Asian Science Citation Index is committed to provide an authoritative, trusted and significant information by the coverage of the most important and influential journals to meet the needs of the global scientific community.  
ASCI Database
308-Lasani Town,
Sargodha Road,
Faisalabad, Pakistan
Fax: +92-41-8815544
Contact Via Web
Suggest a Journal
 
Articles by J Gu
Total Records ( 11 ) for J Gu
  J Gu , D Sun , Q Zheng , X Wang , H Yang , J Miao , J Jiang and W. Wei
 

Elongator complex has been associated with hyperphosphorylated RNA polymerase II and is known to play critical roles in transcriptional elongation, as well as in tRNA modification and exocytosis. However, the specific mechanism of how human Elongator complex regulates cell growth and cell cycle remains unclear. To investigate the composition of human Elongator complex and its effects on cell growth, 293T cells were established that stably overexpressed Flag-Elp3 and Flag-Elp4. By using anti-Flag M2 antibody-bound resin, a core Elongator complex was purified from cells that stably overexpressed Flag-Elp3. No Elongator complex was purified from cells stably transfected with pFlagCMV4-Elp4. Interestingly, the cell growth was inhibited in 293T cells transfected with pFlagCMV4-Elp3. Flow cytometry analysis showed that most of the cells stably overexpressing Flag-Elp3 were found in G1 stage, indicating a role of the core Elongator in the G1 checkpoint for the regulation of cell cycle. We observed increased basal transcription and remarkably enhanced transcription stimulated by VP16 in 293T cells overexpressing Flag-Elp3. The transcription could also be synergistically activated by overexpressing both Elp3 and Elp4. Taken together, our results suggested that the core Elongator complex formed by Elp1, Elp2, and Elp3 was rather stable, whereas Elp4, Elp5, and Elp6 might loosely contact and work together with the core Elongator to regulate cell functions.

  Q Wang , J Li , J Gu , B Huang , Y Zhao , D Zheng , Y Ding and L. Zeng
 

The green tea constituent, (–)-epigallocatechin-3-gallate (EGCG), has chemopreventive and anticancer effects. This is partially because of the selective ability of EGCG to induce apoptosis and death in cancer cells without affecting normal cells. In the present study, the activity of EGCG against the myeloma cell line, KM3, was examined. Our results demonstrated, for the first time, that the treatment of the KM3 cell line with EGCG inhibits cell proliferation and induces apoptosis, and there is a synergistic effect when EGCG and bortezomib are combined. Further experiments showed that this effect involves the NF-B pathway. EGCG inhibits the expression of the P65 mRNA and P65/pP65 protein, meanwhile it downregulates pIB expression and upregulates IB expression. EGCG also activates caspase-3, -8, cleaved caspase-9, and poly-ADP-ribose polymerase (PARP) and subsequent apoptosis. These findings provided experimental evidence for efficacy of EGCG alone or in combination with bortezomib in multiple myeloma therapy.

  F Liu , J Shi , H Tanimukai , J Gu , I Grundke Iqbal , K Iqbal and C. X. Gong
 

It has been established for a long time that brain glucose metabolism is impaired in Alzheimer's disease. Recent studies have demonstrated that impaired brain glucose metabolism precedes the appearance of clinical symptoms, implying its active role in the development of Alzheimer's disease. However, the molecular mechanism by which this impairment contributes to the disease is not known. In this study, we demonstrated that protein O-GlcNAcylation, a common post-translational modification of nucleocytoplasmic proteins with β-N-acetyl-glucosamine and a process regulated by glucose metabolism, was markedly decreased in Alzheimer's disease cerebrum. More importantly, the decrease in O-GlcNAc correlated negatively with phosphorylation at most phosphorylation sites of tau protein, which is known to play a crucial role in the neurofibrillary degeneration of Alzheimer's disease. We also found that hyperphosphorylated tau contained 4-fold less O-GlcNAc than non-hyperphosphorylated tau, demonstrating for the first time an inverse relationship between O-GlcNAcylation and phosphorylation of tau in the human brain. Downregulation of O-GlcNAcylation by knockdown of O-GlcNAc transferase with small hairpin RNA led to increased phosphorylation of tau in HEK-293 cells. Inhibition of the hexosamine biosynthesis pathway in rat brain resulted in decreased O-GlcNAcylation and increased phosphorylation of tau, which resembled changes of O-GlcNAcylation and phosphorylation of tau in rodent brains with decreased glucose metabolism induced by fasting, but not those in rat brains when protein phosphatase 2A was inhibited. Comparison of tau phosphorylation patterns under various conditions suggests that abnormal tau hyperphosphorylation in Alzheimer's disease brain may result from downregulation of both O-GlcNAcylation and protein phosphatase 2A. These findings suggest that impaired brain glucose metabolism leads to abnormal hyperphosphorylation of tau and neurofibrillary degeneration via downregulation of tau O-GlcNAcylation in Alzheimer's disease. Thus, restoration of brain tau O-GlcNAcylation and protein phosphatase 2A activity may offer promising therapeutic targets for treating Alzheimer's disease.

