Relationship between driver gene mutation and clinicopathological features in 300 cases of non-small cell lung cancer based on next generation sequencing / 临床与实验病理学杂志

Purpose To explore the mutation characteristics of common driver genes in non-small cell lung cancer (NSCLC) and its relationship with clinicopathological features.Methods Next generation sequencing (NGS) was used to detect the mutations of common driving genes such as EGFR, KRAS, ALK, ROS1, BRAF, MET, RET and HER-2 in 300 paraffin-embedded NSCLC tissues. Results In 300 patients with NSCLC, the mutation rates of EGFR, KRAS, ALK, ROS1, BRAF, MET, RET, HER-2 were 52.00％, 10.33％, 6.67％, 1.67％, 3.67％, 3.33％, 1.00％, and 2.33％, respectively. A case of EGFR 21 exon L858 R mutation was combined with LINCO1446-EGFR gene fusion. EGFR 20 th exon C797 S and T790 M existed in cis or trans form and merged with EGFR sensitive mutations in 1 case each. 3 cases of EGFR gene point mutation was associated with MET gene copy number amplification. EGFR mutations were more commonly detected in non-smoking women with lung adenocarcinoma (P<0.05).KRAS mutations were more commonly found in smoking men (P<0.05). ALK mutations were associated with age (P<0.05), and more commonly noted in patients younger than 60 years.ROS1 fusion mutations were associated with gender (P<0.05), more commonly detected in women. BRAF, MET, RET, and HER-2 gene mutations were not associated with gender, age, smoking, histological type, and c TNM stage. Conclusion EGFR can coexist with other driver gene mutations. Gene mutations and clinicopathological features like gender, age, smoking, and histological types have corresponding links. The incidence of BRAF, MET, RET, and HER-2 mutations is low, and its clinical significance remains to be explored. Coexisting gene mutations and rare mutations discovered by NGS should be taken seriously.

Inhibition effects of all trans-retinoic acid on the growth and angiogenesis of esophageal squamous cell carcinoma in nude mice / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The potential application of retinoic acid receptor activators, such as all trans-retinoic acid (ATRA), for treating various cancers have been studied both pre-clinically and clinically. Whether ATRA has an anticancer effect on human esophageal squamous cancer cell (ESCC) is still unknown. We have explored the anticancer effect of ATRA in ESCC, and in this study, the effects of ATRA on levels and patterns of expression of the vascular endothelial growth factor (VEGF) signal transduction pathway in transplantable tumor growth of the human ESCC cell line, EC9706, in nude mice.</p><p><b>METHODS</b>The animal model of the ESCC xenograft was made by subcutaneous implantation of tumor cells into nude mice. Reverse transcription-polymerase chain reaction (RT-PCR), Western blotting and immunohistochemical assays were used to detect the expression of the VEGF signal transduction pathway in ESCC xenograft tissues.</p><p><b>RESULTS</b>Compared to the control group, the tumor inhibition rates in the low dose ATRA, high dose ATRA, and 5-FU groups were 83.21%, 88.32%, 91.02%, respectively. The protein and mRNA levels of VEGF were down-regulated after being treated with ATRA and 5-FU compared to the control group (P < 0.05). The study also revealed that ATRA specifically down-regulated VEGF and the component of the VEGF signal transduction pathway of CD31, CD34, and CD105 (component of the TGF-β receptor) in ESCC xenograft tissues (P < 0.05).</p><p><b>CONCLUSIONS</b>ATRA can significantly inhibit tumor growth and has anticancer effects on transplantable tumor growth of human ESCC cell line EC9706 in nude mice. These findings indicate that ATRA specifically down regulated VEGF and the components of VEGF signal transduction, which may be an important mechanism responsible for the neoangiogenesis inhibition of ESCC cells.</p>

Retrovirus-mediated RNA inhibition of EphA2 gene expression in colon adenocarcinoma HCT-8 cells / 中华病理学杂志

<p><b>OBJECTIVE</b>To explore novel cancer gene therapy by retrovirus-mediated RNAi technique to suppress the endogenous EphA2 oncogene expression in colon adenocarcinoma HCT-8 cells.</p><p><b>METHODS</b>Sequence information of EphA2 mRNA was selected and two complementary oligonucleotides with hairpin loop were designed. Retrovirus-mediated RNAi expression vector (pSIREN-EphA2) was then constructed and transfected into the HCT-8 cells. Inhibition of EphA2 protein expression was quantitatively determined by Western blot and immunohistochemistry assay (SP method).</p><p><b>RESULTS</b>The construction of pSIREN-EphA2 vector was successful and confirmed by restriction enzyme analysis and DNA sequencing. The post-transfection level of EphA2 protein expressions was greatly reduced in HCT-8 cells transfected with pSIREN-EphA2, as compared with those of untransfected cells and the vector control (P < 0.001).</p><p><b>CONCLUSIONS</b>EphA2 protein expression in HCT-8 cell line can be suppressed using recombinant retrovirus-mediated RNAi technique. This approach may provide a novel gene therapy against colonic adenocarcinoma.</p>

The expression of erythropoitin-producing hepatocellular A-2 gene in colorectal adenocarcinoma and its impact on DNA pioid types and cell proliferation / 中华消化杂志

0.05),but correlated with age and invasion depth of tumor(P