Biomedical subjects

Q Wei

Publications and source records attributed to Q Wei.

At least 19 recordsLinked to original sources

PubMed2007

Global analysis of differentially expressed genes in androgen-independent prostate cancer.

Progression to androgen independent (AI) is the main cause of death in prostate cancer, and the mechanism is still unclear. By reviewing the expression profiles of 26 prostate cancer samples in a holistic view, we found a group of genes differentially expressed in AI compared with androgen-dependent groups (P-value<0.01, t-test). Focusing on apoptosis, proliferation, hormone and angiogenesis, we found a group of genes such as thioredoxin domain containing 5 , tumor necrosis factor receptor superfamily, member 10a , ribosomal protein S19 and Janus kinase 2 upregulated in AI prostate cancer, could play important roles in the transition from AD to AI and could be biomarkers of prognosis.

Androgen Antagonists↗

PubMed2006

Benzo(a)pyrene inhibits expression of inducible heat shock protein 70 in vascular endothelial cells.

Benzo(a)pyrene (BaP), a ubiquitous environmental pollutant known to cause many diseases including atherosclerosis, induces a dose-dependent reduction in the levels of the inducible Hsp70. To explore the mechanism underlying the reduction of Hsp70, we measured the levels of Hsp70, cytoplasmic and nuclear heat shock factor 1 (HSF1) in porcine aortic endothelial cells using Western blot, and then further characterized the binding ability of HSF1 and heat shock element (HSE) by electrophoretic mobility shift assay. We found that when porcine aortic endothelial cells were treated by 0.1-10 microM of BaP for 24 h, there was a significant reduction of Hsp70, cytoplasmic and nuclear HSF1 and the binding rate of HSF1 and HSE at 5, 10 microM of BaP but less effective at lower concentrations. The effect of BaP on the Hsp70 expression level was markedly attenuated by co-treatment with phorbol 12-myristate 13-acetate (PMA), an activator of protein kinase C (PKC). Staurosporine (STP), an inhibitor of PKC, blocked the effect of PMA treatment in combination with BaP. These results suggest that BaP might inhibit Hsp70 levels by reducing the expression of HSF1 and decreasing binding of HSF1 and HSE via PKC-dependent signaling pathways that might be involved in the regulation of Hsp70 gene expression under BaP.

Animals↗

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↗

PubMed2006

Regulation of PUMA-alpha by p53 in cisplatin-induced renal cell apoptosis.

Nephrotoxicity is a major side effect of cisplatin, a widely used cancer therapy drug. Depending on its concentration, cisplatin induces necrosis or apoptosis of tubular cells in the kidneys, whereas the underlying injury mechanism is unclear. Our recent work has suggested a critical role for p53 in cisplatin-induced tubular cell apoptosis; nevertheless, the apoptotic events triggered by p53 remain elusive. The current study has examined Bcl-2 family proteins, critical regulators of apoptosis that may be subjected to p53 regulation. Following cisplatin treatment, the expression of Bcl-xL, an antiapoptotic molecule, was suppressed, while the expression of Bak, a proapoptotic molecule, increased slightly. Of interest, PUMA-alpha, a newly identified p53-responsive proapoptotic Bcl-2 family protein, was drastically induced by cisplatin. PUMA-alpha induction preceded or paralleled the development of apoptosis. Induced PUMA-alpha was localized in mitochondria and appeared to antagonize Bcl-xL via molecular interaction. PUMA-alpha induction during cisplatin treatment was attenuated by pifithrin-alpha, a pharmacological inhibitor of p53, which was accompanied by the amelioration of Bax activation, cytochrome c release and apoptosis. Moreover, PUMA-alpha induction was suppressed by dominant-negative p53. Importantly, cisplatin-induced apoptosis was ameliorated in PUMA-alpha knockout cells. In vivo, cisplatin induced PUMA-alpha in the kidneys, and the inductive response was abrogated in p53-deficient animals. Together, this study has demonstrated the first compelling evidence for the involvement of PUMA-alpha in p53-mediated renal cell apoptosis during cisplatin nephrotoxicity.

Animals↗

PubMed2006

Electrodynamic heart model construction and ECG simulation.

