Changes in serum proteomic patterns by presurgical alpha-tocopherol and L-selenomethionine supplementation in prostate cancer

BACKGROUND: Evidence of the chemopreventive effects of the dietary antioxidants alpha-tocopherol (vitamin E) and l-selenomethionine (selenium) comes from secondary analysis of two phase III clinical trials that found treatment with these antioxidants reduced the incidence of prostate cancer. To determine the effects of selenium and vitamin E in blood and prostate tissue, we undertook a preoperative feasibility study complementary to the currently ongoing Selenium and Vitamin E Cancer Prevention Trial. METHODS: Forty-eight patients with clinically localized prostate cancer enrolled on this 2 x 2 factorial design study were randomized to take selenium, vitamin E, both, or placebo for 3 to 6 weeks before prostatectomy. Sera were collected from patients before and after dietary supplementation. Thirty-nine patients were evaluable, and 29 age-matched disease-free men served as controls. Mass profiling of lipophilic serum proteins of lower molecular weight (2-13.5 kDa) was conducted, and mass spectra data were analyzed using custom-designed software. RESULTS: Weighted voting analyses showed a change in sera classification from cancerous to healthy for some patients with prostate cancer after dietary intervention. ANOVA analysis showed significantly different treatment effects on prediction strength changes among the four groups at a 95% confidence level. Eliminating an outlying value and performing post hoc analysis using Fisher\u27s least significant difference method showed that effects in the group treated with the combination were significantly different from those of the other groups. CONCLUSION: In sera from patients with prostate cancer, selenium and vitamin E combined induced statistically significant proteomic pattern changes associated with prostate cancer-free status

Effects of mTOR Inhibitor Everolimus (RAD0011) On Bladder Cancer Cells

Purpose: We investigated the effect of the mTOR inhibitor everolimus (RAD001) on human bladder cancer cells in vitro and in vivo. Experimental Design: The UM-UC-3, UM-UC-6, UM-UC-9 and UM-UC-14 cell lines were treated at different concentrations of RAD001. Growth effect was assessed by crystal violet assays at different time courses, with or without RAD001 re-dosing. Flow cytometric cell cycle analyses, propidium iodide exclusion and annexin V assays were performed. Tritium radiolabeled leucine incorporation and western blot assays were also performed. In vivo experiments were performed using nude mice subcutaneously implanted with UM-UC-3, UM-UC-6, and UM-UC-9 and treated with orally RAD001 or placebo. Tumors were harvested for immunohistochemistry. Results: The RAD001 treated bladder cancer cells showed transient growth inhibition in a dosedependent manner, with growth inhibition augmented by re-treatment after 3 days. UMUC-14 was most sensitive to RAD001 therapy while UM-UC-9 was least sensitive.RAD001 showed G1 growth phase arrest only after prolonged treatment in sensitive cell lines. There was no evidence of apoptosis. Significant tumor growth inhibition compared to controls was shown in murine subcutaneous tumors from UM-UC-3, UM-UC-6, and UM-UC-9 cell lines. Protein synthesis inhibition via S6K and 4EBP1 pathway appears to be the main mechanism of bladder cancer cell growth inhibition by RAD001. However, inhibition of angiogenesis was the predominant mechanism for UM-UC-9 cells. Conclusions: The mTOR inhibitor RAD001 inhibits growth of bladder cancer cells in vitro. RAD001 is effective in treating bladder cancer in vivo, in spite of heterogeneity of tumor response in vitro

Deployment of cisplatin in Veterans with oropharyngeal cancer: toxicity and impact on oncologic outcomes

Abstract Objective Cisplatin forms the backbone of systemic chemotherapy treatment for oropharyngeal squamous cell carcinoma (OPSCC). The ideal cisplatin dosing regimen remains yet to be fully defined for achieving optimal efficacy and toxicity profiles in patients with comorbidity. Methods We retrospectively reviewed oncologic and toxicity data for patients with OPSCC treated at the Michael E. DeBakey Veterans Affairs Medical Center between 2000 and 2020 who initiated curative intent, definitive chemo‐radiation with one of three single agent regimens: high dose (HD) cisplatin, low dose (LD) cisplatin or cetuximab. Results Patients with HPV‐associated tumors and nonsmokers demonstrated improved overall and disease‐free survival along with locoregional and distant metastatic control regardless of chemotherapy regimen. Regardless of regimen selection, patients which received a cumulative cisplatin dose ≥200 mg/m2 had a lower rate of distant metastasis. The HD regimen resulted in a greater fraction (75% vs. 50%) of patients receiving a cumulative cisplatin dose ≥200 mg/m2 and a comparable measured toxicity burden compared to the LD regimen. Conclusions Both HD and LD cisplatin regimens can be safely delivered to a Veteran OPSCC patient population which should allow for straightforward application of conclusions drawn from completed and active clinical trials testing cisplatin regimens. Level of Evidence 4