Previous studies have shown that small-molecule BCL-2 inhibitors can have a synergistic interaction with ABCG2 substrates in chemotherapy. Venetoclax is a potent and selective BCL-2 inhibitor, approved by the FDA in 2016 for the treatment of patients with chronic lymphocytic leukemia (CLL). This study showed that, at a non-toxic concentration, venetoclax at 10 µM significantly reversed multidrug resistance (MDR) mediated by wild-type ABCG2, without significantly affecting MDR mediated by mutated ABCG2 (R482G and R482T) and ABCB1, while moderate or no reversal effects were observed at lower concentrations (0.5 to 1 µM). The results showed that venetoclax increased the intracellular accumulation of chemotherapeutic agents, which was the result of directly blocking the wild-type ABCG2 efflux function and inhibiting the ATPase activity of ABCG2. Our study demonstrated that venetoclax potentiates the efficacy of wild-type ABCG2 substrate drugs. These findings may provide useful guidance in combination therapy against wild-type ABCG2-mediated MDR cancer in clinical practice.
Background: Website content and accessibility has the potential to influence the applicant's decision whether to interview for the program or not. The objective of our study is to determine the content and accessibility of the American Academy of Family Physicians (AAFP) Directory and accredited geriatric (family medicine) fellowship program websites. Methods: A list of geriatric (family medicine) fellowship programs was retrieved using the AAFP Directory and verified for accreditation. Contact information was compared between the directory and the fellowship websites. The programs' website links from the directory were evaluated and compared with Google search. The websites' accessibility and content were assessed for program, education, and application overview. Results: Fifty programs were identified, but 43 programs were chosen for analysis. There was an incongruence of over 50% of contact information between the AAFP Directory and the website page. Regarding content, most websites were lacking in fellows' profile information, previous research studies, and application ID. Conclusion: AAFP Directory and fellowship websites can improve geriatric (family medicine) fellowship recruitment by updating their information and providing more accessible and accurate content.