Abstract POSTER-TECH-1122: Mass spectrometric imaging of ovarian cancer mouse model tissue: searching for high-grade serous carcinoma biomarkers

2015 ◽  
Author(s):  
Martin R. L. Paine ◽  
Rachel V. Bennett ◽  
Jaeyeon Kim ◽  
M. Cameron Sullards ◽  
Martin M. Matzuk ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Mouse Model ◽  
Mass Spectrometric ◽  
Serous Carcinoma ◽  
High Grade ◽  
Mass Spectrometric Imaging

scholarly journals A genetically engineered ovarian cancer mouse model based on fallopian tube transformation mimics human high-grade serous carcinoma development

2014 ◽  
Vol 233 (3) ◽  
pp. 228-237 ◽  
Author(s):  
Cheryl A Sherman-Baust ◽  
Elisabetta Kuhn ◽  
Blanca L Valle ◽  
Ie-Ming Shih ◽  
Robert J Kurman ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Mouse Model ◽  
Fallopian Tube ◽  
Genetically Engineered ◽  
Serous Carcinoma ◽  
High Grade ◽  
Model Based

scholarly journals Targeting progesterone signaling prevents metastatic ovarian cancer

2020 ◽  
Vol 117 (50) ◽  
pp. 31993-32004
Author(s):  
Olga Kim ◽  
Eun Young Park ◽  
Sun Young Kwon ◽  
Sojin Shin ◽  
Robert E. Emerson ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Deleterious Mutation ◽  
Peritoneal Metastases ◽  
Cancer Development ◽  
Serous Carcinoma ◽  
Cancer Type ◽  
High Grade ◽  
Primary Tumors ◽  
High Risk Populations ◽  
Genetic Deletion

Effective cancer prevention requires the discovery and intervention of a factor critical to cancer development. Here we show that ovarian progesterone is a crucial endogenous factor inducing the development of primary tumors progressing to metastatic ovarian cancer in a mouse model of high-grade serous carcinoma (HGSC), the most common and deadliest ovarian cancer type. Blocking progesterone signaling by the pharmacologic inhibitor mifepristone or by genetic deletion of the progesterone receptor (PR) effectively suppressed HGSC development and its peritoneal metastases. Strikingly, mifepristone treatment profoundly improved mouse survival (∼18 human years). Hence, targeting progesterone/PR signaling could offer an effective chemopreventive strategy, particularly in high-risk populations of women carrying a deleterious mutation in the BRCA gene.

scholarly journals Tumour Versus Germline BRCA Testing in Ovarian Cancer: A Single-Site Institution Experience in the United Kingdom

Diagnostics ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 547
Author(s):  
Iolia Akaev ◽  
Siavash Rahimi ◽  
Olubukola Onifade ◽  
Francis John Edward Gardner ◽  
David Castells-Rufas ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Unknown Origin ◽  
Parp Inhibitors ◽  
Serous Carcinoma ◽  
High Grade ◽  
Brca1 And Brca2 ◽  
Brca Mutations ◽  
Epithelial Cancers ◽  
Pathogenic Variants ◽  
Pathogenic Mutations

The aim of this audit was to evaluate the usefulness and serviceability of testing for pathogenic mutations in BRCA1 or BRCA2 (BRCA1/2) genes in ovarian cancer (OC) patients. One hundred and thirty-five patients with more common histological sub-types of OC were retrospectively identified between 2011 and 2019. The fail rate of the molecular analysis was 7.4% (10/135). One hundred and twenty-five records were evaluated: 99 (79.2%) patients had wild-type BRCA (both somatic and germline); tumour BRCA1/2 (tBRCA1/2) pathogenic mutations were found in 20 (16%) patients with distribution between BRCA1 and BRCA2 being 40% and 60%, respectively; 13 (10.4%) patients with pathogenic variants had germline mutations; and tBRCA1/2 with variant of unknown significance (VUS), in the absence of pathogenic BRCA1 or BRCA2 variants, was detected in 6 (4.8%) patients. Our data show that expanding the molecular service to the routine first-tumour testing for patients with OC will potentially increase the detection rate of BRCA mutations, thereby providing early benefits of PARP inhibitors therapy. The tumour testing service should continue to be offered to newly diagnosed patients with high-grade epithelial cancers, including high-grade serous carcinoma, but also with carcinosarcomas and poorly-differentiated metastatic adenocarcinomas of unknown origin.