OBJECTIVES: In this paper, we present a unified electrodynamic heart model that permits simulations of the body surface potentials generated by the heart in motion. The inclusion of motion in the heart model significantly improves the accuracy of the simulated body surface potentials and therefore also the 12-lead ECG. METHODS: The key step is to construct an electromechanical heart model. The cardiac excitation propagation is simulated by an electrical heart model, and the resulting cardiac active forces are used to calculate the ventricular wall motion based on a mechanical model. The source-field point relative position changes during heart systole and diastole. These can be obtained, and then used to calculate body surface ECG based on the electrical heart-torso model. RESULTS: An electromechanical biventricular heart model is constructed and a standard 12-lead ECG is simulated. Compared with a simulated ECG based on the static electrical heart model, the simulated ECG based on the dynamic heart model is more accordant with a clinically recorded ECG, especially for the ST segment and T wave of a V1-V6 lead ECG. For slight-degree myocardial ischemia ECG simulation, the ST segment and T wave changes can be observed from the simulated ECG based on a dynamic heart model, while the ST segment and T wave of simulated ECG based on a static heart model is almost unchanged when compared with a normal ECG. CONCLUSIONS: This study confirms the importance of the mechanical factor in the ECG simulation. The dynamic heart model could provide more accurate ECG simulation, especially for myocardial ischemia or infarction simulation, since the main ECG changes occur at the ST segment and T wave, which correspond with cardiac systole and diastole phases.

Electrocardiography↗

PubMed2005

An object-oriented designed finite-difference time-domain simulator for electromagnetic analysis and design in MRI--applications to high field analyses.

This paper presents a finite-difference time-domain (FDTD) simulator for electromagnetic analysis and design applications in MRI. It is intended to be a complete FDTD model of an MRI system including all RF and low-frequency field generating units and electrical models of the patient. The program has been constructed in an object-oriented framework. The design procedure is detailed and the numerical solver has been verified against analytical solutions for simple cases and also applied to various field calculation problems. In particular, the simulator is demonstrated for inverse RF coil design, optimized source profile generation, and parallel imaging in high-frequency situations. The examples show new developments enabled by the simulator and demonstrate that the proposed FDTD framework can be used to analyze large-scale computational electromagnetic problems in modern MRI engineering.

Algorithms↗

PubMed2005

A common polymorphism in the 3'UTR of cyclooxygenase 2/prostaglandin synthase 2 gene and risk of lung cancer in a Chinese population.

Cyclooxygenases (COXs) are key enzymes that convert arachidonic acid to prostaglandins. Overexpression of COX-2, one of the COX isozymes, has been shown to be an early event in lung carcinogenesis and may play an important role in lung cancer development. A common single nucleotide polymorphism, T8473C, located within a potential functional region in the 3'UTR of COX-2 gene was identified and we hypothesized that this COX-2 variant is associated with lung cancer risk. To test this hypothesis, we genotyped this variant in a case-control study of 322 histologically-confirmed lung cancer patients and 323 age and sex frequency-matched cancer-free controls in a Chinese population. The results showed that the frequencies of variant genotypes 8473CT/CC were significantly less common in the cases (27.3%) than in the controls (35.3%) (P=0.034), suggesting that the 8473C allele was protective against lung cancer. Multivariate logistic regression analyses revealed that the COX-2 variant genotypes (8473CT/CC) were associated with a significantly decreased risk of lung cancer compared with the 8473TT wild-type homozygotes (OR=0.64, 95% CI=0.45-0.92). When we defined the reference group as non-smokers having the 8473CT/CC variant genotypes, the smokers with the 8473TT wild-type genotype had the greatest risk (adjusted OR=5.28, 95% CI=3.10-9.00). These findings indicate that the COX-2 T8473C polymorphism may contribute to lung cancer susceptibility in the Chinese population. Further larger molecular epidemiological studies are warranted to confirm these findings.

3' Untranslated Regions↗

PubMed2004

Efficient preparation of L-cysteic acid and its esters.

L-Cysteic acid and its esters were prepared in good yields from the oxidation of L-cystine by chlorine in water and in alcohols. When the reaction was carried out in alcohols the corresponding esters were produced.

Alcohols↗

PubMed2004

DNA repair gene XPD polymorphism and lung cancer risk: a meta-analysis.

