visualizing-dna-damage-repair-proteins-patient-derived-ovarian-cancer

Visualizing DNA Damage Repair Proteins in Patient-Derived Ovarian Cancer Organoids <em>via</em> Immunofluorescence Assays

Immunofluorescence is one of the most widely used techniques to visualize target antigens with high sensitivity and specificity, allowing for the accurate ...

generation-culturing-high-grade-serous-ovarian-cancer-patient-derived

Generation and Culturing of High-Grade Serous Ovarian Cancer Patient-Derived Organoids

Organoids are 3D dynamic tumor models that can be grown successfully from patient-derived ovarian tumor tissue, ascites, or pleural fluid and aid in the ...

ovarian-cancer-patient-derived-organoid-models-for-pre-clinical-drug

Ovarian Cancer Patient-Derived Organoid Models for Pre-Clinical Drug Testing

Ovarian cancer is a fatal gynecologic cancer and the fifth leading cause of cancer death among women in the United States. Developing new drug treatments ...

Washington University in St. Louis

Washington University of Medicine in St. Louis

To determine the role of race and gender in the career experience of Black/AA academic surgeons and to quantify the prevalence of experience with racial and gender bias stratified by gender.

The Role of Race and Gender in the Career Experiences of Black/African American Academic Surgeons: A Survey of the Society of Black Academic Surgeons and a Call to Action.

A Perspective on James Marion Sims, MD, and Antiblack Racism in Obstetrics and Gynecology.

Poly ADP ribose polymerase inhibitors (PARPi) are most effective in BRCA1/2 mutated ovarian tumors. Better treatments are needed for homologous recombination HR-proficient cancer, including CCNE1 amplified subtypes. We have shown that histone deacetylase inhibitors (HDACi) sensitize HR-proficient ovarian cancer to PARPi. In this study, we provide complementary preclinical data for an investigator-initiated phase 1/2 clinical trial of the combination of olaparib and entinostat in recurrent, HR-proficient ovarian cancer.

Entinostat, a selective HDAC1/2 inhibitor, potentiates the effects of olaparib in homologous recombination proficient ovarian cancer.

The advancement of women leaders in obstetrics and gynecology does not reflect the changes in the physician workforce seen over the last 50 years. A core value of our culture in obstetrics and gynecology must be gender equity. Departmental, institutional, and professional society efforts should explicitly prioritize and demonstrate a commitment to gender equity with tangible actions. This commentary from the American Gynecological and Obstetrical Society synthesizes available information about women holding academic leadership roles within obstetrics and gynecology. We propose specific principles and leadership practices to promote gender equity.

Promotion of gender equity in obstetrics and gynecology: principles and practices for academic leaders.

Histone deacetylase inhibitors (HDACi) sensitize homologous recombination (HR)-proficient human ovarian cancer cells to PARP inhibitors (PARPi). To investigate mechanisms of anti-tumor effects of combined HDACi/PARPi treatment we performed transcriptome analysis in HR- proficient human ovarian cancer cells and tested drug effects in established immunocompetent mouse ovarian cancer models. Human SKOV-3 cells were treated with vehicle (Con), olaparib (Ola), panobinostat (Pano) or Pano+Ola and RNA-seq analysis performed. DESeq2 identified differentially expressed HR repair and immune transcripts. Luciferised syngeneic mouse ovarian cancer cells (ID8-luc) were treated with the HDACi panobinostat alone or combined with olaparib and effects on cell viability, apoptosis, DNA damage and HR efficiency determined. C57BL/6 mice with intraperitoneally injected ID8-luc cells were treated with panobinostat and/or olaparib followed by assessment of tumor burden, markers of cell proliferation, apoptosis and DNA damage, tumor-infiltrating T cells and macrophages, and other immune cell populations in ascites fluid. There was a significant reduction in expression of 20/37 HR pathway genes by Pano+Ola, with immune and inflammatory-related pathways also significantly enriched by the combination. In ID8 cells, Pano+Ola decreased cell viability, HR repair, and enhanced DNA damage. Pano+Ola also co-operatively reduced tumor burden and proliferation, increased tumor apoptosis and DNA damage, enhanced infiltration of CD8+ T cells into tumors, and decreased expression of M2-like macrophage markers. In conclusion, panobinostat in combination with olaparib targets ovarian tumors through both direct cytotoxic and indirect immune-modulating effects.

Panobinostat enhances olaparib efficacy by modifying expression of homologous recombination repair and immune transcripts in ovarian cancer.

Cyclin E1 (CCNE1) is a potential predictive marker and therapeutic target in tubo-ovarian high-grade serous carcinoma (HGSC). Smaller studies have revealed unfavorable associations for CCNE1 amplification and CCNE1 overexpression with survival, but to date no large-scale, histotype-specific validation has been performed. The hypothesis was that high-level amplification of CCNE1 and CCNE1 overexpression, as well as a combination of the two, are linked to shorter overall survival in HGSC.

Dineo Khabele

Washington University in St. Louis

Visualizing DNA Damage Repair Proteins in Patient-Derived Ovarian Cancer Organoids via Immunofluorescence Assays

Generation and Culturing of High-Grade Serous Ovarian Cancer Patient-Derived Organoids

Ovarian Cancer Patient-Derived Organoid Models for Pre-Clinical Drug Testing