The a v b 3 integrin is involved in various physiologic and pathologic processes such as wound healing, angiogenesis, tumor growth, and metastasis. The impact of a v b 3 integrin on the radiosensitivity of prostate cancer cells and the molecular mechanism controlling cell survival in response to ionizing radiation (IR) was investigated. Both LNCaP cells stably transfected with a v b 3 integrin and PC-3 cells that contain endogenous b 3 integrin were used. This study demonstrated that a v b 3 integrin increases survival of a v b 3 -LNCaP cells upon IR while small hairpin RNA (shRNA)-mediated knockdown of a v b 3 integrin in PC-3 cells sensitizes to radiation. Expression of a v b 3 integrin in LNCaP cells also enhances anchorageindependent cell growth while knockdown of a v b 3 integrin in PC-3 cells inhibits anchorage-independent cell growth. The a v b 3 antagonist, cRGD, significantly increases radiosensitivity in both a v b 3 -LNCaP and PC-3 cells. Moreover, a v b 3 integrin prevents radiation-induced downregulation of survivin. Inhibition of survivin expression by siRNA or shRNA enhances IR-induced inhibition of anchorage-independent cell growth. Overexpression of wild-type survivin in PC-3 cells treated with a v b 3 integrin shRNA increases survival of cells upon IR. These findings reveal that a v b 3 integrin promotes radioresistance and regulates survivin levels in response to IR.Implications: Future translational research on targeting a v b 3 integrin and survivin may reveal novel approaches as an adjunct to radiotherapy for patients with prostate cancer.

Background-Cell adhesion plays an important role in proliferation, metastasis, and tumor growth and may represent a potential vulnerability in treatment of prostate cancer patients. Bicalutamide (Casodex) has been used as an anti-androgen agent for prostate cancer patients during hormone ablation therapy. This study focuses on the effect of Bicalutamide on cell adhesion to fibronectin in prostate cancer cells.

A variety of methods for testosterone replacement therapy (TRT) exist, and the major potential risks of TRT have been well established. The risk of developing polycythemia secondary to exogenous testosterone (T) has been reported to range from 0.4% to 40%. Implantable T pellets have been used since 1972, and secondary polycythemia has been reported to be as low as 0.4% with this administration modality. However, our experience has suggested a higher rate. We conducted an institutional review board-approved, single-institution, retrospective chart review (2009–2013) to determine the rate of secondary polycythemia in 228 men treated with subcutaneously implanted testosterone pellets. Kaplan–Meyer failure curves were used to estimate time until the development of polycythemia (hematocrit >50%). The mean number of pellets administered was 12 (range: 6–16). The mean follow-up was 566 days. The median time to development of polycythemia whereby 50% of patients developed polycythemia was 50 months. The estimated rate of polycythemia at 6 months was 10.4%, 12 months was 17.3%, and 24 months was 30.2%. We concluded that the incidence of secondary polycythemia while on T pellet therapy may be higher than previously established.

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