Genetic Analysis of the Liver Putative Tumor Suppressor (LPTS) Gene in Gastric Cancer

Hai Bing Zhang,Qu Zhang,Li Sa Wang,Fei Yan,Yun Lu,Zhi Qiang Wang,Jing Li,Liang Liang Zhang,Ying Yan Yu,Zheng Gang Zhu,Xiang Yin Kong,Lan Dian Hu 한국유전학회 2005 Genes & Genomics Vol.27 No.4

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.

Soluble expression, purification and the role of C-terminal glycine residues in scorpion toxin BmK AGP-SYPU2

( Rong Zhang ),( Yong Cui ),( Xi Zhang ),( Zhuo Yang ),( Yong Shan Zhao ),( Yong Bo Song ),( Chun Fu Wu ),( Jing Hai Zhang ) 생화학분자생물학회 (구 한국생화학분자생물학회) 2010 BMB Reports Vol.43 No.12

The existence of glycine residues in long-chain scorpion toxins has been well documented. However, their role as analgesics has not been evaluated. To address this issue, we investigated the functional role of glycines in the C-terminal end of Chinese-scorpion toxin from Buthus martensii Karsch (BmK AGP-SYPU2) using site-directed mutagenesis and analgesic activity assays. Recombinant BmK AGP-SYPU2 and its mutants were efficiently expressed in E. coli and purified to homogeneity using immobilized metal ion affinity chromatography (IMAC) and cation exchange chromatography. The mouse-twisting test was used to detect the analgesic activity of BmK AGP-SYPU2 and its mutants. As a result, we identified glycines at the C-terminal end that, when altered, significantly affected analgesic activity. Also, Mut6566 was significantly decreased compared to BmK AGP-SYPU2. These data indicate that the glycines at the C-terminal end are important for the analgesic activity of BmK AGP-SYPU2. [BMB reports 2010; 43(12): 801-806]

Construction and Characterization of Vitreoscilla Hemoglobin (VHb) with Enhanced Peroxidase Activity for Efficient Degradation of Textile Dye

( Zi Dong Zhang ),( Wei Li ),( Hai Chao Li ),( Jing Zhangi ),( Yue Bin Zhang ),( Yu Feng Cao ),( Jian Zhang Ma ),( Zheng Qiang Li ) 한국미생물 · 생명공학회 2015 Journal of microbiology and biotechnology Vol.25 No.9

Pollution resulting from the discharge of textile dyes into water systems has become a major global concern. Because peroxidases are known for their ability to decolorize and detoxify textile dyes, the peroxidase activity of Vitreoscilla hemoglobin (VHb) has recently been studied. It is found that VHb and variants of this enzyme show great promise for enzymatic decolorization of dyes and may play a role in achieving their successful removal from industrial wastewater. The level of VHb peroxidase activity correlates with two amino acid residues present within the conserved distal pocket, at positions 53 and 54. In this work, sitedirected mutagenesis of these residues was performed and resulted in improved VHb peroxidase activity. The double mutant, Q53H/P54C, shows the highest dye decolorization and removal efficiency, with 70% removal efficiency within 5 min. UV spectral studies of Q53H/P54C reveals a more compact structure and an altered porphyrin environment (λSoret = 413 nm) relative to that of wild-type VHb (λSoret = 406), and differential scanning calorimetry data indicate that the VHb variant protein structure is more stable. In addition, circular dichroism spectroscopic studies indicate that this variant’s increased protein structural stability is due to an increase in helical structure, as deduced from the melting temperature, which is higher than 90°C. Therefore, the VHb variant Q53H/P54C shows promise as an excellent peroxidase, with excellent dye decolorization activity and a more stable structure than wild-type VHb under high-temperature conditions.

