PubMed Health⌕ Search

Biomedical subjects

Hong-Tao Zhang

Publications and source records attributed to Hong-Tao Zhang.

12 recordsLinked to original sources

DNA repair gene XRCC3 polymorphisms and cancer risk: a meta-analysis of 48 case-control studies.

The X-ray repair cross-complementing group 3 (XRCC3) is a highly suspected candidate gene for cancer susceptibility. However, association studies on the XRCC3 polymorphisms (4541A>G, Thr(241)Met, 17893A>G) in cancer have shown conflicting results. Therefore, we performed a meta-analysis to better assess the purported associations. Forty eight eligible case-control studies including 24,975 cancer patients and 34, 209 controls were selected for our meta-analysis. Overall, individuals carrying the XRCC3 Met/Met genotype showed a small cancer risk under a recessive genetic model. The subgroup and meta-regression analysis demonstrated different scenarios concerning the XRCC3 Met/Met genotype's role in cancer susceptibility for different subgroups. Specially, there was a significantly increased risk of breast cancer (OR, 1.14; P=0.0004; 95% CI, 1.06-1.23; P=0.37 for heterogeneity), elevated but not significant risk of cancer for head and neck, bladder, surprisingly, a significantly decreased risk of non-melanoma skin cancer (OR, 0.76; P=0.007; 95% CI, 0.62-0.93; P=0.61 for heterogeneity). A significantly elevated risk of cancer was observed in population-based case-control studies but not in nested or hospital based studies. Similarly, we found a significantly increased risk of cancer for A4541G and a decreased risk for A17893G under dominant genetic models. Our meta-analysis results support that the XRCC3 might represent a low-penetrance susceptible gene especially for cancer of breast, bladder, head and neck, and non-melanoma skin cancer. A single larger study should be required to further evaluate gene-gene and gene-environment interactions on XRCC3 polymorphisms and tissue-specific cancer risk in an ethnicity specific population.

Amino Acid Substitution↗

[Functional expression of an omega-3 fatty acid desaturase gene from Glycine max in Saccharomyces cerevisiae].

Alpha-linolenic acid(ALA, C18:3delta9,12,15 ) is an essential fatty acid which has many sanitary functions to human. However, its contents in diets are often not enough. In plants, omega-3 fatty acid desaturases(FAD) catalyze linoleic acid(LA, C18:2delta9,12) into ALA. The seed oil of Glycine max contains high level of ALA. To investigate the functions of Glycine max omega-3FAD, the cDNA of GmFAD3 C was amplified by RT-PCR from immature seeds, then cloned into the shuttle expression vector p416 to generate the recombinant vector p4GFAD3C. The resulting vector was transformed into Saccharomyces cerevisiae K601 throuth LiAc method. The positive clones were screened on the CM(Ura-) medium and identified by PCR, and then cultured in CM (Ura-) liquid medium with exogenous LA in 20 degrees C for three days. The intracellular fatty acid composition of the engineering strain Kp416 and Kp4GFAD3C was analyzed by gas chromatography (GC). A novel peak in strain Kp4GFAD3C was detected,which was not detectable in control, Comparison of the retention times of the newly yielded peak with that of authentic standard indicated that the fatty acid is ALA. The content of ALA reached to 3.1% of the total fatty acid in recombinant strain, the content of LA correspondingly decreased from 22% to 16.2% by contrast. It was suggested that the protein encoded by GmFAD3 C can specifically catalyze 18 carbon PUFA substrate of LA into ALA by taking off hydrogen atoms at delta15 location. In this study, we expressed a Glycine max omega-3 fatty acid desaturase gene in S. cerevisiae; An efficient and economical yeast expressing system(K601-p416 system) which is suitable for the expression of FAD was built.

Chromatography, Gas↗

[Advances in plant metallothionein and its heavy metal detoxification mechanisms].

Metallothioneins, which widely distribute in eukaryotic and prokaryotic organisms, are a class of cystein-rich and heavy metal-binding proteins with low molecular weights. Many genes encoding plant metallothioneins have been cloned in the past years. There is certain progress on the expression patterns, tissue specificities and structures of these genes such as the loci of promoters and introns in chromosomes, however, their exact functions remain unknown. The expressions of many plant metallothionein genes under environmental stresses suggested that they may function in both metal chaperoning and scavenging of reactive oxygen species with their large number of cysteine residues to protect plants from oxidative damage. The classification, characteristics, gene structure of plant metallothioneins, and recent advances in heavy metal detoxification are summarized in detail.

Metallothionein↗

Serum levels of leptin, insulin, and lipids in relation to breast cancer in china.

