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Biomedical subjects

G Liang

Publications and source records attributed to G Liang.

At least 19 recordsLinked to original sources
PubMed2006

A novel T-77C polymorphism in DNA repair gene XRCC1 contributes to diminished promoter activity and increased risk of non-small cell lung cancer.

X-ray repair cross-complementing 1 (XRCC1) plays a key role in DNA base excision repair and cells lacking its activity are hypersensitive to DNA damage. Recently, we reported a SNP (rs3213245, -77T>C) in the XRCC1 gene 5' untranslated region (UTR) was significantly associated with the risk of developing esophageal squamous-cell carcinoma. Computer analysis predicted that this SNP was in the core of Sp1-binding motif, which suggested its functional significance. Gel shift and super shift assays confirmed that -77T>C polymorphic site in the XRCC1 promoter was within the Sp1-binding motif and the T>C substitution greatly enhanced the binding affinity of Sp1 to this region. Luciferase assays indicated that the Sp1-high-affinity C-allelic XRCC1 promoter was associated with a reduced transcriptional activity. The association between -77T>C and three other amino-acid substitution-causing polymorphisms in XRCC1 and risk of lung cancer was examined in 1024 patients and 1118 controls and the results showed that only the -77T>C polymorphism was significantly associated with an increased risk of developing lung cancer. Multivariate logistic regression analysis found that an increased risk of lung cancer was associated with the variant XRCC1 -77 genotypes (TC and CC) compared with the TT genotype (OR=1.46, 95% CI=1.18-1.82; P=0.001) and the increased risk was more pronounced in smokers (OR=1.63, 95% CI=1.20-2.21) than in non-smokers (OR=1.28, 95% CI=0.94-1.76). Taken together, these results showed that the functional SNP -77T>C in XRCC1 5'UTR was associated with cancer development owing to the decreased transcriptional activity of C-allele-containing promoter with higher affinity to Sp1 binding.

Adult↗
PubMed2001

Susceptibility of nonpromoter CpG islands to de novo methylation in normal and neoplastic cells.

BACKGROUND: Many cancers display alterations in methylation patterns of CpG islands--stretches of DNA rich in CpG dinucleotides often associated with gene promoters that are involved in initiation of gene transcription. This methylation may perturb expression of genes critical to the regulation of cell proliferation. Aberrant methylation is not limited to a few genes or to promoter regions but has been found on a genome-wide scale in a variety of neoplasias, including colorectal cancer and acute myelogenous leukemia. Our goal was to characterize, in a quantitative manner, the profiles of abnormally methylated genes that may be specific for different cancers. METHODS: Using a quantitative assay, methylation-sensitive single nucleotide primer extension (MS-SNuPE), we have analyzed the methylation levels of promoter and exonic (coding region) CpG islands of two cyclin-dependent kinase inhibitors [p15(INK4B) and p16(INK4A)] and the PAX6 gene, which encodes a transcriptional factor involved in neuronal proliferation, in DNA samples taken from patients with chronic myelogenous leukemia, acute myelogenous leukemia, myelodysplastic syndrome, and colorectal cancer. RESULTS: De novo methylation of all three exonic loci in tumors--relative to baseline levels found in nontumor tissue or blood--was observed in hematologic neoplasias and in solid tumors as well as in normal colonic tissue. However, methylation of promoter regions was more limited. Moreover, two different patterns of promoter methylation distinguished the leukemias from colorectal cancer: p15 promoter hypermethylation was found only in the leukemias, and p16 promoter hypermethylation occurred only in colon tumors. However, we did not address this issue prospectively; therefore, such an observation is only hypothesis generating. CONCLUSIONS: The methylation patterns that we observed suggest that exonic CpG islands are more susceptible to de novo methylation than promoter islands and that methylation may be seeded in exonic regions, from which it can spread to other islands, including promoter regions. Subsequent selection of cells with a growth advantage conferred by spread of methylation into and inactivation of a particular promoter might then contribute to the genesis of a specific type of cancer.

Acute Disease↗
PubMed2001

Global and gene-specific epigenetic patterns in human bladder cancer genomes are relatively stable in vivo and in vitro over time.

