Guangyuan Hu

Tongji Hospital, Wu-han-shih, Hubei, China

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Publications (15)27.49 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Objective: Several studies have demonstrated that a serum-based proteomic test (VeriStrat*) is able to predict the clinical outcome of non-small-cell lung cancer (NSCLC) patients treated with epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs). However, these studies have limited power to draw a precise conclusion because of their small sample sizes and inconsistent results. Therefore, a meta-analysis was carried out in an attempt to provide more persuasive evidence. Research design and methods: Electronic searches for relevant articles in PubMed, Embase, Medline, and Web of Science published up to May 2013 were conducted. Stata Statistical Software version 12.0 was applied for statistical analysis. The combined hazard ratio (HR) and 95% confidence interval (CI) were estimated using fixed-effects models. Results: Eleven cohorts involving 706 patients collected from seven studies were subjected to final analysis. This serum-based proteomic test’s ‘good’ status predicted a better clinical outcome with a pooled HR of 0.40 (95% CI 0.32 to 0.49; p < 0.001) for overall survival (OS), and 0.49 (95% CI 0.39 to 0.60; p < 0.001) for progression-free survival (PFS). There was no significant heterogeneity, but a slight publication bias in this study. Conclusions: Our meta-analysis demonstrated that this serum-based proteomic test has a predictive value for NSCLC patients treated with EGFR-TKIs. Future data are needed to validate and update our results.
    Current Medical Research and Opinion 07/2014; · 2.37 Impact Factor
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    ABSTRACT: We previously showed that human papillomavirus (HPV) serostatus was not an independent risk factor for esophageal squamous cell carcinoma(ESCC) in nonsmokers and nondrinkers; however, HPV increased the risk in smokers.
    BMC Cancer 07/2014; 14(1):501. · 3.33 Impact Factor
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    ABSTRACT: Telomere shortening has been suggested to be a genetic predictor for various cancers. However, evidences about this point with respect to esophageal squamous cell carcinoma (ESCC) in Han Chinese populations remain limited. Our previous study demonstrated that p53 Arg72Pro polymorphism was associated with the risk of human papillomavirus (HPV)-related ESCC. Telomeres and p53 play important roles in maintaining genomic stability and regulating the cell cycle. HPV impacts both telomere length stabilization and p53 degradation. Given the roles of the three factors, we evaluated leukocyte telomere length, p53 variants and HPV-16 serology to examine the potential associations between them and ESCC risk in a case–control study with 308 patients and 309 cancer-free controls matched by age and sex. Compared with long telomere length, short telomere length was significantly associated with an increased risk of ESCC (adjusted OR 2.01; 95% CI 1.41–2.80). Moreover, this association was enhanced when combined with HPV-16 seropositivity and p53 Arg/Arg or Arg/Pro genotypes. Notably, individuals with short telomere length, Arg/Pro or Arg/Arg genotypes and HPV-16 seropositivity had a 12.08-fold (95% CI 5.49–26.56) increased risk of ESCC compared to those with none of the three investigated risk factors. Taken together, these results indicate that short telomere length in peripheral blood leukocytes is a biomarker for ESCC risk, and has statistically additive effects with p53 variants and HPV seropositivity with regard to the risk of ESCC in a Han Chinese population.
    Cancer Epidemiology. 01/2014;
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    ABSTRACT: The predictive value of thymidine phosphorylase gene variants (TP, also called platelet-derived endothelial cell growth factor) and thrombocytosis were controversial and worthy of further study in gastrointestinal cancer (GIC) patients. We screened all of the common missense single nucleotide polymorphisms (MAF ≥ 0.1) in fluoropyrimidines (FU) pathway genes (including TP, TS, ENOSF1 and DPD). Three of them were selected and genotyped using Sequenom MassARRAY in 141 GIC patients. TP expression was assessed by immunohistochemistry. Our aim was to evaluate the prognostic significance of studied genes and platelet counts in GIC patients. Multivariate analyses indicated in rs11479-T allele carriers, platelet counts negatively correlated to overall survival. In addition, T allele of TP: rs11479 was associated with higher TP expression in cancer tissues. We suggest TP: rs11479 variant combined with platelet counts may be useful prognostic makers in GIC patients receiving first-line FU chemotherapy and thrombopoietin factor should be used with caution in the rs11479 T allele bearing patients.
    Scientific reports. 01/2014; 4:5697.