scholarly journals Precision Oncology of High-Grade Ovarian Cancer Defined through Targeted Sequencing

Cancers ◽  
2021 ◽  
Vol 13 (20) ◽  
pp. 5240
Author(s):  
Sandra Wessman ◽  
Beatriz Bohorquez Fuentes ◽  
Therese Törngren ◽  
Anders Kvist ◽  
Georgia Kokaraki ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Molecular Characterization ◽  
Parp Inhibitor ◽  
Clinical Information ◽  
Undifferentiated Carcinoma ◽  
Serous Carcinoma ◽  
Precision Oncology ◽  
High Grade ◽  
Histologic Diagnosis ◽  
Germline Testing

Background: We examined whether molecular characterization of high-grade epithelial ovarian cancer can inform the diagnosis and/or identify potential actionable targets. Methods: All of the consecutively sequenced high-grade ovarian tumours with consent between 2014 until 2019 were included. A total of 274 tumours underwent next generation sequencing using a targeted panel. Results: Patients with high-grade ovarian epithelial cancer were consented to prospective molecular characterization. Clinical information was extracted from their medical record. Tumour DNA was subjected to sequencing, and selected patients received PARP inhibitor therapy. Conclusions: Tumours from 274 women were sequenced, including high-grade serous carcinoma (n = 252), clear cell carcinoma (n = 4), carcinosarcoma (n = 9), endometrioid carcinoma (n = 3), undifferentiated carcinoma (n = 1), and mixed tumours (n = 5). Genomic profiling did not influence histologic diagnosis. Mutations were identified in TP53, BRCA1, BRCA2, as well as additional homologous recombination repair pathway genes BARD1, ATR, CHEK2, PALB2, RAD51D, RAD50, SLX4, FANCA, RAD51C, and RAD54L. In addition, mutations in PTEN and CDKN2A were identified. Several somatic mutations with implications for germline testing were identified, including RMI1, STK11, and CDH1. Germline testing identified 16 previously unknown BRCA1/2 carriers. Finally, 20 patients were treated with the PARP inhibitor olaparib based on the sequencing results.

scholarly journals Genomics and molecular mechanisms of high grade serous ovarian cancer: the 12th Biennial Rivkin Center Ovarian Cancer Research Symposium

2019 ◽  
Vol 29 (Suppl 2) ◽  
pp. s7-s11
Author(s):  
Erinn B Rankin
Keyword(s):  
Ovarian Cancer ◽  
Cancer Research ◽  
Dna Repair ◽  
Molecular Mechanisms ◽  
New Technologies ◽  
Serous Carcinoma ◽  
High Grade ◽  
Serous Ovarian Cancer ◽  
Poster Presentations ◽  
Oral Presentations

ObjectiveThe aim of this study was to review current research efforts in genomics and molecular mechanisms of high grade serous ovarian cancer, presented at the 12th Biennial Rivkin Center Ovarian Cancer Research Symposium, held at the University of Washington.MethodsThe 12th Biennial Rivkin Center Ovarian Cancer Research Symposium brought together leaders in the field to discuss recent advances in ovarian cancer research and therapy.ResultsThe genomics and molecular mechanisms of ovarian cancer session featured invited speaker presentations by Dr Alan D’ Andrea on ‘Deoxyribonucleic acid (DNA) repair in ovarian cancer’ and Dr Kathleen Cho on ‘Modeling the genomics of high grade serous carcinoma in the mouse’. Eight additional oral presentations and 46 poster presentations were selected from the submitted abstracts that highlighted current research efforts in p53, DNA repair, genomic instability and modeling disease in mice, and organoids in high grade serous ovarian cancer.ConclusionsNew technologies utilizing clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR associated protein 9 (CAS9) approaches in mice, organoids, and cell based screens continue to advance our knowledge of key molecular drivers of ovarian cancer initiation, progression, and drug resistance. Improved understanding of the mechanisms of poly ADP ribose polymerase inhibitor resistance may lead to new therapeutic strategies to enhance outcomes in women with high grade serous ovarian cancer.

