@article {pmid35749404,
year = {2022},
author = {Hardeman, AA and Han, YJ and Grushko, TA and Mueller, J and Gomez, MJ and Zheng, Y and Olopade, OI},
title = {Subtype-specific expression of MELK is partly due to copy number alterations in breast cancer.},
journal = {PloS one},
volume = {17},
number = {6},
pages = {e0268693},
doi = {10.1371/journal.pone.0268693},
pmid = {35749404},
issn = {1932-6203},
mesh = {*Breast Neoplasms/genetics/pathology ; *Carcinoma, Intraductal, Noninfiltrating ; DNA Copy Number Variations ; Female ; Humans ; Protein Serine-Threonine Kinases ; RNA, Messenger/genetics ; *Triple Negative Breast Neoplasms/genetics ; },
abstract = {Maternal embryonic leucine-zipper kinase (MELK) regulates cell cycle progression and is highly expressed in many cancers. The molecular mechanism of MELK dysregulation has not been determined in aggressive forms of breast cancer, such as triple negative breast cancer (TNBC). To evaluate molecular markers of MELK aberrations in aggressive breast cancer, we assessed MELK gene amplification and expression in breast tumors. MELK mRNA expression is highly up-regulated in basal-like breast cancer (BLBC), the major molecular subtype of TNBC, compared to luminal or other subtypes of breast tumors. MELK copy number (CN) gains are significantly associated with BLBC, whereas no significant association of CpG site methylation or histone modifications with breast cancer subtypes was observed. Accordingly, the CN gains appear to contribute to an increase in MELK expression, with a significant correlation between mRNA expression and CN in breast tumors and cell lines. Furthermore, immunohistochemistry (IHC) assays revealed that both nuclear and cytoplasmic staining scores of MELK were significantly higher in invasive ductal carcinoma (IDC) tumors compared to ductal carcinoma in situ (DCIS) and normal breast tissues. Our data showed that upregulation of MELK in BLBC may be in part driven by CN gains, rather than epigenetic modifications, indicating a potential for overexpression and CN gains of MELK to be developed as a diagnostic and prognostic marker to identify patients who have more aggressive breast cancer.},
}

*Breast Neoplasms/genetics/pathology
*Carcinoma, Intraductal, Noninfiltrating
DNA Copy Number Variations
Female
Humans
Protein Serine-Threonine Kinases
RNA, Messenger/genetics
*Triple Negative Breast Neoplasms/genetics

@article {pmid35749114,
year = {2022},
author = {Weis, S and Hagel, S and Palm, J and Scherag, A and Kolanos, S and Bahrs, C and Löffler, B and Schmitz, RPH and Rißner, F and Brunkhorst, FM and Pletz, MW and , },
title = {Effect of Automated Telephone Infectious Disease Consultations to Nonacademic Hospitals on 30-Day Mortality Among Patients With Staphylococcus aureus Bacteremia: The SUPPORT Cluster Randomized Clinical Trial.},
journal = {JAMA network open},
volume = {5},
number = {6},
pages = {e2218515},
doi = {10.1001/jamanetworkopen.2022.18515},
pmid = {35749114},
issn = {2574-3805},
abstract = {Importance: Staphylococcus aureus bacteremia (SAB) is a common and potentially severe infectious disease (ID). Retrospective studies and derived meta-analyses suggest that bedside infectious disease consultation (IDC) for SAB is associated with improved survival; however, such IDCs might not always be possible because of the lack of ID specialists, particularly at nonacademic hospitals.

Objectives: To investigate whether unsolicited telephone IDCs (triggered by an automated blood stream infection reporting system) to nonacademic hospitals improved 30-day all-cause mortality in patients with SAB.

This patient-blinded, multicenter, interventional, cluster randomized, controlled, crossover clinical trial was conducted in 21 rural, nonacademic hospitals in Thuringia, Germany. From July 1, 2016, to December 31, 2018, 1029 blood culture reports were assessed for eligibility. A total of 386 patients were enrolled, whereas 643 patients were not enrolled for the following reasons: death before enrollment (n = 59); palliative care (n = 41); recurrence of SAB (n = 9); discharge from the hospital before enrollment (n = 77); age younger than 18 years (n = 5); duplicate report from a single patient (n = 26); late report (n = 17); blood culture reported during the washout phase (n = 48); and no signed informed consent for other or unknown reasons (n = 361).

Interventions: During the ID intervention phase, ID specialists from Jena University Hospital provided unsolicited telephone IDCs to physicians treating patients with SAB. During the control phase, patients were treated according to local standards. Crossover was performed after including 15 patients or, at the latest, 1 year after the first patient was included.

Main Outcomes and Measures: Thirty-day all-cause mortality.

Results: A total of 386 patients (median [IQR] age, 75 [63-82] years; 261 [67.6%] male) were included, with 177 randomized to the IDC group and 209 to the control group. The 30-day all-cause mortality rate did not differ between the IDC and control groups (relative risk reduction [RRR], 0.12; 95% CI, -2.17 to 0.76; P = .81). No evidence was found of a difference in secondary outcomes, including 90-day mortality (RRR, 0.17; 95% CI, -0.59 to 0.57; P = .62), 90-day recurrence (RRR, 0.10; 95% CI, -2.51 to 0.89; P = .89), and hospital readmission (RRR, 0.04; 95% CI, -0.63 to 0.48; P = .90). Exploratory evidence suggested that indicators of quality of care were potentially realized more often in the IDC group than in the control group (relative quality improvement, 0.16; 95% CI, 0.08-0.26; P = .01).

Conclusions and Relevance: In this cluster randomized clinical trial, unsolicited telephone IDC, although potentially enhancing quality of care, did not improve 30-day all-cause mortality in patients with SAB.

Trial Registration: drks.de Identifier: DRKS00010135.},
}

@article {pmid35743985,
year = {2022},
author = {Ortega, MA and Fraile-Martinez, O and García-Montero, C and Borja-Vergel, S and Torres-Carranza, D and Pekarek, L and Arribas, CB and De León-Luis, JA and Sánchez-Rojo, C and Alvarez-Mon, MA and García-Honduvilla, N and Buján, J and Coca, S and Alvarez-Mon, M and Saez, MA and Guijarro, LG},
title = {Patients with Invasive Lobular Carcinoma Show a Significant Increase in IRS-4 Expression Compared to Infiltrative Ductal Carcinoma-A Histopathological Study.},
journal = {Medicina (Kaunas, Lithuania)},
volume = {58},
number = {6},
pages = {},
doi = {10.3390/medicina58060722},
pmid = {35743985},
issn = {1648-9144},
support = {MITICAD//Comunidad de Madrid/ ; },
abstract = {Background and Objectives: Breast cancer (BC) is the first diagnosed type of cancer and the second leading cause of cancer-related mortality in women. In addition, despite the improvement in treatment and survival in these patients, the global prevalence and incidence of this cancer are rising, and its mortality may be different according to the histological subtype. Invasive lobular carcinoma (ILC) is less common but entails a poorer prognosis than infiltrative ductal carcinoma (IDC), exhibiting a different clinical and histopathological profile. Deepening study on the molecular profile of both types of cancer may be of great aid to understand the carcinogenesis and progression of BC. In this sense, the aim of the present study was to explore the histological expression of Insulin receptor substrate 4 (IRS-4), cyclooxygenase 2 (COX-2), Cyclin D1 and retinoblastoma protein 1 (Rb1) in patients with ILC and IDC. Patients and Methods: Thus, breast tissue samples from 45 patients with ILC and from 45 subjects with IDC were analyzed in our study. Results: Interestingly, we observed that IRS-4, COX-2, Rb1 and Cyclin D1 were overexpressed in patients with ILC in comparison to IDC. Conclusions: These results may indicate a differential molecular profile between both types of tumors, which may explain the clinical differences among ILC and IDC. Further studies are warranted in order to shed light onto the molecular and translational implications of these components, also aiding to develop a possible targeted therapy to improve the clinical management of these patients.},
}

@article {pmid35714104,
year = {2022},
author = {Icht, M and Bergerzon-Bitton, O and Ben-David, BM},
title = {Validation and cross-linguistic adaptation of the Frenchay Dysarthria Assessment (FDA-2) speech intelligibility tests: Hebrew version.},
journal = {International journal of language & communication disorders},
volume = {},
number = {},
pages = {},
doi = {10.1111/1460-6984.12737},
pmid = {35714104},
issn = {1460-6984},
abstract = {'Dysarthria' is a group of motor speech disorders resulting from a disturbance in neuromuscular control. Most individuals with dysarthria cope with communicative restrictions due to speech impairments and reduced intelligibility. Thus, language-sensitive measurements of intelligibility are important in dysarthria neurological assessment. The Frenchay Dysarthria Assessment, 2nd edition (FDA-2), is a validated tool for the identification of the nature and patterns of oro-motor movements associated with different types of dysarthria. The current study conducted a careful culture- and linguistic-sensitive adaption of the two intelligibility subtests of the FDA-2 to Hebrew (words and sentences) and performed a preliminary validation with relevant clinical populations. First, sets of Hebrew words and sentences were constructed, based on the criteria defined in FDA-2, as well as on several other factors that may affect performance: emotional valence, arousal and familiarity. Second, the new subtests were validated in healthy older adults (n = 20), and in two clinical groups (acquired dysarthria, n = 15; and developmental dysarthria, n = 19). Analysis indicated that the new subtests were found to be specific and sensitive, valid and reliable, as scores significantly differ between healthy older adults and adults with dysarthria, correlated with other subjective measures of intelligibility, and showed high test-retest reliability. The words and sentences intelligibility subtests can be used to evaluate speech disorders in various populations of Hebrew speakers, thus may be an important addition to the speech-language pathologist's toolbox, for clinical work as well as for research purposes. WHAT THIS PAPER ADDS: What is already known on the subject 'Dysarthria' is a group of disorders reflecting impairments in the strength, speed and precision of movements required for adequate control of the various speech subsystems. Reduced speech intelligibility is one of the main consequences of all dysarthria subtypes, irrespective of their underlying cause. Indeed, most individuals with dysarthria cope with communicative restrictions due to speech impairments. Thus, language-sensitive measurements of intelligibility are important in dysarthria assessment. The FDA-2's words and sentences subtests present standardized and validated tools for the identification of the nature and patterns of oro-motor movements associated with different types of dysarthria. What this paper adds to existing knowledge The lack of assessment tools in Hebrew poses challenges to clinical evaluation as well as research purposes. The current study conducted a careful culture- and linguistic-sensitive adaption of the FDA-2 intelligibility subtests to Hebrew and performed a preliminary validation with relevant clinical populations. First, sets of Hebrew words and sentences were constructed, based on the criteria defined in FDA-2, as well as on several other factors that may affect performance: emotional valence, arousal and familiarity. Second, the new subtests were validated in healthy older adults (n = 20), and in two clinical groups (adults with acquired dysarthria, n = 15; and young adults with developmental dysarthria, n = 19). What are the potential or actual clinical implications of this work? Analyses indicated that the new word and sentence subtests are specific, sensitive, valid and reliable. Namely, (1) they successfully differentiate between healthy individuals and individuals with dysarthria; (2) they correlate with other subjective measures of intelligibility; and (3) they show high test-retest reliability. The words and sentences intelligibility subtests can be used to evaluate speech disorders in various populations of Hebrew speakers. Thus, they may be an important addition to the speech-language pathologist's toolbox, for clinical and research purposes. The methods described here can be emulated for the adaptation of speech assessment tools to other languages.},
}

@article {pmid35711899,
year = {2022},
author = {Choi, JDW and Hughes, TMD and Marx, G and Boyages, J and Rutovitz, J and Hasovits, C and Parasyn, A and Edirimanne, S and Ngui, NK},
title = {The Utility of the Oncotype DX Test for Breast Cancer Patients in an Australian Multidisciplinary Setting.},
journal = {The breast journal},
volume = {2022},
number = {},
pages = {1199245},
doi = {10.1155/2022/1199245},
pmid = {35711899},
issn = {1524-4741},
mesh = {Australia ; *Breast Neoplasms/drug therapy/genetics/pathology ; Female ; Gene Expression Profiling/methods ; Humans ; Neoplasm Recurrence, Local/pathology ; Prognosis ; Receptors, Estrogen/genetics ; Retrospective Studies ; },
abstract = {Introduction: The Oncotype DX test is a genomic assay that generates a Recurrence Score (RS) predicting the 10-year risk of recurrence and response to adjuvant chemotherapy in ER+/HER2- breast cancer patients. The aims were to determine breast cancer distant recurrence and correlate with adjuvant chemoendocrine prescribing patterns based on the Oncotype DX recurrence score.

Methods: We conducted a retrospective single-institution case series of 71 patients who had Oncotype DX assay testing after definitive surgery between 2012 and 2016. Both node-positive and node-negative patients were included. Patients were divided into Oncotype DX low risk (RS < 11) (n = 10, 14%), intermediate risk (RS 11-25) (n = 45, 63%), and high risk (RS > 25) (n = 16, 23%). Median follow-up was 6.1 years (range 4-8.9 years). Adjuvant treatment regimens and oncological outcomes were determined. Results. Mean age at diagnosis was 56 years (range, 33-77). Invasive ductal carcinoma (IDC) accounted for the majority (87%), with most tumors measuring between 10-20 mm (52%). 48% of the cohort were node positive. 15 of 16 high-risk patients (94%) received chemotherapy. 96% of intermediate-risk patients received endocrine therapy alone, one patient received chemoendocrine therapy (2%), and one declined systemic therapy (2%). In the low-risk group, 100% received endocrine therapy only. The high-risk group had the lowest mean ER% (P < 0.05), greatest mean mitotic rate (P < 0.05), and greatest proportion of Ki67% > 14. Five patients developed distant recurrence (7%): three from the intermediate-risk group (7%), one from the low-risk group (10%), and one from the high-risk group (6%).

Conclusion: This is the first Australian study reporting the experience with medium-term recurrence outcomes of using the Oncotype DX assay in breast cancer. Chemotherapy was rarely given for patients with low-to-intermediate RS and always offered in high RS. This pattern of prescribing was associated with low rates of distant recurrence. National funding models should be considered.},
}

Australia
*Breast Neoplasms/drug therapy/genetics/pathology
Female
Gene Expression Profiling/methods
Humans
Neoplasm Recurrence, Local/pathology
Prognosis
Receptors, Estrogen/genetics
Retrospective Studies

@article {pmid35538223,
year = {2022},
author = {Simond, AM and Bui, T and Zuo, D and Sanguin-Gendreau, V and Rao, T and Phillips, WA and Cardiff, RD and Muller, WJ},
title = {Physiological expression of PI3K H1047R mutation reveals its anti-metastatic potential in ErbB2-driven breast cancer.},
journal = {Oncogene},
volume = {41},
number = {25},
pages = {3445-3451},
pmid = {35538223},
issn = {1476-5594},
support = {CIHR-FDN-148373//Gouvernement du Canada | Canadian Institutes of Health Research (Instituts de Recherche en Santé du Canada)/ ; },
mesh = {*Breast Neoplasms/genetics/pathology ; *Carcinoma, Intraductal, Noninfiltrating ; Class I Phosphatidylinositol 3-Kinases/genetics ; Female ; Humans ; Mutation ; Phosphatidylinositol 3-Kinase/genetics ; Phosphatidylinositol 3-Kinases/genetics/metabolism ; Receptor, ErbB-2/genetics ; },
abstract = {p110α is a catalytic subunit of phosphoinositide 3-kinase (PI3K), a major downstream effector of receptor tyrosine kinase ErbB2, that is amplified and overexpressed in 20-30% of breast cancers, 40% of which have an activating mutation in p110α. Despite the high frequency of PIK3CA gain-of-function mutations, their prognostic value is controversial. Here, we employ a knock-in transgenic strategy to restrict the expression of an activated form of ErbB2 and p110α kinase domain mutation (p110αHR) in the mammary epithelium. Physiological levels of transgene expression under the control of their endogenous promoters did not result in a major synergistic effect. However, tumors arising in ErbB2/p110αHR bi-genic strain metastasized to the lung with significantly reduced capacity compared to tumors expressing ErbB2 alone. The reduced metastasis was further associated with retention of the myoepithelial layer reminiscent of ductal carcinoma in situ (DCIS), a non-invasive stage of human breast cancer. Molecular and biochemical analyses revealed that these poorly metastatic tumors exhibited a significant decrease in phospho-myosin light chain 2 (MLC2) associated with cellular contractility and migration. Examination of human samples for MLC2 activity revealed a progressive increase in cellular contractility between non-invasive DCIS and invasive ductal carcinoma. Collectively, these data argue that p110αHR mutation attenuates metastatic behavior in the context of ErbB2-driven breast cancer.},
}

*Breast Neoplasms/genetics/pathology
*Carcinoma, Intraductal, Noninfiltrating
Class I Phosphatidylinositol 3-Kinases/genetics
Female
Humans
Mutation
Phosphatidylinositol 3-Kinase/genetics
Phosphatidylinositol 3-Kinases/genetics/metabolism
Receptor, ErbB-2/genetics

@article {pmid35522890,
year = {2022},
author = {Butcher, MR and White, MJ and Rooper, LM and Argani, P and Cimino-Mathews, A},
title = {MYB RNA In Situ Hybridization Is a Useful Diagnostic Tool to Distinguish Breast Adenoid Cystic Carcinoma From Other Triple-negative Breast Carcinomas.},
journal = {The American journal of surgical pathology},
volume = {46},
number = {7},
pages = {878-888},
doi = {10.1097/PAS.0000000000001913},
pmid = {35522890},
issn = {1532-0979},
mesh = {Biomarkers, Tumor/genetics ; *Breast Neoplasms/pathology ; *Carcinoma, Adenoid Cystic/diagnosis/genetics/pathology ; *Carcinoma, Ductal, Breast/pathology ; *Carcinoma, Intraductal, Noninfiltrating ; Female ; Humans ; In Situ Hybridization ; RNA ; *Salivary Gland Neoplasms/pathology ; *Triple Negative Breast Neoplasms/diagnosis/genetics/pathology ; },
abstract = {Breast adenoid cystic carcinoma (AdCC) has overlapping features with basal-like triple-negative breast carcinoma (TNBC), yet carries a more favorable prognosis, and accurate diagnosis is critical. Like salivary gland AdCC, breast AdCC demonstrates recurrent alterations in the MYB gene. Novel chromogenic RNA in situ hybridization (ISH) for MYB has emerged as sensitive and specific for salivary gland AdCC. Here, we evaluate MYB RNA ISH in invasive ductal carcinomas (IDCs) including basal-like TNBC, and in the histologic mimics ductal carcinoma in situ (DCIS) and collagenous spherulosis. MYB RNA ISH was also performed on previously constructed tissue microarrays containing 78 evaluable IDC, including 30 basal-like TNBC (EGFR+ and/or CK5/6+), 19 luminal A (ER+/HER-2-), 12 HER-2+ (ER-/HER-2+), 11 non-basal-like TNBC, and 6 luminal B (ER+/HER-2+). MYB RNA ISH overexpression was seen in 100% (n=18/18) of primary breast AdCC and 10% (n=8/78) of IDC (P<0.0001). MYB RNA ISH was overexpressed in 37% (n=7/19) of luminal A and 8% (n=1/12) of HER-2+ IDC, and in no cases of TNBC or luminal B IDC. The majority (67%, n=8/12) of DCIS and all (n=7) cases of collagenous spherulosis demonstrated overexpression of MYB RNA. MYB gene rearrangement was detected in 67% (n=4/6) evaluable AdCC. Although MYB RNA ISH overexpression cannot be used to distinguish between cribriform DCIS or collagenous spherulosis and AdCC, MYB RNA ISH is absent in basal-like TNBC and rare in ER+ or HER-2+ IDC. MYB RNA ISH could be a useful, sensitive, and rapid diagnostic adjunct in the workup of a triple-negative carcinoma in the breast.},
}

Biomarkers, Tumor/genetics
*Breast Neoplasms/pathology
*Carcinoma, Adenoid Cystic/diagnosis/genetics/pathology
*Carcinoma, Ductal, Breast/pathology
*Carcinoma, Intraductal, Noninfiltrating
Female
Humans
In Situ Hybridization
RNA
*Salivary Gland Neoplasms/pathology
*Triple Negative Breast Neoplasms/diagnosis/genetics/pathology

@article {pmid35697697,
year = {2022},
author = {Rebbeck, CA and Xian, J and Bornelöv, S and Geradts, J and Hobeika, A and Geiger, H and Alvarez, JF and Rozhkova, E and Nicholls, A and Robine, N and Lyerly, HK and Hannon, GJ},
title = {Gene expression signatures of individual ductal carcinoma in situ lesions identify processes and biomarkers associated with progression towards invasive ductal carcinoma.},
journal = {Nature communications},
volume = {13},
number = {1},
pages = {3399},
pmid = {35697697},
issn = {2041-1723},
mesh = {Biomarkers ; Biomarkers, Tumor/genetics ; *Breast Neoplasms/pathology ; *Carcinoma, Ductal, Breast/metabolism ; *Carcinoma, Intraductal, Noninfiltrating/genetics/pathology ; Disease Progression ; Female ; Homeodomain Proteins/genetics/metabolism ; Humans ; Transcription Factors/genetics ; Transcriptome ; },
abstract = {Ductal carcinoma in situ (DCIS) is considered a non-invasive precursor to breast cancer, and although associated with an increased risk of developing invasive disease, many women with DCIS will never progress beyond their in situ diagnosis. The path from normal duct to invasive ductal carcinoma (IDC) is not well understood, and efforts to do so are hampered by the substantial heterogeneity that exists between patients, and even within patients. Here we show gene expression analysis from > 2,000 individually micro-dissected ductal lesions representing 145 patients. Combining all samples into one continuous trajectory we show there is a progressive loss in basal layer integrity heading towards IDC, coupled with two epithelial to mesenchymal transitions, one early and a second coinciding with the convergence of DCIS and IDC expression profiles. We identify early processes and potential biomarkers, including CAMK2N1, MNX1, ADCY5, HOXC11 and ANKRD22, whose reduced expression is associated with the progression of DCIS to invasive breast cancer.},
}

Biomarkers
Biomarkers, Tumor/genetics
*Breast Neoplasms/pathology
*Carcinoma, Ductal, Breast/metabolism
*Carcinoma, Intraductal, Noninfiltrating/genetics/pathology
Disease Progression
Female
Homeodomain Proteins/genetics/metabolism
Humans
Transcription Factors/genetics
Transcriptome

@article {pmid35687769,
year = {2022},
author = {Silva, DJ and Miranda, G and Mesquita, A},
title = {Clinical relevance of receptor conversion in metastatic breast cancer: Case report.},
journal = {Medicine},
volume = {101},
number = {23},
pages = {e29136},
doi = {10.1097/MD.0000000000029136},
pmid = {35687769},
issn = {1536-5964},
mesh = {Adult ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; *Breast Neoplasms/drug therapy/therapy ; Disease Progression ; Female ; Humans ; Mastectomy ; Quality of Life ; Receptor, ErbB-2/genetics/metabolism ; },
abstract = {INTRODUCTION: Breast cancer comprises several different pathological entities defined by the presence or absence of hormonal receptors and human epidermal growth factor receptor 2 (HER2). During the disease course, the increase in tumor heterogeneity contributes to the discordant expression of estrogen/progesterone receptors and HER2 status between primary and metastatic lesions. We describe a case that demonstrates the clinical relevance of molecular reassessment during metastatic breast cancer progression.

PATIENT CONCERNS: A 40-year-old Caucasian woman with germline breast cancer gene mutation was referred to a general surgery appointment after breast ultrasound revealed a suspicious nodular lesion in 2012.

DIAGNOSIS: Ultrasound-guided microbiopsy revealed an invasive ductal carcinoma of no special type, hormone receptor-positive, and HER2-negative.

INTERVENTIONS: The patient underwent modified radical left mastectomy, adjuvant radiotherapy, chemotherapy, and endocrine therapy. Four years after the diagnosis, HER2 positive lung progression was documented, and the patient received anti-HER2 targeted systemic therapy for 15 months. New disease progression with a triple-negative profile was found, and palliative systemic treatment was changed to carboplatin for 3 months until new progression. Based on the results of the OlympiAD trial, monotherapy with Olaparib 300 mg twice daily for 28 days was initiated.

OUTCOMES: After seven cycles of treatment, patient showed progressive improvement in quality of life and maintained stable disease without significant adverse events.

CONCLUSION: The clinical relevance of hormone receptor and HER2 status discordance between primary tumors and metastatic lesions has been studied in recent years. This case report illustrates the clinical impact of molecular changes during disease progression and the adaptation of treatment options. This allows for an increase in both survival and quality of life in patients with metastatic breast cancer.},
}

Adult
Antineoplastic Combined Chemotherapy Protocols/therapeutic use
*Breast Neoplasms/drug therapy/therapy
Disease Progression
Female
Humans
Mastectomy
Quality of Life
Receptor, ErbB-2/genetics/metabolism

@article {pmid35337805,
year = {2022},
author = {Rajabi, F and Mozdarani, H},
title = {Expression level of miR-155, miR-15a and miR-19a in peripheral blood of ductal carcinoma breast cancer patients: Possible bioindicators for cellular inherent radiosensitivity.},
journal = {Experimental and molecular pathology},
volume = {126},
number = {},
pages = {104758},
doi = {10.1016/j.yexmp.2022.104758},
pmid = {35337805},
issn = {1096-0945},
mesh = {Biomarkers, Tumor/genetics ; *Breast Neoplasms/diagnosis/genetics/radiotherapy ; *Carcinoma, Ductal, Breast/genetics/radiotherapy ; Environmental Biomarkers ; Female ; Humans ; *MicroRNAs ; ROC Curve ; Radiation Tolerance/genetics ; },
abstract = {Examination of cellular radiosensitivity (RS) helps prevent the adverse side-effects of radiotherapy in radioresistant tumors. We aim to study whether miRNA-155 (miR-155), miR-19a and miR-15a can predict inherent RS according to cellular RS in breast cancer (BC) patients. This study was done on the blood samples of 40 invasive ductal carcinoma (IDC) BC patients and 15 healthy women. G2 assay was performed to evaluate cellular RS. To study the expression level of these miRNAs in blood, qRT-PCR was used. The sensitivity and specificity of the studied miRNAs were assessed by the receiver operating characteristic (ROC) curve. The yield of spontaneous (SY) and radiation-induced (RIY) chromatid breaks (CBs) was significantly different between control and patient groups (p < 0.0001). A cut-off value was specified to recognize the patients with cellular RS from those without. Expression of miR-15a was significantly downregulated (p < 0.0001) in BC patients. However, miR-19a showed upregulation in the blood of BC patients. It was also found the expression level of miR-155 and miR-19a were significantly associated with frequency of CBs (FCB) (p < 0.05). ROC curve analysis manifested that the miR-15a and miR-19a differentiate BC patients and healthy women with 0.91 and 0.68 yielding an area under the ROC curve, respectively. miR-155 and miR-19a discriminate between BC patients with and without cellular RS with area under the ROC curve 0.98 and 0.68. Our findings uncovered miR-155 and miR-19a could be applied as a bioindicator to predict cellular radiosensitivity of BC patients.},
}

Biomarkers, Tumor/genetics
*Breast Neoplasms/diagnosis/genetics/radiotherapy
*Carcinoma, Ductal, Breast/genetics/radiotherapy
Environmental Biomarkers
Female
Humans
*MicroRNAs
ROC Curve
Radiation Tolerance/genetics

@article {pmid35372457,
year = {2022},
author = {Niknam, K and Safaei, A and Ghaderi, A},
title = {Evaluation of the Prognostic Value of CD56 (140 kDa Isoform) Expression in Breast Cancer Tissues: an Eight-Year Retrospective Study.},
journal = {Iranian biomedical journal},
volume = {26},
number = {3},
pages = {175-182},
doi = {10.52547/ibj.26.3.175},
pmid = {35372457},
issn = {2008-823X},
mesh = {Biomarkers, Tumor/genetics ; *Breast Neoplasms/diagnosis/pathology ; *CD56 Antigen/genetics ; Female ; Humans ; Mastectomy ; Prognosis ; Protein Isoforms/genetics ; Retrospective Studies ; },
abstract = {Background: Identification of specific antigens is highly beneficial for early detection, diagnosis, staging, and outcome prediction of cancer. This study aimed to evaluate the expression and prognostic value of CD56 (140 kDa isoform) in IDC.

Methods: Sixty-five patients with IDC who underwent radical surgery or mastectomy as the primary treatment were included. Proper formalin-fixed and paraffin embedded tissue blocks of the patients were prepared and stained by IHC for CD56 (140 kDa isoform) molecule. Chi-square and fisher exact tests were used to compare the results against the clinicopathologic data of patients. Kaplan-Meier and log-rank test were employed to study the prognostic value of the target antigen.

Results: The expression pattern of CD56 was granular and cytoplasmic. There were significant associations between the intensity of CD56 expression in invasive cells and carcinoma in situ (p = 0.005) and normal ducts (p = 0.010). Among all clinicipathologic parameters, there was only a significant association between the expression of ER and CD56 (p = 0.023). Neither OS (p = 0.356) nor DFS (p = 0.976) had significant correlation with CD56 expression.

Conclusion: Our data indicated that the CD56 marker offers no prognostic value in terms of predicting the OS or DFS for up to eight years after primary surgery. Furthermore, the intensity of its expression is similar between normal, non-invasive, and invasive cells. Considering the generally better outcome of ER+ BC patients than their ER- counterparts, the CD56 marker may be indirectly associated with a more favorable prognosis among IDC patients.},
}

Biomarkers, Tumor/genetics
*Breast Neoplasms/diagnosis/pathology
*CD56 Antigen/genetics
Female
Humans
Mastectomy
Prognosis
Protein Isoforms/genetics
Retrospective Studies

@article {pmid35647336,
year = {2022},
author = {Hamed, MM and Gouida, MS and Abd El-Aziz, SR and El-Sokkary, AMA},
title = {Evaluation PD-L1, CD8 and CD20 as early predictor and tracking markers for breast cancer (BC) in Egypt.},
journal = {Heliyon},
volume = {8},
number = {5},
pages = {e09474},
doi = {10.1016/j.heliyon.2022.e09474},
pmid = {35647336},
issn = {2405-8440},
abstract = {Background: Breast cancer (BC) is considered as a common type of cancer threatening women throughout the world. Therefore, development of early predication biomarkers for BC got more concern especially for Egyptian females. This study was aimed to evaluate PD-L1, CD8, and CD20 as early prediction breast cancer biomarkers.

Methods: Flow cytometry (FC), immunohistochemistry (IHC), Western Blot, and q-PCR were used to compare PD-L1, CD20, and CD8 levels in tissues and blood samples of Breast Cancer and controls.