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    ABSTRACT: Non-small cell lung cancer (NSCLC) metastasizes fairly often to the brain, but identifying which patients will develop brain metastases (BM) is problematic. The phosphatidylinositol-3 kinase (PI3K)-AKT-mammalian target of rapamycin (mTOR) signaling pathway is important in the control of cell growth, tumorigenesis, and cell invasion. We hypothesized that genotype variants in this pathway could predict BM in patients with NSCLC. We genotyped 16 single nucleotide polymorphisms (SNPs) in 5 core genes (PIK3CA, PTEN, AKT1, AKT2, and FRAP1) by using DNA from blood samples of 317 patients with NSCLC and evaluated potential associations with the subsequent development of BM, the cumulative incidence of which was estimated with Kaplan-Meier analysis. Multivariate Cox regression analysis was used to analyze correlations between genotype variants and the occurrence of BM. In analysis of individual SNPs, the GT/GG genotype of AKT1: rs2498804, CT/TT genotype of AKT1: rs2494732 and AG/AA genotype of PIK3CA: rs2699887 were associated with higher risk of BM at 24 months' follow-up (respective hazard ratios [HRs] 1.860, 95% confidence interval [CI] 1.199-2.885, P=0.006; HR 1.902, 95% CI 1.259-2.875, P = 0.002; and HR 1.933, 95% CI 1.168-3.200, P=0.010). We further found that these SNPs had a cumulative effect on BM risk, with that risk being highest for patients carrying both of these unfavorable genotypes (P=0.003). Confirmation of our findings, the first to indicate that genetic variations in PI3K-AKT-mTOR can predict BM, in prospective studies would facilitate stratification of patients for BM prevention trials.
    Clinical Cancer Research 09/2013; · 7.84 Impact Factor
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    ABSTRACT: Though polymorphisms of the tumor suppressor gene p53 have been extensively investigated in numerous tumors, particularly tumors associated with human papillomavirus (HPV) infection. However, the results remain controversial. Our previous study showed that HPV serostatus is not an independent risk factor for esophageal squamous cell carcinoma (ESCC) in nonsmokers and nondrinkers. Given the roles of p53 and HPV E6 as well as MDM2 oncoproteins in p53 degradation, we validated the association of p53 and MDM2 polymorphisms with ESCC risk stratified by HPV16 sero-status. Single nucleotide polymorphisms of p53 Arg72Pro (rs1042522) and MDM2 (rs937283) in 307 ESCC patients and 311 healthy controls were genotyped. The presence or absence of HPV16 in serum was measured by enzyme-linked immunosorbent assay. Multivariable logistic regression analysis was used to evaluate the possible associations of p53 and MDM2 polymorphisms with ESCC risk stratified by HPV16 sero-status. Patients carrying p53 Arg/Arg or Arg/Pro had a higher risk of esophageal SCC (P<0.001, Odds ratio [OR] 4.98, 95% confidential interval [CI] 3.46-7.17), however, not found in MDM2 rs937283. The risk of esophageal SCC increased significantly among patients carrying p53 Arg/Arg, or Arg/Pro and HPV16-seropositivity (P<0.001, OR 9.33, 95% CI 5.44-16.0), but not for MDM2 rs937283. The risk of esophageal SCC was further elevated among patients carrying Arg/Arg or Arg/Pro and HPV16-seropositivity who were smokers (P<0.001, OR 27.05, 95% CI 11.06-66.16) or drinkers (P<0.001, OR 13.20, 95% CI 5.74-30.38). HPV16 seropositivity synergized with p53 Arg/Arg or Arg/Pro and increased ESCC risk, especially in smokers or drinkers.
    Cancer epidemiology. 07/2013;
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    ABSTRACT: Three recent genome-wide association studies (GWASs) have reported that three SNPs (rs4072037, rs13361707 and rs2274223) located on genes related to host inflammatory response are significantly associated with susceptibility to gastric cancer (GC) in Chinese populations. Helicobacter pylori infection is also an important risk factor for GC through causing inflammatory response in the gastric mucosa. However, no study has established whether there are potential gene-environment interactions between these genetic variants and H. pylori infection to the risk of GC. We genotyped three polymorphisms (rs4072037 at 1q22, rs13361707 at 5p13, and rs2274223 at 10q23) in 335 Chinese gastric adenocarcinoma patients and 334 controls. H. pylori serology was examined by enzyme-linked immunosorbent assay. Multivariable logistic regression models were used to evaluate the association between the variables and GC risk. We confirmed that the three SNPs (rs4072037, rs13361707 and rs2274223) were significantly associated with GC susceptibility. H. pylori infection also significantly increased the risk of GC. Furthermore, there were joint effects between H. pylori infection and the three SNPs on the risk of GC. The most elevated risk of GC was found in subjects with H. pylori seropositivity and AA genotypes for rs4072037 [odds ratio (OR), 3.95; 95% confidence interval (CI), 2.29-6.79], H. pylori seropositivity and CT/CC genotypes for rs13361707 (OR, 2.68; 95% CI, 1.62-4.43), H. pylori seropositivity and AG/GG genotypes for rs2274223 (OR, 2.45; 95% CI, 1.55-3.88) compared with those with H. pylori seronegativity and other genotypes of each SNP. Significant interactions were observed between H. pylori seropositivity and the three SNPs (all P G× E <0.05) to the risk of GC. These findings indicate that the three SNPs (rs4072037, rs13361707 and rs2274223) identified in the GWASs may interact with H. pylori infection to increase the risk of GC.