Epidemiological studies have found obesity to be a risk factor for women's breast cancer. The present study was to investigate whether there is a relationship between serum levels of leptin, insulin, and lipids and breast cancer incidence, in order to find experimental evidence that would be helpful in the diagnosis and prevention of breast cancer. Blood samples were collected from 130 patients with mammary disease and 103 healthy control subjects. Serum leptin, insulin, and lipids were determined by radioimmunoassay (RIA), enzyme-linked immunosorbent assays (ELISA), and Biochemistry Auto-analyzer, respectively. The data analysis was performed by use of the SPSS10.0 computer software. We found that the serum levels of leptin, insulin, and triglyceride (TG) were clearly higher in patients with breast cancer than in patients with benign breast disease and healthy controls, while serum HDL-C levels were lower in breast cancer patients (p < 0.03). Moreover, serum leptin levels were significantly correlated with BMI (body mass index) among three groups, whereas serum insulin levels were unrelated to BMI among three groups. Furthermore, the serum levels of leptin and insulin were not associated with menopausal status in patients with mammary disease (p > 0.05); however, the serum levels of F-Chol, T-Chol, TG, LDL-C, and APOB were significant higher in postmenopausal cases than those in premenopausal cases (p < 0.025). Interestingly, logistic regression analysis showed that subjects with elevated serum levels of leptin, insulin, TG, APOA1, and reduced level of serum HDL-C displayed increased risk of developing breast cancer than those with the normal levels, respectively. In conclusion, the present study suggested that aberrant serum levels of leptin, insulin, and lipids might play an important role in carcinogenesis of breast cancer. The elevated serum levels of leptin, insulin, TG, APOA1, and reduced level of serum HDL-C may be correlated with increased risk of breast cancer, suggesting that one way of preventing breast cancer would be carried out by controlling the intake of food.

Adult↗

Expression of E-cadherin and nm23 is associated with the clinicopathological factors of human non-small cell lung cancer in China.

E-cadherin, a calcium-dependent cell-cell adhesion molecule, functions as maintenance of epithelial integrity. nm23, encoded by non-metastatic 23 gene, plays a key role in differentiation of many kinds of epithelium. Loss or dysfunction of E-cadherin and nm23 was frequently identified in many types of human cancers and is considered to correlate with invasive/metastatic phenotype. We previously reported that defective expression of E-cadherin might play a role in the development of the malignant phenotype in non-small cell lung cancer (NSCLC) [Q.Y. Fei, H.T. Zhang, X.F. Chen, et al., Defected expression of Ecadherin in non-small cell lung cancer, Lung Cancer 37 (2002) 147-152]. In an attempt to evaluate the significance of E-cadherin and nm23 in human non-small cell lung cancer, we performed mRNA expression and genetic structure analyses of the E-cadherin and nm23 genes in 54 NSCLCs and 46 normal lung tissues. The mRNA expression was determined by semi-quantitative RT-PCR, and genetic structure was examined through PCR-SSCP followed by sequencing. Although no mutation of the E-cadherin and nm23 genes was detected, the results obtained in the present study showed that reduction of E-cadherin and nm23 mRNA expression remarkably correlated with low histological differentiation, increasing stage as well as lymph node metastases (P<0.05). These data provide us with support for the idea that dysfunction of E-cadherin and nm23 has a role in progression of NSCLC and that the examination of E-cadherin and nm23 expression can provide experimental evidence for clinical treatment.

Antigens, Neoplasm↗

Defective expression of transforming growth factor beta receptor type II is associated with CpG methylated promoter in primary non-small cell lung cancer.

PURPOSE: Reduced expression of the transforming growth factor beta receptor type II (TGF beta RII), a key inhibitor of epithelial cell growth and tumor suppressor gene, was reported frequently in many types of tumors including non-small cell lung cancer (NSCLC). This study explored the significance of the TGF beta RII gene in NSCLC carcinogenesis. EXPERIMENTAL DESIGN: With 43 independent pairs of tumor and paracarcinoma tissue samples from patients with primary NSCLC, we carried out PCR-denaturing gradient gel electrophoresis screening for DNA variants over the coding sequence of the TGF beta RII gene, immunohistochemical assay of TGF beta RII expression, methylation-specific PCR analysis, and semiquantitative reverse transcription-PCR. RESULTS: The PCR-denaturing gradient gel electrophoresis did not detect variation in the whole coding sequence of the TGF beta RII gene, but the immunohistochemistry experiment revealed reduced or lost expression of the gene in 44% (19 of 43) of the tumor samples. The methylation analysis on the 19 pairs detected the frequent occurrence of methylated TGF beta RII promoter in tumor tissues, whereas most of the paracarcinoma tissues were free of methylation. The reduced TGF beta RII expression was highly significantly associated with the methylation event (P < 10(-4)). The reverse transcription-PCR analysis demonstrated a clear agreement between reduced TGF beta RII expression and decreased mRNA level of the gene in the tumor tissue samples. CONCLUSIONS: TGF beta RII plays an important role as a tumor suppressor in NSCLC carcinogenesis. The defective expression may serve as one of most important molecular mechanisms in explaining progression of the disease. In particular, aberrant 5' CpG methylation of the gene has explained the down-regulation of the gene at a transcriptional level.

