ABSTRACT
BACKGROUND: Platinum resistance may be attributable to inherent or acquired proficiency in homologous recombination repair (HRR) in epithelial ovarian cancer (EOC). The objective of this study was to evaluate the efficacy of the small molecule inhibitor triapine to disrupt HRR and sensitise BRCA wild-type EOC cells to platinum-based combination therapy in vitro and in vivo. METHODS: The sensitivity of BRCA wild-type cancer cells to olaparib, cisplatin, carboplatin, doxorubicin, or etoposide in combination with triapine was evaluated by clonogenic survival assays. The effects of triapine on HRR activity in cells were measured with a DR-GFP reporter assay. The ability of triapine to enhance the effects of the carboplatin-doxil combination on EOC tumour growth delay was determined using a xenograft tumour mouse model. RESULTS: Platinum resistance is associated with wild-type BRCA status. Triapine inhibits HRR activity and enhances the sensitivity of BRCA wild-type cancer cells to cisplatin, olaparib, and doxorubicin. However, sequential combination of triapine and cisplatin is necessary to achieve synergism. Moreover, triapine potentiates platinum-based combination therapy against BRCA wild-type EOC cells and produces significant delay of EOC tumour growth. CONCLUSIONS: Triapine promises to augment the clinical efficacy of platinum-based combination regimens for treatment of platinum-resistant EOC with wild-type BRCA and proficient HRR activity.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/pharmacology , Breast Neoplasms/drug therapy , Drug Resistance, Neoplasm/drug effects , Neoplasms, Glandular and Epithelial/drug therapy , Ovarian Neoplasms/drug therapy , Recombinational DNA Repair/drug effects , Animals , Breast Neoplasms/pathology , Carboplatin/administration & dosage , Carcinoma, Ovarian Epithelial , Cisplatin/administration & dosage , Doxorubicin/administration & dosage , Doxorubicin/analogs & derivatives , Female , Humans , Mice , Mice, Nude , Neoplasms, Glandular and Epithelial/pathology , Ovarian Neoplasms/pathology , Phthalazines/administration & dosage , Piperazines/administration & dosage , Polyethylene Glycols/administration & dosage , Tumor Cells, Cultured , Xenograft Model Antitumor AssaysABSTRACT
COVID-19 presented learning and social challenges for dental and high-school students alike due to isolating environments with fewer interpersonal interactions. After recognizing these challenges, two pre-doctoral dental students developed Penntorship, a program at University of Pennsylvania, School of Dental Medicine, where dental students' mentor students at West Philadelphia High School (WPHS) utilizing online technology. PURPOSE: This survey study explored the benefits of a newly developed mentoring program, Penntorship, for mentors and mentees. METHODS: Seventy dental students volunteered to mentor WPHS students throughout the 2020-2021 school year. After receiving training by Mentor Independence Region, mentors coordinated weekly meetings with mentees on Zoom to assist with homework assignments, discuss interests, and assess mentee's career goals. Over six months, 185 mentor meetings were held by 56 dental students with 28 different high-school students participating in the program. Surveys were distributed and analyzed to determine outcomes of the program. RESULTS: Survey results revealed that both dental students and high-school students gained new friendships, improved communication skills, and developed a positive perspective during the pandemic. CONCLUSION: With online learning formats and social distancing during the pandemic, dental students expressed a need for more social interaction. Penntorship served to support dental students during this challenging year and filled a social need for young individuals in the community. Both mentors and mentees benefited from the program and will continue to work together in the coming academic year. *IRB approval obtained 8/30/2021.