Analysis on Survival and Prognostic Factors for Cancer Patients with Malignancy-associated Hypercalcemia

Zhang, Su-Jie,Hu, Yi,Cao, Jing,Qian, Hai-Li,Jiao, Shun-Chang,Liu, Zhe-Feng,Tao, Hai-Tao,Han, Lu Asian Pacific Journal of Cancer Prevention 2013 Asian Pacific journal of cancer prevention Vol.14 No.11

Objective: To explore the incidence, clinical characteristics, diagnosis and treatment strategies, prognosis of patients with malignancy-associated hypercalcemia (MAH). Methods: The data of 115 patients with MAH who were treated at the Medical Oncology Department of Chinese PLA General Hospital from Jan., 2001 to Dec., 2010 was retrospectively reviewed. Survival analysis was performed using the Kaplan-Meier method and the Cox proportional hazard model with statistic software SPSS 18.0. Results: The patients had blood calcium levels ranging from 2.77 to 4.87 mmol/L. Except for 9 cases who died or were discharged within 5 days after admission, all other patients recovered to normal blood calcium level after treatment with bisphosphonates or intravenous hydration and diuretics; their survival after occurrence of MAH was from 1 day to 4,051 days, and the median survival time was only 50 days. In the log-rank test, the male, renal metastasis, central nervous system symptoms and hypercalcemia occurring over 140 days after cancer diagnosis were predictors of poor survival (P=0.002, P=0.046, P=0.000, P=0.009). In the COX analysis, being male, central nervous system symptoms and hypercalcemia lasting over 140 days after cancer diagnosis were independent prognostic factors for survival time (RR=2.131, P=0.027; RR=3.054, P=0.002; RR=2.403, P=0.001). According to these factors, a score system was established to predict the patient prognosis and adjust the treatment. Conclusion: Cancer patients with MAH have an extremely poor median survival. Some independent factors indicate poor prognosis, including male gender, central nervous system symptoms and hypercalcemia lasting over 140 days after cancer diagnosis. The prognostic score can serve as a reference for MAH prognosis and treatment, worthy of further investigation.

Memory Enhancing and Neuroprotective Effects of Selected Ginsenosides

Hai Ying Bao,Jing Zhang,여수정,Chang-Seon Myung,Hyang Mi Kim,Jong Moon Kim,박정일,조정숙,Jong Seong Kang 대한약학회 2005 Archives of Pharmacal Research Vol.28 No.3

The effects of ginsenosides Rg3(R), Rg3(S) and Rg5/Rk1 (a mixture of Rg5 and Rk1, 1:1, w/w), which are components isolated from processed Panax ginseng C.A. Meyer (Araliaceae), on memory dysfunction were examined in mice using a passive avoidance test. The ginsenosides Rg3(R), Rg3(S) or Rg5/Rk1, when orally administered for 4 days, significantly ameliorated the memory impairment induced by the single oral administration of ethanol. The memory impairment induced by the intraperitoneal injection of scopolamine was also significantly recovered by ginsenosides Rg3(S) and Rg5/Rk1. Among the three ginsenosides tested in this study, Rg5/Rk1 enhanced the memory function of mice most effectively in both the ethanoland scopolamine-induced amnesia models. Moreover, the latency period of the Rg5/Rk1-treated mice was 1.2 times longer than that of the control (no amnesia) group in both models, implying that Rg5/Rk1 may also exert beneficial effects in the normal brain. We also evaluated the effects of these ginsenosides on the excitotoxic and oxidative stress-induced neuronal cell damage in primary cultured rat cortical cells. The excitotoxicity induced by glutamate or Nmethyl- D-aspartate (NMDA) was dramatically inhibited by the three ginsenosides. Rg3(S) and Rg5/Rk1 exhibited a more potent inhibition of excitotoxicity than did Rg3(R). In contrast, these ginsenosides were all ineffective against the H2O2- or xanthine/xanthine oxidase-induced oxidative neuronal damage. Taken together, these results indicate that ginsenosides Rg3(S) and Rg5/Rk1 significantly reversed the memory dysfunction induced by ethanol or scopolamine, and their neuroprotective actions against excitotoxicity may be attributed to their memory enhancing effects.

