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The occurrence and development of colorectal cancer are regulated by many factors and circular RNAs are also involved.The studies have shown that some circular RNAs have high sensitivity and specificity in the diagnosis of colorectal cancer,and have a certain promoting effect on liver and lung metastasis of colorectal cancer involved in signal transduction,DNA repair.The expressions of some circular RNAs are related to the survival time of patients.In addition,down-regulation of partial circular RNAs enhances radiosensitivity of colorectal cancer cells and participates in a variety of tumor-associated signaling pathways in chemotherapeutic-resistant colorectal cancer cells.
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Objective To investigate the effect of enhancer of zeste homolog 2 (EZH2) knockdown on chemosensitivity to oxaliplatin in human gastric cancer cell line SGC7901.Methods Small interfering RNA (siRNA) fragments were designed and synthesized for EZH2 mRNA sequence and divided into siRNA-1 group,siRNA-2 group and siRNA-3 group.They were transfected into gastric cancer cell line SGC7901.The negative control group and blank control group were set up at the same time.The expressions of EZH2 mRNA and protein in the SGC7901 cells were detected by quantitative real-time polyme-rase chain reaction (qRT-PCR) and Western blotting.CCK-8 assay was used to detect cell proliferation inhibition rates of SGC7901 cells treated by different concentrations of oxaliplatin.Results After transfection of EZH2 siRNA,the relative expression levels of EZH2 mRNA in siRNA-1 group,siRNA-2 group,siRNA-3 group were 0.615 ±0.190,0.241 ±0.152 and 0.450 ± 0.097.The relative expression levels of EZH2 mRNA of the three groups were lower than that in the negative control group (1.165 ± 0.376),and the differences were statistically significant (P =0.028;P =0.002;P =0.007).After transfection of the best siRNA fragment into SGC7901 gastric cancer cells,the relative expre-ssion levels of EZH2 protein in interference group,blank control group and negative control group were 0.036 ± 0.017,0.362 ± 0.026 and 0.398 ± 0.036,and the diffe-rence among the three groups was statistically significant (F =157.745,P ＜ 0.001).The difference between interference group and negative control group was statistically significant (P =0.001),as compared with the blank control group (P =0.002).When oxaliplatin concentration was 2,4,8 and 16 μg/ml,the differences of cell proliferation inhibition rate among interference group,negative control group and blank control group were statistically significant [(18.107 ± 2.822)％,(5.867±2.272)％,(5.333 ±1.883)％,F=28.185,P=0.001;(54.953 ±2.550)％,(22.177±1.871)％,(20.077±6.032)％,F=74.206,P＜0.001;(60.337±1.641)％,(34.597± 3.592)％,(30.227 ±5.273)％,F=54.897,P＜0.001;(78.340 ±2.081)％,(61.857 ±3.507)％,(63.077 ± 8.473) ％,F =8.586,P =0.017].There was no significant difference among groups of oxaliplatin at the concentration of 32 μg/ml [(83.450 ±3.715)％,(72.190 ±3.948)％,(70.731 ± 17.080)％,F=1.358,P =0.326].The median inhibitory concentration (IC50) of oxaliplatin in siRNA group,negative control group and blank control group were 5.178,12.643,13.601 μg/ml.Conclusion Down-regulation of EZH2 gene expression can significantly inhibit the proliferation of gastric cancer cells,and effectively enhance the sensitivity of gastric cancer cells to oxaliplatin,which indicates EZH2 may play important roles in the development of gastric cancer chemotherapy.These results provide an important theoretical basis for gene therapy of gastric cancer.
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With the development of molecular biology of cancer,molecular targeted therapy which tar-geted the driver genes in lung cancer has become an inevitable part of the treatment of advanced lung cancer. The most successful examples of targeted therapy are targeting epidermal growth factor receptor (EGFR)and anaplastic lymphoma kinase (ALK).More and more driver genes have been discovered,including ROS1 gene fusion,fibroblast growth factor receptor 1 amplification,KRAS,BRAF,PIK3CA gene mutation and so on.It is meaningful for guiding the treatment of lung cancer that defines the mutation incidence and clinical significance of driver genes in lung cancer.
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Molecular targeted therapy plays an important role in the treatment of gastrointestinal cancer.In recent years,a large number of targeted drugs have been developed and tested in clinical trials to verify their efficacy and security.The better efficacy and security of targeted drugs represented by monoclonal antibodies and tyrosine kinase inhibitors have been demonstrated in each phase of clinical trials.