We used a methylation-sensitive arbitrarily primed PCR technique to analyze, in a nonselective manner, methylation alterations at GC-rich regions of the genome in metachronous tumors and their derived cell lines from two patients with transitional cell carcinoma of the bladder. The methylation status of the majority of evaluable sequences (83%) remained unchanged in the tumors from both patients relative to a panel of normal urothelium samples obtained from individuals free of bladder disease, in which we measured <1% interindividual variation. The 17% of methylation alterations represents sequences altered in either a cancer-specific (3%), tumor-specific (1%), or patient-specific (13%) manner. The proportion of the altered sequences analyzed that were CpG islands corresponds to approximately 7000 CpG islands altered in the genome. Surprisingly, few additional changes in methylation patterns were observed in cell lines derived from the tumors; however, all of the cell lines showed altered methylation in a common set of 3% of evaluable sequences. Three genes known to be aberrantly methylated in bladder cancer (p16, p15, and PAX6) were studied in detail by methylation-sensitive single nucleotide primer extension and showed increased methylation in culture at preexisting methylated sites for all of the exons but no de novo methylation in culture for the promoters in any cell line. Therefore, our investigation provides the first serial as well as parallel quantitation of the global epigenetic stability in two independent bladder cancer genomes over the course of progression and in culture. In addition, our investigation also provides the first direct comparison of the epigenetic and genetic patterns on the global scale, showing the epigenetic pattern to be relatively stable in vivo and in vitro over time within an individual.

Carcinoma, Transitional Cell↗
PubMed2001

The endothelin receptor B (EDNRB) promoter displays heterogeneous, site specific methylation patterns in normal and tumor cells.

The 5' region for the endothelin receptor B (EDNRB) gene is a complex CpG island giving rise to four individual transcripts initiating within the island. Here, for the first time, we analyze the relationship between methylation and gene expression in a CpG island located in the 5' region of a gene with multiple transcription start sites. The CpG island was unmethylated in normal prostate and bladder tissue, whereas it became methylated in apparently normal colonic epithelium. Tumors derived from these tissues were frequently hypermethylated relative to the respective normal tissues. Analysis of 11 individual CpG sites located throughout the CpG island showed that specific sites with high methylation levels in several tumors were also methylated in normal tissues, suggesting that they might serve as foci for further de novo methylation. This region also had high levels of methylation in several cancer cell lines, and we found that a low methylation level in a small region within the 5' region correlated with expression of the 5'-most transcript. Interestingly, almost complete methylation 200-1000 bp downstream of the transcriptional start site did not block expression of this transcript. Finally, we show that treatment with 5-aza-2'-deoxycytidine can induce transcriptional activation of the four EDNRB transcripts. Our results show the existence of differential, tissue-dependent methylation at the EDNRB 5' region, suggest the existence of a spreading mechanism for de novo methylation, starting from methylation hotspots, and show that hypermethylation immediately 3' to a transcriptional start site does not prevent initiation.

Colonic Neoplasms↗
PubMed2001

[The roles of vascular endothellial growth factor and endothelin-1 on pulmonary vascular remodelling in rats with hypoxia-induced pulmonary hypertension].

OBJECTIVE: To investigate the roles of the vascular endothelial growth factor(VEGF) and endothelin-1(ET-1) in pulmonary vascular remodelling in rats with hypoxia-induced pulmonary hypertension(HPH) and the effect of pinacidil on VEGF and ET-1 in rats with HPH. METHOD: 46 male Wister rats were divided into three groups i.e. control group, hypoxic group and treated group (hypoxic rats treated with pinacidil for 4 weeks). Rat models with chronic HPH were established by chronic hypobaric hypoxia [(10.0 +/- 0.5)% O2, 4 weeks]. The levels of VEGF and ET-1 in serum and the mean pulmonary arterial pressure (mPAP) and the weight ratio of right ventricle (RV)/left ventricle and septum (LV + S) [RV/(LV + S)] were measured and the small pulmonary arterial morphologic changes were observed with morphometric analysis under microscopes in the three groups. RESULTS: (1) The levels of VEGF[(118.73 +/- 55.40) ng/L] and ET-1[(221.2 +/- 56.2) ng/L] in serum, mPAP [(28.4 +/- 2.8) mm Hg, 1 mm Hg = 0.133 kPa] and RV/(LV + S) (0.296 +/- 0.033) were significantly higher in the hypoxic group than those in the control group (P < 0.01). Morphometry showed that the external diameter of the small pulmonary arteries became smaller and the ratio of vascular wall thickness to external diameter (MT%) (25.70 +/- 2.58)% and ratio of vascular wall area to total area (MA%) (75.300 +/- 5.600)% significantly increased in the hypoxic group. (2) The levels of VEGF[(78.20 +/- 16.45) ng/L] and ET-1[(181.6 +/- 30.5) ng/L] in serum, mPAP[(23.3 +/- 2.6) mm Hg], RV/(LV + S) (0.266 +/- 0.037), MT%(22.10 +/- 2.51)% and MA% (66.900 +/- 0.061)% significantly decreased in the treated group. CONCLUSION: VEGF and ET-1 play important roles in the development of HPH and pulmonary vascular remodelling. Pinacidil may partly inhibit the development of HPH and pulmonary vascular remodelling by decreasing VEGF and ET-1.