Results: Blood samples showed a significant increase in PD-L1, CD20, and CD8 compared to controls (p˂0.005). A Significant correlation was shown between PD-L1, CD8, and CD20 in tissue and breast cancer subtypes. Whereas, invasive lobular carcinoma (ILC) was characterized by superior PD-L1 and CD20 levels compared to invasive ductal carcinoma (IDC). FC studies on Blood showed 83% and 45.7% PD-L1 expressions for IDC and ILC, respectively. CD20 in ILC and IDC were 78.2% and 62.5%, respectively. Nevertheless, CD8 was 74.2% for IDC and 67.7% for ILC. Whereas, FC studies for PD-L1, CD20, and CD8 in ILC in tissues gave 34.4%, 30.2% and 35.1%, respectively. In addition, IDC tissue samples showed 16%, 12.5, and 13.5% for PD-L1, CD20, and CD8. The moderate stage of adenocarcinoma caused expression of PD-L1 within inflammatory cells, while expression was within neoplastic glandular cells in late stage.

Conclusion: PD-L1, CD8, and CD20 are considered as early predictor and tracking markers for breast cancer.},
}

@article {pmid35636710,
year = {2022},
author = {Willemsen, N and Arigoni, I and Studencka-Turski, M and Krüger, E and Bartelt, A},
title = {Proteasome dysfunction disrupts adipogenesis and induces inflammation via ATF3.},
journal = {Molecular metabolism},
volume = {},
number = {},
pages = {101518},
doi = {10.1016/j.molmet.2022.101518},
pmid = {35636710},
issn = {2212-8778},
abstract = {OBJECTIVE: Regulation of proteasomal activity is an essential component of cellular proteostasis and function. This is evident in patients with mutations in proteasome subunits and associated regulators, who suffer from proteasome-associated autoinflammatory syndromes (PRAAS). These patients display lipodystrophy and fevers, which may be partly related to adipocyte malfunction and abnormal thermogenesis in adipose tissue. However, the cell-intrinsic pathways that could underlie these symptoms are unclear. Here, we investigate the impact of two proteasome subunits implicated in PRAAS, Psmb4 and Psmb8, on differentiation, function and proteostasis of brown adipocytes.

METHODS: In immortalized mouse brown pre-adipocytes, levels of Psmb4, Psmb8, and downstream effectors genes were downregulated through reverse transfection with siRNA. Adipocytes were differentiated and analyzed with various assays of adipogenesis, lipogenesis, lipolysis, inflammation, and respiration.

RESULTS: Loss of Psmb4, but not Psmb8, disrupted proteostasis and adipogenesis. Proteasome function was reduced upon Psmb4 loss, but partly recovered by the activation of Nuclear factor, erythroid-2, like-1 (Nfe2l1). In addition, cells displayed higher levels of surrogate inflammation and stress markers, including Activating transcription factor-3 (Atf3). Simultaneous silencing of Psmb4 and Atf3 lowered inflammation and restored adipogenesis.

CONCLUSIONS: Our study shows that Psmb4 is required for adipocyte development and function in cultured adipocytes. These results imply that in humans with PSMB4 mutations, PRAAS-associated lipodystrophy is partly caused by disturbed adipogenesis. While we uncover a role for Nfe2l1 in the maintenance of proteostasis under these conditions, Atf3 is a key effector of inflammation and blocking adipogenesis. In conclusion, our work highlights how proteasome dysfunction is sensed and mitigated by the integrated stress response in adipocytes with potential relevance for PRAAS patients and beyond.},
}

@article {pmid35621626,
year = {2022},
author = {Cho, YA and Ko, SY and Suh, YJ and Kim, S and Park, JH and Park, HR and Seo, J and Choi, HG and Kang, HS and Lim, H and Park, HY and Kwon, MJ},
title = {PIK3CA Mutation as Potential Poor Prognostic Marker in Asian Female Breast Cancer Patients Who Received Adjuvant Chemotherapy.},
journal = {Current oncology (Toronto, Ont.)},
volume = {29},
number = {5},
pages = {2895-2908},
doi = {10.3390/curroncol29050236},
pmid = {35621626},
issn = {1718-7729},
support = {NRF-2019R1C1C1004463//National Research Foundation of Korea/ ; },
mesh = {B7-H1 Antigen/metabolism ; *Breast Neoplasms/drug therapy/genetics/metabolism ; Chemotherapy, Adjuvant ; Class I Phosphatidylinositol 3-Kinases/genetics ; Female ; Humans ; Microsatellite Instability ; Middle Aged ; Mutation ; Prognosis ; },
abstract = {BACKGROUND: The prognostic relevance of the PIK3CA mutation together with PD-L1, c-Met, and mismatch repair deficiency (dMMR) have not been fully investigated in Asian women with breast cancer (BC) who have undergone postoperative adjuvant chemotherapy.

METHODS: We analyzed PIK3CA mutations via peptide nucleic acid (PNA)-mediated real-time PCR assay, PD-L1/c-Met expression via immunohistochemistry (IHC), and microsatellite instability (MSI) status using PCR and IHC, in 191 resected BCs from 2008 to 2011. The Cancer Genome Atlas (TCGA) dataset for the involvement of the PIK3CA mutation with PD-L1/c-Met/MMR was explored.

RESULTS: The PNA clamp-mediated assay was able to detect the PIK3CA mutation in 1% of the mutant population in the cell line validation. Using this method, the PIK3CA mutation was found in 78 (49.4%) of 158 samples. c-Met and PD-L1 positivity were identified in 31.4 and 21.8% of samples, respectively, which commonly correlated with high histologic grade and triple-negative subtype. MSI/dMMR was observed in 8.4% of patients, with inconsistency between MMR IHC and the MSI PCR. The PIK3CA mutation exhibited a poor prognostic association regarding recurrence-free survival (RFS) in both overall and triple-negative BCs. In subgroup analyses, the PIK3CA-mutated tumors showed poorer RFS than the PIK3CA-wildtype within the c-Met-positive, MSS, triple-negative, or age onset <50 years subgroups, which showed a similar trend of association in TCGA data.

CONCLUSIONS: PIK3CA mutation together with c-Met or dMMR/MSI status might be relevant to poor prognosis in BC subsets, especially in Asian women.},
}

B7-H1 Antigen/metabolism
*Breast Neoplasms/drug therapy/genetics/metabolism
Chemotherapy, Adjuvant
Class I Phosphatidylinositol 3-Kinases/genetics
Female
Humans
Microsatellite Instability
Middle Aged
Mutation
Prognosis

@article {pmid35567670,
year = {2022},
author = {Wilson, GM and Dinh, P and Pathmanathan, N and Graham, JD},
title = {Ductal Carcinoma in Situ: Molecular Changes Accompanying Disease Progression.},
journal = {Journal of mammary gland biology and neoplasia},
volume = {27},
number = {1},
pages = {101-131},
pmid = {35567670},
issn = {1573-7039},
mesh = {Biomarkers ; *Breast Neoplasms/genetics ; *Carcinoma, Ductal, Breast/pathology ; *Carcinoma, Intraductal, Noninfiltrating/pathology ; Disease Progression ; Female ; Humans ; Tumor Microenvironment/genetics ; },
abstract = {Ductal carcinoma in situ (DCIS) is a non-obligate precursor of invasive ductal carcinoma (IDC), whereby if left untreated, approximately 12% of patients develop invasive disease. The current standard of care is surgical removal of the lesion, to prevent potential progression, and radiotherapy to reduce risk of recurrence. There is substantial overtreatment of DCIS patients, considering not all DCIS lesions progress to invasive disease. Hence, there is a critical imperative to better predict which DCIS lesions are destined for poor outcome and which are not, allowing for tailored treatment. Active surveillance is currently being trialed as an alternative management practice, but this approach relies on accurately identifying cases that are at low risk of progression to invasive disease. Two DCIS-specific genomic profiling assays that attempt to distinguish low and high-risk patients have emerged, but imperfections in risk stratification coupled with a high price tag warrant the continued search for more robust and accessible prognostic biomarkers. This search has largely turned researchers toward the tumor microenvironment. Recent evidence suggests that a spectrum of cell types within the DCIS microenvironment are genetically and phenotypically altered compared to normal tissue and play critical roles in disease progression. Uncovering the molecular mechanisms contributing to DCIS progression has provided optimism for the search for well-validated prognostic biomarkers that can accurately predict the risk for a patient developing IDC. The discovery of such markers would modernize DCIS management and allow tailored treatment plans. This review will summarize the current literature regarding DCIS diagnosis, treatment, and pathology.},
}

Biomarkers
*Breast Neoplasms/genetics
*Carcinoma, Ductal, Breast/pathology
*Carcinoma, Intraductal, Noninfiltrating/pathology
Disease Progression
Female
Humans
Tumor Microenvironment/genetics

@article {pmid35585552,
year = {2022},
author = {Oride, Y and Koi, Y and Sasada, T and Kajitani, K and Ohara, M and Kondo, T and Daimaru, Y and Kawamura, S},
title = {Endobronchial ultrasound-guided transbronchial needle aspiration facilitating diagnosis of sarcoidosis in a breast cancer patient with multiple lymphadenopathy: a case report.},
journal = {Journal of medical case reports},
volume = {16},
number = {1},
pages = {194},
pmid = {35585552},
issn = {1752-1947},
abstract = {BACKGROUND: Sarcoidosis is a benign systemic granulomatous disorder of unknown etiology. Cell-mediated immunity disorder is often found in sarcoidosis patients, and an association between malignant tumors and sarcoidosis has been suggested. Sarcoidosis and malignant disease can occur simultaneously or sequentially, leading to misdiagnosis and mistreatment. Sarcoidosis is diagnosed clinically, radiologically, and histologically. We report herein a case of sarcoidosis diagnosed by endobronchial ultrasound-guided transbronchial needle aspiration from the mediastinal lymph nodes of a breast cancer patient.

CASE PRESENTATION: The patient was a 70-year-old Asian woman who presented with right breast tumor. A 20-mm movable mass was identified in the inferolateral quadrant of the right breast, and mammography revealed a spiculated mass with calcification. Ultrasonography revealed a mass with internal hypoechogenicity, and biopsy revealed estrogen receptor-positive, human epidermal growth factor receptor 2-positive invasive ductal carcinoma. Positron emission tomography/computed tomography showed multiple lymphadenopathy including mediastinal lymph nodes, with fluorodeoxyglucose accumulation in those nodes suggesting breast cancer metastases. Endobronchial ultrasound-guided transbronchial needle aspiration of a mediastinal lymph node revealed noncaseous epithelioid granuloma. Due to a history of uveitis and elevated soluble interleukin 2 receptor, lymphadenopathy due to sarcoidosis and stage IIA breast cancer were diagnosed. Right partial mastectomy and axillary lymph node dissection were performed after preoperative chemotherapy. No exacerbation of sarcoidosis symptoms has been observed during treatment.

CONCLUSION: We report a case of breast cancer in which sarcoidosis could be diagnosed based on endobronchial ultrasound-guided transbronchial needle aspiration, a history of uveitis, and elevated soluble interleukin 2 receptor despite fluorodeoxyglucose positron emission tomography/computed tomography suggesting multiple lymph node metastases. This report emphasizes the importance of differential diagnosis of lymph node involvements in cancer patients.},
}

@article {pmid35578939,
year = {2022},
author = {Higashi, T and Ozawa, K and Takei, S and Takagi, S and Yokoyama, M and Mase, K and Moriya, T and Takeshita, A and Mizutani, M},
title = {[A Case of Postoperative Pulmonary Metastasis of Breast Cancer with Complete Response by Abemaciclib plus Fulvestrant Therapy].},
journal = {Gan to kagaku ryoho. Cancer & chemotherapy},
volume = {49},
number = {5},
pages = {581-583},
pmid = {35578939},
issn = {0385-0684},
abstract = {A 66-year-old woman underwent total mastectomy with level Ⅰ and Ⅱ axillary lymph node dissection for right breast cancer in July 2007. The pathology results indicated the presence of T2N0M0 invasive ductal carcinoma(tubule forming type), that was estrogen receptor-positive and human epidermal growth factor 2-negative. She received postoperative adjuvant therapy with oral anastrozole(ANA)for 5 years. Eleven years after surgery, at the age of 77 years, a chest X-ray examination during a routine health checkup identified a mass shadow in the right lung. Further investigation revealed bilateral multiple lung metastases due to breast cancer recurrence. Histological examination of a tissue obtained by computed tomography(CT)-guided lung biopsy confirmed that the histological type and subtype were identical to those found in the initial surgery. Hence, endocrine therapy with ANA plus CDK4/6 inhibitor was started in November 2018. However, the first CDK4/6 inhibitor, palbociclib, caused severe myelosuppression even when the dose was reduced by 2 levels. Therefore in January 2019, the patient was switched to abemaciclib, with the dose reduced by 1 level initially and then reduced by 2 levels from August 2019. In June 2019, new multiple lung metastases appeared, and the patient was switched from ANA to fulvestrant, after which complete response was achieved in 6 months. CT in June 2021 showed no recurrence, and the patient(now 80-year-old)continues to take abemaciclib plus fulvestrant therapy.},
}

@article {pmid35576836,
year = {2022},
author = {He, S and Jia, Q and Zhou, L and Wang, Z and Li, M},
title = {SIRT5 is involved in the proliferation and metastasis of breast cancer by promoting aerobic glycolysis.},
journal = {Pathology, research and practice},
volume = {235},
number = {},
pages = {153943},
doi = {10.1016/j.prp.2022.153943},
pmid = {35576836},
issn = {1618-0631},
abstract = {OBJECTIVE: Breast cancer (BC) is the most commonly diagnosed cancer among females and has a poor prognosis, breast invasive ductal carcinoma is the most common histological type. The occurrence and development of BC is closely related to aberrant glucose metabolism. In the hyperglycemic environment caused by abnormal glucose metabolism, hypoxia-inducible factor-1 alpha (HIF-1α) enables tumor cells to absorb large amounts of glucose and enhance glycolysis by inducing the expression of glucose transporter type1 (GLUT1) and glycolysis genes, thus promoting tumor cell proliferation and metastasis. Mitochondrial Sirtuin5 (SIRT5) plays a role in the rewiring of glucose metabolism during the progression of cancers. Thus, we aimed to elucidate whether SIRT5 promotes BC proliferation and metastasis by facilitating aerobic glycolysis in BC.

METHODS: The expression of SIRT5 in breast carcinoma tissue and cells was evaluated using immunohistochemical staining, western blot and quantitative reverse transcription-polymerase chain reaction (qRT-PCR) analysis to confirm the biological role of SIRT5 in breast carcinoma. We established a stable cell line with SIRT5 knockdown using lentiviral transduction in T47D cells to reduce SIRT5 expression and then evaluated the effect of SIRT5 on cells cultured in the presence of high glucose (4500 mg/L) and normal glucose (2000 mg/L) concentrations. Cell proliferation was detected using the CCK-8 assay, the cell cycle and cell apoptosis were measured using flow cytometry and Annexin V staining, and cell migration was tested by performing Celigo scratch and Transwell assays. The expression of PKM2, HK2, mTOR and HIF-1α, which play roles in aerobic glycolysis, was investigated using western blot.

RESULTS: SIRT5 was overexpressed in BC tissues compared with paired normal tissues. Prognostic and OS analyses showed that the SIRT5 expression level was an individual prognostic factor for patients with BC. SIRT5 knockdown inhibited proliferation and metastasis and slightly increased apoptosis in T47D cells under high-glucose conditions. Furthermore, the downregulation of HK2 and HIF-1α caused by SIRT5 knockdown was a high glucose-dependent process, while the downregulation of PKM2 was mediated by a high glucose-independent process.

CONCLUSIONS: SIRT5 is an independent prognostic factor for BC and contributes to cell proliferation and metastasis in a high glucose-dependent manner to some degree, which might be mediated by promoting aerobic glycolysis.},
}

@article {pmid35547416,
year = {2022},
author = {Smith, PD and Bhenderu, LS and Kommuri, S and Fleener, EE and Hoover, JM},
title = {Treatment of Leptomeningeal Carcinomatosis Following Treatment of Cerebellar Metastasis of HER2+ (Human Epidermal Growth Factor Receptor 2 Positive) Breast Cancer: Case Report and Review of Literature.},
journal = {Cureus},
volume = {14},
number = {4},
pages = {e24008},
doi = {10.7759/cureus.24008},
pmid = {35547416},
issn = {2168-8184},
abstract = {Leptomeningeal carcinomatosis (LC) after metastasis of breast cancer is a rare occurrence with potentially devastating complications. Treatment options are limited, and there is a lack of literature on this topic. We report the case of a 38-year-old woman with estrogen/progesterone receptor negative (ER/PR-), human epidermal growth factor receptor 2 positive (HER2+) invasive ductal carcinoma of the left breast who underwent bilateral mastectomies with axillary lymph node dissection and chemotherapy treatment. The patient returned 11 months later with persistent headaches. Imaging and resection found cerebellar metastasis of the breast carcinoma. The brain metastasis was treated with further chemotherapy and stereotactic radiosurgery. Follow-up imaging showed the development of small lesions outside the radiation site. Metabolic studies were performed to determine if the new lesions were due to tumor recurrence or radiation necrosis, but the studies were inconclusive as to the etiology of these lesions. The patient later developed LC that was successfully treated with full resolution of the disease using intrathecal trastuzumab. There are currently no consensuses on treatment guidelines for treating LC. Here, we demonstrate successful treatment of LC from an ER/PR-, HER2+ breast carcinoma with intrathecal trastuzumab.},
}

@article {pmid35324454,
year = {2022},
author = {Wang, K and Schütze, I and Gulde, S and Bechmann, N and Richter, S and Helm, J and Lauseker, M and Maurer, J and Reul, A and Spoettl, G and Klink, B and William, D and Knösel, T and Friemel, J and Bihl, M and Weber, A and Fankhauser, M and Schober, L and Vetter, D and Broglie Däppen, M and Ziegler, CG and Ullrich, M and Pietzsch, J and Bornstein, SR and Lottspeich, C and Kroiss, M and Fassnacht, M and Wenter, VUJ and Ladurner, R and Hantel, C and Reincke, M and Eisenhofer, G and Grossman, AB and Pacak, K and Beuschlein, F and Auernhammer, CJ and Pellegata, NS and Nölting, S},
title = {Personalized drug testing in human pheochromocytoma/paraganglioma primary cultures.},
journal = {Endocrine-related cancer},
volume = {29},
number = {6},
pages = {285-306},
doi = {10.1530/ERC-21-0355},
pmid = {35324454},
issn = {1479-6821},
mesh = {*Adrenal Gland Neoplasms/drug therapy/genetics/metabolism ; Animals ; *Antineoplastic Agents/pharmacology/therapeutic use ; Everolimus/therapeutic use ; Humans ; Mice ; *Paraganglioma/drug therapy/genetics/pathology ; *Pheochromocytoma/drug therapy/genetics/metabolism ; Zoledronic Acid/therapeutic use ; },
abstract = {Aggressive pheochromocytomas and paragangliomas (PPGLs) are difficult to treat, and molecular targeting is being increasingly considered, but with variable results. This study investigates established and novel molecular-targeted drugs and chemotherapeutic agents for the treatment of PPGLs in human primary cultures and murine cell line spheroids. In PPGLs from 33 patients, including 7 metastatic PPGLs, we identified germline or somatic driver mutations in 79% of cases, allowing us to assess potential differences in drug responsivity between pseudohypoxia-associated cluster 1-related (n = 10) and kinase signaling-associated cluster 2-related (n = 14) PPGL primary cultures. Single anti-cancer drugs were either more effective in cluster 1 (cabozantinib, selpercatinib, and 5-FU) or similarly effective in both clusters (everolimus, sunitinib, alpelisib, trametinib, niraparib, entinostat, gemcitabine, AR-A014418, and high-dose zoledronic acid). High-dose estrogen and low-dose zoledronic acid were the only single substances more effective in cluster 2. Neither cluster 1- nor cluster 2-related patient primary cultures responded to HIF-2a inhibitors, temozolomide, dabrafenib, or octreotide. We showed particular efficacy of targeted combination treatments (cabozantinib/everolimus, alpelisib/everolimus, alpelisib/trametinib) in both clusters, with higher efficacy of some targeted combinations in cluster 2 and overall synergistic effects (cabozantinib/everolimus, alpelisib/trametinib) or synergistic effects in cluster 2 (alpelisib/everolimus). Cabozantinib/everolimus combination therapy, gemcitabine, and high-dose zoledronic acid appear to be promising treatment options with particularly high efficacy in SDHB-mutant and metastatic tumors. In conclusion, only minor differences regarding drug responsivity were found between cluster 1 and cluster 2: some single anti-cancer drugs were more effective in cluster 1 and some targeted combination treatments were more effective in cluster 2.},
}

*Adrenal Gland Neoplasms/drug therapy/genetics/metabolism
Animals
*Antineoplastic Agents/pharmacology/therapeutic use
Everolimus/therapeutic use
Humans
Mice
*Paraganglioma/drug therapy/genetics/pathology
*Pheochromocytoma/drug therapy/genetics/metabolism
Zoledronic Acid/therapeutic use

@article {pmid35266635,
year = {2022},
author = {Karabid, NM and Wiedemann, T and Gulde, S and Mohr, H and Segaran, RC and Geppert, J and Rohm, M and Vitale, G and Gaudenzi, G and Dicitore, A and Ankerst, DP and Chen, Y and Braren, R and Kaissis, G and Schilling, F and Schillmaier, M and Eisenhofer, G and Herzig, S and Roncaroli, F and Honegger, JB and Pellegata, NS},
title = {Angpt2/Tie2 autostimulatory loop controls tumorigenesis.},
journal = {EMBO molecular medicine},
volume = {14},
number = {5},
pages = {e14364},
doi = {10.15252/emmm.202114364},
pmid = {35266635},
issn = {1757-4684},
support = {//Deutsche Krebshilfe (German Cancer Aid)/ ; 2017.012.1//Wilhelm Sander-Stiftung (Wilhelm Sander Foundation)/ ; 314061271-TRR 205//Deutsche Forschungsgemeinschaft (DFG)/ ; SFB-824//Deutsche Forschungsgemeinschaft (DFG)/ ; },
mesh = {*Angiopoietin-2/metabolism ; Animals ; Carcinogenesis ; Endothelial Cells/metabolism ; Humans ; Mice ; Neoplasm Recurrence, Local ; *Pituitary Neoplasms/genetics/metabolism/pathology ; Rats ; Receptor, TIE-2/genetics/metabolism ; Zebrafish ; },
abstract = {Invasive nonfunctioning (NF) pituitary neuroendocrine tumors (PitNETs) are non-resectable neoplasms associated with frequent relapses and significant comorbidities. As the current therapies of NF-PitNETs often fail, new therapeutic targets are needed. The observation that circulating angiopoietin-2 (ANGPT2) is elevated in patients with NF-PitNET and correlates with tumor aggressiveness prompted us to investigate the ANGPT2/TIE2 axis in NF-PitNETs in the GH3 PitNET cell line, primary human NF-PitNET cells, xenografts in zebrafish and mice, and in MENX rats, the only autochthonous NF-PitNET model. We show that PitNET cells express a functional TIE2 receptor and secrete bioactive ANGPT2, which promotes, besides angiogenesis, tumor cell growth in an autocrine and paracrine fashion. ANGPT2 stimulation of TIE2 in tumor cells activates downstream cell proliferation signals, as previously demonstrated in endothelial cells (ECs). Tie2 gene deletion blunts PitNETs growth in xenograft models, and pharmacological inhibition of Angpt2/Tie2 signaling antagonizes PitNETs in primary cell cultures, tumor xenografts in mice, and in MENX rats. Thus, the ANGPT2/TIE2 axis provides an exploitable therapeutic target in NF-PitNETs and possibly in other tumors expressing ANGPT2/TIE2. The ability of tumor cells to coopt angiogenic signals classically viewed as EC-specific expands our view on the microenvironmental cues that are essential for tumor progression.},
}

*Angiopoietin-2/metabolism
Animals
Carcinogenesis
Endothelial Cells/metabolism
Humans
Mice
Neoplasm Recurrence, Local
*Pituitary Neoplasms/genetics/metabolism/pathology
Rats
Receptor, TIE-2/genetics/metabolism
Zebrafish

@article {pmid35478129,
year = {2022},
author = {Salih, MM and Higgo, AA and Khalifa, AS and Eed, EM},
title = {Incidence of Epstein-Barr Virus Among Women With Breast Cancer Using Monoclonal Antibodies for Latent Membrane Protein 1 (LMP1).},
journal = {In vivo (Athens, Greece)},
volume = {36},
number = {3},
pages = {1513-1518},
doi = {10.21873/invivo.12860},
pmid = {35478129},
issn = {1791-7549},
mesh = {Adult ; Antibodies, Monoclonal ; *Antineoplastic Agents, Immunological ; *Breast Neoplasms/epidemiology/pathology ; *Carcinoma, Ductal/complications ; *Epstein-Barr Virus Infections/complications/epidemiology/pathology ; Female ; Herpesvirus 4, Human ; Humans ; Incidence ; Male ; Membrane Proteins ; Middle Aged ; Viral Proteins ; },
abstract = {BACKGROUND/AIM: Breast cancer is a common type of cancer in Sudan. Numerous studies propose viral oncogenesis as an etiological factor for breast cancer. The aim of the study was to analyze the presence of the Epstein-Barr virus (EBV) using monoclonal antibodies against latent membrane protein 1 (LAMP1) and determine the correlation between the presence of EBV and clinicopathological characteristics.

PATIENTS AND METHODS: This study used immunohistochemistry to analyze the presence of EBV in 202 samples from Sudanese women diagnosed with breast cancer. Clinicopathological data were collected from patient records from the Radiation and Isotopes Centre in Khartoum State, Republic of Sudan.

RESULTS: This study included 202 patients 168 (83.2%), 16 (7.9%), and 18 (8.9%), diagnosed with invasive ductal carcinoma, invasive lobular carcinoma, and papillary carcinoma, respectively. Axillary lymph node metastasis was present in 57 (28.2%) of cases, while 11 patients (5.4%) tested positive for EBV. The mean age of patients was 48.14±14.4 years. EBV infection was more frequently detected in invasive ductal carcinoma cases, and EBV positivity was not associated with cancer type, grade, progesterone levels, and HER2 expression. On the other hand, a statistically significant association was found between EBV presence and lymph node involvement, estrogen receptor status, and age group.

CONCLUSION: EBV may not play a vital role in the pathogenesis of breast carcinoma in Sudanese women.},
}

Adult
Antibodies, Monoclonal
*Antineoplastic Agents, Immunological
*Breast Neoplasms/epidemiology/pathology
*Carcinoma, Ductal/complications
*Epstein-Barr Virus Infections/complications/epidemiology/pathology
Female
Herpesvirus 4, Human
Humans
Incidence
Male
Membrane Proteins
Middle Aged
Viral Proteins

@article {pmid35405500,
year = {2022},
author = {Acevedo, DS and Fang, WB and Rao, V and Penmetcha, V and Leyva, H and Acosta, G and Cote, P and Brodine, R and Swerdlow, R and Tan, L and Lorenzi, PL and Cheng, N},
title = {Regulation of growth, invasion and metabolism of breast ductal carcinoma through CCL2/CCR2 signaling interactions with MET receptor tyrosine kinases.},
journal = {Neoplasia (New York, N.Y.)},
volume = {28},
number = {},
pages = {100791},
doi = {10.1016/j.neo.2022.100791},
pmid = {35405500},
issn = {1476-5586},
support = {P30 CA168524/CA/NCI NIH HHS/United States ; R01 CA172764/CA/NCI NIH HHS/United States ; },
mesh = {Animals ; *Breast Neoplasms/metabolism ; *Carcinoma, Ductal, Breast/pathology ; *Carcinoma, Intraductal, Noninfiltrating/metabolism ; Cell Line, Tumor ; Chemokine CCL2/genetics ; Disease Progression ; Female ; Humans ; Neoplasm Recurrence, Local ; Proto-Oncogene Proteins c-met/genetics ; Receptors, CCR2/genetics/metabolism ; },
abstract = {With over 60,000 cases diagnosed annually in the US, ductal carcinoma in situ (DCIS) is the most prevalent form of early-stage breast cancer. Because many DCIS cases never progress to invasive ductal carcinomas (IDC), overtreatment remains a significant problem. Up to 20% patients experience disease recurrence, indicating that standard treatments do not effectively treat DCIS for a subset of patients. By understanding the mechanisms of DCIS progression, we can develop new treatment strategies better tailored to patients. The chemokine CCL2 and its receptor CCR2 are known to regulate macrophage recruitment during inflammation and cancer progression. Recent studies indicate that increased CCL2/CCR2 signaling in breast epithelial cells enhance formation of IDC. Here, we characterized the molecular mechanisms important for CCL2/CCR2-mediated DCIS progression. Phospho-protein array profiling revealed that CCL2 stimulated phosphorylation of MET receptor tyrosine kinases in breast cancer cells. Co-immunoprecipitation and proximity ligation assays demonstrated that CCL2-induced MET activity depended on interactions with CCR2 and SRC. Extracellular flux analysis and biochemical assays revealed that CCL2/CCR2 signaling in breast cancer cells enhanced glycolytic enzyme expression and activity. CRISPR knockout and pharmacologic inhibition of MET revealed that CCL2/CCR2-induced breast cancer cell proliferation, survival, migration and glycolysis through MET-dependent mechanisms. In animals, MET inhibitors blocked CCR2-mediated DCIS progression and metabolism. CCR2 and MET were significantly co-expressed in patient DCIS and IDC tissues. In summary, MET receptor activity is an important mechanism for CCL2/CCR2-mediated progression and metabolism of early-stage breast cancer, with important clinical implications.},
}

Animals
*Breast Neoplasms/metabolism
*Carcinoma, Ductal, Breast/pathology
*Carcinoma, Intraductal, Noninfiltrating/metabolism
Cell Line, Tumor
Chemokine CCL2/genetics
Disease Progression
Female
Humans
Neoplasm Recurrence, Local
Proto-Oncogene Proteins c-met/genetics
Receptors, CCR2/genetics/metabolism

@article {pmid35456414,
year = {2022},
author = {Zadrożna-Nowak, A and Romanowicz, H and Zadrożny, M and Bryś, M and Forma, E and Smolarz, B},
title = {Analysis of Long Non-Coding RNA (lncRNA) uc.38 and uc.63 Expression in Breast Carcinoma Patients.},
journal = {Genes},
volume = {13},
number = {4},
pages = {},
pmid = {35456414},
issn = {2073-4425},
mesh = {*Breast Neoplasms/pathology ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Neoplasm Staging ; *RNA, Long Noncoding/genetics/metabolism ; },
abstract = {BACKGROUND: The role of the transcribed ultra-conserved regions (T-UCRs) has not yet been fully discovered, but the studies showed some indications that impaired expression of T-UCRS were present in malignant tumors, including breast cancer.

