Vavoulidis, E and Papanastasiou, A and Maretis, T and Tsampazis, N and Margioula-Siarkou, C and Chatzinikolaou, F and Giasari, S and Nasioutziki, M and Daniilidis, A and Zepiridis, L and Dinas, K}, title = {Evaluating the potential role of human papilloma virus infection in breast carcinogenesis via real-time polymerase chain reaction analyzes of breast fine needle aspiration samples from Greek patients.}, journal = {Diagnostic cytopathology}, volume = {51}, number = {7}, pages = {414-422}, doi = {10.1002/dc.25130}, pmid = {36939123}, issn = {1097-0339}, mesh = {Humans ; Female ; Biopsy, Fine-Needle ; Real-Time Polymerase Chain Reaction ; Human Papillomavirus Viruses ; Greece/epidemiology ; *Papillomavirus Infections ; *Breast Neoplasms/pathology ; Carcinogenesis ; Papillomaviridae/genetics ; }, abstract = {BACKGROUND: Human papilloma virus (HPV), in addition to its known clinical contribution to cervical cancer is probably actively involved in the development of breast tumors in various populations worldwide. Predominant HPV types in breast cancer patients vary geographically. The present study further examines HPV incidence in Greece, based on molecular analysis of clinical cytological samples.

METHODS: Greek patient fine needle aspiration (FNA) biopsy samples were examined using RT-PCR and immunohistological staining. FNA biopsy samples were collected from 114 female patients, diagnosed between the years 2018 and 2021, 57 with C5 diagnosed breast cancer lesions and 57 diagnosed with benign diseases.

RESULTS: A total of three different HPV types were identified within the patient sample. HPV-39 was found only in the control group, in 1.8% of patients, while HPV-59 was present in both control and study groups in 1.8% and 3.5% respectively. HPV-16, on the other hand, was present only in the study group in 12.3% of cases. HPV type presence was statistically differentiated between histological groups. HPV-16 was exclusively in IDC, HPV-39 was present in one cyst diagnosed sample and HPV-59 was present in 3 samples that included fibroadenoma, IDC and LN diagnosis.

CONCLUSION: More international comparative studies are required to investigate population differences and HPV genotype distribution to offer definite answers to the effect that certain HPV types might have a role in breast cancer, as this study also supports, albeit in a cofactory role.}, } @article {pmid36933394, year = {2023}, author = {Vormittag-Nocito, E and Acosta, AM and Agarwal, S and Narayan, KD and Kumar, R and Al Rasheed, MRH and Kajdacsy-Balla, A and Behm, FG and Mohapatra, G}, title = {In-Depth Comparison of Genetic Variants Demonstrates a Close Relationship Between Invasive and Intraductal Components of Prostate Cancer.}, journal = {Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc}, volume = {36}, number = {6}, pages = {100130}, doi = {10.1016/j.modpat.2023.100130}, pmid = {36933394}, issn = {1530-0285}, mesh = {Male ; Humans ; *Prostatic Intraepithelial Neoplasia/genetics/pathology ; *Prostatic Neoplasms/pathology ; Prostate/pathology ; *Carcinoma, Intraductal, Noninfiltrating/pathology ; Prostatectomy ; }, abstract = {Intraductal carcinoma (IDC) of the prostate is often associated with concurrent high-grade invasive prostate cancer (PCa) and poor clinical outcomes. In this context, IDC is thought to represent the retrograde spread of invasive prostatic adenocarcinoma into the acini and ducts. Prior studies have demonstrated a concordance of PTEN loss and genomic instability between the IDC and high-grade invasive components of PCa, but larger genomic association studies to solidify our understanding of the relationship between these 2 lesions are lacking. Here, we evaluate the genomic relationship between duct-confined (high-grade prostatic intraepithelial neoplasia and IDC) and invasive components of high-grade PCa using genetic variants generated by whole exome sequencing. High-grade prostatic intraepithelial neoplasia and IDC were laser-microdissected, and PCa and nonneoplastic tissue was manually dissected from 12 radical prostatectomies. A targeted next-generation sequencing panel was used to identify disease-relevant variants. Additionally, the degree of overlap between adjacent lesions was determined by comparing exome-wide variants detected using whole exome sequencing data. Our results demonstrate that IDC and invasive high-grade PCa components show common genetic variants and copy number alterations. Hierarchical clustering of genome-wide variants suggests that in these tumors, IDC is more closely related to the high-grade invasive components of the tumor compared with high-grade prostatic intraepithelial neoplasia. In conclusion, this study reinforces the concept that, in the context of high-grade PCa, IDC likely represents a late event associated with tumor progression.}, } @article {pmid36897545, year = {2023}, author = {Kikuchi, M and Gomi, N and Ueki, A and Osako, T and Terauchi, T}, title = {Effectiveness and tasks of breast MRI surveillance for high-risk women with cancer susceptibility genes other than BRCA1/2: a single institution study.}, journal = {Breast cancer (Tokyo, Japan)}, volume = {30}, number = {4}, pages = {577-583}, pmid = {36897545}, issn = {1880-4233}, mesh = {*Breast Neoplasms/diagnostic imaging/genetics/pathology ; Magnetic Resonance Imaging ; Risk ; *Genetic Predisposition to Disease ; Japan ; Ataxia Telangiectasia Mutated Proteins/genetics ; Fanconi Anemia Complementation Group N Protein/genetics ; Antigens, CD/genetics ; Cadherins/genetics ; Tumor Suppressor Protein p53/genetics ; *Early Detection of Cancer/methods ; *Genes, Neoplasm ; Neoplasm Staging ; Humans ; Female ; Adult ; Middle Aged ; Aged ; }, abstract = {BACKGROUND: In Japan, with the introduction of multigene panel testing, there is an urgent need to build a new medical system for hereditary breast cancer patients that covers pathogenic variants other than BRCA1/2. The aim of this study was to reveal the current status of breast MRI surveillance for high-risk breast cancer susceptibility genes other than BRCA1/2 and the characteristics of detected breast cancer.

METHODS: We retrospectively examined 42 breast MRI surveillance with contrast performed on patients with hereditary tumors other than BRCA1/2 pathogenic variants at our hospital from 2017 to 2021. MRI exams were evaluated independently by two radiologists. Final histopathological diagnosis for malignant lesions were obtained from surgical specimen.

RESULTS: A total of 16 patients included TP53, CDH1, PALB2, ATM pathogenic variants and 3 variant of unknown significance. 2 patients with TP53 pathogenic variants were detected breast cancer by annual MRI surveillance. The rate of cancer detection was 12.5% (2/16). One patient was detected synchronous bilateral breast cancer and unilateral multiple breast cancers (3 lesions in 1 patient), so there were 4 malignant lesions in total. Surgical pathology of 4 lesions were 2 ductal carcinoma in situ, 1 invasive lobular carcinoma, and 1 invasive ductal carcinoma. MRI findings of 4 malignant lesions were detected as 2 non mass enhancement, 1 focus and 1 small mass. All of 2 patients with PALB2 pathogenic variants had previously developed breast cancer.

CONCLUSIONS: Germline TP53 and PALB2 were strongly associated with breast cancer, suggesting that MRI surveillance is essential for breast cancer-related hereditary predisposition.}, } @article {pmid36893606, year = {2023}, author = {Göransson, S and Chen, S and Olofsson, H and Larsson, O and Strömblad, S}, title = {An extracellular matrix stiffness-induced breast cancer cell transcriptome resembles the transition from ductal carcinoma in situ (DCIS) to invasive ductal carcinoma (IDC).}, journal = {Biochemical and biophysical research communications}, volume = {654}, number = {}, pages = {73-79}, doi = {10.1016/j.bbrc.2023.03.001}, pmid = {36893606}, issn = {1090-2104}, mesh = {Humans ; Female ; *Carcinoma, Intraductal, Noninfiltrating/genetics/pathology ; *Carcinoma, Ductal, Breast/genetics/pathology ; Transcriptome ; Extracellular Matrix/genetics/pathology ; *Breast Neoplasms/genetics/pathology ; *Carcinoma in Situ ; }, abstract = {Identifying mechanisms driving the transition from ductal carcinoma in situ (DCIS) to invasive breast cancer remains a challenge in breast cancer research. Breast cancer progression is accompanied by remodelling and stiffening of the extracellular matrix, leading to increased proliferation, survival, and migration. Here, we studied stiffness-dependent phenotypes in MCF10CA1a (CA1a) breast cancer cells cultured on hydrogels with stiffness corresponding to normal breast and breast cancer. This revealed a stiffness-associated morphology consistent with acquisition of an invasive phenotype in breast cancer cells. Surprisingly, this strong phenotypic switch was accompanied by relatively modest transcriptome-wide alterations in mRNA levels, as independently quantified using both DNA-microarrays and bulk RNA sequencing. Strikingly, however, the stiffness-dependent alterations in mRNA levels overlapped with those contrasting ductal carcinoma in situ (DCIS) and invasive ductal carcinoma (IDC). This supports a role of matrix stiffness in driving the pre-invasive to invasive transition and suggests that mechanosignalling may be a target for prevention of invasive breast cancer.}, } @article {pmid36883155, year = {2022}, author = {Ali Khadem, Z and Abdul Wadood Al-Shammaree, S}, title = {Prognostic Value of Intracellular Transcription of Factors HIF-1α and p53 and Their Relation to Estradiol and TNM Parameters of Breast Cancer Tissues in Women with Invasive Ductal Carcinoma in Thi-Qar Province, Iraq.}, journal = {Archives of Razi Institute}, volume = {77}, number = {4}, pages = {1341-1348}, pmid = {36883155}, issn = {2008-9872}, mesh = {Adolescent ; Adult ; Female ; Humans ; Young Adult ; *Breast Neoplasms/chemistry/genetics/metabolism/pathology ; *Carcinoma, Ductal, Breast/chemistry/genetics/metabolism/pathology ; *Estradiol/analysis/genetics/metabolism ; *Hypoxia-Inducible Factor 1, alpha Subunit/analysis/genetics/metabolism ; Iraq/epidemiology ; Prognosis ; *Tumor Suppressor Protein p53/analysis/genetics/metabolism ; }, abstract = {Breast cancer is the most common malignancy affecting women's health, with an increasing incidence worldwide. This study aimed to measure the intracellular concentration of the hypoxia-inducible factor 1 α (HIF-1α), tumor suppression protein p53, and estradiol (E2) in tumor tissues of adult females with breast cancer and their relation to tumor grade, tumor size, and lymph node metastases (LNM). The study was conducted on 65 adult female participants with breast mass admitted to the operating theater in Al-Hussein Teaching Hospital and Al-Habboby Teaching Hospital in Nasiriyah, Iraq, from January to November 2021. Fresh breast tumor tissues were collated and homogenized for intracellular biochemical analysis using the enzyme-linked immunosorbent assay method. In total, 44 (58%) out of 65 patients, in the age range of 18-42 years and the mean±SD age of 32.55±6.40 years, had fibroadenomas, and other 21 (42%) cases, in the age range of 32-80 years and the mean±SD age of 56±14.4 years had invasive ductal carcinoma (IDC) breast cancer. Intracellular levels of HIF-1α, p53, and E2 were elevated significantly (P<0.001) in IDC cases compared to the benign group. The most malignant tumors of IDC cases were in grade III and sizes T2 and T3. The tissue concentrations of HIF-1α, P53, and E2 were significantly elevated in patients with tumor stage T3 compared to T2 and T1. A significant elevation was found in the levels of HIF-1α, p53, and E2 in the positive LNM subgroup compared to the negative LNM group. Based on the obtained results, the prognostic value of the intracellular HIF-1α is considered to be a useful prognostic factor in Iraqi women with ICD and the combination of a HIF-1α protein with the nonfunctional p53 and E2 tends to indicate the proliferation, invasiveness, and metastases of the breast tumors.}, } @article {pmid36868097, year = {2023}, author = {Aktan, Ç and Küçükaslan, AŞ and Türk, BA and Yildirim, I}, title = {Expression analysis of novel long non-coding RNAs for invasive ductal and invasive lobular breast carcinoma cases.}, journal = {Pathology, research and practice}, volume = {244}, number = {}, pages = {154391}, doi = {10.1016/j.prp.2023.154391}, pmid = {36868097}, issn = {1618-0631}, mesh = {Female ; Humans ; *RNA, Long Noncoding/genetics ; *Carcinoma, Ductal, Breast/genetics/pathology ; *Carcinoma, Lobular/genetics/pathology ; Treatment Outcome ; *Breast Neoplasms/pathology ; }, abstract = {AIM: Long non-coding RNAs (LncRNAs) serve as important regulatory molecules of gene expression and protein functionality at multiple biological levels, and their deregulation plays a key role in tumorigenesis including in breast cancer metastasis. Therefore, in this study, we aim to compare the expression of novel lncRNAs in the landscape of invasive ductal carcinoma (IDC) and invasive lobular (ILC) carcinoma of breast.

MAIN METHODS: We have designed an in-silico approach to find the lncRNAs that regulate the breast cancer. Then, we used the clinical samples to carry out the verification of our in silico finding. In the present study, the tissues of breast cancer were deparaffinized. RNA was extracted by the TRIzole method. After synthesizing cDNA from the extracted RNA, expression levels of lncRNAs were analyzed by qPCR using primers specifically designed and validated for the targeted lncRNAs. In this study, breast biopsy materials from 41 female patients with IDC and 10 female patients with ILC were examined histopathological and expression changes of candidate lncRNAs were investigated in line with the findings. The results were analyzed using IBM SPSS Statistics 25 version.

RESULTS: The mean age of the cases was 53.78 ± 14.96. The minimum age was 29, while the maximum age was 87. While 27 of the cases were pre-menopausal, 24 cases were post-menopausal. The number of hormone receptor-positive cases was found to be 40, 35, and 27 for ER, PR, and cerb2/neu, respectively. While the expressions of LINC00501, LINC00578, LINC01209, LINC02015, LINC02584, ABCC5-AS1, PEX5L-AS2, SHANK2-AS3 and SOX2-OT showed significant differences (p < 0.05), the expressions of LINC01206, LINC01994, SHANK2-AS1, and TPRG1-AS2 showed no significant differences (p > 0.05). In addition, it was determined that the regulation of all lncRNAs could be able to involve in the development of cancer such as the NOTCH1, NFKB, and estrogen receptor signalings.

CONCLUSION: As a result, it was thought that the discovery of novel lncRNAs might be an important player in the diagnosis, prognosis and therapeutic development of breast cancer.}, } @article {pmid36769184, year = {2023}, author = {Górnicki, T and Lambrinow, J and Mrozowska, M and Romanowicz, H and Smolarz, B and Piotrowska, A and Gomułkiewicz, A and Podhorska-Okołów, M and Dzięgiel, P and Grzegrzółka, J}, title = {Expression of RBMS3 in Breast Cancer Progression.}, journal = {International journal of molecular sciences}, volume = {24}, number = {3}, pages = {}, pmid = {36769184}, issn = {1422-0067}, mesh = {Humans ; Female ; *Breast Neoplasms/metabolism ; Breast/metabolism ; *Carcinoma, Ductal, Breast/pathology ; MCF-7 Cells ; RNA, Messenger/genetics ; Cell Line, Tumor ; Trans-Activators/metabolism ; RNA-Binding Proteins/metabolism ; }, abstract = {The aim of the study was to evaluate the localization and intensity of RNA-binding motif single-stranded-interacting protein 3 (RBMS3) expression in clinical material using immunohistochemical (IHC) reactions in cases of ductal breast cancer (in vivo), and to determine the level of RBMS3 expression at both the protein and mRNA levels in breast cancer cell lines (in vitro). Moreover, the data obtained in the in vivo and in vitro studies were correlated with the clinicopathological profiles of the patients. Material for the IHC studies comprised 490 invasive ductal carcinoma (IDC) cases and 26 mastopathy tissues. Western blot and RT-qPCR were performed on four breast cancer cell lines (MCF-7, BT-474, SK-BR-3 and MDA-MB-231) and the HME1-hTERT (Me16C) normal immortalized breast epithelial cell line (control). The Kaplan-Meier plotter tool was employed to analyze the predictive value of overall survival of RBMS3 expression at the mRNA level. Cytoplasmatic RBMS3 IHC expression was observed in breast cancer cells and stromal cells. The statistical analysis revealed a significantly decreased RBMS3 expression in the cancer specimens when compared with the mastopathy tissues (p < 0.001). An increased expression of RBMS3 was corelated with HER2(+) cancer specimens (p < 0.05) and ER(-) cancer specimens (p < 0.05). In addition, a statistically significant higher expression of RBMS3 was observed in cancer stromal cells in comparison to the control and cancer cells (p < 0.0001). The statistical analysis demonstrated a significantly higher expression of RBMS3 mRNA in the SK-BR-3 cell line compared with all other cell lines (p < 0.05). A positive correlation was revealed between the expression of RBMS3, at both the mRNA and protein levels, and longer overall survival. The differences in the expression of RBMS3 in cancer cells (both in vivo and in vitro) and the stroma of breast cancer with regard to the molecular status of the tumor may indicate that RBMS3 could be a potential novel target for the development of personalized methods of treatment. RBMS3 can be an indicator of longer overall survival for potential use in breast cancer diagnostic process.}, } @article {pmid36671532, year = {2023}, author = {Yang, Y and Luo, D and Gao, W and Wang, Q and Yao, W and Xue, D and Ma, B}, title = {Combination Analysis of Ferroptosis and Immune Status Predicts Patients Survival in Breast Invasive Ductal Carcinoma.}, journal = {Biomolecules}, volume = {13}, number = {1}, pages = {}, pmid = {36671532}, issn = {2218-273X}, support = {81602337//National Natural Science Foundation of China/ ; 81702564//National Natural Science Foundation of China/ ; 81570579//National Natural Science Foundation of China/ ; UNPYSCT-2017062//Education Department of Heilongjiang Province/ ; LH2021H050//Natural Science Foundation of Heilongjiang Province/ ; }, mesh = {Humans ; *Ferroptosis/genetics ; Algorithms ; Cell Death ; Iron ; *Carcinoma, Ductal ; }, abstract = {Ferroptosis is a new form of iron-dependent cell death and plays an important role during the occurrence and development of various tumors. Increasingly, evidence shows a convincing interaction between ferroptosis and tumor immunity, which affects cancer patients' prognoses. These two processes cooperatively regulate different developmental stages of tumors and could be considered important tumor therapeutic targets. However, reliable prognostic markers screened based on the combination of ferroptosis and tumor immune status have not been well characterized. Here, we chose the ssGSEA and ESTIMATE algorithms to evaluate the ferroptosis and immune status of a TCGA breast invasive ductal carcinoma (IDC) cohort, which revealed their correlation characteristics as well as patients' prognoses. The WGCNA algorithm was used to identify genes related to both ferroptosis and immunity. Univariate COX, LASSO regression, and multivariate Cox regression models were used to screen prognostic-related genes and construct prognostic risk models. Based on the ferroptosis and immune scores, the cohort was divided into three groups: a high-ferroptosis/low-immune group, a low-ferroptosis/high-immune group, and a mixed group. These three groups exhibited distinctive survival characteristics, as well as unique clinical phenotypes, immune characteristics, and activated signaling pathways. Among them, low-ferroptosis and high-immune statuses were favorable factors for the survival rates of patients. A total of 34 differentially expressed genes related to ferroptosis-immunity were identified among the three groups. After univariate, Lasso regression, and multivariate stepwise screening, two key prognostic genes (GNAI2, PSME1) were identified. Meanwhile, a risk prognosis model was constructed, which can predict the overall survival rate in the validation set. Lastly, we verified the importance of model genes in three independent GEO cohorts. In short, we constructed a prognostic model that assists in patient risk stratification based on ferroptosis-immune-related genes in IDC. This model helps assess patients' prognoses and guide individualized treatment, which also further eelucidatesthe molecular mechanisms of IDC.}, } @article {pmid36641655, year = {2022}, author = {Kridis, WB and Feki, A and Khmiri, S and Toumi, N and Chaabene, K and Daoud, J and Ayedi, I and Khanfir, A}, title = {Prognostic factors in inflammatory breast cancer: A single-center study.}, journal = {Breast disease}, volume = {41}, number = {1}, pages = {461-469}, doi = {10.3233/BD-220034}, pmid = {36641655}, issn = {1558-1551}, mesh = {Female ; Humans ; Middle Aged ; *Breast Neoplasms/diagnosis/genetics ; Hormones ; *Inflammatory Breast Neoplasms/diagnosis/genetics ; Neoplasm Recurrence, Local ; Prognosis ; Receptor, ErbB-2/genetics/metabolism ; Receptors, Progesterone/metabolism ; Retrospective Studies ; Adult ; Aged ; Aged, 80 and over ; }, abstract = {BACKGROUND: Previous studies have shown that poor prognostic indicators of inflammatory breast cancer (IBC) include younger age at diagnosis, poorer tumor grade, negative estrogen receptor, lesser degree of pathological response in the breast and lymph nodes.

METHODS: This is a retrospective study conducted over a period of 12 years between January 2008 and December 2019 at the medical oncology department at Habib Bourguiba University Hospital in Sfax. We included in this study women with confirmed IBC. We excluded patients with no histological evidence, those whose medical records were unusable. Data collection was done from patient files. The aim of this study was to analyze the factors of poor prognosis of this entity.

RESULTS: During a period of 12 years (2008-2019), 2879 cases of breast cancer were treated at Habib Bourguiba hospital in Sfax. 81 IBC were included. The incidence of IBC was 3%. The average age was 52.4 years (26-87 years). Invasive ductal carcinoma was the most frequent histological type (85.7%). Hormone receptor were positive in 64%. Human Epidermal Growth Factor Receptor-2 (HER2) was overexpressed in 35.9% of cases. The proliferation index Ki-67 was analyzed in 34 cases. It was >20% in 24 cases. Luminal A, luminal B, HER2+++, triple negative were found in 13%, 50.7%, 16% and 20% respectively. Metastases at diagnosis were found in 38%. Poor prognostic factors significantly influencing overall survival in univariate analysis were metastatic stage, high SBR grade, lymph node involvement, in particular greater than 3 nodes, negative hormone receptors, triple-negative molecular profile and occurrence of relapse.

CONCLUSION: Number of positive lymph nodes greater than 3 and the occurrence of relapse were independent prognostic factors in case of localized IBC. Metastatic stage was associated with a very poor prognosis.}, } @article {pmid36637351, year = {2023}, author = {Zhi, R and Wu, K and Zhang, J and Liu, H and Niu, C and Li, S and Fu, L}, title = {PRMT3 regulates the progression of invasive micropapillary carcinoma of the breast.}, journal = {Cancer science}, volume = {114}, number = {5}, pages = {1912-1928}, pmid = {36637351}, issn = {1349-7006}, support = {31870860//National Natural Science Foundation of China/ ; 81872164//National Natural Science Foundation of China/ ; 82173344//National Natural Science Foundation of China/ ; }, mesh = {Humans ; Female ; *Carcinoma, Ductal, Breast/metabolism ; Breast/pathology ; *Breast Neoplasms/pathology ; Histones ; *Carcinoma, Papillary/metabolism ; Protein-Arginine N-Methyltransferases/genetics/metabolism ; }, abstract = {Invasive micropapillary carcinoma (IMPC) is a special histopathological subtype of breast cancer. Clinically, IMPC exhibits a higher incidence of lymphovascular invasion and lymph node metastasis compared with that of invasive ductal carcinoma (IDC), the most common type. However, the metabolic characteristics and related mechanisms underlying malignant IMPC biological behaviors are unknown. We performed large-scale targeted metabolomics analysis on resected tumors obtained from chemotherapy-naïve IMPC (n = 25) and IDC (n = 26) patients to investigate metabolic alterations, and we integrated mass spectrometry analysis, RNA sequencing, and ChIP-sequencing data to elucidate the potential molecular mechanisms. The metabolomics revealed distinct metabolic profiles between IMPC and IDC. For IMPC patients, the metabolomic profile was characterized by significantly high levels of arginine methylation marks, and protein arginine methyltransferase 3 (PRMT3) was identified as a critical regulator that catalyzed the formation of these arginine methylation marks. Notably, overexpression of PRMT3 was an independent risk factor for poor IMPC prognosis. Furthermore, we demonstrated that PRMT3 was a key regulator of breast cancer cell proliferation and metastasis both in vitro and in vivo, and treatment with a preclinical PRMT3 inhibitor decreased the xenograft tumorigenic capacity. Mechanistically, PRMT3 regulated the endoplasmic reticulum (ER) stress signaling pathway by facilitating histone H4 arginine 3 asymmetric dimethylation (H4R3me2a), which may endow breast cancer cells with great proliferative and metastatic capacity. Our findings highlight PRMT3 importance in regulating the malignant biological behavior of IMPC and suggest that small-molecule inhibitors of PRMT3 activity might be promising breast cancer treatments.}, } @article {pmid38384043, year = {2023}, author = {Soman, PS and Hemalatha, A and Sreeramulu, PN}, title = {Expression of BRCA1 by immunohistochemistry and its association with ER, PR, Her2neu status in infiltrative ductal carcinoma of breast.}, journal = {Journal of cancer research and therapeutics}, volume = {19}, number = {Suppl 2}, pages = {S706-S711}, doi = {10.4103/jcrt.jcrt_639_22}, pmid = {38384043}, issn = {1998-4138}, mesh = {Humans ; Female ; *Breast Neoplasms/pathology ; Receptors, Estrogen/genetics/metabolism ; Receptors, Progesterone/genetics/metabolism ; Immunohistochemistry ; Receptor, ErbB-2/genetics/metabolism ; Mastectomy ; *Carcinoma, Ductal, Breast/genetics/therapy/metabolism ; Biomarkers, Tumor/genetics/metabolism ; BRCA1 Protein/genetics ; }, abstract = {BACKGROUND: Breast cancer is a heterogeneous disease, which differs in its clinical behaviors and responses to treatment and outcome. The prognosis of breast cancer depends on histopathological parameters and molecular subtypes. Among more than 300 genes, which are involved in the pathogenesis of breast cancer tumor suppressor gene such as BRCA1 is known to play a significant role in hereditary cancers. However, its role in sporadic cases of infiltrating ductal carcinoma is yet to be established.

AIMS AND OBJECTIVES: To evaluate the expression of BRCA1 in infiltrative ductal carcinoma and to analyze the association of BRCA1 with histopathological parameters and estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor2 (Her2) neu expression.

MATERIALS AND METHODS: This was a laboratory-based exploratory study in which 56 patients with infiltrative ductal carcinoma who underwent radical mastectomy from October 2019 to July 2021 were included. Patients with chemotherapy and radiotherapy, trucut biopsies, and incomplete patient details were excluded. Immunostaining for BRCA1 was performed. Individual clinicopathological parameters were compared with the BRCA1 mutation. Statistical analysis was done using SPSS 22. A P value of < 0.05 was considered statistically significant.

RESULTS: Among 56 cases of IDC, 18 cases (32.1%) showed BRCA1 mutation. BRCA1 mutation was associated with postmenopausal age, larger tumor size, lower tumor grade, and higher tumor staging. When we analyzed the biomarkers with BRCA1 mutation, it showed a negative association with ER, PR, and Her2 neu and a high Ki67 proliferation index. No family history of breast carcinoma was seen in 34/56 patients where history was available.

CONCLUSION: Our study showed BRCA1 mutation in 32.1% and associated with postmenopausal age group, larger tumor size, and higher staging and negative hormonal status of breast carcinoma.}, } @article {pmid38375814, year = {2023}, author = {Huang, T and Lu, C and Zhang, Y and Lin, BY and Zhang, ZJ and Zhu, D and Wang, L and Lu, Y}, title = {Effect of activating cancer-associated fibroblasts biomarker TNC on immune cell infiltration and prognosis in breast cancer.}, journal = {Annals of medicine}, volume = {55}, number = {2}, pages = {2250987}, pmid = {38375814}, issn = {1365-2060}, mesh = {Humans ; Female ; *Breast Neoplasms/genetics ; *Cancer-Associated Fibroblasts/metabolism/pathology ; Phosphatidylinositol 3-Kinases/metabolism ; Prognosis ; Biomarkers/metabolism ; Tumor Microenvironment ; }, abstract = {BACKGROUND: Cancer-associated fibroblasts (CAFs) are the most important components of the tumor microenvironment (TME). CAFs are heterogeneous and involved in tumor tumorigenesis and drug resistance, contributing to TME remodeling and predicting clinical outcomes as prognostic factors. However, the effect of CAFs the TME and the prognosis of patients with breast cancer (BC) is not fully understood. This study investigated the correlation between CAFs-activating biomarkers immune cell infiltration and survival in patients with breast cancer.

METHODS: RNA sequencing data and survival information for patients with breast cancer were downloaded from The Cancer Genome Atlas (TCGA) using R software. We then analyzed the correlation between CAFs-expressing biomarkers and immune cells using the clusterProfiler package, and evaluated the prognostic role of appealing genes using the Survminer package. Immunohistochemical (IHC) staining was used to determine the expression levels of TNC in 160 breast cancer samples pathologically diagnosed as invasive ductal carcinoma that were not otherwise specified (IDC-NOS).

RESULTS: Data analysis showed that CAFs-expressing genes was higher than in normal tissues (p < 0.05). Pathway enrichment revealed that the overexpression of CAFs-related genes was mainly enriched in the focal adhesion and phosphoinositol-3 kinase-serine/threonine kinase (PI3K-AKT) signaling pathways. Immune infiltration analysis suggested that high expression of CAFs-related genes was significantly positively correlated with the infiltration of naive B cells and resting dendritic cells and inversely correlated with macrophages cell infiltration. In addition, high TNC expression in tumor cells was associated with the most adverse clinicopathological features and reduced metastasis-free survival (MFS) (hazard ratio (HR) 0.574, 95% confidence interval (CI) 0.404-0.815, p = 0.035).

CONCLUSIONS: This study found that CAFs may participate in immunosuppression and regulate tumor cell proliferation and invasion. High TNC expression is associated with several adverse clinicopathological features, and high TNC expression in tumor cells has been identified as an independent prognostic factor for IDC-NOS.}, } @article {pmid36587134, year = {2023}, author = {Levy-Jurgenson, A and Tekpli, X and Kristensen, VN and Yakhini, Z}, title = {Analysis of Spatial Molecular Data.}, journal = {Methods in molecular biology (Clifton, N.J.)}, volume = {2614}, number = {}, pages = {349-356}, pmid = {36587134}, issn = {1940-6029}, mesh = {Humans ; *Neoplasms/diagnosis/genetics ; Phenotype ; Algorithms ; Microscopy/methods ; }, abstract = {Digital analysis of pathology whole-slide images has been recently gaining interest in the context of cancer diagnosis and treatment. In particular, deep learning methods have demonstrated significant potential in supporting pathology analysis, recently detecting molecular traits never before recognized in pathology H&E whole-slide images (WSIs). Alongside these advancements in the digital analysis of WSIs, it is becoming increasingly evident that both spatial and overall tumor heterogeneity may be significant determinants of cancer prognosis and treatment outcome. In this chapter, we describe methods that aim to support these two elements. We describe both an end-to-end deep learning pipeline for producing limited spatial transcriptomics from WSIs with associated bulk gene expression data, as well as an algorithm for quantifying spatial tumor heterogeneity based on the results of this pipeline.}, } @article {pmid36574856, year = {2023}, author = {Ying, Z and van Eenige, R and Beerepoot, R and Boon, MR and Kloosterhuis, NJ and van de Sluis, B and Bartelt, A and Rensen, PCN and Kooijman, S}, title = {Mirabegron-induced brown fat activation does not exacerbate atherosclerosis in mice with a functional hepatic ApoE-LDLR pathway.}, journal = {Pharmacological research}, volume = {187}, number = {}, pages = {106634}, doi = {10.1016/j.phrs.2022.106634}, pmid = {36574856}, issn = {1096-1186}, mesh = {Animals ; Humans ; Mice ; *Adipose Tissue, Brown ; Adrenergic Agonists/metabolism/pharmacology ; Apolipoproteins E/genetics/metabolism ; *Atherosclerosis/drug therapy/metabolism ; Cholesterol/metabolism ; Fatty Acids/metabolism ; Lipoproteins, LDL/metabolism ; Liver/metabolism ; Triglycerides ; Receptors, LDL/metabolism ; }, abstract = {Activation of brown adipose tissue (BAT) with the β3-adrenergic receptor agonist CL316,243 protects mice from atherosclerosis development, and the presence of metabolically active BAT is associated with cardiometabolic health in humans. In contrast, exposure to cold or treatment with the clinically used β3-adrenergic receptor agonist mirabegron to activate BAT exacerbates atherosclerosis in apolipoprotein E (ApoE)- and low-density lipoprotein receptor (LDLR)-deficient mice, both lacking a functional ApoE-LDLR pathway crucial for lipoprotein remnant clearance. We, therefore, investigated the effects of mirabegron treatment on dyslipidemia and atherosclerosis development in APOE*3-Leiden.CETP mice, a humanized lipoprotein metabolism model with a functional ApoE-LDLR clearance pathway. Mirabegron activated BAT and induced white adipose tissue (WAT) browning, accompanied by selectively increased fat oxidation and attenuated fat mass gain. Mirabegron increased the uptake of fatty acids derived from triglyceride (TG)-rich lipoproteins by BAT and WAT, which was coupled to increased hepatic uptake of the generated cholesterol-enriched core remnants. Mirabegron also promoted hepatic very low-density lipoprotein (VLDL) production, likely due to an increased flux of fatty acids from WAT to the liver, and resulted in transient elevation in plasma TG levels followed by a substantial decrease in plasma TGs. These effects led to a trend toward lower plasma cholesterol levels and reduced atherosclerosis. We conclude that BAT activation by mirabegron leads to substantial metabolic benefits in APOE*3-Leiden.CETP mice, and mirabegron treatment is certainly not atherogenic. These data underscore the importance of the choice of experimental models when investigating the effect of BAT activation on lipoprotein metabolism and atherosclerosis.}, } @article {pmid36548300, year = {2022}, author = {Shapiro-Kulnane, L and Selengut, M and Salz, HK}, title = {Safeguarding Drosophila female germ cell identity depends on an H3K9me3 mini domain guided by a ZAD zinc finger protein.}, journal = {PLoS genetics}, volume = {18}, number = {12}, pages = {e1010568}, pmid = {36548300}, issn = {1553-7404}, support = {R01 GM129478/GM/NIGMS NIH HHS/United States ; S10 OD016164/OD/NIH HHS/United States ; }, mesh = {Animals ; Male ; *Drosophila/metabolism ; Drosophila melanogaster/genetics/metabolism ; *Drosophila Proteins/genetics/metabolism ; Germ Cells/metabolism ; Homeodomain Proteins/metabolism ; Zinc Fingers/genetics ; Female ; }, abstract = {H3K9me3-based gene silencing is a conserved strategy for securing cell fate, but the mechanisms controlling lineage-specific installation of this epigenetic mark remain unclear. In Drosophila, H3K9 methylation plays an essential role in securing female germ cell fate by silencing lineage inappropriate phf7 transcription. Thus, phf7 regulation in the female germline provides a powerful system to dissect the molecular mechanism underlying H3K9me3 deposition onto protein coding genes. Here we used genetic studies to identify the essential cis-regulatory elements, finding that the sequences required for H3K9me3 deposition are conserved across Drosophila species. Transposable elements are also silenced by an H3K9me3-mediated mechanism. But our finding that phf7 regulation does not require the dedicated piRNA pathway components, piwi, aub, rhino, panx, and nxf2, indicates that the mechanisms of H3K9me3 recruitment are distinct. Lastly, we discovered that an uncharacterized member of the zinc finger associated domain (ZAD) containing C2H2 zinc finger protein family, IDENTITY CRISIS (IDC; CG4936), is necessary for H3K9me3 deposition onto phf7. Loss of idc in germ cells interferes with phf7 transcriptional regulation and H3K9me3 deposition, resulting in ectopic PHF7 protein expression. IDC's role is likely to be direct, as it localizes to a conserved domain within the phf7 gene. Collectively, our findings support a model in which IDC guides sequence-specific establishment of an H3K9me3 mini domain, thereby preventing accidental female-to-male programming.}, } @article {pmid36510982, year = {2022}, author = {Azmat, H and Faridi, J and Habib, HM and Bugti, UJ and Sheikh, AK and Riaz, SK}, title = {Correlation of B-cell lymphoma 2 immunoexpression in invasive carcinoma of breast, no special type with hormone receptor status, proliferation index, and molecular subtypes.}, journal = {Journal of cancer research and therapeutics}, volume = {18}, number = {Supplement}, pages = {S313-S319}, doi = {10.4103/jcrt.JCRT_735_20}, pmid = {36510982}, issn = {1998-4138}, mesh = {Humans ; Female ; Receptor, ErbB-2/genetics/metabolism ; Ki-67 Antigen/genetics/metabolism ; Receptors, Progesterone/metabolism ; Receptors, Estrogen/metabolism ; *Carcinoma/pathology ; *Breast Neoplasms/pathology ; Prognosis ; Hormones ; Cell Proliferation/genetics ; Proto-Oncogene Proteins c-bcl-2 ; Biomarkers, Tumor/metabolism ; }, abstract = {BACKGROUND: B-cell lymphoma 2 is involved in various cancers including breast carcinoma. Its expression in breast cancer has been associated with good prognostic factors such as hormone receptor expression, low Ki-67, low grade, and earlier stage. It is also considered to be an independent prognostic factor for luminal and triple-negative tumors.

OBJECTIVE: We aimed to determine the expression of B-cell lymphoma 2 (BCL2) in different molecular subtypes of invasive ductal carcinoma of breast and its association with prognostic indicators.

MATERIALS AND METHODS: Fifty samples of invasive carcinoma of breast, no special type (NST), were categorized into molecular subtypes according to immunohistochemical expression of estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor 2 (HER2), and Ki-67 and then evaluated for BCL2 expression. The expression of BCL2 was correlated with ER, PR, HER2, and Ki-67 and compared between luminal and nonluminal subtypes.

RESULTS: The BCL2 expression was seen in 68% of the cases with a significant association with ER, PR, and luminal subtypes. No significant association of BCL2 expression was seen with grade, HER2 and Ki-67 status of the tumor, or age group of the patients. BCL2 expression is significantly associated with ER, PR, and luminal subtypes in breast cancer.

CONCLUSION: BCL2 is a marker of good prognosis in invasive carcinoma of breast, NST.}, } @article {pmid36501121, year = {2022}, author = {Leikin-Frenkel, A and Schnaider Beeri, M and Cooper, I}, title = {How Alpha Linolenic Acid May Sustain Blood-Brain Barrier Integrity and Boost Brain Resilience against Alzheimer's Disease.}, journal = {Nutrients}, volume = {14}, number = {23}, pages = {}, pmid = {36501121}, issn = {2072-6643}, mesh = {Humans ; *Alzheimer Disease/drug therapy ; Blood-Brain Barrier/metabolism ; alpha-Linolenic Acid/metabolism ; Brain/metabolism ; Apolipoprotein E4/genetics/metabolism ; }, abstract = {Cognitive decline, the primary clinical phenotype of Alzheimer's disease (AD), is currently attributed mainly to amyloid and tau protein deposits. However, a growing body of evidence is converging on brain lipids, and blood-brain barrier (BBB) dysfunction, as crucial players involved in AD development. The critical role of lipids metabolism in the brain and its vascular barrier, and its constant modifications particularly throughout AD development, warrants investigation of brain lipid metabolism as a high value therapeutic target. Yet, there is limited knowledge on the biochemical and structural roles of lipids in BBB functionality in AD. Within this framework, we hypothesize that the ApoE4 genotype, strongly linked to AD risk and progression, may be related to altered fatty acids composition in the BBB. Interestingly, alpha linolenic acid (ALA), the precursor of the majoritarian brain component docosahexaenoic acid (DHA), emerges as a potential novel brain savior, acting via BBB functional improvements, and this may be primarily relevant to ApoE4 carriers.}, } @article {pmid36472800, year = {2023}, author = {Chang, YS and Tu, SJ and Chen, HD and Hsu, MH and Chen, YC and Chao, DS and Chung, CC and Chou, YP and Chang, CM and Lee, YT and Yen, JC and Jeng, LB and Chang, JG}, title = {Integrated genomic analyses of hepatocellular carcinoma.}, journal = {Hepatology international}, volume = {17}, number = {1}, pages = {97-111}, pmid = {36472800}, issn = {1936-0541}, support = {DMR-111-135//China Medical University Hospital/ ; MOST-109-2320-B-039-052//Ministry of Science and Technology (TW)/ ; MOST-110-2321-B-039-002//Ministry of Science and Technology (TW)/ ; }, mesh = {Humans ; *Carcinoma, Hepatocellular/genetics/pathology ; *Liver Neoplasms/genetics/pathology ; Mutation ; Genomics ; Gene Expression Profiling ; Aldehyde Dehydrogenase, Mitochondrial/genetics ; }, abstract = {BACKGROUND: Genomic alterations play important roles in the development of cancer. We explored the impact of protein-coding genes and transcriptomic changes on clinical and molecular alterations in Taiwanese hepatocellular carcinoma (HCC) patients.

METHODS: We analyzed 147 whole-exome sequencing and 100 RNA sequencing datasets of HCC and compared them with The Cancer Genome Atlas (TCGA)-Liver Hepatocellular Carcinoma cohort and develop a panel of 81 apoptosis-related genes for molecular classification.

RESULTS: TERT (50%), TP53 (25%), CTNNB1 (14%), ARID1A (12%), and KMT2C (11%) were the most common genetic alterations of cancer-related genes. ALDH2 and KMT2C mutated at much higher frequencies in our cohort than in TCGA, whereas CTNNB1 was found only in 14% of our Taiwanese patients. A high germline mutation rate of ALDH2 in the APOBEC mutational signature and herb drug-related aristolochic acid-associated signature was also observed. Groups A and B of HCC were identified when we used apoptosis-related genes for molecular classification. The latter group, which had poorer survival outcomes, had significantly more aDC, CD4+ Tem, macrophages M2, NKT, plasma cells, and Th1 cells, and less CD4+ memory T cells, CD8+ Tcm, cDC, iDC, and Th2 cells, as well as more inter-chromosome fusion genes. Metatranscriptomic analysis revealed 54 cases of HBV infection. Moreover, we found that the main target gene of HBV integration is ALB.

CONCLUSIONS: Unique genomic alterations were observed in our Taiwanese HCC patients. Molecular classification using apoptosis-related genes could lead to new therapeutic approaches for HCC.}, } @article {pmid36472055, year = {2022}, author = {Ortiz-Rey, JA and Bellas-Pereira, A and San Miguel-Fraile, P and Morellón-Baquera, R and Domínguez-Arístegui, P and González-Carreró Fojón, J}, title = {Intraductal Carcinoma of the Prostate without High-Grade Invasive Adenocarcinoma: Report of Two Cases and Review of the Literature.}, journal = {Archivos espanoles de urologia}, volume = {75}, number = {9}, pages = {738-745}, doi = {10.56434/j.arch.esp.urol.20227509.108}, pmid = {36472055}, issn = {0004-0614}, mesh = {Male ; Humans ; Aged ; Prostate/pathology ; *Prostatic Intraepithelial Neoplasia/genetics/pathology/surgery ; *Carcinoma, Intraductal, Noninfiltrating/genetics/pathology/surgery ; Prostatectomy ; Neoplasm Grading ; *Prostatic Neoplasms/pathology ; *Adenocarcinoma/surgery ; }, abstract = {OBJECTIVES: Intraductal carcinoma of the prostate (IDC-P) is usually associated with high grade, aggresive acinar adenocarcinomas. IDC-P is supposed to result from the spread of the adenocarcinoma along the prostatic ducts. IDC-P rarely occurs without invasive carcinoma or with a coexistent low grade adenocarcinoma.

MATERIAL AND METHODS: We report two patients, 66 and 75 year-old, who presented IDC-P and low-grade acinar adenocarcinoma foci in their radical prostatectomy surgical specimens.

RESULTS: Acinar adenocarcinomas were grade group 1, PTEN+, pT2. In the first case, the invasive adenocarcinoma was adjacent but nor intermingled with the IDC-P, and a discordance in the immunophenotype between them was outstanding (positivity for ERG in the acinar carcinoma being negative in the IDC-P). In the second case, the foci of adenocarcinoma were distant from the IDC-P. The first patient had not biochemical recurrence after a 34 month follow-up period.

CONCLUSIONS: This kind of cases supports the existence of an infrequent subtype of IDC-P that could be considered as an in situ neoplasia.}, } @article {pmid36412439, year = {2022}, author = {Abbas, Z and Nouroz, F and Ejaz, S}, title = {Exceptional behavior of breast cancer-associated type 1 gene in breast invasive carcinoma.}, journal = {Journal of cancer research and therapeutics}, volume = {18}, number = {6}, pages = {1743-1753}, doi = {10.4103/jcrt.JCRT_1310_20}, pmid = {36412439}, issn = {1998-4138}, mesh = {Humans ; Female ; *Breast Neoplasms/pathology ; Genes, BRCA1 ; BRCA1 Protein/genetics ; *Carcinoma/genetics ; *Antineoplastic Agents ; }, abstract = {BACKGROUND: Cellular expression level of Breast Cancer-Associated Type 1 (BRCA1) encoded protein is the sign of genome integrity, stability, and surveillance. BRCA1 after sensing DNA damage activates repairing system and if mutated leaves genomic lesions unrepaired and triggers transformation of normal breast cells into cancerous ones.

AIMS OF STUDY: We conducted in silico study to have a holistic view of BRCA1's correlation with multiple variables of breast invasive carcinoma.

MATERIALS AND METHODS: We used user-friendly online GeneCardsSuite pathway-level enrichment analysis, UALCAN portal differential expression analysis, cBioPortal cancer genome platform for mutatome map construction, and cancer cell lines encyclopedia genomics of drug sensitivity toolkit to understand correlation of BRCA1 expression with the effectiveness of anti-cancer drugs.

RESULTS: Contrary to general behavior of a tumor suppressor gene our study revealed BRCA1 overexpression under all circumstances. This novel finding needs to be explored further to understand functional impact of BRCA1 overexpression on the expression of many genes which are transcriptionally regulated by BRCA1 and promotion of tumriogenesis.

CONCLUSION: Our study highlights the potential role of BRCA1-regulated genes in oncogenesis and recommends use of BRCA1-linked genes as future therapeutic targets for effective disease management.}, } @article {pmid36411355, year = {2022}, author = {Kalyan, VSRK and Meena, S and Karthikeyan, S and Jawahar, D}, title = {Isolation, screening, characterization, and optimization of bacteria isolated from calcareous soils for siderophore production.}, journal = {Archives of microbiology}, volume = {204}, number = {12}, pages = {721}, pmid = {36411355}, issn = {1432-072X}, support = {E28ACC//Science and Engineering Research Board/ ; }, mesh = {*Siderophores ; *Soil ; India ; Bacteria/genetics ; Iron Chelating Agents ; }, abstract = {The most effective agricultural practice to prevent iron deficiency in calcareous soils is fertilizing with synthetic chelates. These compounds are non-biodegradable, and persistent in the environment; hence, there is a risk of leaching metals into the soil horizon. To tackle iron deficiency-induced chlorosis (IDC) in crops grown on calcareous soils, environmentally friendly solutions are needed rather than chemical application as it affects the soil health further. Hence, the present work focused on isolating and screening calcareous soil-specific bacteria capable of producing iron-chelating siderophores. Siderophore-producing bacteria (SPB) was isolated from the groundnut (Arachis hypogea L.) rhizosphere region, collected from Coimbatore district, Tamil Nadu, of which 17 bacterial isolates were positive for siderophore production assayed by chrome azurol sulphonate. The performance of SPB isolates was compared for siderophore kinetics, level of siderophore production, type of siderophore produced and iron-chelating capacity under 15 mM KHCO3. Four best performing isolates were screened, with average siderophores yield ranging ∼60-80% under pH 8, with sucrose as carbon source and NH2SO4 as nitrogen source at 37 °C. The four efficient SPB were molecularly identified as B. licheniformis, B. subtilis, B. licheniformis, and O. grignonense based on 16S rDNA sequencing. The simultaneous inhibition method showed T.viride has the highest antagonistic effect against S.rolfsii, and M.phaseolina with a reduction of mycelial growth by 69.3 and 65.1%, respectively, compared to control. Our results indicate that the optimized conditions enhanced siderophores chelation by suppressing the stem and root rot fungi, which could help in a cost-effective and environmentally friendly manner.}, } @article {pmid36394689, year = {2023}, author = {Mamtani, A and Grabenstetter, A and Sevilimedu, V and Morrow, M and Gemignani, ML}, title = {Do non-classic invasive lobular carcinomas derive a benefit from neoadjuvant chemotherapy?.}, journal = {Breast cancer research and treatment}, volume = {197}, number = {2}, pages = {417-423}, pmid = {36394689}, issn = {1573-7217}, support = {P30 CA008748/CA/NCI NIH HHS/United States ; P30CA008748//NIH/NCI Cancer Center Support Grant/ ; }, mesh = {Humans ; Female ; *Breast Neoplasms/drug therapy/genetics/pathology ; *Carcinoma, Lobular/pathology ; *Carcinoma, Ductal, Breast/pathology ; Neoadjuvant Therapy ; Breast/pathology ; }, abstract = {PURPOSE: Invasive lobular breast cancers (ILCs) respond poorly to neoadjuvant chemotherapy (NAC). The degree of benefit of NAC among non-classic ILC (NC-ILC) variants compared with classic ILCs (C-ILCs) is unknown.

METHODS: Consecutive patients with Stage I-III ILC treated from 2003 to 2019 with NAC and surgery were identified, and grouped as C-ILC or NC-ILC as per the original surgical pathology report, with pathologist (A.G.) review performed if original categorization was unclear. A subset of similarly treated invasive ductal cancers (IDCs) was identified for comparison. Clinicopathologic characteristics and pathologic complete response (pCR) rates were evaluated.

RESULTS: Of 145 patients with ILC, 101 (70%) were C-ILC and 44 (30%) were NC-ILC (IDC cohort: 1157 patients). ILC patients were older, more often cT3/T4 and cN2/N3, and less often high-grade compared to IDC patients. Those with NC-ILC were less often ER+/HER2- (55% versus 93%), and more often HER2 + (25% versus 7%) and TN (21% versus 0%, all p < 0.001). Breast pCR was more common among NC-ILC, but most frequent in IDC. Nodal pCR rates were also lowest among C-ILC patients, but similar among NC-ILC and IDC patients. On multivariable analysis, C-ILC (OR 0.09) and LVI (OR 0.51) were predictive of lack of breast pCR; non-ER+/HER2- subtypes and breast pCR were predictive of nodal pCR. When our analysis was repeated with patients stratified by receptor subtype, histology was not independently predictive of either breast or nodal pCR.

CONCLUSION: NC-ILC patients were significantly more likely to achieve breast and nodal pCR compared with C-ILC patients, but when stratified by subtype, histology was not independently predictive of breast or nodal pCR.}, } @article {pmid36357366, year = {2022}, author = {Willemsen, N and Kotschi, S and Bartelt, A}, title = {Fire up the pyre: inosine thermogenic signaling for obesity therapy.}, journal = {Signal transduction and targeted therapy}, volume = {7}, number = {1}, pages = {375}, pmid = {36357366}, issn = {2059-3635}, support = {PROTEOFIT/ERC_/European Research Council/International ; }, mesh = {Humans ; *Bacterial Proteins ; *Signal Transduction ; Inosine ; Obesity/genetics ; }, } @article {pmid36350000, year = {2022}, author = {Chen, W and Wang, G and Zhang, G}, title = {Insights into the transition of ductal carcinoma in situ to invasive ductal carcinoma: morphology, molecular portraits, and the tumor microenvironment.}, journal = {Cancer biology & medicine}, volume = {19}, number = {10}, pages = {1487-1495}, pmid = {36350000}, issn = {2095-3941}, mesh = {Humans ; Female ; *Carcinoma, Intraductal, Noninfiltrating/pathology ; Tumor Microenvironment/genetics ; *Carcinoma, Ductal, Breast/pathology ; Biomarkers, Tumor ; *Breast Neoplasms/genetics ; }, } @article {pmid36332363, year = {2022}, author = {Davis, AA and Gerratana, L and Clifton, K and Medford, AJ and Velimirovic, M and Hensing, WL and Bucheit, L and Shah, AN and D'Amico, P and Reduzzi, C and Zhang, Q and Dai, CS and Denault, EN and Bagegni, NA and Opyrchal, M and Ademuyiwa, FO and Bose, R and Gradishar, WJ and Behdad, A and Ma, CX and Bardia, A and Cristofanilli, M}, title = {Circulating tumour DNA characterisation of invasive lobular carcinoma in patients with metastatic breast cancer.}, journal = {EBioMedicine}, volume = {86}, number = {}, pages = {104316}, pmid = {36332363}, issn = {2352-3964}, support = {UL1 TR001422/TR/NCATS NIH HHS/United States ; }, mesh = {Humans ; Female ; *Breast Neoplasms/pathology ; *Carcinoma, Lobular/genetics/metabolism/pathology ; *Carcinoma, Ductal, Breast/genetics/metabolism/pathology ; *Circulating Tumor DNA/genetics ; Retrospective Studies ; DNA Copy Number Variations ; Phosphatidylinositol 3-Kinases/genetics ; }, abstract = {BACKGROUND: Limited data exist to characterise molecular differences in circulating tumour DNA (ctDNA) for patients with invasive lobular carcinoma (ILC). We analysed metastatic breast cancer patients with ctDNA testing to assess genomic differences among patients with ILC, invasive ductal carcinoma (IDC), and mixed histology.

METHODS: We retrospectively analysed 980 clinically annotated patients (121 ILC, 792 IDC, and 67 mixed histology) from three academic centers with ctDNA evaluation by Guardant360™. Single nucleotide variations (SNVs), copy number variations (CNVs), and oncogenic pathways were compared across histologies.

FINDINGS: ILC was significantly associated with HR+ HER2 negative and HER2 low. SNVs were higher in patients with ILC compared to IDC or mixed histology (Mann Whitney U test, P < 0.05). In multivariable analysis, HR+ HER2 negative ILC was significantly associated with mutations in CDH1 (odds ratio (OR) 9.4, [95% CI 3.3-27.2]), ERBB2 (OR 3.6, [95% confidence interval (CI) 1.6-8.2]), and PTEN (OR 2.5, [95% CI 1.05-5.8]) genes. CDH1 mutations were not present in the mixed histology cohort. Mutations in the PI3K pathway genes (OR 1.76 95% CI [1.18-2.64]) were more common in patients with ILC. In an independent cohort of nearly 7000 metastatic breast cancer patients, CDH1 was significantly co-mutated with targetable alterations (PIK3CA, ERBB2) and mutations associated with endocrine resistance (ARID1A, NF1, RB1, ESR1, FGFR2) (Benjamini-Hochberg Procedure, all q < 0.05).

INTERPRETATION: Evaluation of ctDNA revealed differences in pathogenic alterations and oncogenic pathways across breast cancer histologies with implications for histologic classification and precision medicine treatment.

FUNDING: Lynn Sage Cancer Research Foundation, OncoSET Precision Medicine Program, and UL1TR001422.}, } @article {pmid36308374, year = {2022}, author = {Gautam, P and Feroz, Z and Tiwari, S and Vijayraghavalu, S and Shukla, GC and Kumar, M}, title = {Investigating the Role of Glutathione S- Transferase Genes, Histopathological and Molecular Subtypes, Gene-Gene Interaction and Its Susceptibility to Breast Carcinoma in Ethnic North- Indian Population.}, journal = {Asian Pacific journal of cancer prevention : APJCP}, volume = {23}, number = {10}, pages = {3481-3490}, pmid = {36308374}, issn = {2476-762X}, support = {R15 CA252997/CA/NCI NIH HHS/United States ; }, mesh = {Female ; Humans ; *Breast Neoplasms/epidemiology/genetics ; Case-Control Studies ; *Genetic Predisposition to Disease ; Genotype ; Glutathione ; Glutathione S-Transferase pi/genetics ; Glutathione Transferase/genetics ; Risk Factors ; }, abstract = {BACKGROUND: Breast Cancer (BC) is a genetically and clinically heterogeneous disease including complex interactions between gene-gene and gene-environment components. This study aimed, to explore whether the Glutathione S- transferase (GSTs) gene polymorphism has role in BC susceptibility. We further evaluated the frequency of four subtypes of BC based on molecular classification followed by microscopic histological analysis to study the grades of invasive ductal carcinoma (IDC).

MATERIALS AND METHOD: Polymorphism in GST genes in North-Indian BC patients was assessed by multiplex-PCR and PCR-RFLP methods. 105 BC patients and 145 healthy controls were enrolled for this study. Data was analyzed by calculating the odds ratio (OR) and 95% CI from logistic regression analyses.

RESULTS: Our findings revealed that GSTM1 null genotype (OR = 2.231; 95% CI = 1.332-3.737; p-value= 0.002) is significantly associated to BC risk in ethnic North- Indian population. However, the risk for BC susceptibility in North-Indians does not appear to be associated with GSTT1 null genotype. The GSTP1 (Val/Val) genotype (OR=1.545; CI=0.663-3.605; p-value= 0.314) was also found to be susceptible for BC risk. Combination of three high risk GST genotypes association exhibiting gene-gene interaction further confirmed the increased risk to BC in this region.

CONCLUSIONS: The results of present study indicated that polymorphism in GSTM1 and rs1695 of GSTP1 genes may influence BC development among North-Indian women. Thus, the screening of GSTM1 and GSTP1 gene should be recommended for the earlier investigation for BC as a precautionary measure.}, } @article {pmid36245246, year = {2022}, author = {Blawski, R and Toska, E}, title = {A Unique FOXA1-Associated Chromatin State Dictates Therapeutic Resistance in Lobular Breast Cancer.}, journal = {Cancer research}, volume = {82}, number = {20}, pages = {3668-3670}, pmid = {36245246}, issn = {1538-7445}, support = {K22 CA245487/CA/NCI NIH HHS/United States ; P30 CA006973/CA/NCI NIH HHS/United States ; R21 CA252530/CA/NCI NIH HHS/United States ; }, mesh = {*Breast Neoplasms/drug therapy/genetics/pathology ; *Carcinoma, Ductal, Breast/pathology ; *Carcinoma, Lobular/drug therapy/genetics/metabolism ; Chromatin/genetics ; Drug Resistance, Neoplasm/genetics ; Female ; Hepatocyte Nuclear Factor 3-alpha/genetics ; Humans ; Receptors, Estrogen/genetics/metabolism ; Retrospective Studies ; Tamoxifen/pharmacology/therapeutic use ; }, abstract = {Invasive lobular carcinomas (ILC) are the second most common histologic subtype of breast cancer, accounting for up to 15% of cases. ILC is estrogen receptor (ER) positive, yet its biology is distinct from invasive ductal carcinomas (IDC), and retrospective analyses have indicated a poorer outcome with endocrine therapy. In this issue of Cancer Research, Nardone and colleagues investigated the mechanisms of this differential therapy response in ILC, which cannot be solely explained by the genetic profile of these tumors. The authors conducted a thorough examination of the epigenome of ILC compared with IDC in clinical and preclinical models and revealed an alternative chromatin accessibility state in ILC driven by the pioneer factor FOXA1. FOXA1 regulates its own expression in a feed-forward mechanism by binding to an ILC-unique FOXA1 enhancer site. This results in a FOXA1-ER axis that promotes the transcription of genes associated with tumor progression and tamoxifen resistance. Targeting the FOXA1 enhancer region blocks this transcriptional program and inhibits ILC proliferation. These results shed light on a new epigenetic mechanism driving ILC tumor progression and treatment resistance, which may have profound therapeutic implications. See related article by Nardone et al., p. 3673.}, } @article {pmid36238494, year = {2022}, author = {Zhao, W and Wu, T and Zhan, J and Dong, Z}, title = {Identification of the Immune Status of Hypertrophic Cardiomyopathy by Integrated Analysis of Bulk- and Single-Cell RNA Sequencing Data.}, journal = {Computational and mathematical methods in medicine}, volume = {2022}, number = {}, pages = {7153491}, pmid = {36238494}, issn = {1748-6718}, mesh = {Animals ; Biomarkers ; *Cardiomyopathy, Hypertrophic/genetics/metabolism ; Gene Regulatory Networks ; Mice ; *MicroRNAs ; Sequence Analysis, RNA ; }, abstract = {OBJECTIVES: Hypertrophic cardiomyopathy (HCM) is the most common hereditary cardiomyopathy and immune infiltration is considered an indispensable factor involved in its pathogenesis. In this study, we attempted to combine bulk sequencing and single-cell sequencing to map the immune infiltration-related genes in hypertrophic cardiomyopathy.

METHODS: The GSE36961, GSE160997, and GSE122930 datasets were obtained from the Gene Expression Omnibus database. The compositional patterns of the 18 types of immune cell fraction and pathway enrichment score in control and HCM patients were estimated based on the GSE36961 cohort using xCell algorithm. The Weighted Gene Coexpression Network Analysis (WGCNA) was performed to identify genes associated with immune infiltration for hypertrophic cardiomyopathy. The area under the curve (AUC) value was obtained and used to evaluate the discriminatory ability of common immune-related DEGs. "NetworkAnalyst" platform was used to identify TF-gene and TF-miRNA interaction with identified common genes. Heat map was used to determine the association between common DEGs and various immune cells.

RESULTS: Immune infiltration analysis by the xCell algorithm showed a higher level of CD8+ naive T cells, CD8+ T cells, as well as a lower level of activated dendritic cells (aDC), dendritic cells (DC), immature dendritic cells (iDC), conventional dendritic cells (cDC), macrophages, M1 macrophages, monocytes, and NKT cell in HCM compared with the control group in GSE36961 dataset. aDC, macrophages, and M1 macrophages were the top three discriminators between HCM and control groups with the area under the curve (AUC) of 0.907, 0.867, and 0.941. WGCNA analysis showed that 1258 immune-related genes were included in four different modules. Of these modules, the turquoise module showed a pivotal correlation with HCM. 13 common immune-related DEGs were found by intersecting common DEGs in GSE36961 and GSE160997 datasets with genes from the genes in turquoise module. 5 hub immune-related genes (S100A9, TYROBP, FCER1G, CD14, and S100A8) were identified by protein interaction network. Through analysis of single-cell sequencing data, S100a9, TYROBP, FCER1G, and S100a8 were mainly expressed by infiltrated M1 proinflammatory cells, especially Ccr2-M1 proinflammatory macrophage cells in the heart immune microenvironment while Cd14 was expressed by infiltrated M1 proinflammatory macrophage cells and M2 macrophages in transverse aortic constriction (TAC) mice at 1 week. Higher M2 macrophage and M1 proinflammatory macrophage infiltration as well as lower Ccr2-M1 proinflammatory macrophage and dendritic cells were shown in TAC 1week mice compared with sham mice.

CONCLUSIONS: There was a difference in immune infiltration between HCM patients and normal groups. aDC, macrophages, and M1 macrophages were the top three discriminator immune cell subsets between HCM and control groups. S100A9, TYROBP, FCER1G, CD14, and S100A8 were identified as potential biomarkers to discriminate HCM from the control group. S100a9, TYROBP, FCER1G, and S100a8 were mainly expressed by infiltrated M1 proinflammatory cells, especially Ccr2-M1 proinflammatory cells in the heart immune microenvironment while Cd14 was expressed by M2 macrophages in transverse aortic constriction (TAC) mice at 1 week.}, } @article {pmid36229464, year = {2022}, author = {Wong, HY and Sheng, Q and Hesterberg, AB and Croessmann, S and Rios, BL and Giri, K and Jackson, J and Miranda, AX and Watkins, E and Schaffer, KR and Donahue, M and Winkler, E and Penson, DF and Smith, JA and Herrell, SD and Luckenbaugh, AN and Barocas, DA and Kim, YJ and Graves, D and Giannico, GA and Rathmell, JC and Park, BH and Gordetsky, JB and Hurley, PJ}, title = {Single cell analysis of cribriform prostate cancer reveals cell intrinsic and tumor microenvironmental pathways of aggressive disease.}, journal = {Nature communications}, volume = {13}, number = {1}, pages = {6036}, pmid = {36229464}, issn = {2041-1723}, support = {S10 OD023475/OD/NIH HHS/United States ; R01 CA194024/CA/NCI NIH HHS/United States ; S10 OD016355/OD/NIH HHS/United States ; T32 CA009582/CA/NCI NIH HHS/United States ; P30 CA068485/CA/NCI NIH HHS/United States ; T32 CA009592/CA/NCI NIH HHS/United States ; R01 CA214494/CA/NCI NIH HHS/United States ; R01 CA218526/CA/NCI NIH HHS/United States ; R01 CA217987/CA/NCI NIH HHS/United States ; R01 CA211695/CA/NCI NIH HHS/United States ; U24 DK059637/DK/NIDDK NIH HHS/United States ; }, mesh = {Apolipoproteins E ; *Carcinoma, Intraductal, Noninfiltrating/genetics ; Extracellular Matrix Proteins ; Humans ; Ligands ; Male ; Neoplasm Grading ; *Prostatic Neoplasms/pathology ; RNA ; Receptors, Antigen, T-Cell ; Single-Cell Analysis ; Tumor Microenvironment/genetics ; }, abstract = {Cribriform prostate cancer, found in both invasive cribriform carcinoma (ICC) and intraductal carcinoma (IDC), is an aggressive histological subtype that is associated with progression to lethal disease. To delineate the molecular and cellular underpinnings of ICC/IDC aggressiveness, this study examines paired ICC/IDC and benign prostate surgical samples by single-cell RNA-sequencing, TCR sequencing, and histology. ICC/IDC cancer cells express genes associated with metastasis and targets with potential for therapeutic intervention. Pathway analyses and ligand/receptor status model cellular interactions among ICC/IDC and the tumor microenvironment (TME) including JAG1/NOTCH. The ICC/IDC TME is hallmarked by increased angiogenesis and immunosuppressive fibroblasts (CTHRC1[+]ASPN[+]FAP[+]ENG[+]) along with fewer T cells, elevated T cell dysfunction, and increased C1QB[+]TREM2[+]APOE[+]-M2 macrophages. These findings support that cancer cell intrinsic pathways and a complex immunosuppressive TME contribute to the aggressive phenotype of ICC/IDC. These data highlight potential therapeutic opportunities to restore immune signaling in patients with ICC/IDC that may afford better outcomes.}, } @article {pmid36223973, year = {2022}, author = {Singh, N and Singh, R and Decker, B and Robins, D and Vidal, G}, title = {Metastatic triple negative breast cancer with NTRK gene fusion on tissue but not on ctDNA molecular profile.}, journal = {BMJ case reports}, volume = {15}, number = {10}, pages = {}, pmid = {36223973}, issn = {1757-790X}, mesh = {*Breast Neoplasms/genetics/pathology ; Carcinoma ; *Circulating Tumor DNA/genetics ; Female ; Gene Fusion ; Humans ; Oncogene Proteins, Fusion/genetics ; Protein Kinase Inhibitors ; *Triple Negative Breast Neoplasms/drug therapy/genetics ; }, abstract = {A woman presented to medical oncology with almost 4 years of untreated, slowly progressing, triple negative metastatic breast cancer to the lung. About 15 years prior, she was diagnosed with invasive ductal carcinoma of the right breast with ipsilateral chest wall recurrence 6 years later. Comprehensive molecular profiling of a metastatic lesion detected a hotspot ETV6-NTRK3 fusion, which was not present on circulating tumour DNA or molecular profile performed 4 years prior. A second look pathological examination demonstrated tumour characteristics consistent with secretory breast carcinoma. Identification of ETV6--NKRT3 fusion allowed for treatment with larotrectinib, a tyrosine kinase inhibitor specifically indicated for secretory breast carcinoma. After 3 months, she experienced a partial response.}, } @article {pmid36208091, year = {2023}, author = {Lu, X and Ying, Y and Zhang, W and Li, R and Zhang, J}, title = {High MutS homolog 2 expression predicts poor prognosis and is related to immune infiltration in endometrial carcinoma.}, journal = {Cell biology international}, volume = {47}, number = {1}, pages = {201-215}, doi = {10.1002/cbin.11925}, pmid = {36208091}, issn = {1095-8355}, support = {182102410095//Science and Technology Department of Henan Province/ ; 212102310466//Science and Technology Department of Henan Province/ ; 2019GGJS004//Education Department of Henan Province/ ; LHGJ20220473//Health Commission of Henan Province/ ; SBGJ202002119//Health Commission of Henan Province/ ; }, mesh = {Female ; Humans ; *Endometrial Neoplasms/diagnosis/pathology ; *MutS Homolog 2 Protein/genetics/metabolism ; Promoter Regions, Genetic ; *Biomarkers, Tumor/genetics/metabolism ; }, abstract = {Several studies have shown that MutS homolog 2 (MSH2) is highly expressed in many cancer tissues. Transcriptome expression data were collected from the Cancer Genome Atlas (TCGA) database. We analyzed the expression of MSH2 in normal and tumor tissues, the relationship between MSH2 expression and various prognostic factors, and the relationship between MSH2 expression and overall survival, disease specific survival, and progression free interval. We also examined MSH2 promoter methylation between endometrial cancer and normal endometrial tissues, and identified the prognostic value of MSH2 methylation in endometrial cancer. MSH2 was highly expressed in endometrial cancer tumor tissues compared with normal tissues. High MSH2 expression might be an independent prognostic factor for OS, DSS, and PFI. Further, high MSH2 expression was correlated with age and histological type, but not with BMI, clinical stage, tumor invasion, or other clinical features. MSH2 promoter methylation in endometrial cancer was significantly lower than in normal tissues. Additionally, MSH2 levels, OS, DSS, and PFI were associated with BMI, age, tumor invasion, and histological type. ssGSEA showed that MSH2 expression was positively correlated with the infiltration of Th2 cells, Tcm cells, T helper cells, and Tgd cells, whereas it was negatively correlated with NK CD56 bright cells, pDC cells, iDC cells, cytotoxic cells, and neutrophils. Increased MSH2 expression and reduced MSH2 methylation in endometrial cancer predicts poor prognosis. MSH2 may be used as a biomarker for the diagnosis and prognosis of endometrial cancer and as an immunotherapy target.}, } @article {pmid36175695, year = {2022}, author = {Silva, FHS and Underwood, A and Almeida, CP and Ribeiro, TS and Souza-Fagundes, EM and Martins, AS and Eliezeck, M and Guatimosim, S and Andrade, LO and Rezende, L and Gomes, HW and Oliveira, CA and Rodrigues, RC and Borges, IT and Cassali, GD and Ferreira, E and Del Puerto, HL}, title = {Transcription factor SOX3 upregulated pro-apoptotic genes expression in human breast cancer.}, journal = {Medical oncology (Northwood, London, England)}, volume = {39}, number = {12}, pages = {212}, pmid = {36175695}, issn = {1559-131X}, support = {05/20160//PRPq UFMG/ ; }, mesh = {*Breast Neoplasms/genetics ; *Carcinoma, Ductal, Breast/genetics ; Caspase 3 ; Female ; Fluorescein-5-isothiocyanate ; Humans ; RNA, Messenger ; SOXB1 Transcription Factors ; Tumor Suppressor Proteins ; Up-Regulation ; bcl-2-Associated X Protein ; }, abstract = {BACKGROUND: Sex-determining region Y-box 3 (SOX3) protein, a SOX transcriptions factors group, has been identified as a key regulator in several diseases, including cancer. Downregulation of transcriptions factors in invasive ductal carcinoma (IDC) can interfere in neoplasia development, increasing its aggressiveness. We investigated SOX3 protein expression and its correlation with apoptosis in the MDA-MB-231 cell line, as SOX3 and Pro-Caspase-3 immunoexpression in paraffin-embedded invasive ductal carcinoma tissue samples from patients (n = 27). Breast cancer cell line MDA-MD-231 transfected with pEF1-SOX3 + and pEF1-Empty vector followed by cytotoxicity assay (MTT), Annexin-V FITC PI for apoptosis percentage assessment by flow cytometry, qPCR for apoptotic-related gene expression, immunofluorescence, and immunohistochemistry to SOX3 immunolocalization in culture cells, and paraffin-embedded invasive ductal carcinoma tissue samples.

RESULTS: Apoptotic rate was higher in cells transfected with pEF1-SOX3 + (56%) than controls (10%). MDA-MB-231 transfected with pEF1-SOX3 + presented upregulation of pro-apoptotic mRNA from CASP3, CASP8, CASP9, and BAX genes, contrasting with downregulation antiapoptotic mRNA from BCL2, compared to non-transfected cells and cells transfected with pEF1-empty vector (p < 0.005). SOX3 protein nuclear expression was detected in 14% (4/27 cases) of ductal carcinoma cases, and pro-Caspase-3 expression was positive in 50% of the cases.

CONCLUSION: Data suggest that SOX3 transcription factor upregulates apoptosis in breast cancer cell line MDA-MB-231, and has a down nuclear expression in ductal carcinoma cases, and need to be investigated as a tumor suppressor protein, and its loss of expression and non-nuclear action turn the cells resistant to apoptosis. Further studies are necessary to understand how SOX3 protein regulates the promoter regions of genes involved in apoptosis.}, } @article {pmid36172685, year = {2022}, author = {Alinezhadi, M and Makvandi, M and Kaydani, GA and Jazayeri, SN and Charostad, J and Talaeizadeh, AT and Angali, KA}, title = {Detection of High-Risk Human Papillomavirus DNA in Invasive Ductal Carcinoma Specimens.}, journal = {Asian Pacific journal of cancer prevention : APJCP}, volume = {23}, number = {9}, pages = {3201-3207}, pmid = {36172685}, issn = {2476-762X}, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; *Alphapapillomavirus/genetics ; *Breast Neoplasms/genetics ; *Carcinoma, Ductal ; Case-Control Studies ; DNA ; DNA, Viral/genetics ; Female ; *Fibroadenoma/genetics ; Formaldehyde ; Humans ; Middle Aged ; Papillomaviridae/genetics ; *Papillomavirus Infections ; Paraffin Embedding ; Young Adult ; }, abstract = {BACKGROUND: According to several studies, there is an association between human papillomavirus (HPV) and breast cancer. Therefore, detection and genotyping of HPV seem important. The present study aimed to investigate the presence of HPV DNA in breast tissues by analyzing the L1 gene.

MATERIALS AND METHODS: This case-control study was conducted on 63 formalin-fixed paraffin-embedded (FFPE) tissues of invasive ductal carcinoma (IDC) as the case group and 32 FFPE tissues of fibroadenoma as the control group. HPV DNA was detected using the polymerase chain reaction assay. Positive samples were then subjected to genotyping. All statistical analyses were performed in SPSS version 22.0.

RESULTS: The patients' age ranged from 15 to 92 years, with a mean age of 43.54±16.36 years. HPV DNA was detected in 17/95 (17.89%) samples, including 9/32 (28.12%) fibroadenoma samples and 8/63 (12.69%) IDC samples. No significant difference was observed regarding the presence of HPV DNA between the IDC and fibroadenoma tissues (P=0.08). However, a significant difference was found in the detection of high-risk HPV (HR-HPV) between the case and control groups (P=0.03). In the case group, 87.5% of the detected viruses (7/8 samples) were HR-HPV, while in the control group, 22.22% of positive samples (2/9 samples) were HR-HPV (P=0.03). Based on the results, HR-HPV and low-risk HPV genotypes were detected in 53% (9/17) and 47% (8/17) of positive samples, respectively.

