Alterations in p53 and Rb pathways are observed frequently in epithelial ovarian cancer (EOC).However, their roles in EOC initiation remain uncertain. Using a single intrabursal administration of recombinant adenovirus expressing Cre, we demonstrate that concurrent inactivation of p53 and Rb1 is sufficient for reproducible induction of ovarian epithelial carcinogenesis in mice homozygous for conditional gene alleles. Similarly to progression of disease in women, ovarian neoplasms spread i.p., forming ascites, and metastasize to the contralateral ovary, the lung, and the liver. These results establish critical interactions between p53 and Rb1 pathways in EOC pathogenesis, and provide a genetically defined immunocompetent mouse model of sporadic EOC.
Download full-text PDF |
Source |
|---|
Publication Analysis
Top Keywords
Similar Publications
Real-world clinical multi-omics analyses reveal bifurcation of ER-independent and ER-dependent drug resistance to CDK4/6 inhibitors.
Nat Commun
January 2025
Oncology Research & Development, Pfizer Inc., San Diego, CA, USA.
To better understand drug resistance mechanisms to CDK4/6 inhibitors and inform precision medicine, we analyze real-world multi-omics data from 400 HR+/HER2- metastatic breast cancer patients treated with CDK4/6 inhibitors plus endocrine therapies, including 200 pre-treatment and 227 post-progression samples. The prevalences of ESR1 and RB1 alterations significantly increase in post-progression samples. Integrative clustering analysis identifies three subgroups harboring different resistance mechanisms: ER driven, ER co-driven and ER independent.
View Article and Find Full Text PDFMolecular and Immunohistochemical Classification of Extrapulmonary Small Cell Neuroendocrine Carcinomas: A Study of 181 Cases.
Lab Invest
January 2025
Department of Pathology and Molecular Medicine, Thomayer University Hospital, 3rd Faculty of Medicine, Charles University, Prague, Czech Republic; Department of Pathology, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic; Department of Pathology, University Hospital Kralovske Vinohrady, 3rd Faculty of Medicine, Charles University, Prague, Czech Republic. Electronic address:
Extrapulmonary small cell neuroendocrine carcinoma (EP-SCNC) is a rare malignancy with a poor prognosis. Most patients with EP-SCNC have metastatic disease upon presentation, and their average overall survival (OS) is less than 12 months. Our study aimed to conduct a complex analysis of EP-SCNC.
View Article and Find Full Text PDFConcurrent RB1 and P53 pathway disruption predisposes to the development of a primitive neuronal component in high-grade gliomas depending on MYC-driven EBF3 transcription.
Acta Neuropathol
January 2025
Pathology Unit, Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy.
The foremost feature of glioblastoma (GBM), the most frequent malignant brain tumours in adults, is a remarkable degree of intra- and inter-tumour heterogeneity reflecting the coexistence within the tumour bulk of different cell populations displaying distinctive genetic and transcriptomic profiles. GBM with primitive neuronal component (PNC), recently identified by DNA methylation-based classification as a peculiar GBM subtype (GBM-PNC), is a poorly recognized and aggressive GBM variant characterised by nodules containing cells with primitive neuronal differentiation along with conventional GBM areas. In addition, the presence of a PNC component has been also reported in IDH-mutant high-grade gliomas (HGGs), and to a lesser extent to other HGGs, suggesting that regardless from being IDH-mutant or IDH-wildtype, peculiar genetic and/or epigenetic events may contribute to the phenotypic skewing with the emergence of the PNC phenotype.
View Article and Find Full Text PDFCharacterization of the genomic landscape in liver oligometastatic NSCLC.
BMC Cancer
January 2025
Department of Cancer Center, Second Affiliated Hospital, Chongqing Medical University, Chongqing, China.
Objectives: Emerging data have shown that local treatment could provide clinical benefit for non-small cell lung cancer (NSCLC) patients with oligometastasis. Liver metastases have the worst prognosis in advanced NSCLC, but the genomic characteristics of liver oligometastasis remain unclear. The aim of our study was to elucidate the molecular features of liver oligometastatic NSCLC.
View Article and Find Full Text PDFKRT20-/SATB2+/MCPyV+ Sinonasal Merkel Cell Carcinoma: A Detailed Immunohistochemical and In Situ Hybridization Study.
Int J Surg Pathol
January 2025
Department of Pathology and Forensic Medicine, Ribeirão Preto Medical School (FMRP/USP), University of São Paulo, Ribeirão Preto, SP, Brazil.
Merkel cell carcinoma (MCC) is an uncommon aggressive neoplasm, usually arising in sun-exposed skin of the head and neck. By immunohistochemistry, KRT20 and MCPyV positivity are found in about 90% and 80% of MCCs, respectively. Noteworthy, viral status in lip/oral cavity MCCs is poorly known.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!