    PLoS ONE 01/2013; 8(9):e74976. · 3.53 Impact Factor
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    ABSTRACT: Endogenous estrogens may play a vital role in colorectal tumorigenesis. Estrogen receptor beta is the predominant subtype which mediates the biological effect of estrogens, while loss of expression of estrogen receptor beta has been indicated as a common step in the development of colorectal cancer (CRC). Epidemiological studies have revealed several functional polymorphisms of estrogen receptor beta (ESR2) for cancer risk, but relevant study in CRC is limited, particularly in men. This study aimed to investigate the association of circulating estradiol and variations of ESR2 with CRC risk in men. We initiated a case-control study consisting of 390 patients with CRC and 445 healthy controls in men only. We genotyped ESR2 single nucleotide polymorphisms (SNPs) rs1256049 and rs4986938 and measured serum estradiol concentration using chemilluminescence immunoassay. Multivariable logistic regression model was performed to evaluate the associations between these variables and CRC risk. ESR2 rs1256049 CT/TT genotypes were associated with reduced risk of CRC (odds ratio [OR], 0.7, 95% confidence interval [CI], 0.5-1.0), while rs4986938 CT/TT genotypes were associated with increased risk of CRC (OR, 1.5, 95% CI, 1.0-2.1). In addition, the CRC risk increased with the number of risk genotypes of these two SNPs in a dose-response manner (Ptrend, 0.003). Specifically, subjects carrying risk genotypes of both SNPs had the highest risk of CRC (OR, 2.0, 95% CI, 1.3-3.3.). Moreover, serum estradiol concentration alone was associated with risk of CRC in men (OR, 1.2, 95% CI, 1.0-1.3). However, individuals presenting both rs4986938 CT/TT genotypes and high level of serum estradiol had a high risk of CRC (OR, 2.3, 95% CI, 1.4-3.9), compared with those presenting CC genotype and low level of serum estradiol. The similar joint results were not observed for SNP rs1256049. These results suggest that endogenous estrogen and genetic variations in ESR2 may individually, or more likely jointly, affect CRC risk in male Han Chinese population, while larger studies are needed to validate our findings.
    BMC Cancer 07/2012; 12:276. · 3.33 Impact Factor
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    ABSTRACT: Brain metastasis (BM) from non-small cell lung cancer (NSCLC) is relatively common, but identifying which patients will develop brain metastasis has been problematic. We hypothesized that genotype variants in the TGF-β signaling pathway could be a predictive biomarker of brain metastasis. We genotyped 33 SNPs from 13 genes in the TGF-β signaling pathway and evaluated their associations with brain metastasis risk by using DNA from blood samples from 161 patients with NSCLC. Kaplan-Meier analysis was used to assess brain metastasis risk; Cox hazard analyses were used to evaluate the effects of various patient and disease characteristics on the risk of brain metastasis. The median age of the 116 men and 45 women in the study was 58 years; 62 (39%) had stage IIIB or IV disease. Within 24 months after initial diagnosis of lung cancer, brain metastasis was found in 60 patients (37%). Of these 60 patients, 16 had presented with BM at diagnosis. Multivariate analysis showed the GG genotype of SMAD6: rs12913975 and TT genotype of INHBC: rs4760259 to be associated with a significantly higher risk of brain metastasis at 24 months follow-up (hazard ratio [HR] 2.540, 95% confidence interval [CI] 1.204-5.359, P = 0.014; and HR 1.885, 95% CI 1.086-3.273, P = 0.024), compared with the GA or CT/CC genotypes, respectively. When we analyzed combined subgroups, these rates showed higher for those having both the GG genotype of SMAD6: rs12913975 and the TT genotype of INHBC: rs4760259 (HR 2.353, 95% CI 1.390-3.985, P = 0.001). We found the GG genotype of SMAD6: rs12913975 and TT genotype of INHBC: rs4760259 to be associated with risk of brain metastasis in patients with NSCLC. This finding, if confirmed, can help to identify patients at high risk of brain metastasis.
