25 results on '"Sun, Qian"'
Search Results
2. Radiological appearance of hepatocellular carcinoma predicts the response to trans-arterial chemoembolization in patients undergoing liver transplantation
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Zhang, Wei, Xu, An-Hui, Wang, Wei, Wu, Yan-Hui, Sun, Qian-Ling, and Shu, Chang
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- 2019
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3. Notch1 signaling contributes to the oncogenic effect of HBx on human hepatic cells
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Wang, Fan, Xia, Xiumei, Wang, Jinling, Sun, Qian, Luo, Jin, and Cheng, Bin
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- 2013
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4. Syntheses and anti-cancer activities of derivatives of tetrandrine and fangchinoline
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Sun Qian-yun, Huang Lan, Pan Weidong, Liu Yazhou, LI Tianlei, Zhang Mao-sheng, and Liang Guang-yi
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A549 cell ,Chemistry ,Stereochemistry ,Cancer ,General Chemistry ,Pharmacology ,medicine.disease ,Tetrandrine ,chemistry.chemical_compound ,Hepatocellular carcinoma ,medicine ,Adenocarcinoma ,Cytotoxicity ,IC50 ,K562 cells - Abstract
A series of derivatives of tetrandrine and fangchinoline was designed and synthesized to find more active anti-cancer compounds. Their anti-cancer activities were tested against human hepatocellular carcinoma BEL-7402 and PLC/PRF/5 cells, human lung adenocarcinoma A549 cells as well as human leukaemia K562 cells, and the structure-activity relationship(SAR) was also studied. All the compounds except B1 exhibited superior inhibitory activities against PLC/PRF/5 cells with half maximal inhibitory concentration(IC50) values of less than 15 μmol/L, and compounds A2, A4, B2 and B4 showed IC50 values of less than 9 μmol/L. Compounds A2, A6, B2 and B4 showed potent anti-cancer activities against all the tested cells with IC50 values of less than 10 μmol/L. The results show that terandrine and fangchinoline derivatives are potential suppressors to human cancer.
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- 2014
5. A simple AGED score for risk classification of primary liver cancer: development and validation with long-term prospective HBsAg-positive cohorts in Qidong, China
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Chunsun Fan, Yan Jin, Mengge Li, Yu Gan, Yan Sun, Jianguo Chen, Jianren Gu, Taoyang Chen, Jian-Hua Lu, Jianquan Lu, Jinbing Wang, Hong Tu, and Geng Sun Qian
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0301 basic medicine ,medicine.medical_specialty ,HBsAg ,business.industry ,Surrogate endpoint ,Gastroenterology ,Hepatitis B ,medicine.disease ,digestive system diseases ,Transplantation ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,Internal medicine ,Hepatocellular carcinoma ,Cohort ,Epidemiology of cancer ,Medicine ,030211 gastroenterology & hepatology ,business ,Prospective cohort study - Abstract
We read with great interest the recent publication by Kim et al 1 showing that patients with untreated immune tolerant (IT) chronic hepatitis B with normal alanine aminotransferase (ALT) levels had significantly higher risks of hepatocellular carcinoma (HCC) and death/transplantation than treated immune active (IA) patients who had elevated ALT levels. These results indicate that ALT is not a sensitive surrogate marker for liver cell damage, and the IT phase of HBV infection cannot be considered fully benign.2 Chu and Liaw3 have challenged this view because they speculated that the IT group in that study might include IA patients who were in remission state after experiencing unrecognised minimal ALT elevations. Apparently, the highly dynamic nature of ALT perturbation makes it inadequate to act as a predictor for HCC. We have developed and validated an easy-to-use scoring system for primary liver cancer (PLC) risk prediction. The development data set was set up in 1996 based on a community-based prospective cohort (qidong hepatitis B infection cohort (QBC)) established in Qidong, China.4 It contained …
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- 2018
6. Reevaluation of glypican-3 as a serological marker for hepatocellular carcinoma
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Geng Sun Qian, Jianwei Cui, Wei-Zhong Cheng, Xiuzhi Lu, Guohua Li, Hong Tu, Jing Zhang, Jian Yan, Zhengxian Ni, and Min Chen
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Male ,Oncology ,medicine.medical_specialty ,Carcinoma, Hepatocellular ,Cirrhosis ,Clinical Biochemistry ,Enzyme-Linked Immunosorbent Assay ,Sensitivity and Specificity ,Biochemistry ,Glypican 3 ,Serology ,Glypicans ,Cell Line, Tumor ,Neoplasms ,Internal medicine ,Biomarkers, Tumor ,Carcinoma ,Humans ,Medicine ,Lung cancer ,neoplasms ,Thyroid cancer ,Aged ,business.industry ,Liver Neoplasms ,Biochemistry (medical) ,Cancer ,Hep G2 Cells ,General Medicine ,Middle Aged ,Reference Standards ,medicine.disease ,Immunohistochemistry ,digestive system diseases ,Gene Expression Regulation, Neoplastic ,Hepatocellular carcinoma ,Female ,business - Abstract
Glypican-3 (GPC3) is a novel histochemical marker of hepatocellular carcinoma (HCC). However, its utility as a serologic marker for HCC is not conclusive.A total of 1037 subjects, including 155 patients with HCC, 180 with chronic hepatitis, 124 with liver cirrhosis, 442 with non-HCC cancer and 136 healthy controls, were analyzed for serum GPC3 (sGPC3) by an ELISA constructed with 2 monoclonal antibodies.The average level of sGPC3 in HCC patients was 99.94±267.2ng/ml, which was significantly higher than in patients with chronic hepatitis (10.45±46.02ng/ml, P0.0001), liver cirrhosis (19.44±50.88ng/ml, P=0.0013), non-HCC cancer (20.50±98.33ng/ml, P0.0001) and healthy controls (4.14±31.65ng/ml, P0.0001). The sensitivity of sGPC3 in HCC diagnosis was 40.0%, whereas the specificity was 98.5%, 94.4% and 87.1% in healthy controls, chronic hepatitis patients and liver cirrhosis patients, respectively. In addition, 13.5% (28/207) of lung cancer patients and 13.2% (9/68) of thyroid cancer patients had positive results with sGPC3.Serum GPC3 is a potential marker for HCC. However, the presence of sGPC3 in patients with lung cancer and thyroid cancer might limit its application as a single marker in the diagnosis of HCC.
