Genetic variants in CHEK1 gene are associated with the prognosis of thoracic esophageal squamous cell carcinoma patients treated with radical resection / 华中科技大学学报（医学）（英德文版）

CHEK1 gene is known to play an important role in tumor progression by cell cycle control. However, the association between CHEK1 and the prognosis of esophageal squamous cell carcinoma (ESCC) is unclear. In this study, we explored the association between genetic variants in CHEK1 gene and prognosis of ESCC patients treated with radical resection. A total of 131 thoracic ESCC patients who underwent radical resection were included in this retrospective study and genotyped using the MassArray method. According to the univariate Cox hazard analysis, the GT/TT genotype of CHEK1 rs555752 was shown to be strongly related to a decreased overall survival (OS) (HR=2.560, 95% CI: 1.415-4.631, P=0.002) and disease-free survival (DFS) (HR=2.160, 95% CI: 1.258-3.710, P=0.005). Furthermore, according to the multivariate Cox hazard analysis and multiple testing, patients with the GT/TT genotype of CHEK1 rs555752 had a notably decreased OS (HR=2.735, 95% CI: 1.468-5.096, P=0.002, Pc=0.006) and DFS (HR=2.282, 95% CI: 1.292-4.023, P=0.004, Pc=0.012). In conclusion, genetic variants of the CHEK1 gene are significantly related to OS and DFS of ESCC patients, and may therefore be predictors of the prognosis of thoracic ESCC after surgery.

Impact of 5-fluorouracil on glucose metabolism and pancreatic pathology in rats / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To explore the impact of 5-fluorouracil (5-FU) on glucose metabolism and pancreatic pathology.</p><p><b>METHODS</b>Twenty Wistar rats were divided into 5-FU group(n=10, chemotherapy was administered intraperitoneally to animals at a dose of 20 mg/kg daily for continuous 5 days) and control group (n=10, sodium chloride was administered intraperitoneally to animals with the same dose at the same time ). Glucose tolerance was evaluated 2 and 7 days following 5-FU treatment by serial measurement of blood glucose before and after an oral glucose load. Plasma insulin concentration was determined by radioimmunoassay. Pancreatic pathology was examined with morphological method and the ultrastructural changes of β cells were observed by transmission electron microscope.</p><p><b>RESULTS</b>Fasting blood glucose level was significantly higher in the 5-FU group than that in the control group [(7.6±0.9) mmol/L vs. (4.6±0.6) mmol/L at day 2; (8.9±1.0) mmol/L vs. (4.7±0.6) mmol/L at day 7, P<0.01]. Insulin releasing test indicated that the early phase insulin response to glucose load was significantly diminished in animals treated with 5-FU at day 2. Insulin level was significantly lower in the 5-FU group than that in the control group at 30 min (P<0.01). The peak secretion time of plasma insulin in 5-FU group was at 60 min, similar to the control group; and plasma insulin level decreased more slowly. Plasma insulin level was higher in 5-FU groups than in control groups on 120 min and 180 min. At day 7, Insulin level was lower in the 5-FU group than that in the control group on 60 min, and the peak secretion time of plasma insulin was delayed to 120 min. Plasma insulin level was significantly increased in 5-FU group than that in control group on 180 min(P<0.01). No gross histopathological damage to the pancreas was observed at day 2 and 7 following administration of 5-FU. The structural changes of mitochondria were mainly the quantities of secretory granule diminished at day 7 under transmission electron microscope. Dilated rough endoplasmic reticula, swollen mitochondria, and the presence of adipose drops in lysosomes were found in few cells.</p><p><b>CONCLUSIONS</b>5-FU-induced hyperglycemia appears to be mediated in part by a relatively deficient insulin secretion to glucose stimulation. A relative deficiency in insulin secretion following 5-FU treatment appears to be related to β cells function impairs with islet cell ultrastructural changes induced by 5-FU.</p>

Relationship between VEGF-C expression and nasopharyngeal carcinoma proliferation and metastasis / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To detect the expression of VEGF-C in nasopharyngeal carcinoma (NPC) and explore its relationship with proliferation and metastasis of NPC.</p><p><b>METHODS</b>Biopsy specimens of 62 NPC patients were divided into 2 equal portions, one for immunohistochemical staining with VEGF-C polyclonal antibody by streptavidin peroxidase method, another for flow cytometry with Ki67 antibody to analyze the proliferation of tumors. The patients were followed up periodically, and then their 3-year survival and the cause of death were statistically analyzed.</p><p><b>RESULTS</b>Of the 62 patients, the percentage of VEGF-C positive cells in the tumors ranged from 0 - 82%, 17 (27.4%) were negative, 13 (21.0%) weak positive, 18 (29.0%) moderate positive and 14 (22.6%) strong positive. Ki67 positive tumor cells ranged from 0 - 52%, 40 cases (64.5%) showed low expression which include 15 cases of negative, 22 (35.5%) showed high expression. There was a direct relationship between the expression of VEGF-C and Ki67 (r = 0.323, P < 0.05). The 3-year survival rate of 62 patients was 66.1%. The expression of VEGF-C in the patients with positive lymph node was much higher than that with negative lymph node (P < 0.01). Among the 8 patients with distant metastasis, their VEGF-C expression was strong positive while among the 21 disease free survival patients, their VEGF-C expression was (-) or (+) account for 80.9%. An inverse correlation was found between the VEGF-C expression and prognosis of NPC patients, but the difference has no statistical significance (r = -0.219, P > 0.05).</p><p><b>CONCLUSION</b>High expression of VEGF-C is related with proliferation and metastasis of NPC cells. It is not an independent prognostic factor, but a predictive marker of disease-free survival of NPC patients.</p>