Targeting HCCR expression resensitizes gastric cancer cells to chemotherapy via down-regulating the activation of STAT3.

The human cervical cancer oncogene (HCCR) has been found to be overexpressed in a variety of human cancers. However, the level of expression of HCCR and its biological function in gastric cancer are largely unknown. In this study, we evaluated HCCR expression in several gastric cancer cell lines and in one normal gastric mucosal cell line. We established a 5-FU-resistant gastric cancer cell subline, and we evaluated its HCCR expression. HCCR expression levels were high in gastric cancer lines, and expression was significantly increased in the 5-FU-resistant cancer cell subline. HCCR expression affected cell growth by regulating apoptosis in the cancer cells, and it had a positive correlation with p-STAT3 expression. Western blot and luciferase reporter assays showed that the activation of STAT3 upregulated HCCR expression in a positive feedback loop model. In vivo and in vitro studies showed that HCCR plays an important role in the apoptosis induced by 5-FU. Our data demonstrate that HCCR is probably involved in apoptosis and cancer growth and that it functions as a p-STAT3 stimulator in a positive feedback loop model. In gastric cancer cells, HCCR confers a more aggressive phenotype and resistance to 5-FU-based chemotherapy.

[Clinical significance of radical cystectomy with extended lymphadenectomy].

OBJECTIVE: To evaluate the prognosis of patients treated with radical cystectomy and extended lymphadenectomy for invasive bladder cancer and to describe the association of the primary bladder tumor grade, stage, lymph node status and lymph node density with clinical outcomes. METHODS: A retrospective analysis was done of 32 consecutive cases with bladder cancer who received radical cystectomy and extended lymph node dissection from January 2006 to December 2010 in the Department of Urology, Peking University First Hospital. All the patients were scheduled for the follow-up. The survival data were analyzed with the tumor grade, stage, lymph node status and other factors that might relate to the prognosis by statistics. RESULTS: All the cases were diagnosed as invasive urothelial bladder cancer by preoperative biopsy or TUR-Bt. During the follow-up, 6 patients (18.8%) got disease progression, and 4 patients died (12.5%). Overall survival rate was 87.5%. In 32 patients, 17 months and 3 year survival rates were (88.7 ± 12.1)% and (81.8 ± 17.0)%, respectively. From the tumor grade point of view, 6 patients belonged to G2, and 26 cases G3. All deaths were graded G3. G3-class 3-year survival rate was (74.6 ± 23.9)% (P> 0.05, compared with G2). From the analysis of stage, T1 and T2 stages had no death during the follow-up. The 17-month survival rate of T3 group was (60.0 ± 42.9)%, the 8-month survival rate of T4 group was (87.5 ± 22.9)%. There were 9 patients with positive lymph nodes (28.1%) and 23 with negative in (71.9%). The number of dissection lymph nodes was from 7-50 ( average 22.8 ). The 17-month survival rate of patients with positive lymph node was (50.0 ± 44.6)%. The 3-year survival rate of patients with negative lymph node was (92.3 ± 14.5)% (P<0.05). The 3-year survival rate of patients with lymph node density less than 20% was (88.8 ± 15.4)%. The 8-month survival rate of patients with lymph node density greater than 20% was (66.7 ± 53.3)% (P<0.05). CONCLUSION: Radical cystectomy with extended lymph node dissection can improve the prognosis of patients with invasive bladder cancer. Tumor stage, lymph node status and lymph node density are closely related to the patient's survival.