    PLoS ONE 01/2012; 7(12):e51713. · 3.53 Impact Factor
  • Hong Qiu, Guangyuan Hu, Huihua Xiong
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    ABSTRACT: The chronic-hypoxia-resistant gastric cancer cell line was established, and its biological characteristics were explored and compared with the parental cell line. Gastric cancer cell lines were cultured under the degressive oxygen concentration. Cell doubling time was calculated by cell counting method. Chemo-resistance ability of cells was tested by MTT assay. Irradiation tolerance of cells was evaluated by colony forming method. Cell cycle distribution was tested with flow cytometry. Invasive ability was tested by Transwell method. The expression levels of GLUT-1 and HIF-1α were detected by using Western blot. MNK45/HYP cells successfully survived under the 1% concentration of oxygen and its cell doubling time was 35.01±1.02 h, while that of MNK45 was 27.35±0.83 h (P<0.01). The percentage of MNK45/HYP cells in G(0)/G(1) stage was (58.3±6.1)%, and that of MNK45 cells was (42.2±6.0)% (P<0.05). Comparing with the parental cells MNK45, drug resistance indexes of 5-Fu, PTX, OXA, Sn38, GEM and VP16 in MNK45/HYP cells were respectively 5.3, 1.3, 3.6, 2.2, 4.8 and 4.4. Colony forming ability of MNK45/HYP cells after irradiation was also significantly higher than MNK45 cells. The invasive number of MNK45/HYP cells was 107.7±17.5, while that of MNK45 cells was 59.0±9.9. The expression levels of GLUT-1 and HIF-1α in MNK45/HYP cells were significantly higher than those in MNK45 cells. MNK45/HYP cells hold biological characteristics of hypoxia tumor with good tolerance to chronic hypoxia, and can be used for the research of solid tumor under chronic hypoxia condition.
    Journal of Huazhong University of Science and Technology 02/2011; 31(1):52-7. · 0.58 Impact Factor
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    ABSTRACT: An accurate definition of clinical target volume (CTV) is essential for the application of radiotherapy in nasopharyngeal carcinoma (NPC) treatment. A novel epidermal growth factor receptor (EGFR)-targeting contrast agent (C225-USPIO) was designed by conjugating ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles with cetuximab (C225), to non-invasively define the CTV of tumor. The immunobinding activity of C225-USPIO to NPC cell line CNE1 was confirmed by flow cytometry and immunofluorescence. The time-dependent accumulation of C225-USPIO in CNE1 cells was evaluated using Prussian blue staining. Targeted internalization and subcellular localization of C225-USPIO was confirmed by transmission electron microscope. The results indicated that C225-USPIO specifically bound to EGFR on the surface of CNE1 cells and was taken up into the cell. The uptake of C225-USPIO by CNE1 cells increased significantly with time, when compared with human IgG-USPIO. In addition, 4.7 T magnetic resonance imaging (MRI) revealed that C225-USPIO had a capacity to accumulate in the CNE1 cells, with a resultant marked decrease in MRI T2-weighted signal intensity over time. These findings imply that C225-USPIO has the potential as an MRI contrast agent and can be employed to non-invasively detect early-stage NPC with EGFR overexpression. This provides sufficient theoretical basis for commencing in vivo experiments with the compound.
    Acta Biochimica et Biophysica Sinica 02/2011; 43(4):301-6. · 1.81 Impact Factor
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    ABSTRACT: The inhibitory effects of Endostar in combination with radiotherapy in BALB/c nude mice model of human CNE2 nasopharyngeal carcinoma and the mechanism were investigated. In nude mice model of CNE2 nasopharyngeal carcinoma, the inhibitory rate and the sensitizing enhancement ratio (E/O) were calculated according to the tumor volumes in different groups. The expression of microvascular density (MVD) in tumor tissues was examined by using immunohistochemistry staining. The transcription of VEGF gene was detected by using RT-PCR. The inhibitory rate in Endostar+ radiotherapy group was higher than in other groups. In Endostar+radiotherapy group, the tumor volume was significantly decreased and the E/O ratio was 2.335, suggesting that Endostar could be a radiosensitizer. The expression of MVD of tumor tissues in Endostar+radiotherapy group was reduced significantly. The expression of the MVD in treatment groups was significantly different from that in control group (P<0.05). Compared to other groups, VEGF mRNA expression in Endostar+radiotherapy group was decreased remarkably. Endostar in combination with radiotherapy significantly inhibited the growth of CNE2 tumor. The combination therapy decreased the expression of VEGF, and inhibited tumor angiogenesis and proliferation. When combined with radiotherapy, Endostar acted as a radiosensitizer.