CONCLUSION: In this study, 12.69% of IDC samples were positive for HPV genomes, and HR-HPV was detected in 87.5% of these samples. The present results suggest the important role of HR-HPV in the development of breast cancer.}, } @article {pmid36107313, year = {2022}, author = {Walth-Hummel, AA and Herzig, S and Rohm, M}, title = {Nuclear Receptors in Energy Metabolism.}, journal = {Advances in experimental medicine and biology}, volume = {1390}, number = {}, pages = {61-82}, pmid = {36107313}, issn = {0065-2598}, mesh = {Adipose Tissue/metabolism ; *Diabetes Mellitus, Type 2/genetics/metabolism ; Energy Metabolism/physiology ; Humans ; *Metabolic Diseases/genetics/metabolism ; Receptors, Cytoplasmic and Nuclear/genetics/metabolism ; }, abstract = {Nuclear receptors are master regulators of energy metabolism through the conversion of extracellular signals into gene expression signatures. The function of the respective nuclear receptor is tissue specific, signal and co-factor dependent. While normal nuclear receptor function is central to metabolic physiology, aberrant nuclear receptor signaling is linked to various metabolic diseases such as type 2 diabetes mellitus, obesity, or hepatic steatosis. Thus, the tissue specific manipulation of nuclear receptors is a major field in biomedical research and represents a treatment approach for metabolic syndrome. This chapter focuses on key nuclear receptors involved in regulating the metabolic function of liver, adipose tissue, skeletal muscle, and pancreatic β-cells. It also addresses the importance of nuclear co-factors for fine-tuning of nuclear receptor function. The mode of action, role in energy metabolism, and therapeutic potential of prominent nuclear receptors is outlined.}, } @article {pmid36040027, year = {2023}, author = {Thompson, LDR and Bishop, JA}, title = {Salivary Gland Intraductal Carcinoma: How Do 183 Reported Cases Fit Into a Developing Classification.}, journal = {Advances in anatomic pathology}, volume = {30}, number = {2}, pages = {112-129}, pmid = {36040027}, issn = {1533-4031}, mesh = {Humans ; *Carcinoma, Intraductal, Noninfiltrating/genetics/pathology ; *Salivary Gland Neoplasms/pathology ; Transcription Factors ; Salivary Glands/pathology ; Biomarkers, Tumor/genetics ; }, abstract = {Salivary gland intraductal carcinoma (IDC) is a very uncommon group of neoplasms. Many names, variations in diagnostic criteria, and newly observed molecular findings (including NCOA4 :: RET , TRIM27 :: RET , HRAS point mutations, and PIK3CA pathway alterations) have generated further confusion in being able to recognize and categorize this group of tumors. Different histologic appearances and patterns of growth suggest there is more than one tumor category, with intercalated duct, apocrine, oncocytic, and hybrid features seen. Frankly destructive invasion further complicates the category, as the name "intraductal" would suggest an "in situ" neoplasm. Recent evidence on fusion-positive IDC demonstrates the same molecular underpinnings in both the ductal and the myoepithelial cells, which aids in further separating these tumors. This article summarizes the historical group of 183 neoplasms classified under the umbrella of IDC and highlights the unique histologic, immunohistochemistry, and molecular features that may further guide nomenclature standardization and harmonization.}, } @article {pmid36012443, year = {2022}, author = {Kmiecik, A and Ratajczak-Wielgomas, K and Grzegrzółka, J and Romanowicz, H and Smolarz, B and Dziegiel, P}, title = {Expression of NUCB2/NESF-1 in Breast Cancer Cells.}, journal = {International journal of molecular sciences}, volume = {23}, number = {16}, pages = {}, pmid = {36012443}, issn = {1422-0067}, support = {STM.A350.20.064//Wrocław Medical University/ ; }, mesh = {*Breast Neoplasms/genetics/metabolism ; *Carcinoma, Ductal, Breast/pathology ; Cytoplasm/metabolism ; Female ; Humans ; RNA, Messenger/genetics/metabolism ; }, abstract = {Recently, the expression of NUCB2/NESF-1 has been linked to tumor development. We report NUCB2/NESF-1 expression and its relation to clinicopathological parameters in breast cancer cells. Immunohistochemical reactions were conducted on 446 cases of invasive ductal carcinoma (IDC) and 36 cases of mastopathy. The expression of NUCB2/NESF-1 was also examined at the mRNA and protein levels in breast cancer cell lines. A statistically significant higher level of NUCB2/NESF-1 in IDC cells was noted compared to that in mastopathy samples. The level of NUCB2 expression in the cytoplasm of IDC cells decreased with the increasing degree of tumor malignancy (G). Higher NUCB2 expression was found in tumors with estrogen receptor (ER)-positive and progesterone receptor (PR)-positive phenotypes compared to that in estrogen-receptor-negative and progesterone-receptor-negative cases. Moreover, a higher expression was shown in ER(+) and PR(+) MCF-7 and T47D cell lines compared to that in triple-negative MDA-MB-468 and normal human breast epithelial cells. The analysis of the five-year survival rate indicated that a positive NUCB2/NESF-1 expression in tumor cells was also associated with longer patient survival. The study results suggest that NUCB2/NESF1 may play an important role in malignant transformation and may be a positive prognostic factor in IDC.}, } @article {pmid35982591, year = {2022}, author = {Kovalenko, I and Roy, P and Soni, B and Sangha, L and Toom, S}, title = {Secretory Carcinoma of the Breast Mimicking Invasive Ductal Carcinoma: A Case Report.}, journal = {The American journal of case reports}, volume = {23}, number = {}, pages = {e936665}, pmid = {35982591}, issn = {1941-5923}, mesh = {*Breast Neoplasms/diagnosis/genetics/therapy ; *Carcinoma/pathology ; *Carcinoma, Ductal/genetics/surgery ; *Carcinoma, Ductal, Breast/diagnosis/therapy ; Female ; Humans ; In Situ Hybridization, Fluorescence/methods ; Mastectomy ; Translocation, Genetic ; }, abstract = {BACKGROUND Secretory breast carcinoma (SBC), an extremely rare malignancy, is related to a chromosomal translocation which leads to an ETV6-NTRK3 fusion mutation. SBC is characterized by eosinophilic secretions and is usually triple-negative, with a small number of patients demonstrating ER-positivity of the tumors. Diagnosis can be challenging and requires genomic testing for confirmation. CASE REPORT A 40-year-old woman presented with a breast mass found on mammography. She underwent an ultrasound-guided biopsy of the tumor. Initial pathology evaluation revealed features consistent with invasive ductal carcinoma. The immunochemistry report described an ER-positive, PR-negative, and HER2-negative tumor. The specimen was sent for oncotype scoring, which was not performed due to the specimen not meeting the criteria for invasive ductal carcinoma and displaying pathological features of SBC. A fluorescent in situ hybridization (FISH) study revealed ETV6 translocation, consistent with the diagnosis of SBC. The patient underwent lumpectomy followed by adjuvant radiotherapy and endocrine therapy. She remains in complete remission 3 years after treatment. CONCLUSIONS Accurately diagnosing SBC is of extreme importance as it has an indolent clinical course, but has a favorable prognosis if detected early. Due to nonspecific imaging findings, pathology evaluation with immunohistochemical staining followed by genomic testing is required. Our case highlights the challenges associated with SBC diagnosis requiring genomic testing due to equivocal pathological findings, along with increasing incidence of SBT in adults. There are no established guidelines for SBC management. The mainstay of treatment is partial or total mastectomy. Data on the benefits of adjuvant endocrine therapy, chemotherapy, and radiotherapy are inconclusive.}, } @article {pmid35976519, year = {2023}, author = {Eum, SY and Schurhoff, N and Teglas, T and Wolff, G and Toborek, M}, title = {Circadian disruption alters gut barrier integrity via a ß-catenin-MMP-related pathway.}, journal = {Molecular and cellular biochemistry}, volume = {478}, number = {3}, pages = {581-595}, pmid = {35976519}, issn = {1573-4919}, support = {DA050528/DA/NIDA NIH HHS/United States ; DA047157/DA/NIDA NIH HHS/United States ; DA039576/DA/NIDA NIH HHS/United States ; MH128022/MH/NIMH NIH HHS/United States ; DA040537/DA/NIDA NIH HHS/United States ; DA044579/DA/NIDA NIH HHS/United States ; MH072567/MH/NIMH NIH HHS/United States ; MH122235/MH/NIMH NIH HHS/United States ; R01 HL126559/HL/NHLBI NIH HHS/United States ; R01 DA047157/DA/NIDA NIH HHS/United States ; HL126559/HL/NHLBI NIH HHS/United States ; R01 MH072567/MH/NIMH NIH HHS/United States ; }, mesh = {Animals ; Mice ; *Catenins/genetics ; *Circadian Rhythm ; Gene Expression Regulation ; }, abstract = {We evaluated the mechanistic link between circadian rhythms and gut barrier permeability. Mice were subjected to either constant 24-h light (LL) or 12-h light/dark cycles (LD). Mice housed in LL experienced a significant increase in gut barrier permeability that was associated with dysregulated ß-catenin expression and altered expression of tight junction (TJ) proteins. Silencing of ß-catenin resulted in disruption of barrier function in SW480 cells, with ß-catenin appearing to be an upstream regulator of the core circadian components, such as Bmal1, Clock, and Per1/2. In addition, ß-catenin silencing downregulated ZO-1 and occludin TJ proteins with only limited or no changes at their mRNA levels, suggesting post transcriptional regulation. Indeed, silencing of ß-catenin significantly upregulated expression of matrix metallopeptidase (MMP)-2 and MMP-9, and blocking MMP-2/9 activity attenuated epithelial disruption induced by ß-catenin silencing. These results indicate the regulatory role of circadian disruption on gut barrier integrity and the associations between TJ proteins and circadian rhythms, while demonstrating the regulatory role of ß-catenin in this process.}, } @article {pmid35950920, year = {2022}, author = {Nardone, A and Qiu, X and Spisak, S and Nagy, Z and Feiglin, A and Feit, A and Cohen Feit, G and Xie, Y and Font-Tello, A and Guarducci, C and Hermida-Prado, F and Syamala, S and Lim, K and Munoz Gomez, M and Pun, M and Cornwell, M and Liu, W and Ors, A and Mohammed, H and Cejas, P and Brock, JB and Freedman, ML and Winer, EP and Fu, X and Schiff, R and Long, HW and Metzger Filho, O and Jeselsohn, R}, title = {A Distinct Chromatin State Drives Therapeutic Resistance in Invasive Lobular Breast Cancer.}, journal = {Cancer research}, volume = {82}, number = {20}, pages = {3673-3686}, pmid = {35950920}, issn = {1538-7445}, support = {K08 CA191058/CA/NCI NIH HHS/United States ; P01 CA250959/CA/NCI NIH HHS/United States ; R01 CA193910/CA/NCI NIH HHS/United States ; R01 CA237414/CA/NCI NIH HHS/United States ; }, mesh = {*Breast Neoplasms/drug therapy/genetics/pathology ; *Carcinoma, Ductal, Breast/pathology ; *Carcinoma, Lobular/drug therapy/genetics/metabolism ; Chromatin/genetics ; Drug Resistance, Neoplasm/genetics ; Female ; Humans ; Prognosis ; Receptors, Estrogen/metabolism ; Tamoxifen/pharmacology/therapeutic use ; }, abstract = {UNLABELLED: Most invasive lobular breast cancers (ILC) are of the luminal A subtype and are strongly hormone receptor-positive. Yet, ILC is relatively resistant to tamoxifen and associated with inferior long-term outcomes compared with invasive ductal cancers (IDC). In this study, we sought to gain mechanistic insights into these clinical findings that are not explained by the genetic landscape of ILC and to identify strategies to improve patient outcomes. A comprehensive analysis of the epigenome of ILC in preclinical models and clinical samples showed that, compared with IDC, ILC harbored a distinct chromatin state linked to gained recruitment of FOXA1, a lineage-defining pioneer transcription factor. This resulted in an ILC-unique FOXA1-estrogen receptor (ER) axis that promoted the transcription of genes associated with tumor progression and poor outcomes. The ILC-unique FOXA1-ER axis led to retained ER chromatin binding after tamoxifen treatment, which facilitated tamoxifen resistance while remaining strongly dependent on ER signaling. Mechanistically, gained FOXA1 binding was associated with the autoinduction of FOXA1 in ILC through an ILC-unique FOXA1 binding site. Targeted silencing of this regulatory site resulted in the disruption of the feed-forward loop and growth inhibition in ILC. In summary, ILC is characterized by a unique chromatin state and FOXA1-ER axis that is associated with tumor progression, offering a novel mechanism of tamoxifen resistance. These results underscore the importance of conducting clinical trials dedicated to patients with ILC in order to optimize treatments in this breast cancer subtype.

SIGNIFICANCE: A unique FOXA1-ER axis in invasive lobular breast cancer promotes disease progression and tamoxifen resistance, highlighting a potential therapeutic avenue for clinical investigations dedicated to this disease. See related commentary by Blawski and Toska, p. 3668.}, } @article {pmid35945526, year = {2022}, author = {Xu, A and Chu, X and Zhang, S and Zheng, J and Shi, D and Lv, S and Li, F and Weng, X}, title = {Development and validation of a clinicoradiomic nomogram to assess the HER2 status of patients with invasive ductal carcinoma.}, journal = {BMC cancer}, volume = {22}, number = {1}, pages = {872}, pmid = {35945526}, issn = {1471-2407}, support = {2021KY1161 and 2022KY1316//Medical and Health Research Project of Zhejiang Province/ ; 2021ZA138//Zhejiang Province Chinese Medicine Science Research Fund Project/ ; }, mesh = {Bayes Theorem ; *Breast Neoplasms/diagnostic imaging/genetics ; *Carcinoma, Ductal ; China ; Female ; Humans ; Ki-67 Antigen ; Nomograms ; Retrospective Studies ; }, abstract = {BACKGROUND: The determination of HER2 expression status contributes significantly to HER2-targeted therapy in breast carcinoma. However, an economical, efficient, and non-invasive assessment of HER2 is lacking. We aimed to develop a clinicoradiomic nomogram based on radiomics scores extracted from multiparametric MRI (mpMRI, including ADC-map, T2W1, DCE-T1WI) and clinical risk factors to assess HER2 status.

METHODS: We retrospectively collected 214 patients with pathologically confirmed invasive ductal carcinoma between January 2018 to March 2021 from Fudan University Shanghai Cancer Center, and randomly divided this cohort into training set (n = 128, 42 HER2-positive and 86 HER2-negative cases) and validation set (n = 86, 28 HER2-positive and 58 HER2-negative cases) at a ratio of 6:4. The original and transformed pretherapy mpMRI images were treated by semi-automated segmentation and manual modification on the DeepWise scientific research platform v1.6 (http://keyan.deepwise.com/), then radiomics feature extraction was implemented with PyRadiomics library. Recursive feature elimination (RFE) based on logistic regression (LR) and LASSO regression were adpoted to identify optimal features before modeling. LR, Linear Discriminant Analysis (LDA), support vector machine (SVM), random forest (RF), naive Bayesian (NB) and XGBoost (XGB) algorithms were used to construct the radiomics signatures. Independent clinical predictors were identified through univariate logistic analysis (age, tumor location, ki-67 index, histological grade, and lymph node metastasis). Then, the radiomics signature with the best diagnostic performance (Rad score) was further combined with significant clinical risk factors to develop a clinicoradiomic model (nomogram) using multivariate logistic regression. The discriminative power of the constructed models were evaluated by AUC, DeLong test, calibration curve, and decision curve analysis (DCA).

RESULTS: 70 (32.71%) of the enrolled 214 cases were HER2-positive, while 144 (67.29%) were HER2-negative. Eleven best radiomics features were retained to develop 6 radiomcis classifiers in which RF classifier showed the highest AUC of 0.887 (95%CI: 0.827-0.947) in the training set and acheived the AUC of 0.840 (95%CI: 0.758-0.922) in the validation set. A nomogram that incorporated the Rad score with two selected clinical factors (Ki-67 index and histological grade) was constructed and yielded better discrimination compared with Rad score (p = 0.374, Delong test), with an AUC of 0.945 (95%CI: 0.904-0.987) in the training set and 0.868 (95%CI: 0.789-0.948; p = 0.123) in the validation set. Moreover, calibration with the p-value of 0.732 using Hosmer-Lemeshow test demonstrated good agreement, and the DCA verified the benefits of the nomogram.

CONCLUSION: Post largescale validation, the clinicoradiomic nomogram may have the potential to be used as a non-invasive tool for determination of HER2 expression status in clinical HER2-targeted therapy prediction.}, } @article {pmid34624832, year = {2021}, author = {Mohammed, AA}, title = {The clinical behavior of different molecular subtypes of breast cancer.}, journal = {Cancer treatment and research communications}, volume = {29}, number = {}, pages = {100469}, doi = {10.1016/j.ctarc.2021.100469}, pmid = {34624832}, issn = {2468-2942}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*genetics/pathology ; Female ; Humans ; Middle Aged ; Prognosis ; Retrospective Studies ; }, abstract = {BACKGROUND: Breast cancer is a heterogeneous group of tumors classified, according to different gene expressions that encodes for the hormone receptor status, into 4 main categories which are: luminal types A and B, triple negative/basal-like, and Her-2 molecular subtypes.

PATIENTS AND METHODS: This retrospective study included 311 breast cancer females. Patients were classified according to the expression of hormone receptors into: Luminal-A, luminal-B, HER-2 enriched and basal-like types. All groups were then studied for differences in clinical course of the disease.

RESULTS: Luminal-B type was the commonest molecular type (43.73%). Invasive ductal carcinoma was the commonest histological type (89.1%). Stages IIB and IIIA were the commonest clinical stages (24.4% & 22.2%) respectively. Most patients had no recurrence (85.5%), the commonest recurrence was local and axillary ones (7.1%). Low grade tumors were less frequent than intermediate and high grades (3.5%, 51.1%, and 45.3%). We found a significant correlation between molecular subtypes and survival status, tumor grade, and histopathological types (P values 0.029, 0.001, and 0.006) respectively, while it was not significant with age, BMI, recurrence & metastatic disease, overall survival, and TNM stage (P values 0.648, 0.398, 0.5, 0.063 and 0.319).

CONCLUSION: Luminal types A and B are the commonest molecular subtypes of breast cancer. Luminal type A is associated with improved survival, and basal like has the highest breast cancer fatality rates. Invasive ductal carcinomas of specific types mostly found in patients with luminal types A and B, while other rare forms like Paget's disease was diagnosed HER-2 enriched types.}, } @article {pmid34238275, year = {2021}, author = {Samson, J and Derlipanska, M and Zaheed, O and Dean, K}, title = {Molecular and cellular characterization of two patient-derived ductal carcinoma in situ (DCIS) cell lines, ETCC-006 and ETCC-010.}, journal = {BMC cancer}, volume = {21}, number = {1}, pages = {790}, pmid = {34238275}, issn = {1471-2407}, mesh = {Carcinoma, Intraductal, Noninfiltrating/*genetics/pathology ; Cell Line, Tumor ; Cell Proliferation ; Female ; Humans ; }, abstract = {BACKGROUND: Currently it is unclear how in situ breast cancer progresses to invasive disease; therefore, a better understanding of the events that occur during the transition to invasive carcinoma is warranted. Here we have conducted a detailed molecular and cellular characterization of two, patient-derived, ductal carcinoma in situ (DCIS) cell lines, ETCC-006 and ETCC-010.

METHODS: Human DCIS cell lines, ETCC-006 and ETCC-010, were compared against a panel of cell lines including the immortalized, breast epithelial cell line, MCF10A, breast cancer cell lines, MCF7 and MDA-MB-231, and another DCIS line, MCF10DCIS.com. Cell morphology, hormone and HER2/ERBB2 receptor status, cell proliferation, survival, migration, anchorage-independent growth, indicators of EMT, cell signalling pathways and cell cycle proteins were examined using immunostaining, immunoblots, and quantitative, reverse transcriptase PCR (qRT-PCR), along with clonogenic, wound-closure and soft agar assays. RNA sequencing (RNAseq) was used to provide a transcriptomic profile.

RESULTS: ETCC-006 and ETCC-010 cells displayed notable differences to another DCIS cell line, MCF10DCIS.com, in terms of morphology, steroid-receptor/HER status and markers of EMT. The ETCC cell lines lack ER/PR and HER, form colonies in clonogenic assays, have migratory capacity and are capable of anchorage-independent growth. Despite being isogenic, less than 30% of differentially expressed transcripts overlapped between the two lines, with enrichment in pathways involving receptor tyrosine kinases and DNA replication/cell cycle programs and in gene sets responsible for extracellular matrix organisation and ion transport.

CONCLUSIONS: For the first time, we provide a molecular and cellular characterization of two, patient-derived DCIS cell lines, ETCC-006 and ETCC-010, facilitating future investigations into the molecular basis of DCIS to invasive ductal carcinoma transition.}, } @article {pmid25260852, year = {2015}, author = {Moccia, M and Mosca, L and Erro, R and Cervasio, M and Allocca, R and Vitale, C and Leonardi, A and Caranci, F and Del Basso-De Caro, ML and Barone, P and Penco, S}, title = {Hypomorphic NOTCH3 mutation in an Italian family with CADASIL features.}, journal = {Neurobiology of aging}, volume = {36}, number = {1}, pages = {547.e5-11}, doi = {10.1016/j.neurobiolaging.2014.08.021}, pmid = {25260852}, issn = {1558-1497}, mesh = {Adult ; Aged ; Animals ; CADASIL/*genetics ; *Codon, Nonsense ; Exons/genetics ; Female ; Humans ; Italy ; Male ; Mice ; Middle Aged ; RNA, Messenger ; Receptor, Notch3 ; Receptors, Notch/*genetics ; Signal Transduction/genetics/physiology ; Young Adult ; }, abstract = {The cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy (CADASIL) is because of NOTCH3 mutations affecting the number of cysteine residues. In this view, the role of atypical NOTCH3 mutations is still debated. Therefore, we investigated a family carrying a NOTCH3 nonsense mutation, with dominantly inherited recurrent cerebrovascular disorders. Among 7 family members, 4 received a clinical diagnosis of CADASIL. A heterozygous truncating mutation in exon 3 (c.307C>T, p.Arg103X) was found in the 4 clinically affected subjects and in one 27-year old lady, only complaining of migraine with aura. Magnetic resonance imaging scans found typical signs of small-vessel disease in the 4 affected subjects, supporting the clinical diagnosis. Skin biopsies did not show the typical granular osmiophilic material, but only nonspecific signs of vascular damage, resembling those previously described in Notch3 knockout mice. Interestingly, messenger RNA (mRNA) analysis supports the hypothesis of an atypical NOTCH3 mutation, suggesting a nonsense-mediated mRNA decay. In conclusion, the present study broadens the spectrum of CADASIL mutations, and, therefore, opens new insights about Notch3 signaling.}, } @article {pmid22712893, year = {2012}, author = {Van Balkom, ID and Vuijk, PJ and Franssens, M and Hoek, HW and Hennekam, RC}, title = {Development, cognition, and behaviour in Pitt-Hopkins syndrome.}, journal = {Developmental medicine and child neurology}, volume = {54}, number = {10}, pages = {925-931}, doi = {10.1111/j.1469-8749.2012.04339.x}, pmid = {22712893}, issn = {1469-8749}, mesh = {Adolescent ; Basic Helix-Loop-Helix Leucine Zipper Transcription Factors/*genetics ; Belgium ; Child ; Child Behavior Disorders/*diagnosis/genetics/*psychology ; Child Development Disorders, Pervasive/*diagnosis/genetics/*psychology ; Child, Preschool ; Cognition Disorders/*diagnosis/genetics/*psychology ; DNA Mutational Analysis ; Developmental Disabilities/diagnosis/genetics/psychology ; Diagnosis, Differential ; Facies ; Female ; Humans ; Hyperventilation/*diagnosis/genetics/*psychology ; Intellectual Disability/*diagnosis/genetics/*psychology ; Language Development Disorders/diagnosis/genetics/psychology ; Male ; Netherlands ; Neuropsychological Tests ; Stereotypic Movement Disorder/diagnosis/genetics/psychology ; Transcription Factor 4 ; Transcription Factors/*genetics ; Young Adult ; }, abstract = {AIM: The aim of the study was to collect detailed data on behavioural, adaptive, and psychological functioning in 10 individuals with Pitt-Hopkins syndrome (PTHS), with specific attention to manifestations of autism spectrum disorder (ASD).

METHOD: The participants (four females, six males), residing in the Netherlands and Belgium, were ascertained through the Dutch national PTHS support group. Median age of participants was 10 years, the age range was between 32 and 289 months. They underwent psychiatric examinations and neuropsychological measurements using a comprehensive assessment battery. Additionally, parental information was gathered through standardized interviews and questionnaires. Findings were compared with those from the literature.

RESULTS: All participants showed profound intellectual disability, amiable demeanour with minimal maladaptive behaviours, severe impairments of communication and language, and intense, frequent motor stereotypies. Impairments in all participants were beyond what would be expected for cognitive abilities, fitting a classification of ASD.

INTERPRETATION: Patients with PTHS are characterized not only by specific physical and genetic manifestations but also by specific behavioural and cognitive characteristics. Studying behaviour and cognition may improve diagnosis and prognosis, allows recognition of comorbidities, and contributes to adequate counselling of families.}, } @article {pmid21790824, year = {2011}, author = {van Balkom, ID and Shaw, A and Vuijk, PJ and Franssens, M and Hoek, HW and Hennekam, RC}, title = {Development and behaviour in Marshall-Smith syndrome: an exploratory study of cognition, phenotype and autism.}, journal = {Journal of intellectual disability research : JIDR}, volume = {55}, number = {10}, pages = {973-987}, doi = {10.1111/j.1365-2788.2011.01451.x}, pmid = {21790824}, issn = {1365-2788}, mesh = {Abnormalities, Multiple/*diagnosis/*genetics/psychology ; Adaptation, Psychological ; Adolescent ; Autistic Disorder/*diagnosis/*genetics/psychology ; Bone Diseases, Developmental/*diagnosis/*genetics/psychology ; Child ; Child Behavior Disorders/*diagnosis/*genetics/psychology ; Child, Preschool ; Communication ; Craniofacial Abnormalities/*diagnosis/*genetics/psychology ; DNA Mutational Analysis ; Developmental Disabilities/diagnosis/genetics/psychology ; Female ; Humans ; Intellectual Disability/*diagnosis/*genetics/psychology ; Male ; NFI Transcription Factors/genetics ; Neurologic Examination ; Neuropsychological Tests ; Personality Assessment ; *Phenotype ; Prognosis ; Septo-Optic Dysplasia/*diagnosis/*genetics/psychology ; }, abstract = {BACKGROUND: Marshall-Smith syndrome (MSS) is an infrequently described entity characterised by failure to thrive, developmental delay, abnormal bone maturation and a characteristic face. In studying the physical features of a group of patients, we noticed unusual behavioural traits. This urged us to study cognition, behavioural phenotype and autism in six patients.

METHODS: Information on development, behavioural characteristics, autism symptoms, and adaptive and psychological functioning of six MSS children was collected through in-person examinations, questionnaires, semi-structured interviews of parents and neuropsychological assessments.

RESULTS: Participants showed moderate to severe delays in mental age, motor development and adaptive functioning, with several similarities in communication, social interactions and behaviour. There was severe delay of speech and motor milestones, a friendly or happy demeanour and enjoyment of social interactions with familiar others. They exhibited minimal maladaptive behaviours. Deficits in communication and social interactions, lack of reciprocal social communication skills, limited imaginary play and the occurrence of stereotyped, repetitive behaviours were noted during assessments.

CONCLUSIONS: Systematic collection of developmental and behavioural data in very rare entities such as MSS allows recognition of specific patterns in these qualities. Clinical recognition of physical,developmental and behavioural features is important not only for diagnosis, prognosis and counselling of families, but also increases our understanding of the biological basis of the human physical and behavioural phenotype.}, } @article {pmid9892111, year = {1999}, author = {Tsuda, H and Takarabe, T and Fukutomi, T and Hirohashi, S}, title = {der(16)t(1;16)/der(1;16) in breast cancer detected by fluorescence in situ hybridization is an indicator of better patient prognosis.}, journal = {Genes, chromosomes & cancer}, volume = {24}, number = {1}, pages = {72-77}, doi = {10.1002/(sici)1098-2264(199901)24:1<72::aid-gcc10>3.0.co;2-m}, pmid = {9892111}, issn = {1045-2257}, mesh = {Breast Neoplasms/*diagnosis/*genetics ; Chromosomes, Human, Pair 1/*genetics ; Chromosomes, Human, Pair 16/*genetics ; DNA Probes ; DNA, Neoplasm ; Female ; Genetic Markers ; Humans ; In Situ Hybridization, Fluorescence/methods ; Prognosis ; *Translocation, Genetic ; }, abstract = {By two-color fluorescence in situ hybridization (FISH), der(16)t(1;16) or der(1;16) was frequently detected in low-grade papillary carcinoma but not in benign intraductal papilloma of the breast. In order to clarify the incidence and clinicopathological significance of der(16)t(1;16)/der(1;16) in common breast cancers, der(16)t(1;16)/der(1;16) was examined by two-color FISH in breast cancers resected from 51 patients by using DNA probes for 16cen, 16q11.2, and 1q12 labeled with biotin or digoxigenin. der(16)t(1;16)/der(1;16) was clonally detected in 16 cancers (31%), being more frequent in ductal carcinomas of lower grade and invasive lobular carcinoma than in high-grade invasive ductal carcinoma (P<0.001). der(16)t(1;16)/der(1;16) was also correlated with a higher amount of hormone receptors in the tumor (P<0.05). Disease-free and overall survival rates of the patient group with der(16)t(1;16)/der(1;16)-positive cancer were higher (88% and 94%) than those of the group with der(16)t(1;16)/der(1; 16)-negative cancer (39% and 68%) (P<0.05). Among the 16 patients with lymph node metastasis who received one of two similar forms of postsurgical adjuvant chemo-endocrine therapy, the prognosis of those with der(16)t(1;16)/der(1;16)-positive cancer was better than that of those with der(16)t(1;16)/der(1;16)-negative cancer (P<0.05). der(16)t(1;16)/der(1;16) detected by FISH is considered helpful in identifying patients with a better prognosis and for stratification of patients in randomized clinical trials of adjuvant chemo-endocrine therapies.}, } @article {pmid9831206, year = {1998}, author = {Zhu, XL and Hartwick, W and Rohan, T and Kandel, R}, title = {Cyclin D1 gene amplification and protein expression in benign breast disease and breast carcinoma.}, journal = {Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc}, volume = {11}, number = {11}, pages = {1082-1088}, pmid = {9831206}, issn = {0893-3952}, mesh = {Breast/chemistry/metabolism/pathology ; Breast Diseases/*genetics/metabolism ; Breast Neoplasms/*genetics/metabolism ; Carcinoma in Situ/metabolism/pathology ; Carcinoma, Ductal, Breast/genetics/metabolism ; Cyclin D1/*genetics/metabolism ; DNA, Neoplasm/analysis/genetics ; Gene Amplification ; Gene Expression ; Gene Expression Regulation, Neoplastic ; Humans ; Immunohistochemistry ; Tumor Cells, Cultured/cytology/metabolism ; }, abstract = {Cyclin D1 plays a critical role in regulating cell-cycle progression. Gene amplification and protein overexpression of cyclin D1 have been detected in breast cancer but little is known concerning whether these changes occur in normal breast tissue and in breast lesions associated with increased risk of development of invasive breast cancer. We looked for cyclin D1 gene amplification and protein overexpression in 30 cases of benign breast disease (16 epithelial hyperplasias without atypia and 14 atypical ductal hyperplasias) and 18 ductal carcinomas in situ by use of differential PCR and immunohistochemical staining. We compared the resulting frequencies to those in 15 cases of normal breast tissue and 17 invasive ductal carcinomas. We found cyclin D1 gene amplification in 15% of those with normal breast tissue, 19% of those with epithelial hyperplasia without atypia, 27% of those with atypical ductal hyperplasia, 35% of those with ductal carcinoma in situ, and 25% of those with invasive ductal carcinoma; corresponding figures for protein overexpression were 13, 13, 57, 50, and 64%. These results suggest that cyclin D1 amplification and protein overexpression can occur before histologic alterations are seen but that the frequencies of these changes are higher in histologic lesions with cellular atypia (atypical hyperplasia and ductal carcinoma in situ), reaching frequencies similar to those observed in invasive carcinoma.}, } @article {pmid9828838, year = {1998}, author = {Lee, AH and Dublin, EA and Bobrow, LG and Poulsom, R}, title = {Invasive lobular and invasive ductal carcinoma of the breast show distinct patterns of vascular endothelial growth factor expression and angiogenesis.}, journal = {The Journal of pathology}, volume = {185}, number = {4}, pages = {394-401}, doi = {10.1002/(SICI)1096-9896(199808)185:4<394::AID-PATH117>3.0.CO;2-S}, pmid = {9828838}, issn = {0022-3417}, mesh = {Breast/metabolism ; Breast Neoplasms/blood supply/*metabolism/pathology ; Carcinoma, Ductal, Breast/blood supply/*metabolism/pathology ; Carcinoma, Lobular/blood supply/*metabolism/pathology ; Endothelial Growth Factors/genetics/*metabolism ; Female ; Gene Expression ; Humans ; Immunoenzyme Techniques ; In Situ Hybridization ; Lymphokines/genetics/*metabolism ; Neoplasm Invasiveness ; Neovascularization, Pathologic/*metabolism ; RNA, Messenger/genetics ; RNA, Neoplasm/genetics ; Vascular Endothelial Growth Factor A ; Vascular Endothelial Growth Factors ; }, abstract = {Angiogenesis is essential for tumour growth and important in tumour metastasis and prognosis. Vascular endothelial growth factor (VEGF) stimulates endothelial proliferation in vitro and angiogenesis in vivo. VEGF expression has been correlated with high vascularity in tumours, including carcinoma of the breast. This study investigated VEGF expression and vascularity of invasive lobular (n = 10) and invasive ductal carcinoma (n = 28), and pure ductal carcinoma in situ of the breast (n = 33). VEGF protein expression was studied with immunohistochemistry and VEGF mRNA with in situ hybridization. Vascular density was assessed on sections stained for von Willebrand factor. There was more expression of both VEGF protein (P = 0.006) and mRNA (P = 0.002) in invasive ductal than in invasive lobular carcinoma. VEGF protein (rs = 0.32, P = 0.047) and mRNA (rs = 0.56, P = 0.04) correlated with vascular density in invasive ductal carcinoma. In invasive lobular carcinoma, vascular density did not correlate with VEGF mRNA (rs = 0.15, P = 0.35) and was inversely related to VEGF protein (rs = -0.57, P = 0.04). There were no significant differences in vascular density between the two types of invasive carcinoma, suggesting that VEGF is important in angiogenesis in invasive ductal carcinoma, but that other angiogenic factors are important in invasive lobular carcinoma. Although VEGF protein was frequently expressed in ductal carcinoma in situ, no relationship was found between VEGF and the two patterns of angiogenesis previously described.}, } @article {pmid9815608, year = {1997}, author = {Tamagawa, E and Ueda, M and Takahashi, S and Sugano, K and Uematsu, S and Mukai, M and Ogata, Y and Kitajima, M}, title = {Pancreatic lymph nodal and plexus micrometastases detected by enriched polymerase chain reaction and nonradioisotopic single-strand conformation polymorphism analysis: a new predictive factor for recurrent pancreatic carcinoma.}, journal = {Clinical cancer research : an official journal of the American Association for Cancer Research}, volume = {3}, number = {11}, pages = {2143-2149}, pmid = {9815608}, issn = {1078-0432}, mesh = {Adult ; Aged ; Carcinoma, Intraductal, Noninfiltrating/*genetics/mortality/*pathology/surgery ; Codon ; DNA, Neoplasm/genetics/isolation & purification ; Disease-Free Survival ; Female ; *Genes, ras ; Humans ; Lymphatic Metastasis ; Male ; Middle Aged ; Neoplasm Invasiveness ; Neoplasm Metastasis ; Pancreatic Neoplasms/*genetics/mortality/*pathology/surgery ; *Point Mutation ; Polymerase Chain Reaction/methods ; *Polymorphism, Single-Stranded Conformational ; Predictive Value of Tests ; Recurrence ; Survival Analysis ; Treatment Outcome ; }, abstract = {K-ras point mutations have been observed in approximately 90% of pancreatic carcinomas. We genetically analyzed cases of pancreatic regional lymph nodal and plexus micrometastases in invasive ductal carcinoma of the pancreas who were node negative or had metastases limited histopathologically to pancreaticoduodenal lymph nodes. These cases underwent curative resection in our institute. The utility of genetic analysis was compared with that of histopathological study, in terms of postoperative clinical outcome, as a predictive factor for recurrent pancreatic carcinoma. Samples for DNA extraction were obtained from formalin-fixed, paraffin-embedded specimens. A 0.5-microg quantity of DNA was subjected to enriched PCR and nonradioisotopic single-strand conformation polymorphism analysis. K-ras codon 12 mutations were detected in 83% (10 of 12) of invasive ductal carcinomas. In four cases, the genetic analysis of regional lymph nodal metastases and pancreatic plexus invasion of the pancreatic carcinoma yielded results concordant with those of histopathological analysis. In six cases, however, the metastases detected by genetic analysis were more advanced than was indicated by the histopathological examination. The survival rate of cases with metastases beyond the pancreaticoduodenal lymph nodes was significantly lower than that of cases with metastases limited to the pancreaticoduodenal lymph nodes or with no nodal involvement based on genetic analysis (P < 0.05). Intraoperative analysis of point mutations at K-ras codon 12 in the regional lymph nodes and the pancreatic plexus by enriched PCR/nonradioisotopic single-strand conformation polymorphism analysis is a highly accurate predictive factor for recurrent pancreatic carcinoma.}, } @article {pmid9769473, year = {1998}, author = {Tsuda, H and Takarabe, T and Shimamura, K and Hirohashi, S}, title = {Detection of alterations in chromosomes 16 and 1 by fluorescence in situ hybridization in breast tumors cytologically or histologically equivocal for malignancy.}, journal = {Pathobiology : journal of immunopathology, molecular and cellular biology}, volume = {66}, number = {6}, pages = {268-273}, doi = {10.1159/000028033}, pmid = {9769473}, issn = {1015-2008}, mesh = {Biopsy, Needle ; Breast Neoplasms/diagnosis/*genetics/*pathology ; Carcinoma, Ductal, Breast/diagnosis/genetics/pathology ; Case-Control Studies ; *Chromosome Aberrations ; Chromosomes, Human, Pair 1/*genetics ; Chromosomes, Human, Pair 16/*genetics ; Female ; Humans ; In Situ Hybridization, Fluorescence ; Middle Aged ; Phyllodes Tumor/diagnosis/genetics/pathology ; }, abstract = {Structural and numerical alterations, and fusion of chromosomes 16 and 1 have been shown to occur frequently in low-grade breast carcinoma, but not in benign papilloma by fluorescence in situ hybridization (FISH). We carried out FISH analysis of 11 benign tumors and 3 breast tumors for which the preoperative diagnosis was equivocal for cancer. In 11 benign lesions and 1 benign phyllode tumor which was cytologically equivocal for malignancy, alteration of the chromosome 16 or 1 signal was not detected as a predominant cell clone. On the other hand, in 1 grade 1 invasive ductal carcinoma which was judged as equivocal for malignancy and 1 marked adenosis with atypia which was judged as malignant by fine-needle aspiration cytology, the majority of constituent tumor cells showed fusion of chromosomes 16 and 1. Detection of alterations in chromosomes 16 and 1 as a predominant clone was suggested to be an indicator of lesion malignancy even though the grade of malignancy may not be high. As a supportive diagnostic procedure, FISH analysis may give information about the nature of lesions, when the lesions are clinically or pathologically equivocal for cancer.}, } @article {pmid9767470, year = {1998}, author = {Downing, JE and Virag, L and Jones, IW}, title = {NADPH diaphorase-positive dendritic profiles in rat thymus are discrete from autofluorescent cells, immunoreactive for inducible nitric oxide synthase, and show strain-specific abundance differences.}, journal = {Immunology}, volume = {95}, number = {1}, pages = {148-155}, pmid = {9767470}, issn = {0019-2805}, mesh = {Animals ; Autoimmune Diseases/*immunology ; Dendritic Cells/*enzymology ; Female ; Genetic Predisposition to Disease/immunology ; Histocytochemistry ; Male ; NADPH Dehydrogenase/analysis/*metabolism ; Nitric Oxide Synthase/analysis/antagonists & inhibitors/*metabolism ; Nitric Oxide Synthase Type II ; Rats ; Rats, Inbred F344 ; Rats, Inbred Lew ; Rats, Sprague-Dawley ; Thymus Gland/immunology ; }, abstract = {Predisposition to autoimmune disorder in Lewis rats has been associated with abnormal hypothalamic regulation of circulating steroids, leading to inadequate suppression of T helper 1 (Th1) cell-mediated inflammatory reactions. In addition, autoimmune syndromes can be triggered within formerly resistant animals, following damage to the negative selection process of the thymus. A contribution to the autoimmune-susceptible phenotype may therefore derive from the status of thymic tolerance. One mechanism of intrathymic negative selection may involve nitric oxide. Because inducible nitric oxide synthase (iNOS) is known to be inhibitable by steroids, its expression might be different within strains having neuroendocrine disturbance. We report on a study to compare intrathymic iNOS expression in autoimmune-prone Lewis rats with other resistant strains. Interdigitating cells (IDC), darkly stained for diaphorase, were confirmed as immunoreactive for iNOS. They were located towards the medullary side of an accumulation of unstained, but autofluorescent cells (presumed to be macrophages) that circumscribes the corticomedullary zone. The role of iNOS+ IDC in the apoptotic deletion of T cells has been suggested by other studies. Despite the blunted steroidal condition reported for Lewis, nitrergic cell abundance was shown, by quantitative analysis of histochemical stain, to be on average approximately twofold lower compared with resistant strains (Fischer and Sprague-Dawley). This trend was evident in males and females, and confirmed by independent observers. We hypothesize that an intrathymic, iNOS-dependent mechanism may be important for the suppression of potentially autoreactive T-cell clones.}, } @article {pmid9758360, year = {1998}, author = {Bentz, JS and Yassa, N and Clayton, F}, title = {Pleomorphic lobular carcinoma of the breast: clinicopathologic features of 12 cases.}, journal = {Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc}, volume = {11}, number = {9}, pages = {814-822}, pmid = {9758360}, issn = {0893-3952}, mesh = {Adult ; Aneuploidy ; *Apolipoproteins ; Apolipoproteins D ; Breast Neoplasms/genetics/mortality/*pathology ; Carcinoma, Lobular/genetics/mortality/*pathology ; Carrier Proteins/metabolism ; *Glycoproteins ; Humans ; Immunohistochemistry ; *Membrane Transport Proteins ; Middle Aged ; Neoplasm Proteins/metabolism ; Prognosis ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; Retrospective Studies ; Survival Rate ; }, abstract = {Pleomorphic lobular carcinoma (PLC) of the breast was recently identified as a histologic variant of infiltrating lobular carcinoma (ILC) with a poor prognosis. Twelve cases identified from a large series of breast carcinomas were studied retrospectively. Of 11 cases with adequate follow up, 9 were fatal. This was significantly worse than either infiltrating ductal carcinoma (IDC) or classical ILC (P < or = .002), even when stratified by axillary lymph node status. Among the fatal cases, the median survival time was 2.1 years, significantly shorter than that for classical lobular, but not ductal, carcinoma A distinctive pattern of in situ carcinoma, which has been described as PLC in situ, was identified in 7 of the 12 patients. This in situ component was composed of tumor cells with nuclear atypia, cytologically similar to the invasive tumor. Most PLCs lacked estrogen and progesterone receptors and stained with BRST-2, an antibody to gross cystic disease fluid protein-15, suggesting the presence of apocrine differentiation. In summary, PLC has many of the histologic features of ILC but has anaplastic nuclei, abundant cytoplasm, and apocrine differentiation. PLC is often aneuploid, usually lacks steroid receptors, and has a significantly poorer prognosis than does classical ILC.}, } @article {pmid9735416, year = {1998}, author = {Rio, PG and Pernin, D and Bay, JO and Albuisson, E and Kwiatkowski, F and De Latour, M and Bernard-Gallon, DJ and Bignon, YJ}, title = {Loss of heterozygosity of BRCA1, BRCA2 and ATM genes in sporadic invasive ductal breast carcinoma.}, journal = {International journal of oncology}, volume = {13}, number = {4}, pages = {849-853}, doi = {10.3892/ijo.13.4.849}, pmid = {9735416}, issn = {1019-6439}, mesh = {Adult ; Aged ; Aged, 80 and over ; Ataxia Telangiectasia Mutated Proteins ; BRCA1 Protein/*genetics ; BRCA2 Protein ; Breast Neoplasms/*genetics/pathology ; Carcinoma, Ductal, Breast/*genetics/pathology ; Cell Cycle Proteins ; DNA-Binding Proteins ; Data Interpretation, Statistical ; Female ; Genes/*genetics ; Humans ; Loss of Heterozygosity/genetics ; Microsatellite Repeats/genetics ; Middle Aged ; Neoplasm Proteins/*genetics ; *Protein Serine-Threonine Kinases ; Proteins/*genetics ; Transcription Factors/*genetics ; Tumor Suppressor Proteins ; }, abstract = {The present study was undertaken to analyse the loss of heterozygosity (LOH) of the three genes, BRCA1, BRCA2 and ATM, and their correlation to clinicopathological parameters in sporadic breast cancer. We studied 59 sets of invasive ductal carcinoma, compared to matched normal control DNA. Microsatellite markers intragenic to BRCA1 (D17S1323, D17S1322, D17S855), BRCA2 (D13S1699, D13S1701, D13S1695) and ATM (D11S2179) were simultaneously used. In addition, one marker telomeric to BRCA2 (D13S1694) and four markers flanking ATM were analysed (D11S1816, D11S1819, D11S1294, D11S1818). Thirty-one per cent of the informative cases showed loss of heterozygosity for the BRCA1 gene, 22.8% for BRCA2 gene and 40% for ATM. LOH of BRCA1 correlated with high grade tumors (p=0.0005) and negative hormone receptors (p=0.01). LOH of ATM correlated with higher grade (p=0.03) and a younger age at diagnosis (p=0.03) in our set of tumors. No correlations were detected between BRCA2 LOH and any of the analysed clinicopathological parameters. However, a correlation was detected between allelic loss of the D13S1694 marker, telomeric to BRCA2, and larger tumor sizes and negative estrogen receptors, favoring the hypothesis of the presence of another putative tumor suppressor gene, telomeric to BRCA2, in the 13q12-q14 region. Only 11 tumors had LOH at more than one of the three genes, most of them (6/11) associated LOH of BRCA1 and ATM. One tumor only combined loss of the three genes BRCA1, BRCA2 and ATM.}, } @article {pmid9665177, year = {1998}, author = {Campbell, ID and Downing, AK}, title = {NMR of modular proteins.}, journal = {Nature structural biology}, volume = {5 Suppl}, number = {}, pages = {496-499}, doi = {10.1038/733}, pmid = {9665177}, issn = {1072-8368}, support = {//Wellcome Trust/United Kingdom ; }, mesh = {Amino Acid Sequence ; Fibrillin-1 ; Fibrillins ; Fibronectins/chemistry ; Humans ; Magnetic Resonance Spectroscopy/*methods ; Microfilament Proteins/chemistry/genetics ; Models, Molecular ; Molecular Sequence Data ; Mutation ; Protein Conformation ; Proteins/*chemistry ; Sequence Homology, Amino Acid ; }, abstract = {NMR studies of domains, dissected from large modular proteins, are described. Particular emphasis is placed on modules from the extracellular proteins fibrillin-1 and fibronectin.}, } @article {pmid9635530, year = {1998}, author = {Shen, KL and Harn, HJ and Ho, LI and Yu, CP and Chiu, SC and Lee, WH}, title = {The extent of proliferative and apoptotic activity in intraductal and invasive ductal breast carcinomas detected by Ki-67 labeling and terminal deoxynucleotidyl transferase-mediated digoxigenin-11-dUTP nick end labeling.}, journal = {Cancer}, volume = {82}, number = {12}, pages = {2373-2381}, doi = {10.1002/(sici)1097-0142(19980615)82:12<2373::aid-cncr11>3.0.co;2-m}, pmid = {9635530}, issn = {0008-543X}, mesh = {*Apoptosis ; Biomarkers, Tumor/*genetics ; Breast Neoplasms/genetics/*pathology ; Carcinoma in Situ/genetics/*pathology ; Carcinoma, Ductal, Breast/genetics/*pathology ; Cell Division ; Cell Survival ; DNA Fragmentation ; DNA Nucleotidylexotransferase/physiology ; DNA, Neoplasm/analysis ; Deoxyuracil Nucleotides ; Digoxigenin/analogs & derivatives ; Female ; Genes, bcl-2/*genetics ; Humans ; Immunohistochemistry ; Ki-67 Antigen ; Middle Aged ; Neoplasm Invasiveness ; Receptors, Estrogen/*genetics ; Receptors, Progesterone/*genetics ; Tumor Suppressor Protein p53/genetics/*metabolism ; }, abstract = {BACKGROUND: The balance among cell proliferation, cell differentiation, and cell death determines the cell number in a population as well as the size or even the stage of a tumor. Thus, to improve our understanding of the pathogenesis of neoplasms, it is important to investigate the regulation of both cell proliferation and cell death.

METHODS: This study examined the occurrence of apoptosis and proliferative capacity in 46 breast carcinomas: 20 intraductal carcinomas (ductal carcinomas in situ [DCIS]) and 26 infiltrative ductal carcinomas (IDC). Terminal deoxynucleotidyl transferase-mediated digoxigenin-11-dUTP nick end labeling (TUNEL) and immunostaining with the Ki-67 antibody were used in the examination. A ladder of DNA fragments induced by apoptosis was demonstrated by means of DNA agarose gel electrophoresis in 10 of the available TUNEL positive and negative samples.

RESULTS: The results were correlated with p53, bcl-2, estrogen receptor (ER), and progesterone receptor (PR) protein expression, which would suggest association with apoptosis by immunohistochemistry. The apoptosis and proliferation of each cancer were expressed as the number of tumor cells undergoing apoptosis and proliferation per 1000 tumor cells. The extent of apoptosis was more frequently observed in DCIS than in IDC (21.9+/-6.8 vs. 4.0+/-0.9, P < 0.001), and the proliferation activity was significantly higher in IDC than in DCIS (16.8+/-6.5 vs. 3.5+/-0.8, P < 0.006). Apoptosis associated with MIB-1 positive cells and TUNEL labeling was significantly higher in IDC than in DCIS (3.26 vs. 0.42, P=0.001). In DCIS, apoptosis was correlated with p53 (r=0.663, P=0.005), and p53 had a reverse correlation with bcl-2 (r=0.620, P= 0.018). Moreover, bcl-2 expression was associated with ER (P=0.028) and PR (P= 0.005) expression in both DCIS and IDC.

CONCLUSIONS: The results of this study show that a higher degree of apoptosis and lower proliferation activity in intraductal carcinoma result in a steady-state, self-renewing condition in which net growth of the tumor is rare. The results also indicate that apoptosis was altered by the expression of p53, bcl-2, ER, and PR.}, } @article {pmid9652759, year = {1998}, author = {Marsh, KL and Varley, JM}, title = {Loss of heterozygosity at chromosome 9p in ductal carcinoma in situ and invasive carcinoma of the breast.}, journal = {British journal of cancer}, volume = {77}, number = {9}, pages = {1439-1447}, pmid = {9652759}, issn = {0007-0920}, mesh = {Breast Neoplasms/*genetics/pathology ; Carcinoma in Situ/*genetics/secondary ; Carcinoma, Ductal, Breast/*genetics/secondary ; Chromosomes, Human, Pair 9/*genetics ; DNA, Neoplasm/*genetics ; Female ; Genetic Markers/*genetics ; Humans ; Loss of Heterozygosity/*genetics ; Neoplasm Invasiveness/genetics ; }, abstract = {Twenty-three cases of ductal carcinoma in situ (DCIS), ten of which had an associated invasive component, were studied for loss of heterozygosity (LOH) of microsatellite markers on chromosome 9p and the results compared with a panel of 20 invasive breast carcinomas. In addition to the gene encoding p16, chromosome 9p is also thought to contain other putative tumour-suppressor genes. If the three panels of breast tumours showed LOH of markers in this region this would suggest that such putative genes were important in breast carcinogenesis. By studying both preinvasive and invasive breast tumours, it should also be possible to gain further information about the relationship between lesions of a different stage and to determine whether DCIS is indeed a precursor of invasive ductal carcinoma. Levels of LOH were low in the invasive-only set of tumours. Surprisingly, considerably higher levels of loss were observed in the tumours with an in situ component. Also, much heterogeneity was observed between different DCIS ducts or invasive tumour and DCIS from the same case.}, } @article {pmid9617588, year = {1998}, author = {Gunnes, G and Press, CM and Tverdal, A and Landsverk, T}, title = {Compartments within the lymph node cortex of calves and adult cattle differ in the distribution of leukocyte populations: an immunohistochemical study using computer-assisted morphometric analysis.}, journal = {Developmental and comparative immunology}, volume = {22}, number = {1}, pages = {111-123}, doi = {10.1016/s0145-305x(97)00038-4}, pmid = {9617588}, issn = {0145-305X}, mesh = {Age Factors ; Analysis of Variance ; Animals ; Antigens, CD/analysis ; B-Lymphocytes/cytology ; CD4-Positive T-Lymphocytes/cytology ; CD8-Positive T-Lymphocytes/cytology ; Cattle ; Histocompatibility Antigens Class II/analysis ; Image Processing, Computer-Assisted ; Immunohistochemistry ; *Jejunum ; Lymph Nodes/*anatomy & histology/*immunology ; *Lymphocyte Subsets ; Receptors, Antigen, T-Cell, gamma-delta/analysis ; }, abstract = {The combination of an immunohistochemical technique and a panel of monoclonal antibodies was used to investigate the presence of leukocyte populations in the distal jejunal lymph node of 3-4 week old calves and adult cattle. The application of computer-assisted morphometric analysis enabled information to be obtained on the distribution of leukocyte populations in lymphoid compartments of the lymph node cortex. Semi-quantitative estimates of the areas of staining in histological sections showed that calves possessed significantly fewer B-cells and CD4+ cells in the outer cortex and significantly fewer T-cells (CD4+, CD8+ and gamma delta T-cells) in the deep cortex. These findings were interpreted to be a possible consequence of immunosuppression resulting from the passive transfer of maternal immunity in colostrum. The presence of some B-cell follicles in the region defined as the deep cortex suggested the on-going differentiation of this predominantly T-cell compartment. The larger presence of interdigitating cells (IDC) in the deep cortex of calves than adults was suggested by significantly larger CD1+ populations and it was argued that this could be the result of the confrontation with exogenous antigen faced by calves in early postnatal life. Antigen presenting populations, pan MHC II+ and MHC II DQ+ populations, were increased in all compartments of calf lymph nodes but were not significantly different from the populations in adult lymph nodes. Variance component analysis of the data generated in the present study showed that the image analysis technique was an effective and statistically powerful approach to investigate leukocyte populations within the specific microenvironments of the lymph node.}, } @article {pmid9562249, year = {1998}, author = {Holt, JC and Hatcher, VB and Caulfield, JB and Norton, P and Umeda, PK and Melendez, JA and Martino, L and Mudzinsky, SP and Blumenstock, F and Slayter, HS and Margossian, SS}, title = {Cloning of the cDNA and nucleotide sequence of a skeletal muscle protease from myopathic hamsters.}, journal = {Molecular and cellular biochemistry}, volume = {181}, number = {1-2}, pages = {125-135}, pmid = {9562249}, issn = {0300-8177}, support = {HL44094/HL/NHLBI NIH HHS/United States ; HL49597/HL/NHLBI NIH HHS/United States ; }, mesh = {Amino Acid Sequence ; Animals ; Base Sequence ; *Cardiac Myosins ; Cardiomyopathy, Dilated/*enzymology ; Cloning, Molecular ; Cricetinae ; DNA, Complementary/*genetics ; Dogs ; Humans ; Molecular Sequence Data ; Molecular Weight ; Muscle, Skeletal/*enzymology ; Muscular Diseases/enzymology ; Myocardium/enzymology ; Myofibrils/enzymology ; Myosin Light Chains/metabolism ; Rats ; Sequence Analysis, DNA ; Sequence Homology, Amino Acid ; Sequence Homology, Nucleic Acid ; Serine Endopeptidases/chemistry/*genetics/isolation & purification/metabolism ; Species Specificity ; }, abstract = {A neutral protease with an estimated Mr of about 26 kD and responsible for cleavage ofmyosin LC2 was isolated from hamster skeletal muscle. Complementary DNAs were generated by RT-PCR using total hamster muscle RNA and degenerate oligonucleotide primers based on the sequences of two internal peptides. The nucleotide sequences of the resultant cDNAs were subsequently determined and the complete amino acid sequence of the protease deduced. Although the hamster protein shared 63-85% identity in nucleotide and amino acid sequences with rat and mouse mast cell proteases, it had a higher degree of specificity for myosin LC2 than mast cell proteases which also digested myosin LC1 and myosin heavy chains. As a result, the hamster protease was designated mekratin because of its unique enzymatic specificities to distinguish it from other mast cell proteases. A polyclonal antibody was raised specific to the hamster muscle and human cardiac muscle mekratins without apparent cross-reaction with rat mast cell proteases. We have earlier demonstrated the presence in excess of a neutral protease that specifically cleaves LC2 in human hearts obtained at end stage idiopathic dilated cardiomyopathy (IDC). Western analyses revealed that heart tissue from patients with IDC contained 5-10 fold more mekratin than control samples. Furthermore, the level of the protease in human IDC tissues was similar to that seen in myopathic hamster skeletal muscle. No bands were recognized by the antibody when IDC myofibrils were probed due to the removal of soluble proteins during sample preparation. Thus, these results strongly suggest that the anti-mekratin antibody will provide positive identification of IDC in many cases and diagnosis by exclusion may be replaced.}, } @article {pmid9554529, year = {1998}, author = {Ghoussoub, RA and Dillon, DA and D'Aquila, T and Rimm, EB and Fearon, ER and Rimm, DL}, title = {Expression of c-met is a strong independent prognostic factor in breast carcinoma.}, journal = {Cancer}, volume = {82}, number = {8}, pages = {1513-1520}, doi = {10.1002/(sici)1097-0142(19980415)82:8<1513::aid-cncr13>3.0.co;2-7}, pmid = {9554529}, issn = {0008-543X}, mesh = {Adult ; Age Factors ; Aged ; Aged, 80 and over ; Breast/metabolism/pathology ; Breast Neoplasms/*metabolism/mortality/pathology ; Carcinoma, Ductal, Breast/*metabolism/mortality/pathology ; Female ; Fluorescent Antibody Technique, Indirect ; Humans ; Lymphatic Metastasis ; Middle Aged ; Neoplasm Proteins/genetics/*metabolism ; Prognosis ; Proto-Oncogene Proteins c-met/genetics/*metabolism ; Receptors, Estrogen/metabolism ; Survival Rate ; Tumor Cells, Cultured ; }, abstract = {BACKGROUND: The c-met protooncogene encodes the met protein, the receptor for scatter factor/hepatocyte growth factor, a growth factor that modulates the motility and stable interaction of the epithelial cells. This study assesses the expression of met receptor in breast carcinoma and its prognostic value with respect to survival.

METHODS: Immunofluorescence was used to evaluate 91 archival breast carcinoma specimens using a polyclonal antibody to the cytoplasmic domain of the receptor. Cases were scored by two pathologists on a percentage basis and then converted to binary scores (positive or negative) on the basis of a bimodal distribution.

RESULTS: Strong expression of met was found in 20 invasive ductal breast tumor specimens (22%). The 5-year survival of patients whose tumors showed decreased met expression was 89%, in contrast to a 52% 5-year survival rate in patients whose tumors expressed met (P = 0.008). This trend also was observed in patients without lymph node metastases at presentation, in whom met negative patients had a 95% 5-year survival compared with only 62% for met positive patients (P = 0.006) Multivariate analysis using the Cox proportional hazards model showed met expression to be an independent predictor of survival, with a predictive value nearly equivalent to that associated with lymph node status.

CONCLUSIONS: The authors conclude that expression of met in patients with invasive ductal carcinoma of the breast is a strong, independent predictor of decreased survival and may be a useful prognostic marker with which to identify a subset of patients with more aggressive disease.}, } @article {pmid9541473, year = {1998}, author = {Berndt, A and Borsi, L and Luo, X and Zardi, L and Katenkamp, D and Kosmehl, H}, title = {Evidence of ED-B+ fibronectin synthesis in human tissues by non-radioactive RNA in situ hybridization. Investigations on carcinoma (oral squamous cell and breast carcinoma), chronic inflammation (rheumatoid synovitis) and fibromatosis (Morbus Dupuytren).}, journal = {Histochemistry and cell biology}, volume = {109}, number = {3}, pages = {249-255}, doi = {10.1007/s004180050224}, pmid = {9541473}, issn = {0948-6143}, mesh = {Arthritis, Rheumatoid/*metabolism/pathology ; Breast Neoplasms/*metabolism/pathology ; Carcinoma, Ductal, Breast/*metabolism/pathology ; Carcinoma, Squamous Cell/*metabolism/pathology ; Chronic Disease ; Dupuytren Contracture/*metabolism/pathology ; Female ; Fibronectins/*biosynthesis/genetics ; Humans ; In Situ Hybridization/*methods ; Inflammation ; Mouth Neoplasms/*metabolism/pathology ; Neoplasm Invasiveness ; RNA ; Synovial Fluid ; Synovitis/metabolism/pathology ; }, abstract = {The splicing variant of fibronectin containing the ED-B domain (oncofoetal fibronectin) occurs in foetal tissues, reparative processes, organ fibrosis and in tumour tissues. Consequently, a supportive effect of ED-B+ fibronectin for tissue remodelling and tumour progression is assumed. A non-radioactive RNA-RNA in situ hybridization protocol for the investigation of ED-B+ fibronectin synthesis applicable in human tissues is introduced. The ED-B+ fibronectin synthesis was investigated in human disease processes, for which the occurrence of ED-B+ fibronectin is well demonstrated by immunohistochemistry (rheumatoid arthritis, oral squamous cell carcinoma, invasive ductal carcinoma of the breast and nodular palmar fibromatosis). The ED-B+ fibronectin synthesis could be shown in lining cells and in endothelial cells of synovial villi in rheumatoid arthritis, in stromal cells of oral squamous cell carcinoma and invasive ductal carcinoma and in fibro-/myofibroblasts in the proliferative and early involutional phase of nodular palmar fibromatosis. By means of double labelling (alpha-smooth muscle actin immunostaining - ED-B+ fibronectin in situ hybridization), the ED-B+ fibronectin synthesis could be shown to be a typical feature of myofibroblasts. In contrast to the often diffuse ED-B+ fibronectin immunostaining, only a few synthetically active stromal cells were observed focally accentuated within the tumour, which were interpreted as hot spots of tumour-stroma interaction.}, } @article {pmid9521061, year = {1998}, author = {Gerloni, M and Lo, D and Zanetti, M}, title = {DNA immunization in relB-deficient mice discloses a role for dendritic cells in IgM-->IgG1 switch in vivo.}, journal = {European journal of immunology}, volume = {28}, number = {2}, pages = {516-524}, doi = {10.1002/(SICI)1521-4141(199802)28:02<516::AID-IMMU516>3.0.CO;2-M}, pmid = {9521061}, issn = {0014-2980}, support = {AI31583/AI/NIAID NIH HHS/United States ; AI36467/AI/NIAID NIH HHS/United States ; AI38375/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; DNA/*administration & dosage/*immunology ; Dendritic Cells/*immunology ; Granulocyte-Macrophage Colony-Stimulating Factor/genetics ; Humans ; Immunoglobulin Class Switching/*genetics ; Immunoglobulin Constant Regions/genetics ; Immunoglobulin G/*biosynthesis/genetics ; Immunoglobulin M/*biosynthesis ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; *Proto-Oncogene Proteins ; Radiation Chimera ; Recombinant Fusion Proteins/genetics ; Spleen ; Transcription Factor RelB ; Transcription Factors/*deficiency/genetics ; Transgenes/immunology ; }, abstract = {A single intraspleen inoculation of plasmid DNA coding for an immunoglobulin heavy chain gene initiates immunity and establishes immunologic memory against the antigenic determinants of transgenic immunoglobulins, somatic transgene immunization. During priming mice produce IgM but not IgG1 antibodies. Since IgM --> IgG1 class switch occurs spontaneously during the primary immune response to protein antigens we investigated possible mechanisms for failure of spontaneous isotype switch in vivo in this model of immunity. We found that inoculation of plasmid DNA in the form of a chimeric gene coding for granulocyte-macrophage colony-stimulating factor (GM-CSF) was able to drive IgG1 class switch readily after priming. Since GM-CSF activates cells of the dendritic lineage we tested the possibility that dendritic cells (DC) may be involved in regulating IgM --> IgG1 switch. To this end we used bone marrow chimeras constructed from mice carrying the null mutation for the relB member of the NF-kappaB/Rel family as these mice lack bone marrow-derived mature DC. RelB (-/-) mice and (-/-) bone marrow chimeras inoculated with DNA/GM-CSF did not produce IgG1 antibodies during the primary immune response. Since relB (-/-) bone marrow chimeras lack DC of donor origin but possess resident follicular dendritic cells we conclude that Ig class switch in vivo is regulated by the function of interdigitating dendritic cells (IDC). Thus, IDC may contribute to the qualitative aspects of the emerging immune response.}, } @article {pmid9502414, year = {1998}, author = {Ahmad, A and Hanby, A and Dublin, E and Poulsom, R and Smith, P and Barnes, D and Rubens, R and Anglard, P and Hart, I}, title = {Stromelysin 3: an independent prognostic factor for relapse-free survival in node-positive breast cancer and demonstration of novel breast carcinoma cell expression.}, journal = {The American journal of pathology}, volume = {152}, number = {3}, pages = {721-728}, pmid = {9502414}, issn = {0002-9440}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*enzymology/pathology ; Carcinoma in Situ/*enzymology/pathology/secondary ; Carcinoma, Ductal, Breast/*enzymology/pathology/secondary ; Carcinoma, Lobular/*enzymology/pathology/secondary ; Disease-Free Survival ; Female ; Follow-Up Studies ; Humans ; Immunohistochemistry ; In Situ Hybridization ; Lymph Nodes/enzymology ; Lymphatic Metastasis ; Matrix Metalloproteinase 11 ; Metalloendopeptidases/genetics/*metabolism ; Middle Aged ; Prognosis ; RNA, Messenger/biosynthesis ; Retrospective Studies ; }, abstract = {Stromelysin 3 (ST3) is a matrix metalloproteinase implicated in mammary carcinoma progression. To date, localization of ST3 expression in breast cancer by in situ hybridization and immunocytochemistry has shown that the expression of the enzyme is limited to only the stromal fibroblasts surrounding the cancer cells. We have immunostained a large group of ductal carcinoma in situ and invasive breast carcinomas using a monoclonal antibody (5ST-4A9) raised against the hemopexin-like domain of human ST3. We show that invasive lobular carcinomas express significantly less ST3 than invasive ductal carcinomas (IDCs) (P = 0.002). We also show, for the first time, that certain breast carcinoma cells that have undergone a degree of epithelial-to-mesenchymal transition, the so-called metaplastic carcinomas, can express ST3 mRNA and protein, which may in part explain the increased metastatic propensity seen in a number of these tumors. In addition, patients with IDC who had moderate to strong ST3 levels had significantly shorter disease-free survival than those with negative or weak ST3 levels (P = 0.02). Furthermore, in node-positive IDC patients, multivariate analysis revealed that ST3 level was a strong, independent prognostic parameter for disease-free survival (P = 0.005).}, } @article {pmid9498754, year = {1998}, author = {Leenen, PJ and Radosević, K and Voerman, JS and Salomon, B and van Rooijen, N and Klatzmann, D and van Ewijk, W}, title = {Heterogeneity of mouse spleen dendritic cells: in vivo phagocytic activity, expression of macrophage markers, and subpopulation turnover.}, journal = {Journal of immunology (Baltimore, Md. : 1950)}, volume = {160}, number = {5}, pages = {2166-2173}, pmid = {9498754}, issn = {0022-1767}, mesh = {Animals ; Biomarkers/analysis ; CD13 Antigens/analysis/biosynthesis ; Clodronic Acid ; Dendritic Cells/classification/drug effects/*immunology/metabolism ; Ganciclovir/administration & dosage ; HIV Long Terminal Repeat/genetics ; Herpesvirus 1, Human/enzymology/genetics ; Infusion Pumps, Implantable ; Liposomes/immunology ; Macrophages/*immunology ; Mice ; Mice, Inbred C57BL ; Mice, Inbred DBA ; Mice, Transgenic ; Phagocytosis/*immunology ; Radiation Chimera/immunology ; Spleen/anatomy & histology/cytology/*immunology ; Thymidine Kinase/genetics ; }, abstract = {In the normal mouse spleen, two distinct populations of dendritic cells (DC) are present that differ in microanatomical location. The major population of marginal DC is found in the "marginal zone bridging channels" and extends into the red pulp. The interdigitating cells (IDC) are localized in the T cell areas in the white pulp. The aim of the present study was to characterize these two splenic DC populations with regard to their phenotype, in vivo phagocytic function, and turnover. Both marginal DC and IDC are CD11c+ and CD13+, but only IDC are NLDC-145+ and CD8alpha+. Notably, both populations, when freshly isolated, express the macrophage markers F4/80, BM8, and Mac-1. To study the phagocytic capacity of these cells, we employed the macrophage "suicide" technique by injecting liposomes loaded with clodronate i.v. Marginal DC, but not IDC, were eliminated by this treatment. Phagocytosis of DiI-labeled liposomes by DC confirmed this finding. The two DC populations differed significantly with regard to their turnover rates, as studied in a transgenic mouse model of conditional depletion of DC populations with high turnover. In these mice, marginal DC were completely eliminated, but the IDC population remained virtually intact. From these data we conclude that the marginal DC population has a high turnover, in contrast to the IDC population. Taken together, the present results indicate that marginal DC and IDC represent two essentially distinct populations of DC in the mouse spleen. They differ not only in location, but also in phenotype, phagocytic ability, and turnover.}, } @article {pmid9467958, year = {1998}, author = {Burger, A and Li, H and Zhang, XK and Pienkowska, M and Venanzoni, M and Vournakis, J and Papas, T and Seth, A}, title = {Breast cancer genome anatomy: correlation of morphological changes in breast carcinomas with expression of the novel gene product Di12.}, journal = {Oncogene}, volume = {16}, number = {3}, pages = {327-333}, doi = {10.1038/sj.onc.1201517}, pmid = {9467958}, issn = {0950-9232}, mesh = {Amino Acid Sequence ; Animals ; Breast Neoplasms/*genetics/pathology ; Carcinoma, Ductal, Breast/*genetics/pathology ; Cloning, Molecular ; DNA, Complementary ; DNA, Neoplasm ; Female ; Gene Expression ; Humans ; Molecular Sequence Data ; Neoplasm Proteins/biosynthesis/chemistry/*genetics ; Protein Biosynthesis ; Proteins/chemistry/*genetics ; RNA, Messenger ; RNA, Neoplasm ; Rabbits ; Sequence Analysis ; Tumor Cells, Cultured ; }, abstract = {To determine which genes may be activated or inactivated during breast cancer development, we employed two cloning strategies (subtractive hybridization and differential display) using RNA samples from a human breast tumor and its matching normal breast cell line. Of 950 clones isolated, 102 cDNA inserts were analysed by DNA sequencing and database searching. We found 30 clones that were obviously unidentified, with no significant homology to any listed human gene. We focused upon one of the novel genes, Di12, that is differentially expressed as a 1.35 kb RNA in breast cancer tissues and cell-lines, and in several normal tissues. A full length cDNA of this gene was cloned, and its DNA sequence revealed an open reading frame of 339 amino acids. Antibodies to the ten N-terminal amino acids were developed to investigate the expression of Di12 in breast cancer cell-lines and tumors. The Di12 protein was found in tissue sections of infiltrating ductal carcinomas (IDCs), but not in benign or normal breast specimens. RT-PCR analysis confirmed expression of Di12 in 80% of infiltrating ductal carcinomas (IDCs). As IDC constitutes approximately 70% of breast cancers seen clinically, the level of Di12 expression may be predictive of disease progression.}, } @article {pmid9410910, year = {1997}, author = {Lowes, BD and Minobe, W and Abraham, WT and Rizeq, MN and Bohlmeyer, TJ and Quaife, RA and Roden, RL and Dutcher, DL and Robertson, AD and Voelkel, NF and Badesch, DB and Groves, BM and Gilbert, EM and Bristow, MR}, title = {Changes in gene expression in the intact human heart. Downregulation of alpha-myosin heavy chain in hypertrophied, failing ventricular myocardium.}, journal = {The Journal of clinical investigation}, volume = {100}, number = {9}, pages = {2315-2324}, pmid = {9410910}, issn = {0021-9738}, support = {5MO 1 RR00051/RR/NCRR NIH HHS/United States ; HL-48013/HL/NHLBI NIH HHS/United States ; }, mesh = {Atrial Natriuretic Factor/metabolism ; Calcium-Transporting ATPases/genetics ; Cardiomegaly/genetics ; Gene Expression Regulation ; Heart Failure/genetics ; Humans ; Hypertension, Pulmonary/genetics ; Myocardium/*metabolism ; Myosin Heavy Chains/*genetics ; RNA, Messenger/genetics ; Receptors, Adrenergic, beta/genetics ; Tissue Distribution ; }, abstract = {Using quantitative RT-PCR in RNA from right ventricular (RV) endomyocardial biopsies from intact nonfailing hearts, and subjects with moderate RV failure from primary pulmonary hypertension (PPH) or idiopathic dilated cardiomyopathy (IDC), we measured expression of genes involved in regulation of contractility or hypertrophy. Gene expression was also assessed in LV (left ventricular) and RV free wall and RV endomyocardium of hearts from end-stage IDC subjects undergoing heart transplantation or from nonfailing donors. In intact failing hearts, downregulation of beta1-receptor mRNA and protein, upregulation of atrial natriuretic peptide mRNA expression, and increased myocyte diameter indicated similar degrees of failure and hypertrophy in the IDC and PPH phenotypes. The only molecular phenotypic difference between PPH and IDC RVs was upregulation of beta2-receptor gene expression in PPH but not IDC. The major new findings were that (a) both nonfailing intact and explanted human ventricular myocardium expressed substantial amounts of alpha-myosin heavy chain mRNA (alpha-MHC, 23-34% of total), and (b) in heart failure alpha-MHC was downregulated (by 67-84%) and beta-MHC gene expression was upregulated. We conclude that at the mRNA level nonfailing human heart expresses substantial alpha-MHC. In myocardial failure this alteration in gene expression of MHC isoforms, if translated into protein expression, would decrease myosin ATPase enzyme velocity and slow speed of contraction.}, } @article {pmid9370944, year = {1997}, author = {Poulsom, R and Hanby, AM and Lalani, EN and Hauser, F and Hoffmann, W and Stamp, GW}, title = {Intestinal trefoil factor (TFF 3) and pS2 (TFF 1), but not spasmolytic polypeptide (TFF 2) mRNAs are co-expressed in normal, hyperplastic, and neoplastic human breast epithelium.}, journal = {The Journal of pathology}, volume = {183}, number = {1}, pages = {30-38}, doi = {10.1002/(SICI)1096-9896(199709)183:1<30::AID-PATH1085>3.0.CO;2-K}, pmid = {9370944}, issn = {0022-3417}, support = {//Wellcome Trust/United Kingdom ; }, mesh = {Blotting, Northern ; Breast/*metabolism/pathology ; Breast Neoplasms/*metabolism/pathology ; Carcinoma, Ductal, Breast/metabolism ; Carcinoma, Lobular/metabolism ; Female ; Growth Substances/genetics/*metabolism ; Humans ; Hyperplasia/metabolism ; Immunoenzyme Techniques ; In Situ Hybridization ; *Mucins ; *Muscle Proteins ; Neoplasm Invasiveness ; Neoplasm Proteins/metabolism ; *Neuropeptides ; Peptides/genetics/*metabolism ; Precancerous Conditions/*metabolism ; Proteins/genetics/*metabolism ; RNA, Messenger/genetics ; Trefoil Factor-1 ; Trefoil Factor-2 ; Trefoil Factor-3 ; Tumor Suppressor Proteins ; }, abstract = {pS2-TFF 1 is expressed in breast cancers and has been investigated as a potential prognostic factor reflecting oestrogen dependence. The relationship to the expression of other trefoil peptides, human spasmolytic polypeptide (hSP-TFF 2) and intestinal trefoil factor (hITF/hPI.B-TFF 3) is documented here. Fifty-seven breast specimens were selected from surgical pathology archives and included five normal breasts (two lactating), seven benign proliferative lesions, 11 ductal carcinomas in situ (DCIS), three lobular carcinomas in situ (LCIS), 24 invasive ductal carcinomas (IDC), and seven invasive lobular carcinomas (ILC). The comparative distribution of trefoil mRNAs was assessed by in situ hybridization using 35S-labelled riboprobes and immunohistochemical staining for pS2-TFF 1 and hSP-TFF 2. pS2-TFF 1 and hITF/hPI.B-TFF 3 mRNA were focally present at low signal intensity in normal and benign breast. Both pS2-TFF 1 and hITF/hPI.B-TFF 3 were expressed in all DCIS, LCIS and ILC, and 21/24 IDC. Overall, expression patterns of pS2-TFF 1 and hITF/hPI.B-TFF 3 coincided, but hITF/hPI.B-TFF 3 mRNA was usually found in a greater proportion of cells. Expression of hSP-TFF 2 peptide or mRNA was not detected in any of these cases. MCF 7 breast carcinoma cells also expressed hITF/hPI.B-TFF 3 and pS2-TFF 1 mRNAs but not hSP-TFF 2. hITF/hPI.B-TFF 3 co-expression with pS2-TFF 1 may act as a prognostic factor, but also raises questions about the regulatory pathway for pS2-TFF 1 hITF/hPI.B-TFF 3. Trefoil factors have effects on cell motility and spreading in vitro, and co-expression of hITF/hPI.B-TFF 3 with pS2-TFF 1 could be functionally significant if they form a heterodimer or compete for receptor binding. Absence of hSP-TFF 2 expression may be of equal relevance to tumour cell biology.}, } @article {pmid9355973, year = {1997}, author = {Nishizaki, T and Chew, K and Chu, L and Isola, J and Kallioniemi, A and Weidner, N and Waldman, FM}, title = {Genetic alterations in lobular breast cancer by comparative genomic hybridization.}, journal = {International journal of cancer}, volume = {74}, number = {5}, pages = {513-517}, doi = {10.1002/(sici)1097-0215(19971021)74:5<513::aid-ijc6>3.0.co;2-6}, pmid = {9355973}, issn = {0020-7136}, support = {CA44768/CA/NCI NIH HHS/United States ; }, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*genetics/metabolism ; Bromodeoxyuridine/metabolism ; Cadherins/analysis ; Carcinoma, Ductal, Breast/genetics/metabolism ; Carcinoma, Lobular/*genetics/metabolism ; Chromosome Aberrations ; DNA, Neoplasm/*genetics/metabolism ; Female ; Humans ; Immunohistochemistry ; Middle Aged ; Nucleic Acid Hybridization ; }, abstract = {Infiltrating lobular carcinoma (ILC) and infiltrating ductal carcinoma (IDC) are distinguished by their histopathological appearance. However, little is known about the differences in genetic changes between lobular cancers and ductal cancers. We used comparative genomic hybridization (CGH) and compared aberrations in 19 ILCs and 46 IDCs. The total number of aberrations was lower in ILC than in IDC. While the average number of DNA copy number losses did not reach significance between them, copy number gains were significantly lower in ILCs. Fifteen of 19 ILCs (79%) showed increased copy number of 1q, and 12 cases (63%) revealed loss of 16q. The presence of these aberrations was independent of nodal status, histologic subtypes (pleomorphic or classic ILC), or BrdUrd-labeling index. ILCs had a higher frequency of 16q loss than did ductal cancers, and a lower frequency of 8q and 20q gains. Our data suggest that the altered growth pattern and clinical presentation which characterize infiltrating lobular cancers are correlated with distinct genetic alterations.}, } @article {pmid9271010, year = {1997}, author = {Mourad, WA}, title = {Aneuploidy in sclerosing adenosis may predict an increased risk of malignancy. A study using the AgNOR silver stain.}, journal = {Pathology}, volume = {29}, number = {3}, pages = {255-259}, doi = {10.1080/00313029700169015}, pmid = {9271010}, issn = {0031-3025}, mesh = {Adult ; Aged ; Aged, 80 and over ; *Aneuploidy ; Breast Neoplasms/genetics/*pathology ; Diploidy ; Female ; Fibrocystic Breast Disease/genetics/*pathology ; Follow-Up Studies ; Humans ; Middle Aged ; Nucleolus Organizer Region/*chemistry ; Predictive Value of Tests ; Risk Factors ; Sclerosis/genetics/pathology ; Silver Staining ; }, abstract = {Sclerosing adenosis (SA) of the breast if a disease associated with an increase relative risk of malignancy. The exact incidence and factors influencing malignant transformation in association with SA are not well established. Two counts of the AgNOR silver staining technique have been correlated with ploidy and proliferative activity. The first count which is the mean number of AgNOR granules (mAgNOR), correlates with ploidy. The second count is the percentage of nuclei exhibiting > or = 5 AgNORs/nucleus (pAgNOR) and reflects proliferative activity. The hypothesis in the current study was that aneuploidy, as determined by the AgNOR silver staining technique, may potentially identify lesions of SA with an increased association with malignant breast disease. The AgNOR silver staining technique was performed on 69 cases of SA with the application of the two counts. Of these cases 53 were not associated with malignancy and 16 were associated with synchronous or metachronous carcinoma of the breast, these being 11 cases of invasive ductal carcinoma (IDC), four cases of ductal carcinoma in situ (DCIS) and one case of lobular carcinoma in situ (LCIS). The patient ages ranged from 27 to 84 years (median 53 years) with a median follow up of 28 months. Six of the 53 cases of SA no associated with malignancy (11%) had aneuploid mAgNOR counts of > or = 2.4 whereas 12 of the 16 cases associated with carcinoma (80%) had such counts (p < 0.0005). This included nine cases of IDC, two cases of DCIS and the case of LCIS. Of the six aneuploid cases not associated with malignancy, two cases showed cytological atypia, one case was associated with atypical ductal hyperplasia and one case was seen in a leukemic patient who had received chemotherapy and radiation therapy. The pAgNOR counts showed a statistically less significant correlation with malignancy (p < 0.03). These findings suggest that aneuploidy, measured by the AgNOR silver stein, seen in SA may help identify lesions with a higher relative risk of being associated with breast carcinoma and hence that may require more aggressive management than diploid ones.}, } @article {pmid9226257, year = {1997}, author = {Kikuchi, Y and Kojima, H and Tanaka, T and Takatsuka, Y and Kamio, Y}, title = {Characterization of a second lysine decarboxylase isolated from Escherichia coli.}, journal = {Journal of bacteriology}, volume = {179}, number = {14}, pages = {4486-4492}, pmid = {9226257}, issn = {0021-9193}, mesh = {Amino Acid Sequence ; Base Sequence ; Blotting, Southern ; Carboxy-Lyases/chemistry/*genetics/isolation & purification/metabolism ; Chromosomes, Bacterial ; Cloning, Molecular ; DNA, Bacterial/genetics ; Escherichia coli/*enzymology/genetics ; Gene Expression Regulation, Bacterial ; Genes, Bacterial ; Hydrogen-Ion Concentration ; Molecular Sequence Data ; Promoter Regions, Genetic ; Sequence Analysis, DNA ; }, abstract = {We report here on the existence of a new gene for lysine decarboxylase in Escherichia coli K-12. The hybridization experiments with a cadA probe at low stringency showed that the homologous region of cadA was located in lambda Kohara phage clone 6F5 at 4.7 min on the E. coli chromosome. We cloned the 5.0-kb HindIII fragment of this phage clone and sequenced the homologous region of cadA. This region contained a 2,139-nucleotide open reading frame encoding a 713-amino-acid protein with a calculated molecular weight of 80,589. Overexpression of the protein and determination of its N-terminal amino acid sequence defined the translational start site of this gene. The deduced amino acid sequence showed 69.4% identity to that of lysine decarboxylase encoded by cadA at 93.7 min on the E. coli chromosome. In addition, the level of lysine decarboxylase activity increased in strains carrying multiple copies of the gene. Therefore, the gene encoding this lysine decarboxylase was designated Idc. Analysis of the lysine decarboxylase activity of strains containing cadA, ldc, or cadA ldc mutations indicated that ldc was weakly expressed under various conditions but is a functional gene in E. coli.}, } @article {pmid9167459, year = {1997}, author = {}, title = {Pathology of familial breast cancer: differences between breast cancers in carriers of BRCA1 or BRCA2 mutations and sporadic cases. Breast Cancer Linkage Consortium.}, journal = {Lancet (London, England)}, volume = {349}, number = {9064}, pages = {1505-1510}, pmid = {9167459}, issn = {0140-6736}, support = {CA61231/CA/NCI NIH HHS/United States ; }, mesh = {Adenocarcinoma/genetics/pathology ; Adenocarcinoma, Mucinous/genetics/pathology ; Adult ; Aged ; BRCA2 Protein ; Breast/pathology ; Breast Neoplasms/*genetics/pathology ; Carcinoma in Situ/genetics/pathology ; Carcinoma, Ductal, Breast/genetics/pathology ; Carcinoma, Lobular/genetics/pathology ; Carcinoma, Medullary/genetics/pathology ; Case-Control Studies ; Female ; *Genes, BRCA1 ; *Genes, Tumor Suppressor ; Genetic Markers/*genetics ; Genetic Predisposition to Disease ; *Heterozygote ; Humans ; Middle Aged ; Mitosis ; Mutation/*genetics ; Neoplasm Proteins/*genetics ; Transcription Factors/*genetics ; }, abstract = {BACKGROUND: A few breast cancer cases are attributable to a hereditary predisposition to the disease. We aimed to compare the histological features of breast cancer in women carrying mutations in the susceptibility genes BRCA1 and BRCA2 with controls unselected for family history.