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- 2013
7. Circular RNA circ-CSPP1 regulates CCNE2 to facilitate hepatocellular carcinoma cell growth via sponging miR-577.
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Sun, Qian, Yu, Rui, Wang, Chunfeng, Yao, Jianning, and Zhang, Lianfeng
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CIRCULAR RNA , *HEPATOCELLULAR carcinoma , *CELL growth , *BINDING site assay , *RNA-binding proteins , *LUCIFERASES - Abstract
Objective: Circ-centro-some/spindle pole-associated protein (CSPP1) has been confirmed to be characterized in diverse human malignancies and its ectopic expression may regulate tumor progression and development. However, in hepatocellular carcinoma (HCC), its biological role, clinical significance and molecular mechanism are still unclear. Methods: Circ-CSPP1 expression and its prognostic values in HCC tissues were detected by qRT-PCR or in situ hybridization (ISH), and enriched by using Rnase R. The functional experiments (Circ-CSPP1 was overexpressed or knocked down) were performed in HCC cells. The HCC cell growth was analyzed by CCK-8 assay, transwell, wound healing and colony formation assays. The interation between circ-CSPP1 and miR-577/miR-577 and cyclin E2 (CCNE2) were determined by dual luciferase assay or RNA binding protein immunoprecipitation (RIP) assay. The RNA fluorescence in situ hybridization (FISH) assay was used to detect the subcellular distribution. Finally, an in vivo nude mouse tumor model was constructed. Results: In HCC patients and cells, circ-CSPP1 was aberrantly expressed, and its upregulation predicted poor prognosis, and closely correlated with tumor size and TNM stage. Circ-CSPP1 resisted RnaseR digestion, indicating it is a circular RNA structure. Moreover, overexpression of circ-CSPP1 promoted HCC cell viability, colony formation, migration, and invasion in vitro. Knockdown of circ-CSPP1 showed contrary results. Circ-CSPP1 acts as a miR-577 sponge and positively regulated the target of miR-577, CCNE2. Besides, miR-577 inhibitor rescued the suppressive effects of circ-CSPP1 knockdown on HCC cell growth, whereas was completely reversed by silencing of CCNE2. Finally, the in vivo experiments confirmed that circ-CSPP1 knockdown regulated xenograft tumor volume and downregulated CCNE2, p-Rb, E2F1 and c-myc expression. Conclusion: These findings revealed that circ-CSPP1 contributed to HCC progression by positively regulating CCNE2 via miR-577, thus established its potential as new a prognostic and therapeutic marker for HCC patients. [ABSTRACT FROM AUTHOR]
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- 2020
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8. Retraction Note: circular RNA circ-CSPP1 regulates CCNE2 to facilitate hepatocellular carcinoma cell growth via sponging miR-577.
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Sun, Qian, Yu, Rui, Wang, Chunfeng, Yao, Jianning, and Zhang, Lianfeng
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CIRCULAR RNA , *CELL growth , *HEPATOCELLULAR carcinoma , *CANCER cell growth - Abstract
The online version of the original article can be found at https://doi.org/10.1186/s12935-020-01287-8. References 1 Zhang J, Duan H, Feng Z. Acetyl-CoA synthetase 3 promotes bladder cancer cell growth under metabolic stress. [Extracted from the article]
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- 2023
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9. Specific mutations of hepatitis B virus in plasma predict liver cancer development
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Alvaro Muñoz, Pei Xing Lu, John D. Groopman, Thomas W. Kensler, Shuang Yuan Kuang, Geng Sun Qian, Jin Bing Wang, and Peta E. Jackson
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Adult ,Male ,China ,Hepatitis B virus ,medicine.medical_specialty ,Carcinoma, Hepatocellular ,DNA Mutational Analysis ,Biology ,medicine.disease_cause ,Gastroenterology ,Cohort Studies ,Liver disease ,Risk Factors ,Internal medicine ,medicine ,Humans ,Prospective Studies ,Aged ,Hepatitis ,Multidisciplinary ,Virulence ,Liver Neoplasms ,Cancer ,Biological Sciences ,Middle Aged ,Hepatitis B ,Prognosis ,medicine.disease ,digestive system diseases ,Hepatocellular carcinoma ,DNA, Viral ,Mutation ,Immunology ,Biomarker (medicine) ,Female ,Liver cancer ,Follow-Up Studies - Abstract
A major risk factor for hepatocellular carcinoma (HCC) is hepatitis B virus (HBV), whose pathogenesis is exacerbated by the acquisition of mutations that accelerate carcinogenesis. We examined, with mass spectrometry, the temporality of an HBV 1762 T /1764 A double mutation in plasma and tumors. Initial studies found that 52 of 70 (74.3%) tumors from patients residing in Qidong, People's Republic of China, contained this HBV mutation. Paired plasma samples were available for six of the tumor specimens; four tumors had the HBV 1762 T /1764 A mutation, whereas three of the paired plasma samples were also positive. The potential predictive value of this biomarker was explored by using stored plasma samples from a study of 120 residents of Qidong who had been monitored for aflatoxin exposure and HBV infection. After 10 years of passive follow-up, there were six cases of major liver disease including HCC (four cases), hepatitis (one case), and cirrhosis (one case). All six cases had detectable levels of the HBV 1762 T /1764 A mutation up to 8 years before diagnosis. Finally, 15 liver cancers were selected from a prospective cohort of 1,638 high-risk individuals in Qidong on the basis of available plasma samples spanning the years before and after diagnosis. The HBV 1762 T /1764 A mutation was detected in 8 of the 15 cases (53.3%) before cancer. The persistence of detection of this mutation was statistically significant ( P = 0.022, two-tailed). We therefore found that a prediagnosis biomarker of specific HBV mutations can be measured in plasma and suggest this marker for use as an intermediate endpoint in prevention and intervention trials.