  X Wu , M. R Spitz , J. J Lee , S. M Lippman , Y Ye , H Yang , F. R Khuri , E Kim , J Gu , R Lotan and W. K. Hong
 

This study was aimed to identify novel susceptibility variants for second primary tumor (SPT) or recurrence in curatively treated early-stage head and neck squamous cell carcinoma (HNSCC) patients.

We constructed a custom chip containing a comprehensive panel of 9,645 chromosomal and mitochondrial single nucleotide polymorphisms (SNP) representing 998 cancer-related genes selected by a systematic prioritization schema. Using this chip, we genotyped 150 early-stage HNSCC patients with and 300 matched patients without SPT/recurrence from a prospectively conducted randomized trial and assessed the association of these SNPs with risk of SPT/recurrence.

Individually, six chromosomal SNPs and seven mitochondrial SNPs were significantly associated with risk of SPT/recurrence after adjustment for multiple comparisons. A strong gene-dosage effect was observed when these SNPs were combined, as evidenced by a progressively increasing SPT/recurrence risk as the number of unfavorable genotypes increased (P for trend < 1.00 x 10–20). Several polygenic analyses suggest an important role of interconnected functional network and gene-gene interaction in modulating SPT/recurrence. Furthermore, incorporation of these genetic markers into a multivariate model improved significantly the discriminatory ability over the models containing only clinical and epidemiologic variables.

This is the first large-scale systematic evaluation of germ-line genetic variants for their roles in HNSCC SPT/recurrence. The study identified several promising susceptibility loci and showed the cumulative effect of multiple risk loci in HNSCC SPT/recurrence. Furthermore, this study underscores the importance of incorporating germ-line genetic variation data with clinical and risk factor data in constructing prediction models for clinical outcomes.

  M Chen , M. A. T Hildebrandt , J Clague , A. M Kamat , A Picornell , J Chang , X Zhang , J Izzo , H Yang , J Lin , J Gu , S Chanock , M Kogevinas , N Rothman , D. T Silverman , M Garcia Closas , H. B Grossman , C. P Dinney , N Malats and X. Wu
 

Sonic hedgehog (Shh) pathway genetic variations may affect bladder cancer risk and clinical outcomes. Therefore, we genotyped 177 single-nucleotide polymorphisms (SNP) in 11 Shh pathway genes in a study including 803 bladder cancer cases and 803 controls. We assessed SNP associations with cancer risk and clinical outcomes in 419 cases of non–muscle-invasive bladder cancer (NMIBC) and 318 cases of muscle-invasive and metastatic bladder cancer (MiMBC). Only three SNPs (GLI3 rs3823720, rs3735361, and rs10951671) reached nominal significance in association with risk (P ≤ 0.05), which became nonsignificant after adjusting for multiple comparisons. Nine SNPs reached a nominally significant individual association with recurrence of NMIBC in patients who received transurethral resection (TUR) only (P ≤ 0.05), of which two (SHH rs1233560 and GLI2 rs11685068) were replicated independently in 356 TUR-only NMIBC patients, with P values of 1.0 x 10–3 (SHH rs1233560) and 1.3 x 10–3 (GLI2 rs11685068). Nine SNPs also reached a nominally significant individual association with clinical outcome of NMIBC patients who received Bacillus Calmette-Guérin (BCG; P ≤ 0.05), of which two, the independent GLI3 variants rs6463089 and rs3801192, remained significant after adjusting for multiple comparisons (P = 2 x 10–4 and 9 x 10–4, respectively). The wild-type genotype of either of these SNPs was associated with a lower recurrence rate and longer recurrence-free survival (versus the variants). Although three SNPs (GLI2 rs735557, GLI2 rs4848632, and SHH rs208684) showed nominal significance in association with overall survival in MiMBC patients (P ≤ 0.05), none remained significant after multiple-comparison adjustments. Germ-line genetic variations in the Shh pathway predicted clinical outcomes of TUR and BCG for NMIBC patients. Cancer Prev Res; 3(10); 1235–45. ©2010 AACR.

