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        Associations of hypoxia inducible factor-1a gene polymorphisms with susceptibility to digestive tract cancers: a case–control study and meta-analysis

        Zhi-Hai Ni,Xian-Jun Liang,Jing-Gang Mo,Yi Zhang,Jian-Hua Liang,Yu-Sha Yang,Yong Zhou,Zhao-Hua Li,Jian-Liang Zhang,Yin-Lu Ding,Peng Zhang,Jin-Qing Wang 한국유전학회 2015 Genes & Genomics Vol.37 No.11

        We aim to investigate the correlations of hypoxia inducible factor-1a (HIF-1a) C1772T (rs11549465) and G1790A (rs11549467) gene polymorphisms with digestive tract cancers. A sum of 267 digestive tract cancers patients were hospitalized in Taizhou Central Hospital of Zhejiang Province as case group between December 2012 and December 2014. Additionally, 275 healthy people who had a physical examination in our hospital at the same time were selected as control group. Polymerase chain reaction-restriction fragment length polymorphism was utilized for detecting allele and genotype frequency of different locus in case and control group. Meta-analysis was performed using Comprehensive Metaanalysis 2.0 (Biostat Inc., Englewood, New Jersey, USA). Our result showed statistical significance only exists in family history of cancer between case and control group (P\0.05). Both C1772T (rs11549465) and G1790A (rs11549467) polymorphisms showed positive correlations with an increasing risk of digestive tract cancers. The frequencies of TT genotype of C1772T (rs11549465) and GA, AA genotypes of G1790A (rs11549467) polymorphisms in case group were evidently higher compared with the controls (all P\0.05). Besides, the comparison of allele and dominant models of HIF-1a C1772T (rs11549465) and G1790A (rs11549467) between two groups showed a significant difference (all P\0.05). Meta-analysis results further confirmed that the onset risk of digestive tract cancers may be improved under allele and dominant models of HIF-1a C1772T (rs11549465) and G1790A (rs11549467) (all P\0.05). Single nucleotide polymorphisms of HIF-1a C1772T (rs11549465) and G1790A (rs11549467) may play a role in development of digestive tract cancers.

      • DH332, a Synthetic β-Carboline Alkaloid, Inhibits B Cell Lymphoma Growth by Activation of the Caspase Family

        Gao, Pan,Tao, Ning,Ma, Qin,Fan, Wen-Xi,Ni, Chen,Wang, Hui,Qin, Zhi-Hai Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.9

        Aim: The purpose of this study was to investigate anti-tumor effects and safety of DH332, a new ${\beta}$-carboline alkaloids derivatives in vitro and in vivo. Materials and Methods: The effects of DH332 on human (RAMOS RA.1) and mouse (J558) B lymphoma cell lines were detected using a CCK-8 kit (Cell Counting Kit-8), and apoptosis was detected by flow cytometry with PI/annexinV staining. Western blotting was used to detected caspase-3 and caspase-8. Neurotoxic and anti-tumor effects were evaluated in animal experiments. Results: DH332 exerts a lower neurotoxicity compared with harmine. It also possesses strong antitumor effects against two B cell lymphoma cell lines with low $IC_{50s}$. Moreover, DH332 could inhibit the proliferation and induce the apoptosis of RAMOS RA.1 and J558 cell lines in a dose-dependent manner. Our results suggest that DH332 triggers apoptosis by mainly activating the caspase signaling pathway. In vivo studies of tumor-bearing BALB/c mice showed that DH332 significantly inhibited growth of J558 xenograft tumors. Conclusions: DH332 exerts effective antitumor activity in vitro and in vivo, and has the potential to be a promising drug candidate for lymphoma therapy.

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