Association between single nucleotide polymorphisms of the transforming growth factor-ß1 gene and overall survival in unresectable locally advanced non-small-cell lung cancer patients treated with radio(chemo)therapy in a Chinese population.

The outcome is variable for unresectable locally advanced non-small-cell lung cancer (ULANSCLC) patients treated with radio(chemo)therapy. The aim of this study is to investigate whether single-nucleotide polymorphisms (SNPs) in the transforming growth factor-beta1 (TGF-ß1) gene are associated with overall survival (OS) in ULANSCLC patients treated with definitive radio(chemo)therapy. A total of 109 patients who had available blood samples and complete clinical and follow-up information were enrolled. DNA from blood was genotyped for two SNPs: TGF-ß1 C-509T and T+869C. Kaplan-Meier survival analysis, log-rank test, and Cox's proportional hazard model were used to evaluate associations between genotypes and OS. Log-rank test showed that TGF-ß1 C-509T significantly correlated with OS (pooled P = 0.017). Both univariate and multivariate analyses showed that TGF-ß1 C-509T CC genotype was significantly associated with better OS than CT or TT genotypes. These results indicate that TGF-ß1 C-509T CC genotype is significantly associated with better OS in ULANSCLC patients treated with radio(chemo)therapy as a potential independent survival predictor.

Intraperitoneal recombinant human endostatin combined with chemotherapy for refractory malignant ascites due to gastrointestinal cancer: a pilot study.

BACKGROUND/AIMS: To evaluate the efficacy, safety and consequent impact on quality of life of a combined-modality using intraperitoneal recombinant human endostatin, Endostar and chemotherapy in patients with refractory malignant ascites caused by gastrointestinal cancer. METHODOLOGY: Patients received combined intraperitoneal therapy repeated 3 weeks, which consisted of 5-fluorouracil 600 mg/m2 and cisplatin 30 mg/m2 on day 1-3 followed by Endostar 60 mg on day 4. RESULTS: A total of 18 patients were treated. The overall response rate was 55.6%, with a complete remission rate of 22.2%. The malignant ascites controlled rate was 77.8%. The median time to progression and overall survival was 2.6 and 4.9 months, respectively. Therapy-associated toxicities were generally mild to moderate treatment-related deaths. The mean Karnofsky performance status score was significantly improved from 59.4±2.49 at enrollment to 69.4±3.18 at 2 weeks after the first cycle of therapy (p=0.001). The mean score for overall ascites-associated symptoms was improved from 5.3±0.35 to 4.0±0.23 (p=0.004). Significant improvements of 6 individual symptoms were also observed. CONCLUSIONS: The combined-modality using intraperitoneal Endostar and chemotherapy is effective and safe in selected patients with refractory malignant ascites due to gastrointestinal cancer and significantly improves patient's quality of life with encouraging survival, which merits further investigation.

Adjuvant combined systemic chemotherapy and intraperitoneal chemotherapy for locally advanced gastric cancer.

The optimal adjuvant treatment modality for gastric cancer has not been well defined. The aim of this study was to evaluate the efficacy and feasibility of adjuvant combined systemic and intraperitoneal chemotherapy (ACSIP) in high-risk patients with locally advanced gastric cancer. Between June 2003 and December 2008, 62 eligible patients with serosa-infiltrating and/or node-positive gastric cancer following curative gastrectomy with D2 lymphadenectomy received ACSIP, consisting of intravenous oxaliplatin 85 mg/m(2) on day 1 followed by leucovorin (LV) 200 mg/m(2) and 5-fluorouracil (5-FU) 450 mg/m(2) on days 1-3, intraperitoneal 5-FU 600 mg/m(2) on days 4-5 and cisplatin (CDDP) 40 mg/m(2) on day 5. Survival rates, the sites of first treatment failure and safety were analyzed. At a median follow-up of 45 months (range 7-101), the 3-year disease-free survival (DFS) and overall survival (OS) rates were 66.1 and 74.2%, respectively. Initial peritoneal and hepatic failures were found in 6 (24.0%) and 3 (12.0%) of the 25 patients with recurrence, respectively. Neutropenia, gastrointestinal side effects and peripheral neuropathy were the most common grade 3-4 toxicities; however, they were all infrequent and manageable. No serious surgical complications or treatment-related mortality was observed. The results of this study indicate that ACSIP is effective and feasible for locally advanced gastric cancer with encouraging survival rates and possibly decreased peritoneal and hepatic recurrences. The benefits of this promising combined adjuvant treatment modality warrant further studies.

Cell proliferation, apoptosis and the related regulators p27, p53 expression in hepatocellular carcinoma.

AIM: To investigate the expression of cell apoptosis, proliferation and the related regulators p27, p53 in hepatocellular carcinoma (HCC). METHODS: The expression of p27, p53, proliferating cell nuclear antigen (PCNA) and apoptosis in 47 HCC specimens and 42 surrounding non-cancerous tissues were detected by the immunohistochemistry and terminal deoxy-nucleotidyl transferase-mediated nick end labeling (TUNEL) technique. Meanwhile, the clinical significance of them was analyzed combining with the clinicopathological factors and follow-up data. RESULTS: (1) The average proliferating index and apoptotic index in HCC were significantly higher than that in adjacent liver tissues. The proliferating index was associated with extrahepatic metastasis. The apoptotic index was significantly lower in TNM stage I-II than in stage III-IV. The proliferating index of groups with p53-/p27+ was significantly lower than that in group with p53+/p27- (P = 0.030); (2) The level of p27 in the cytoplasmic fraction was higher in non-tumoral liver tissues and was associated with clinical stage; (3) Survival analysis showed advanced stage (P = 0.031) and with extrahepatic metastasis (P = 0.045) was significantly associated with shorter survival. In addition, the prognosis of patients with p53-/p27+ was longer than that of patients with p53+/p27- (P = 0.0356). CONCLUSION: The p53 mutation and decreased p27 expression might be involved in the imbalance of proliferation and apoptosis in HCC. Cytoplasmic displacement might lead to the inactivation of p27 protein in HCC cells and acts early during carcinogenesis of HCC. The combined examination of p27, and p53 expression allows reliable estimation of prognosis for patients with primary hepatic carcinoma.