Association Between C1019T Polymorphism in the Connexin 37 Gene and Helicobacter Pylori Infection in Patients with Gastric Cancer

Jing, Yuan-Ming,Guo, Su-Xia,Zhang, Xiao-Ping,Sun, Ai-Jing,Tao, Feng,Qian, Hai-Xin Asian Pacific Journal of Cancer Prevention 2012 Asian Pacific journal of cancer prevention Vol.13 No.5

Objective: To investigate the association between the connexin 37 C1019T polymorphism and Helicobacter pylori infection in patients with gastric cancer. Methods: 388 patients with gastric cancer (GC), 204 with chronic superficial gastritis (CSG) were studied. H. pylori was detected by gastric mucosal biopsies biopsy dyeing method. Connexin 37 gene polymorphism 1019 site genotypes were determined by gene sequencing technology. Genotypes and alleles frequencies were compared. Results: (1) Connexin37 gene 1019 site distribution frequency (CC type, TC type, TT type) in the CSG group was 18.1%, 45.1% and 36.8%; in the stomach cancer group it was 35.1%, 45.9% and 19.%, conforming to the Hardy-Weinberg euilibrium. (2) In comparison with CSG group, the frequency of Connexin37 C allele was higher in the gastric cancer group (58.0% vs 40.7%, OR = 2.01, 95%CI = 1.58-2.57, P < 0.01). The prevalence of gastric cancer risk was significantly increased in the carriers of C allele (CC+TC) than in TT homozygote (OR = 2.47, 5%CI = 1.68- 3.610. (3) Gastric cancer patients complicated with Hp infection 211 cases, gastric cancer group of the male patients with HP positive patients with 187 cases, 40 cases of female patients with negative patients, 24 cases were HP positive, negative in 137 cases, control group male patients, 28 cases were Hp positive, negative in 95 patients, female patients with Hp positive 6 cases, 75 cases were negative. On hierarchical analysis, the male group OR value was 15.9 (95%CI to 9.22-27.3), and the female OR was 2.19 (95%CI 0.88-5.59), indicating a greater contribution in males (P <0.01). After elimination of gender effects, positive HP and gastric cancer were closely related (OR 8.82, 95% CI: 5.45-14.3). (4) The distribution frequency of C allele in patients with Hp infection was much higher than that in Hp negative cases in the GC group (64.5% vs 47.0%, OR = 2.05, 95%CI = 1.54-2.74, P < 0.01). Compared with TT homozygotes, (CC+TC) genotype prevalence of gastric cancer risk increased significantly (OR = 2.96, 5%CI = 1.76-2.99 ). Conclusion: The T allele in the connexin37 gene might not only be associated with gastric cancer but also with H. pylori infection.

VHL Gene Mutation Analysis of a Chinese Family with Non-Syndromic Pheochromocytomas and Patients with Apparently Sporadic Pheochromocytoma

Zhang, Bin,Qian, Jing,Chang, De-Hui,Wang, Yang-Min,Zhou, Da-Hai,Qiao, Gou-Mei Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.5

Objective: The Von Hippel-Lindau syndrome (VHLD), an inherited neoplastic syndrome predisposing to central nervous system hemangioblastoma (CNS), pheochromocytoma (PCC), renal cell carcinoma(RCC), retinal hemangioma (RA) and renal cysts, is caused by mutations or deletions of the VHL tumor-suppressor gene. To assess VHL genotype-phenotype correlations with function of pVHL a gene mutation analysis of members in a Chinese family with non-syndromic PCCs and individuals with apparently sporadic pheochromocytoma (ASP) was performed. Materials and Methods: DNA samples of 20 members from the Chinese family with non-syndromic PCCs and 41 patients with ASP were analyzed by polymerase chain reaction and direct sequencing, confirmed by Taqman probe. Results: Three novel mutations (H125P, 623(^TTTGTtG) and R120T) were identified in the Chinese family and in 3 among 41 ASP patients. The mutations were all located in exon 2 of VHL gene encoding ${\beta}$-domain of pVHL. The tumor type in H125P carriers and R120T carriers was VHL type 2C. And 623(^TTTGTtG) carriers presented VHL type 2B or type 2C. Conclusions: VHL gene abnormalities were identified in the Chinese family with non-syndromic PCCs and patients with APS, resulting in dysfunction of pVHL. H125P and R120T could be associated with VHL type 2C, while 623(^TTTGTtG) might be linked with VHL type 2B or type 2C. Not only is the genetic analysis helpful for early diagnosis and treatment of patients with VHLD, it is also benefitial for research intoVHLD pathogenesis.

