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

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

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

CONCLUSION: We provide novel data on the effects of elevated sex hormone levels, potentially seen during pregnancy or hormone replacement therapy, on PPGL/GEP-NET tumor growth. G-1 might offer a novel therapeutic approach for some PPGLs depending on patient's sex and the individual tumor's genetic/molecular background. All HNPGLs showed ERα positivity.},
}

Humans
*Pheochromocytoma/metabolism/pathology/drug therapy
Female
*Adrenal Gland Neoplasms/metabolism/pathology/drug therapy
*Neuroendocrine Tumors/metabolism/pathology/drug therapy
Male
*Gonadal Steroid Hormones/pharmacology
*Pancreatic Neoplasms/metabolism/pathology/drug therapy
*Paraganglioma/metabolism/genetics/pathology/drug therapy
*Intestinal Neoplasms/pathology/metabolism
*Stomach Neoplasms/metabolism/pathology/drug therapy
Middle Aged
Estradiol/pharmacology
Testosterone/pharmacology/metabolism
Adult
Progesterone/pharmacology/metabolism
Dehydroepiandrosterone Sulfate/metabolism
Cell Survival/drug effects
Tumor Cells, Cultured
Estrogen Receptor alpha/metabolism/genetics

@article {pmid39799921,
year = {2025},
author = {Fu, J and Wang, J and Ma, Z and Yuan, D and Zhang, Y and Wang, L and Luo, Y},
title = {CaCO3-coated indoxacarb deep eutectic solvent complexed with diatomaceous earth improves insecticidal activity against the red imported fire ants.},
journal = {Ecotoxicology and environmental safety},
volume = {289},
number = {},
pages = {117709},
doi = {10.1016/j.ecoenv.2025.117709},
pmid = {39799921},
issn = {1090-2414},
abstract = {The red imported fire ants (RIFAs) are a globally important invasive pest that severely affects the ecosystem and human health, and its current control is primarily through chemical pesticides. However, the extensive use of chemical pesticides causes environmental problems, and alternative strategies for controlling this pest are being explored. In our study, we aimed to design a deep eutectic solvent (DES)-CaCO3 system in which RIFAs were used as target insects to increase the lethal activity and behavioural regulation effects on RIFAs via contact and feeding. Indoxacarb (IDC) was made into DESs with three fatty acids, oleic acid (OA), linoleic acid (LA), and linolenic acid (LNA), which showed a significant increase in lethal activity against worker ants compared with IDC. OA@IDC@CaCO3, LA@IDC@CaCO3, and LNA@IDC@CaCO3 nanoparticles were prepared via interfacial precipitation. Characterization of the structures of the three pesticide-carrying nanoparticles revealed that all three fatty acid eutectic solvents formed spherical CaCO3 nanoparticles, with average particle sizes between 0.59 and 0.90 μm, which increased with increasing degree of fatty acid unsaturation. The pesticide loading ranged from 2.13 %⁓3.43 %, and the surfaces were all positively charged and well dispersed. OA@IDC@CaCO3 was relatively more effective and was able to dramatically inhibit the abandonment and foraging behaviours of RIFAs, prolong the time required for these behaviours, and decrease the number of feeding worker ants and the amount of food consumed. OA@IDC@CaCO3 was subsequently compounded with diatomaceous earth (DA), and spiked into baits, which significantly increased the contact and feeding activity of worker ants, inhibited the feeding, digging, and corpse-discarding behaviours of RIFAs. In the field trial, the combined control effect of the DA + OA@IDC@CaCO3 group was 83.38 %, which was greater than the 69.65 % of the commercial agent control group. In this study, IDC bait was co-prepared by using acid as a comelting solvent, CaCO3 as a coating, and DA as a pesticide adjuvant, which improved the activity against RIFAs, prolonged the holding period of IDC, and improved the prevention and control of RIFAs. Therefore, our research provides a simple and feasible approach for designing and constructing novel nanopesticides for RIFAs control.},
}

@article {pmid39724992,
year = {2025},
author = {Wang, Y and Zhang, J and Wang, Y and Liu, Y and Shi, B and Li, X and He, J and Zhang, H},
title = {Lower expression of MMP2, FLNA, and CFL1 is correlated with favorable prognosis in invasive micropapillary breast cancer.},
journal = {Gene},
volume = {940},
number = {},
pages = {149192},
doi = {10.1016/j.gene.2024.149192},
pmid = {39724992},
issn = {1879-0038},
mesh = {Humans ; Female ; *Breast Neoplasms/genetics/pathology/mortality ; *Filamins/genetics/metabolism ; Prognosis ; Middle Aged ; *Matrix Metalloproteinase 2/genetics/metabolism ; *Cofilin 1/genetics/metabolism ; Retrospective Studies ; *Gene Expression Regulation, Neoplastic ; Aged ; Carcinoma, Ductal, Breast/genetics/pathology/mortality/metabolism ; Biomarkers, Tumor/genetics/metabolism ; Nomograms ; Carcinoma, Papillary/genetics/pathology ; Adult ; },
abstract = {PURPOSE: Despite its recognized aggressive clinical manifestations, invasive micropapillary carcinoma has a controversial prognosis in comparison to invasive ductal carcinoma of the breast. This retrospective study aimed to explore the prognosis and underlying molecular mechanisms of invasive micropapillary carcinoma.

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

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

CONCLUSIONS: Patients with invasive micropapillary carcinoma generally have a better prognosis than those with invasive ductal carcinoma does, which could be attributed to the lower expression of pro-oncogenic genes in the former group; however, the underlying mechanism needs further investigation.},
}

Humans
Female
*Breast Neoplasms/genetics/pathology/mortality
*Filamins/genetics/metabolism
Prognosis
Middle Aged
*Matrix Metalloproteinase 2/genetics/metabolism
*Cofilin 1/genetics/metabolism
Retrospective Studies
*Gene Expression Regulation, Neoplastic
Aged
Carcinoma, Ductal, Breast/genetics/pathology/mortality/metabolism
Biomarkers, Tumor/genetics/metabolism
Nomograms
Carcinoma, Papillary/genetics/pathology
Adult

@article {pmid39795975,
year = {2024},
author = {Caca, J and Bartelt, A and Egea, V},
title = {Hypoxia Regulates Brown Adipocyte Differentiation and Stimulates miR-210 by HIF-1α.},
journal = {International journal of molecular sciences},
volume = {26},
number = {1},
pages = {},
pmid = {39795975},
issn = {1422-0067},
mesh = {*MicroRNAs/genetics/metabolism ; *Hypoxia-Inducible Factor 1, alpha Subunit/metabolism/genetics ; Animals ; *Adipocytes, Brown/metabolism ; *Cell Differentiation/genetics ; Mice ; Thermogenesis/genetics ; Cell Hypoxia ; },
abstract = {MicroRNAs (miRNAs) are short sequences of single-stranded non-coding RNAs that target messenger RNAs, leading to their repression or decay. Interestingly, miRNAs play a role in the cellular response to low oxygen levels, known as hypoxia, which is associated with reactive oxygen species and oxidative stress. However, the physiological implications of hypoxia-induced miRNAs ("hypoxamiRs") remain largely unclear. Here, we investigate the role of miR-210 in brown adipocyte differentiation and thermogenesis. We treated the cells under sympathetic stimulation with hypoxia, CoCl2, or IOX2. To manipulate miR-210, we performed reverse transfection with antagomiRs. Adipocyte markers expression, lipid accumulation, lipolysis, and oxygen consumption were measured. Hypoxia hindered BAT differentiation and suppressed sympathetic stimulation. Hypoxia-induced HIF-1α stabilization increased miR-210 in brown adipocytes. Interestingly, miR-210-5p enhanced differentiation under normoxic conditions but was insufficient to rescue the inhibition of brown adipocyte differentiation under hypoxic conditions. Although adrenergic stimulation activated HIF-1α signaling and upregulated miR-210 expression, inhibition of miR-210-5p did not significantly influence UCP1 expression or oxygen consumption. In summary, hypoxia and adrenergic stimulation upregulated miR-210, which impacted brown adipocyte differentiation and thermogenesis. These findings offer new insights for the physiological role of hypoxamiRs in brown adipose tissue, which could aid in understanding oxidative stress and treatment of metabolic disorders.},
}

*MicroRNAs/genetics/metabolism
*Hypoxia-Inducible Factor 1, alpha Subunit/metabolism/genetics
Animals
*Adipocytes, Brown/metabolism
*Cell Differentiation/genetics
Mice
Thermogenesis/genetics
Cell Hypoxia

@article {pmid39721789,
year = {2024},
author = {Nagahara, M and Tezuka, K},
title = {[Invasive Ductal Carcinoma with Total Infarction and Necrosis-Case Report and Literature Review].},
journal = {Gan to kagaku ryoho. Cancer & chemotherapy},
volume = {51},
number = {12},
pages = {1255-1258},
pmid = {39721789},
issn = {0385-0684},
mesh = {Humans ; Female ; Aged ; *Necrosis ; *Breast Neoplasms/pathology/complications/surgery ; *Infarction/etiology/pathology ; *Carcinoma, Ductal, Breast/complications/pathology/surgery ; Mastectomy ; },
abstract = {A 71-year-old woman visited our hospital with pain and itching in her left breast which had commenced the day before admission. On palpation, we detected a 2.0 cm nodule, indicative of an elastic and hard tumor located centrally in the left breast. Mammography revealed an oval, microlobulated mass in the central quadrant of the left breast. Ultrasonography indicated a 1.5×1.3 cm hypoechoic lesion at the 12 o'clock position near the left nipple. Core needle biopsy revealed an invasive ductal carcinoma. Therefore, we mastectomized the left breast. Histologically, the tumor mass exhibited total necrosis, with viable carcinoma cells detected in a paramammary lymph node at the resected breast edge. Consequently, the tumor was diagnosed as a solid tubular carcinoma with total infarction and necrosis. Here, we present a rare case of breast cancer associated with infarction and necrosis.},
}

Humans
Female
Aged
*Necrosis
*Breast Neoplasms/pathology/complications/surgery
*Infarction/etiology/pathology
*Carcinoma, Ductal, Breast/complications/pathology/surgery
Mastectomy

@article {pmid39708123,
year = {2024},
author = {Xie, T and Fan, G and Tang, L and Xing, P and Shi, Y},
title = {Artificial neural network systems to predict the response to sintilimab in squamous-cell non-small-cell lung cancer based on data of ORIENT-3 study.},
journal = {Cancer immunology, immunotherapy : CII},
volume = {74},
number = {1},
pages = {29},
pmid = {39708123},
issn = {1432-0851},
mesh = {Humans ; *Carcinoma, Non-Small-Cell Lung/drug therapy/immunology ; *Neural Networks, Computer ; *Lung Neoplasms/drug therapy/immunology ; *Antibodies, Monoclonal, Humanized/therapeutic use ; Male ; Female ; Biomarkers, Tumor ; Prognosis ; Middle Aged ; Carcinoma, Squamous Cell/drug therapy/immunology ; Aged ; },
abstract = {BACKGROUND: Existing biomarkers and models for predicting response to programmed cell death protein 1 monoclonal antibody in advanced squamous-cell non-small cell lung cancer (sqNSCLC) did not have enough accuracy. We used data from the ORIENT-3 study to construct artificial neural network (ANN) systems to predict the response to sintilimab for sqNSCLC.

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

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

INTERPRETATION: The four ANN systems showed high accuracy, robustness and stability in predicting the response to sintilimab for patients with sqNSCLC.},
}

Humans
*Carcinoma, Non-Small-Cell Lung/drug therapy/immunology
*Neural Networks, Computer
*Lung Neoplasms/drug therapy/immunology
*Antibodies, Monoclonal, Humanized/therapeutic use
Male
Female
Biomarkers, Tumor
Prognosis
Middle Aged
Carcinoma, Squamous Cell/drug therapy/immunology
Aged

@article {pmid39684874,
year = {2024},
author = {Galappaththi, SPL and Smith, KR and Alsatari, ES and Hunter, R and Dyess, DL and Turbat-Herrera, EA and Dasgupta, S},
title = {The Genomic and Biologic Landscapes of Breast Cancer and Racial Differences.},
journal = {International journal of molecular sciences},
volume = {25},
number = {23},
pages = {},
pmid = {39684874},
issn = {1422-0067},
support = {1R21MD019400-01/MD/NIMHD NIH HHS/United States ; },
mesh = {Humans ; *Breast Neoplasms/genetics/pathology/epidemiology ; Female ; *Genomics/methods ; Dysbiosis ; Racial Groups/genetics ; },
abstract = {Breast cancer is a significant health challenge worldwide and is the most frequently diagnosed cancer among women globally. This review provides a comprehensive overview of breast cancer biology, genomics, and microbial dysbiosis, focusing on its various subtypes and racial differences. Breast cancer is primarily classified into carcinomas and sarcomas, with carcinomas constituting most cases. Epidemiology and breast cancer risk factors are important for public health intervention. Staging and grading, based on the TNM and Nottingham grading systems, respectively, are crucial to determining the clinical outcome and treatment decisions. Histopathological subtypes include in situ and invasive carcinomas, such as invasive ductal carcinoma (IDC) and invasive lobular carcinoma (ILC). The review explores molecular subtypes, including Luminal A, Luminal B, Basal-like (Triple Negative), and HER2-enriched, and delves into breast cancer's histological and molecular progression patterns. Recent research findings related to nuclear and mitochondrial genetic alterations, epigenetic reprogramming, and the role of microbiome dysbiosis in breast cancer and racial differences are also reported. The review also provides an update on breast cancer's current diagnostics and treatment modalities.},
}

Humans
*Breast Neoplasms/genetics/pathology/epidemiology
Female
*Genomics/methods
Dysbiosis
Racial Groups/genetics

@article {pmid39513960,
year = {2025},
author = {Huang, H and Couch, RE and Karam, R and Hu, C and Boddicker, N and Polley, EC and Na, J and Ambrosone, CB and Yao, S and Trentham-Dietz, A and Eliassen, AH and Penney, K and Brantley, K and Bodelon, C and Teras, LR and Hodge, J and Patel, A and Haiman, CA and John, EM and Neuhausen, SL and Martinez, E and Lacey, JV and O'Brien, KM and Sandler, DP and Weinberg, CR and Palmer, JR and Bertrand, KA and Vachon, CM and Olson, JE and Ruddy, KE and Anton-Culver, H and Ziogas, A and Goldgar, DE and Nathanson, KL and Domchek, SM and Weitzel, JN and Kraft, P and Dolinsky, JS and Pesaran, T and Richardson, ME and Yadav, S and Couch, FJ},
title = {Pathogenic Variants in Cancer Susceptibility Genes Predispose to Ductal Carcinoma In Situ of the Breast.},
journal = {Clinical cancer research : an official journal of the American Association for Cancer Research},
volume = {31},
number = {1},
pages = {130-138},
pmid = {39513960},
issn = {1557-3265},
support = {R35CA253187//National Cancer Institute (NCI)/ ; R01CA225662//National Cancer Institute (NCI)/ ; P50CA116201//National Cancer Institute (NCI)/ ; K12CA090628//National Cancer Institute (NCI)/ ; //Breast Cancer Research Foundation (BCRF)/ ; //Breast Cancer Research Foundation (BCRF)/ ; //Breast Cancer Research Foundation (BCRF)/ ; //Breast Cancer Research Foundation (BCRF)/ ; },
mesh = {Humans ; Female ; *Genetic Predisposition to Disease ; *Breast Neoplasms/genetics/pathology/epidemiology ; *Carcinoma, Intraductal, Noninfiltrating/genetics/pathology/epidemiology ; Middle Aged ; Adult ; *Germ-Line Mutation ; Aged ; Carcinoma, Ductal, Breast/genetics/pathology/epidemiology ; },
abstract = {PURPOSE: To determine the relationship between germline pathogenic variants (PV) in cancer predisposition genes and the risk of ductal carcinoma in situ (DCIS).

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

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

CONCLUSIONS: The enrichment of PV in ATM, BRCA1, BRCA2, CHEK2, and PALB2 among women with DCIS suggests that multigene panel testing may be appropriate for women with DCIS. Elevated risks of CBC in carriers of PV in high-penetrance genes with DCIS confirmed the utility of testing for surgical decision-making.},
}

Humans
Female
*Genetic Predisposition to Disease
*Breast Neoplasms/genetics/pathology/epidemiology
*Carcinoma, Intraductal, Noninfiltrating/genetics/pathology/epidemiology
Middle Aged
Adult
*Germ-Line Mutation
Aged
Carcinoma, Ductal, Breast/genetics/pathology/epidemiology

@article {pmid39684409,
year = {2024},
author = {Feng, M and Cui, H and Li, S and Li, L and Zhou, C and Chen, L and Cao, Y and Gao, Y and Li, D},
title = {Ubiquitin-Activating Enzyme E1 (UBA1) as a Prognostic Biomarker and Therapeutic Target in Breast Cancer: Insights into Immune Infiltration and Functional Implications.},
journal = {International journal of molecular sciences},
volume = {25},
number = {23},
pages = {},
pmid = {39684409},
issn = {1422-0067},
support = {22YF1407800//Shanghai Municipal Commission of Science and Technology/ ; No.82103429//National Natural Science Foundation of China/ ; No.82303311//National Natural Science Foundation of China/ ; },
mesh = {Humans ; *Breast Neoplasms/genetics/immunology/pathology/metabolism ; Female ; *Ubiquitin-Activating Enzymes/genetics/metabolism ; *Biomarkers, Tumor/genetics/metabolism ; Prognosis ; *Gene Expression Regulation, Neoplastic ; Cell Line, Tumor ; },
abstract = {Ubiquitin-Activating Enzyme E1 (UBA1), an E1 enzyme involved in the activation of ubiquitin enzymes, has been involved in the onset and progression of different cancers in humans. Nevertheless, the precise contribution of UBA1 in breast cancer (BC) is still poorly characterized. In this study, a thorough investigation was carried out to elucidate the significance of UBA1 and validate its functionality in BC. Through the analysis of mRNA sequencing data of BC patients, the mRNA expression of UBA1 was observed to be notably enhanced in cancer tissues relative to controls, and high UBA1 expression was linked to worse overall survival (OS), disease-specific survival (DSS), and progress-free survival (PFS). Moreover, UBA1 exhibited potential as an independent prognostic and diagnostic biomarker for individuals with BC. Additionally, functional enrichment analysis revealed the involvement of UBA1 in inflammation-linked pathways, like the TNF-α signaling pathway, the IL-6 signaling pathway, and various immune-related biological processes. Notably, single-sample gene set enrichment analysis (ssGSEA) aided in the identification of a negative link between UBA1 expression and the levels of infiltrating mast cells, Th1 cells, iDC cells, B cells, DC cells, Tem cells, Cytotoxic cells, T cells, CD8T cells, and pDC cells. Finally, this study demonstrated that silencing UBA1 significantly impeded the growth and development of BC cell lines. These findings highlight UBA1 as a potential prognostic biomarker linked to immune infiltration in BC, thereby depicting its potential as a new therapeutic target for individuals with BC.},
}

Humans
*Breast Neoplasms/genetics/immunology/pathology/metabolism
Female
*Ubiquitin-Activating Enzymes/genetics/metabolism
*Biomarkers, Tumor/genetics/metabolism
Prognosis
*Gene Expression Regulation, Neoplastic
Cell Line, Tumor

@article {pmid39654135,
year = {2024},
author = {Rasheed, U and Khalid, M and Noor, A and Saeed, U and Uppal, R and Zafar, S},
title = {Genetic assessment of apolipoprotein E polymorphism and PRNP genotypes in rapidly progressive dementias in Pakistan.},
journal = {Prion},
volume = {18},
number = {1},
pages = {1-7},
doi = {10.1080/19336896.2024.2439598},
pmid = {39654135},
issn = {1933-690X},
mesh = {Humans ; Pakistan ; *Prion Proteins/genetics ; *Genotype ; *Apolipoproteins E/genetics ; Female ; Male ; Polymorphism, Genetic/genetics ; Creutzfeldt-Jakob Syndrome/genetics ; Dementia/genetics ; Mutation/genetics ; Alleles ; Gene Frequency/genetics ; Middle Aged ; Alzheimer Disease/genetics ; Aged ; },
abstract = {Rapidly progressive dementias (RPDs) are a type of fatal dementias that cause rapid progression of neuronal dysfunction. This study aimed to assess the prevalence of APOE genotypes (ε2, ε3, ε4) and PRNP mutations (E200K, M129V) in the general population of Pakistan because of their association with RPDs, including Rapidly Progressive Alzheimer's Disease (rpAD) and Creutzfeldt-Jakob Disease (CJD). Blood samples (n = 100) were collected from healthy Pakistani population and the stated mutations were assessed using polymerase chain reaction. In the analysis of the APOE genotype, ε3/ε3 genotype was the most common (95%), followed by ε3/ε4 (5%) and ε2 allele was completely absent. A low frequency of ε4 allele and the absence of a protective ε2 allele is associated with an increased risk of rpAD. In the case of PRNP mutations, the most common genotype was M129-Ε200 (71%) and V129-Ε200 (29%). E200K mutation was completely absent from the given population. It is noteworthy that the MM homozygous genotype was present in 71 samples, VV genotype was present in 29. Homozygosity on codon 129, as observed in most of our samples, has been associated with more efficient production of PrP[Sc] and disease pathology. This study provides preliminary data indicating that rpAD and CJD pose a significant threat to the Pakistani population.},
}

Humans
Pakistan
*Prion Proteins/genetics
*Genotype
*Apolipoproteins E/genetics
Female
Male
Polymorphism, Genetic/genetics
Creutzfeldt-Jakob Syndrome/genetics
Dementia/genetics
Mutation/genetics
Alleles
Gene Frequency/genetics
Middle Aged
Alzheimer Disease/genetics
Aged

@article {pmid39578650,
year = {2024},
author = {Berriel Diaz, M and Rohm, M and Herzig, S},
title = {Cancer cachexia: multilevel metabolic dysfunction.},
journal = {Nature metabolism},
volume = {6},
number = {12},
pages = {2222-2245},
pmid = {39578650},
issn = {2522-5812},
support = {949017//EC | EU Framework Programme for Research and Innovation H2020 | H2020 Priority Excellent Science | H2020 European Research Council (H2020 Excellent Science - European Research Council)/ ; },
mesh = {*Cachexia/metabolism/etiology ; Humans ; *Neoplasms/complications/metabolism ; *Energy Metabolism ; Animals ; Metabolic Diseases/metabolism/complications/etiology ; },
abstract = {Cancer cachexia is a complex metabolic disorder marked by unintentional body weight loss or 'wasting' of body mass, driven by multiple aetiological factors operating at various levels. It is associated with many malignancies and significantly contributes to cancer-related morbidity and mortality. With emerging recognition of cancer as a systemic disease, there is increasing awareness that understanding and treatment of cancer cachexia may represent a crucial cornerstone for improved management of cancer. Here, we describe the metabolic changes contributing to body wasting in cachexia and explain how the entangled action of both tumour-derived and host-amplified processes induces these metabolic changes. We discuss energy homeostasis and possible ways that the presence of a tumour interferes with or hijacks physiological energy conservation pathways. In that context, we highlight the role played by metabolic cross-talk mechanisms in cachexia pathogenesis. Lastly, we elaborate on the challenges and opportunities in the treatment of this devastating paraneoplastic phenomenon that arise from the complex and multifaceted metabolic cross-talk mechanisms and provide a status on current and emerging therapeutic approaches.},
}

*Cachexia/metabolism/etiology
Humans
*Neoplasms/complications/metabolism
*Energy Metabolism
Animals
Metabolic Diseases/metabolism/complications/etiology

@article {pmid39418320,
year = {2025},
author = {Schwarz, D and Le Marois, M and Sturm, V and Peters, AS and Longuespée, R and Helm, D and Schneider, M and Eichmüller, B and Hidmark, AS and Fischer, M and Kender, Z and Schwab, C and Hausser, I and Weis, J and Dihlmann, S and Böckler, D and Bendszus, M and Heiland, S and Herzig, S and Nawroth, PP and Szendroedi, J and Fleming, T},
title = {Exploring Structural and Molecular Features of Sciatic Nerve Lesions in Diabetic Neuropathy: Unveiling Pathogenic Pathways and Targets.},
journal = {Diabetes},
volume = {74},
number = {1},
pages = {65-74},
doi = {10.2337/db24-0493},
pmid = {39418320},
issn = {1939-327X},
support = {GRK 1874/2//DFG/ ; //Deutsche Forschungsgemeinschaft/ ; //German Centre for Diabetes Research/ ; },
mesh = {*Diabetic Neuropathies/metabolism/pathology ; Humans ; *Sciatic Nerve/metabolism/pathology ; Male ; *Diabetes Mellitus, Type 2/metabolism/complications ; Middle Aged ; *Proteomics ; Female ; Aged ; Blood-Nerve Barrier/metabolism ; Magnetic Resonance Imaging ; Adult ; },
abstract = {Lesioned fascicles (LFs) in the sciatic nerves of individuals with diabetic neuropathy (DN) correlate with clinical symptom severity. This study aimed to characterize the structural and molecular composition of these lesions to better understand DN pathogenesis. Sciatic nerves from amputees with and without type 2 diabetes (T2D) were examined using ex vivo magnetic resonance neurography, in vitro imaging, and proteomic analysis. Lesions were only found in T2D donors and exhibited significant structural abnormalities, including axonal degeneration, demyelination, and impaired blood-nerve barrier (BNB). Although non-LFs from T2D donors showed activation of neuroprotective pathways, LFs lacked this response and instead displayed increased complement activation via the classical pathway. The detection of liver-derived acute-phase proteins suggests that BNB disruption facilitates harmful interorgan communication between the liver and nerves. These findings reveal key molecular mechanisms contributing to DN and highlight potential targets for therapeutic intervention.},
}

