Biomedical subjects

Shu Zheng

Publications and source records attributed to Shu Zheng.

At least 91 records · Page 5Linked to original sources

PubMed2004

[Induction of HSF1 expression and sporadic colorectal cancer].

OBJECTIVE: To explore the activation of the signal transduction pathways related with the carcinogenesis of sporadic colon cancers. METHODS: A gene microarray monitoring activation of 8 signal transduction pathways (PathwayFinder GEArray) was used to screen the differentially expressed genes between colorectal cancer and normal colon tissue. The differentially expressed genes were further analyzed by RT-PCR, using RNA extracted from cancer tissue and matched normal colon mucosa of 35 patients with colorectal cancer. RESULTS: The expression of hsf1, hsf27 and inos was increased in colon cancer compared with normal colon mucosa using PathwayFinder GEArray. The RT-PCR results showed that the expression of hsf1 was detected in 86% of patients(30/35)and the expression of inos detected in 63% patients(22/35). CONCLUSION: Hsf1 induces heat shock stress signaling pathway, which might play a role in the carcinogenesis of sporadic colorectal cancer.

Cell Cycle Proteins↗

PubMed2004

[Hypermethylation of hMLH1 promoter in sporadic colorectal cancer].

OBJECTIVE: To identify CpG island hypermethylation of 5'region of hMLH1 promotor and to explore its relationship to microsatellite instability(MSI)in sporadic colorectal carcinoma. METHODS: Forty-one pairs of tissue specimens (normal and cancer) were collected from 41 patients with colorectal cancer. Hypermethylation of hMLH1 promoter was detected by methylation specific PCR; the relationship between methylation and clinicopathological features was analyzed. Combined with BAT25 and BAT26, the MSI status was detected using an automated fluorescent DNA sequencer. RESULTS: Hypermethylation of hMLH1 promoter was detected in 75.6 % (31/41) of samples. Mean age of unmethylation cases (49.2 y) was significantly younger than that of methylation cases (63.6 y) (P<0.05), but there were no differences between two groups in other clinicopathological features. MSI was detected in 43.9 % samples (18/41); hypermethylation of hMLH1 promoter was detected in 94.4 % (17/18) of MSI(+) samples, which was higher than that in MSI(-) samples (60.9 %,14/23, P<0.05). CONCLUSION: Age-related hypermethylation is generally found in patients with sporadic colorectal cancers, which may cause MSI and might be the mechanism in the development of colorectal cancer of elderly people.

Adaptor Proteins, Signal Transducing↗

PubMed2004

[Significance of CK20 mRNA expression in peripheral blood of colorectal cancer patients by real-time fluorescent quantitative RT-PCR].

OBJECTIVE: To detect the expression of cytokeratin 20 (CK20) mRNA in peripheral blood of colorectal carcinoma and to discuss its clinical value. METHODS: Real-time fluorescent quantitative RT-PCR was used to detect the CK20 mRNA expression in the peripheral blood of 51 patients with colorectal carcinoma and 30 healthy volunteers. RESULTS: 27.45% of the patients showed CK20 mRNA expression, while it was 6.67% for the control group (P<0.025). With the progress of Dukes' stages, the expression level of CK20 mRNA increased, but there was no statistic significance (P<0.05). More samples in Dukes'C and D than in Dukes'A and B stages showed >10 copies/ml. CONCLUSION: The detection of CK20 mRNA expression in peripheral blood of patients with colorectal carcinoma may be helpful to identify early shedding tumor cells. It is also useful to monitor the progression of the disease and observe the effect of clinical treatment.

Adult↗

PubMed2004

[The optimal combination of serum tumor markers with bioinformatics in diagnosis of colorectal carcinoma].