    Journal of Huazhong University of Science and Technology 02/2011; 31(1):62-6. · 0.58 Impact Factor
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    ABSTRACT: The effects of hypoxia on the invasion and the related protein expression of Hela cells and the role of hypoxia inducible factor-1α (HIF-1α) were investigated. The Hela cells were divided into three groups, namely, H0 (non-transfected Hela cells), H1 (pGenesil-1 empty plasmid-transfected Hela cells), and H2 (HIF-1α-shRNA plasmid-transfected Hela cells), and were cultured under hypoxia (1% O2) and normoxia for 48 h. The expression of HIF-1α, E-cadherin, β-catenin, and actin was detected using Western blot. The scratch test and the invasion assay were applied to examine the invasion in each group. The expression of HIF-1α, E-cadherin, and β-catenin in tumor grafts was assayed immunohistochemically. Western blot results revealed that the bands of HIF-1α, E-cadherin, β-catenin, and actin proteins were detected in the H0 and H1 groups under hypoxia for 48 h. The expression of Ecadherin, β-catenin, and actin was detected in the H2 group under hypoxia for 48 h, and normoxia. In the H0, H1, and H2 groups under normoxia, and the H2 group under hypoxia for 48 h, no expression of HIF-1α was detectable. The scratch test showed that the invasive ability in the H2 group was significantly alleviated. Immunohistochemically, it was found that there was a significant difference in the expression of HIF-1α, E-cadherin, and β-catenin between the H1 and H2 groups (P<0.05), but the difference was not significant between the H0 and H1 groups. It was concluded that the effects of hypoxia on the invasion of human cervical cancer Hela cells and the expression of related proteins (E-cadherin, β-catenin, and actin) depend on HIF-1α.
    Frontiers of Medicine in China 01/2009; 3(3):303-308.
  • Qingsong Xi, Shiying Yu, Guangyuan Hu
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    ABSTRACT: Objective: To investigate the therapeutic effects of stereotactic radiotherapy for retroperitoneal metastatic tumor. Methods: From August 1997 to October 2004, 44 patients with retroperitoneal metastatic tumors were treated with stereotactic radiotherapy. The planning target volume was encompassed by 90%–95% isodose line. Fractional dose was from 6 Gy to 8 Gy, and they were treated 2–3 times per-week and 4–8 times in all. The total radiation doses of PTV were from 32 Gy to 48 Gy. Results: After the radiotherapy, the pain was obviously relieved in 81.8% patients. Three months after completion of radiotherapy passed and then, abdominal CT was performed to evaluate the results. The whole effective rate was 81.8% [CR 27.7% (12/44) and PR 54.5% (24/44)], and six months after radiotherapy, CR was 27.7% (12/44) and PR was 59.1% (26/44). The middle survival time was 12 months. Conclusion: It is suggested that stereotactic radiotherapy for retroperitoneal metastatic tumor is a safe and effective method.
    The Chinese-German Journal of Clinical Oncology 09/2006; 5(5):347-349.
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    ABSTRACT: In order to investigate the effects of short hairpin RNA (shRNA) on the expression of Survivin, cell cycle and cell proliferation in MCF-7 cells, using a pEGFP vector which contained a U6 promoter shRNA plasmid targeted against survivin was constructed and transfected into MCF-7 cells. The change of the expression of Survivin and cell proliferation rates were detected by semiquantitative reverse transcription polymerase chain reaction (RT-PCR) and MTT methods respectively. The change of cell cycle after transfection was analyzed by flow cytometry. The results indicated that the recombinant plasmid containing Survivin shRNA was constructed successfully, which could suppress the expression of Survivin at mRNA and protein level. The growth of MCF-7 cells was arrested in G1 phase of the cell cycle and the proliferation activity was suppressed after transfection. It was concluded that Survivin shRNA plasmid could knock down the expression of Survivin in MCF-7 cells specifically. In addition, Survivin shRNA plasmid could lead to G1 arrest and inhibit the proliferation of MCF-7 cells, which suggested that Survivin shRNA might be used as a new therapeutic method for breast cancer.
    Journal of Huazhong University of Science and Technology 02/2006; 26(3):305-7. · 0.58 Impact Factor