AIM: The presented work assessed the expression of two transcribed-ultra conserved regions-uc.63 and uc.38-in breast cancer tissue samples.

MATERIAL AND METHODS: The research was carried out on a group of 100 patients with invasive ductal carcinoma and 100 patients (test group) with benign tumors in breast tissue (control group).

RESULTS: As a result of the statistical analysis, it was shown that the expression of uc.63 and uc.38 is statistically significant, and, accordingly, higher (p < 0.0001) and lower (p < 0.0001) in the test group than in the control group. Statistical dependency analysis of the expression of uc.63 and uc.38 and the selected clinical and pathological factors showed that the expression of uc.63 statistically drops with the patient's age (p = 0.04), and is higher in the breast cancer tissue type M1 according to the TNM classification (p = 0.036) and in tissues with overexpressed HER2 (p = 0.035).

CONCLUSION: The obtained results of the statistical analysis indicate a relationship between the expression of uc.63 and uc.38 and the occurrence of breast cancer.},
}

*Breast Neoplasms/pathology
Female
Gene Expression Regulation, Neoplastic
Humans
Neoplasm Staging
*RNA, Long Noncoding/genetics/metabolism

@article {pmid33415472,
year = {2022},
author = {Zimmerman-Brenner, S and Pilowsky-Peleg, T and Rachamim, L and Ben-Zvi, A and Gur, N and Murphy, T and Fattal-Valevski, A and Rotstein, M},
title = {Group behavioral interventions for tics and comorbid symptoms in children with chronic tic disorders.},
journal = {European child & adolescent psychiatry},
volume = {31},
number = {4},
pages = {637-648},
pmid = {33415472},
issn = {1435-165X},
mesh = {Behavior Therapy ; Child ; Comorbidity ; Humans ; Severity of Illness Index ; *Tic Disorders/complications/therapy ; *Tics/therapy ; *Tourette Syndrome/complications/therapy ; },
abstract = {Exposure and Response Prevention (ERP), Habit Reversal Training (HRT) and Comprehensive Behavioral Intervention for Tics (CBIT) are effective in reducing tic severity. ERP and HRT have recently gained primary support in a group setting, while CBIT has not been examined similarly. We compared the efficacy of group-CBIT to group-Educational Intervention for Tics (group-EIT) for tics and comorbid symptoms. Children with Tourette Syndrome (TS) or Chronic Tic Disorder (CTD) were randomized to group-CBIT or group-EIT. Tics and comorbid symptoms were assessed in forty-six children pre- and postintervention, and 3-month later. Yale Global Tic Severity Scale (YGTSS) Motor tic severity decreased following both interventions, and was maintained at follow-up for group-CBIT only. The Parent Tic Questionnaire (PTQ) showed significant decrease in total and motor tic severity following group-CBIT only, a gain maintained three months later. YGTSS impairment score decreased following both interventions and was maintained at follow-up. YGTSS vocal tic severity score increased following both interventions, and then decreased significantly at follow up. Co-morbid symptoms including anxiety, behavioral problems, and aggressive behavior decreased following both interventions. Children with behavioral problems benefitted less while children with higher intellectual ability benefit more from intervention. Both group interventions showed efficacy in reducing tic impairment and comorbid symptoms. Group-CBIT was superior to group-EIT in reducing motor tic severity at 3-month follow-up, showing an advantage for tic-focused treatment. Based on the PTQ, group-CBIT was superior to group-EIT in reducing motor, vocal, and total tic scores, a gain maintained three months later. Clinical trial registry information-Group Intervention for Children with Chronic Tics Syndrome: CBIT vs Psychoeducational Intervention URL: http://clinicaltrials.gov , Identifier: NCT02407951, http://www.controlled-trials.com).},
}

Behavior Therapy
Child
Comorbidity
Humans
Severity of Illness Index
*Tic Disorders/complications/therapy
*Tics/therapy
*Tourette Syndrome/complications/therapy

@article {pmid35231053,
year = {2022},
author = {Troughton, LD and O'Loughlin, DA and Zech, T and Hamill, KJ},
title = {Laminin N-terminus α31 is upregulated in invasive ductal breast cancer and changes the mode of tumour invasion.},
journal = {PloS one},
volume = {17},
number = {3},
pages = {e0264430},
pmid = {35231053},
issn = {1932-6203},
support = {BB/L020513/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; BB/P0257731/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; },
mesh = {*Breast Neoplasms/pathology ; *Carcinoma, Ductal ; Cell Line, Tumor ; Cell Movement ; Female ; Humans ; Immunohistochemistry ; Laminin/genetics/metabolism ; Neoplasm Invasiveness ; },
abstract = {Laminin N-terminus α31 (LaNt α31) is an alternative splice isoform derived from the laminin α3 gene. The LaNt α31 protein is enriched around the terminal duct lobular units in normal breast tissue. In the skin and cornea the protein influences epithelial cell migration and tissue remodelling. However, LaNt α31 has never been investigated in a tumour environment. Here we analysed LaNt α31 in invasive ductal carcinoma and determined its contribution to breast carcinoma invasion. LaNt α31 expression and distribution were analysed by immunohistochemistry in human breast tissue biopsy sections and tissue microarrays covering 232 breast cancer samples. This analysis revealed LaNt α31 to be upregulated in 56% of invasive ductal carcinoma specimens compared with matched normal tissue, and further increased in nodal metastasis compared with the tumour mass in 45% of samples. 65.8% of triple negative cases displayed medium to high LaNt α31 expression. To study LaNt α31 function, an adenoviral system was used to induce expression in MCF-7 and MDA-MB-231 cells. 2D cell migration and invasion into collagen hydrogels were not significantly different between LaNt α31 overexpressing cells and control treated cells. However, LaNt α31 overexpression reduced the proliferation rate of MCF-7 and MDA-MB-231 cells. Moreover, LaNt α31 overexpressing MDA-MB-231 cells displayed a striking change in their mode of invasion into laminin-containing Matrigel; changing from multicellular streaming to individual cellular-invasion. In agreement with these results, 66.7% of the tumours with the highest LaNt α31 expression were non-cohesive. Together these findings indicate that breast cancer-associated changes in LaNt α31 expression could contribute to the processes involved in tumour invasion and may represent a new therapeutic target.},
}

*Breast Neoplasms/pathology
*Carcinoma, Ductal
Cell Line, Tumor
Cell Movement
Female
Humans
Immunohistochemistry
Laminin/genetics/metabolism
Neoplasm Invasiveness

@article {pmid34987224,
year = {2022},
author = {Rasmussen, M and Reddy, M and Nolan, R and Camunas-Soler, J and Khodursky, A and Scheller, NM and Cantonwine, DE and Engelbrechtsen, L and Mi, JD and Dutta, A and Brundage, T and Siddiqui, F and Thao, M and Gee, EPS and La, J and Baruch-Gravett, C and Santillan, MK and Deb, S and Ame, SM and Ali, SM and Adkins, M and DePristo, MA and Lee, M and Namsaraev, E and Gybel-Brask, DJ and Skibsted, L and Litch, JA and Santillan, DA and Sazawal, S and Tribe, RM and Roberts, JM and Jain, M and Høgdall, E and Holzman, C and Quake, SR and Elovitz, MA and McElrath, TF},
title = {RNA profiles reveal signatures of future health and disease in pregnancy.},
journal = {Nature},
volume = {601},
number = {7893},
pages = {422-427},
pmid = {34987224},
issn = {1476-4687},
support = {P50 HD103556/HD/NICHD NIH HHS/United States ; },
mesh = {*Cell-Free Nucleic Acids ; Female ; Humans ; Placenta ; *Pre-Eclampsia/genetics ; Pregnancy ; RNA ; Retrospective Studies ; },
abstract = {Maternal morbidity and mortality continue to rise, and pre-eclampsia is a major driver of this burden1. Yet the ability to assess underlying pathophysiology before clinical presentation to enable identification of pregnancies at risk remains elusive. Here we demonstrate the ability of plasma cell-free RNA (cfRNA) to reveal patterns of normal pregnancy progression and determine the risk of developing pre-eclampsia months before clinical presentation. Our results centre on comprehensive transcriptome data from eight independent prospectively collected cohorts comprising 1,840 racially diverse pregnancies and retrospective analysis of 2,539 banked plasma samples. The pre-eclampsia data include 524 samples (72 cases and 452 non-cases) from two diverse independent cohorts collected 14.5 weeks (s.d., 4.5 weeks) before delivery. We show that cfRNA signatures from a single blood draw can track pregnancy progression at the placental, maternal and fetal levels and can robustly predict pre-eclampsia, with a sensitivity of 75% and a positive predictive value of 32.3% (s.d., 3%), which is superior to the state-of-the-art method2. cfRNA signatures of normal pregnancy progression and pre-eclampsia are independent of clinical factors, such as maternal age, body mass index and race, which cumulatively account for less than 1% of model variance. Further, the cfRNA signature for pre-eclampsia contains gene features linked to biological processes implicated in the underlying pathophysiology of pre-eclampsia.},
}

*Cell-Free Nucleic Acids
Female
Humans
Placenta
*Pre-Eclampsia/genetics
Pregnancy
RNA
Retrospective Studies

@article {pmid34597458,
year = {2021},
author = {Viswanathan, K and Sadow, PM and Maleki, Z and Nishino, M and Baloch, ZW and Abbott, TE and Rao, R and Faquin, WC},
title = {Cytomorphologic features of intraductal salivary gland carcinoma: A multi-institutional study of 13 FNA cases with histologic, molecular, and clinical correlations.},
journal = {Cancer cytopathology},
volume = {129},
number = {12},
pages = {928-946},
doi = {10.1002/cncy.22504},
pmid = {34597458},
issn = {1934-6638},
support = {1PO1CA240239-01//National Cancer Institute of the National Institutes of Health/ ; },
mesh = {Biopsy, Fine-Needle/methods ; *Carcinoma, Intraductal, Noninfiltrating/genetics/pathology ; Gene Fusion ; Humans ; *Salivary Gland Neoplasms/pathology ; Salivary Glands/pathology ; },
abstract = {BACKGROUND: Intraductal carcinoma of the salivary gland (IDC) is a rare cancer with potential actionable targets, including RET fusions. Histologic and molecular features of IDC were recently reported, but cytomorphologic data are limited. In the largest multi-institutional fine-needle aspiration (FNA) series, the authors describe the cytomorphologic features of 13 IDC cases with available clinical, radiologic, histopathologic, and molecular data.

METHODS: The cases included 13 FNAs for 9 low-grade (LG) IDCs and 4 high-grade (HG) IDCs with corresponding histopathology and available molecular, imaging, and clinical data. Smears and liquid-based preparations available for 12 FNAs were semiquantitatively scored for key cytomorphologic findings and correlated with the corresponding resection.

RESULTS: LG IDC FNAs showed a cellular, biphasic population of large, atypical ductal cells with mildly pleomorphic nuclei in a clean background and a minor population of small, uniform myoepithelial cells. In contrast, all HG IDC FNAs showed predominantly ductal cells with marked nuclear pleomorphism, coarse chromatin, and necrosis. With the Milan system, most LG and HG IDC FNAs were classified as either salivary gland neoplasms of uncertain malignant potential (54%) or malignant (31%). Immunohistochemistry showed ductal epithelial reactivity with mammaglobin, androgen receptor, and S100, whereas myoepithelial cells were positive for p63 and/or calponin. Among cases with next-generation sequencing, 4 LG IDCs showed NCOA4-RET gene fusions, whereas an HG IDC showed HRAS and PIK3CA mutations.

CONCLUSIONS: The cytomorphology of IDC overlaps with other benign and malignant salivary gland neoplasms. Immunohistochemistry limits the differential diagnosis, but definitive classification requires molecular analysis. A diagnosis of IDC has potential implications for patient management.},
}

Biopsy, Fine-Needle/methods
*Carcinoma, Intraductal, Noninfiltrating/genetics/pathology
Gene Fusion
Humans
*Salivary Gland Neoplasms/pathology
Salivary Glands/pathology

@article {pmid34185954,
year = {2022},
author = {Zhao, J and Sun, G and Zhu, S and Dai, J and Chen, J and Zhang, M and Ni, Y and Zhang, H and Shen, P and Zhao, X and Zhang, B and Pan, X and Nie, L and Yin, X and Liang, J and Zhang, X and Wang, Z and Zhu, X and Liao, B and Liu, Z and Armstrong, CM and Gao, AC and Huang, H and Chen, N and Zeng, H},
title = {Circulating tumour DNA reveals genetic traits of patients with intraductal carcinoma of the prostate.},
journal = {BJU international},
volume = {129},
number = {3},
pages = {345-355},
doi = {10.1111/bju.15530},
pmid = {34185954},
issn = {1464-410X},
mesh = {*Carcinoma, Intraductal, Noninfiltrating/genetics/pathology ; *Circulating Tumor DNA/genetics ; Humans ; Male ; Phenotype ; Prostate/pathology ; *Prostatic Neoplasms/pathology ; },
abstract = {OBJECTIVES: To investigate the genetic alterations of patients with prostate cancer (PCa) with and without intraductal carcinoma of the prostate (IDC-P).

PATIENTS AND METHODS: We performed targeted sequencing of plasma cell-free DNA on 161 patients with prostate adenocarcinoma (PAC) with IDC-P and 84 without IDC-P. Genomic alterations were compared between these two groups. The association between genetic alterations and patients' survival outcomes was also explored.

RESULTS: We identified that 29.8% (48/161) and 21.4% (18/84) of patients with and without IDC-P harboured genomic alterations in DNA repair pathways, respectively (P = 0.210). Pathogenic germline DNA repair alterations were frequently detected in IDC-P carriers compared to IDC-P non-carriers (11.8% [19/161] vs 2.4% [two of 84], P = 0.024). Germline BReast CAncer type 2 susceptibility protein (BRCA2) and somatic cyclin-dependent kinase 12 (CDK12) defects were specifically identified in IDC-P carriers relative to PAC (BRCA2: 8.7% [14/161] vs 0% and CDK12: 6.8% [11/161] vs 1.2% [one of 84]). Patients with IDC-P had a distinct androgen receptor (AR) pathway alteration, characterised by an enrichment of nuclear receptor corepressor 2 (NCOR2) mutations compared with patients with pure PAC (21.1% [34/161] vs 6.0% [five of 84], P = 0.004). Increased AR alterations were detected in patients harbouring tumours with an IDC-P proportion of ≥10% vs those with an IDC-P proportion of <10% (6.4% [five of 78] vs 18.1% [15/83], P = 0.045). For IDC-P carriers, tumour protein p53 (TP53) mutation was associated with shorter castration-resistant-free survival (median 10.9 vs 28.9 months, P = 0.026), and BRCA2 alteration was related to rapid prostate-specific antigen progression for those receiving abiraterone treatment (median 9.1 vs 11.9 months, P = 0.036).

CONCLUSION: Our findings provide genomic evidence explaining the aggressive phenotype of tumours with IDC-P, highlighting the potential therapeutic strategies for this patient population.},
}

*Carcinoma, Intraductal, Noninfiltrating/genetics/pathology
*Circulating Tumor DNA/genetics
Humans
Male
Phenotype
Prostate/pathology
*Prostatic Neoplasms/pathology

@article {pmid33132109,
year = {2021},
author = {Zong, Y and Montironi, R and Massari, F and Jiang, Z and Lopez-Beltran, A and Wheeler, TM and Scarpelli, M and Santoni, M and Cimadamore, A and Cheng, L},
title = {Intraductal Carcinoma of the Prostate: Pathogenesis and Molecular Perspectives.},
journal = {European urology focus},
volume = {7},
number = {5},
pages = {955-963},
doi = {10.1016/j.euf.2020.10.007},
pmid = {33132109},
issn = {2405-4569},
mesh = {*Carcinoma, Intraductal, Noninfiltrating/diagnosis/genetics/therapy ; Diagnosis, Differential ; Humans ; Male ; Pelvis/pathology ; Prostate/pathology ; *Prostatic Neoplasms/diagnosis/genetics/therapy ; },
abstract = {Intraductal carcinoma of the prostate (IDC-P), a clinicopathological entity characterized by malignant prostatic epithelial cells growing within ducts and/or acini, has a distinct architectural pattern, cytological features, and biological behavior. Whereas most IDC-P tumors could be derived from adjacent high-grade invasive cancer via retrograde spreading of cancer cells along benign ducts and acini, a small subset of IDC-P may arise from the transformation and intraductal proliferation of precancerous cells induced by various oncogenic events. These isolated IDC-P tumors possess a distinct mutational profile and may function as a carcinoma in situ lesion with de novo intraductal outgrowth of malignant cells. Further molecular characterization of these two types of IDC-P and better understanding of the mechanisms underlying IDC-P formation and progression could be translated into valuable biomarkers for differential diagnosis and actionable targets for therapeutic interventions. PATIENT SUMMARY: Intraductal carcinoma of the prostate is an aggressive type of prostate cancer associated with high risk for local recurrence and distant metastasis. In this review, we discussed pathogenesis, biomarkers, differential diagnoses, and therapeutic strategies for this tumor.},
}

*Carcinoma, Intraductal, Noninfiltrating/diagnosis/genetics/therapy
Diagnosis, Differential
Humans
Male
Pelvis/pathology
Prostate/pathology
*Prostatic Neoplasms/diagnosis/genetics/therapy

@article {pmid35137951,
year = {2022},
author = {Weiser, R and Polychronopoulou, E and Hatch, SS and Haque, W and Ghani, HA and He, J and Kuo, YF and Gradishar, WJ and Klimberg, VS},
title = {Adjuvant chemotherapy in patients with invasive lobular carcinoma and use of the 21-gene recurrence score: A National Cancer Database analysis.},
journal = {Cancer},
volume = {128},
number = {9},
pages = {1738-1747},
doi = {10.1002/cncr.34127},
pmid = {35137951},
issn = {1097-0142},
support = {//Courtney M. Townsend, Jr. M.D. Distinguished Chair in General Surgery, University of Texas Medical Branch, Galveston, TX/ ; },
mesh = {*Breast Neoplasms/drug therapy/genetics/pathology ; *Carcinoma, Ductal, Breast/drug therapy/genetics ; *Carcinoma, Lobular/drug therapy/genetics/pathology ; Chemotherapy, Adjuvant ; Female ; Humans ; Prognosis ; },
abstract = {BACKGROUND: Invasive lobular carcinoma (ILC) is traditionally considered less responsive to chemotherapy. Although the Oncotype recurrence score (RS) has been validated to identify high-risk patients who benefit from chemotherapy, some studies have questioned its relevance in patients with ILC. The objective of this study was to better characterize potential use of the RS in these patients.

METHODS: The National Cancer Database was used to identify women with stage I through III, T1 through T3, N0 or N1, hormone receptor-positive, HER2-negative ILC or invasive ductal carcinoma (IDC) who had an available RS between 2010 and 2016. Multivariable Cox regression was used to model the effect of variables on 5-year overall survival (OS). The Kaplan-Meier method was used to estimate OS according to the RS, nodal status, and chemotherapy.

RESULTS: In total, 15,763 patients with ILC and 100,070 with IDC were identified. The mean age of patients with ILC and IDC was 59.2 ± 9.1 and 57.2 ± 9.8, respectively. A lower percentage of patients with ILC versus those with IDC had a high RS, defined as >25 (6.6% vs 16.0%; P < .0001). ILC patients with a high RS who had N0 or N1 disease received approximately 10% less chemotherapy compared with similar patients who had IDC. The results indicated that the RS had statistically significant prognostic value for patients with ILC. In addition, an absolute OS advantage was correlated with the receipt of chemotherapy by patients with ILC who had a high RS with N0 or N1 disease.

CONCLUSIONS: Patients with ILC who have a high RS are treated less often with chemotherapy compared with similar patients who have IDC. Nevertheless, the RS has a prognostic as well as a predictive value in ILC, with an association between OS benefit and chemotherapy receipt in patients who have ILC with a high RS, especially if they have N1 disease.

LAY SUMMARY: Invasive lobular carcinoma (ILC) is a subtype of breast cancer comprising about 15% of cases. The Oncotype recurrence score (RS) is a genetic test of breast tumors that helps predict which patients might benefit from chemotherapy. Some have doubted the relevance of the RS for patients with ILC. In this study, the authors show that the RS is relevant for patients who have ILC. The RS has the potential of predicting the risk of recurrence and identifying patients with ILC who might benefit from chemotherapy.},
}

*Breast Neoplasms/drug therapy/genetics/pathology
*Carcinoma, Ductal, Breast/drug therapy/genetics
*Carcinoma, Lobular/drug therapy/genetics/pathology
Chemotherapy, Adjuvant
Female
Humans
Prognosis

@article {pmid35393463,
year = {2022},
author = {Foroozani, E and Akbari, A and Amanat, S and Rashidi, N and Bastam, D and Ataee, S and Sharifnia, G and Faraouei, M and Dianatinasab, M and Safdari, H},
title = {Adherence to a western dietary pattern and risk of invasive ductal and lobular breast carcinomas: a case-control study.},
journal = {Scientific reports},
volume = {12},
number = {1},
pages = {5859},
pmid = {35393463},
issn = {2045-2322},
mesh = {*Breast Neoplasms/complications/etiology ; *Carcinoma, Ductal, Breast/complications/etiology ; *Carcinoma, Lobular/epidemiology/etiology/pathology ; Case-Control Studies ; Diet, Western ; Female ; Humans ; },
abstract = {Little is known about the role of diet in the risk of invasive ductal carcinoma (IDC) and invasive lobular carcinoma (ILC) of the breast, the most common histological subtypes of breast cancer (BC). This is because, the majority of studies on the association of diet and the risk of BC are focused on single food items, and studies considering the overall diet in terms of dietary patterns are limited. Also, the potential heterogeneity in the impact of Western diet (WD) on histological subtypes of BC is not established. This, the age-frequency-matched case-control study included 1009 incident BC cases and 1009 healthy controls. The required data was obtained from the patients' medical files and interviews using a previously validated researcher-designed questionnaire for collecting data on socio-economic and anthropometric statuses and a valid food frequency questionnaire (FFQ) to measure the participants' dietary intake. We used multinomial logistic regression, and odds ratios (ORs) with 95% confidence intervals (CIs) were calculated. A positive and significant association was observed between higher adherence to a WD and risk of IDC (OR comparing highest with the lowest tertile: 2.45, 95% CI 1.88, 3.17; p-trend < 0.001), whereas no significant association was observed between adherence to the WD and the risk of ILC (OR comparing highest with the lowest tertile: 1.63, 95% CI 0.63, 3.25) (p for heterogeneity = 0.03). The results of an analysis stratified by menopausal status suggested a similar pattern. We provided evidence that adherence to a WD raises the risk of IDC, but not ILC, suggesting different etiological mechanisms for IDC and ILC.},
}

*Breast Neoplasms/complications/etiology
*Carcinoma, Ductal, Breast/complications/etiology
*Carcinoma, Lobular/epidemiology/etiology/pathology
Case-Control Studies
Diet, Western
Female
Humans

@article {pmid35389579,
year = {2022},
author = {Clarey, D and DiMaio, D and Trowbridge, R},
title = {Deep Sweet Syndrome Secondary to Pegfilgrastim.},
journal = {Journal of drugs in dermatology : JDD},
volume = {21},
number = {4},
pages = {422-424},
doi = {10.36849/JDD.4794},
pmid = {35389579},
issn = {1545-9616},
mesh = {Filgrastim/adverse effects ; Granulocyte Colony-Stimulating Factor/adverse effects ; Humans ; Polyethylene Glycols/adverse effects ; *Sweet Syndrome/chemically induced/diagnosis/drug therapy ; },
abstract = {Sweet syndrome, or acute febrile neutrophilic dermatosis, is a skin condition consisting of erythematous papules and plaques in association with fever, neutrophilia, and a neutrophilic infiltrate that typically involves the papillary dermis. Although development is most commonly idiopathic, medications are also frequently associated with the eruption, notably, the granulocyte colony-stimulating factor (G-CSF), filgrastim. Pegylated G-CSF, despite similar activity, is not commonly reported, with only four published cases. We present a case of drug-induced sweet syndrome with unique histologic features (deep inflammatory infiltrate) in association with the usage of pegfilgrastim in the treatment of invasive ductal carcinoma of the breast. J Drugs Dermatol. 2022;21(4):422-424. doi:10.36849/JDD.4794.},
}

Filgrastim/adverse effects
Granulocyte Colony-Stimulating Factor/adverse effects
Humans
Polyethylene Glycols/adverse effects
*Sweet Syndrome/chemically induced/diagnosis/drug therapy

@article {pmid35178446,
year = {2022},
author = {Li, X and Zhao, G and Mi, X and Xu, T and Li, X and Liu, B},
title = {Ajuba Overexpression Promotes Breast Cancer Chemoresistance and Glucose Uptake through TAZ-GLUT3/Survivin Pathway.},
journal = {BioMed research international},
volume = {2022},
number = {},
pages = {3321409},
pmid = {35178446},
issn = {2314-6141},
mesh = {*Breast Neoplasms/drug therapy/genetics/metabolism ; Cell Line, Tumor ; Cell Proliferation ; DNA-Binding Proteins/genetics ; Drug Resistance, Neoplasm/genetics ; Female ; Gene Expression Regulation, Neoplastic ; Glucose ; Glucose Transporter Type 3/metabolism ; Humans ; LIM Domain Proteins/genetics/metabolism ; Muscle Proteins/metabolism ; Survivin/genetics ; TEA Domain Transcription Factors ; Transcription Factors/genetics/metabolism ; },
abstract = {The LIM protein Ajuba has been implicated in the development of human cancers. To date, its expression pattern and biological significance in breast cancers (BC) have not been fully investigated. In the current study, we examined Ajuba protein levels in 93 invasive ductal carcinoma specimens by immunohistochemistry. The Ajuba expression level was elevated in breast cancer tissue compared with normal tissue. Ajuba overexpression is correlated with advanced tumor-node-metastasis (TNM) stage, positive node status, and adverse patient outcomes. The Ajuba protein level was also higher in BC cell lines compared to normal breast epithelial cell line MCF-10A. Ectopically expressed Ajuba in MCF-7 cells stimulated in vitro and in vivo cell growth, invasion, cell cycle progression, and decreased paclitaxel-induced apoptosis. RNA-sequencing (RNA-seq) followed by gene set enrichment analysis (GSEA) analysis showed that Ajuba overexpression regulated the Hippo signaling pathway. Ajuba overexpression also increased glucose uptake and increased expression of TAZ, GLUT3, and Survivin. TAZ knockdown abolished the role of Ajuba on GLUT3 and Survivin induction. The ChIP assay showed that TEAD4, a major TAZ binding transcription factor, could bind to the GLUT3 and Survivin promoter regions. In conclusion, our data demonstrated that elevated Ajuba expression is correlated with poor BC prognosis and regulated malignant behavior through TAZ-GLUT3/Survivin signaling in BC cells.},
}

*Breast Neoplasms/drug therapy/genetics/metabolism
Cell Line, Tumor
Cell Proliferation
DNA-Binding Proteins/genetics
Drug Resistance, Neoplasm/genetics
Female
Gene Expression Regulation, Neoplastic
Glucose
Glucose Transporter Type 3/metabolism
Humans
LIM Domain Proteins/genetics/metabolism
Muscle Proteins/metabolism
Survivin/genetics
TEA Domain Transcription Factors
Transcription Factors/genetics/metabolism

@article {pmid35340411,
year = {2022},
author = {Du, W and Miao, Y and Zhang, G and Luo, G and Yang, P and Chen, F and Zhang, B and Yang, C and Li, G and Chang, J},
title = {The Regulatory Role of Neuropeptide Gene Glucagon in Colorectal Cancer: A Comprehensive Bioinformatic Analysis.},
journal = {Disease markers},
volume = {2022},
number = {},
pages = {4262600},
pmid = {35340411},
issn = {1875-8630},
mesh = {Biomarkers, Tumor/metabolism ; *Colonic Neoplasms/genetics ; Computational Biology ; Gene Expression Regulation, Neoplastic ; *Glucagon/genetics/metabolism ; Humans ; },
abstract = {Background: Colorectal cancer is highly prevalent and causes high global mortality, and glucagon axis has been implicated in colon cancer. The present study is aimed at investigating the regulating mechanisms of glucagon involvement in colorectal cancer.

Methods: Publicly available data from the TCGA database was utilized to explore the expression pattern and regulating role of glucagon (GCG) in colorectal cancer (COADREAD) including colon adenocarcinomas (COAD) and rectum adenocarcinomas (READ). Statistical analyses were performed using the R software packages and public web servers. The expression pattern and prognostic significance of GCG gene in pan-cancer and TCGA-COADREAD data were investigated by performing unpaired and paired sample analyses. The association of GCG expression with clinical characteristics was investigated using logistic regression analysis. Univariate cox regression analysis was performed to test the prognostic value of GCG expression for overall survival in COADREAD patients. GCG-significantly correlated genes were obtained. Biological functions and signaling pathways were identified by performing functional enrichment analysis and Gene Set Enrichment Analysis (GSEA). Additionally, the potential involvement of GCG in tumor immunity was researched by investigating the correlation between GCG expression and 24 tumor infiltrating immune cells.

Results: GCG was found to be significantly downregulated in COADREAD tumor samples compared with healthy control samples. GCG gene was shown to be associated with the prognostic outcomes of COADREAD, whereby its upregulation predicted improved survival outcomes. Functional enrichment analysis showed that the top 100 positively and top 100 negatively GCG-correlated genes were mainly enriched in three signaling pathways including ribosome, nitrogen metabolism, and proximal tubule bicarbonate reclamation. The GSEA showed that GCG-significantly correlated genes were mainly enriched in cell cycle-related pathways (reactome cell cycle, reactome cell cycle mitotic, reactome cell cycle checkpoints, reactome M phase, Reactome G2 M DNA damage checkpoint, and Reactome G2 M checkpoints), neuropeptide ligand receptor interaction, RHO GTPases signaling, WNT signaling, RUNX1 signaling, NOTCH signaling, ESR signaling, HCMV infection, and oxidative stress-related signaling. GCG was positively correlated with Th17 cells, pDC, macrophages, TFH cells, iDC, Tem, B cells, dendritic cells, neutrophils, mast cells, and eosinophils and was negatively associated with NK cells.