*Diabetic Neuropathies/metabolism/pathology
Humans
*Sciatic Nerve/metabolism/pathology
Male
*Diabetes Mellitus, Type 2/metabolism/complications
Middle Aged
*Proteomics
Female
Aged
Blood-Nerve Barrier/metabolism
Magnetic Resonance Imaging
Adult

@article {pmid39645755,
year = {2024},
author = {Parmar, DS and Thakur, MN and Agarwal, I and Ganesh, SR and Vogel, G},
title = {Report of stray sightings of Dendrelaphis proarchos (Wall, 1909) (Serpentes: Colubridae) in Surat, Gujarat, western India.},
journal = {Zootaxa},
volume = {5433},
number = {2},
pages = {231-248},
doi = {10.11646/zootaxa.5433.2.4},
pmid = {39645755},
issn = {1175-5334},
mesh = {Animals ; India ; Male ; *Animal Distribution ; Female ; *Colubridae/anatomy & histology/classification/growth & development ; Animal Structures/anatomy & histology/growth & development ; Body Size ; Ecosystem ; Organ Size ; Humans ; },
abstract = {We here report on likely human-mediated, stray sightings of Dendrelaphis proarchos (Wall, 1909) in an unnatural range-Surat, Gujarat in western India. This population shows the following characters: (1) vertebral scales distinctly enlarged, larger than the dorsals of the first row; (2) 185-194 ventrals; (3) 139-142 divided subcaudals in complete tails; (4) 15 dorsal scale rows at midbody; (5) cloacal shield undivided; (6) one loreal scale; (7) three supralabials touching the eye; (8) a moderate first sublabial that touches two infralabials; (9) 11-12 temporal scales; (10) preoculars 1 or 2; (11) two or three postoculars; (12) maximum total length 1150 mm; (13) interparietal spot absent; (14) a black temporal stripe that does not starts on the postnasal or loreal but starts on the center of the eye follows postoculars (middle or second postocular) covers the majority of the temporal region and extends onto the neck; (15) a distinct, bright ventrolateral stripe bordered by one black line at the bottom; (16) dorsal interstitial color blue and (17) tongue color red with black tip. Data from a partial fragment of the mitochondrial 16S gene also reveal genetic congruence with published sequences from Sagaing and Ayeyarwady in Myanmar and Mizoram, India, further attesting the morphological conclusions. Absence of any sighting of this form in the wild despite long-term (> 15 years) studies in south Gujarat by us, the lack of previous reports of this population especially in natural habitats in Gujarat by colleagues, and reports of many such stray populations of non-native herpetofauna in the coastal port city of Surat together, indicate an unnatural, probably human-mediated, transportation of D. proarchos to Surat. Such likely human-mediated introductions of species outside their native range are a cause for concern and require awareness campaigns among snake rescuers not to 'release' such snakes in the Gujarat forests, but to keep them in zoos or return to the actual point of wild origin, if known or feasible.},
}

Animals
India
Male
*Animal Distribution
Female
*Colubridae/anatomy & histology/classification/growth & development
Animal Structures/anatomy & histology/growth & development
Body Size
Ecosystem
Organ Size
Humans

@article {pmid39639228,
year = {2024},
author = {Hu, J and Ke, J and Xu, S and Pei, L and Cao, L and Zhou, H and Zhu, X},
title = {The combination of focal breast edema and adjacent vessel sign to assess the behavior of mass-type invasive ductal carcinoma.},
journal = {BMC medical imaging},
volume = {24},
number = {1},
pages = {332},
pmid = {39639228},
issn = {1471-2342},
mesh = {Humans ; Female ; *Breast Neoplasms/diagnostic imaging/pathology/complications ; Middle Aged ; Retrospective Studies ; *Carcinoma, Ductal, Breast/diagnostic imaging/pathology/complications ; *Magnetic Resonance Imaging/methods ; *Edema/diagnostic imaging/pathology ; Adult ; Aged ; Breast/diagnostic imaging/pathology/blood supply ; Lymphatic Metastasis/diagnostic imaging ; Neoplasm Invasiveness ; Neoplasm Grading ; },
abstract = {BACKGROUND: The objective of this study was to investigate the association between focal breast edema (FBE) and adjacent vessel sign (AVS) with tumor size, histologic grade, lymphovascular invasion, axillary lymph node status, Ki-67 index, and molecular subtype in breast cancer. These findings have provided valuable insights into the biological characteristics and prognosis of mass-type invasive ductal carcinoma (M-IDC).

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

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

CONCLUSIONS: The BPS is a valuable, non-invasive biomarker for assessing the aggressiveness of M-IDC and can facilitate treatment planning.},
}

Humans
Female
*Breast Neoplasms/diagnostic imaging/pathology/complications
Middle Aged
Retrospective Studies
*Carcinoma, Ductal, Breast/diagnostic imaging/pathology/complications
*Magnetic Resonance Imaging/methods
*Edema/diagnostic imaging/pathology
Adult
Aged
Breast/diagnostic imaging/pathology/blood supply
Lymphatic Metastasis/diagnostic imaging
Neoplasm Invasiveness
Neoplasm Grading

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

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

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

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

FUNDING: Work supported by NSW Health for the NSW Vaccine, Infection and Immunology Collaborative (VIIM).},
}

Humans
*COVID-19 Vaccines/immunology/administration & dosage
*SARS-CoV-2/immunology
*Memory B Cells/immunology
*COVID-19/immunology/prevention & control
*Antibodies, Viral/immunology
*Antibodies, Neutralizing/immunology
*Immunization, Secondary
*Spike Glycoprotein, Coronavirus/immunology
Adult
Female
Male
Middle Aged
Immunologic Memory
B-Lymphocytes/immunology

@article {pmid38833720,
year = {2025},
author = {Wang, L and Vasudevaraja, V and Tran, I and Sukhadia, P and Reuter, VE and Abu-Rustum, NR and Rubinstein, MM and Gopalan, A and Ross, D and Snuderl, M and Chiang, S},
title = {Novel Androgen Receptor Splice Variant 7 in Gynecologic Tumors.},
journal = {International journal of gynecological pathology : official journal of the International Society of Gynecological Pathologists},
volume = {44},
number = {1},
pages = {88-93},
doi = {10.1097/PGP.0000000000001029},
pmid = {38833720},
issn = {1538-7151},
mesh = {Humans ; Female ; *Receptors, Androgen/genetics ; Ovarian Neoplasms/pathology/genetics ; Biomarkers, Tumor/genetics ; Middle Aged ; Uterine Neoplasms/genetics/pathology ; Genital Neoplasms, Female/genetics/pathology ; DNA Methylation ; Aged ; },
abstract = {Androgen receptor splicing variant 7 (AR-V7) is a truncated variant of the AR mRNA that may be a predictive biomarker for AR-targeted therapy. AR-V7 has been described in prostate, breast, salivary duct, and hepatocellular carcinomas as well as mammary and extra-mammary Paget disease. We report 2 gynecologic cancers occurring in the lower uterine segment and ovary and both harboring AR-V7 by targeted RNA sequencing. The uterine tumor was an undifferentiated carcinoma consisting of epithelioid cells and focally spindled cells arranged in sheets, nests, and cords associated with brisk mitotic activity and tumor necrosis. The ovarian tumor consisted of glands with cribriform and solid architecture and uniform cytologic atypia. ER and PR were positive in the ovarian tumor and negative in the uterine tumor. Both were positive for AR and negative for HER2, GATA3, and NKX3.1. DNA methylation profiling showed epigenetic similarity of the AR-V7-positive gynecologic cancers to AR-V7-positive breast cancers rather than to prostate cancers. AR-V7 may underpin rare gynecologic carcinomas with undifferentiated histology or cribriform growth reminiscent of prostatic adenocarcinoma and breast invasive ductal carcinoma.},
}

Humans
Female
*Receptors, Androgen/genetics
Ovarian Neoplasms/pathology/genetics
Biomarkers, Tumor/genetics
Middle Aged
Uterine Neoplasms/genetics/pathology
Genital Neoplasms, Female/genetics/pathology
DNA Methylation
Aged

@article {pmid39639029,
year = {2024},
author = {Nayak, S and Peto, TJ and Kucharski, M and Tripura, R and Callery, JJ and Quang Huy, DT and Gendrot, M and Lek, D and Nghia, HDT and van der Pluijm, RW and Dong, N and Long, LT and Vongpromek, R and Rekol, H and Hoang Chau, N and Miotto, O and Mukaka, M and Dhorda, M and von Seidlein, L and Imwong, M and Roca, X and Day, NPJ and White, NJ and Dondorp, AM and Bozdech, Z},
title = {Population genomics and transcriptomics of Plasmodium falciparum in Cambodia and Vietnam uncover key components of the artemisinin resistance genetic background.},
journal = {Nature communications},
volume = {15},
number = {1},
pages = {10625},
pmid = {39639029},
issn = {2041-1723},
mesh = {*Artemisinins/pharmacology/therapeutic use ; *Plasmodium falciparum/genetics/drug effects ; Cambodia ; *Drug Resistance/genetics ; Humans ; *Malaria, Falciparum/parasitology/drug therapy ; *Antimalarials/pharmacology/therapeutic use ; *Polymorphism, Single Nucleotide ; Vietnam ; Protozoan Proteins/genetics/metabolism ; Transcriptome ; Genomics ; Gene Expression Profiling ; },
abstract = {The emergence of Plasmodium falciparum parasites resistant to artemisinins compromises the efficacy of Artemisinin Combination Therapies (ACTs), the global first-line malaria treatment. Artemisinin resistance is a complex genetic trait in which nonsynonymous SNPs in PfK13 cooperate with other genetic variations. Here, we present population genomic/transcriptomic analyses of P. falciparum collected from patients with uncomplicated malaria in Cambodia and Vietnam between 2018 and 2020. Besides the PfK13 SNPs, several polymorphisms, including nonsynonymous SNPs (N1131I and N821K) in PfRad5 and an intronic SNP in PfWD11 (WD40 repeat-containing protein on chromosome 11), appear to be associated with artemisinin resistance, possibly as new markers. There is also a defined set of genes whose steady-state levels of mRNA and/or splice variants or antisense transcripts correlate with artemisinin resistance at the base level. In vivo transcriptional responses to artemisinins indicate the resistant parasite's capacity to decelerate its intraerythrocytic developmental cycle (IDC), which can contribute to the resistant phenotype. During this response, PfRAD5 and PfWD11 upregulate their respective alternatively/aberrantly spliced isoforms, suggesting their contribution to the protective response to artemisinins. PfRAD5 and PfWD11 appear under selective pressure in the Greater Mekong Sub-region over the last decade, suggesting their role in the genetic background of the artemisinin resistance.},
}

*Artemisinins/pharmacology/therapeutic use
*Plasmodium falciparum/genetics/drug effects
Cambodia
*Drug Resistance/genetics
Humans
*Malaria, Falciparum/parasitology/drug therapy
*Antimalarials/pharmacology/therapeutic use
*Polymorphism, Single Nucleotide
Vietnam
Protozoan Proteins/genetics/metabolism
Transcriptome
Genomics
Gene Expression Profiling

@article {pmid38348593,
year = {2024},
author = {Schweiger, M and Arredondo-Lasso, MN and Friano, ME and Gil-Lozano, M and Herzig, S and Uhlenhaut, NH},
title = {Lipid sensing nuclear receptors involved in the pathogenesis of fatty liver disease.},
journal = {FEBS letters},
volume = {598},
number = {23},
pages = {2854-2855},
doi = {10.1002/1873-3468.14818},
pmid = {38348593},
issn = {1873-3468},
support = {UH 275/6-1-ID 457050056//German Research Foundation DFG/ ; TRR333 BATEnergy ID 450149205//German Research Foundation DFG/ ; TRR205 Adrenal Gland ID 314061271//German Research Foundation DFG/ ; CRC1064 Chromatin Dynamics ID 213249687//German Research Foundation DFG/ ; 457050056//German Research Foundation/ ; 450149205//TRR333 BAT-Energy/ ; },
mesh = {Humans ; *Receptors, Cytoplasmic and Nuclear/metabolism/genetics ; Animals ; *Lipid Metabolism ; *Non-alcoholic Fatty Liver Disease/metabolism/pathology/genetics ; Fatty Liver/metabolism/pathology/genetics ; },
abstract = {Non-alcoholic fatty liver disease (NAFLD) begins with lipid accumulation and progresses toward inflammation and fibrosis. Nuclear receptors (NRs), like the Peroxisome Proliferator-Activated Receptors alpha and gamma (PPARα and PPARy), the Farnesoid X Receptor (FXR), and the Liver X receptor (LXR), regulate genes by heterodimerizing with Retinoid X receptor (RXR). These receptors are emerging targets for pharmaceutical intervention for metabolic diseases.},
}

Humans
*Receptors, Cytoplasmic and Nuclear/metabolism/genetics
Animals
*Lipid Metabolism
*Non-alcoholic Fatty Liver Disease/metabolism/pathology/genetics
Fatty Liver/metabolism/pathology/genetics

@article {pmid39637037,
year = {2024},
author = {Jha, A and Chaudhary, RK and Shrivastav, S and Khanal, U},
title = {Ultrasonographic and pathological correlation of asymmetric retroareolar density on mammogram.},
journal = {PloS one},
volume = {19},
number = {12},
pages = {e0301180},
pmid = {39637037},
issn = {1932-6203},
mesh = {Humans ; Female ; Middle Aged ; *Mammography/methods ; Adult ; *Breast Neoplasms/diagnostic imaging/pathology ; Aged ; Nipples/diagnostic imaging/pathology ; Mastitis/diagnostic imaging/pathology ; Ultrasonography/methods ; Breast Density ; Carcinoma, Ductal, Breast/diagnostic imaging/pathology ; Ultrasonography, Mammary/methods ; },
abstract = {BACKGROUND: Retroareolar region refers to the region within two centimeters from the nipple and/or involves the nipple-areolar complex on mammogram. In this study, we graded asymmetric retroareolar density on mammography and determined the underlying cause.

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

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

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

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

CONTRIBUTION: Grading retroareolar density in mammogram may improve the evaluation of retroareolar region and increase emphasis on higher grades.},
}

Humans
Female
Middle Aged
*Mammography/methods
Adult
*Breast Neoplasms/diagnostic imaging/pathology
Aged
Nipples/diagnostic imaging/pathology
Mastitis/diagnostic imaging/pathology
Ultrasonography/methods
Breast Density
Carcinoma, Ductal, Breast/diagnostic imaging/pathology
Ultrasonography, Mammary/methods

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

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

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

CONCLUSIONS: PNTS to the BP can occur years after initial cancer diagnosis and may signify cancer progression. A high index of suspicion is crucial for timely diagnosis, particularly in patients with cancer and progressive upper extremity symptoms. Comprehensive imaging, including BP MRI and PET/CT, is essential for diagnosis. Despite treatment, prognosis remains poor, highlighting the need for improved diagnostic and therapeutic strategies.},
}

Humans
Middle Aged
Female
Retrospective Studies
*Brachial Plexus Neuropathies/diagnosis/etiology
Male
Adult
*Positron Emission Tomography Computed Tomography/methods
Aged
*Breast Neoplasms/pathology/diagnostic imaging
*Peripheral Nervous System Neoplasms/diagnostic imaging/pathology/diagnosis
Lung Neoplasms/pathology/diagnostic imaging/diagnosis
Treatment Outcome
Magnetic Resonance Imaging
Carcinoma, Ductal, Breast/pathology/diagnostic imaging/diagnosis
Thyroid Cancer, Papillary/pathology/diagnostic imaging/diagnosis/surgery/therapy
Fluorodeoxyglucose F18
Brachial Plexus/pathology/diagnostic imaging
Adenocarcinoma of Lung/pathology/diagnostic imaging/diagnosis

@article {pmid39616738,
year = {2024},
author = {Rivera, A and Plumber, N and Louis, M and Grabill, N and Strom, P},
title = {Surgical stress as a potential trigger for spontaneous coronary artery dissection: A case report.},
journal = {International journal of surgery case reports},
volume = {126},
number = {},
pages = {110644},
doi = {10.1016/j.ijscr.2024.110644},
pmid = {39616738},
issn = {2210-2612},
abstract = {INTRODUCTION AND IMPORTANCE: Spontaneous coronary artery dissection (SCAD) is a rare cause of acute coronary syndrome, predominantly affecting women without traditional cardiovascular risk factors. It is often underdiagnosed, especially in postoperative patients, due to its atypical presentation and the challenges in distinguishing it from other causes of chest pain.

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

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

CONCLUSION: SCAD should be considered in the differential diagnosis of acute coronary syndrome in postoperative patients presenting with chest pain, even in the absence of significant cardiovascular risk factors. Early recognition and appropriate management are crucial for improving patient outcomes.},
}

@article {pmid39610583,
year = {2024},
author = {Yasin, R and Zafar, G and Rooman Ali Syed, F and Afzal, S and Fatima, M and Rathore, Z and Chughtai, A and Chughtai, A},
title = {CK5/6 Expression in Molecular Subtypes of Invasive Ductal Carcinoma.},
journal = {Cureus},
volume = {16},
number = {10},
pages = {e72608},
pmid = {39610583},
issn = {2168-8184},
abstract = {Background Breast cancer (BC) is the leading cause of cancer-related deaths in women worldwide. There has been a significant increase in the incidence of BC in Pakistan. Family history, older age, obesity, tobacco use, oral contraceptive use, early menarche, and hormonal replacement therapy are among the major risk factors. The most common histological subtype of BC is invasive ductal carcinoma (IDC). Molecular subtypes of BC include mainly Luminal A, Luminal B, human epidermal growth factor receptor 2 (HER-2) enriched, and triple-negative BC subtypes, with the triple-negative subtype having the worst prognosis. CK5/6 serves as a basal keratin biomarker. This aimed to assess the expression of CK5/6 in IDC of the breast belonging to different molecular classes and to compare its expression with traditionally defined prognostic factors for different molecular subtypes. Methodology A cross-sectional, observational study was conducted at the Chughtai Institute of Pathology after approval from the Institutional Review Board (approval number: 1198/IRB/CIP). All cases during a period of six months (April 2023 to September 2023) were sampled using non-probability convenient sampling. All mastectomy samples diagnosed as IDC were included in the study. After standard tissue processing, paraffin tissue blocks and slides were prepared followed by hematoxylin & eosin staining. Hormonal receptors (estrogen receptor, progesterone receptor, HER-2) were assessed for cases to segregate them into molecular subtypes. CK5/6 antibody was then applied and the data were collected on a pre-designed proforma. SPSS version 25.0 (IBM Corp., Armonk, NY, USA) was used for data analysis. Results Of a total of 85 cases, 19 (22.3%) were positive for CK5/6. Of these 19 cases, the majority (68%, p = 0.001) belonged to the triple-negative class of tumors, comprising 13 cases. No case from the Luminal A class showed expression for CK5/6 stain (p = 0.028). Overall, four cases of the Luminal B subtype showed CK5/6 positivity (10.8%, p = 0.022) while two cases of the HER-2-enriched subtype were positive for the stain (33.3%, p > 0.05). These results were analyzed in relation to different prognostic factors. The majority of CK5/6-positive cases showed lymphovascular invasion (42%) and belonged to grade 3 tumors (57.8%). Conclusions The expression of CK5/6 in IDC of the breast is associated with poor prognostic factors such as triple-negative molecular subtypes, high histological grade, lymphovascular invasion, positive nodal status, and high pathological stage.},
}

@article {pmid39605123,
year = {2024},
author = {Noroozpoor, M and Mozdarani, H and Rahbar Parvaneh, R and Lashkari, M},
title = {Evaluation of TP53TG1 and PANDA lncRNAs expression in association with adjuvant chemotherapy response in the peripheral blood of invasive ductal carcinoma patients.},
journal = {Cellular and molecular biology (Noisy-le-Grand, France)},
volume = {70},
number = {10},
pages = {58-63},
doi = {10.14715/cmb/2024.70.10.9},
pmid = {39605123},
issn = {1165-158X},
mesh = {Humans ; Female ; Chemotherapy, Adjuvant ; *RNA, Long Noncoding/genetics/blood ; *Breast Neoplasms/drug therapy/genetics/blood ; Middle Aged ; *Gene Expression Regulation, Neoplastic/drug effects ; Carcinoma, Ductal, Breast/drug therapy/genetics/blood ; Adult ; Biomarkers, Tumor/genetics/blood ; },
abstract = {Breast cancer is the most common malignancy in women. Breast cancer, the second leading cause of cancer deaths, affects 2.1 million women each year and is estimated to have killed 627,000 women worldwide in 2018. Unfortunately, the age of onset of this cancer in our country IRAN is about 10 years lower than the global average and is close to 45 years. Chemotherapy is one of the basic treatments for cancer. Predicting the benefits of chemotherapy is challenging. Studies are now underway to use gene expression tests to pinpoint patients who are most likely to benefit from adjuvant chemotherapy. In the present study, the expression of two long non-coding RNAs TP53TG1 and PANDA in the blood of breast cancer patients before and after receiving chemotherapy compared with this amount in the blood of normal people using Real-Time RT PCR technique to find a meaningful relationship ¬ Compared statistically. Compared to normal samples, the expression level of TP53TG1 in the blood of patients was reduced. Although it was not statistically significant. Its expression also increased after receiving chemotherapy. Compared to normal samples, the expression of PANDA in the blood of patients was increased, which was statistically significant. Also, its expression decreased after receiving chemotherapy. These findings suggest that PANDA and TP53TG1 expression levels may be possible markers associated with tumorigenesis and may also be considered as possible indicators of response to chemotherapy.},
}

Humans
Female
Chemotherapy, Adjuvant
*RNA, Long Noncoding/genetics/blood
*Breast Neoplasms/drug therapy/genetics/blood
Middle Aged
*Gene Expression Regulation, Neoplastic/drug effects
Carcinoma, Ductal, Breast/drug therapy/genetics/blood
Adult
Biomarkers, Tumor/genetics/blood

@article {pmid39593081,
year = {2024},
author = {Trippler, L and Ali, SM and Masoud, MO and Mohammed, ZH and Amour, AK and Suleiman, KR and Ame, SM and Kabole, F and Hattendorf, J and Knopp, S},
title = {Impact of chemical snail control on intermediate host snail populations for urogenital schistosomiasis elimination in Pemba, Tanzania: findings of a 3-year intervention study.},
journal = {Parasites & vectors},
volume = {17},
number = {1},
pages = {489},
pmid = {39593081},
issn = {1756-3305},
support = {PR00P3_179753 / 1//Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung/ ; },
mesh = {Animals ; Tanzania/epidemiology ; *Schistosomiasis haematobia/prevention & control/epidemiology/drug therapy/transmission ; *Schistosoma haematobium/drug effects/physiology ; *Bulinus/parasitology ; Humans ; *Niclosamide/pharmacology ; Snails/parasitology ; Disease Eradication ; Fresh Water/parasitology ; },
abstract = {BACKGROUND: The World Health Organization (WHO) has set the goal of eliminating schistosomiasis as a public health problem globally by 2030 and to interrupt transmission in selected areas. Chemical snail control is one important measure to reduce transmission and achieve local elimination. We aimed to assess the impact of several rounds of chemical snail control on the presence and number of the Schistosoma haematobium intermediate snail host (Bulinus spp.) in water bodies (WBs) on Pemba Island, Tanzania, a setting targeted for elimination of urogenital schistosomiasis.