METHODS: The morphological characteristics of specimens from 440 patients with familial breast cancer, including 118 in carriers of BRCA1 mutations and 78 in carriers of BRCA2 mutations, were compared with those from 547 age-matched controls, unselected for family history, by seven pathologists.

FINDINGS: Cancers in carriers of BRCA1 (p < 0.0001) and BRCA2 mutations (p = 0.04) were, on average, of a higher overall grade than in controls. For example, the proportions in grade 3 were 66% of 139, 41% of 58 and 36% of 368 specimens, respectively. However, when the three grade indices were considered independently, breast cancers in BRCA1-mutation carriers showed more pleomorphism (p = 0.006), a higher mitotic count (p < 0.0001), and less tubule formation than controls (p = 0.006), whereas cancers in BRCA2-mutation carriers showed less tubule formation (p = 0.003), but no difference in pleomorphism or mitotic count. The occurrence of invasive lobular carcinoma and invasive ductal carcinoma was not significantly different between carriers of BRCA1 or BRCA2 mutations and controls. Medullary or atypical medullary carcinoma was, however, found more often in BRCA1 (13%, p < 0.0001) than in BRCA2-mutation carriers (3%) or controls (2%). Tubular carcinoma was less common in BRCA2-mutation carriers. The few mucoid carcinomas were all in familial cases. Carriers of BRCA1 mutations showed less ductal carcinoma in situ around the invasive lesion than controls (41 vs 56%, p = 0.001). Lobular carcinoma in situ was less common in familial cancers (p = 0.013), but differences were not significant for BRCA1-mutations or BRCA2-mutation carriers, separately.

INTERPRETATION: The histology of breast cancers in predisposed women differs from that in sporadic cases, and there are differences between breast cancers in carriers of BRCA1 and BRCA2 mutations. The findings suggest that breast cancer due to BRCA1, has a different natural history to BRCA2 or apparently sporadic disease, which may have implications for screening and management.}, } @article {pmid9095001, year = {1997}, author = {Kuukasjärvi, T and Tanner, M and Pennanen, S and Karhu, R and Kallioniemi, OP and Isola, J}, title = {Genetic changes in intraductal breast cancer detected by comparative genomic hybridization.}, journal = {The American journal of pathology}, volume = {150}, number = {4}, pages = {1465-1471}, pmid = {9095001}, issn = {0002-9440}, mesh = {Breast Neoplasms/*genetics/pathology ; Carcinoma in Situ/*genetics/pathology ; Carcinoma, Ductal, Breast/*genetics/pathology ; Carcinoma, Intraductal, Noninfiltrating/*genetics/pathology ; Chromosome Mapping ; Female ; Humans ; In Situ Hybridization, Fluorescence ; Nucleic Acid Hybridization ; Polymerase Chain Reaction ; }, abstract = {Ductal carcinoma in situ (DCIS) is considered a direct precursor of invasive ductal breast cancer (IDC). We combined tissue microdissection and comparative genomic hybridization to identify genetic changes in five DCIS lesions with no invasion and in two that were adjacent to IDC. Extensive genetic changes characterized pure DCIS cases with gains of 1q, 6q, 8q, and Xq as well as losses of 17p and chromosome 22 being most often involved. Except for the Xq gain, these changes are also common to IDC. Separate analysis of DCIS and IDC components in the same tumor revealed an almost identical pattern of genetic changes in one case, whereas substantial differences were found in another. We conclude that many of the common genetic changes in IDC may take place before development of invasive growth. However, a simple linear progression model may not always account for the DCIS-IDC transition.}, } @article {pmid9088975, year = {1997}, author = {Björck, P and Banchereau, J and Flores-Romo, L}, title = {CD40 ligation counteracts Fas-induced apoptosis of human dendritic cells.}, journal = {International immunology}, volume = {9}, number = {3}, pages = {365-372}, doi = {10.1093/intimm/9.3.365}, pmid = {9088975}, issn = {0953-8178}, mesh = {Antibodies, Monoclonal/pharmacology ; Apoptosis/*drug effects ; CD40 Antigens/*drug effects/physiology ; CD40 Ligand ; Cell Differentiation/drug effects ; Cell Separation ; Cells, Cultured ; Coculture Techniques ; DNA Fragmentation ; Dendritic Cells/*cytology/immunology ; Fibroblasts ; Granulocyte-Macrophage Colony-Stimulating Factor/pharmacology ; Hematopoietic Stem Cells/drug effects ; Humans ; Membrane Glycoproteins/genetics/*pharmacology ; Palatine Tonsil/cytology ; Proto-Oncogene Proteins c-bcl-2/physiology ; Recombinant Fusion Proteins/pharmacology ; Signal Transduction/physiology ; Transfection ; Tumor Necrosis Factor-alpha/pharmacology ; fas Receptor/*immunology ; }, abstract = {Dendritic cells (DC) are cells of the hematopoletic system specialized in capturing antigens and initiating T cell-mediated immune responses. We show here that human DC generated in vitro by culturing CD34+ cord blood progenitor cells in granulocyte macrophage colony stimulating factor plus tumor necrosis factor-alpha express the Fas antigen (APO-1, CD95) and undergo apoptosis upon triggering of Fas by mAb. However, only a proportion of the cells die in response to Fas ligation, an observation that may be related to the virtual absence of the bcl-2 protein in about half of the cells. Ligation of DC CD40 by culture on CD40L-transfected fibroblastic cells up-regulates the expression of bcl-2 and, concomitantly, renders DC virtually resistant to Fas-induced apoptosis. Parallel experiments with mature, interdigitating dendritic cells (IDC) isolated from tonsils revealed that IDC express Fas but do not enter into apoptosis following Fas ligation, a finding that may be explained by their high levels of bcl-2. Thus, upon encountering antigen-specific T cells, DC become resistant to Fas-induced apoptosis, as a consequence of CD40 ligation and possibly by mechanisms associated to the up-regulation of bcl-2 protein expression.}, } @article {pmid9042800, year = {1997}, author = {Yonezawa, S and Sueyoshi, K and Nomoto, M and Kitamura, H and Nagata, K and Arimura, Y and Tanaka, S and Hollingsworth, MA and Siddiki, B and Kim, YS and Sato, E}, title = {MUC2 gene expression is found in noninvasive tumors but not in invasive tumors of the pancreas and liver: its close relationship with prognosis of the patients.}, journal = {Human pathology}, volume = {28}, number = {3}, pages = {344-352}, doi = {10.1016/s0046-8177(97)90134-9}, pmid = {9042800}, issn = {0046-8177}, support = {CA24321/CA/NCI NIH HHS/United States ; }, mesh = {Aged ; Bile Duct Neoplasms/*genetics/metabolism/pathology ; Cystadenocarcinoma/*genetics/metabolism/pathology ; Female ; Gene Expression ; Humans ; Immunohistochemistry ; In Situ Hybridization ; Male ; Middle Aged ; Mucin-2 ; Mucins/*genetics/metabolism ; *Neoplasm Invasiveness ; Pancreatic Neoplasms/*genetics/metabolism/pathology ; Polymerase Chain Reaction ; Prognosis ; RNA, Messenger/analysis ; }, abstract = {We have previously reported that MUC2 apomucin was highly expressed in noninvasive tumors of the pancreas (intraductal papillary tumor [IdPT]) and liver (bile duct cystadenocarcinoma [BdCC]), which show more favorable outcomes than invasive carcinomas. In contrast, MUC2 was rarely expressed in invasive carcinomas of the pancreas (invasive ductal carcinoma [IDC]) and the liver (invasive cholangiocarcinoma [ICC]). In the present study, we examined localization of MUC2 messenger RNA (MUC2 mRNA) by using a complementary DNA (cDNA) probe for the MUC2 tandem repeat for in situ hybridization (pHAM1). Localization of MUC2 apomucin was determined by using an antibody directed against MUC2 apomucin (anti-MRP) for immunohistochemistry study. Eleven IdPTs and 10 IDCs of the pancreas, and 8 BdCC and 8 ICCs of the liver were examined. Nine (82%) of 11 IdPTs showed positive expression of MUC2 mRNA in the neoplastic cells, whereas none (0%) of the IDCs showed expression of MUC2 mRNA. Six (75%) of the 8 BdCCs showed positive expression of MUC2 mRNA in the neoplastic cells, whereas none (0%) of the 8 ICCs showed expression of MUC2 mRNA. The localization of MUC2 mRNA and that of MUC2 apomucin usually coincided, although a few cases (1 IDC, 1 BdCC, and 1 ICC) showed focal expression of MUC2 apomucin despite the absence of detectable MUC2 mRNA. These results indicate that the expression of MUC2 apomucin in IdPTs and BdCCs correlates with expression of MUC2 mRNA. In both patient groups with pancreatic tumors and hepatic tumors, patients with positive MUC2 mRNA expression in the tumors showed significantly better survival than those with negative MUC2 mRNA expression in the tumors. The production of MUC2, an abundant extracellular mucin, by most IdPTs and BdCCs may be correlated with tumors that display lower levels of invasion and metastasis.}, } @article {pmid9042790, year = {1997}, author = {Nayar, R and Zhuang, Z and Merino, MJ and Silverberg, SG}, title = {Loss of heterozygosity on chromosome 11q13 in lobular lesions of the breast using tissue microdissection and polymerase chain reaction.}, journal = {Human pathology}, volume = {28}, number = {3}, pages = {277-282}, doi = {10.1016/s0046-8177(97)90124-6}, pmid = {9042790}, issn = {0046-8177}, mesh = {Breast Neoplasms/*genetics/pathology ; Carcinoma in Situ/*genetics/pathology ; Carcinoma, Lobular/*genetics/pathology ; *Chromosome Deletion ; Chromosomes, Human, Pair 11/*genetics ; Female ; Heterozygote ; Humans ; Hyperplasia/genetics/pathology ; Polymerase Chain Reaction ; }, abstract = {Demonstration of identical allelic loss on chromosome 11q13 in synchronous in situ (DCIS) and invasive ductal (IDC) breast carcinoma has provided molecular evidence of the progression of DCIS to IDC. We investigated loss of heterozygosity (LOH) at chromosome 11q13 in the spectrum of "marker/premalignant" and "malignant" lobular lesions of the breast, including atypical lobular hyperplasia (ALH), lobular carcinoma in situ (LCIS), and infiltrating lobular carcinoma (ILC). Thirty-eight cases with various combinations of ALH, LCIS, and ILC were studied. Synchronous ductal lesions were present in 9 of 38 cases. Areas of interest were specifically isolated by tissue microdissection. The extracted DNA was amplified by polymerase chain reaction (PCR) and analyzed with two polymorphic markers for chromosome 11q13 (INT2 and PYGM). LOH at 11q13 was identified in ILC and LCIS in approximately one third of informative cases. LCIS in association with ILC showed a loss in 50% of cases, whereas pure LCIS in the absence of ILC had a much lower frequency of LOH, which was comparable to that of pure ALH. These results suggest that LOH on chromosome 11q13 may play an important role in development of ILC, similar to that of IDC from DCIS/ADH. Additionally, frequent LOH in ILC and LCIS associated with ILC and a significantly lower and comparable frequency of LOH in LCIS without ILC and ALH implies that genetic alteration(s) on chromosome 11q13 may be important in the transition of LCIS to ILC. LOH was detected in three of nine synchronous ductal lesions (one IDC and two DCIS), confirming our earlier findings and indicating that lobular and ductal neoplasia in the breast show some similar genetic changes. We hypothesize that LOH may help in separating morphologically similar yet genetically different subgroups of ALH and LCIS into one group with genetic changes and an increased potential to progress to invasive cancer and another group, the "marker" lesions of LCIS/ALH, that remain stable or possibly regress.}, } @article {pmid9066738, year = {1997}, author = {Sogawa, K and Masaki, T and Miyauchi, A and Sugita, A and Kito, K and Ueda, N and Miyamoto, K and Okazaki, K and Okutani, K and Matsumoto, K}, title = {Enhanced expression of PP1 gamma 1, a catalytic subunit isoform of protein phosphatase type 1, in invasive ductal carcinoma of the breast.}, journal = {Cancer letters}, volume = {112}, number = {2}, pages = {263-268}, doi = {10.1016/s0304-3835(96)04589-2}, pmid = {9066738}, issn = {0304-3835}, mesh = {Adult ; Antigens, Neoplasm/*analysis ; Breast Neoplasms/*enzymology/pathology ; Carcinoma, Ductal, Breast/*enzymology/genetics ; Catalysis ; Female ; Flow Cytometry ; Humans ; Immunohistochemistry ; Isoenzymes/*analysis ; Macromolecular Substances ; Middle Aged ; Phosphoprotein Phosphatases/*analysis ; S Phase/physiology ; }, abstract = {Breast cancer is one of the most common malignancies of women. Assessing the biological parameters of malignant tumors may facilitate predictions of clinical outcome. The expression of the three catalytic subunits of protein phosphatase (PP) type 1, PP1 alpha, PP1 gamma 1 and PP1 delta, as well as the one catalytic subunit of PP type 2, PP2AC, were examined in ten cases of mammary dysplasia, ten cases of fibroadenoma and 12 cases of invasive ductal carcinoma, using immunohistochemical analysis. Moreover, we measured the S-phase fraction of the cell cycle for use as a marker value of cell growth, using flow cytometric analysis. The percentage of proliferating cells that stained positive with antisera against PP1 gamma 1 was significantly higher in invasive ductal carcinoma than in mammary dysplasia and fibroadenoma. Furthermore, invasive ductal carcinoma showed a markedly high number of tumor cells in the S-phase of the cell cycle, as compared to mammary dysplasia and fibroadenoma. Our results indicate that PP1 gamma 1 may be involved in the accelerated growth of malignant cells in breast tumors.}, } @article {pmid9365176, year = {1997}, author = {Toikkanen, S and Pylkkänen, L and Joensuu, H}, title = {Invasive lobular carcinoma of the breast has better short- and long-term survival than invasive ductal carcinoma.}, journal = {British journal of cancer}, volume = {76}, number = {9}, pages = {1234-1240}, pmid = {9365176}, issn = {0007-0920}, mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/epidemiology/genetics/*mortality/pathology ; Carcinoma, Ductal, Breast/epidemiology/genetics/*mortality/pathology ; Carcinoma, Lobular/epidemiology/genetics/*mortality/pathology ; Female ; Flow Cytometry ; Follow-Up Studies ; Humans ; Lymphatic Metastasis/diagnosis ; Middle Aged ; Multivariate Analysis ; Prognosis ; S Phase ; Survival Rate ; }, abstract = {The outcome and prognostic factors of 217 women with invasive lobular carcinoma (ILC) and those of 1121 women with invasive ductal carcinoma (IDC) of the breast were compared. The patients were followed up for 10-43 years. Women with ILC had axillary nodal metastases less frequently than those with IDC (43% vs 53%, P = 0.02), although there was no difference in the primary tumour size between the groups. ILCs were more frequently of low grade, had lower mitotic counts and had less tumour necrosis. Furthermore, ILCs had lower S-phase fractions and were more often DNA diploid in flow cytometric analysis than IDCs (P < 0.0001 for all comparisons). The 5- and 30-year corrected survival rates of women with ILC were 78% and 50%, respectively, compared with 63% and 37% for women with IDC (P = 0.001). Small pT1NOMO ILCs (n = 41) had 100% 10-year and 83% 20-year corrected survival rates. In a multivariate analysis, a large primary tumour size, the presence of axillary nodal metastases, a high mitotic count and the presence of tumour necrosis all had an independent prognostic value in ILC. We conclude that ILC is associated with better survival than IDC.}, } @article {pmid9365159, year = {1997}, author = {Vos, CB and Cleton-Jansen, AM and Berx, G and de Leeuw, WJ and ter Haar, NT and van Roy, F and Cornelisse, CJ and Peterse, JL and van de Vijver, MJ}, title = {E-cadherin inactivation in lobular carcinoma in situ of the breast: an early event in tumorigenesis.}, journal = {British journal of cancer}, volume = {76}, number = {9}, pages = {1131-1133}, pmid = {9365159}, issn = {0007-0920}, mesh = {Breast Neoplasms/*genetics/*metabolism ; Cadherins/*genetics/*metabolism ; Carcinoma in Situ/genetics/*metabolism ; Carcinoma, Ductal, Breast/metabolism ; Carcinoma, Lobular/genetics/*metabolism ; Chromosome Deletion ; DNA/analysis ; Heterozygote ; Humans ; Immunohistochemistry ; }, abstract = {In breast cancer, inactivating point mutations in the E-cadherin gene are frequently found in invasive lobular carcinoma (ILC) but never in invasive ductal carcinoma (IDC). Lobular carcinoma in situ (LCIS) adjacent to ILC has previously been shown to lack E-cadherin expression, but whether LCIS without adjacent invasive carcinoma also lacks E-cadherin expression and whether the gene mutations present in ILC are already present in LCIS is not known. We report here that E-cadherin expression is absent in six cases of LCIS and present in 150 cases of ductal carcinoma in situ (DCIS), both without an adjacent invasive component. Furthermore, using mutation analysis, we could demonstrate the presence of the same truncating mutations and loss of heterozygosity (LOH) of the wild-type E-cadherin in the LCIS component and in the adjacent ILC. Our results indicate that E-cadherin is a very early target gene in lobular breast carcinogenesis and plays a tumour-suppressive role, additional to the previously suggested invasion-suppressive role.}, } @article {pmid9214117, year = {1997}, author = {Bychkova, NV and Pozharisskiĭ, KM}, title = {[Aneuploidy and proliferative activity in breast cancer (flow-cytometric investigation)].}, journal = {Voprosy onkologii}, volume = {43}, number = {2}, pages = {171-175}, pmid = {9214117}, issn = {0507-3758}, mesh = {Adult ; Aged ; *Aneuploidy ; Breast Neoplasms/*genetics/*pathology ; Carcinoma, Ductal, Breast/*genetics/*pathology ; Cell Division ; DNA, Neoplasm/genetics ; Female ; Flow Cytometry ; Humans ; Middle Aged ; }, abstract = {Flow-cytometric assay of DNA levels and proliferative activity of cell in 43 cancers of the breast was carried out. The cytometric data were evaluated versus age, histological malignancy and regional metastasis incidence. The study pointed to a direct correlation between malignancy and aneuploidy (increased fraction of cells featuring unbalanced levels of DNA as well as enhanced DNA index) involved in invasive ductal carcinoma. Aneuploidy and proliferative activity frequency is relatively higher in cases of regionally disseminated tumors. Aneuploidy tumor incidence is higher in age groups under 50 than in older patients.}, } @article {pmid8881501, year = {1996}, author = {Mestroni, L and Milasin, J and Vatta, M and Pinamonti, B and Sinagra, G and Rocco, C and Matulic, M and Falaschi, A and Giacca, M and Camerini, F}, title = {Genetic factors in dilated cardiomyopathy.}, journal = {Archives des maladies du coeur et des vaisseaux}, volume = {89 Spec No 2}, number = {}, pages = {15-20}, pmid = {8881501}, issn = {0003-9683}, support = {E.0291/TI_/Telethon/Italy ; }, mesh = {Cardiomyopathy, Dilated/diagnosis/*genetics ; Chromosome Mapping ; Chromosomes, Human, Pair 1/genetics ; Chromosomes, Human, Pair 14/genetics ; Chromosomes, Human, Pair 3/genetics ; Chromosomes, Human, Pair 9/genetics ; Dystrophin/genetics ; Genes, Dominant ; Humans ; *Molecular Biology ; Pedigree ; X Chromosome/genetics ; }, abstract = {Recent studies have demonstrated that genetic factors are likely to play a major role in the pathogenesis of idiopathic dilated cardiomyopathy (IDC). In clinical surveys, a familial trait has been demonstrated in 20 to 30% of idiopathic dilated cardiomyopathy patients (familial dilated cardiomyopathy). Molecular genetic studies have confirmed the clinical hypothesis of genetic heterogeneity in familial dilated cardiomyopathy, and are currently producing relevant advances in the understanding of this disease. The autosomal dominant form is considered to be the most frequent form of inherited idiopathic dilated cardiomyopathy. After the exclusion of a large series of candidate genes, the first familial dilated cardiomyopathy gene has been mapped to the long arm of chromosome 9. A second locus has been found on chromosome 1. Moreover, in two large families, characterized by a peculiar form of conduction delays and later development of myocardial dysfunction, the disease loci have been mapped to chromosome 1 and 3, respectively. The identification of the disease genes is in progress. In families with X-linked dilated cardiomyopathy, the disease gene has been identified as the dystrophin gene. The 5' end of the gene appears to be the critical region for the development of dilated cardiomyopathy without clinical evidence of muscle dystrophy. Furthermore, other cytoskeletal proteins, such as adhalin, could be involved in the pathogenesis of familial dilated cardiomyopathy. In familial right ventricular cardiomyopathy (or arrhythmogenic right ventricular dysplasia) characterized by isolated or prevalent right ventricular involvement, three different disease loci have been identified so far: two localized on the long arm of chromosome 14 and one on chromosome 1. The disease genes are still unknown and are currently under investigation. The study of the genetic factors at the molecular level is starting to elucidate the pathogenetic mechanisms of idiopathic dilated cardiomyopathy. These findings will also have relevant clinical and therapeutic implications.}, } @article {pmid8814452, year = {1996}, author = {Yaremko, ML and Kutza, C and Lyzak, J and Mick, R and Recant, WM and Westbrook, CA}, title = {Loss of heterozygosity from the short arm of chromosome 8 is associated with invasive behavior in breast cancer.}, journal = {Genes, chromosomes & cancer}, volume = {16}, number = {3}, pages = {189-195}, doi = {10.1002/(SICI)1098-2264(199607)16:3<189::AID-GCC6>3.0.CO;2-V}, pmid = {8814452}, issn = {1045-2257}, support = {CA14559/CA/NCI NIH HHS/United States ; P20CA66132/CA/NCI NIH HHS/United States ; R55CA5607/CA/NCI NIH HHS/United States ; }, mesh = {Breast Neoplasms/*genetics/pathology ; Carcinoma, Ductal, Breast/*genetics/pathology ; *Chromosome Deletion ; *Chromosomes, Human, Pair 8 ; DNA, Neoplasm ; Female ; Genetic Markers ; Humans ; Microsatellite Repeats ; Neoplasm Invasiveness ; Polymerase Chain Reaction ; Polymorphism, Genetic ; }, abstract = {Loss of heterozygosity (LOH) from the short arm of chromosome 8 (8p) is frequent in many human cancers, including breast, colon, prostate, and bladder cancers. LOH occurs in two regions of 8p, 8p21 and 8p22, and suggests the presence of two separate tumor suppressor genes. In breast cancers, 8p LOH occurs in both early and late clinical stage tumors, while in colon, prostate, and bladder cancers, there is an association between 8p LOH and advanced clinical stage. We investigated this discrepancy by comparing 8p LOH in infiltrating ductal carcinomas (IDC) to breast cancers of earlier clinical stage, i.e., tumors with no invasion [ductal carcinoma in situ (DCIS)-only tumors]. We used three markers which sample several reported loci of 8p LOH. We microdissected tumor from paraffin blocks of 39 IDC and 23 DCIS-only breast cancers and amplified tumor/normal DNA pairs for the microsatellite markers D8S254 (8p22), D8S133 (8p21.3), and NEFL (8p21). All cases of IDC were informative with at least one marker, with a combined rate of LOH of 46%. The results for each marker were [no. LOH/no. informative (%)]: D8S254, 8/26 (31%); D8S133 12/31 (39%), and NEFL, 9/25 (36%). In the DCIS-only group, all 23 were informative for at least one marker, but 8p LOH was absent. We conclude that 8p LOH from 8p21-22 is frequent in IDC of the breast, but absent in DCIS-only cases, and may play a role in breast cancer progression by conferring invasive ability.}, } @article {pmid8732665, year = {1996}, author = {Ram, TG and Ethier, SP}, title = {Phosphatidylinositol 3-kinase recruitment by p185erbB-2 and erbB-3 is potently induced by neu differentiation factor/heregulin during mitogenesis and is constitutively elevated in growth factor-independent breast carcinoma cells with c-erbB-2 gene amplification.}, journal = {Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research}, volume = {7}, number = {5}, pages = {551-561}, pmid = {8732665}, issn = {1044-9523}, support = {CA40064/CA/NCI NIH HHS/United States ; T32CA09676/CA/NCI NIH HHS/United States ; }, mesh = {Androstadienes/pharmacology ; Antineoplastic Agents/*metabolism ; Blotting, Northern ; Blotting, Southern ; Blotting, Western ; Breast Neoplasms ; Cell Division/drug effects/physiology ; DNA, Neoplasm/analysis ; Enzyme Inhibitors/pharmacology ; Epidermal Growth Factor/pharmacology ; Epithelial Cells ; Epithelium/physiology ; ErbB Receptors/*physiology ; Female ; Gene Amplification ; Gene Expression Regulation, Neoplastic/physiology ; Genes, erbB-2/genetics ; Glycoproteins/*physiology ; Humans ; Insulin-Like Growth Factor I/pharmacology ; Mitogens/physiology ; Neuregulins ; Phosphatidylinositol 3-Kinases ; Phosphorylation ; Phosphotransferases (Alcohol Group Acceptor)/*metabolism ; Proto-Oncogene Proteins/*physiology ; RNA, Messenger/analysis ; Receptor, ErbB-2/*genetics/metabolism ; Receptor, ErbB-3 ; Signal Transduction/genetics ; Tumor Cells, Cultured/cytology/enzymology ; Tyrosine/metabolism ; Wortmannin ; }, abstract = {Amplification and overexpression of the c-erbB-2 gene in 21MT-2 and 21MT-1 human breast carcinoma cells results in progressively elevated levels of constitutively tyrosine-phosphorylated p185erbB-2 and is associated with progressive insulin-like growth factor (IGF) and combined IGF/epidermal growth factor (EGF) independence in culture. In addition, the neu differentiation factor/heregulins (HRGs), a family of ligands that activate p185erbB-2 through direct binding to erbB-3 or erbB-4, are potent mitogens for various nonneoplastic mammary epithelial cells and carcinoma cell lines in the absence of both IGF and EGF in culture. We have investigated the ability of ligand induction with HRGs or the constitutive activation of p185erbB-2 in the 21MT breast carcinoma cells to induced the recruitment of phosphatidylinositol 3-kinase (PI3K) by p185erbB-2 and erbB-3. HRG was found to potently induce the recruitment of the M(r) 85,000 regulatory subunit of PI3K by phosphotyrosine proteins in both nonneoplastic H16N-2 mammary epithelial cells (which express normal c-erbB-2 levels) and in the 21MT-2 and 21MT-1 cell lines, which were all isolated from a single patient with intraductal and invasive ductal carcinoma of the breast and express c-erbB-3 but not c-erbB-4 in culture. The activation of PI3K in these cells was also associated with high-level mitogenic responsiveness to HRG, as well as the IGF/EGF-independent proliferation of the 21MT cell lines in culture. The recruitment of PI3K by phosphotyrosine protein during ligand-induced activation, or that seen constitutively in the 21MT tumor cells, did not involve detectable tyrosine phosphorylation of p85. The HRG-induced recruitment of p85 and the constitutive recruitment of p85 in the 21MT cell lines involved direct association with both p185erbB-2 and erbB-3, although greater levels were recruited directly by erbB-3. Wortmannin, a potent inhibitor of PI3K enzymatic activity, also blocked the autonomous proliferation of the 21MT cells, and this effect was reversible in long-term cultures. These data indicate that PI3K may be an especially important mediator of HRG-induced proliferation in mammary epithelial cells and is involved in the autonomous proliferation of growth factor-independent breast carcinoma cells with c-erbB-2 gene amplification.}, } @article {pmid8630282, year = {1996}, author = {Beckmann, MW and Picard, F and An, HX and van Roeyen, CR and Dominik, SI and Mosny, DS and Schnürch, HG and Bender, HG and Niederacher, D}, title = {Clinical impact of detection of loss of heterozygosity of BRCA1 and BRCA2 markers in sporadic breast cancer.}, journal = {British journal of cancer}, volume = {73}, number = {10}, pages = {1220-1226}, pmid = {8630282}, issn = {0007-0920}, mesh = {Age Factors ; BRCA1 Protein ; BRCA2 Protein ; Base Sequence ; Breast Neoplasms/*genetics ; Carcinoma, Ductal, Breast/*genetics ; Carcinoma, Lobular/*genetics ; Chromosomes, Human, Pair 17 ; DNA Primers/chemistry ; Genetic Markers ; Heterozygote ; Humans ; Lymphatic Metastasis ; Microsatellite Repeats ; Middle Aged ; Molecular Sequence Data ; Neoplasm Proteins/*genetics ; Sequence Deletion ; Transcription Factors/*genetics ; }, abstract = {The development of familial and sporadic breast cancer is based on genetic alterations of tumour-suppressor genes, for which loss of heterozygosity (LOH) is one mechanism of gene inactivation. To investigate LOH of BRCA1 (17q21) and BRCA2 (13-q12-13) in sporadic breast cancer, polymerase chain reaction (PCR)-based fluorescent DNA technology for detection of microsatellite polymorphisms was applied. A total of 137 breast cancer and 15 benign breast specimens with matched normal tissue were examined. Fluorescent-labelled PCR products were analysed in an automated DNA sequencer (ALFTM Pharmacia). Losses at both loci were correlated with different histological types, age, tumour size, lymph node status, grading and steroid hormone receptor expression, [SHR: oestrogen receptor (ER), progesterone receptor (PgR)]. For BRCA1 (D17S855, THRA1, D17S579) losses could be detected in invasive ductal carcinoma (IDC; n = 108) in 32-38%, invasive lobular carcinoma (ILC; n = 19) in 21-42% depending on the marker applied, but not in benign breast tumours (n = 15). Losses of BRCA1 markers correlated with larger tumour size, higher grade, and PgR expression. For BRCA2 (D13S260, D13S267, D13S171) losses could be detected in 108 IDCs in 30-38%, in 19 ILCs in 17-39% depending on the marker applied, but not in benign breast tumours. Losses of BRCA2 markers correlated only with higher grade. Microsatellite analyses combined with detection of fluorescent-labelled PCR products by an automated laser DNA sequencer can be used for routine determination of LOH. In sporadic breast cancer, LOH of BRCA1 of BRCA2 does not add decisive prognostic value as stated for familial breast cancer.}, } @article {pmid8689655, year = {1996}, author = {Linck, B and Bokník, P and Eschenhagen, T and Müller, FU and Neumann, J and Nose, M and Jones, LR and Schmitz, W and Scholz, H}, title = {Messenger RNA expression and immunological quantification of phospholamban and SR-Ca(2+)-ATPase in failing and nonfailing human hearts.}, journal = {Cardiovascular research}, volume = {31}, number = {4}, pages = {625-632}, pmid = {8689655}, issn = {0008-6363}, mesh = {*Adenosine Triphosphate ; Adult ; Autoradiography ; Base Sequence ; Blotting, Northern ; Calcium-Binding Proteins/analysis/*genetics ; Calcium-Transporting ATPases/analysis/*genetics ; Cardiomyopathy, Dilated/metabolism ; DNA Primers/genetics ; Electrophoresis, Polyacrylamide Gel ; Female ; Heart Failure/*metabolism ; Humans ; Male ; Middle Aged ; Molecular Sequence Data ; Myocardium/chemistry/*metabolism ; RNA, Messenger/analysis/*metabolism ; }, abstract = {OBJECTIVES: Human heart failure is associated with prolonged relaxation and prolonged Ca2+ transients which indicates an impaired function of the sarcoplasmic reticulum (SR) and may be detrimental for cardiac function. Controversy exists whether the altered SR function is accompanied by changes in the expression of phospholamban (PLB) and cardiac SR-Ca(2+)-ATPase (SERCA2) on mRNA and/or protein levels.

METHODS: We determined mRNA and/or protein levels for PLB and SERCA2 in the same left ventricular tissue of patients undergoing heart transplantation due to idiopathic dilated cardiomyopathy (IDC) or ischemic cardiomyopathy (ICM) in comparison to left ventricular tissue from nonfailing human hearts (NF). Total protein extracts were prepared and subjected to SDS gel electrophoresis. PLB and SERCA2 were identified with specific antibodies. Total RNA was isolated and hybridized with 32P-labeled cDNAs for human PLB and rat SERCA2.

RESULTS: Hybridization revealed the three expected mRNAs with the PLB probe (3.3 kb, 1.9 kb and 0.6 kb) and a single band with the SERCA2 probe (4.5 kb). Determination of respective proteins by immunoblotting revealed unchanged protein levels for PLB and SERCA2, whereas the mRNA levels for PLB and SERCA2 were reduced by about 30% and 50%, respectively.

CONCLUSIONS: These data show the level of SERCA2 and PLB protein and mRNA in the same hearts. The reduced mRNA level of SERCA2 and PLB is in accordance with previous data. However, the unchanged protein levels may indicate that the diminished RNA expression is not accompanied by a corresponding decrease for these proteins in human heart failure. These data also show that the altered SR function in human heart failure cannot be explained by altered protein levels of PLB and SERCA2. Furthermore, it is suggested that extrapolations from cardiac mRNA levels to protein expression may be misleading.}, } @article {pmid7501973, year = {1996}, author = {Haines, GK and Cajulis, R and Hayden, R and Duda, R and Talamonti, M and Radosevich, JA}, title = {Expression of the double-stranded RNA-dependent protein kinase (p68) in human breast tissues.}, journal = {Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine}, volume = {17}, number = {1}, pages = {5-12}, doi = {10.1159/000217961}, pmid = {7501973}, issn = {1010-4283}, mesh = {Breast/*enzymology/pathology ; Breast Neoplasms/*enzymology ; DEAD-box RNA Helicases ; Female ; Gene Expression ; *Genes, Tumor Suppressor ; Humans ; Hyperplasia/enzymology ; Immunohistochemistry ; Nuclear Proteins/*genetics ; Precancerous Conditions/enzymology ; *Protein Kinases ; *RNA Helicases ; RNA, Double-Stranded/metabolism ; }, abstract = {P68 is a potent inhibitor of protein synthesis in virally infected cells and has been suggested to function in noninfected cells as a tumor suppressor gene. We have previously demonstrated that p68 expression correlates directly with cellular differentiation and inversely with proliferative activity in normal epithelium and in several human tumor systems. In order to determine the role of p68 in human breast cancer, we utilized immunohistochemistry and mapped the expression of p68 in tissue from 200 breast biopsy specimens. A total of 434 foci, ranging from normal breast tissue to infiltrating carcinoma were examined. We found that p68 was present at basal levels in normal lobular and luminal ductal epithelial cells, with higher levels present in myoepithelial cells. Nonproliferative fibrocystic lesions showed variable expression of p68, with high levels seen within foci of apocrine metaplasia and low levels in cystically dilated terminal duct units. Low levels of p68 were seen in typical ductal proliferations, lobular neoplasia (atypical lobular hyperplasia and lobular carcinoma in situ), and in fibroadenomas. Foci of atypical ductal hyperplasia in situ and invasive ductal carcinoma generally showed higher levels of p68 expression. Among the infiltrating carcinomas, p68 expression correlated with nuclear grade. This suggests that the ability of p68 to inhibit cellular proliferation may be impaired in breast cancer and that its expression, although modestly paralleling cellular differentiation, is not a predictive indicator of improved survival.}, } @article {pmid8682101, year = {1995}, author = {Mestroni, L and Krajinovic, M and Severini, GM and Milasin, J and Pinamonti, B and Rocco, C and Vatta, M and Falaschi, A and Giacca, M and Camerini, F}, title = {Molecular genetics of dilated cardiomyopathies.}, journal = {European heart journal}, volume = {16 Suppl O}, number = {}, pages = {5-9}, doi = {10.1093/eurheartj/16.suppl_o.5}, pmid = {8682101}, issn = {0195-668X}, mesh = {Cardiomyopathy, Dilated/diagnosis/*genetics ; Chromosome Aberrations/genetics ; Chromosome Disorders ; Chromosomes, Human, Pair 14 ; DNA, Mitochondrial/genetics ; Dystrophin/genetics ; Female ; Genes, Dominant/genetics ; Genes, Recessive/genetics ; Genetic Linkage/genetics ; Humans ; Hypertrophy, Right Ventricular/diagnosis/genetics ; Male ; Molecular Biology ; Myosin Heavy Chains/genetics ; Pedigree ; Prospective Studies ; Sex Chromosome Aberrations/genetics ; X Chromosome ; }, abstract = {The application of molecular genetics in cardiology is currently producing important results in the study of the pathogenetic mechanisms underlying cardiomyopathies. Recent clinical surveys have indicated that genetic factors play a major pathogenetic role in idiopathic dilated cardiomyopathy (IDC). Familial IDC is frequent (20-30%) and is probably a heterogeneous entity, as suggested by the clinical variability and the different pattern of inheritance in the affected families. Molecular genetic studies have demonstrated the existence of heterogeneity also at the genetic level. In a series of families with X-linked IDC, the disease gene has been identified as the dystrophin gene. In familial right ventricular cardiomyopathy (or right ventricular dysplasia), a new nosological entity characterized by isolated right ventricular involvement that can mimic IDC, the disease gene has been localized in the long arm of chromosome 14. In families with matrilineal transmission, the cardiomyopathy could be linked to mitochondrial DNA alterations. Autosomal dominant familial IDC, considered to be the most frequent form, is currently under active investigation. Our preliminary data have excluded a large series of candidate genes, among which are the cardiac beta-myosin heavy chain and several other genes encoding for cardiac contractile proteins, genes of the HLA region, and about 60 genes involved in the immune regulation.}, } @article {pmid7611175, year = {1995}, author = {Cook, DL and Weaver, DL}, title = {Comparison of DNA content, S-phase fraction, and survival between medullary and ductal carcinoma of the breast.}, journal = {American journal of clinical pathology}, volume = {104}, number = {1}, pages = {17-22}, doi = {10.1093/ajcp/104.1.17}, pmid = {7611175}, issn = {0002-9173}, mesh = {Adult ; Aged ; Aneuploidy ; *Breast Neoplasms/genetics/mortality/pathology ; *Carcinoma, Ductal, Breast/genetics/mortality/pathology ; *Carcinoma, Medullary/genetics/mortality/pathology ; DNA, Neoplasm/*analysis/genetics ; Flow Cytometry ; Humans ; Middle Aged ; Mitotic Index ; Prognosis ; S Phase ; Survival Rate ; }, abstract = {Medullary carcinoma (MC) of the breast has been regarded as a subtype of breast carcinoma with a relatively favorable prognosis despite its high nuclear grade and high mitotic index. High nuclear grade and high mitotic index have been correlated with DNA aneuploidy and high S-phase fraction (SPF) by flow cytometry. Generally in breast cancer, these histologic and DNA content features predict a less favorable prognosis. To address this paradox, all cases of MC of the breast (20 of 1,365 carcinomas [1.5%]) diagnosed between 1968 and 1982 were compared to age- and stage-matched cases of infiltrating ductal carcinoma (IDC) diagnosed during the same time period. All of the MC and 80% of the IDC had one or more DNA aneuploid stem lines. Average total SPF was 8.1% for MC and 4.8% for IDC. DNA analysis was performed from paraffin blocks (average CV: 4.5% DNA diploid; 4.1% DNA aneuploid), and subjected to computer modeled analysis. Statistically significant differences between presence or absence of DNA aneuploidy (P = .035) and total SPF (P = .029) were demonstrated between the two groups. Thirteen of 20 patients (65%) with MC (average followup 130 months) were alive at the end of the study period compared to 12 of 20 patients (60%) with IDC (average follow-up 160 months). The difference in crude survival was not statistically significant (P = .867). However, there was a tendency toward early death in MC and late death in IDC. Within the TNM stage-matched patients, no significant difference was demonstrated for tumor size or nodal status when these variables were examined separately. In conclusion, statistically significant differences in DNA content and proliferative fraction exist between medullary carcinoma of the breast and ductal carcinoma. The biologic and clinical differences demonstrated in this analysis warrant careful consideration before including cases of medullary carcinoma in studies evaluating newer prognostic variables in breast cancer.}, } @article {pmid7560165, year = {1995}, author = {Lakhani, SR and Collins, N and Stratton, MR and Sloane, JP}, title = {Atypical ductal hyperplasia of the breast: clonal proliferation with loss of heterozygosity on chromosomes 16q and 17p.}, journal = {Journal of clinical pathology}, volume = {48}, number = {7}, pages = {611-615}, pmid = {7560165}, issn = {0021-9746}, mesh = {Aged ; Aged, 80 and over ; Breast/*pathology ; Breast Neoplasms/*genetics ; Carcinoma in Situ/genetics ; Carcinoma, Ductal, Breast/genetics ; Cell Division ; *Chromosome Deletion ; Chromosomes, Human, Pair 16/*genetics ; Chromosomes, Human, Pair 17/*genetics ; Clone Cells/pathology ; Female ; Humans ; Hyperplasia/genetics ; Middle Aged ; Polymerase Chain Reaction ; }, abstract = {AIMS: To determine if allelic loss on chromosomes 16q and 17p, commonly encountered in in situ and invasive ductal carcinomas, is present in atypical ductal hyperplasia (ADH); to determine whether ADH is a neoplastic (clonal) or hyperplastic (polyclonal) proliferation.

METHODS: Fourteen cases of ADH were examined for allele loss at loci on chromosome 16q and 17p using a microdissection technique, polymorphic DNA markers and the polymerase chain reaction (PCR).

RESULTS: Loss of heterozygosity (LOH) was detected in five of nine informative cases on chromosome 16q at the microsatellite D16S413 and two of eight informative cases on chromosome 17p at D17S796.

CONCLUSIONS: The incidence of LOH at these loci is similar to that previously observed in ductal carcinoma in situ and in invasive ductal carcinoma. Because of the nature of the technique used, our findings also demonstrate that ADH is a monoclonal, and hence, neoplastic proliferation rather than a hyperplastic (polyclonal) condition as its name suggests. There is thus a case for including ADH, as presently defined, within the spectrum of ductal carcinoma in situ.}, } @article {pmid7543649, year = {1995}, author = {Barrón, S and Tusell, JM and Serratosa, J}, title = {Effect of hexachlorocyclohexane isomers on calmodulin mRNA expression in the central nervous system.}, journal = {Brain research. Molecular brain research}, volume = {30}, number = {2}, pages = {279-286}, doi = {10.1016/0169-328x(95)00015-k}, pmid = {7543649}, issn = {0169-328X}, mesh = {Animals ; Blotting, Northern ; Calmodulin/*biosynthesis/genetics ; Central Nervous System/drug effects/*metabolism ; Gene Expression ; Hexachlorocyclohexane/*pharmacology ; In Situ Hybridization ; Male ; RNA, Messenger/metabolism ; Rats ; Rats, Wistar ; Time Factors ; }, abstract = {Three different calmodulin genes that encode the same protein have been found in the brain of all mammalian species so far examined. Little is known about the factors involved in regulating the expression of this gene family in the central nervous system. We have investigated the possibility of differential expression of two calmodulin genes, CaM I and CaM II, which are expressed strongly in neuronal cells in the adult rat brain, after treatment with the gamma (lindane) and the delta isomers of the hexachlorocyclohexane (HCH). In this study a decrease of CaM I mRNA (mainly in the 4.0 kb transcript) was found in the cortex of the rats after 24 h of isomer administration. CaM I expression seemed to be more sensitive to delta isomer action, whereas the gamma isomer acted mainly at CaM II level. The levels of mRNA of calmodulin CaM II gene were also found to decrease after lindane administration; delta-HCH produced an increase of this transcript. These results were obtained by Northern blot analysis and confirmed by means of in situ hybridization. Our results suggest that levels of neuronal calmodulin mRNA species are modified in response to changes in neuronal activity.}, } @article {pmid7878527, year = {1995}, author = {Gaffney, EV and Halpin, DP and Blakemore, WS}, title = {Relationship between low estrogen receptor values and other prognostic factors in primary breast tumors.}, journal = {Surgery}, volume = {117}, number = {3}, pages = {241-246}, doi = {10.1016/s0039-6060(05)80196-5}, pmid = {7878527}, issn = {0039-6060}, mesh = {Adult ; Aneuploidy ; Breast Neoplasms/*chemistry/genetics/pathology ; Carcinoma, Ductal, Breast/*chemistry/genetics/pathology ; DNA, Neoplasm/genetics ; Diploidy ; Female ; Humans ; Immunohistochemistry ; Prognosis ; Radioligand Assay ; Receptors, Estrogen/*analysis ; Receptors, Progesterone/*analysis ; S Phase ; }, abstract = {BACKGROUND: The current study compared the immunocytochemical expression of estrogen (ER) and progesterone (PgR) receptors by malignant breast cells to the hormone receptor concentrations reported from radioligand assays. These values were examined in relation to DNA ploidy and the fraction of cells in S phase.

METHODS: ER and PgR concentrations, DNA ploidy, and S-phase fractions were measured by standard techniques with 124 samples of invasive ductal carcinoma. Suspensions of tumor cells were examined by immunocytochemical assay (ICA) for the percentages of ER and PgR positive cells.

RESULTS: Twenty-six of the 38 tumors from patients 50 years of age or younger were classified as high S-phase fraction, and 28 tumors had aneuploid levels of DNA. The 20 ER positive tumors each contained less than 100 fmol/mg. Thirty-nine of the 86 tumors from patients older than 50 years were classified as high S phase, and 41 were aneuploid. Sixty-five samples were considered ER positive by radioligand assay. ICA showed that tumors in either age group with less than 40 fmol/mg did not contain ER positive cells. The proportion of samples with PgR levels between 10 and 100 fmol/mg was small, and fewer PgR positive tumors were categorized as negative when examined by ICA for receptor containing cells. The reclassification of the hormone receptor status of a tumor based on ICA appeared to be independent of S-phase and ploidy values.

CONCLUSIONS: Tumors that are classified as ER or PgR positive based on accepted cutoff values for radioligand assays may actually be receptor negative because the tumors do not appear to contain receptor positive cells.}, } @article {pmid7665243, year = {1995}, author = {Murphy, DS and McHardy, P and Coutts, J and Mallon, EA and George, WD and Kaye, SB and Brown, R and Keith, WN}, title = {Interphase cytogenetic analysis of erbB2 and topoII alpha co-amplification in invasive breast cancer and polysomy of chromosome 17 in ductal carcinoma in situ.}, journal = {International journal of cancer}, volume = {64}, number = {1}, pages = {18-26}, doi = {10.1002/ijc.2910640106}, pmid = {7665243}, issn = {0020-7136}, mesh = {Aneuploidy ; Breast Neoplasms/*genetics ; Carcinoma in Situ/*genetics ; Carcinoma, Ductal, Breast/*genetics ; Chromosome Aberrations/*genetics ; Chromosome Disorders ; *Chromosomes, Human, Pair 17 ; DNA Topoisomerases, Type II/*genetics ; Gene Amplification ; *Genes, erbB-2 ; Humans ; In Situ Hybridization, Fluorescence ; Receptor, ErbB-2/*genetics ; }, abstract = {Breast cancer is a genetically complex disease. Fluorescence in situ hybridisation can be used to analyse the genetics of breast-cancer progression in interphase cytogenetics. We have analysed the histological distribution of erbB2 and topoll alpha co-amplification in paraffin sections of invasive breast cancer and show that the co-amplified loci share the same histological distribution in the tumour and have a similar nuclear distribution within individual nuclei. Regions of the tumours without amplification are easily recognized and tumours with erbB2 and topoll alpha co-amplification can be distinguished from those with erbB2 amplification alone. In addition, FISH was used to show polysomy of chromosome 17 in non-invasive ductal carcinoma in situ of the breast and erbB2 amplification in both the invasive and non-invasive components of a breast cancer biopsy. This report of an interphase cytogenetic analysis of non-invasive breast carcinoma in situ demonstrates the usefulness of FISH for the genetic study of breast cancer progression.}, } @article {pmid7895264, year = {1995}, author = {Maeda, K and Kosco-Vilbois, MH and Burton, GF and Szakal, AK and Tew, JG}, title = {Expression of the intercellular adhesion molecule-1 on high endothelial venules and on non-lymphoid antigen handling cells: interdigitating cells, antigen transporting cells and follicular dendritic cells.}, journal = {Cell and tissue research}, volume = {279}, number = {1}, pages = {47-54}, pmid = {7895264}, issn = {0302-766X}, support = {AI-17412/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; Antibodies, Monoclonal/immunology ; Antigen-Presenting Cells/*metabolism ; Dendritic Cells/*metabolism ; Endothelium, Vascular/cytology/*metabolism ; Female ; Immunoenzyme Techniques ; Intercellular Adhesion Molecule-1/*biosynthesis/genetics ; Lymph Nodes/cytology ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C3H ; Microscopy, Immunoelectron ; }, abstract = {Intercellular adhesion molecule-1 (ICAM-1) has been implicated in the development of germinal center reactions in vitro, and the present study was undertaken to determine the distribution of ICAM-1 in active germinal centers in vivo and in murine secondary lymphoid tissues in general. Anti-ICAM-1-specific monoclonal antibodies were used in conjunction with immunohistochemistry at both the light and ultrastructural levels of resolution. Examination of cryostat sections of lymph nodes, spleens, and Peyer's patches revealed that anti-ICAM-1 distinctly labeled cells in the light zones of germinal centers, a few cells in the T cell zones (e.g. paracortex of lymph nodes), cells in the sinus floor of the subcapsular sinuses of lymph nodes, and high endothelial venules (HEV). Ultrastructural studies revealed that the cells labeling with anti-ICAM-1 in germinal centers were follicular dendritic cells (FDC) which appeared to have more ICAM-1 than any other cell type. The surfaces of well-developed, intricate, convoluted FDC processes were intensely labeled even under conditions where B cells appeared negative. Interdigitating cells (IDC) were also labeled as were certain endothelial cells in the HEV. The cells in the subcapsular sinus floor labeling with anti-ICAM-1 were the "antigen transporting cells" (ATC) that carry antigen-antibody complexes into lymph node follicles. We suspect ATC are FDC precursors which mature into FDC in the follicles. Interestingly, FDC, IDC, and ATC are 3 important accessory cells known to handle antigens in specific compartments of lymphoid tissues.(ABSTRACT TRUNCATED AT 250 WORDS)}, } @article {pmid7530588, year = {1995}, author = {Storm, FK and Gilchrist, KW and Warner, TF and Mahvi, DM}, title = {Distribution of Hsp-27 and HER-2/neu in in situ and invasive ductal breast carcinomas.}, journal = {Annals of surgical oncology}, volume = {2}, number = {1}, pages = {43-48}, pmid = {7530588}, issn = {1068-9265}, mesh = {Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/genetics/*metabolism ; Breast Neoplasms/genetics/*metabolism ; Carcinoma in Situ/genetics/*metabolism ; Carcinoma, Ductal, Breast/genetics/*metabolism ; Female ; Gene Expression Regulation, Neoplastic ; Heat-Shock Proteins/genetics/*metabolism ; Humans ; Immunohistochemistry ; Middle Aged ; Neoplasm Invasiveness ; Prognosis ; Receptor, ErbB-2/genetics/*metabolism ; Staining and Labeling ; }, abstract = {BACKGROUND: The overexpression of heat shock protein 27 (hsp-27) in early-stage breast cancer is associated with histopathologic features of poor prognosis and clinically with an increased probability of disease recurrence. Hsp-27 is overexpressed in 25% of invasive ductal carcinomas (IDC); however, its distribution in ductal carcinoma in situ (DCIS) and DCIS associated with IDC has not been investigated. We postulated that hsp-27 might be detected and variably expressed in DCIS and, like HER-2/neu oncoprotein expression, might be a tumor-specific marker worthy of future clinical investigation.

METHODS: To test these hypotheses, the distribution of hsp-27 in noncomedo and comedo DCIS, and DCIS associated with IDC, was evaluated by immunohistochemistry and compared with HER-2/neu expression within the same cancers.

RESULTS: Hsp-27 was overexpressed in 28 of 47 (approximately 60%) cases of DCIS; expression in pure DCIS was 16 of 24 (67%), and 12 of 23 (approximately 50%) in DCIS associated with IDC. Hsp-27 expression by in situ and invasive components of the same neoplasm were concordant in 22 of 23 (approximately 95%) cases tested. Comedo variants appeared to have somewhat higher hsp-27 expression than noncomedo DCIS, whether or not there was an associated IDC. These results are reminiscent of HER-2/neu oncoprotein expression in DCIS and DCIS associated with IDC observed by others. However, although 4 of 22 (18%) cancers containing DCIS + IDC expressed HER-2/neu, no relationship with hsp-27 expression in the same cancers was observed.

CONCLUSIONS: We found a high incidence of hsp-27 overexpression in DCIS and in DCIS associated with IDC. This rate is twice that previously observed in IDC alone. Hsp-27 expression is independent of HER-2/neu expression.}, } @article {pmid7927891, year = {1994}, author = {Kaczmarek, J and Castellani, P and Nicolo, G and Spina, B and Allemanni, G and Zardi, L}, title = {Distribution of oncofetal fibronectin isoforms in normal, hyperplastic and neoplastic human breast tissues.}, journal = {International journal of cancer}, volume = {59}, number = {1}, pages = {11-16}, doi = {10.1002/ijc.2910590104}, pmid = {7927891}, issn = {0020-7136}, mesh = {Adenocarcinoma, Mucinous/chemistry ; Antibodies, Monoclonal ; Breast/*chemistry/pathology ; Breast Neoplasms/*chemistry ; Carcinoma, Ductal, Breast/chemistry ; Carcinoma, Lobular/chemistry ; Female ; Fibroadenoma/chemistry ; Fibrocystic Breast Disease/metabolism ; Fibronectins/*analysis/genetics ; Glycosylation ; Humans ; Hyperplasia ; Immunohistochemistry ; RNA Splicing ; Tissue Distribution ; }, abstract = {Two different oncofetal fibronectins (FN) have been reported: one, generated by O-glycosylation in the splicing region IIICS that is recognized by monoclonal antibody (MAb) FDC-6, and another, recognized by MAb BC-I, generated by the alternative splicing of the FN pre-mRNA which includes an extra type-III repeat called ED-B. Using these and 2 other MAbs (IST-4 which recognizes all different FN isoforms and IST-6 which recognizes only the FN molecules that do not include the ED-B sequence) we have immunohistochemically studied 171 normal, hyperplastic and neoplastic breast-tissue specimens. Although all normal specimens reacted strongly with MAbs IST-4 and IST-6, they did not show the presence of oncofetal FNs as established by the use of BC-I and FDC-6. In contrast, out of the 97 cases of invasive ductal carcinomas studied, 90 (93%) and 96 (99%) reacted positively with BC-I and FDC-6, respectively, the reaction being observed in the tumoral stroma connective tissue and in tumoral vessels. Furthermore, invasive lobular carcinoma showed less intense and less frequent staining with BC-1 and FDC-6 (10 and 11 out of 14, respectively). We found differences in the distribution of the 2 oncofetal fibronectin isoforms within the same specimens. The most remarkable difference was observed in the tumoral vessels: in invasive ductal carcinoma MAb BC-1 revealed a positive reaction with vessels in 78% of cases while FDC-6 showed such a reaction in only 59% of cases.}, } @article {pmid8082076, year = {1994}, author = {Mourad, WA and Setrakian, S and Hales, ML and Abdulla, M and Trucco, G}, title = {The argyrophilic nucleolar organizer regions in ductal carcinoma in situ of the breast. The significance of ploidy and proliferative activity analysis using this silver staining technique.}, journal = {Cancer}, volume = {74}, number = {6}, pages = {1739-1745}, doi = {10.1002/1097-0142(19940915)74:6<1739::aid-cncr2820740616>3.0.co;2-t}, pmid = {8082076}, issn = {0008-543X}, mesh = {Breast Neoplasms/*genetics/ultrastructure ; Carcinoma in Situ/*genetics/ultrastructure ; Carcinoma, Ductal, Breast/*genetics/ultrastructure ; Female ; Humans ; Nucleolus Organizer Region/*pathology ; Ploidies ; }, abstract = {BACKGROUND: Two interphase argyrophilic nucleolar organizer region (AgNOR) counts have been correlated with ploidy and proliferative activity in patients with ductal carcinoma in situ (DCIS) of the breast. The first is the mean number of AgNORs (mAgNOR); it reflects ploidy. The second is the percentage of nuclei with greater than or equal to five AgNORs/nucleus (pAgNOR); it correlates with proliferative activity. DCIS of the breast is a heterogeneous group of lesions that is not associated uniformly with invasive ductal carcinoma. A significant number of patients with DCIS will, however, progress to invasive ductal carcinoma. Factors identifying the invasive potential of DCIS in these patients have not been defined clearly. The authors postulated that pAgNOR in DCIS may predict the invasive potential of these lesions.

METHODS: The authors studied 86 cases of DCIS of the breast by the AgNOR silver stain using the two above-mentioned counts.

RESULTS: There were 54 comedo and 32 noncomedo DCIS cases. Forty-one cases (47%) were associated with invasive ductal carcinoma. Thirty cases of comedo DCIS (55%) showed mAgNOR counts suggestive of aneuploidy (> or = 2.4/nucleus), whereas only seven cases of noncomedo DCIS (22%) showed such counts (P = 0.001). Cases associated with invasion had higher incidence of aneuploid mAgNOR counts (P = 0.0003). The pAgNOR counts in comedo DCIS ranged from 1% to 36% (median, 11%), whereas in noncomedo DCIS pAgNOR counts ranged from 0% to 22% (median, 7%) (P = 0.007). The 41 cases associated with invasion had pAgNOR counts ranging from 3% to 36% (median, 12%), whereas those not associated with invasion had pAgNOR counts ranging from 0% to 24% (median, 5%) (P = 0.000001). This difference was irrespective of the type of DCIS or mAgNOR counts.