OBJECTIVE: To identify the optimal combination of serum tumor markers with bioinformatics in diagnosis of colorectal cancer. METHODS: The serum levels of CEA, AFP, NSE, CA199, CA242, CA724, CA211 and TPA were detected in 128 patients with colorectal carcinoma and 113 health subjects. The serum tumor markers were evaluated with the area under curves. The optimal combination of serum tumor markers was selected and the diagnostic model with artificial neural network was established. RESULTS: CEA, CA199, CA242, CA211, CA724 were selected for the optimal combination and the artificial neural network was built. The model was evaluated by a 5-cross validation approach. The model had a specificity of 95%, sensitivity of 83% and positive predictive value of 95% in diagnosis of colorectal carcinoma. CONCLUSION: The combination of optimal serum tumor markers has a high sensitivity and specificity in diagnosis of colorectal carcinoma.

Adult↗

PubMed2004

[Alcohol drinking and colorectal cancer: a population-based prospective cohort study].

OBJECTIVE: To understand the incidence of colorectal cancer in population drinking or not and to validate the relationship between drinking and colorectal cancer. METHODS: The data obtained from a questionnaire used in a population-based prospective screenings study in ten countries of Jiashan County was examined. A total of 64,102 men and women aged 30 y and older without history of cancer at baseline and a subcohort of 29,044 of them drinking past and current was conducted. Cox regression model was applied to estimate relative risk (RR). RESULTS: After 10 years follow-up,107 colon cancer and 135 rectal cancer cases were identified. Among drinkers and abstainers, the incidence density of colorectal cancer was 36.18 per 100 thousand and 37.26 per 100 thousand, respectively and there wasn't statistical significance(Z=0.52, P>0.05); The crude RR (95%CI) for drinker compared with never drinkers was 0.97(0.75 approximately 1.25), and the multivariable-adjusted RR (95%CI) was 1.13(0.87 approximately 1.48). The research power of this study was 96.99%. CONCLUSION: Alcohol drinking isn't one of the risk factors of colorectal cancer among Jiashan County population.

Adult↗

PubMed2004

[Localization and screening of autosomal dominant coralliform cataract associated gene].

OBJECTIVE: To identify the genetic defect for the autosomal dominant coralliform cataract affecting a four-generation Chinese family. METHODS: Genomic DNA from the family members was typed for whole genomic linkage analysis. Two-point LOD scores were calculated using the LINKAGE program package (version 5.1). Mutation analysis of candidate genes was performed by direct sequencing. RESULTS: Thirteen of the 38 individuals had congenital cataracts. The maximum two point LOD score, 3.5 at theta=0.1 was obtained for the marker D2S325. Mutation analysis of the gamma-crystallin gene cluster identified a C --> A mutation in exon 2 of gamma-D crystallin gene (CRYGD) associated with cataracts in this family. This mutation resulted in a substitution of threonine for proline at amino acid 23 (P23T) of the protein. CONCLUSION: The results suggest that the coralliform cataract phenotype is due to a mutated gamma-D gene, and the sequence change is identical with that recently reported to be related with lamellar cataract, a distinct clinical entity, thus providing evidence that the same genetic defect may be associated with different opacity location. The pathogenesis needs further investigation.

Base Sequence↗

PubMed2004

[Rapid detection of 18-trisomy syndrome using primed in situ labeling technique].

OBJECTIVE: To develop a rapid method for the detection of chromosomes and try to verify the feasibility of using modified primed in situ labeling (PRINS) technique for rapid detection of the interphase nuclei of uncultured amniocytes. METHODS: Chromosome 18 was detected and analyzed by the modified PRINS in 262 amniotic fluid samples. RESULTS: The specific chromosomes were obtained on both metaphase and interphase nuclei. In more than 95% of the samples, PRINS reactions with primer 18cen were successfully induced. Two samples were properly identified and correctly scored as trisomic 18. CONCLUSION: The results suggest that PRINS technique is simple, rapid and cost-effective. It is sensitive, specific, and thus can enhance the accuracy of standard cytogenetic analysis.

Amniocentesis↗

PubMed2004

[First-line Xeloda (Capecitabine) treatment for advanced and recurrent colorectal cancer].