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

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

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

TRIAL REGISTRATION: ISRCTN, ISRCTN91431493. Registered 11 February. 2020, https://www.isrctn.com/ISRCTN91431493.},
}

Animals
Tanzania/epidemiology
*Schistosomiasis haematobia/prevention & control/epidemiology/drug therapy/transmission
*Schistosoma haematobium/drug effects/physiology
*Bulinus/parasitology
Humans
*Niclosamide/pharmacology
Snails/parasitology
Disease Eradication
Fresh Water/parasitology

@article {pmid39341603,
year = {2024},
author = {Pereira, LHS and Alves, ADC and Lopes, GFM and da Silva, BF and Vieira, MS and Lopes, DO and Ferreira, JMS and Lara Dos Santos, L},
title = {Soluble isoforms of the DC-SIGN receptor can increase the dengue virus infection in immature dendritic cells.},
journal = {The Brazilian journal of infectious diseases : an official publication of the Brazilian Society of Infectious Diseases},
volume = {28},
number = {6},
pages = {103873},
pmid = {39341603},
issn = {1678-4391},
mesh = {*Cell Adhesion Molecules/metabolism ; *Receptors, Cell Surface/metabolism ; *Lectins, C-Type/metabolism ; *Dengue Virus/immunology ; *Dendritic Cells/virology/immunology ; Humans ; Animals ; *Protein Isoforms ; Viral Load ; Dengue/immunology ; Aedes/virology ; },
abstract = {Dengue is a disease with a high-impact on public health worldwide. Many researches have focused on the cell receptors involved in its pathogenesis. The role of soluble isoforms of DC-SIGN (Dendritic Cell-Specific ICAM-3 Grabbing Non-integrin) receptor in the process of Dengue Virus (DENV) infection is not well understood. This work proposes to evaluate changes in the infection process of Immature Dendritic Cells (iDCs) by DENV in the presence of DC-SIGN recombinant soluble isoforms 8, 10, and 12. The recombinant isoforms were built by heterologous expression, the DENV-2 was multiplied in the Aedes albopictus C6/36 cells and quantified in BHK-21 cells, and the iDCs were produced from the THP-1 strain. Infection assays were performed in the presence of iDCs, DENV-2, and isoforms 8, 10, and 12 separately at 25, 50 and 100 ng/mL. The final viral load was estimated by qPCR and statistical analysis was performed by Kruskal-Wallis and ANOVA tests. The iDC profile was confirmed by increasing expression of CD11c, CD86, and CD209 surface markers and maintaining CD14 expression. Infection assays demonstrated a 23-fold increase in DENV viral load in the presence of isoforms 8 and 10 at 100 ng/mL compared to the viral control (p < 0.05), while isoform 12 did not alter the viral load. It was possible to conclude that at 100 ng/mL isoforms (8 and 10) can interact with DENV, increasing viral infection, and potentially acting as opsonins.},
}

*Cell Adhesion Molecules/metabolism
*Receptors, Cell Surface/metabolism
*Lectins, C-Type/metabolism
*Dengue Virus/immunology
*Dendritic Cells/virology/immunology
Humans
Animals
*Protein Isoforms
Viral Load
Dengue/immunology
Aedes/virology

@article {pmid39567714,
year = {2024},
author = {Khan, B and Qahwaji, R and Alfaifi, MS and Athar, T and Khan, A and Mobashir, M and Ashankyty, I and Imtiyaz, K and Alahmadi, A and Rizvi, MMA},
title = {Deciphering molecular landscape of breast cancer progression and insights from functional genomics and therapeutic explorations followed by in vitro validation.},
journal = {Scientific reports},
volume = {14},
number = {1},
pages = {28794},
pmid = {39567714},
issn = {2045-2322},
mesh = {Humans ; *Breast Neoplasms/genetics/pathology/drug therapy ; Female ; *Gene Expression Regulation, Neoplastic ; Genomics/methods ; Gene Regulatory Networks ; Disease Progression ; Biomarkers, Tumor/genetics/metabolism ; Carcinoma, Ductal, Breast/genetics/pathology/drug therapy ; Carcinoma, Intraductal, Noninfiltrating/genetics/pathology/drug therapy ; Molecular Docking Simulation ; Gene Expression Profiling ; Prognosis ; Cell Line, Tumor ; },
abstract = {Breast cancer is caused by aberrant breast cells that proliferate and develop into tumors. Tumors have the potential to spread throughout the body and become lethal if ignored. Metastasis is the process by which invasive tumors move to neighboring lymph nodes or other organs. Metastasis can be lethal and perhaps fatal. The objective of our study was to elucidate the molecular mechanisms underlying the transition of Ductal Carcinoma In Situ (DCIS) to Invasive Ductal Carcinoma (IDC), with a particular focus on hub genes and potential therapeutic agents. Using Weighted Gene Co-expression Network Analysis (WGCNA), we built a comprehensive network combining clinical and phenotypic data from both DCIS and IDC. Modules within this network, correlated with specific phenotypic traits, were identified, and hub genes were identified as critical markers. Receiver Operating Characteristic (ROC) analysis assessed their potential as biomarkers, while survival curve analysis gauged their prognostic value. Furthermore, molecular docking predicted interactions with potential therapeutic agents. Ten hub genes-CDK1, KIF11, NUF2, ASPM, CDCA8, CENPF, DTL, EXO1, KIF2C, and ZWINT-emerged as pivotal fibroblast-specific genes potentially involved in the DCIS to IDC transition. These genes exhibited pronounced positive correlations with key pathways like the cell cycle and DNA repair, Molecular docking revealed Fisetin, an anti-inflammatory compound, effectively binding to both CDK1 and DTL underscoring their role in orchestrating cellular transformation. CDK1 and DTL were selected for molecular docking with CDK1 inhibitors, revealing effective binding of Fisetin, an anti-inflammatory compound, to both. Of the identified hub genes, DTL-an E3 ubiquitin ligase linked to the CRL4 complex-plays a central role in cancer progression, impacting tumor growth, invasion, and metastasis, as well as cell cycle regulation and epithelial-mesenchymal transition (EMT). CDK1, another hub gene, is pivotal in cell cycle progression and associated with various biological processes. In conclusion, our study offers insights into the complex mechanisms driving the transition from DCIS to IDC. It underscores the importance of hub genes and their potential interactions with therapeutic agents, particularly Fisetin. By shedding light on the interplay between CDK1 and DTL expression, our findings contribute to understanding the regulatory landscape of invasive ductal carcinoma and pave the way for future investigations and novel therapeutic avenues.},
}

Humans
*Breast Neoplasms/genetics/pathology/drug therapy
Female
*Gene Expression Regulation, Neoplastic
Genomics/methods
Gene Regulatory Networks
Disease Progression
Biomarkers, Tumor/genetics/metabolism
Carcinoma, Ductal, Breast/genetics/pathology/drug therapy
Carcinoma, Intraductal, Noninfiltrating/genetics/pathology/drug therapy
Molecular Docking Simulation
Gene Expression Profiling
Prognosis
Cell Line, Tumor

@article {pmid39560723,
year = {2024},
author = {Cendrowski, J and Wrobel, M and Mazur, M and Jary, B and Maurya, R and Wang, S and Korostynski, M and Dziewulska, A and Rohm, M and Kuropka, P and Pudelko-Malik, N and Mlynarz, P and Dobrzyn, A and Zeigerer, A and Miaczynska, M},
title = {NFκB and JNK pathways mediate metabolic adaptation upon ESCRT-I deficiency.},
journal = {Cellular and molecular life sciences : CMLS},
volume = {81},
number = {1},
pages = {458},
pmid = {39560723},
issn = {1420-9071},
support = {POIR.04.04.00-00-1C54/16-00//Fundacja na rzecz Nauki Polskiej/ ; POIR.04.04.00-00-20CE/16-00//Fundacja na rzecz Nauki Polskiej/ ; },
mesh = {*Endosomal Sorting Complexes Required for Transport/metabolism/genetics ; Humans ; *NF-kappa B/metabolism ; *Glycolysis/genetics ; Lysosomes/metabolism ; MAP Kinase Signaling System ; Mitochondria/metabolism ; Adaptation, Physiological/genetics ; Transcription Factors/metabolism/genetics ; Glucose/metabolism ; DNA-Binding Proteins ; },
abstract = {Endosomal Sorting Complexes Required for Transport (ESCRTs) are crucial for delivering membrane receptors or intracellular organelles for lysosomal degradation which provides the cell with lysosome-derived nutrients. Yet, how ESCRT dysfunction affects cell metabolism remained elusive. To address this, we analyzed transcriptomes of cells lacking TSG101 or VPS28 proteins, components of ESCRT-I subcomplex. ESCRT-I deficiency reduced the expression of genes encoding enzymes involved in oxidation of fatty acids and amino acids, such as branched-chain amino acids, and increased the expression of genes encoding glycolytic enzymes. The changes in metabolic gene expression were associated with Warburg effect-like metabolic reprogramming that included intracellular accumulation of lipids, increased glucose/glutamine consumption and lactate production. Moreover, depletion of ESCRT-I components led to expansion of the ER and accumulation of small mitochondria, most of which retained proper potential and performed ATP-linked respiration. Mechanistically, the observed transcriptional reprogramming towards glycolysis in the absence of ESCRT-I occurred due to activation of the canonical NFκB and JNK signaling pathways and at least in part by perturbed lysosomal degradation. We propose that by activating the stress signaling pathways ESCRT-I deficiency leads to preferential usage of extracellular nutrients, like glucose and glutamine, for energy production instead of lysosome-derived nutrients, such as fatty acids and branched-chain amino acids.},
}

*Endosomal Sorting Complexes Required for Transport/metabolism/genetics
Humans
*NF-kappa B/metabolism
*Glycolysis/genetics
Lysosomes/metabolism
MAP Kinase Signaling System
Mitochondria/metabolism
Adaptation, Physiological/genetics
Transcription Factors/metabolism/genetics
Glucose/metabolism
DNA-Binding Proteins

@article {pmid39557919,
year = {2024},
author = {Rusak, A and Kątnik, E and Górnicki, T and Schmuttermaier, C and Kujawa, K and Piotrowska, A and Ratajczak-Wielgomas, K and Kmiecik, A and Wojnar, A and Dzięgiel, P and Kzhyshkowska, J},
title = {New insights into the role of the CHI3L2 protein in invasive ductal breast carcinoma.},
journal = {Scientific reports},
volume = {14},
number = {1},
pages = {28529},
pmid = {39557919},
issn = {2045-2322},
support = {2021/05/X/NZ2/01698//National Science Center, Poland (NCN)/ ; },
mesh = {Humans ; Female ; *Carcinoma, Ductal, Breast/metabolism/pathology/genetics ; *Breast Neoplasms/metabolism/pathology/genetics ; Middle Aged ; STAT3 Transcription Factor/metabolism ; Cell Line, Tumor ; Phosphorylation ; Chitinase-3-Like Protein 1/metabolism/genetics ; Gene Expression Regulation, Neoplastic ; Adult ; Macrophages/metabolism ; Aged ; MAP Kinase Signaling System ; Chitinases ; },
abstract = {Chitinase-like proteins have multiple biological functions that promote tumor growth, angiogenesis and metastasis. Expression of CHI3L2, which is similar in structure to CHI3L1, is detected in glioma cells and tumor-associated macrophages (TAMs) in glioma and breast cancer. However, its exact role remains unclear. We analyzed the expression of CHI3L2 in 74 invasive ductal breast carcinoma (IDC) tumors, breast cancer and macrophages cell cultures using immunohistochemistry, immunofluorescence, Western blot and PCR methods. Clinicopathologic data were included in the analysis. The results obtained show that CHI3L2 expression decreases with increasing degree of tumor grade and negative status of estrogen (ER) and progesterone receptors (PR). Furthermore, CHI3L2 is significantly and positively correlated with phosphorylation of STAT-3 and ERK1/2 signaling pathways, but negatively correlated with macrophage infiltration. CHI3L2 is expressed both in the cytoplasm of cancer cells and in macrophages and may regulate STAT-3 and ERK1/2 phosphorylation in breast cancer cell lines. Analysis of the clinicopathologic data revealed that CHI3L2 levels had no effect on patient survival. CHI3L2 expression may be specific for cancer cells in IDC and involved in cross-talk with the tumor microenvironment. Our study has shown that IDC cancer cells express the CHI3L2 protein, possibly indicating a novel function of this protein.},
}

Humans
Female
*Carcinoma, Ductal, Breast/metabolism/pathology/genetics
*Breast Neoplasms/metabolism/pathology/genetics
Middle Aged
STAT3 Transcription Factor/metabolism
Cell Line, Tumor
Phosphorylation
Chitinase-3-Like Protein 1/metabolism/genetics
Gene Expression Regulation, Neoplastic
Adult
Macrophages/metabolism
Aged
MAP Kinase Signaling System
Chitinases

@article {pmid39382167,
year = {2024},
author = {Koumantou, D and Adiko, AC and Bourdely, P and Nugue, M and Boedec, E and El-Benna, J and Monteiro, R and Saveanu, C and Laffargue, M and Wymann, MP and Dalod, M and Guermonprez, P and Saveanu, L},
title = {Specific Requirement of the p84/p110γ Complex of PI3Kγ for Antibody-Activated, Inducible Cross-Presentation in Murine Type 2 DCs.},
journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)},
volume = {11},
number = {44},
pages = {e2401179},
doi = {10.1002/advs.202401179},
pmid = {39382167},
issn = {2198-3844},
support = {ANR-11-IDEX-0005-02//Agence Nationale de la Recherche/ ; ANR-15-CE15-0005//Agence Nationale de la Recherche/ ; ANR-17-CE11-0001//Agence Nationale de la Recherche/ ; //Fondation pour la Recherche Medicale/ ; ANR-10-EQPX-03//ICGex NGS platform of the Institut Curie/ ; ANR-10-INBS-09-08//ICGex NGS platform of the Institut Curie/ ; INCa-DGOS-465//SiRIC-Curie program/ ; INCa-DGOS- Inserm_12554//SiRIC-Curie program/ ; SNF-310030-189065/SNSF_/Swiss National Science Foundation/Switzerland ; },
mesh = {Animals ; Mice ; *Dendritic Cells/immunology/metabolism ; *Cross-Priming/immunology ; *Mice, Inbred C57BL ; Class Ib Phosphatidylinositol 3-Kinase/metabolism/immunology/genetics ; Antigen Presentation/immunology ; },
abstract = {Cross-presentation by MHCI is optimally efficient in type 1 dendritic cells (DC) due to their high capacity for antigen processing. However, through specific pathways, other DCs, such as type 2 DCs and inflammatory DCs (iDCs) can also cross-present antigens. FcγR-mediated uptake by type 2 DC and iDC subsets mediates antibody-dependent cross-presentation and activation of CD8[+] T cell responses. Here, an important role for the p84 regulatory subunit of PI3Kγ in mediating efficient cross-presentation of exogenous antigens in otherwise inefficient cross-presenting cells, such as type 2 DCs and GM-CSF-derived iDCs is identified. FcγR-mediated cross-presentation is shown in type 2 and iDCs depend on the enzymatic activity of the p84/p110γ complex of PI3Kγ, which controls the activity of the NADPH oxidase NOX2 and ROS production in murine spleen type 2 DCs and GM-CSF-derived iDCs. In contrast, p84/p110γ is largely dispensable for cross-presentation by type 1 DCs. These findings suggest that PI3Kγ-targeted therapies, currently considered for oncological practice, may interfere with the ability of type 2 DCs and iDCs to cross-present antigens contained in immune complexes.},
}

Animals
Mice
*Dendritic Cells/immunology/metabolism
*Cross-Priming/immunology
*Mice, Inbred C57BL
Class Ib Phosphatidylinositol 3-Kinase/metabolism/immunology/genetics
Antigen Presentation/immunology

@article {pmid39541956,
year = {2024},
author = {Abdelwahab, RM and Aghazadeh Mohandesi, N and Sturgis, CD and Alavi, A},
title = {Squamous Metaplasia of Lactiferous Ducts (Zuska's disease) of the Breast: Clinical and Histopathologic Manifestations.},
journal = {Dermatology (Basel, Switzerland)},
volume = {},
number = {},
pages = {1-9},
doi = {10.1159/000542622},
pmid = {39541956},
issn = {1421-9832},
abstract = {Squamous metaplasia of lactiferous ducts (SMOLD), also known as Zuska's disease, is an uncommon, recurrent inflammatory fistulizing disease of the breast that strongly correlates with smoking in premenopausal patients .1 Clinical and imaging findings may overlap with other breast conditions/ SMOLD is well-recognized by breast pathologists, however, the dermatology literature on this condition remains scarce. In this retrospective study, we reviewed 29 patients with SMOLD diagnosed at Mayo Clinic. The mean age of the patient cohort is 50.3 with a range of 30 to 81 years. One patient (3.7%) had hidradenitis suppurativa of the retro-areolar area. Patient smoking history demonstrated prior/current smokers 37.9% (11/29), lifetime nonsmokers with significant secondhand exposure 6.9% (2/29), and unknown smoking status 3.4% (1/29). One patient had a personal history of invasive ductal carcinoma and 10.3% (3/29) had a history of breast cancer in a first-degree relative. The clinical presentation of the patient cohort includes areolar papules, nodules and draining tract/fistula 13.7% (4/29), pustular cyst/abscess on the breast 13.7% (4/29), breast mass 3.4% (1/29), pain breast discomfort/pain 13.7% (4/29), nipple retraction 3.4% (1/29), and asymptomatic with nipple calcifications on mammogram 3.4% (1/29). 77.8% (7/9) patients with bacterial cultures demonstrated polymicrobial growth. 37.9% (11/29) patients received at least one round of antibiotic therapy. 27.6% (8/29) patients underwent invasive intervention. Staphylococcus, Streptococcus, and Cutibacterium species were the most frequent causes of infection in our patient cohort. We confirm previous findings of strong association between SMOLD & current/former smoking status and a potential, novel correlation between extensive secondhand exposure and SMOLD development. While both medical and surgical interventions are employed in patient management, many patients ultimately require complete excision of the involved duct(s). Dermatologists should consider SMOLD in the differential diagnosis of patients presenting with breast abscess, fistulizing tracts with mass, and breast pain.},
}

@article {pmid39520846,
year = {2024},
author = {Turk, A and Metin, TO and Kuloglu, T and Yilmaz, M and Artas, G and Ozercan, IH and Hancer, S},
title = {Isthmin-1 and spexin as promising novel biomarker candidates for invasive ductal breast carcinoma.},
journal = {Tissue & cell},
volume = {91},
number = {},
pages = {102601},
doi = {10.1016/j.tice.2024.102601},
pmid = {39520846},
issn = {1532-3072},
abstract = {INTRODUCTION: Breast cancer is one of the most common malignant tumors and a leading cause of cancer-related death in women. Research is focusing on biomarkers linked to breast cancer, particularly two novel proteins: isthmin-1 (ISM-1) and spexin (SPX), which require further investigation.

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

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

CONCLUSIONS: This study presents new findings on ISM-1 and SPX expression in invasive ductal breast carcinoma. The decrease in ISM-1 and increase in SPX suggest a need for further research into the relationship between adipokines and tumor development in breast cancer.},
}

@article {pmid39519098,
year = {2024},
author = {Kim, YJ and Nanda, SS and Jiang, F and Pyo, SY and Han, JY and Koh, SS and Kang, TH},
title = {Pancreatic Adenocarcinoma Up-Regulated Factor (PAUF) Transforms Human Monocytes into Alternative M2 Macrophages with Immunosuppressive Action.},
journal = {International journal of molecular sciences},
volume = {25},
number = {21},
pages = {},
pmid = {39519098},
issn = {1422-0067},
mesh = {Humans ; *Pancreatic Neoplasms/pathology/metabolism/immunology ; *Monocytes/metabolism/immunology ; *Cell Differentiation ; *Macrophages/metabolism/immunology ; *Tumor Microenvironment/immunology ; Toll-Like Receptor 2/metabolism ; Tumor-Associated Macrophages/metabolism/immunology ; Cell Proliferation ; Adenocarcinoma/pathology/metabolism/immunology ; Cell Line, Tumor ; Intercellular Signaling Peptides and Proteins ; },
abstract = {Tumor-associated macrophages (TAMs) in the tumor microenvironment (TME) promote immune evasion, cancer cell proliferation, and metastasis. Ongoing research is focused on finding ways to prevent tumor growth by inhibiting TAM polarization, which has shown a correlation with unfavorable prognosis in clinical studies. Pancreatic adenocarcinoma up-regulated factor (PAUF) is a protein secreted from pancreatic cancer (PC) and acts as a TME modulator that affects the TME by acting on not only cancer cells but also stromal cells and immune cells. Tumor cells can evade the immune system by PAUF binding to Toll-like receptor (TLR) in monocytes, as this research shows. In this study, the examination centered around the recruitment of human monocytes by PAUF and the subsequent differentiation into macrophages. In an in vitro chemotaxis assay, PAUF induced chemotactic migration of TLR2-mediated monocytes. In addition, PAUF induced differentiation of monocytes into M2 macrophages, which was verified based on expressing surface markers and cytokines and morphological analysis. The inhibition of T cell proliferation and function was observed in differentiated M2 macrophages. To conclude, these findings indicate that PAUF functions as a promoter of cancer progression by regulating the recruitment and differentiation of macrophages within TMEs, ultimately causing immunosuppression.},
}

Humans
*Pancreatic Neoplasms/pathology/metabolism/immunology
*Monocytes/metabolism/immunology
*Cell Differentiation
*Macrophages/metabolism/immunology
*Tumor Microenvironment/immunology
Toll-Like Receptor 2/metabolism
Tumor-Associated Macrophages/metabolism/immunology
Cell Proliferation
Adenocarcinoma/pathology/metabolism/immunology
Cell Line, Tumor
Intercellular Signaling Peptides and Proteins

@article {pmid39519012,
year = {2024},
author = {Newman, NA and Burke, MA},
title = {Dilated Cardiomyopathy: A Genetic Journey from Past to Future.},
journal = {International journal of molecular sciences},
volume = {25},
number = {21},
pages = {},
pmid = {39519012},
issn = {1422-0067},
mesh = {Humans ; *Cardiomyopathy, Dilated/genetics ; *Genetic Predisposition to Disease ; Genetic Testing ; },
abstract = {Dilated cardiomyopathy (DCM) is characterized by reduced systolic function and cardiac dilation. Cases without an identified secondary cause are classified as idiopathic dilated cardiomyopathy (IDC). Over the last 35 years, many cases of IDC have increasingly been recognized to be genetic in etiology with a core set of definitively causal genes in up to 40% of cases. While over 200 genes have been associated with DCM, the evidence supporting pathogenicity for most remains limited. Further, rapid advances in sequencing and bioinformatics have recently revealed a complex genetic spectrum ranging from monogenic to polygenic in DCM. These advances have also led to the discovery of causal and modifier genetic variants in secondary forms of DCM (e.g., alcohol-induced cardiomyopathy). Current guidelines recommend genetic counseling and screening, as well as endorsing a handful of genotype-specific therapies (e.g., device placement in LMNA cardiomyopathy). The future of genetics in DCM will likely involve polygenic risk scores, direct-to-consumer testing, and pharmacogenetics, requiring providers to have a thorough understanding of this rapidly developing field. Herein we outline three decades of genetics in DCM, summarize recent advances, and project possible future avenues for the field.},
}

Humans
*Cardiomyopathy, Dilated/genetics
*Genetic Predisposition to Disease
Genetic Testing

@article {pmid39512981,
year = {2024},
author = {Eshaqi, MJ and Al Shamsi, SA and Al Saidi, AM and Mahesh, S},
title = {Clinical Insights Into Ductal Carcinoma In Situ in Males: A Report of Two Cases From the Sultanate of Oman.},
journal = {Cureus},
volume = {16},
number = {10},
pages = {e71071},
pmid = {39512981},
issn = {2168-8184},
abstract = {Breast cancer is a disease that predominantly affects the female population; however, rarely it can manifest in males, yet its etiology remains poorly elucidated. The scarcity of literature reviews and case reports done on male breast cancer in comparison to the female counterpart makes it difficult to understand the risk factors, treatment options, and extension of the disease. Moreover, high-grade ductal carcinoma in situ (DCIS) is exceptionally uncommon among male patients. The prognosis for male patients diagnosed with DCIS is similar to that of females at the same disease stage making early recognition and diagnosis significant. However, more efforts are being made to understand the clinical presentation, increase awareness, and acknowledge the etiology of this disease. This study addresses this gap by presenting two distinctive cases of invasive ductal carcinoma in males from the Sultanate of Oman. The aim of this study is to contribute to the growing efforts in comprehending the unclear landscape of male breast cancer, fostering awareness, and advancing knowledge of its etiology.},
}

@article {pmid39506855,
year = {2024},
author = {Kook, Y and Lee, YJ and Chu, C and Jang, JS and Baek, SH and Bae, SJ and Cha, YJ and Gong, G and Jeong, J and Lee, SB and Ahn, SG},
title = {Differentiating HER2-low and HER2-zero tumors with 21-gene multigene assay in 2,295 h + HER2- breast cancer: a retrospective analysis.},
journal = {Breast cancer research : BCR},
volume = {26},
number = {1},
pages = {154},
pmid = {39506855},
issn = {1465-542X},
support = {2021M3H9A2096954//National Research Foundation of Korea/ ; RS-2024-00343001//Korean government/ ; },
mesh = {Humans ; Female ; *Breast Neoplasms/genetics/pathology/mortality/drug therapy ; *Receptor, ErbB-2/genetics/metabolism ; Retrospective Studies ; Middle Aged ; *Biomarkers, Tumor/genetics ; Adult ; Aged ; Gene Expression Profiling ; Immunohistochemistry ; Prognosis ; },
abstract = {BACKGROUND: HER2-positivity is an essential marker for therapeutic decisions, while HER2 expression is heterogenous. In recent years, there has been increasing recognition of a subgroup of breast cancer patients who have low levels of HER2 expression, also known as HER2-low because trastuzumab deruxtecan offers clinical benefit for patients with HER2-low metastatic breast cancer. Despite the growing interest in HER2-low breast cancer, there is limited research on how multigene assays can help differentiate between HER2-low and HER2-negative breast cancer. Among HR + HER2- breast cancer, we compared genomic characteristics between HER2-low and HER2-zero using the 21-gene assay.