Animals↗
PubMed2001

[The study on subclinical Epstein-Barr virus infection of heroin addicts].

OBJECTIVE: To study the subclinical EBV infection and related factors among heroin addicts. METHODS: Three hundred and twelve heroin addicts were tested for serum EBV-VCA-IgA antibody by immunoenzyme technique population, four hundred and twenty one serum specimens from general were selected as control. RESULTS: Ninty nine heroin addicts (31.51%) were found to be EBV positive. Three people from control group (0.7%) were found to be EBV positive. EBV prevalence rates were significantly different among heroin addict groups according to a group (P = 0.05), duration of addiction. However the dose and sex difference of heroin addicts was not associated with EBV infection rate. CONCLUSION: The high infection rate of EBV in heroin addicts might be connected with different kinds of factors, hence worthy of supervising the subclinical EBV infection of heroin addicts.

Adult↗
PubMed2001

[Controlling effect of parasitoids on population of vegetable leaf miner Liriomyza sativae Blanchard].

The controlling effect of parasitoids on vegetable leaf miner, Liriomyza sativae Blanchard, was evaluated by using acting factor life tables and exclusion inex of population control(EPIC). The results showed that Chrysocharis pentheus, Neuchrysocharis formosa, Chrysonotomyia okazakii, Hemiptarsenus varicornis, Chrysocharis sp., Opius dimidiatus and Opius dissitus played an important role in controlling the population of vegetable leaf miner. The EIPCs of parasitoids were 1.23, 2.73, 5.98, 5.92 and 5.71, respectively for the five generations of L. sativae on kidney bean planted in spring, from the 1st to the 5th generation and, for the 2nd generation in particular, they were 2.73, 2.87, 2.24 and 1.89, respectively on kidney bean, cowpea, luffa and cucumber, indicating that if the parasitoids were excluded, the population of the next generation of L. sativae would increase by times accordingly. The EIPC of parasitoids for the 3rd instar larvae was usually the largest among different instar larvae and pupae, and the EIPCs for the 3rd to 5th generation of L. sativae on spring kidney bean were higher than those for the 1st and the 2nd. The EIPCs of parasitoids for L. sativae on kidney bean and cowpea were larger than those on luffa and cucumber.

Animals↗
PubMed2001

Diagnosis and treatment of spinal fractures combined with paraplegia and diaphragm injury.

OBJECTIVE: To study the mechanism and treatment principle of spinal fractures combined with paraplegia and diaphragm injury. METHODS: A total of 16 patients (14 males and 2 females, aged from 18 to 50 years) with spinal fractures combined with paraplegia and diaphragm injury, receiving emergency treatment and admitted to our hospital in the past 20 years, were retrospectively analyzed in this study. RESULTS: The injuries were caused by direct or indirect violence. Six cases were of fractures of cervical spine combined with paraplegia and diaphragm injury, 2 of fractures of thoracic vertebra combined with paraplegia and diaphragm injury, and 8 of thoracolumbar fractures combined with paraplegia and diaphragm injury. Six cases received non-operative treatment, but died finally. Ten cases received spine surgical treatment, of which 4 died and 6 were improved. The total mortality rate was 62.5%. CONCLUSIONS: Spinal fractures combined with paraplegia and diaphragm injury are one of the most severe traumas in departments of orthopaedics. Paraplegia can be found easily, but diaphragm injury is often neglected and missed. When a patient suffers from both of them, he is in danger of death. What measures should be taken to rescue the patient's life depends on the severity of the wounds.

Adolescent↗
PubMed2000

Regulation of mouse sterol regulatory element-binding protein-1c gene (SREBP-1c) by oxysterol receptors, LXRalpha and LXRbeta.

