HMGB1-mediated autophagy confers resistance to gemcitabine in hormone-independent prostate cancer cells.

As a main treatment of prostate cancer, castration therapy has been widely applied in the clinic. However, the therapeutic strategy for hormone-independent prostate cancer (HIPC) was not satisfied. Gemcitabine is an important chemotherapeutic agent that has been approved for the treatment of numerous human solid tumors, including HIPC, whereas the gemcitabine resistance has become a serious problem in clinical chemotherapy. In the present study, the mechanisms of resistance to gemcitabine were investigated in HIPC cell lines. The results demonstrated that the autophagy markers were induced significantly in HIPC cells subsequent to gemcitabine treatment. Meanwhile, administration of gemcitabine to HIPC cells increased the expression of high mobility group box1 (HMGB1). Furthermore, the gemcitabine-induced autophagy response was attenuated in stable HIPC cells harboring HMGB1 shRNA. Notably, the HIPC cells stably transfected with HMGB1 shRNA or treated with autophagy inhibitors were more sensitive to gemcitabine compared with the control group. These data suggested that inhibition of HMGB1 increased the sensitivity to gemcitabine by decreasing autophagy response in HIPC cells. Overall, the present findings demonstrate a new mechanism for the resistance to gemcitabine in HIPC cell lines.

[Nine cases of laparoscopic retroperitoneal lymph node dissection].

OBJECTIVE: To assess the effects of laparoscopic retroperitoneal lymph node dissection in the treatment of stage I nonseminomatous testicular cancer. METHODS: From January 2001 to May 2002, laparoscopic retroperitoneal lymph node dissection was performed on 9 patients with stage I nonseminomatous testicular cancer. RESULTS: The procedure was successful in all patients. The mean operation time was 260 minutes. None of the patients required blood transfusion and had major complications intraoperatively or postoperatively. The average period of hospitalization after the operation was 5.5 days. With a mean following-up of 9 months, retroperitoneal recurrence was not seen. CONCLUSIONS: Laparoscopic retroperitoneal lymph node dissection is feasible for stage I nonseminomatous testicular cancer and its procedure is safe, effective and minimally invasive.