OBJECTIVE: To evaluate the efficacy and safety of capecitabine as first-line therapy in patients with advanced and recurrent colorectal cancer. METHODS: From December 2000 to November 2001, sixty patients with advanced and recurrent colorectal cancer received first-line capecitabine treatment given at a dose of 1250 mg/m(2) twice daily, on days 1 - 14 every 21 days. At least 2 cycles were administered. RESULTS: The overall response rate was 23.3% with 14 PR, 24 SD (40.0%) and 15 PD. The median survival time was 14.7 months. The survival rate was 63.9% at 12-months and 33.4% at 24-months. Grade III-IV adverse effects were diarrhea in 4 patients (6.6%), anemia in 2 (3.3%) and hand-foot syndrome (HFS) in 1 (1.7%); Grade I-II adverse effects were hyperpigmentation in 20 (33.3%), HFS in 18 (30.0%) and diarrhea in 10 (16.7%). CONCLUSION: Capecitabine is an efficacious and better-tolerated alternative treatment for the patients with advanced and recurrent colorectal cancer.

Adult↗

PubMed2004

[Association of drinking water source and colorectal cancer incidence: a prospect cohort study].

BACKGROUND & OBJECTIVE: The pollution of drinking water, for example river and pool, has long been recognized to be associated with an increased risk of colorectal cancer (CRC) in previous epidemiological studies. There is little prospect cohort study with person-years directly on the relative risks of different sources of drinking water for CRC. METHODS: From May 1989 to April 1990, a screening for CRC was carried out among residents aged 30 and over 30 years in 10 villages and towns of Jiashan in China. A total of 64115 residents who participated the screening were classified into 5 cohorts by the source of drinking water and were followed-up for CRC incidence through a tumor reporting system including a rapid reporting system of CRC Registry and for death instance through Death Registration of Jiashan. After 11 years of follow-up, person-years calculated with every cohort member, the incidence densities of CRC with different sources of drinking water were analyzed respectively. Poisson regression was used to control potential confounding variables including demography variables and smoke history and to attain crude and adjusted relative risks based on person-years. RESULTS: A trend was seen toward increasing incidence rates of colorectal cancer from municipal, river, channel, mixed water to well source in turn as shown as 29.61, 32.67, 33.45, 40.87, 58.67 per 100,000 inhabitants, and only the role in risk of well water was marked different from municipal water (P< 0.05). After adjusted the confounding variables by multi-Poisson regression, we found the significant risk of drinking well water for colon cancer, rectal cancer, and colorectal cancer. The relative risks were 1.741 (95%CI 1.001-3.029), 2.228 (95%CI 1.432-3.466), and 2.022 (95%CI 1.432-2.854), respectively. CONCLUSION: Drinking well water long is a risk factor for colorectal cancer in Jiashan, especially for rectal cancer.

Adult↗

PubMed2004

Autosomal dominant coralliform cataract related to a missense mutation of the gammaD-crystallin gene.

BACKGROUND: Congenital cataract is a sight-threatening disease that affects about 1 - 6 cases per 10000 live births and causes 10% - 30% of all blindness in children. About 25% of all cases are due to genetic defects. We identified autosomal dominant congenital coralliform cataracts-related genetic defect in a four-generation Chinese family. METHODS: Complete ophthalmological examinations were performed prior to lens extraction. Lens samples were then studied by electron microscopy. Genomic DNA from family members were examined using whole-genomic linkage analysis, with two-point logarithm of odds (LOD) scores calculated using the Linkage program package (version 5.1). Mutation analysis of candidate genes was performed by direct sequencing. Finally, a three-dimensional protein model was predicted using Swiss-Model (version 2.0). RESULTS: Eleven of the 23 examined individuals had congenital cataracts. Ultrastructure studies revealed crystal deposits in the lens, and granules extensively dispersed in transformed lens fiber cells. The maximum two-point LOD score, 3.5 at theta = 0.1, was obtained for the marker D2S325. Mutation analysis of the gamma-crystallin (CRYG) gene cluster identified a mutation (P23T) in exon 2 of gammaD-crystallin (CRYGD). Protein structure modeling demonstrated that the P23T mutation caused a subtle change on the surface of the gammaD protein. CONCLUSIONS: The results suggest that the coralliform cataract phenotype is due to a mutated CRYGD gene, and that this sequence change is identical to one reported by Santhiya to be related to another distinct clinical condition, lamellar cataract. This study provides evidence that this same genetic defect may be associated with a different phenotype. This is the first report identifying the genetic defect associated with an autosomal dominant congenital coralliform cataract.

