CASC15 Gene Polymorphisms and Glioma Susceptibility in Chinese Children.

OBJECTIVE: Gliomas are the most common tumors in the central nervous system. The cancer susceptibility candidate 15 (CASC15) gene has been reported to be a susceptibility gene for several types of cancer. No studies have been carried out on the predisposing effect of CASC15 gene single nucleotide polymorphisms (SNPs) on glioma risk. METHODS: In order to determine whether CASC15 gene SNPs are involved in glioma susceptibility, the first association study in a relatively large sample, which consisted of 171 patients and 228 healthy controls recruited from China, was performed. The contribution of SNPs (rs6939340 A>G, rs4712653 T>C and rs9295536 C>A) to the risk of glioma was evaluated by multinomial logistic regression, based on the calculation of the odds ratio (OR) and 95% confidence interval (CI). RESULTS: In the single locus and combined analysis, it was revealed that the genetic risk score had no significant associations between CASC15 gene SNPs and glioma risk. However, in the stratified analysis, a significant decrease in risk of glioma was observed in subjects of <60 months old with the rs4712653 TT genotype, when compared to those with the CC/CT genotype (OR=0.12, 95% CI=0.02-0.91, P=0.041). CONCLUSION: The present study provides referential evidence on the association between the genetic predisposition of the CASC15 gene and glioma risk in Chinese children. However, more well-designed case-control studies and functional experiments are needed to further explore the role of CASC15 gene SNPs.

Genetic variants in XPD gene and glioma susceptibility in Chinese children: A multicenter case-control study.

Background: Glioma is one of the central nervous system (CNS) tumors in children, accounting for 80% of malignant brain tumors. Nucleotide excision repair (NER) is a vital pathway during DNA damage repair progression. Xeroderma pigmentosum group D (XPD) or excision repair cross-complementing group 2 (ERCC2) is a critical factor in the NER pathway, playing an indispensable role in the DNA repair process. Therefore, the genetic variants in XPD may be associated with carcinogenesis induced by defects in DNA repair. Methods: We are the first to conduct a multi-center case-control study to investigate the correlation between XPD gene polymorphisms and pediatric glioma risk. We chose three single nucleotide polymorphisms and genotyped them using the TaqMan assay. Results: Although there is no significant association of these genetic variations with glioma susceptibility, the stratified analysis revealed that in the subtype of astrocytic tumors, the rs13181 TG/GG genotype enhanced glioma risk than the TT genotype, and carriers with two to three genotypes also elevated the tumor risk than 0-1 genotypes. Conclusion: In conclusion, our findings provided an insight into the impact of XPD genetic variants on glioma risk.

AURKA gene polymorphisms and central nervous system tumor susceptibility in Chinese children.

INTRODUCTION: Central nervous system (CNS) tumors comprise 15-20% of all malignancies occurring in childhood and adolescence. Previous researches have shown that overexpression and amplification of the AURKA gene could induce multiple human malignancies, with which the connection of CNS tumor susceptibility has not been extensively studied. MATERIAL AND METHODS: In this study, we assessed whether and to what extent AURKA gene single nucleotide polymorphisms (SNPs) (rs1047972 C > T, rs2273535 T > A, rs8173 G > C) were associated with CNS tumor susceptibility, based on a case-control analysis in 191 CNS tumor patients and 248 controls. We determined this correlation using odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: AURKA gene rs8173 G > C exhibited a crucial function to CNS tumor susceptibility fall-off (GC/CC vs. GG: adjusted OR = 0.68, 95% CI = 0.46-0.998, P = 0.049). In addition, the combined effect of lowering the risk of developing CNS tumors was more pronounced in carriers with 3 protective genotypes than others (adjusted OR = 0.55, 95% CI = 0.31-0.98, P = 0.044). Further stratification analysis illustrated that the existence of rs8173 GC/CC and three protective genotypes lowered CNS tumor risk in some subgroups. CONCLUSIONS: Our research suggested that the AURKA gene rs8173 G > C could significantly reduce CNS tumor susceptibility in Chinese children. More functional experiments are needed to explore the role of the AURKA gene rs8173 G > C.