Interindividual variation in lung cancer susceptibility may be modulated in part through genetic polymorphisms in the DNA repair genes, especially the genes involved in the nucleotide excision repair (NER) pathway. The xeroderma pigmentosum complementary group D (XPD) is one of the NER genes, and two of the XPD polymorphisms 751A --> C and 312G --> A have been extensively studied in the association with lung cancer, although published studies have been inconclusive. To clarify the impact of XPD polymorphisms on lung cancer risk, we performed a meta-analysis of the published data from nine (10 comparisons) individual case-control studies of 3725 lung cancer cases and 4152 controls. The results showed that individuals with the XPD 751CC genotype had a 21% (odds ratio (OR)= 1.21, 95% confidence interval (CI) = 1.02-1.43) increased risk of lung cancer compared with individuals with the 751AA genotype without any between-study heterogeneity (P = 0.26). There was also a significant association in the recessive model of 751 C allele by comparing the CC with AC + AA genotypes (OR = 1.19, 95% CI = 1.02-1.40). The results also showed a significantly increased risk of lung cancer associated with the 312AA homozygous genotype compared with the GG genotype and the 312 A allele in the recessive model (compared with GA + AA genotypes) (OR = 1.27, 95% CI = 1.04-1.56 and OR = 1.32, 95% CI = 1.09-1.59, respectively). These results support the hypothesis that both the XPD 751 C and 312 A are risk alleles and individuals with the XPD 751 CC and 312 AA genotypes are at higher risk of developing lung cancer. Large multi-center studies with precise design, and stratified/adjusted analyses of the gene-gene (haplotypes) and gene-environment interactions are needed.

DNA Helicases↗

PubMed2004

Safety of mycophenolate mofetil versus azathioprine in renal transplantation: a systematic review.

INTRODUCTION: To evaluate the safety of mycophenolate mofetil (MMF) versus azathioprine (Aza) in renal transplantation, we compared their side effects using evidence-based methods. METHODS: Medline, Embase, Cochrane library, and Chinese Biomedicine database (CBM) were searched to select randomized clinical trials that had one group using MMF and another group using Aza as an immunosuppressive drugs. Safety analysis consist of the following factors: diarrhea, abdominal pain, vomiting, nausea, constipation, CMV infection, leukopenia, anemia, thrombocytopenia or skin malignancy. RevMan 4.11 software was used for the systematic review analysis. RESULT: Twenty trials including 6387 patients were identified. The diarrhea incidence with MMF (3 g/d) was higher than for Aza at 1 and 3 years (P < .05). Diarrhea on MMF (2 g/d) was higher than for Aza within 6 months (P < .05). CMV infection incidence on MMF (3 g/d) was higher than for Aza's at 3 years (P < .05), but MMF (2 g/d) did not show a statistical significance compared with Aza. Leukopenia incidence on MMF (3 g/d) was higher than that on Aza, whereas the incidence with MMF (2 g/d) was not significantly different from Aza. Skin malignancy incidence showed no statistical difference between MMF 3 g/d, MMF 2 g/d, or Aza. CONCLUSION: The use of MMF is associated with slight increases in gastrointestinal adverse effects, some hematologic adverse events, and CMV infections compared with Aza. Larger sample sizes of randomized controlled trials are needed to evaluate the safety of MMF.

Azathioprine↗

PubMed2004

Efficacy of mycophenolate mofetil versus azathioprine after renal transplantation: a systematic review.

INTRODUCTION: Our objective was to evaluate the efficacy of mycophenolate acid (MMF) versus azathioprine (AZA) after renal transplantation. MATERIALS AND METHODS: The following electronic databases were searched: Medline, Embase, Cochrane library, and Chinese Biomedicine database (CBM). Randomized controlled trials (RCTs) were subjected to Revman 4.11 for statistical analyses. RESULTS: Twenty-three RCTs were identified to compare MMF and AZA for antirejection, prophylaxis after renal transplantation. The data showed that MMF (2 g/d) was more beneficial than AZA to improve graft and long-term patient survivals, but there was no statistical differences between MMF (3 g/d) and AZA. Whether at 6 months or at 1 year after renal transplantation, the use of MMF (2 g/d) or MMF (3 g/d) markedly reduced the incidence of biopsy-proven rejection. CONCLUSION: Compared with AZA, MMF is a more potent immunosuppressive drug, that is more efficient in reducing the incidence of acute rejection episodes after renal transplantation. MMF can improve the graft and patient survival rate. The 2 g per day dosage is more acceptable.

Azathioprine↗

PubMed2004

Study of renal function matching between Banna Minipig Inbred line and human.

Pigs have been thought to be ideal candidates for xenotransplant donors. However besides the immunological barrier, physiological and pharmacokinetic comparabilities of kidney function between donor animals and humans are important factors for successful xenotransplantation. As a unique large inbred animal, Banna Minipig Inbred (BMI) has been reported to be a potential large animal suitable for xenotransplantation. However, its physical and pharmacokinetic compatibilities with humans have not been documented. The purpose of this investigation was to measure renal routine function, glomerular filtration rate (GFR), renal blood flow (ERPF), and drug metabolism to evaluate comparability to humans. The results suggested that the renal function of BMI was similar to that of humans to eliminate nonprotein nitrogenous end products of metabolism. Pharmacokinetics of p-aminohippurate (PAH) and inulin--the most widely used methods to assess ERPF and GFR--showed that BMI showed lower values than humans for GFR, but similar function to humans in ERPF. The pharmacokinetics of cefazolin; a widely used model drug to study kidney drug metabolizing capacity, showed greater overall renal drug elimination of BMI than of humans. These results suggested that BMI did show comparable data to human renal function.