Cataract↗

PubMed2004

Clinical and genetic features of International Collaborative Group-hereditary nonpolyposis colorectal cancer families and suspected hereditary nonpolyposis colorectal cancer families.

BACKGROUND: Hereditary nonpolyposis colorectal cancer (HNPPC) is one of the most common genetic syndrome related with mutation of human mismatch repair genes. This study was to evaluate the clinical significance of suspected hereditary nonpolyposis colorectal cancer (sHNPCC) criteria I and the clinical and genetic features of International Collaborative Group-HNPCC (ICG-HNPCC) and sHNPCC families. METHODS: Twenty-nine ICG-HNPCC families fulfilling the Amsterdam criteria and 34 sHNPCC families fulfilling the sHNPCC criteria I were collected. PCR-SSCP and DNA sequencing analysis were employed to screen the germline mutations of the hMLH1 and hMSH2 genes in these families. RESULTS: The ICG group had more colorectal cancer (CRC) patients per family than did the suspected group (P < 0.05). No statistical difference was observed in Lynch classification and familial tumor spectrum. In both groups of families, colorectal cancer was the most frequent malignancy, and carcinomas of the stomach, pancreas and uterus were the three most common extracolonic malignancies. Mutation screening showed that ICG-HNPCC and sHNPCC families had a similar mutation rate (31.0% vs 29.4%, P > 0.05), mutation type, and mutation distribution. Comparison of the families with and without mutation showed no significant difference in CRC patients per family, Lynch classification, and tumor spectrum. CONCLUSIONS: ICG-HNPCC and sHNPCC families that have similar clinical manifestations and genetic basis indicate a similar nature for cancer development. The application of sHNPCC criteria I will facilitate clinical diagnosis and treatment of small families.

Adaptor Proteins, Signal Transducing↗

PubMed2004

[Structural characterization of 5' flanking regulatory region of DNA repair gene Rad51].

OBJECTIVE: To clarify the regulatory elements of Rad51 gene in its 5'flanking region. METHODS: Various constructs were obtained by cloning different DNA fragments into pGL3 reporter vector. These constructs were then introduced into osteosarcoma cell line U2-OS by calcium phosphate method for transient expression of reporter gene, and luciferase activities were measured by luciferase assay. RESULTS: Cells transfected with pGL3 constructs containing fragment -964 to +1430 and -733 to +1430 showed high luciferase activities. Obvious elevation of luciferase activities was also observed in cells transfected with pGL3 constructs containing four shorter derivative fragments -964 to -412, -746 to -412, -651 to -412 and -536 to -412. The highest luciferase activities were measured in transfected cells with plasmids containing fragment -964 to -412, and the lowest were in transfected cells with plasmids containing fragment -536 to -412. Luciferase activities in transfected cells with plasmids containing fragment -651 to -412 were higher than that in transfected cells with plasmids containing fragment -746 to -412. CONCLUSION: It is believable that the basic transcription-promoting element (promoter) for Rad51 gene resides between -536 to -412, and two transcription-enhancing elements (enhancer) or binding sites of positive transcription factors reside between -651 to -536 and -964 to -746, whereas one transcription-inhibiting element (silencer) or binding site of negative transcription factor may reside between -746 to -651.

5' Flanking Region↗

PubMed2004

[Relationship between organochlorine pollution in soil and rice and the incidence of colorectal cancer in Jiashan county, Zhejiang province].

