ABSTRACT
Secondary plasma cell leukemia (sPCL) is a rare form of aggressive plasma cell malignancy arising mostly at end-stage refractory multiple myeloma and consequently presenting limited therapeutic options. We analyzed 13 sPCL for their sensitivity to BH3 mimetics targeting either BCL2 (venetoclax) or BCLXL (A1155463) and showed that 3 sPCL were efficiently killed by venetoclax and 3 sPCL by A1155463. Accordingly, BH3 profiling of 2 sPCL sensitive to BCLXL inhibition confirmed their high BCLXL primed profile. While targeting BCLXL using BH3 mimetics induces platelets on-target drug toxicity, the recent development of DT2216, a clinical-stage BCLXL proteolysis targeting chimera PROTAC compound, provides an alternative strategy to target BCLXL. Indeed, DT2216 specifically degrades BCLXL via VHL E3 ligase, without inducing thrombocytopenia. We demonstrated in human myeloma cell lines and sPCL that sensitivity to DT2216 strongly correlated with the sensitivity to A1155463. Interestingly, we showed that low doses of DT2216 (nM range) were sufficient to specifically degrade BCLXL after 48 hours of treatment, consistent with VHL expression, in all cell lines but irrespectively to DT2216 sensitivity. In myeloma cells, DT2216 induced apoptotic cell death and triggered BAX and BAK activation. In conclusion, our study demonstrated that patients with sPCL addicted to BCLXL, a small but a very challenging group, could potentially receive therapeutic benefit from DT2216. Clinical trials of DT2216 in this subset of sPCL patients are warranted.
ABSTRACT
OBJECTIVE: To describe how a community-academic partnership between Taller Salud Inc., a community-based organization, and the Puerto Rico Community Cancer Control Outreach Program of the University of Puerto Rico was crucial in the adaptation and implementation of Cultivando La Salud (CLS), an evidencebased educational outreach program designed to increase breast and cervical cancer screening among Hispanic women living in Puerto Rico. This collaboration facilitated the review and adaptation of the CLS intervention to improve cultural appropriateness, relevance, and acceptability for Puerto Rican women. METHODS: A total of 25 interviewers and 12 Lay Health Workers (LHWs) were recruited and trained to deliver the program. The interviewers recruited women who were non-adherent to recommended screening guidelines for both breast and cervical cancer. LHWs then provided one-on-one education using the adapted CLS materials. RESULTS: A total of 444 women were recruited and 48% of them were educated through this collaborative effort. CONCLUSION: Our main accomplishment was establishing the academic-community partnership to implement the CLS program. Nevertheless, in order to promote better collaborations with our community partners, it is important to carefully delineate and establish clear roles and shared responsibilities for each partner for the successful execution of research activities, taking into consideration the community's needs.
Subject(s)
Breast Neoplasms/diagnosis , Community-Institutional Relations , Mass Screening/methods , Uterine Cervical Neoplasms/diagnosis , Adult , Cooperative Behavior , Female , Hispanic or Latino , Humans , Middle Aged , Patient Acceptance of Health Care , Patient Compliance , Patient Education as Topic/methods , Practice Guidelines as Topic , Puerto Rico , Young AdultABSTRACT
OBJECTIVE: "Arte con Salud" is an HIV/AIDS prevention intervention tailored for Puerto Rican women who have sex with men. The intervention curriculum was refined through a community-academic collaboration between Taller Salud, the UPRCayey Campus, and the UCC-School of Medicine, subsided in 2012-13 by PRCTRC. The collaboration has been crucial to validate the impact of using art as a tool to facilitate sexual negotiation skills and safer sexual practices among adult women have sex with men participating in HIV prevention education. METHODS: This article describes the vision, valley, victory phases endured to establish a community-academia partnership based on the CPPR framework as an effective mean to implement a randomized controlled trial intervention (RCT). We also discuss the barriers, outcomes, and lessons learned from this partnership. RESULTS: Some of the identified solutions include: setting goals to secure funding, regular meetings, and the inclusion of undergraduate level students to assist in the implementation of the intervention. These solutions helped to build trust among the community and academic partners. As a result of this collaboration, a total of 86 participants were enrolled and 5 competitive research grants have been submitted. CONCLUSION: The community-academic collaboration was essential in order to build a solid research infrastructure that addresses the complexities of HIV prevention education among groups of Puerto Rican women.
