Description
- Abstract:
- Ovarian cancer carries a disproportionately high mortality rate relative to its incidence, largely due to late-stage diagnosis and the frequent development of resistance to standard chemotherapy. Among the most clinically significant contributors to poor prognosis are mutations in the BRCA1 and BRCA2 genes, which compromise homologous recombination repair and promote genomic instability. Despite the established clinical relevance of these mutations, how they shape cellular responses to chemotherapy and hypoxic stress remains incompletely understood. This study investigated nuclear morphology and polyploid giant cancer cell (PGCC) formation in ID8 BRCA1 and ID8 BRCA2 mutant ovarian cancer cells under hypoxic and normoxic conditions, and examined the effect of paclitaxel and carboplatin treatment on these parameters. PGCCs are an understudied population of abnormally enlarged cancer cells with documented roles in chemoresistance and tumor repopulation following treatment. Results showed that hypoxia promoted nuclear enlargement and irregularity in both BRCA mutant cell lines, and that chemotherapeutic treatment dramatically amplified PGCC formation from a baseline of approximately 0.75-2.06% to as high as 63% regardless of oxygen conditions. DNA damage signaling was confirmed within PGCC nuclei through H2AX immunofluorescence staining. These findings suggest that standard chemotherapy may enrich for a resistant PGCC population in BRCA mutant ovarian cancer cells, with implications for understanding treatment resistance and developing more targeted therapeutic strategies.
- Notes:
- Thesis (Sc. M.)--Brown University, 2026
Citation
Savani, Kruti,
"Analyzing the Independent Effects of Paclitaxel and Carboplatin on BRCA-Mutant Ovarian Cancer Cells Under Hypoxia"
(2026).
Biomedical Engineering Theses and Dissertations.
Brown Digital Repository. Brown University Library.
https://repository.library.brown.edu/studio/item/bdr:rbu6p296/
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Collection:
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Biomedical Engineering Theses and Dissertations
Theses and Dissertations for the Biomedical Engineering department....