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- 2004
10. Prospective detection of codon 249 mutations in plasma of hepatocellular carcinoma patients
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Alvaro Muñoz, John D. Groopman, Peta E. Jackson, Jin Bing Wang, Paul T. Strickland, Shuang Yuan Kuang, Geng Sun Qian, and Thomas W. Kensler
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Adult ,Male ,Cancer Research ,medicine.medical_specialty ,Pathology ,Carcinoma, Hepatocellular ,Mutation, Missense ,Biology ,Polymerase Chain Reaction ,Gastroenterology ,Mass Spectrometry ,HaeIII ,Internal medicine ,Blood plasma ,Biomarkers, Tumor ,medicine ,Humans ,Missense mutation ,Prospective Studies ,Codon ,Deoxyribonucleases, Type II Site-Specific ,Prospective cohort study ,Liver Neoplasms ,DNA ,General Medicine ,Middle Aged ,Genes, p53 ,medicine.disease ,Hepatocellular carcinoma ,Mutation (genetic algorithm) ,Female ,Liver cancer ,medicine.drug ,Cohort study - Abstract
A specific missense mutation in the p53 tumor gene at codon 249 has been reported in over 50% of hepatocellular carcinoma (HCC) tumors and in paired blood samples from areas of high dietary exposure to aflatoxin B1, including Qidong, People's Republic of China. Using a combination of pre-digestion with HaeIII, PCR and mass spectrometry, the temporality of this mutation in plasma before and after the clinical diagnosis of HCC was examined. Sixteen liver cancer cases, diagnosed between 1997 and 2001, were selected from a prospective cohort of 1638 high-risk individuals in Qidong on the basis of available annual plasma samples spanning the years before and after diagnosis. The codon 249 mutation was detected in plasma samples obtained after diagnosis in seven of the 15 cases (46.7%) with PCR amplifiable DNA, which is in accord with the reported prevalence of this mutation in HCC. The persistent detection of this mutation in plasma collected annually following diagnosis was statistically significant (P = 0.024, two-tailed) in repetitive samples following diagnosis. Moreover, the mutation was detected in the plasma of four of eight cases positive at the time of diagnosis at least 1 year and in one case 5 years prior to diagnosis. Tracking of the marker in pre-diagnostic samples was borderline statistically significant (P = 0.066). None of the 18 healthy US control plasma samples had any detectable mutations. We have therefore found that pre-diagnosis biomarkers of specific p53 mutations can be measured in plasma and this suggests a paradigm for developing these markers for use in prevention and intervention trials.
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- 2003
11. Chlorophyllin intervention reduces aflatoxin–DNA adducts in individuals at high risk for liver cancer
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Jin Bing Wang, Lisa P. Jacobson, Shuang Yuan Kuang, Thomas W. Kensler, Patricia A. Egner, Kathy J. Helzlsouer, Geng Sun Qian, Qi Nan Zhang, John D. Groopman, Stephen J. Gange, George S. Bailey, Bao Chu Zhang, Yuan Rong Zhu, and Yan Wu
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Adult ,Male ,China ,Aflatoxin ,Aflatoxin B1 ,Carcinoma, Hepatocellular ,Guanine ,Food Contamination ,Urine ,Pharmacology ,Toxicology ,DNA Adducts ,chemistry.chemical_compound ,Aflatoxins ,Risk Factors ,medicine ,Animals ,Humans ,Carcinogen ,Aged ,Multidisciplinary ,Chlorophyllides ,Chemistry ,Chlorophyllin ,Liver Neoplasms ,Middle Aged ,Biological Sciences ,medicine.disease ,Effective dose (pharmacology) ,Bioavailability ,Hepatocellular carcinoma ,Female ,Liver cancer ,Biomarkers - Abstract
Residents of Qidong, People's Republic of China, are at high risk for development of hepatocellular carcinoma, in part from consumption of foods contaminated with aflatoxins. Chlorophyllin, a mixture of semisynthetic, water-soluble derivatives of chlorophyll that is used as a food colorant and over-the-counter medicine, has been shown to be an effective inhibitor of aflatoxin hepatocarcinogenesis in animal models by blocking carcinogen bioavailability. In a randomized, double-blind, placebo-controlled chemoprevention trial, we tested whether chlorophyllin could alter the disposition of aflatoxin. One hundred and eighty healthy adults from Qidong were randomly assigned to ingest 100 mg of chlorophyllin or a placebo three times a day for 4 months. The primary endpoint was modulation of levels of aflatoxin-N 7 -guanine adducts in urine samples collected 3 months into the intervention measured by using sequential immunoaffinity chromatography and liquid chromatography–electrospray mass spectrometry. This aflatoxin–DNA adduct excretion product serves as a biomarker of the biologically effective dose of aflatoxin, and elevated levels are associated with increased risk of liver cancer. Adherence to the study protocol was outstanding, and no adverse events were reported. Aflatoxin-N 7 -guanine could be detected in 105 of 169 available samples. Chlorophyllin consumption at each meal led to an overall 55% reduction ( P = 0.036) in median urinary levels of this aflatoxin biomarker compared with those taking placebo. Thus, prophylactic interventions with chlorophyllin or supplementation of diets with foods rich in chlorophylls may represent practical means to prevent the development of hepatocellular carcinoma or other environmentally induced cancers.