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Objective To investigate the expression of human ribonucleotide reductase large subunit M1 (RRM1) in the patients with gastric adenocarcinoma and its clinical significance.Methods The expressions of RRM1 were detected in 88 cases of gastric adenocarcinoma and 20 cases of nonnal gastric tissues by immunohistochemical method.The correlations between the expression of RRM1 and clinicopathological characteristics were analyzed.Results The positive expression rate of RRM1 in gastric adenocarcinoma was 83.0％(73/88).And RRM1 was negative in the entire normal gastric tissues.The positive expression of RRM1 was not associated with patient's age (x2 =0.352,P=0.553),gender (x2 =0.493,P=0.482),depth of tumor infiltration depth (x2 =0.007,P =0.933),lymph nodes metastasis (x2 =0.121,P =0.728) and distant metastasis (P =0.415).But it was related to the degree of tumor differentiation (x2 =7.740,P =0.021) and clinical stage (x2 =5.733,P =0.017).Conclusion The expression of RRM1 is positive expression in most gastric adenocarcinoma,and is associated with the degree of tumor differentiation and clinical stage.It is of great significance to detect the expression of RRM1 in gastric adenocarcinoma for confirming the diagnosis and judging malignant degree of the tumor.It also may have potential value in choosing the best therapeutic scheme and estimating prognosis.
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Objective To explore the expressions ofβ-catenin in gastric adenocarcinoma primary tumors and metastatic lymph nodes,and to determine if it is associated with infiltration degree and whether it can provide the basis for gastric cancer metastasis.Methods The expressions ofβ-catenin were detected in 156 patients with gastric adenocarcinoma specimens,40 cases with the corresponding lymph nodes and 12 cases of normal gastric tissues by the method of immunohistochemistry.The expressions ofβ-catenin in gastric adenocarcinoma and corre-sponding lymph node metastases were analysed.The relationship between the expression of β-catenin and the clinical pathological features of gastric adenocarcinoma was ascertained,and difference between them was observed.Results The positive expression rate ofβ-catenin in normal gastric tissue membrane was 100.0%(12/12).The expression rate ofβ-catenin was 29.5%(46/156)in adenocarcinoma cell membrane,and it was 10.0%(4/40)in metastatic lymph nodes cell membrane.The positive expression ofβ-catenin was not associated with patient′s age(χ2 =2.160,P=0.142),gender (χ2 =1.229,P=0.268),but it was associated with tumor infiltration degree (χ2 =4.032,P=0.045 ),degree of tumor differentiation (χ2 =6.093,P=0.048),tumor stage (χ2 =4.591,P=0.032),and metastasis lymph nodes (χ2 =4.485,P=0.034).The incidence of abnor-mal or loss expression ofβ-catenin in gastric adenocarcinoma metastatic lymph nodes was higer than that in gastric adenocarcinoma (χ2 =6.362,P=0.012).Conclusion The expression of β-catenin will be a great help to judge the biological behaviors such as the malignant degree of tumor and the capacity of tumor invasion and metas-tasis.
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Combined therapy consisting of radiotherapy,chemotherapy and palliative surgery is the primary management for locally advanced pancreatic cancer,with the purpose of prolonging survival and improving life quality.Gemcitabine is the standard chemotherapy at present.Gemcitabine-based combinations show a definite effect,and the combination with targeted drugs also has a certain degree of efficacy.The development of new chemotherapy drugs and targeted drugs provides more ways for the teatment of locally advanced pancreatic cancer.
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EML4-ALK fusion oncogene represents a new molecular target which appears mainly in lung adenocarcinoma.EML4-ALK is detected more frequently in young non-small-cell lung cancer patients who never or light smoke.ALK inhibitors(crizotinib)for the treatment of the EML4-ALK-positive non-small cell lung cancer has a high response rate.This finding can improve the individual treatment of non-small cell lung cancer.
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Regulatory T cells are a specialized subpopulation of T lymphocytes that play important roles in immunosuppression, maintaining immune balance and self-immune tolerance. The latest researches show that not only that FOXP3 + CD25+ CD4 + regulatory T cells (Tregs) are expressed in tumor tissues and peripheral blood of patients of various forms of cancers, Tregs also participate in the occurrence, development and prognosis of tumors.
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Objective To study the expression of vascular endothelial growth factor-C (VEGF-C) and VEGF receptor-3 (VEGFR-3) in non-small cell lung cancer (NSCLC), and to explore its relationship with lymph node metastasis. Methods Sixty patients with NSCLC were studied. The expression of VEGF-C and VEGFR-3 was detected by immunohistochemistry in lung cancer samples, and its relationship to clinical and pathological data was analyzed. Results The positive expression rate of VEGF-C in NSCLC tissues was 68.3% (41/60), the expression rate of VEGFR-3 was 53.3% (32/60). The expression of VEGF-C was related with the degree of cell differentiation in lung cancer. Both the expressions of VEGF-C and VEGFR-3 were positively associated with lymph node metastasis. There was a positive correlation between VEGF-C and VEGFR-3 expressions (r=0.27). Conclusion The expressions of VEGF-C and VEGFR-3 are related to lymph node metastasis in NSCLC. VEGF-C may promote intratumoral lymphangiogenesis via VEGFR-3 and lymphatic metastasis.