OBJECTIVE: To study the relationship between organochlorine and colorectal cancer. METHODS: With multistage cluster random sampling, 11 towns were drawn based on the standardized incidence of colorectal cancer. Administrative and natural villages were drawn subsequently. Rice and soil samples in the paddy fields were collected in the villages. The contents of organochlorine were detected. Rank correlation analysis was performed together with the data of colorectal cancer incidence. RESULTS: The contents of hexachlorocyclohexane (HCH) and dichlorodiphenyltrichloroethane (DDT) in both rice and soil samples were below the amounts of the country. Statistics showed that the standardized incidence rates were significantly different among the 11 towns. The contents of delta-HCH, gamma-HCH, sodium pentachlorophenate in rice and those of delta-HCH in soil were statistically different among the towns through the rank sum test. The standardized incidence of colorectal cancer was significantly connected with the content of total DDT in rice while rectal cancer with total DDT and PP'-DDE and colon cancer with 1245 of polychlorinated biphenyl (PCBs). The correlation coefficients were 0.636, 0.691, 0.716 and 0.658 respectively (P < 0.05). CONCLUSIONS: Rectal cancer was statistically correlated with organochlorine, mainly for total DDT and dichlorodiphenyldichloroethylene (PP'-DDE). Colon cancer was significantly associated with 1245 of PCBs. Further study should be performed since this research was only an ecological study.

Adult↗

PubMed2004

[Combined detection of CEA mRNA and CK 19 mRNA in peripheral blood cells of patients with lung cancer].

OBJECTIVE: To investigate the expression of CEA mRNA and CK(19) mRNA in peripheral blood cells of patients with lung cancer and evaluate its clinical significance. METHODS: Peripheral blood nucleated cells of 50 patients with lung cancer were studied by RT-PCR to detect the expression of CEA mRNA and CK(19) mRNA. RESULTS: The combined positive rate of CEA mRNA and CK(19) mRNA in patients with lung cancer (82.0%) was significantly higher than that in patients with benign lung diseases (28.0%) and healthy volunteers (8.1%) (P < 0.001). The expression rate had no relation to the clinical staging or histological type. Compared with single detection, combined detection increased the detection rate but did not decrease the specificity. CONCLUSION: Combined detection of CEA mRNA and CK(19) mRNA expression in peripheral blood nucleated cells increase the sensitivity of detecting hematogenous dissemination of cancer cells. Long-term survival analysis and more specimens would be helpful for evaluating its clinical significance.

Adenocarcinoma↗

PubMed2004

[Application of serum protein pattern model in diagnosis of colorectal cancer].

OBJECTIVE: To explore the application of serum protein pattern models in diagnosis of colorectal cancer (CRC) by proteinchip technology. METHODS: One hundred and forty-seven serum samples (55 CRC patients and 92 healthy individuals) randomly divided into training set (n = 87, 32 CRC patients and 55 healthy individuals) and test set (n = 60), were subjected for analysis by surface enhanced laser desorption/ionization-time of flight-mass spectrometry (SELDI-TOF-MS). Four top-scored peaks in 5910, 8930, 4476 and 8817 were detected by proteinchip software version 3.0. and were trained by a multi-layer artificial neural network (ANN) with a back propagation algorithm. An artificial neural network classifier had developed for separating CRC from the healthy group. The classifier was then challenged with the test set (60 samples including 23 CRC patients and 37 healthy individuals) to determine the validity and accuracy of the classification system. RESULTS: The artificial neural network classifier separated the CRC from the healthy samples, with sensitivity of 82.6% and specificity of 91.9%. CONCLUSION: Combination of SELDI-TOF-MS with the artificial neural network yields significant higher sensitivity and specificity than CEA in the diagnosis of CRC, which should be further studied.

Adult↗

PubMed2004

Biological activity of the virulence factor cagA of Helicobacter pylori.