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

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

CONCLUSION: Within HR + HER2- breast cancer, HER2-low tumors are associated with high RS, especially for histologically invasive ductal carcinoma. A prognostic influence of HER2-low expression among HR + HER2- breast cancer remains as an area that requires further study.},
}

Humans
Female
*Breast Neoplasms/genetics/pathology/mortality/drug therapy
*Receptor, ErbB-2/genetics/metabolism
Retrospective Studies
Middle Aged
*Biomarkers, Tumor/genetics
Adult
Aged
Gene Expression Profiling
Immunohistochemistry
Prognosis

@article {pmid39505971,
year = {2024},
author = {Olbromski, M and Mrozowska, M and Smolarz, B and Romanowicz, H and Rusak, A and Piotrowska, A},
title = {ERα status of invasive ductal breast carcinoma as a result of regulatory interactions between lysine deacetylases KAT6A and KAT6B.},
journal = {Scientific reports},
volume = {14},
number = {1},
pages = {26935},
pmid = {39505971},
issn = {2045-2322},
mesh = {Humans ; Female ; *Estrogen Receptor alpha/metabolism/genetics ; *Breast Neoplasms/pathology/metabolism/genetics ; *Histone Acetyltransferases/metabolism/genetics ; *Carcinoma, Ductal, Breast/genetics/metabolism/pathology ; Cell Line, Tumor ; Middle Aged ; Gene Expression Regulation, Neoplastic ; Adult ; Histone Deacetylases/metabolism/genetics ; MCF-7 Cells ; Aged ; Lysine/metabolism ; },
abstract = {Breast cancer (BC) is the leading cause of death among cancer patients worldwide. In 2020, almost 12% of all cancers were diagnosed with BC. Therefore, it is important to search for new potential markers of cancer progression that could be helpful in cancer diagnostics and successful anti-cancer therapies. In this study, we investigated the potential role of the lysine acetyltransferases KAT6A and KAT6B in the outcome of patients with invasive breast carcinoma. The expression profiles of KAT6A/B in 495 cases of IDC and 38 cases of mastopathy (FBD) were examined by immunohistochemistry. KAT6A/B expression was also determined in the breast cancer cell lines MCF-7, BT-474, SK-BR-3, T47D, MDA-MB-231, and MDA-MB-231/BO2, as well as in the human epithelial mammary gland cell line hTERT-HME1 - ME16C, both at the mRNA and protein level. Statistical analysis of the results showed that the nuclear expression of KAT6A/B correlates with the estrogen receptor status: KAT6ANUC vs. ER r = 0.2373 and KAT6BNUC vs. ER r = 0.1496. Statistical analysis clearly showed that KAT6A cytoplasmic and nuclear expression levels were significantly higher in IDC samples than in FBD samples (IRS 5.297 ± 2.884 vs. 2.004 ± 1.072, p < 0.0001; IRS 5.133 ± 4.221 vs. 0.1665 ± 0.4024, p < 0.0001, respectively). Moreover, we noticed strong correlations between ER and PR status and the nuclear expression of KAT6A and KAT6B (nucKAT6A vs. ER, p = 0.0048; nucKAT6A vs. PR p = 0.0416; nucKAT6B vs. ER p = 0.0306; nucKAT6B vs. PR p = 0.0213). Significantly higher KAT6A and KAT6B expression was found in the ER-positive cell lines T-47D and BT-474, whereas significantly lower expression was observed in the triple-negative cell lines MDA-MB-231 and MDA-MB-231/BO2. The outcomes of small interfering RNA (siRNA)-mediated suppression of KAT6A/B genes revealed that within estrogen receptor (ER) positive and negative cell lines, MCF-7 and MDA-MB-231, attenuation of KAT6A led to concurrent attenuation of KAT6A, whereas suppression of KAT6B resulted in simultaneous attenuation of KAT6A. Furthermore, inhibition of KAT6A/B genes resulted in a reduction in estrogen receptor (ER) mRNA and protein expression levels in MCF-7 and MDA-MMB-231 cell lines. Based on our findings, the lysine acetyltransferases KAT6A and KAT6B may be involved in the progression of invasive ductal breast cancer. Further research on other types of cancer may show that KAT6A and KAT6B could serve as diagnostic and prognostic markers for these types of malignancies.},
}

Humans
Female
*Estrogen Receptor alpha/metabolism/genetics
*Breast Neoplasms/pathology/metabolism/genetics
*Histone Acetyltransferases/metabolism/genetics
*Carcinoma, Ductal, Breast/genetics/metabolism/pathology
Cell Line, Tumor
Middle Aged
Gene Expression Regulation, Neoplastic
Adult
Histone Deacetylases/metabolism/genetics
MCF-7 Cells
Aged
Lysine/metabolism

@article {pmid39500528,
year = {2024},
author = {Degavre, C and Lepez, A and Ibanez, S and François, C and Głowacka, K and Guilbaud, C and Laloux-Morris, F and Esfahani, H and Brusa, D and Bouzin, C and Feron, O},
title = {In situ endoscopic photodynamic therapy combined with immature DC vaccination induces a robust T cell response against peritoneal carcinomatosis.},
journal = {Journal for immunotherapy of cancer},
volume = {12},
number = {11},
pages = {},
pmid = {39500528},
issn = {2051-1426},
mesh = {*Photochemotherapy/methods ; Animals ; Mice ; *Peritoneal Neoplasms/immunology/therapy/secondary ; *Dendritic Cells/immunology ; Humans ; Female ; Cancer Vaccines/therapeutic use/pharmacology/immunology ; Photosensitizing Agents/pharmacology/therapeutic use ; Cell Line, Tumor ; Vaccination/methods ; },
abstract = {BACKGROUND: Immunogenic cell death (ICD) and ferroptosis have recently emerged as key factors in the anticancer immune response. Among the treatments able to induce ICD and the associated release of danger signals is photodynamic therapy (PDT). Ferroptosis for its part results from lipid peroxidation and is induced by CD8[+] T cells to kill nearby cancer cells on IFN-γ production. We aimed to combine the two concepts, that is, to evaluate whether the strong pro-oxidant effects of PDT may promote ferroptosis and antigen release and to develop a procedure for in situ PDT to prepare the soil for highly endocytotic immature dendritic cell (iDC) adoptive transfer. This approach was implemented for managing peritoneal carcinomatosis, a lesion often associated with poor outcomes.

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

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

CONCLUSIONS: The combination of in situ PDT locally delivered by an endoscope light and iDC administration induces a durable memory immune response against peritoneal carcinomatosis thereby opening new perspectives for the treatment of a life-threatening condition.},
}

*Photochemotherapy/methods
Animals
Mice
*Peritoneal Neoplasms/immunology/therapy/secondary
*Dendritic Cells/immunology
Humans
Female
Cancer Vaccines/therapeutic use/pharmacology/immunology
Photosensitizing Agents/pharmacology/therapeutic use
Cell Line, Tumor
Vaccination/methods

@article {pmid39331289,
year = {2024},
author = {Vasigh, M and Mohamed, A and Jacobs, L and Lange, J and Camp, M and Sun, B and Wright, P and O'Donnell, M and Tran, HT and Sogunro, O and Habibi, M and Johnston, F and Euhus, D},
title = {The Association Between Breast Cancer Predisposing Genetic Variants and Multifocal, Multicentric Breast Cancer.},
journal = {Annals of surgical oncology},
volume = {31},
number = {13},
pages = {8891-8899},
pmid = {39331289},
issn = {1534-4681},
mesh = {Humans ; Female ; *Breast Neoplasms/genetics/pathology ; Retrospective Studies ; Middle Aged ; *Genetic Predisposition to Disease ; Adult ; Prognosis ; Follow-Up Studies ; Carcinoma, Ductal, Breast/genetics/pathology ; Aged ; Biomarkers, Tumor/genetics ; Genetic Variation ; },
abstract = {BACKGROUND: Breast-conserving surgery is often discouraged in BRCA gene carriers with early onset breast cancer. The genetic variant carrier breast cancers are more likely to be multifocal or multicentric (MFMC).

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

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

CONCLUSION: Genetic variant carrier cancers are not more likely to be MCMF than sporadic cancers.},
}

Humans
Female
*Breast Neoplasms/genetics/pathology
Retrospective Studies
Middle Aged
*Genetic Predisposition to Disease
Adult
Prognosis
Follow-Up Studies
Carcinoma, Ductal, Breast/genetics/pathology
Aged
Biomarkers, Tumor/genetics
Genetic Variation

@article {pmid38195987,
year = {2024},
author = {Knödlseder, N and Fábrega, MJ and Santos-Moreno, J and Manils, J and Toloza, L and Marín Vilar, M and Fernández, C and Broadbent, K and Maruotti, J and Lemenager, H and Carolis, C and Zouboulis, CC and Soler, C and Lood, R and Brüggemann, H and Güell, M},
title = {Delivery of a sebum modulator by an engineered skin microbe in mice.},
journal = {Nature biotechnology},
volume = {42},
number = {11},
pages = {1661-1666},
pmid = {38195987},
issn = {1546-1696},
support = {Marie Skłodowska-Curie Grant Agreement 882387//EC | Horizon 2020 Framework Programme (EU Framework Programme for Research and Innovation H2020)/ ; Award N62909-18-1-2155//United States Department of Defense | United States Navy | Office of Naval Research (ONR)/ ; - IdC 2019 PROD 00057//Government of Catalonia | Agència de Gestió d'Ajuts Universitaris i de Recerca (Agency for Management of University and Research Grants)/ ; Fellowship number 8240//European Molecular Biology Organization (EMBO)/ ; Award Juan de la Cierva FJC 2018-037096-I//Ministerio de Economía y Competitividad (Ministry of Economy and Competitiveness)/ ; Grant Agreement 882387//EC | EU Framework Programme for Research and Innovation H2020 | H2020 Priority Excellent Science | H2020 Marie Skłodowska-Curie Actions (H2020 Excellent Science - Marie Skłodowska-Curie Actions)/ ; },
mesh = {*Sebum/metabolism ; Animals ; Mice ; *Skin/microbiology/metabolism ; Humans ; Propionibacteriaceae/genetics ; },
abstract = {Microorganisms can be equipped with synthetic genetic programs for the production of targeted therapeutic molecules. Cutibacterium acnes is the most abundant commensal of the human skin, making it an attractive chassis to create skin-delivered therapeutics. Here, we report the engineering of this bacterium to produce and secrete the therapeutic molecule neutrophil gelatinase-associated lipocalin, in vivo, for the modulation of cutaneous sebum production.},
}

*Sebum/metabolism
Animals
Mice
*Skin/microbiology/metabolism
Humans
Propionibacteriaceae/genetics

@article {pmid39445528,
year = {2024},
author = {Zhao, Z and Li, L and He, M and Li, Y and Ma, X and Zhao, B},
title = {Prognostic and Predictive Markers for Early Stage Triple-Negative Breast Cancer Treated With Platinum-Based Neoadjuvant Chemotherapy.},
journal = {Cancer medicine},
volume = {13},
number = {20},
pages = {e70336},
pmid = {39445528},
issn = {2045-7634},
support = {2019D01C258//The Natural Science Foundation of Xinjiang Uygur Autonomous Region/ ; },
mesh = {Humans ; *Triple Negative Breast Neoplasms/drug therapy/genetics/mortality/pathology ; Female ; *Neoadjuvant Therapy/methods ; Middle Aged ; *Polymorphism, Single Nucleotide ; Prognosis ; *BRCA1 Protein/genetics ; *Biomarkers, Tumor/genetics ; Adult ; *Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Neoplasm Staging ; BRCA2 Protein/genetics ; Aged ; X-ray Repair Cross Complementing Protein 1/genetics ; Prospective Studies ; Treatment Outcome ; },
abstract = {BACKGROUND: Emerging evidence has indicated possible efficacy benefit of platinum-based chemotherapy as neoadjuvant treatment for invasive ductal carcinoma triple-negative breast cancer (TNBC). However, it has not been endorsed by current guidelines due to highly controversial results.

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

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

CONCLUSIONS: Platinum-based chemotherapy might serve as a therapeutic option for TNBC patients who were resistant to anthracycline- and taxane-based neoadjuvant therapy. Our study identified several genetic and clinical features that might function as prognostic and predictive markers.},
}

Humans
*Triple Negative Breast Neoplasms/drug therapy/genetics/mortality/pathology
Female
*Neoadjuvant Therapy/methods
Middle Aged
*Polymorphism, Single Nucleotide
Prognosis
*BRCA1 Protein/genetics
*Biomarkers, Tumor/genetics
Adult
*Antineoplastic Combined Chemotherapy Protocols/therapeutic use
Neoplasm Staging
BRCA2 Protein/genetics
Aged
X-ray Repair Cross Complementing Protein 1/genetics
Prospective Studies
Treatment Outcome

@article {pmid39435217,
year = {2024},
author = {Kumaravel, A and Esakki, M},
title = {Comparing CD10 Expression With the Clinicopathological Features and Hormone Status of Invasive Breast Cancer.},
journal = {Cureus},
volume = {16},
number = {9},
pages = {e69836},
pmid = {39435217},
issn = {2168-8184},
abstract = {Background Worldwide, female breast cancer is the most common cancer (11.7%), followed by lung (11.4%), colorectal, prostate, and stomach. Breast cancer is the fifth most common cause of cancer-related mortality, with lung cancer being the leading cause. In India, breast and cervical cancers are the two most common cancers among women. This study was undertaken to analyse the expression of CD10 in invasive duct cancer (IDC) and its correlation with the various clinicopathological features and hormone status. Materials and methods This study was conducted in the Department of Pathology, Saveetha Medical College and Hospital on 42 cases of invasive ductal carcinoma - no special type (IDC NST). The clinical and histopathologic parameters such as age, tumor site, tumor size, histologic type, histologic grade, lymph node metastases, lymphovascular invasion, and perineural invasion were assessed in hematoxylin and eosin-stained sections of the tumor tissue along with the hormone status of positivity for ER, PR and Her2Neu. These parameters were subsequently compared with the expression of CD10 in the corresponding slides and statsitical correlation was done using the chi square test. Results The most common age group was more than 40 years, with 41-50 years, and 51-60 years in particular. CD10 was positive in 93% of cases. There was a positive correlation between CD 10 expression and lymphovascular invasion in the study (p-0.006). There was no significant relationship between hormone status and CD10 expression. Conclusion A significant association was seen between CD10 expression and lymphovascular invasion. No relation was found between CD10 and the other parameters such as tumour grade, lymph node metastases, lymphovascular invasion, perineural invasion and hormone status. Further studies are required to explore the potential of CD10 as a prognostic marker for IDC.},
}

@article {pmid39392173,
year = {2024},
author = {Huang, YJ and Lin, JA and Chen, WM and Shia, BC and Wu, SY},
title = {Statin Therapy Reduces Radiation-Induced Cardiotoxicity in Patients With Breast Cancer Receiving Adjuvant Radiotherapy.},
journal = {Journal of the American Heart Association},
volume = {13},
number = {20},
pages = {e036411},
doi = {10.1161/JAHA.124.036411},
pmid = {39392173},
issn = {2047-9980},
mesh = {Humans ; Female ; *Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use ; Middle Aged ; Retrospective Studies ; *Cardiotoxicity ; Radiotherapy, Adjuvant/adverse effects ; Taiwan/epidemiology ; Aged ; Breast Neoplasms/radiotherapy ; Incidence ; Mastectomy, Segmental ; Registries ; Risk Assessment ; Radiation Injuries/epidemiology/prevention & control/etiology ; Adult ; Carcinoma, Ductal, Breast/radiotherapy ; Risk Factors ; Treatment Outcome ; },
abstract = {BACKGROUND: To evaluate the efficacy of statin therapy in reducing major adverse cardiovascular event (MACE) risk among patients with breast cancer undergoing breast-conserving surgery and adjuvant whole breast radiotherapy.

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

CONCLUSIONS: Statin therapy is associated with a reduced risk of MACE in patients with breast cancer undergoing breast-conserving surgery and adjuvant whole breast radiotherapy. Hydrophilic statins rosuvastatin and pravastatin exhibit the most pronounced cardioprotective effects. These findings suggest a potential role for statins in mitigating cardiovascular complications in this population and highlight the need for further research to optimize statin therapy in survivors of breast cancer undergoing radiotherapy.},
}

Humans
Female
*Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use
Middle Aged
Retrospective Studies
*Cardiotoxicity
Radiotherapy, Adjuvant/adverse effects
Taiwan/epidemiology
Aged
Breast Neoplasms/radiotherapy
Incidence
Mastectomy, Segmental
Registries
Risk Assessment
Radiation Injuries/epidemiology/prevention & control/etiology
Adult
Carcinoma, Ductal, Breast/radiotherapy
Risk Factors
Treatment Outcome

@article {pmid39284909,
year = {2024},
author = {Brunetta, HS and Jung, AS and Valdivieso-Rivera, F and de Campos Zani, SC and Guerra, J and Furino, VO and Francisco, A and Berçot, M and Moraes-Vieira, PM and Keipert, S and Jastroch, M and Martinez, LO and Sponton, CH and Castilho, RF and Mori, MA and Bartelt, A},
title = {IF1 is a cold-regulated switch of ATP synthase hydrolytic activity to support thermogenesis in brown fat.},
journal = {The EMBO journal},
volume = {43},
number = {21},
pages = {4870-4891},
pmid = {39284909},
issn = {1460-2075},
support = {2022/00358-1//Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)/ ; 852742//EC | European Research Council (ERC)/ ; BA4925/2-1//Deutsche Forschungsgemeinschaft (DFG)/ ; 81X3600212//Deutsches Zentrum für Herz-Kreislaufforschung (DZHK)/ ; 310287/2018-9//Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)/ ; 88881.143924/2017-01//Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)/ ; },
mesh = {Animals ; *Thermogenesis/genetics ; Mice ; *Adipose Tissue, Brown/metabolism ; *Cold Temperature ; *ATPase Inhibitory Protein ; *Mitochondrial Proton-Translocating ATPases/metabolism/genetics ; Hydrolysis ; Mitochondria/metabolism ; Mice, Inbred C57BL ; Male ; Adipocytes, Brown/metabolism ; Membrane Potential, Mitochondrial ; Energy Metabolism ; },
abstract = {While mechanisms controlling uncoupling protein-1 (UCP1) in thermogenic adipocytes play a pivotal role in non-shivering thermogenesis, it remains unclear whether F1Fo-ATP synthase function is also regulated in brown adipose tissue (BAT). Here, we show that inhibitory factor 1 (IF1, encoded by Atp5if1), an inhibitor of ATP synthase hydrolytic activity, is a critical negative regulator of brown adipocyte energy metabolism. In vivo, IF1 levels are diminished in BAT of cold-adapted mice compared to controls. Additionally, the capacity of ATP synthase to generate mitochondrial membrane potential (MMP) through ATP hydrolysis (the so-called "reverse mode" of ATP synthase) is increased in brown fat. In cultured brown adipocytes, IF1 overexpression results in an inability of mitochondria to sustain the MMP upon adrenergic stimulation, leading to a quiescent-like phenotype in brown adipocytes. In mice, adeno-associated virus-mediated IF1 overexpression in BAT suppresses adrenergic-stimulated thermogenesis and decreases mitochondrial respiration in BAT. Taken together, our work identifies downregulation of IF1 upon cold as a critical event for the facilitation of the reverse mode of ATP synthase as well as to enable energetic adaptation of BAT to effectively support non-shivering thermogenesis.},
}

Animals
*Thermogenesis/genetics
Mice
*Adipose Tissue, Brown/metabolism
*Cold Temperature
*ATPase Inhibitory Protein
*Mitochondrial Proton-Translocating ATPases/metabolism/genetics
Hydrolysis
Mitochondria/metabolism
Mice, Inbred C57BL
Male
Adipocytes, Brown/metabolism
Membrane Potential, Mitochondrial
Energy Metabolism

@article {pmid38621672,
year = {2024},
author = {Sánchez-Dávila, JN and Verástegui, EL and Peña-Nieves, A and Allende-Pérez, SR},
title = {Integration of the geriatric palliative care in oncological care of elderly patient with cancer.},
journal = {Palliative & supportive care},
volume = {22},
number = {4},
pages = {792-800},
doi = {10.1017/S1478951524000294},
pmid = {38621672},
issn = {1478-9523},
mesh = {Humans ; Aged ; *Palliative Care/methods/standards ; Aged, 80 and over ; Female ; Male ; *Neoplasms/complications/therapy ; *Geriatrics/methods ; Geriatric Assessment/methods ; },
abstract = {OBJECTIVES: The objective of this article is to describe the profile of the population attended to by the palliative geriatrics clinic and to evaluate the symptomatic control derived from the care provided.

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

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

SIGNIFICANCE OF RESULTS: Elderly cancer patients have a complex profile and may have multiple needs. Integrating geriatric palliative care can help to provide better and personalized care along with symptomatic control. Further studies are required to establish the ideal care model for these patients. Importantly, a personalized treatment with a geriatric palliative care specialist is a key element.},
}

Humans
Aged
*Palliative Care/methods/standards
Aged, 80 and over
Female
Male
*Neoplasms/complications/therapy
*Geriatrics/methods
Geriatric Assessment/methods

@article {pmid39315404,
year = {2024},
author = {Liu, Y and Lin, D and Najam, SS and Huang, S and Song, M and Sirakawin, C and Zhao, C and Jiang, H and Konopka, W and Herzig, S and Vinnikov, IA},
title = {Functional redundancy between glucocorticoid and mineralocorticoid receptors in mature corticotropin-releasing hormone neurons protects from obesity.},
journal = {Obesity (Silver Spring, Md.)},
volume = {32},
number = {10},
pages = {1885-1896},
doi = {10.1002/oby.24116},
pmid = {39315404},
issn = {1930-739X},
support = {31771433//National Natural Science Foundation of China/ ; 32241020//National Natural Science Foundation of China/ ; 32350610254//National Natural Science Foundation of China/ ; },
mesh = {Animals ; Male ; Mice ; *Corticosterone/blood/metabolism ; *Corticotropin-Releasing Hormone/metabolism ; *Energy Metabolism ; Insulin Resistance ; Mice, Inbred C57BL ; *Mice, Knockout ; *Neurons/metabolism ; *Obesity/metabolism ; Paraventricular Hypothalamic Nucleus/metabolism ; *Receptors, Glucocorticoid/metabolism/genetics ; *Receptors, Mineralocorticoid/metabolism/genetics ; Female ; },
abstract = {OBJECTIVE: Here, we aimed to investigate the role of glucocorticoid and mineralocorticoid receptors (GRs and MRs, respectively) in the regulation of energy homeostasis.