Conclusions: GCG dysregulation with high prognostic value in COADREAD was noted. Several tumor progression-related pathways and tumor immune-modulatory cells were linked to GCG expression in COADREAD. Therefore, GCG may be regarded as a potential therapeutic target for treating colorectal cancer.},
}

Biomarkers, Tumor/metabolism
*Colonic Neoplasms/genetics
Computational Biology
Gene Expression Regulation, Neoplastic
*Glucagon/genetics/metabolism
Humans

@article {pmid34083791,
year = {2021},
author = {Zhao, E and Stone, MR and Ren, X and Guenthoer, J and Smythe, KS and Pulliam, T and Williams, SR and Uytingco, CR and Taylor, SEB and Nghiem, P and Bielas, JH and Gottardo, R},
title = {Spatial transcriptomics at subspot resolution with BayesSpace.},
journal = {Nature biotechnology},
volume = {39},
number = {11},
pages = {1375-1384},
pmid = {34083791},
issn = {1546-1696},
support = {P30 CA015704/CA/NCI NIH HHS/United States ; S10 OD028685/OD/NIH HHS/United States ; P01 CA225517/CA/NCI NIH HHS/United States ; F30 CA254168/CA/NCI NIH HHS/United States ; T32 CA080416/CA/NCI NIH HHS/United States ; },
mesh = {Bayes Theorem ; Cluster Analysis ; Gene Expression Profiling/methods ; Sequence Analysis, RNA/methods ; *Single-Cell Analysis/methods ; *Transcriptome/genetics ; },
abstract = {Recent spatial gene expression technologies enable comprehensive measurement of transcriptomic profiles while retaining spatial context. However, existing analysis methods do not address the limited resolution of the technology or use the spatial information efficiently. Here, we introduce BayesSpace, a fully Bayesian statistical method that uses the information from spatial neighborhoods for resolution enhancement of spatial transcriptomic data and for clustering analysis. We benchmark BayesSpace against current methods for spatial and non-spatial clustering and show that it improves identification of distinct intra-tissue transcriptional profiles from samples of the brain, melanoma, invasive ductal carcinoma and ovarian adenocarcinoma. Using immunohistochemistry and an in silico dataset constructed from scRNA-seq data, we show that BayesSpace resolves tissue structure that is not detectable at the original resolution and identifies transcriptional heterogeneity inaccessible to histological analysis. Our results illustrate BayesSpace's utility in facilitating the discovery of biological insights from spatial transcriptomic datasets.},
}

Bayes Theorem
Cluster Analysis
Gene Expression Profiling/methods
Sequence Analysis, RNA/methods
*Single-Cell Analysis/methods
*Transcriptome/genetics

@article {pmid35348061,
year = {2021},
author = {Khan, NA and Nguyen, ST and Teh, PG and Ranpura, VN and Bhatia, T},
title = {Duodenal Metastasis in Triple-Negative Invasive Ductal Breast Carcinoma With Negative Mammography: A Case Report and Review of the Literature.},
journal = {The Permanente journal},
volume = {25},
number = {},
pages = {},
pmid = {35348061},
issn = {1552-5775},
mesh = {*Breast Neoplasms/diagnostic imaging/pathology ; *Carcinoma, Ductal, Breast/diagnostic imaging/pathology/secondary ; *Carcinoma, Lobular/pathology/secondary ; Female ; Humans ; Mammography ; Receptors, Estrogen ; },
abstract = {Breast cancer metastasis to the gastrointestinal tract is uncommon, and duodenal involvement is exceptionally rare. Those cases that do metastasize are reported to be lobular, with ductal carcinomas comprising only a small percentage of reported cases. Furthermore, these invasive carcinomas are typically estrogen receptor-, progesterone receptor-positive ± human epidermal growth factor receptor 2 malignancies. We present a unique case of a patient with duodenal metastasis as the first sign of metastatic breast cancer. The rarity of this case is highlighted by the fact that the patient had no known breast malignancy, and pathological findings revealed triple-negative invasive ductal carcinoma consistent with primary breast cancer. Diagnostic mammogram and ultrasound were negative for any lesions.},
}

*Breast Neoplasms/diagnostic imaging/pathology
*Carcinoma, Ductal, Breast/diagnostic imaging/pathology/secondary
*Carcinoma, Lobular/pathology/secondary
Female
Humans
Mammography
Receptors, Estrogen

@article {pmid35343265,
year = {2022},
author = {Zhao, CM and Li, LL and Xu, JW and Li, ZW and Shi, P and Jiang, R},
title = {LINC00092 Suppresses the Malignant Progression of Breast Invasive Ductal Carcinoma Through Modulating SFRP1 Expression by Sponging miR-1827.},
journal = {Cell transplantation},
volume = {31},
number = {},
pages = {9636897221086967},
pmid = {35343265},
issn = {1555-3892},
mesh = {*Carcinoma, Ductal/genetics ; Cell Line, Tumor ; Cell Movement/genetics ; Gene Expression Regulation, Neoplastic ; Humans ; Intercellular Signaling Peptides and Proteins/genetics/metabolism ; Membrane Proteins/genetics/metabolism ; *MicroRNAs/genetics/metabolism ; },
abstract = {Breast invasive ductal carcinoma (IDC) is a most common kind of breast cancer (BC), yet to date the corresponding effective therapies are limited. Extensive evidence has indicated that lncRNAs are involved in multiple cancers, and the potential mechanism of lncRNAs, such as LINC00092, mentioned in IDC remains elusive. IDC clinical samples from TCGA database were used to analyze the expression levels of LINC00092, miR-1827 and SFRP1. Kaplan-Meier method was applied to plot the overall survival curves. KEGG and GO were employed to screen the pathway that LINC00092 participated in. Pearson's correlation analysis determined the relationship between LINC00092 and SFRP1. Bioinformatics analysis and dual-luciferase reporter assay examined the association among LINC00092, miR-1827, and SFRP1. Cell counting kit-8, colony formation and transwell assays were performed to detect cell viability, colony formation, and migration and invasion, respectively. Quantitative reverse-transcription polymerase chain reaction and western blot were utilized to investigate the expression at RNA and protein levels. LINC00092 expression was down-regulated in IDC tissues and cells, which was correlated with poor prognosis. Down-regulated LINC00092 facilitated cell proliferation, colony formation, and cell migration and invasion, while up-regulated LINC00092 inhibited cell malignant behaviors. LINC00092/SFRP1 physically bound to miR-1827 in IDC. SFRP1 expression was proportional to LINC00092 expression and inversely proportional to miR-1827 expression. The inhibitory effects of LINC00092 on cell aggressive behaviors were partially regulated by miR-1827/SFRP1. In summary, our results indicated that overexpression of LINC00092 inhibited the development of IDC through modulating miR-1827/SFRP1 axis, suggesting new therapeutic targets to treat IDC.},
}

*Carcinoma, Ductal/genetics
Cell Line, Tumor
Cell Movement/genetics
Gene Expression Regulation, Neoplastic
Humans
Intercellular Signaling Peptides and Proteins/genetics/metabolism
Membrane Proteins/genetics/metabolism
*MicroRNAs/genetics/metabolism

@article {pmid34999280,
year = {2022},
author = {Kotschi, S and Jung, A and Willemsen, N and Ofoghi, A and Proneth, B and Conrad, M and Bartelt, A},
title = {NFE2L1-mediated proteasome function protects from ferroptosis.},
journal = {Molecular metabolism},
volume = {57},
number = {},
pages = {101436},
doi = {10.1016/j.molmet.2022.101436},
pmid = {34999280},
issn = {2212-8778},
mesh = {Animals ; *Ferroptosis ; Homeostasis ; Humans ; Mice ; Mitochondria/metabolism ; NF-E2-Related Factor 1/genetics/metabolism ; Phospholipid Hydroperoxide Glutathione Peroxidase ; Proteasome Endopeptidase Complex/metabolism ; },
abstract = {OBJECTIVE: Ferroptosis continues to emerge as a novel modality of cell death with important therapeutic implications for a variety of diseases, most notably cancer and degenerative diseases. While susceptibility, initiation, and execution of ferroptosis have been linked to reprogramming of cellular lipid metabolism, imbalances in iron-redox homeostasis, and aberrant mitochondrial respiration, the detailed mechanisms of ferroptosis are still insufficiently well understood.

METHODS AND RESULTS: Here we show that diminished proteasome function is a new mechanistic feature of ferroptosis. The transcription factor nuclear factor erythroid-2, like-1 (NFE2L1) protects from ferroptosis by sustaining proteasomal activity. In cellular systems, loss of NFE2L1 reduced cellular viability after the induction of both chemically and genetically induced ferroptosis, which was linked to the regulation of proteasomal activity under these conditions. Importantly, this was reproduced in a Sedaghatian-type Spondylometaphyseal Dysplasia (SSMD) patient-derived cell line carrying mutated glutathione peroxidase-4 (GPX4), a critical regulator of ferroptosis. Also, reduced proteasomal activity was associated with ferroptosis in Gpx4-deficient mice. In a mouse model for genetic Nfe2l1 deficiency, we observed brown adipose tissue (BAT) involution, hyperubiquitination of ferroptosis regulators, including the GPX4 pathway, and other hallmarks of ferroptosis.

CONCLUSION: Our data highlight the relevance of the NFE2L1-proteasome pathway in ferroptosis. Manipulation of NFE2L1 activity might enhance ferroptosis-inducing cancer therapies as well as protect from aberrant ferroptosis in neurodegeneration, general metabolism, and beyond.},
}

Animals
*Ferroptosis
Homeostasis
Humans
Mice
Mitochondria/metabolism
NF-E2-Related Factor 1/genetics/metabolism
Phospholipid Hydroperoxide Glutathione Peroxidase
Proteasome Endopeptidase Complex/metabolism

@article {pmid33828234,
year = {2022},
author = {Hu, A and Hong, F and Li, D and Xie, Q and Chen, K and Zhu, L and He, H},
title = {KDM3B-ETF1 fusion gene downregulates LMO2 via the WNT/β-catenin signaling pathway, promoting metastasis of invasive ductal carcinoma.},
journal = {Cancer gene therapy},
volume = {29},
number = {2},
pages = {215-224},
pmid = {33828234},
issn = {1476-5500},
mesh = {Adaptor Proteins, Signal Transducing/genetics/metabolism ; Animals ; *Breast Neoplasms/genetics/pathology ; *Carcinoma, Ductal/genetics ; Cell Line, Tumor ; Cell Movement/genetics ; Cell Proliferation/genetics ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Jumonji Domain-Containing Histone Demethylases/genetics/metabolism ; LIM Domain Proteins ; Mice ; Mice, Nude ; Neoplasm Invasiveness/genetics ; Proto-Oncogene Proteins/genetics/metabolism ; Wnt Signaling Pathway ; beta Catenin/genetics/metabolism ; },
abstract = {Breast cancer is the most common malignancy for women, with invasive ductal carcinoma being the largest subtype of breast cancers, accounting for 75-80% of cases. However, the underlying mechanism of invasive ductal carcinoma remains unclear. In this study, we investigate the possible effects KDM3B-ETF1 fusion gene has on breast cancer cell metastasis, invasion and its downstream signaling mediators as revealed from RNA sequence data analysis. As predicted, KDM3B-ETF1 expression was increased in breast cancer tissues and cells. Overexpression of KDM3B-ETF1 in cancer cell lines promoted the growth and invasion of breast cancer cells, while KDM3B-ETF1 knockdown showed the opposite effects on malignant cell growth and invasion both in vivo and in vitro as evidenced by cell counting kit-8, Transwell assay and tumor xenograft in nude mice. On the contrary, LIM Domain Only 2 (LMO2) expression was significantly reduced in breast cancer tissues and cells. According to chromatin immunoprecipitation and Western blot analysis, KDM3B-ETF1 targets LMO2 and reduced the expression of LMO2, leading to an increase in WNT/β-catenin signaling pathway and thus promoting invasion. In conclusion, fusion gene KDM3B-ETF1 inhibits LMO2, activates the Wnt/β-catenin signaling pathway that leads to increased breast cancer cell invasion and metastasis, providing a novel insight into developing therapeutic strategies. These results provide novel insights into the molecular mechanism of invasive ductal carcinomas, which may lead to potential therapeutic targets.},
}

Adaptor Proteins, Signal Transducing/genetics/metabolism
Animals
*Breast Neoplasms/genetics/pathology
*Carcinoma, Ductal/genetics
Cell Line, Tumor
Cell Movement/genetics
Cell Proliferation/genetics
Female
Gene Expression Regulation, Neoplastic
Humans
Jumonji Domain-Containing Histone Demethylases/genetics/metabolism
LIM Domain Proteins
Mice
Mice, Nude
Neoplasm Invasiveness/genetics
Proto-Oncogene Proteins/genetics/metabolism
Wnt Signaling Pathway
beta Catenin/genetics/metabolism

@article {pmid33667646,
year = {2021},
author = {He, B and Chen, J and Song, W and Bai, Y},
title = {miR-646/TET1 mediated demethylation of IRX1 promoter upregulates HIST2H2BE and promotes the progression of invasive ductal carcinoma.},
journal = {Genomics},
volume = {113},
number = {3},
pages = {1469-1481},
doi = {10.1016/j.ygeno.2020.12.044},
pmid = {33667646},
issn = {1089-8646},
mesh = {*Carcinoma, Ductal ; Cell Line, Tumor ; DNA Methylation ; Demethylation ; Gene Expression Regulation, Neoplastic ; Homeodomain Proteins/genetics/metabolism ; Humans ; *MicroRNAs/genetics/metabolism ; Mixed Function Oxygenases/genetics/metabolism ; Promoter Regions, Genetic ; Proto-Oncogene Proteins/genetics/metabolism ; Transcription Factors/genetics/metabolism ; },
abstract = {BACKGROUND: This study aimed to explore role of miR-646 in breast IDC.

METHODS: miR-646, TET1, IRX1, and HIST2H2BE expression was detected by RT-qPCR and/or Western blot analysis. The methylation status of IRX1 promoter region was evaluated by methylation specific PCR. ChIP assay was used to determine the enrichment of TET1 at IRX1 promoter region. Loss- and gain-of functions were performed to determine the roles of miR-646, TET1, IRX1, and HIST2H2BE in cell proliferation, migration, invasion, and apoptosis. The tumor growth, volume, weight, and apoptosis status were measured.

RESULTS: miR-646 was upregulated while TET1 was downregulated in IDC tissues. miR-646 targeted TET1. Downregulated TET1 impairs demethylation of IRX1 promoter region resulting in reduced expression of IRX1, which subsequently leads to upregulation of HIST2H2BE in IDC. Consequently, elevated HIST2H2BE promotes progression of IDC.

CONCLUSION: Our study has demonstrated that miR-646 facilitates the tumorigenesis of IDC via regulating TET1/IRX1/HIST2H2BE axis.},
}

*Carcinoma, Ductal
Cell Line, Tumor
DNA Methylation
Demethylation
Gene Expression Regulation, Neoplastic
Homeodomain Proteins/genetics/metabolism
Humans
*MicroRNAs/genetics/metabolism
Mixed Function Oxygenases/genetics/metabolism
Promoter Regions, Genetic
Proto-Oncogene Proteins/genetics/metabolism
Transcription Factors/genetics/metabolism

@article {pmid35155685,
year = {2022},
author = {Zhang, L and Du, J and Song, Q and Zhang, C and Wu, X},
title = {A Novel In Situ Dendritic Cell Vaccine Triggered by Rose Bengal Enhances Adaptive Antitumour Immunity.},
journal = {Journal of immunology research},
volume = {2022},
number = {},
pages = {1178874},
pmid = {35155685},
issn = {2314-7156},
mesh = {Adaptive Immunity ; Animals ; Antigen Presentation ; Antigens, Neoplasm/immunology ; CD8-Positive T-Lymphocytes/*immunology ; Cancer Vaccines/*immunology ; Cell Differentiation ; Dendritic Cells/*immunology/transplantation ; Humans ; Immunization ; Immunotherapy/*methods ; Lung Neoplasms/*immunology/secondary ; Lymphocytes, Tumor-Infiltrating/*immunology ; Melanoma/*immunology/pathology ; Melanoma, Experimental ; Mice ; Mice, Inbred C57BL ; Rose Bengal/metabolism ; },
abstract = {Dendritic cell- (DC-) based vaccination has emerged as a promising antitumour immunotherapy. However, overcoming immune tolerance and immunosuppression in the tumour microenvironment (TME) is still a great challenge. Recent studies have shown that Rose Bengal (RB) can effectively induce immunogenic cell death (ICD) in cancer cells, presenting whole tumour antigens for DC processing and presentation. However, the synergistic antitumour effect of combining intralesional RB with immature DCs (RB-iDCs) remains unclear. In the present study, we investigated whether RB-iDCs have superior antitumour effects compared with either single agent and evaluated the immunological mechanism of RB-iDCs in a murine lung cancer model. The results showed that intralesional RB-iDCs suppressed subcutaneous tumour growth and lung metastasis, which resulted in 100% mouse survival and significantly increased TNF-α production by CD8+ T cells. These effects were closely related to the induction of the expression of distinct ICD hallmarks by RB in both bulk cancer cells and cancer stem cells (CSCs), especially calreticulin (CRT), thus enhancing immune effector cell (i.e., CD4+, CD8+, and memory T cells) infiltration and attenuating the accumulation of immunosuppressive cells (i.e., Tregs, macrophages, and myeloid-derived suppressor cells (MDSCs)) in the TME. This study reveals that the RB-iDC vaccine can synergistically destroy the primary tumour, inhibit distant metastasis, and prevent tumour relapse in a lung cancer mouse model, which provides important preclinical data for the development of a novel combinatorial immunotherapy.},
}

Adaptive Immunity
Animals
Antigen Presentation
Antigens, Neoplasm/immunology
CD8-Positive T-Lymphocytes/*immunology
Cancer Vaccines/*immunology
Cell Differentiation
Dendritic Cells/*immunology/transplantation
Humans
Immunization
Immunotherapy/*methods
Lung Neoplasms/*immunology/secondary
Lymphocytes, Tumor-Infiltrating/*immunology
Melanoma/*immunology/pathology
Melanoma, Experimental
Mice
Mice, Inbred C57BL
Rose Bengal/metabolism

@article {pmid34812516,
year = {2022},
author = {Verbrugge, SAJ and Alhusen, JA and Kempin, S and Pillon, NJ and Rozman, J and Wackerhage, H and Kleinert, M},
title = {Genes controlling skeletal muscle glucose uptake and their regulation by endurance and resistance exercise.},
journal = {Journal of cellular biochemistry},
volume = {123},
number = {2},
pages = {202-214},
doi = {10.1002/jcb.30179},
pmid = {34812516},
issn = {1097-4644},
mesh = {Animals ; *Blood Glucose/genetics/metabolism ; *Diabetes Mellitus, Type 2/genetics/metabolism ; Humans ; Insulin Resistance/*genetics ; Muscle, Skeletal/*metabolism ; Physical Endurance/*genetics ; *Resistance Training ; },
abstract = {Exercise improves the insulin sensitivity of glucose uptake in skeletal muscle. Due to that, exercise has become a cornerstone treatment for type 2 diabetes mellitus (T2DM). The mechanisms by which exercise improves skeletal muscle insulin sensitivity are, however, incompletely understood. We conducted a systematic review to identify all genes whose gain or loss of function alters skeletal muscle glucose uptake. We subsequently cross-referenced these genes with recently generated data sets on exercise-induced gene expression and signaling. Our search revealed 176 muscle glucose-uptake genes, meaning that their genetic manipulation altered glucose uptake in skeletal muscle. Notably, exercise regulates the expression or phosphorylation of more than 50% of the glucose-uptake genes or their protein products. This included many genes that previously have not been associated with exercise-induced insulin sensitivity. Interestingly, endurance and resistance exercise triggered some common but mostly unique changes in expression and phosphorylation of glucose-uptake genes or their protein products. Collectively, our work provides a resource of potentially new molecular effectors that play a role in the incompletely understood regulation of muscle insulin sensitivity by exercise.},
}

Animals
*Blood Glucose/genetics/metabolism
*Diabetes Mellitus, Type 2/genetics/metabolism
Humans
Insulin Resistance/*genetics
Muscle, Skeletal/*metabolism
Physical Endurance/*genetics
*Resistance Training

@article {pmid34778983,
year = {2022},
author = {O'Donnell, AJ and Greischar, MA and Reece, SE},
title = {Mistimed malaria parasites re-synchronize with host feeding-fasting rhythms by shortening the duration of intra-erythrocytic development.},
journal = {Parasite immunology},
volume = {44},
number = {3},
pages = {e12898},
doi = {10.1111/pim.12898},
pmid = {34778983},
issn = {1365-3024},
mesh = {Animals ; Circadian Rhythm/physiology ; Fasting ; *Malaria/parasitology/prevention & control ; *Parasites ; *Plasmodium chabaudi/physiology ; },
abstract = {AIMS: Malaria parasites exhibit daily rhythms in the intra-erythrocytic development cycle (IDC) that underpins asexual replication in the blood. The IDC schedule is aligned with the timing of host feeding-fasting rhythms. When the IDC schedule is perturbed to become mismatched to host rhythms, it readily reschedules but it is not known how.

METHODS: We intensively follow four groups of infections that have different temporal alignments between host rhythms and the IDC schedule for 10 days, before and after the peak in asexual densities. We compare how the duration, synchrony and timing of the IDC differs between parasites in control infections and those forced to reschedule by 12 hours and ask whether the density of parasites affects the rescheduling process.

RESULTS AND CONCLUSIONS: Our experiments reveal parasites shorten the IDC duration by 2-3 hours to become realigned to host feeding-fasting rhythms with 5-6 days, in a density-independent manner. Furthermore, parasites are able to reschedule without significant fitness costs for them or their hosts. Understanding the extent of, and limits on, plasticity in the IDC schedule may reveal targets for novel interventions, such as drugs to disrupt IDC regulation and preventing IDC dormancy conferring tolerance to existing drugs.},
}

Animals
Circadian Rhythm/physiology
Fasting
*Malaria/parasitology/prevention & control
*Parasites
*Plasmodium chabaudi/physiology

@article {pmid33945869,
year = {2021},
author = {Sethy, C and Goutam, K and Das, B and Dash, SR and Kundu, CN},
title = {Nectin-4 promotes lymphangiogenesis and lymphatic metastasis in breast cancer by regulating CXCR4-LYVE-1 axis.},
journal = {Vascular pharmacology},
volume = {140},
number = {},
pages = {106865},
doi = {10.1016/j.vph.2021.106865},
pmid = {33945869},
issn = {1879-3649},
mesh = {*Breast Neoplasms/genetics/metabolism/pathology ; Female ; Humans ; Lymphangiogenesis/physiology ; Lymphatic Metastasis/pathology ; *Lymphatic Vessels/metabolism ; Nectins/metabolism ; Receptors, CXCR4/metabolism ; },
abstract = {Tumor-induced lymphangiogenesis promotes tumor progression by generating new lymphatic vessels that helps in tumor dissemination to regional lymph nodes and distant sites. Recently, the role of Nectin-4 in cancer metastasis and angiogenesis has been studied, but its role in lymphangiogenesis is unknown. Here, we systematically delineated the role of Nectin-4 in lymphangiogenesis and its regulation in invasive duct carcinoma (IDC). Nectin-4 expression positively correlated with occurrence risk factors associated with breast cancer (alcohol, smoke, lifestyle habit, etc), CXCR4 expression, and LYVE-1-lymphatic vessel density (LVD). LVD was significantly higher in axillary lymph node (ALN) than primary tumor. Depleting Nectin-4, VEGF-C or both attenuated the important lymphangiogenic marker LYVE-1 expression, tube formation, and migration of ALN derived primary cells. Nectin-4 stimulated the expressions of CXCR4 and CXCL12 under hypoxic conditions in ALN derived primary cells. Further, Nectin-4 augmented expressions of lymphatic metastatic markers (e.g. eNOS, TGF-β, CD-105) and MMPs. Induced expressions of Nectin-4 along with other representative metastatic markers were noted in lymph and blood circulating tumor cells (LCTCs and BCTCs) of local and distant metastatic samples. Thus, Nectin-4 displayed a predominant role in promoting tumor-induced lymphangiogenesis and lymphatic metastasis by modulating CXCR4/CXCL12-LYVE-1- axis.},
}

*Breast Neoplasms/genetics/metabolism/pathology
Female
Humans
Lymphangiogenesis/physiology
Lymphatic Metastasis/pathology
*Lymphatic Vessels/metabolism
Nectins/metabolism
Receptors, CXCR4/metabolism

@article {pmid35311108,
year = {2022},
author = {Zhang, J and Chang, CL and Lu, CY and Chen, HM and Wu, SY},
title = {Anesthesia With Propofol Sedation Reduces Locoregional Recurrence in Patients With Breast Cancer Receiving Total Mastectomy Compared With Non-Propofol Anesthesia.},
journal = {Frontiers in oncology},
volume = {12},
number = {},
pages = {708632},
pmid = {35311108},
issn = {2234-943X},
abstract = {Purpose: We examined locoregional recurrence (LRR) in patients with breast invasive ductal carcinoma (IDC) receiving total mastectomy (TM) under propofol-based paravertebral block-regional anesthesia (PB-RA) versus sevoflurane-based inhalational general anesthesia (INHA-GA) without propofol. All-cause death and distant metastasis were secondary endpoints.

Patients and Methods: Patients with breast IDC receiving TM were recruited through propensity score matching and categorized into INHA-GA with sevoflurane and PB-RA with propofol groups. Cox regression analysis was performed to calculate hazard ratios (HRs) and 95% confidence intervals (CIs).

Results: In the multivariate Cox regression analysis, the adjusted HR (aHR; 95% CI) of LRR for the PB-RA with propofol group was 0.52 (0.28-0.96) compared with the INHA-GA with sevoflurane group. The aHRs of LRR for differentiation grade II, grade III, the American Joint Committee on Cancer clinical stage II, stage III, pathological tumor (pT) stage 2, pT stage 3-4, pathological nodal (pN) stage 1, and pN stage 2-3 were 1.16 (1.04-2.08), 1.28 (1.07-2.12), 3.71 (1.82-7.59), 4.67 (1.65-13.18), 1.09 (1.02-1.21), 1.17 (1.03-2.16), 1.10 (1.03-1.33), and 1.22 (1.06-2.41), respectively, compared with differentiation grade I, clinical stage I, pT1, and pN0. The aHR of LRR for adjuvant RT was 0.88 (0.64-0.94) compared with that for no adjuvant RT.

Conclusion: PB-RA with propofol might be beneficial for reducing LRR in women with breast IDC receiving TM compared with INHA-GA without propofol.},
}

@article {pmid34401774,
year = {2021},
author = {Madhavan, BK and Han, Z and Sickmann, A and Pepperkok, R and Nawroth, PP and Kumar, V},
title = {A laser-mediated photo-manipulative toolbox for generation and real-time monitoring of DNA lesions.},
journal = {STAR protocols},
volume = {2},
number = {3},
pages = {100700},
pmid = {34401774},
issn = {2666-1667},
mesh = {Biomechanical Phenomena/*physiology ; DNA/genetics ; DNA Breaks, Double-Stranded ; DNA Breaks, Single-Stranded ; DNA Damage/genetics ; DNA Repair/genetics/*physiology ; Kinetics ; Lasers ; Microscopy, Confocal/*methods ; },
abstract = {With the advancement of laser-based microscopy tools, it is now possible to explore mechano-kinetic processes occurring inside the cell. Here, we describe the advanced protocol for studying the DNA repair kinetics in real time using the laser to induce the DNA damage. This protocol can be used for inducing, testing, and studying the repair mechanisms associated with DNA double-strand breaks, interstrand cross-link repair, and single-strand break repair. For complete details on the use and execution of this protocol, please refer to Kumar et al. (2017, 2020).},
}

Biomechanical Phenomena/*physiology
DNA/genetics
DNA Breaks, Double-Stranded
DNA Breaks, Single-Stranded
DNA Damage/genetics
DNA Repair/genetics/*physiology
Kinetics
Lasers
Microscopy, Confocal/*methods

@article {pmid33983449,
year = {2022},
author = {March, DS and Lai, KB and Neal, T and Graham-Brown, MPM and Highton, PJ and Churchward, DR and Young, HML and Dungey, M and Stensel, DJ and Smith, AC and Bishop, NC and Szeto, CC and Burton, JO},
title = {Circulating endotoxin and inflammation: associations with fitness, physical activity and the effect of a 6-month programme of cycling exercise during haemodialysis.},
journal = {Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association},
volume = {37},
number = {2},
pages = {366-374},
doi = {10.1093/ndt/gfab178},
pmid = {33983449},
issn = {1460-2385},
mesh = {*Endotoxins ; Exercise ; Humans ; Inflammation/etiology ; Physical Fitness ; *Renal Dialysis/adverse effects ; },
abstract = {BACKGROUND: Intradialytic cycling (IDC) may provide cardiovascular benefits to individuals receiving haemodialysis, but the exact mechanism behind these improvements remains unclear. The primary aim of this study was to investigate the effect of a 6-month programme of IDC on circulating endotoxin (secondary analysis from the CYCLE-HD trial). Secondary aims were to investigate changes in circulating cytokines [interleukin-6 (IL-6), IL-10, tumour necrosis factor-α, C-reactive protein (CRP) and the IL-6:IL-10 ratio] and their associations with physical activity, fitness and cardiovascular outcomes.

METHODS: Participants were randomized to either a 6-month programme of IDC (thrice weekly, moderate intensity cycling at a rating of perceived exertion of 12-14) in addition to usual care (n = 46) or usual care only (control group; n = 46). Outcome measures were obtained at baseline and then again at 6 months.

RESULTS: There was no significant (P = 0.137) difference in circulating endotoxin between groups at 6 months (IDC group: 0.34 ± 0.08 EU/mL; control group: 0.37 ± 0.07 EU/mL). There were no significant between-group differences in any circulating cytokine following the 6-month programme of IDC. Higher levels of physical activity and fitness were associated with lower levels of endotoxin, IL-6, CRP and IL-6:IL-10 ratio.

