Search

Background/aim The purpose of the present study was to clarify whether treatment with YM155, a novel small-molecule inhibitor of survivin, reversed cabazitaxel resistance in castration-resistant prostate cancer (CRPC). Materials and methods Cabazitaxel resistance was induced in the castration-resistant prostate cancer cell line, 22Rv1-CR. In vitro and in vivo models were used to test the efficacy of YM155 and cabazitaxel. Results Survivin gene expression was significantly higher in 22Rv1-CR than its parent cells (22Rv1). In 22Rv1-CR cells, YM155 significantly reduced expression of the survivin gene in a concentration-dependent manner. YM155 alone was poorly effective; however, it significantly enhanced the anticancer effects of cabazitaxel on 22Rv1-CR in vitro and in vivo. Conclusion Inhibition of survivin by YM155 overcomes cabazitaxel resistance in CRPC cells.

BACKGROUND/AIM Androgen deprivation therapy (ADT) is a mainstay therapy for prostate cancer (PCa). ADT induces bone loss and increases the risk of osteoporosis and fractures. Recently, loss of bone quality has received attention as a factor that causes loss of bone strength independent of bone mineral density (BMD). Pentosidine has been identified as a surrogate marker of bone quality. Therefore, bone quality markers were evaluated retrospectively in PCa patients receiving ADT with or without denosumab. PATIENTS AND METHODS This study included 46 PCa patients. Twenty patients received denosumab. We measured pentosidine as bone quality marker and TRACP-5b as bone turnover marker. Pre- and 12-month BMD was measured in the lumbar spine and femoral neck. RESULTS In the denosumab group (D+), BMD at the lumbar spine was increased by 6.7% compared with the group that did not receive denosumab (D-) at 12 months (p=0.0015). BMD at the femoral neck was increased by 3.1% at 12 months (p=0.0076). The mean value of TRAP-5b was lower in the D+ group than the D- group at 12 months (p

Aim: The purpose of the present study was to clarify whether treatment with YM155, a novel small-molecule inhibitor of survivin, reverses statin resistance in statin-resistant renal cell cancer (RCC). Materials and Methods: We induced simvastatin resistance in a renal clear cell carcinoma cell line (Caki-1-staR). In vitro and in vivo models were used to test the efficacy of YM155 and simvastatin. Results: Survivin gene expression was significantly stronger in Caki-1-staR cells than in its parent cells (Caki-1). In Caki-1-staR cells, YM155 significantly reduced expression of survivin gene and cell proliferation in a dose-dependent manner. Treatment with YM155 significantly reversed simvastatin resistance in Caki-1-staR cells. YM155 significantly inhibited the growth of Caki-1-staR tumors in a nude mouse tumor xenograft model. Furthermore, YM155 significantly enhanced the antitumor effects of simvastatin on Caki-1-staR tumors. Conclusion: Our results indicate that inhibition of survivin by YM155 overcomes statin resistance in RCC cells.

Background/Aim: Recent studies have shown that an early prostate-specific antigen (PSA) response to androgen receptor (AR)-targeting agents in metastatic castration-resistant prostate cancer (mCRPC) is associated with a better prognosis. We analyzed early PSA response to enzalutamide and oncological outcomes to study their prognostic significance in the Japanese population. Patients and Methods: Fifty-one patients with mCRPC (26 of pre-docetaxel and 25 of post-docetaxel status) were treated with enzalutamide. The PSA progression-free survival (PFS), radiographic PFS (rPFS) and overall survival (OS) were assessed. The association of rPFS and OS in patients with an early PSA response at 4 weeks after commencement of enzalutamide was studied. Results: Early PSA responses were significantly associated with a longer rPFS (median of 47.9 vs. 20.1 weeks, p