CONCLUSIONS: Comedo DCIS of the breast may show a higher incidence of aneuploidy and increased proliferative activity and invasive ductal carcinoma than does noncomedo DCIS. Ploidy and proliferative activity, measured by AgNOR staining in DCIS, may have a significant predictive value in identifying the invasive potential of these lesions.}, } @article {pmid8180021, year = {1994}, author = {Qi, CF and Liscia, DS and Normanno, N and Merlo, G and Johnson, GR and Gullick, WJ and Ciardiello, F and Saeki, T and Brandt, R and Kim, N}, title = {Expression of transforming growth factor alpha, amphiregulin and cripto-1 in human breast carcinomas.}, journal = {British journal of cancer}, volume = {69}, number = {5}, pages = {903-910}, pmid = {8180021}, issn = {0007-0920}, mesh = {Amphiregulin ; Biomarkers, Tumor/*analysis ; Breast Neoplasms/*chemistry ; EGF Family of Proteins ; *Epidermal Growth Factor ; Female ; GPI-Linked Proteins ; Genes, p53/genetics ; Glycoproteins/*analysis ; Growth Substances/*analysis ; Humans ; *Intercellular Signaling Peptides and Proteins ; *Membrane Glycoproteins ; Neoplasm Proteins/*analysis ; Point Mutation/genetics ; RNA, Messenger/analysis ; RNA, Neoplasm/analysis ; Transforming Growth Factor alpha/*analysis ; }, abstract = {The expression of three epidermal growth factor (EGF)-related peptides, transforming growth factor alpha (TGF-alpha), amphiregulin (AR) and cripto-1 (CR-1), was examined by immunocytochemistry (ICC) in 68 primary infiltrating ductal (IDCs) and infiltrating lobular breast carcinomas (ILCs), and in 23 adjacent non-involved human mammary tissue samples. Within the 68 IDC and ILC specimens, 54 (79%) expressed immunoreactive TGF-alpha, 52 (77%) expressed AR and 56 (82%) expressed CR-1. Cytoplasmic staining was observed with all of the antibodies, and this staining could be eliminated by preabsorption of the antibodies with the appropriate peptide immunogen. Cytoplasmic staining with all of the antibodies was confined to the carcinoma cells, since no specific immunoreactivity could be detected in the surrounding stromal or endothelial cells. In addition to cytoplasmic reactivity, the AR antibody also exhibited nuclear staining in a number of the carcinoma specimens. No significant correlations were found between the percentage of carcinoma cells that were positive for TGF-alpha, AR or CR-1 and oestrogen receptor status, axillary lymph node involvement, histological grade, tumour size, proliferative index, loss of heterozygosity on chromosome 17p or overall patient survival. However, a highly significant inverse correlation was observed between the average percentage of carcinoma cells that expressed AR in individual tumours and the presence of a point-mutated p53 gene. Likewise, a significantly higher percentage of tumour cells in the ILC group expressed AR as compared with the average percentage of tumour cells that expressed AR in the IDC group. Of the 23 adjacent, non-involved breast tissue samples, CR-1 could be detected by ICC in only three (13%), while TGF-alpha was found in six (26%) and AR in ten (43%) of the non-involved breast tissues. These data demonstrate that breast carcinomas express multiple EGF-related peptides and show that the differential expression of CR-1 in malignant breast epithelial cells may serve as a potential tumour marker for breast cancer.}, } @article {pmid8176940, year = {1994}, author = {Sasa, M and Kondo, K and Komaki, K and Morimoto, T and Monden, Y}, title = {p53 alteration correlates with negative ER, negative PgR, and high histologic grade in breast cancer.}, journal = {Journal of surgical oncology}, volume = {56}, number = {1}, pages = {46-50}, doi = {10.1002/jso.2930560110}, pmid = {8176940}, issn = {0022-4790}, mesh = {Adult ; Aged ; Base Sequence ; Breast Neoplasms/*genetics/metabolism/*pathology ; Female ; Genes, p53/*genetics ; Humans ; Middle Aged ; Molecular Sequence Data ; Mutation ; Polymerase Chain Reaction/methods ; Polymorphism, Genetic ; Receptors, Estrogen/*analysis ; Receptors, Progesterone/*analysis ; }, abstract = {Seventy tumors of invasive ductal carcinoma of the breast were examined for p53 alteration by the RT-PCR-SSCP method. Sixty-five samples (92.9%) were investigated in the regions of codons 101-200 and 201-300. In total, 16 samples (24.6%) showed p53 gene alteration. We found that p53 gene alteration showed a correlation with (1) a negative ER status, (2) a negative PgR status, and (3) a high histologic grade (especially numerous mitotic figures) of the tumor. However, we found no correlation between p53 gene alteration and the lymph node status or clinical stage. Thus, p53 gene alteration in breast cancer may occur in highly malignant breast cancer other than advanced clinical stage cancer or node-positive cancer.}, } @article {pmid7908995, year = {1994}, author = {Horiguchi, J and Iino, Y and Takei, H and Morishita, Y and Nakajima, T}, title = {Expression of proliferating cell nuclear antigen in invasive ductal carcinoma of the breast.}, journal = {Japanese journal of clinical oncology}, volume = {24}, number = {2}, pages = {79-84}, pmid = {7908995}, issn = {0368-2811}, mesh = {Adenocarcinoma/genetics/pathology/secondary ; Adenocarcinoma, Scirrhous/genetics/pathology/secondary ; Adult ; Age Factors ; Antigens, Neoplasm/*analysis/genetics ; Breast Neoplasms/*genetics/pathology ; Carcinoma, Ductal, Breast/*genetics/pathology/secondary ; Carcinoma, Papillary/genetics/pathology/secondary ; Cell Nucleus/ultrastructure ; Female ; *Gene Expression Regulation, Neoplastic ; Humans ; Immunoenzyme Techniques ; Lymphatic Metastasis ; Middle Aged ; Nuclear Proteins/*analysis/genetics ; Prognosis ; Proliferating Cell Nuclear Antigen ; Receptors, Estrogen/analysis ; Survival Rate ; }, abstract = {Formalin-fixed, paraffin-embedded sections from 92 breast cancers (invasive ductal carcinomas) were immunostained with a monoclonal antibody against proliferating cell nuclear antigen (PCNA). The labeling index of PCNA ranged widely from 2 to 76 (mean 24.8)%. The labeling index was classified into three groups: low (< 25%), intermediate (25-50%), high proliferation (> 50%). Younger patients seemed to have a higher labeling index than older ones. The labeling index for tumors < or = 2 cm was lower than that of tumors larger than 2 cm. The labeling index in patients with high estrogen receptor (ER) levels (> 100 fmol/mg cytosol protein) was significantly lower than that in patients with low ER levels (< 10 fmol/mg cytosol protein). In relation to histological type, the labeling index of scirrhous carcinoma was significantly lower than that of papillotubular carcinoma or solid-tubular carcinoma. The high proliferating group had a significantly worse overall survival rate than the low proliferating group. Labeling index was shown to be a possible prognostic indicator.}, } @article {pmid7913368, year = {1994}, author = {Umekita, Y and Takasaki, T and Yoshida, H}, title = {Expression of p53 protein in benign epithelial hyperplasia, atypical ductal hyperplasia, non-invasive and invasive mammary carcinoma: an immunohistochemical study.}, journal = {Virchows Archiv : an international journal of pathology}, volume = {424}, number = {5}, pages = {491-494}, pmid = {7913368}, issn = {0945-6317}, mesh = {Breast/*pathology ; Breast Neoplasms/chemistry/*genetics/pathology ; Carcinoma, Ductal, Breast/chemistry/*genetics/pathology ; ErbB Receptors/analysis/genetics ; Female ; *Gene Expression ; Humans ; Hyperplasia ; Immunohistochemistry ; Proto-Oncogene Proteins/analysis/genetics ; Receptor, ErbB-2 ; Tumor Suppressor Protein p53/analysis/*genetics ; }, abstract = {To clarify whether p53 protein expression is involved in multistep carcinogenesis or the progression of mammary ductal carcinoma, we investigated p53 protein expression in 83 invasive ductal carcinomas (IDC), 10 IDC with a predominant intraductal component, 13 non-invasive ductal carcinoma (NIDC), 16 atypical ductal hyperplasia (ADH) and 39 benign epithelial hyperplasia (EH), using immunohistochemistry. Expression of p53 protein was detected in 24 (28.9%) cases of IDC, 5 (50%) cases of IDC with a predominant intraductal component and 1 (7.6%) case of NIDC. No expression was observed in either ADH or EH. In IDC, including cases with a predominant intraductal component, p53 protein expression was associated with a higher histological grade (P < 0.0001) or mitotic index (P < 0.0005). Although overexpression of c-erbB-2 protein has also shown a similar association with these prognostic indicators, expression of p53 protein correlated regardless of the status of c-erbB-2 overexpression. Completely coordinated expression of p53 protein was seen in both intraductal and invasive components. The intraductal component in IDC including cases with a predominant intraductal component which expresses p53 protein had significantly higher histological grade (P < 0.0005) or more comedo-subtypes (P < 0.0001). These results suggested that p53 protein expression occurs at a stage of NIDC with high histological grade or in comedo-subtypes. Its expression is maintained throughout invasion.}, } @article {pmid7904475, year = {1994}, author = {Bellamy, CO and Harrison, DJ}, title = {Evaluation of glutathione S-transferase Pi in non-invasive ductal carcinoma of breast.}, journal = {British journal of cancer}, volume = {69}, number = {1}, pages = {183-185}, pmid = {7904475}, issn = {0007-0920}, mesh = {Adult ; Aged ; Breast Neoplasms/*enzymology/pathology ; Carcinoma in Situ/*enzymology/pathology/secondary ; Carcinoma, Ductal, Breast/*enzymology/pathology/secondary ; ErbB Receptors/analysis/genetics ; Evaluation Studies as Topic ; Female ; Follow-Up Studies ; Gene Expression/genetics ; Glutathione Transferase/*analysis ; Humans ; Immunohistochemistry ; Isoenzymes/*analysis ; Middle Aged ; Proto-Oncogene Proteins/analysis/genetics ; Receptor, ErbB-2 ; }, abstract = {Glutathione S-transferase Pi (GST P) has been reported to be a marker of dysplastic lesions. For this reason expression of GST P by intraduct breast carcinoma was evaluated by immunohistochemistry. Thirty-seven of 92 carcinomas (40%) were GST P positive. GST P staining did not correlate with histological variables, c-erbB-2 overexpression or with clinical outcome. The GST P status of recurrences did not correlate with that of the index lesion. There is little evidence that GST P is a useful marker of the potential of intraduct breast carcinoma to become invasive.}, } @article {pmid8302815, year = {1993}, author = {Gaffey, MJ and Frierson, HF and Mills, SE and Boyd, JC and Zarbo, RJ and Simpson, JF and Gross, LK and Weiss, LM}, title = {Medullary carcinoma of the breast. Identification of lymphocyte subpopulations and their significance.}, journal = {Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc}, volume = {6}, number = {6}, pages = {721-728}, pmid = {8302815}, issn = {0893-3952}, mesh = {Adult ; Breast Neoplasms/microbiology/*pathology ; Carcinoma, Ductal, Breast/microbiology/pathology ; Carcinoma, Medullary/microbiology/*pathology ; DNA, Viral/analysis ; Female ; Herpesvirus 4, Human/genetics ; Humans ; Immunohistochemistry ; Lymphocyte Subsets/*pathology ; Middle Aged ; Polymerase Chain Reaction ; }, abstract = {Fifty-two infiltrating breast carcinomas with medullary features (BCMF) were studied immunohistochemically to determine the immunophenotype of the mononuclear tumor inflammatory cells (MTIC) in formalin-fixed, paraffin-embedded material. The neoplasms were also examined for Epstein-Barr virus (EBV) DNA by the polymerase chain reaction (PCR). BCMF were independently classified as medullary carcinoma (MC) or infiltrating ductal carcinoma (IDC) by six observers according to the criteria of Pedersen et al. DNA from 35 BCMF was successfully amplified using PCR, but all were negative for EBV DNA. These included, by 4/6 consensus diagnosis, 16 MC, 18 IDC, and one BCMF which failed to achieve consensus diagnosis. MTIC were present to a mild degree in 19 BCMF (37%) and to moderate to severe degrees in 33 (63%). MTIC were predominantly (> or = 75%) lymphocytic in 31 BCMF (13 MC, 16 IDC, two without consensus diagnostic agreement), and plasmacytic in 10 (six MC, four IDC); equal proportions of lymphocytes and plasma cells occurred in 11 (six MC, five IDC). Lymphocytic MTIC were mostly CD45RO+/CD3+ T-cells in nearly all cases, and showed a predominant CD3+/CD4+ and CD3+/CD4- immunophenotype in 36% and 64% of cases, respectively. Natural killer cells (CD57+) and histiocytes (MAC 387+) were virtually absent. The number, cell type, and T-cell subsets of the MTIC were unrelated to consensus diagnosis, axillary lymph node status, or overall survival. EBV is unassociated with MC, despite the histologic similarities of MC to EBV-associated lymphoepithelial lesions of other organs.(ABSTRACT TRUNCATED AT 250 WORDS)}, } @article {pmid8312582, year = {1993}, author = {Sasa, M and Kondo, K and Komaki, K and Uyama, T and Morimoto, T and Monden, Y}, title = {Frequency of spontaneous p53 mutations (CpG site) in breast cancer in Japan.}, journal = {Breast cancer research and treatment}, volume = {27}, number = {3}, pages = {247-252}, pmid = {8312582}, issn = {0167-6806}, mesh = {Adult ; Aged ; Base Sequence ; Breast Neoplasms/*genetics ; Female ; *Genes, p53 ; Humans ; Middle Aged ; Molecular Sequence Data ; *Mutation ; Polymerase Chain Reaction ; }, abstract = {Sixty-five tumors of invasive ductal carcinoma of the breast were examined for p53 alteration by the reverse transcription-polymerase chain reaction-single strand conformation polymorphism (RT-PCR-SSCP) method and sequencing analysis. In total, 16 samples (24.6%) showed p53 gene alteration. Sixteen of these alterations were evaluated by sequencing analysis, and 15 showed missense point mutations while one showed a 9-base pair deletion. In the 15 point mutations, G:C to A:T transitions constituted the majority (53%), and five tumors (33%) had a transition at the CpG site, which are mutational patterns not commonly found in breast tumors from Europe and America. On the other hand, there were no G:C to T:A transversions in our cases, which were frequently observed transversions in Europe and America. These p53 mutation patterns in breast cancer in Japan are not similar to those in Europe and America reported by Hollstein et al. and Coles et al.. These findings suggest that there are some differences between mechanisms of breast cancer in Japan and in Europe and America.}, } @article {pmid8500519, year = {1993}, author = {Faas, SJ and Rothstein, JL and Kreider, BL and Rovera, G and Knowles, BB}, title = {Phenotypically diverse mouse thymic stromal cell lines which induce proliferation and differentiation of hematopoietic cells.}, journal = {European journal of immunology}, volume = {23}, number = {6}, pages = {1201-1214}, doi = {10.1002/eji.1830230602}, pmid = {8500519}, issn = {0014-2980}, support = {CA-10815/CA/NCI NIH HHS/United States ; CA-18470/CA/NCI NIH HHS/United States ; CA-21124/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Antigens, Polyomavirus Transforming/genetics ; Cell Differentiation ; Cell Division ; Cell Line ; Cytokines/genetics ; Female ; Gene Expression ; Granulocyte-Macrophage Colony-Stimulating Factor/biosynthesis ; *Hematopoiesis ; Hematopoietic Stem Cells/*cytology ; Histocompatibility Antigens Class I/metabolism ; Histocompatibility Antigens Class II/metabolism ; Immunophenotyping ; Liver/embryology ; Male ; Mice ; Mice, Nude ; Mice, Transgenic ; RNA, Messenger/genetics ; Thymus Gland/*cytology/immunology ; }, abstract = {The heterogeneity of the thymic stroma has made careful characterization of particular thymic stromal cell types difficult. To this end, we have derived a panel of cloned thymic stromal cell lines from simian virus 40 T antigen (SV40-T antigen) transgenic mice. Based on their analysis with monoclonal antibodies that distinguish among subsets of thymic stroma cells, and on the morphology and ultrastructural features of the different clones, we suggest that our panel includes representatives of the thymic subcapsular cortex or thymic nurse cells (427.1), the deep cortex or cortical reticular cells (1308.1) and the medulla including medullary interdigitating (IDC)-like cells (6.1.1) and medullary epithelial cells (6.1.7). A fifth cell type of undesignated but apparent medullary origin (6.1.11) was also isolated. All of the cell lines constitutively express the SV40 T antigen transgene and the class I antigens of the major histocompatibility complex (MHC), and they can be induced to express MHC class II antigens upon stimulation with recombinant interferon-gamma (IFN-gamma). These cell lines elaborate a factor(s) that induces the proliferation of cells from the fetal liver and bone marrow, but not from the neonatal thymus. A factor(s) elaborated by the 1308.1 cell line also induces the proliferation of fetal thymocytes in the absence of mitogens, phorbol esters or calcium ionophore which is augmented with the addition of recombinant interleukin-2 (IL-2). Analysis by reverse transcription polymerase chain reaction with primers for some mouse cytokines reveals that each of these cell lines contain granulocyte-macrophage colony-stimulating factor (GM-CSF) transcripts and that 1308.1, 6.1.1 and 6.1.7 produce IL-6 mRNA. Cell lines 1308.1 and 6.1.1 also produce IL-7; 6.1.1 produces IL-1 beta and tumor necrosis factor (TNF)-alpha while the 427.1 cell line produces IL-5 and IFN-gamma mRNA. None of the cell lines tested express the IL-2 receptor, IL-2, IL-3, IL-4, TNF-beta or macrophage inflammatory proteins mRNA. Conditioned medium (CM) from 1308.1 and 6.1.11 induced differentiation of cells purified from the mouse fetal liver into granulocytes; 1308.1 CM also induced differentiation of the mouse hematopoietic stem cell line 32DCl3(G) suggesting that the CM contains granulocyte (G)-CSF activity. Each cell line produces GM-CSF but the greatest activity is associated with 1308.1 and 6.1.11 CM. The availability of these well-characterized, functional, cloned thymic stromal cells will allow a more detailed analysis of the role of each cell type in both myeloid and T cell development.}, } @article {pmid8419551, year = {1993}, author = {Cortés, R and Mengod, G and Celada, P and Artigas, F}, title = {p-chlorophenylalanine increases tryptophan-5-hydroxylase mRNA levels in the rat dorsal raphe: a time course study using in situ hybridization.}, journal = {Journal of neurochemistry}, volume = {60}, number = {2}, pages = {761-764}, doi = {10.1111/j.1471-4159.1993.tb03213.x}, pmid = {8419551}, issn = {0022-3042}, mesh = {Animals ; Blotting, Northern ; Fenclonine/*pharmacology ; In Situ Hybridization ; Kinetics ; Male ; Oligonucleotide Probes ; RNA, Messenger/*metabolism ; Raphe Nuclei/drug effects/*enzymology ; Rats ; Time Factors ; Tryptophan Hydroxylase/*genetics ; }, abstract = {The effects of a single dose of p-chlorophenylalanine on the mRNA encoding tryptophan-5-hydroxylase (EC 1.14.16.4) in the rat dorsal raphe nucleus were analyzed using in situ hybridization. The levels of tryptophan-5-hydroxylase mRNA were markedly increased in cell bodies located in the ventromedial part of the dorsal raphe 1-2 days after p-chlorophenylalanine (300 mg/kg, i.p.) administration. This was followed by a decrease in the amount of tryptophan-5-hydroxylase mRNA, which returned to basal values by 5 days after treatment. An almost symmetric time course was observed for the midbrain serotonin concentration. Our results on the temporal pattern of changes in tryptophan-5-hydroxylase mRNA levels in the ventromedial part of the dorsal raphe are opposite to those reported for the enzyme activity and serotonin concentration after p-chlorophenylalanine treatment. These changes may result from modifications in enzyme mRNA expression, suggesting that tryptophan-5-hydroxylase gene transcription is involved in feedback mechanisms regulating serotonin synthesis.}, } @article {pmid8381766, year = {1993}, author = {Raju, U and Zarbo, RJ and Kubus, J and Schultz, DS}, title = {The histologic spectrum of apocrine breast proliferations: a comparative study of morphology and DNA content by image analysis.}, journal = {Human pathology}, volume = {24}, number = {2}, pages = {173-181}, doi = {10.1016/0046-8177(93)90297-t}, pmid = {8381766}, issn = {0046-8177}, mesh = {Breast Neoplasms/*genetics/*pathology ; Carcinoma in Situ/genetics/pathology ; Carcinoma, Intraductal, Noninfiltrating/genetics/pathology ; DNA, Neoplasm/*analysis ; Female ; Humans ; Ploidies ; }, abstract = {Apocrine features occurring in sclerosing adenosis (apocrine adenosis), atypical ductal hyperplasia (ADH), and non-comedo ductal carcinoma in situ (DCIS) often add to diagnostic difficulty. We have evaluated the usefulness of DNA content determined by image analysis in apocrine metaplasia and hyperplasia, apocrine adenosis, ADH, DCIS, lobular carcinoma in situ, invasive ductal carcinoma, and infiltrating lobular carcinoma as a potential diagnostic aid in some of these problematic breast lesions with apocrine features. Infiltrating ductal carcinoma and DCIS were further subdivided into high- or low-grade category based on nuclear features. Microscopic fields containing 63 lesions were identified in slides from breast excisions. From each selected area 100 cells in corresponding fields in paired Feulgen-stained sections were digitized for computerized ploidy analysis with lymphocyte nuclei in the same slides serving as internal diploid controls. Aneuploidy was assessed using combined DNA index and modified Auer histogram criteria for DNA content abnormalities. There was strong association between the assessment of nuclear grade and ploidy (Fisher's exact test, P < .00001). All but one of the benign and low-grade malignant lesions (97%) were in the diploid range (six of seven apocrine metaplasia cases, three of three apocrine adenosis cases, 14 of 14 ADH cases, 10 of 10 low-grade DCIS cases, two of two lobular carcinoma in situ cases, and two of two infiltrating lobular carcinoma cases). In contrast, 24 of 25 (96%) of the high-grade malignant lesions were aneuploid (10 of 10 DCIS cases and 14 of 15 infiltrating ductal carcinoma cases). We conclude that DNA ploidy status does not offer additional diagnostic information to light microscopy in distinguishing among benign apocrine proliferations, ADH, and low-grade DCIS since these proliferations share a diploid range DNA content.}, } @article {pmid6585136, year = {1984}, author = {Anderson, JL and Carlquist, JF and Lutz, JR and DeWitt, CW and Hammond, EH}, title = {HLA A, B and DR typing in idiopathic dilated cardiomyopathy: a search for immune response factors.}, journal = {The American journal of cardiology}, volume = {53}, number = {9}, pages = {1326-1330}, doi = {10.1016/0002-9149(84)90088-2}, pmid = {6585136}, issn = {0002-9149}, mesh = {ABO Blood-Group System/immunology ; Adult ; Aged ; Cardiomyopathy, Dilated/*immunology ; Female ; HLA Antigens/*immunology ; HLA-A Antigens ; HLA-B Antigens ; HLA-DR Antigens ; Haploidy ; Heart Failure/*immunology ; Histocompatibility Antigens Class II/*immunology ; Histocompatibility Testing/*methods ; Humans ; Male ; Middle Aged ; }, abstract = {Several autoimmune diseases have been associated with increased frequencies of various histocompatibility antigen (HLA) types that may be linked to immune response genes. Idiopathic dilated cardiomyopathy (IDC) has been proposed as a disease with autoimmune features, but HLA associations have not been evaluated. We performed HLA typing in 37 consecutive patients with IDC. Patients with habitual alcoholism were excluded. Results showed that no single HLA type could account for most cases; IDC is a genetically heterogeneous disease. However, uneven distributions were noted for certain types. Haplotype frequency of B27 was 0.145 in patients vs 0.033 in 5,726 local control subjects (p less than 0.001). Other A and B frequencies (except A2) were evenly distributed. HLA DR typing also revealed differences. The DR4 locus was present in 54% (19 of 35) of patients, vs 32% (26 of 82) of blood bank control subjects (p less than 0.02). The associated relative risk of DR4 was 2.2 and the etiologic fraction 0.29. Sex, disease chronicity, functional class, ejection fraction and biopsy evidence of myocarditis did not distinguish DR4-positive from DR4-negative patients, but they were older (54 +/- 12 vs 42 +/- 14 years, p less than 0.02). Of note, 68% were positive for DR4 or B27, or both. HLA DR6Y was underrepresented; it was present in 9% (3 of 35) of patients, vs 26% (21 of 82) of control subjects (p less than 0.04). The relative risk of DR6Y was 0.27 and the preventive fraction 0.19. These associations will require independent confirmation. However, they suggest that genetically determined immune response factors associated with HLA loci may play a role in pathogenesis in certain patients with IDC.}, } @article {pmid6421928, year = {1984}, author = {Kazdin, DS and Gilman-Sachs, A and Dray, S and Horng, WJ}, title = {Induction of "latent a2" allotype in a1a1 homozygous rabbits as the major part of a bidirectional immune response to immunization with anti-a2 antibody.}, journal = {Journal of immunology (Baltimore, Md. : 1950)}, volume = {132}, number = {4}, pages = {1909-1916}, pmid = {6421928}, issn = {0022-1767}, support = {A1-07043//PHS HHS/United States ; A1-15228//PHS HHS/United States ; }, mesh = {Animals ; Antibodies, Anti-Idiotypic/*administration & dosage/biosynthesis/physiology ; Antibody Specificity ; Binding Sites, Antibody ; Binding, Competitive ; Genotype ; Homozygote ; *Immunization ; Immunoglobulin Allotypes/*biosynthesis/genetics/immunology ; Immunoglobulin G/metabolism/physiology ; Immunoglobulin Heavy Chains/biosynthesis/genetics/immunology ; Immunoglobulin Idiotypes/genetics/*immunology ; Immunoglobulin Variable Region/biosynthesis/genetics/immunology ; Rabbits ; }, abstract = {Previously, we induced Ab to a common idiotypic specificity (IdC) of rabbit anti-a2 VH Ab. We observed then that some of the putative anti-IdC Ab molecules induced by immunizing a1a1 rabbits with anti-a2 Ab did not have the expected nominal allotypic markers (a1, x32, or y33) characteristic of the genotype of the immunized rabbits. Thus, immunization of a1 a1 rabbits with a1 anti-a2 Ab induced population of molecules that reacted with anti-a2 Ab but bore an unidentified (unknown) VH region marker. The following observations indicate that these molecules bear a "latent a2" allotypic marker: (a) when the unknown VH molecules were used to immunize a1 a1 and a3 a3 rabbits, anti-a2 Ab was produced; (b) when an a2 a2 rabbit was immunized with the same preparation of unknown VH molecules, an anti-idiotypic Ab was produced; and (c) when the unknown VH molecules were used to inhibit the binding of labeled a2 IgG to anti-a2 Ab, the inhibition curve obtained was essentially the same as that obtained by using normal a2 IgG. Thus, immunization of a1 a1 rabbits with a1 anti-a2 Ab provided a bidirectional stimulus to produce both nominal "a1" anti-IdC Ab and a "latent a2" allotype. The distribution of nominal to latent allotypes induced ranged from 3% nominal/92% latent to 57% nominal/23% latent. In absolute terms, the maximum amount of "latent a2" molecules was 1.18 mg/ml of serum, which far exceeds the amount of latent allotype described by others (0.3 mg/ml of serum). The effective induction of large amounts of "latent a2" allotype may have resulted from a simultaneous stimulation of an idiotope and a paratope on the surface of the "latent a2"-producing cells.}, } @article {pmid39363164, year = {2024}, author = {Sun, Y and Pan, Z and Wang, Z and Wang, H and Wei, L and Cui, F and Zou, Q and Zhang, Z}, title = {Single-cell transcriptome analysis reveals immune microenvironment changes and insights into the transition from DCIS to IDC with associated prognostic genes.}, journal = {Journal of translational medicine}, volume = {22}, number = {1}, pages = {894}, pmid = {39363164}, issn = {1479-5876}, support = {62102064//National Natural Science Foundation of China/ ; 62261018//National Natural Science Foundation of China/ ; 62262015//National Natural Science Foundation of China/ ; ZDYF2024GXJS01//Science and Technology special fund of Hainan Province/ ; 324MS009//Hainan Provincial Natural Science Foundation of China/ ; }, mesh = {Humans ; *Single-Cell Analysis ; Female ; *Tumor Microenvironment/genetics/immunology ; *Gene Expression Profiling ; Prognosis ; *Carcinoma, Intraductal, Noninfiltrating/genetics/immunology/pathology ; *Breast Neoplasms/genetics/immunology/pathology ; *Gene Expression Regulation, Neoplastic ; *Carcinoma, Ductal, Breast/genetics/pathology/immunology ; *Disease Progression ; Transcriptome/genetics ; Single-Cell Gene Expression Analysis ; }, abstract = {BACKGROUND: Ductal carcinoma in situ (DCIS) of the breast is an early stage of breast cancer, and preventing its progression to invasive ductal carcinoma (IDC) is crucial for the early detection and treatment of breast cancer. Although single-cell transcriptome analysis technology has been widely used in breast cancer research, the biological mechanisms underlying the transition from DCIS to IDC remain poorly understood.

RESULTS: We identified eight cell types through cell annotation, finding significant differences in T cell proportions between DCIS and IDC. Using this as a basis, we performed pseudotime analysis on T cell subpopulations, revealing that differentially expressed genes primarily regulate immune cell migration and modulation. By intersecting WGCNA results of T cells highly correlated with the subtypes and the differentially expressed genes, we identified six key genes: FGFBP2, GNLY, KLRD1, TYROBP, PRF1, and NKG7. Excluding PRF1, the other five genes were significantly associated with overall survival in breast cancer, highlighting their potential as prognostic biomarkers.

CONCLUSIONS: We identified immune cells that may play a role in the progression from DCIS to IDC and uncovered five key genes that can serve as prognostic markers for breast cancer. These findings provide insights into the mechanisms underlying the transition from DCIS to IDC, offering valuable perspectives for future research. Additionally, our results contribute to a better understanding of the biological processes involved in breast cancer progression.}, } @article {pmid37792368, year = {2023}, author = {Martelli, G and Barretta, F and Vernieri, C and Folli, S and Pruneri, G and Segattini, S and Trapani, A and Carolla, C and Spatti, G and Miceli, R and Ferraris, C}, title = {Prophylactic Salpingo-Oophorectomy and Survival After BRCA1/2 Breast Cancer Resection.}, journal = {JAMA surgery}, volume = {158}, number = {12}, pages = {1275-1284}, pmid = {37792368}, issn = {2168-6262}, mesh = {Female ; Humans ; Adult ; *Breast Neoplasms/genetics/prevention & control/surgery ; Salpingo-oophorectomy ; BRCA1 Protein/genetics ; Mastectomy ; Retrospective Studies ; BRCA2 Protein/genetics ; Genes, BRCA1 ; Neoplasm Recurrence, Local/genetics ; Ovariectomy ; *Ovarian Neoplasms/genetics/prevention & control ; Mutation ; }, abstract = {IMPORTANCE: Few studies have investigated whether prophylactic salpingo-oophorectomy (PSO) for patients with previously resected breast cancer who carry pathogenic germline BRCA1 or BRCA2 variants is associated with a reduced risk of cancer-specific death.

OBJECTIVE: To assess the association of PSO and prophylactic mastectomy (PM) with prognosis after quadrantectomy or mastectomy as primary treatment for patients with BRCA1 or BRCA2 breast cancer.

This retrospective cohort study was performed in a single-institution, tertiary referral center. Consecutive patients with invasive breast cancer treated surgically between 1972 and 2019 were recruited and followed up prospectively after they were found to carry the BRCA1 or BRCA2 gene variant. The data analysis was performed between April 2022 and July 2023.

EXPOSURE: Following breast surgery, some patients underwent PSO, PM, or both, whereas others did not.

MAIN OUTCOMES AND MEASURES: The primary study end point was overall survival as measured by the Kaplan-Meier method. Secondary end points were crude cumulative incidence of breast cancer-specific mortality, ipsilateral breast tumor recurrence (IBTR), contralateral breast cancer, ovarian cancer, and ovarian cancer-specific mortality.

RESULTS: Of 480 patients included in the cohort (median age at initial surgery, 40.0 years; IQR, 34.0-46.0 years), PSO was associated with a significantly reduced risk of death (hazard ratio [HR], 0.40; 95% CI, 0.25-0.64; P < .001). This reduction was most evident for patients carrying the BRCA1 variant (HR, 0.35; 95% CI, 0.20-0.63; P = .001), those with triple-negative disease (HR, 0.21; 95% CI, 0.09-0.46; P = .002), and those with invasive ductal carcinoma (HR, 0.51; 95% CI, 0.31-0.84; P = .008). Prophylactic salpingo-oophorectomy was not associated with risk of contralateral breast cancer or IBTR. Initial or delayed PM was associated with a reduced risk of IBTR but not with overall survival or breast cancer-specific mortality.

CONCLUSIONS: The study findings suggest that PSO should be offered to all patients with BRCA1/2 breast cancer who undergo surgery with curative intent to reduce risk of death. In particular, PSO should be offered to patients with the BRCA1 variant at the time of breast surgery.}, } @article {pmid39365417, year = {2024}, author = {Taira, S and Kawagoe, M and Anzai, H and Yasukawa, M and Asakawa, S and Arai, S and Yamazaki, O and Tamura, Y and Oshima, Y and Numakura, S and Ohashi, R and Shibata, S and Fujigaki, Y}, title = {Immunoglobulin A-dominant membranoproliferative glomerulonephritis-like pattern of injury as a possible paraneoplastic nephropathy in a breast cancer patient.}, journal = {CEN case reports}, volume = {}, number = {}, pages = {}, pmid = {39365417}, issn = {2192-4449}, abstract = {A middle-aged woman was found to have proteinuria during a health check-up. About sixteen months later, she was diagnosed with stage IIA invasive ductal carcinoma of the right breast. Her proteinuria progressed to nephrotic syndrome with significant hematuria. Hormone therapy was initiated for her estrogen and progesterone receptor-positive breast cancer. A kidney biopsy performed 47 days after starting the therapy revealed an IgA-dominant membranoproliferative glomerulonephritis-like pattern of injury. Electron microscopy showed subendothelial-dominant electron-dense deposits (EDD), with small amounts of mesangial EDD and a single occurrence of subepithelial hump-like EDD, along with occasional mesangial interpositions. Similar pathology can be caused by IgA vasculitis with nephritis, IgA-dominant infection-associated glomerulonephritis, and liver disease-associated glomerulopathy, but all of these were ruled out. The deposited IgA was found to be galactose-deficient IgA1. Thus, IgA nephropathy with glomerular capillary IgA deposition was considered. She underwent a right partial mastectomy and sentinel lymph node biopsy in the right axilla 75 days after starting hormone therapy, followed by adjuvant radiation. Proteinuria and hematuria tended to decrease after the treatment, and this trend continued even after corticosteroid therapy for glomerulonephritis, which was administered 156 days after starting hormone therapy. Approximately 15 months after starting hormone therapy, her proteinuria had reduced to around 1.0 g/g of creatinine, and her hematuria was negative. IgA nephropathy with glomerular capillary IgA deposition is known to be resistant to corticosteroid therapy. The favorable clinical course of the rare glomerulopathy following breast cancer treatment suggested a diagnosis of paraneoplastic glomerulopathy secondary to breast cancer in our patient.}, } @article {pmid39341718, year = {2024}, author = {Drake, MJ and Clavica, F and Murphy, C and Fader, MJ}, title = {Innovating Indwelling Catheter Design to Counteract Urinary Tract Infection.}, journal = {European urology focus}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.euf.2024.09.015}, pmid = {39341718}, issn = {2405-4569}, abstract = {BACKGROUND AND OBJECTIVE: Bacteriuria is anticipated in long-term indwelling catheter (IDC) use, and urinary tract infections (UTIs) and related issues are common. Defence mechanisms against infection are undermined by the presence of a Foley catheter, and adjustments to design could influence UTI risk.

METHODS: We reviewed the various aspects of IDCs and ureteric stent designs to discuss potential impact on UTI risk.

KEY FINDINGS AND LIMITATIONS: Design adaptations have focussed on reducing the sump of undrained urine, potential urinary tract trauma, and bacterial adherence. Experimental and computational studies on ureteral stents found an interplay between urine flow, bacterial microcolony formation, and accumulation of encrusting particles. The most critical regions for biofilm and crystal accumulation are associated with low shear stress. The full drainage system is the functioning unit, not just the IDC in isolation. This means reliably keeping the drainage system closed and considering whether a valve is preferred to a collection bag. Other developments may include one-way valves, obstacles to "bacterial swimming", and ultrasound techniques. Preventing or clearing IDC blockage can exploit access via the lumen or retaining balloon. Progress in computational fluid dynamics, energy delivery, and soft robotics may increase future options. Clinical data on the effectiveness of IDC design features are lacking, which is partly due to reliance on proxy measures and the challenges of undertaking trials.

Design changes are legitimate lines of development, but are only indirect for UTI prevention. Modifications may be advantageous, but might potentially bring problems in other ways. Education of health care professionals can improve UTIs and should be prioritised.

PATIENT SUMMARY: Catheters used to help bladder drainage can cause urinary infections, and improvements in design might reduce the risk. Several approaches are described in this review. However, proving that these approaches work is a challenge. Training professionals in the key aspects of catheter care is important.}, } @article {pmid39328281, year = {2024}, author = {Shrestha, P and Hsieh, MC and Ferguson, T and Peters, ES and Trapido, E and Yu, Q and Chu, QD and Wu, XC}, title = {Higher 10-Year Survival with Breast-Conserving Therapy over Mastectomy for Women with Early-Stage (I-II) Breast Cancer: Analysis of the CDC Patterns of Care Data Base.}, journal = {Breast cancer : basic and clinical research}, volume = {18}, number = {}, pages = {11782234241273666}, pmid = {39328281}, issn = {1178-2234}, abstract = {BACKGROUND: Studies in the United States are scarce that assess the survival differences between breast-conserving surgery plus radiation (Breast-Conserving Therapy; BCT) and mastectomy groups using population-based data while accounting for sociodemographic and clinical factors that affect the survival of women with early-stage breast cancer (ESBC).

OBJECTIVE: To assess whether BCT provides superior long-term overall survival (OS) and breast cancer-specific survival (BCSS) compared with mastectomy in women with ESBC, while considering key factors that impact survival.

DESIGN: Cohort study.

METHODS: We analyzed data on women aged 20 years and older diagnosed with stage I-II breast cancer (BC) in 2004 who received either BCT or mastectomy. The data were collected by 5 state cancer registries through the Centers for Disease Control and Prevention-funded Patterns of Care study. Multivariable Cox proportional hazard models, accounting for sociodemographic and clinical factors, were used to calculate hazard ratios (HRs) with 95% confidence intervals (CI). Sensitivity analysis involved optimal caliper propensity score (PS) matching to address residual confounding.

RESULTS: Of the 3495 women, 41.5% underwent mastectomy. The 10-year OS and BCSS were 82.7% and 91.1% for BCT and 72.3% and 85.7% for mastectomy, respectively. Adjusted models showed that mastectomy recipients had a 22% higher risk of all-cause deaths (ACD) (HR = 1.22, 95% CI = [1.06, 1.41]) and a 26% higher risk of breast cancer-specific deaths (BCD) (HR = 1.26, 95% CI = [1.02, 1.55]) than BCT recipients. Sensitivity analysis demonstrated that mastectomy was associated with a higher risk of ACD (P < .05) but did not exhibit a statistically significant risk for BCD. Women with HR+/HER2+ (luminal B) or invasive ductal carcinoma BC who underwent mastectomy had higher risks of ACD and BCD compared with BCT recipients, while the hazards for ACD in triple-negative BC did not remain significant after adjusting for covariates.

CONCLUSION: ESBC BCT recipients demonstrate superior OS and BCSS compared with mastectomy recipients.}, } @article {pmid39320077, year = {2024}, author = {Hadad, Z and Wahid, W and Afzelius, P}, title = {[Not Available].}, journal = {Ugeskrift for laeger}, volume = {186}, number = {36}, pages = {}, doi = {10.61409/V01240024}, pmid = {39320077}, issn = {1603-6824}, mesh = {Humans ; Female ; *Breast Neoplasms/pathology ; *Liver Neoplasms/secondary/diagnostic imaging ; *Carcinoma, Ductal, Breast/secondary/pathology/diagnostic imaging ; *Neoplasm Recurrence, Local/pathology ; *Lymphatic Metastasis/diagnostic imaging ; Middle Aged ; }, abstract = {Breast cancer usually metastasizes by haematogenous spread. This is a case report of a woman with unusual liver metastases from a recurrent invasive ductal carcinoma via a lymphatic route draining the outer part of the breast to the liver running parallelly with the right rectus abdominis muscle, depicted by preoperative sentinel node lymphoscintigraphy. Realizing this route of metastasis can impact survival, as it has a favourable prognosis compared with haematogenous metastasis, we want to draw attention to this.}, } @article {pmid39317017, year = {2024}, author = {Louis, M and Fang, J and Grabill, N and Singh, H and Strom, P}, title = {Her2-positive breast cancer in a young patient with Li-Fraumeni syndrome: A comprehensive case study.}, journal = {International journal of surgery case reports}, volume = {124}, number = {}, pages = {110323}, doi = {10.1016/j.ijscr.2024.110323}, pmid = {39317017}, issn = {2210-2612}, abstract = {INTRODUCTION AND IMPORTANCE: Li-Fraumeni syndrome (LFS) is a rare hereditary disorder caused by mutations in the TP53 gene, leading to a significantly increased risk of developing various cancers at a young age, including breast cancer.

CLINICAL PRESENTATION: This case report details the clinical journey of a 21-year-old female diagnosed with Grade 3 invasive ductal carcinoma, which was estrogen receptor low positive and progesterone receptor negative but positive for Her2 (3+) with a high Ki67 proliferation index.

CLINICAL DISCUSSION: Genetic testing confirmed a TP53 mutation, establishing the diagnosis of LFS. The patient underwent neoadjuvant chemotherapy with TCHP (docetaxel, carboplatin, trastuzumab, pertuzumab), resulting in a complete clinical response. This was followed by bilateral skin-sparing and nipple-sparing mastectomy with sentinel lymph node biopsy and immediate reconstruction. Postoperative pathology confirmed a complete response to neoadjuvant therapy. The patient's treatment plan includes 12 cycles of trastuzumab and pertuzumab, with regular echocardiograms to monitor cardiac function and fertility preservation strategies involving monthly Lupron injections. Given the association of LFS with a high risk of multiple primary cancers, a rigorous surveillance strategy is essential. The psychological impact of a cancer diagnosis and the burden of living with a hereditary cancer syndrome were significant, necessitating comprehensive psychosocial support.

CONCLUSION: Managing Li-Fraumeni syndrome (LFS) and its associated cancers, particularly in young patients, necessitates a comprehensive and multidisciplinary approach. Early genetic testing for TP53 mutations is crucial in identifying LFS, enabling personalized treatment plans and proactive surveillance strategies.}, } @article {pmid39302353, year = {2024}, author = {Ben Kridis, W and Lajnef, M and Khanfir, A}, title = {Synchronous primary breast angiosarcoma with invasive ductal carcinoma.}, journal = {Breast disease}, volume = {43}, number = {1}, pages = {271-274}, doi = {10.3233/BD-240003}, pmid = {39302353}, issn = {1558-1551}, mesh = {Humans ; Female ; *Hemangiosarcoma/secondary/pathology ; *Breast Neoplasms/pathology ; Middle Aged ; *Carcinoma, Ductal, Breast/pathology/secondary ; *Neoplasms, Multiple Primary/pathology ; Ovarian Neoplasms/pathology/secondary ; }, abstract = {Primary angiosarcoma (PAS) of the breast is an extremely uncommon variant of breast malignancies. Highly aggressiveness and dismal prognosis characterize this endothelial neoplasm. We report here an unusual case of PAS of the breast occurring in a 46-year-old woman associated with concurrent bilateral invasive ductal carcinoma and ovarian metastases.}, } @article {pmid39280872, year = {2024}, author = {Jackson, I and Isern, R and Jesina, S and Velagapudi, M and Pruett, W}, title = {Pneumocystis jirovecii Pneumonia in Patients Treated for Solid Organ Malignancy.}, journal = {Ochsner journal}, volume = {24}, number = {3}, pages = {225-228}, pmid = {39280872}, issn = {1524-5012}, abstract = {Background: Pneumocystis jirovecii is a fungal pathogen that can present as an opportunistic cause of pneumonia and can occur in individuals with various causes of immunosuppression, including malignancy and treatments for malignancy that confer increased risk. Although the guidelines for use of Pneumocystis prophylaxis in certain populations are clear, the rapid development of novel cancer therapies elicits the need to accurately assess the degree of immunosuppression conferred by these regimens and to determine if patients receiving these therapies warrant Pneumocystis prophylaxis. Case Series: We present 2 cases of Pneumocystis jirovecii pneumonia in patients with invasive ductal carcinoma of the breast treated with a dose-dense chemotherapy regimen consisting of doxorubicin, cyclophosphamide, and paclitaxel. Conclusion: The use of a dose-dense regimen, in which the interval between doses is shortened compared to a standard regimen, has become a common therapy for patients diagnosed with early breast cancer. Although this approach leads to improved disease-free and overall survival, it has also been associated with an increased risk of developing Pneumocystis jirovecii pneumonia. Further research involving patients receiving dose-dense chemotherapy regimens is needed to determine their risk of developing opportunistic infections and whether that risk warrants changes in clinical management.}, } @article {pmid39256827, year = {2024}, author = {Phung, AT and Shah, JR and Dong, T and Reid, T and Larson, C and Sanchez, AB and Oronsky, B and Trogler, WC and Kummel, AC and Aisagbonhi, O and Blair, SL}, title = {CAR expression in invasive breast carcinoma and its effect on adenovirus transduction efficiency.}, journal = {Breast cancer research : BCR}, volume = {26}, number = {1}, pages = {131}, pmid = {39256827}, issn = {1465-542X}, mesh = {Humans ; Female ; *Breast Neoplasms/therapy/genetics/metabolism/pathology ; *Adenoviridae/genetics ; *Transduction, Genetic ; *Coxsackie and Adenovirus Receptor-Like Membrane Protein/metabolism/genetics ; Cell Line, Tumor ; Carcinoma, Lobular/metabolism/therapy/genetics/pathology ; Carcinoma, Ductal, Breast/metabolism/genetics/pathology/therapy ; Cadherins/metabolism/genetics ; Genetic Vectors/genetics/administration & dosage ; Liposomes ; }, abstract = {BACKGROUND: Breast cancer is the second leading cause of death in women, with invasive ductal carcinoma (IDC) and invasive lobular carcinoma (ILC) as the two most common forms of invasive breast cancer. While estrogen receptor positive (ER+) IDC and ILC are treated similarly, the multifocality of ILC presents challenges in detection and treatment, worsening long-term clinical outcomes in patients. With increasing documentation of chemoresistance in ILC, additional treatment options are needed. Oncolytic adenoviral therapy may be a promising option, but cancer cells must express the coxsackievirus & adenovirus receptor (CAR) for adenoviral therapy to be effective. The present study aims to evaluate the extent to which CAR expression is observed in ILC in comparison to IDC, and how the levels of CAR expression correlate with adenovirus transduction efficiency. The effect of liposome encapsulation on transduction efficiency is also assessed.

METHODS: To characterize CAR expression in invasive breast carcinoma, 36 formalin-fixed paraffin-embedded (FFPE) human breast tumor samples were assayed by CAR immunohistochemistry (IHC). Localization of CAR in comparison to other junctional proteins was performed using a multiplex immunofluorescence panel consisting of CAR, p120-catenin, and E-cadherin. ILC and IDC primary tumors and cell lines were transduced with E1- and E3-deleted adenovirus type 5 inserted with a GFP transgene (Ad-GFP) and DOTAP liposome encapsulated Ad-GFP (DfAd-GFP) at various multiplicities of infection (MOIs). Transduction efficiency was measured using a fluorescence plate reader. CAR expression in the human primary breast carcinomas and cell lines was also evaluated by IHC.

RESULTS: We observed membranous CAR, p120-catenin and E-cadherin expression in IDC. In ILC, we observed cytoplasmic expression of CAR and p120-catenin, with absent E-cadherin. Adenovirus effectively transduced high-CAR IDC cell lines, at MOIs as low as 12.5. Ad-GFP showed similar transduction as DfAd-GFP in high-CAR IDC cell lines. Conversely, Ad-GFP transduction of ILC cell lines was observed only at MOIs of 50 and 100. Furthermore, Ad-GFP did not transduce CAR-negative IDC cell lines even at MOIs greater than 100. Liposome encapsulation (DfAd-GFP) improved transduction efficiency 4-fold in ILC and 17-fold in CAR-negative IDC cell lines.

CONCLUSION: The present study demonstrates that oncolytic adenoviral therapy is less effective in ILC than IDC due to differences in spatial CAR expression. Liposome-enhanced delivery may be beneficial for patients with ILC and tumors with low or negative CAR expression to improve adenoviral therapeutic effectiveness.}, } @article {pmid39241490, year = {2024}, author = {Vanni, G and Pellicciaro, M and Materazzo, M and Berretta, M and Meucci, R and Perretta, T and Portarena, I and Pistolese, CA and Buonomo, OC}, title = {Radiological and pathological predictors of post-operative upstaging of breast ductal carcinoma in situ (DCIS) to invasive ductal carcinoma and lymph-nodes metastasis; a potential algorithm for node surgical de-escalation.}, journal = {Surgical oncology}, volume = {56}, number = {}, pages = {102128}, doi = {10.1016/j.suronc.2024.102128}, pmid = {39241490}, issn = {1879-3320}, mesh = {Humans ; Female ; *Breast Neoplasms/pathology/surgery ; Retrospective Studies ; Middle Aged ; *Carcinoma, Intraductal, Noninfiltrating/surgery/pathology/secondary ; *Lymphatic Metastasis ; *Carcinoma, Ductal, Breast/surgery/pathology/secondary ; *Algorithms ; Adult ; Aged ; Sentinel Lymph Node Biopsy/methods ; Prognosis ; Follow-Up Studies ; Mammography ; Mastectomy ; Neoplasm Staging ; }, abstract = {BACKGROUND/AIM: Ductal carcinoma in situ is considered a local disease with no metastatic potential, thus sentinel lymph node biopsy (SLNB) may be deemed an overtreatment. SLNB should be reserved for patients with invasive cancer, even though the risk of upstaging rises to 25 %. We aimed to identify clinicopathological predictors of post-operative upstaging in invasive carcinoma.

METHODS: We retrospectively analyzed patients with a pre-operative diagnosis of DCIS subjected to breast surgery between January 2017 to December 2021, and evaluated at the Breast Unit of PTV (Policlinico Tor Vergata, Rome).

RESULTS: Out of 267 patients diagnosed with DCIS, 33(12.4 %) received a diagnosis upstaging and 9(3.37 %) patients presented with sentinel lymph node (SLN) metastasis. In multivariate analysis, grade 3 tumor (OR 1.9; 95 % CI 1.2-5.6), dense nodule at mammography (OR 1.3; 95 % CI 1.1-2.6) and presence of a solid nodule at ultrasonography (OR 1.5; 95 % CI 1.2-2.6) were independent upstaging predictors. Differently, the independent predictors for SLNB metastasis were: upstaging (OR 2.1.; 95 % CI 1.2-4.6; p = 0.0079) and age between 40 and 60yrs (OR 1.4; 95 % CI 1.4-2.7; p = 0.027). All 9 patients with SLN metastasis received a diagnosis upstaging and were aged between 40 and 60 years old.

CONCLUSION: We identified pre-operative independent predictors of upstaging to invasive ductal carcinoma. The combined use of different predictors in an algorithm for surgical treatments of DCIS could reduce the numbers of unnecessary SLNB.}, } @article {pmid39219256, year = {2024}, author = {Lu, N and Zhang, M and Lu, L and Liu, YZ and Zhang, HH and Liu, XD}, title = {[Retracted] miRNA‑490‑3p promotes the metastatic progression of invasive ductal carcinoma.}, journal = {Oncology reports}, volume = {52}, number = {5}, pages = {}, doi = {10.3892/or.2024.8802}, pmid = {39219256}, issn = {1791-2431}, abstract = {Following the publication of this paper, it was drawn to the Editor's attention by a concerned reader that certain of the western blotting data shown in Fig. 2D, the cell migration and invasion assay data in Fig. 3C, the mouse imaging pictures in Fig. 4C and D, and the H&E‑stained images in Fig. 4E and F were strikingly similar to data appearing in different form in other articles written by different authors at different research institutes that had already been submitted or published elsewhere prior to the submission of this paper to Oncology Reports. Given that the abovementioned data had already apparently been submitted or published prior to the receipt of this paper at Oncology Reports, the Editor has decided that this paper should be retracted from the Journal. After having been in contact with the authors, they accepted the decision to retract the paper. The Editor apologizes to the readership for any inconvenience caused. [Oncology Reports 45: 706‑716, 2021; DOI: 10.3892/or.2020.7880].}, } @article {pmid39215495, year = {2024}, author = {Islam, T and Hoque, ME and Ullah, M and Islam, T and Nishu, NA and Islam, R}, title = {CNN-based deep learning approach for classification of invasive ductal and metastasis types of breast carcinoma.}, journal = {Cancer medicine}, volume = {13}, number = {16}, pages = {e70069}, pmid = {39215495}, issn = {2045-7634}, mesh = {Humans ; Female ; *Deep Learning ; *Breast Neoplasms/pathology/classification/diagnostic imaging ; *Neural Networks, Computer ; *Carcinoma, Ductal, Breast/pathology/classification/diagnostic imaging/secondary ; Neoplasm Metastasis ; }, abstract = {OBJECTIVE: Breast cancer is one of the leading cancer causes among women worldwide. It can be classified as invasive ductal carcinoma (IDC) or metastatic cancer. Early detection of breast cancer is challenging due to the lack of early warning signs. Generally, a mammogram is recommended by specialists for screening. Existing approaches are not accurate enough for real-time diagnostic applications and thus require better and smarter cancer diagnostic approaches. This study aims to develop a customized machine-learning framework that will give more accurate predictions for IDC and metastasis cancer classification.

METHODS: This work proposes a convolutional neural network (CNN) model for classifying IDC and metastatic breast cancer. The study utilized a large-scale dataset of microscopic histopathological images to automatically perceive a hierarchical manner of learning and understanding.

RESULTS: It is evident that using machine learning techniques significantly (15%-25%) boost the effectiveness of determining cancer vulnerability, malignancy, and demise. The results demonstrate an excellent performance ensuring an average of 95% accuracy in classifying metastatic cells against benign ones and 89% accuracy was obtained in terms of detecting IDC.

CONCLUSIONS: The results suggest that the proposed model improves classification accuracy. Therefore, it could be applied effectively in classifying IDC and metastatic cancer in comparison to other state-of-the-art models.}, } @article {pmid39207954, year = {2024}, author = {Yates, ME and Waltermire, H and Mori, K and Li, Z and Li, Y and Guzolik, H and Wang, X and Liu, T and Atkinson, JM and Hooda, J and Lee, AV and Oesterreich, S}, title = {ESR1 Fusions Invoke Breast Cancer Subtype-Dependent Enrichment of Ligand-Independent Oncogenic Signatures and Phenotypes.}, journal = {Endocrinology}, volume = {165}, number = {10}, pages = {}, pmid = {39207954}, issn = {1945-7170}, support = {P30 CA047904/CA/NCI NIH HHS/United States ; S10OD028483/NH/NIH HHS/United States ; S10 OD028483/OD/NIH HHS/United States ; F30CA250167/CA/NCI NIH HHS/United States ; RRID:SCR_022735//University of Pittsburgh/ ; //The Breasties/ ; P30CA047904-31//UPMC Hillman Cancer Biology Program/ ; //Hillman Foundation/ ; //Breast Cancer Alliance/ ; //Shear Family Foundation/ ; //Pennsylvania Department of Health/ ; R21 CA237964/CA/NCI NIH HHS/United States ; //PA Breast Cancer Coalition/ ; }, mesh = {Humans ; *Breast Neoplasms/genetics/pathology/metabolism ; Female ; *Estrogen Receptor alpha/genetics/metabolism ; Cell Line, Tumor ; Phenotype ; YAP-Signaling Proteins/genetics/metabolism ; SOX9 Transcription Factor/genetics/metabolism ; Carcinoma, Ductal, Breast/genetics/pathology/metabolism ; Oncogene Proteins, Fusion/genetics/metabolism ; Signal Transduction/genetics ; Carcinoma, Lobular/genetics/metabolism/pathology ; Transcription Factors/genetics/metabolism ; Gene Expression Regulation, Neoplastic ; Adaptor Proteins, Signal Transducing/genetics/metabolism ; Ligands ; Cell Proliferation/genetics ; }, abstract = {Breast cancer is a leading cause of female mortality and despite advancements in personalized therapeutics, metastatic disease largely remains incurable due to drug resistance. The estrogen receptor (ER, ESR1) is expressed in two-thirds of all breast cancer, and under endocrine stress, somatic ESR1 mutations arise in approximately 30% of cases that result in endocrine resistance. We and others reported ESR1 fusions as a mechanism of ER-mediated endocrine resistance. ER fusions, which retain the activation function 1- and DNA-binding domains, harbor ESR1 exons 1 to 6 fused to an in-frame gene partner resulting in loss of the ER ligand-binding domain (LBD). We demonstrate that in a no-special type (invasive ductal carcinoma [IDC]-NST) and an invasive lobular carcinoma (ILC) cell line, ER fusions exhibit robust hyperactivation of canonical ER signaling pathways independent of estradiol or antiendocrine therapies. We employ cell line models stably overexpressing ER fusions with concurrent endogenous ER knockdown to minimize endogenous ER influence. Cell lines exhibited shared transcriptomic enrichment in pathways known to be drivers of metastatic disease, notably MYC signaling. Cells expressing the 3' fusion partners SOX9 and YAP1 consistently demonstrated enhanced growth and cell survival. ILC cells expressing the DAB2 fusion led to enhanced growth, survival, and migration, phenotypes not appreciated in the IDC-NST DAB2 model. Herein, we report that cell line activity is subtype-, fusion-, and assay-specific, suggesting that LBD loss, the fusion partner, and the cellular landscape all influence fusion activities. Therefore, it will be critical to assess fusion frequency in the context of the clinicopathology.}, } @article {pmid39195215, year = {2024}, author = {Zavaglio, F and Cassaniti, I and d'Angelo, P and Zelini, P and Comolli, G and Gregorini, M and Rampino, T and Del Frate, L and Meloni, F and Pellegrini, C and Abelli, M and Ticozzelli, E and Lilleri, D and Baldanti, F}, title = {Immune Control of Human Cytomegalovirus (HCMV) Infection in HCMV-Seropositive Solid Organ Transplant Recipients: The Predictive Role of Different Immunological Assays.}, journal = {Cells}, volume = {13}, number = {16}, pages = {}, pmid = {39195215}, issn = {2073-4409}, support = {FRRB 2015-043//Fondazione Regionale per la ricerca Biomedica/ ; PE 2016-02362470//Ministero della salute Ricerca Finalizzata/ ; 1032-rcr2023-43//Ministero della salute Ricerca Corrente/ ; 20179JHAM//Ministero dell'Università e della Ricerca, PRIN/ ; }, mesh = {Humans ; *Cytomegalovirus Infections/immunology/virology ; *Cytomegalovirus/immunology ; Female ; Male ; Middle Aged ; *Transplant Recipients ; Adult ; Organ Transplantation/adverse effects ; CD8-Positive T-Lymphocytes/immunology ; CD4-Positive T-Lymphocytes/immunology ; Aged ; DNA, Viral ; Dendritic Cells/immunology ; Enzyme-Linked Immunospot Assay ; Immunologic Tests/methods ; Cytokines/metabolism ; }, abstract = {Human cytomegalovirus (HCMV) infection remains a major complication for solid organ transplant recipients (SOTRs). The aim of this study was to evaluate the role of HCMV-specific T cell immunity measured at the time of the HCMV-DNA peak in predicting the spontaneous clearance of infection. The performance of cytokine flow cytometry using infected dendritic cells (CFC-iDC), infected cell lysate (CFC-iCL) and pp65 peptide pool (CFC-pp65 pool) as stimuli, as well as ELISPOT assays using infected cell lysate (ELISPOT-iCL) and the pp65 peptide pool (ELISPOT-pp65 pool), was analysed. Among the 40 SOTRs enrolled, 16 patients (40%) required antiviral treatment for an HCMV infection (Non-Controllers), while the others spontaneously cleared the infection (Controllers). At the HCMV-DNA peak, the number of HCMV-specific CD4[+] T cells detected by the CFC-iDC, CFC-iCL and CFC-pp65 pool assays in Controllers was higher than that detected in Non-Controllers, while no difference was observed in terms of HCMV-specific CD8[+] T cell response. The same trend was observed when the HCMV-specific T cell response was measured by ELISPOT-iCL and ELISPOT-pp65 pool. We observed that the CD4[+] CFC-pp65 pool assay was the best predictor of self-resolving HCMV infection at the time of the HCVM-DNA peak. The CFC-pp65 pool assay is able to discriminate between CD4[+] and CD8[+] T cell responses and could be used in daily clinical practice.}, } @article {pmid39142851, year = {2024}, author = {Kosáč, P and Zábojníková, M and Vážan, P and Petrů, V and Ratajský, M and Lajmar, K and Dudešek, B and Kudlová, P and Duben, J and Podrazká, L and Gatěk, J}, title = {Breast cancer in 80+ year olds.}, journal = {Rozhledy v chirurgii : mesicnik Ceskoslovenske chirurgicke spolecnosti}, volume = {103}, number = {7}, pages = {258-262}, doi = {10.48095/ccrvch2024258}, pmid = {39142851}, issn = {0035-9351}, mesh = {Humans ; Aged, 80 and over ; *Breast Neoplasms/pathology/surgery ; Female ; Retrospective Studies ; Male ; Axilla ; Breast Neoplasms, Male/pathology/surgery ; Lymph Node Excision ; Carcinoma, Ductal, Breast/surgery/pathology/mortality ; Sentinel Lymph Node Biopsy ; Chemotherapy, Adjuvant ; Radiotherapy, Adjuvant ; Mastectomy, Segmental ; }, abstract = {INTRODUCTION: The risk of breast cancer increases with increasing age. The aim of our retrospective study was to determine the extent of breast and axillary surgery, including subsequent adjuvant therapy, in 80-year and older patients.

METHODS: Between 2017 and 2021, 834 breast cancer patients were operated in the Surgical Department of the EUC Clinic. Ninety-eight women (2× with bilateral cancer) and 2 men were included in this retrospective study. A total of 102 breast cancer cases in patients older than 80 years were analyzed. The surgical procedure corresponded to the stage of the disease and the general condition of the patient. Adjuvant systemic therapy was indicated according to the same principles.

RESULTS: At the time of surgery, the patients were more than 80 years old (80-96 years). The predominant type of invasive ductal carcinoma was diagnosed 83×, lobular carcinoma 6×, mucinous 6×, papillary carcinoma 4×, other 3×, with luminal A, B predominating (89×). The breast-conserving procedures were performed 63×. Sentinel node biopsy was performed 65×, supplemented by axillary lymph node dissection 13×. Primary axillary lymph node dissection was performed 15×. No axillary procedure was performed 23×. Radiotherapy was given 49×, chemotherapy 9× and hormonal therapy 82×. Local and regional recurrences were each observed 2×. A total of 37 patients died, 10 of them from breast cancer.

CONCLUSION: The most common cause of death in patients aged 80+ years is a cardiovascular disease, not breast cancer itself. This fact should be taken into account when determining the treatment plan.}, } @article {pmid39123374, year = {2024}, author = {Muñoz-Casares, FC and Martín-Broto, J and Cascales-Campos, P and Torres-Melero, J and López-Rojo, I and Gómez-Barbadillo, J and González-Bayón, L and Sebio, A and Serrano, C and Carvalhal, S and Abreu de Souza, J and Souza, A and Flores-Ayala, G and Palacios Fuenmayor, LJ and Lopes-Bras, R and González-López, JA and Vasques, H and Asencio-Pascual, JM}, title = {Ibero-American Consensus for the Management of Peritoneal Sarcomatosis: Updated Review and Clinical Recommendations.}, journal = {Cancers}, volume = {16}, number = {15}, pages = {}, pmid = {39123374}, issn = {2072-6694}, abstract = {Peritoneal sarcomatosis is a rare malignant disease with a poor prognosis, secondary to peritoneal dissemination of abdominopelvic soft tissue sarcomas. Its rarity, together with the characteristic histological heterogeneity and the historically poor response to systemic treatments, has prevented the establishment of widely accepted treatment criteria with curative intent. In this sense, radical cytoreductive surgery (CRS) with peritonectomy procedures and hyperthermic intraperitoneal chemotherapy (HIPEC), widely used in peritoneal carcinomatosis with excellent results, have not had the same evolutionary development in patients with peritoneal sarcomatosis. A multidisciplinary working group of experts in sarcomas and peritoneal oncological surgery established a series of recommendations based on current scientific evidence for the management of peritoneal sarcomatosis, taking into account the different histological subgroups of abdominopelvic sarcomas that can cause it depending on their origin: retroperitoneal sarcomas, uterine sarcomas, and visceral/peritoneal sarcomas of GIST (gastrointestinal stromal tumor) and non-GIST origin. This article shows the results of sarcoma experts' voting on the recommendations presented during the I Ibero-American Consensus on the Management of Peritoneal Sarcomatosis, which took place during the recent celebration of the III Hispanic-Portuguese Meeting for Updates on the Treatment of Sarcomas.}, } @article {pmid39101021, year = {2024}, author = {Sood, A and Mishra, G and Khandelwal, S and Bhoyar, M and Manuja, N}, title = {Tumour thrombosis of the left axillary vein due to infiltrative ductal carcinoma causing superior vena cava obstruction.}, journal = {Radiology case reports}, volume = {19}, number = {10}, pages = {4195-4200}, pmid = {39101021}, issn = {1930-0433}, abstract = {Invasive ductal carcinoma is the most common type of breast cancer and can affect any age group, predominantly females older than 55 years of age. We present a case of a female in her mid-30s complaining of a fungating mass in the upper outer quadrant of the left anterior chest wall. On workup of the patient, it was histopathologically found that the patient was affected by infiltrating ductal carcinoma of the left breast, which was causing tumoral thrombosis of the left axillary vein. Also, thrombosis of the right axillary vein, bilateral brachiocephalic veins, and superior vena cava with a focal hepatic hotspot sign were appreciated on contrast-enhanced computed tomography scan. No such case of tumoral thrombosis of the axillary vein causing superior vena cava obstruction has been reported in recent literature.}, } @article {pmid39097872, year = {2024}, author = {Gilani, N and Ozaslan, M}, title = {Association of XRCC2 with breast cancer, a multi-omics analysis at genomic, transcriptomic, and epigenomic level.}, journal = {Cellular and molecular biology (Noisy-le-Grand, France)}, volume = {70}, number = {7}, pages = {252-259}, doi = {10.14715/cmb/2024.70.7.36}, pmid = {39097872}, issn = {1165-158X}, mesh = {Adult ; Female ; Humans ; Middle Aged ; *Breast Neoplasms/genetics/pathology ; *DNA Methylation/genetics ; *DNA-Binding Proteins/genetics/metabolism ; Epigenomics/methods ; Gene Expression Regulation, Neoplastic ; Genetic Predisposition to Disease ; Genomics/methods ; *Multiomics/methods ; Transcriptome/genetics ; }, abstract = {One of the main causes of cancer-related mortality for women worldwide is breast cancer (BC). The XRCC2 gene, essential for DNA repair, has been implicated in cancer susceptibility. This study aims to evaluate the association between XRCC2 and BC risk. The study was conducted at Zheen International Hospital in Erbil, Iraq, between 2021 and 2024 with a total of 88 samples, including 44 paired normal and cancer tissue samples. Mutation analysis was performed using Next-Generation Sequencing, coupled with in silico tools for variant impact prediction. Expression levels were assessed through RT-PCR, and methylation status was determined using methylation-sensitive restriction enzyme digestion PCR. The study identified seven inherited germline variants in the XRCC2 gene, with five of these mutations being Uncertain Significance, one being Likely Pathogenic, and one being Likely benign. RNA purity was found high with mean A260/280 ratios of 1.986 ± 0.097 in normal (N) and 1.963 ± 0.092 in tumor (T) samples. Tumor samples exhibited a higher RNA concentration (78.56 ± 40.87 ng/µL) than normal samples (71.44 ± 40.79 ng/µL). XRCC2 gene expression was significantly upregulated in tumor tissue, with marked increases in patients aged 40-55 and >56 years and in higher cancer grades (II and III) and invasive ductal carcinoma (p-values ranging from <0.0001 to 0.0392). DNA methylation rates in tumor tissues were low (7%), suggesting limited regulation by methylation. The study suggests that XRCC2 can be classified as an oncogene and that its structural investigation by targeted NGS and expression evaluation can be used as a potential biomarker in BC.}, } @article {pmid39090623, year = {2024}, author = {Phongpreecha, T and Mathi, K and Cholerton, B and Fox, EJ and Sigal, N and Espinosa, C and Reincke, M and Chung, P and Hwang, LJ and Gajera, CR and Berson, E and Perna, A and Xie, F and Shu, CH and Hazra, D and Channappa, D and Dunn, JE and Kipp, LB and Poston, KL and Montine, KS and Maecker, HT and Aghaeepour, N and Montine, TJ}, title = {Single-cell peripheral immunoprofiling of lewy body and Parkinson's disease in a multi-site cohort.}, journal = {Molecular neurodegeneration}, volume = {19}, number = {1}, pages = {59}, pmid = {39090623}, issn = {1750-1326}, mesh = {Humans ; *Parkinson Disease/immunology/metabolism ; *Lewy Body Disease/immunology ; Male ; Female ; Aged ; Case-Control Studies ; *Leukocytes, Mononuclear/metabolism/immunology ; Biomarkers/metabolism ; Middle Aged ; Cohort Studies ; Aged, 80 and over ; Lewy Bodies/pathology/metabolism ; Single-Cell Analysis/methods ; }, abstract = {BACKGROUND: Multiple lines of evidence support peripheral organs in the initiation or progression of Lewy body disease (LBD), a spectrum of neurodegenerative diagnoses that include Parkinson's Disease (PD) without or with dementia (PDD) and dementia with Lewy bodies (DLB). However, the potential contribution of the peripheral immune response to LBD remains unclear. This study aims to characterize peripheral immune responses unique to participants with LBD at single-cell resolution to highlight potential biomarkers and increase mechanistic understanding of LBD pathogenesis in humans.

METHODS: In a case-control study, peripheral mononuclear cell (PBMC) samples from research participants were randomly sampled from multiple sites across the United States. The diagnosis groups comprise healthy controls (HC, n = 159), LBD (n = 110), Alzheimer's disease dementia (ADD, n = 97), other neurodegenerative disease controls (NDC, n = 19), and immune disease controls (IDC, n = 14). PBMCs were activated with three stimulants (LPS, IL-6, and IFNa) or remained at basal state, stained by 13 surface markers and 7 intracellular signal markers, and analyzed by flow cytometry, which generated 1,184 immune features after gating.

RESULTS: The model classified LBD from HC with an AUROC of 0.87 ± 0.06 and AUPRC of 0.80 ± 0.06. Without retraining, the same model was able to distinguish LBD from ADD, NDC, and IDC. Model predictions were driven by pPLCγ2, p38, and pSTAT5 signals from specific cell populations under specific activation. The immune responses characteristic for LBD were not associated with other common medical conditions related to the risk of LBD or dementia, such as sleep disorders, hypertension, or diabetes.

CONCLUSIONS AND RELEVANCE: Quantification of PBMC immune response from multisite research participants yielded a unique pattern for LBD compared to HC, multiple related neurodegenerative diseases, and autoimmune diseases thereby highlighting potential biomarkers and mechanisms of disease.}, } @article {pmid39072314, year = {2024}, author = {Habanjar, O and Nehme, R and Goncalves-Mendes, N and Cueff, G and Blavignac, C and Aoun, J and Decombat, C and Auxenfans, C and Diab-Assaf, M and Caldefie-Chézet, F and Delort, L}, title = {The obese inflammatory microenvironment may promote breast DCIS progression.}, journal = {Frontiers in immunology}, volume = {15}, number = {}, pages = {1384354}, pmid = {39072314}, issn = {1664-3224}, mesh = {Humans ; Female ; *Obesity/metabolism/pathology ; *Breast Neoplasms/pathology/immunology/metabolism ; *Tumor Microenvironment/immunology ; *Carcinoma, Intraductal, Noninfiltrating/pathology/metabolism/immunology ; *Disease Progression ; *Coculture Techniques ; *Macrophages/immunology/metabolism ; Inflammation/pathology/metabolism ; Adipocytes/metabolism/pathology ; Adipose Tissue/pathology/metabolism ; Cell Line, Tumor ; }, abstract = {INTRODUCTION: Ductal carcinoma in situ (DCIS), characterized by a proliferation of neoplastic cells confined within the mammary ducts, is distinctly isolated from the surrounding stroma by an almost uninterrupted layer of myoepithelial cells (MECs) and by the basement membrane. Heightened interactions within the adipose microenvironment, particularly in obese patients, may play a key role in the transition from DCIS to invasive ductal carcinoma (IDC), which is attracting growing interest in scientific research. Adipose tissue undergoes metabolic changes in obesity, impacting adipokine secretion and promoting chronic inflammation. This study aimed to assess the interactions between DCIS, including in situ cancer cells and MECs, and the various components of its inflammatory adipose microenvironment (adipocytes and macrophages).

METHODS: To this end, a 3D co-culture model was developed using bicellular bi-fluorescent DCIS-like tumoroids, adipose cells, and macrophages to investigate the influence of the inflammatory adipose microenvironment on DCIS progression.

RESULTS: The 3D co-culture model demonstrated an inhibition of the expression of genes involved in apoptosis (BAX, BAG1, BCL2, CASP3, CASP8, and CASP9), and an increase in genes related to cell survival (TP53, JUN, and TGFB1), inflammation (TNF-α, PTGS2, IL-6R), invasion and metastasis (TIMP1 and MMP-9) in cancer cells of the tumoroids under inflammatory conditions versus a non-inflammatory microenvironment. On the contrary, it confirmed the compromised functionality of MECs, resulting in the loss of their protective effects against cancer cells. Adipocytes from obese women showed a significant increase in the expression of all studied myofibroblast-associated genes (myoCAFs), such as FAP and α-SMA. In contrast, adipocytes from normal-weight women expressed markers of inflammatory fibroblast phenotypes (iCAF) characterized by a significant increase in the expression of LIF and inflammatory cytokines such as TNF-α, IL-1β, IL-8, and CXCL-10. These changes also influenced macrophage polarization, leading to a pro-inflammatory M1 phenotype. In contrast, myoCAF-associated adipocytes, and the cancer-promoting microenvironment polarized macrophages towards an M2 phenotype, characterized by high CD163 receptor expression and IL-10 and TGF-β secretion.

DISCUSSION: Reciprocal interactions between the tumoroid and its microenvironment, particularly in obesity, led to transcriptomic changes in adipocytes and macrophages, may participate in breast cancer progression while disrupting the integrity of the MEC layer. These results underlined the importance of adipose tissue in cancer progression.}, } @article {pmid39051633, year = {2024}, author = {Liu, T and Jin, D and Le, SB and Chen, D and Sebastian, M and Riva, A and Liu, R and Tran, DD}, title = {Machine Learning-Directed Conversion of Glioblastoma Cells to Dendritic Cell-Like Antigen-Presenting Cells as Cancer Immunotherapy.}, journal = {Cancer immunology research}, volume = {12}, number = {10}, pages = {1340-1360}, doi = {10.1158/2326-6066.CIR-23-0721}, pmid = {39051633}, issn = {2326-6074}, support = {R42 CA228875/CA/NCI NIH HHS/United States ; F30CA232641//National Cancer Institute (NCI)/ ; 6BC04//Florida Department of Health (DOH)/ ; R42CA228875//National Cancer Institute (NCI)/ ; P30CA014089//USC Norris Comprehensive Cancer Center (USC Norris)/ ; }, mesh = {*Glioblastoma/immunology/therapy/pathology ; Animals ; *Dendritic Cells/immunology ; Humans ; Mice ; *Machine Learning ; *Immunotherapy/methods ; Tumor Microenvironment/immunology ; Brain Neoplasms/immunology/therapy/pathology ; Antigen-Presenting Cells/immunology ; Cell Line, Tumor ; Mice, Inbred C57BL ; }, abstract = {Immunotherapy has limited efficacy in glioblastoma (GBM) due to the blood-brain barrier and the immunosuppressed or "cold" tumor microenvironment (TME) of GBM, which is dominated by immune-inhibitory cells and depleted of CTL and dendritic cells (DC). Here, we report the development and application of a machine learning precision method to identify cell fate determinants (CFD) that specifically reprogram GBM cells into induced antigen-presenting cells with DC-like functions (iDC-APC). In murine GBM models, iDC-APCs acquired DC-like morphology, regulatory gene expression profile, and functions comparable to natural DCs. Among these acquired functions were phagocytosis, direct presentation of endogenous antigens, and cross-presentation of exogenous antigens. The latter endowed the iDC-APCs with the ability to prime naïve CD8+ CTLs, a hallmark DC function critical for antitumor immunity. Intratumor iDC-APCs reduced tumor growth and improved survival only in immunocompetent animals, which coincided with extensive infiltration of CD4+ T cells and activated CD8+ CTLs in the TME. The reactivated TME synergized with an intratumor soluble PD1 decoy immunotherapy and a DC-based GBM vaccine, resulting in robust killing of highly resistant GBM cells by tumor-specific CD8+ CTLs and significantly extended survival. Lastly, we defined a unique CFD combination specifically for the human GBM to iDC-APC conversion of both glioma stem-like cells and non-stem-like cell GBM cells, confirming the clinical utility of a computationally directed, tumor-specific conversion immunotherapy for GBM and potentially other solid tumors.}, } @article {pmid39044875, year = {2024}, author = {Kocaman, N and Onat, E and Balta, H and Üçer, Ö}, title = {Are Meteorin-Like Peptide and Asprosin Important in the Diagnosis of Breast Tumors?.}, journal = {Cureus}, volume = {16}, number = {6}, pages = {e62979}, pmid = {39044875}, issn = {2168-8184}, abstract = {INTRODUCTION: Breast cancer (BC) is one of the most common and leading causes of death in women. Therefore, early and accurate diagnosis is vital. In this study, meteorin-like (METRNL) peptide and asprosin levels were examined in breast tissue in invasive ductal carcinoma (IDC) of the breast, and the roles of these molecules in the diagnosis of BC were investigated.

METHODS: In this retrospective study, tissues from patients with BC in the Pathology Department Laboratory of Fırat University Faculty of Medicine, Elazığ, Turkey, were used. Samples from 30 patients were used. The control group consisted of healthy breast tissues from the same patients. The pathology group consisted of breast tissues with IDC from the same patients. Breast tissue samples from both groups were evaluated immunohistochemically for METRNL and asprosin.

RESULTS: Statistically significant differences were observed between both groups in terms of METRNL and asprosin. It was observed that METRNL and asprosin immunoreactivities were higher in breast tissues with IDC than in healthy breast tissues (p<0.001).

CONCLUSION: When the study results were evaluated, it was seen that there was a significant relationship between healthy breast tissues and the ones with IDC in terms of METRNL and asprosin. It is thought that both METRNL and asprosin may be really important in the future for the early diagnosis and treatment of BC.}, } @article {pmid39032239, year = {2024}, author = {Davies, LSC and McDaid, L and Anandadas, C and Amaro, PF and Chuter, R and Woolf, D and Eccles, CL}, title = {Does the presence of Magtrace preclude adaptive breast radiotherapy on an MR-Linac?.}, journal = {Journal of medical imaging and radiation sciences}, volume = {55}, number = {4}, pages = {101716}, doi = {10.1016/j.jmir.2024.101716}, pmid = {39032239}, issn = {1876-7982}, abstract = {INTRODUCTION: This work reports on an unusual finding observed during image quality assessment in the preparation for the clinical implementation of breast magnetic resonance image-guided radiotherapy (MRIgRT) on a 1.5 Tesla (T) magnetic resonance linear accelerator (MR-Linac) (Elekta AB, Stockholm, Sweden).

CASE AND OUTCOMES: A patient with T2 N0 M0 right breast invasive ductal carcinoma, receiving adjuvant radiotherapy, underwent two imaging sessions on the MR-Linac. The imaging protocol included T1- and T2-weighted (W) turbo spin echo (TSE) sequences, a T1W mDixon, and a T2W TSE navigated sequence acquired on end-expiration. All images were reconstructed in the axial plane. Images were assessed for image quality and appropriateness for use within the treatment pathway using visual grading analysis (VGA). An artefact in the right breast was noted independently by all observers. The patient's skin and medical notes were reviewed for possible explanation. The findings were discussed with the patient's responsible clinician, and subsequent referral to the local multi-disciplinary team (MDT) for radiologist review was made. On further investigation, the patient's images demonstrated a signal void in the subareolar region of the right breast coinciding with the surgical site. This was distal from the tumour bed and deemed unlikely to be related to a Magseed marker or intraoperative clips. The patient reported no history of nipple tattoo or piercing. There was nothing on clothing that this could be attributed to.

DISCUSSION: Following MDT review, where all potential sources of signal void were considered, it was concluded that the cause was Magtrace, a superparamagnetic iron oxide tracer, recommended for sentinel lymph node localisation in patients with breast cancer in the United Kingdom. The artefact was characteristic of a magnetic susceptibility artefact. These can arise from local magnetic field inhomogeneities caused by the presence of the metal compounds in MagTrace. For breast MRIgRT on the MR-Linac, treatment verification and the possibility of real-time replanning is a critical aspect. The magnetic susceptibility artefact significantly inhibited plan adaption and confidence in the online image registration process making the patient ineligible for treatment on the MR-Linac.

CONCLUSION: As part of ongoing work-up for breast MRIgRT, the screening of patients for Magtrace is now included. Optimisation of MR imaging sequences for radiotherapy planning and image review to minimise distortion are being developed.}, } @article {pmid39005669, year = {2024}, author = {Olbromski, M and Mrozowska, M and Piotrowska, A and Kmiecik, A and Smolarz, B and Romanowicz, H and Blasiak, P and Maciejczyk, A and Wojnar, A and Dziegiel, P}, title = {Prognostic significance of alpha-2-macrglobulin and low-density lipoprotein receptor-related protein-1 in various cancers.}, journal = {American journal of cancer research}, volume = {14}, number = {6}, pages = {3036-3058}, pmid = {39005669}, issn = {2156-6976}, abstract = {Cancer is the leading cause of death worldwide. The World Health Organization (WHO) estimates that 10 million fatalities occurred in 2023. Breast cancer (BC) ranked first among malignancies with 2.26 million cases, lung cancer (LC) second with 2.21 million cases, and colon and rectum cancers (CC, CRC) third with 1.93 million cases. These results highlight the importance of investigating novel cancer prognoses and anti-cancer markers. In this study, we investigated the potential effects of alpha-2 macroglobulin and its receptor, LRP1, on the outcomes of breast, lung, and colorectal malignancies. Immunohistochemical staining was used to analyze the expression patterns of A2M and LRP1 in 545 cases of invasive ductal breast carcinoma (IDC) and 51 cases of mastopathies/fibrocystic breast disease (FBD); 256 cases of non-small cell lung carcinomas (NSCLCs) and 45 cases of non-malignant lung tissue (NMLT); and 108 cases of CRC and 25 cases of non-malignant colorectal tissue (NMCT). A2M and LRP1 expression levels were also investigated in breast (MCF-7, BT-474, SK-BR-3, T47D, MDA-MB-231, and MDA-MB-231/BO2), lung (NCI-H1703, NCI-H522, and A549), and colon (LS 180, Caco-2, HT-29, and LoVo) cancer cell lines. Based on our findings, A2M and LRP1 exhibited various expression patterns in the examined malignancies, which were related to one another. Additionally, the stroma of lung and colorectal cancer has increased levels of A2M/LRP1 areas, which explains the significance of the stroma in the development and maintenance of tumor homeostasis. A2M expression was shown to be downregulated in all types of malignancies under study and was positively linked with an increase in cell line aggressiveness. Although more invasive cells had higher levels of A2M expression, an IHC analysis showed the opposite results. This might be because exogenous alpha-2-macroglobulin is present, which has an inhibitory effect on several cancerous enzymes and receptor-dependent signaling pathways. Additionally, siRNA-induced suppression of the transcripts for A2M and LRPP1 revealed their connection, which provides fresh information on the function of the LRP1 receptor in A2M recurrence in cancer. Further studies on different forms of cancer may corroborate the fact that both A2M and LRP1 have high potential as innovative therapeutic agents.}, } @article {pmid38992932, year = {2024}, author = {Jamjoum, G and Arab, FS and Tayeb, R and Samkari, A and Johari, AA and Ashkar, L and Akbar, J}, title = {Cutaneous Metastasis in Breast Cancer: A Case Report.}, journal = {The American journal of case reports}, volume = {25}, number = {}, pages = {e943999}, pmid = {38992932}, issn = {1941-5923}, mesh = {Humans ; Female ; *Breast Neoplasms/pathology ; Adult ; *Skin Neoplasms/secondary/pathology ; Carcinoma, Ductal, Breast/secondary ; Lung Neoplasms/secondary/pathology ; }, abstract = {BACKGROUND Breast cancer (BC) is the most common malignant disease in females and one of the leading causes of death worldwide. Its treatment plan includes a long-term follow-up and close surveillance, as recurrence is a well-acknowledged concern. BC can recur either locally or as a metastasis, and skin metastasis is a common complication in advanced breast cancer patients. It can present as a skin nodule, plaque, or erythematous lesion, and can be difficult to distinguish from benign skin conditions. The risk of skin metastasis is higher in patients with inflammatory BC. Treatment of such a complex condition is even more challenging, with poor prognosis. Here, we report a case of a 42-year-old woman with stage 4 luminal A BC who had soft tissue recurrence. CASE REPORT A 42-year-old woman with a history of left-sided BC diagnosed and treated 10 years ago presented with multiple soft tissue masses mimicking abscesses at the right lower middle of the back, bilateral thighs, and back of the neck, in the last 6 months, the largest measuring 8×10 cm. The masses were found to be metastatic BC that had spread to the skin and lungs. Because it was invasive ductal carcinoma with positive ER and PR receptors, she was started on hormonal treatment and chemotherapy. CONCLUSIONS This case report highlights the importance of follow-up in patients with a history of BC, as the cancer can recur and spread many years after treatment.}, } @article {pmid38985057, year = {2024}, author = {Uppal, R and Saeed, U and Uppal, MR and Khan, AA and Ahmad, M and Piracha, ZZ}, title = {SARS-CoV-2 clearance in term of Cycle Threshold (Ct) during first two waves of COVID-19 in Pakistan: a phenomenon of delayed viral clearance post-corticosteroid treatment.}, journal = {Brazilian journal of biology = Revista brasleira de biologia}, volume = {84}, number = {}, pages = {e271452}, doi = {10.1590/1519-6984.271452}, pmid = {38985057}, issn = {1678-4375}, mesh = {Humans ; *COVID-19 ; Pakistan/epidemiology ; *Viral Load/drug effects ; *SARS-CoV-2 ; Male ; Female ; COVID-19 Drug Treatment ; Adult ; RNA, Viral/analysis ; Middle Aged ; Time Factors ; Adrenal Cortex Hormones/therapeutic use ; Young Adult ; Pandemics ; Adolescent ; Real-Time Polymerase Chain Reaction ; COVID-19 Nucleic Acid Testing ; }, abstract = {SARS-CoV-2 is recently emerged virus, which caused millions of deaths, all over the world. To tackle COVID-19 pandemic, there is an utmost need for in-depth analysis of viral replication. We aimed to examine viral load in SARS-CoV-2 patients during first two waves of COVID-19 in Pakistan. 225,615 suspected subjects from 75 different regions of Pakistan were selected in the study. SARS-CoV-2 RNAs were detected via real time PCR. During first wave (period of June-July, 2020) of COVID-19 the prevalence of SARS-CoV-2 was 20.38%. However, during second wave (period of November-December, 2020) of COVID-19, the rate of prevalence was 9.41%. During first wave of COVID-19 96.31% of participants remained PCR positive for 14 to 21 days, 3.39% of subjects showed positive results for 22 to 35 days, while delayed Ct values were observed among 0.26% of participants for 36 to 49 days. However, during second wave of COVID-19 89.31% of the subjects exhibited symptoms and showed real-time PCR positive results for 14 to 21 days, 9.42% showed positive results for 22 to 35 days, while significantly delayed Ct value results were observed among 1.026% of participants for 36 to 63 days (3.95 times higher than first wave). In contrast to first wave of COVID-19, the factors that were different in second wave were neither viral (different strains) nor host (same population). But treatment factors changed significantly. As during second wave besides azithromycin, corticosteroid dexamethasone consumption was increased consequently causing delayed Ct value negativity. This suggests that corticosteroid treatment might be linked with delayed Ct value or viral clearance. This study is crucial for re-considering effective therapeutic options against COVID-19.}, } @article {pmid38977136, year = {2024}, author = {Kwon, Y and Gottmann, P and Wang, S and Tissink, J and Motzler, K and Sekar, R and Albrecht, W and Cadenas, C and Hengstler, JG and Schürmann, A and Zeigerer, A}, title = {Induction of steatosis in primary human hepatocytes recapitulates key pathophysiological aspects of metabolic dysfunction-associated steatotic liver disease.}, journal = {Journal of hepatology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jhep.2024.06.040}, pmid = {38977136}, issn = {1600-0641}, abstract = {BACKGROUND & AIMS: Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common cause of chronic liver disease. Owing to limited available treatment options, novel pre-clinical models for target selection and drug validation are warranted. We have established and extensively characterized a primary human steatotic hepatocyte in vitro model system that could guide the development of treatment strategies for MASLD.