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

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

CONCLUSIONS: Our data demonstrate the functional redundancy of GRs and MRs in CRH neurons to maintain energy homeostasis and prevent obesity. Simultaneous targeting of both receptors might represent an unprecedented approach to counteract obesity.},
}

Animals
Male
Mice
*Corticosterone/blood/metabolism
*Corticotropin-Releasing Hormone/metabolism
*Energy Metabolism
Insulin Resistance
Mice, Inbred C57BL
*Mice, Knockout
*Neurons/metabolism
*Obesity/metabolism
Paraventricular Hypothalamic Nucleus/metabolism
*Receptors, Glucocorticoid/metabolism/genetics
*Receptors, Mineralocorticoid/metabolism/genetics
Female

@article {pmid39296436,
year = {2024},
author = {Mihai, AM and Ianculescu, LM and Suciu, N},
title = {MiRNAs as potential biomarkers in early breast cancer detection: a systematic review.},
journal = {Journal of medicine and life},
volume = {17},
number = {6},
pages = {549-554},
pmid = {39296436},
issn = {1844-3117},
mesh = {Female ; Humans ; *Biomarkers, Tumor/blood/genetics ; *Breast Neoplasms/blood/diagnosis/genetics ; *Early Detection of Cancer/methods ; *Circulating MicroRNA/blood/genetics ; },
abstract = {Breast cancer remains a significant global health challenge, with high incidence and mortality rates. While mammography has contributed to declining mortality, its limitations in sensitivity and specificity for early detection, particularly in distinguishing between pure atypical ductal hyperplasia (ADH), ductal carcinoma in situ (DCIS), and invasive ductal carcinoma (IDC), highlight the need for more precise tools. Even with core needle biopsy (CNB), conclusive diagnoses often require surgical excision. This underscores the urgency for non-invasive biomarkers to improve early detection and differentiation, potentially reducing invasive procedures. Recent research has shifted focus from mRNA to microRNAs (miRNAs) as promising biomarkers for breast cancer screening. These small non-coding RNAs, which exhibit abnormal expression patterns in breast cancer patients' tissue and serum/plasma, play crucial roles in early breast cancer development by modulating proto-oncogenes or tumor suppressor genes at the post-transcriptional level. Notably, miRNAs such as miR-21, miR-155, and miR-200c are key regulators of cell proliferation and apoptosis, with the potential to distinguish between normal tissue and various stages of breast lesions, including ADH, DCIS, and IDC. Additionally, miRNAs in serum and plasma offer a non-invasive method to differentiate breast cancer stages. This review aims to consolidate current knowledge on early breast lesions and explore the potential of miRNAs as biomarkers for early breast cancer detection, which could enhance risk prediction and reduce reliance on invasive diagnostic procedures.},
}

Female
Humans
*Biomarkers, Tumor/blood/genetics
*Breast Neoplasms/blood/diagnosis/genetics
*Early Detection of Cancer/methods
*Circulating MicroRNA/blood/genetics

@article {pmid39283254,
year = {2024},
author = {Cai, F and Li, Y and Liu, H and Luo, J},
title = {Single-cell and Spatial Transcriptomic Analyses Implicate Formation of the Immunosuppressive Microenvironment during Breast Tumor Progression.},
journal = {Journal of immunology (Baltimore, Md. : 1950)},
volume = {213},
number = {9},
pages = {1392-1401},
doi = {10.4049/jimmunol.2400025},
pmid = {39283254},
issn = {1550-6606},
support = {62072058//MOST | National Natural Science Foundation of China (NSFC)/ ; 82073339//MOST | National Natural Science Foundation of China (NSFC)/ ; BK20231271//JST | Natural Science Foundation of Jiangsu Province (Jiangsu Natural Science Foundation)/ ; },
mesh = {Humans ; *Tumor Microenvironment/immunology/genetics ; *Breast Neoplasms/immunology/genetics/pathology ; Female ; *Single-Cell Analysis ; *Disease Progression ; *Transcriptome ; Gene Expression Profiling ; Carcinoma, Intraductal, Noninfiltrating/immunology/genetics/pathology ; Carcinoma, Ductal, Breast/immunology/genetics/pathology ; Gene Expression Regulation, Neoplastic/immunology ; },
abstract = {Ductal carcinoma in situ and invasive ductal carcinoma represent two stages of breast cancer progression. A multitude of studies have shown that genomic instability increases during tumor development, as manifested by higher mutation and copy number variation rates. The advent of single-cell and spatial transcriptomics has enabled the investigation of the subtle differences in cellular states during the tumor progression at single-cell level, thereby providing more nuanced understanding of the intercellular interactions within the solid tumor. However, the evolutionary trajectory of tumor cells and the establishment of the immunosuppressive microenvironment during breast cancer progression remain unclear. In this study, we performed an exploratory analysis of the single-cell sequencing dataset of 13 ductal carcinoma in situ and invasive ductal carcinoma samples. We revealed that tumor cells became more malignant and aggressive during their progression, and T cells transited to an exhausted state. The tumor cells expressed various coinhibitory ligands that interacted with the receptors of immune cells to create an immunosuppressive tumor microenvironment. Furthermore, spatial transcriptomics data confirmed the spatial colocalization of tumor and immune cells, as well as the expression of the coinhibitory ligand-receptor pairs. Our analysis provides insights into the cellular and molecular mechanism underlying the formation of the immunosuppressive landscape during two typical stages of breast cancer progression.},
}

Humans
*Tumor Microenvironment/immunology/genetics
*Breast Neoplasms/immunology/genetics/pathology
Female
*Single-Cell Analysis
*Disease Progression
*Transcriptome
Gene Expression Profiling
Carcinoma, Intraductal, Noninfiltrating/immunology/genetics/pathology
Carcinoma, Ductal, Breast/immunology/genetics/pathology
Gene Expression Regulation, Neoplastic/immunology

@article {pmid39226766,
year = {2024},
author = {Madrigal, JM and Pruitt, CN and Fisher, JA and Liao, LM and Graubard, BI and Gierach, GL and Silverman, DT and Ward, MH and Jones, RR},
title = {Carcinogenic industrial air pollution and postmenopausal breast cancer risk in the National Institutes of Health AARP Diet and Health Study.},
journal = {Environment international},
volume = {191},
number = {},
pages = {108985},
pmid = {39226766},
issn = {1873-6750},
support = {Z99 CA999999/ImNIH/Intramural NIH HHS/United States ; ZIA CP010125/ImNIH/Intramural NIH HHS/United States ; },
mesh = {Humans ; Female ; *Breast Neoplasms/epidemiology/chemically induced ; *Postmenopause ; Middle Aged ; United States/epidemiology ; Aged ; *Air Pollution/statistics & numerical data ; Air Pollutants/analysis ; Prospective Studies ; Carcinogens/analysis ; Risk Factors ; National Institutes of Health (U.S.) ; Environmental Exposure/statistics & numerical data ; Benzene/analysis ; },
abstract = {BACKGROUND: Chemicals emitted from industrial facilities include known or suspected mammary carcinogens and endocrine disruptors, but epidemiologic studies are limited. We evaluated associations between air emissions of multiple carcinogenic chemicals and postmenopausal breast cancer risk in a large prospective U.S.

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

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

CONCLUSIONS: An increased risk of breast cancer associated with relatively high levels of industrial benzene emissions warrants additional study, particularly among participants with diverse sociodemographic characteristics that live in areas with higher density of industrial facilities.},
}

Humans
Female
*Breast Neoplasms/epidemiology/chemically induced
*Postmenopause
Middle Aged
United States/epidemiology
Aged
*Air Pollution/statistics & numerical data
Air Pollutants/analysis
Prospective Studies
Carcinogens/analysis
Risk Factors
National Institutes of Health (U.S.)
Environmental Exposure/statistics & numerical data
Benzene/analysis

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

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

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

CONCLUSION: Most BC patients who developed a SPM had ER/PR positive tumors and a family history of malignancy, with most <50 years old. Although chemotherapy and radiation increase cancer risk, there were an equal number of patients with SPMs who did or did not receive either treatment. Most SPMs were breast, soft tissue, gynecologic, hematologic, or colorectal. BC patients should be followed closely given an elevated propensity for developing SPMs.},
}

Humans
Female
*Neoplasms, Second Primary/epidemiology/pathology
Middle Aged
*Breast Neoplasms/pathology/therapy/genetics
Adult
Aged
Aged, 80 and over
Retrospective Studies
Young Adult
Carcinoma, Ductal, Breast/pathology/therapy/epidemiology/genetics
Prospective Studies
Follow-Up Studies
Risk Factors

@article {pmid38215056,
year = {2024},
author = {Schimpfle, L and Tsilingiris, D and Mooshage, CM and Kender, Z and Sulaj, A and von Rauchhaupt, E and Szendroedi, J and Herzig, S and Goepfert, J and Groener, J and Nawroth, PP and Bendszus, M and Heiland, S and Kurz, FT and Jende, JME and Kopf, S},
title = {Phase Angle of Bioelectrical Impedance Analysis as an Indicator for Diabetic Polyneuropathy in Type 2 Diabetes Mellitus.},
journal = {The Journal of clinical endocrinology and metabolism},
volume = {109},
number = {11},
pages = {e2110-e2119},
pmid = {38215056},
issn = {1945-7197},
support = {B05//Collaborative Research Council 1118/ ; A03//Collaborative Research Council 1158/ ; //Deutsches Zentrum für Diabetesforschung (DZD e.V.)/ ; },
mesh = {Humans ; *Diabetes Mellitus, Type 2/complications/physiopathology ; *Diabetic Neuropathies/diagnosis/physiopathology ; Female ; Male ; *Electric Impedance ; Middle Aged ; Cross-Sectional Studies ; Aged ; Neural Conduction/physiology ; Adult ; },
abstract = {CONTEXT: Due to the heterogenous clinical symptoms and deficits, the diagnosis of diabetic polyneuropathy (DPN) is still difficult in clinical routines, leading to increased morbidity and mortality.

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

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

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

CONCLUSION: The study shows that PhA is, in comparison to other test systems used, at least an equally good and much easier to handle investigator-independent marker for detection of DPN.},
}

Humans
*Diabetes Mellitus, Type 2/complications/physiopathology
*Diabetic Neuropathies/diagnosis/physiopathology
Female
Male
*Electric Impedance
Middle Aged
Cross-Sectional Studies
Aged
Neural Conduction/physiology
Adult

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

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

CONCLUSION: Impaired macrophage CB1 signalling is atheroprotective by limiting their arterial recruitment, proliferation, and inflammatory reprogramming in male mice. The importance of macrophage CB1 signalling appears to be sex-dependent.},
}

Animals
Male
Female
*Cell Proliferation
*Macrophages/metabolism/pathology
*Receptor, Cannabinoid, CB1/metabolism/genetics
*Signal Transduction
*Disease Models, Animal
*Atherosclerosis/genetics/pathology/metabolism/prevention & control/enzymology
Sex Factors
*Plaque, Atherosclerotic
Humans
*Mice, Knockout
*Phenotype
Estrogen Receptor alpha/metabolism/genetics/deficiency
Mice, Inbred C57BL
Carotid Artery Diseases/genetics/pathology/metabolism/prevention & control
Tumor Suppressor Protein p53/metabolism/genetics/deficiency
Estradiol/pharmacology
Aortic Diseases/genetics/pathology/prevention & control/metabolism/enzymology

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

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

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

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

LEVEL OF EVIDENCE: 2 Laryngoscope, 134:4661-4666, 2024.},
}

Humans
Female
Male
Prospective Studies
Adult
*Vocal Cords/surgery/physiopathology
*Voice Quality
Time Factors
Treatment Outcome
Middle Aged
*Laryngeal Diseases/surgery/physiopathology
Rest/physiology
Voice Disorders/etiology/surgery/physiopathology
Phonation/physiology
Postoperative Period
Postoperative Care/methods

@article {pmid38414161,
year = {2024},
author = {Geppert, J and Rohm, M},
title = {Cancer cachexia: biomarkers and the influence of age.},
journal = {Molecular oncology},
volume = {18},
number = {9},
pages = {2070-2086},
doi = {10.1002/1878-0261.13590},
pmid = {38414161},
issn = {1878-0261},
support = {//Helmholtz-Gemeinschaft/ ; 949017//European Commission/ ; },
mesh = {*Cachexia/metabolism/diagnosis ; Humans ; *Neoplasms/complications/metabolism ; *Aging/metabolism ; Animals ; Biomarkers/metabolism ; Biomarkers, Tumor/metabolism ; Inflammation/metabolism ; },
abstract = {Cancer cachexia (Ccx) is a complex metabolic condition characterized by pronounced muscle and fat wasting, systemic inflammation, weakness and fatigue. Up to 30% of cancer patients succumb directly to Ccx, yet therapies that effectively address this perturbed metabolic state are rare. In recent decades, several characteristics of Ccx have been established in mice and humans, of which we here highlight adipose tissue dysfunction, muscle wasting and systemic inflammation, as they are directly linked to biomarker discovery. To counteract cachexia pathogenesis as early as possible and mitigate its detrimental impact on anti-cancer treatments, identification and validation of clinically endorsed biomarkers assume paramount importance. Ageing was recently shown to affect both the validity of Ccx biomarkers and Ccx development, but the underlying mechanisms are still unknown. Thus, unravelling the intricate interplay between ageing and Ccx can help to counteract Ccx pathogenesis and tailor diagnostic and treatment strategies to individual needs.},
}

*Cachexia/metabolism/diagnosis
Humans
*Neoplasms/complications/metabolism
*Aging/metabolism
Animals
Biomarkers/metabolism
Biomarkers, Tumor/metabolism
Inflammation/metabolism

@article {pmid38795111,
year = {2024},
author = {Voß, F and Zweck, E and Ipek, R and Schultheiss, HP and Roden, M and Kelm, M and Szendroedi, J and Polzin, A and Westenfeld, R and Scheiber, D},
title = {Myocardial Mitochondrial Function Is Impaired in Cardiac Light-Chain Amyloidosis Compared to Transthyretin Amyloidosis.},
journal = {JACC. Heart failure},
volume = {12},
number = {10},
pages = {1778-1780},
doi = {10.1016/j.jchf.2024.03.012},
pmid = {38795111},
issn = {2213-1787},
mesh = {Humans ; *Amyloid Neuropathies, Familial/metabolism/physiopathology/complications ; *Cardiomyopathies/etiology/physiopathology/metabolism ; Mitochondria, Heart/metabolism ; Male ; Female ; Immunoglobulin Light-chain Amyloidosis ; Aged ; Middle Aged ; Myocardium/pathology/metabolism ; },
}

Humans
*Amyloid Neuropathies, Familial/metabolism/physiopathology/complications
*Cardiomyopathies/etiology/physiopathology/metabolism
Mitochondria, Heart/metabolism
Male
Female
Immunoglobulin Light-chain Amyloidosis
Aged
Middle Aged
Myocardium/pathology/metabolism

@article {pmid39187318,
year = {2024},
author = {Kolia, A and Frountzas, M and Liatsou, E and Samelis, G and Zagouri, F and Zografos, GC and Gazouli, M and Michalopoulos, NV},
title = {The Role of Serum Nestin in Diagnosis and Prognosis of Breast Cancer: A Prospective Observational Study.},
journal = {In vivo (Athens, Greece)},
volume = {38},
number = {5},
pages = {2399-2403},
pmid = {39187318},
issn = {1791-7549},
mesh = {Humans ; *Breast Neoplasms/blood/diagnosis/pathology/metabolism ; Female ; *Nestin/metabolism/blood ; Middle Aged ; Prognosis ; *Biomarkers, Tumor/blood ; Aged ; Adult ; Prospective Studies ; Neoplasm Staging ; Receptor, ErbB-2/metabolism/genetics ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; Aged, 80 and over ; },
abstract = {BACKGROUND/AIM: The molecular classification of breast cancer has enabled targeted therapy for specific molecular subtypes. Nestin, which has been studied for its role in oncogenesis, could contribute to this direction. This study aimed to investigate the differences between serum nestin levels and molecular profiling, as well as histopathological tumor types, in women who underwent surgery for breast cancer.

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

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

CONCLUSION: The diagnostic and prognostic role of circulating nestin for breast cancer was not confirmed and no correlation with immunohistochemistry results was observed. Thus, the necessity of larger prospective studies is enhanced.},
}

Humans
*Breast Neoplasms/blood/diagnosis/pathology/metabolism
Female
*Nestin/metabolism/blood
Middle Aged
Prognosis
*Biomarkers, Tumor/blood
Aged
Adult
Prospective Studies
Neoplasm Staging
Receptor, ErbB-2/metabolism/genetics
Receptors, Estrogen/metabolism
Receptors, Progesterone/metabolism
Aged, 80 and over

@article {pmid39148033,
year = {2024},
author = {Chen, JH and Addanki, S and Roy, D and Bassett, R and Kalashnikova, E and Spickard, E and Kuerer, HM and Meas, S and Sarli, VN and Korkut, A and White, JB and Rauch, GM and Tripathy, D and Arun, BK and Barcenas, CH and Yam, C and Sethi, H and Rodriguez, AA and Liu, MC and Moulder, SL and Lucci, A},
title = {Monitoring response to neoadjuvant chemotherapy in triple negative breast cancer using circulating tumor DNA.},
journal = {BMC cancer},
volume = {24},
number = {1},
pages = {1016},
pmid = {39148033},
issn = {1471-2407},
mesh = {Humans ; *Triple Negative Breast Neoplasms/drug therapy/blood/mortality/genetics/pathology ; *Circulating Tumor DNA/blood/genetics ; Female ; *Neoadjuvant Therapy/methods ; Middle Aged ; Adult ; *Neoplastic Cells, Circulating/pathology/metabolism ; Biomarkers, Tumor/blood ; Aged ; Prognosis ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Treatment Outcome ; },
abstract = {BACKGROUND: Triple negative breast cancer (TNBC) is an aggressive subtype with poor prognosis. We aimed to determine whether circulating tumor DNA (ctDNA) and circulating tumor cell (CTC) could predict response and long-term outcomes to neoadjuvant chemotherapy (NAC).

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

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

CONCLUSIONS: Early clearance of ctDNA served as a predictive and prognostic marker in TNBC. Personalized ctDNA monitoring during NAC may help predict response and guide treatment.},
}

Humans
*Triple Negative Breast Neoplasms/drug therapy/blood/mortality/genetics/pathology
*Circulating Tumor DNA/blood/genetics
Female
*Neoadjuvant Therapy/methods
Middle Aged
Adult
*Neoplastic Cells, Circulating/pathology/metabolism
Biomarkers, Tumor/blood
Aged
Prognosis
Antineoplastic Combined Chemotherapy Protocols/therapeutic use
Treatment Outcome

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

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

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

CONCLUSIONS: Together with our patient database data, these proof-of-concept results reveal new SEMA3F-mediated mechanisms occurring in the most common preinvasive BC lesion, DCIS, and represent potent and direct activation of its transition to invasion. Moreover, and of clinical and therapeutic relevance, the effects of SEMA3F can be blocked directly through its coreceptors, thus preventing invasion and keeping DCIS lesions in the preinvasive state.},
}

Humans
*Neuropilin-1/metabolism/genetics
Female
*Breast Neoplasms/pathology/metabolism/genetics
*Neuropilin-2/metabolism/genetics
*Neoplasm Invasiveness
*Carcinoma, Intraductal, Noninfiltrating/metabolism/pathology/genetics
Cell Line, Tumor
*Nerve Tissue Proteins/metabolism/genetics
Epithelial-Mesenchymal Transition/genetics
Animals
Membrane Proteins/metabolism/genetics
Mice
Carcinoma, Ductal, Breast/pathology/metabolism/genetics
Gene Expression Regulation, Neoplastic
Signal Transduction

@article {pmid39103259,
year = {2024},
author = {Wang, DH and Yin, WL and Pan, XY and Zhang, MN and Nie, L and Chen, XQ and Zeng, H and Zhou, Q and Chen, N},
title = {[Prostate cancer with BRCA2 pathogenic mutation: a clinicopathological analysis].},
journal = {Zhonghua bing li xue za zhi = Chinese journal of pathology},
volume = {53},
number = {8},
pages = {789-796},
doi = {10.3760/cma.j.cn112151-20240402-00216},
pmid = {39103259},
issn = {0529-5807},
support = {82273047, 82273073, 82203280//National Natural Science Foundation of China/ ; 24SYSX0223, 2022YFS0305//Foundation of Science and Technology Department of Sichuan Province/ ; },
mesh = {Humans ; Male ; *Prostatic Neoplasms/genetics/pathology ; *BRCA2 Protein/genetics ; Aged ; Retrospective Studies ; Middle Aged ; *Mutation ; Prognosis ; Aged, 80 and over ; Bone Neoplasms/genetics/secondary/pathology ; },
abstract = {Objective: To analyze the clinicopathological features of prostate cancers with BRCA2 pathogenic mutations, and the association between BRCA2 pathogenic mutation and clinicopathological characteristics. Patient survivals were also examined. Methods: Clinicopathological data of 249 prostate cancer patients who underwent genetic testing in West China Hospital of Sichuan University, Chengdu, China from June 2014 to August 2021 were collected. A retrospective analysis of histopathological morphology, clinicopathological characteristics, and patient survivals was conducted. Results: The genetic testing in the 249 prostate cancer patients showed a pathogenic mutation of DNA damage repair gene (DRG) in 73 cases (73/249, 29.3%), including 22 cases (8.8%) with BRCA2 pathogenic mutation and 51 cases with pathogenic mutations of other DRG. Among the 22 patients with BRCA2 pathogenic mutation, 14 patients (5.6%) harbored germline mutations and 8 patients (3.2%) somatic mutations. Their ages ranged from 48 to 91 years, with a median of 67 years. Seventeen patients (77.3%) had distant metastasis, including 16 cases with bone metastasis and 1 case with multiple metastases. Thirteen patients (59.1%) were castration-resistant prostate cancer. The histological type was mainly classical prostatic acinar adenocarcinoma, including 16 cases (72.7%) with intraductal carcinoma of the prostate (IDC-P). Six cases (27.3%) showed focal neuroendocrine differentiation. Perineural/vascular invasion and extraprostatic extension were seen in 11 cases (50.0%) and 8 cases (36.4%), respectively. The Gleason scores of 19 patients (86.4%) were≥8. IDC-P was more commonly found in patients with BRCA2 germline pathogenic mutation than those with BRCA2 somatic pathogenic mutation, other DRG pathogenic mutation or no-DRG pathogenic mutation (P=0.002). With a total follow-up time of 189 months, the median overall survival (OS) was 132.3 months. Patients with DRG pathogenic mutation had shorter OS than those with no-DRG pathogenic mutation (P=0.040). The OS of patients with BRCA2 germline pathogenic mutation did not significantly differ from that of patients with BRCA2 somatic pathogenic mutation, other DRG pathogenic mutation or no-DRG pathogenic mutation (P=0.216). Conclusions: The presence of BRCA2 gene pathogenic mutation is common in the prostate cancers with high Gleason grade, advanced clinical stage, and castration resistance. IDC-P is more commonly noted in cases with BRCA2 germline pathogenic mutation than those without. Patients with DRG pathogenic mutation have shorter OS than those with no-DRG pathogenic mutation, but there is no significant association between BRCA2 pathogenic mutations and OS.},
}

Humans
Male
*Prostatic Neoplasms/genetics/pathology
*BRCA2 Protein/genetics
Aged
Retrospective Studies
Middle Aged
*Mutation
Prognosis
Aged, 80 and over
Bone Neoplasms/genetics/secondary/pathology

@article {pmid39069624,
year = {2024},
author = {Imamura, T and Komatsu, S and Nishibeppu, K and Kiuchi, J and Ohashi, T and Konishi, H and Shiozaki, A and Yamamoto, Y and Moriumura, R and Ikoma, H and Ochiai, T and Otsuji, E},
title = {Urinary microRNA-210-3p as a novel and non-invasive biomarker for the detection of pancreatic cancer, including intraductal papillary mucinous carcinoma.},
journal = {BMC cancer},
volume = {24},
number = {1},
pages = {907},
pmid = {39069624},
issn = {1471-2407},
mesh = {Humans ; *MicroRNAs/urine/blood/genetics ; Female ; Male ; *Biomarkers, Tumor/urine/genetics/blood ; *Pancreatic Neoplasms/urine/genetics/diagnosis/blood ; Middle Aged ; Aged ; Adenocarcinoma, Mucinous/urine/genetics/diagnosis ; ROC Curve ; Case-Control Studies ; Gene Expression Regulation, Neoplastic ; Adult ; Carcinoma, Pancreatic Ductal/urine/genetics/diagnosis/blood ; },
abstract = {BACKGROUND: This study aims to explore novel microRNAs in urine for screening and predicting clinical characteristics in pancreatic cancer (PC) patients using a microRNA array-based approach.

