Biomedical subjects

Hua Zhao

Publications and source records attributed to Hua Zhao.

48 records · Page 3Linked to original sources

PubMed2003

XPA polymorphism associated with reduced lung cancer risk and a modulating effect on nucleotide excision repair capacity.

XPA, a DNA binding protein in the nucleotide excision repair (NER) pathway, modulates damage recognition. Recently, a common single-nucleotide polymorphism (A --> G) of unknown function was identified in the 5' non-coding region of the XPA gene. Because a deficiency in NER is associated with an increased risk of lung cancer, we evaluated the role of this polymorphism in 695 lung cancer case patients and 695 age-, sex-, ethnicity- and smoking-matched control subjects. We also studied the effect of this polymorphism on NER capacity in a subset sample for whom the host cell reactivation data were available. The presence of one or two copies of the G allele was associated with a reduced lung cancer risk for Caucasians [adjusted odds ratio (ORadj) = 0.69 [95% confidence interval (CI) = 0.53-0.90]], Mexican-Americans [ORadj = 0.32 (95% CI = 0.12-0.83)] and African-Americans [ORadj = 0.45 (95% CI = 0.16-1.22)]. In Caucasians, ever smokers with one or more copies of the G allele were observed to have a significantly reduced risk of lung cancer. Control subjects with one or two copies of the G allele demonstrated more efficient DRC than did those with the homozygous A allele. Our data suggest that the XPA 5' non-coding region polymorphism modulates NER capacity and is associated with decreased lung cancer risk, especially in the presence of exposure to tobacco carcinogens.

Base Sequence↗

PubMed2003

Plasma levels of insulin-like growth factor-1 and binding protein-3, and their association with bladder cancer risk.

PURPOSE: Because insulin-like growth factors (IGFs) and their binding proteins have been implicated in the development of prostate, breast, colon and lung cancer, we examined the role of IGF-1 and IGF binding protein-3 levels in bladder cancer risk. MATERIALS AND METHODS: We used an enzyme-linked immunosorbent assay to compare plasma levels of IGF-1 and IGF binding protein-3 in 154 patients with bladder cancer and 154 controls from an ongoing case-control study. RESULTS: Mean IGF-1 was significantly higher in cases than in controls (175.8 versus 153.2 ng./ml., p <0.01). Mean IGF binding protein-3 was significantly lower in cases than in controls (2,632.9 versus 3,056.6 ng./ml., p <0.01). The highest quartile plasma levels of IGF-1 were associated with an increased risk of bladder cancer (OR 3.10, 95% CI 1.43 to 6.70) and the highest quartile plasma levels of IGF binding protein-3 were associated with a reduced risk of bladder cancer (OR 0.38, 95% CI 0.19 to 0.78). The effects were more striking when IGF-1 and IGF binding protein-3 levels were analyzed together. In addition, a higher molar ratio of IGF-1-to-IGF binding protein-3 was associated with an increased risk of bladder cancer (OR 4.30, 95% CI 1.99 to 9.28). Dose-response relationships were evident when subjects were categorized into quartiles by the values of IGF-1, IGF binding protein-3 and the molar ratio in controls. CONCLUSIONS: To our knowledge this is the first study to suggest that patients with bladder cancer have higher plasma levels of IGF-1 and lower levels of IGF binding protein-3 than controls. Thus, measuring plasma IGF-1 and IGF binding protein-3 may be useful for assessing bladder cancer risk.

Case-Control Studies↗

PubMed2003

Influence of platelet activating factor on expression of adhesion molecules in experimental pancreatitis.