METHODS: Cryopreserved primary human hepatocytes from five donors varying in sex and ethnicity were cultured with free fatty acids in a 3D collagen sandwich for 7 days and the development of MASLD was followed by assessing classical hepatocellular functions. As proof of concept, the effects of the drug firsocostat (GS-0976) on in vitro MASLD phenotypes were evaluated.

RESULTS: Incubation with free fatty acids induced steatosis, insulin resistance, mitochondrial dysfunction, inflammation, and alterations in prominent human gene signatures similar to patients with MASLD, indicating the recapitulation of human MASLD in this system. The application of firsocostat rescued clinically observed fatty liver disease pathologies, highlighting the ability of the in vitro system to test the efficacy and potentially characterize the mode of action of drug candidates.

CONCLUSIONS: Altogether, our human MASLD in vitro model system could guide the development and validation of novel targets and drugs for the treatment of MASLD.

IMPACT AND IMPLICATIONS: Due to low drug efficacy and high toxicity, clinical treatment options for metabolic dysfunction-associated steatotic liver disease (MASLD) are currently limited. To facilitate earlier stop-go decisions in drug development, we have established a primary human steatotic hepatocyte in vitro model. As the model recapitulates clinically relevant MASLD characteristics at high phenotypic resolution, it can serve as a pre-screening platform and guide target identification and validation in MASLD therapy.}, } @article {pmid38964999, year = {2024}, author = {Yan, X and Yang, L and Ye, X and Chen, J and Wang, T and Du, M}, title = {Unpacking the hazards: An analytic study of injury patterns and risk factors in urban instant delivery.}, journal = {Injury}, volume = {55}, number = {9}, pages = {111706}, doi = {10.1016/j.injury.2024.111706}, pmid = {38964999}, issn = {1879-0267}, mesh = {Humans ; Female ; Risk Factors ; Male ; China/epidemiology ; *Accidents, Traffic/statistics & numerical data ; *Wounds and Injuries/epidemiology ; Middle Aged ; Adult ; Risk-Taking ; Urban Population/statistics & numerical data ; Young Adult ; }, abstract = {The rapid growth of urban instant delivery, facilitated by digital platforms and characterized by on-demand, short-term, task-based labor, has raised concerns about safety, particularly with the increasing frequency of instant delivery crashes (IDCs). This study addresses knowledge gaps in understanding injury patterns and risk factors associated with IDCs. Utilizing data extracted from judicial verdicts on IDC disputes in China, encompassing demographic, contextual, crash, and injury information, the research employs ordered logit regression to identify significant factors affecting injury patterns, the number of injuries per person (IPP), and injury severity. Overall, traffic injuries related to instant delivery services have gradually improved since 2020, as evidenced by the severity of individual accidents, the number of injuries, and the economic losses. Analysis of 648 injuries among 448 non-fatal victims reveals a prevalence of lower extremity injuries, followed by external, upper extremity, and head injuries. While the majority of victims suffered a single injury, approximately 22 % experienced major injuries. Female delivery riders exhibited higher injury ratios across various body regions. Rider risk behavior, type of delivery vehicles, and the mode of transport of non-delivery travelers emerged as significant influencers of injury patterns. Notably, functional and physical intersection areas exhibited the highest injury ratios among facility types. Contrary to conventional wisdom, older riders and travelers aged above 50 were associated with higher injury severity, challenging the perception of young age as the primary risk factor. The prominence of lower extremity injuries underscores the necessity for heightened protective measures for delivery riders. Major injuries among victims emphasize potential long-term consequences and associated costs. The significance of gender, age, and risk behavior as determining factors highlights the need for targeted safety interventions. These findings offer crucial insights for stakeholders, guiding the formulation of precise safety measures and informed policy initiatives within the dynamic landscape of instant delivery safety.}, } @article {pmid38951766, year = {2024}, author = {Nisar, MI and Kabole, I and Khanam, R and Shahid, S and Bakari, BA and Chowdhury, NH and Qazi, MF and Dutta, A and Rahman, S and Khalid, J and Dhingra, U and Hasan, T and Ansari, N and Deb, S and Mitra, DK and Mehmood, U and Aftab, F and Ahmed, S and Khan, S and Ali, SM and Ahmed, S and Manu, A and Yoshida, S and Bahl, R and Baqui, AH and Sazawal, S and Jehan, F}, title = {Does the implementation of revised American College of Cardiology and American Heart Association (ACC/AHA) guidelines improve the identification of stillbirths and preterm births in hypertensive pregnancies: a population-based cohort study from South Asia and sub-Saharan Africa.}, journal = {BMC pregnancy and childbirth}, volume = {24}, number = {1}, pages = {451}, pmid = {38951766}, issn = {1471-2393}, support = {001/WHO_/World Health Organization/International ; I64438//Bill and Melinda Gates Foundation/ ; }, mesh = {Humans ; Female ; Pregnancy ; *Premature Birth/epidemiology ; *Stillbirth/epidemiology ; Adult ; *Hypertension, Pregnancy-Induced/diagnosis/epidemiology ; *Practice Guidelines as Topic ; United States/epidemiology ; Pakistan/epidemiology ; Cohort Studies ; American Heart Association ; Bangladesh/epidemiology ; Tanzania/epidemiology ; Young Adult ; Blood Pressure ; Infant, Newborn ; Asia, Southern ; }, abstract = {BACKGROUND: Hypertensive disorders of pregnancy (HDP) are a significant cause of maternal mortality worldwide. The classification and treatment of hypertension in pregnancy remain debated. We aim to compare the effectiveness of the revised 2017 ACC/AHA blood pressure threshold in predicting adverse pregnancy outcomes.

METHODS: We conducted a secondary data analysis of the Alliance for Maternal and Newborn Health Improvement (AMANHI) biorepository study, including 10,001 pregnant women from Bangladesh, Pakistan, and Tanzania. Blood pressure was measured using validated devices at different antenatal care visits. The blood pressure readings were categorized as: normal blood pressure (systolic blood pressure (sBP) < 120 mm Hg and diastolic blood pressure (dBP) < 80 mm Hg), elevated blood pressure (sBP 120-129 and dBP < 80), stage 1 hypertension (sBP 130-139 or dBP 80-89, or both), and stage 2 hypertension (sBP ≥ 140 or dBP ≥ 90, or both). We estimated risk ratios for stillbirths and preterm births, as well as diagnostic test properties of both the pre-existing JNC7 (≥ 140/90) and revised ACC/AHA (≥ 130/80) thresholds using normal blood pressure as reference group.

RESULTS: From May 2014 to June 2018, blood pressure readings were available for 9,448 women (2,894 in Bangladesh, 2,303 in Pakistan, and 4,251 in Tanzania). We observed normal blood pressure in 70%, elevated blood pressure in 12.4%, stage 1 hypertension in 15.2%, and stage 2 hypertension in 2.5% of the pregnant women respectively. Out of these, 310 stillbirths and 9,109 live births were recorded, with 887 preterm births. Using the ACC/AHA criteria, the stage 1 hypertension cut-off revealed 15.3% additional hypertension diagnoses as compared to JNC7 criteria. ACC/AHA defined hypertension was significantly associated with stillbirths (RR 1.8, 95% CI 1.4, 2.3). The JNC 7 hypertension cut-off of ≥ 140/90 was significantly associated with a higher risk of preterm births (RR 1.6, 95% CI 1.2, 2.2) and stillbirths (RR 3.6, 95% CI 2.5, 5.3). Both criteria demonstrated low sensitivities (8.4 for JNC-7 and 28.1 for ACC/AHA) and positive predictive values (11.0 for JNC7 and 5.2 for ACC/AHA) in predicting adverse outcomes.

CONCLUSION: The ACC/AHA criteria (≥ 130/80) identified additional cases of hypertension but had limited predictive accuracy for stillbirths and preterm births, highlighting the ongoing need for improved criteria in managing pregnancy-related hypertension.}, } @article {pmid38942922, year = {2024}, author = {Pantazi, V and Miklós, V and Smith, P and Oláh-Németh, O and Pankotai-Bodó, G and Teja Dondapati, D and Ayaydin, F and D'Angiolella, V and Pankotai, T}, title = {Prognostic potential of CUL3 ligase with differential roles in luminal A and basal type breast cancer tumors.}, journal = {Scientific reports}, volume = {14}, number = {1}, pages = {14912}, pmid = {38942922}, issn = {2045-2322}, support = {Medical Research Council (MRC) grant MR/X006980/1//Vincenzo D'Angiolella/ ; National Research, Development and Innovation Office under NKFI-FK 13208//Tibor Pankotai/ ; }, mesh = {Humans ; *Cullin Proteins/metabolism/genetics ; Female ; Prognosis ; *Breast Neoplasms/pathology/genetics/metabolism ; *Biomarkers, Tumor/metabolism/genetics ; *Gene Expression Regulation, Neoplastic ; Cell Line, Tumor ; Gene Expression Profiling ; MCF-7 Cells ; Triple Negative Breast Neoplasms/genetics/pathology/metabolism ; }, abstract = {Breast cancer is a prevalent and significant cause of mortality in women, and manifests as six molecular subtypes. Its further histologic classification into non-invasive ductal or lobular carcinoma (DCIS) and invasive carcinoma (ILC or IDC) underscores its heterogeneity. The ubiquitin-proteasome system plays a crucial role in breast cancer, with inhibitors targeting the 26S proteasome showing promise in clinical treatment. The Cullin-RING ubiquitin ligases, including CUL3, have direct links to breast cancer. This study focuses on CUL3 as a potential biomarker, leveraging high-throughput sequencing, gene expression profiling, experimental and data analysis tools. Through comprehensive analysis using databases like GEPIA2 and UALCAN, as well as TCGA datasets, CUL3's expression and its association with prognostic values were assessed. Additionally, the impact of CUL3 overexpression was explored in MCF-7 and MDA-MB-231 breast cancer cell lines, revealing distinct differences in molecular and phenotypic characteristics. We further profiled its expression and localization in breast cancer tissues identifying prominent differences between luminal A and TNBC tumors. Conclusively, CUL3 was found to be associated with cell cycle progression, and DNA damage response, exhibiting diverse roles depending on the tumor's molecular type. It exhibits a tendency to act as an oncogene in triple-negative tumors and as a tumor suppressor in luminal A types, suggesting a potential significance in breast cancer progression and therapeutic directions.}, } @article {pmid38929597, year = {2024}, author = {Yoo, KC and Kim, DH and Park, S and Yun, H and Ryu, DH and Lee, J and Son, SM}, title = {Gastric Metastasis Mimicking Early Gastric Cancer from Invasive Ductal Carcinoma of the Breast: Case Report and Literature Review.}, journal = {Medicina (Kaunas, Lithuania)}, volume = {60}, number = {6}, pages = {}, pmid = {38929597}, issn = {1648-9144}, mesh = {Humans ; Female ; *Stomach Neoplasms/pathology/diagnosis ; Aged ; *Breast Neoplasms/pathology ; *Carcinoma, Ductal, Breast/secondary/diagnosis ; *Gastrectomy/methods ; Diagnosis, Differential ; Lymphatic Metastasis ; }, abstract = {Backgound and Objectives: Gastric metastasis from invasive ductal breast cancer (BC) is rare. It mainly occurs in patients with lobular BC. The occurrence of multiple metastases is typically observed several years after the primary diagnosis. Endoscopic findings of gastric metastasis of the BC were usually the linitis plastic type. Case presentation: A 72-year-old women who underwent right modified radical mastectomy (MRM) 10 month ago was referred after being diagnosed with early gastric cancer (EGC) during systemic chemotherapy. EGC type I was found at gastric fundus, and pathologic finding showed poorly differentiated adenocarcinoma. Metachronous double primary tumor EGC was considered. Management and Outcome: A laparoscopic total gastrectomy was performed, and postoperative pathology revealed submucosa invasion and two lymph node metastases. A pathologic review that focused on immunohistochemical studies of selected antibodies such as GATA binding protein 3 (GATA3), gross cystic disease fluid protein-15 (GCDFP-15), cytokeratin 7 (CK7) was performed again, comparing previous results. As a result, gastric metastasis from BC was diagnosed. After totally laparoscopic total gastrectomy, palliative first-line chemotherapy with paclitaxel/CDDP was performed. Two months after gastrectomy, she was diagnosed with para-aortic lymph node metastasis and multiple bone metastases. She expired six months after gastrectomy. Conclusions: Gastric metastasis from invasive ductal carcinoma of the breast, which is clinically manifested as EGC, is a very rare condition. If there is a history of BC, careful pathological review will be required.}, } @article {pmid38923054, year = {2024}, author = {Sendag, S and Koca, D and Arslan, T and Schuler, G and Wehrend, A}, title = {Oestrogen and progesterone concentrations in intrapartum cows with insufficient cervix dilation.}, journal = {Reproduction in domestic animals = Zuchthygiene}, volume = {59}, number = {6}, pages = {e14656}, doi = {10.1111/rda.14656}, pmid = {38923054}, issn = {1439-0531}, mesh = {Animals ; Female ; Cattle ; *Progesterone/blood ; Pregnancy ; *Cervix Uteri ; *Estrogens/blood ; Dystocia/veterinary ; Estradiol/blood ; Cattle Diseases/blood ; }, abstract = {The cervix is an important organ that has to dilate sufficiently at delivery to allow the foetus to transition to extrauterine life. Insufficient dilatation of the cervix (IDC) is a frequent cause of dystocia in cattle. The mechanisms underlying cervical opening and the pathogenesis of IDC are still widely unclear. Systematic studies on the relationship between IDC and steroid hormones have been limited and have yielded inconsistent findings. This study aimed to measure oestrogen and progesterone (P4) concentrations in intrapartum cows presented with dystocia due to IDC and in a comparison (C) group of cows with eutocic delivery. Before any obstetrical procedures, and right after the initial evaluation, blood samples were taken from IDC and C animals. Concentrations of P4, oestradiol-17β (E2), free total oestrogens (FTE) and conjugated total oestrogens (CTE) were measured by established radioimmunoassays. Concentrations of P4 (p = .538), FTE (p = .065) and CTE (p = .605) were not statistically different between C and IDC groups. However, E2 levels in group C were significantly lower when compared to those in the IDC group (p = .013), which is inconsistent with the function of oestrogens in cervical dilatation. The correlation analysis demonstrated significant positive correlations between the pairs P4 versus FTE, P4 versus E2 and FTE versus E2 in group C and between the pair FTE versus E2 in group IDC. In conclusion, the results suggest that local activities of steroids relevant to the aetiology of IDC are not reflected by concentrations in the systemic circulation or that other factors are clearly more important.}, } @article {pmid38908072, year = {2024}, author = {Berndt, C and Alborzinia, H and Amen, VS and Ayton, S and Barayeu, U and Bartelt, A and Bayir, H and Bebber, CM and Birsoy, K and Böttcher, JP and Brabletz, S and Brabletz, T and Brown, AR and Brüne, B and Bulli, G and Bruneau, A and Chen, Q and DeNicola, GM and Dick, TP and Distéfano, A and Dixon, SJ and Engler, JB and Esser-von Bieren, J and Fedorova, M and Friedmann Angeli, JP and Friese, MA and Fuhrmann, DC and García-Sáez, AJ and Garbowicz, K and Götz, M and Gu, W and Hammerich, L and Hassannia, B and Jiang, X and Jeridi, A and Kang, YP and Kagan, VE and Konrad, DB and Kotschi, S and Lei, P and Le Tertre, M and Lev, S and Liang, D and Linkermann, A and Lohr, C and Lorenz, S and Luedde, T and Methner, A and Michalke, B and Milton, AV and Min, J and Mishima, E and Müller, S and Motohashi, H and Muckenthaler, MU and Murakami, S and Olzmann, JA and Pagnussat, G and Pan, Z and Papagiannakopoulos, T and Pedrera Puentes, L and Pratt, DA and Proneth, B and Ramsauer, L and Rodriguez, R and Saito, Y and Schmidt, F and Schmitt, C and Schulze, A and Schwab, A and Schwantes, A and Soula, M and Spitzlberger, B and Stockwell, BR and Thewes, L and Thorn-Seshold, O and Toyokuni, S and Tonnus, W and Trumpp, A and Vandenabeele, P and Vanden Berghe, T and Venkataramani, V and Vogel, FCE and von Karstedt, S and Wang, F and Westermann, F and Wientjens, C and Wilhelm, C and Wölk, M and Wu, K and Yang, X and Yu, F and Zou, Y and Conrad, M}, title = {Ferroptosis in health and disease.}, journal = {Redox biology}, volume = {75}, number = {}, pages = {103211}, pmid = {38908072}, issn = {2213-2317}, support = {P30 CA008748/CA/NCI NIH HHS/United States ; }, mesh = {*Ferroptosis ; Humans ; Animals ; Iron/metabolism ; Neoplasms/metabolism/drug therapy/pathology ; Lipid Peroxidation ; Oxidation-Reduction ; Disease Susceptibility ; }, abstract = {Ferroptosis is a pervasive non-apoptotic form of cell death highly relevant in various degenerative diseases and malignancies. The hallmark of ferroptosis is uncontrolled and overwhelming peroxidation of polyunsaturated fatty acids contained in membrane phospholipids, which eventually leads to rupture of the plasma membrane. Ferroptosis is unique in that it is essentially a spontaneous, uncatalyzed chemical process based on perturbed iron and redox homeostasis contributing to the cell death process, but that it is nonetheless modulated by many metabolic nodes that impinge on the cells' susceptibility to ferroptosis. Among the various nodes affecting ferroptosis sensitivity, several have emerged as promising candidates for pharmacological intervention, rendering ferroptosis-related proteins attractive targets for the treatment of numerous currently incurable diseases. Herein, the current members of a Germany-wide research consortium focusing on ferroptosis research, as well as key external experts in ferroptosis who have made seminal contributions to this rapidly growing and exciting field of research, have gathered to provide a comprehensive, state-of-the-art review on ferroptosis. Specific topics include: basic mechanisms, in vivo relevance, specialized methodologies, chemical and pharmacological tools, and the potential contribution of ferroptosis to disease etiopathology and progression. We hope that this article will not only provide established scientists and newcomers to the field with an overview of the multiple facets of ferroptosis, but also encourage additional efforts to characterize further molecular pathways modulating ferroptosis, with the ultimate goal to develop novel pharmacotherapies to tackle the various diseases associated with - or caused by - ferroptosis.}, } @article {pmid38894870, year = {2024}, author = {Ramamoorthy, P and Ramakantha Reddy, BR and Askar, SS and Abouhawwash, M}, title = {Histopathology-based breast cancer prediction using deep learning methods for healthcare applications.}, journal = {Frontiers in oncology}, volume = {14}, number = {}, pages = {1300997}, pmid = {38894870}, issn = {2234-943X}, abstract = {Breast cancer (BC) is the leading cause of female cancer mortality and is a type of cancer that is a major threat to women's health. Deep learning methods have been used extensively in many medical domains recently, especially in detection and classification applications. Studying histological images for the automatic diagnosis of BC is important for patients and their prognosis. Owing to the complication and variety of histology images, manual examination can be difficult and susceptible to errors and thus needs the services of experienced pathologists. Therefore, publicly accessible datasets called BreakHis and invasive ductal carcinoma (IDC) are used in this study to analyze histopathological images of BC. Next, using super-resolution generative adversarial networks (SRGANs), which create high-resolution images from low-quality images, the gathered images from BreakHis and IDC are pre-processed to provide useful results in the prediction stage. The components of conventional generative adversarial network (GAN) loss functions and effective sub-pixel nets were combined to create the concept of SRGAN. Next, the high-quality images are sent to the data augmentation stage, where new data points are created by making small adjustments to the dataset using rotation, random cropping, mirroring, and color-shifting. Next, patch-based feature extraction using Inception V3 and Resnet-50 (PFE-INC-RES) is employed to extract the features from the augmentation. After the features have been extracted, the next step involves processing them and applying transductive long short-term memory (TLSTM) to improve classification accuracy by decreasing the number of false positives. The results of suggested PFE-INC-RES is evaluated using existing methods on the BreakHis dataset, with respect to accuracy (99.84%), specificity (99.71%), sensitivity (99.78%), and F1-score (99.80%), while the suggested PFE-INC-RES performed better in the IDC dataset based on F1-score (99.08%), accuracy (99.79%), specificity (98.97%), and sensitivity (99.17%).}, } @article {pmid38837155, year = {2024}, author = {Wang, WE and Ho, CC and Chang, CH}, title = {Taxane-Induced Cutaneous Toxic Effects.}, journal = {JAMA dermatology}, volume = {160}, number = {7}, pages = {771-772}, doi = {10.1001/jamadermatol.2024.1204}, pmid = {38837155}, issn = {2168-6084}, mesh = {Humans ; *Taxoids/adverse effects ; Female ; Drug Eruptions/etiology/pathology ; Antineoplastic Agents/adverse effects ; Middle Aged ; }, } @article {pmid38831458, year = {2024}, author = {Morla-Barcelo, PM and Laguna-Macarrilla, D and Cordoba, O and Matheu, G and Oliver, J and Roca, P and Nadal-Serrano, M and Sastre-Serra, J}, title = {Unraveling malignant phenotype of peritumoral tissue: transcriptomic insights into early-stage breast cancer.}, journal = {Breast cancer research : BCR}, volume = {26}, number = {1}, pages = {89}, pmid = {38831458}, issn = {1465-542X}, mesh = {Humans ; Female ; *Breast Neoplasms/genetics/pathology/mortality/metabolism ; *Gene Expression Profiling ; *Transcriptome ; *Gene Expression Regulation, Neoplastic ; *Neoplasm Staging ; Prognosis ; *Protein Interaction Maps/genetics ; Middle Aged ; Biomarkers, Tumor/genetics ; Gene Regulatory Networks ; Carcinoma, Ductal, Breast/genetics/pathology/metabolism ; Phenotype ; Neoplasm Recurrence, Local/genetics/pathology ; Aged ; Adult ; }, abstract = {BACKGROUND: Early-stage invasive ductal carcinoma displays high survival rates due to early detection and treatments. However, there is still a chance of relapse of 3-15% after treatment. The aim of this study was to uncover the distinctive transcriptomic characteristics and monitoring prognosis potential of peritumoral tissue in early-stage cases.

METHODS: RNA was isolated from tumoral, peritumoral, and non-tumoral breast tissue from surgical resection of 10 luminal early-stage invasive ductal carcinoma patients. Transcriptome expression profiling for differentially expressed genes (DEGs) identification was carried out through microarray analysis. Gene Ontology and KEGG pathways enrichment analysis were explored for functional characterization of identified DEGs. Protein-Protein Interactions (PPI) networks analysis was performed to identify hub nodes of peritumoral tissue alterations and correlated with Overall Survival and Relapse Free Survival.

RESULTS: DEGs closely related with cell migration, extracellular matrix organization, and cell cycle were upregulated in peritumoral tissue compared to non-tumoral. Analyzing PPI networks, we observed that the proximity to tumor leads to the alteration of gene modules involved in cell proliferation and differentiation signaling pathways. In fact, in the peritumoral area were identified the top ten upregulated hub nodes including CDK1, ESR1, NOP58, PCNA, EZH2, PPP1CA, BUB1, TGFBR1, CXCR4, and CCND1. A signature performed by four of these hub nodes (CDK1, PCNA, EZH2, and BUB1) was associated with relapse events in untreated luminal breast cancer patients.

CONCLUSIONS: In conclusion, our study characterizes in depth breast peritumoral tissue providing clues on the changes that tumor signaling could cause in patients with early-stage breast cancer. We propose that the use of a four gene signature could help to predict local relapse. Overall, our results highlight the value of peritumoral tissue as a potential source of new biomarkers for early detection of relapse and improvement in invasive ductal carcinoma patient's prognosis.}, } @article {pmid38784039, year = {2024}, author = {Ahmad, H and Ali, A and Khalil, AT and Ali, R and Khan, I and Khan, MM and Ahmed, I and Basharat, Z and Alorini, M and Mehmood, A}, title = {Clinico-genomic findings, molecular docking, and mutational spectrum in an understudied population with breast cancer patients from KP, Pakistan.}, journal = {Frontiers in genetics}, volume = {15}, number = {}, pages = {1383284}, pmid = {38784039}, issn = {1664-8021}, abstract = {In this study, we report the mutational profiles, pathogenicity, and their association with different clinicopathologic and sociogenetic factors in patients with Pashtun ethnicity for the first time. A total of 19 FFPE blocks of invasive ductal carcinoma (IDC) from the Breast Cancer (BC) tissue and 6 normal FFPE blocks were analyzed by whole-exome sequencing (WES). Various somatic and germline mutations were identified in cancer-related genes, i.e., ATM, CHEK2, PALB2, and XRCC2. Among a total of 18 mutations, 14 mutations were somatic and 4 were germline. The ATM gene exhibited the maximum number of mutations (11/18), followed by CHEK2 (3/18), PALB2 (3/18), and XRCC2 (1/18). Except one frameshift deletion, all other 17 mutations were nonsynonymous single-nucleotide variants (SNVs). SIFT prediction revealed 7/18 (38.8%) mutations as deleterious. PolyPhen-2 and MutationTaster identified 5/18 (27.7%) mutations as probably damaging and 10/18 (55.5%) mutations as disease-causing, respectively. Mutations like PALB2 p.Q559R (6/19; 31.5%), XRCC2 p.R188H (5/19; 26.31%), and ATM p.D1853N (4/19; 21.05%) were recurrent mutations and proposed to have a biomarker potential. The protein network prediction was performed using GeneMANIA and STRING. ISPRED-SEQ indicated three interaction site mutations which were further used for molecular dynamic simulation. An average increase in the radius of gyration was observed in all three mutated proteins revealing their perturbed folding behavior. Obtained SNVs were further correlated with various parameters related to the clinicopathological status of the tumors. Three mutation positions (ATM p. D1853N, CHEK2 p.M314I, and PALB2 p.T1029S) were found to be highly conserved. Finally, the wild- and mutant-type proteins were screened for two drugs: elagolix (DrugBank ID: DB11979) and LTS0102038 (a triterpenoid, isolated from the anticancer medicinal plant Fagonia indica). Comparatively, a higher number of interactions were noted for normal ATM with both compounds, as compared to mutants.}, } @article {pmid38751260, year = {2024}, author = {Shirazi, B and Niaz, M and Khan, MA}, title = {The characteristics and risk factors of breast cancer patients trend distinctive regional differences: a cross-sectional study.}, journal = {JPMA. The Journal of the Pakistan Medical Association}, volume = {74}, number = {4}, pages = {672-676}, doi = {10.47391/JPMA.9360}, pmid = {38751260}, issn = {0030-9982}, mesh = {Humans ; Female ; *Breast Neoplasms/epidemiology/pathology ; Cross-Sectional Studies ; Pakistan/epidemiology ; Middle Aged ; Risk Factors ; Adult ; Retrospective Studies ; Male ; Neoplasm Staging ; Breast Neoplasms, Male/epidemiology/pathology ; Breast Feeding/statistics & numerical data ; Carcinoma, Ductal, Breast/epidemiology/pathology ; Parity ; Aged ; Neoplasm Grading ; Marital Status ; }, abstract = {OBJECTIVE: To determine the characteristics and risk factors of breast cancer patients in a tertiary care setting.

METHODS: The retrospective, cross-sectional study was conducted at the Sindh Institute of Urology and Transplantation, Karachi, and comprised data of all patients diagnosed with breast cancer from March 2017 to December 2021. Demographic characteristics, clinical presentation, stage of the disease and histopathological characteristics were noted. Data related to all the variables was not available in all cases. Data was analysed using SPSS 23.

RESULTS: Of the 690 patients, 683(99%) were females and 7(1%) were males. The mean age at presentation was 49.3±13.5 years, while the mean duration of symptoms was 10.24±17.64) months. Most of the females were married 642(93%) and multiparous 484(70.9%), while 293(42.5%) had breastfed their children for >1 year, and 412(59.7%) had no history of contraception use. The most common stage at presentation was stage II (48.6%), and most patients had grade II 395(57.2%) invasive ductal carcinoma, with Luminal A molecular subtype noted in 287(41.6%) cases.

CONCLUSIONS: The characteristics of breast cancer in the sample had certain distinctions compared to other populations. It is important to integrate all datasets and develop guidelines appropriate to Pakistani population.}, } @article {pmid38741627, year = {2024}, author = {Ahuja, S and G, K and Zaheer, S}, title = {Evaluation of Histomorphological Changes in Breast Cancer Post-Neoadjuvant Chemotherapy.}, journal = {Indian journal of surgical oncology}, volume = {15}, number = {2}, pages = {236-240}, pmid = {38741627}, issn = {0975-7651}, abstract = {Breast cancer, a leading cause of global female mortality, demands comprehensive diagnostic and therapeutic strategies. This study delves into the nuanced realm of post-neoadjuvant chemotherapy breast cancer specimens, emphasizing the imperative need for pathologists to discern stromal and nuclear alterations adeptly. The investigation, encompassing 100 female patients with a mean age of 47.5 years, elucidates the demographic and clinicopathological parameters. Predominantly presenting as palpable lumps (85%), invasive ductal carcinoma emerged as the predominant histological type (98%). The primary focus of the study revolves around the morphological changes post-neoadjuvant chemotherapy, with a meticulous qualitative analysis encompassing stromal elements (fibrosis, elastosis, calcification) and nuclear features (pyknosis, hyperchromasia). Notably, the response to chemotherapy, classified by the International Union against Cancer criteria, delineates a substantial pathological complete response (55%), partial response (35%), and limited non-response (10%). The therapeutic landscape includes a majority of cases undergoing extensive chemotherapy cycles, primarily featuring the cyclophosphamide, doxorubicin, and paclitaxel regimen. Remarkably, this investigation unveils fibrosis (63%) and elastosis/collagenization (51%) as prevalent stromal changes, while pyknosis (58%) and hyperchromasia (48%) dominate nuclear alterations. In conclusion, this retrospective study provides a comprehensive overview of post-neoadjuvant chemotherapy breast cancer specimens, shedding light on the intricate interplay of clinical parameters, treatment responses, and histopathological changes. The findings underscore the pivotal role of pathologists in accurately diagnosing and grading tumors in the evolving landscape of breast cancer management.}, } @article {pmid38734115, year = {2024}, author = {Clark, AB and Conzen, SD}, title = {Glucocorticoid receptor-mediated oncogenic activity is dependent on breast cancer subtype.}, journal = {The Journal of steroid biochemistry and molecular biology}, volume = {243}, number = {}, pages = {106518}, doi = {10.1016/j.jsbmb.2024.106518}, pmid = {38734115}, issn = {1879-1220}, mesh = {Humans ; *Receptors, Glucocorticoid/metabolism/genetics ; Female ; *Breast Neoplasms/pathology/metabolism/genetics ; Receptors, Estrogen/metabolism/genetics ; Signal Transduction ; Gene Expression Regulation, Neoplastic ; Triple Negative Breast Neoplasms/genetics/pathology/metabolism/classification ; Animals ; Carcinogenesis/genetics/metabolism ; }, abstract = {Breast cancer incidence has been steadily rising and is the leading cause of cancer death in women due to its high metastatic potential. Individual breast cancer subtypes are classified by both cell type of origin and receptor expression, namely estrogen, progesterone and human epidermal growth factor receptors (ER, PR and HER2). Recently, the importance and context-dependent role of glucocorticoid receptor (GR) expression in the natural history and prognosis of breast cancer subtypes have been uncovered. In ER-positive breast cancer, GR expression is associated with a better prognosis as a result of ER-GR crosstalk. GR appears to modulate ER-mediated gene expression resulting in decreased tumor cell proliferation and a more indolent cancer phenotype. In ER-negative breast cancer, including GR-positive triple-negative breast cancer (TNBC), GR expression enhances migration, chemotherapy resistance and cell survival. In invasive lobular carcinoma, GR function is relatively understudied, and more work is required to determine whether lobular subtypes behave similarly to their invasive ductal carcinoma counterparts. Importantly, understanding GR signaling in individual breast cancer subtypes has potential clinical implications because of the recent development of highly selective GR non-steroidal ligands, which represent a therapeutic approach for modulating GR activity systemically.}, } @article {pmid38699697, year = {2024}, author = {Geng, J and Jinli, S and Guo, W and Li, H and Dan, Y and Gao, Y}, title = {Expression and clinical significance of CA125, CA153 and CEA in nipple discharge of breast cancer patients.}, journal = {Journal of medical biochemistry}, volume = {43}, number = {2}, pages = {234-242}, pmid = {38699697}, issn = {1452-8258}, abstract = {BACKGROUND: It is an important clinical means to identify benign and malignant breast diseases caused by nipple discharge through the detection and analysis of components in nipple discharge. This study was aimed to test the expression and clinical significance of carbohydrate antigen 125 (CA125), carbohydrate antigen 153 (CA153) and carcinoembryonic antigen (CEA) in nipple discharge of breast cancer patients.

METHODS: From January 2017 to December 2018, 86 patients with invasive ductal carcinoma of the breast with nipple discharge (breast cancer group) and 50 patients with ordinary breast duct hyperplasia with nipple discharge (benign control group) were selected, and the levels of CA125, CA153 and CEA in nipple discharge and serum were detected by electrochemiluminescence immunoassay.}, } @article {pmid38695948, year = {2024}, author = {Agreda-Castañeda, F and Freixa-Sala, R and Franco, M and Bultó-Gonzalvo, R and Areal-Calama, J}, title = {Predictive factors of post-HoLEP incontinence: differences between stress and urgency urinary incontinence.}, journal = {World journal of urology}, volume = {42}, number = {1}, pages = {281}, pmid = {38695948}, issn = {1433-8726}, mesh = {Humans ; Male ; *Urinary Incontinence, Stress/surgery/epidemiology ; *Urinary Incontinence, Urge/epidemiology/etiology ; Aged ; Middle Aged ; *Prostatectomy/methods ; Postoperative Complications/epidemiology/etiology ; Retrospective Studies ; Risk Factors ; Prostatic Hyperplasia/surgery/complications ; Urodynamics/physiology ; Age Factors ; }, abstract = {INTRODUCTION: The analysis of post-HoLEP urinary incontinence (UI) has traditionally focused on stress UI. Our aim is to evaluate the factors associated with stress and urgency UI in the first month after the surgery.

METHODS: Data were obtained from patients who underwent HoLEP by the same experienced surgeon. UI was evaluated at one month and at 6 months after the surgery. Three groups were defined: continent patients, patients with pure urgency UI and patients with stress or mixed UI. Preoperative, intraoperative, urodynamic and clinical variables were analyzed and compared between the three groups.

RESULTS: In total, 235 subjects were included. One month after the surgery, 156 (66.5%) were continent (group 1), 49 (20.8%) reported pure urgency UI (group 2), and 30 (12.7%) reported some level of stress UI (group 3). In Group 2, the factors associated with urgency UI in the univariate analysis were age, presurgical urgency UI, having diabetes or hypertension. In Group 3, age, prostatic volume, preoperative PSA, time of enucleation, weight of the resection in grams, having an IDC or being diabetic were significant in the univariate analysis. In the multivariate analysis, age predicts both types of UI, while prostatic volume and having an IDC predict stress or mixed UI.

CONCLUSION: In the first month post-HoLEP, age is a predictive factor of urgency UI and stress UI. In addition, prostatic volume and the presence of an indwelling urinary catheter are predictive factors of stress UI.}, } @article {pmid38695332, year = {2024}, author = {Iradukunda, Y and Kang, JY and Zhao, XB and Fu, XK and Nsanzamahoro, S and Ha, W and Shi, YP}, title = {Triple Sensing Modes for Triggered β-Galactosidase Activity Assays Based on Kaempferol-Deduced Silicon Nanoparticles and Biological Imaging of MCF-7 Breast Cancer Cells.}, journal = {ACS applied bio materials}, volume = {7}, number = {5}, pages = {3154-3163}, doi = {10.1021/acsabm.4c00185}, pmid = {38695332}, issn = {2576-6422}, mesh = {Female ; Humans ; *beta-Galactosidase/metabolism ; Biocompatible Materials/chemistry/pharmacology/chemical synthesis ; *Breast Neoplasms/diagnosis/pathology ; Colorimetry ; *Kaempferols/chemistry/pharmacology ; MCF-7 Cells ; Molecular Structure ; *Nanoparticles/chemistry ; Particle Size ; *Silicon/chemistry ; }, abstract = {β-Galactosidase (β-Gala) is an essential biomarker enzyme for early detection of breast tumors and cellular senescence. Creating an accurate way to monitor β-Gala activity is critical for biological research and early cancer detection. This work used fluorometric, colorimetric, and paper-based color sensing approaches to determine β-Gala activity effectively. Via the sensing performance, the catalytic activity of β-Gala resulted in silicon nanoparticles (SiNPs), fluorescent indicators obtained via a one-pot hydrothermal process. As a standard enzymatic hydrolysis product of the substrate, kaempferol 3-O-β-d-galactopyranoside (KOβDG) caused the fluorometric signal to be attenuated on kaempferol-silicon nanoparticles (K-SiNPs). The sensing methods demonstrated a satisfactory linear response in sensing β-Gala and a low detection limit. The findings showed the low limit of detection (LOD) as 0.00057 and 0.098 U/mL for fluorometric and colorimetric, respectively. The designed probe was then used to evaluate the catalytic activity of β-Gala in yogurt and human serum, with recoveries ranging from 98.33 to 107.9%. The designed sensing approach was also applied to biological sample analysis. In contrast, breast cancer cells (MCF-7) were used as a model to test the in vitro toxicity and molecular fluorescence imaging potential of K-SiNPs. Hence, our fluorescent K-SiNPs can be used in the clinic to diagnose breast cellular carcinoma, since they can accurately measure the presence of invasive ductal carcinoma in serologic tests.}, } @article {pmid38684702, year = {2024}, author = {de Oliveira, RM and Paiva, MUB and Picossi, CRC and Paiva, DVN and Ricart, CAO and Ruperez, FJ and Barbas, C and Atik, FA and Martins, AMA}, title = {Metabolomic insights in advanced cardiomyopathy of chronic chagasic and idiopathic patients that underwent heart transplant.}, journal = {Scientific reports}, volume = {14}, number = {1}, pages = {9810}, pmid = {38684702}, issn = {2045-2322}, support = {EADS CASA 002/DCTA-COPAC/2014//Airbus Spain/ ; }, mesh = {Humans ; *Heart Transplantation ; Male ; Female ; Middle Aged ; *Chagas Cardiomyopathy/metabolism/blood ; *Metabolomics/methods ; *Cardiomyopathy, Dilated/metabolism/surgery/blood ; Adult ; Metabolome ; Heart Failure/metabolism/etiology ; Aged ; Chronic Disease ; Gas Chromatography-Mass Spectrometry ; }, abstract = {Heart failure (HF) studies typically focus on ischemic and idiopathic heart diseases. Chronic chagasic cardiomyopathy (CCC) is a progressive degenerative inflammatory condition highly prevalent in Latin America that leads to a disturbance of cardiac conduction system. Despite its clinical and epidemiological importance, CCC molecular pathogenesis is poorly understood. Here we characterize and discriminate the plasma metabolomic profile of 15 patients with advanced HF referred for heart transplantation - 8 patients with CCC and 7 with idiopathic dilated cardiomyopathy (IDC) - using gas chromatography/quadrupole time-of-flight mass spectrometry. Compared to the 12 heart donor individuals, also included to represent the control (CTRL) scenario, patients with advanced HF exhibited a metabolic imbalance with 21 discriminating metabolites, mostly indicative of accumulation of fatty acids, amino acids and important components of the tricarboxylic acid (TCA) cycle. CCC vs. IDC analyses revealed a metabolic disparity between conditions, with 12 CCC distinctive metabolites vs. 11 IDC representative metabolites. Disturbances were mainly related to amino acid metabolism profile. Although mitochondrial dysfunction and loss of metabolic flexibility may be a central mechanistic event in advanced HF, metabolic imbalance differs between CCC and IDC populations, possibly explaining the dissimilar clinical course of Chagas' patients.}, } @article {pmid38680708, year = {2024}, author = {Shaghaghi Torkdari, Z and Khalaj-Kondori, M and Hosseinpour Feizi, MA}, title = {Plasma Circulating Terminal Differentiation-Induced Non-Coding RNA Serves as a Biomarker in Breast Cancer.}, journal = {International journal of hematology-oncology and stem cell research}, volume = {18}, number = {1}, pages = {1-6}, pmid = {38680708}, issn = {2008-3009}, abstract = {Background: Breast cancer is identified as the most common malignancy and cause of cancer-related death worldwide. Compared with healthy controls, this study evaluated the expression level and diagnostic power of lncRNA plasma TINCR in breast cancer patients. Materials and Methods: Fifty-eight women diagnosed with invasive ductal carcinoma and fifty healthy age- matched controls were included in the study. TRIzol[®] LS regent was used to isolate the total RNA from the whole plasma. Total RNA was converted to cDNA using Prime Script[TM] RT reagent kit and the expression levels of TINCR were quantified by qRT-PCR. Results: Low levels of TINCR lncRNA were observed in the plasma of breast cancer patients compared with control subjects. Plasma TINCR level was also positively correlated with the diagnostic age of breast cancer patients. Conclusion: A low level of plasma TINCR could discriminate breast cancer patients from healthy control subjects.}, } @article {pmid38677859, year = {2024}, author = {de Souza, IC and Langer, FW}, title = {Post-radiation angiosarcoma of the breast in a patient with a history of invasive ductal carcinoma.}, journal = {Lancet (London, England)}, volume = {403}, number = {10437}, pages = {1681-1682}, doi = {10.1016/S0140-6736(24)00688-3}, pmid = {38677859}, issn = {1474-547X}, mesh = {Female ; Humans ; Middle Aged ; *Breast Neoplasms/radiotherapy ; *Carcinoma, Ductal, Breast/radiotherapy ; *Hemangiosarcoma/etiology ; *Neoplasms, Radiation-Induced/etiology ; Neoplasms, Second Primary/etiology ; }, } @article {pmid38672600, year = {2024}, author = {Yousef, YA and Mohammad, M and Khalil, H and Khouri, T and Alsweiti, R and Khzouz, J and Abu Laban, D and Jaradat, I and Ibrahimi, AK and Al-Ibraheem, A and Masri, MA and AlNawiaseh, I and Abdel-Razeq, H}, title = {Ocular and Periocular Metastasis in Breast Cancer: Clinical Characteristics, Prognostic Factors and Treatment Outcome.}, journal = {Cancers}, volume = {16}, number = {8}, pages = {}, pmid = {38672600}, issn = {2072-6694}, abstract = {BACKGROUND: Breast cancer remains a leading cause of cancer-related mortality and morbidity worldwide. Ocular and periocular metastasis present as a rare but clinically significant manifestation. This study aims to explore demographics and clinical aspects of ocular and periocular metastasis in breast cancer patients.

METHODS: A retrospective cohort study comprising 45 breast cancer patients with ocular or periocular metastasis treated between 2013 and 2023. Patient demographics, tumor characteristics, diagnostic methods, treatment modalities, visual outcomes, and survival data were analyzed.

RESULTS: Among 9902 breast cancer patients, 0.5% developed ocular or periocular metastasis, constituting 2.4% of metastatic cases. The median age was 50 years. Ocular metastasis timing varied: 5% before breast cancer, 24% concurrent, 22% within a year, and 49% after. The most common presentations included incidental MRI findings (42%) and vision decline (31%). Metastasis involved the orbit (47%), choroid (40%), optic nerve (11%), and iris (2%), with 44% having bilateral involvement. Predictive factors included invasive lobular carcinoma (ILC) (p < 0.0001) and brain metastasis (p < 0.0001), with ILC exhibiting a sixfold higher likelihood of ocular metastasis than invasive ductal carcinoma (IDC). Primary treatment was radiation therapy (89%), yielding a 55% maintenance of excellent vision (<0.5), with 93% developing dry eye disease. Patients with ocular metastasis faced an increased risk of disease-related mortality (p < 0.0001), with 71% succumbing within 10 months post-diagnosis.

CONCLUSIONS: Ocular metastasis in breast cancer is rare (0.5%) but signifies poor outcome. It is linked to ILC and concurrent brain metastasis. Primary treatment involves radiation therapy, with a favorable visual prognosis.}, } @article {pmid38656713, year = {2024}, author = {Kikuchi, M and Miyabe, R and Matsushima, H and Kita, H and Kobayashi, J and Ando, T and Atsuta, K and Shintani, T}, title = {Tumor lysis syndrome following letrozole for locally advanced breast cancer: a case report.}, journal = {Surgical case reports}, volume = {10}, number = {1}, pages = {100}, pmid = {38656713}, issn = {2198-7793}, abstract = {BACKGROUND: Letrozole, an aromatase inhibitor, is used to treat breast cancer in postmenopausal women. Tumor lysis syndrome (TLS) is a complication that can trigger multiple organ failure caused by the release of intracellular nucleic acids, phosphate, and potassium into the blood due to rapid tumor cell disintegration induced by drug therapy. TLS is uncommon in solid tumors and occurs primarily in patients receiving chemotherapy. Herein, we report a rare occurrence of TLS that developed in a patient with locally advanced breast cancer following treatment with letrozole.

CASE PRESENTATION: An 80-year-old woman with increased bleeding from a fist-sized left-sided breast mass presented to our hospital. Histological examination led to a diagnosis of invasive ductal carcinoma of the luminal type. The patient refused chemotherapy and was administered hormonal therapy with letrozole. Seven days after letrozole initiation, she complained of anorexia and diarrhea. Blood test results revealed elevated blood urea nitrogen (BUN) and creatinine (Cr) levels, and she was admitted to our hospital for intravenous infusions. On the second day after admission, marked elevations of LDH, BUN, Cr, potassium, calcium, and uric acid levels were observed. Furthermore, metabolic acidosis and prolonged coagulation capacity were observed. We suspected TLS and discontinued letrozole, and the patient was treated with hydration, febuxostat, and maintenance hemodialysis. On the third day after admission, her respiratory status worsened because of acute respiratory distress syndrome associated with hypercytokinemia, and she was intubated. On the fourth day after admission, her general condition did not improve, and she died.

CONCLUSIONS: Although TLS typically occurs after chemotherapy initiation, the findings from the present case confirm that this syndrome can also occur after hormonal therapy initiation and should be treated with caution.}, } @article {pmid38644311, year = {2024}, author = {Satoh, E and Innami, Y and Uehira, D and Yonekura, K and Murakata, A and Ohinata, R and Toyofuku, Y and Tanami, H and Osanai, T and Sugano, N and Sakoma, T}, title = {[A Long-Surviving Case of Locally Advanced Breast Cancer with Multiple Lung Metastasis].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {51}, number = {4}, pages = {427-429}, pmid = {38644311}, issn = {0385-0684}, mesh = {Humans ; Female ; *Breast Neoplasms/pathology/drug therapy ; *Lung Neoplasms/secondary/drug therapy ; Aged ; *Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Time Factors ; Carcinoma, Ductal, Breast/secondary/therapy/drug therapy ; Mastectomy ; }, abstract = {We report a case of right advanced breast cancer with multiple lung metastases in a 66-year-old woman. Her breast cancer(invasive ductal carcinoma, cT4bN1M1, Stage Ⅳ)was resected in October 2007(mastectomy plus axillary lymph node dissection)after local arterial infusion therapy(total dose 5-FU 4,735 mg plus adriamycin 180 mg), which caused bilateral lung arterial embolism due to deep vein thrombosis in right her leg. She had to be treated by anticoagulant therapy, mechanical ventilation and placement of IVC filter before her operation. Subsequent chemo-endocrine therapy(docetaxel 6 courses plus anastrozole)was continued. In October 2008, a CT scan showed disappearance of multiple lung metastases (complete response). In November 2015 (8 years after her operation), a CT scan showed recurrence of multiple lung metastases and endocrine therapy was changed to tamoxifen. A year later, a CT scan showed disappearance of multiple lung metastases(complete response)again and keep a condition of complete response in her breast cancer until May 2023 (15 years after her operation).}, } @article {pmid38638844, year = {2024}, author = {Zhou, H and Liu, D and Chen, L and Zhang, Y and Zhao, X and Ge, Y and Liu, M and Kong, T}, title = {Metastasis to the bladder from primary breast cancer: A case report and literature review.}, journal = {Oncology letters}, volume = {27}, number = {6}, pages = {249}, pmid = {38638844}, issn = {1792-1082}, abstract = {Breast cancer is the most prevalent malignant tumor affecting women and represents the leading cause of female cancer-related mortality worldwide. Although distant organ metastasis accounts for the majority of breast cancer-related deaths, reports on bladder metastasis are limited in the existing literature. The present study describes the case of a patient with bladder metastasis originating from breast cancer. In addition, the present study also provides a review of 54 cases of similar disease that have been documented in the currently available literature. The literature review aims to elucidate the clinicopathological characteristics and therapeutic approaches for such conditions. The median time from breast cancer diagnosis to bladder metastasis was found to be 5.6 years (range, 0-28 years). The origin of the bladder metastases was predominantly invasive ductal carcinoma (IDC) accounting for 52.3% of cases, followed by invasive lobular carcinoma, accounting for 40.9% of cases. The pathology in the primary tumor was the same as the pathology of the bladder metastases in all cases. There was an 88.9% concordance rate for estrogen receptor status, while the progesterone receptor status was 83.3% and the human epidermal growth factor receptor 2 expression status was 100%. The primary initial symptoms included urinary system manifestations, such as increased frequency, urgency, dysuria, urinary incontinence, nocturia and gross hematuria. For the cystoscopic examination, the predominant findings were bladder wall thickening or masses, along with ureteral orifice masses. Overall, the present study demonstrated that the occurrence of bladder metastasis often follows the metastasis of other organs, with IDC being the most prevalent subtype. The pathological characteristics between the primary tumor and bladder metastasis exhibit a high degree of concordance.}, } @article {pmid38624259, year = {2024}, author = {Petrakis, IL and Meshberg-Cohen, S and Nich, C and Kelly, MM and Claudio, T and Jane, JS and Pisani, E and Ralevski, E}, title = {Cognitive processing therapy (CPT) versus individual drug counseling (IDC) for PTSD for veterans with opioid use disorder maintained on buprenorphine.}, journal = {The American journal on addictions}, volume = {33}, number = {5}, pages = {525-533}, doi = {10.1111/ajad.13557}, pmid = {38624259}, issn = {1521-0391}, support = {1 I01 CX001517-01//VA MERIT grant, Division of Clinical Science Research and Development/ ; }, mesh = {Humans ; *Stress Disorders, Post-Traumatic/therapy/drug therapy/psychology/complications ; *Buprenorphine/therapeutic use ; *Veterans/psychology ; Male ; *Opioid-Related Disorders/drug therapy/therapy/psychology/complications ; *Cognitive Behavioral Therapy/methods ; *Opiate Substitution Treatment/methods ; Middle Aged ; Female ; Counseling/methods ; Adult ; Narcotic Antagonists/therapeutic use ; }, abstract = {BACKGROUND AND OBJECTIVES: There are high rates of comorbidity between posttraumatic stress disorder (PTSD) and opioid use disorder (OUD). Evidence-based trauma-focused psychotherapies such as Cognitive Processing Therapy (CPT) are a first-line treatment for PTSD. Veterans with OUD are treated primarily in substance use disorder (SUD) clinics where the standard of care is drug counseling; they often do not have access to first-line PTSD treatments. This study tested whether CPT can be conducted safely and effectively in veterans with comorbid OUD treated with buprenorphine.

METHODS: This 12-week, 2-site, randomized clinical trial (RCT) included open-label randomization to two groups: (a) CPT versus (b) Individual Drug Counselling (IDC) in veterans with PTSD and comorbid OUD who were maintained on buprenorphine (N = 38).

RESULTS: Veterans randomized to either IDC (n = 18) or CPT (n = 20) showed a significant reduction in self-reported PTSD symptoms over time as measured by the PTSD checklist (PCL-5) but there were no treatment group differences; there was some indication that reduction in PTSD symptoms in the CPT group were sustained in contrast to the IDC group. Recruitment was significantly impacted by COVID-19 pandemic, so this study serves as a proof-of-concept pilot study.

DISCUSSION AND CONCLUSIONS: Veterans with OUD and PTSD can safely and effectively participate in evidence-based therapy for PTSD; further work should confirm that trauma-focused treatment may be more effective in leading to sustained remission of PTSD symptoms than drug counseling.

SCIENTIFIC SIGNIFICANCE: This is the first study to evaluate CPT for PTSD in the context of buprenorphine treatment for OUD.}, } @article {pmid38577141, year = {2024}, author = {Sukhija, S and Purohit, P and Pareek, P and Garg, PK and Vishnoi, JR and Elhence, PA and Varthya, SB and Sharma, P and Ambwani, S and Charan, J}, title = {Circulating miRNA-21 Levels in Breast Cancer Patients Before and After Chemotherapy and Its Association with Clinical Improvement.}, journal = {Indian journal of clinical biochemistry : IJCB}, volume = {39}, number = {2}, pages = {214-220}, pmid = {38577141}, issn = {0970-1915}, abstract = {Breast cancer is the most frequent type of cancer in women, many patients experience recurrences and metastasis. miR-21 (microRNA-21) as biomarker is under investigation for breast cancer. At present, there is very limited information available regarding effect of chemotherapy on miR-21 expression in breast cancer and its correlation with the clinical improvement. Hence, this study was planned to evaluate the effect of chemotherapy on miR-21 in metastatic breast cancer and its relationship with the clinical outcome. Females, aged-18-90 years diagnosed with Invasive Ductal Carcinoma of breast and candidate of neoadjuvant chemotherapy including Adriamycin (60 mg/m[2]), Cyclophosphamide (600 mg/m[2]) with or without Taxane (75-175 mg/m[2]) were included in the study. Before and after 42 days of staring of chemotherapy sample was collected for circulatory miR-21 and RECIST 1.1 criteria was applied to assess the clinical status. Blood samples for routine clinical biomarkers including liver function test and renal function tests was also collected. miR-21 expression before and after chemotherapy was assessed using standard method based on real time PCR. Expression of miR-21, RECIST criteria and other liver and kidney related biomarkers were compared before and after chemotherapy. After neoadjuvant chemotherapy expression of miR-21 was significantly increased by 5.65-fold. There was significant improvement in clinical scores based on RECIST criteria (0.046). No significant correlation was observed between miR-21 expression and difference in RECIST score (r = - 0.122, p = 0.570). Neoadjuvant chemotherapy causes clinical improvement in breast cancer patients however it is not correlated with the miR-21 expression which significantly increased after chemotherapy.}, } @article {pmid38576929, year = {2024}, author = {Jamal, O and Makhchoune, M and Laidi, A and Misbahi, T and Haouas, MY and Chellaoui, A and Bertal, A and Hilmani, S and Ibahiouine, K and Naja, A and Lakhder, A}, title = {Rupture of a dermoid cyst in the subarachnoid space: a case report.}, journal = {Annals of medicine and surgery (2012)}, volume = {86}, number = {4}, pages = {2366-2369}, pmid = {38576929}, issn = {2049-0801}, abstract = {INTRODUCTION AND IMPORTANCE: Intracranial dermoid cysts (IDC) are defined as rare, slow-growing cystic congenital neoplasms. Rupture of an intracranial dermoid cyst occurs rarely and most often spontaneously and results in potentially serious symptoms.

CASE PRESENTATION: A39-year-old female, with mechanical prosthetic heart valve presented with history of headache for 10 months and generalized tonicoclonic seizures. On the admission, the patient had a normal neurological and cranial nerve exam. The authors performed a computed tomography of the brain, The MRI could not be performed because of the presence of the prosthetic valve, revealed rupture of the dermoid cyst in the bilateral subarachnoid spaces. The patient underwent a large temporal craniotomy and the tumour was well exposed and completely removed without incident, the histopathological examination concludes to dermoid cyst, the patient recovered well from surgery.

CLINICAL DISCUSSION: Rupture is a very rare phenomenon. there are about 60 cases reported in the literature. the contents of the cyst disseminate into the subarachnoid and ventricular spaces in the event of rupture. A variety of clinical symptoms is usually caused. The mechanism of spontaneous rupture of the dermoid cyst is unclear. Among the proposed mechanisms is a rapid expansion of the cyst. Complete surgical resection of dermoid cysts is the only effective treatment for the prevention of recurrences and/or complications.

CONCLUSION: Rupture of an intracranial dermoid cyst is associated with significant morbidity and mortality, although it remains a rare phenomenon. Surgical excision should be considered as soon as the diagnosis is made in order to prevent more severe intracranial complication.}, } @article {pmid38571894, year = {2024}, author = {Maiti, S and Nayak, S and Hebbar, KD and Pendem, S}, title = {Differentiation of invasive ductal and lobular carcinoma of the breast using MRI radiomic features: a pilot study.}, journal = {F1000Research}, volume = {13}, number = {}, pages = {91}, pmid = {38571894}, issn = {2046-1402}, mesh = {Female ; Humans ; *Carcinoma, Lobular/diagnostic imaging/pathology ; Pilot Projects ; Retrospective Studies ; Radiomics ; *Breast Neoplasms/diagnostic imaging/pathology ; Magnetic Resonance Imaging/methods ; }, abstract = {BACKGROUND: Breast cancer (BC) is one of the main causes of cancer-related mortality among women. For clinical management to help patients survive longer and spend less time on treatment, early and precise cancer identification and differentiation of breast lesions are crucial. To investigate the accuracy of radiomic features (RF) extracted from dynamic contrast-enhanced Magnetic Resonance Imaging (DCE MRI) for differentiating invasive ductal carcinoma (IDC) from invasive lobular carcinoma (ILC).

METHODS: This is a retrospective study. The IDC of 30 and ILC of 28 patients from Dukes breast cancer MRI data set of The Cancer Imaging Archive (TCIA), were included. The RF categories such as shape based, Gray level dependence matrix (GLDM), Gray level co-occurrence matrix (GLCM), First order, Gray level run length matrix (GLRLM), Gray level size zone matrix (GLSZM), NGTDM (Neighbouring gray tone difference matrix) were extracted from the DCE-MRI sequence using a 3D slicer. The maximum relevance and minimum redundancy (mRMR) was applied using Google Colab for identifying the top fifteen relevant radiomic features. The Mann-Whitney U test was performed to identify significant RF for differentiating IDC and ILC. Receiver Operating Characteristic (ROC) curve analysis was performed to ascertain the accuracy of RF in distinguishing between IDC and ILC.

RESULTS: Ten DCE MRI-based RFs used in our study showed a significant difference (p <0.001) between IDC and ILC. We noticed that DCE RF, such as Gray level run length matrix (GLRLM) gray level variance (sensitivity (SN) 97.21%, specificity (SP) 96.2%, area under curve (AUC) 0.998), Gray level co-occurrence matrix (GLCM) difference average (SN 95.72%, SP 96.34%, AUC 0.983), GLCM interquartile range (SN 95.24%, SP 97.31%, AUC 0.968), had the strongest ability to differentiate IDC and ILC.

CONCLUSIONS: MRI-based RF derived from DCE sequences can be used in clinical settings to differentiate malignant lesions of the breast, such as IDC and ILC, without requiring intrusive procedures.}, } @article {pmid38553788, year = {2024}, author = {Dreindl, R and Bolsa-Ferruz, M and Fayos-Sola, R and Padilla Cabal, F and Scheuchenpflug, L and Elia, A and Amico, A and Carlino, A and Stock, M and Grevillot, L}, title = {Commissioning and clinical implementation of an independent dose calculation system for scanned proton beams.}, journal = {Journal of applied clinical medical physics}, volume = {25}, number = {5}, pages = {e14328}, pmid = {38553788}, issn = {1526-9914}, mesh = {Humans ; *Proton Therapy/methods ; *Radiotherapy Dosage ; *Radiotherapy Planning, Computer-Assisted/methods ; *Software ; *Organs at Risk/radiation effects ; Quality Assurance, Health Care/standards ; Phantoms, Imaging ; Radiotherapy, Intensity-Modulated/methods ; Calibration ; Neoplasms/radiotherapy ; Tomography, X-Ray Computed/methods ; Algorithms ; }, abstract = {PURPOSE: Experimental patient-specific QA (PSQA) is a time and resource-intensive process, with a poor sensitivity in detecting errors. Radiation therapy facilities aim to substitute it by means of independent dose calculation (IDC) in combination with a comprehensive beam delivery QA program. This paper reports on the commissioning of the IDC software tool myQA iON (IBA Dosimetry) for proton therapy and its clinical implementation at the MedAustron Ion Therapy Center.

METHODS: The IDC commissioning work included the validation of the beam model, the implementation and validation of clinical CT protocols, and the evaluation of patient treatment data. Dose difference maps, gamma index distributions, and pass rates (GPR) have been reviewed. The performance of the IDC tool has been assessed and clinical workflows, simulation settings, and GPR tolerances have been defined.

RESULTS: Beam model validation showed agreement of ranges within ± 0.2 mm, Bragg-Peak widths within ± 0.1 mm, and spot sizes at various air gaps within ± 5% compared to physical measurements. Simulated dose in 2D reference fields deviated by -0.3% ± 0.5%, while 3D dose distributions differed by 1.8% on average to measurements. Validation of the CT calibration resulted in systematic differences of 2.0% between IDC and experimental data for tissue like samples. GPRs of 99.4 ± 0.6% were found for head, head and neck, and pediatric CT protocols on a 2%/2 mm gamma criterion. GPRs for the adult abdomen protocol were at 98.9% on average with 3%/3 mm. Root causes of GPR outliers, for example, implants were identified and evaluated.

CONCLUSION: IDC has been successfully commissioned and integrated into the MedAustron clinical workflow for protons in 2021. IDC has been stepwise and safely substituting experimental PSQA since February 2021. The initial reduction of proton experimental PSQA was about 25% and reached up to 90% after 1 year.}, } @article {pmid38539179, year = {2024}, author = {Esmat, E and Haidary, AM and Saadaat, R and Rizvi, SN and Aleena, S and Haidari, M and Hofiani, SMS and Hussaini, N and Hakimi, A and Khairy, A and Abdul-Ghafar, J}, title = {Association of hormone receptors and human epidermal growth factor receptor-2/neu expressions with clinicopathologic factors of breast carcinoma: a cross-sectional study in a tertiary care hospital, Kabul, Afghanistan.}, journal = {BMC cancer}, volume = {24}, number = {1}, pages = {388}, pmid = {38539179}, issn = {1471-2407}, mesh = {Adult ; Aged ; Female ; Humans ; Middle Aged ; Afghanistan/epidemiology ; Biomarkers, Tumor/metabolism ; *Breast Neoplasms/epidemiology/genetics/metabolism ; Cross-Sectional Studies ; Hormones ; *Receptor, ErbB-2/metabolism ; Receptors, Progesterone/metabolism ; Tertiary Care Centers ; }, abstract = {BACKGROUND: Breast cancer (BC) is one of the major causes of death worldwide. It is the most common cause of death before the age of 70 years. The incidence and mortality of BC are rapidly increasing, posing great challenges to the health system and economy of every nation.

METHODOLOGY: A cross-sectional analytical study was conducted at the Department of Pathology and Clinical Laboratory of the French Medical Institute for Mothers and Children (FMIC) to demonstrate the association of human epidermal growth factor receptor 2 (Her2/Neu) and estrogen receptor (ER)/ progesterone receptor (PR) with clinical as well as pathological parameters among women with BC. A consecutive nonprobability sampling method was used for this study over a span of one and a half years.

RESULTS: One hundred twenty participants diagnosed with breast cancer were included in the study. The mean age at diagnosis was 44.58 ± 11.16 years. Out of the total patients, 68 (56.7%) were above 40 years old, 108 (90%) were married, 94 (78.3%) were multiparous, and 88 (73.3%) had a history of breastfeeding. 33.3% of cases were within the age range of menopause (40-50 years). The positive expression rates of ER, PR, and Her2/neu were found to be 48.8%, 44.6%, and 44.6%, respectively, and Her2/neu overexpression was found to be higher among ER/PR-negative cases.

CONCLUSION: In our study, we demonstrated that among Afghan women, grade II invasive ductal carcinoma, not otherwise specified, was the most common type of BC and frequently affected women above the age of 40. We also revealed that the percentage of negative ER (50.4%), negative PR (54.4%), and concordant ER/PR-negative cases were high compared to other possibilities. Additionally, the study revealed that expression of Her2/neu was in contrast with the expression of ER and PR receptors. The findings of our study still support the importance of performing immunohistochemical stains for hormonal receptor classification in terms of better clinical outcomes and prognosis.}, } @article {pmid38525191, year = {2024}, author = {Lopez-Vazquez, P and Fernandez-Caggiano, M and Barge-Caballero, E and Barge-Caballero, G and Couto-Mallon, D and Grille-Cancela, Z and Blanco-Canosa, P and Paniagua-Martin, MJ and Enriquez-Vazquez, D and Vazquez-Rodriguez, JM and Domenech, N and Crespo-Leiro, MG}, title = {Reduced mitochondrial pyruvate carrier expression in hearts with heart failure and reduced ejection fraction patients: ischemic vs. non-ischemic origin.}, journal = {Frontiers in cardiovascular medicine}, volume = {11}, number = {}, pages = {1349417}, pmid = {38525191}, issn = {2297-055X}, abstract = {INTRODUCTION AND OBJECTIVES: Mitochondrial pyruvate carrier (MPC) mediates the entry of pyruvate into mitochondria, determining whether pyruvate is incorporated into the Krebs cycle or metabolized in the cytosol. In heart failure (HF), a large amount of pyruvate is metabolized to lactate in the cytosol rather than being oxidized inside the mitochondria. Thus, MPC activity or expression might play a key role in the fate of pyruvate during HF. The purpose of this work was to study the levels of the two subunits of this carrier, named MPC1 and MPC2, in human hearts with HF of different etiologies.

METHODS: Protein and mRNA expression analyses were conducted in cardiac tissues from three donor groups: patients with HF with reduced ejection fraction (HFrEF) with ischemic cardiomyopathy (ICM) or idiopathic dilated cardiomyopathy (IDC), and donors without cardiac pathology (Control). MPC2 plasma levels were determined by ELISA.

RESULTS: Significant reductions in the levels of MPC1, MPC2, and Sirtuin 3 (SIRT3) were observed in ICM patients compared with the levels in the Control group. However, no statistically significant differences were revealed in the analysis of MPC1 and MPC2 gene expression among the groups. Interestingly, Pyruvate dehydrogenase complex (PDH) subunits expression were increased in the ICM patients. In the case of IDC patients, a significant decrease in MPC1 was observed only when compared with the Control group. Notably, plasma MPC2 levels were found to be elevated in both disease groups compared with that in the Control group.

CONCLUSION: Decreases in MPC1 and/or MPC2 levels were detected in the cardiac tissues of HFrEF patients, with ischemic or idiopatic origen, indicating a potential reduction in mitochondrial pyruvate uptake in the heart, which could be linked to unfavorable clinical features.}, } @article {pmid38523415, year = {2024}, author = {Seth, A and Slama, EM}, title = {Delayed Diagnosis of Inflammatory Breast Cancer Presenting as Acute Mastitis in a Patient One Month Postpartum.}, journal = {The American surgeon}, volume = {90}, number = {7}, pages = {1925-1927}, doi = {10.1177/00031348241241736}, pmid = {38523415}, issn = {1555-9823}, mesh = {Humans ; Female ; Adult ; *Mastitis/diagnosis/etiology ; *Inflammatory Breast Neoplasms/diagnosis ; *Delayed Diagnosis ; *Postpartum Period ; Diagnosis, Differential ; Acute Disease ; }, abstract = {Inflammatory breast cancer (IBC) is a rare yet aggressive form of invasive ductal carcinoma, with a poor prognosis and decreased 5-year survival rates. Characteristic findings for IBC include rapid onset of breast edema, peau d'orange appearance, and involvement of the breast skin. Additionally, diagnosis is confirmed with a skin punch biopsy. With such nonspecific features, IBC can be mistaken for benign etiologies, causing delays in diagnosis and treatment. This patient is a 44-year-old woman presenting with left breast swelling while concurrently breastfeeding. Following antibiotic treatment but no symptom resolution, the patient was referred out for further follow-up. Despite multiple imaging studies, suggesting benign findings, clinical suspicion prompted continued evaluation and finally diagnosis of triple-negative inflammatory breast cancer with distant metastases. Further awareness of the presentation of IBC and its mimicking of other disease processes such as mastitis is paramount to earlier detection and improved outcomes in future patients.}, } @article {pmid38523303, year = {2024}, author = {Yanase, Y and Bando, H and Sato, R and Matsuo, T and Ueda, A and Okazaki, M and Hashimoto, S and Iguchi-Manaka, A and Hara, H}, title = {Recurrent severe hypocalcemia following chemotherapy regimen changes in advanced breast cancer: two case reports.}, journal = {Journal of medical case reports}, volume = {18}, number = {1}, pages = {150}, pmid = {38523303}, issn = {1752-1947}, mesh = {Female ; Humans ; Adult ; Aged ; *Breast Neoplasms/drug therapy/pathology ; *Hypocalcemia/chemically induced ; Lapatinib/adverse effects ; Denosumab/adverse effects ; Calcium/therapeutic use ; *Bone Neoplasms/secondary ; }, abstract = {BACKGROUND: As an oncologic emergency related to abnormalities in calcium metabolism, hypercalcemia associated with paraneoplastic syndrome and bone metastases is well known. Meanwhile, the incidence of hypocalcemia is low, except in cases associated with bone-modifying agents used for bone metastases. Hypocalcemia induced by bone-modifying agents typically occurs early after the initial administration, and its incidence can be significantly reduced by preventive administration of calcium and vitamin D3 supplements.

CASE REPORT: We report two cases of recurrent severe hypocalcemia occurring during chemotherapy for metastatic breast cancer with multiple bone metastases. Case 1: A 35-year-old Japanese woman developed metastases in the bone, liver, and ovaries during postoperative endocrine therapy for invasive lobular carcinoma of the breast. She underwent chemotherapy and treatment with denosumab. She experienced recurrent episodes of severe hypocalcemia subsequent to a change in the chemotherapy regimen. Case 2: A 65-year-old Japanese woman encountered multiple bone metastases after postoperative anti-human epidermal growth factor receptor 2 therapy and during endocrine therapy for invasive ductal carcinoma of the breast. She underwent anti-human epidermal growth factor receptor 2 therapy and treatment with denosumab. She experienced recurrent severe hypocalcemia subsequent to a change in the chemotherapy regimen to letrozole + lapatinib, trastuzumab emtansine, and lapatinib + capecitabine.