The liver X receptors (LXRs) are members of the nuclear hormone receptor superfamily that are bound and activated by oxysterols. These receptors serve as sterol sensors to regulate the transcription of gene products that control intracellular cholesterol homeostasis through catabolism and transport. In this report, we describe a novel LXR target, the sterol regulatory element-binding protein-1c gene (SREBP-1c), which encodes a membrane-bound transcription factor of the basic helix-loop-helix-leucine zipper family. SREBP-1c expression was markedly increased in mouse tissues in an LXR-dependent manner by dietary cholesterol and synthetic agonists for both LXR and its heterodimer partner, the retinoid X receptor (RXR). Expression of the related gene products, SREBP-1a and SREBP-2, were not increased. Analysis of the mouse SREBP-1c gene promoter revealed an RXR/LXR DNA-binding site that is essential for this regulation. The transcriptional increase in SREBP-1c mRNA by RXR/LXR was accompanied by a similar increase in the level of the nuclear, active form of the SREBP-1c protein and an increase in fatty acid synthesis. Because this active form of SREBP-1c controls the transcription of genes involved in fatty acid biosynthesis, our results reveal a unique regulatory interplay between cholesterol and fatty acid metabolism.

Animals↗
PubMed2000

The gene for a novel transmembrane protein containing epidermal growth factor and follistatin domains is frequently hypermethylated in human tumor cells.

A DNA fragment frequently hypermethylated in tumor cells was isolated using a novel screening strategy termed methylation-sensitive arbitrarily primed PCR. The isolated sequence corresponded to a CpG island at the 5' end of a previously unknown gene, TPEF (transmembrane protein containing epidermal growth factor and follistatin domains). Expression of TPEF was observed using Northern master blot analysis of a variety of normal tissues including colon, bladder, and prostate tissue. TPEF maps to human chromosome 2q33, where frequent loss of heterozygosity is seen in various human tumors, and TPEF was not expressed in most human colon and various other tumor cell lines examined by reverse transcription-PCR. Nine of 11 tumor cell lines were highly methylated in the 5' region and the first exon of the gene that demonstrated features characteristic of a CpG island. However the other two cell lines, which expressed TPEF, were hypomethylated in the 5' end of the gene. The region was also hypermethylated in 11 of 16 primary bladder tumors and in 3 of 4 primary colon tumors when compared with adjacent normal tissue. Our results suggest that potential tumor suppressor genes can be isolated from human tumors by virtue of their altered methylation patterns.

Amino Acid Sequence↗
PubMed2000

PAX6 methylation and ectopic expression in human tumor cells.

The mechanisms underlying the de novo methylation of CpG islands in human cancer remain almost completely unknown. We used a methylation-sensitive arbitrarily primed polymerase chain reaction (Ms AP-PCR) technique to scan genomic DNA for differential methylation patterns and identified a 550 bp band that was hypermethylated in a majority of colon and bladder cancer cells. This band corresponded to a CpG-rich region in exon 5 of PAX6, which is a highly conserved transcription regulatory factor involved in embryogenesis. Interestingly, exon 5 was very frequently methylated in solid tumors compared with adjacent normal tissues, 17 out of 27 (63%) in bladder, and colon, but the promoter remained unmethylated in all these cases. This methylation was not effective in blocking transcription since ectopic expression of PAX6 was seen in several tumors and cell lines with extensive exon 5 methylation. De novo methylation of the promoter was only seen in tumor cell lines and was associated with gene silencing since treatment with 5-aza-2'-deoxycytidine restored expression to the cells and resulted in a less methylated promoter. Thus, ectopic expression and hypermethylation of exon 5 of PAX6 demonstrate that methylation within a transcribed region, as opposed to promoter methylation, does not block gene expression.

Antimetabolites, Antineoplastic↗
PubMed2000

Transcriptional autorepression of the stress-inducible gene ATF3.

Previously, we demonstrated that ATF3 (activating transcription factor-3) is a stress-inducible gene, and the protein it encodes is a transcriptional repressor. In this report, we present evidence suggesting that ATF3 represses the transcription of its own gene. Interestingly, efficient repression requires a consensus ATF/cAMP-responsive element site in the promoter and a previously unidentified ATF3-binding site immediately downstream from the TATA box. Although this new site resembles the known ATF/cAMP-responsive element sequences at the flanking sequence, it differs from them at the center key residues. These observations indicate that ATF3 can tolerate variations in the center of the binding sites if the flanking sequences are favorable. The repression of the ATF3 promoter by its own gene product provides a mechanistic explanation, at least in part, for the transient expression pattern of the ATF3 gene upon stress induction.

Activating Transcription Factor 3↗
PubMed2000

Progressive increases in de novo methylation of CpG islands in bladder cancer.