AIM: To determine whether Platelet activating factor (PAF) has a regulation role in the expression of adhesion molecules and accumulation of neutrophils in a murine model of acute pancreatitis. METHODS: One hundred twenty-eight Kunming mice were divided into four groups. Group 1 received 0.1 ml saline s.c. every hour for three hours (sham). Group 2 received cerulein (50 microg/kg dose s.c.) every hour for three hours. Group 3 received AP and additional challenge of PAF (50 mg/kg in absolute ethanol) (AP/PAF). Group 4 received AP, plus therapeutic treatment with GAB (25 mg dose i.p.) immediately after the first challenge of cerulein (AP/GAB). Animals were sacrificed at 12 h after the first challenge of saline or cerulein. Adhesion molecules of pancreas were semi-quantified by SP methods. Standard assays were performed for serum amylase and myeloperoxidase activity (MPO) of pancreas. Histology of pancreas was scored in a blind manner. Water content of pancreas was also measured at the same time. RESULTS: Control pancreata showed negligible adhesion molecule expression and neutrophil accumulation. There were evident adhesion molecules expression and neutrophil accumulation in AP and AP/PAF compared with sham (P<0.05). AP/GAB had a lower level of adhesion molecules, neutrophils, and water content versus AP and AP/PAF (P<0.05). Histology showed a trend toward improvement in AP/GAB, but did not reach statistical significance. CONCLUSION: PAF can induce the expression of adhesion molecules that mediate neutrophil accumulation. The PAF antagonist reduces the expression of adhesion molecules and the severity of inflammation when given immediately after the induction of mild AP in mice. These results suggest that PAF antagonism may be useful in the treatment of mild pancreatitis after its clinical onset.

Amylases↗

PubMed2003

[Multivariate analysis for prognostic predictors in the cN0 squamous cell carcinoma of the tongue].

BACKGROUND & OBJECTIVE: There is controversy in therapy strategy for the cN0 squamous cell carcinoma of the tongue. The aim of this study was to explore the relative factors of prognosis for the cN0 squamous cell carcinoma of the tongue and to identify the risk population. METHODS: Cox regression model was used to analyze the clinical data of 109 patients with cN0 tongue cancer treated in Cancer Center, Sun Yat-sen University from January 1990 to March 1998. The prognostic index (PI) of the patients was calculated on basis of the results of multivariate analysis. According to the individualized PI, the patients were classified to different hazard groups. RESULTS: The 3, 5 years survival rates were 74.40%and 69.31%, respectively. Multivariate analysis showed the prognosis statistically correlated with T grade, therapy manner of primary tumor, differentiation grade, age, and occult neck lymph node metastasis. T stage was found to be the most important prognostic factor. The prognosis of the patients in comprehensive therapy group is better than that in surgery alone group, chemotherapy alone,or radiotherapy alone group. The patients with tongue carcinoma in low differentiation group, the older group, or occult neck lymph node metastasis group showed a poor prognosis. The patients were divided into high-risk group,moderate-risk group, and low-risk group according to the PI value and there was significant difference in the survival rates between each two groups of the three groups (P< 0.05), and the 5-year survival rates were 83.33%, 64.12%, and 27.65%, respectively. CONCLUSION: The prognosis of cN0 squamous cell carcinoma of the tongue is associated with T grade, therapy manner of primary tumor, differentiation grade, age, and occult neck lymph node metastasis. PI value could be used to predict the prognosis of the patients with the cN0 squamous cell carcinoma of the tongue.

Adult↗

PubMed2003

[Survey research of serum anti-influenza virus antibody levels in Chinese young people during 1997-2000].

AIM: To survery the levels of serum anti-influenza virus antibodies and variable extent of the virus in the young people. METHODS: The levels of anti-influenza virus antibody in the serum samples collected from 3 000 young people of eight different areas in China in spring and autumn per year during 1997-2000 were detected by microhemagglutination inhibition test. RESULTS: The antibody levels of the young people fluctuated between the spring and autumn per year. The levels of antibody against type A3 virus (H3N2) preserved high from 1999-2000, while the level of antibody to type A1 (H1N1) decreased from 1998 to 2000 and the percentages of people susceptible to this type rose from 15% to 75%. CONCLUSION: The epidemic of H3N2, H1N1 viruses and influenza virus type has occurred at some areas in China. Significant variation appeared in H1N1 virus, while the variation of H3N2 virus will be expected.

Antibodies, Viral↗

PubMed2002

p53 Genotypes and Haplotypes Associated With Lung Cancer Susceptibility and Ethnicity.