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

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

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

TRIAL REGISTRATION: Not applicable.},
}

Humans
*MicroRNAs/urine/blood/genetics
Female
Male
*Biomarkers, Tumor/urine/genetics/blood
*Pancreatic Neoplasms/urine/genetics/diagnosis/blood
Middle Aged
Aged
Adenocarcinoma, Mucinous/urine/genetics/diagnosis
ROC Curve
Case-Control Studies
Gene Expression Regulation, Neoplastic
Adult
Carcinoma, Pancreatic Ductal/urine/genetics/diagnosis/blood

@article {pmid39062707,
year = {2024},
author = {Corrêa, TS and Asprino, PF and de Oliveira, ESC and Leite, ACR and Weis, L and Achatz, MI and de Oliveira, CP and Sandoval, RL and Barroso-Sousa, R},
title = {TP53 p.R337H Germline Variant among Women at Risk of Hereditary Breast Cancer in a Public Health System of Midwest Brazil.},
journal = {Genes},
volume = {15},
number = {7},
pages = {},
pmid = {39062707},
issn = {2073-4425},
mesh = {Humans ; Female ; *Breast Neoplasms/genetics/epidemiology ; Brazil/epidemiology ; *Germ-Line Mutation ; Adult ; *Tumor Suppressor Protein p53/genetics ; Middle Aged ; *Genetic Predisposition to Disease ; Genetic Testing/methods ; Public Health ; Li-Fraumeni Syndrome/genetics/epidemiology ; Aged ; },
abstract = {Despite the high prevalence of TP53 pathogenic variants (PV) carriers in the South and Southeast regions of Brazil, germline genetic testing for hereditary breast cancer (HBC) is not available in the Brazilian public health system, and the prevalence of Li-Fraumeni syndrome (LFS) is not well established in other regions of Brazil. We assessed the occurrence of TP53 p.R337H carriers among women treated for breast cancer (BC) between January 2021 and January 2022 at public hospitals of Brasilia, DF, Brazil. A total of 180 patients who met at least one of the NCCN criteria for HBC underwent germline testing; 44.4% performed out-of-pocket germline multigene panel testing, and 55.6% were tested for the p.R337H variant by allelic discrimination PCR. The median age at BC diagnosis was 43.5 years, 93% had invasive ductal carcinoma, 50% had estrogen receptor-positive/HER2 negative tumors, and 41% and 11% were diagnosed respectively at stage III and IV. Two patients (1.11%) harbored the p.R337H variant, and cascade family testing identified 20 additional carriers. The TP53 p.R337H detection rate was lower than that reported in other studies from south/southeast Brazil. Nonetheless, identifying TP53 PV carriers through genetic testing in the Brazilian public health system could guide cancer treatment and prevention.},
}

Humans
Female
*Breast Neoplasms/genetics/epidemiology
Brazil/epidemiology
*Germ-Line Mutation
Adult
*Tumor Suppressor Protein p53/genetics
Middle Aged
*Genetic Predisposition to Disease
Genetic Testing/methods
Public Health
Li-Fraumeni Syndrome/genetics/epidemiology
Aged

@article {pmid39039278,
year = {2024},
author = {Das, M and Semple, JI and Haemmerli, A and Volodkina, V and Scotton, J and Gitchev, T and Annan, A and Campos, J and Statzer, C and Dakhovnik, A and Ewald, CY and Mozziconacci, J and Meister, P},
title = {Condensin I folds the Caenorhabditis elegans genome.},
journal = {Nature genetics},
volume = {56},
number = {8},
pages = {1737-1749},
pmid = {39039278},
issn = {1546-1718},
support = {31003A_176226/PP00P3_159320//Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (Swiss National Science Foundation)/ ; },
mesh = {Animals ; *Caenorhabditis elegans/genetics ; *Adenosine Triphosphatases/genetics/metabolism ; *Multiprotein Complexes/genetics/metabolism ; *DNA-Binding Proteins/genetics/metabolism ; *Caenorhabditis elegans Proteins/genetics/metabolism ; *X Chromosome/genetics ; Chromosomal Proteins, Non-Histone/metabolism/genetics ; Cohesins ; Cell Cycle Proteins/metabolism/genetics ; Interphase/genetics ; Genome, Helminth ; Genes, X-Linked ; Chromosomes/genetics ; },
abstract = {The structural maintenance of chromosome (SMC) complexes-cohesin and condensins-are crucial for chromosome separation and compaction during cell division. During the interphase, mammalian cohesins additionally fold the genome into loops and domains. Here we show that, in Caenorhabditis elegans, a species with holocentric chromosomes, condensin I is the primary, long-range loop extruder. The loss of condensin I and its X-specific variant, condensin I[DC], leads to genome-wide decompaction, chromosome mixing and disappearance of X-specific topologically associating domains, while reinforcing fine-scale epigenomic compartments. In addition, condensin I/I[DC] inactivation led to the upregulation of X-linked genes and unveiled nuclear bodies grouping together binding sites for the X-targeting loading complex of condensin I[DC]. C. elegans condensin I/I[DC] thus uniquely organizes holocentric interphase chromosomes, akin to cohesin in mammals, as well as regulates X-chromosome gene expression.},
}

Animals
*Caenorhabditis elegans/genetics
*Adenosine Triphosphatases/genetics/metabolism
*Multiprotein Complexes/genetics/metabolism
*DNA-Binding Proteins/genetics/metabolism
*Caenorhabditis elegans Proteins/genetics/metabolism
*X Chromosome/genetics
Chromosomal Proteins, Non-Histone/metabolism/genetics
Cohesins
Cell Cycle Proteins/metabolism/genetics
Interphase/genetics
Genome, Helminth
Genes, X-Linked
Chromosomes/genetics

@article {pmid39038425,
year = {2024},
author = {Bar, Y and Bar, K and Feldman, D and Dror, JB and Shahoha, M and Lerner, S and Shachar, SS and Weiss-Meilik, A and Dershowitz, N and Wolf, I and Sonnenblick, A},
title = {The impact of extensive intraductal component (EIC) on the genomic risk of recurrence in early hormone receptor positive breast cancer.},
journal = {Breast (Edinburgh, Scotland)},
volume = {77},
number = {},
pages = {103777},
pmid = {39038425},
issn = {1532-3080},
mesh = {Humans ; Female ; *Breast Neoplasms/genetics/pathology/surgery ; Middle Aged ; *Neoplasm Recurrence, Local/genetics ; *Carcinoma, Intraductal, Noninfiltrating/genetics/pathology ; *Carcinoma, Ductal, Breast/genetics/pathology/surgery ; Aged ; Adult ; Receptor, ErbB-2/genetics/metabolism ; Receptors, Estrogen/metabolism/analysis ; Receptors, Progesterone/metabolism ; Risk Assessment ; Retrospective Studies ; Genomics ; Risk Factors ; },
abstract = {BACKGROUND: Early invasive ductal carcinoma (IDC) breast cancer often presents with a coexisting ductal carcinoma in situ (DCIS) component, while about 5 % of cases present with an extensive (>25 %) intraductal component (EIC). The impact of EIC on the genomic risk of recurrence is unclear.

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

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

CONCLUSIONS: In early HR + HER2- IDC, an EIC correlates with a reduced genomic recurrence risk. The impact on genomic risk seems to be influenced by the extent, not merely the presence, of DCIS.},
}

Humans
Female
*Breast Neoplasms/genetics/pathology/surgery
Middle Aged
*Neoplasm Recurrence, Local/genetics
*Carcinoma, Intraductal, Noninfiltrating/genetics/pathology
*Carcinoma, Ductal, Breast/genetics/pathology/surgery
Aged
Adult
Receptor, ErbB-2/genetics/metabolism
Receptors, Estrogen/metabolism/analysis
Receptors, Progesterone/metabolism
Risk Assessment
Retrospective Studies
Genomics
Risk Factors

@article {pmid39012819,
year = {2024},
author = {Zin, I and China, A and Khan, K and Nag, JK and Vasu, K and Deshpande, GM and Ghosh, PK and Khan, D and Ramachandiran, I and Ganguly, S and Tamagno, I and Willard, B and Gogonea, V and Fox, PL},
title = {AKT-dependent nuclear localization of EPRS1 activates PARP1 in breast cancer cells.},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
volume = {121},
number = {30},
pages = {e2303642121},
pmid = {39012819},
issn = {1091-6490},
support = {R01 AG067146/AG/NIA NIH HHS/United States ; R01 NS124547/NS/NINDS NIH HHS/United States ; R01 DK123236/DK/NIDDK NIH HHS/United States ; R01 DK124203/DK/NIDDK NIH HHS/United States ; R01 NS124581/NS/NINDS NIH HHS/United States ; },
mesh = {Humans ; *Breast Neoplasms/metabolism/genetics/pathology ; Female ; *Poly (ADP-Ribose) Polymerase-1/metabolism/genetics ; *Cell Nucleus/metabolism ; *Proto-Oncogene Proteins c-akt/metabolism/genetics ; Cell Line, Tumor ; PTEN Phosphohydrolase/metabolism/genetics ; Amino Acyl-tRNA Synthetases/metabolism/genetics ; Active Transport, Cell Nucleus ; Nuclear Localization Signals/metabolism ; },
abstract = {Glutamyl-prolyl-tRNA synthetase (EPRS1) is a bifunctional aminoacyl-tRNA-synthetase (aaRS) essential for decoding the genetic code. EPRS1 resides, with seven other aaRSs and three noncatalytic proteins, in the cytoplasmic multi-tRNA synthetase complex (MSC). Multiple MSC-resident aaRSs, including EPRS1, exhibit stimulus-dependent release from the MSC to perform noncanonical activities distinct from their primary function in protein synthesis. Here, we show EPRS1 is present in both cytoplasm and nucleus of breast cancer cells with constitutively low phosphatase and tensin homolog (PTEN) expression. EPRS1 is primarily cytosolic in PTEN-expressing cells, but chemical or genetic inhibition of PTEN, or chemical or stress-mediated activation of its target, AKT, induces EPRS1 nuclear localization. Likewise, preferential nuclear localization of EPRS1 was observed in invasive ductal carcinoma that were also P-Ser[473]-AKT[+]. EPRS1 nuclear transport requires a nuclear localization signal (NLS) within the linker region that joins the catalytic glutamyl-tRNA synthetase and prolyl-tRNA synthetase domains. Nuclear EPRS1 interacts with poly(ADP-ribose) polymerase 1 (PARP1), a DNA-damage sensor that directs poly(ADP-ribosyl)ation (PARylation) of proteins. EPRS1 is a critical regulator of PARP1 activity as shown by markedly reduced ADP-ribosylation in EPRS1 knockdown cells. Moreover, EPRS1 and PARP1 knockdown comparably alter the expression of multiple tumor-related genes, inhibit DNA-damage repair, reduce tumor cell survival, and diminish tumor sphere formation by breast cancer cells. EPRS1-mediated regulation of PARP1 activity provides a mechanistic link between PTEN loss in breast cancer cells, PARP1 activation, and cell survival and tumor growth. Targeting the noncanonical activity of EPRS1, without inhibiting canonical tRNA ligase activity, provides a therapeutic approach potentially supplementing existing PARP1 inhibitors.},
}

Humans
*Breast Neoplasms/metabolism/genetics/pathology
Female
*Poly (ADP-Ribose) Polymerase-1/metabolism/genetics
*Cell Nucleus/metabolism
*Proto-Oncogene Proteins c-akt/metabolism/genetics
Cell Line, Tumor
PTEN Phosphohydrolase/metabolism/genetics
Amino Acyl-tRNA Synthetases/metabolism/genetics
Active Transport, Cell Nucleus
Nuclear Localization Signals/metabolism

@article {pmid38994984,
year = {2024},
author = {Nascimento, KCG and São Marcos, BF and Fontes, PHB and Isídio, BEO and Leão, SL and da Silva, GRP and Lussón, DB and Dos Santos, DL and Leal, LRS and Espinoza, BCF and de Macêdo, LS and de França Neto, PL and Silva, AJD and Silva Neto, JC and Santos, VEP and de Freitas, AC},
title = {HPV Detection in Breast Tumors and Associated Risk Factors in Northeastern Brazil.},
journal = {Cells},
volume = {13},
number = {13},
pages = {},
pmid = {38994984},
issn = {2073-4409},
support = {444606/2023-8//National Council for Scientific and Technological Development/ ; 444156/2023-2//National Council for Scientific and Technological Development/ ; 308684/2023-0//National Council for Scientific and Technological Development/ ; },
mesh = {Humans ; Brazil/epidemiology ; Female ; Middle Aged ; Risk Factors ; *Breast Neoplasms/virology ; *Papillomavirus Infections/virology/complications/epidemiology ; Adult ; Aged ; Papillomaviridae ; Viral Load ; },
abstract = {Breast cancer risk factors include lifestyle, genetic-hormonal influences, and viral infections. Human papillomavirus (HPV), known primarily as the etiological agent of cervical cancer, also appears active in breast carcinogenesis, as evidenced in our study of 56 patients from northeastern Brazil. We assessed the clinical and sociodemographic characteristics, correlating them with various breast cancer tumor types. HPV detection involved amplifying the L1 region, with viral load measured using the E2/E6 ratio and viral activity indicated by E5 oncogene expression. Predominantly, patients over 56 years of age with healthy lifestyles showed a high incidence of invasive ductal carcinoma and triple-negative breast cancer. HPV was detected in 35.7% of cases, mostly HPV16, which is associated with high viral loads (80 copies per cell) and significant E5 expression. These results hint at a possible link between HPV and breast carcinogenesis, necessitating further studies to explore this association and the underlying viral mechanisms.},
}

Humans
Brazil/epidemiology
Female
Middle Aged
Risk Factors
*Breast Neoplasms/virology
*Papillomavirus Infections/virology/complications/epidemiology
Adult
Aged
Papillomaviridae
Viral Load

@article {pmid38968480,
year = {2024},
author = {Zhang, Z and Huang, C and Wu, J and Cheng, Q and Wang, S},
title = {TICRR as a potential prognostic biomarker for lung adenocarcinoma: A comprehensive analysis using TCGA database.},
journal = {Medicine},
volume = {103},
number = {27},
pages = {e38660},
pmid = {38968480},
issn = {1536-5964},
mesh = {Humans ; *Adenocarcinoma of Lung/genetics/mortality/pathology ; Male ; *Biomarkers, Tumor/genetics/metabolism ; Female ; Prognosis ; *Lung Neoplasms/genetics/mortality/pathology ; Middle Aged ; Nomograms ; Kaplan-Meier Estimate ; Aged ; ROC Curve ; Neoplasm Staging ; Databases, Genetic ; },
abstract = {To investigate the role of TopBP1-interacting checkpoint and replication regulator (TICRR) in the tumorigenesis and prognosis of lung adenocarcinoma (LUAD) patients. Wilcoxon signed-rank test and logistic regression were utilized to analyze the relationship between clinical characteristics and TICRR expression in LUAD from TCGA dataset. Kaplan-Meier plots and Cox regressions were used to assess the impact of TICRR impact on prognosis. ROC curves and nomograms were generated to further evaluate the relationship between TICRR expression and the risk of LUAD. Gene set enrichment analysis (GSEA) was conducted on TCGA dataset, and ssGSEA was employed to investigate the association between TICRR and immune infiltrates. The results showed that high TICRR expression was significantly associated with various clinical factors including gender, age, pathological stage, T stage, N stage, M stage, outcome of primary therapy and smoking status. ROC curves also demonstrated that TICRR was a promising biomarker for molecular pathology diagnosis in LUAD patients (AUC = 0.952). Further analysis using gene ontology (GO) term enrichment and GSEA revealed an abnormal correlation between TICRR expression and cell division. Interestingly, ssGSEA analysis showed that TICRR expression correlated with multiple immune cell types, such as Th2 cell, TFH cell, mast cell, iDC, eosinophils, and dendritic cell. Lastly, the KM-plotters indicated that LUAD patients with high TICRR expression obtained worse life expectancy (P < .001). TICRR has proven to be a valuable tool in predicting disease progression and prognosis in patients with LUAD, thereby establishing itself as a fitting biomarker for forecasting overall survival (OS) of LUAD patients.},
}

Humans
*Adenocarcinoma of Lung/genetics/mortality/pathology
Male
*Biomarkers, Tumor/genetics/metabolism
Female
Prognosis
*Lung Neoplasms/genetics/mortality/pathology
Middle Aged
Nomograms
Kaplan-Meier Estimate
Aged
ROC Curve
Neoplasm Staging
Databases, Genetic

@article {pmid38944914,
year = {2024},
author = {Bogaard, M and Strømme, JM and Kidd, SG and Johannessen, B and Bakken, AC and Lothe, RA and Axcrona, K and Skotheim, RI and Axcrona, U},
title = {GRIN3A: A biomarker associated with a cribriform pattern and poor prognosis in prostate cancer.},
journal = {Neoplasia (New York, N.Y.)},
volume = {55},
number = {},
pages = {101023},
pmid = {38944914},
issn = {1476-5586},
mesh = {Humans ; Male ; *Prostatic Neoplasms/genetics/pathology/metabolism/surgery ; *Biomarkers, Tumor/genetics/metabolism ; Prognosis ; *Neoplasm Grading ; Middle Aged ; Aged ; Gene Expression Regulation, Neoplastic ; Prostatectomy ; Gene Expression Profiling ; },
abstract = {Prostate cancer with a cribriform pattern, including invasive cribriform carcinoma (ICC) and/or intraductal carcinoma (IDC) is associated with a poor prognosis, and the underlying mechanisms are unclear. Therefore, we aimed to identify biomarkers for this feature. Using a radical prostatectomy cohort, we performed within-patient differential expression analyses with RNA sequencing data to compare samples with a cribriform pattern to those with non-cribriform Gleason pattern 4 (NcGP4; n=13). ACSM1, GRIN3A, PCDHB2, and REG4 were identified as differentially expressed, and validation was performed using real-time reverse transcription polymerase chain reaction (n=99; 321 RNA samples) and RNA in situ hybridization on tissue microarrays (n=479; 2047 tissue cores). GRIN3A was significantly higher expressed in cribriform pattern vs. NcGP4, when assessed within the same patient (n=27; p=0.005) and between different patients (n=83; p=0.001). Tissue cores with IDC more often expressed GRIN3A compared to ICC, NcGP4, and benign tissue (52 % vs. ≤ 32 %). When IDC and NcGP4 was compared within the same patient (173 pairs of tissue cores; 54 patients), 38 (22 %) of the tissue microarray core pairs had GRIN3A expression in only IDC, 33 (19 %) had expression in both IDC and NcGP4, 14 (8 %) in only NcGP4 and 88 (51 %) were negative in both entities (p=0.001). GRIN3A was as well associated with biochemical recurrence (log-rank, p=0.002). In conclusion, ectopic GRIN3A expression is an RNA-based biomarker for the presence of cribriform prostate cancer, particularly for IDC.},
}

Humans
Male
*Prostatic Neoplasms/genetics/pathology/metabolism/surgery
*Biomarkers, Tumor/genetics/metabolism
Prognosis
*Neoplasm Grading
Middle Aged
Aged
Gene Expression Regulation, Neoplastic
Prostatectomy
Gene Expression Profiling

@article {pmid38935197,
year = {2024},
author = {Delfin, L and Doff, JJ and Gagan, J and Flack, A and Krane, JF and Jo, VY and Torell, AG and Palsgrove, D and Bishop, JA},
title = {Pure Apocrine Intraductal Carcinoma of Salivary Glands: Reassessment of Molecular Underpinnings and Behavior.},
journal = {Head and neck pathology},
volume = {18},
number = {1},
pages = {58},
pmid = {38935197},
issn = {1936-0568},
mesh = {Humans ; Male ; Middle Aged ; Aged ; Female ; *Salivary Gland Neoplasms/pathology/genetics ; Aged, 80 and over ; Carcinoma, Intraductal, Noninfiltrating/pathology/genetics ; Biomarkers, Tumor/analysis/genetics ; Adult ; Carcinoma, Ductal/pathology/genetics ; },
abstract = {BACKGROUND: Intraductal carcinoma (IDC) of the salivary glands is a confounding entity, our understanding of which continues to evolve. At least four forms have been elucidated based on histomorphology, immunophenotype, and molecular profile: (1) intercalated duct-like, S100/SOX10+ with frequent NCOA4::RET fusions; (2) oncocytic, S100/SOX10+ with TRIM33::RET, NCOA4::RET, and BRAF V600E; (3) apocrine, AR+ with PI3 kinase pathway mutations; and (4) mixed/hybrid intercalated duct-like/apocrine, with S100/SOX10+ and AR+ areas and frequent TRIM27::RET. The revelation that myoepithelial cells harbor the same fusion as luminal cells suggested that fusion-positive cases are not in situ carcinomas as previously believed. To this point, purely apocrine IDC with entirely intraductal growth has not been found to harbor fusions, but very few cases have been tested.

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

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

CONCLUSIONS: Purely apocrine IDC is a heterogeneous disease. A subset seems to be genetically similar to salivary duct carcinoma and may indeed represent carcinoma in situ. The other group harbors fusions, similar to other forms of IDC. Moreover, the occurrence of lymph node metastasis discredits the idea that any fusion-positive IDC with a complete myoepithelial cell layer has no metastatic potential. With the wide use of RET-and ALK-based targeted therapies, our findings further underscore the importance of fusion analysis for IDC.},
}

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

@article {pmid38927753,
year = {2024},
author = {Markalunas, EG and Arnold, DH and Funkhouser, AT and Martin, JC and Shtutman, M and Edenfield, WJ and Blenda, AV},
title = {Correlation Analysis of Genetic Mutations and Galectin Levels in Breast Cancer Patients.},
journal = {Genes},
volume = {15},
number = {6},
pages = {},
pmid = {38927753},
issn = {2073-4425},
mesh = {Humans ; *Breast Neoplasms/genetics/blood/pathology ; Female ; *Galectins/genetics/blood ; *Mutation ; *Biomarkers, Tumor/genetics/blood ; Galectin 1/genetics/blood ; Middle Aged ; Galectin 3/genetics/blood ; Adult ; Blood Proteins ; },
abstract = {Galectins are innate immune system regulators associated with disease progression in cancer. This paper aims to investigate the correlation between mutated cancer-critical genes and galectin levels in breast cancer patients to determine whether galectins and genetic profiles can be used as biomarkers for disease and potential therapy targets. Prisma Health Cancer Institute's Biorepository provided seventy-one breast cancer samples, including all four stages spanning the major molecular subtypes and histologies. Hotspot mutation statuses of cancer-critical genes were determined using multiplex PCR in tumor samples from the same patients by Precision Genetics and the University of South Carolina Functional Genomics Core Facility. The galectin-1, -3, and -9 levels in patients' sera were analyzed using Enzyme-linked Immunosorbent Assay (ELISA). An analysis was performed using JMP software to compare mean and median serum galectin levels between samples with and without specific cancer-critical genes, including pooled t-test, Wilcoxon Rank Sum Test, ANOVA, and Steel Dwass Test (α=0.05). Our analysis indicates that KIT mutations correlate with elevated serum levels of galectin-9 in patients with breast cancer. In patients with Luminal A subtype, FLT3 mutation correlates with lower serum galectin-1 and -9 levels and TP53 mutations correlate with higher serum galectin-3 levels. Patients with invasive ductal carcinoma had significantly higher serum galectin-3 levels than patients with ductal carcinoma in situ. Patients with both TP53 and PIK3CA mutations exhibit elevated serum galectin-3 levels, while patients with one or neither mutation show no significant difference in serum galectin-3 levels. In addition, metastatic breast cancer samples were more likely to have a KIT or PIK3CA mutation compared to primary breast cancer samples. The relationship between genetic mutations and galectin levels has the potential to identify appropriate candidates for combined therapy, targeting genetic mutations and galectins. Further understanding of the effect of genetic mutations and galectin levels on cancer progression and metastasis could aid in the search for biomarkers for breast cancer diagnosis, disease progression, and prognosis.},
}

Humans
*Breast Neoplasms/genetics/blood/pathology
Female
*Galectins/genetics/blood
*Mutation
*Biomarkers, Tumor/genetics/blood
Galectin 1/genetics/blood
Middle Aged
Galectin 3/genetics/blood
Adult
Blood Proteins

@article {pmid38926485,
year = {2024},
author = {Baranová, I and Samec, M and Dvorská, D and Šťastný, I and Janíková, K and Kašubová, I and Hornáková, A and Lukáčová, E and Kapinová, A and Biringer, K and Halašová, E and Danková, Z},
title = {Droplet digital PCR analysis of CDH13 methylation status in Slovak women with invasive ductal breast cancer.},
journal = {Scientific reports},
volume = {14},
number = {1},
pages = {14700},
pmid = {38926485},
issn = {2045-2322},
support = {1/0286/22//Ministry of Education, Science, Research and Sport of the Slovak Republic and Slovak Academy of Sciences/ ; },
mesh = {Humans ; *Cadherins/genetics ; Female ; *DNA Methylation ; *Breast Neoplasms/genetics/pathology ; Middle Aged ; *Carcinoma, Ductal, Breast/genetics/pathology/metabolism ; Aged ; *Promoter Regions, Genetic ; Slovakia ; Biomarkers, Tumor/genetics ; Adult ; Polymerase Chain Reaction/methods ; },
abstract = {Identifying novel epigenetic biomarkers is a promising way to improve the clinical management of patients with breast cancer. Our study aimed to determine the methylation pattern of 25 tumor suppressor genes (TSG) and select the best methylation biomarker associated with clinicopathological features in the cohort of Slovak patients diagnosed with invasive ductal carcinoma (IDC). Overall, 166 formalin-fixed, paraffin-embedded (FFPE) tissues obtained from patients with IDC were included in the study. The methylation status of the promoter regions of 25 TSG was analyzed using semiquantitative methylation-specific MLPA (MS-MLPA). We identified CDH13 as the most frequently methylated gene in our cohort of patients. Further analysis by ddPCR confirmed an increased level of methylation in the promoter region of CDH13. A significant difference in CDH13 methylation levels was observed between IDC molecular subtypes LUM A versus HER2 (P = 0.0116) and HER2 versus TNBC (P = 0.0234). In addition, significantly higher methylation was detected in HER2+ versus HER2- tumors (P = 0.0004) and PR- versus PR+ tumors (P = 0.0421). Our results provide evidence that alteration in CDH13 methylation is associated with clinicopathological features in the cohort of Slovak patients with IDC. In addition, using ddPCR as a methylation-sensitive method represents a promising approach characterized by higher precision and technical simplicity to measure the methylation of target CpGs in CDH13 compared to other conventional methods such as MS-MLPA.},
}

Humans
*Cadherins/genetics
Female
*DNA Methylation
*Breast Neoplasms/genetics/pathology
Middle Aged
*Carcinoma, Ductal, Breast/genetics/pathology/metabolism
Aged
*Promoter Regions, Genetic
Slovakia
Biomarkers, Tumor/genetics
Adult
Polymerase Chain Reaction/methods

@article {pmid38897820,
year = {2024},
author = {Corso, G and Fusco, N and Guerini-Rocco, E and Leonardi, MC and Criscitiello, C and Zagami, P and Nicolò, E and Mazzarol, G and La Vecchia, C and Pesapane, F and Zanzottera, C and Tarantino, P and Petitto, S and Bianchi, B and Massari, G and Boato, A and Sibilio, A and Polizzi, A and Curigliano, G and De Scalzi, AM and Lauria, F and Bonanni, B and Marabelli, M and Rotili, A and Nicosia, L and Albini, A and Calvello, M and Mukhtar, RA and Robson, ME and Sacchini, V and Rennert, G and Galimberti, V and Veronesi, P and Magnoni, F},
title = {Invasive lobular breast cancer: Focus on prevention, genetics, diagnosis, and treatment.},
journal = {Seminars in oncology},
volume = {51},
number = {3-4},
pages = {106-122},
doi = {10.1053/j.seminoncol.2024.05.001},
pmid = {38897820},
issn = {1532-8708},
mesh = {Humans ; *Breast Neoplasms/diagnosis/genetics/therapy/pathology/prevention & control ; Female ; *Carcinoma, Lobular/diagnosis/therapy/genetics/pathology ; },
abstract = {Invasive lobular cancer (ILC) is the most common of the breast cancer special types, accounting for up to 15% of all breast malignancies. The distinctive biological features of ILC include the loss of the cell adhesion molecule E-cadherin, which drives the tumor's peculiar discohesive growth pattern, with cells arranged in single file and dispersed throughout the stroma. Typically, such tumors originate in the lobules, are more commonly bilateral compared to invasive ductal cancer (IDC) and require a more accurate diagnostic examination through imaging. They are luminal in molecular subtype, and exhibit estrogen and progesterone receptor positivity and HER2 negativity, thus presenting a more unpredictable response to neoadjuvant therapies. There has been a significant increase in research focused on this distinctive breast cancer subtype, including studies on its pathology, its clinical and surgical management, and the high-resolution definition of its genomic profile, as well as the development of new therapeutic perspectives. This review will summarize the heterogeneous pattern of this unique disease, focusing on challenges in its comprehensive clinical management and on future insights and research objectives.},
}