  M Chen , A Cassidy , J Gu , G. L Delclos , F Zhen , H Yang , M. A.T Hildebrandt , J Lin , Y Ye , R. M Chamberlain , C. P Dinney and X. Wu
 

Genetic variations in phosphoinositide-3 kinase (PI3K)-AKT-mammalian target of rapamycin (mTOR) pathway may affect critical cellular functions and increase an individual's cancer risk. We systematically evaluate 231 single-nucleotide polymorphisms (SNPs) in 19 genes in the PI3K-AKT-mTOR signaling pathway as predictors of bladder cancer risk. In individual SNP analysis, four SNPs in regulatory associated protein of mTOR (RAPTOR) remained significant after correcting for multiple testing: rs11653499 [odds ratio (OR): 1.79, 95% confidence interval (CI): 1.24–2.60, P = 0.002], rs7211818 (OR: 2.13, 95% CI: 1.35–3.36, P = 0.001), rs7212142 (OR: 1.57, 95% CI: 1.19–2.07, P = 0.002) and rs9674559 (OR: 2.05, 95% CI: 1.31–3.21, P = 0.002), among which rs7211818 and rs9674559 are within the same haplotype block. In haplotype analysis, compared with the most common haplotypes, haplotype containing the rs7212142 wild-type allele showed a protective effect of bladder cancer (OR: 0.83, 95% CI: 0.70–0.97). In contrast, the haplotype containing the rs7211818 variant allele showed a 1.32-fold elevated bladder cancer risk (95% CI: 1.09–1.60). In combined analysis of three independent significant RAPTOR SNPs (rs11653499, rs7211818 and rs7212142), a significant trend was observed for increased risk with an increase in the number of unfavorable genotypes (P for trend <0.001). Compared with the subjects without any of the unfavorable genotypes, those carrying all three unfavorable genotypes showed a 2.22-fold (95% CI: 1.33–3.71) increased bladder cancer risk. This is the first study to evaluate the role of germ line genetic variations in PI3K-AKT-mTOR pathway as cancer susceptibility factors that will help us identify high-risk individuals for bladder cancer.

  X. L Xu , B. C Xing , H. B Han , W Zhao , M. H Hu , Z. L Xu , J. Y Li , Y Xie , J Gu , Y Wang and Z. Q. Zhang
 

Hepatocellular carcinoma (HCC) is associated with a high morbidity and mortality due to its high rate of recurrence. However, little is known about the biological characteristics of recurrent HCC cells. A single patient's primary and recurrent HCC-derived cell lines, Hep-11 and Hep-12, respectively, were established by primary culture. These two cell lines have the same hepatitis B virus integration site and share many common amplifications and deletions, which suggest that they have the same clonal origin. While Hep-11 cells were non-tumorigenic at 16 weeks following injection of up to 10 000 cells, injection of only 100 Hep-12 cells was sufficient to initiate tumor growth, and all single Hep-12 clones were tumorigenic in immunodeficient mice. Compared with Hep-11, Hep-12 cells expressed the oval cell markers AFP, NCAM/CD56, c-kit/CD117, as well as multiple stem cell markers such as Nanog, OCT4 and SOX2. In addition, >90% of Hep-12 cells were aldehyde dehydrogenase positive. They were also less resistant to paclitaxel, but more resistant to doxorubicin, cisplatin and hydroxycamptothecin (HCPT), which had been administrated to the patient. Furthermore, Hep-12 cells expressed higher levels of poly (adenosine diphosphate-ribose) polymerase-1 (PARP-1) than Hep-11, and PARP-1 inhibition potentiated the sensitivity to HCPT in Hep-12 cells but not in Hep-11 cells. These results indicate that a large population of the recurrent HCC-derived Hep-12 cells were tumor-initiating cells and that elevated expression of PARP-1 was related to their resistance to HCPT.

