Antiproliferative effect of octreotide on gastric cancer cells mediated by inhibition of Akt／PKB and telomerase

AIM: To investigate the antiproliferative effect of octreotide,a long-acting analogue of somatostatin, on gastric cancer cell line SGC7901 and its possible molecular mechanisms.METHODS: Gastric cancer cell line SGC7901 employed in the study was treated with 0.008, 0.04, 0.2, 1, 5 and 25μg@ml-1 of octreotide respectively for 24 h to evaluate the antiproliferative effect of somatostatin analog on the tumor cells by MTT assay method. To elucidate the underlying mechanism, the cells were exposed to 1 μg@ml-1 of octreotide for 0, 12, 24 and 48 h, when their Akt/PKB and telomerase activities were respectively determined using PCR-ELSIA and nonradioactive protein kinase assay protocols. The same experimental procedures were also performed in the control cells that were treated with corresponding vehicles instead of somatostatin analog.RESULTS: After exposed to octreotide for 24 h at the concentrations of more than 1 μg@ml-1 SGC7901 cells exhibited a dose-dependent inhibition of growth with the inhibiting rate to be as high as 34.66 % when 25 μg@ml-1 of octreotide was applied. The Akt/PKB and telomerase activity of SGC7901 cells was significantly inhibited when the cells were exposed to 1 μg@ml-1 of octreotide for 12, 24 and 48 h compared with that of their control counterparts (P＜0.01),both of which exhibited in a time-dependent manner.CONCLUSION: The antiproliferative effect of octreotide on SGC7901 cells might be mediated by the inhibition of Akt/PKB and telomerase.     

High expression of Sirt7 served as a predictor of adverse outcome in breast cancer

Objective: Sirt7, as one of the seven Sirtuin family members, which plays distinct roles in cancer progression, is bringing emerging attention due to its oncogenic characteristic. The expression of Sirt7 in breast cancer remained unclear, and the aim of this study was to elucidate its role in breast cancer. Methods: A total of 188 cases included in this study were immunohistochemically evaluated for Sirt7, and western blot assay was used to assess its expression in breast cell lines as well as 36 breast cancer tissues and 36 paired non-cancerous tissues. Results: Upregulation of Sirt7 was found in breast cancer cell lines and breast cancer tissues (P < 0.001) by western blot analysis. Sirt7 was highly expressed in breast cancer tissue samples (67.8%) compared to adjacent normal breast tissues (31.8%) by immunohistochemical assay. It was also observed that the high expression level of Sirt7 was significantly correlated with high histological grade (P = 0.039) and negatively related to overall survival (P = 0.006). Sirt7 proved to be an independent prognostic factor (P = 0.007) in breast cancer. Conclusions: Sirt7 expression was implicated with high histological grade and independently predicted poor clinical outcome in patients with breast cancer, suggesting that Sirt7 might play a role in the malignant progression of breast cancer.     

Relationship between the expression of MDR1 in hepatocellular cancer and its biological behaviors

Objective: By the detection of HBV infection, AFP and AST, the targets of biological behavior and the gene expression of multi-drug resistance gene 1 (MDR1) in hepatocellular carcinoma (HCC), we investigate characteristics of the expression of MDR1 in HCC and its relationship with HCC biological behavior. Methods: Using real-time fluorescence quantitative PCR (FQ-PCR) to detect the expressions of MDR1 in 102 samples of HCC tissue and 20 samples of non-cancerous tissue, we analyze the relationship between expressions of MDR1 and biological characteristics of HCC. Results: The expression of MDR1 in HCC is 0.55±0.27, and in normal liver tissues is 0.23±0.10, respectively. The expression in HCC is higher than it in normal liver tissue, the difference is statistically significant (P<0.05) and the difference between the expression and the HCC envelopes is statistically significant, and the expression increases along with the increase of Edmondson classification (P<0.05). HBV infection, AFP positive, the rise of AST, all these factors have positive correlations with the expression (r=0.463, 0.473, 0.299). In MDR1 expressions of HCC patients, the survival curve of the negative is higher than that of the positive, but the difference is not statistically significant. Conclusion: There are drug resistance phenomena in HCC, MDR1 expression may play an important role in primary HCC drug resistance. HBV infection can be detected as a reference indicator of HCC chemotherapy resistance, plasma levels of AFP, AST can be used as a reference index change dynamic monitoring of MDR1 expression.     