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- 2001
12. Genetic alterations in hepatocellular carcinomas: association between loss of chromosome 4q and p53 gene mutations
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Stanley R. Hamilton, Asif Rashid, John D. Groopman, Geng Sun Qian, B. X. Lu, and J. S. Wang
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China ,Cancer Research ,Carcinoma, Hepatocellular ,Loss of Heterozygosity ,hepatocellular carcinomas ,Gene mutation ,Biology ,medicine.disease_cause ,Polymerase Chain Reaction ,Hepatitis B Antigens ,Loss of heterozygosity ,medicine ,Humans ,neoplasms ,Glutathione Transferase ,Epoxide Hydrolases ,Hepatitis B virus ,Mutation ,Point mutation ,Liver Neoplasms ,aflatoxin ,Regular Article ,p53 gene ,DNA ,HCCS ,Genes, p53 ,Hepatitis B ,medicine.disease ,Immunohistochemistry ,digestive system diseases ,Chromosome 4 ,Oncology ,Hepatocellular carcinoma ,Cancer research ,Chromosomes, Human, Pair 4 ,Hepatitis C Antigens ,hepatitis B virus ,Chromosomes, Human, Pair 17 ,Microsatellite Repeats - Abstract
The major risk factors for hepatocellular carcinomas (HCC) in high incidence areas include infection with hepatitis B and C viruses (HBV, HCV) and exposure to aflatoxin. Genetic alterations in 24 liver resection specimens from Shanghai and Qidong were studied. Hepatitis B virus was integrated in all patient samples, and a null phenotype for the GSTM1 enzyme was present in 63% of patients. Alteration of p53 was present in 95% (23/24) of cases: mutations of the p53 gene in 12 HCC, p53 overexpression in 13 and loss of heterozygosity (LOH) of chromosome 17p in 17. All seven HCCs with a p53 mutation from Qidong and three of five from Shanghai had the aflatoxin-associated point mutation with a G to T transversion at codon 249, position 3. No HCC had microsatellite instability. LOH of chromosome 4q, 1p, 16q and 13q was present in 50%, 46%, 42% and 38%, respectively, and 4q was preferentially lost in HCCs containing a p53 mutation: LOH of 4q was present in 75% (9/12) of HCC with, but only 25% (3/12) of HCC without, a p53 gene mutation (P = 0.01). These data indicate a possible interaction between p53 gene mutation and 4q loss in the pathogenesis of HCC. © 1999 Cancer Research Campaign
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- 1999
13. Protective Alterations in Phase 1 and 2 Metabolism of Aflatoxin B1 by Oltipraz in Residents of Qidong, People's Republic of China
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Geng Sun Qian, Lisa P. Jacobson, Audrey Zarba, Patricia A. Egner, Jia-Sheng Wang, Alvaro Muñoz, Thomas W. Kensler, Yuan Rog Zhu, John D. Groopman, Xia He, Bao Chu Zhang, Xinnan Shen, Shuang Yuan Kuang, Jin Bing Wang, and Katy J. Helzlsouer
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China ,Cancer Research ,Pathology ,medicine.medical_specialty ,Aflatoxin ,Aflatoxin B1 ,Metabolite ,Thiophenes ,Urine ,Pharmacology ,Drug Administration Schedule ,Gas Chromatography-Mass Spectrometry ,Excretion ,chemistry.chemical_compound ,Double-Blind Method ,Cytochrome P-450 CYP1A2 ,Oltipraz ,Anticarcinogenic Agents ,Humans ,Medicine ,Anticarcinogen ,Carcinogen ,Glutathione Transferase ,business.industry ,Liver Neoplasms ,Reproducibility of Results ,Thiones ,food and beverages ,medicine.disease ,Acetylcysteine ,Treatment Outcome ,Oncology ,chemistry ,Pyrazines ,Hepatocellular carcinoma ,Carcinogens ,Feasibility Studies ,business - Abstract
Background: Residents of Qidong, People’s Republic of China, are at high risk for development of hepatocellular carcinoma, in part due to consumption of foods contaminated with aflatoxins, which require metabolic activation to become carcinogenic. In a randomized, placebo-controlled, double-blind phase IIa chemoprevention trial, we tested oltipraz, an antischistosomal drug that has been shown to be a potent and effective inhibitor of aflatoxin-induced hepatocarcinogenesis in animal models. Methods: In 1995, 234 adults from Qidong were enrolled. Healthy eligible individuals were randomly assigned to receive by mouth 125 mg oltipraz daily, 500 mg oltipraz weekly, or a placebo. Sequential immunoaffinity chromatography and liquid chromatography coupled to mass spectrometry or to fluorescence detection were used to identify and quantify phase 1 and phase 2 metabolites of aflatoxin B1 in the urine of study participants. Reported P values are two-sided. Results: One month of weekly administration of 500 mg oltipraz led to a 51% decrease in median levels of the phase 1 metabolite aflatoxin M1 excreted in urine compared with administration of a placebo (P = .030), but it had no effect on levels of a phase 2 metabolite, aflatoxin‐mercapturic acid (P = .871). By contrast, daily intervention with 125 mg oltipraz led to a 2.6-fold increase in median aflatoxin‐mercapturic acid excretion (P = .017) but had no effect on excreted aflatoxin M 1 levels (P = .682). Conclusions: Intermittent, high-dose oltipraz inhibited phase 1 activation of aflatoxins, and sustained low-dose oltipraz increased phase 2 conjugation of aflatoxin, yielding higher levels of aflatoxin‐mercapturic acid. While both mechanisms can contribute to protection, this study highlights the feasibility of inducing phase 2 enzymes as a chemopreventive strategy in humans. [J Natl Cancer Inst 1999; 91:347‐54]
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- 1999
14. Correction to: Circular RNA circ-CSPP1 regulates CCNE2 to facilitate hepatocellular carcinoma cell growth via sponging miR-577.