Patchouli Oil Attenuates High Fat Diet-induced Non-alcoholic Hepatic Steatosis.

Non-alcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases worldwide. Nevertheless, no first-line therapy exists. Hepatic steatosis is the earliest stage of NAFLD, which is characterized by an accumulation of hepatic lipids. Patchouli oil (PO), which is isolated from the well-known Chinese herb named Pogostemon cablin (Blanco) Benth. (Lamiaceae), inhibits hepatic lipid accumulation effectively. However, its potential ability for the treatment of NAFLD had not been reported before. Thus, the objective of this study was to investigate the effectiveness of PO against hepatic steatosis and its underlying mechanisms. We used a high fat diet (HFD)-induced hepatic steatosis model of rats to estimate the effect of PO against NAFLD. Hematoxylin-eosin and oil red O staining were used to analyze the hepatic histopathological changes. ELISA, RT-qPCR, and Western blotting analysis were applied to evaluate the parameters for hepatic steatosis. Our results showed that PO significantly attenuated the lipid profiles and the serum enzymes, evidenced by quantitative and histopathological analyses. It also markedly down-regulated the expression of sterol regulatory element-binding protein 1 (SREPB-1c) with its downstream factors in de novo lipogenesis. And, likewise, in lipid export by very low-density lipoproteins (VLDL), related molecules were dramatically improved. Furthermore, PO observably normalized the aberrant peroxisome proliferator-activated receptor α (PPAR-α) signal in fatty acids oxidation. In conclusion, PO exerted a preventing effect against HFD-induced steatosis and might be due to decrease de novo lipogenesis, promote export of lipids, as well as owing to improve fatty acids oxidation.

HIF-1α rs11549465 C>T polymorphism contributes to increased cancer susceptibility: Evidence from 49 studies.

HIF-1α (hypoxia-inducible factor-1α) is a transcriptional factor that participates in the regulation of oxygen homeostasis. Despites numbers of case-control studies working on this area, the actual relationship of HIF-1α gene generic variant rs11549465 C>T imposing on cancer susceptibility remains unveiled. To get a better understanding of such relationship, this meta-analysis was carried out by incorporating all eligible case-control studies. Qualified articles were acquired from PubMed, CNKI, EMBASE, PMC, and Wanfang database update to April 2019. Odds ratios (ORs) and their corresponding 95% confidence intervals (CIs) were employed to estimate the relationship of interest. Heterogeneity tests, sensitivity analyses and publication bias assessments were also carried out to ensure the strength of our conclusion. A total of 46 articles with 49 studies including 12920 cases and 13363 controls were included. The results indicated that HIF-1α rs11549465 C>T was significantly related to the increased risk of overall cancer under four genetic models (TT vs. CC: OR=2.06, 95% CI=1.34-3.16; TT vs. CC/CT: OR=2.42, 95% CI=1.60-3.65; CT/TT vs. CC: OR=1.21, 95% CI=1.04-1.40; T vs. C: OR=1.29, 95% CI=1.12-1.48). Furthermore, enhanced cancer risk was detected after stratification by cancer type, ethnicity, the source of controls and HWE. These results suggest that HIF-1α rs11549465 C>T polymorphism may predispose to cancer susceptibility.

IL-33/ST2 axis promotes glioblastoma cell invasion by accumulating tenascin-C.