Increased expression of HMGB3: a novel independent prognostic marker of worse outcome in patients with esophageal squamous cell carcinoma

HMGB3, an X-linked member of the high-mobility group (HMG) superfamily of HMG proteins, has been shown to affect numerous tumorigenic progression. However, the expression and the prognostic role of HMGB3 in esophageal squamous cell carcinoma (ESCC) remained unknown. In this study, we examined the HMGB3 expression in ESCC tissues and adjacent nontumorous tissues by qRT-PCR and immuohistochemistry. Statistical analyses were applied to test for prognostic and diagnostic associations. The mRNA levels of HMGB3 were found to be significantly higher in tumorous tissues than in the adjacent normal tissues. We found that the HMGB3 expression was higher in tumorous tissues than in the adjacent non-tumorous tissues by immunohistochemical analysis of paired tissue specimens (P < 0.001). Moreover, there was a significant correlation between HMGB3 expression and gender (P = 0.037), clinical stage (P = 0.038), T classification (P = 0.013) and N classification (P = 0.017). Patients with higher HMGB3 expression had shorter overall survival than those with lower HMGB3 expression. Multivariate Cox analysis indicated that HMGB3 expression is an independent prognostic factor for overall survival (HR = 0.591, 95% CI = 0.379-0.793, P = 0.039). In summary, these findings demonstrate that HMBG3 may be a potential molecular marker for predicting the prognosis of ESCC patients.     

Impact of chemokine receptor CXCR3 on tumor-infiltrating lymphocyte recruitment associated with favorable prognosis in advanced gastric cancer

Chemokine receptor CXCR3 has been proved to play an important role in tumorigenesis and tumor progression in many malignancies, but its precise efficacy on gastric cancer (GC) has not been evaluated yet. The present study was aimed to explore the correlation of chemokine receptor CXCR3 with tumor-infiltrating lymphocytes (TILs) and prognosis in advanced gastric cancer (GC). Expression of CXCR3 and CD4+, CD8+ TILs was conducted in 192 advanced GC specimens and 48 corresponding paracancerous tissues by immunohistochemical (IHC) analysis. CXCR3 expression in GC tissues was significantly higher than that in paracancerous tissues (P<0.001) and CD8+, CD4+ TILs infiltration increased with high CXCR3 expression (P=0.032 and P<0.001, respectively). Our study showed significantly lower CXCR3 expression in patients with greater tumor invasion depth and lymph node metastasis compared with patients with lesser tumor invasion depth and without lymph node metastasis (P=0.002 and P=0.001, respectively). Univariate analysis indicated that patients with high CXCR3 expression and high CD8+ TILs infiltration had longer overall survival (OS) (log-rank test, P<0.001 and P=0.002, respectively). Univariate and multivariate analyses indicated that CXCR3 expression was an independent prognostic factor for OS (P=0.002). The present study suggested that CXCR3 expression was upregulated in advanced GC and was associated with increased CD4+, CD8+ TILs infiltration and improved OS. Therefore, CXCR3 overexpression is implicated as a favorable prognostic biomarker in human advanced GC.     

Genetic polymorphisms of pharmacogenomic VIP variants in the lhoba population of southwest China

Background: It is well-established that differences among ethnic groups in drug responses are primarily due to the genetic diversity of pharmacogenes. A number of genes or variants that play a crucial role in drug responses have been designated Very Important Pharmacogenes (VIP) by the PharmGKB database. Clarifying the polymorphic distribution of VIPs in different ethnic groups will aid in personalized medicine for specific populations. Methods: We sequenced 85 VIP variants in the Lhoba population based on the PharmGKB database. The polymorphic distribution of the 85 VIP variants in 100 Lhoba subjects was determined and compared with that of 11 major HapMap populations, including ASW, CEU, CHB, CHD, GIH, JPT, LWK, MEX, MKK, TSI, and YRI. We used χ² tests to identify significantly different loci between these populations. We downloaded SNP allele frequencies from the ALlele FREquency Database to observe the global genetic variation distribution for these specific loci. And then we used Structure software to perform the genetic structure analysis of 12 populations. Results: Based on comparisons of selected available loci, we found that 23, 28, 16, 10, 20, 16, 24, 19, 22, 21 and 36 of the selected VIP variant genotype frequencies in the Lhoba population differed from those of the ASW, CEU, CHB, CHD, GIH, JPT, LWK, MEX, MKK, TSI, and YRI populations, respectively. In addition, Pairwise FST values and clustering analyses also showed the VIP variants in Lhoba exhibited a close genetic affinity with CHD, CHB and JPT populations. Conclusion: Our results complement pharmacogenomic data on the Lhoba ethnic group and may be helpful in the diagnosis of certain diseases in minorities.     

