Browsing by Author "May, Brian L"
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Item Open Access Co-Treatment of Chloroquine and Trametinib Inhibits Melanoma Cell Proliferation and Decreases Immune Cell Infiltration(Frontiers in Oncology) Degan, Simone; May, Brian L; Jin, Yingai J; Hammoda, Manel Ben; Sun, Huiying; Zhang, Guoqiang; Wang, Yan; Erdmann, Detlev; Warren, Warren; Zhang, Jennifer YAutophagy is characterized as a cytoprotective process and inhibition of autophagy with medicinally active agents, such as chloroquine (CQ) is proposed as a prospective adjuvant therapy for cancer. Here, we examined the preclinical effects of CQ combined with the MEK inhibitor trametinib (TRA) on melanoma. We found that cotreatment of CQ and TRA markedly slowed melanoma growth induced in Tyr-CreER.BrafCa.Ptenfl/fl mice. Immunostaining showed that trametinib decreased Ki-67+ proliferating cells, and increased TUNEL+ apoptotic cells. The combo treatment induced a further decrease of Ki-67+ proliferating cells. Consistent with the in vivo findings, CQ and TRA inhibited melanoma cell proliferation in vitro, which was correlated by decreased cyclin D1 expression. In addition, we found that tissues treated with CQ and TRA had significantly decreased numbers of CD4+ and CD8+ T-lymphocytes and F4/80+ macrophages. Together, these results indicate that cotreatment of CQ and TRA decreases cancer cell proliferation, but also dampens immune cell infiltration. Further study is warranted to understand whether CQ-induced immune suppression inadvertently affects therapeutic benefits.Item Open Access Salvage of Exposed Groin Vascular Grafts with Early Intervention Using Local Muscle Flaps.(Plastic and reconstructive surgery. Global open, 2015-09-22) May, Brian L; Zelenski, Nicole A; Daluvoy, Sanjay V; Blanton, Matthew W; Shortell, Cynthia K; Erdmann, DetlevBACKGROUND:Peripheral vascular surgery may be complicated by wound infection and potential graft exposure in the groin area. Muscle flap coverage of the graft has been promoted to address these wound complications. The authors present their findings regarding graft salvage rates and patient outcomes using local muscle flaps to address vascular graft complications of the groin. METHODS:Data were obtained by retrospective cohort study of patients who underwent a local muscle flap procedure by a single surgeon following vascular graft complication in the groin. RESULTS:Seventeen patients undergoing local muscle flap coverage of a vascular graft were reviewed. Six men and 9 women, 51-80 years old, were included in the study. Wound complications in the groin occurred anywhere from 3 days to 3.5 years following graft placement. Graft exposure was the most common presenting complication (14 of 17 patients). Muscle flap coverage occurred within 15 days of complication presentation in all patients (average, 6.4 days). Seven of the 15 patients experienced postoperative complications within 6 months of the procedure, most commonly wound dehiscence. However, analysis demonstrated that vascular grafts were successfully salvaged in 10 of the 17 patients (59%) over the course of follow-up (range, 104-1748 days). Average time to muscle flap coverage was 4.2 days in patients who retained the graft and 9.6 days in patients who ultimately lost their vascular graft. CONCLUSION:The authors demonstrate improved vascular graft salvage rate when local muscle flap procedure is performed early after initial wound complication presentation.