CONCLUSIONS: We observed two cases of recurrent severe hypocalcemia in patients with advanced breast cancer and bone metastases after modifications to their therapy regimens. These cases differed from the typical hypocalcemia induced by bone-modifying agents. It is possible that antitumor drugs affect calcium and bone metabolism associated with bone metastases. While these cases are rare, it is crucial for oncologists to be aware of hypocalcemia not only at the initiation of bone-modifying agents but also throughout the entire antitumor therapy, as hypocalcemia can lead to fatal outcomes.}, } @article {pmid38485913, year = {2024}, author = {Heidari, N and Abbasi-Kenarsari, H and Niknam, B and Asadirad, A and Amani, D and Mirsanei, Z and Hashemi, SM}, title = {Exosomes Derived from Heat-shocked Tumor Cells Promote In vitro Maturation of Bone Marrow-derived Dendritic Cells.}, journal = {Iranian journal of allergy, asthma, and immunology}, volume = {23}, number = {1}, pages = {97-106}, doi = {10.18502/ijaai.v23i1.14957}, pmid = {38485913}, issn = {1735-5249}, mesh = {*Exosomes ; Dendritic Cells ; Bone Marrow ; T-Lymphocytes ; Coculture Techniques ; Cell Differentiation ; }, abstract = {Dendritic cells (DCs), professional antigen-presenting cells that process and deliver antigens using MHC II/I molecules, can be enhanced in numerous ways. Exosomes derived from heat-shocked tumor cells (HS-TEXs) contain high amounts of heat-shock proteins (HSPs). HSPs, as chaperons, can induce DC maturation. This study aimed to investigate whether HS-TEXs can promote DC maturation. To generate DC, bone marrow-derived cells were treated with Interleukin-4 and GM-CSF. Exosomes were isolated from heat-treated CT-26 cells. The expression level of HSP in exosomes was checked by western blot and the increase in the expression of this protein was observed. Then, HS-TEXs were co-cultured with iDCs to determine DC maturity, and then DCs were co-cultured with lymphocytes to determine DC activity. Our results showed that DCs treated with HS-TEXs express high levels of molecules involved in DC maturation and function including MHCII, CD40, CD83, and CD86. HS-TEXs caused phenotypic and functional maturation of DCs. In addition, flow cytometric results reflected a higher proliferative response of lymphocytes in the iDC / Tex + HSP group. HS-TEXs could be used as a strategy to improve DC maturation and activation.}, } @article {pmid38485644, year = {2024}, author = {Shi, Y and Wang, H and Golijanin, B and Amin, A and Lee, J and Sikov, M and Hyams, E and Pareek, G and Carneiro, BA and Mega, AE and Lagos, GG and Wang, L and Wang, Z and Cheng, L}, title = {Ductal, intraductal, and cribriform carcinoma of the prostate: Molecular characteristics and clinical management.}, journal = {Urologic oncology}, volume = {42}, number = {5}, pages = {144-154}, doi = {10.1016/j.urolonc.2024.01.037}, pmid = {38485644}, issn = {1873-2496}, mesh = {Male ; Humans ; Prostate/pathology ; *Adenocarcinoma/pathology ; *Prostatic Neoplasms/genetics/therapy/pathology ; Cell Proliferation ; }, abstract = {Prostatic acinar adenocarcinoma accounts for approximately 95% of prostate cancer (CaP) cases. The remaining 5% of histologic subtypes of CaP are known to be more aggressive and have recently garnered substantial attention. These histologic subtypes - namely, prostatic ductal adenocarcinoma (PDA), intraductal carcinoma of the prostate (IDC-P), and cribriform carcinoma of the prostate (CC-P) - typically exhibit distinct growth characteristics, genomic features, and unique oncologic outcomes. For example, PTEN mutations, which cause uncontrolled cell growth, are frequently present in IDC-P and CC-P. Germline mutations in homologous DNA recombination repair (HRR) genes (e.g., BRCA1, BRCA2, ATM, PALB2, and CHEK2) are discovered in 40% of patients with IDC-P, while only 9% of patients without ductal involvement had a germline mutation. CC-P is associated with deletions in common tumor suppressor genes, including PTEN, TP53, NKX3-1, MAP3K7, RB1, and CHD1. Evidence suggests abiraterone may be superior to docetaxel as a first-line treatment for patients with IDC-P. To address these and other critical pathological attributes, this review examines the molecular pathology, genetics, treatments, and oncologic outcomes associated with CC-P, PDA, and IDC-P with the objective of creating a comprehensive resource with a centralized repository of information on PDA, IDC-P, and CC-P.}, } @article {pmid38471320, year = {2024}, author = {Niu, Q and Li, H and Du, L and Wang, R and Lin, J and Chen, A and Jia, C and Jin, L and Li, F}, title = {Development of a Multi-Parametric ultrasonography nomogram for prediction of invasiveness in ductal carcinoma in situ.}, journal = {European journal of radiology}, volume = {175}, number = {}, pages = {111415}, doi = {10.1016/j.ejrad.2024.111415}, pmid = {38471320}, issn = {1872-7727}, mesh = {Humans ; Female ; Middle Aged ; *Breast Neoplasms/diagnostic imaging/pathology ; *Nomograms ; *Neoplasm Invasiveness/diagnostic imaging ; *Ultrasonography, Mammary/methods ; *Carcinoma, Intraductal, Noninfiltrating/diagnostic imaging/pathology ; Aged ; *Elasticity Imaging Techniques/methods ; Adult ; Prospective Studies ; Contrast Media ; Risk Factors ; Predictive Value of Tests ; Sensitivity and Specificity ; Risk Assessment ; }, abstract = {OBJECTIVE: To investigate the independent risk variables associated with the potential invasiveness of ductal carcinoma in situ (DCIS) on multi-parametric ultrasonography, and further construct a nomogram for risk assessment.

METHODS: Consecutive patients from January 2017 to December 2022 who were suspected of having ductal carcinoma in situ (DCIS) based on magnetic resonance imaging or mammography were prospectively enrolled. Histopathological findings after surgical resection served as the gold standard. Grayscale ultrasound, Doppler ultrasound, shear wave elastography (SWE), and contrast-enhanced ultrasound (CEUS) examinations were preoperative performed. Binary logistic regression was used for multifactorial analysis to identify independent risk factors from multi-parametric ultrasonography. The correlation between independent risk factors and pathological prognostic markers was analyzed. The predictive efficacy of DCIS associated with invasiveness was assessed by logistic analysis, and a nomogram was established.

RESULTS: A total of 250 DCIS lesions were enrolled from 249 patients, comprising 85 pure DCIS and 165 DCIS with invasion (DCIS-IDC), of which 41 exhibited micro-invasion. The multivariate analysis identified independent risk factors for DCIS with invasion on multi-parametric ultrasonography, including image size (>2cm), Doppler ultrasound RI (≥0.72), SWE's Emax (≥66.4 kPa), hyper-enhancement, centripetal enhancement, increased surrounding vessel, and no contrast agent retention on CEUS. These factors correlated with histological grade, Ki-67, and human epidermal growth factor receptor 2 (HER2) (P < 0.1). The multi-parametric ultrasound approach demonstrated good predictive performance (sensitivity 89.7 %, specificity 73.8 %, AUC 0.903), surpassing single US modality or combinations with SWE or CEUS modalities. Utilizing these factors, a predictive nomogram achieved a respectable performance (AUC of 0.889) for predicting DCIS with invasion. Additionally, a separate nomogram for predicting DCIS with micro-invasion, incorporating independent risk factors such as RI (≥0.72), SWE's Emax (≥65.2 kPa), and centripetal enhancement, demonstrated an AUC of 0.867.

CONCLUSION: Multi-parametric ultrasonography demonstrates good discriminatory ability in predicting both DCIS with invasion and micro-invasion through the analysis of lesion morphology, stiffness, neovascular architecture, and perfusion. The use of a nomogram based on ultrasonographic images offers an intuitive and effective method for assessing the risk of invasion in DCIS. Although the nomogram is not currently considered a clinically applicable diagnostic tool due to its AUC being below the threshold of 0.9, further research and development are anticipated to yield positive outcomes and enhance its viability for clinical utilization.}, } @article {pmid38461375, year = {2024}, author = {Turhan, Ş and Sultan, DAO and Altuner, EM and Kurnaz, A and Bakır, TK and Altamemi, RAA}, title = {Determination of radon concentrations and physicochemical parameters of non-alcoholic carbonated beverages consumed in Türkiye and assessment of radiological health risk.}, journal = {International journal of environmental health research}, volume = {}, number = {}, pages = {1-11}, doi = {10.1080/09603123.2024.2327530}, pmid = {38461375}, issn = {1369-1619}, abstract = {The strategy for controlling the existence of radionuclides in drinking water depends upon an individual dose criterion (IDC) of 0.1 mSv/y, which represents a very low level of risk that is not expected to cause any identified adverse health effects. Radon gas, considered a carcinogenic radionuclide, can dissolve and accumulate in drinking water. Non-alcoholic carbonated beverages (NACBs), which mainly contain drinking water, phosphoric acid, citric acid, caffeine, and sugar, represent one of the most consumed groups worldwide and in Türkiye. In this study, the radon activity concentration and some physicochemical characteristics of 45 NACB samples from 24 most preferred commercial brands in Türkiye were determined to assess the radiological health risk associated with the ingestion of these samples. Radon activity concentrations measured in NACB samples using the AlphaGUARD radon analyzer ranged from 22.8 ± 0.7 to 54.9 ± 1.7 mBq/L. The pH, conductivity, total dissolved solids, and brix values in NACB samples ranged from 2.31 to 7.29, 401 to 3281 μSv/cm, 355 to 2453 mg/L, and 0.10 to 12.95%, respectively. Total (ingestion and inhalation) annual effective doses and the corresponding excess lifetime cancer risks estimated for adults to assess the radiological health risk are significantly below the IDC and advised safety limit (10[-3]), respectively.}, } @article {pmid38432595, year = {2024}, author = {Chuang, ML}, title = {Analyzing key elements of breathing patterns, deriving remaining variables, and identifying cutoff values in individuals with chronic respiratory disease and healthy subjects.}, journal = {Respiratory physiology & neurobiology}, volume = {324}, number = {}, pages = {104242}, doi = {10.1016/j.resp.2024.104242}, pmid = {38432595}, issn = {1878-1519}, mesh = {Humans ; Healthy Volunteers ; Respiration ; Exhalation ; *Respiration Disorders ; *Pulmonary Disease, Chronic Obstructive ; *Lung Diseases, Interstitial ; }, abstract = {BACKGROUND: Pulmonary physiology encompasses intricate breathing patterns (BPs), characterized by breathing frequency (Bf), volumes, and flows. The complexities intensify in the presence of interstitial lung disease (ILD) and chronic obstructive pulmonary disease (COPD), especially during exercise. This study seeks to identify pivotal factors driving changes among these variables and establish cutoff values, comparing their efficacy in differentiating BPs to traditional methods, specifically a breathing reserve (BR) of 30% and a Bf of 50 bpm.

METHODS: Screening 267 subjects revealed 23 with ILD, 126 with COPD, 33 healthy individuals, and the exclusion of 85 subjects. Lung function tests and ramp-pattern cardiopulmonary exercise testing (CPET) were conducted, identifying crucial BP elements. Changes were compared between groups at peak exercise. The area under the receiver operating characteristic curve (AUC) analysis determined cutoff values.

RESULTS: Inspiratory time (TI) remained constant at peak exercise for all subjects (two-group comparisons, all p=NS). Given known differences in expiratory time (TE) and tidal volume (VT) among ILD, COPD, and healthy states, constant TI could infer patterns for Bf, total breathing cycle time (TTOT=60/Bf), I:E ratio, inspiratory duty cycle (IDC, TI/TTOT), rapid shallow breathing index (Bf/VT), tidal inspiratory and expiratory flows (VT/TI and VT/TE), and minute ventilation (V̇E=Bf×VT) across conditions. These inferences aligned with measurements, with potential type II errors causing inconsistencies. RSBI of 23 bpm/L and VT/TI of 104 L/min may differentiate ILD from control, while V̇E of 54 L/min, BR of 30%, and VT/TE of 108 may differentiate COPD from control. BR of 21%, TE of 0.99 s, and IDC of .45 may differentiate ILD from COPD. The algorithm outperformed traditional methods (AUC 0.84-0.91 versus 0.59-0.90).

CONCLUSION: The quasi-fixed TI, in conjunction with TE and VT, proves effective in inferring time-related variables of BPs. The findings have the potential to significantly enhance medical education in interpreting cardiopulmonary exercise testing. Moreover, the study introduces a novel algorithm for distinguishing BPs among individuals with ILD, COPD, and those who are healthy.}, } @article {pmid38416170, year = {2024}, author = {Maggi, G and Loayza, F and Vitale, C and Santangelo, G and Obeso, I}, title = {Anatomical correlates of apathy and impulsivity co-occurrence in early Parkinson's disease.}, journal = {Journal of neurology}, volume = {271}, number = {5}, pages = {2798-2809}, pmid = {38416170}, issn = {1432-1459}, mesh = {Humans ; *Parkinson Disease/complications/pathology/diagnostic imaging/physiopathology ; *Apathy/physiology ; Male ; Female ; Middle Aged ; Aged ; *Magnetic Resonance Imaging ; *Gray Matter/diagnostic imaging/pathology ; *Disruptive, Impulse Control, and Conduct Disorders/etiology/physiopathology/diagnostic imaging/pathology ; Longitudinal Studies ; Impulsive Behavior/physiology ; }, abstract = {BACKGROUND: Although apathy and impulse control disorders (ICDs) are considered to represent opposite extremes of a continuum of motivated behavior (i.e., hypo- and hyperdopaminergic behaviors), they may also co-occur in Parkinson's disease (PD).

OBJECTIVES: We aimed to explore the co-occurrence of ICDs and apathy and its neural correlates analyzing gray matter (GM) changes in early untreated PD patients. Moreover, we aimed to investigate the possible longitudinal relationship between ICDs and apathy and their putative impact on cognition during the first five years of PD.

METHODS: We used the Parkinson's Progression Markers Initiative (PPMI) database to identify the co-occurrence of apathy and ICDs in 423 early drug-naïve PD patients at baseline and at 5-year follow-up. Baseline MRI volumes and gray matter changes were analyzed between groups using voxel-based morphometry. Multi-level models assessed the longitudinal relationship (across five years) between apathy and ICDs and cognitive functioning.

RESULTS: At baseline, co-occurrence of apathy and ICDs was observed in 23 patients (5.4%). This finding was related to anatomical GM reduction along the cortical regions involved in the limbic circuit and cognitive control systems. Longitudinal analyses indicated that apathy and ICDs were related to each other as well as to the combined use of levodopa and dopamine agonists. Worse apathetic and ICDs states were associated with poorer executive functions.

CONCLUSIONS: Apathy and ICDs are joint non-exclusive neuropsychiatric disorders also in the early stages of PD and their co-occurrence was associated with GM decrease in several cortical regions of the limbic circuit and cognitive control systems.}, } @article {pmid38406950, year = {2023}, author = {Asad, S and Khan, SA and Khan, FA and Jalal-Ud-Din, M and Bhatti, G and Kamran, H}, title = {Pattern Of Breast Cancer: Experience At Ayub Teaching Hospital, Abbottabad.}, journal = {Journal of Ayub Medical College, Abbottabad : JAMC}, volume = {35}, number = {4}, pages = {629-632}, doi = {10.55519/JAMC-04-12089}, pmid = {38406950}, issn = {1819-2718}, mesh = {Humans ; Female ; *Breast Neoplasms/pathology ; Lymph Nodes/pathology ; Hospitals, Teaching ; Biopsy ; Axilla/pathology ; }, abstract = {BACKGROUND: Breast cancer is the most common malignancy found in females all over the world and the second leading cause of cancer death in European countries. The purpose of this study was to find out the pattern of disease presentation in our region where a proper tumour registry system is lacking.

METHODS: This descriptive study was carried out in the Department of Surgery, Ayub Teaching Hospital Abbottabad, from July 2021 to June 2022. All female patients with biopsy-proven breast cancer were included in the study: benign lumps, refused to enrol, and those who were lost to follow-up were excluded.

RESULTS: A total of 87 patients with carcinoma breast were included: 92 % (n=80) had invasive ductal carcinoma. Axillary lymph nodes were involved in 88.5% (n=77), 75.8% of the tumours, (n=66), were Grade 2, 34.5% (n=30) were in the 40-49 years age group, and 30 % (n=27) of the disease was categorized as Stage III or IV. In 55 % (n=48), the tumour was on the right side and in 39% (n=34), the upper outer quadrant was involved. Most of the patients, 90.8% (n=79), were married and had used contraceptive measures. Only 19.5% of patients (n=17), had a history of nipple discharge and 56% (n=49) had a positive family history: 71% (n=62) had nipple retraction, and 54% (n=47), proved to be ER PR positive.

CONCLUSIONS: Our patients presented late: axilla was commonly involved and a third had advanced disease. Screening and community awareness programs may help in early detection. Hormone use for contraception needs to be weighed carefully. Better data collection may help in designing screening and care programs.}, } @article {pmid38406898, year = {2023}, author = {, and Haider, G and Shaikh, Z and Memon, P and Shahid, A and Rahul, R and Kumar, P and Beg, S and Parkash, J}, title = {Significance of ca15-3 in carcinoma of the breast with Visceral metastases.}, journal = {Journal of Ayub Medical College, Abbottabad : JAMC}, volume = {35(Suppl 1)}, number = {4}, pages = {S710-S714}, pmid = {38406898}, issn = {1819-2718}, mesh = {Female ; Humans ; Middle Aged ; Cross-Sectional Studies ; Mucin-1 ; Biomarkers, Tumor ; *Breast Neoplasms/diagnosis ; *Carcinoma ; Prognosis ; }, abstract = {BACKGROUND: The most common malignancy and second most common cause of death is breast cancer among women. About 2.09 million fatalities from breast cancer happened in 2018. The objective was to evaluate the elevated CA15-3 in breast cancer patients with visceral metastases presenting at the tertiary care hospital of Karachi.

METHODS: It was a cross-sectional study conducted at the Department of Oncology of Jinnah Postgraduate Medical Center from 15th December 2018 to 15th November 2019. Female patients aged 26-80 years diagnosed with visceral metastatic (defined as metastasis to lung, liver, brain and adrenal glands) breast cancer were included in the study. The diagnosis of breast cancer was confirmed on histopathology whereas the metastatic sites were evaluated using physical examination and imaging. The serum CA15-3 concentration was assessed using assay kits. The serum CA15-3 level of 0-32 U/ml was taken as normal range for all the patients whereas CA15-3 level greater than 32 U/L was considered as elevated CA15-3. SPSS version 23 was used to enter and analyze data.

RESULTS: A total of 139 females were included in the study. The mean age & BMI of the patients were reported as 46.5 years & 26.69 kg/m2. In the majority of the patients' metastases were detected in the liver (n=54), 92 in the lungs+ parenchymal disease, 20 in adrenal glands, 12 in pleural effusion and 10 in the brain. Out of 139 patients with visceral metastases, 52(37.4%) had normal CA15-3 level whereas 87 (62.6%) had elevated serum CA15-3 levels (>32 U/L).

CONCLUSION: The serum CA15-3 tumour marker is elevated significantly in visceral metastases and can be used as a prognostic marker in metastatic breast cancer patients.}, } @article {pmid38399000, year = {2024}, author = {Khan, MRR}, title = {Development of a Battery-Free, Chipless, and Highly Sensitive Radio Frequency Glucose Biosensor.}, journal = {Micromachines}, volume = {15}, number = {2}, pages = {}, pmid = {38399000}, issn = {2072-666X}, abstract = {In our study, we designed and developed a glucose biosensor that operates without a battery or chip. This biosensor utilizes the principles of radio frequency (RF) to operate. For the construction of a glucose-sensitive interdigitated capacitor (IDC), a famous glucose-sensitive substance called phenylboronic acid (PBA) is combined with a polyvinyl chloride (PVC) and n,n-dimethylacetamide (DMAC) solution. According to the theory of radio frequency sensing, the resonance frequency shifts whenever there is a change in the capacitance of the glucose-sensitive IDC. This change is caused by the fluctuations in glucose concentrations. As far as we are aware, this is the first glucose sensor that employs the RF principle to detect changes in glucose solution concentrations using PBA as the principal glucose-sensitive material. The sensor can detect glucose levels with remarkable sensitivity, around 40.89 kHz/decade, and a broad dynamic range covering 10 μM to 1 M. Additionally, the designed biosensor has excellent linearity performance, with a value of around 0.988. The proposed glucose biosensor has several benefits: lightweight, inexpensive, easy to build, and an acceptable selectivity response. Our study concludes by comparing the proposed RF sensor's effectiveness to that of existing glucose sensors, which it outperforms.}, } @article {pmid38396137, year = {2024}, author = {Matsumoto, T and Tanaka, G and Mori, S and Niki, M and Sato, S and Shiraki, T and Iso, Y and Nagashima, K and Irisawa, A and Nozawa, Y and Takada-Owada, A and Ishida, K and Aoki, T}, title = {A resected case of pancreatic head cancer developing 40 years after lateral pancreaticojejunostomy for chronic pancreatitis.}, journal = {Clinical journal of gastroenterology}, volume = {17}, number = {3}, pages = {537-542}, pmid = {38396137}, issn = {1865-7265}, mesh = {Humans ; Male ; *Pancreaticojejunostomy ; Aged ; *Pancreatic Neoplasms/surgery ; *Pancreatitis, Chronic/surgery/complications/etiology ; Pancreaticoduodenectomy/adverse effects ; Carcinoma, Pancreatic Ductal/surgery ; Postoperative Complications/etiology ; Tomography, X-Ray Computed ; }, abstract = {A 72-year-old male patient presented to our department complaining of with upper abdominal pain and jaundice. He had a history of a side-to-side pancreaticojejunostomy performed 40 years previously for chronic pancreatitis. A diagnostic workup revealed a tumor 3 cm in size in the pancreatic head as the etiology of the jaundice. Subsequently, the patient was diagnosed with resectable pancreatic cancer. Following two cycles of neoadjuvant chemotherapy, an extended pancreatoduodenectomy was performed because of tumor invasion at the previous pancreaticojejunostomy site. Concurrent portal vein resection and reconstruction were performed. Pathological examination confirmed invasive ductal carcinoma (T2N1M0, Stage IIB). This case highlights the clinical challenges in pancreatic head carcinoma following a side-to-side pancreaticojejunostomy. Although pancreaticojejunostomy is believed to reduce the risk of pancreatic cancer in patients with chronic pancreatitis, clinicians should be aware that, even after this surgery, there is still a chance of developing pancreatic cancer during long-term follow-up.}, } @article {pmid38368669, year = {2024}, author = {Gomez, D and Seneviratne, S}, title = {Invasive breast carcinoma with ipsilateral axillary squamous carcinoma of unknown primary: A case report.}, journal = {International journal of surgery case reports}, volume = {116}, number = {}, pages = {109397}, pmid = {38368669}, issn = {2210-2612}, abstract = {INTRODUCTION & IMPORTANCE: Invasive ductal carcinoma is the commonest primary breast carcinoma to metastasize to the axillary nodes. Squamous carcinoma (SCC) of the breast is seen rarely as a primary breast malignancy. Breast SCC with coexistent invasive ductal/lobular carcinoma as a 'collision tumour' is rare.

CASE PRESENTATION: A 52-year-old Sri Lankan female presented with a right sided breast lump and ipsilateral cystic axillary mass. She was diagnosed with locally advanced invasive breast carcinoma and underwent neoadjuvant chemotherapy followed by mastectomy and axillary clearance where tumour infiltration of the brachial plexus was observed. Histology revealed two separate carcinomas; an invasive carcinoma of the breast and squamous carcinoma in the axilla. A squamous primary was not found despite evaluation. The patient developed recurrent axillary ulceration due to residual tumour and was transferred for oncological care.

CLINICAL DISCUSSION: This patient had a biopsy-proven invasive breast carcinoma with a cystic axillary mass with lymphadenopathy. This was concluded as locally advanced breast cancer. Pathological examination of the specimen indicated the presence of two separate malignancies of the breast and axilla. No evidence of squamous metaplasia or carcinoma of the breast was seen on histology, neither was a squamous primary identified on imaging or endoscopy. Neoadjuvant therapy may have caused resolution of the squamous component.

CONCLUSION: The presence of two separate cancers of varied histology in the breast and ipsilateral axilla in close proximity to each other is a rare phenomenon. Clinicians must be cautious not to misinterpret it as evidence of lymphatic spread.}, } @article {pmid38336663, year = {2024}, author = {Ye, C and Shi, M and Xie, D and Wu, H and Chen, Q and Yang, L}, title = {A rare case of intervertebral disc calcification combined with ossification of the posterior longitudinal ligament in a child: a case report and literature review.}, journal = {BMC musculoskeletal disorders}, volume = {25}, number = {1}, pages = {118}, pmid = {38336663}, issn = {1471-2474}, support = {82372431//National Natural Science Foundation of China/ ; 2022LJ007//Shanghai Municipal Health Commission Health Leading Talents Program/ ; 22ZR1476700//the Natural Science Foundation of the Science and Technology Commission of Shanghai Municipality/ ; 201409003200//the Science and Technology Innovation Action Plan of the Science and Technology Commission of Shanghai Municipality/ ; 0906//the Fifth Round Innovation Team of Shanghai Changning District, the Pyramid Talent Project of Shanghai Changzheng Hospital in 2020/ ; 2021X002//the Discipline Team Support Project of No. 905 Hospital of PLA Navy/ ; }, mesh = {Humans ; Child ; Longitudinal Ligaments/diagnostic imaging ; Osteogenesis ; *Intervertebral Disc Degeneration/complications/diagnostic imaging ; *Ossification of Posterior Longitudinal Ligament/complications/diagnostic imaging/therapy ; *Calcinosis/complications/diagnostic imaging/therapy ; *Chondrocalcinosis/complications ; Cervical Vertebrae/diagnostic imaging ; *Intervertebral Disc/diagnostic imaging ; }, abstract = {BACKGROUND: Intervertebral disc calcification (IDC) combined with calcification in children has been sporadically reported, while ossification of the posterior longitudinal ligament (OPLL) in the cervical spine in pediatric patients is exceedingly rare. The aim of this study is to investigate the potential prognosis and outcomes associated with this condition.

CASE PRESENTATION: We present an unusual case involving a 10-year-old Chinese child diagnosed with calcified cervical disc herniation and ossification of the posterior longitudinal ligament. Conservative treatment measures were implemented, and at the 1-month and 6-month follow-up, the patient's pain exhibited significant improvement. Subsequent cervical MRI and CT scans revealed the complete disappearance of OPLL and substantial absorption of the calcified disc. During the three-month follow-up, CT demonstrated slight residual disc calcification, however, the patient remained asymptomatic with no discernible limitation in cervical motion.

CONCLUSIONS: We conducted a comprehensive review of several cases presenting with the same diagnosis. It is noteworthy that IDC combined with OPLL in children constitutes a rare clinical entity. Despite imaging indications of potential spinal canal occupation, the majority of such cases demonstrate complete absorption following conservative treatment, with OPLL exhibiting a faster absorption rate than calcified discs.}, } @article {pmid38329829, year = {2024}, author = {Fang, L and Simman, R and Workman, L and Ayoub, S and Bratton, C}, title = {Malignant wound aetiology, diagnosis and management: a case series and literature review.}, journal = {Journal of wound care}, volume = {33}, number = {2}, pages = {102-117}, doi = {10.12968/jowc.2024.33.2.102}, pmid = {38329829}, issn = {0969-0700}, mesh = {Aged ; Humans ; *Carcinoma, Squamous Cell/diagnosis/therapy/complications ; *Melanoma/diagnosis/therapy ; Neoplasm Recurrence, Local ; Skin/pathology ; *Skin Neoplasms/diagnosis/therapy ; }, abstract = {OBJECTIVE: Malignant wounds develop when neoplastic cells invade the skin either locally or by lymphatic and haematogenous spread. They can present as hard-to-heal wounds and underlying causes include: primary skin cancer; metastasis of extracutaneous primary malignancy; malignant transformation of a hard-to-heal wound; iatrogenic injury; and cutaneous forms of cancers of non-skin origin. High clinical suspicion for a malignant wound should be confirmed with skin biopsy. The aim of this case series is to highlight a combination of both clinically clear cutaneous malignancies and not-so-obvious wounds caused by malignancy.

METHOD: This case series examines patients with malignant wounds of varying aetiology and appearance. For each case, we explain the pathophysiology, atypical features, diagnostic approach and treatment. We also discuss types of wound biopsy and general wound management principles.

RESULTS: Among the 11 cases analysed using descriptive statistics, median wound duration before presentation at our clinic was one year, while median age at presentation was 65 years. Our case series included the following diagnoses: cutaneous metastasis of invasive ductal carcinoma of the breast (n=2); cutaneous metastasis of colorectal adenocarcinoma (n=1); Marjolin's ulcer (n=1), basal cell carcinoma (BCC) (n=2), primary cutaneous squamous cell carcinoma (SCC) (n=1), metastatic malignant melanoma (n=1), cutaneous T-cell lymphoma (n=1), cutaneous angiosarcoma (n=1), Kaposi sarcoma (n=1) and recurrent tonsillar SCC with osteoradionecrosis (n=1); one case had both BCC and SCC.

CONCLUSION: Punch and excisional biopsies were the most frequently used diagnostic techniques. Local wound therapy addressed bleeding, malodour, exudate, pain and infection. However, wound healing is usually achieved once the underlying malignancy is treated. In advanced or metastatic disease, palliative wound care aims to prevent exacerbation of existing wounds and focuses on patient comfort.}, } @article {pmid38318566, year = {2024}, author = {Youh, J and Yamaguchi, Y and Hiraguchi, E}, title = {Centrifugally Spreading Annular Erythema as a Dermatological Indicator of Metastatic Breast Carcinoma.}, journal = {Cureus}, volume = {16}, number = {1}, pages = {e51641}, pmid = {38318566}, issn = {2168-8184}, abstract = {Breast cancer is the leading cause of skin metastasis in women with internal malignancies. This report highlights an atypical case of cutaneous metastasis of breast cancer (CMBC) in a 66-year-old woman. Starting four months before her dermatology consultation, the patient underwent a chemotherapy regimen comprising pertuzumab, trastuzumab, and vinorelbine for right breast cancer, right axillary lymph node enlargement, and bone metastases. After commencing chemotherapy, erythematous macules appeared around her right nipple. Subsequently, the cutaneous lesions developed into annular erythematous patches around her right nipple and began to coalesce and expand to the contralateral breast. A skin biopsy revealed dysplastic cells indicative of metastasis from invasive ductal carcinoma. In addition, lymphovascular tumor cell invasion was noted in the reticular dermis. Based on these clinical progressions and histopathologic findings, a diagnosis of CMBC was made, specifically considering the possibility of inflammatory breast cancer (IBC). The patient continued the same chemotherapy regimen for 17 cycles, which improved the skin lesions, but she succumbed to breast cancer two years later. This case emphasizes the importance of considering CMBC in breast cancer patients with expanding, treatment-resistant thoracic cutaneous lesions, especially in aggressive subtypes like IBC. The diverse presentations of CMBC require thorough histopathological evaluation.}, } @article {pmid38305220, year = {2024}, author = {Tsilingiris, D and Schimpfle, L and Κender, Z and Sulaj, A and von Rauchhaupt, E and Herzig, S and Szendroedi, J and Kopf, S}, title = {Utility of bioelectrical phase angle for cardiovascular risk assessment among individuals with and without diabetes mellitus.}, journal = {Diabetes & vascular disease research}, volume = {21}, number = {1}, pages = {14791641231223701}, pmid = {38305220}, issn = {1752-8984}, mesh = {Adult ; Humans ; Male ; Female ; *Cardiovascular Diseases/diagnosis/etiology ; Carotid Intima-Media Thickness ; Pulse Wave Analysis ; *Diabetes Mellitus, Type 1 ; Risk Factors ; Heart Disease Risk Factors ; *Diabetes Mellitus, Type 2 ; Natriuretic Peptide, Brain ; Peptide Fragments ; Biomarkers ; }, abstract = {PURPOSE: Low values of bioimpedance-derived phase angle (PA) have been associated with various adverse outcomes. We investigated the association of PA with cardiovascular markers in individuals with and without diabetes mellitus (DM).

METHODS: PA was measured in 452 adults (without DM n = 153, T1DM n = 67, T2DM n = 232). Carotid intima-media thickness (IMT), renal resistive index (RRI), ankle-brachial index (ABI) and carotid-femoral Pulse Wave Velocity (cfPWV) were estimated. Furthermore, the levels of high-sensitive Troponin-T [hsTnT], N-terminal brain natriuretic peptide [NT-pro-BNP]) were measured.

RESULTS: PA values were lower in DM independently of age, gender, and BMI (estimated marginal means 6.21, 5.83, 5.95 for controls, T1DM, T2DM p < .05), a finding which persisted after propensity score matching. PA correlated negatively with IMT (r = -0.181), RRI (r = -0.374), cfPWV (r = -0.358), hsTnT (r = -0.238) and NT-pro-BNP (r = -0.318) (all p < .001). In multivariable analysis, the associations with RRI, cfPWV, hsTnT and NT-pro-BNP remained unchanged. PA values 6.0-6.5° for males and 5.2-5.8° for females were predictive of commonly used cutoffs. The combination of ΑCC/AHA ASCVD Score with PA outperformed either factor in predicting cfPWV, RRI for males and hsTnT, BNP for both genders.

CONCLUSIONS: PA exhibits independent correlations with various parameters pertinent to cardiovascular risk and may be useful for cardiovascular assessment.}, } @article {pmid38303174, year = {2023}, author = {Takeda, Y and Ohmura, Y and Katsura, Y and Shinke, G and Kinoshita, M and Aoyama, S and Kihara, Y and Yanagisawa, K and Katsuyama, S and Ikeshima, R and Hiraki, M and Sugimura, K and Masuzawa, T and Hata, T and Murata, K}, title = {[Robotic and Laparoscopic Pancreaticoduodenectomy for the Elderly Patients-A Single Institutional Experience].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {50}, number = {13}, pages = {1688-1690}, pmid = {38303174}, issn = {0385-0684}, mesh = {Humans ; Male ; Female ; Aged ; Middle Aged ; Pancreaticoduodenectomy/adverse effects ; *Pancreatic Neoplasms/surgery/complications ; Pancreatic Fistula/etiology ; *Robotic Surgical Procedures/adverse effects ; Retrospective Studies ; *Laparoscopy/adverse effects ; Postoperative Complications/epidemiology/etiology ; Length of Stay ; *Carcinoma, Ductal/complications ; }, abstract = {INTRODUCTION: Laparoscopic pancreaticoduodenectomy(LPD)has been covered by insurance since 2016 in Japan. Advance LPD and robotic pancreaticoduodenectomy(RPD)has been also covered by insurance since 2020 in Japan. The aim of this study was to analyze the perioperative results and outcomes of RPD and LPD for the elderly patients and to compare to the non-elderly patients.

PATIENTS AND METHOD: Between July 2020 and April 2023, 67 patients underwent RPD and between May 2012 and February 2021, 63 patients underwent LPD at Kansai Rosai Hospital. Sixty-seven RPD and 62 LPD patients without extended resection were divided into 2 groups those who were over 75 years old(R/LPD E)(n=55)and under 74 years old(R/LPD non-E)(n=74). Control patients who received open pancreaticoduodenectomy(OPD)without extended resection between April 2010 and April 2023 were also divided into 2 groups those who were over 75 years old(OPD E)(n =60)and under 74 years old(OPD non-E)(n=78). The patient age was 79.0 and 60.5 years, the male to female ratio was 35/20 and 45/29, disease ratio(invasive ductal carcinoma or not)was 7/48 and 9/65 in R/LPD E and R/LPD non-E groups, respectively. The patient age was 79.0 and 79.5 years, the male to female ratio was 35/20 and 31/29, disease ratio (invasive ductal carcinoma or not)was 7/48 and 30/30(p<0.0001)in R/LPD E and OPD E groups, respectively. This study was approved by the Human Ethics Review Committee of Kansai Rosai Hospital(Certificate Number: 2001019).

RESULTS: The average operation time was 644.6 and 675.2 minutes, an estimated blood loss was 220.8 and 134.4 g, postoperative pancreatic fistula(ISGPS 2016, [-]/BL/Grade B/C)was 24/18/13/0 and 28/25/21/0, delayed gastric emptying(ISGPS 2007, [-]/Grade A/B/C)was 48/0/4/3 and 61/2/6/5 and postoperative hospital stay was 27.9 and 25.9 and in R/LPD E and R/LPD non-E groups, respectively. No significant differences were noted between the groups, However, postoperative complication over Ⅲa Clavien-Dindo classification was 8(15.7%)and 3(4.4%)cases(p=0.0319)in R/LPD E and R/ LPD non-E groups. The average operation time was 644.6 and 492.1 minutes(p<0.0001), an estimated blood loss was 220.8 and 534.8 g(p=0.0004), postoperative pancreatic fistula(ISGPS 2016, [-]/BL/Grade B/C)was 24/18/13/0 and 27/8/24/1(p=0.0442), postoperative hospital stay was 27.9 and 42.0(p=0.0490)in R/LPD E and OPD E groups, respectively.

CONCLUSION: The R/LPD was undergone in safety, even for the over 75 years old patients.}, } @article {pmid38284471, year = {2024}, author = {Shoshani, A and Kor, A and Farbstein-Yavin, S and Gvion, Y}, title = {Risk and protective factors for substance use and media addictive behaviors in adolescents during the COVID-19 pandemic.}, journal = {Journal of adolescence}, volume = {96}, number = {4}, pages = {746-759}, doi = {10.1002/jad.12295}, pmid = {38284471}, issn = {1095-9254}, mesh = {Humans ; Adolescent ; *COVID-19/epidemiology/psychology/prevention & control ; Male ; Female ; Israel/epidemiology ; *Substance-Related Disorders/epidemiology/psychology ; *Behavior, Addictive/psychology/epidemiology ; Risk Factors ; *Protective Factors ; *Social Media/statistics & numerical data ; Longitudinal Studies ; Child ; Adolescent Behavior/psychology ; Internet Addiction Disorder/epidemiology/psychology ; SARS-CoV-2 ; Surveys and Questionnaires ; Screen Time ; }, abstract = {OBJECTIVE: This study examined the long-term effects of the COVID-19 pandemic on adolescents' substance use, digital media use, and symptoms of internet, gaming, and social media addiction.

METHOD: A nationally representative longitudinal cohort of 1665 Israeli teens and preteens, aged 9-16, completed questionnaires assessing substance use prevalence, daily screen time, symptoms of media addiction, and potential risk and protective factors. Data were collected before the pandemic (October 2019), after the second wave lockdown (November 2020), and after the fifth wave (April 2022) in Israel.

RESULTS: The analysis documented significant increases in substance use, daily screen time, and social media addiction indices over time. Gratitude, life satisfaction, positive emotions, future orientation, grit, and secure attachment emerged as significant protective factors. Sensation-seeking, negative emotions, and mental health symptoms were identified as risk factors.

CONCLUSIONS: These findings highlight the importance of educational and public mental health services in addressing the pandemic's long-term impact on the mental health and addictive behaviors of adolescents. They also emphasize the significance of enhancing protective factors and reducing risk factors to effectively mitigate substance and digital media abuse among adolescents.}, } @article {pmid38273260, year = {2024}, author = {Saad, HA and Baz, A and Riad, M and Eraky, ME and El-Taher, A and Farid, MI and Sharaf, K and Said, HEM and Ibrahim, LA}, title = {Tumor microenvironment and immune system preservation in early-stage breast cancer: routes for early recurrence after mastectomy and treatment for lobular and ductal forms of disease.}, journal = {BMC immunology}, volume = {25}, number = {1}, pages = {9}, pmid = {38273260}, issn = {1471-2172}, mesh = {Humans ; Female ; *Breast Neoplasms/surgery ; Mastectomy ; Vimentin/therapeutic use ; *Carcinoma, Ductal, Breast/pathology/secondary/surgery ; Tumor Microenvironment ; Matrix Metalloproteinase 1/therapeutic use ; *Carcinoma, Lobular/pathology/secondary/surgery ; }, abstract = {BACKGROUND: Intra-ductal cancer (IDC) is the most common type of breast cancer, with intra-lobular cancer (ILC) coming in second. Surgery is the primary treatment for early stage breast cancer. There are now irrefutable data demonstrating that the immune context of breast tumors can influence growth and metastasis. Adjuvant chemotherapy may be administered in patients who are at a high risk of recurrence. Our goal was to identify the processes underlying both types of early local recurrences.

METHODS: This was a case-control observational study. Within 2 years of receiving adjuvant taxan and anthracycline-based chemotherapy, as well as modified radical mastectomy (MRM), early stage IDC and ILC recurred. Vimentin, α-smooth muscle actin (SMA), platelet-derived growth factor (PDGF), matrix metalloproteinase (MMP1), and clustered differentiation (CD95) were investigated.

RESULTS: Of the samples in the ductal type group, 25 showed local recurrence, and 25 did not. Six individuals in the lobular-type group did not experience recurrence, whereas seven did. Vimentin (p = 0.000 and 0.021), PDGF (p = 0.000 and 0.002), and CD95 (p = 0.000 and 0.045) expressions were significantly different in ductal and lobular carcinoma types, respectively. Measurement of ductal type was the sole significant difference found in MMP1 (p = 0.000) and α-SMA (p = 0.000). α-SMA and CD95 were two variables that helped the recurrence mechanism in the ductal type according to the pathway analysis. In contrast, the CD95 route is a recurrent mechanism for the lobular form.

CONCLUSIONS: While the immune system plays a larger role in ILC, the tumor microenvironment and immune system both influence the recurrence of IDC. According to this study, improving the immune system may be a viable cancer treatment option.}, } @article {pmid38272241, year = {2024}, author = {Failayev, H and Ganoth, A and Tsfadia, Y}, title = {Molecular insights on the coronavirus MERS-CoV interaction with the CD26 receptor.}, journal = {Virus research}, volume = {342}, number = {}, pages = {199330}, pmid = {38272241}, issn = {1872-7492}, mesh = {Humans ; Animals ; Dogs ; Dipeptidyl Peptidase 4/genetics ; *Middle East Respiratory Syndrome Coronavirus/genetics ; Spike Glycoprotein, Coronavirus/genetics ; *Coronavirus Infections ; Amino Acids ; }, abstract = {The Middle East respiratory syndrome (MERS) is a severe respiratory disease with high fatality rates, caused by the Middle East respiratory syndrome coronavirus (MERS-CoV). The virus initiates infection by binding to the CD26 receptor (also known as dipeptidyl peptidase 4 or DPP4) via its spike protein. Although the receptor-binding domain (RBD) of the viral spike protein and the complex between RBD and the extracellular domain of CD26 have been studied using X-ray crystallography, conflicting studies exist regarding the importance of certain amino acids outside the resolved RBD-CD26 complex interaction interface. To gain atomic-level knowledge of the RBD-CD26 complex, we employed computational simulations to study the complex's dynamic behavior as it evolves from its crystal structure to a conformation stable in solution. Our study revealed previously unidentified interaction regions and interacting amino acids within the complex, determined a novel comprehensive RBD-binding domain of CD26, and by that expanded the current understanding of its structure. Additionally, we examined the impact of a single amino acid substitution, E513A, on the complex's stability. We discovered that this substitution disrupts the complex through an allosteric domino-like mechanism that affects other residues. Since MERS-CoV is a zoonotic virus, we evaluated its potential risk of human infection via animals, and suggest a low likelihood for possible infection by cats or dogs. The molecular structural information gleaned from our insights into the RBD-CD26 complex pre-dissociative states may be proved useful not only from a mechanistic view but also in assessing inter-species transmission and in developing anti-MERS-CoV antiviral therapeutics.}, } @article {pmid38265547, year = {2024}, author = {Dai, Q and Feng, K and Liu, G and Cheng, H and Tong, X and Wang, X and Feng, L and Wang, Y}, title = {Prognostic Impact of HER2-Low and HER2-Zero in Resectable Breast Cancer with Different Hormone Receptor Status: A Landmark Analysis of Real-World Data from the National Cancer Center of China.}, journal = {Targeted oncology}, volume = {19}, number = {1}, pages = {81-93}, pmid = {38265547}, issn = {1776-260X}, support = {CIFMS//Cancer Institute and Hospital, Chinese Academy of Medical Sciences/ ; ID Number: 2021-I2M-1-014//Cancer Institute and Hospital, Chinese Academy of Medical Sciences/ ; ID Number: LC2022A02//Beijing Hope Run Special Fund of Cancer Foundation of China/ ; }, mesh = {Humans ; Female ; Prognosis ; *Breast Neoplasms/drug therapy/pathology ; Receptor, ErbB-2 ; Retrospective Studies ; Hormones ; }, abstract = {BACKGROUND: The prognostic impact of HER2-low on overall survival (OS) and disease-free survival (DFS) in patients with resectable breast cancer (BC) remains controversial, partly resulting from the hormone receptor (HR) status.

OBJECTIVE: To investigate the prognostic impact of HER2-low in different HR subgroups.

PATIENTS AND METHODS: We retrospectively retrieved medical records of treatment-naive primary HER2-low and HER2-zero BC patients who were diagnosed with invasive ductal carcinoma and underwent surgery in the Cancer Hospital of the Chinese Academy of Medical Sciences from January 2009 to September 2017 (n = 7371). We compared the clinicopathologic features and performed Cox regression and landmark survival analyses to explore the prognostic impact of HER2-low on survival outcomes during distinct post-surgery intervals-36 months, 60 months, and 120 months.

RESULTS: HER2-low BC, compared to HER2-zero BC, exhibited less aggressive clinicopathologic features, such as smaller invasion size, lower grade, increased nerve invasion, higher HR positivity, and a higher proportion of low-Ki67 cases. In the HR-positive subgroup, HER2-low demonstrated improved OS (p = 0.046) and DFS (p = 0.026) within 60 months. Conversely, HER2-low displayed worse DFS (p = 0.046) in the HR-negative subgroup after 36 months from surgery. The findings remained robust in uni- and multi-variable Cox models.

CONCLUSIONS: HER2-low BCs manifested less aggressive clinicopathologic features than the HER2-zero cases. The prognostic impact of HER2-low in resectable BCs exhibits variability contingent upon the patients' HR status.}, } @article {pmid38250443, year = {2023}, author = {Wang, Y and Zhang, X and Yan, Y and Niu, T and Zhang, M and Fan, C and Liang, W and Shu, Y and Guo, C and Guo, D and Bi, Y}, title = {GmABCG5, an ATP-binding cassette G transporter gene, is involved in the iron deficiency response in soybean.}, journal = {Frontiers in plant science}, volume = {14}, number = {}, pages = {1289801}, pmid = {38250443}, issn = {1664-462X}, abstract = {Iron deficiency is a major nutritional problem causing iron deficiency chlorosis (IDC) and yield reduction in soybean, one of the most important crops. The ATP-binding cassette G subfamily plays a crucial role in substance transportation in plants. In this study, we cloned the GmABCG5 gene from soybean and verified its role in Fe homeostasis. Analysis showed that GmABCG5 belongs to the ABCG subfamily and is subcellularly localized at the cell membrane. From high to low, GmABCG5 expression was found in the stem, root, and leaf of young soybean seedlings, and the order of expression was flower, pod, seed stem, root, and leaf in mature soybean plants. The GUS assay and qRT-PCR results showed that the GmABCG5 expression was significantly induced by iron deficiency in the leaf. We obtained the GmABCG5 overexpressed and inhibitory expressed soybean hairy root complexes. Overexpression of GmABCG5 promoted, and inhibition of GmABCG5 retarded the growth of soybean hairy roots, independent of nutrient iron conditions, confirming the growth-promotion function of GmABCG5. Iron deficiency has a negative effect on the growth of soybean complexes, which was more obvious in the GmABCG5 inhibition complexes. The chlorophyll content was increased in the GmABCG5 overexpression complexes and decreased in the GmABCG5 inhibition complexes. Iron deficiency treatment widened the gap in the chlorophyll contents. FCR activity was induced by iron deficiency and showed an extraordinary increase in the GmABCG5 overexpression complexes, accompanied by the greatest Fe accumulation. Antioxidant capacity was enhanced when GmABCG5 was overexpressed and reduced when GmABCG5 was inhibited under iron deficiency. These results showed that the response mechanism to iron deficiency is more actively mobilized in GmABCG5 overexpression seedlings. Our results indicated that GmABCG5 could improve the plant's tolerance to iron deficiency, suggesting that GmABCG5 might have the function of Fe mobilization, redistribution, and/or secretion of Fe substances in plants. The findings provide new insights into the ABCG subfamily genes in the regulation of iron homeostasis in plants.}, } @article {pmid38233262, year = {2024}, author = {Wang, B and Fu, Y and Chen, M and Peng, S and Marra, G and Zhuang, J and Zhang, S and Guo, H and Qiu, X}, title = {The presence of intraductal carcinoma of prostate is a risk factor for poor pathologic response in men with high-risk prostate cancer receiving neoadjuvant therapy.}, journal = {Urologic oncology}, volume = {42}, number = {3}, pages = {67.e9-67.e15}, doi = {10.1016/j.urolonc.2023.11.018}, pmid = {38233262}, issn = {1873-2496}, mesh = {Male ; Humans ; Prostate/surgery/pathology ; *Prostatic Neoplasms/drug therapy/pathology ; *Carcinoma, Intraductal, Noninfiltrating/pathology/surgery ; Neoadjuvant Therapy ; Androgen Antagonists/therapeutic use ; Prospective Studies ; Prostatectomy ; Risk Factors ; }, abstract = {OBJECTIVE: To explore the potential association between the presence of intraductal carcinoma of the prostate (IDC-P) on biopsy and pathologic response of primary tumor to neoadjuvant therapy in patients with high-risk prostate cancer.

METHODS: Eighty-five patients with high-risk localized/locally advanced prostate cancer (CaP) who were given 6-month neoadjuvant therapies of androgen deprivation therapy plus docetaxel or abiraterone prior to radical prostatectomy in 2 prospective trials were included in this study. The presence of IDC-P in biopsy pathology was rereviewed by 2 experienced pathologists. Favorable pathologic response was defined as pathologic complete response or minimal residual disease <5 mm on whole-mount histopathology. Characteristics of clinical and biopsy pathology variables were included in univariate and multivariate logistic regression analyses to identify risk factors for the prediction of favorable pathologic response on final pathology.

RESULTS: IDC-P was identified to be present on biopsy pathology of 35 patients (41.2%) while favorable pathologic responses were confirmed in 25 patients (29.4%). Initial prostate-specific antigen (PSA) (OR 3.592, 95% CI 1.176-10.971, P = 0.025) and the presence of IDC-P on biopsy pathology (OR 3.837, 95% CI 1.234-11.930, P = 0.020) were found to be significantly associated with favorable pathologic response in multivariate logistic regression analysis.

CONCLUSION: IDC-P on biopsy pathology was found to be an independent risk factor to predict a poor pathology response of primary CaP to neoadjuvant therapies.}, } @article {pmid38231374, year = {2024}, author = {Maggi, G and Vitale, C and Giacobbe, C and Barone, A and Mastromarino, C and Iannotta, F and Amboni, M and Weintraub, D and Santangelo, G}, title = {Validation of the Italian version of the Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease-Rating Scale (QUIP-RS) in an Italian Parkinson's disease cohort.}, journal = {Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology}, volume = {45}, number = {7}, pages = {3153-3161}, pmid = {38231374}, issn = {1590-3478}, mesh = {Humans ; *Parkinson Disease/complications/psychology/diagnosis ; Female ; Male ; Italy ; *Disruptive, Impulse Control, and Conduct Disorders/diagnosis/etiology ; Aged ; Middle Aged ; *Psychiatric Status Rating Scales/standards ; Reproducibility of Results ; Cohort Studies ; Severity of Illness Index ; Surveys and Questionnaires/standards ; Psychometrics/standards ; }, abstract = {INTRODUCTION: Impulse control disorders (ICDs) frequently occur in Parkinson's disease (PD), and an early identification is essential to prevent severe psychosocial consequences. The Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease-Rating Scale (QUIP-RS) has been developed to evaluate the severity of ICDs along with a range of impulsive-compulsive behaviors (ICBs) in PD; however, its Italian version has not yet been validated.

METHODS: One hundred consecutive outpatients with PD were administered an Italian version of the QUIP-RS and a brief neuropsychological assessment to evaluate global cognitive status and scales to measure depression, apathy and impulsive disorders. We evaluated the internal consistency, convergent and divergent validity, and factorial structure of QUIP-RS. We also explored the possible association between QUIP-RS scores and clinical factors and dopaminergic medication.

RESULTS: Subsyndromal ICDs manifestations were observed in 54% of the patients, and one in four (22%) reported two or more ICDs or related behaviors. The QUIP-RS demonstrated good internal consistency (Cronbach's alpha = 0.806) and construct validity, and its factorial structure reflected different ICDs and ICBs domains. No association emerged between QUIP-RS scores and the clinical aspects of PD and dopaminergic medication.

CONCLUSION: We provided, for the first time, an Italian translation of the QUIP-RS and demonstrated its feasibility in clinical and research settings. Severity of ICDs was independent of clinical factors and dopaminergic medication, underlining the need to adopt a broader perspective on their etiopathology in PD.}, } @article {pmid38193247, year = {2024}, author = {Okano, K and Miyai, K and Mikoshi, A and Edo, H and Ito, K and Tsuda, H and Shinmoto, H}, title = {Histological parameters and stromal desmoplastic status affecting accurate diagnosis of extraprostatic extension of prostate cancer using multi-parametric magnetic resonance imaging.}, journal = {International journal of urology : official journal of the Japanese Urological Association}, volume = {31}, number = {5}, pages = {475-482}, doi = {10.1111/iju.15385}, pmid = {38193247}, issn = {1442-2042}, mesh = {Humans ; Male ; *Prostatic Neoplasms/pathology/diagnostic imaging/surgery ; Aged ; Middle Aged ; *Prostatectomy ; *Multiparametric Magnetic Resonance Imaging ; Prostate/pathology/diagnostic imaging ; Cell Adhesion Molecules/analysis/metabolism ; Neoplasm Grading ; Retrospective Studies ; Magnetic Resonance Imaging ; }, abstract = {OBJECTIVE: To investigate the clinicopathological factors affecting discrepancies between multi-parametric magnetic resonance imaging (mpMRI) and histopathological evaluation for diagnosis of extraprostatic extension (EPE) of prostate cancer.

METHODS: One hundred-and-three lesions from 96 cases with suspected EPE on preoperative mpMRI, of which 60 and 43 showed bulging and frank capsular breach, respectively, were grouped according to pathological (p)EPE in radical prostatectomy specimens. Additionally, clinicopathological/immunohistochemical findings for periostin reflecting a desmoplastic stromal reaction were compared between these groups.

RESULTS: pEPE was detected in 49 (48%) of the 103 lesions. Of these, 25 (42%) showed bulging and 24 (56%) showed frank capsular breach on MRI. In the total cohort, the absence of pEPE was significantly associated with a lower Gleason Grade Group (GG) (p < 0.0001), anterior location (p = 0.003), absence of intraductal carcinoma of the prostate (IDC-P) (p = 0.026), and high stromal periostin expression (p < 0.0001). These trends were preserved in subgroups defined by MRI findings, except for anterior location/IDC-P in the bulging subgroup.

CONCLUSIONS: GG, anterior location, and periostin expression may cause mpMRI-pathological discrepancies regarding EPE. Periostin expression was a significant pEPE-negative factor in all subgroup analyses. Our results indicate that patients with suspected EPE on MRI, regardless of their pEPE results, should be followed as carefully as those with definite pEPE.}, } @article {pmid38190207, year = {2024}, author = {Elshanbary, AA and Zaazouee, MS and Nourelden, AZ and Al-Kafarna, M and Matar, SG and Elsaeidy, AS and Ragab, KM and Elhady, MM and Albadrani, GM and Altyar, AE and Kensara, OA and Abdel-Daim, MM}, title = {Risk factors of diabetes and cancer-specific mortalities in patients with infiltrating ductal carcinoma of the breast: a population-based study.}, journal = {European journal of cancer prevention : the official journal of the European Cancer Prevention Organisation (ECP)}, volume = {33}, number = {4}, pages = {321-333}, pmid = {38190207}, issn = {1473-5709}, mesh = {Humans ; Female ; *Breast Neoplasms/mortality/pathology/therapy ; Middle Aged ; Risk Factors ; *Carcinoma, Ductal, Breast/mortality/pathology/therapy/epidemiology ; *SEER Program/statistics & numerical data ; Aged ; Adult ; Diabetes Mellitus/mortality/epidemiology ; Prognosis ; United States/epidemiology ; Survival Rate ; Follow-Up Studies ; Neoplasm Staging ; }, abstract = {BACKGROUND AND AIMS: Breast cancer is considered one of the most common neoplasms worldwide. Diabetes (DM) increases mortality among postmenopausal patients with breast cancer. Our study aims to identify the risk factors of DM-specific mortality and infiltrating ductal carcinoma (IDC) mortality in patients with IDC of the breast.

MATERIALS AND METHODS: Data of IDC patients were obtained from the Surveillance, Epidemiology, and End Results database from 1975 to 2016. Independent variables included age, race, marital status, the primary site of IDC, breast subtype, the disease stage, grade, chemotherapy, radiation, and surgery. Kaplan-Meier, Cox and Binary regression tests were used to analyze the data using SPSS software.

RESULTS: A total of 673 533 IDC patients were analyzed. Of them, 4224 died due to DM and 116 822 died due to IDC. Factors that increase the risk of overall, IDC-specific, and DM-specific mortalities include older age, black race, widowed, uninsured, regional and distant stages, grade II and III, and no treatment with chemotherapy or radiotherapy or surgery. Additionally, the IDC mortality increased with separated status, all primary sites, all breast subtypes, and stage IV.

CONCLUSION: In patients with IDC, controlling DM besides cancer is recommended to reduce the mortality risk. Old, black, widowed, uninsured, regional and distant stages, grade II and III, and no treatment are common risk factors for DM- and IDC-mortality.}, } @article {pmid38157332, year = {2023}, author = {Shinohara, T and Asoda, T and Nakano, Y and Yamada, H and Fujimori, Y}, title = {Germline BRCA2 Pathogenic Variant in Primary Breast Cancer of a Down Syndrome Individual.}, journal = {The American journal of case reports}, volume = {24}, number = {}, pages = {e942208}, pmid = {38157332}, issn = {1941-5923}, mesh = {Female ; Humans ; Adult ; *Breast Neoplasms/pathology ; Mastectomy ; *Down Syndrome/complications/surgery ; Biomarkers, Tumor ; *Carcinoma, Ductal/surgery ; Germ Cells/pathology ; BRCA2 Protein/genetics ; }, abstract = {BACKGROUND Down syndrome (DS) is the most common genetic disorder, and individuals with DS are known to have a low risk for solid tumors, including breast cancer. In contrast, Breast Cancer Susceptibility Gene (BRCA) pathogenic variant can cause breast cancer. We report a case of primary breast cancer harboring a BRCA2 pathogenic variant in a 35-year-old woman with DS. CASE REPORT A 35-year-old woman with DS presented with a palpable 2-cm mass in the upper-inner quadrant of the left breast. A biopsy confirmed an invasive ductal carcinoma of the breast. Her clinical diagnosis was cT2, N0, M0, cStageIIA. A left modified radical mastectomy with axillary node dissection was performed. Her final pathological diagnosis was invasive ductal carcinoma (T2, pN1, M0, stageIIB), positive estrogen receptors, negative progesterone receptors, negative human epidermal receptor-2 status. She was started on adjuvant hormonal therapy. Unfortunately, 23 months after the operation, multiple metastases were detected. Testing for a BRCA pathogenic variant was performed, and a BRCA2 pathogenic variant was detected. Olaparib was orally administered, and the levels of tumor markers rapidly declined; however, the levels of the tumor markers started to increase again 5 months after the initiation of olaparib. Subsequently, she developed bilateral carcinomatous lymphangiomatosis and died 59 months after the operation. CONCLUSIONS This report highlights a rare case of primary breast cancer harboring a germline BRCA2 pathogenic variant in an individual with DS. Our study highlights the importance of genetic testing as part of breast cancer management in these patients.}, } @article {pmid38131316, year = {2024}, author = {Özden, A and Dalgıç, B and Demir, M and Hazırolan, G and Uzun, Ö and Metan, G}, title = {Impact of a hospital sepsis management protocol on the selection of empirical antibiotics in infectious disease consultations.}, journal = {Journal of chemotherapy (Florence, Italy)}, volume = {36}, number = {3}, pages = {190-197}, doi = {10.1080/1120009X.2023.2296146}, pmid = {38131316}, issn = {1973-9478}, mesh = {Aged ; Female ; Humans ; Male ; Middle Aged ; Anti-Bacterial Agents/therapeutic use ; *Bacteremia/drug therapy ; beta-Lactamases ; Carbapenems ; *Communicable Diseases/drug therapy ; Escherichia coli ; *Escherichia coli Infections/drug therapy ; Hospitals ; *Klebsiella Infections/microbiology ; Piperacillin, Tazobactam Drug Combination/therapeutic use ; Referral and Consultation ; Retrospective Studies ; *Sepsis/drug therapy ; Clinical Trials as Topic ; }, abstract = {It is well-established that Infectious Diseases consultation (IDC) enhances the prognosis of bloodstream infections. However, it is unclear if adoption of an institutional sepsis protocol would lead to any further improvement in a setting where IDC and infectious diseases approval (IDA) - available throughout 7 days/24 hours -are mandatory for administering broad spectrum antibiotics. We aimed to evaluate the influence of the institutional sepsis protocol developed by Department of Infectious Diseases and Clinical Microbiology on the selection of appropriate empirical antibiotics by IDC through focusing on patients who had bloodstream infections caused by Extended-spectrum β-lactamase (ESBL) producing Escherichia coli and Klebsiella pneumoniae, which poses a therapeutic challenge. One hundred and fifty-three adult patients (58 patients in the pre-protocol period and 95 patients in the post-protocol period), who received empirical antibiotic treatment for ESBL-producing E. coli and K. pneumoniae, in whom at least one systemic antibiotic was started either on the day blood cultures were drawn or not later than 24 hours were included in the study, retrospectively. The primary outcome was whether the empirical treatment regimen included a carbapenem that was accepted as the appropriate treatment based on the results of the MERINO trial. Secondary outcomes included empirical treatment based on pre-defined risk factors suggesting multidrug resistance (MDR), 30-day inpatient mortality, and appropriate antibacterial treatment according to antimicrobial susceptibility test (AST) results. The median age (Interquartile range) was 61 (48-70.5) years and 76 (49.7%) out of 153 patients were male. The patients in the post-protocol period were older compared to the pre-protocol period (54 years vs 64 years, p = 0.045). The Charlson Comorbidity Index was higher during the post-protocol period compared to the pre-protocol period (4 vs 5, p=0.038). At least one risk factor for MDR bacteria infection was present in 147 (96.1%) of the 153 patients. While the rate of risk factors for MDR bacteria infections did not differ significantly between the pre-protocol and post-protocol periods, the post-protocol period showed a significantly higher level of appropriate antibiotic treatment according to the presence of MDR risk factors compared to the pre-protocol period (44.8% vs 64.2%, p=0.019). There was a significant increase in the use of carbapenems in the post-protocol period compared to the pre-protocol period (34.5% vs. 56.8%, p=0.007). When the subgroup of patients who were likely to have infection caused by ESBL-producing bacteria is taken into consideration, the carbapenem use was more frequent in the post-protocol period (37.8% vs 68.9%, p=0.002). The rate of appropriate empirical treatment according to AST was not statistically different between pre-protocol and post-protocol period. The 30-day mortality rates were similar in both periods (24.1% vs 31.5, p=0.33). However, the rate of susceptibility to piperacillin-tazobactam was statistically higher in the pre-protocol period (82.6% vs 46.2%, p=0.016) when 39.7% of the patients received piperacillin-tazobactam as the empirical treatment. This study highlights the significance of using a structured protocol to attain appropriate empirical treatment for patients suspected of sepsis, even in a setting where IDC is readily available.}, } @article {pmid38104283, year = {2023}, author = {Maman, A and Senol, O}, title = {Evaluating Alterations in Breast Cancer Patients after Recovery Via A PET/CT-Assisted Metabolomics Approach.}, journal = {Puerto Rico health sciences journal}, volume = {42}, number = {4}, pages = {276-282}, pmid = {38104283}, issn = {2373-6011}, mesh = {Humans ; Female ; *Positron Emission Tomography Computed Tomography ; *Breast Neoplasms/pathology ; Metabolome ; Metabolomics/methods ; Biomarkers ; }, abstract = {OBJECTIVE: Breast cancer is a mortal disease that causes many deaths, especially in women. Improved therapies could contribute positively to survival rates. Metabolomics is an important tool for monitoring the alterations of several metabolites in clinical cases. This study aimed to develop a metabolomics model to observe (via mass spectroscopy) metabolic alterations in patients who suffered from breast cancer (BC), both before and after their recovery.

MATERIALS AND METHODS: Grades 1 and 2 invasive ductal carcinoma patients were evaluated based on their positron emission tomography/computed tomography results. Fourteen patients who had fully recovered from BC were subjected to metabolomics analysis. Plasma samples were extracted and analyzed via quadrupole time-of-flight mass tandem spectroscopy. A chemometrics analysis was performed in order to determine the statistically significant metabolites. All the metabolites were annotated via the mummichog algorithm.

RESULTS AND DISCUSSION: According to the data analysis, glucose, ornithine, phenyalanine, some vitamins, and metabolites in the fatty acid metabolism were statistically altered after recovery of each patient.

CONCLUSION: Untargeted metabolomics studies can be used to understand the etiopathogenesis of breast cancer, finding new biomarkers and alterations of metabolic pathways. After the tumor burden was removed, homeostasis was restored and the concentration of several metabolites began to normalize. This study elucidated the effects of breast cancer at the molecular level.}, } @article {pmid38076287, year = {2023}, author = {Tractenberg, RE and Groah, SL and Frost, JK and Yumoto, F and Rounds, AK and Ljungberg, IH}, title = {Urinary Symptoms Among People With Neurogenic Lower Urinary Tract Dysfunction (NLUTD) Vary by Bladder Management.}, journal = {Topics in spinal cord injury rehabilitation}, volume = {29}, number = {3}, pages = {31-43}, pmid = {38076287}, issn = {1945-5763}, mesh = {Humans ; Urinary Bladder ; *Urinary Bladder, Neurogenic/therapy/diagnosis ; *Spinal Cord Injuries/complications ; Catheters, Indwelling ; Pain/complications ; }, abstract = {OBJECTIVES: To determine whether assessment and decision-making around urinary symptoms in people with neurogenic lower urinary tract dysfunction (NLUTD) should depend on bladder management.

METHODS: Three surveys of urinary symptoms associated with NLUTD (USQNBs) were designed specific to bladder management method for those who manage their bladders with indwelling catheter (IDC), intermittent catheter (IC), or voiding (V). Each was deployed one time to a national sample. Subject matter experts qualitatively assessed the wording of validated items to identify potential duplicates. Clustering by unsupervised structural learning was used to analyze duplicates. Each item was classified into mutually exclusive and exhaustive categories: clinically actionable ("fever"), bladder-specific ("suprapubic pain"), urine quality ("cloudy urine"), or constitutional ("leg pain").

RESULTS: A core of 10 "NLUTD urinary symptoms" contains three clinically actionable, bladder-specific, and urine quality items plus one constitutional item. There are 9 (IDC), 11 (IC), and 8 (V) items unique to these instruments. One decision-making protocol applies to all instruments.

CONCLUSION: Ten urinary symptoms in NLUTD are independent of bladder management, whereas a similar number depend on bladder management. We conclude that assessment of urinary symptoms for persons with NLUTD should be specific to bladder management method, like the USQNBs are.}, } @article {pmid38067216, year = {2023}, author = {Bernhardt, M and Kristiansen, G}, title = {Molecular Alterations in Intraductal Carcinoma of the Prostate.}, journal = {Cancers}, volume = {15}, number = {23}, pages = {}, pmid = {38067216}, issn = {2072-6694}, abstract = {Intraductal carcinoma of the prostate is most commonly associated with high-grade invasive prostate cancer. However, isolated IDC-P without adjacent cancer or high-grade cancer is also well known. Common genetic alterations present in IDC-P with adjacent high-grade prostate cancer are those described in high-grade tumors, such as PTEN loss (69-84%). In addition, the rate of LOH involving TP53 and RB1 is significantly higher. IDC-P is common in the TCGA molecular subset of SPOP mutant cancers, and the presence of SPOP mutations are more likely in IDC-P bearing tumors. IDC-P without adjacent high-grade cancers are by far less common. They are less likely to have PTEN loss (47%) and rarely harbor an ERG fusion (7%). Molecular alterations that may predispose a person to the development of IDC-P include the loss of BRCA2 and PTEN as well as mutations in SPOP. However, the causative nature of these genetic alterations is yet to be validated.}, } @article {pmid38049608, year = {2024}, author = {Maggi, G and Giacobbe, C and Vitale, C and Amboni, M and Obeso, I and Santangelo, G}, title = {Theory of mind in mild cognitive impairment and Parkinson's disease: The role of memory impairment.}, journal = {Cognitive, affective & behavioral neuroscience}, volume = {24}, number = {1}, pages = {156-170}, pmid = {38049608}, issn = {1531-135X}, mesh = {Humans ; *Parkinson Disease/complications/psychology ; *Theory of Mind ; *Cognitive Dysfunction/etiology/psychology ; Executive Function ; *Cognition Disorders ; Memory Disorders ; Neuropsychological Tests ; }, abstract = {BACKGROUND: Social cognition is impaired in Parkinson's disease (PD). Whether social cognitive impairment (iSC) is a by-product of the underlying cognitive deficits in PD or a process independent of cognitive status is unknown. To this end, the present study was designed to investigate the weight of specific cognitive deficits in social cognition, considering different mild cognitive impairment subtypes of PD (PD-MCI).

METHODS: Fifty-eight PD patients underwent a neuropsychological battery assessing executive functions, memory, language, and visuospatial domains, together with social cognitive tests focused on theory of mind (ToM). Patients were divided into subgroups according to their clinical cognitive status: amnestic PD-MCI (PD-aMCI, n = 18), non-amnestic PD-MCI (PD-naMCI, n = 16), and cognitively unimpaired (PD-CU, n = 24). Composite scores for cognitive and social domains were computed to perform mediation analyses.

RESULTS: Memory and language impairments mediated the effect of executive functioning in social cognitive deficits in PD patients. Dividing by MCI subgroups, iSC occurred more frequently in PD-aMCI (77.8%) than in PD-naMCI (18.8%) and PD-CU (8.3%). Moreover, PD-aMCI performed worse than PD-CU in all social cognitive measures, whereas PD-naMCI performed worse than PD-CU in only one subtype of the affective and cognitive ToM tests.

CONCLUSIONS: Our findings suggest that ToM impairment in PD can be explained by memory dysfunction that mediates executive control. ToM downsides in the amnesic forms of PD-MCI may suggest that subtle changes in social cognition could partly explain future transitions into dementia. Hence, the evaluation of social cognition in PD is critical to characterize a possible behavioral marker of cognitive decline.}, } @article {pmid38026906, year = {2023}, author = {Günay, S and Gökçek, B and Kandemir, Ö and Akan, A and Yalçın, O}, title = {Long-term results of breast cancer patients who received IOERT as boost during BCS: A single-institution retrospective analysis.}, journal = {Turkish journal of surgery}, volume = {39}, number = {2}, pages = {115-120}, pmid = {38026906}, issn = {2564-6850}, abstract = {OBJECTIVES: Intraoperative electron radiotherapy (IOERT) applied as boost to the tumor bed during breast conserving surgery is advantageous in terms of local recurrence in breast cancer patients. In addition, it has other advantages over the adjuvant boost RT such as no risk of tumor bed change, ease of sequencing radiotherapy chemotherapy, and reduced workload of the radiotherapy clinic. This study aimed to evaluate the long-term results of our patients who were treated with this method in our institution and are still being followed up.

MATERIAL AND METHODS: One hundred and three patients enrolled in this study received IOERT equivalent to 10 Gy as boost during BCS and were subsequently given adjuvant WBI according to the biological subtype of the tumor systemic therapy. These patients were analyzed using their files and hospital records. Patients were evaluated for overall survival, local recurrence, distant metastasis, and cosmetic outcome (using LENT-SOMA scale).

RESULTS: Median age was 53,5 (27-74), mean follow-up time was 75 (48-106) months. Mean pathological tumor size was 18 mm (4-30), 90 of the patients had invasive ductal carcinoma, eight of them were lobular and five of them had mixed histological structure. Ninety-three of the patients presented histological grade II, 15 grade III; 74 patients were luminal A-like, 15 luminal B-like, eight HER2 positive and six triple negative breast cancer. According to the LENT-SOMA scale, 35 had grade 0, 42 each had grade I, 23 had grade II, and two had grade III. All patients underwent whole breast irradiation after surgery, 81 received chemotherapy and 90 endocrine therapy. There was one local recurrence, distant recurrence was seen in four patients and one patient died of non-breast cancer causes. Overall survival was %99, and event free survival %96.

CONCLUSION: IOERT for breast cancer treatment during BCS is a safe option with low chronic toxicity and the cosmetic outcome gets better over time.}, } @article {pmid38024052, year = {2023}, author = {Prabhu, SD and Rai, HS and Nayak, R and Naik, R and Jayasheelan, S}, title = {Study of the Immunohistochemical Expression of p63 in Benign Lesions and Carcinoma of the Breast at a Tertiary Hospital in South India.}, journal = {Cureus}, volume = {15}, number = {11}, pages = {e48557}, pmid = {38024052}, issn = {2168-8184}, abstract = {BACKGROUND: Invasive breast carcinoma is among the most common female cancers worldwide, causing high morbidity and mortality. Considerable disagreement in the interpretation of diagnostically challenging breast lesions based on histology alone has been documented. One of the essential histopathological findings that help distinguish benign from malignant lesions is the presence of the myoepithelial cell layer. Myoepithelial markers such as tumor protein 63 (p63) help distinguish invasive carcinoma from benign proliferations. p63 antibody is superior to other myoepithelial markers as it selectively stains the nuclei and is negative in stromal cells.

OBJECTIVE: To study the expression of p63 in various histological subtypes and grades of breast carcinomas.

METHODS: After routine hematoxylin and eosin stain, 65 cases of breast lesions were subjected to immunohistochemistry for p63 antigen using Novacastra ready-to-use monoclonal antibody p6. All cases were analyzed for p63 expression, and its staining arrangement was interpreted.

RESULTS: In all benign lesions, immunoreactivity was noted in the myoepithelial cells, forming a continuous layer surrounding the luminal epithelial cells. The benign papillary lesions showed p63 staining in the fibrovascular core of the papillary fronds and at the periphery. A few single myoepithelial cells stained by p63 were also seen scattered discontinuously in ductal carcinoma in situ (DCIS). All invasive carcinomas and encapsulated papillary carcinomas were completely devoid of peripheral p63 staining of myoepithelial cells.

CONCLUSION: p63 is a specific nuclear marker of myoepithelial cells in the breast and can, therefore, aid in distinguishing invasive ductal carcinoma from DCIS or rare questionable hyperplastic lesions. They also play a significant role in distinguishing various papillary lesions of the breast and, hence, can be incorporated into routine reporting for definitive diagnosis and accurate treatment.}, } @article {pmid38022397, year = {2023}, author = {Zhu, XD and Yu, JH and Ai, FL and Wang, Y and Lv, W and Yu, GL and Cao, XK and Lin, J}, title = {Construction and Validation of a Novel Nomogram for Predicting the Risk of Metastasis in a Luminal B Type Invasive Ductal Carcinoma Population.}, journal = {World journal of oncology}, volume = {14}, number = {6}, pages = {476-487}, pmid = {38022397}, issn = {1920-454X}, abstract = {BACKGROUND: Postoperative distant metastasis is the main cause of death in breast cancer patients. We aimed to construct a nomogram to predict the risk of metastasis of luminal B type invasive ductal carcinoma.

METHODS: We applied the data of 364 luminal B type breast cancer patients between 2008 and 2013. Patients were categorized into modeling group and validation group randomly (1:1). The breast cancer metastasis nomogram was developed from the logistic regression model using clinicopathological variables. The area under the receiver-operating characteristic curve (AUC) was calculated in modeling group and validation group to evaluate the predictive accuracy of the nomogram.

RESULTS: The multivariate logistic regression analysis showed that tumor size, No. of the positive level 1 axillary lymph nodes, human epidermal growth factor receptor 2 (HER2) status and Ki67 index were the independent predictors of the breast cancer metastasis. The AUC values of the modeling group and the validation group were 0.855 and 0.818, respectively. The nomogram had a well-fitted calibration curve. The positive and negative predictive values were 49.3% and 92.7% in the modeling group, and 47.9% and 91.0% in the validation group. Patients who had a score of 60 or more were thought to have a high risk of breast cancer metastasis.

CONCLUSIONS: The nomogram has a great predictive accuracy of predicting the risk of breast cancer metastasis. If patients had a score of 60 or more, necessary measures, like more standard treatment methods and higher treatment adherence of patients, are needed to take to lower the risk of metastasis and improve the prognosis.}, } @article {pmid38012767, year = {2023}, author = {Deguchi, S and Iwakami, A and Tujigiwa, M and Otake, H and Mano, Y and Yamamoto, N and Nakazawa, Y and Misra, M and Nagai, N}, title = {Recovery from indomethacin-induced gastrointestinal bleeding by treatment with teprenone.}, journal = {Journal of pharmaceutical health care and sciences}, volume = {9}, number = {1}, pages = {44}, pmid = {38012767}, issn = {2055-0294}, abstract = {BACKGROUND: Gastrointestinal injuries caused by nonsteroidal anti-inflammatory drugs (NSAIDs) is a serious side effect in patients with rheumatoid arthritis (RA). However, effective therapeutic strategies have yet to be established. In this study, we investigated the therapeutic effects of teprenone (TEP), a gastric mucosal protective drug, on NSAID-induced gastrointestinal injuries in rats with RA (AA rats).

METHODS: Gastrointestinal injury was induced by oral administration of indomethacin (IMC), a typical NSAID. TEP was orally administered after IMC-induced gastrointestinal bleeding, and the stomach, jejunum, and ileum were excised.

RESULTS: On day 14 of IMC administration, lesion areas in the stomach, jejunum, and ileum were significantly larger in AA rats than in normal rats. When TEP was orally administered to AA rats, the lesion areas in the stomach, jejunum, and ileum significantly decreased compared with those in control rats (IMC-induced AA rats). Therefore, we measured NOS2 mRNA and NO levels, which were significantly decreased in rats with IMC-induced AA after treatment with TEP.