CONCLUSIONS: Our data show no change in circulating endotoxin or cytokines following a 6-month programme of IDC. However, higher levels of physical activity outside of haemodialysis were associated with lower levels of inflammation.},
}

*Endotoxins
Exercise
Humans
Inflammation/etiology
Physical Fitness
*Renal Dialysis/adverse effects

@article {pmid34014371,
year = {2021},
author = {Giroud, M and Tsokanos, FF and Caratti, G and Kotschi, S and Khani, S and Jouffe, C and Vogl, ES and Irmler, M and Glantschnig, C and Gil-Lozano, M and Hass, D and Khan, AA and Garcia, MR and Mattijssen, F and Maida, A and Tews, D and Fischer-Posovszky, P and Feuchtinger, A and Virtanen, KA and Beckers, J and Wabitsch, M and Uhlenhaut, H and Blüher, M and Tuckermann, J and Scheideler, M and Bartelt, A and Herzig, S},
title = {HAND2 is a novel obesity-linked adipogenic transcription factor regulated by glucocorticoid signalling.},
journal = {Diabetologia},
volume = {64},
number = {8},
pages = {1850-1865},
pmid = {34014371},
issn = {1432-0428},
mesh = {Adipocytes/*metabolism ; Adipogenesis/physiology ; Adipose Tissue, Brown/metabolism ; Adult ; Aged ; Animals ; Basic Helix-Loop-Helix Transcription Factors/*genetics ; Cross-Sectional Studies ; Female ; Gene Expression Regulation/*physiology ; Gene Silencing ; Glucocorticoids/*pharmacology ; Humans ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Middle Aged ; Obesity/*genetics ; Real-Time Polymerase Chain Reaction ; Signal Transduction ; Transcription Factors/*genetics ; Young Adult ; },
abstract = {AIMS/HYPOTHESIS: Adipocytes are critical cornerstones of energy metabolism. While obesity-induced adipocyte dysfunction is associated with insulin resistance and systemic metabolic disturbances, adipogenesis, the formation of new adipocytes and healthy adipose tissue expansion are associated with metabolic benefits. Understanding the molecular mechanisms governing adipogenesis is of great clinical potential to efficiently restore metabolic health in obesity. Here we investigate the role of heart and neural crest derivatives-expressed 2 (HAND2) in adipogenesis.

METHODS: Human white adipose tissue (WAT) was collected from two cross-sectional studies of 318 and 96 individuals. In vitro, for mechanistic experiments we used primary adipocytes from humans and mice as well as human multipotent adipose-derived stem (hMADS) cells. Gene silencing was performed using siRNA or genetic inactivation in primary adipocytes from loxP and or tamoxifen-inducible Cre-ERT2 mouse models with Cre-encoding mRNA or tamoxifen, respectively. Adipogenesis and adipocyte metabolism were measured by Oil Red O staining, quantitative PCR (qPCR), microarray, glucose uptake assay, western blot and lipolysis assay. A combinatorial RNA sequencing (RNAseq) and ChIP qPCR approach was used to identify target genes regulated by HAND2. In vivo, we created a conditional adipocyte Hand2 deletion mouse model using Cre under control of the Adipoq promoter (Hand2AdipoqCre) and performed a large panel of metabolic tests.

RESULTS: We found that HAND2 is an obesity-linked white adipocyte transcription factor regulated by glucocorticoids that was necessary but insufficient for adipocyte differentiation in vitro. In a large cohort of humans, WAT HAND2 expression was correlated to BMI. The HAND2 gene was enriched in white adipocytes compared with brown, induced early in differentiation and responded to dexamethasone (DEX), a typical glucocorticoid receptor (GR, encoded by NR3C1) agonist. Silencing of NR3C1 in hMADS cells or deletion of GR in a transgenic conditional mouse model results in diminished HAND2 expression, establishing that adipocyte HAND2 is regulated by glucocorticoids via GR in vitro and in vivo. Furthermore, we identified gene clusters indirectly regulated by the GR-HAND2 pathway. Interestingly, silencing of HAND2 impaired adipocyte differentiation in hMADS and primary mouse adipocytes. However, a conditional adipocyte Hand2 deletion mouse model using Cre under control of the Adipoq promoter did not mirror these effects on adipose tissue differentiation, indicating that HAND2 was required at stages prior to Adipoq expression.

CONCLUSIONS/INTERPRETATION: In summary, our study identifies HAND2 as a novel obesity-linked adipocyte transcription factor, highlighting new mechanisms of GR-dependent adipogenesis in humans and mice.

DATA AVAILABILITY: Array data have been submitted to the GEO database at NCBI (GSE148699).},
}

Adipocytes/*metabolism
Adipogenesis/physiology
Adipose Tissue, Brown/metabolism
Adult
Aged
Animals
Basic Helix-Loop-Helix Transcription Factors/*genetics
Cross-Sectional Studies
Female
Gene Expression Regulation/*physiology
Gene Silencing
Glucocorticoids/*pharmacology
Humans
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Middle Aged
Obesity/*genetics
Real-Time Polymerase Chain Reaction
Signal Transduction
Transcription Factors/*genetics
Young Adult

@article {pmid35260605,
year = {2022},
author = {McLamore, Q and Syropoulos, S and Leidner, B and Hirschberger, G and Young, K and Zein, RA and Baumert, A and Bilewicz, M and Bilgen, A and van Bezouw, MJ and Chatard, A and Chekroun, P and Chinchilla, J and Choi, HS and Euh, H and Gomez, A and Kardos, P and Khoo, YH and Li, M and Légal, JB and Loughnan, S and Mari, S and Tan-Mansukhani, R and Muldoon, O and Noor, M and Paladino, MP and Petrović, N and Selvanathan, HP and Uluğ, ÖM and Wohl, MJ and Yeung, WLV and Burrows, B},
title = {Trust in scientific information mediates associations between conservatism and coronavirus responses in the U.S., but few other nations.},
journal = {Scientific reports},
volume = {12},
number = {1},
pages = {3724},
pmid = {35260605},
issn = {2045-2322},
support = {2028922//National Science Foundation/ ; 2028922//National Science Foundation/ ; 2028922//National Science Foundation/ ; 2028922//National Science Foundation/ ; },
mesh = {Adult ; Aged ; Attitude ; COVID-19/*epidemiology/virology ; Canada ; Female ; Health Behavior ; Humans ; Indonesia ; Male ; Middle Aged ; *Politics ; Quarantine ; SARS-CoV-2/isolation & purification ; Surveys and Questionnaires ; *Trust ; United States/epidemiology ; },
abstract = {U.S.-based research suggests conservatism is linked with less concern about contracting coronavirus and less preventative behaviors to avoid infection. Here, we investigate whether these tendencies are partly attributable to distrust in scientific information, and evaluate whether they generalize outside the U.S., using public data and recruited representative samples across three studies (Ntotal = 34,710). In Studies 1 and 2, we examine these relationships in the U.S., yielding converging evidence for a sequential indirect effect of conservatism on compliance through scientific (dis)trust and infection concern. In Study 3, we compare these relationships across 19 distinct countries. Although the relationships between trust in scientific information about the coronavirus, concern about coronavirus infection, and compliance are consistent cross-nationally, the relationships between conservatism and trust in scientific information are not. These relationships are strongest in North America. Consequently, the indirect effects observed in Studies 1-2 only replicate in North America (the U.S. and Canada) and in Indonesia. Study 3 also found parallel direct and indirect effects on support for lockdown restrictions. These associations suggest not only that relationships between conservatism and compliance are not universal, but localized to particular countries where conservatism is more strongly related to trust in scientific information about the coronavirus pandemic.},
}

Adult
Aged
Attitude
COVID-19/*epidemiology/virology
Canada
Female
Health Behavior
Humans
Indonesia
Male
Middle Aged
*Politics
Quarantine
SARS-CoV-2/isolation & purification
Surveys and Questionnaires
*Trust
United States/epidemiology

@article {pmid34725819,
year = {2022},
author = {Chen, X and Zhang, C and Guo, D and Wang, Y and Hu, J and Hu, J and Wang, S and Liu, X},
title = {Distant metastasis and prognostic factors in patients with invasive ductal carcinoma of the breast.},
journal = {European journal of clinical investigation},
volume = {52},
number = {4},
pages = {e13704},
doi = {10.1111/eci.13704},
pmid = {34725819},
issn = {1365-2362},
support = {2017YFC0108602//The National Key Research and Development Program of China/ ; },
mesh = {Adult ; Aged ; Breast Neoplasms/*pathology ; Carcinoma, Ductal, Breast/*mortality/pathology/*secondary ; Female ; Humans ; Middle Aged ; Neoplasm Invasiveness ; Nomograms ; Prognosis ; Risk Factors ; Survival Rate ; },
abstract = {OBJECTIVE: To explore the risk factors and prognostic factors of invasive ductal carcinoma (IDC) and to predict the survival of IDC patients with metastasis.

METHOD: We used multivariate logistic regression to identify independent risk factors affecting metastasis in IDC patients and used Cox regression to identify independent prognostic factors affecting the overall survival of patients with metastasis. Nomogram was used to predict survival, while C-index and calibration curves were used to measure the performance of nomogram. Kaplan-Meier method was used to calculate the survival curves of patients with different independent prognostics factors and different metastatic sites, and the differences were compared by log-rank test. The data of our study were obtained from the Surveillance, Epidemiology and End Results cancer registry.

RESULT: Our study included 226,094 patients with IDC. In multivariate analysis, independent risk factors of metastasis included age, race, marital status, income, geographic region, grade, T stage, N stage, subtype, surgery and radiotherapy. Independent prognostic factors included age, race, marital status, income, geographic region, grade, T stage, N stage, subtype, surgery and chemotherapy. We established a nomogram, of which the C-index was 0.701 (0.693, 0.709), with the calibration curves showing that the disease-specific survival between actual observation and prediction had a good consistency. The survival curves of different metastatic patterns were significantly different (log-rank test: χ2 = 18784, p < 0.001; χ2 = 47.1, p < 0.001; χ2 = 20, p < 0.001).

CONCLUSION: The nomogram we established may provide risk assessment and survival prediction for IDC patients with metastasis, which can be used for clinical decision-making and reference.},
}

Adult
Aged
Breast Neoplasms/*pathology
Carcinoma, Ductal, Breast/*mortality/pathology/*secondary
Female
Humans
Middle Aged
Neoplasm Invasiveness
Nomograms
Prognosis
Risk Factors
Survival Rate

@article {pmid34561670,
year = {2021},
author = {Kumar, V and Nawroth, PP},
title = {Is the association between diabetes mellitus and pulmonary fibrosis real?.},
journal = {Nature reviews. Endocrinology},
volume = {17},
number = {12},
pages = {703-704},
pmid = {34561670},
issn = {1759-5037},
mesh = {*Diabetes Mellitus/epidemiology ; Humans ; *Pulmonary Fibrosis/epidemiology ; Risk Factors ; },
}

*Diabetes Mellitus/epidemiology
Humans
*Pulmonary Fibrosis/epidemiology
Risk Factors

@article {pmid34527961,
year = {2021},
author = {Loft, A and Herzig, S and Schmidt, SF},
title = {Purification of GFP-tagged nuclei from frozen livers of INTACT mice for RNA- and ATAC-sequencing.},
journal = {STAR protocols},
volume = {2},
number = {3},
pages = {100805},
pmid = {34527961},
issn = {2666-1667},
mesh = {Animals ; Cell Nucleus/*chemistry/metabolism ; *Chromatin Immunoprecipitation Sequencing ; Cytological Techniques/*methods ; Female ; Green Fluorescent Proteins/*chemistry/genetics/metabolism ; Liver/chemistry/*cytology ; Male ; Mice ; *RNA-Seq ; },
abstract = {Isolation of nuclei tagged in specific cell types (INTACT) allows for stress-free and high-throughput analyses of cellular subpopulations. Here, we present an improved protocol for isolation of pure and high-quality GFP-labeled nuclei from frozen livers of INTACT mice, as well as protocols for downstream sequencing analyses. The adaptation to frozen tissue provides a pause point that allows sampling at multiple time points and/or phenotypic characterization of livers prior to nuclei isolation and downstream analyses. For complete details on the use of this protocol, please refer to Loft et al. (2021).},
}

Animals
Cell Nucleus/*chemistry/metabolism
*Chromatin Immunoprecipitation Sequencing
Cytological Techniques/*methods
Female
Green Fluorescent Proteins/*chemistry/genetics/metabolism
Liver/chemistry/*cytology
Male
Mice
*RNA-Seq

@article {pmid34117742,
year = {2021},
author = {Fortunato, A and Mallo, D and Rupp, SM and King, LM and Hardman, T and Lo, JY and Hall, A and Marks, JR and Hwang, ES and Maley, CC},
title = {A new method to accurately identify single nucleotide variants using small FFPE breast samples.},
journal = {Briefings in bioinformatics},
volume = {22},
number = {6},
pages = {},
pmid = {34117742},
issn = {1477-4054},
support = {U54 CA217376/CA/NCI NIH HHS/United States ; R01 CA185138/CA/NCI NIH HHS/United States ; U2C CA233254/CA/NCI NIH HHS/United States ; P01 CA091955/CA/NCI NIH HHS/United States ; R01 CA170595/CA/NCI NIH HHS/United States ; R01 CA140657/CA/NCI NIH HHS/United States ; },
mesh = {*Biomarkers, Tumor ; Breast Neoplasms/*diagnosis/*genetics ; Computational Biology/*methods ; DNA, Neoplasm ; Female ; Genetic Heterogeneity ; Genetic Testing/methods/standards ; High-Throughput Nucleotide Sequencing ; Humans ; Mutation ; *Polymorphism, Single Nucleotide ; Workflow ; },
abstract = {Most tissue collections of neoplasms are composed of formalin-fixed and paraffin-embedded (FFPE) excised tumor samples used for routine diagnostics. DNA sequencing is becoming increasingly important in cancer research and clinical management; however it is difficult to accurately sequence DNA from FFPE samples. We developed and validated a new bioinformatic pipeline to use existing variant-calling strategies to robustly identify somatic single nucleotide variants (SNVs) from whole exome sequencing using small amounts of DNA extracted from archival FFPE samples of breast cancers. We optimized this strategy using 28 pairs of technical replicates. After optimization, the mean similarity between replicates increased 5-fold, reaching 88% (range 0-100%), with a mean of 21.4 SNVs (range 1-68) per sample, representing a markedly superior performance to existing tools. We found that the SNV-identification accuracy declined when there was less than 40 ng of DNA available and that insertion-deletion variant calls are less reliable than single base substitutions. As the first application of the new algorithm, we compared samples of ductal carcinoma in situ of the breast to their adjacent invasive ductal carcinoma samples. We observed an increased number of mutations (paired-samples sign test, P < 0.05), and a higher genetic divergence in the invasive samples (paired-samples sign test, P < 0.01). Our method provides a significant improvement in detecting SNVs in FFPE samples over previous approaches.},
}

*Biomarkers, Tumor
Breast Neoplasms/*diagnosis/*genetics
Computational Biology/*methods
DNA, Neoplasm
Female
Genetic Heterogeneity
Genetic Testing/methods/standards
High-Throughput Nucleotide Sequencing
Humans
Mutation
*Polymorphism, Single Nucleotide
Workflow

@article {pmid35272171,
year = {2022},
author = {Acikgoz, E and Duzagac, F and Guven, U and Yigitturk, G and Kose, T and Oktem, G},
title = {"Double hit" strategy: Removal of sialic acid from the dendritic cell surface and loading with CD44+/CD24-/low cell lysate inhibits tumor growth and metastasis by targeting breast cancer stem cells.},
journal = {International immunopharmacology},
volume = {107},
number = {},
pages = {108684},
doi = {10.1016/j.intimp.2022.108684},
pmid = {35272171},
issn = {1878-1705},
abstract = {Cancer stem cells (CSCs), which represent the root cause of resistance to conventional treatments, recurrence, and metastasis, constitute the critical point of failure in cancer treatments. Targeting CSCs with dendritic cell (DC)-based vaccines have been an effective strategy, but sialic acids on the surface of DCs limit the interaction with loaded antigens. We hypothesized that removal of sialic acid moieties on immature DCs (iDCs) could significantly affect DC-CSC-antigen loading, thereby leading to DC maturation and improving immune recognition and activity. The lysate of CD44+/CD24-/low breast CSCs (BCSCs) was pulsed with sialidase-treated DCs to obtain mature dendritic cells (mDCs). The roles of cytoskeletal elements in antigen uptake and dendritic cell maturation were determined by immunofluorescence staining, flow cytometry, and cytokine measurement, respectively. To test the efficacy of the vaccine in vivo, CSCs tumor-bearing mice were immunized with iDC or mDC. Pulsing DCs with antigen increased the expression levels of actin, gelsolin, talin, WASp, and Arp2, especially in podosome-like regions. Compared with iDCs, mDCs expressed high levels of CD40, CD80, CD86 costimulatory molecules and increased IL-12 production. Vaccination with mDC: i) increased CD8+ and CD4 + T-cell numbers, ii) prevented tumor growth with anti-mitotic activity and apoptotic induction, iii) suppressed metastasis by decreasing Snail, Slug, and Twist expressions. This study reveals for the first time that sialic acid removal and loading with CSC antigens induces significant molecular, morphological, and functional changes in DCs and that this new DC identity may be considered for future combined immunotherapy strategies against breast tumors.},
}

@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.},
}

Adult
Aged
Aged, 80 and over
Breast Neoplasms/*genetics/pathology
Female
Humans
Middle Aged
Prognosis
Retrospective Studies

@article {pmid33966256,
year = {2021},
author = {Tsokanos, FF and Muley, C and Khani, S and Hass, D and Fleming, T and Wolff, G and Bartelt, A and Nawroth, P and Herzig, S},
title = {Methylglyoxal Drives a Distinct, Nonclassical Macrophage Activation Status.},
journal = {Thrombosis and haemostasis},
volume = {121},
number = {11},
pages = {1464-1475},
doi = {10.1055/s-0041-1726346},
pmid = {33966256},
issn = {2567-689X},
support = {Deutsche Forschungsgemeinschaft//SFB1118/ ; },
mesh = {Animals ; Cells, Cultured ; Gene Expression Profiling ; Glycolysis/*drug effects ; Macrophage Activation/*drug effects ; Macrophages/*drug effects/immunology/metabolism ; Mice ; Phenotype ; Phosphorylation ; Pyruvaldehyde/*toxicity ; Signal Transduction ; Transcriptome ; p38 Mitogen-Activated Protein Kinases/metabolism ; },
abstract = {Metabolic complications in diabetic patients are driven by a combination of increased levels of nutrients and the presence of a proinflammatory environment. Methylglyoxal (MG) is a toxic byproduct of catabolism and has been strongly associated with the development of such complications. Macrophages are key mediators of inflammatory processes and their contribution to the development of metabolic complications has been demonstrated. However, a direct link between reactive metabolites and macrophage activation has not been demonstrated yet. Here, we show that acute MG treatment activated components of the p38 MAPK pathway and enhanced glycolysis in primary murine macrophages. MG induced a distinct gene expression profile sharing similarities with classically activated proinflammatory macrophages as well as metabolically activated macrophages usually found in obese patients. Transcriptomic analysis revealed a set of 15 surface markers specifically upregulated in MG-treated macrophages, thereby establishing a new set of targets for diagnostic or therapeutic purposes under high MG conditions, including diabetes. Overall, our study defines a new polarization state of macrophages that may specifically link aberrant macrophage activation to reactive metabolites in diabetes.},
}

Animals
Cells, Cultured
Gene Expression Profiling
Glycolysis/*drug effects
Macrophage Activation/*drug effects
Macrophages/*drug effects/immunology/metabolism
Mice
Phenotype
Phosphorylation
Pyruvaldehyde/*toxicity
Signal Transduction
Transcriptome
p38 Mitogen-Activated Protein Kinases/metabolism

@article {pmid33370550,
year = {2021},
author = {Wang, M and Zeng, W and Zhang, Z and Zhang, W and Su, H and Zhang, Z and Jiang, L and Liu, Y and Shi, Q},
title = {The Improvement of Immune Effect of Recombinant Human Beta-Defensin 2 on Hepatitis B Vaccine in Mice.},
journal = {Viral immunology},
volume = {34},
number = {2},
pages = {96-111},
doi = {10.1089/vim.2020.0052},
pmid = {33370550},
issn = {1557-8976},
mesh = {Animals ; *Hepatitis B/prevention & control ; Hepatitis B Antibodies ; Hepatitis B Surface Antigens/genetics ; Hepatitis B Vaccines ; Hepatitis B virus ; Humans ; Mice ; Mice, Inbred BALB C ; *beta-Defensins/genetics ; },
abstract = {Immunization with hepatitis B vaccine is an effective measure for prevention and control of hepatitis B Virus (HBV) infection. Although lots of efforts to improve the effect of hepatitis B vaccine have been made, the function of human beta defensin 2 (hBD2) on hepatitis B vaccine keeps unclear. In this article, we report that hBD2 not only promoted the activation and maturation of immature dendritic cells (iDCs) by increasing MHC II and CD86 expression, but it also significantly upregulated the mRNA level of IL-6 and IL-12B in mouse bone marrow-derived dendritic cells. The serum concentrations of IFN-γ in mice stimulated with 300 ng hBD2 increased from 25.21 to 42.04 pg/mL, with a time extension from 4 to 12 h post-injection. During the process of three times immunization (1, 14, 28 days) with 3 μg hepatitis B vaccine combined with or without 300 ng hBD2 with a 2 week interval in BALB/c mice, the antibody against HBsAg (HBsAb) concentration in serum at every time point of observation in the combined group was statistically higher than the hepatitis B vaccine group. The serum concentration of IgG2a subclass HBsAb on the 14th day post last injection in the combined group was significantly higher than the hepatitis B vaccine group. Further, the splenic cells from the mice treated with both hBD2 and hepatitis B vaccine possessed a greater ability to produce a surface antigen of hepatitis B virus (HBsAg) specific IFN-γ than those treated with hepatitis B vaccine alone. The percentages of CD3+/CD4+ T cells and CD3+/CD8+ T lymphocytes in spleens from the mice treated with 300 ng hBD2 were statistically higher than the phosphate buffered saline group. These data suggest that hBD2 improves iDC maturation and the immune efficiency of hepatitis B vaccine in BALB/c mice.},
}

Animals
*Hepatitis B/prevention & control
Hepatitis B Antibodies
Hepatitis B Surface Antigens/genetics
Hepatitis B Vaccines
Hepatitis B virus
Humans
Mice
Mice, Inbred BALB C
*beta-Defensins/genetics

@article {pmid35247977,
year = {2022},
author = {Foster, GJ and Sievert, MAC and Button-Simons, K and Vendrely, KM and Romero-Severson, J and Ferdig, MT},
title = {Cyclical regression covariates remove the major confounding effect of cyclical developmental gene expression with strain-specific drug response in the malaria parasite Plasmodium falciparum.},
journal = {BMC genomics},
volume = {23},
number = {1},
pages = {180},
pmid = {35247977},
issn = {1471-2164},
support = {P01 AI127338/NH/NIH HHS/United States ; },
mesh = {Animals ; *Antimalarials/pharmacology/therapeutic use ; Drug Resistance ; Genes, Developmental ; Humans ; *Malaria, Falciparum/parasitology ; *Parasites/genetics ; Plasmodium falciparum ; Protozoan Proteins/genetics ; },
abstract = {BACKGROUND: The cyclical nature of gene expression in the intraerythrocytic development cycle (IDC) of the malaria parasite, Plasmodium falciparum, confounds the accurate detection of specific transcriptional differences, e.g. as provoked by the development of drug resistance. In lab-based studies, P. falciparum cultures are synchronized to remove this confounding factor, but the rapid detection of emerging resistance to artemisinin therapies requires rapid analysis of transcriptomes extracted directly from clinical samples. Here we propose the use of cyclical regression covariates (CRC) to eliminate the major confounding effect of developmentally driven transcriptional changes in clinical samples. We show that elimination of this confounding factor reduces both Type I and Type II errors and demonstrate the effectiveness of this approach using a published dataset of 1043 transcriptomes extracted directly from patient blood samples with different patient clearance times after treatment with artemisinin.

RESULTS: We apply this method to two publicly available datasets and demonstrate its ability to reduce the confounding of differences in transcript levels due to misaligned intraerythrocytic development time. Adjusting the clinical 1043 transcriptomes dataset with CRC results in detection of fewer functional categories than previously reported from the same data set adjusted using other methods. We also detect mostly the same functional categories, but observe fewer genes within these categories. Finally, the CRC method identifies genes in a functional category that was absent from the results when the dataset was adjusted using other methods. Analysis of differential gene expression in the clinical data samples that vary broadly for developmental stage resulted in the detection of far fewer transcripts in fewer functional categories while, at the same time, identifying genes in two functional categories not present in the unadjusted data analysis. These differences are consistent with the expectation that CRC reduces both false positives and false negatives with the largest effect on datasets from samples with greater variance in developmental stage.

CONCLUSIONS: Cyclical regression covariates have immediate application to parasite transcriptome sequencing directly from clinical blood samples and to cost-constrained in vitro experiments.},
}

Animals
*Antimalarials/pharmacology/therapeutic use
Drug Resistance
Genes, Developmental
Humans
*Malaria, Falciparum/parasitology
*Parasites/genetics
Plasmodium falciparum
Protozoan Proteins/genetics

@article {pmid35220223,
year = {2022},
author = {Dantas, FT and Felix-Silva, PH and Angotti-Carrara, HH and Dos-Reis, FJC and Junior, MT and DE-Souza, SLS and Palioto, DB},
title = {A New Method for Obtaining Tumor Interstitial Fluid Applied to Cytokine Analysis of Breast Carcinoma Samples.},
journal = {Anticancer research},
volume = {42},
number = {3},
pages = {1327-1332},
doi = {10.21873/anticanres.15600},
pmid = {35220223},
issn = {1791-7530},
mesh = {Adult ; Aged ; Biomarkers, Tumor/*analysis ; Biopsy, Large-Core Needle ; Breast Neoplasms/*immunology ; Carcinoma, Ductal, Breast/*immunology ; Enzyme-Linked Immunosorbent Assay ; Extracellular Fluid/*immunology ; Female ; Humans ; Interleukin-1beta/*analysis ; Middle Aged ; Tumor Microenvironment ; },
abstract = {BACKGROUND/AIM: Tumor interstitial fluid (TIF), a component of the tumor microenvironment, is a valuable source of molecules and substances that help in diagnosis and prognosis of solid tumors. There is still no consensus on the optimal method for collecting TIF. Therefore, this study aimed to evaluate the effectiveness of a new method of collecting TIF in invasive ductal carcinoma (IDC) samples for cytokine interleukin 1β (IL1β) quantification.

MATERIALS AND METHODS: Forty women allowed the collection of TIF using absorbent paper strips during the performance of the core biopsy. The samples were stored at a temperature of -80°C and then analyzed using an enzyme-linked immunoassay.

RESULTS: The mean values for IL1β and total protein were 11.39 mg/ml and 2.15 mg/ml, respectively.

CONCLUSION: it was possible to quantify the cytokine IL1β and the total protein concentration present in the tumor tissue through TIF collection with the use of absorbent paper filters, demonstrating the effectiveness of this new method in oncology.},
}

Adult
Aged
Biomarkers, Tumor/*analysis
Biopsy, Large-Core Needle
Breast Neoplasms/*immunology
Carcinoma, Ductal, Breast/*immunology
Enzyme-Linked Immunosorbent Assay
Extracellular Fluid/*immunology
Female
Humans
Interleukin-1beta/*analysis
Middle Aged
Tumor Microenvironment

@article {pmid34975349,
year = {2021},
author = {Rafiq, MT and Hamid, MSA and Hafiz, E},
title = {Short-Term Effects of Strengthening Exercises of the Lower Limb Rehabilitation Protocol on Pain, Stiffness, Physical Function, and Body Mass Index among Knee Osteoarthritis Participants Who Were Overweight or Obese: A Clinical Trial.},
journal = {TheScientificWorldJournal},
volume = {2021},
number = {},
pages = {6672274},
pmid = {34975349},
issn = {1537-744X},
mesh = {*Body Mass Index ; *Exercise Therapy ; Female ; Humans ; Lower Extremity/*physiopathology ; Male ; Middle Aged ; Obesity/*complications ; Osteoarthritis, Knee/complications/physiopathology/*rehabilitation ; Overweight/*complications ; Pain/*complications ; Range of Motion, Articular ; Single-Blind Method ; },
abstract = {Background: Osteoarthritis (OA) of the knee is defined as a progressive disease of the synovial joints and is characterized by wear and tear of the cartilage and underlying bone. This study aimed to determine the short-term effects of the lower limb rehabilitation protocol (LLRP) on pain, stiffness, physical function, and body mass index (BMI) among knee OA participants who were overweight or obese. Methodology. A single-blinded randomized controlled trial of one-month duration was conducted at Rehmatul-Lil-Alameen Postgraduate Institute, Lahore, Pakistan. Fifty overweight or obese participants with knee OA were randomly divided into two groups by a computer-generated number. Participants in the rehabilitation protocol group (RPG) were provided with leaflets explaining the strengthening exercises of the LLRP and instruction of daily care (IDC), while the participants in the control group (CG) were provided with leaflets explaining the IDC only for a duration of four weeks. The primary outcome measures were the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores for pain, stiffness, and physical function. The secondary outcome measures were BMI, exercise adherence, and patients' satisfaction assessed by using the numeric rating scale ranging from 0 to 10. The paired-sample t-test was used to analyze the differences within groups from baseline to posttest evaluations. The analysis of variance 2 × 2 factor was used to analyze the differences in BMI, knee pain, stiffness, and physical function between the groups.

Results: Participants in the RPG and CG reported a statistically significant reduction in knee pain and stiffness (p ≤ 0.05) within the group. The reduction in the scores of knee pain was higher in participants in the RPG than that in participants in the CG (p=0.001). Additionally, participants in the RPG reported greater satisfaction (p=0.001) and higher self-reported exercise adherence (p=0.010) and coordinator-reported exercise adherence (p=0.046) than the participants in the CG.