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Sun, Qian, Yu, Rui, Wang, Chunfeng, Yao, Jianning, and Zhang, Lianfeng
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CIRCULAR RNA , *HEPATOCELLULAR carcinoma , *CELL growth - Abstract
An amendment to this paper has been published and can be accessed via the original article. [ABSTRACT FROM AUTHOR]
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- 2020
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15. Oltipraz chemoprevention trial in Qidong, Jiangsu Province, People's Republic of China
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Thomas W. Kensler, Hans J. Prochaska, Shuang Yuan Kuang, Baibai Chen, Jia-Sheng Wang, Geng Sun Qian, Mary B. Gorman, John D. Groopman, Xia He, Yuan Rong Zhu, Bao Chu Zhang, Audrey Zarba, Lu Yi Yu, Kathy J. Helzlsouer, Patricia A. Egner, Yan Wu, Xi Fang, Alvaro Muñoz, Yan Feng Li, Cheryl Enger, Lisa P. Jacobson, Gary B. Gordon, Jin Bing Wang, Silvio De Flora, Qi Nan Zhang, and Nancy E. Davidson
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Aflatoxin ,medicine.medical_specialty ,business.industry ,Cell Biology ,Urine ,Pharmacology ,medicine.disease ,Placebo ,Biochemistry ,chemistry.chemical_compound ,chemistry ,Hepatocellular carcinoma ,Internal medicine ,Oltipraz ,medicine ,Tingling ,Objective evaluation ,business ,Adverse effect ,Molecular Biology - Abstract
Oltipraz has been used clinically in many regions of the world as an antischistosomal agent and is an effective inhibitor of aflatoxin hepatocarcinogenesis in rats. This chemopreventive action of oltipraz results primarily from an altered balance in aflatoxin metabolic activation and detoxication. In 1995, a randomized, placebo-controlled, double-blind intervention was conducted in residents of Qidong, People's Republic of China, who are at high risk for exposure to aflatoxin and development of hepatocellular carcinoma. The major study objectives were to define a dose and schedule for oltipraz that would reduce levels of aflatoxin biomarkers in biofluids of the participants, and to further characterize dose-limiting side effects. Two hundred thirty-four healthy eligible individuals, including those infected with HBV, were randomized to receive either 125 mg oltipraz daily, 500 mg oltipraz weekly, or placebo. Blood and urine specimens were collected to monitor potential toxicities and evaluate biomarkers over the 8-week intervention and subsequent 8-week follow-up periods. Overall, compliance in the intervention was excellent; approximately 85% of the participants completed the study. Objective evaluation of adverse events was greatly facilitated by inclusion of a placebo arm in the study design. A syndrome involving numbness, tingling, and pain in the fingertips was the only event that occurred more frequently among the active groups (18 and 14% of the daily 125 mg and weekly 500 mg arms, respectively) compared to placebo (3%). These symptoms were reversible and could be relieved with non-steroidal antiinflammatory agents. A more complete understanding of the chemopreventive utility of oltipraz awaits completion of an assessment of the efficacy of oltipraz in modulating levels of aflatoxin biomarkers. J. Cell. Biochem. Suppls. 28/29:166–173. © 1998 Wiley-Liss, Inc.
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- 1997
16. Flavan enantiomers from Daphne giraldii selectively induce apoptotic cell death in p53-null hepatocarcinoma cells in vitro.
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Yao, Guo-Dong, Sun, Qian, Song, Xiao-Yu, Huang, Xiao-Xiao, and Song, Shao-Jiang
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FLAVANS , *ENANTIOMERS , *APOPTOSIS , *CANCER cells , *LIVER cancer - Abstract
Hepatocellular carcinoma (HCC) is a primary malignant tumor with very poor prognosis. To search for more effective compounds for HCC treatment, two new pairs of flavan enantiomers, daphnegiranol C 1 /C 2 ( 1a/1b ) and daphnegiranol D 1 /D 2 ( 2a/2b ), were isolated from the stem bark and roots of Daphne giraldii by using chiral chromatography. MTT assay was applied to evaluate their cytotoxicity against three hepatocarcinoma cell lines (Hep3B, MHCC97H, HepG2) as well as a normal liver cell line L02. The results showed that these compounds preferred to inhibit the growth of Hep3B cells (p53 null). Among them, 2a/2b (the IC 50 value was 4.87 and 3.35 μM, respectively) exhibited a stronger cytotoxic effect than sorafenib (IC 50 = 6.59 μM) in Hep3B cells. A further study demonstrated that 2a/2b could induce apoptotic cell death with an increase in reactive oxygen species (ROS) in Hep3B cells. In addition, the IC 50 values of 2a/2b in HepG2 and MHCC97H cells (both harbored p53 gene) were more than 10-folds greater when compared with Hep3B cells, indicating that 2a/2b selectively exhibited cytotoxicity in p53-null hepatocarcinoma cells. Moreover, inhibition of p53 increased the inhibitory effect in p53-wild hepatocarcinoma cells, as well as apoptotic cells and ROS generation. Taken together, flavan enantiomers 2a/2b selectively induced apoptosis in Hep3B cells because of p53 deficiency. [ABSTRACT FROM AUTHOR]
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- 2018
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17. 1,3-Diphenylpropanes from Daphne giraldii induced apoptosis in hepatocellular carcinoma cells through nuclear factor kappa-B inhibition.
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Yao, Guo-Dong, Sun, Qian, Song, Xiao-Yu, Huang, Xiao-Xiao, Zhang, Yan, and Song, Shao-Jiang
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DIBENZOYLMETHANE , *LIVER cancer , *CELL lines , *CELL death , *CARCINOMA - Abstract
One new 1,3-diphenylpropane ( 1 ) together with six known analogues ( 2 – 7 ) were firstly isolated from the stem and root bark of Daphne giraldii . Their structures were determined by comprehensive NMR and HRESIMS spectroscopic data analyses. All the isolates were evaluated for their cytotoxicity against two hepatocellular carcinoma cell lines (HepG2 and Hep3B). Among them, compound 5 showed the most significant cytotoxicity against Hep3B cells, with an IC 50 value of 17.21 μM. A further study demonstrated that 5 obviously induced apoptotic cell death as well as the inactivation of nuclear factor kappa B p65 (NF-κB p65) in Hep3B cells. In addition, BAY 11-7082 (BAY), a NF-кB inhibitor, was used to determine the role of NF-кB signaling in 5 -treated Hep3B cells. The results suggested that BAY could enhance 5 -induced apoptosis of Hep3B cells. In conclusion, the data provided that 5 might be a potential candidate for the treatment of hepatocellular carcinoma through NF-κB inhibition. [ABSTRACT FROM AUTHOR]
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- 2018
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18. Chemoprevention of Hepatic Cancer in Aflatoxin Endemic Areas
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Patricia A. Egner, Geng Sun Qian, John D. Groopman, Thomas W. Kensler, Jianguo Chen, and Alvaro Muñoz
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Hepatitis B virus ,Aflatoxin ,business.industry ,Psychological intervention ,Cancer ,medicine.disease_cause ,medicine.disease ,Bioinformatics ,law.invention ,Vaccination ,Randomized controlled trial ,law ,Hepatocellular carcinoma ,Medicine ,business ,Liver cancer - Abstract
Hepatocellular carcinoma is one of the most common cancers worldwide. Infection with hepatitis B virus and exposure to aflatoxins in the diet act synergistically to amplify risk. Although primary prevention, based on vaccination and avoiding exposure to these agents, is an appealing option, such strategies will require considerable investment of time and resources to be successful. In the economically developing world—where the burden of liver cancer is highest—immediate, practical approaches are essential. So, targeted chemoprevention might be most appropriate for the present generation of individuals at risk. Experimentally, aflatoxin-induced hepatocarcinogenesis can be inhibited by over a score of different chemopreventive agents with multiple mechanisms of action. This chapter highlights the findings of randomized clinical trials conducted in individuals exposed to dietary aflatoxins and at high risk of development of liver cancer. Several preventive interventions, both primary and secondary in approach, have succeeded in modulating levels of aflatoxin biomarkers in the study participants in manners consonant with protection. Although pharmacological approaches establish proof-of-principle and help identify key molecular targets for interventions, food-based approaches that also use these molecular targets may be the most practical for widespread application in high-risk populations.