Humans
*Breast Neoplasms/diagnosis/genetics/therapy/pathology/prevention & control
Female
*Carcinoma, Lobular/diagnosis/therapy/genetics/pathology

@article {pmid38830849,
year = {2024},
author = {Wearn, A and Tremblay, SA and Tardif, CL and Leppert, IR and Gauthier, CJ and Baracchini, G and Hughes, C and Hewan, P and Tremblay-Mercier, J and Rosa-Neto, P and Poirier, J and Villeneuve, S and Schmitz, TW and Turner, GR and Spreng, RN and , },
title = {Neuromodulatory subcortical nucleus integrity is associated with white matter microstructure, tauopathy and APOE status.},
journal = {Nature communications},
volume = {15},
number = {1},
pages = {4706},
pmid = {38830849},
issn = {2041-1723},
support = {AARG-22-927100/ALZ/Alzheimer's Association/United States ; NIA R01 AG068563//U.S. Department of Health & Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging)/ ; },
mesh = {Humans ; *White Matter/diagnostic imaging/pathology/metabolism ; Female ; Male ; Aged ; Middle Aged ; *Alzheimer Disease/genetics/pathology/cerebrospinal fluid/metabolism/diagnostic imaging ; *Tauopathies/diagnostic imaging/metabolism/pathology/genetics/cerebrospinal fluid ; *tau Proteins/metabolism/cerebrospinal fluid ; *Magnetic Resonance Imaging ; Brain/pathology/diagnostic imaging/metabolism ; Apolipoproteins E/genetics/metabolism ; Apolipoprotein E4/genetics/metabolism ; Neurites/metabolism/pathology ; },
abstract = {The neuromodulatory subcortical nuclei within the isodendritic core (IdC) are the earliest sites of tauopathy in Alzheimer's disease (AD). They project broadly throughout the brain's white matter. We investigated the relationship between IdC microstructure and whole-brain white matter microstructure to better understand early neuropathological changes in AD. Using multiparametric quantitative magnetic resonance imaging we observed two covariance patterns between IdC and white matter microstructure in 133 cognitively unimpaired older adults (age 67.9 ± 5.3 years) with familial risk for AD. IdC integrity related to 1) whole-brain neurite density, and 2) neurite orientation dispersion in white matter tracts known to be affected early in AD. Pattern 2 was associated with CSF concentration of phosphorylated-tau, indicating AD specificity. Apolipoprotein-E4 carriers expressed both patterns more strongly than non-carriers. IdC microstructure variation is reflected in white matter, particularly in AD-affected tracts, highlighting an early mechanism of pathological development.},
}

Humans
*White Matter/diagnostic imaging/pathology/metabolism
Female
Male
Aged
Middle Aged
*Alzheimer Disease/genetics/pathology/cerebrospinal fluid/metabolism/diagnostic imaging
*Tauopathies/diagnostic imaging/metabolism/pathology/genetics/cerebrospinal fluid
*tau Proteins/metabolism/cerebrospinal fluid
*Magnetic Resonance Imaging
Brain/pathology/diagnostic imaging/metabolism
Apolipoproteins E/genetics/metabolism
Apolipoprotein E4/genetics/metabolism
Neurites/metabolism/pathology

@article {pmid38747597,
year = {2024},
author = {Stindt, KR and McClean, MN},
title = {Tuning interdomain conjugation to enable in situ population modification in yeasts.},
journal = {mSystems},
volume = {9},
number = {6},
pages = {e0005024},
pmid = {38747597},
issn = {2379-5077},
support = {R01 AI154940/AI/NIAID NIH HHS/United States ; P30CA014520//University of Wisconsin Carbone Cancer Center (UWCCC)/ ; P30 CA014520/CA/NCI NIH HHS/United States ; R35 GM128873/GM/NIGMS NIH HHS/United States ; 135AAI9593//Wisconsin Alumni Research Foundation (WARF)/ ; R35GM128873//HHS | NIH | National Institute of General Medical Sciences (NIGMS)/ ; T32 GM130550/GM/NIGMS NIH HHS/United States ; T32GM130550//Molecular Biophysics Training Grant/ ; R01AI154940//HHS | NIH | National Institute of Allergy and Infectious Diseases (NIAID)/ ; },
mesh = {*Saccharomyces cerevisiae/genetics ; *Escherichia coli/genetics/metabolism ; Conjugation, Genetic ; },
abstract = {The ability to modify and control natural and engineered microbiomes is essential for biotechnology and biomedicine. Fungi are critical members of most microbiomes, yet technology for modifying the fungal members of a microbiome has lagged far behind that for bacteria. Interdomain conjugation (IDC) is a promising approach, as DNA transfer from bacterial cells to yeast enables in situ modification. While such genetic transfers have been known to naturally occur in a wide range of eukaryotes and are thought to contribute to their evolution, IDC has been understudied as a technique to control fungal or fungal-bacterial consortia. One major obstacle to the widespread use of IDC is its limited efficiency. In this work, we manipulated metabolic and physical interactions between genetically tractable Escherichia coli and Saccharomyces cerevisiae to control the incidence of IDC. We test the landscape of population interactions between the bacterial donors and yeast recipients to find that bacterial commensalism leads to maximized IDC, both in culture and in mixed colonies. We demonstrate the capacity of cell-to-cell binding via mannoproteins to assist both IDC incidence and bacterial commensalism in culture and model how these tunable controls can predictably yield a range of IDC outcomes. Furthermore, we demonstrate that these controls can be utilized to irreversibly alter a recipient yeast population, by both "rescuing" a poor-growing recipient population and collapsing a stable population via a novel IDC-mediated CRISPR/Cas9 system.IMPORTANCEFungi are important but often unaddressed members of most natural and synthetic microbial communities. This work highlights opportunities for modifying yeast microbiome populations through bacterial conjugation. While conjugation has been recognized for its capacity to deliver engineerable DNA to a range of cells, its dependence on cell contact has limited its efficiency. Here, we find "knobs" to control DNA transfer, by engineering the metabolic dependence between bacterial donors and yeast recipients and by changing their ability to physically adhere to each other. Importantly, we functionally validate these "knobs" by irreversibly altering yeast populations. We use these controls to "rescue" a failing yeast population, demonstrate the capacity of conjugated CRISPR/Cas9 to depress or collapse populations, and show that conjugation can be easily interrupted by disrupting cell-to-cell binding. These results offer building blocks toward in situ mycobiome editing, with significant implications for clinical treatments of fungal pathogens and other fungal system engineering.},
}

*Saccharomyces cerevisiae/genetics
*Escherichia coli/genetics/metabolism
Conjugation, Genetic

@article {pmid38734990,
year = {2024},
author = {Greenland, NY and Cooperberg, MR and Carroll, PR and Cowan, JE and Simko, JP and Stohr, BA and Chan, E},
title = {Morphologic patterns observed in prostate biopsy cases with discrepant grade group and molecular risk classification.},
journal = {The Prostate},
volume = {84},
number = {11},
pages = {1076-1085},
doi = {10.1002/pros.24725},
pmid = {38734990},
issn = {1097-0045},
mesh = {Humans ; Male ; *Prostatic Neoplasms/pathology/genetics ; *Neoplasm Grading ; *Prostate/pathology ; Biopsy ; Middle Aged ; Aged ; Biomarkers, Tumor/genetics ; Risk Assessment ; Prostatectomy ; },
abstract = {BACKGROUND: Molecular-based risk classifier tests are increasingly being utilized by urologists and radiation oncologists to guide clinical decision making. The Decipher prostate biopsy test is a 22-gene RNA biomarker assay designed to predict likelihood of high-grade disease at radical prostatectomy and risk of metastasis and mortality. The test provides a risk category of low, intermediate, or high. We investigated histologic features of biopsies in which the Grade Group (GG) and Decipher risk category (molecular risk) were discrepant.

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

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

CONCLUSIONS: In GG1-2 high Decipher risk cases, difficult to grade patterns were frequently seen in the absence of other known high risk morphologic features; whether these constitute true high risk cases requires further study. In the GG ≥ 3 low Decipher risk cases, aggressive histologic patterns such as large cribriform and IDC were observed in half (50%) of cases; therefore, the molecular classifier may not capture all high risk histologic patterns.},
}

Humans
Male
*Prostatic Neoplasms/pathology/genetics
*Neoplasm Grading
*Prostate/pathology
Biopsy
Middle Aged
Aged
Biomarkers, Tumor/genetics
Risk Assessment
Prostatectomy

@article {pmid38684889,
year = {2024},
author = {Khani, S and Topel, H and Kardinal, R and Tavanez, AR and Josephrajan, A and Larsen, BDM and Gaudry, MJ and Leyendecker, P and Egedal, NM and Güller, AS and Stanic, N and Ruppert, PMM and Gaziano, I and Hansmeier, NR and Schmidt, E and Klemm, P and Vagliano, LM and Stahl, R and Duthie, F and Krause, JH and Bici, A and Engelhard, CA and Gohlke, S and Frommolt, P and Gnad, T and Rada-Iglesias, A and Pradas-Juni, M and Schulz, TJ and Wunderlich, FT and Pfeifer, A and Bartelt, A and Jastroch, M and Wachten, D and Kornfeld, JW},
title = {Cold-induced expression of a truncated adenylyl cyclase 3 acts as rheostat to brown fat function.},
journal = {Nature metabolism},
volume = {6},
number = {6},
pages = {1053-1075},
pmid = {38684889},
issn = {2522-5812},
support = {675014//EC | EC Seventh Framework Programm | FP7 Ideas: European Research Council (FP7-IDEAS-ERC - Specific Programme: "Ideas" Implementing the Seventh Framework Programme of the European Community for Research, Technological Development and Demonstration Activities (2007 to 2013))/ ; PROTEOFIT//EC | EC Seventh Framework Programm | FP7 Ideas: European Research Council (FP7-IDEAS-ERC - Specific Programme: "Ideas" Implementing the Seventh Framework Programme of the European Community for Research, Technological Development and Demonstration Activities (2007 to 2013))/ ; 33444//Novo Nordisk Fonden (Novo Nordisk Foundation)/ ; 28416//Novo Nordisk Fonden (Novo Nordisk Foundation)/ ; A/12/97620//Deutscher Akademischer Austauschdienst (German Academic Exchange Service)/ ; TRR333/1 (450149205)//Deutsche Forschungsgemeinschaft (German Research Foundation)/ ; SFB 1454 (432325352)//Deutsche Forschungsgemeinschaft (German Research Foundation)/ ; TRR83//Deutsche Forschungsgemeinschaft (German Research Foundation)/ ; SPP1926//Deutsche Forschungsgemeinschaft (German Research Foundation)/ ; SPP1726//Deutsche Forschungsgemeinschaft (German Research Foundation)/ ; FOR2743//Deutsche Forschungsgemeinschaft (German Research Foundation)/ ; SFB1123-B10//Deutsche Forschungsgemeinschaft (German Research Foundation)/ ; 676-2021//European Molecular Biology Organization (EMBO)/ ; },
mesh = {*Adenylyl Cyclases/metabolism/genetics ; *Adipose Tissue, Brown/metabolism ; Animals ; Mice ; *Cold Temperature ; Male ; Humans ; Thermogenesis/genetics ; Energy Metabolism ; Cyclic AMP/metabolism ; Mice, Knockout ; },
abstract = {Promoting brown adipose tissue (BAT) activity innovatively targets obesity and metabolic disease. While thermogenic activation of BAT is well understood, the rheostatic regulation of BAT to avoid excessive energy dissipation remains ill-defined. Here, we demonstrate that adenylyl cyclase 3 (AC3) is key for BAT function. We identified a cold-inducible promoter that generates a 5' truncated AC3 mRNA isoform (Adcy3-at), whose expression is driven by a cold-induced, truncated isoform of PPARGC1A (PPARGC1A-AT). Male mice lacking Adcy3-at display increased energy expenditure and are resistant to obesity and ensuing metabolic imbalances. Mouse and human AC3-AT are retained in the endoplasmic reticulum, unable to translocate to the plasma membrane and lack enzymatic activity. AC3-AT interacts with AC3 and sequesters it in the endoplasmic reticulum, reducing the pool of adenylyl cyclases available for G-protein-mediated cAMP synthesis. Thus, AC3-AT acts as a cold-induced rheostat in BAT, limiting adverse consequences of cAMP activity during chronic BAT activation.},
}

*Adenylyl Cyclases/metabolism/genetics
*Adipose Tissue, Brown/metabolism
Animals
Mice
*Cold Temperature
Male
Humans
Thermogenesis/genetics
Energy Metabolism
Cyclic AMP/metabolism
Mice, Knockout

@article {pmid38678597,
year = {2024},
author = {Rostami, B and Kahrizi, S and Ghorbani Yekta, B and Ghadyani, R and Keramatinia, A and Hoseini, SJ and Karima, S and Nikzamir, AR and Mansouri, N and Chen, M and Movafagh, A},
title = {Correlation of IDH1 gene expression error in breast tumor biopsy in patients with invasive ductal carcinoma.},
journal = {Cellular and molecular biology (Noisy-le-Grand, France)},
volume = {70},
number = {4},
pages = {242-247},
doi = {10.14715/cmb/2024.70.4.38},
pmid = {38678597},
issn = {1165-158X},
mesh = {Humans ; *Isocitrate Dehydrogenase/genetics ; Female ; *Breast Neoplasms/genetics/pathology ; Middle Aged ; *Carcinoma, Ductal, Breast/genetics/pathology ; *Gene Expression Regulation, Neoplastic ; Adult ; Biopsy ; RNA, Messenger/genetics/metabolism ; Aged ; },
abstract = {One of the most important cancers in terms of worldwide prevalence is breast tumors, which have been less investigated in correlation with the enzyme Isocitrate Dehydrogenase 1 (IDH1) gene. The aim of this study was that expression of this gene could have significant effects on the progression of metastasis and invasive disease in breast cancer patients. We used the molecular method of RT-PCR with SYBR-Green to analyze breast tumor tissue from patients with metastasis and non-metastasis, the latter confirmed by the pathology department of Shohada-e Tajrish Hospital (serving as a control group). Also, patients population and its relationship with the degree of tumor in the IDH1 gene was investigated. The IDH1 gene has shown high expression in patients with metastatic breast cancer rather than in patients with non-metastatic breast cancer. The metastatic samples were compared with non-metastatic samples for IDH1 mRNA expression. In this research work, 72.5% (29 samples) were up-regulated in comparison to 27.5% of samples (11 samples) that did not exhibit high expression (P=0.000). This study examined the IDH1 gene expression, suggesting that changes in this gene's expression could impact the prognosis of breast cancer. However, further research is needed to draw definitive conclusions.},
}

Humans
*Isocitrate Dehydrogenase/genetics
Female
*Breast Neoplasms/genetics/pathology
Middle Aged
*Carcinoma, Ductal, Breast/genetics/pathology
*Gene Expression Regulation, Neoplastic
Adult
Biopsy
RNA, Messenger/genetics/metabolism
Aged

@article {pmid38592540,
year = {2024},
author = {Rukhsana, and Supty, AT and Hussain, M and Lee, Y},
title = {STK3 higher expression association with clinical characteristics in intrinsic subtypes of breast cancer invasive ductal carcinoma patients.},
journal = {Breast cancer research and treatment},
volume = {206},
number = {1},
pages = {119-129},
pmid = {38592540},
issn = {1573-7217},
support = {2022R1F1A1069631//National Research Foundation of Korea/ ; },
mesh = {Aged ; Female ; Humans ; Middle Aged ; *Biomarkers, Tumor/genetics ; *Breast Neoplasms/genetics/pathology/mortality/metabolism ; *Carcinoma, Ductal, Breast/genetics/pathology/mortality/metabolism ; Gene Expression Profiling ; *Gene Expression Regulation, Neoplastic ; Kaplan-Meier Estimate ; Neoplasm Staging ; Prognosis ; Protein Serine-Threonine Kinases/genetics/metabolism ; *Serine-Threonine Kinase 3/analysis/genetics ; },
abstract = {PURPOSE: STK3 has a central role in maintaining cell homeostasis, proliferation, growth, and apoptosis. Previously, we investigated the functional link between STK3/MST2, and estrogen receptor in MCF-7 breast cancer cells. To expand the investigation, this study evaluated STK3's higher expression and associated genes in breast cancer intrinsic subtypes using publicly available data.

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

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

CONCLUSION: By introducing a novel bioinformatics approach that combines GSEA and WSM, the study successfully identified the top 5% of genes associated with higher expression of STK3.},
}

Aged
Female
Humans
Middle Aged
*Biomarkers, Tumor/genetics
*Breast Neoplasms/genetics/pathology/mortality/metabolism
*Carcinoma, Ductal, Breast/genetics/pathology/mortality/metabolism
Gene Expression Profiling
*Gene Expression Regulation, Neoplastic
Kaplan-Meier Estimate
Neoplasm Staging
Prognosis
Protein Serine-Threonine Kinases/genetics/metabolism
*Serine-Threonine Kinase 3/analysis/genetics

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

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

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

CONCLUSIONS: We postulate that telangiectasias may be a previously unreported dermatologic side effect of combination treatment with tucatinib and T-DM1. Electrocautery is a safe and effective procedure to reduce the appearance of telangiectasias and improve patient satisfaction during chemotherapy.},
}

Female
Humans
Aged
Ado-Trastuzumab Emtansine/therapeutic use
*Breast Neoplasms/pathology
Trastuzumab/adverse effects
Quinazolines/therapeutic use
Receptor, ErbB-2/genetics/metabolism
Antineoplastic Combined Chemotherapy Protocols/adverse effects
*Oxazoles
*Pyridines

@article {pmid38570490,
year = {2024},
author = {Wang, J and Li, B and Luo, M and Huang, J and Zhang, K and Zheng, S and Zhang, S and Zhou, J},
title = {Progression from ductal carcinoma in situ to invasive breast cancer: molecular features and clinical significance.},
journal = {Signal transduction and targeted therapy},
volume = {9},
number = {1},
pages = {83},
pmid = {38570490},
issn = {2059-3635},
support = {82172344//National Natural Science Foundation of China (National Science Foundation of China)/ ; LY21H160039//Natural Science Foundation of Zhejiang Province (Zhejiang Provincial Natural Science Foundation)/ ; LGF21H030010//Natural Science Foundation of Zhejiang Province (Zhejiang Provincial Natural Science Foundation)/ ; },
mesh = {Humans ; Female ; *Carcinoma, Intraductal, Noninfiltrating/genetics/metabolism/pathology ; *Breast Neoplasms/pathology ; Clinical Relevance ; Artificial Intelligence ; Gene Expression Profiling ; Tumor Microenvironment/genetics ; },
abstract = {Ductal carcinoma in situ (DCIS) represents pre-invasive breast carcinoma. In untreated cases, 25-60% DCIS progress to invasive ductal carcinoma (IDC). The challenge lies in distinguishing between non-progressive and progressive DCIS, often resulting in over- or under-treatment in many cases. With increasing screen-detected DCIS in these years, the nature of DCIS has aroused worldwide attention. A deeper understanding of the biological nature of DCIS and the molecular journey of the DCIS-IDC transition is crucial for more effective clinical management. Here, we reviewed the key signaling pathways in breast cancer that may contribute to DCIS initiation and progression. We also explored the molecular features of DCIS and IDC, shedding light on the progression of DCIS through both inherent changes within tumor cells and alterations in the tumor microenvironment. In addition, valuable research tools utilized in studying DCIS including preclinical models and newer advanced technologies such as single-cell sequencing, spatial transcriptomics and artificial intelligence, have been systematically summarized. Further, we thoroughly discussed the clinical advancements in DCIS and IDC, including prognostic biomarkers and clinical managements, with the aim of facilitating more personalized treatment strategies in the future. Research on DCIS has already yielded significant insights into breast carcinogenesis and will continue to pave the way for practical clinical applications.},
}

Humans
Female
*Carcinoma, Intraductal, Noninfiltrating/genetics/metabolism/pathology
*Breast Neoplasms/pathology
Clinical Relevance
Artificial Intelligence
Gene Expression Profiling
Tumor Microenvironment/genetics

@article {pmid38554305,
year = {2024},
author = {Dogan, I and Khanmammadov, N and Ozkurt, S and Aydiner, A and Saip, P},
title = {Outcomes of the patients with metastatic male breast cancer.},
journal = {Journal of cancer research and therapeutics},
volume = {20},
number = {1},
pages = {98-102},
doi = {10.4103/jcrt.jcrt_1829_22},
pmid = {38554305},
issn = {1998-4138},
mesh = {Humans ; Male ; Adult ; Middle Aged ; Aged ; Aged, 80 and over ; *Breast Neoplasms, Male/drug therapy ; Retrospective Studies ; Receptor, ErbB-2 ; Disease-Free Survival ; *Breast Neoplasms/pathology ; Trastuzumab/therapeutic use ; Prognosis ; *Brain Neoplasms/drug therapy/secondary ; Kaplan-Meier Estimate ; },
abstract = {BACKGROUND: The goal of this research is to investigate the clinical characteristics and prognosis of men with metastatic breast cancer (mMBC).

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

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

CONCLUSIONS: The data on mMBC is restricted because of its rarity. The prognosis of mMBC was shown to be poor in this investigation. Despite the small number of patients, we discovered that in univariate analysis, having brain metastases, the number of metastatic locations, and a history of alcohol intake may be prognostic factors.},
}

Humans
Male
Adult
Middle Aged
Aged
Aged, 80 and over
*Breast Neoplasms, Male/drug therapy
Retrospective Studies
Receptor, ErbB-2
Disease-Free Survival
*Breast Neoplasms/pathology
Trastuzumab/therapeutic use
Prognosis
*Brain Neoplasms/drug therapy/secondary
Kaplan-Meier Estimate

@article {pmid38451627,
year = {2024},
author = {Saeed, U and Uppal, R and Khan, AA and Uppal, MR and Piracha, ZZ and Uppal, SR},
title = {Analytical assessment of clinical sensitivity and specificities of pharmaceutical rapid SARS-CoV-2 detection nasopharyngeal swab testing kits in Pakistan.},
journal = {Brazilian journal of biology = Revista brasleira de biologia},
volume = {84},
number = {},
pages = {e265550},
doi = {10.1590/1519-6984.265550},
pmid = {38451627},
issn = {1678-4375},
mesh = {Humans ; *COVID-19/diagnosis ; Cross-Sectional Studies ; Nasopharynx/virology ; Pakistan ; Pandemics ; *SARS-CoV-2/genetics ; *Reagent Kits, Diagnostic ; Sensitivity and Specificity ; },
abstract = {Despite of the global unity against COVID-19 pandemic, the threat of SARS-CoV-2 variants on the lives of human being is still not over. SARS-CoV-2 pandemic has urged the need of rapid viral detection at earliest. To cope with gradually expanding scenario of SARS-CoV-2, accurate diagnosis is extremely crucial factor which should be noticed by international health organizations. Limited research followed by sporadic marketing of SARS-CoV-2 rapid pharmaceutical detection kits raises critical questions against quality assurance and quality control measures. Herein we aimed to interrogate effectivity and specificity analysis of SARS-CoV-2 pharmaceutical rapid detection kits (nasopharyngeal swab based) using conventional gold standard triple target real-time polymerase chain reaction (USFDA approved). A cross-sectional study was conducted over 1500 suspected SARS-CoV-2 patients. 100 real time-PCR confirmed patients were evaluated for pharmaceutical RDT kits based upon nasopharyngeal swab based kits. The SARS-CoV-2 nasopharyngeal swab based rapid diagnostic kit (NSP RDTs) analysis showed 78% reactivity. Among real time PCR confirmed negative subjects, 49.3% represented false positivity. The positive predictive analysis revealed 67.82%, while negative predictive values were 64.40%. The NSP RDTs showed limited sensitivities and specificities as compared to gold standard real time PCR. Valid and authentic detection of SARS-CoV-2 is deemed necessary for accurate COVID-19 surveillance across the globe. Current study highlights the potential consequences of inadequate detection of SARS-CoV-2 and emerging novel mutants, compromising vaccine preventable diseases. Current study emphasizes need to wake higher authorities including strategic organizations for designing adequate measures to prevent future SARS-CoV-2 epidemics.},
}

Humans
*COVID-19/diagnosis
Cross-Sectional Studies
Nasopharynx/virology
Pakistan
Pandemics
*SARS-CoV-2/genetics
*Reagent Kits, Diagnostic
Sensitivity and Specificity