Prognostic significance of obesity in high-grade serous carcinoma of the ovary

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e16528-e16528 ◽  
Author(s):  
M. Schlumbrecht ◽  
D. Urbauer ◽  
D. Gershenson ◽  
R. Broaddus
Keyword(s):  
Ovarian Cancer ◽  
Body Mass Index ◽  
Overall Survival ◽  
Body Mass ◽  
Neoadjuvant Treatment ◽  
The United States ◽  
Wilcoxon Test ◽  
Serous Carcinoma ◽  
Low Grade ◽  
High Grade

e16528 Background: Obesity is an epidemic public health problem in the United States. In gynecologic oncology, obesity is an established risk factor for endometrial cancer. However, its role in the pathogenesis and survival in ovarian cancer is debated. Recent studies have attempted to elucidate a possible relationship, but variations in design and heterogeneity in patient characteristics make it difficult to draw definitive conclusions. The purpose of our study was to determine if body mass index at the time of treatment initiation for high grade serous ovarian carcinoma has an effect on patient outcome. Methods: Nine-hundred four patients treated for ovarian cancer at M.D. Anderson Cancer Center were identified between 2002 and 2007. Patients were excluded for low grade or non-serous histology, neoadjuvant treatment, or if presenting with recurrent disease. Clinicopathologic data were extracted by retrospective chart review. Patients were stratified by body mass index (BMI) as normal (BMI<25), overweight (BMI 25-<30), or obese (BMI>30). All were treated with primary cytoreduction and standard platinum/taxane chemotherapy. Chemotherapy was dosed using adjusted body weights. Outcomes included time to recurrence, overall survival, success of surgical debulking, and chemotherapeutic toxicities. Statistical analysis was performed using Fisher's exact test, Wilcoxon test, and Kaplan-Meier estimates. Results: A total of 127 patients were included for analysis. Patients were followed for a mean of 37 months (range 3–86 months). Twenty-one patients were obese (16.5%), and 35 were overweight (27.5%). Diabetes was more prevalent in the obese cohort (p = 0.0038). There was a trend towards greater likelihood of suboptimal debulking in obese patients, but this did not reach statistical significance (p = 0.06). BMI had no effect on recurrence-free survival (HR 0.69 [CI 0.39–1.23], p = 0.21) or overall survival (HR 0.95 [CI 0.68–2.43], p = 0.91). There was no difference in chemotherapy side effects or chemoresistance across BMI strata. Conclusions: Body mass index has no effect on survival in women with high grade serous ovarian cancer. Effectively managing comorbidities and ensuring adequate chemotherapy dosing in the obese patient is crucial for optimizing outcome. No significant financial relationships to disclose.

scholarly journals The impact of the ovarian microenvironment on the anti-tumor effect of SPARC on ovarian cancer1This article is part of Special Issue entitled Asilomar Chromatin and has undergone the Journal’s usual peer review process.

2012 ◽  
Vol 90 (1) ◽  
pp. 96-107 ◽  
Author(s):  
James B. Greenaway ◽  
Anne Koehler ◽  
Christopher A. McCulloch ◽  
James Petrik ◽  
Theodore J. Brown ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Mouse Model ◽  
Review Process ◽  
Peer Review Process ◽  
High Grade ◽  
Wild Type ◽  
Special Issue ◽  
Reactive Stroma ◽  
Abdominal Lesions ◽  
The Impact

A lack of host-derived SPARC promotes disease progression in an intraperitoneal (IP) ID8 mouse model of epithelial ovarian cancer (EOC). Since orthotopic injection (OT) of ID8 cells better recapitulates high-grade serous cancer, we examined the impact of host-derived SPARC following OT injection. Sparc−/− and wild-type (WT) mice were injected with ID8 cells either OT or IP and tumors were analyzed at the moribund stage. Sparc−/− mice had reduced survival and fewer well-defined abdominal lesions compared with WT controls after IP injection, whereas no differences were observed in survival or abdominal lesions between Sparc−/− and WT mice after OT injection. No differences in mass or collagen content were observed in ovarian tumors between OT-injected Sparc−/− and WT mice. The abdominal wall of the IP-injected Sparc−/− mice exhibited immature and less abundant collagen fibrils compared with WT mice both in injected and non-injected controls. In contrast to human EOC, SPARC was expressed by the tumor cells but was absent in reactive stroma of WT mice. Exposure to the ovarian microenvironment through OT injections alters the metastatic behaviour of ID8 cells, which is not affected by the absence of host-derived SPARC.

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