We conducted a quantitative analysis of the extent of de novo methylation of four CpG islands in human urinary transitional cell carcinomas of different stages and grades to determine how frequently these CpG islands became methylated in transition cell carcinomas during progression. The CpG islands included exon 5 of PAX6, exon 2 of p16, the 5' end of the deleted in bladder cancer gene, and the 5' end of transmembrane protein containing epidermal growth factor and follistatin domains. These sequences were not methylated in normal urothelial tissues; however, 48 of the 54 tumors examined (89%) showed methylation levels in excess of 20% for at least one of the markers. The number of markers concurrently methylated in individual tumors increased with the stage of the tumor, with several of the more aggressive invasive cancers showing hypermethylation of all four markers compared with the less aggressive invasive cancers. However, considerable methylation defects were present in superficial, preinvasive, papillary tumors. These data demonstrate that 89% of bladder cancers have increased methylation of CpG islands relative to their normal counterparts and suggest the occurrence of a hypermethylator phenotype in which multiple independent CpG islands become concurrently methylated in individual tumors in a process associated with tumor progression.

Carcinoma, Transitional Cell↗
PubMed2000

DNA methylator and mismatch repair phenotypes are not mutually exclusive in colorectal cancer cell lines.

A potential link between DNA repair and de novo methylation of exogenous sequences in colorectal cancer cell lines suggested that cells deficient in mismatch repair (MMR-) had an increased ability to silence the introduced virus promoter by DNA methylation due to the presence of a methylator phenotype (MET+) (Lengauer et al., 1997a). We explored this relationship in more detail and found that although there was a clear difference in the abilities of MMR+ cells to express the viral promoter compared to their MMR- counterparts, this difference was not consistently explained by levels of methylation in the viral promoter. Furthermore, we were unable to distinguish differences between the levels of methylation of six endogenous known CpG islands or 100 random DNA fragments containing CCGG sites within the cells. No consistent differences between the abilities of the cells to methylate the CpG island in exon 2 of the p16 gene were observed after transient demethylation by 5-aza-2'-deoxycytidine nor in the levels of expression of three human methyltransferase enzymes. Our results do not therefore support the existence of mutually exclusive DNA methylation (MET) and DNA repair (MMR) phenotypes. Oncogene (2000) 19, 943 - 952.

Azacitidine↗
PubMed2000

Amido-(propyl and allyl)-hydroxybenzamidines: development of achiral inhibitors of factor Xa.

The design, synthesis and SAR of amido-(propyl and allyl)-hydroxybenzamidine coagulation factor Xa inhibitors is described. These achiral inhibitors are selective for fXa vis a vis structurally related serine proteases and are readily prepared in 6-7 linear steps. The most potent member 9j (fXa Ki = 0.75 nM) is selective (>1000-fold) and an effective anticoagulant in mammalian plasma.

Animals↗
PubMed2000

Synchronization of hyperchaotic harmonics in time-delay systems and its application to secure communication

We present a predictor-feedback method for synchronizing chaotic systems in this paper. By using this method, two structurally equivalent or nonequivalent systems can be synchronized very effectively and quickly. Moreover, the feedback perturbation can be switched on even if trajectories of the two systems are far from each other. Therefore, this method is applicable to real-world experimental systems, especially to some fast experimental systems. The validity of this method is demonstrated by synchronizing hyperchaotic harmonics in a time-delay system. As an application, we introduce how messages can be encoded, transmitted, and decoded using this technique. We suggest taking use of the multistability of time-delay systems to improve the performance of the secure communication.

Journal Article↗
PubMed2000

[Effect of Sindbis XJ-160 virus structural proteins on BHK-21 cell].

OBJECTIVE: To study the effect of Sindbis XJ-160 virus structural proteins on BHK-21 cell. METHODS: We constructed the expressing vector pcDNA3.1 ABC that contains the XJ-160 virus structural protein gene and then transfected it to BHK-21 cell. RESULTS: The expressed products can be detected by RNA dot blot hybridization or immUnofluorescent assay. The cytopathic effect was observed in BHK-21 cells transfected with pcDNA3.1 ABC. There was also condensed chromatin found accumulated. BHK-21 cell death and marked cell cycle changes were observed. CONCLUSIONS: These results indicate that cell apoptosis might be one of the mechanisms inducing cell death by XJ - 160 virus and its structural protein gene probably plays a role in this programmed cell death.

Apoptosis↗