Adult↗

PubMed2004

Study of hepatic function matching between Banna minipig inbred and humans.

As a unique inbred pig Banna minipig inbred (BMI) is potentially suitable for pig-to-human xenotransplantation due to its clear genetic background and minor interindividual differences. Previous studies of BMI have focused on immunological barriers between BMI and humans. However, a comparison of liver function between donor animals and humans is an essential premise for successful xenotransplantation. In this study, we investigated routine hepatic functions, protein electrophoresis, and drug metabolism to compare capacity of liver synthesis, metabolism, and drainage between BMI and humans. The results showed no significant differences in the concentrations of albumin and globulin synthesized in the liver (alpha1, alpha2, and beta-globulin). Serum enzyme activities in BMI were higher than those in humans, and levels of total bilirubin and direct-reacting bilirubin of BMI were lower than those of humans. In BMI, the clearance of antipyrine, a widely used model drug to study hepatic drug metabolism, was 16 times greater than that by humans, with a mean residual time of antipyrine in BMI, one-tenth of that in human. These findings suggested that BMI livers are similar to humans in albumin and alpha, beta-globulin synthesis, but stronger in bilirubin elimination, enzyme activity, and drug metabolism. BMI livers may have stronger functions compared with those of humans. No incompatibility was identified in hepatic function between BMI and humans.

Adult↗

PubMed2001

Sensitivity to benzo(a)pyrene diol-epoxide associated with risk of breast cancer in young women and modulation by glutathione S-transferase polymorphisms: a case-control study.

Mounting epidemiological evidence suggests that smoking may play a role in the etiology of breast cancer. Because smoking-related DNA adducts are detectable in both normal and malignant breast tissues, we hypothesized that breast cancer patients may be sensitive to tobacco-induced carcinogenesis, and this sensitivity could be modulated by variants of metabolic genes. To test this hypothesis, we evaluated benzo(a)pyrene diol-epoxide (BPDE)-induced mutagen sensitivity and polymorphisms of GSTM1 and GSTT1 in a pilot case-control study of breast cancer. Short-term cell cultures were established from blood samples of 100 female breast cancer patients and 105 healthy controls. After 5 h of in vitro exposure to 4 microM of BPDE, we harvested the lymphocytes for cytogenetic evaluation and recorded and compared the frequency of BPDE-induced chromatid breaks between cases and controls. We used a multiplex PCR-based assay to simultaneously detect polymorphisms of GSTM1 and GSTT1 from genomic DNA. We performed univariate and multivariate logistic regression analyses and calculated odds ratios (OR) and 95% confidence intervals (CIs). Cases had a significantly higher frequency of chromatid breaks than did controls (P < 0.0001). The level of chromatid breaks greater than the median value of controls was associated with a >3-fold increased risk of breast cancer [adjusted odds ratio (ORadj) = 3.11; 95% CI = 1.72-5.64]. The risk was more pronounced in those who were < 45 years (ORadj = 4.79; 95% CI = 1.87-12.3), ever-smokers (ORadj = 5.55; 95% CI = 1.85-16.6), alcohol drinkers (ORadj = 4.64; 95% CI = 1.70-12.7), and those who had the GSTT1 null variant (ORadj = 8.01; 95% CI = 1.16-55.3). These data suggest that sensitivity to BPDE-induced chromosomal aberrations may contribute to the risk of developing breast cancer, and such sensitivity may be modulated by both genetic and environmental factors. Larger studies are needed to confirm our findings.

7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide↗

PubMed2001

RNAi as random degradative PCR: siRNA primers convert mRNA into dsRNAs that are degraded to generate new siRNAs.

In posttranscriptional gene silencing (PTGS), "quelling," and RNA interference (RNAi), 21-25 nucleotide RNA fragments are produced from the initiating dsRNA. These short interfering RNAs (siRNAs) mediate RNAi by an unknown mechanism. Here, we show that GFP and Pp-Luc siRNAs, isolated from a protein complex in Drosophila embryo extract, target mRNA degradation in vitro. Most importantly, these siRNAs, as well as a synthetic 21-nucleotide duplex GFP siRNA, serve as primers to transform the target mRNA into dsRNA. The nascent dsRNA is degraded to eliminate the incorporated target mRNA while generating new siRNAs in a cycle of dsRNA synthesis and degradation. Evidence is presented that mRNA-dependent siRNA incorporation to form dsRNA is carried out by an RNA-dependent RNA polymerase activity (RdRP).