CONCLUSIONS: These results suggest that the oral administration of TEP may be useful for the treatment of NSAID-induced gastrointestinal injuries in patients with RA.}, } @article {pmid38007354, year = {2024}, author = {Miyajima, K and Sato, S and Uchida, N and Suzuki, H and Iwatani, K and Imai, Y and Aikawa, K and Yanagisawa, T and Kimura, S and Tashiro, K and Tsuzuki, S and Honda, M and Koike, Y and Miki, J and Miki, K and Shimomura, T and Yuen, S and Yamada, Y and Aoki, M and Takahashi, H and Urabe, F and Kimura, T}, title = {Clinical Significance of Intraductal Carcinoma of the Prostate After High-Dose Brachytherapy With External Beam Radiation Therapy: A Single Institution Series and an Updated Meta-Analysis.}, journal = {Clinical genitourinary cancer}, volume = {22}, number = {2}, pages = {149-156.e1}, doi = {10.1016/j.clgc.2023.10.005}, pmid = {38007354}, issn = {1938-0682}, mesh = {Male ; Humans ; *Brachytherapy/adverse effects ; Prostate/pathology ; Retrospective Studies ; *Carcinoma, Intraductal, Noninfiltrating/etiology ; Clinical Relevance ; *Prostatic Neoplasms/pathology ; }, abstract = {BACKGROUND: We compared oncological outcomes between prostate cancer (PCa) patients with and without intraductal carcinoma of the prostate (IDC-P) after high-dose-rate brachytherapy (HDR-BT) with external beam radiation therapy (EBRT).

METHODS: We performed a retrospective analysis of 138 patients with clinically high-risk, very high-risk, or locally advanced PCa who received HDR-BT with EBRT. Of these, 70 (50.7 %) patients were diagnosed with IDC-P; 68 (49.3 %) patients with acinar adenocarcinoma of prostate. The oncological outcomes, including biochemical recurrence-free survival (BCRFS) and clinical progression-free survival (CPFS), were assessed using Kaplan-Meier curves. Additionally, Cox proportional hazards models were used to identify significant prognostic indicators or biochemical recurrence (BCR). Meta-analysis of existing literatures was performed to evaluate the risk of BCR in patients with IDC-P after radiation therapy, compared to those without IDC-P.

RESULTS: Kaplan-Meier curves demonstrated significantly inferior BCRFS and CPFS in patients with IDC-P. Multivariate analysis revealed that IDC-P and Grade Group 5 status were associated with increased BCR risk. in our meta-analysis, IDC-P was associated with BCR (HR = 2.13, P = .003).

CONCLUSION: Amongst the patients who received HDR-BT, patients with IDC-P displayed significantly more rapid disease progression, compared with patients who did not have IDC-P.}, } @article {pmid37993256, year = {2023}, author = {Wang, H and Ma, X and Li, S and Ni, X}, title = {SEL1L3 as a link molecular between renal cell carcinoma and atherosclerosis based on bioinformatics analysis and experimental verification.}, journal = {Aging}, volume = {15}, number = {22}, pages = {13150-13162}, pmid = {37993256}, issn = {1945-4589}, mesh = {Humans ; Biomarkers, Tumor/genetics ; *Carcinoma, Renal Cell/genetics/pathology ; Computational Biology/methods ; Gene Expression Profiling/methods ; Gene Regulatory Networks ; *Kidney Neoplasms/genetics ; Transcription Factors/genetics ; }, abstract = {BACKGROUND: Renal cancer, the most common type of kidney cancer, develops in the renal tubular epithelium. Atherosclerosis of the aorta is the primary cause of atherosclerosis. However, the underlying mechanisms remain unclear.

METHODS: The renal clear cell carcinoma RNA sequence profile was obtained from The Cancer Genome Atlas (TCGA) database, and the atherosclerosis datasets GSE28829 and GSE43292 based on GPL570 and GPL6244 was obtained from the Gene Expression Omnibus (GEO) database. The difference and hub genes were identified by the Limma protein-protein interaction (PPI) network in R software. Functional enrichment, survival, and immunoinfiltration analyses were performed. The role of SEL1L3 in the ErbB/PI3K/mTOR signaling pathway, apoptosis, invasion, cell cycle, and inflammation was analyzed using western blotting.

RESULTS: 764 DEGs were identified from TCGA Kidney Renal Clear Cell Carcinoma (KIRC) dataset. A total of 344 and 117 DEGs were screened from the GSE14762 and GSE53757 datasets, respectively. Functional enrichment analysis results primarily indicated enrichment in the transporter complex, DNA-binding transcription activator activity, morphogenesis of the embryonic epithelium, stem cell proliferation, adrenal overactivity and so on. Fifteen common DEGs overlapped among the three datasets. The PPI network revealed that SEL1L3 was the core gene. Survival analysis showed that lower SEL1L3 expression levels led to a worse prognosis. Immune cell infiltration analysis showed that SEL1L3 expression was significantly correlated with antibody-drug conjugates (aDC), B cells, eosinophils, interstitial dendritic cells (iDC), macrophages, and more.

CONCLUSIONS: SEL1L3 plays an important role in renal clear cell carcinoma and atherosclerosis and may be a potential link between them.}, } @article {pmid37978324, year = {2023}, author = {Stead, Z and Capuano, R and Di Natale, C and Pain, A}, title = {The volatilome signatures of Plasmodium falciparum parasites during the intraerythrocytic development cycle in vitro under exposure to artemisinin drug.}, journal = {Scientific reports}, volume = {13}, number = {1}, pages = {20167}, pmid = {37978324}, issn = {2045-2322}, support = {BAS/1/1020-01-01//KAUST faculty baseline fund/ ; BAS/1/1020-01-01//KAUST faculty baseline fund/ ; Giunta Regionale n. G10795//Regione Lazio/ ; Giunta Regionale n. G10795//Regione Lazio/ ; }, mesh = {Humans ; Animals ; Plasmodium falciparum ; *Parasites ; *Antimalarials/pharmacology/therapeutic use ; *Volatile Organic Compounds/pharmacology ; Drug Resistance ; *Artemisinins/pharmacology/therapeutic use ; *Malaria, Falciparum/drug therapy/parasitology ; *Malaria/drug therapy ; Protozoan Proteins/pharmacology ; }, abstract = {Volatile organic compounds (VOCs) comprise a diverse range of metabolites with high vapour pressure and low boiling points. Although they have received attention, they are a largely unexplored part of the metabolome. Previous studies have shown that malaria infections produce characteristic, definitive, and detectable volatile signatures. Many transcriptional and metabolic differences are observed at different stages of the parasite Intraerythrocytic Developmental Cycle (IDC) as well as when artemisinin-resistant parasites are put under drug pressure. This prompted our research to characterize whether these responses are reflected at a volatile level in malaria during the IDC stages using gas chromatography-mass spectrometry. We investigated whether the resistant P. falciparum parasites would produce their own characteristic volatilome profile compared to near-isogenic wild-type parasite in vitro; firstly at three different stages of the IDC and secondly in the presence or absence of artemisinin drug treatment. Finally, we explored the VOC profiles from two media environments (Human serum and Albumax) of recently lab-adapted field parasite isolates, from Southeast Asia and West/East Africa, compared to long-term lab-adapted parasites. Recognizable differences were observed between IDC stages, with schizonts having the largest difference between wild type and resistant parasites, and with cyclohexanol and 2,5,5-trimethylheptane only present for resistant schizonts. Artemisinin treatment had little effect on the resistant parasite VOC profile, whilst for the wild type parasites compounds ethylbenzene and nonanal were greatly affected. Lastly, differing culturing conditions had an observable impact on parasite VOC profile and clustering patterns of parasites were specific to geographic origin. The results presented here provide the foundation for future studies on VOC based characterization of P. falciparum strains differing in abilities to tolerate artemisinin.}, } @article {pmid37922498, year = {2024}, author = {Maggi, G and Giacobbe, C and Iannotta, F and Santangelo, G and Vitale, C}, title = {Prevalence and clinical aspects of obstructive sleep apnea in Parkinson disease: A meta-analysis.}, journal = {European journal of neurology}, volume = {31}, number = {2}, pages = {e16109}, pmid = {37922498}, issn = {1468-1331}, mesh = {Humans ; Male ; *Parkinson Disease/complications/epidemiology ; Polysomnography ; Prevalence ; *REM Sleep Behavior Disorder/etiology/complications ; *Sleep Apnea, Obstructive/epidemiology/complications ; }, abstract = {BACKGROUND AND PURPOSE: Obstructive sleep apnea (OSA) frequently occurs in Parkinson Disease (PD), probably caused by upper airway dysfunctions or shared pathogenetic mechanisms. OSA may precede PD diagnosis or worsen throughout its course, but its relationship with clinical features and dopaminergic medication remains unclear. This meta-analysis aimed to provide a reliable estimate of OSA prevalence in the PD population (PD-OSA) and to clarify its clinical associated factors to help clinicians in understanding the underlying pathophysiological mechanisms.

METHODS: A systematic literature search was performed up to April 2023 using the PubMed, Scopus, and PsycINFO databases. Articles were included if they provided data on PD patients with and without OSA. Pooled prevalence for PD-OSA was calculated using the proportions of PD participants diagnosed with OSA. Demographic and clinical features associated with PD-OSA were explored by comparing PD patients with and without OSA.

RESULTS: Seventeen studies were included in the meta-analysis. Pooled OSA prevalence was 45% of a total sample of 1448 PD patients and was associated with older age, male sex, higher body mass index (BMI), more severe motor disturbances and periodic limb movements, reduced risk of rapid eye movement sleep behavior disorder, intake of dopamine agonists, and worse excessive daytime sleepiness. No relationship emerged with cognitive functioning and neuropsychiatric manifestations.

CONCLUSIONS: OSA affects nearly half of PD patients as a secondary outcome of predisposing factors such as older age and higher BMI in addition to PD-related motor impairment. Future studies should focus on determining the impact of both clinical features and dopaminergic medication on the development of PD-OSA.}, } @article {pmid37919558, year = {2024}, author = {Avatefi, M and HadavandSiri, F and Nazari, SSH and Akbari, ME}, title = {Risk factors of developing contralateral breast cancer after first primary breast cancer treatment.}, journal = {Cancer reports (Hoboken, N.J.)}, volume = {7}, number = {1}, pages = {e1927}, pmid = {37919558}, issn = {2573-8348}, mesh = {Female ; Humans ; *Breast Neoplasms/diagnosis/epidemiology/therapy ; Retrospective Studies ; *Neoplasms, Second Primary/diagnosis/epidemiology/etiology ; Risk Factors ; Proportional Hazards Models ; }, abstract = {BACKGROUND: Breast cancer (BC) is the most common cancer among women worldwide. Increased survival of primary BC (PBC) has increased contralateral breast cancer (CBC) and become a health problem.

AIMS: This study aimed to determine the effect of disease-free interval (DFI), risk factors and PBC characteristics on the progression of CBC within primary BC survivors.

METHODS AND RESULTS: This retrospective study identified 5003 women diagnosed with breast cancer between 2000 and 2020 in the cancer research center. The study included 145 CBC and 4858 PBC survivors, with CBC diagnosed at least 6 months after the detection of primary BC. ER+, PR+, and HER2+ were reported in 72.13%, 66.67%, and 30% of CBC patients. Invasive ductal carcinoma (IDC) BC was reported in 69.57% of patients, and 81.90% and 83.64% of the patients were treated with adjuvant chemotherapy and external radiotherapy. The Kaplan-Meier method indicated that the median time interval between PBC and CBC was 3.92 years, and the 5-year DFI was 97%. The Cox proportional hazard regression model indicated that although more than half of the participants had no family history of BC (69.57%), women 60 years and older were negatively associated with CBC.

CONCLUSION: This study provides the first investigation of CBC and DFI risk factors among PBC survivors in Iran. Age was found to be negatively associated with CBC development particularly after the age of 60, indicating the necessity of tracking CBC survivors carefully in this age group.}, } @article {pmid37914605, year = {2024}, author = {Shuman, E and Goldenberg, A and Saguy, T and Halperin, E and van Zomeren, M}, title = {When Are Social Protests Effective?.}, journal = {Trends in cognitive sciences}, volume = {28}, number = {3}, pages = {252-263}, doi = {10.1016/j.tics.2023.10.003}, pmid = {37914605}, issn = {1879-307X}, abstract = {Around the world, people engage in social protests aimed at addressing major societal problems. Certain protests have led to significant progress, yet other protests have resulted in little demonstrable change. We introduce a framework for evaluating the effectiveness of social protest made up of three components: (i) what types of action are being considered; (ii) what target audience is being affected; and (iii) what outcomes are being evaluated? We then review relevant research to suggest how the framework can help synthesize conflicting findings in the literature. This synthesis points to two key conclusions: that nonviolent protests are effective at mobilizing sympathizers to support the cause, whereas more disruptive protests can motivate support for policy change among resistant individuals.}, } @article {pmid37873952, year = {2024}, author = {Patel, K and Rao, DM and Sundersingh, S and Velusami, S and Rajkumar, T and Nair, B and Pandey, A and Chatterjee, A and Mani, S and Gowda, H}, title = {MicroRNA Expression Profile in Early-Stage Breast Cancers.}, journal = {MicroRNA (Shariqah, United Arab Emirates)}, volume = {13}, number = {1}, pages = {71-81}, pmid = {37873952}, issn = {2211-5374}, support = {BT/PR8152/AGR/36/739/2013//Department of Biotechnology, Govt. of India/ ; }, mesh = {Humans ; Female ; *MicroRNAs/genetics ; *Breast Neoplasms/genetics/pathology/mortality ; *Gene Expression Regulation, Neoplastic/genetics ; *Carcinoma, Intraductal, Noninfiltrating/genetics/pathology ; *Carcinoma, Ductal, Breast/genetics/pathology ; Middle Aged ; Neoplasm Staging ; Gene Expression Profiling ; Biomarkers, Tumor/genetics ; Transcriptome/genetics ; }, abstract = {BACKGROUND: Breast cancer is one of the leading causes of cancer deaths in women. Early diagnosis offers the best hope for a cure. Ductal carcinoma in situ is considered a precursor of invasive ductal carcinoma of the breast. In this study, we carried out microRNA sequencing from 7 ductal carcinoma in situ (DCIS), 6 infiltrating ductal carcinomas (IDC Stage IIA) with paired normal, and 5 unpaired normal breast tissue samples.

METHODS: We have deployed miRge for microRNA analysis, DESeq for differential expression analysis, and Cytoscape for competing endogenous RNA network investigation.

RESULTS: Here, we identified 76 miRNAs that were differentially expressed in DCIS and IDC. Additionally, we provide preliminary evidence of miR-365b-3p and miR-7-1-3p being overexpressed, and miR-6507-5p, miR-487b-3p, and miR-654-3p being downregulated in DCIS relative to normal breast tissue. We also identified a miRNA miR-766-3p that was overexpressed in earlystage IDCs. The overexpression of miR-301a-3p in DCIS and IDC was confirmed in 32 independent breast cancer tissue samples.

CONCLUSION: Higher expression of miR-301a-3p is associated with poor overall survival in The Cancer Genome Atlas Breast Cancer (TCGA-BRCA) dataset, indicating that it may be associated with DCIS at high risk of progressing to IDC and warrants deeper investigation.}, } @article {pmid37855288, year = {2024}, author = {Mohammed, BT and Uzodi, N and Gotimukul, A and Kokebie, R}, title = {Case Report of MPO+ ANCA Vasculitis with Pauci-immune GN Associated with Invasive Ductal Carcinoma of the Breast.}, journal = {Current rheumatology reviews}, volume = {20}, number = {2}, pages = {213-218}, doi = {10.2174/0115733971246438230924163114}, pmid = {37855288}, issn = {1875-6360}, mesh = {Female ; Humans ; Aged ; Antibodies, Antineutrophil Cytoplasmic ; *Glomerulonephritis ; Abscess ; *Breast Neoplasms/complications ; Mastectomy ; *Vasculitis ; Peroxidase ; *Carcinoma, Ductal ; }, abstract = {BACKGROUND: Malignancy-associated vasculitis usually presents in the form of polyarteritis nodosa or leukocytoclastic vasculitis. However, ANCA vasculitis associated with malignancy is rare. Here, we present a case of MPO+ ANCA vasculitis with pauci-immune GN associated with invasive ductal carcinoma of the breast.

CASE PRESENTATION: A 66-year-old female with a history of rheumatoid arthritis, Hashimoto's thyroiditis, and psoriasis presented with multiple joint pain, body aches, petechial rash, paresthesia and numbness, and deranged renal function a month after diagnosis of localized left breast invasive ductal carcinoma. Renal biopsy showed crescentic pauci-immune glomerulonephritis, and serology was positive for Perinuclear Antineutrophil Cytoplasmic Antibody (P-ANCA) and myeloperoxidase (MPO). The disease course was complicated by diverticulitis with peritonitis and intraperitoneal abscess collection, which required laparoscopic peritoneal lavage and additional interventional radiology-guided drainage of the abscess. We treated the patient successfully with steroids, rituximab, and mastectomy for left breast malignant lesions, resulting in the resolution of symptoms, normalization of inflammatory markers, and ANCA seroconversion.

CONCLUSION: Treating ANCA-associated Vasculitis (AAV) in surgical emergencies like bowel perforation can be challenging. Individualized treatment strategy tailored to patients' acute needs is crucial. In this case, we considered malignancy-associated vasculitis and pursued treatment that fit the patient's clinical situation in a multidisciplinary approach.}, } @article {pmid37835856, year = {2023}, author = {Khalid, A and Mehmood, A and Alabrah, A and Alkhamees, BF and Amin, F and AlSalman, H and Choi, GS}, title = {Breast Cancer Detection and Prevention Using Machine Learning.}, journal = {Diagnostics (Basel, Switzerland)}, volume = {13}, number = {19}, pages = {}, pmid = {37835856}, issn = {2075-4418}, abstract = {Breast cancer is a common cause of female mortality in developing countries. Early detection and treatment are crucial for successful outcomes. Breast cancer develops from breast cells and is considered a leading cause of death in women. This disease is classified into two subtypes: invasive ductal carcinoma (IDC) and ductal carcinoma in situ (DCIS). The advancements in artificial intelligence (AI) and machine learning (ML) techniques have made it possible to develop more accurate and reliable models for diagnosing and treating this disease. From the literature, it is evident that the incorporation of MRI and convolutional neural networks (CNNs) is helpful in breast cancer detection and prevention. In addition, the detection strategies have shown promise in identifying cancerous cells. The CNN Improvements for Breast Cancer Classification (CNNI-BCC) model helps doctors spot breast cancer using a trained deep learning neural network system to categorize breast cancer subtypes. However, they require significant computing power for imaging methods and preprocessing. Therefore, in this research, we proposed an efficient deep learning model that is capable of recognizing breast cancer in computerized mammograms of varying densities. Our research relied on three distinct modules for feature selection: the removal of low-variance features, univariate feature selection, and recursive feature elimination. The craniocaudally and medial-lateral views of mammograms are incorporated. We tested it with a large dataset of 3002 merged pictures gathered from 1501 individuals who had digital mammography performed between February 2007 and May 2015. In this paper, we applied six different categorization models for the diagnosis of breast cancer, including the random forest (RF), decision tree (DT), k-nearest neighbors (KNN), logistic regression (LR), support vector classifier (SVC), and linear support vector classifier (linear SVC). The simulation results prove that our proposed model is highly efficient, as it requires less computational power and is highly accurate.}, } @article {pmid37800299, year = {2023}, author = {Takashima, Y and Terasawa, R and Hirata, A and Morita, S and Kimura, K and Iwamoto, M and Hayashi, M}, title = {[A Case of COVID-19 Infection during Postoperative Chemotherapy for Breast Cancer Treated with Antibody Cocktail Therapy to Prevent Disease Aggravation].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {50}, number = {9}, pages = {1009-1011}, pmid = {37800299}, issn = {0385-0684}, mesh = {Female ; Humans ; Middle Aged ; *Breast Neoplasms/drug therapy/surgery/pathology ; Capecitabine/therapeutic use ; Combined Antibody Therapeutics ; *COVID-19 ; COVID-19 Drug Treatment ; Mastectomy ; }, abstract = {The outbreak of COVID-19 has caused a global pandemic, and it has been reported that patients with cancer are at high risk of developing complications from the disease. However, we believe that prolonged interruption of chemotherapy due to extended COVID-19 treatment is not desirable, given the intensity of cancer treatment. We report a case of COVID-19 infection during postoperative chemotherapy for breast cancer, in which antibody cocktail therapy prevented disease aggravation and delayed breast cancer treatment. The patient is a 45-year-old woman who came to our hospital with a complaint of a right mammary mass. The mass was diagnosed as invasive ductal carcinoma with an ER and PR of 0%, a HER2 score of 1+, and a Ki-67 of 90%. After preoperative chemotherapy, she underwent a right mastectomy and axillary dissection. The pathology result showed non-pCR. The administration of capecitabine was started as adjuvant therapy. On day 8 of cycle 3, she developed a fever in the 39℃ range, and on the next day, a COVID-19 POC gene test confirmed that the patient was positive for infection. On the same day, neutralizing antibody drugs(casirivimab and imdevimab)were administered as antibody cocktail therapy. Two days after treatment(day 11), a blood test showed Grade 3 neutropenia, but there was no recurrence of fever or evidence of pneumonia. After 2 weeks, capecitabine was resumed, and the patient was able to complete 8 cycles of capecitabine therapy without any major complications.}, } @article {pmid37769530, year = {2023}, author = {Siregar, KB and Al Anas, M}, title = {Unveiling bone metastasis: Exploring histological subtypes of breast cancer in Indonesia's tertiary referral hospital.}, journal = {Cancer treatment and research communications}, volume = {37}, number = {}, pages = {100764}, doi = {10.1016/j.ctarc.2023.100764}, pmid = {37769530}, issn = {2468-2942}, mesh = {Humans ; Female ; Adult ; Middle Aged ; *Breast Neoplasms/pathology ; *Carcinoma, Lobular/secondary ; *Carcinoma, Ductal, Breast/secondary ; Retrospective Studies ; Indonesia/epidemiology ; Tertiary Care Centers ; *Bone Neoplasms ; }, abstract = {INTRODUCTION: The histological grade of a tumor is an important prognostic indicator in both primary breast cancer and metastatic. We aimed to show the distribution of bone metastasis locations across different histological subtypes of breast cancer and how they relate to each.

METHODS: The cohort retrospective study comprised 65 patients diagnosed with bone-only metastatic breast cancer, all female. The secondary statistics for 2014 to 2022 were derived from breast cancer registration data collected to determine the relationships between patterns of bone metastases sites and histopathological grading in various histological categories.

RESULTS: The average age was 44.28±9.80 years (25-62 years), with 38 patients (58.5%) diagnosed with Invasive Ductal Carcinoma (IDC) and 27 patients (41.5%) with Invasive Lobular Carcinoma (ILC). Grade III were found in 34 patients (50.8%), Grade II in 31 patients (47.7%) and Grade I in one patient (1.5%). The most common sites of bone metastases are costae, followed by femur, vertebrae and pelvic. Vertebrae and costae metastasis are significantly correlated with histological grading and breast cancer pathology (p: 0.027 and 0.033, respectively).

CONCLUSION: There is a considerable difference between vertebrae and costae metastasis in terms of histological grading and breast cancer pathology which indicates the higher grade contains a greater variety of bone metastases sites.}, } @article {pmid37761331, year = {2023}, author = {Al-Refai, R and Bendari, A and Morrar, D and Sham, S and Kataw, L and Garajayev, A and Hajiyeva, S}, title = {Immunohistochemical Staining Characteristics of Low-Grade Invasive Ductal Carcinoma Using the ADH5 Cocktail (CK5/14, P63, and CK7/18): A Potential Interpretative Pitfall.}, journal = {Diagnostics (Basel, Switzerland)}, volume = {13}, number = {18}, pages = {}, pmid = {37761331}, issn = {2075-4418}, abstract = {Background: In our practice, the antibody cocktail ADH5 (CK5/14, p63, and CK7/18) helps with diagnostic challenges, such as identifying microinvasion and foci of invasive carcinoma, differentiating atypical ductal hyperplasia from hyperplasia of the usual type, and distinguishing basal phenotypes in triple-negative carcinomas. However, the ADH5 cocktail does have pitfalls and caveats. Methods: We describe our experience with the ADH5 cocktail of antibodies in breast pathology. Institutional knowledge and a literature search form our data sources. Results: We analyzed 44 cases. Four out of a total of 44 cases (9.1%)-two tubular carcinomas and two low-grade invasive breast carcinomas of no special type (ductal) with tubular features-showed an expected pattern of staining for ADH5 with a loss of brown (P63, CK5/14) staining around invasive glands and diffuse red (CK7/18) expression. Forty out of 44 (90.9%) cases showed an unexpected staining pattern (mixture of cytoplasmic brown and red). All 44 cases (100%) showed negative myoepithelial staining around invasive foci when separately stained for P63 and SMMH (Smooth Muscle Myosin Heavy). Conclusions: The unexpected staining pattern of ADH5 in low-grade invasive ductal carcinomas can be challenging to interpret in these lesions with low-grade cytology. The occurrence can cause confusion among users who employ multiplex stains, and it is important for users to be aware of this potential pitfall.}, } @article {pmid37749321, year = {2023}, author = {Taylor, J and Uhl, L and Moll, I and Hasan, SS and Wiedmann, L and Morgenstern, J and Giaimo, BD and Friedrich, T and Alsina-Sanchis, E and De Angelis Rigotti, F and Mülfarth, R and Kaltenbach, S and Schenk, D and Nickel, F and Fleming, T and Sprinzak, D and Mogler, C and Korff, T and Billeter, AT and Müller-Stich, BP and Berriel Diaz, M and Borggrefe, T and Herzig, S and Rohm, M and Rodriguez-Vita, J and Fischer, A}, title = {Endothelial Notch1 signaling in white adipose tissue promotes cancer cachexia.}, journal = {Nature cancer}, volume = {4}, number = {11}, pages = {1544-1560}, pmid = {37749321}, issn = {2662-1347}, support = {394046768 - SFB1366//Deutsche Forschungsgemeinschaft (German Research Foundation)/ ; SFB1118-A04/S01//Deutsche Forschungsgemeinschaft (German Research Foundation)/ ; BO 1639/9-1//Deutsche Forschungsgemeinschaft (German Research Foundation)/ ; }, mesh = {Animals ; Humans ; Male ; Mice ; *Adipose Tissue, White/pathology ; *Cachexia/pathology ; *Neoplasms/complications ; Signal Transduction ; Tretinoin ; *Receptor, Notch1/metabolism ; }, abstract = {Cachexia is a major cause of morbidity and mortality in individuals with cancer and is characterized by weight loss due to adipose and muscle tissue wasting. Hallmarks of white adipose tissue (WAT) remodeling, which often precedes weight loss, are impaired lipid storage, inflammation and eventually fibrosis. Tissue wasting occurs in response to tumor-secreted factors. Considering that the continuous endothelium in WAT is the first line of contact with circulating factors, we postulated whether the endothelium itself may orchestrate tissue remodeling. Here, we show using human and mouse cancer models that during precachexia, tumors overactivate Notch1 signaling in distant WAT endothelium. Sustained endothelial Notch1 signaling induces a WAT wasting phenotype in male mice through excessive retinoic acid production. Pharmacological blockade of retinoic acid signaling was sufficient to inhibit WAT wasting in a mouse cancer cachexia model. This demonstrates that cancer manipulates the endothelium at distant sites to mediate WAT wasting by altering angiocrine signals.}, } @article {pmid37743485, year = {2023}, author = {Pourriahi, R and Omranipour, R and Alipour, S and Hajimaghsoudi, L and Mashoori, N and Kenary, AY and Motamedi, M and Tavakol, M and Mohammadzadeh, M and Hessamiazar, S and Shabani, S and Mahmoodi, F and Goodarzi, MM and Eslami, B}, title = {Clinical characteristics of breast cancer patients admitted to academic surgical wards in Tehran, Iran: an analytical cross-sectional study.}, journal = {BMC women's health}, volume = {23}, number = {1}, pages = {511}, pmid = {37743485}, issn = {1472-6874}, mesh = {Humans ; Female ; Middle Aged ; *Breast Neoplasms/diagnosis/epidemiology ; Iran/epidemiology ; Cross-Sectional Studies ; Hospitalization ; Palpation ; }, abstract = {BACKGROUND: Breast cancer (BC) is the most commonly diagnosed cancer and the leading cause of cancer death among women. Knowledge of the clinical characteristics of BC in a population may be informative for disease prediction or diagnosis and for developing screening and diagnostic guidelines. This study aimed to evaluate the clinical characteristics of female patients with BC who were admitted to academic surgical wards in Tehran, Iran.

METHODS: In this cross-sectional study, demographic information and clinical characteristics of Iranian females with BC who had undergone breast surgery from 2017-2021 in four academic Breast Surgery Units were extracted from medical files and recorded via a pre-designed checklist.

RESULTS: A total of 1476 patients with a mean age of 48.03 (± 11.46) years were enrolled. Among them, 10.4% were aged less than 35. In younger patients, Triple-negative and Her2-enriched subtypes of BC were significantly higher compared to older ones. Overall, 85.7% of tumors were invasive ductal carcinoma, 43.3% were grade 2, 41.4% were located in the UOQ, and 65.2% had presented with mass palpation. The mean pathologic tumor size was 28.94 mm, and the most common subtype was luminal B.

CONCLUSIONS: Many characteristics of breast cancer in this study were similar to other countries and previous studies in Iran. However, a higher proportion of young BC compared with Western countries, and even with older studies in Iran, suggest a trend toward lower age for BC in recent years. These results indicate the need for preventive measures and screening in Iranian women at a younger age.}, } @article {pmid37737015, year = {2023}, author = {Sijnesael, T and Richard, F and Rätze, MA and Koorman, T and Bassey-Archibong, B and Rohof, C and Daniel, J and Desmedt, C and Derksen, PW}, title = {Canonical Kaiso target genes define a functional signature that associates with breast cancer survival and the invasive lobular carcinoma histological type.}, journal = {The Journal of pathology}, volume = {261}, number = {4}, pages = {477-489}, doi = {10.1002/path.6205}, pmid = {37737015}, issn = {1096-9896}, support = {2018NovPCC1297/BBC_/Breast Cancer Now/United Kingdom ; }, mesh = {Humans ; Female ; *Breast Neoplasms/pathology ; *Carcinoma, Lobular/metabolism ; Neoplasm Recurrence, Local ; Prognosis ; Cadherins/genetics/metabolism ; Transcription Factors/metabolism ; *Carcinoma, Ductal, Breast/pathology ; }, abstract = {Invasive lobular carcinoma (ILC) is a low- to intermediate-grade histological breast cancer type caused by mutational inactivation of E-cadherin function, resulting in the acquisition of anchorage independence (anoikis resistance). Most ILC cases express estrogen receptors, but options are limited in relapsed endocrine-refractory disease as ILC tends to be less responsive to standard chemotherapy. Moreover, ILC can relapse after >15 years, an event that currently cannot be predicted. E-cadherin inactivation leads to p120-catenin-dependent relief of the transcriptional repressor Kaiso (ZBTB33) and activation of canonical Kaiso target genes. Here, we examined whether an anchorage-independent and ILC-specific transcriptional program correlated with clinical parameters in breast cancer. Based on the presence of a canonical Kaiso-binding consensus sequence (cKBS) in the promoters of genes that are upregulated under anchorage-independent conditions, we defined an ILC-specific anoikis resistance transcriptome (ART). Converting the ART genes into human orthologs and adding published Kaiso target genes resulted in the Kaiso-specific ART (KART) 33-gene signature, used subsequently to study correlations with histological and clinical variables in primary breast cancer. Using publicly available data for ER[POS] Her2[NEG] breast cancer, we found that expression of KART was positively associated with the histological ILC breast cancer type (p < 2.7E-07). KART expression associated with younger patients in all invasive breast cancers and smaller tumors in invasive ductal carcinoma of no special type (IDC-NST) (<2 cm, p < 6.3E-10). We observed associations with favorable long-term prognosis in both ILC (hazard ratio [HR] = 0.51, 95% CI = 0.29-0.91, p < 3.4E-02) and IDC-NST (HR = 0.79, 95% CI = 0.66-0.93, p < 1.2E-04). Our analysis thus defines a new mRNA expression signature for human breast cancer based on canonical Kaiso target genes that are upregulated in E-cadherin deficient ILC. The KART signature may enable a deeper understanding of ILC biology and etiology. © 2023 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.}, } @article {pmid37697863, year = {2023}, author = {Lu, D and Li, F and Zhao, C and Ye, Y and Zhang, X and Yang, P and Zhang, X}, title = {A Remineralizing and Antibacterial Coating for Arresting Caries.}, journal = {Journal of dental research}, volume = {102}, number = {12}, pages = {1315-1325}, doi = {10.1177/00220345231189992}, pmid = {37697863}, issn = {1544-0591}, mesh = {Humans ; *Dental Caries/prevention & control ; Dental Caries Susceptibility ; *Tooth Demineralization/prevention & control ; Dental Enamel ; Composite Resins ; Anti-Bacterial Agents/pharmacology/therapeutic use ; Tooth Remineralization/methods ; }, abstract = {Dental caries is a dynamic disease induced by the unbalance between demineralization of dental hard tissues caused by biofilm and remineralization of them; however, although various effective remineralization methods have been well documented, it is a challenge to reestablish the balance by enhancing remineralization alone while ignoring the antibacterial therapy. Therefore, the integration of remineralizing and antibacterial technologies offers a promising strategy to halt natural caries progression in clinical practice. Here, the conception of interrupting dental caries (IDC) was proposed based on the development of dual-functional coating with remineralizing and antibacterial properties. In this study, bovine serum albumin (BSA) loaded octenidine (OCT) successfully to form a BSA-OCT composite. Subsequently, through fast amyloid-like aggregation, the phase-transited BSA-OCT (PTB-OCT) coating can be covered on teeth, resin composite, or sealant surfaces in 30 min by a simple smearing process. The PTB-OCT coating showed satisfactory effects in promoting the remineralization of demineralized enamel and dentin in vitro. Moreover, this coating also exerted significant acid-resistance stability and anti-biofilm properties. Equally importantly, this coating exhibited promising abilities in reducing the microleakage between the tooth and resin composite in vitro and preventing primary and secondary caries in vivo. In conclusion, this novel dual-functional PTB-OCT coating could reestablish the balance between demineralization and remineralization in the process of caries, thereby potentially preventing or arresting caries.}, } @article {pmid37683019, year = {2023}, author = {Moon, SY and Lim, KR and Son, JS}, title = {The role of infectious disease consultations in the management of patients with fever in a long-term care facility.}, journal = {PloS one}, volume = {18}, number = {9}, pages = {e0291421}, pmid = {37683019}, issn = {1932-6203}, mesh = {Humans ; Long-Term Care ; Retrospective Studies ; Nursing Homes ; Fever ; Referral and Consultation ; Tertiary Care Centers ; *Cardiomyopathy, Dilated ; *Communicable Diseases/therapy ; }, abstract = {BACKGROUND: Infectious disease (ID) clinicians can provide essential services for febrile patients in tertiary hospitals. The aim of this study was to evaluate the role of ID consultations (IDC) in managing hospitalized patients with infections in an oriental medical hospital (OMH), which serves as a long-term care facility. To our knowledge, this is the first study on the role of IDCs in managing patients in an OMH.

METHODS: This retrospective study was conducted in an OMH in Seoul, Korea, from June 2006 to June 2013.

RESULTS: Among the 465 cases of hospital-acquired fever, 141 (30.3%) were referred for ID. The most common cause of fever was infection in both groups. The peak body temperature of the patient was higher in IDC group (38.8±0.6°C vs. 38.6±0.5°C, p<0.001). Crude mortality at 30 days (14.6% vs. 7.8%, p = 0.043) and infection-attributable mortality (15.3% vs. 6.7%, p = 0.039) were higher in the No-IDC group. Multivariable analysis showed that infection as the focus of fever (adjusted Odd ratio [aOR] 3.49, 95% confidence interval (CI) 1.64-7.44), underlying cancer (aOR 10.32, 95% CI 4.34-24.51,), and multiorgan dysfunction syndrome (aOR 15.68, 95% CI 2.06-119.08) were associated with increased 30-day mortality. Multivariate analysis showed that in patients with infectious fever, appropriate antibiotic therapy (aOR 0.19, 95% CI 0.05-0.76) was the only factor associated with decreased infection-attributable mortality while underlying cancer (aOR 7.80, 95% CI 2.555-23.807) and severe sepsis or septic shock at the onset of fever (aOR 10.15, 95% CI 1.00-102.85) were associated with increased infection-attributable mortality.

CONCLUSION: Infection was the most common cause of fever in patients hospitalized for OMH. Infection as the focus of fever, underlying cancer, and MODS was associated with increased 30-day mortality in patients with nosocomial fever. Appropriate antibiotic therapy was associated with decreased infection-attributable mortality in patients with infectious fever.}, } @article {pmid37652705, year = {2023}, author = {Li, X and Stitt, D and Lanzino, G and Giannini, C and Dubey, D and Carabenciov, ID}, title = {Teaching NeuroImage: Pachymeningitis and Aortitis as the Initial Presentation of Granulomatosis With Polyangiitis.}, journal = {Neurology}, volume = {101}, number = {21}, pages = {979-980}, pmid = {37652705}, issn = {1526-632X}, mesh = {Humans ; *Aortitis/complications/diagnostic imaging ; *Granulomatosis with Polyangiitis/complications/diagnostic imaging ; *Meningitis/complications/diagnostic imaging ; }, } @article {pmid37637763, year = {2023}, author = {Abbasi, A and Ghaffarizadeh, F and Mojdeganlou, H}, title = {Prognostic Significance of Microvessel Density in Invasive Ductal Carcinoma of Breast.}, journal = {International journal of hematology-oncology and stem cell research}, volume = {17}, number = {2}, pages = {100-105}, pmid = {37637763}, issn = {2008-3009}, abstract = {Background: Breast cancer is the most common malignant tumor and cause of death in women. Factors that play role in tumor metastasis are lymph node involvement, lack of tumor differentiation and hormone receptor expression, high proliferation rate, and angiogenesis. In the present study, we tried to evaluate the microvessel density (MVD) using Immunohistochemistry for the CD34 marker to investigate the amount of angiogenesis in breast cancer and its relationship with other histopathological parameters and compare it with normal tissue. Materials and Methods: 58 paraffin-embedded samples of breast cancer were enrolled. All blocks were sectioned and stained for estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor 2(HER 2/neu), ki67, and CD34 by immunohistochemistry (IHC) method. Results: The mean age of patients in this study was 49.6 ± 10.6 years. Statistically, there was a significant relationship between the grade of the tumor (P = 0.01), absence of expression of estrogen receptor (P = 0.008), and progesterone receptor (P = 0.003) with MVD. Conclusion: Due to the association between MVD, tumor grade, and absence of ER and PR expression, this valuable marker can play an important role in the prediction of prognosis in breast cancer patients and can lead to new-targeted therapy in the future.}, } @article {pmid37559588, year = {2023}, author = {Bai, X and Fang, C and Liu, B and Huagn, J and Chen, X and Xie, X and Zhang, Q and Liu, M and Liang, J and Guo, J and Song, L and Lan, X and Chen, L and Huang, S and Deng, W and Luo, Z and Du, C}, title = {Breast cancer metastases to the thyroid and stomach: A case report.}, journal = {Oncology letters}, volume = {26}, number = {3}, pages = {386}, pmid = {37559588}, issn = {1792-1082}, abstract = {The most common sites of metastasis for breast cancer are the soft tissues, bones, lungs, liver and brain; however, metastases to the gastrointestinal tract and thyroid gland from breast cancer rarely occur. The present study describes the case of a 30-year-old woman who developed gastric and thyroid metastases 5 years after her initial diagnosis of invasive ductal breast carcinoma. The initial pathological diagnosis when receiving modified radical mastectomy was invasive ductal carcinoma, and further immunohistochemical examination revealed the cancer to be estrogen receptor (-), progesterone receptor (-), human epidermal growth factor receptor 2 (HER2; ++) and Ki-67 (70%). Genetic testing indicated the HER2 amplification mutation, whereas BRCA1/2 testing was negative. A total of 21 months after surgery, during regular follow-up, the patient was revealed to have developed an enlarged lymph node in the left side of the neck and the first recurrence was confirmed. Approximately 5 years after surgery, the patient gradually developed multi-site metastasis, and developed metastases to the thyroid gland and stomach confirmed by pathology and imaging. Combined chemotherapy and targeted therapy were administered and exhibited good efficacy; however, the patient subsequently died due to heart failure. This case report describes the occurrence of gastric and thyroid metastases from breast cancer, and highlights the importance of distinguishing between metastatic and primary tumors. Distinguishing between a metastatic and primary tumor is crucial as treatment protocols vary significantly for these two types of tumors. For patients with a history of breast cancer it should first be considered whether they have metastasis of the primary disease or discomfort caused by treatment; however, the possibility of a second primary tumor cannot be ignored. If the patient has symptoms such as loss of appetite, nausea, vomiting, stomach pain and stomach discomfort, a gastroscopy should be performed in a timely manner.}, } @article {pmid37548682, year = {2024}, author = {Mooshage, CM and Schimpfle, L and Kender, Z and Tsilingiris, D and Aziz-Safaie, T and Hohmann, A and Szendroedi, J and Nawroth, P and Sturm, V and Heiland, S and Bendszus, M and Kopf, S and Kurz, FT and Jende, JME}, title = {Association of Small Fiber Function with Microvascular Perfusion of Peripheral Nerves in Patients with Type 2 Diabetes : Study using Quantitative Sensory Testing and Magnetic Resonance Neurography.}, journal = {Clinical neuroradiology}, volume = {34}, number = {1}, pages = {55-66}, pmid = {37548682}, issn = {1869-1447}, mesh = {Humans ; *Diabetes Mellitus, Type 2/complications/pathology ; Cross-Sectional Studies ; Pain/complications ; Sciatic Nerve ; Perfusion ; Magnetic Resonance Spectroscopy ; Magnetic Resonance Imaging ; }, abstract = {INTRODUCTION/AIMS: Diabetic small fiber neuropathy (SFN) is caused by damage to thinly myelinated A‑fibers (δ) and unmyelinated C‑fibers. This study aimed to assess associations between quantitative sensory testing (QST) and parameters of peripheral nerve perfusion obtained from dynamic contrast enhanced (DCE) magnetic resonance neurography (MRN) in type 2 diabetes patients with and without SFN.

METHODS: A total of 18 patients with type 2 diabetes (T2D, 8 with SFN, 10 without SFN) and 10 healthy controls (HC) took part in this cross-sectional single-center study and underwent QST of the right leg and DCE-MRN of the right thigh with subsequent calculation of the sciatic nerve constant of capillary permeability (K[trans]), extravascular extracellular volume fraction (Ve), and plasma volume fraction (Vp).

RESULTS: The K[trans] (HC 0.031 min[-1] ± 0.009, T2D 0.043 min[-1] ± 0.015; p = 0.033) and Ve (HC 1.2% ± 1.5, T2D: 4.1% ± 5.1; p = 0.027) were lower in T2D patients compared to controls. In T2D patients, compound z‑scores of thermal and mechanical detection correlated with K[trans] (r = 0.73; p = 0.001, and r = 0.57; p = 0.018, respectively) and Ve (r = 0.67; p = 0.002, and r = 0.69; p = 0.003, respectively). Compound z‑scores of thermal pain and Vp (r = -0.57; p = 0.015) correlated negatively.

DISCUSSION: The findings suggest that parameters of peripheral nerve microcirculation are related to different symptoms in SFN: A reduced capillary permeability may result in a loss of function related to insufficient nutritional supply, whereas increased capillary permeability may be accompanied by painful symptoms related to a gain of function.}, } @article {pmid37530887, year = {2023}, author = {Kishore, A and Venkataramana, L and Prasad, DVV and Mohan, A and Jha, B}, title = {Enhancing the prediction of IDC breast cancer staging from gene expression profiles using hybrid feature selection methods and deep learning architecture.}, journal = {Medical & biological engineering & computing}, volume = {61}, number = {11}, pages = {2895-2919}, pmid = {37530887}, issn = {1741-0444}, mesh = {Humans ; Female ; *Breast Neoplasms/genetics ; Transcriptome ; Neoplasm Staging ; *Deep Learning ; Gene Expression Profiling/methods ; }, abstract = {Prediction of the stage of cancer plays an important role in planning the course of treatment and has been largely reliant on imaging tools which do not capture molecular events that cause cancer progression. Gene-expression data-based analyses are able to identify these events, allowing RNA-sequence and microarray cancer data to be used for cancer analyses. Breast cancer is the most common cancer worldwide, and is classified into four stages - stages 1, 2, 3, and 4 [2]. While machine learning models have previously been explored to perform stage classification with limited success, multi-class stage classification has not had significant progress. There is a need for improved multi-class classification models, such as by investigating deep learning models. Gene-expression-based cancer data is characterised by the small size of available datasets, class imbalance, and high dimensionality. Class balancing methods must be applied to the dataset. Since all the genes are not necessary for stage prediction, retaining only the necessary genes can improve classification accuracy. The breast cancer samples are to be classified into 4 classes of stages 1 to 4. Invasive ductal carcinoma breast cancer samples are obtained from The Cancer Genome Atlas (TCGA) and Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) datasets and combined. Two class balancing techniques are explored, synthetic minority oversampling technique (SMOTE) and SMOTE followed by random undersampling. A hybrid feature selection pipeline is proposed, with three pipelines explored involving combinations of filter and embedded feature selection methods: Pipeline 1 - minimum-redundancy maximum-relevancy (mRMR) and correlation feature selection (CFS), Pipeline 2 - mRMR, mutual information (MI) and CFS, and Pipeline 3 - mRMR and support vector machine-recursive feature elimination (SVM-RFE). The classification is done using deep learning models, namely deep neural network, convolutional neural network, recurrent neural network, a modified deep neural network, and an AutoKeras generated model. Classification performance post class-balancing and various feature selection techniques show marked improvement over classification prior to feature selection. The best multiclass classification was found to be by a deep neural network post SMOTE and random undersampling, and feature selection using mRMR and recursive feature elimination, with a Cohen-Kappa score of 0.303 and a classification accuracy of 53.1%. For binary classification into early and late-stage cancer, the best performance is obtained by a modified deep neural network (DNN) post SMOTE and random undersampling, and feature selection using mRMR and recursive feature elimination, with an accuracy of 81.0% and a Cohen-Kappa score (CKS) of 0.280. This pipeline also showed improved multiclass classification performance on neuroblastoma cancer data, with a best area under the receiver operating characteristic (auROC) curve score of 0.872, as compared to 0.71 obtained in previous work, an improvement of 22.81%. The results and analysis reveal that feature selection techniques play a vital role in gene-expression data-based classification, and the proposed hybrid feature selection pipeline improves classification performance. Multi-class classification is possible using deep learning models, though further improvement particularly in late-stage classification is necessary and should be explored further.}, } @article {pmid37517027, year = {2023}, author = {Amato, S and Ramsey, J and Ahern, TP and Rovnak, J and Barlow, J and Weaver, D and Eyasu, L and Singh, R and Cintolo-Gonzalez, J}, title = {Exploring the presence of bovine leukemia virus among breast cancer tumors in a rural state.}, journal = {Breast cancer research and treatment}, volume = {202}, number = {2}, pages = {325-334}, pmid = {37517027}, issn = {1573-7217}, mesh = {Cattle ; Humans ; Female ; Animals ; Sheep/genetics ; *Breast Neoplasms/epidemiology/genetics ; *Leukemia Virus, Bovine/genetics ; DNA, Viral/genetics ; Breast ; *Mammary Neoplasms, Animal ; }, abstract = {PURPOSE: The bovine leukemia virus (BLV) is a deltaretrovirus that causes malignant lymphoma and lymphosarcomas in cattle globally and has high prevalence among large scale U.S. dairy herds. Associations between presence of BLV DNA in human mammary tissue and human breast cancer incidence have been reported. We sought to estimate the prevalence of BLV DNA in breast cancer tissue samples in a rural state with an active dairy industry.

METHODS: We purified genomic DNA from 56 fresh-frozen breast cancer tissue samples (51 tumor samples, 5 samples representing adjacent normal breast tissue) banked between 2016 and 2019. Using nested PCR assays, multiple BLV tax sequence primers and primers for the long terminal repeat (LTR) were used to detect BLV DNA in tissue samples and known positive control samples, including the permanently infected fetal lamb kidney cell line (FLK-BLV) and blood from BLV positive cattle.

RESULTS: The median age of patients from which samples were obtained at the time of treatment was 60 (40-93) and all were female. Ninety percent of patients had invasive ductal carcinoma. The majority were poorly differentiated (60%). On PCR assay, none of the tumor samples tested positive for BLV DNA, despite having consistent signals in positive controls.

CONCLUSION: We did not find BLV DNA in fresh-frozen breast cancer tumors from patients presenting to a hospital in Vermont. Our findings suggest a low prevalence of BLV in our patient population and a need to reevaluate the association between BLV and human breast cancer.}, } @article {pmid37513591, year = {2023}, author = {Hardt, LM and Herrmann, HJ and Reljic, D and Jaensch, P and Zerth, J and Neurath, MF and Zopf, Y}, title = {Are Guideline Recommendations on Supportive Nutrition and Exercise Therapy for Cancer Patients Implemented in Clinical Routine? A National Survey with Real-Life Data.}, journal = {Nutrients}, volume = {15}, number = {14}, pages = {}, pmid = {37513591}, issn = {2072-6643}, support = {MED1710//Hector-Stiftung/ ; N.N.//Research Foundation for Medicine at the University Hospital Erlangen/ ; }, mesh = {Humans ; Quality of Life ; Nutritional Support ; *Malnutrition/diagnosis ; *Neoplasms/complications/therapy ; Exercise Therapy ; }, abstract = {Malnutrition and cancer cachexia are highly prevalent comorbidities of cancer, limiting patients' quality of life and being relevant to prognosis. International and national clinical guidelines recommend supportive nutrition and exercise therapy for cancer patients. However, there is little current epidemiological evidence on the implementation of these guideline recommendations in clinical routine. To close this data gap, a national survey in Germany using an online questionnaire was conducted. There were 261 of a total of 5074 contacted hospitals and medical offices who participated in the survey (5.1% response rate). The data indicated that nutrition and exercise therapy for cancer patients is so far inadequately implemented, with 59% of the respondents reporting nutrition therapy as an integral part of oncological treatment, 66.7% having a nutrition specialist/team, and 65.1% routinely conducting a screening for nutritional status. Only half of the participants stated that there are defined goals in nutrition therapy. The majority of respondents (85.8%) generally recommend exercise therapy, but only a few of them provide specific offers at their own institution (19.6%) or at cooperation partners (31.7%). In order to implement the recommended combined nutrition and exercise therapy as part of regular care, there is a need for nationwide availability of multidisciplinary nutrition teams and targeted offers of individualized exercise therapy. Health policy support would be important to create the structural, financial, and staff conditions for appropriate guideline implementation in order to achieve the optimal treatment of cancer patients.}, } @article {pmid37500355, year = {2023}, author = {Ding, W and Ye, D and Zhu, H and Lin, Y and Li, Z and Ruan, G}, title = {Survival Benefit of Adjuvant Chemotherapy in Node-Positive Breast Cancer With a 21-Gene Recurrence Score of 14 to 25: A Real-World Study Based on the Inverse Probability of Treatment Weighting Method.}, journal = {Clinical breast cancer}, volume = {23}, number = {7}, pages = {e441-e450}, doi = {10.1016/j.clbc.2023.07.004}, pmid = {37500355}, issn = {1938-0666}, mesh = {Humans ; Female ; *Breast Neoplasms/drug therapy/genetics/pathology ; Retrospective Studies ; Biomarkers, Tumor ; Prognosis ; Chemotherapy, Adjuvant ; Proportional Hazards Models ; Neoplasm Recurrence, Local/pathology ; }, abstract = {INTRODUCTION: The role of recurrence score in predicting the benefits of adjuvant chemotherapy for lymph-node-positive breast cancer remains uncertain. We studied chemotherapy usage in patients with 1 to 3 positive lymph nodes and a recurrence score (RS) of 25 or lower to assess changes in clinical practice based on the RxPONDER trial.

METHODS: A retrospective study using the SEER database identified female patients diagnosed with ER-positive, HER2-negative breast cancer, 1 to 3 positive lymph nodes, and an RS of 25 or lower between 2010 and 2015. Patients were divided into nonchemotherapy and chemotherapy groups, with propensity score weighting to balance clinicopathologic factors.

RESULTS: Among 7965 patients, 5774 (72.5%) were in the nonchemotherapy group, while 2191 (27.5%) were in the chemotherapy group. Median follow-up was 39 months. Breast cancer accounted for 67 deaths, while 128 deaths were due to other causes. The weighted 5-year overall survival (OS) rates were 95.7% for the nonchemotherapy group and 97.2% for the chemotherapy group. For high-risk patients, the weighted 5-year OS rates were 95.2% and 97.0% for the nonchemotherapy and chemotherapy groups, respectively, with a significant absolute difference of 1.8% (P = .014). Multivariate analysis showed a significant difference in weighted hazard ratios for OS between the nonchemotherapy and chemotherapy groups in high-risk patients (hazard ratio: 0.64; 95% CI: 0.48-0.86). However, there were no significant differences in weighted hazard ratios for lower-risk patients, and similar results were observed for breast cancer-specific survival (BCSS).

CONCLUSION: Patients with ER-positive, HER2-negative breast cancer and 1 to 3 positive lymph nodes, assessed by a 21-gene RS of 0 to 25, exhibited heterogeneous prognosis. Adjuvant chemotherapy provided a significant survival benefit, especially for patients with RS of 14 to 25, particularly those with invasive ductal carcinoma (IDC) and 2 to 3 positive lymph nodes.}, } @article {pmid37498719, year = {2024}, author = {Shoshani, A}, title = {Longitudinal changes in children's and adolescents' mental health and well-being and associated protective factors during the COVID-19 pandemic.}, journal = {Psychological trauma : theory, research, practice and policy}, volume = {16}, number = {7}, pages = {1158-1168}, doi = {10.1037/tra0001556}, pmid = {37498719}, issn = {1942-969X}, mesh = {Humans ; *COVID-19/psychology/prevention & control ; Child ; Adolescent ; Male ; Female ; Longitudinal Studies ; *Protective Factors ; *Social Support ; Israel ; Mental Health ; Resilience, Psychological ; Personal Satisfaction ; Depression/psychology ; }, abstract = {OBJECTIVE: The COVID-19 pandemic has heightened children's and adolescents' risk of experiencing long-term mental health problems and a decline in subjective well-being. To better understand the longitudinal impact of COVID-19, this study explored the role of demographic variables and the potential moderating effects of social support and daily routines as resilience factors.

METHOD: A nationally representative, longitudinal cohort of 5,217 Israeli children and adolescents aged 10-15 at baseline completed measures of mental health symptoms, life satisfaction, positive and negative emotions, gratitude, social support, and daily routines. Data were collected in school at four measurement points: September 2019 (before the outbreak of COVID-19; N = 5,127), May 2020 (after the first lockdown; N = 4,698), May 2021 (after the third wave lockdown; N = 4,813), and May 2022 (after the fourth and fifth waves of the pandemic; N = 4,897). The data were analyzed using multilevel mixed models.

RESULTS: Significant increases in depression, anxiety, and panic along with decreases in psychological well-being were found as a function of time. These effects were moderated by age and gender. Participants with high social support and structured daily routines reported smaller increases in mental health symptoms than students with low social support or irregular daily routines.

CONCLUSION: There is a critical need for clinical and educational interventions for young people during this period to promote the resilience factors that can moderate well-being and counter the decline in mental health. (PsycInfo Database Record (c) 2024 APA, all rights reserved).}, } @article {pmid37496230, year = {2023}, author = {Konishi, K and Araya, J and Nagabuchi, M and Sakamoto, T and Ogino, J and Hirano, S}, title = {[A Case of Breast Carcinoma That Changed Subtype to Squamous Cell Carcinoma after Chemotherapy].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {50}, number = {7}, pages = {825-827}, pmid = {37496230}, issn = {0385-0684}, mesh = {Female ; Humans ; *Breast Neoplasms/drug therapy/surgery/pathology ; Docetaxel/therapeutic use ; Mastectomy ; Quality of Life ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; *Carcinoma, Squamous Cell/drug therapy/surgery/pathology ; Capecitabine/therapeutic use ; Cyclophosphamide/therapeutic use ; *Liver Neoplasms/drug therapy/surgery/secondary ; }, abstract = {Metaplastic carcinoma is a rare histological malignancy, often triple-negative, and has a poor prognosis. Here, we report a case of breast cancer in which the primary lesion degenerated into squamous cell carcinoma(triple negative)after drug treatment for invasive ductal carcinoma(Luminal type). The patient was a 41-year-old woman who was diagnosed with Stage Ⅳ left breast cancer T2N2bM1(HEP)(ER 90%, PR 70%, HER2 2+, FISH-)at another hospital and participated in the PATHWAY study(tamoxifen plus goserelin plus palbociclib/placebo). Since the primary lesion and liver metastasis increased in size, the study was discontinued after 8 weeks. She was treated at our hospital thereafter, with capecitabine plus cyclophosphamide, palbociclib plus fulvestrant plus leuprorelin, paclitaxel plus bevacizumab, eribulin, EC therapy, and docetaxel. However, both the primary lesion and liver metastasis increased. In particular, the increase in primary lesion size was remarkable, and the QOL significantly reduced due to bleeding and exudation. Biopsy performed during docetaxel treatment revealed metaplastic/squamous cell carcinoma(ER-, PR-, HER2 0, Ki-67 90-100%)histopathological findings. BRCA and microsatellite instability tests were negative, and PDL1 expression was less than 1%. Although Mohs ointment was used, tumor bleeding, exudate, and stink were poorly controlled, and the patient experienced painful symptoms due to the weight of the tumor. Therefore, left mastectomy plus pectoralis major muscle resection was performed. The patient died one month after the operation.}, } @article {pmid37490055, year = {2023}, author = {Choo, ZY and Xu, AZ}, title = {Predictors and outcomes of cutaneous metastatic breast carcinoma: a retrospective, single-institution review.}, journal = {Archives of dermatological research}, volume = {315}, number = {9}, pages = {2725-2728}, pmid = {37490055}, issn = {1432-069X}, mesh = {Humans ; Female ; Retrospective Studies ; *Breast Neoplasms/therapy ; Skin/pathology ; Administration, Cutaneous ; *Carcinoma, Lobular/pathology/secondary ; }, } @article {pmid37480503, year = {2023}, author = {D'Iorio, A and Aiello, EN and Amboni, M and Vitale, C and Verde, F and Silani, V and Ticozzi, N and Ciammola, A and Poletti, B and Santangelo, G}, title = {Validity and diagnostics of the Italian version of the Montreal Cognitive Assessment (MoCA) in non-demented Parkinson's disease patients.}, journal = {Aging clinical and experimental research}, volume = {35}, number = {10}, pages = {2157-2163}, pmid = {37480503}, issn = {1720-8319}, mesh = {Humans ; *Parkinson Disease/complications/diagnosis ; Retrospective Studies ; Mental Status and Dementia Tests ; *Cognitive Dysfunction/diagnosis/etiology ; Language ; }, abstract = {BACKGROUND: This study aimed at: (1) assessing, in an Italian cohort of non-demented Parkinson's disease (PD) patients, the construct validity of the Montreal Cognitive Assessment (MoCA) against both first- and second-level cognitive measures; (2) delivering an exhaustive and updated evaluation of its diagnostic properties.

METHODS: A retrospective cohort of N = 237 non-demented PD patients having been administered the MoCA was addressed, of whom N = 169 further underwent the Mini-Mental State Examination (MMSE) and N = 68 the Parkinson's Disease Cognitive Rating Scale (PD-CRS). A subsample (N = 60) also underwent a second-level cognitive battery encompassing measures of attention/executive functioning, language, memory, praxis and visuo-spatial abilities. Construct validity was assessed against both the PD-CRS and the second-level cognitive battery. Diagnostics were tested via receiver-operating characteristics analyses against a below-cut-off MMSE score.

RESULTS: The MoCA was associated with both PD-CRS scores (p < .001) and the vast majority of second-level cognitive measures (ps < .003). Both raw and adjusted MoCA scores proved to be highly accurate to the aim of identifying patients with MMSE-confirmed cognitive dysfunctions. A MoCA score adjusted for age and education according to the most recent normative dataset and < 19.015 is herewith suggested as indexing cognitive impairment in this population (AUC = .92; sensitivity = .92; specificity = .80).

DISCUSSION: The Italian MoCA is a valid and diagnostically sound screener for global cognitive inefficiency in non-demented PD patients. Further studies are nevertheless needed that confirm its diagnostic values against a measure other than the MMSE.}, } @article {pmid37480256, year = {2023}, author = {White, D and Sadough Shahmirzadi, M and Boulmay, B}, title = {Multi-Phenotypic Breast Cancer Post-Radiotherapy for Hodgkin Lymphoma: A Case of Secondary Malignancy.}, journal = {Journal of investigative medicine high impact case reports}, volume = {11}, number = {}, pages = {23247096231188251}, pmid = {37480256}, issn = {2324-7096}, mesh = {Female ; Humans ; Middle Aged ; *Carcinoma, Intraductal, Noninfiltrating/pathology/surgery ; *Breast Neoplasms/radiotherapy ; *Hodgkin Disease/radiotherapy ; Mastectomy ; Breast/pathology ; *Neoplasms, Second Primary/etiology ; }, abstract = {Morbidity and mortality associated with radiation-induced secondary malignancies (RISMs) have shifted treatment paradigms to minimize or eliminate radiation from treatment regimens. In this case, a 48-year-old woman was diagnosed with Hodgkin lymphoma (HL) and treated with radiotherapy in 2000. In 2018, she was diagnosed with ductal carcinoma in situ (DCIS) of the right breast and treated with a mastectomy. Soon after, she developed triple-negative invasive ductal carcinoma (IDC) in her reconstructed breast. The patient underwent a left lumpectomy, and pathology showed ER-/PR-/HER2+ IDC. This patient's multi-phenotypic DCIS and IDC presentation are suspected to be RISM due to her previous HL treatment regimen.}, } @article {pmid37479782, year = {2023}, author = {Fond, G and Falissard, B and Nuss, P and Collin, C and Duret, S and Rabbani, M and De Chefdebien, I and Tonelli, I and Llorca, PM and Boyer, L}, title = {How can we improve the care of patients with schizophrenia in the real-world? A population-based cohort study of 456,003 patients.}, journal = {Molecular psychiatry}, volume = {28}, number = {12}, pages = {5328-5336}, pmid = {37479782}, issn = {1476-5578}, mesh = {Humans ; *Schizophrenia/drug therapy/epidemiology ; Male ; Female ; Middle Aged ; Adult ; *Antipsychotic Agents/therapeutic use ; Cohort Studies ; Aged ; Comorbidity ; Antidepressive Agents/therapeutic use ; Anticonvulsants/therapeutic use ; Adolescent ; Young Adult ; }, abstract = {An important step to improve outcomes for patients with schizophrenia is to understand treatment patterns in routine practice. The aim of the current study was to describe the long-term management of patients with schizophrenia treated with antipsychotics (APs) in real-world practice. This population-based study included adults with schizophrenia and who had received ≥3 deliveries of an AP from 2012-2017, identified using a National Health Data System. Primary endpoints were real-life prescription patterns, patient characteristics, healthcare utilization, comorbidities and mortality. Of the 456,003 patients included, 96% received oral APs, 17.5% first-generation long-acting injectable APs (LAIs), and 16.1% second generation LAIs. Persistence rates at 24 months after treatment initiation were 23.9% (oral APs), 11.5% (first-generation LAIs) and 20.8% (second-generation LAIs). Median persistence of oral APs, first-generation LAIs and second-generation LAIs was 5.0, 3.3, and 6.1 months, respectively. Overall, 62.1% of patients were administered anxiolytics, 45.7% antidepressants and 28.5% anticonvulsants, these treatments being more frequently prescribed in women and patients aged ≥50 years. Dyslipidemia was the most frequent metabolic comorbidity (16.2%) but lipid monitoring was insufficient (median of one occasion). Metabolic comorbidities were more frequent in women. Standardized patient mortality remained consistently high between 2013 and 2015 (3.3-3.7 times higher than the general French population) with a loss of life expectancy of 17 years for men and 8 years for women. Cancer (20.2%) and cardiovascular diseases (17.2%) were the main causes of mortality, and suicide was responsible for 25.4% of deaths among 18-34-year-olds. These results highlight future priorities for care of schizophrenia patients. The global persistence of APs used in this population was low, whereas rates of psychiatric hospitalization remain high. More focus on specific populations is needed, such as patients aged >50 years to prevent metabolic disturbances and 18-34-year-olds to reduce suicide rates.}, } @article {pmid37435234, year = {2023}, author = {Li, S and Tong, J and Li, H and Mao, C and Shen, W and Lei, Y and Hu, P}, title = {L. pneumophila Infection Diagnosed by tNGS in a Lady with Lymphadenopathy.}, journal = {Infection and drug resistance}, volume = {16}, number = {}, pages = {4435-4442}, pmid = {37435234}, issn = {1178-6973}, abstract = {We report a case of a 34-year-old lady with multiple joint pain. Autoimmune diseases were considered first with a positive result of anti-Ro antibody and her right knee joint cavity effusion. Later, bilateral interstitial changes in her lungs and mediastinal lymphadenopathy were found after chest CT scanning. Empirical quinolone therapy was given although pathological examinations of blood, sputum and bronchoalveolar lavage fluid (BALF) did not find anything. Finally, Legionella pneumophila was identified by target next-generation sequencing (tNGS) detection. This case highlighted the timely use of tNGS, a new tool with fast speed, high accuracy and effective cost, could help to identify atypical infection and start an early therapy.}, } @article {pmid37408309, year = {2023}, author = {Ji, H and Englmaier, F and Morigny, P and Giroud, M and Gräsle, P and Brings, S and Szendrödi, J and Berriel Diaz, M and Plettenburg, O and Herzig, S and Rohm, M}, title = {Development of a peptide drug restoring AMPK and adipose tissue functionality in cancer cachexia.}, journal = {Molecular therapy : the journal of the American Society of Gene Therapy}, volume = {31}, number = {8}, pages = {2408-2421}, pmid = {37408309}, issn = {1525-0024}, support = {R01 GM129325/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Humans ; Adipose Tissue/metabolism ; *AMP-Activated Protein Kinases/metabolism ; Cachexia/drug therapy/etiology/metabolism ; *Neoplasms/complications/metabolism ; Peptides/pharmacology ; Pharmaceutical Preparations/metabolism ; Quality of Life ; }, abstract = {Cancer cachexia is a severe systemic wasting disease that negatively affects quality of life and survival in patients with cancer. To date, treating cancer cachexia is still a major unmet clinical need. We recently discovered the destabilization of the AMP-activated protein kinase (AMPK) complex in adipose tissue as a key event in cachexia-related adipose tissue dysfunction and developed an adeno-associated virus (AAV)-based approach to prevent AMPK degradation and prolong cachexia-free survival. Here, we show the development and optimization of a prototypic peptide, Pen-X-ACIP, where the AMPK-stabilizing peptide ACIP is fused to the cell-penetrating peptide moiety penetratin via a propargylic glycine linker to enable late-stage functionalization using click chemistry. Pen-X-ACIP was efficiently taken up by adipocytes, inhibited lipolysis, and restored AMPK signaling. Tissue uptake assays showed a favorable uptake profile into adipose tissue upon intraperitoneal injection. Systemic delivery of Pen-X-ACIP into tumor-bearing animals prevented the progression of cancer cachexia without affecting tumor growth and preserved body weight and adipose tissue mass with no discernable side effects in other peripheral organs, thereby achieving proof of concept. As Pen-X-ACIP also exerted its anti-lipolytic activity in human adipocytes, it now provides a promising platform for further (pre)clinical development toward a novel, first-in-class approach against cancer cachexia.}, } @article {pmid37402637, year = {2023}, author = {Shulder, S and Tamma, PD and Fiawoo, S and Dzintars, K and Escobar, D and Livorsi, DJ and Malani, AN and Palacio, D and Spivak, ES and Zimmerman, M and Bork, JT}, title = {Infectious Diseases Consultation Associated With Reduced Mortality in Gram-Negative Bacteremia.}, journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America}, volume = {77}, number = {9}, pages = {1234-1237}, doi = {10.1093/cid/ciad383}, pmid = {37402637}, issn = {1537-6591}, mesh = {Humans ; *Communicable Diseases ; Cohort Studies ; *Bacteremia ; Referral and Consultation ; Retrospective Studies ; *Gram-Negative Bacterial Infections ; }, abstract = {Gram-negative bacteremia (GN-BSI) can cause significant morbidity and mortality, but the benefit of infectious diseases consultation (IDC) is not well defined. A 24-site observational cohort study of unique hospitalized patients with 4861 GN-BSI episodes demonstrated a 40% decreased risk of 30-day mortality in patients with IDC compared to those without IDC.}, } @article {pmid37371442, year = {2023}, author = {Maggi, G and Vitale, C and Delle Curti, A and Amboni, M and Santangelo, G}, title = {Unawareness of Apathy in Parkinson's Disease: The Role of Executive Dysfunction on Symptom Recognition.}, journal = {Brain sciences}, volume = {13}, number = {6}, pages = {}, pmid = {37371442}, issn = {2076-3425}, abstract = {Altered self-awareness or anosognosia may impact patients' everyday life by interfering with their safe and independent functioning. Symptom awareness has been linked to executive dysfunctions caused by damage to frontal regions. Apathy is a frequent neuropsychiatric manifestation of Parkinson's disease (PD) and is considered a consequence of altered functioning of cortico-subcortical circuitries connecting the prefrontal cortex (PFC) with the basal ganglia. Thus, apathetic PD patients may be not be fully aware of their condition due to shared neuropathophysiological mechanisms. The present study aimed to explore the awareness of apathy in PD patients by comparing the self-reported evaluations with their caregivers' ratings. Moreover, we explored the clinical predictors of possible discrepancies and their consequences on patients' self-reported evaluation of quality of life (QoL). We found a fair agreement between patients' self-reports and caregivers' ratings on apathy scores, with patients reporting less severe apathetic symptoms, especially those related to executive and auto-activation processing, compared to their caregivers' reports. Executive functioning was found to mediate the relationship between disease stage and awareness of the apathetic state. Awareness of executive apathy impacted patients' self-reported QoL. Therefore, PD patients might be unaware of their apathetic symptoms, especially those with worse executive functioning, which plays a key role in metacognitive processes such as self-monitoring and error detection. Anosognosia for apathy in PD patients may affect their QoL perception and leads to misleading self-report evaluations that delay diagnosis and treatment.}, } @article {pmid37363526, year = {2023}, author = {Kara Tahhan, N and Abou Azan, A and Jomaa Al Ali, I and Abdul Aziz, J and Sara, S}, title = {Cutaneous metastases as a primary manifestation of invasive ductal carcinoma of the breast: a case report.}, journal = {Annals of medicine and surgery (2012)}, volume = {85}, number = {6}, pages = {3062-3065}, pmid = {37363526}, issn = {2049-0801}, abstract = {UNLABELLED: Cutaneous metastases as the first sign of invasive ductal carcinoma are not common. The ambiguous presentation of asymptomatic lesions may result in various diagnoses including dermatologic causes. Early diagnosis is essential in such cases.

CASE PRESENTATION: A 43-year-old woman with no risk factors for developing breast cancer at a young age was diagnosed with invasive ductal carcinoma of the left breast after dermatologic complaints of diffuse lesions on the left-back and right subclavian region. The patient remained asymptomatic except for the recent cutaneous presentation, which did not arouse much suspicion.

CONCLUSION: Cutaneous metastases of breast cancer remain uncommon, but at the same time represent a poor prognosis for the patient, and when they do occur, treatment options are limited. The delay in taking the proper diagnostic measures in such cases imposes a need to adopt a wider perspective when dealing with the possible occurrence of advanced disease. This also adds up to the importance of breast self-examination by women at a young age and full examination by physicians, especially when they encounter a misguiding presentation.}, } @article {pmid37363420, year = {2023}, author = {Singh, S and Singh, AL and Pal, KK and Reddy, KK and Gangadhara, K and Dey, R and Mahatma, MK and Verma, A and Kumar, N and Patel, CB and Thawait, LK and Ahmed, S and Navapara, R and Rani, K and Kona, P}, title = {Accumulation of resveratrol, ferulic acid and iron in seeds confer iron deficiency chlorosis tolerance to a novel genetic stock of peanut (Arachis hypogaea L.) grown in calcareous soils.}, journal = {Physiology and molecular biology of plants : an international journal of functional plant biology}, volume = {29}, number = {5}, pages = {725-737}, pmid = {37363420}, issn = {0971-5894}, abstract = {UNLABELLED: Peanut is mostly grown in calcareous soils with high pH which are deficient in available iron (Fe[2+]) for plant uptake causing iron deficiency chlorosis (IDC). The most pertinent solution is to identify efficient genotypes showing tolerance to limited Fe availability in the soil. A field screening of 40 advanced breeding lines of peanut using NRCG 7472 and ICGV 86031 as IDC susceptible and tolerant checks, respectively, was envisaged for four years. PBS 22040 and 29,192 exhibited maximum tolerance while PBS 12215 and 12,185 were most susceptible. PBS 22040 accumulated maximum seed resveratrol (5.8 ± 0.08 ppm), ferulic acid (378.6 ± 0.31 ppm) and Fe (45.59 ± 0.41 ppm) content. Enhanced chlorophyll retention (8.72-9.50 µg ml[-1]), carotenoid accumulation (1.96-2.08 µg ml[-1]), and antioxidant enzyme activity (APX: 35.9-103.9%; POX: 51- 145%) reduced the MDA accumulation (5.61-9.11 µM cm[-1]) in tolerant lines. The overexpression of Fe transporters IRT1, ZIP5, YSL3 was recorded to the tune of 2.3-9.54; 1.45-3.7; 2.20-2.32- folds respectively in PBS 22040 and 29,192, over NRCG 7472. PBS 22040 recorded the maximum pod yield (282 ± 4.6 g/row), hundred kernel weight (55 ± 0.7 g) and number of pods per three plants (54 ± 1.7). The study thus reports new insights into the roles of resveratrol, ferulic acid and differential antioxidant enzyme activities in imparting IDC tolerance. PBS 22040, being the best performing line, can be the potent source of IDC tolerance for introgression in high yielding but susceptible genotypes under similar edaphic conditions.

SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12298-023-01321-9.}, } @article {pmid37363122, year = {2023}, author = {Wani, K and Patel, K and Dabak, V}, title = {Hepatotoxicity After CDK 4/6 Inhibitor Initiation in the Treatment of Hormone-Positive Metastatic Breast Cancer.}, journal = {Cureus}, volume = {15}, number = {6}, pages = {e40871}, pmid = {37363122}, issn = {2168-8184}, abstract = {Cancer cells proliferate using various mechanisms. One mechanism of preventing tumor cell growth is blockade of the cyclin-dependent kinase (CDK) 4/6 axis. Multiple CDK 4/6 inhibitors - ribociclib, palbociclib, and abemaciclib - have significantly improved progression-free survival rates. However, they can cause hepatotoxicity. We present a case of a 67-year-old female who was diagnosed with stage 1C invasive ductal carcinoma. She was treated with letrozole and ribociclib due to recurrence as metastatic disease, but within 10 days, she developed transaminitis. She then started palbociclib but experienced elevated transaminases within two weeks, needing discontinuation of palbociclib. Subsequent positron-emission tomography/computed tomography imaging showed disease progression, and she was started on fulvestrant. We considered adding abemaciclib, but the patient declined and has had stable disease for more than a year on fulvestrant. CDK 4/6 inhibitors are used to treat metastatic breast cancer and are generally well tolerated. The most common side effect is neutropenia; however, our patient developed transaminitis. The novelty of our case is the development of hepatotoxicity even after the introduction of another CDK 4/6 inhibitor, indicating at least some degree of class effect. In summary, CDK 4/6 inhibitors have significantly improved outcomes in hormone-positive metastatic breast cancers. However, a small percentage suffer from hepatic injury enough to warrant discontinuation of the drug, and we must continue to assess the risk versus benefit profile when offering them to our patients.}, } @article {pmid37324312, year = {2023}, author = {Jain, AK}, title = {Locally Advanced Breast Cancer: Response Evaluation to Neoadjuvant Chemotherapy by Clinico-Histopathological Parameters and Molecular Imaging.}, journal = {Indian journal of surgical oncology}, volume = {14}, number = {2}, pages = {279-287}, pmid = {37324312}, issn = {0975-7651}, abstract = {In India, breast cancer (BC) is not only the commonest cancer but also the commonest cause of cancer mortality among females. Advanced BC constitutes >70% of BC cases at initial presentation in India, among which locally advanced breast cancer (LABC) requires a multi-disciplinary approach with a combination of systemic and locoregional therapies. This descriptive hospital-based study was conducted over 1½ years after seeking approval from the institutional ethics committee. Fifty-five patients satisfying all the criteria of the study were enrolled. The data, thus, collected was pooled into Excel spreadsheet and analyzed using appropriate statistical tools. Most of the patients were postmenopausal, multiparous with breast lump being the commonest symptom. Mean baseline characteristics were age - 48 years, SUV max - 9.2, and Ki-67 - 17.8%. cT4 and cN2 were the commonest pre-NACT tumor and lymph node stage. Invasive ductal carcinoma was the commonest tumor type with the most common tumor grade being grade 3. Hormone receptor positivity and HER2 overexpression were seen in 33 and 17 patients respectively. Post-NACT 32 patients underwent breast-conserving surgery. Pathological complete response (pCR), i.e., ypT0N0, was seen in 13 patients (23.6%). There was slight alteration in hormone receptor status, HER2 expression and Ki-67 in the post-NACT resected tumor. pCR, which is a surrogate marker for improved clinical outcome (DFS and OS) in LABC patients, occurred more commonly in patients with pre-NACT grade 3 tumors, high Ki-67, hormone receptor-negative, and HER2 overexpressing BC (overall, in triple negative BC) but was statistically significant only with Ki-67. Post-NACT, SUV max with a cut off ≤1.5, and ΔSUV max of >80% correlated closely with pCR.}, } @article {pmid37290673, year = {2023}, author = {Nieborak, A and Lukauskas, S and Capellades, J and Heyn, P and Santos, GS and Motzler, K and Zeigerer, A and Bester, R and Protzer, U and Schelter, F and Wagner, M and Carell, T and Hruscha, A and Schmid, B and Yanes, O and Schneider, R}, title = {Depletion of pyruvate kinase (PK) activity causes glycolytic intermediate imbalances and reveals a PK-TXNIP regulatory axis.}, journal = {Molecular metabolism}, volume = {74}, number = {}, pages = {101748}, pmid = {37290673}, issn = {2212-8778}, mesh = {Animals ; *Pyruvate Kinase/genetics ; Reactive Oxygen Species ; Basic Helix-Loop-Helix Leucine Zipper Transcription Factors/metabolism ; *Neoplasms/genetics/metabolism ; Thioredoxins/chemistry/metabolism ; }, abstract = {OBJECTIVE: Cancer cells convert more glucose into lactate than healthy cells, what contributes to their growth advantage. Pyruvate kinase (PK) is a key rate limiting enzyme in this process, what makes it a promising potential therapeutic target. However, currently it is still unclear what consequences the inhibition of PK has on cellular processes. Here, we systematically investigate the consequences of PK depletion for gene expression, histone modifications and metabolism.

METHODS: Epigenetic, transcriptional and metabolic targets were analysed in different cellular and animal models with stable knockdown or knockout of PK.

RESULTS: Depleting PK activity reduces the glycolytic flux and causes accumulation of glucose-6-phosphate (G6P). Such metabolic perturbation results in stimulation of the activity of a heterodimeric pair of transcription factors MondoA and MLX but not in a major reprogramming of the global H3K9ac and H3K4me3 histone modification landscape. The MondoA:MLX heterodimer upregulates expression of thioredoxin-interacting protein (TXNIP) - a tumour suppressor with multifaceted anticancer activity. This effect of TXNIP upregulation extends beyond immortalised cancer cell lines and is applicable to multiple cellular and animal models.

CONCLUSIONS: Our work shows that actions of often pro-tumorigenic PK and anti-tumorigenic TXNIP are tightly linked via a glycolytic intermediate. We suggest that PK depletion stimulates the activity of MondoA:MLX transcription factor heterodimers and subsequently, increases cellular TXNIP levels. TXNIP-mediated inhibition of thioredoxin (TXN) can reduce the ability of cells to scavenge reactive oxygen species (ROS) leading to the oxidative damage of cellular structures including DNA. These findings highlight an important regulatory axis affecting tumour suppression mechanisms and provide an attractive opportunity for combination cancer therapies targeting glycolytic activity and ROS-generating pathways.}, } @article {pmid37251671, year = {2023}, author = {Kender, Z and von Rauchhaupt, E and Schwarz, D and Tsilingiris, D and Schimpfle, L and Bartl, H and Longo, VD and Bendszus, M and Kopf, S and Herzig, S and Heiland, S and Szendroedi, J and Sulaj, A}, title = {Six-month periodic fasting does not affect somatosensory nerve function in type 2 diabetes patients.}, journal = {Frontiers in endocrinology}, volume = {14}, number = {}, pages = {1143799}, pmid = {37251671}, issn = {1664-2392}, mesh = {Humans ; Action Potentials ; *Diabetes Mellitus, Type 2/complications/pathology ; *Diabetic Neuropathies/diagnosis ; Fasting ; Pain ; }, abstract = {BACKGROUND AND AIM: Current strategies for preventing diabetic sensorimotor polyneuropathy (DSPN) are limited mainly to glucose control but rapid decrease of glycemia can lead to acute onset or worsening of DSPN. The aim of this study was to examine the effects of periodic fasting on somatosensory nerve function in patients with type 2 diabetes (T2D).

STUDY DESIGN AND METHODS: Somatosensory nerve function was assessed in thirty-one patients with T2D (HbA1c 7.8 ± 1.3% [61.4 ± 14.3 mmol/mol]) before and after a six-month fasting-mimicking diet (FMD; n=14) or a control Mediterranean diet (M-diet; n=17). Neuropathy disability score (NDS), neuropathy symptoms score (NSS), nerve conduction velocity and quantitative sensory testing (QST) were analyzed. 6 participants of the M-Diet group and 7 of the FMD group underwent diffusion-weighted high-resolution magnetic resonance neurography (MRN) of the right leg before and after the diet intervention.

RESULTS: Clinical neuropathy scores did not differ between study groups at baseline (64% in the M-Diet group and 47% in the FMD group had DSPN) and no change was found after intervention. The differences in sensory NCV and sensory nerve action potential (SNAP) of sural nerve were comparable between study groups. Motor NCV of tibial nerve decreased by 12% in the M-Diet group (P=0.04), but did not change in the FMD group (P=0.39). Compound motor action potential (CMAP) of tibial nerve did not change in M-Diet group (P=0.8) and increased in the FMD group by 18% (P=0.02). Motor NCV and CMAP of peroneal nerve remained unchanged in both groups. In QST M-diet-group showed a decrease by 45% in heat pain threshold (P=0.02), FMD group showed no change (P=0.50). Changes in thermal detection, mechanical detection and mechanical pain did not differ between groups. MRN analysis showed stable fascicular nerve lesions irrespective of the degree of structural pathology. Fractional anisotropy and T2-time did not change in both study groups, while a correlation with the clinical degree of DSPN could be confirmed for both.

CONCLUSIONS: Our study shows that six-month periodic fasting was safe in preserving nerve function and had no detrimental effects on somatosensory nerve function in T2D patients.

CLINICAL TRIAL REGISTRATION: https://drks.de/search/en/trial/DRKS00014287, identifier DRKS00014287.}, } @article {pmid37217416, year = {2023}, author = {Rummel, KA and Gao, RW and Francis, LN and Petersen, IA and Mutter, RW and Corbin, KS}, title = {Secondary breast angiosarcoma following accelerated partial breast irradiation with intracavitary multicatheter applicator brachytherapy.}, journal = {Brachytherapy}, volume = {22}, number = {4}, pages = {487-490}, doi = {10.1016/j.brachy.2023.04.007}, pmid = {37217416}, issn = {1873-1449}, mesh = {Female ; Humans ; Aged ; *Hemangiosarcoma/etiology ; *Brachytherapy/methods ; *Breast Neoplasms/surgery ; Breast/pathology ; Mastectomy, Segmental ; }, abstract = {PURPOSE: Secondary angiosarcoma of the breast is a rare complication of breast radiotherapy and is associated with a poor prognosis. There are many reported cases of secondary angiosarcoma following whole breast irradiation (WBI), however development of secondary angiosarcoma following brachytherapy-based accelerated partial breast irradiation (APBI) is not as well characterized.

METHODS AND MATERIALS: We reviewed and reported a case of a patient who developed secondary angiosarcoma of the breast following intracavitary multicatheter applicator brachytherapy APBI.

RESULTS: A 69-year-old female was originally diagnosed with T1N0M0 invasive ductal carcinoma of the left breast and treated with lumpectomy followed by adjuvant intracavitary multicatheter applicator brachytherapy APBI. Seven years following her treatment, she developed secondary angiosarcoma. However, the diagnosis of secondary angiosarcoma was delayed due to nonspecific imaging findings and a negative biopsy.

CONCLUSIONS: Our case highlights the need for secondary angiosarcoma to be considered in the differential diagnosis when patients present with symptoms such as breast ecchymosis and skin thickening following WBI or APBI. Prompt diagnosis and referral to a high-volume sarcoma treatment center for multidisciplinary evaluation is vital.}, } @article {pmid37202608, year = {2023}, author = {Shawky, A and Sabit, H and Nazih, M and Baraka, K and El-Zawahry, M}, title = {CYP2C19 Polymorphism in Ischemic Heart Disease Patients Taking Clopidogrel After Percutaneous Coronary Intervention in Egypt.}, journal = {Journal of epidemiology and global health}, volume = {13}, number = {2}, pages = {374-383}, pmid = {37202608}, issn = {2210-6014}, mesh = {Humans ; *Cardiovascular Diseases ; Clopidogrel/adverse effects/metabolism/therapeutic use ; Cytochrome P-450 CYP2C19/genetics/metabolism ; Egypt/epidemiology ; *Myocardial Ischemia/genetics/therapy/chemically induced ; *Percutaneous Coronary Intervention ; Platelet Aggregation Inhibitors/adverse effects/metabolism/therapeutic use ; Treatment Outcome ; }, abstract = {BACKGROUND: Cardiovascular diseases (CVDs) are considered a leading cause of death worldwide. Allelic variation in the CYP2C19 gene leads to a dysfunctional enzyme, and patients with this loss-of-function allele will have an impaired clopidogrel metabolism, which eventually results in major adverse cardiovascular events (MACE). Ischemic heart disease patients (n = 102) who underwent percutaneous cardiac intervention (PCI) followed by clopidogrel were enrolled in the present study.

METHODS: The genetic variations in the CYP2C19 gene were identified using the TaqMan chemistry-based qPCR technique. Patients were followed up for 1 year to monitor MACE, and the correlations between the allelic variations in CYP2C19 and MACE were recorded.

RESULTS: During the follow-up, we reported 64 patients without MACE (29 with unstable angina (UA), 8 with myocadiac infarction (MI), 1 patient with non-STEMI, and 1 patient with ischemic dilated cardiomyopathy (IDC)). Genotyping of CYP2C19 in the patients who underwent PCI and were treated with clopidogrel revealed that 50 patients (49%) were normal metabolizers for clopidogrel with genotype CYP2C19*1/*1 and 52 patients (51%) were abnormal metabolizers, with genotypes CYP2C19*1/*2 (n = 15), CYP2C19*1/*3 (n = 1), CYP2C19*1/*17 (n = 35), and CYP2C19*2/*17 (n = 1). Demographic data indicated that age and residency were significantly associated with abnormal clopidogrel metabolism. Moreover, diabetes, hypertension, and cigarette smoking were significantly associated with the abnormal metabolism of clopidogrel. These data shed light on the inter-ethnic variation in metabolizing clopidogrel based on the CYP2C19 allelic distribution.

CONCLUSION: This study, along with other studies that address genotype variation of clopidogrel-metabolizing enzymes, might pave the way for further understanding of the pharmacogenetic background of CVD-related drugs.}, } @article {pmid37201361, year = {2023}, author = {Mekni, K and Mejri, O and Ayadi, A and ElFekif, C}, title = {Unexpected association between breast cancer and molar pregnancy in a 52-year-old woman: A case report.}, journal = {International journal of surgery case reports}, volume = {107}, number = {}, pages = {108253}, pmid = {37201361}, issn = {2210-2612}, abstract = {INTRODUCTION: There was no prior discussion about the association between breast cancer and molar pregnancy, particularly at an advanced age. Through our case and a systematic review, we will discuss the relevance of ovarian castration in hormone-receptor-positive breast cancer.

CASE PRESENTATION: We reported the case of a 52-year-old woman, not yet menopausal, who was diagnosed with a right breast tumor classified as BI-RADS category 4. The anatomopathological analysis of mammary biopsy revealed an invasive ductal carcinoma of no special type (grade 2). Hormone receptors were positive. It was a HER2-negative Breast cancer. It was then decided to treat the patient with radical surgery followed by chemotherapy, radiotherapy, and hormonotherapy. The patient had a "Patey operation". The postoperative course was without significant complications. No medical or surgical castration was indicated in the expectation that chemotherapy would cause ovarian failure. Unlikely, during chemotherapy course our patient developed a molar pregnancy.

CLINICAL DISCUSSION: Our case illustrates the possibility of pregnancy in non-menopausal women with estrogen-receptor-positive breast cancer. The combination of tamoxifen or aromatase inhibitors with ovarian suppression as standard adjuvant therapy may be recommended in such cases.

CONCLUSIONS: Ovarian function suppression in non-menopausal women with hormone receptor-positive breast cancer seems to be necessary. So that, we can avoid unexpected manifestations like molar pregnancy.}, } @article {pmid37195240, year = {2023}, author = {Murata, S and Yamashita, H and Kido, S and Harada, D and Ohtsuru, S and Sato, N}, title = {DYNAMIC METABOLIC CHANGES OBSERVED IN AN LPS-INDUCED SYSTEMIC INFLAMMATION RAT MODEL USING CONTINUOUS LONG-TERM INDIRECT CALORIMETRY EXPERIMENTS.}, journal = {Shock (Augusta, Ga.)}, volume = {60}, number = {1}, pages = {130-136}, pmid = {37195240}, issn = {1540-0514}, mesh = {Humans ; *Lipopolysaccharides/toxicity ; Calorimetry, Indirect/methods ; *Critical Illness ; Energy Metabolism/physiology ; Critical Care ; }, abstract = {Background : Nutritional management is crucial for severely ill patients. Measuring metabolism is believed to be necessary for the acute sepsis phase to accurately estimate nutrition. Indirect calorimetry (IDC) is assumed to be useful for acute intensive care; however, there are few studies on long-term IDC measurement in patients with systemic inflammation. Methods : Rats were categorized into the LPS received or control groups; LPS rats were categorized into underfeeding (UF), adjusted feeding (AF), and overfeeding (OF) groups. Indirect calorimetry measurement was performed until 72 or 144 h. Body composition was measured at -24 and 72 or 144 h, and tissue weight was measured at 72 or 144 h. Results : Low energy consumption and loss of diurnal variation of resting energy expenditure were observed in the LPS group compared with the control group until 72 h, after which the LPS group recovered. The resting energy expenditure in the OF group was higher than that in the UF and AF groups. In the first phase, low energy consumption was observed in all groups. In the second and third phases, higher energy consumption occurred in the OF group than in the UF and AF groups. In the third phase, diurnal variation recovered in all groups. Muscle atrophy caused body weight loss, but fat tissue loss did not occur. Conclusions : We observed metabolic changes with IDC during the acute systemic inflammation phase owing to differences in calorie intake. This is the first report of long-term IDC measurement using the LPS-induced systemic inflammation rat model.}, } @article {pmid37170638, year = {2024}, author = {Antón Rodriguez, Á and Odriozola Herrán, A and Echavarría Rodríguez, VJ and Alonso Fernández, S}, title = {Secondary sclerosing cholangitis induced by systemic chemotherapy.}, journal = {Revista espanola de enfermedades digestivas}, volume = {116}, number = {3}, pages = {173-174}, doi = {10.17235/reed.2023.9653/2023}, pmid = {37170638}, issn = {1130-0108}, mesh = {Female ; Humans ; Middle Aged ; *Cholangitis, Sclerosing/chemically induced/complications ; Cholangiopancreatography, Endoscopic Retrograde ; Liver ; Paclitaxel/adverse effects ; Immunoglobulin G ; }, abstract = {There are multiple causes of secondary sclerosing cholangitis (SSC), including mechanical obstruction, ischemia, congenital abnormalities, cholangiopathy of the critically ill patient and rarely, chemotherapy (1,2). We present the case of a 52-year-old female with a history of left breast invasive ductal carcinoma treated with neoadjuvant chemotherapy (adriamycin, cyclophosphamide and paclitaxel), surgery and radiotherapy in March 2021. She was admitted in July 2022 due to painless jaundice and pruritus with marked serum cholestasis. Magnetic resonance cholangiopancreatography showed multiple strictures and dilatations involving the intra and extrahepatic bile ducts (Figure 1.A), without any extrinsic stenotic cause. Findings were confirmed by endoscopic retrograde cholangiopancreatography (ERCP) with cholangioscopy (Figure 1.B). Biopsies were negative for malignancy and IgG4 disease. In addition, autoantibodies were negative and serum IgG4 levels were normal. Due to these findings and the history of recent chemotherapy, the patient was diagnosed with paclitaxel-induced sclerosing cholangitis, initiating treatment with ursodeoxycholic acid. Over the following two months, she suffered two episodes of Klebsiella Pneumoniae bacteraemia due to acute cholangitis. Dilatation and placement of plastic stents in both biliary trees were performed and prophylactic antibiotherapy was started. The patient had a poor evolution and was not candidate for liver transplantation on account of a recent neoplasia. She died six months later due to sepsis secondary to multiple hepatic abscesses.}, } @article {pmid37139855, year = {2023}, author = {Tsilingiris, D and Schimpfle, L and von Rauchhaupt, E and Sulaj, A and Seebauer, L and Bartl, H and Herzig, S and Szendroedi, J and Kopf, S and Kender, Z}, title = {Dysmetabolism-related Early Sensory Deficits and Their Relationship With Peripheral Neuropathy Development.}, journal = {The Journal of clinical endocrinology and metabolism}, volume = {108}, number = {10}, pages = {e979-e988}, pmid = {37139855}, issn = {1945-7197}, mesh = {Humans ; Male ; *Diabetes Mellitus, Type 2/complications ; *Metabolic Syndrome/complications/epidemiology ; *Peripheral Nervous System Diseases/epidemiology/etiology ; *Insulin Resistance ; Glycation End Products, Advanced ; }, abstract = {AIM: To investigate the association of early peripheral sensory dysfunction (EPSD) identified through quantitative sensory testing (QST) with factors related to a dysmetabolic status in individuals with and without type 2 diabetes (T2DM) without peripheral neuropathy (PN), and the impact of those factors on PN development.

METHODS: A total of 225 individuals (117 and 108 without and with T2DM, respectively) without PN based on clinical and electrophysiological criteria were analyzed. Comparative analysis was conducted between those identified as "healthy" and those with EPSD based on a standardized QST protocol. A total of 196 were followed-up over a mean of 2.64 years for PN occurrence.

RESULTS: Among those without T2DM, apart from male sex, height, and higher fat and lower lean mass, only higher insulin resistance (IR; homeostatic model assessment for IR: odds ratio [OR], 1.70; P = .009; McAuley index OR, 0.62, P = .008), was independently associated with EPSD. In T2DM, metabolic syndrome (OR, 18.32; P < .001) and skin advanced glycation end-products (AGEs; OR, 5.66; P = .003) were independent predictors of EPSD. In longitudinal analysis, T2DM (hazard ratio [HR], 3.32 vs no diabetes mellitus; P < .001), EPSD (adjusted HR, 1.88 vs healthy; P = .049 adjusted for diabetes mellitus and sex), higher IR and AGEs predicted PN development. Among the 3 EPSD-associated sensory phenotypes, "sensory loss" was most strongly associated with PN development (adjusted HR, 4.35; P = .011).

CONCLUSION: We demonstrate for the first time the utility of a standardized QST-based approach in identifying early sensory deficits in individuals with and without T2DM. These are associated with a dysmetabolic status signified by IR markers, metabolic syndrome, and higher AGEs, which in turn are shown to influence PN development.}, } @article {pmid37101747, year = {2023}, author = {Xiang, S and Wei, M and Zhao, L and Lin, A and Xiong, Z}, title = {Integrated Analyses of the Expression and Prognostic Value of EPHB6 in Cervical Cancer and Its Correlation with Immune Infiltrates.}, journal = {Journal of oncology}, volume = {2023}, number = {}, pages = {2258906}, pmid = {37101747}, issn = {1687-8450}, abstract = {Among women, cervical cancer (CC) ranks as the third most frequent form of carcinoma and the fourth greatest cancer-related cause of deaths. There is increasing evidence that points to the dysregulation of EPH receptor B6 (EPHB6) in various cancers. On the other hand, neither the expression nor the function of EPHB6 in CC has been researched. In the first part of this investigation, we analyzed the data from the TCGA and discovered that the level of EPHB6 was much lower in CC tissues than in normal cervical tissues. ROC assays revealed that high EPHB6 expression had an AUC value of 0.835 for CC. The survival study revealed that both the overall and disease-specific survivals in this condition were considerably lower among patients who had a low EPHB6 level compared to those who had a high EPHB6 level. It is important to note that the multivariate COX regression analysis indicated that the expression of EPHB6 was an independent predictive factor. In addition to this, the C-indexes and calibration plots of a nomogram derived from multivariate assays revealed an accurate prediction performance among patients with CC. Immune infiltration analysis indicated that the expression of EPHB6 was positively associated with the levels of Tcm, TReg, B cells, T cells, iDC, T helper cells, cytotoxic cells, and DC, while negatively associated with NK CD56bright cells and neutrophils. In summary, the downregulation of EPHB6 was strongly linked to a more aggressive clinical development of CC, suggesting its potential utility as a diagnostic and therapeutic target in CC.}, } @article {pmid37095978, year = {2023}, author = {Norooznezhad, AH and Yarani, R and Payandeh, M and Hoseinkhani, Z and Mahmoudi, H and Kiani, S and Mansouri, K}, title = {Treatment of persistent chemotherapy-induced hair loss (Alopecia) with human mesenchymal stromal cells exosome enriched extracellular vesicles: A case report.}, journal = {Heliyon}, volume = {9}, number = {4}, pages = {e15165}, pmid = {37095978}, issn = {2405-8440}, abstract = {INTRODUCTION: Cancer is among the leading causes of death worldwide and affects a considerable number of individuals. Chemotherapy is one the most common treatment for this condition and hair loss is among one of the most prevalent side effects. In this study, we report successful treatment of a patient suffering from persistent chemotherapy-induced alopecia (PCIA) with extracellular enriched vesicles (EVs) derived from human placental mesenchymal stromal cells (MSCs).

CASE PRESENTATION: The patient was a 36-year-old woman with a history of invasive ductal carcinoma, underwent six courses of chemotherapy with paclitaxel and adriamycin. Following this treatment and for almost 18 months, she, unfortunately, had no regrowth of hair except some light vellus hairs on the scalp. She then received MSC-derived EVs with scalp injection (subcutaneous) every 4 weeks for 3 continuous months at which point she presented complete regrowth of terminal hair on her scalp.

CONCLUSION: This report demonstrates that MSC-derived EVs could be a possible treatment for permanent chemotherapy-induced alopecia; however, further studies and trials are necessary.}, } @article {pmid37094629, year = {2023}, author = {Chovsepian, A and Prokopchuk, O and Petrova, G and Gjini, T and Kuzi, H and Heisz, S and Janssen, KP and Martignoni, ME and Friess, H and Hauner, H and Rohm, M}, title = {Diabetes increases mortality in patients with pancreatic and colorectal cancer by promoting cachexia and its associated inflammatory status.}, journal = {Molecular metabolism}, volume = {73}, number = {}, pages = {101729}, pmid = {37094629}, issn = {2212-8778}, mesh = {Humans ; Cachexia/metabolism ; Retrospective Studies ; C-Reactive Protein ; *Diabetes Mellitus, Type 2/complications ; *Pancreatic Neoplasms/complications/metabolism ; Body Weight ; Obesity/complications ; Biomarkers ; *Colorectal Neoplasms/complications ; }, abstract = {OBJECTIVES: Cancer is considered an emerging diabetes complication, with higher incidence and worse prognosis in patients with diabetes. Cancer is frequently associated with cachexia, a systemic metabolic disease causing wasting. It is currently unclear how diabetes affects the development and progression of cachexia.

METHODS: We investigated the interplay between diabetes and cancer cachexia retrospectively in a cohort of 345 patients with colorectal and pancreatic cancer. We recorded body weight, fat mass, muscle mass, clinical serum values, and survival of these patients. Patients were grouped either into diabetic/non-diabetic groups based on previous diagnosis, or into obese/non-obese groups based on body mass index (BMI ≥30 kg/m[2] was considered obese).

RESULTS: The pre-existence of type 2 diabetes, but not obesity, in patients with cancer led to increased cachexia incidence (80%, compared to 61% without diabetes, p ≤ 0.05), higher weight loss (8.9% vs. 6.0%, p ≤ 0.001), and reduced survival probability (median survival days: 689 vs. 538, Chi square = 4.96, p ≤ 0.05) irrespective of the initial body weight or tumor progression. Patients with diabetes and cancer showed higher serum levels of C-reactive protein (0.919 μg/mL vs. 0.551 μg/mL, p ≤ 0.01) and interleukin 6 (5.98 pg/mL vs. 3.75 pg/mL, p ≤ 0.05) as well as lower serum albumin levels (3.98 g/dL vs. 4.18 g/dL, p ≤ 0.05) than patients with cancer without diabetes. In a sub-analysis of patients with pancreatic cancer, pre-existing diabetes worsened weight loss (9.95% vs. 6.93%, p ≤ 0.01), and increased the duration of hospitalization (24.41 days vs. 15.85 days, p ≤ 0.001). Further, diabetes aggravated clinical manifestations of cachexia, as changes in the aforementioned biomarkers were more pronounced in patients with diabetes and cachexia co-existence, compared to cachectic patients without diabetes (C-reactive protein: 2.300 μg/mL vs. 0.571 μg/mL, p ≤ 0.0001; hemoglobin: 11.24 g/dL vs. 12.52 g/dL, p ≤ 0.05).

CONCLUSIONS: We show for the first time that pre-existing diabetes aggravates cachexia development in patients with colorectal and pancreatic cancer. This is important when considering cachexia biomarkers and weight management in patients with co-existing diabetes and cancer.}, } @article {pmid37085500, year = {2023}, author = {Zhou, D and Li, M and Yasin, MH and Lu, Q and Fu, J and Jiang, K and Hong, R and Wang, S and Xu, F}, title = {The prognostic value and immune microenvironment association of AR in HER2+ nonmetastatic breast cancer.}, journal = {NPJ breast cancer}, volume = {9}, number = {1}, pages = {30}, pmid = {37085500}, issn = {2374-4677}, support = {320.6750.2021-10-97//Ministry of Health of China | Wu Jieping Medical Foundation/ ; 2019A1515011945//Natural Science Foundation of Guangdong Province (Guangdong Natural Science Foundation)/ ; }, abstract = {This study aimed to investigate the prognostic value of AR in HER2+ nonmetastatic breast invasive ductal carcinoma (IDC) and its relationship with the immune microenvironment. HER2+ nonmetastatic breast IDC patients diagnosed by pathology who underwent surgery at Sun Yat-sen University Cancer Center from 2016 to 2017 were included. AR+ and AR- breast IDC samples were matched 1:1 in age, T stage, and N stage for immune infiltration analysis. A total of 554 patients with HER2+ nonmetastatic breast cancer were included in this retrospective study, regardless of HR status. The cut-off value for AR was set at 10%. ER+ (p < 0.001) and PR+ (p < 0.001) were associated with positive AR expression. Kaplan-Meier survival curve analysis suggested that AR was closely correlated with overall survival (OS) (p = 0.001) but not disease-free survival (DFS) (p = 0.051). After eliminating the potential impact caused by HR, AR also predicted longer OS (p = 0.014) and was an independent predictive factor for OS of HER2+HR- nonmetastatic breast IDC patients, as revealed by multivariate analysis (p = 0.036). For AR+ and AR- matched HER2+HR- patients, TILs (p = 0.043) and PD-L1 (p = 0.027) levels were significantly lower in AR+ patients. The strongest negative correlation was observed between AR and PD-L1 (Pearson's r = -0.299, p = 0.001). AR+ status was markedly related to better OS in HER2+HR- nonmetastatic breast cancer patients, while a negative correlation was observed between AR and PD-L1/TILs. We provide new insights into the prognostic value of AR and its association with the immune microenvironment to optimize treatment strategies in HER2+ nonmetastatic breast IDCs.}, } @article {pmid37085014, year = {2023}, author = {van Balkom, IDC and Burdeus-Olavarrieta, M and Cooke, J and de Cuba, AG and Turner, A and , and Vogels, A and Maruani, A}, title = {Consensus recommendations on mental health issues in Phelan-McDermid syndrome.}, journal = {European journal of medical genetics}, volume = {66}, number = {6}, pages = {104770}, doi = {10.1016/j.ejmg.2023.104770}, pmid = {37085014}, issn = {1878-0849}, mesh = {Humans ; Consensus ; *Mental Health ; Quality of Life ; *Chromosome Disorders/genetics/psychology ; Chromosome Deletion ; Chromosomes, Human, Pair 22/genetics ; }, abstract = {Phelan-McDermid syndrome is a rare genetic condition caused by a deletion encompassing the 22q13.3 region or a pathogenic variant of the gene SHANK3. The clinical presentation is variable, but main characteristics include global developmental delay/intellectual disability (ID), marked speech impairment or delay, along with other features like hypotonia and somatic or psychiatric comorbidities. This publication delineates mental health, developmental and behavioural themes across the lifetime of individuals with PMS as informed by parents/caregivers, experts, and other key professionals involved in PMS care. We put forward several recommendations based on the available literature concerning mental health and behaviour in PMS. Additionally, this article aims to improve our awareness of the importance of considering developmental level of the individual with PMS when assessing mental health and behavioural issues. Understanding how the discrepancy between developmental level and chronological age may impact concerning behaviours offers insight into the meaning of those behaviours and informs care for individuals with PMS, enabling clinicians to address unmet (mental health) care needs and improve quality of life.}, } @article {pmid37028455, year = {2023}, author = {Lin, Y and Amkul, K and Laosatit, K and Liu, J and Yimram, T and Chen, J and Yuan, X and Chen, X and Somta, P}, title = {Fine mapping of QTL conferring resistance to calcareous soil in mungbean reveals VrYSL3 as candidate gene for the resistance.}, journal = {Plant science : an international journal of experimental plant biology}, volume = {332}, number = {}, pages = {111698}, doi = {10.1016/j.plantsci.2023.111698}, pmid = {37028455}, issn = {1873-2259}, mesh = {Quantitative Trait Loci/genetics ; *Vigna/genetics/metabolism ; Genome-Wide Association Study ; Soil ; Iron/metabolism ; *Iron Deficiencies ; }, abstract = {Iron is a crucial nutrient for biological functions in plants. High-pH and calcareous soil is a major stress causing iron deficiency chlorosis (IDC) symptoms and yield losses in crops. Use of calcareous soil-tolerance genetic resources is the most effective preventative method to combat the effects of high-pH and calcareous soils. A previous study using a mungbean recombinant inbred line (RIL) population of the cross Kamphaeg Saen 2 (KPS2; IDC susceptible) × NM-10-12 identified a major quantitative trait locus (QTL), qIDC3.1, which controls resistance and explains more than 40% of IDC variation. In this study, we fine-mapped qIDC3.1 and identified an underlying candidate gene. A genome wide association analysis (GWAS) using 162 mungbean accessions identified single nucleotide polymorphisms (SNPs) on chromosome 6; several SNPs were associated with soil plant analysis development (SPAD) values and IDC visual scores of mungbeans planted on calcareous soil, respectively. These SNPs corresponded to qIDC3.1. Using the same RIL population as in the previous study and an advanced backcross population developed from KPS2 and IDC-resistant inbred line RIL82, qIDC3.1 was further confirmed and fine-mapped to an interval of 217 kilobases harboring five predicted genes, including LOC106764181 (VrYSL3), which encodes a yellow stripe1-like-3 (YSL3) protein, YSL3 is involved in iron deficiency resistance. Gene expression analysis revealed that VrYSL3 was highly expressed in mungbean roots. In calcareous soil, expression of VrYSL3 was significantly up-regulated, and it was more obviously upregulated in the roots of RIL82, than in those of KPS2. Sequence comparison of VrYSL3 between the RIL82 and KPS2 revealed four SNPs that result in amino acid changes in the VrYSL3 protein and a 20-bp insertion/deletion in the promoter where a cis-regulatory element resides. Transgenic Arabidopsis thaliana plants overexpressing VrYSL3 showed enhanced iron and zinc contents in the leaves. Taken together, these results indicate that VrYSL3 is a strong candidate gene responsible for calcareous soil resistance in mungbean.}, } @article {pmid37020090, year = {2023}, author = {Kawaguchi, S and Kinowaki, K and Tamura, N and Masumoto, T and Nishikawa, A and Shibata, A and Tanaka, K and Kobayashi, Y and Ogura, T and Sato, J and Kawabata, H}, title = {High-accuracy prediction of axillary lymph node metastasis in invasive lobular carcinoma using focal cortical thickening on magnetic resonance imaging.}, journal = {Breast cancer (Tokyo, Japan)}, volume = {30}, number = {4}, pages = {637-646}, pmid = {37020090}, issn = {1880-4233}, mesh = {Humans ; Female ; Middle Aged ; Aged ; *Breast Neoplasms/pathology ; Lymphatic Metastasis/diagnostic imaging/pathology ; *Carcinoma, Lobular/diagnostic imaging/surgery/pathology ; Retrospective Studies ; *Carcinoma, Ductal, Breast/pathology ; Lymph Nodes/pathology ; Magnetic Resonance Imaging ; }, abstract = {BACKGROUND: Invasive lobular carcinoma (ILC) grows diffusely in a single-cell fashion, sometimes presenting only subtle changes in preoperative imaging; therefore, axillary lymph node (ALN) metastases of ILC are difficult to detect using magnetic resonance imaging (MRI). Preoperative underestimation of nodal burden occurs more frequently in ILC than in invasive ductal carcinoma (IDC), however, the morphological assessment for metastatic ALNs of ILC have not fully been investigated. We hypothesized that the high false-negative rate in ILC is caused by the discrepancy in the MRI findings of ALN metastases between ILC and IDC and aimed to identify the MRI finding with a strong correlation with ALN metastasis of ILC.

METHOD: This retrospective analysis included 120 female patients (mean ± standard deviation age, 57.2 ± 11.2 years) who underwent upfront surgery for ILC at a single center between April 2011 and June 2022. Of the 120 patients, 35 (29%) had ALN metastasis. Using logistic regression, we constructed prediction models based on MRI findings: primary tumor size, focal cortical thickening (FCT), cortical thickness, long-axis diameter (LAD), and loss of hilum (LOH).

RESULTS: The area under the curves were 0.917 (95% confidence interval [CI] 0.869-0.968), 0.827 (95% CI 0.758-0.896), 0.754 (95% CI 0.671-0.837), and 0.621 (95% CI 0.531-0.711) for the FCT, cortical thickness, LAD, and LOH models, respectively.

CONCLUSIONS: FCT may be the most relevant MRI finding for ALN metastasis of ILC, and although its prediction model may lead to less underestimation of the nodal burden, rigorous external validation is required.}, } @article {pmid37013774, year = {2023}, author = {Oh, J and Oh, JM and Cho, SY}, title = {METTL3-mediated downregulation of splicing factor SRSF11 is associated with carcinogenesis and poor survival of cancer patients.}, journal = {European review for medical and pharmacological sciences}, volume = {27}, number = {6}, pages = {2561-2570}, doi = {10.26355/eurrev_202303_31793}, pmid = {37013774}, issn = {2284-0729}, mesh = {Humans ; *Adenocarcinoma of Lung ; Carcinogenesis ; *Colonic Neoplasms ; Down-Regulation ; *Lung Neoplasms/genetics/pathology ; *Methyltransferases/genetics ; *Serine-Arginine Splicing Factors/genetics ; }, abstract = {OBJECTIVE: N6-methyladenosine (m6A) is one of the most abundant post-transcriptional modifications in eukaryotic RNA. As m6A modifications play an important role in RNA processing, abnormal m6A regulation caused by aberrant expression of m6A regulators is closely related to carcinogenesis. In this study, we aimed to determine the role of METTL3 expression in carcinogenesis, regulation of splicing factor expression by METTL3, and their effects in survival period and cancer-related metabolisms.

MATERIALS AND METHODS: We investigated the correlation between each splicing factor and METTL3 in breast invasive ductal carcinoma (BRCA), colon adenocarcinoma (COAD), lung adenocarcinoma (LUAD) and gastric adenocarcinoma (STAD). Survival analysis was performed based on the expression of each splicing factor. To determine the molecular mechanism of SRSF11 in carcinogenesis, gene set enrichment analysis using RNA sequencing data was performed according to SRSF11 expression.

RESULTS: Among the 64 splicing factors used for correlation analysis, 13 splicing factors showed a positive correlation with METTL3 in all four cancer types. We found that when METTL3 expression was decreased, the expression of SRSF11 was also decreased in all four types of cancer tissue when compared to that in normal tissue. Decreased SRSF11 expression was associated with poor survival in patients with BRCA, COAD, LUAD, and STAD. Gene set enrichment analysis according to SRSF11 expression showed that the p53/apoptosis, inflammation/immune response, and ultraviolet/reactive oxygen species stimulus-response pathways were enriched in cancers with decreased SRSF11 expression.

CONCLUSIONS: These results suggest that METTL3 regulates SRSF11 expression, which could influence mRNA splicing in m6A modified cancer cells. METTL3-mediated downregulation of SRSF11 expression in cancer patients correlates with poor prognosis.}, } @article {pmid37008917, year = {2023}, author = {Kender, Z and Jende, JME and Kurz, FT and Tsilingiris, D and Schimpfle, L and Sulaj, A and von Rauchhaupt, E and Bartl, H and Mooshage, C and Göpfert, J and Nawroth, P and Herzig, S and Szendroedi, J and Bendszus, M and Kopf, S}, title = {Sciatic nerve fractional anisotropy and neurofilament light chain protein are related to sensorimotor deficit of the upper and lower limbs in patients with type 2 diabetes.}, journal = {Frontiers in endocrinology}, volume = {14}, number = {}, pages = {1046690}, pmid = {37008917}, issn = {1664-2392}, mesh = {Humans ; *Diabetes Mellitus, Type 2/pathology ; Anisotropy ; Intermediate Filaments ; Sciatic Nerve/diagnostic imaging/pathology ; *Diabetic Neuropathies/complications ; Lower Extremity/diagnostic imaging ; Biomarkers ; }, abstract = {BACKGROUND: Diabetic sensorimotor polyneuropathy (DSPN) is one of the most prevalent and poorly understood diabetic microvascular complications. Recent studies have found that fractional anisotropy (FA), a marker for microstructural nerve integrity, is a sensitive parameter for the structural and functional nerve damage in DSPN. The aim of this study was to investigate the significance of proximal sciatic nerve's FA on different distal nerve fiber deficits of the upper and lower limbs and its correlation with the neuroaxonal biomarker, neurofilament light chain protein (NfL).

MATERIALS AND METHODS: Sixty-nine patients with type 2 diabetes (T2DM) and 30 healthy controls underwent detailed clinical and electrophysiological assessments, complete quantitative sensory testing (QST), and diffusion-weighted magnetic resonance neurography of the sciatic nerve. NfL was measured in the serum of healthy controls and patients with T2DM. Multivariate models were used to adjust for confounders of microvascular damage.

RESULTS: Patients with DSPN showed a 17% lower sciatic microstructural integrity compared to healthy controls (p<0.001). FA correlated with tibial and peroneal motor nerve conduction velocity (NCV) (r=0.6; p<0.001 and r=0.6; p<0.001) and sural sensory NCV (r=0.50; p<0.001). Participants with reduced sciatic nerve´s FA showed a loss of function of mechanical and thermal sensation of upper (r=0.3; p<0.01 and r=0.3; p<0.01) and lower (r=0.5; p<0.001 and r=0.3; p=<0.01) limbs and reduced functional performance of upper limbs (Purdue Pegboard Test for dominant hand; r=0.4; p<0.001). Increased levels of NfL and urinary albumin-creatinine ratio (ACR) were associated with loss of sciatic nerve´s FA (r=-0.5; p<0.001 and r= -0.3, p= 0.001). Of note, there was no correlation between sciatic FA and neuropathic symptoms or pain.

CONCLUSION: This is the first study showing that microstructural nerve integrity is associated with damage of different nerve fiber types and a neuroaxonal biomarker in DSPN. Furthermore, these findings show that proximal nerve damage is related to distal nerve function even before clinical symptoms occur. The microstructure of the proximal sciatic nerve and is also associated with functional nerve fiber deficits of the upper and lower limbs, suggesting that diabetic neuropathy involves structural changes of peripheral nerves of upper limbs too.}, } @article {pmid36976351, year = {2023}, author = {Aiello, EN and D'Iorio, A and Solca, F and Torre, S and Bonetti, R and Scheveger, F and Colombo, E and Maranzano, A and Maderna, L and Morelli, C and Doretti, A and Amboni, M and Vitale, C and Verde, F and Ferrucci, R and Barbieri, S and Zirone, E and Priori, A and Pravettoni, G and Santangelo, G and Silani, V and Ticozzi, N and Ciammola, A and Poletti, B}, title = {Clinimetrics and feasibility of the Italian version of the Frontal Assessment Battery (FAB) in non-demented Parkinson's disease patients.}, journal = {Journal of neural transmission (Vienna, Austria : 1996)}, volume = {130}, number = {5}, pages = {687-696}, pmid = {36976351}, issn = {1435-1463}, mesh = {Humans ; *Parkinson Disease/complications/diagnosis/psychology ; Reproducibility of Results ; Cross-Sectional Studies ; Feasibility Studies ; Neuropsychological Tests ; *Cognitive Dysfunction/etiology/complications ; Language ; }, abstract = {BACKGROUND: This study aimed at assessing the cross-sectional and longitudinal clinimetrics and feasibility of the Frontal Assessment Battery (FAB) in non-demented Parkinson's disease (PD) patients.

METHODS: N = 109 PD patients underwent the FAB and the Montreal Cognitive Assessment (MoCA). A subsample of patients further underwent a thorough motor, functional and behavioral evaluation (the last including measures of anxiety, depression and apathy). A further subsample was administered a second-level cognitive battery tapping on attention, executive functioning, language, memory, praxis and visuo-spatial abilities. The following properties of the FAB were tested: (1) concurrent validity and diagnostics against the MoCA; (2) convergent validity against the second-level cognitive battery; (4) association with motor, functional and behavioral measures; (5) capability to discriminate patients from healthy controls (HCs; N = 96); (6) assessing its test-retest reliability, susceptibility to practice effects and predictive validity against the MoCA, as well as deriving reliable change indices (RCIs) for it, at a ≈ 6-month interval, within a subsample of patients (N = 33).

RESULTS: The FAB predicted MoCA scores at both T0 and T1, converged with the vast majority of second-level cognitive measures and was associated with functional independence and apathy. It accurately identified cognitive impairment (i.e., a below-cut-off MoCA score) in patients, also discriminating patients from HCs. The FAB was reliable at retest and free of practice effects; RCIs were derived according to a standardized regression-based approach.

DISCUSSION: The FAB is a clinimetrically sound and feasible screener for detecting dysexecutive-based cognitive impairment in non-demented PD patients.}, } @article {pmid36934657, year = {2023}, author = {Varun, K and Zoltan, K and Alba, S and Manuel, B and Elisabeth, K and Dimitrios, T and Jan B, G and Maik, B and Khurrum, S and Berend, I and Stephen, H and Thomas, F and Julia, S and Peter, N and Stefan, K}, title = {Elevated markers of DNA damage and senescence are associated with the progression of albuminuria and restrictive lung disease in patients with type 2 diabetes.}, journal = {EBioMedicine}, volume = {90}, number = {}, pages = {104516}, pmid = {36934657}, issn = {2352-3964}, mesh = {Mice ; Animals ; *Diabetes Mellitus, Type 2/complications ; Follow-Up Studies ; Interleukin-6 ; *Prediabetic State ; Albuminuria/complications ; Cross-Sectional Studies ; Prospective Studies ; *Lung Diseases ; Fibrosis ; DNA Damage ; Cellular Senescence ; }, abstract = {BACKGROUND: This study was conducted to investigate the cascade involving DNA damage, senescence, and senescence-associated secretory phenotype (SASP) in experimental diabetes and in a four-year follow-up study in patients with pre-diabetes and type 2 diabetes.

METHODS: Kidney, lung, and liver were studied in 4 months diabetic db/db mice and age-matched controls for the presence of DNA damage and fibrosis. DNA damage (comet-tail-length and ɤH2Ax-positivity in white blood cells), urinary p21-excretion, and plasma IL-6 and TGF-β1 were determined from 115 healthy participants, 34 patients with pre-diabetes and 221 with type 2 diabetes. Urinary albumin-creatinine-ratio, lung function, and transient elastography of the liver were performed in a prospective follow-up study over 4 years.

FINDINGS: db/db mice showed an increased nuclear ɤH2AX signal in all tissues as compared to the background control. Markers for DNA damage, senescence, and SASP were increased in patients with diabetes. The presence of nephropathy, restrictive lung disease (RLD), and increased liver stiffness was in a cross-sectional design associated with increased markers for DNA damage, senescence, and SASP. The progression of nephropathy over 4 years was predicted by increased DNA damage, senescence, and SASP, while the progression of RLD was associated with increased DNA damage and IL-6 only. The progression of liver stiffness was not associated with any of these parameters. HbA1c was not predictive for progression.

INTERPRETATION: In db/db mice, the cascade of DNA damage is associated with diabetes-related complications. In patients with diabetes, the progression of complications in the kidney and lung is predicted by markers reflecting DNA damage, and senescence-triggered organ fibrosis.

FUNDING: This work was supported by the German Research Foundation (DFG) in the CRC 1118 and CRC 1158, by the GRK DIAMICOM, by the German Center for Diabetes Research (DZD e.V.), and by the Ministry of Science, Research and the Arts, Baden-Württemberg (Kompetenznetzwerk Präventivmedizin).}, } @article {pmid36931261, year = {2023}, author = {Cardona Barberán, A and Bonte, D and Boel, A and Thys, V and Paredis, R and Machtelinckx, F and De Sutter, P and De Croo, I and Leybaert, L and Stoop, D and Coucke, P and Vanden Meerschaut, F and Heindryckx, B}, title = {Assisted oocyte activation does not overcome recurrent embryo developmental problems.}, journal = {Human reproduction (Oxford, England)}, volume = {38}, number = {5}, pages = {872-885}, doi = {10.1093/humrep/dead051}, pmid = {36931261}, issn = {1460-2350}, mesh = {Pregnancy ; Child ; Humans ; Male ; Female ; Animals ; Mice ; *Sperm Injections, Intracytoplasmic/methods ; *Calcium ; Ionomycin ; Calcimycin ; Prospective Studies ; Semen ; Pregnancy Rate ; Oocytes ; Embryonic Development ; Retrospective Studies ; Adaptor Proteins, Signal Transducing ; Apoptosis Regulatory Proteins ; }, abstract = {STUDY QUESTION: Can recurrent embryo developmental problems after ICSI be overcome by assisted oocyte activation (AOA)?

SUMMARY ANSWER: AOA did not improve blastocyst formation in our patient cohort with recurrent embryo developmental problems after ICSI.

WHAT IS KNOWN ALREADY: The use of AOA to artificially induce calcium (Ca2+) rises by using Ca2+ ionophores (mainly calcimycin and ionomycin) has been reported as very effective in overcoming fertilization failure after ICSI, especially in patients whose Ca2+ dynamics during fertilization are deficient. However, there is only scarce and contradictory literature on the use of AOA to overcome embryo developmental problems after ICSI, and it is not clear whether abnormal Ca2+ patterns during fertilization disturb human preimplantation embryo development. Moreover, poor embryo development after ICSI has also been linked to genetic defects in the subcortical maternal complex (SCMC) genes.

STUDY DESIGN, SIZE, DURATION: This prospective cohort single-center study compared ICSI-AOA cycles and previous ICSI cycles in couples with normal fertilization rates (≥60%) but impaired embryonic development (≤15% blastocyst formation) in at least two previous ICSI cycles. In total, 42 couples with embryo developmental problems were included in this study from January 2018 to January 2021.

Of the 42 couples included, 17 underwent an ICSI-AOA cycle consisting of CaCl2 injection and double ionomycin exposure. Fertilization, blastocyst development, pregnancy, and live birth rates after ICSI-AOA were compared to previous ICSI cycles. In addition, the calcium pattern induced by the male patient's sperm was investigated by mouse oocyte calcium analysis. Furthermore, all 42 couples underwent genetic screening. Female patients were screened for SCMC genes (TLE6, PADI6, NLRP2, NLRP5, NLRP7, and KHDC3L) and male patients were screened for the sperm-oocyte-activating factor PLCZ1.

We compared 17 AOA cycles to 44 previous ICSI cycles from the same patient cohort. After AOA, a total fertilization rate of 68.95% (131/190), a blastocyst development rate of 13.74% (18/131), a pregnancy rate of 29.41% (5/17), and a live birth rate of 23.53% (4/17) were achieved, which was not different from the previous ICSI cycles (76.25% (321/421, P-value = 0.06); 9.35% (30/321, P-value = 0.18), 25.00% (11/44, P-value = 0.75), and 15.91% (7/44, P-value = 0.48), respectively). Calcium analysis showed that patient's sperm induced calcium patterns similar to control sperm samples displaying normal embryo developmental potential. Genetic screening revealed 10 unique heterozygous variants (in NLRP2, NLRP5, NLRP7, TLE6, and PADI6) of uncertain significance (VUS) in 14 females. Variant NLRP5 c.623-12_623-11insTTC (p.?) was identified in two unrelated individuals and variant NLRP2 c.1572T>C (p.Asp524=) was identified in four females. Interestingly, we identified a previously reported homozygous mutation PLCZ1, c.1499C>T (p.Ser500Leu), in a male patient displaying impaired embryonic development, but not showing typical fertilization failure.

Our strict inclusion criteria, requiring at least two ICSI cycles with impaired embryo development, reduced cycle-to-cycle variability, while the requirement of a lower blastocyst development not influenced by a poor fertilization excluded couples who otherwise would be selective cases for AOA; however, these criteria limited the sample size of this study. Targeted genetic screening might be too restricted to identify a genetic cause underlying the phenotype of poor embryo development for all patients. Moreover, causality of the identified VUS should be further determined.

Strong evidence for AOA overcoming impaired embryonic development is still lacking in the literature. Thus far, only one article has reported a beneficial effect of AOA (using calcimycin) compared to previous ICSI cycles in this patient population, whilst two more recent sibling-oocyte control studies (one using calcimycin and the other ionomycin) and our research (using ionomycin) could not corroborate these findings. Although no major abnormalities have been found in children born after AOA, this technique should be reserved for couples with a clear Ca2+-release deficiency. Finally, genetic screening by whole-exome sequencing may reveal novel genes and variants linked to embryo developmental problems and allow the design of more personalized treatment options, such as wild-type complementary RNA or recombinant protein injection.

This study was supported by the Flemish Fund for Scientific Research (grant FWO.OPR.2015.0032.01 to B.H. and grant no. 1298722N to A.B.). A.C.B., D.B., A.B., V.T., R.P., F.M., I.D.C., L.L., D.S., P.D.S., P.C., and F.V.M. have nothing to disclose. B.H. reports a research grant from the Flemish Fund for Scientific Research and reports being a board member of the Belgian Society for Reproductive Medicine and the Belgian Ethical Committee on embryo research.

TRIAL REGISTRATION NUMBER: NCT03354013.}, } @article {pmid36927911, year = {2023}, author = {Mitsuyoshi, A and Yanagawa, T and Kikumori, K and Hori, A and Oshima, K and Shinke, G and Katsuyama, S and Ikeshima, R and Hiraki, M and Ohmura, Y and Sugimura, K and Masuzawa, T and Hata, T and Takeda, Y and Murata, K}, title = {[A Case of De Novo Stage Ⅳ Breast Cancer with Umbilical Metastasis and Peritoneal Dissemination].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {50}, number = {3}, pages = {366-368}, pmid = {36927911}, issn = {0385-0684}, mesh = {Female ; Humans ; Middle Aged ; Peritoneum ; *Breast Neoplasms/surgery/pathology ; Positron Emission Tomography Computed Tomography ; Umbilicus/surgery/pathology ; *Carcinoma, Ductal ; }, abstract = {The patient was a 48-year-old woman. At the time of consultation, a hard mass of 30 mm in size was palpated in area A of the right breast, and a firm mass of about 10 mm was seen in the umbilical region. Histological diagnosis of the breast mass was invasive ductal carcinoma. PET-CT scan showed accumulation in the right breast, as well as suspicion of umbilical metastasis and peritoneal dissemination, uterine mass, and left ovarian cancer. Since this is an atypical metastatic site for invasive ductal carcinoma of the breast, and the possibility of peritoneal dissemination due to gynecological cancer complications cannot be ruled out, resection of the umbilical mass and laparoscopy was performed. The review laparoscopy revealed no evidence of primary cancer in the uterine body or left ovary, and a white nodular lesion of suspected seeding in the peritoneum around the left ovary. The histology and immunostaining results of the umbilical mass and left peri-ovarian nodule both showed glandular luminal structures similar to those of the primary breast cancer, and the left peri-ovarian nodule was ER positive, GATA3 positive, and PAX8 negative, leading to the diagnosis of umbilical metastasis and peritoneal seeding derived from breast cancer. Umbilical metastasis is often referred to as Sister Mary Joseph's nodule in the case of visceral malignancies and is often associated with peritoneal dissemination and is often caused by invasive metastasis of peritoneal dissemination lesions on the dorsal side of the umbilical region. In this case, histological examination of the umbilical specimen showed no disseminated lesion on the peritoneal side, so it was not considered to be an invasive metastasis due to peritoneal dissemination.}, } @article {pmid36890060, year = {2023}, author = {Verspyck, E and Attal, N}, title = {Diagnosing nociplastic pain in cancer survivors: a major step forward.}, journal = {British journal of anaesthesia}, volume = {130}, number = {5}, pages = {515-518}, doi = {10.1016/j.bja.2023.02.006}, pmid = {36890060}, issn = {1471-6771}, mesh = {Humans ; *Cancer Survivors ; Pain ; *Fibromyalgia/complications/diagnosis/therapy ; Headache ; Pain Management ; *Neoplasms/complications ; }, abstract = {Nociplastic pain syndromes include particular fibromyalgia, irritable bowel syndrome, headache, complex regional pain syndrome, and idiopathic orofacial pain. Several mechanisms have been proposed to account for nociplastic pain including central sensitisation, alterations of pain modulatory controls, epigenetic changes, and peripheral mechanisms. Importantly, nociplastic pain might also be present in patients with cancer pain, particularly those with pain related to complications of cancer treatment. Increased awareness of nociplastic pain associated with cancer should have important implications for monitoring and managing such patients.}, } @article {pmid36797734, year = {2023}, author = {Arias Ramos, D and Alzate, JA and Moreno Gómez, GA and Hoyos Pulgarín, JA and Olaya Gómez, JC and Cortés Bonilla, I and Vargas Mosquera, C}, title = {Empirical treatment and mortality in bacteremia due to extended spectrum β-lactamase producing Enterobacterales (ESβL-E), a retrospective cross-sectional study in a tertiary referral hospital from Colombia.}, journal = {Annals of clinical microbiology and antimicrobials}, volume = {22}, number = {1}, pages = {13}, pmid = {36797734}, issn = {1476-0711}, mesh = {Humans ; Retrospective Studies ; Cross-Sectional Studies ; *Escherichia coli Infections/drug therapy ; Tertiary Care Centers ; Colombia/epidemiology ; beta-Lactamases/genetics ; Anti-Bacterial Agents/therapeutic use ; Risk Factors ; *Bacteremia/drug therapy/microbiology ; }, abstract = {BACKGROUND: Infections caused by extended spectrum β-lactamase (ESβL) producing bacteria are common and problematic. When they cause bloodstream infections, they are associated with significant morbidity and mortality.

METHODS: A retrospective cross-sectional observational study was conducted in a single center in Pereira, Colombia. It included people hospitalized with bacteremia due to gram-negative bacilli with the extended-spectrum β-lactamase producing phenotype. A logistic regression analysis was constructed. Clinical characteristics and risk factors for death from sepsis were established.

RESULTS: The prevalence of bacteremia due to Enterobacterales with extended-spectrum β-lactamase producing phenotype was 17%. 110 patients were analyzed. Most patients were men (62%) with a median age of 58 years, hospital mortality was 38%. Admission to intensive care was 45%. The following risk factors for mortality were established: shock requiring vasoactive support, Pitt score > 3 points, and not having an infectious disease consultation (IDC).

CONCLUSIONS: bacteremia due to Enterobacterales with extended-spectrum β-lactamase producing phenotype have a high mortality. Early recognition of sepsis, identification of risk factors for antimicrobial resistance, and prompt initiation of appropriate empiric antibiotic treatment are important. An infectious disease consultation may help improve outcomes.}, } @article {pmid36781838, year = {2023}, author = {Sekido, N and Matsuoka, M and Takahashi, R and Sengoku, A and Nomi, M and Matsuyama, F and Murata, T and Kitta, T and Mitsui, T}, title = {Cross-sectional internet survey exploring symptomatic urinary tract infection by type of urinary catheter in persons with spinal cord lesion in Japan.}, journal = {Spinal cord series and cases}, volume = {9}, number = {1}, pages = {3}, pmid = {36781838}, issn = {2058-6124}, mesh = {Humans ; *Urinary Catheters/adverse effects ; Cross-Sectional Studies ; Urinary Catheterization/adverse effects ; Japan/epidemiology ; *Urinary Tract Infections/epidemiology/etiology ; Spinal Cord ; }, abstract = {STUDY DESIGN: Cross-sectional study by members of patient advocacy groups.

OBJECTIVES: To evaluate the incidence and frequency of symptomatic urinary tract infection (sUTI) in persons with spinal cord lesion (SCL) using different types of catheters based on an internet survey in Japan.

SETTING: An internet survey.

METHODS: We conducted an Internet survey of persons with SCL who were considered to be able to perform intermittent self-catheterization (ISC). We evaluated the incidence and frequency of sUTI over the last year in persons performing ISC and those managed by indwelling catheterization (IDC). We also compared the same parameters between persons in the ISC group using reusable silicone catheters and single-use catheters and those with and without a concomitant use of intermittent balloon catheters (i-IDC).

RESULTS: Two-hundred and eighty-two persons were analyzed. In the ISC and IDC groups, sUTI occurred in 52.2% and 31.4% of persons (p = 0.021), respectively, in the last year, and the frequencies were 2.8 and 3.5 times a year (p = 0.127), respectively. There were no significant differences in the incidence or frequency of sUTI between persons using reusable catheters and single-use catheters or those with and without the concomitant use of i-IDC.

CONCLUSIONS: sUTI occurred in about 1 in 2 persons with SCL performing ISC, which was significantly higher than in the IDC group, and the frequency of sUTI in persons performing ISC was about 3 times a year. The different types of catheters used for ISC were not associated with the incidence or frequency of sUTI. Sponsorship Coloplast Japan Inc.}, } @article {pmid36765396, year = {2023}, author = {Sui, Y and Li, S and Fu, XQ and Zhao, ZJ and Xing, S}, title = {Bioinformatics analyses of combined databases identify shared differentially expressed genes in cancer and autoimmune disease.}, journal = {Journal of translational medicine}, volume = {21}, number = {1}, pages = {109}, pmid = {36765396}, issn = {1479-5876}, mesh = {Humans ; *Lupus Erythematosus, Systemic/genetics ; Janus Kinases/therapeutic use ; *Neoplasms ; Carcinogenesis ; Computational Biology ; RNA, Messenger/metabolism ; }, abstract = {BACKGROUND: Inadequate immunity caused by poor immune surveillance leads to tumorigenesis, while excessive immunity due to breakdown of immune tolerance causes autoimmune genesis. Although the function of immunity during the onset of these two processes appears to be distinct, the underlying mechanism is shared. To date, gene expression data for large bodies of clinical samples are available, but the resemblances of tumorigenesis and autoimmune genesis in terms of immune responses remains to be summed up.

METHODS: Considering the high disease prevalence, we chose invasive ductal carcinoma (IDC) and systemic lupus erythematosus (SLE) to study the potential commonalities of immune responses. We obtained gene expression data of IDC/SLE patients and normal controls from five IDC databases (GSE29044, GSE21422, GSE22840, GSE15852, and GSE9309) and five SLE databases (GSE154851, GSE99967, GSE61635, GSE50635, and GSE17755). We intended to identify genes differentially expressed in both IDC and SLE by using three bioinformatics tools including GEO2R, the limma R package, and Weighted Gene Co-expression Network Analysis (WGCNA) to perform function enrichment, protein-protein network, and signaling pathway analyses.

RESULTS: The mRNA levels of signal transducer and activator of transcription 1 (STAT1), 2'-5'-oligoadenylate synthetase 1 (OAS1), 2'-5'-oligoadenylate synthetase like (OASL), and PML nuclear body scaffold (PML) were found to be differentially expressed in both IDC and SLE by using three different bioinformatics tools of GEO2R, the limma R package and WGCNA. From the combined databases in this study, the mRNA levels of STAT1 and OAS1 were increased in IDC while reduced in SLE. And the mRNA levels of OASL and PML were elevated in both IDC and SLE. Based on Kyoto Encyclopedia of Genes and Genomes pathway analysis and QIAGEN Ingenuity Pathway Analysis, both IDC and SLE were correlated with the changes of multiple components involved in the Interferon (IFN)-Janus kinase (JAK)-signal transducer and activator of transcription (STAT) signaling pathway.

CONCLUSION: The expression levels of STAT1 and OAS1 manifest the opposite expression tendency across cancer and autoimmune disease. They are components in the IFN-JAK-STAT signaling pathway related to both tumorigenesis and autoimmune genesis. STAT1 and OAS1-associated IFN-JAK-STAT signaling could explain the commonalities during tumorigenesis and autoimmune genesis and render significant information for more precise treatment from the point of immune homeostasis.}, } @article {pmid36763857, year = {2023}, author = {Langley, RG and Sofen, H and Dei-Cas, I and Reich, K and Sigurgeirsson, B and Warren, RB and Paul, C and Szepietowski, JC and Tsai, TF and Hampele, I and You, R and Charef, P and Papavassilis, C}, title = {Secukinumab long-term efficacy and safety in psoriasis through to year 5 of treatment: results of a randomized extension of the phase III ERASURE and FIXTURE trials.}, journal = {The British journal of dermatology}, volume = {188}, number = {2}, pages = {198-207}, doi = {10.1093/bjd/ljac040}, pmid = {36763857}, issn = {1365-2133}, mesh = {Humans ; Quality of Life ; *Nasopharyngitis/chemically induced ; Antibodies, Monoclonal, Humanized/adverse effects ; *Psoriasis/drug therapy ; *Respiratory Tract Infections ; Treatment Outcome ; Severity of Illness Index ; Double-Blind Method ; }, abstract = {BACKGROUND: In the long-term extension study of the ERASURE and FIXTURE trials, the efficacy of secukinumab (a fully human anti-interleukin-17A monoclonal antibody) was demonstrated to have been maintained through to year 3 of treatment in moderate-to-severe plaque psoriasis.

OBJECTIVES: To assess the efficacy and safety of secukinumab through to year 5 of treatment in moderate-to-severe plaque psoriasis.

METHODS: Responders with ≥ 75% improvement in Psoriasis Area and Severity Index (PASI 75) from two core trials - ERASURE and FIXTURE - were randomized 2 : 1 at year 1 (end of core trials) to either the same dose (300 or 150 mg, continuous treatment) or placebo (treatment withdrawal) every 4 weeks, until year 3 or relapse (> 50% reduction in maximal PASI from core study baseline). Partial responders (achieving PASI 50 but not PASI 75) at year 1 continued at the same dose as in the core trials. At year 3, all patients received open-label secukinumab treatment, with those on secukinumab 300 mg continuing on their dose, while those on secukinumab 150 mg or placebo received secukinumab 150 or 300 mg based on the physician's discretion. The study is registered on ClinicalTrials.gov with the identifier NCT01544595.

RESULTS: Most patients randomized to placebo at year 1 relapsed, but the response was rapidly recaptured upon reinitiation of treatment. PASI responses were sustained with secukinumab through to year 5. The PASI responses for the 300 mg responders + partial responders group at year 1 (PASI 75/90/100: 86.8%/72.8%/45.9%) trended downwards until year 3 (PASI 75/90/100: 82.3%/58.4%/32.7%) and then remained stable through year 4 (PASI 75/90/100: 83.3%/60.1%/32.2%) until year 5 (PASI 75/90/100: 81.1%/62.8%/35.1%). Dermatology Life Quality Index showed sustained benefit up to year 5. Absolute PASI responses were maintained throughout the study. The most common adverse events (AEs) were infections and infestations, nasopharyngitis, and upper respiratory tract infections (URTIs). The overall exposure-adjusted incidence rate (EAIR; with 95% confidence interval) for all AEs was 139.9 (130.3-149.9). EAIRs for Crohn's disease and neutropenia were 0.1 (0.0-0.3) and 0.5 (0.3-0.8), respectively.

CONCLUSIONS: The 4-year extension of two pivotal phase III trials demonstrated that secukinumab treatment was effective through to year 5 and improved quality of life in patients with moderate-to-severe plaque psoriasis. The most common AEs were infections and infestations, nasopharyngitis, and URTIs. The safety profile was consistent with that in the secukinumab phase II/III clinical development programme.}, } @article {pmid36730303, year = {2023}, author = {Chang, H and Hu, T and Hu, J and Ding, T and Wang, Q and Cheng, J}, title = {Complete response in patient with liver metastasis of HER2-positive breast cancer following therapy with margetuximab: a case report.}, journal = {Anti-cancer drugs}, volume = {34}, number = {7}, pages = {883-887}, pmid = {36730303}, issn = {1473-5741}, mesh = {Female ; Humans ; Aged ; *Breast Neoplasms/pathology ; Antineoplastic Combined Chemotherapy Protocols/adverse effects ; Trastuzumab ; Receptor, ErbB-2/metabolism ; *Liver Neoplasms/drug therapy/etiology ; }, abstract = {Metastatic human epidermal growth factor receptor 2 (HER2) positive breast cancer has a poor prognosis and few effective targeted therapies. However, several anti-HER2 agents are emerging in conjunction with chemotherapy, which may lead to increased rates of pathological complete response in patients with HER2-positive metastatic breast cancer. Among them, margetuximab demonstrated a significant improvement in progression-free survival compared with trastuzumab, when combined with chemotherapy in pretreated patients. Here we present a case of a 67-year-old female patient who was diagnosed with HER2-positive, histological grade III and invasive ductal carcinoma of the left breast in September 2018. She received postoperative adjuvant therapy with EC-TH plus radiotherapy, followed by therapy with HER2-targeted trastuzumab for 1 year (till December 2019). In May 2020, routine reexamination showed a supraclavicular lymph node and bone metastasis. Patient was then treated with pyrotinib, capecitabine and bisphosphonate for a period of 3 months. In December 2020, liver MRI revealed multiple liver metastases. The patient received eight cycles of second-line therapy (vinorelbine plus margetuximab) from January 2021. Since the ninth cycle, the patient was continued with only margetuximab. In March 2021, MRI showed a 70% decrease in the liver metastasis lesions. By June 2021, liver lesions were totally disappeared. During therapy, patient experienced only grade-1 anemia. This case demonstrates that margetuximab plus chemotherapy is safe and might bring clinical benefits for patients with HER2-positive breast cancer with liver metastasis. Further studies evaluating the efficacy and safety of margetuximab in Chinese HER2-positive breast cancer patients are needed.}, } @article {pmid36708642, year = {2023}, author = {Maggi, G and Vitale, C and Cerciello, F and Santangelo, G}, title = {Sleep and wakefulness disturbances in Parkinson's disease: A meta-analysis on prevalence and clinical aspects of REM sleep behavior disorder, excessive daytime sleepiness and insomnia.}, journal = {Sleep medicine reviews}, volume = {68}, number = {}, pages = {101759}, doi = {10.1016/j.smrv.2023.101759}, pmid = {36708642}, issn = {1532-2955}, mesh = {Humans ; *REM Sleep Behavior Disorder/etiology/complications ; *Parkinson Disease/complications/epidemiology/drug therapy ; Wakefulness ; *Sleep Initiation and Maintenance Disorders/epidemiology/complications ; Quality of Life ; Prevalence ; Sleep ; *Disorders of Excessive Somnolence/epidemiology/diagnosis ; *Sleep Wake Disorders ; }, abstract = {Sleep disorders (SDs) are common non-motor symptoms of Parkinson's disease (PD) with wide variability in their prevalence rates. The etiology of SDs in PD is multifactorial because the degenerative processes underlying the disease and their interaction with drugs and clinical features may promote REM sleep behavior disorder (RBD), excessive daytime sleepiness (EDS) and insomnia. Therefore, we designed a meta-analytic study to provide a reliable estimate of the prevalence and associated clinical and neuropsychiatric aspects of SDs in PD. A systematic literature search was performed up to February 2022. Pooled RBD prevalence was 46%, and its occurrence was associated with older age, lower education, longer disease duration, higher levodopa equivalent daily dose (LEDD), worse motor and autonomic manifestations, poorer quality of life and autonomy, and more severe neuropsychiatric symptoms. The pooled prevalence of EDS was 35% and was associated with older age, longer disease duration, worse motor and autonomic symptoms, higher LEDD, reduced autonomy, and more severe neuropsychiatric symptoms. Insomnia was reported in 44% of PD patients and was related to longer disease duration, higher LEDD, and more severe depression. SDs are associated with a more severe PD clinical phenotype; further studies should explore the pathophysiological mechanisms underlying SDs and develop targeted therapeutic strategies.}, } @article {pmid36678422, year = {2023}, author = {Feredj, E and Audureau, E and Boueilh, A and Fihman, V and Fourati, S and Lelièvre, JD and Gallien, S and Grimbert, P and Matignon, M and Melica, G}, title = {Impact of a Dedicated Pretransplant Infectious Disease Consultation on Respiratory Tract Infections in Kidney Allograft Recipients: A Retrospective Study of 516 Recipients.}, journal = {Pathogens (Basel, Switzerland)}, volume = {12}, number = {1}, pages = {}, pmid = {36678422}, issn = {2076-0817}, abstract = {BACKGROUND: Respiratory tract infections (RTIs) are a leading cause of death after kidney transplant. Preventive strategies may be implemented during a dedicated infectious disease consultation (IDC) before transplantation. Impact of IDC on RTIs after transplant has not been determined.

METHODS: We conducted a monocentric retrospective cohort analysis including all kidney transplant recipients from January 2015 to December 2019. We evaluated the impact of IDC on RTIs and identified risk and protective factors associated with RTIs.

RESULTS: We included 516 kidney transplant recipients. Among these, 145 had an IDC before transplant. Ninety-five patients presented 123 RTIs, including 75 (61%) with pneumonia. Patient that benefited from IDC presented significantly less RTIs (p = 0.049). RTIs were an independent risk factor of mortality (HR = 3.64 (1.97-6.73)). Independent risk factors for RTIs included HIV (OR = 3.33 (1.43-7.74)) and HCV (OR = 3.76 (1.58-8.96)). IDC was identified as an independent protective factor (OR = 0.48 (0.26-0.88)). IDC prior to transplantation is associated with diminished RTIs and is an independent protective factor. RTIs after kidney transplant are an independent risk factor of death. Implementing systematic IDC may have an important impact on reducing RTIs and related morbidity and mortality.}, } @article {pmid36653542, year = {2023}, author = {Maggi, G and D'Iorio, A and Aiello, EN and Poletti, B and Ticozzi, N and Silani, V and Amboni, M and Vitale, C and Santangelo, G}, title = {Psychometrics and diagnostics of the Italian version of the Beck Depression Inventory-II (BDI-II) in Parkinson's disease.}, journal = {Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology}, volume = {44}, number = {5}, pages = {1607-1612}, pmid = {36653542}, issn = {1590-3478}, mesh = {Humans ; Psychometrics ; *Depression/diagnosis/etiology ; *Parkinson Disease/complications/diagnosis/psychology ; Quality of Life ; Reproducibility of Results ; Psychiatric Status Rating Scales ; }, abstract = {INTRODUCTION: Depression is one of the most disabling neuropsychiatric manifestations of Parkinson's disease (PD) and requires proper screening and diagnosis because it affects the overall prognosis and quality of life of patients. This study aimed to assess the psychometric and diagnostic properties of the Beck Depression Inventory-II (BDI-II) in an Italian PD cohort.

MATERIALS AND METHODS: Fifty consecutive outpatients with PD underwent the Italian version of the BDI-II and other questionnaires to evaluate anxiety and apathetic symptoms. Patients' caregivers completed the depression/dysphoria domain of the Neuropsychiatric Inventory (NPI-D). We evaluated the internal consistency, convergent and divergent validity, and factorial structure of BDI-II. Sensitivity, specificity, positive and negative predictive values, and likelihood ratios were computed using ROC analyses, and an optimal cutoff was defined using the Youden index.

RESULTS: The BDI-II proved to be internally consistent (Cronbach's α = 0.840) and substantially met the bi-factorial structure. Regarding construct validity, the BDI-II was substantially related to anxiety measures, but not to apathy. With the combination of the NPI-D and anxiety score used as the gold standard, the BDI-II overall showed good accuracy (AUC = 0.859) with adequate sensitivity (75%) and specificity (87%). The optimal cutoff point was defined at 14.50.

CONCLUSIONS: We provide evidence of the psychometric and diagnostic properties of the Italian version of the BDI-II as a screening tool for depression in patients with PD. The BDI-II was found to be reliable and valid for the measurement of depression in patients with PD; therefore, it is available for use in clinical research and practice.}, } @article {pmid36641657, year = {2022}, author = {Manginstar, C and Oley, MH and Oley, MC and Merung, M and Langi, FLFG and Kepel, BJ and Rusli, LV and Islam, AA and Faruk, M}, title = {Correlation analysis of HIF-1α and Ca15-3 in response to neoadjuvant chemotherapy in locally advanced breast cancer: A cohort study in Indonesia.}, journal = {Breast disease}, volume = {41}, number = {1}, pages = {481-487}, doi = {10.3233/BD-229004}, pmid = {36641657}, issn = {1558-1551}, mesh = {Humans ; Female ; *Breast Neoplasms/pathology ; Prognosis ; Biomarkers, Tumor/metabolism ; Cohort Studies ; Neoadjuvant Therapy ; Prospective Studies ; Hypoxia-Inducible Factor 1, alpha Subunit/therapeutic use ; Indonesia ; Hypoxia ; Tumor Microenvironment ; }, abstract = {BACKGROUND: Breast cancer (BC) is the most common cancer among women worldwide and a leading cause of death in Indonesia. The primary treatment of locally advanced BC is neoadjuvant chemotherapy (NAC). The rapid proliferation of tumor cells in a neoplastic microenvironment is largely due to hypoxia, which also encourages the development of chemoresistant BC. The master regulator of the hypoxia response is hypoxia-inducible factor-1α (HIF-1α). The response evaluation criteria in solid tumors (RECIST) is an objective response metric that demonstrates the efficacy of a NAC based mostly on the size of the tumor. Ca15-3 is the protein product of the MUC1 gene and is the most widely used serum marker in BC. The purpose of this study is to investigate the relationship between HIF-1α and RECIST and between Ca15-3 and RECIST and to assess the relationship among all of them in BC.

METHODS: This observational study used the prospective cohort method included 11 patients with histopathologically confirmed BC, specifically invasive ductal carcinoma. We evaluated the changes in HIF-1α and Ca15-3 serum levels using ELISA and measured tumor lesions with RECIST. The procedure was carried out twice. Serum levels were measured at baseline, and after receiving two cycles of NAC (5 weeks).

RESULTS: Among the 11 patie