Minoru Kato

Expression of androgen receptor (AR) splice variant 7 (AR-V7) has been identified as the mechanism associated with the development of castration-resistant prostate cancer (CRPC). However, a potential link between AR-V7 expression and resistance to taxanes, such as docetaxel or cabazitaxel, has not been unequivocally demonstrated. To address this, we used LNCaP95-DR cells, which express AR-V7 and exhibit resistance to enzalutamide and docetaxel. Interestingly, LNCaP95-DR cells showed cross-resistance to cabazitaxel. Furthermore, these cells had increased levels of P-glycoprotein (P-gp) and their sensitivity to both docetaxel and cabazitaxel was restored through treatment with tariquidar, a P-gp antagonist. Results generated demonstrated that P-gp mediated cross-resistance between docetaxel and cabazitaxel. Although the LNCaP95-DR cells had increased expression of AR-V7 and its target genes (UBE2C, CDC20), the knockdown of AR-V7 did not restore sensitivity to docetaxel or cabazitaxel. However, despite resistance to docetaxel and carbazitaxel, EPI-002, an antagonist of the AR amino-terminal domain (NTD), had an inhibitory effect on the proliferation of LNCaP95-DR cells, which was similar to that achieved with the parental LNCaP95 cells. On the other hand, enzalutamide had no effect on the proliferation of either cell line. In conclusion, our results suggested that EPI-002 may be an option for the treatment of AR-V7-driven CRPC, which is resistant to taxanes.

Androgen signal has been recently suggested to be associated with the progression of bladder cancer. Steroid sulfatase (STS) is a steroid sulfate activation enzyme, considered to be one of the key enzymes in the androgen signaling pathway. However, the role of STS in bladder cancer has not been elucidated. The purpose of the present study was to determine the clinical and functional significance of STS in bladder cancer. Immunohistochemical analysis of surgical specimens obtained by radical cystectomy (n=114) demonstrated that overexpression of STS was associated with the invasion of bladder cancer, as evidenced by the incidence of STS‑positive cancers (11.5 and 37.1% in non‑muscle invasive and muscle invasive bladder cancers, respectively; P=0.003). STS‑positive cancer demonstrated shorter recurrence‑free survival and cancer‑specific survival (P=0.0027 and 0.0030, respectively). Furthermore, knockdown of STS significantly reduced cell migration and invasion capacities of bladder cancer cells (P<0.001 and P=0.005, respectively), accompanied by the upregulation of E‑cadherin and downregulation of vimentin. In summary, the present study demonstrated that STS promotes the invasion capability of bladder cancer via regulation of the epithelial‑mesenchymal transition, and may be a useful marker for predicting the progression of bladder cancers.

The aim of this study was to evaluate the efficacy and toxicities of second-line chemotherapy regimens with docetaxel and gemcitabine (GD), or paclitaxel and gemcitabine (GP) for advanced or metastatic urothelial carcinoma (UC) that did not respond to first-line platinum-based chemotherapy.

We investigated therapeutic outcomes in consecutive patients with metastatic renal cell carcinoma treated with targeted anticancer agents from 2008 to 2014 in order to determine the efficacy of adverse event management for such agents and the best sequence in which to use them. We analyzed 132 consecutive patients who had taken targeted anticancer agents for metastatic renal cell carcinoma. Of these, 101 patients received therapy between 2008 and 2011 (pioneer group) and 31 patients received therapy between 2011 and 2014 (contemporary group). Patients of the contemporary group were provided with aggressive adverse event management and education on such management, were treated according to a standard therapeutic strategy, and were able to receive axitinib as a second-line drug. We analyzed the incidence of hand-foot syndrome. Furthermore, we compared relative dose intensity between patients in the pioneer and contemporary groups who took sunitinib as first-line therapy. We also compared overall survival between the two groups to determine whether adverse event management improved prognosis. The incidence of hand-foot syndrome was significantly reduced by aggressive adverse event management. Relative dose intensity was significantly higher in the contemporary group than in the pioneer group. Median survival time was significantly longer in the contemporary group than in the pioneer group. Our results suggest that aggressive management of adverse events associated with targeted drugs, the use of sunitinib as a first-line therapy, and the availability of axitinib as a second-line therapy all contribute to prolonged survival for metastatic renal cell carcinoma patients.

We report a case of renal cell carcinoma in a horseshoe kidney in a 48-year-old man. A medical checkup revealed a renal tumor in the right kidney. Computed tomographic scan (CT) showed a renal tumor measuring about 4 cm in diameter on the right side of a horseshoe kidney. Right heminephrectomy was performed for renal cell carcinoma. Pathologic examination revealed renal cell carcinoma, clear cell subtype, G1>G2, INF alpha, pT3a, V (-). In addition to our case, we review 66 cases of renal cell carcinoma occurring in a horseshoe kidney which have been reported in Japanese publications; our case is the 67th.