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- 2012
19. Temporal acquisition of sequential mutations in the enhancer II and basal core promoter of HBV in individuals at high risk for hepatocellular carcinoma
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Xin Bai, Taoyang Chen, Yan Jin, Jianren Gu, Geng Sun Qian, Jing Zhang, Xia Guo, Yu Zhu, Jinbing Wang, John D. Groopman, and Hong Tu
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Male ,Cancer Research ,medicine.medical_specialty ,Pathology ,Hepatitis B virus ,Carcinoma, Hepatocellular ,Genes, Viral ,Biology ,medicine.disease_cause ,Gastroenterology ,Orthohepadnavirus ,Risk Factors ,Internal medicine ,medicine ,Carcinoma ,Humans ,Longitudinal Studies ,Promoter Regions, Genetic ,neoplasms ,Mutation ,Molecular Epidemiology ,Reverse Transcriptase Polymerase Chain Reaction ,Point mutation ,Liver Neoplasms ,General Medicine ,Middle Aged ,medicine.disease ,biology.organism_classification ,Hepatitis B ,digestive system diseases ,Cross-Sectional Studies ,Hepadnaviridae ,Hepatocellular carcinoma ,Female ,Liver cancer - Abstract
To investigate the roles of mutations in enhancer II (Enh II) and basal core promoter (BCP) of hepatitis B virus (HBV) in hepatocellular carcinoma (HCC), we determined the sequence of Enh II/BCP in 152 HCC and 136 non-HCC patients from a high-incidence area of East China. A longitudinal study was conducted on 21 cases in which serial plasma samples were available before HCC. In total, six point mutations, including T1653, V1753, T1762, A1764, T1766 and A1768, were found to occur more frequently in HCC patients. Multivariate analysis showed that the T1653 [odds ratio (OR), 2.07; 95% confidence interval (CI), 1.114–3.845] and V1753 (OR, 3.099; 95% CI, 1.520–6.317) were independent factors that were associated with HCC. Although a T1762/A1764 double mutation was found in 73.0% of the HCC patients and 66.9% of the non-HCC patients, if the combined pattern with other adjacent mutations was not taken into account, it alone showed a lower frequency in HCC patients compared with non-HCC patients (19.7 versus 34.6%, P = 0.005). Interestingly, while the OR of HCC patients with a double mutation was only 0.393 (95% CI, 0.234–0.660), it increased to 1.861 (95% CI, 1.161–2.984) with a triple mutation and to 4.434 (95% CI, 1.630–12.063) with a quadruple mutation. The longitudinal study demonstrated that the mutations in Enh II/BCP accumulated during the development of HCC. In conclusion, the T1653 and V1753 mutations were independent risk factors for HCC in East China. The T1762/A1764 double mutation was necessary but not sufficient to produce an association between Enh II/BCP mutations and HCC.
- Published
- 2010
20. Comparison study on the complete sequence of hepatitis B virus identifies new mutations in core gene associated with hepatocellular carcinoma
- Author
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Jinbing Wang, Yan Jin, Hong Tu, Xin Bai, Jinjun Li, Geng Sun Qian, John D. Groopman, Xia Guo, Yu Zhu, Jianren Gu, and Taoyang Chen
- Subjects
Oncology ,Adult ,Male ,medicine.medical_specialty ,Hepatitis B virus ,Carcinoma, Hepatocellular ,Genotype ,Epidemiology ,Genome, Viral ,medicine.disease_cause ,Liver disease ,Orthohepadnavirus ,Internal medicine ,Molecular genetics ,medicine ,Humans ,Point Mutation ,Longitudinal Studies ,neoplasms ,biology ,Point mutation ,Liver Neoplasms ,Reproducibility of Results ,Middle Aged ,biology.organism_classification ,medicine.disease ,Virology ,digestive system diseases ,Hepadnaviridae ,Hepatocellular carcinoma ,Case-Control Studies ,DNA, Viral ,Female ,Liver cancer - Abstract
Background: Mutations in the hepatitis B virus (HBV) genome may influence the activity of liver disease. The aim of this study was to identify new viral variations associated with hepatocellular carcinoma (HCC). Methods: We carried out a comparison study on the complete sequence of HBV isolated from 20 HCC and 35 non-HCC patients in Qidong, China, an area with a high incidence of HCC. We compared the HBV sequences in a consecutive series of plasma samples from four HCC cases before and after the occurrence of HCC. In addition, we selected four mutations in the HBV core (C) gene to verify their relationships to HCC in an independent set of 103 HCC cases and 103 sex- and age-matched non-HCC controls. Results: The pre-S deletion and 12 point mutations, namely, the pre-S2 start codon mutation, T53C in the pre-S2 gene, T766A in the S gene, G1613A, C1653T, A1762T, G1764A in the X gene, and G1899A, C2002T, A2159G, A2189C, and G2203W (A or T) in the pre-C/C gene, showed close associations with HCC. In the validation study, A2159G, A2189C, and G2203W showed consistent associations with HCC by univariate analysis. Multivariate analysis showed that A2189C and G2203W were independent risk factors for HCC. The odds ratios (95% confidence interval) were 3.99 (1.61-9.92) and 9.70 (1.17-80.58), respectively, for A2189C and G2203W. Conclusions: These results implicate A2189C and G2203W as new predictive markers for HCC. Impact: The complete genome analysis of HBV provided pilot data for the identification of novel mutations that could serve as markers for HCC. Cancer Epidemiol Biomarkers Prev; 19(10); 2623–30. ©2010 AACR.