Animals↗

PubMed2001

Gamma-radiation sensitivity and risk of glioma.

BACKGROUND: About 9% of human cancers are brain tumors, of which 90% are gliomas. gamma-Radiation has been identified as a risk factor for brain tumors. In a previous pilot study, we found that lymphocytes from patients with glioma were more sensitive to gamma-radiation than were lymphocytes from matched control subjects. In this larger case-control study, we compared the gamma-radiation sensitivity of lymphocytes from glioma patients with those from control subjects and investigated the association between mutagen sensitivity and the risk for developing glioma. METHODS: We used a mutagen sensitivity assay (an indirect measure of DNA repair activity) to assess chromosomal damage. We gamma-irradiated (1.5 Gy) short-term lymphocyte cultures from 219 case patients with glioma and from 238 healthy control subjects frequency matched by age and sex. After irradiation, cells were cultured for 4 hours, and then Colcemid was added for 1 hour to arrest cells in mitosis. Fifty metaphases were randomly selected for each sample and scored for chromatid breaks. All statistical tests were two-sided. RESULTS: We observed a statistically significantly higher frequency of chromatid breaks per cell from case patients with glioma (mean = 0.55; 95% confidence interval [CI] = 0.50 to 0.59) than from control subjects (mean = 0.44; 95% CI = 0.41 to 0.48) (P<.001). Using 0.40 (the median number of chromatid breaks per cell in control subjects) as the cut point for defining mutagen sensitivity and adjusting for age, sex, and smoking status, we found that mutagen sensitivity was statistically significantly associated with an increased risk for glioma (odds ratio = 2.09; 95% CI = 1.43 to 3.06). When the data were divided into tertiles, the relative risk for glioma increased from the lowest tertile to the highest tertile (trend test, P<.001). CONCLUSION: gamma-Radiation-induced mutagen sensitivity of lymphocytes may be associated with an increased risk for glioma, a result that supports our earlier preliminary findings.

Adult↗

PubMed2001

Polymorphisms of 5,10-methylenetetrahydrofolate reductase and risk of gastric cancer in a Chinese population: a case-control study.

Low dietary folate intake has been associated with increased risk of gastric cancer. The 5,10-methylenetetrahydrofolate reductase (MTHFR) involved in folate metabolism has 2 variants, C677T and A1298C, that result in decreased MTHFR activity and lower plasma folate levels. Therefore, we hypothesized that these 2 variants play a role in gastric carcinogenesis. We tested this hypothesis in a Chinese population-based case-control study of 187 histopathologically confirmed gastric cancer cases and 166 healthy controls frequency-matched by age (+/-5 years), gender and residential area. The 677TT genotype was associated with increased risk for gastric cancer [adjusted odds ratio (OR) = 1.87, 95% confidence interval (CI) = 1.00-3.48] compared to the 677CC genotype. This association was more pronounced for gastric cardia cancer (adjusted OR = 2.47, 95% CI = 1.14-5.32). However, no evidence was found for risk associated with the MTHFR A1298C polymorphism. Our findings support the hypothesis that MTHFR C677T variants contribute to gastric carcinogenesis, particularly in gastric cardia. Larger studies incorporating dietary folate intake and serum levels are needed to confirm our findings.

Adenocarcinoma↗

PubMed2001

Nanowire nanosensors for highly sensitive and selective detection of biological and chemical species.

Boron-doped silicon nanowires (SiNWs) were used to create highly sensitive, real-time electrically based sensors for biological and chemical species. Amine- and oxide-functionalized SiNWs exhibit pH-dependent conductance that was linear over a large dynamic range and could be understood in terms of the change in surface charge during protonation and deprotonation. Biotin-modified SiNWs were used to detect streptavidin down to at least a picomolar concentration range. In addition, antigen-functionalized SiNWs show reversible antibody binding and concentration-dependent detection in real time. Lastly, detection of the reversible binding of the metabolic indicator Ca2+ was demonstrated. The small size and capability of these semiconductor nanowires for sensitive, label-free, real-time detection of a wide range of chemical and biological species could be exploited in array-based screening and in vivo diagnostics.

Antibodies, Monoclonal↗