MiR-193b enhanced proliferation and migration and inhibits apoptosis through targeting RAB7A in osteosarcoma cell

Zhang Yuan-yuan,Xu Hai-yan,Dai Jing-jing 대한독성 유전단백체 학회 2021 Molecular & cellular toxicology Vol.17 No.1

Background Accumulating study indicated that microRNA (miRNA) played critical role in the osteosarcoma (OS). The role and mechanisms of miR-193b in OS cell lines were still unknown. Objective We resolved the miR-193b expression in OS cell line and normal cell by RT-PCR assay. The effects of upregulated miR-193b on OS cell proliferation, migration, invasion and apoptosis were evaluated using CCK-8 assay, transwell assay, would-healing assay and flow cytometric analysis in vitro, respectively. We investigated the effect of upregulated miR-193b on the mRNA level of cell cycle protein CCND1 and CCNE1 using RT-PCR assay and the protein level of epithelial to mesenchymal transition (EMT)-related protein E-cadherin, vimentin, and N-cadherin by western blotting assay in MG-63 and U2SO cells. Furthermore, luciferase reporter assays were employed to identify the candidate target gene RAB7A of miR-193b. Results The expression of miR-193b was downregulated in OS cells. In MG-63 and U2SO cells, ectopic miR-193b expression inhibited cell proliferation, migration, invasion, and induced apoptosis. We found that miR-193b reduced the mRNA expression of CCND1 and CCNE1, and regulated the associated proteins of EMT including E-cadherin, vimentin and N-cadherin in MG-63and U2SO cell lines. Moreover, the candidate target gene RAB7A was negatively regulated by miR-193b. In addition, upregulated RAB7A rescued the inhibitory effect of miR-193b mimics on the development of OS cell. Conclusion In conclusion, this study suggested that miR-193b overexpression inhibited cell proliferation, migration, invasion, and induced cell apoptosis by down-regulating RAB7A in OS cell lines.

Residential Radon and Lung Cancer Risk: An Updated Meta-analysis of Case-control Studies

Zhang, Zeng-Li,Sun, Jing,Dong, Jia-Yi,Tian, Hai-Lin,Xue, Lian,Qin, Li-Qiang,Tong, Jian Asian Pacific Journal of Cancer Prevention 2012 Asian Pacific journal of cancer prevention Vol.13 No.6

Background: Numbers of epidemiological studies assessing residential radon exposure and risk of lung cancer have yielded inconsistent results. Methods: We therefore performed a meta-analysis of relevant published case-control studies searched in the PubMed database through July 2011 to examine the association. The combined odds ratio (OR) were calculated using fixed- or random-effects models. Subgroup and dose-response analyses were also performed. Results: We identified 22 case-control studies of residential radon and lung cancer risk involving 13,380 cases and 21,102 controls. The combined OR of lung cancer for the highest with the lowest exposure was 1.29 (95% CI 1.10-1.51). Dose-response analysis showed that every 100 Bq/$m^3$ increment in residential radon exposure was associated with a significant 7% increase in lung cancer risk. Subgroup analysis displayed a more pronounced association in the studies conducted in Europe. Studies restricted to female or non-smokers demonstrated weakened associations between exposure and lung cancer. Conclusions: This meta-analysis provides new evidence supporting the conclusion that residential exposure to radon can significantly increase the risk of lung cancer in a dose-response manner.