  M Chen , J Gu , G. L Delclos , A. M Killary , Z Fan , M. A. T Hildebrandt , R. M Chamberlain , H. B Grossman , C. P Dinney and X. Wu
 

The phosphoinositide-3 kinase (PI3K)–AKT– mammalian target of rapamycin (mTOR) pathway is an important cellular pathway controlling cell growth, tumorigenesis, cell invasion and drug response. We hypothesized that genetic variations in the PI3K–AKT–mTOR pathway may affect the survival in muscle invasive and metastatic bladder cancer (MiM-BC) patients. We conducted a follow-up study of 319 MiM-BC patients to systematically evaluate 289 single-nucleotide polymorphisms (SNPs) of 20 genes in the PI3K–AKT–mTOR pathway as predicators of survival. In multivariate Cox regression, AKT2 rs3730050, PIK3R1 rs10515074 and RAPTOR rs9906827 were significantly associated with survival. In combined analysis, we found a cumulative effect of these three SNPs on survival. With the increasing number of unfavorable genotypes, there was a significant trend of higher risk of death in multivariate Cox regression (P for trend <0.001) and shorter median survival time in Kaplan–Meier estimates (P log rank <0.001). This is the first study to evaluate the role of germ line genetic variations in the PI3K–AKT–mTOR pathway genes as predictors of MiM-BC clinical outcomes. These findings warrant further replication in independent populations and may provide information on disease management and development of target therapies.

  J Gu , W Yang , J Cheng , T Yang , Y Qu , Y Kuang , H Huang , L Yang , W He and L. Min
  Objective

To analyse the temporal and spatial characteristics of traumatic brain injury and the distribution of combined injuries in the Wenchuan earthquake, and describe the treatment opportunities and preferences for therapy.

Methods

The diagnosis and treatment of 92 patients with traumatic brain injury who survived the massive earthquake (magnitude 8) in Wenchuan, Sichuan Province, on 12 May 2008 were systematically analysed.

Results

The patients all came from the plains northwest of Chengdu city. Seventy-six patients were admitted during the early stage (within 12 h) after the earthquake. Ten patients underwent surgery and three patients died.

Conclusion

Patients with traumatic brain injury during the early period accounted for a large proportion of the patients wounded in the Wenchuan earthquake, and their conditions changed quickly. The patients all came from the plain area which has convenient transportation. After admission, providing first-aid early had a significant effect on increasing the success of treatment for these patients.

  Y Wei , Y Ge , F Zhou , H Chen , C Cui , D Liu , Z Yang , G Wu , J Gu and J. Jiang
 

ATF5, a member of ATF/CREB family of b-ZIP transcription factors, is highly expressed in a wide variety of neoplasms and regulates cell differentiation, cell survival and apoptosis. However, the mechanism of human ATF5 transcriptional regulation has not been clarified. Here, we identified the transcription start site of the ATF5 gene, cloned its 5'-flanking region and identified the region –105 to +3 relative to the transcription start site as that having promoter activity. This region contained potential binding sites for several transcription factors, including EBF1, Sp1 and E2F1. EBF1 transcription factor binds to the ATF5 promoter and regulates the ATF5 transcription in an EBF-binding site independent manner. Thus, our studies not only provided molecular basis of ATF5 transcriptional regulation, but also identified ATF5 as a target gene of EBF1 transcription factor.

 
 
 
Copyright   |   Desclaimer   |    Privacy Policy   |   Browsers   |   Accessibility