- Published
- 2010
21. Hepatitis B virus core protein variations differ in tumor and adjacent nontumor tissues from patients with hepatocellular carcinoma
- Author
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Yu Zhu, Yan Jin, Jinjun Li, Taoyang Chen, Hong Tu, Min Chen, Geng Sun Qian, Jianren Gu, Jinbing Wang, Xin Bai, and Xiaojin Cai
- Subjects
Adult ,Male ,Hepatitis B virus ,Carcinoma, Hepatocellular ,Sequence analysis ,Molecular Sequence Data ,Mutation, Missense ,Biology ,medicine.disease_cause ,Hepatitis B, Chronic ,Virology ,medicine ,Carcinoma ,Missense mutation ,Humans ,Amino Acid Sequence ,Aged ,Sequence Deletion ,chemistry.chemical_classification ,Polymorphism, Genetic ,virus diseases ,Sequence Analysis, DNA ,Hepatitis B ,Middle Aged ,medicine.disease ,Molecular biology ,Hepatitis B Core Antigens ,digestive system diseases ,Amino acid ,HBcAg ,Infectious Diseases ,chemistry ,Amino Acid Substitution ,Hepatocellular carcinoma ,DNA, Viral ,Female - Abstract
Objectives: To characterize the mutation pattern of a hepatitis B virus (HBV) core protein (HBcAg) derived from hepatocellular carcinoma (HCC) and adjacent nontumor tissues. Methods: HBV core gene fragments (nt. 1901–2365) were amplified from 98 HBV-related HCC tissues and 33 adjacent nontumor tissues. The deduced amino acids (AAs) of the core gene were aligned with the prototype sequences of HBV genotypes B and C. Results: In total, there were 54 positions that showed polymorphism at the deduced AA level. The mutations were predominantly located in three major (codons 83–87, 95–104 and 130–135) and three minor (codons 21–38, 59–63 and 151–155) mutation-clustering regions (MCRs). The substitution rate in MCRs was significantly higher than in mutation-devoid regions (p < 0.001). The most frequently occurring mutations in rank were codon P130T (38.8%), I97L (37.8%) and S87G (23.5%). In addition, there were 7 patients that showed internal deletions in the middle of HBcAg with sizes ranging from 34 to 59 AAs. Unexpectedly, the core genes isolated from tumor tissues had fewer mutations compared with those isolated from adjacent nontumor tissues from the same patients (p < 0.05). Conclusions: Accumulation of naturally occurring mutations in certain restricted segments of HBcAg may be related to the development of HCC.
- Published
- 2010
22. High prevalence of hepatitis B virus pre-S mutation and its association with hepatocellular carcinoma in Qidong, China
- Author
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Xin Bai, Yan Jin, Xia Guo, Geng Sun Qian, Hong Tu, and Zhigang Cao
- Subjects
Adult ,Male ,China ,Hepatitis B virus ,Carcinoma, Hepatocellular ,Population ,Mutation, Missense ,Biology ,medicine.disease_cause ,Virus ,Liver disease ,Hepatitis B, Chronic ,Orthohepadnavirus ,Virology ,medicine ,Humans ,Longitudinal Studies ,Protein Precursors ,education ,Sequence Deletion ,Mutation ,education.field_of_study ,Hepatitis B Surface Antigens ,General Medicine ,Sequence Analysis, DNA ,Middle Aged ,medicine.disease ,biology.organism_classification ,digestive system diseases ,Hepadnaviridae ,Hepatocellular carcinoma ,Immunology ,DNA, Viral ,Female - Abstract
We investigated the frequency and the clinical relevance of hepatitis B virus (HBV) pre-S mutations in Qidong, China. The results showed HBV pre-S mutants were detected in 48.4% (47/97) of patients with HBV infection. Both pre-S deletion and pre-S2 start codon mutations were more frequently found in HCC than in CH patients (51.1% vs. 18.0%, P < 0.01 and 21.2% vs. 8.0%, P = 0.06). In most cases, pre-S mutants coexisted with the wild-type HBV strain. Longitudinal observation clearly revealed that in four of five cases, HBV deletion mutants emerged during the course of HBV infection and eventually became the predominant or exclusive viral population at the stage of HCC. Thus, it was concluded that HBV pre-S mutations were highly prevalent and closely related to HCC in Qidong. Our results also provided direct evidence that pre-S deletion mutants were not acquired from the beginning of infection but arose de novo during the progression of liver disease.
- Published
- 2008
23. Sequential accumulation of the mutations in core promoter of hepatitis B virus is associated with the development of hepatocellular carcinoma in Qidong, China
- Author
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Xia Guo, Yan Jin, Geng Sun Qian, and Hong Tu
- Subjects
Adult ,Male ,China ,Hepatitis B virus ,Carcinoma, Hepatocellular ,Genes, Viral ,medicine.disease_cause ,Cohort Studies ,Hepatitis B, Chronic ,Orthohepadnavirus ,medicine ,Carcinoma ,Humans ,Point Mutation ,Viral Regulatory and Accessory Proteins ,Longitudinal Studies ,Prospective Studies ,Promoter Regions, Genetic ,neoplasms ,DNA Primers ,Hepatology ,biology ,Base Sequence ,Point mutation ,Liver Neoplasms ,Hepatitis B ,Middle Aged ,biology.organism_classification ,medicine.disease ,Virology ,digestive system diseases ,HBx ,Hepadnaviridae ,Amino Acid Substitution ,Hepatocellular carcinoma ,DNA, Viral ,Cancer research ,Trans-Activators ,Female - Abstract
To investigate the mutations in hepatitis B virus (HBV) that might be related to hepatocellular carcinoma (HCC) in the high-risk area Qidong, China.DNA sequences of HBV basal core promoter (BCP) and the overlapping X gene were determined in 58 HCC and 71 chronic hepatitis (CH) patients. In addition, a consecutive series of plasma samples from 15 HCC cases were employed to compare the CP/X sequences before and after the occurrence of HCC.T1762/A1764 double mutation was frequently found in Qidong patients, regardless of clinical status (65.5% in HCC and 73.2% in CH, P0.05). Unexpectedly, the adjacent T1766/A1768 mutation significantly increased the risk of HCC (P0.05). Moreover, the prevalence of triple mutations in BCP was significantly higher in patients with HCC than those with CH (P0.05). The longitudinal study demonstrated that the mutations in BCP were gradually accumulated during the development of HCC. Colony formation assay showed while A1764 mutation alone did not alter the colony-inhibitory activity of HBx, double or triple mutations largely abrogated this effect.The complex mutation involving T1766/A1768 was closely related to HCC. The enhanced risk of HCC caused by BCP variants could be attributable partially to the aberrant activity of HBx.