BACKGROUND: The p53 tumor suppressor protein is important in cell-cycle control, apoptosis, and DNA repair. Mutations in p53 have been associated with inherited cancer susceptibility. Because there is a difference in the risk of lung cancer among different ethnic groups, we examined associations between ethnicity and three polymorphisms in p53 (one exonic and two intronic) and haplotypes for the three loci and risk of lung cancer. We also examined the functionality of the p53 variants in apoptosis and DNA repair. METHODS: In a case-control study, we frequency matched (by age, sex, and ethnicity) 635 lung cancer case patients and 635 control subjects. p53 genotypes and haplotypes at the three polymorphic sites were determined by restriction fragment length polymorphism analysis of lymphocyte DNA. Odds ratios (ORs) and 95% confidence intervals (CIs) for the association between genotype or haplotype and lung cancer risk were determined by logistic regression analysis. Apoptosis and DNA repair capacity were measured in 22 lymphoblastoid cell lines to determine the functional effects of the polymorphisms. All statistical tests were two-sided. RESULTS: Genotype and haplotype frequency distributions were strongly dependent on ethnicity; variant allele frequencies were highest in African-Americans (29.1%) and lowest in Mexican-Americans (12.2%). Each of the three polymorphisms was associated with an increased risk of lung cancer among all ethnic groups. Moreover, for all three polymorphisms, increased variant allele copy number was associated with increased risk of lung cancer. Similarly, the variant haplotypes were also associated with an increased risk for lung cancer. Lymphoblastoid cell lines with all wild-type alleles at the three loci had statistically significantly higher apoptotic indices (13.66%, 95% CI = 8.61% to 18.71%) and DNA repair capacity (27.63%, 95% CI = 21.72% to 33.53%) than cell lines with at least one variant allele at all three loci (3.50%, 95% CI = 1.08% to 5.91%; and 17.48%, 95% CI = 7.99% to 26.96%, respectively). CONCLUSIONS: p53 polymorphisms may be associated with increased lung cancer risk and may affect p53 function.

Black or African American↗

PubMed2002

Microsomal epoxide hydrolase polymorphisms and lung cancer risk in non-Hispanic whites.

Microsomal epoxide hydrolase (mEPHX) is a critical metabolic enzyme involved in the activation and subsequent detoxification of specific tobacco carcinogens. mEPHX harbors polymorphisms in exon 3 and exon 4 that modulate enzymatic activity. The exon 3 polymorphism decreases mEPHX metabolic activity, whereas the exon 4 polymorphism increases activity. We hypothesized that the mEPHX polymorphisms modulate lung cancer risk. Using a case-control study design and restriction fragment length polymorphism polymerase chain reaction assay, we determined the mEPHX polymorphic genotypes of 181 lung cancer cases among non-Hispanic whites and 163 controls (matched for age, sex, ethnicity, and smoking history). Our results showed that the variant allele of mEPHX exon 4 increased the overall lung cancer risk by 56% (odds ratio [OR]=1.56, 95% confidence interval [CI]=0.99-2.46). Additionally, the risk estimates were elevated significantly for younger people (<64 yr) (OR=2.27, 95% CI=1.15-4.50) and current smokers (OR=2.22, 95% CI=1.06-4.65). The variant allele of mEPHX exon 3 had no effect overall (OR=0.88, 95% CI=0.56-1.38), but there was a 53% protective effect (OR=0.47, 95% CI=0.22-0.99) in younger people. When we analyzed the exon 3 and exon 4 polymorphisms together, those people with the high enzymatic activity genotype had an elevated lung cancer risk of 1.72 (95% CI=0.90-3.29). This elevated risk was also evident only in younger people. These findings suggest that these variant alleles of exon 3 and exon 4 of mEPHX modulates lung cancer risk.

Base Sequence↗

PubMed2002

Cholangiocarcinoma cells express somatostatin receptor subtype 2 and respond to octreotide treatment.

BACKGROUND/PURPOSE: We investigated the in vitro and in vivo inhibitory effects of a somatostatin analogue (octreotide, OCT) on cholangiocarcinoma cell lines. METHODS: The reverse transcriptase-polymerase chain reaction (RT-PCR) was employed to detect the gene expression of five somatostatin receptor (SSTR) subtypes in four cholangiocarcinoma cell lines (RBE, NEC, QBC939, and SSP-25). The antiproliferative effects of OCT on these cell lines were determined by means of an MTT assay in vitro, as well as in a nude mouse tumor heterograft model in vivo. Apoptosis and cell cycles in the cholangiocarcinoma cell lines after OCT administration were evaluated by flow cytometry; and the effects of OCT on the expression of cyclin E, cyclin-dependent kinase 2 (CDK2), and p27kipl were evaluated by Western blots. RESULTS: Only SSTR2 mRNA was detected in these four cholangiocarcinoma cell lines. OCT significantly inhibited the proliferation of the four cholangiocarcinoma cell lines in vitro ( P < 0.05 vs control), and the weights of the QBC939 xenografts in the OCT-treated group were lower than those in the control group, but there was no significant difference between them. After 48-h exposure to 10(3) ng/ml OCT, flow cytometric analysis demonstrated an increased number of cells in G0/G1 phase associated with a decreased number of cells in G2/M and S phases ( P < 0.01 vs control). Apoptosis was not observed in any samples. The expression of p27kipl was promoted by OCT administration, while that of cyclin E and that of CDK2 were inhibited. CONCLUSIONS: The results proved that OCT inhibits the proliferation of cholangiocarcinoma cells through G0/G1 cell cycle arrest rather than through the process of apoptosis. These effects are partially mediated by enhancing the expression of p27kipl, and decreasing the amounts of cyclin E-CDK2 complex.