@article {pmid38417222,
year = {2024},
author = {Hu, J and Chen, X and Sun, F and Liu, L and Liu, L and Yang, Z and Zhang, H and Yu, Z and Zhao, R and Wang, Y and Liu, H and Yang, X and Sun, F and Han, B},
title = {Identification of recurrent BRAF non-V600 mutations in intraductal carcinoma of the prostate in Chinese populations.},
journal = {Neoplasia (New York, N.Y.)},
volume = {50},
number = {},
pages = {100983},
pmid = {38417222},
issn = {1476-5586},
mesh = {Humans ; Male ; *Carcinoma, Intraductal, Noninfiltrating/genetics/pathology ; China ; Mutation ; Prostate/pathology ; *Prostatic Neoplasms/genetics/pathology ; *Proto-Oncogene Proteins B-raf/genetics ; },
abstract = {While BRAF alterations have been established as a driver in various solid malignancies, the characterization of BRAF alterations in prostate cancer (PCa) has not been thoroughly interrogated. By bioinformatics analysis, we first found that BRAF alterations were associated with advanced PCa and exhibited mutually exclusive pattern with ERG alteration across multiple cohorts. Of the most interest, recurrent non-V600 BRAF mutations were found in 3 of 21 (14.3 %) PCa patients demonstrating IDC-P morphology. Furthermore, experimental overexpression of BRAF[K601E] and BRAF[L597R] exhibited emergence of oncogenic phenotypes with intensified MAPK signaling in vitro, which could be targeted by MEK inhibitors. Comparison of the incidence of BRAF alterations in IDC-P between western and Chinese ancestry revealed an increased prevalence in the Chinese population. The BRAF mutation may represent important genetic alteration in a subset of IDC-P, highlighting the role of MAPK signaling pathway in this subtype of PCa. To the best of knowledge, this is the first description of non-V600 BRAF mutation in setting of IDC-P, which may in part explain the aggressive phenotype seen in IDC-P and could also bring more treatment options for PCa patients with IDC-P harboring such mutations.},
}

Humans
Male
*Carcinoma, Intraductal, Noninfiltrating/genetics/pathology
China
Mutation
Prostate/pathology
*Prostatic Neoplasms/genetics/pathology
*Proto-Oncogene Proteins B-raf/genetics

@article {pmid38409747,
year = {2024},
author = {Ruan, GJ and Zanwar, S and Ravindran, A and Schram, S and Abeykoon, JP and Hazim, A and Young, JR and Shah, MV and Bennani, NN and Jiang, L and Morlote, D and Rech, KL and Goyal, G and Go, RS and , },
title = {Clinical characteristics, molecular aberrations, treatments, and outcomes of malignant histiocytosis.},
journal = {American journal of hematology},
volume = {99},
number = {5},
pages = {871-879},
pmid = {38409747},
issn = {1096-8652},
support = {P50 CA097274/CA/NCI NIH HHS/United States ; R21 CA097422/CA/NCI NIH HHS/United States ; },
mesh = {Humans ; Child, Preschool ; Child ; Adolescent ; Young Adult ; Adult ; Middle Aged ; Aged ; Aged, 80 and over ; *Histiocytic Sarcoma/genetics/therapy/pathology ; Macrophages/pathology ; Bone Marrow/pathology ; Prognosis ; Liver/pathology ; },
abstract = {Malignant histiocytosis (MH) is an extremely rare neoplasm of the macrophage-dendritic cell lineage. We report the clinical characteristics, molecular aberrations, treatments, and outcomes of patients with MH seen at two referral centers from January 2000 to May 2023. We identified 43 patients with MH, of which 26 had histiocytic sarcoma (MH-H), 9 interdigitating dendritic cell sarcoma (MH-IDC), and 8 Langerhans cell sarcoma (MH-LC). The median age at diagnosis was 61 years (range, 3-83). Thirty-three patients (77%) had multifocal disease, while 10 had unifocal involvement. Tumor specimens from 22 patients (51%) underwent targeted next generation sequencing, and 19 of 22 (86%) had at least one pathogenic mutation, including mutations in MAPK pathway genes (73%). The median overall survival (OS) among the entire cohort was 16 months (95% CI: 8-50). The outcomes of those with multifocal disease were significantly shorter than their unifocal counterpart: median OS of 10 months versus 50 months (p = .07). Patients with risk organ involvement (bone marrow, spleen, or liver) had significantly inferior outcomes. Chemotherapy and surgery were the most common first-line treatments for multifocal and unifocal disease, respectively. While the outcome for patients with multifocal disease was poor, there was a subset of patients who had durable responses to treatment. Our study highlights that MH has heterogeneous clinical presentation, frequent oncogenic mutations, and prognosis, which is strongly tied to disease extent and type of organ involvement.},
}

Humans
Child, Preschool
Child
Adolescent
Young Adult
Adult
Middle Aged
Aged
Aged, 80 and over
*Histiocytic Sarcoma/genetics/therapy/pathology
Macrophages/pathology
Bone Marrow/pathology
Prognosis
Liver/pathology

@article {pmid38379333,
year = {2024},
author = {Zhu, S and Xu, N and Zeng, H},
title = {Molecular complexity of intraductal carcinoma of the prostate.},
journal = {Cancer medicine},
volume = {13},
number = {2},
pages = {e6939},
pmid = {38379333},
issn = {2045-7634},
support = {NSFC 82203110//National Natural Science Foundation of China/ ; 82172785//National Natural Science Foundation of China/ ; 81974398//National Natural Science Foundation of China/ ; 2022-I2M-C&T-B-098//Clinical and Translational Medicine Research Project, Chinese Academy of Medical Sciences/ ; 2021YFS0119//Science and Technology Support Program of Sichuan Province/ ; X-J-2020-016//Bethune Foundation, Oncology Basic Research Program/ ; ZYJC21020//West China Hospital, Sichuan University/ ; ZYGD22004//West China Hospital, Sichuan University/ ; mnzl202002//Bethune Foundation, Urological Oncology Special Research Fund/ ; mnzl202007//Bethune Foundation, Urological Oncology Special Research Fund/ ; },
mesh = {Male ; Humans ; *Carcinoma, Intraductal, Noninfiltrating/pathology ; Prostate/pathology ; *Prostatic Neoplasms/diagnosis/genetics/therapy ; Prognosis ; },
abstract = {Intraductal carcinoma of the prostate (IDC-P) is an aggressive subtype of prostate cancer characterized by the growth of tumor cells within the prostate ducts. It is often found alongside invasive carcinoma and is associated with poor prognosis. Understanding the molecular mechanisms driving IDC-P is crucial for improved diagnosis, prognosis, and treatment strategies. This review summarizes the molecular characteristics of IDC-P and their prognostic indications, comparing them to conventional prostate acinar adenocarcinoma, to gain insights into its unique behavior and identify potential therapeutic targets.},
}

Male
Humans
*Carcinoma, Intraductal, Noninfiltrating/pathology
Prostate/pathology
*Prostatic Neoplasms/diagnosis/genetics/therapy
Prognosis

@article {pmid38379091,
year = {2024},
author = {Bufman, H and Faermann, R and Halshtok-Neiman, O and Shalmon, A and Gotlieb, M and Samoocha, D and Yagil, Y and Feldman, DM and Friedman, E and Sklair-Levy, M},
title = {Breast cancer diagnosed after age 70 years in Israeli BRCA1/BRCA2 pathogenic sequence variant carriers: a single institution experience.},
journal = {Breast cancer research and treatment},
volume = {205},
number = {2},
pages = {281-285},
pmid = {38379091},
issn = {1573-7217},
mesh = {Humans ; Female ; *Breast Neoplasms/genetics/pathology/diagnosis/epidemiology ; Aged ; Israel/epidemiology ; Aged, 80 and over ; *BRCA1 Protein/genetics ; *BRCA2 Protein/genetics ; Heterozygote ; Genetic Predisposition to Disease ; Early Detection of Cancer/methods ; Mutation ; },
abstract = {PURPOSE: A semi-annual surveillance scheme from age 25 to 30 years is offered to BRCA1/BRCA2 pathogenic sequence variants (PSVs) carriers for early detection of breast cancer (BC). There is a paucity of data on the yield of adhering to this scheme beyond 70 years of age.

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

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

CONCLUSION: In ~10% of BRCA1/BRCA2 PSV carriers BC is diagnosed by breast imaging after age 70 years. If these results are validated in a larger study, the guidelines for the maximum age for BC surveillance in high risk women should be revisited and set at 75 years.},
}

Humans
Female
*Breast Neoplasms/genetics/pathology/diagnosis/epidemiology
Aged
Israel/epidemiology
Aged, 80 and over
*BRCA1 Protein/genetics
*BRCA2 Protein/genetics
Heterozygote
Genetic Predisposition to Disease
Early Detection of Cancer/methods
Mutation

@article {pmid38376291,
year = {2023},
author = {Piracha, ZZ and Saeed, U},
title = {Leucine-rich repeats and immunoglobulin-like domains protein 1 (LRIG1) is downregulated in Invasive ductal carcinoma and potential prognostic marker of breast cancer.},
journal = {Journal of cancer research and therapeutics},
volume = {19},
number = {7},
pages = {1870-1879},
pmid = {38376291},
issn = {1998-4138},
mesh = {Female ; Humans ; beta Catenin ; *Breast Neoplasms/genetics ; *Carcinoma, Ductal ; *Fibroadenoma/genetics ; Glycogen Synthase Kinase 3 ; Immunoglobulin Domains ; Leucine ; *Membrane Glycoproteins/genetics ; Prognosis ; Proto-Oncogene Proteins c-akt ; },
abstract = {BACKGROUND: LRIG1 belongs to the family of transmembrane proteins containing leucine-rich repeats. LRIGs are considered as tumor suppressors as they negatively regulate receptor tyrosine kinases. The role of LRIG1 as an EGFR regulator makes it an important marker to be studied in various epithelial-derived cancers.

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

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

CONCLUSION: The fibroadenoma tissue sections were found to express LRIG1 more intensely as compared to the IDC sections, which are in line with the studies reporting reduced copy number of the gene either due to gene deletion or transcriptional inhibition. This further supports that the downregulation of LRIG1 may lead to malignant tumor acting as a tumor suppressor.},
}

Female
Humans
beta Catenin
*Breast Neoplasms/genetics
*Carcinoma, Ductal
*Fibroadenoma/genetics
Glycogen Synthase Kinase 3
Immunoglobulin Domains
Leucine
*Membrane Glycoproteins/genetics
Prognosis
Proto-Oncogene Proteins c-akt

@article {pmid38369589,
year = {2024},
author = {Liu, XS and Chen, YX and Wan, HB and Wang, YL and Wang, YY and Gao, Y and Wu, LB and Pei, ZJ},
title = {TRIP6 a potential diagnostic marker for colorectal cancer with glycolysis and immune infiltration association.},
journal = {Scientific reports},
volume = {14},
number = {1},
pages = {4042},
pmid = {38369589},
issn = {2045-2322},
mesh = {Humans ; *Adaptor Proteins, Signal Transducing/genetics/metabolism ; *Colorectal Neoplasms/diagnosis/genetics/pathology ; Glycolysis ; *LIM Domain Proteins/genetics/metabolism ; Proteasome Endopeptidase Complex/metabolism ; *Transcription Factors/genetics/metabolism ; },
abstract = {Thyroid hormone receptor interactor 6 (TRIP6) it is an adaptor protein belonging to the zyxin family of LIM proteins, participating in signaling events through interactions with various molecules. Despite this, TRIP6's role in colorectal cancer (CRC), particularly its correlation with glucose metabolism and immune cell infiltration, remains unclear. Through the TCGA and GEO databases, we obtained RNA sequencing data to facilitate our in-depth study and analysis of TRIP6 expression. To investigate the prognostic value of TRIP6 in CRC, we also used univariate Cox regression analysis. In addition, this study also covered a series of analyses, including clinicopathological analysis, functional enrichment analysis, glycolysis correlation analysis, immunoinfiltration analysis, immune checkpoint analysis, and angiogenesis correlation analysis, to gain a comprehensive and in-depth understanding of this biological phenomenon. It has been found that TRIP6 expression is significantly upregulated in CRC and correlates with the stage of the disease. Its overexpression portends a worse survival time. Functional enrichment analysis reveals that TRIP6 is associated with focal adhesion and glycolysis. Mechanistically, TRIP6 appears to exert its tumorigenic effect by regulating the glycolysis-related gene GPI. A higher level of expression of TRIP6 is associated with an increase in the number of iDC immune cells and a decrease in the number of Th1 immune cells. Also, TRIP6 may promote angiogenesis in tumor cells by promoting the expression of JAG2. Our study uncovers the upregulation of TRIP6 in CRC, illuminating its prognostic and diagnostic value within this context. Furthermore, we examine the relationship between TRIP6 expression levels, glycolysis, angiogenesis and immune cell infiltration. This underscores its potential as a biomarker for CRC treatment and as a therapeutic target.},
}

Humans
*Adaptor Proteins, Signal Transducing/genetics/metabolism
*Colorectal Neoplasms/diagnosis/genetics/pathology
Glycolysis
*LIM Domain Proteins/genetics/metabolism
Proteasome Endopeptidase Complex/metabolism
*Transcription Factors/genetics/metabolism

@article {pmid38343885,
year = {2023},
author = {Santos, MM and Baerga, CG and Lamsal, S and Engel, C and Ozdemir, S},
title = {Breast cancer in a Hispanic patient with Werner syndrome.},
journal = {Journal of radiology case reports},
volume = {17},
number = {10},
pages = {21-31},
pmid = {38343885},
issn = {1943-0922},
mesh = {Adult ; Female ; Humans ; *Breast Neoplasms/diagnostic imaging/genetics ; Hispanic or Latino ; Mastectomy ; Mutation ; *Werner Syndrome/complications/diagnostic imaging/genetics ; Werner Syndrome Helicase/genetics ; },
abstract = {Werner Syndrome is a rare autosomal recessive condition characterized by premature aging and increased risk of malignancies due to gene mutations associated with DNA stability. We present the first case report of a 29-year-old Hispanic female with WS diagnosed with breast cancer. Diagnostic mammography and ultrasound, breast MRI and PET examinations revealed two lesions biopsy proven as invasive ductal carcinoma. The patient underwent neoadjuvant chemotherapy and radical mastectomy. Recurrence occurred 10 months postoperatively with molecular analysis demonstrating TP53 mutations. The multifactorial assessment of breast cancer in this case study is crucial towards optimizing screening, diagnosis and management of this disease in patients with WS.},
}

Adult
Female
Humans
*Breast Neoplasms/diagnostic imaging/genetics
Hispanic or Latino
Mastectomy
Mutation
*Werner Syndrome/complications/diagnostic imaging/genetics
Werner Syndrome Helicase/genetics

@article {pmid38326829,
year = {2024},
author = {Verma, VK and Beevi, SS and Nair, RA and Kumar, A and Kiran, R and Alexander, LE and Dinesh Kumar, L},
title = {MicroRNA signatures differentiate types, grades, and stages of breast invasive ductal carcinoma (IDC): miRNA-target interacting signaling pathways.},
journal = {Cell communication and signaling : CCS},
volume = {22},
number = {1},
pages = {100},
pmid = {38326829},
issn = {1478-811X},
mesh = {Animals ; Female ; Mice ; Biomarkers ; Biomarkers, Tumor/genetics ; *Breast Neoplasms/pathology ; *Carcinoma, Ductal/genetics ; Gene Expression Profiling ; Gene Expression Regulation, Neoplastic ; *MicroRNAs/genetics/metabolism ; Signal Transduction ; },
abstract = {BACKGROUND: Invasive ductal carcinoma (IDC) is the most common form of breast cancer which accounts for 85% of all breast cancer diagnoses. Non-invasive and early stages have a better prognosis than late-stage invasive cancer that has spread to lymph nodes. The involvement of microRNAs (miRNAs) in the initiation and progression of breast cancer holds great promise for the development of molecular tools for early diagnosis and prognosis. Therefore, developing a cost effective, quick and robust early detection protocol using miRNAs for breast cancer diagnosis is an imminent need that could strengthen the health care system to tackle this disease around the world.

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

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

CONCLUSION: This study revealed potential biomarkers for the robust classification as well as rapid, cost effective and early detection of IDC of breast cancer. It not only confirmed the role of these miRNAs in cancer development but also revealed the oncogenic pathways involved in different progressive grades and stages thus suggesting a role in EMT and cellular plasticity during breast tumorigenesis per se and IDC in particular. Thus, our findings have provided newer insights into the miRNA signatures for the classification and early detection of IDC.},
}

Animals
Female
Mice
Biomarkers
Biomarkers, Tumor/genetics
*Breast Neoplasms/pathology
*Carcinoma, Ductal/genetics
Gene Expression Profiling
Gene Expression Regulation, Neoplastic
*MicroRNAs/genetics/metabolism
Signal Transduction

@article {pmid38308423,
year = {2024},
author = {Agaoglu, NB and Unal, B and Hayes, CP and Walker, M and Ng, OH and Doganay, L and Can, ND and Rana, HQ and Ghazani, AA},
title = {Genomic disparity impacts variant classification of cancer susceptibility genes in Turkish breast cancer patients.},
journal = {Cancer medicine},
volume = {13},
number = {3},
pages = {e6852},
pmid = {38308423},
issn = {2045-7634},
support = {Number YNY2016/144//The Istanbul Development Agency (ISTKA)/ ; },
mesh = {Humans ; Female ; *Breast Neoplasms/epidemiology/genetics ; *Carcinoma, Lobular ; Genomics ; *Carcinoma, Ductal, Breast ; Oncogenes ; },
abstract = {OBJECTIVE: Turkish genome is underrepresented in large genomic databases. This study aims to evaluate the effect of allele frequency in the Turkish population in determining the clinical utility of germline findings in breast cancer, including invasive lobular carcinoma (ILC), mixed invasive ductal and lobular carcinoma (IDC-L), and ductal carcinoma (DC).

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

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

CONCLUSION: To our knowledge, this is the first study of population genetic effects in breast cancer subtypes in Turkish women. Our findings underscore the need for a large genomic database representing Turkish population-specific variants. It further highlights the significance of the ancestry-appropriate population database for accurate variant assessment in clinical settings.},
}

Humans
Female
*Breast Neoplasms/epidemiology/genetics
*Carcinoma, Lobular
Genomics
*Carcinoma, Ductal, Breast
Oncogenes

@article {pmid38307851,
year = {2024},
author = {Coria, LM and Rodriguez, JM and Demaria, A and Bruno, LA and Medrano, MR and Castro, CP and Castro, EF and Del Priore, SA and Hernando Insua, AC and Kaufmann, IG and Saposnik, LM and Stone, WB and Prado, L and Notaro, US and Amweg, AN and Diaz, PU and Avaro, M and Ortega, H and Ceballos, A and Krum, V and Zurvarra, FM and Sidabra, JE and Drehe, I and Baqué, JA and Li Causi, M and De Nichilo, AV and Payes, CJ and Southard, T and Vega, JC and Auguste, AJ and Álvarez, DE and Flo, JM and Pasquevich, KA and Cassataro, J},
title = {A Gamma-adapted subunit vaccine induces broadly neutralizing antibodies against SARS-CoV-2 variants and protects mice from infection.},
journal = {Nature communications},
volume = {15},
number = {1},
pages = {997},
pmid = {38307851},
issn = {2041-1723},
support = {R01 AI153433/AI/NIAID NIH HHS/United States ; },
mesh = {Animals ; Mice ; Humans ; *SARS-CoV-2 ; Broadly Neutralizing Antibodies ; COVID-19 Vaccines ; *COVID-19/prevention & control ; Vaccines, Subunit ; Adjuvants, Immunologic ; Epitopes, B-Lymphocyte ; Antibodies, Viral ; Antibodies, Neutralizing ; Spike Glycoprotein, Coronavirus/genetics ; },
abstract = {In the context of continuous emergence of SARS-CoV-2 variants of concern (VOCs), one strategy to prevent the severe outcomes of COVID-19 is developing safe and effective broad-spectrum vaccines. Here, we present preclinical studies of a RBD vaccine derived from the Gamma SARS-CoV-2 variant adjuvanted with Alum. The Gamma-adapted RBD vaccine is more immunogenic than the Ancestral RBD vaccine in terms of inducing broader neutralizing antibodies. The Gamma RBD presents more immunogenic B-cell restricted epitopes and induces a higher proportion of specific-B cells and plasmablasts than the Ancestral RBD version. The Gamma-adapted vaccine induces antigen specific T cell immune responses and confers protection against Ancestral and Omicron BA.5 SARS-CoV-2 challenge in mice. Moreover, the Gamma RBD vaccine induces higher and broader neutralizing antibody activity than homologous booster vaccination in mice previously primed with different SARS-CoV-2 vaccine platforms. Our study indicates that the adjuvanted Gamma RBD vaccine is highly immunogenic and a broad-spectrum vaccine candidate.},
}

Animals
Mice
Humans
*SARS-CoV-2
Broadly Neutralizing Antibodies
COVID-19 Vaccines
*COVID-19/prevention & control
Vaccines, Subunit
Adjuvants, Immunologic
Epitopes, B-Lymphocyte
Antibodies, Viral
Antibodies, Neutralizing
Spike Glycoprotein, Coronavirus/genetics

@article {pmid38303308,
year = {2023},
author = {Aoyagi, T and Namura, M and Sakata, H and Tamanuki, T and Iwai, M and Iwata, K and Takahashi, H and Matsuzaki, H},
title = {[A Case of Recurrent Breast Cancer That Was BRCA1 Pathogenic Variant-Positive Successfully Treated with PARP Inhibitor].},
journal = {Gan to kagaku ryoho. Cancer & chemotherapy},
volume = {50},
number = {13},
pages = {1462-1464},
pmid = {38303308},
issn = {0385-0684},
mesh = {Female ; Humans ; Aged ; Middle Aged ; *Breast Neoplasms/drug therapy/genetics/surgery ; Poly(ADP-ribose) Polymerase Inhibitors/therapeutic use ; Mastectomy ; Neoplasm Recurrence, Local/drug therapy/surgery ; *Antineoplastic Agents/therapeutic use ; BRCA1 Protein/genetics ; },
abstract = {The patient was a 51-year-old woman at the time of diagnosis of left breast cancer. She underwent a mastectomy and axillary dissection. Pathological findings were invasive ductal carcinoma of the breast, tumor diameter 25 mm, and metastasis in 2 of 16 removed axillary lymph nodes. The subtype was triple negative. Postoperative chemotherapy was administered, and the patient was followed by follow-up imaging. At the age of 63 years, ultrasonography showed local recurrence, and local mass excision was performed. Genetic abnormalities were suspected since she had a family history of breast cancer, and it was a recurrent case. After genetic counseling, she underwent genetic testing, which revealed a BRCA1 pathogenic variant, so we initiated imaging surveillance. At age 65, a chest CT scan was performed due to respiratory symptoms, and she was diagnosed with multiple lung metastases. Respiratory symptoms improved at the examination 1 month after administration of Poly ADP ribose polymerase(PARP)inhibitor, and the metastatic masses shrank at the CT scan 3 months later. She continues to maintain CR and has no respiratory symptoms at present.},
}

Female
Humans
Aged
Middle Aged
*Breast Neoplasms/drug therapy/genetics/surgery
Poly(ADP-ribose) Polymerase Inhibitors/therapeutic use
Mastectomy
Neoplasm Recurrence, Local/drug therapy/surgery
*Antineoplastic Agents/therapeutic use
BRCA1 Protein/genetics

@article {pmid38285770,
year = {2024},
author = {Younas, H and Shahid, M and Khan, Z and Fatima, K and Tasadduq, R},
title = {Investigating the association of Angiotensin II Type I Receptor A1166C Polymorphism with Breast Cancer Risk in the Pakistani Population.},
journal = {Asian Pacific journal of cancer prevention : APJCP},
volume = {25},
number = {1},
pages = {79-85},
pmid = {38285770},
issn = {2476-762X},
mesh = {Humans ; Female ; *Breast Neoplasms/epidemiology/genetics ; Angiotensin II/genetics ; Pakistan/epidemiology ; Polymorphism, Genetic ; Renin-Angiotensin System/genetics ; Genotype ; Genetic Predisposition to Disease ; },
abstract = {The polymorphisms of the Renin-Angiotensin System are related to many disorders like diabetes, cardiovascular disease, and different types of cancer. Among all the polymorphisms related to AGTR1, A1166C has been associated with several disorders, including cardiovascular diseases and breast cancer. This study was conducted to discover the association of AGTR1 polymorphism (A1166C) Renin-Angiotensin and its effect on the development and progression of breast cancer in the Pakistani population. One hundred forty participants, including seventy diagnosed breast cancer patients and seventy healthy individuals, were included in this study and genotyped with an allele-specific polymerase chain reaction. The most frequent genotype in healthy participants and breast cancer patients was CC. An insignificant (p value>0.05) risk of breast cancer was found with A1166C polymorphism in codominant (CC vs. AA OR=1.200 [0.256-5.631] and AC vs. AA 0.941 [OR=0.223-3.976]), dominant (OR=1.00 [0.240-4.167]), recessive (OR=1.230 [0.593-2.552]) and additive models (OR=1.028 [0.533-1.983]) of general population genotypes. Nonetheless, when the AA genotype was considered a reference group, a significant association was found between AC and CC genotypes and invasive ductal and ductal carcinoma development in breast cancer patients. In conclusion, this study demonstrated no significant association between AGTR1 (A1166C) polymorphism and breast cancer risk.},
}

Humans
Female
*Breast Neoplasms/epidemiology/genetics
Angiotensin II/genetics
Pakistan/epidemiology
Polymorphism, Genetic
Renin-Angiotensin System/genetics
Genotype
Genetic Predisposition to Disease