- Published
- 2008
24. Novel approach to identifying the hepatitis B virus pre-S deletions associated with hepatocellular carcinoma
- Author
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Yu Gan, Yan Jin, Jinbing Wang, Zhigang Cao, Taoyang Chen, Zhi-mei Zhao, Yu Zhu, Hong Tu, Geng Sun Qian, and Yan Sun
- Subjects
Adult ,Male ,clone (Java method) ,Carcinoma, Hepatocellular ,Time Factors ,Genotype ,Sequence analysis ,Observational Study ,medicine.disease_cause ,Polymerase Chain Reaction ,Risk Assessment ,law.invention ,Predictive Value of Tests ,Risk Factors ,law ,medicine ,Humans ,Longitudinal Studies ,Protein Precursors ,Polymerase chain reaction ,Aged ,Hepatitis B virus ,Hepatitis B Surface Antigens ,Predictive marker ,business.industry ,Liver Neoplasms ,Gastroenterology ,virus diseases ,Electrophoresis, Capillary ,General Medicine ,Middle Aged ,Hepatitis B ,medicine.disease ,Virology ,Molecular biology ,digestive system diseases ,Case-Control Studies ,Hepatocellular carcinoma ,Female ,Spectrophotometry, Ultraviolet ,business ,Gene Deletion - Abstract
To develop a novel non-sequencing method for the detection of hepatitis B virus (HBV) pre-S deletion mutants in HBV carriers.The entire region of HBV pre-S1 and pre-S2 was amplified by polymerase chain reaction (PCR). The size of PCR products was subsequently determined by capillary gel electrophoresis (CGE). CGE were carried out in a PACE-MDQ instrument equipped with a UV detector set at 254 nm. The samples were separated in 50 μm ID eCAP Neutral Coated Capillaries using a voltage of 6 kV for 30 min. Data acquisition and analysis were performed using the 32 Karat Software. A total of 114 DNA clones containing different sizes of the HBV pre-S gene were used to determine the accuracy of the CGE method. One hundred and fifty seven hepatocellular carcinoma (HCC) and 160 non-HCC patients were recruited into the study to assess the association between HBV pre-S deletion and HCC by using the newly-established CGE method. Nine HCC cases with HBV pre-S deletion at the diagnosis year were selected to conduct a longitudinal observation using serial serum samples collected 2-9 years prior to HCC diagnosis.CGE allowed the separation of PCR products differing in size3 bp and was able to identify 10% of the deleted DNA in a background of wild-type DNA. The accuracy rate of CGE-based analysis was 99.1% compared with the clone sequencing results. Using this assay, pre-S deletion was more frequently found in HCC patients than in non-HCC controls (47.1% vs 28.1%, P0.001). Interestingly, the increased risk of HCC was mainly contributed by the short deletion of pre-S. While the deletion ≤ 99 bp was associated with a 2.971-fold increased risk of HCC (95%CI: 1.723-5.122, P0.001), large deletion (99 bp) did not show any association with HCC (P = 0.918, OR = 0.966, 95%CI: 0.501-1.863). Of the 9 patients who carried pre-S deletions at the stage of HCC, 88.9% (8/9) had deletions 2-5 years prior to HCC, while only 44.4%4 (4/9) contained such deletions 6-9 years prior to HCC.CGE is a sensitive approach for HBV pre-S deletion analysis. Pre-S deletion, especially for short DNA fragment deletion, is a useful predictive marker for HCC.
- Published
- 2014
25. MicroRNA-15b in extracellular vesicles from arsenite-treated macrophages promotes the progression of hepatocellular carcinomas by blocking the LATS1-mediated Hippo pathway.
- Author
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Li, Junjie, Xue, Junchao, Ling, Min, Sun, Jing, Xiao, Tian, Dai, Xiangyu, Sun, Qian, Cheng, Cheng, Xia, Haibo, Wei, Yongyue, Chen, Feng, and Liu, Qizhan
- Subjects
- *
EXTRACELLULAR vesicles , *ARSENIC , *MACROPHAGES , *CELL communication , *NON-coding RNA , *CANCER invasiveness , *CANCER cell culture , *RESEARCH , *ARSENIC compounds , *LIVER tumors , *ANIMAL experimentation , *RESEARCH methodology , *RNA , *APOPTOSIS , *CELL physiology , *MEDICAL cooperation , *EVALUATION research , *COMPARATIVE studies , *TRANSFERASES , *GENES , *HEPATOCELLULAR carcinoma , *MICE - Abstract
Arsenic, a human carcinogen, causes various human cancers, including those of the skin, lung, and liver. Hepatocellular carcinomas (HCCs), which have high mortality, are common malignancies worldwide. Tumor-associated macrophages (TAMs), which are considered to be similar to M2-polarized macrophages, promote tumor invasion and progression. Small non-coding RNAs (miRNAs) regulate expression of genes involved in progression of various malignancies. Extracellular vesicles (EVs), as mediators of cell communication, pass specific miRNAs directly from TAMs to tumor cells, promoting tumor pathogenesis and metastasis. In HCCs, large tumor suppressor kinase 1 (LATS1), functions as a tumor suppressor. However, the molecular mechanism by which miRNA modulates LATS1 expression in HCCs remains unclear. The results show that exposure to arsenite, increased miR-15b levels and induced M2 polarization of THP-1 cells. Elevated levels of miR-15b were transferred from arsenite-treated-THP-1 (As-THP-1) cells to HCC cells via miR-15b in EVs inhibited activation of the Hippo pathway by targeting LATS1, and was involved in promoting the proliferation, migration, and invasion of HCC cells. In conclusion, miR-15b in EVs from As-THP-1 cells is transferred to HCC cells, in which it targets and downregulates LATS1 expression and promotes the proliferation, migration, and invasion of HCC cells. [ABSTRACT FROM AUTHOR]
- Published
- 2021
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