Animals↗

PubMed2002

[Influence of induction chemotherapy on long-time effect of patients with tongue squamous cell carcinoma].

BACKGROUND & OBJECTIVE: Induction chemotherapy is important in comprehensive care of patients with oral tongue squamous cell carcinoma. However, the effect of induction chemotherapy on the long-time effect was not clearly known. This study was designed to investigate the relationship between pathological negativity of primary lesion after induction chemotherapy and long-time effect in tongue squamous cell carcinoma. METHODS: The 3 year survival rate, the 5 year survival rate, survival rate with tumor free, and reasons of treatment failure of 25 patients with tongue squamous cell carcinoma which primary lesion was pathologically negative were analyzed retrospectively. RESULTS: The 3 year survival rate and the 5 year survival rate of the patients which primary lesion (91.75% and 91.66%) was pathologically negative were both higher than the patients with residual tumor (64.52% and 57.0%). The survival rate with tumor free in the former was also higher than that in the latter. The main reasons for treatment failure were local recurrence and/or regional lymph node metastasis/recurrence. CONCLUSION: Induction chemotherapy could increase the long-time survival rate of the patients with tongue squamous cell carcinoma whose primary lesion was pathologically negative.

Adult↗

PubMed2002

[Influence of 4-aminopyridine on voltage-activated K(+) current and cell proliferation in small cell lung cancer].

OBJECTIVE: To study the inhibition of voltage-activated K(+) conductance and cell proliferation by 4-aminopyridine (4-AP) in the human small-cell lung cancer (SCLC). METHODS: Inhibition of voltage-activated K(+) current by 4-AP through the whole-cell patch-clamp technique in SCLC cell line was studied. The influence on the cell-cycle by 4-AP was observed by flow cytometry to identify the in vitro inhibition by 4-AP to the cell proliferation of the SCLC cell line. RESULTS: Exposure of the tumor cells to 5 mmol/L 4-AP reduced the peak outward K(+) current (evoked by a depolarization to +80 mV) from 1.22 +/- 0.11 nA (n = 30) to 0.59 +/- 0.10 nA (n = 28). Flow cytometry results showed that cell population accumulated in the G(0)/G(1) phase and a significantly reduced proportion in the S phase and G(1)/G(2) phase cells after having been exposed to 4-AP for three days. Incubation of the SCLC cells with 0.1, 5, 10, 15, 20 mmol/L 4-AP resulted in a concentration-and time-dependent reduction in the number of viable cells as compared with the control. CONCLUSION: The voltage-activated K(+) channels expressed by SCLC play an important role in SCLC cell proliferation. The proliferation of the SCLC cells is inhibited by K(+) channel antagonists.

4-Aminopyridine↗

PubMedDate not supplied

Kinetic study on the enzymatic resolution of homophenylalanine ester using ionic liquids.

Two ionic liquids (ILs) were investigated as novel media for the enzymatic resolution of amino acid ester to obtain enantiomeric amino acid homophenylalanine. The effects of solvent nature, polarity, and concentration on the kinetic resolution were investigated. With change in solvent concentration, a systematic study shows that an improved enzyme activity can be obtained by adjusting these solvent parameters.

Amino Acids↗

PubMedDate not supplied

Concise synthesis and enzymatic resolution of L-(+)-homophenylalanine hydrochloride.

The N-acetyl-homophenylalanine ethyl ester was synthesized by a simple three-step-reaction strategy. L-(+)-homophenylalanine hydrochloride with 98% ee was obtained through a kinetic resolution process using industrial enzyme alcalase. Compared with other methods, this strategy has the advantage of economical and simple procedure giving high product optical purity.

Journal Article↗