Conclusion: Short-term effects of the LLRP appear to reduce knee pain and stiffness only, but not physical function and BMI.},
}

*Body Mass Index
*Exercise Therapy
Female
Humans
Lower Extremity/*physiopathology
Male
Middle Aged
Obesity/*complications
Osteoarthritis, Knee/complications/physiopathology/*rehabilitation
Overweight/*complications
Pain/*complications
Range of Motion, Articular
Single-Blind Method

@article {pmid35245349,
year = {2022},
author = {Hophan, SL and Odnokoz, O and Liu, H and Luo, Y and Khan, S and Gradishar, W and Zhou, Z and Badve, S and Torres, MA and Wan, Y},
title = {Ductal carcinoma in situ of breast: from molecular etiology to therapeutic management.},
journal = {Endocrinology},
volume = {},
number = {},
pages = {},
doi = {10.1210/endocr/bqac027},
pmid = {35245349},
issn = {1945-7170},
abstract = {Ductal Carcinoma in Situ (DCIS) makes up a majority of the non-invasive breast cancer cases. DCIS is a neoplastic proliferation of epithelial cells within the ductal structure of the breast. Currently, there is little known about the progression of DCIS to invasive ductal carcinoma (IDC), or the molecular etiology behind each DCIS lesion or grade. The DCIS lesions can be heterogeneous in morphology, genetics, cellular biology, and clinical behavior, posing challenges to our understanding of the molecular mechanisms for progression into an invasive status by approximately half of all DCIS lesions. New strategies that target molecular mechanisms are necessary to overcome this gap in understanding, which is a barrier to more targeted therapy. In this review, we will discuss the etiological factors associated with DCIS, as well as the complexity of each nuclear grade lesion. Moreover, we will discuss the possible molecular features that lead to progression of DCIS to IDC. We will highlight current therapeutic management and areas for improvement.},
}

@article {pmid35130270,
year = {2022},
author = {Khanam, R and Applegate, J and Nisar, I and Dutta, A and Rahman, S and Nizar, A and Ali, SM and Chowdhury, NH and Begum, F and Dhingra, U and Tofail, F and Mehmood, U and Deb, S and Ahmed, S and Muhammad, S and Das, S and Ahmed, S and Mittal, H and Minckas, N and Yoshida, S and Bahl, R and Jehan, F and Sazawal, S and Baqui, AH},
title = {Burden and risk factors for antenatal depression and its effect on preterm birth in South Asia: A population-based cohort study.},
journal = {PloS one},
volume = {17},
number = {2},
pages = {e0263091},
pmid = {35130270},
issn = {1932-6203},
mesh = {Adult ; Asia/epidemiology ; Bangladesh/epidemiology ; Cohort Studies ; Depression/complications/*epidemiology ; Female ; Humans ; Infant, Newborn ; Pakistan/epidemiology ; Pregnancy ; Pregnancy Complications/epidemiology/psychology ; Pregnancy Outcome/*epidemiology/psychology ; Premature Birth/*epidemiology ; Prenatal Care/statistics & numerical data ; Risk Factors ; Young Adult ; },
abstract = {INTRODUCTION: Women experience high rates of depression, particularly during pregnancy and the postpartum periods. Using population-based data from Bangladesh and Pakistan, we estimated the burden of antenatal depression, its risk factors, and its effect on preterm birth.

METHODS: The study uses the following data: maternal depression measured between 24 and 28 weeks of gestation using the 9-question Patient Health Questionnaire (PHQ-9); data on pregnancy including an ultrasound before 19 weeks of gestation; data on pregnancy outcomes; and data on woman's age, education, parity, weight, height, history of previous illness, prior miscarriage, stillbirth, husband's education, and household socioeconomic data collected during early pregnancy. Using PHQ-9 cutoff score of ≥12, women were categorized into none to mild depression or moderate to moderately severe depression. Using ultrasound data, preterm birth was defined as babies born <37 weeks of gestation. To identify risk ratios (RR) for antenatal depression, unadjusted and adjusted RR and 95% confidence intervals (CI) were calculated using log- binomial model. Log-binomial models were also used for determining the effect of antenatal depression on preterm birth adjusting for potential confounders. Data were analyzed using Stata version 16 (StataCorp LP).

RESULTS: About 6% of the women reported moderate to moderately severe depressive symptoms during the antenatal period. A parity of ≥2 and the highest household wealth status were associated with an increased risk of depression. The overall incidence of preterm birth was 13.4%. Maternal antenatal depression was significantly associated with the risk of preterm birth (ARR, 95% CI: 1.34, 1.02-1.74).

CONCLUSION: The increased risk of preterm birth in women with antenatal depression in conjunction with other significant risk factors suggests that depression likely occurs within a constellation of other risk factors. Thus, to effectively address the burden of preterm birth, programs require developing and providing integrated care addressing multiple risk factors.},
}

Adult
Asia/epidemiology
Bangladesh/epidemiology
Cohort Studies
Depression/complications/*epidemiology
Female
Humans
Infant, Newborn
Pakistan/epidemiology
Pregnancy
Pregnancy Complications/epidemiology/psychology
Pregnancy Outcome/*epidemiology/psychology
Premature Birth/*epidemiology
Prenatal Care/statistics & numerical data
Risk Factors
Young Adult

@article {pmid34841287,
year = {2021},
author = {Erener, S and Ellis, CE and Ramzy, A and Glavas, MM and O'Dwyer, S and Pereira, S and Wang, T and Pang, J and Bruin, JE and Riedel, MJ and Baker, RK and Webber, TD and Lesina, M and Blüher, M and Algül, H and Kopp, JL and Herzig, S and Kieffer, TJ},
title = {Deletion of pancreas-specific miR-216a reduces beta-cell mass and inhibits pancreatic cancer progression in mice.},
journal = {Cell reports. Medicine},
volume = {2},
number = {11},
pages = {100434},
pmid = {34841287},
issn = {2666-3791},
support = {//CIHR/Canada ; },
mesh = {Animals ; Apoptosis ; Base Sequence ; Cell Line, Tumor ; Cell Movement ; Diet, High-Fat ; *Disease Progression ; *Gene Deletion ; Humans ; Insulin Secretion ; Insulin-Secreting Cells/*metabolism/*pathology ; Mice, Inbred C57BL ; Mice, Knockout ; MicroRNAs/*genetics/metabolism ; Organ Specificity ; Pancreatic Neoplasms/*genetics/*pathology ; Rats ; },
abstract = {miRNAs have crucial functions in many biological processes and are candidate biomarkers of disease. Here, we show that miR-216a is a conserved, pancreas-specific miRNA with important roles in pancreatic islet and acinar cells. Deletion of miR-216a in mice leads to a reduction in islet size, β-cell mass, and insulin levels. Single-cell RNA sequencing reveals a subpopulation of β-cells with upregulated acinar cell markers under a high-fat diet. miR-216a is induced by TGF-β signaling, and inhibition of miR-216a increases apoptosis and decreases cell proliferation in pancreatic cells. Deletion of miR-216a in the pancreatic cancer-prone mouse line Kras G12D ;Ptf1a CreER reduces the propensity of pancreatic cancer precursor lesions. Notably, circulating miR-216a levels are elevated in both mice and humans with pancreatic cancer. Collectively, our study gives insights into how β-cell mass and acinar cell growth are modulated by a pancreas-specific miRNA and also suggests miR-216a as a potential biomarker for diagnosis of pancreatic diseases.},
}

Animals
Apoptosis
Base Sequence
Cell Line, Tumor
Cell Movement
Diet, High-Fat
*Disease Progression
*Gene Deletion
Humans
Insulin Secretion
Insulin-Secreting Cells/*metabolism/*pathology
Mice, Inbred C57BL
Mice, Knockout
MicroRNAs/*genetics/metabolism
Organ Specificity
Pancreatic Neoplasms/*genetics/*pathology
Rats

@article {pmid34781210,
year = {2021},
author = {Jeong, JS and Cho, KJ and Kim, D and Lee, YS and Song, JS},
title = {Genomic alteration in rare subtype of sarcomatoid salivary duct carcinoma.},
journal = {Pathology, research and practice},
volume = {228},
number = {},
pages = {153678},
doi = {10.1016/j.prp.2021.153678},
pmid = {34781210},
issn = {1618-0631},
mesh = {Aged ; Aged, 80 and over ; Biomarkers, Tumor/*analysis ; Carcinoma, Ductal/genetics/*pathology ; Humans ; Male ; Middle Aged ; Salivary Ducts/pathology ; Salivary Gland Neoplasms/genetics/*pathology ; },
abstract = {AIMS: Salivary duct carcinoma (SDC) is an aggressive salivary gland neoplasm with a poor prognosis. Morphologically, it has many variants including sarcomatoid SDC. We evaluated the morphological features, immunohistochemistry profile, and genomic alteration of the rare variant, sarcomatoid SDC.

METHODS AND RESULTS: We evaluated the clinicopathological and molecular pathology for rare variant of sarcomatoid SDC. Among 102 SDC patients, three had sarcomatoid SDC. Review of clinicopathological features and immunohistochemistry and targeted exome sequencing was performed according to carcinomatous and sarcomatoid areas, respectively. The tumors were present in two submandibular glands and one parotid gland. In one case, a SDC arose in carcinoma ex pleomorphic adenoma. All consisted of a conventional invasive ductal carcinoma area and sarcomatoid features including spindle cells and multinucleated giant cells. AR and epithelial membrane antigen (EMA) were positive in both carcinoma and sarcomatoid areas. Cytokeratin AE1/AE3 were negative in all sarcomatoid areas. Targeted exome sequencing revealed multiple heterogeneous alterations including PIK3CA and TP53. Genomic alterations were nearly identical between typical carcinoma and sarcomatoid areas.

CONCLUSIONS: Clinicopathological features of sarcomatoid SDCs were not different from typical SDC, and genomic alteration according to subtypes was also similar to that of the conventional type. Androgen receptor (AR) expression is helpful in the diagnosis of SDC. The findings indicate that EMA and AR are useful in diagnosing sarcomatoid SDC when the tumor is composed of predominantly sarcomatoid components.},
}

Aged
Aged, 80 and over
Biomarkers, Tumor/*analysis
Carcinoma, Ductal/genetics/*pathology
Humans
Male
Middle Aged
Salivary Ducts/pathology
Salivary Gland Neoplasms/genetics/*pathology

@article {pmid34702045,
year = {2021},
author = {Ilbeigi, S and Naeimzadeh, Y and Davoodabadi Farahani, M and Rafi Monjezi, M and Dastsooz, H and Daraei, A and Farahani, F and Dastgheib, A and Mansoori, Y and Tabei, SMB},
title = {Clinical values of two estrogen receptor signaling targeted lncRNAs in invasive ductal breast carcinoma.},
journal = {Klinicka onkologie : casopis Ceske a Slovenske onkologicke spolecnosti},
volume = {34},
number = {5},
pages = {382-391},
doi = {10.48095/ccko2021382},
pmid = {34702045},
issn = {1802-5307},
mesh = {Adult ; Aged ; Breast/metabolism ; Breast Neoplasms/*genetics ; Carcinoma, Ductal, Breast/*genetics ; Cell Line, Tumor ; Computational Biology ; Female ; Humans ; Middle Aged ; *RNA, Long Noncoding ; Receptor, ErbB-2/metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; Signal Transduction ; },
abstract = {BACKGROUND: Invasive ductal carcinoma (IDC) is the most frequent type of breast cancer (BC) in women, with a high clinical burden due to its high invasive properties. Despite of quickly emerging new data regarding the molecular heterogeneity of invasive cancers, far less is known about the molecular patterns among cases of IDC. An expanding body of evidence has demonstrated that dysregulation of long noncoding RNAs (lncRNAs) is involved in the heterogeneity feature of BC.

METHODS: In this study, we analyzed the expression levels of two novel lncRNAs LOC100288637 and RP11-48B3 in 51 IDC tissues in comparison with adjacent non-cancerous tissues. And finally, bio-informatic evaluation has been done.

RESULTS: The results of quantitative polymerase chain reaction showed that LOC100288637 and RP11-48B3 were significantly overexpressed in tumor tissues compared to normal samples (P = 0.0085 and P = 0.0002, respectively). Also, the two lncRNAs were overexpressed in both MDA-MB-231 and MCF-7 BC cell lines, nevertheless, with a higher expression pattern in MDA-MB-231 than MCF7 cell line. Furthermore, LOC100288637 had an elevated expression level in HER-2 positive tumors compared to HER-2 negative tumors (P = 0.031). Interestingly, the lncRNA RP11-48B3.4 was upregulated in IDC subjects with the age at menarche < 14 years compared to patients with the age at menarche 14 (P = 0.041). It was observed in another result that lncRNA RP11-48B3.4 is significantly upregulated in tumors with a lower histological grade compared to tumor samples with higher grades (P = 0.047). And finally, using bio-informatic evaluation, we found a predicted interaction between RP11-48B3.4 and mRNA zinc finger and BTB domain containing 10 (ZBTB10).

CONCLUSION: Altogether, our findings suggest that these lncRNAs with potential oncogenic roles are involved in the pathogenesis of IDC with clinical significance and they may therefore serve as novel markers for the dia-gnosis and treatment of IDC.},
}

Adult
Aged
Breast/metabolism
Breast Neoplasms/*genetics
Carcinoma, Ductal, Breast/*genetics
Cell Line, Tumor
Computational Biology
Female
Humans
Middle Aged
*RNA, Long Noncoding
Receptor, ErbB-2/metabolism
Receptors, Estrogen/metabolism
Receptors, Progesterone/metabolism
Signal Transduction

@article {pmid34219706,
year = {2022},
author = {Avau, F and Chintinne, M and Baudry, S and Buxant, F},
title = {Literature review and case report of bilateral intracystic papillary carcinoma associated with an invasive ductal carcinoma in a male breast.},
journal = {Breast disease},
volume = {41},
number = {1},
pages = {5-13},
doi = {10.3233/BD-210001},
pmid = {34219706},
issn = {1558-1551},
mesh = {Antineoplastic Agents/therapeutic use ; Breast Neoplasms, Male/*complications/drug therapy/*secondary/surgery ; Carcinoma, Intraductal, Noninfiltrating/complications/drug therapy/*secondary ; Carcinoma, Papillary/classification/*diagnostic imaging/drug therapy ; Humans ; Male ; Mammography ; Mastectomy ; Middle Aged ; Sentinel Lymph Node Biopsy ; },
abstract = {Intracystic papillary carcinoma (IPC) is a rare tumor with good prognosis that occurs in only 5% to 7.5% of male breast cancer. We report a case of a 46-year-old man who presented a brown nipple discharge a few months ago. He had a bilateral IPC and an invasive ductal carcinoma on the right breast. A double mastectomy was then performed with a bilateral sentinel lymph node biopsy, and he received chemotherapy, radiotherapy, and hormonotherapy. Two years after the diagnosis, the patient recovered and was free of recurrence. Considering the scarcity of this tumor type, we conducted a systematic literature review on the PubMed of all the cases of IPC in men. The clinical presentation, imaging, and treatment of the 43 case reports from the 41 articles selected were described. Furthermore, no clear guidelines for IPC management are available. Conservative surgery should also be preferred, and a sentinel lymph node biopsy should be performed systematically. Moreover, radiotherapy should be proposed in the case of conservative surgery, and hormone therapy could be proposed in the case of invasive IPC or IPC associated with a ductal carcinoma in situ.},
}

Antineoplastic Agents/therapeutic use
Breast Neoplasms, Male/*complications/drug therapy/*secondary/surgery
Carcinoma, Intraductal, Noninfiltrating/complications/drug therapy/*secondary
Carcinoma, Papillary/classification/*diagnostic imaging/drug therapy
Humans
Male
Mammography
Mastectomy
Middle Aged
Sentinel Lymph Node Biopsy

@article {pmid35114136,
year = {2022},
author = {Bechmann, N and Barthel, A and Schedl, A and Herzig, S and Varga, Z and Gebhard, C and Mayr, M and Hantel, C and Beuschlein, F and Wolfrum, C and Perakakis, N and Poston, L and Andoniadou, CL and Siow, R and Gainetdinov, RR and Dotan, A and Shoenfeld, Y and Mingrone, G and Bornstein, SR},
title = {Sexual dimorphism in COVID-19: potential clinical and public health implications.},
journal = {The lancet. Diabetes & endocrinology},
volume = {10},
number = {3},
pages = {221-230},
doi = {10.1016/S2213-8587(21)00346-6},
pmid = {35114136},
issn = {2213-8595},
mesh = {*COVID-19/complications/epidemiology/physiopathology ; Female ; *Health Status Disparities ; Humans ; Hypothalamo-Hypophyseal System ; Male ; Pituitary-Adrenal System ; Public Health ; *Sex Characteristics ; },
abstract = {Current evidence suggests that severity and mortality of COVID-19 is higher in men than in women, whereas women might be at increased risk of COVID-19 reinfection and development of long COVID. Differences between sexes have been observed in other infectious diseases and in the response to vaccines. Sex-specific expression patterns of proteins mediating virus binding and entry, and divergent reactions of the immune and endocrine system, in particular the hypothalamic-pituitary-adrenal axis, in response to acute stress might explain the higher severity of COVID-19 in men. In this Personal View, we discuss how sex hormones, comorbidities, and the sex chromosome complement influence these mechanisms in the context of COVID-19. Due to its role in the severity and progression of SARS-CoV-2 infections, we argue that sexual dimorphism has potential implications for disease treatment, public health measures, and follow-up of patients predisposed to the development of long COVID. We suggest that sex differences could be considered in future pandemic surveillance and treatment of patients with COVID-19 to help to achieve better disease stratification and improved outcomes.},
}

*COVID-19/complications/epidemiology/physiopathology
Female
*Health Status Disparities
Humans
Hypothalamo-Hypophyseal System
Male
Pituitary-Adrenal System
Public Health
*Sex Characteristics

@article {pmid34717732,
year = {2021},
author = {Ropri, AS and DeVaux, RS and Eng, J and Chittur, SV and Herschkowitz, JI},
title = {Cis-acting super-enhancer lncRNAs as biomarkers to early-stage breast cancer.},
journal = {Breast cancer research : BCR},
volume = {23},
number = {1},
pages = {101},
pmid = {34717732},
issn = {1465-542X},
mesh = {Biomarkers, Tumor/genetics ; Breast Neoplasms/*genetics/*pathology ; Carcinoma, Ductal, Breast/genetics/pathology ; Carcinoma, Intraductal, Noninfiltrating/genetics/pathology ; Cell Line ; Disease Progression ; Enhancer Elements, Genetic/*genetics ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Membrane Proteins/genetics ; MicroRNAs/genetics ; RNA, Long Noncoding/*genetics ; Receptors, Estrogen/metabolism ; Triple Negative Breast Neoplasms/genetics/pathology ; },
abstract = {BACKGROUND: Increased breast cancer screening over the past four decades has led to a substantial rise in the diagnosis of ductal carcinoma in situ (DCIS). Although DCIS lesions precede invasive ductal carcinoma (IDC), they do not always transform into cancer. The current standard-of-care for DCIS is an aggressive course of therapy to prevent invasive and metastatic disease resulting in over-diagnosis and over-treatment. Thus, there is a critical need to identify functional determinants of progression of DCIS to IDC to allow discrimination between indolent and aggressive disease. Recent studies show that super-enhancers, in addition to promoting other gene transcription, are themselves transcribed producing super-enhancer associated long noncoding RNAs (SE-lncRNAs). These SE-lncRNAs can interact with their associated enhancer regions in cis and influence activities and expression of neighboring genes. Furthermore, they represent a novel, untapped group of therapeutic targets.

METHODS: With an integrative analysis of enhancer loci with global expression of SE-lncRNAs in the MCF10A progression series, we have identified differentially expressed SE-lncRNAs which can identify mechanisms for DCIS to IDC progression. Furthermore, cross-referencing these SE-lncRNAs with patient samples in the The Cancer Genome Atlas (TCGA) database, we have unveiled 27 clinically relevant SE-lncRNAs that potentially interact with their enhancer to regulate nearby gene expression. To complement SE-lncRNA expression studies, we conducted an unbiased global analysis of super-enhancers that are acquired or lost in progression.

RESULTS: Here we designate SE-lncRNAs RP11-379F4.4 and RP11-465B22.8 as potential markers of progression of DCIS to IDC through regulation of the expression of their neighboring genes (RARRES1 and miR-200b, respectively). Moreover, we classified 403 super-enhancer regions in MCF10A normal cells, 627 in AT1, 1053 in DCIS, and 320 in CA1 cells. Comparison analysis of acquired/lost super-enhancer regions with super-enhancer regions classified in 47 ER positive patients, 10 triple negative breast cancer (TNBC) patients, and 11 TNBC cell lines reveal critically acquired pathways including STAT signaling and NF-kB signaling. In contrast, protein folding, and local estrogen production are identified as major pathways lost in progression.

CONCLUSION: Collectively, these analyses identify differentially expressed SE-lncRNAs and acquired/lost super-enhancers in progression of breast cancer important for promoting DCIS lesions to IDC.},
}

Biomarkers, Tumor/genetics
Breast Neoplasms/*genetics/*pathology
Carcinoma, Ductal, Breast/genetics/pathology
Carcinoma, Intraductal, Noninfiltrating/genetics/pathology
Cell Line
Disease Progression
Enhancer Elements, Genetic/*genetics
Female
Gene Expression Regulation, Neoplastic
Humans
Membrane Proteins/genetics
MicroRNAs/genetics
RNA, Long Noncoding/*genetics
Receptors, Estrogen/metabolism
Triple Negative Breast Neoplasms/genetics/pathology

@article {pmid34560418,
year = {2021},
author = {Wan, D and Zhang, Y and Yu, Q and Li, F and Zhuo, J},
title = {14-3-3ζ promoted invasion and lymph node metastasis of breast invasive ductal carcinoma with HER2 overexpression.},
journal = {Pathology, research and practice},
volume = {227},
number = {},
pages = {153619},
doi = {10.1016/j.prp.2021.153619},
pmid = {34560418},
issn = {1618-0631},
mesh = {14-3-3 Proteins/genetics/*metabolism ; Adult ; Aged ; Biomarkers, Tumor/*analysis ; Breast Neoplasms/*chemistry/pathology ; Carcinoma, Ductal, Breast/*chemistry/secondary ; Female ; Humans ; Immunohistochemistry ; Lymphatic Metastasis ; Middle Aged ; Nuclear Proteins/analysis ; Predictive Value of Tests ; Prognosis ; Receptor, ErbB-2/*analysis ; Tumor Suppressor Protein p53/analysis ; Up-Regulation ; Young Adult ; Zinc Finger Protein Gli2/analysis ; },
abstract = {BACKGROUND: HER2 was a recognized oncogene that promoted the development and metastasis of breast cancer, but its positive expression rate in invasive ductal carcinoma (IDC) was much lower than that in ductal carcinoma in situ (DCIS). The correlation between the occurrence and development of breast cancer and the amplification and overexpression of HER2 gene alone was still controversial. 14-3-3ζ had a strong protein binding ability and a variety of functions, mainly through the interaction with other proteins to exert its unique biological activities. However, influence and interaction relationship of the two proteins on the development of IDC was not clear. Furthermore, the mutual effect mechanism of synergy effect on lymph node metastasis of IDC was not known well too.

METHODS: Immunohistochemistry experiment was performed to detect expression status of 14-3-3ζ, HER2, TGF-β, p53 and Gli2 in paraffin-embedded samples respectively, including 30 cases of normal breast tissue, 30 cases of usual ductal hyperplasia (UDH), 30 cases of atypical ductal hyperplasia (ADH), 30 cases of DCIS and 120 cases of IDC.

RESULTS: The positive expression rates of 14-3-3ζ/HER2 in Normal group, UDH group, ADH group, DCIS group and IDC group were 30%/0.00%, 26.7%/0.00%, 53.3%/33.3%, 46.7%/53.3% and 50%/24.2%, respectively. Compared with Normal group or UDH group, the expression of 14-3-3ζ was significantly increased in ADH, DCIS and IDC groups. 14-3-3ζ was overexpressed in only 4 of the 16 DCIS cases with HER2 overexpression (25.0%, 4/16), but it was overexpressed in 7 of the 9 IDC cases with DCIS (77.8%, 7/9). Among HER2 overexpression cases, 14-3-3ζ overexpression was significantly different between DCIS group and IDC with DCIS group (P = 0.017). In 18 IDC cases with lymph node metastasis and HER2 overexpression, 14-3-3ζ was overexpressed in 15 cases (83.3%, 15/18), while in the 11 IDC cases without lymph node metastasis, 14-3-3ζ and HER2 were overexpressed in only 5 cases (45.5%, 5/11). Co-overexpression of 14-3-3ζ and HER2 was positively correlated with occurrence of lymph node metastasis (P = 0.048). TGF-β was overexpressed in both precancerous lesion group and IDC group compared with normal group. Compared with the IDC group without lymph node metastasis, TGF-β expression was significantly increased in the IDC group with lymph node metastasis (P = 0.015). In IDC cases with 14-3-3ζ and HER2 co-overexpression, the expression of p53 in IDC with lymph node metastasis was significantly decreased (P = 0.010), while the expression of Gli2 was significantly increased compared with IDC cases without lymph node metastasis (P = 0.038). The co-overexpression of 14-3-3ζ and HER2 was positively correlated with ER negative expression (P < 0.001) and PR negative expression (P = 0.038), respectively.

CONCLUSION: 14-3-3ζ synergistic with HER2 could promote the occurrence and development of breast IDC and induce the lymph node metastasis of IDC, suggesting that combined overexpression of 14-3-3ζ and HER2 would lead to higher invasion and metastasis risk of breast cancer. It was speculated that the combined detection of 14-3-3ζ and HER2 would be one of the key factors affecting the clinical treatment decision and prognosis.},
}

14-3-3 Proteins/genetics/*metabolism
Adult
Aged
Biomarkers, Tumor/*analysis
Breast Neoplasms/*chemistry/pathology
Carcinoma, Ductal, Breast/*chemistry/secondary
Female
Humans
Immunohistochemistry
Lymphatic Metastasis
Middle Aged
Nuclear Proteins/analysis
Predictive Value of Tests
Prognosis
Receptor, ErbB-2/*analysis
Tumor Suppressor Protein p53/analysis
Up-Regulation
Young Adult
Zinc Finger Protein Gli2/analysis

@article {pmid34812466,
year = {2021},
author = {Feresin, RG and Johnson, SA and Elam, ML and Pourafshar, S and Navaei, N and Akhavan, NS and Tenenbaum, G and Figueroa, A and Arjmandi, BH},
title = {Effects of strawberries on bone biomarkers in pre- and stage 1-hypertensive postmenopausal women: a secondary analysis.},
journal = {Food & function},
volume = {12},
number = {24},
pages = {12526-12534},
doi = {10.1039/d1fo01555a},
pmid = {34812466},
issn = {2042-650X},
mesh = {Aged ; Biomarkers/blood ; Bone Density/*drug effects ; Bone Resorption/blood/drug therapy ; Female ; *Fragaria ; Humans ; Hypertension/blood/complications/*drug therapy ; Middle Aged ; Osteoporosis, Postmenopausal/blood/complications/*prevention & control ; Plant Extracts/blood/*pharmacology ; Polyphenols/blood/*pharmacology ; Postmenopause ; },
abstract = {Postmenopausal women experience an increase in bone remodeling with the rate of bone resorption superseding the rate of bone formation. This results in a net bone loss with a subsequent increased risk for osteoporosis and fractures. High blood pressure (BP) has been associated with loss of bone mineral density and increased propensity to fractures. Strawberries are rich in polyphenols, which have been shown to have anti-hypertensive and bone-protective properties. Thus, we examined whether daily intake of strawberries would positively affect biomarkers of bone metabolism in postmenopausal women with pre- and stage 1-hypertension. Participants (age: 59 ± 6 years; body mass index: 31.5 ± 4.1 kg m-2; systolic BP: 140 ± 13 mmHg) were randomly assigned to consume (1) 50 g of freeze-dried strawberry powder (FDSP), (2) 25 g FDSP + 25 g of placebo powder, or (3) 50 g placebo powder for eight weeks. Results indicate a significant time-by-treatment interaction (P = 0.04) for serum insulin-like growth factor (IGF)-1, a hormone that plays a major role in bone formation. Serum concentrations of bone-specific alkaline phosphatase, a marker of bone formation, and tartrate-resistant acid phosphatase-5b, a specific marker of bone resorption, were not affected by FDSP compared to placebo. Although not statistically significant, after eight weeks, osteocalcin increased in the 50 g FDSP group with a large effect size (d = 0.6) when compared to the placebo-control group. Adiponectin increased by 5% and 6% in the 25 g and 50 g FDSP groups, respectively, while it declined in the placebo-control group by 25% (P = 0.03 for time-by-treatment interaction). Our findings suggest that consumption of 25 g FDSP increases IGF-1 in postmenopausal women with pre- and stage 1-hypertension. However, further studies are needed to assert the effectiveness of a strawberry intervention for bone health.},
}

Aged
Biomarkers/blood
Bone Density/*drug effects
Bone Resorption/blood/drug therapy
Female
*Fragaria
Humans
Hypertension/blood/complications/*drug therapy
Middle Aged
Osteoporosis, Postmenopausal/blood/complications/*prevention & control
Plant Extracts/blood/*pharmacology
Polyphenols/blood/*pharmacology
Postmenopause

@article {pmid35207775,
year = {2022},
author = {Huang, CC and Chang, CL and Sun, M and Chiang, MF and Sum, SY and Zhang, J and Wu, SY},
title = {Adjuvant Radiotherapy Is Associated with an Increase in the Survival of Old (Aged over 80 Years) and Very Old (Aged over 90 Years) Women with Breast Cancer Receiving Breast-Conserving Surgery.},
journal = {Journal of personalized medicine},
volume = {12},
number = {2},
pages = {},
doi = {10.3390/jpm12020287},
pmid = {35207775},
issn = {2075-4426},
abstract = {This study is the first to examine the effect of adjuvant whole-breast radiotherapy (WBRT) on oncologic outcomes such as all-cause death, locoregional recurrence (LRR), and distant metastasis (DM) in old (aged ≥80 years) and very old (aged ≥90 years) women with breast invasive ductal carcinoma (IDC) receiving breast-conserving surgery. After propensity score matching, adjuvant WBRT was associated with decreases in all-cause death, LRR, and DM in old and very old women with IDC compared with no use of adjuvant WBRT. Background: To date, no data on the effect of adjuvant whole-breast radiotherapy (WBRT) on oncologic outcomes, such as all-cause death, locoregional recurrence (LRR), and distant metastasis (DM), are available for old (aged ≥80 years) and very old (≥90 years) women with breast invasive ductal carcinoma (IDC) receiving breast-conserving conservative surgery (BCS). Patients and Methods: We enrolled old (≥80 years old) and very old (≥90 years old) women with breast IDC who had received BCS followed by adjuvant WBRT or no adjuvant WBRT. We grouped them based on adjuvant WBRT status and compared their overall survival (OS), LRR, and DM outcomes. To reduce the effects of potential confounders when comparing all-cause mortality between the groups, propensity score matching was performed. Results: Overall, 752 older women with IDC received BCS followed by adjuvant WBRT, and 752 with IDC received BCS with no adjuvant WBRT. In multivariable Cox regression analysis, the adjusted hazard ratio (aHR) and 95% confidence interval (95% CI) of all-cause death for adjuvant WBRT compared with no adjuvant WBRT in older women with IDC receiving BCS was 0.56 (0.44-0.70). The aHRs (95% CIs) of LRR and DM for adjuvant WBRT were 0.29 (0.19-0.45) and 0.45 (0.32-0.62), respectively, compared with no adjuvant WBRT. Conclusions: Adjuvant WBRT was associated with decreases in all-cause death, LRR, and DM in old (aged ≥80 years) and very old (aged ≥90 years) women with IDC compared with no adjuvant WBRT.},
}

@article {pmid35200056,
year = {2022},
author = {Hannarici, Z and Yılmaz, A and Buyukbayram, ME and Turhan, A and Tekin, SB and Bilici, M},
title = {Lipegfilgrastim may cause hyperleukocytosis.},
journal = {Journal of oncology pharmacy practice : official publication of the International Society of Oncology Pharmacy Practitioners},
volume = {},
number = {},
pages = {10781552221082645},
doi = {10.1177/10781552221082645},
pmid = {35200056},
issn = {1477-092X},
abstract = {INTRODUCTION: Granulocyte colony-stimulating factors (G-CSF) are utilized both in the treatment and prophylaxis of chemotherapy-induced neutropenia. Lipegfilgrastim is a long-acting G-CSF. Albeit it provides ease of administration compared to short-acting GCSFs, some lipegfilgrastim-related adverse events may occur. Bone pain, widespread body pain, and feeling of fever are among common adverse effects, while rare but more serious adverse effects such as leukocytosis, spleen rupture, interstitial pneumonia, acute respiratory distress syndrome, capillary leak syndrome, hypokalemia, and glomerulonephritis may occur as well.