Role of transcriptional factor Nrf2 in the acute lung injury of mice

Objective: This study aimed to investigate the expression and role of Nrf2 in the acute lung injury (ALI) of mice. Methods: A total of 60 BABL/c mice were randomly divided into 2 groups: ALI group and control group. In ALI group, ALI was introduced by injection of LPS. Immunohistochemistry was performed to detect Nrf2 expression in the lung; Western blot assay was employed to detect the expression of Nrf2 in the lung homogenate; ELISA was conducted to detect the expression of Nrf2 in the lung homogenate and BALF. Results: As compared to control group, ALI mice had a high Nrf2 expression in the lung as shown in immunohistochemistry, and the Nrf2 expression in the lung homogenate and BALF also increased markedly (P<0.05). Conclusion: The Nrf2 expression increases in the lung and BALF of ALI mice, suggesting that Nrf2 is involved in the inflammation during ALI and may serve as a new target in the therapy of ALI.     

口腔黏膜鳞状细胞癌、上皮异常增生及正常黏膜组织拉曼光谱研究

目的 研究口腔黏膜鳞状细胞癌、上皮重度异常增生及正常黏膜组织的拉曼光谱特征,以期为拉曼光谱诊断口腔黏膜癌变提供依据.方法 收集手术切除的新鲜口腔黏膜鳞状细胞癌组织56例,重度上皮异常增生组织50例及正常黏膜组织32例,采用配备光纤探头的便携式拉曼光谱仪获取拉曼光谱.应用主成分分析法(principle component analysis,PCA)结合判别函数分析(discriminant function analysis,DFA)对不同组织的光谱数据进行分析,建立诊断模型对口腔鳞状细胞癌、上皮重度异常增生及正常黏膜的光谱数据进行鉴别,应用交互验证方法对诊断模型进行验证.结果 口腔鳞状细胞癌、上皮重度异常增生及正常黏膜组织间的拉曼光谱存在差异,主要表现为口腔鳞状细胞癌和上皮重度异常增生组织光谱中对应核酸、蛋白质及脂类物质的谱峰明显高于正常黏膜上皮组织;鉴别诊断建模的总体分类准确率达96.4％(133/138),交互验证的分类准确率达92.8％(128/138).结论 口腔鳞状细胞癌和上皮重度异常增生组织中细胞增殖代谢明显高于正常黏膜组织;应用PCA-DFA建立的分类诊断模型可以很好地区分3种不同组织的光谱数据.     

ε-聚赖氨酸与灭菌注射用水湿化效果二阶段交叉试验分析

目的采用二阶段交叉试验分析ε-聚赖氨酸与灭菌注射用水的湿化效果。方法选择我院神经内科94例长期氧疗患者行分组研究。按患者入院顺序将其编号,再按随机数字表法将其分为A组(n=47)及B组(n=47)。A组第一阶段湿化液为灭菌注射用水,第二阶段湿化液为ε-聚赖氨酸;B组第一阶段湿化液为ε-聚赖氨酸,第二阶段湿化液为灭菌注射用水。对比两组采样菌落数、合格率及氧疗舒适度。结果通过二阶段交叉试验发现:A组及B组在应用ε-聚赖氨酸作为湿化液期间菌落数更少(P0.01)。湿化液灭菌注射用水的合格率为82.98%,明显低于ε-聚赖氨酸的合格率100.00%(P0.01)。与灭菌注射用水相比,应用ε-聚赖氨酸作为湿化液具有更温暖、更湿润、舒适度更高、异味及噪声更少等优点(P0.01)。结论应用ε-聚赖氨酸作为氧疗湿化液可有效减少湿化液污染,增进患者氧疗舒适度,值得临床推广应用。