Adult↗

A one-dimensional zigzag coordination polymer: catena-poly[[diaquapyridinenickel(II)]-mu-pyridine-2,3-dicarboxylato-kappa3N,O2:O3].

The asymmetric unit of the title one-dimensional coordination polymer, [Ni(C(7)H(3)NO(4))(C(5)H(5)N)(H(2)O)(2)](n), contains a quinolinate dianion, a nickel(II) ion, two water molecules and a pyridine molecule. The pyridine-2,3-dicarboxylate (quinolinate) ligands connect the nickel(II) ions in a head-to-tail fashion, resulting in the formation of a one-dimensional zigzag chain. Adjacent chains form pairs via an extensive network of hydrogen-bonding interactions. A weak C--H...O intermolecular hydrogen bond links neighboring pairs of chains, thus generating two-dimensional double-sheet layers that are stabilized via pi-pi-stacking interactions between adjacent quinolinate pyridyl rings.

Journal Article↗

A single-strand helical coordination polymer: catena-poly[[[triaquanickel(II)]-mu-2,2'-bipyridine-3,3'-dicarboxylato-kappa(3)N,N':O] monohydrate].

The asymmetric unit of the title compound, [[Ni(C(12)H(6)N(2)O(4))(H(2)O)(3)].H(2)O](n), is composed of a lattice water molecule and a nickel(II) ion that is coordinated by three water molecules and the two N atoms of a 2,2'-bipyridine-3,3'-dicarboxylate ligand. The twist of the 2,2'-bipyridine-3,3'-dicarboxylate unit and the coordination of one carboxylate group to a symmetry-related Ni(II) atom generate a helical chain that runs along the b axis. Intrahelical hydrogen bonds participate in controlling the orientation of the helices, and both right-handed and left-handed helices are connected by interhelical hydrogen bonds into two-dimensional sheets.

2,2'-Dipyridyl↗

Mutational analysis of the transforming growth factor beta receptor type I gene in primary non-small cell lung cancer.

Transforming growth factor-beta receptor-dependent signals are critical for cell growth and differentiation and are often disrupted during tumorigenesis. The entire coding region of TGFbetaRI and flanking intron sequences from 53 primary non-small cell lung cancer (NSCLC) tissues were examined for alterations using SSCP and direct sequencing. No somatic point mutations other than two silent mutations and a polymorphism were found in the TGFbetaRI gene. The two silent mutations located at codon 344 (AAT to AAC) and codon 406 (TTA to CTA), respectively, and the polymorphism was at the 24th base of intron 7 (G to A). To investigate whether the presence of this polymorphism is associated with NSCLC, we determined its allele distribution in all the 53 carcinomas and 89 normal controls. Interestingly, we found that the subjects with homozygous genotype A/A displayed more than 3-fold increased risk of developing NSCLC than the common wild genotype G/G. As the first report, the present study showed that TGFbetaRI gene is not a frequent site of spontaneous mutational inactivation while the detected polymorphism is frequent in the pathogenesis of NSCLC.

Activin Receptors, Type I↗

Disabling receptor ensembles with rationally designed interface peptidomimetics.

Members of the erbB family receptor tyrosine kinases (erbB1, erbB2, erbB3, and erbB4) are overexpressed in a variety of human cancers and represent important targets for the structure-based drug design. Homo- and heterodimerization (oligomerization) of the erbB receptors are known to be critical events for receptor signaling. To block receptor self-associations, we have designed a series of peptides derived from potential dimerization surfaces in the extracellular subdomain IV of the erbB receptors (erbB peptides). In surface plasmon resonance (BIAcore) studies, the designed peptides have been shown to selectively bind to the erbB receptor ectodomains and isolated subdomain IV of erbB2 with submicromolar affinities and to inhibit heregulin-induced interactions of erbB3 with different erbB receptors. A dose-dependent inhibition of native erbB receptor dimerization by the erbB peptides has been observed in 32D cell lines transfected with different combinations of erbB receptors. The peptides effectively inhibited growth of two types of transformed cells overexpressing different erbB receptors, T6-17 and 32D, in standard MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) and cell viability assays. The study identifies distinct loops within the membrane-proximal part of the subdomain IV as potential receptor-receptor interaction sites for the erbB receptors and demonstrates the possibility of disabling receptor activity by structure-based targeting of the dimerization interfaces. Molecular models for possible arrangement of the erbB1.EGF complex, consistent with the involvement of subdomain IV in inter-receptor interactions, are proposed. Small dimerization inhibitors described herein can be useful as probes to elucidate different erbB signaling pathways and may be developed as therapeutic agents.

Amino Acid Sequence↗