Tenascin-C (TNC), a very large multimeric glycoprotein, is overexpressed in human glioblastomas, leading to a highly motile and invasive phenotype of glioma cells. However, the regulation of TNC expression in glioma has remained unclear until now. Our data suggest that interleukin-33 (IL-33) may promote the accumulation of TNC protein by autocrine or paracrine modes of action in glioma. In the present study, the expression levels of TNC, IL-33, and ST2 were measured in glioma tissue specimens, and the impact of altered IL-33 expression on TNC was investigated in vitro and in vivo. In contrast with control treatment, IL-33 treatment increased TNC expression, and knockdown of IL-33 attenuated TNC expression in glioma cells. Furthermore, IL-33 induced the activation of nuclear factor κB (NF-κB) and increased the expression of TNC in U251 cells. In addition, blockage of the IL-33-ST2-NFκB pathway resulted in downregulation of TNC production. IL-33 promoted glioma cell invasion by stimulating the secretion of TNC. Similarly, knockdown of TNC inhibited the invasiveness of glioma cells. These findings provide a novel perspective on the role of the IL-33/NF-κB/TNC signalling pathway in supporting cancer progression. Thus, targeting the IL-33/NF-κB/TNC signalling pathway may be a useful therapeutic approach in glioma.

Impact of menopausal status and HER-2/neu protein on efficacy of EGFR-TKI in EGFR mutant patients with non-small cell lung cancer.

Clinical studies have confirmed epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) used in lung cancer patients with EGFR mutations can obtain a better result, but still part of the patients with poor efficacy. EGFR mutation is highly related to female, nonsmoking and adenocarcinoma. Thus, we hypothesize that estrogen and circulating HER-2/neu protein might influence the efficacy of EGFR-TKIs in EGFR mutant patients with non-small cell lung cancer. HER-2/neu expression level of 357 eligible patients in its peripheral serum was determined using ELISA. The median progression-free survival (PFS) in five groups (premenopausal group, perimenopause group, peri to postmenopausal group, postmenopausal group and control group) was statistically difference (P = 0.025). Premenopausal group could predict the efficacy of EGFR-TKI (HR = 2.45, 95% CI = 1.42-4.23, P = 0.001). No statistical significance was found in median overall survival (OS) among five groups. Optimal diagnostic cut off value of HER-2/neu was set at 47.5 ng/ml, with P = 0.0607. As the cutoff value to 47.5 ng/ml division, concentrations and menopausal status was of no significant difference (P = 0.874). PFS of the group below 47.5 ng/ml was significantly longer than that of the group over 47.5 ng/ml (P = 0.000). HER-2/neu concentration was positively correlated with optimal efficacy (P = 0.042). HER-2/neu concentration over than 47.5 ng/ml was a risk factor of EGFR-TKI prognosis. Premenopausal status is an independent predictor of EGFR-TKI curative effect and circulating HER-2/neu protein is an independent prognostic factor in patients with advanced NSCLC.

Novel betulin derivative induces anti-proliferative activity by G2/M phase cell cycle arrest and apoptosis in Huh7 cells.

Betulin (BT) has been identified to exhibit potential benefits for treating hepatocellular carcinoma (HCC). The results of the present study demonstrated that a new semisynthetic derivative of BT, 3,28-di-(2-nitroxy-acetyl)-oxy-BT, may effectively decrease the viability of Huh7 cells. Mechanistic studies revealed that 3,28-di-(2-nitroxy-acetyl)-oxy-BT inhibited the transition between G2 and M phase of the cell cycle by regulating cell cycle regulatory proteins. Additional study revealed that 3,28-di-(2-nitroxy-acetyl)-oxy-BT may trigger Huh7 cells to undergo caspase-dependent apoptosis as an increased proportion of cells were identified in the sub-G1 phase, which may be a result of poly(ADP-ribose) polymerase cleavage and caspase activation. Furthermore, 3,28-di-(2-nitroxy-acetyl)-oxy-BT-induced apoptosis was mitochondrion-mediated. The results of the present study demonstrated that Bcl-2-associated X protein translocated to the mitochondria from the cytosol following 3,28-di-(2-nitroxy-acetyl)-oxy-BT treatment. Notably, the phosphoinositide 3-kinase/protein kinase B signaling pathway was involved in 3,28-di-(2-nitroxy-acetyl)-oxy-BT-treated Huh7 cells. Therefore, the results of the present study demonstrated that 3,28-di-(2-nitroxy-acetyl)-oxy-BT may inhibit HCC, which may be a possible application to treat HCC.