BACKGROUND: China is one of the countries with the highest incidence of H. pylori and more than 9090 isolates possessed the cagA gene. This study was to evaluate the biological activity of the H. pylori virulence factor cagA isolated from Chinese patients. METHODS: cagA DNA fragments were amplified from the genomic DNA and subsequently cloned into the mammalian expression vector for cell transfection and DNA sequencing. cagA protein, phosphorylated-tyrosine cagA and the complex of cagA precipitated with SHP-2 were identified respectively by western blot in the crude cell lysate from conditionally immortalized gastric epithelial cells at 48 hours after transfection with cagA DNA. In addition, the ability of induction of scattering phenotype was examined after transient expression of cagA in AGS cells. RESULTS: The C-terminal half of cagA contained only one repeated sequence and three tandem five-amino-acid motifs glutamic acid-proline-isoleucine-tyrosine-alanine (EPIYA). Moreover, the amino acid sequence of D2 region in repeated sequence was aspartic acid-phenylanaline-aspartic acid (D-F-D) which was significantly distinguished from the three repeated sequences and aspartic acid-aspartic adid-leucine (D-D-L) in the western standard strain NCTC11637. Western blot revealed that cagA became phosphorylated in tyrosine site and bound with SHP-2 after transient expression of cagA DNA in gastric epithelial cells. Transient expression of cagA in AGS cells showed that cagA was able to induce the elongation phenotype although to a lesser extent than western strains. CONCLUSIONS: cagA perturbs cell signaling pathways by binding with SHP-2. However, significant difference exists in amino acid sequence and biological function of cagA in Chinese compared with those of western countries.

Amino Acid Sequence↗

PubMed2004

[Study on effect of berbamine on multidrug resistance leukemia K562/Adr cells].

OBJECTIVE: To study the effect and mechanism of berbamine on the apoptosis of multidrug resistant leukemia K562/Adr cells and in reversing the drug resistance. METHODS: IC50 value of K562/Adr cell was determined with MTT method, cell apoptosis rate was analyzed by flow cytometry with Annexin V FITC-PI assay, with the peak and cell cycle detected by PI staining. At the same time, flow cytometry was also used in determining Caspase-3, P-GP protein expression and drug accumulating capacity in cells, and RT-PCR method was used to analyze the gene expression of mdr-1. RESULTS: Berbamine could inhibit human leukemia K562/Adr cell growth in dose-dependent manner, it could also induce cell apoptosis, increase the protein expression of Caspase-3 and the drug excretion capacity of cells, reduce the mRNA and protein expression levels of mdr-1 gene. CONCLUSION: Berbamine could activate Caspase-3 to induce human leukemia K562/Adr cell apoptosis, and by reducing mdr-1 gene expression to reverse its multidrug resistance.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed2004

[CHL prevent colon neoplasms in mice and its selective inhibition on COX-2].

BACKGROUND & OBJECTIVE: Chlorophyllin (CHL) was proved to have strong anti-inducement effect toward many mutagens and epicarcinogens. This study was to explore effect of CHL in preventing colon neoplasms in mice induced by dimethylhydrazine (DMH), and the selective inhibition on cyclooxygenase 2(COX-2). METHODS: The colorectal neoplasms were induced with DMH in mice and the different dose of CHL were administered in different phases, then the prevention of colorectal neoplasms by CHL was examined; The IC50 and growth curve of HT29 cells were measured with MTT method after treated with CHL; The effect of CHL on the expression of COX-1 mRNA and COX-2 mRNA in HT29 cells were measured with RT-PCR method; The effect of CHL on the expression of COX-2 protein and NF-kappaB protein were measured with western blot and immunohistochemistry methods. RESULTS: The incidence of colon cancer, average tumor amount, and percentage of carcinoma in CHL group were significantly lower than those in DMH group (P< .05); CHL could inhibit the growth of HT29 cells. The effects were dose dependent; CHL could selectively inhibit the expression of COX-2mRNA in HT29 cells,the expression of COX-2 protein in colon neoplasms and HT29 cells, and the expression of NF-kappaB protein in colon neoplasms. CONCLUSIONS: CHL could prevent colon neoplasms in mice induced by DMH and the preventive effect related to selective inhibition on COX-2, furthermore, the inhibition of CHL on COX-2 was realized by inhibiting NF-kappaB protein.

Animals↗