CASE REPORT: We reported a case of hyperleukocytosis that developed due to prophylactic administration of lipegfilgrastim following the first course of neoadjuvant pertuzumab (840-420 mg), trastuzumab (8-6mg/kg), and docetaxel (75 mg/m2) in a 45-year-old female patient with a diagnosis of breast invasive ductal carcinoma. The patient, who presented with weakness, loss of appetite, and oral intake disorder, had elevated white blood cell (WBC), lactate dehydrogenase (LDH), and uric acid levels in her test results. Peripheral smear (PS) had a left shift.

MANAGEMENT AND OUTCOME: Intravenous 0.9% NaCl and peroral allopurinol were started to be administered to the patient. On the ninth day of hospitalization, the patient's clinical manifestation improved, and her WBC, LDH, uric acid, and PS returned to normal. Besides, the progression to tumor lysis syndrome (TLS) was prevented by appropriate hydration and allopurinol treatment. In subsequent chemotherapies (CTs), lipegfilgrastim was discontinued and filgrastim was started. The patient whose hyperleukocytosis did not recur was operated on following neoadjuvant CT. The patient's routine follow-up continues without any problems.

DISCUSSION: Although lipegfilgrastim-induced hyperleukocytosis has not been reported in the literature, it should be borne in mind that hyperleukocytosis and related complications may occur, as in our case.},
}

@article {pmid34592934,
year = {2021},
author = {Mathew, D and Gupta, S and Ashman, N},
title = {A case report of breast cancer and membranous nephropathy with positive anti phospholipase A2 receptor antibodies.},
journal = {BMC nephrology},
volume = {22},
number = {1},
pages = {324},
pmid = {34592934},
issn = {1471-2369},
mesh = {Adult ; Autoantibodies/*blood ; Breast Neoplasms/*complications ; Estrogen Receptor beta/analysis ; Female ; Glomerulonephritis, Membranous/*complications/immunology ; Humans ; Kidney/pathology ; Receptors, Phospholipase A2/*immunology ; },
abstract = {BACKGROUND: Testing for antibodies against podocyte phospholipase A2 receptor-1 (PLA2R) allows clinicians to accurately identify primary membranous nephropathy (MN). Secondary MN is associated with a spectrum of pathology including solid organ malignancy. PLA2R positivity in these patients occurs, although no case of PLA2R-positive MN has been definitively linked to cancer.

CASE PRESENTATION: We describe a case of biopsy-proven PLA2R-positive MN, in whom invasive ductal carcinoma of the breast was discovered. The patient underwent surgery and adjuvant chemotherapy (including cyclophosphamide) and went into a sustained complete remission of her nephrotic syndrome.

DISCUSSION AND CONCLUSIONS: Case series have reported PLA2R positivity in patients with solid organ malignancy associated MN. Our case is unusual as it is a breast malignancy, and the patients nephrotic syndrome and anti-PLA2Rab titres improved with treatment of the cancer. Here we report, to the best of our knowledge, the first case of oestrogen receptor-2 positive breast cancer associated with PLA2R positive MN in a young lady that was treated successfully by treating the malignancy.},
}

Adult
Autoantibodies/*blood
Breast Neoplasms/*complications
Estrogen Receptor beta/analysis
Female
Glomerulonephritis, Membranous/*complications/immunology
Humans
Kidney/pathology
Receptors, Phospholipase A2/*immunology

@article {pmid33960872,
year = {2021},
author = {Alvarez, DR and Ospina, A and Barwell, T and Zheng, B and Dey, A and Li, C and Basu, S and Shi, X and Kadri, S and Chakrabarti, K},
title = {The RNA structurome in the asexual blood stages of malaria pathogen plasmodium falciparum.},
journal = {RNA biology},
volume = {18},
number = {12},
pages = {2480-2497},
pmid = {33960872},
issn = {1555-8584},
mesh = {Erythrocytes/*metabolism ; *Gene Expression Regulation ; Humans ; *Life Cycle Stages ; Malaria, Falciparum/*parasitology ; *Nucleic Acid Conformation ; Plasmodium falciparum/*genetics/growth & development/pathogenicity ; Protozoan Proteins/genetics/metabolism ; RNA, Protozoan/*chemistry ; Transcriptome ; },
abstract = {Plasmodium falciparum is a deadly human pathogen responsible for the devastating disease called malaria. In this study, we measured the differential accumulation of RNA secondary structures in coding and non-coding transcripts from the asexual developmental cycle in P. falciparum in human red blood cells. Our comprehensive analysis that combined high-throughput nuclease mapping of RNA structures by duplex RNA-seq, SHAPE-directed RNA structure validation, immunoaffinity purification and characterization of antisense RNAs collectively measured differentially base-paired RNA regions throughout the parasite's asexual RBC cycle. Our mapping data not only aligned to a diverse pool of RNAs with known structures but also enabled us to identify new structural RNA regions in the malaria genome. On average, approximately 71% of the genes with secondary structures are found to be protein coding mRNAs. The mapping pattern of these base-paired RNAs corresponded to all regions of mRNAs, including the 5' UTR, CDS and 3' UTR as well as the start and stop codons. Histone family genes which are known to form secondary structures in their mRNAs and transcripts from genes which are important for transcriptional and post-transcriptional control, such as the unique plant-like transcription factor family, ApiAP2, DNA-/RNA-binding protein, Alba3 and proteins important for RBC invasion and malaria cytoadherence also showed strong accumulation of duplex RNA reads in various asexual stages in P. falciparum. Intriguingly, our study determined stage-specific, dynamic relationships between mRNA structural contents and translation efficiency in P. falciparum asexual blood stages, suggesting an essential role of RNA structural changes in malaria gene expression programs. Abbreviations: CDS: Coding Sequence; DNA: Deoxyribonucleic Acid; dsRNA: double-stranded RNA; IDC: Intra-erythrocytic Developmental Cycle (IDC); m6A: N6-methyladenosine; mRNA: Messenger RNA; ncRNA: Non-coding RNA; RBC: Red Blood cells; RBP: RNA-Binding Protein; REC: Relative Expression Counts; RNA-seq: RNA-sequencing; RNA: Ribonucleic Acid; RNP: Ribonucleoprotein; RPKM: Reads Per Kilobase of transcript Per Million; rRNA: Ribosomal RNA 16. RUFs: RNAs of Unknown Function; SHAPE: Selective 2'-hydroxyl acylation analysed by primer extension; snoRNA: Small Nucleolar RNA; snRNA: Small Nuclear RNA; SRP-RNA: Signal Recognition Particle RNA; ssRNA: (Single-stranded RNA); TE: Translation Efficiency; tRNA: transfer RNA; UTR: Untranslated Region.},
}

Erythrocytes/*metabolism
*Gene Expression Regulation
Humans
*Life Cycle Stages
Malaria, Falciparum/*parasitology
*Nucleic Acid Conformation
Plasmodium falciparum/*genetics/growth & development/pathogenicity
Protozoan Proteins/genetics/metabolism
RNA, Protozoan/*chemistry
Transcriptome

@article {pmid35074971,
year = {2022},
author = {Kumari, S and Mishra, S and Husain, N and Verma, T and Tiwari, V and Kaif, M and Agarwal, A and Rastogi, M and Shukla, S and Sonkar, AA},
title = {Comparison of circulating DNA in malignant neoplasia from diverse locations: Investigating a diagnostic role.},
journal = {Indian journal of pathology & microbiology},
volume = {65},
number = {1},
pages = {93-99},
doi = {10.4103/IJPM.IJPM_474_20},
pmid = {35074971},
issn = {0974-5130},
mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/blood/genetics ; Brain Neoplasms/blood/diagnosis/genetics ; Carcinoma, Squamous Cell/blood/diagnosis/genetics ; Cell-Free Nucleic Acids/*blood ; Female ; Gallbladder Neoplasms/blood/diagnosis/genetics ; Humans ; Male ; Middle Aged ; Neoplasm Staging ; Neoplasms/blood/classification/*diagnosis/*genetics ; Young Adult ; },
abstract = {Context: Circulating free DNA (cfDNA) analysis has emerged as novel noninvasive diagnostic biomarker in several solid tumors. Raised levels have been reported in several malignancies and may correlate with clinicopathological and treatment response. The current study was designed to assess the diagnostics of cfDNA in different tumor types of malignancies correlating with tumor (T), nodes (N), and metastases (M) stage.

Design: Serum samples were collected from treatment naïve cases with histologically diagnosed tumors including 23 brain tumors, 48 breasts, 50 gallbladder carcinoma (GBC), 13 lungs, 68 oral squamous cell carcinoma (OSCC), and 25 normal controls. CfDNA was quantified with real-time polymerase chain reaction (PCR), Invasive ductal carcinoma (IDC) using beta-globin gene amplification. Cut off values for diagnostics were calculated using receiver operating curve analysis.

Results: Contrary to other cfDNA studies where it was postulated that cfDNA would not cross the blood-brain barrier and reach the systemic circulation, we found detectable cfDNA in glioma with median (Q1-Q3) of 349.22 ng/ml (19.87-1276.58). Median cfDNA concentration in breast, gallbladder, lung, oral and normal controls was 328.72 (128.38-624.44), 778.50 (589.88-1864.35), 348.73 (194.67-483.61), 386.27 (47.88-959.67), and 74.12 (49.66-120.00), respectively. Grades I and II glioma had significantly lower levels compared to Grades III and IV (P = 0.0001). Significant difference in median cfDNA values in IDC and GBC was observed with increasing tumor grades, stage, T stage, nodal stage and metastasis and with stage of OSCC cases.

Conclusion: CfDNA levels showed good diagnostic discrimination in glioma, GBC, breast, lung carcinoma, and OSCC. Significant increase in titers was evident with increase in cancer stage from I to IV in breast, GBC and OSCC.},
}

Adolescent
Adult
Aged
Aged, 80 and over
Biomarkers, Tumor/blood/genetics
Brain Neoplasms/blood/diagnosis/genetics
Carcinoma, Squamous Cell/blood/diagnosis/genetics
Cell-Free Nucleic Acids/*blood
Female
Gallbladder Neoplasms/blood/diagnosis/genetics
Humans
Male
Middle Aged
Neoplasm Staging
Neoplasms/blood/classification/*diagnosis/*genetics
Young Adult

@article {pmid35011590,
year = {2021},
author = {Greulich, F and Bielefeld, KA and Scheundel, R and Mechtidou, A and Strickland, B and Uhlenhaut, NH},
title = {Enhancer RNA Expression in Response to Glucocorticoid Treatment in Murine Macrophages.},
journal = {Cells},
volume = {11},
number = {1},
pages = {},
pmid = {35011590},
issn = {2073-4409},
support = {GR 5179/1-1//Deutsche Forschungsgemeinschaft/ ; UH 275/1-1//Deutsche Forschungsgemeinschaft/ ; ERC-2014-StG 638573/ERC_/European Research Council/International ; TRR205, The Adrenal//Deutsche Forschungsgemeinschaft/ ; CRC1064 Chromatin Dynamics//Deutsche Forschungsgemeinschaf/ ; },
mesh = {Acetylation/drug effects ; Animals ; Binding Sites ; *Enhancer Elements, Genetic ; Gene Expression Profiling ; *Gene Expression Regulation/drug effects ; Glucocorticoids/*pharmacology ; Histones/metabolism ; Lysine/metabolism ; Macrophages/drug effects/*metabolism ; Male ; Mice, Inbred C57BL ; Nuclear Proteins/metabolism ; Organ Specificity/drug effects ; RNA/*genetics/metabolism ; Receptors, Glucocorticoid/metabolism ; Transcription Factors/metabolism ; Transcription, Genetic/drug effects ; },
abstract = {Glucocorticoids are potent anti-inflammatory drugs; however, their molecular mode of action remains complex and elusive. They bind to the glucocorticoid receptor (GR), a nuclear receptor that controls gene expression in almost all tissues in a cell type-specific manner. While GR's transcriptional targets mediate beneficial reactions in immune cells, they also harbor the potential of adverse metabolic effects in other cell types such as hepatocytes. Here, we have profiled nascent transcription upon glucocorticoid stimulation in LPS-activated primary murine macrophages using 4sU-seq. We compared our results to publicly available nascent transcriptomics data from murine liver and bioinformatically identified non-coding RNAs transcribed from intergenic GR binding sites in a tissue-specific fashion. These tissue-specific enhancer RNAs (eRNAs) correlate with target gene expression, reflecting cell type-specific glucocorticoid responses. We further associate GR-mediated eRNA expression with changes in H3K27 acetylation and BRD4 recruitment in inflammatory macrophages upon glucocorticoid treatment. In summary, we propose a common mechanism by which GR-bound enhancers regulate target gene expression by changes in histone acetylation, BRD4 recruitment and eRNA expression. We argue that local eRNAs are potential therapeutic targets downstream of GR signaling which may modulate glucocorticoid response in a cell type-specific way.},
}

Acetylation/drug effects
Animals
Binding Sites
*Enhancer Elements, Genetic
Gene Expression Profiling
*Gene Expression Regulation/drug effects
Glucocorticoids/*pharmacology
Histones/metabolism
Lysine/metabolism
Macrophages/drug effects/*metabolism
Male
Mice, Inbred C57BL
Nuclear Proteins/metabolism
Organ Specificity/drug effects
RNA/*genetics/metabolism
Receptors, Glucocorticoid/metabolism
Transcription Factors/metabolism
Transcription, Genetic/drug effects

@article {pmid34272624,
year = {2021},
author = {Considine, B and Adeniran, A and Hurwitz, ME},
title = {Current Understanding and Management of Intraductal Carcinoma of the Prostate.},
journal = {Current oncology reports},
volume = {23},
number = {9},
pages = {110},
pmid = {34272624},
issn = {1534-6269},
mesh = {Carcinoma, Ductal/*genetics/pathology/therapy ; DNA Mismatch Repair/*genetics ; Genetic Predisposition to Disease/*genetics ; Humans ; Male ; *Microsatellite Instability ; *Mutation ; Neoplasm Grading ; Prostatic Neoplasms/*genetics/pathology/therapy ; Signal Transduction/genetics ; },
abstract = {PURPOSE OF REVIEW: This review will discuss current understanding and management approaches of Intraductal carcinoma of the prostate (IDC-P). IDC-P is a histological finding characterized by neoplastic cells that expand but do not invade prostate ducts.

RECENT FINDINGS: The presence of IDC-P on a prostate biopsy is almost always associated with an invasive disease component and is independently associated with worse clinical outcomes in both early and late disease. These tumors are enriched for mutations in homologous DNA recombination repair (HRR) leading to high genomic instability. Multiparametric MRI with targeted biopsy may aid in diagnosis. Given the poor clinical outcomes associated with this histologic entity, its presence in biopsies should warrant consideration of aggressive management.},
}

Carcinoma, Ductal/*genetics/pathology/therapy
DNA Mismatch Repair/*genetics
Genetic Predisposition to Disease/*genetics
Humans
Male
*Microsatellite Instability
*Mutation
Neoplasm Grading
Prostatic Neoplasms/*genetics/pathology/therapy
Signal Transduction/genetics

@article {pmid34816360,
year = {2022},
author = {Mizukoshi, K and Fujii, M and Yamauchi, Y and Fukuda, A and Seno, H},
title = {A rare case of malignant biliary stenosis due to retroperitoneal metastasis from breast invasive ductal carcinoma.},
journal = {Clinical journal of gastroenterology},
volume = {15},
number = {1},
pages = {199-204},
pmid = {34816360},
issn = {1865-7265},
mesh = {*Breast Neoplasms/pathology ; *Carcinoma, Ductal/surgery ; Constriction, Pathologic/etiology/surgery ; Female ; Humans ; Mastectomy ; Middle Aged ; *Retroperitoneal Neoplasms/surgery ; },
abstract = {A 50-year-old woman was referred to our hospital for elevated hepatobiliary enzymes. She had a medical history of mastectomy for left breast invasive ductal carcinoma about 10 years ago, and no apparent recurrence had been observed. Contrast-enhanced computed tomography (CT) revealed soft-tissue shadows surrounding the portal vein, celiac artery, and other vessels. The lesions involved the hilar bile duct, and the upstream bile ducts were dilated. Endoscopic retrograde cholangiography showed an obstruction in the hilar bile duct, and biopsies were taken at the site of biliary stenosis. H&E staining showed that cells with strong nuclear atypia and prominent chromatin staining infiltrated in the stroma. Immunohistochemical analysis revealed that the cells were positive for CK7, GATA3 and weakly positive for CK20. Based on these results, we made the diagnosis of biliary stenosis due to retroperitoneal metastasis from breast invasive ductal carcinoma. Biliary inside stents were placed across the biliary stricture, and she received chemotherapy plus endocrine therapy for breast cancer. So far, the partial response has been maintained for 1 year since the diagnosis of retroperitoneal metastasis. Although retroperitoneal metastasis from breast cancer, especially breast invasive ductal carcinoma, is extremely rare, it could be a differential diagnosis for biliary stenosis.},
}

*Breast Neoplasms/pathology
*Carcinoma, Ductal/surgery
Constriction, Pathologic/etiology/surgery
Female
Humans
Mastectomy
Middle Aged
*Retroperitoneal Neoplasms/surgery

@article {pmid35187122,
year = {2022},
author = {Neves, EGA and Koh, CC and Souza-Silva, TG and Passos, LSA and Silva, ACC and Velikkakam, T and Villani, F and Coelho, JS and Brodskyn, CI and Teixeira, A and Gollob, KJ and Nunes, MDCP and Dutra, WO},
title = {T-Cell Subpopulations Exhibit Distinct Recruitment Potential, Immunoregulatory Profile and Functional Characteristics in Chagas versus Idiopathic Dilated Cardiomyopathies.},
journal = {Frontiers in cardiovascular medicine},
volume = {9},
number = {},
pages = {787423},
doi = {10.3389/fcvm.2022.787423},
pmid = {35187122},
issn = {2297-055X},
abstract = {Chronic Chagas cardiomyopathy (CCC) is one of the deadliest cardiomyopathies known and the most severe manifestation of Chagas disease, which is caused by infection with the parasite Trypanosoma cruzi. Idiopathic dilated cardiomyopathies (IDC) are a diverse group of inflammatory heart diseases that affect the myocardium and are clinically similar to CCC, often causing heart failure and death. While T-cells are critical for mediating cardiac pathology in CCC and IDC, the mechanisms underlying T-cell function in these cardiomyopathies are not well-defined. In this study, we sought to investigate the phenotypic and functional characteristics of T-cell subpopulations in CCC and IDC, aiming to clarify whether the inflammatory response is similar or distinct in these cardiomyopathies. We evaluated the expression of systemic cytokines, determined the sources of the different cytokines, the expression of their receptors, of cytotoxic molecules, and of molecules associated with recruitment to the heart by circulating CD4+, CD8+, and CD4-CD8- T-cells from CCC and IDC patients, using multiparameter flow cytometry combined with conventional and unsupervised machine-learning strategies. We also used an in silico approach to identify the expression of genes that code for key molecules related to T-cell function in hearts of patient with CCC and IDC. Our data demonstrated that CCC patients displayed a more robust systemic inflammatory cytokine production as compared to IDC. While CD8+ T-cells were highly activated in CCC as compared to IDC, CD4+ T-cells were more activated in IDC. In addition to differential expression of functional molecules, these cells also displayed distinct expression of molecules associated with recruitment to the heart. In silico analysis of gene transcripts in the cardiac tissue demonstrated a significant correlation between CD8 and inflammatory, cytotoxic and cardiotropic molecules in CCC transcripts, while no correlation with CD4 was observed. A positive correlation was observed between CD4 and perforin transcripts in hearts from IDC but not CCC, as compared to normal tissue. These data show a clearly distinct systemic and local cellular response in CCC and IDC, despite their similar cardiac impairment, which may contribute to identifying specific immunotherapeutic targets in these diseases.},
}

@article {pmid33827325,
year = {2021},
author = {Weaver, KD and Isom, J and Esnakula, A and Daily, K and Asirvatham, JR},
title = {Acinic Cell Carcinoma of the Breast: Report of a Case With Immunohistochemical and Next-Generation Sequencing Studies.},
journal = {International journal of surgical pathology},
volume = {29},
number = {8},
pages = {882-886},
doi = {10.1177/10668969211008508},
pmid = {33827325},
issn = {1940-2465},
mesh = {Adult ; Anoctamin-1/analysis/metabolism ; Biomarkers, Tumor/*analysis/genetics/metabolism ; Breast/*pathology/surgery ; Carcinoma, Acinar Cell/*diagnosis/genetics/pathology ; DNA Mutational Analysis ; Female ; GATA3 Transcription Factor/analysis/metabolism ; High-Throughput Nucleotide Sequencing ; Humans ; Immunohistochemistry ; Mastectomy ; Neoplasm Proteins/analysis/metabolism ; Polymorphism, Single Nucleotide ; Pregnancy ; Pregnancy Complications, Neoplastic/*diagnosis/genetics/pathology ; Proto-Oncogene Proteins c-ret/genetics ; Sentinel Lymph Node Biopsy ; Triple Negative Breast Neoplasms/*diagnosis/genetics/pathology ; Tumor Suppressor Protein p53/genetics ; },
abstract = {Acinic cell carcinoma of the breast is a rare subtype of triple-negative breast cancer that recapitulates the appearance of tumors seen in salivary glands. We present the case of a 42-year-old woman with an irregular, nontender mass above the left nipple during routine obstetric appointment at 24 weeks gestation. She was subsequently diagnosed with triple-negative invasive ductal carcinoma of the left breast, Nottingham grade 3, via core needle biopsy. She was treated with neoadjuvant therapy (doxorubucin and cyclophosphamide) antenatally and paclitaxel in the postpartum period followed by left mastectomy with sentinel node biopsy. The carcinoma in the mastectomy specimen showed a spectrum of morphologic patterns with immunohistochemistry revealing strong positivity for alpha-1-antichymotrypsin, epithelial membrane antigen (EMA), lysozyme, and S100. The histomorphology paired with the immunoprofile led us to the diagnosis of acinic cell carcinoma. We retrospectively performed immunostains in the core biopsy specimen, which demonstrated GATA-3 and DOG-1 positivity. Next-generation sequencing of the postneoadjuvant specimen using a 70-gene panel revealed 2 single-nucleotide variant (SNV) mutations: tumor protein 53 (TP53) (c.747G>T) SNV mutation and rearranged during transfection (RET) (c.2899G>A) SNV mutation.},
}

Adult
Anoctamin-1/analysis/metabolism
Biomarkers, Tumor/*analysis/genetics/metabolism
Breast/*pathology/surgery
Carcinoma, Acinar Cell/*diagnosis/genetics/pathology
DNA Mutational Analysis
Female
GATA3 Transcription Factor/analysis/metabolism
High-Throughput Nucleotide Sequencing
Humans
Immunohistochemistry
Mastectomy
Neoplasm Proteins/analysis/metabolism
Polymorphism, Single Nucleotide
Pregnancy
Pregnancy Complications, Neoplastic/*diagnosis/genetics/pathology
Proto-Oncogene Proteins c-ret/genetics
Sentinel Lymph Node Biopsy
Triple Negative Breast Neoplasms/*diagnosis/genetics/pathology
Tumor Suppressor Protein p53/genetics

@article {pmid34538726,
year = {2022},
author = {Ramotar, M and Chua, MLK and Truong, H and Hosni, A and Pintilie, M and Davicioni, E and Fleshner, NE and Dicker, AP and Bristow, RG and He, HH and van der Kwast, T and Den, RB and Berlin, A},
title = {Subpathologies and genomic classifier for treatment individualization of post-prostatectomy radiotherapy.},
journal = {Urologic oncology},
volume = {40},
number = {1},
pages = {5.e1-5.e13},
doi = {10.1016/j.urolonc.2021.08.013},
pmid = {34538726},
issn = {1873-2496},
mesh = {Adult ; Aged ; Cohort Studies ; Combined Modality Therapy ; Genome ; Humans ; Male ; Middle Aged ; Postoperative Period ; Prognosis ; *Prostatectomy ; Prostatic Neoplasms/*classification/genetics/*radiotherapy/surgery ; },
abstract = {PURPOSE/OBJECTIVE: Risk-stratification for post-prostatectomy radiotherapy (PORT) using conventional clinicopathologic indexes leads to substantial over- and under-treatment. Better patient selection could spare unnecessary toxicities and improve outcomes. We investigated the prognostic utility of unfavorable subpathologies intraductal carcinoma and cribriform architecture (IDC/CA), and a 22-gene Decipher genomic classifier (GC) in prostate cancer (PCa) patients receiving PORT.

MATERIAL/METHODS: A cohort of 302 men who received PORT at 2 academic institutions was pooled. PORT was predominately delivered as salvage (62% of cases); 20% received HT+PORT. Specimens were centrally reviewed for IDC/CA presence. In 104 cases, GC scores were determined. Endpoints were biochemical relapse-free (bRFR) and metastasis-free (mFR) rates.

RESULTS: After a median follow-up of 6.49-years, 135 (45%) and 40 (13%) men experienced biochemical relapse and metastasis, respectively. IDC/CA were identified in 160 (53%) of cases. Men harboring IDC/CA experienced inferior bRFR (HR 2.6, 95%CI 1.8-3.2, P<0.001) and mFR (HR 3.1, 95%CI 1.5-6.4, P = 0.0014). Patients with GC scores, 22 (21%) were stratified low-, 30 (29%) intermediate-, and 52 (50%) high-risk. GC low-risk was associated with superior bRFR (HR 0.25, 95%CI 0.1-0.5, P<0.001) and mFR (HR 0.15, 95%CI 0.03-0.8, P = 0.025). On multivariable analyses, IDC/CA and GC independently predicted for bRFR, corresponding to improved discrimination (C-index = 0.737 (95%CI 0.662-0.813)).

CONCLUSIONS: IDC/CA subpathologies and GC predict for biochemical relapse and metastasis beyond conventional clinicopathologic indexes in the PORT setting. Patients harboring IDC/CA are at higher risk of relapse after maximal local therapies, thus warranting consideration for treatment intensification strategies. Conversely, for men with absence of IDC/CA and low GC scores, de-intensification strategies could be explored.},
}

Adult
Aged
Cohort Studies
Combined Modality Therapy
Genome
Humans
Male
Middle Aged
Postoperative Period
Prognosis
*Prostatectomy
Prostatic Neoplasms/*classification/genetics/*radiotherapy/surgery

@article {pmid34881777,
year = {2022},
author = {Sidhanth, C and Bindhya, S and Shabna, A and Krishnapriya, S and Manasa, P and Nagare, RP and Joshua, T and Sneha, S and Murhekar, K and Ganesan, TS},
title = {LASP-1 interacts with ErbB2 in ovarian cancer cells.},
journal = {The Biochemical journal},
volume = {479},
number = {1},
pages = {23-38},
doi = {10.1042/BCJ20210173},
pmid = {34881777},
issn = {1470-8728},
mesh = {Adaptor Proteins, Signal Transducing/genetics/*metabolism ; Adult ; Breast Neoplasms/*metabolism/pathology ; Carcinoma, Ductal, Breast/*metabolism/pathology ; Carcinoma, Ovarian Epithelial/*metabolism/pathology ; Cell Line, Tumor ; Cohort Studies ; Cytoskeletal Proteins/genetics/*metabolism ; Female ; HEK293 Cells ; Humans ; LIM Domain Proteins/genetics/*metabolism ; Lapatinib/pharmacology ; Middle Aged ; Ovarian Neoplasms/*metabolism/pathology ; Phosphorylation/drug effects/genetics ; Plasmids ; Protein Kinase Inhibitors/pharmacology ; Quinazolines/pharmacology ; Receptor, ErbB-2/genetics/*metabolism ; Signal Transduction/drug effects/*genetics ; Transfection ; },
abstract = {LASP-1 was identified as a protein following mass spectrometric analysis of phosphoproteins consequent to signaling by ErbB2 in SKOV-3 cells. It has been previously identified as an oncogene and is located on chromosomal arm 17q 0.76 Mb centromeric to ErbB2. It is expressed in serous ovarian cancer cell lines as a 40 kDa protein. In SKOV-3 cells, it was phosphorylated and was inhibited by Lapatinib and CP7274714. LASP-1 co-immunoprecipitated with ErbB2 in SKOV-3 cells, suggesting a direct interaction. This interaction and phosphorylation were independent of the kinase activity of ErbB2. Moreover, the binding of LASP-1 to ErbB2 was independent of the tyrosine phosphorylation of LASP-1. LASP-1 was neither expressed on the surface epithelium of the normal ovary nor in the fallopian tube. It was expressed in 28% of ovarian tumours (n = 101) that did not significantly correlate with other clinical factors. In tumours from patients with invasive ductal carcinoma of the breast who had ErbB2 amplification (3+), LASP-1 was expressed in 3/20 (P < 0.001). Analysis of the expression of an independent dataset of ovarian and breast tumours from TCGA showed the significant co-occurrence of ErbB2 and LASP-1 (P < 0.01). These results suggest that LASP-1 and ErbB2 interaction could be important in the pathogenesis of ovarian cancer.},
}

Adaptor Proteins, Signal Transducing/genetics/*metabolism
Adult
Breast Neoplasms/*metabolism/pathology
Carcinoma, Ductal, Breast/*metabolism/pathology
Carcinoma, Ovarian Epithelial/*metabolism/pathology
Cell Line, Tumor
Cohort Studies
Cytoskeletal Proteins/genetics/*metabolism
Female
HEK293 Cells
Humans
LIM Domain Proteins/genetics/*metabolism
Lapatinib/pharmacology
Middle Aged
Ovarian Neoplasms/*metabolism/pathology
Phosphorylation/drug effects/genetics
Plasmids
Protein Kinase Inhibitors/pharmacology
Quinazolines/pharmacology
Receptor, ErbB-2/genetics/*metabolism
Signal Transduction/drug effects/*genetics
Transfection

@article {pmid34801929,
year = {2022},
author = {Mampel, A and Sottile, ML and Denita-Juárez, SP and Vargas, AL and Vargas-Roig, LM},
title = {Double heterozygous pathogenic variants in the BRCA1 and BRCA2 genes in a patient with bilateral metachronous breast cancer.},
journal = {Cancer genetics},
volume = {260-261},
number = {},
pages = {14-17},
doi = {10.1016/j.cancergen.2021.11.003},
pmid = {34801929},
issn = {2210-7762},
mesh = {Adult ; Aged ; BRCA1 Protein/*genetics ; BRCA2 Protein/*genetics ; Breast Neoplasms/*genetics ; Carcinoma, Ductal, Breast/*genetics ; Female ; Genetic Counseling ; Genetic Predisposition to Disease ; Genetic Testing ; Heterozygote ; Humans ; Male ; Neoplasms, Second Primary/*genetics ; Pedigree ; *Point Mutation ; Sequence Analysis, DNA ; *Sequence Deletion ; },
abstract = {Double heterozygosity pathogenic variants in BRCA1 and BRCA2 genes are a very rare finding, particularly in non-Ashkenazi individuals. We described the first case of double heterozygosity variants in a non-Ashkenazi Argentinean woman with metachronous bilateral breast cancer. The proband is a 65-year-old female diagnosed with invasive ductal carcinoma in the left breast at 45 years old and invasive carcinoma in the right breast at 65 years old. She underwent a multi-gene panel testing indicating the presence of two concurrent heterozygous germline deleterious variants NM_007300.4(BRCA1):c.4201C>T (p.Gln1401Ter), and NM_000059.3(BRCA2):c.5146_5149del (p.Tyr1716fs). . The patient's son (40 years-old) was found to have the inherited pathogenic variant in BRCA2 gene. There are few reports of double heterozygosity variants in BRCA1 and BRCA2 genes in Latin America. The two pathogenic variants identified in our patient have not been described together so far.},
}

Adult
Aged
BRCA1 Protein/*genetics
BRCA2 Protein/*genetics
Breast Neoplasms/*genetics
Carcinoma, Ductal, Breast/*genetics
Female
Genetic Counseling
Genetic Predisposition to Disease
Genetic Testing
Heterozygote
Humans
Male
Neoplasms, Second Primary/*genetics
Pedigree
*Point Mutation
Sequence Analysis, DNA
*Sequence Deletion

@article {pmid34321100,
year = {2021},
author = {Meyer, D and Kames, J and Bar, H and Komar, AA and Alexaki, A and Ibla, J and Hunt, RC and Santana-Quintero, LV and Golikov, A and DiCuccio, M and Kimchi-Sarfaty, C},
title = {Distinct signatures of codon and codon pair usage in 32 primary tumor types in the novel database CancerCoCoPUTs for cancer-specific codon usage.},
journal = {Genome medicine},
volume = {13},
number = {1},
pages = {122},
pmid = {34321100},
issn = {1756-994X},
support = {R01 HL151392/HL/NHLBI NIH HHS/United States ; },
mesh = {Biomarkers, Tumor ; *Codon ; *Codon Usage ; Computational Biology/*methods ; *Databases, Genetic ; Gene Expression Profiling ; Gene Expression Regulation, Neoplastic ; Genome-Wide Association Study ; Genomics/methods ; Humans ; Kaplan-Meier Estimate ; Neoplasms/*diagnosis/*genetics/mortality ; Prognosis ; Transcriptome ; },
abstract = {BACKGROUND: Gene expression is highly variable across tissues of multi-cellular organisms, influencing the codon usage of the tissue-specific transcriptome. Cancer disrupts the gene expression pattern of healthy tissue resulting in altered codon usage preferences. The topic of codon usage changes as they relate to codon demand, and tRNA supply in cancer is of growing interest.

METHODS: We analyzed transcriptome-weighted codon and codon pair usage based on The Cancer Genome Atlas (TCGA) RNA-seq data from 6427 solid tumor samples and 632 normal tissue samples. This dataset represents 32 cancer types affecting 11 distinct tissues. Our analysis focused on tissues that give rise to multiple solid tumor types and cancer types that are present in multiple tissues.

RESULTS: We identified distinct patterns of synonymous codon usage changes for different cancer types affecting the same tissue. For example, a substantial increase in GGT-glycine was observed in invasive ductal carcinoma (IDC), invasive lobular carcinoma (ILC), and mixed invasive ductal and lobular carcinoma (IDLC) of the breast. Change in synonymous codon preference favoring GGT correlated with change in synonymous codon preference against GGC in IDC and IDLC, but not in ILC. Furthermore, we examined the codon usage changes between paired healthy/tumor tissue from the same patient. Using clinical data from TCGA, we conducted a survival analysis of patients based on the degree of change between healthy and tumor-specific codon usage, revealing an association between larger changes and increased mortality. We have also created a database that contains cancer-specific codon and codon pair usage data for cancer types derived from TCGA, which represents a comprehensive tool for codon-usage-oriented cancer research.

CONCLUSIONS: Based on data from TCGA, we have highlighted tumor type-specific signatures of codon and codon pair usage. Paired data revealed variable changes to codon usage patterns, which must be considered when designing personalized cancer treatments. The associated database, CancerCoCoPUTs, represents a comprehensive resource for codon and codon pair usage in cancer and is available at https://dnahive.fda.gov/review/cancercocoputs/ . These findings are important to understand the relationship between tRNA supply and codon demand in cancer states and could help guide the development of new cancer therapeutics.},
}

Biomarkers, Tumor
*Codon
*Codon Usage
Computational Biology/*methods
*Databases, Genetic
Gene Expression Profiling
Gene Expression Regulation, Neoplastic
Genome-Wide Association Study
Genomics/methods
Humans
Kaplan-Meier Estimate
Neoplasms/*diagnosis/*genetics/mortality
Prognosis
Transcriptome

@article {pmid35159086,
year = {2022},
author = {Pantazopoulos, H and Diop, MK and Grosset, AA and Rouleau-Gagné, F and Al-Saleh, A and Boblea, T and Trudel, D},
title = {Intraductal Carcinoma of the Prostate as a Cause of Prostate Cancer Metastasis: A Molecular Portrait.},
journal = {Cancers},
volume = {14},
number = {3},
pages = {},
doi = {10.3390/cancers14030820},
pmid = {35159086},
issn = {2072-6694},
abstract = {Intraductal carcinoma of the prostate (IDC-P) is one of the most aggressive types of prostate cancer (PCa). IDC-P is identified in approximately 20% of PCa patients and is associated with recurrence, metastasis, and PCa-specific death. The main feature of this histological variant is the colonization of benign glands by PCa cells. Although IDC-P is a well-recognized independent parameter for metastasis, mechanisms by which IDC-P cells can spread and colonize other tissues are not fully known. In this review, we discuss the molecular portraits of IDC-P determined by immunohistochemistry and genomic approaches and highlight the areas in which more research is needed.},
}

@article {pmid35159065,
year = {2022},
author = {Chen, YC and Chen, WM and Chiang, MF and Shia, BC and Wu, SY},
title = {Association between Pre-Existing Sleep Disorders and Survival Rates of Patients with Breast Cancer.},
journal = {Cancers},
volume = {14},
number = {3},
pages = {},
doi = {10.3390/cancers14030798},
pmid = {35159065},
issn = {2072-6694},
abstract = {PURPOSE: To investigate the effects of pre-existing sleep disorders on the survival outcomes of women receiving standard treatments for breast invasive ductal carcinoma (IDC).

METHODS: We recruited patients from the Taiwan Cancer Registry Database who had received surgery for clinical stage I-III breast IDC. The Cox proportional hazards model was used to analyze all-cause mortality. We categorized the patients into those with and without sleep disorders (Groups 1 and 2, respectively) through propensity score matching.

RESULTS: In the multivariate Cox regression analysis, the adjusted hazard ratio for all-cause mortality for Group 1 compared with Group 2 was 1.51 (95% confidence interval: 1.19, 1.91; p < 0.001).

CONCLUSION: Our study demonstrated that the sleep disorder group had poorer survival rates than the non-sleep disorder group in breast cancer. Therefore, patients should be screened and evaluated for pre-existing sleep disorders prior to breast surgery, with such disorders serving as a predictor of survival in patients with breast cancer. Future studies may investigate the survival benefits of pharmacological and behavioral treatments for sleep problems in patients with breast cancer.},
}

@article {pmid34098822,
year = {2021},
author = {Maitre, T and Ok, V and Calin, R and Lassel, L and Canestri, A and Denis, M and Hamidi, M and Tavolaro, S and Verdet, C and Parrot, A and Cadranel, J and Pialoux, G},
title = {Pyogenic lung abscess in an infectious disease unit: a 20-year retrospective study.},
journal = {Therapeutic advances in respiratory disease},
volume = {15},
number = {},
pages = {17534666211003012},
pmid = {34098822},
issn = {1753-4666},
mesh = {Hospital Units ; Humans ; *Liver Abscess, Pyogenic/epidemiology/therapy ; Retrospective Studies ; Risk Factors ; },
abstract = {BACKGROUND: Pyogenic lung abscesses are rare and poorly described infections. This study aimed to describe their prognostic factors.

METHODS: We retrospectively included all patients hospitalized between 1 January 1998 and 1 June 2018, with an International Classification of Diseases, version 10 (IDC-10) diagnosis of pyogenic lung abscess, from the Diamm based medical records (Micro6, Nancy, France). Parasitic, fungal, or mycobacterial lung abscesses were excluded.

RESULTS: A total of 64 patients were included. Abscesses were associated with immunosuppression in 28 patients, including HIV infection and immunosuppressive therapy for eight and 12 patients, respectively. Bacterial identification was obtained for 36 patients. Nine patients (14%) developed lung abscesses after hematogenous dissemination. They differed from bronchogenic abscesses by their younger age (p = 0.03), the absence of smoking or emphysema (p = 0.05), Staphylococcus aureus (p = 0.001) or Streptococcus spp. (p = 0.05) isolation, and the smaller size of their abscess (p = 0.02). Overall, evolution was marked by radiological sequelae (46.9%), relapse (12.5%), and death (4.8%). Radiological sequelae occurred more frequently during the course of bronchogenic abscesses (p = 0.02), particularly when they spontaneously discharged (p = 0.04). Relapses were more frequent in patients with emphysema (p = 0.04) and when Haemophilus influenzae was isolated (p = 0.04). In multivariate analysis, poor outcomes, including death, sequelae, and relapse occurred more frequently in patients who had bronchogenic abscess (p = 0.02), and in those who received antibiotics during less than 6 weeks (p = 0.05).

CONCLUSION: A duration of antibiotic treatment of less than 6 weeks and bronchogenic presentation were globally associated with poor outcome of pyogenic lung abscesses. These data should be considered when proposing guidelines for the care of pyogenic lung abscesses.The reviews of this paper are available via the supplemental material section.},
}

Hospital Units
Humans
*Liver Abscess, Pyogenic/epidemiology/therapy
Retrospective Studies
Risk Factors

@article {pmid35151355,
year = {2022},
author = {Zhang, J and Sum, SY and Hsu, JG and Chiang, MF and Lee, TS and Wu, SY},
title = {Adjuvant postmastectomy radiotherapy might be associated with better survival in women with heart failure receiving total mastectomy.},
journal = {Radiation oncology (London, England)},
volume = {17},
number = {1},
pages = {33},
pmid = {35151355},
issn = {1748-717X},
abstract = {BACKGROUND: To date, no data on the effect of adjuvant postmastectomy radiotherapy (PMRT) on oncologic outcomes, such as all-cause death, locoregional recurrence (LRR), and distant metastasis (DM), are available in women with left-side breast invasive ductal carcinoma (IDC) and heart failure with reduced ejection fraction (HFrEF).

PATIENTS AND METHODS: We enrolled 646 women with left-breast IDC at clinical stages I-IIIC and HFrEF receiving radical total mastectomy (TM) followed by adjuvant PMRT or non-adjuvant PMRT. We categorized them into two groups based on their adjuvant PMRT status and compared their overall survival (OS), LRR, and DM outcomes. We calculated the propensity score and applied inverse probability of treatment weighting (IPTW) to create a pseudo-study cohort. Furthermore, we performed a multivariate analysis of the propensity score-weighted population to obtain hazard ratios (HRs).

RESULTS: In the IPTW-adjusted model, adjuvant PMRT (adjusted HR [aHR]: 0.52; 95% confidence interval [CI]: 0.37-0.74) was a significant independent prognostic factor for all-cause death (P = 0.0003), and the aHR (95% CI) of LRR and DM for adjuvant PMRT was 0.90 (0.79-0.96; P = 0.0356) and 0.89 (0.54-1.50; P = 0.6854), respectively, compared with the nonadjuvant PMRT group.

CONCLUSION: Adjuvant PMRT was associated with a decrease in all-cause death, and LRR in women with left IDC and HFrEF compared with nonadjuvant PMRT.},
}

@article {pmid34058243,
year = {2021},
author = {Hesterberg, AB and Gordetsky, JB and Hurley, PJ},
title = {Cribriform Prostate Cancer: Clinical Pathologic and Molecular Considerations.},
journal = {Urology},
volume = {155},
number = {},
pages = {47-54},
doi = {10.1016/j.urology.2021.05.028},
pmid = {34058243},
issn = {1527-9995},
mesh = {Humans ; Male ; Molecular Diagnostic Techniques ; Neoplasm Grading ; Prostatic Neoplasms/*diagnosis/*genetics/pathology ; },
abstract = {Intraductal cribriform (IDC) and invasive cribriform morphologies are associated with worse prostate cancer outcomes. Limited retrospective studies have associated IDC and cribriform morphology with germline mutations in DNA repair genes, particularly BRCA2. These findings, which prompted the National Comprehensive Cancer Network (NCCN) Guidelines for Prostate Cancer and Genetic/Familial High- Risk Assessment to consider germline testing for individuals with IDC/cribriform histology, have been questioned in a recent prospective study. A deepened understanding of the molecular mechanisms driving disease aggressiveness in cribriform morphology is critical to provide more clarity in clinical decision making. This review summarizes the current understanding of IDC and cribriform prostate cancer, with an emphasis on clinical outcomes and molecular alterations.},
}

Humans
Male
Molecular Diagnostic Techniques
Neoplasm Grading
Prostatic Neoplasms/*diagnosis/*genetics/pathology

@article {pmid33947745,
year = {2021},
author = {Sottnik, JL and Bordeaux, EK and Mehrotra, S and Ferrara, SE and Goodspeed, AE and Costello, JC and Sikora, MJ},
title = {Mediator of DNA Damage Checkpoint 1 (MDC1) Is a Novel Estrogen Receptor Coregulator in Invasive Lobular Carcinoma of the Breast.},
journal = {Molecular cancer research : MCR},
volume = {19},
number = {8},
pages = {1270-1282},
pmid = {33947745},
issn = {1557-3125},
support = {P30 CA046934/CA/NCI NIH HHS/United States ; R00 CA193734/CA/NCI NIH HHS/United States ; T32 GM007635/GM/NIGMS NIH HHS/United States ; },
mesh = {Adaptor Proteins, Signal Transducing/*genetics ; Breast/pathology ; Breast Neoplasms/drug therapy/*genetics/pathology ; Carcinoma, Lobular/drug therapy/*genetics/pathology ; Cell Cycle Proteins/*genetics ; Cell Line, Tumor ; Cell Proliferation/drug effects/genetics ; Female ; Humans ; MCF-7 Cells ; Promoter Regions, Genetic/drug effects/genetics ; Receptors, Estrogen/*genetics ; Signal Transduction/genetics ; Tamoxifen/therapeutic use ; Transcriptome/drug effects/genetics ; },
abstract = {Invasive lobular carcinoma (ILC) is the most common special histologic subtype of breast cancer, and nearly all ILC tumors express estrogen receptor alpha (ER). However, clinical and laboratory data suggest ILC are strongly estrogen-driven but not equally antiestrogen-sensitive. We hypothesized ILC-specific ER coregulators mediate ER functions and antiestrogen resistance in ILC, and profiled ER-associated proteins by mass spectrometry. Three ER+ ILC cell lines (MDA MB 134VI, SUM44PE, and BCK4) were compared with ER+ invasive ductal carcinoma (IDC) line data, and we examined whether siRNA of identified proteins suppressed ER-driven proliferation in ILC cells. This identified mediator of DNA damage checkpoint 1 (MDC1), a tumor suppressor in DNA damage response (DDR), as a novel ER coregulator in ILC. We confirmed ER:MDC1 interaction was specific to ILC versus IDC cells, and found MDC1 knockdown suppressed ILC cell proliferation and tamoxifen resistance. Using RNA-sequencing, we found in ILC cells MDC1 knockdown broadly dysregulates the ER transcriptome, with ER:MDC1 target genes enriched for promoter hormone response elements. Importantly, our data are inconsistent with MDC1 tumor suppressor functions in DDR, but suggest a novel oncogenic role for MDC1 as an ER coregulator. Supporting this, in breast tumor tissue microarrays, MDC1 protein was frequently low or absent in IDC, but MDC1 loss was rare in ER+ ILC. ER:MDC1 interaction and MDC1 coregulator functions may underlie ER function in ILC and serve as targets to overcome antiestrogen resistance in ILC. IMPLICATIONS: MDC1 has novel ER coregulator activity in ILC, which may underlie ILC-specific ER functions, estrogen response, and antiestrogen resistance.},
}

Adaptor Proteins, Signal Transducing/*genetics
Breast/pathology
Breast Neoplasms/drug therapy/*genetics/pathology
Carcinoma, Lobular/drug therapy/*genetics/pathology
Cell Cycle Proteins/*genetics
Cell Line, Tumor
Cell Proliferation/drug effects/genetics
Female
Humans
MCF-7 Cells
Promoter Regions, Genetic/drug effects/genetics
Receptors, Estrogen/*genetics
Signal Transduction/genetics
Tamoxifen/therapeutic use
Transcriptome/drug effects/genetics

@article {pmid33561470,
year = {2021},
author = {Kabay, S and Kabay, SC},
title = {The Sustained Therapeutic Effects of Percutaneous Posterior Tibial Nerve Stimulation in the Treatment of Neurogenic Lower Urinary Tract Symptoms in Patients with Parkinson's Disease: 24-months Clinical and Urodynamic Results.},
journal = {Urology},
volume = {153},
number = {},
pages = {49-55},
doi = {10.1016/j.urology.2021.01.044},
pmid = {33561470},
issn = {1527-9995},
mesh = {Aged ; Aged, 80 and over ; Female ; Humans ; Lower Urinary Tract Symptoms/etiology/*therapy ; Male ; Middle Aged ; Parkinson Disease/complications ; Prospective Studies ; *Tibial Nerve ; Time Factors ; *Transcutaneous Electric Nerve Stimulation ; Treatment Outcome ; Urinary Bladder, Neurogenic/etiology/*therapy ; Urodynamics ; },
abstract = {OBJECTIVE: To determine the sustained therapeutic effect of percutaneous posterior tibial nerve stimulation (PTNS) treatment in Parkinson's disease patients with detrusor activity during 24 months.

METHODS: After 12 weeks therapy, PTNS was applied at 14-day intervals for 3 months, 21-day intervals for 3 months and 28-day intervals through 24 months. The patients completed a 3-day voiding diary and ICIQ-SF, OAB-V8, OAB-q SF questionnaires at 3rd, 6th, 9th,12th and 24th month.

RESULTS: A total of 76 patients were enrolled in the study. Of these 44 (57.9%) were men and 32 (42.1%) women. The differences of compared parameters at baseline and at the end of 24 months were as follows; daytime frequency decreased by 4.6 voids daily, urge incontinence decreased by 4.2 episodes daily, urgency episodes decreased by 6.2 episodes daily, nocturia decreased by 2.4 voids (P <.001) and voided volume improved by a mean of 71.4 cc (P <.05). When compared with baseline significant improvements were seen in the volume at the first involuntary detrusor contraction (1st IDCV), maximum cystometric capacity (MCC), maximal detrusor pressure at first involuntary detrusor contraction (1st IDC Pdetmax), maximal detrusor pressure at MCC (MCC Pdetmax), detrusor pressure at maximal flow (PdetQmax) and post-void residual volume (PVR) after PTNS treatment at 3, 12, 24 months (P <.001 for each) except maximal flow rate (Qmax) value (P ˃.05).

CONCLUSIONS: These results have demonstrated the significant improvements both on voiding and urodynamic parameters under PTNS treatment with a tapering protocol for during 24-months in Parkinson's disease with detrusor activity.},
}

Aged
Aged, 80 and over
Female
Humans
Lower Urinary Tract Symptoms/etiology/*therapy
Male
Middle Aged
Parkinson Disease/complications
Prospective Studies
*Tibial Nerve
Time Factors
*Transcutaneous Electric Nerve Stimulation
Treatment Outcome
Urinary Bladder, Neurogenic/etiology/*therapy
Urodynamics

@article {pmid34022480,
year = {2021},
author = {Hoshina, H and Takei, H and Nakamura, M and Nishimoto, F and Hanamura, S},
title = {Carcinomatous cirrhosis as radiographically occult liver metastases of breast cancer: A systematic literature review.},
journal = {Cancer treatment and research communications},
volume = {28},
number = {},
pages = {100388},
doi = {10.1016/j.ctarc.2021.100388},
pmid = {34022480},
issn = {2468-2942},
mesh = {Ascites/*diagnosis/etiology ; Breast Neoplasms/*pathology ; Female ; Humans ; Liver Cirrhosis/*diagnosis/etiology ; Liver Neoplasms/complications/*diagnosis/secondary ; Magnetic Resonance Imaging ; Tomography, X-Ray Computed ; },
abstract = {In the present study, we aimed to clarify features of carcinomatous cirrhosis from breast cancer presenting as refractory transudate ascites and acute liver failure. In our systematic literature review, we identified 26 studies and 31 cases including our case of this rare condition. Our patient was a 49-year-old woman with a history of ascites and liver failure for the past 4 years and currently being treated for invasive ductal breast cancer. On radiography, she had occult liver metastases that were confirmed using laparoscopic liver biopsy. In the 31 cases, data on the reported year, age, type of primary breast cancer, time from breast cancer diagnosis, presence of ascites and/or varices, liver biopsy, diagnostic modalities, outcomes, and survival were documented and analyzed. All cases were reported during 1984-2020, with a mean patient age of 52.9 years. Eighteen patients (58.1%) were diagnosed with ductal breast cancer. Twenty-two patients (70.9%) had ascites. All patients had gradual progression to liver dysfunction. The following tests were performed: computed tomography (77.4%); ultrasound (58.0%); liver biopsy (100%); postmortem biopsy (35.5%), transjugular liver biopsy (32.3%), and laparoscopic liver biopsy (3.2%). Outcomes were reported for 29 patients, of whom 24 (82.3%) died after 1 day to 16 months. Invasive ductal carcinoma was the most common histological type; however, invasive lobular carcinoma was more frequent (32.3%) than its reported incidence in the breast. Carcinomatous cirrhosis has poor prognosis at relatively rash and is difficult to diagnose with usual modalities. It may be associated with E-cadherin loss or CD44 pronouncement.},
}

Ascites/*diagnosis/etiology
Breast Neoplasms/*pathology
Female
Humans
Liver Cirrhosis/*diagnosis/etiology
Liver Neoplasms/complications/*diagnosis/secondary
Magnetic Resonance Imaging
Tomography, X-Ray Computed

@article {pmid34673584,
year = {2021},
author = {Senel, F},
title = {The hormone receptor status in breast cancer and the relationship of subtypes with clinicopathological features.},
journal = {Indian journal of pathology & microbiology},
volume = {64},
number = {4},
pages = {671-676},
doi = {10.4103/IJPM.IJPM_606_20},
pmid = {34673584},
issn = {0974-5130},
mesh = {Adult ; Age Factors ; Biomarkers, Tumor/*genetics/*metabolism ; Breast Neoplasms/*genetics/*metabolism/*physiopathology ; Female ; Genetic Variation ; Genotype ; Humans ; Middle Aged ; Pathology, Clinical/methods ; Receptors, Estrogen/genetics/*metabolism ; Receptors, Progesterone/genetics/*metabolism ; Retrospective Studies ; },
abstract = {Aim: We aimed to determine the hormone receptor status in breast cancers and to investigate the relationship between single hormone receptor-positive, double hormone receptor-positive, double hormone receptor negativity, and human epidermal growth factor receptor 2 (HER2) status and some clinicopathological features.

Materials and Methods: The study includes 85 patients who were diagnosed in our center between 2018 and 2019 and having surgical specimens were included in the study. Data of the cases, such as estrogen receptor (ER), progesterone receptor (PR), HER2 status, silver in situ hybridization (SISH) evaluation results, age distribution, histopathological findings were recorded.

Results and Conclusions: We investigated the relationship between age, grade, tumor size, lymph node metastases and ER, PR, and HER2. However, there was not a significant association between ER, PR, and HER2 and age, tumor size, lymph node metastases (P > 0.05). On the other hand, we found a significant association between grades and ER (P = 0.02) and PR (P = 0.004), but not between grades and HER2 (P > 0.05). High-grade tumors were tumors with the lowest ER, PR positivity rate. Considering the four subtypes, cases aged above 45 years were at most double hormone receptor-positive (75%) and ER-positive/PR-negative (56%), respectively (P < 0.001). High-grade tumors were mostly double hormone receptor-negative and at least double hormone receptor positive. The ER-positive/PR-negative subtype was between these two groups (P < 0.001). The increased tumor size (T3) and increased metastatic lymph node number (N2 and N3) were observed at least in the ER-positive/PR-negative subtype. The majority of cases are in the older age group and invasive ductal carcinoma (IDC) is the most common tumor type. Older cases are most frequently double hormone receptor-positive and ER-positive/PR-negative, respectively. The ER, PR positivity rate is low in high-grade tumors. ER-positive/PR-negative tumors are of a higher grade than double hormone receptor-positive tumors, but they are of a lower grade than double hormone receptor-negative tumors. The increased tumor size and increased lymph node metastasis number are at most in the double hormone negative subtype and at least in the ER-positive/PR-negative subtype. The ER-negative/PR-positive subtype is observed very rarely, which raises the question of whether ER-negative/PR-positive tumors really exist. Further studies are needed to investigate this subtype and its properties.},
}

Adult
Age Factors
Biomarkers, Tumor/*genetics/*metabolism
Breast Neoplasms/*genetics/*metabolism/*physiopathology
Female
Genetic Variation
Genotype
Humans
Middle Aged
Pathology, Clinical/methods
Receptors, Estrogen/genetics/*metabolism
Receptors, Progesterone/genetics/*metabolism
Retrospective Studies

@article {pmid34668757,
year = {2021},
author = {Saelens, JW and Petersen, JEV and Freedman, E and Moseley, RC and Konaté, D and Diakité, SAS and Traoré, K and Vance, N and Fairhurst, RM and Diakité, M and Haase, SB and Taylor, SM},
title = {Impact of Sickle Cell Trait Hemoglobin on the Intraerythrocytic Transcriptional Program of Plasmodium falciparum.},
journal = {mSphere},
volume = {6},
number = {5},
pages = {e0075521},
pmid = {34668757},
issn = {2379-5042},
support = {R21 AI125988/AI/NIAID NIH HHS/United States ; UL1 TR002553/TR/NCATS NIH HHS/United States ; },
mesh = {Adolescent ; Child ; Child, Preschool ; Female ; Hemoglobin A/*genetics ; Hemoglobin, Sickle/*genetics ; Hemoglobins/metabolism ; Humans ; Malaria, Falciparum/blood/*genetics/parasitology ; Male ; Plasmodium falciparum/physiology ; Sickle Cell Trait/blood/*genetics/parasitology ; Transcriptional Activation ; },
abstract = {Sickle-trait hemoglobin (HbAS) confers nearly complete protection from severe, life-threatening falciparum malaria in African children. Despite this clear protection, the molecular mechanisms by which HbAS confers these protective phenotypes remain incompletely understood. As a forward genetic screen for aberrant parasite transcriptional responses associated with parasite neutralization in HbAS red blood cells (RBCs), we performed comparative transcriptomic analyses of Plasmodium falciparum in normal (HbAA) and HbAS erythrocytes during both in vitro cultivation of reference parasite strains and naturally occurring P. falciparum infections in Malian children with HbAA or HbAS. During in vitro cultivation, parasites matured normally in HbAS RBCs, and the temporal expression was largely unperturbed of the highly ordered transcriptional program that underlies the parasite's maturation throughout the intraerythrocytic development cycle (IDC). However, differential expression analysis identified hundreds of transcripts aberrantly expressed in HbAS, largely occurring late in the IDC. Surprisingly, transcripts encoding members of the Maurer's clefts were overexpressed in HbAS despite impaired parasite protein export in these RBCs, while parasites in HbAS RBCs underexpressed transcripts associated with the endoplasmic reticulum and those encoding serine repeat antigen proteases that promote parasite egress. Analyses of P. falciparum transcriptomes from 32 children with uncomplicated malaria identified stage-specific differential expression: among infections composed of ring-stage parasites, only cyclophilin 19B was underexpressed in children with HbAS, while trophozoite-stage infections identified a range of differentially expressed transcripts, including downregulation in HbAS of several transcripts associated with severe malaria in collateral studies. Collectively, our comparative transcriptomic screen in vitro and in vivo indicates that P. falciparum adapts to HbAS by altering its protein chaperone and folding machinery, oxidative stress response, and protein export machinery. Because HbAS consistently protects from severe P. falciparum, modulation of these responses may offer avenues by which to neutralize P. falciparum parasites. IMPORTANCE Sickle-trait hemoglobin (HbAS) confers nearly complete protection from severe, life-threatening malaria, yet the molecular mechanisms that underlie HbAS protection from severe malaria remain incompletely understood. Here, we used transcriptome sequencing (RNA-seq) to measure the impact of HbAS on the blood-stage transcriptome of Plasmodium falciparum in in vitro time series experiments and in vivo samples from natural infections. Our in vitro time series data reveal that, during its blood stage, P. falciparum's gene expression in HbAS is impacted primarily through alterations in the abundance of gene products as opposed to variations in the timing of gene expression. Collectively, our in vitro and in vivo data indicate that P. falciparum adapts to HbAS by altering its protein chaperone and folding machinery, oxidative stress response, and protein export machinery. Due to the persistent association of HbAS and protection from severe disease, these processes that are modified in HbAS may offer strategies to neutralize P. falciparum.},
}