Objective To investigate the mechanisms of inhibitory effect of Erlotinib,an epidermal growth factor(VEGF) receptor inhibitor,on angiogenesis of pancreatic carncer.Methods①In a tube formation assay,Erlotinib(100?mol/L) was applied to the culture media and compared to the serum free media.The expression of vascular endothelial growth factor(VEGF) in BxPC-3 cells treated with Erlo- tinib at different concentrations(5,50,100,200?mol/L) was determined by RT-PCR.②The xeno grafts derived from BxPC 3 cancer cells were inoculated into the BALB/C nude mice.The mice were treated with either Erlotinib(100 mg/kg of Erlotinib oral lavage daily) or saline for four weeks.The vol- ume of the xenografts was measured and the tumor growth rate was calculated.The microvessel density (MVD) of tumor tissue was determined by immunohistochemistry with an antibody against factorⅧ. Results There were less endothelium cells and close hollow tubular structures in grlotinib treated group compared to the control group in the tube formation assay.The mean weight of xenografts in Erlotinib treated group[(0.397?0.550)g] was significantly lower than that in the control group[(1.570?1.060)g] with a inhibitary rate of 74.5%.The expression of VEGF mRNA in Ertotinib treated groups (=50?mol/L) were decreased comparing to the control group.The VEGF expression in xeno- grafts tumor tissues was also markedly down-regulated.The MVI) was significantly decreased in Erlotinib treated group( 1.86?0.43)than that in the control group (5.98?1.27,P

OBJECTIVETo investigate the influence of hepatitis C virus (HCV) serotype on the interferon (IFN) treatment of patients with chronic hepatitis C.

METHODSNinety-eight patients with chronic hepatitis C were divided into two groups: patients in group 1 (n=53) were treated with Pegasys, 180 ug injected subcutaneously once a week for 24 weeks, and those in group 2 (n=45) were injected with Roferon-A 3 MU three times a week for 24 weeks and then patients in both groups were followed up for another 24 weeks. The virological response at the end of follow up was the primary endpoint for evaluating the effects of IFN treatment. The HCV RNA levels of the chronic hepatitis C patients were determined with COBAS AMPLICOR MONITOR Test, version 2.0, and the HCV serotypes were examined by the means of ELISA using Murex HCV Serotyping 1-6 Assay.

RESULTSOf the 98 cases, HCV in 44 cases was serotype 1, in 23 was serotype 2, in 10 was serotype 3, in 1 was serotype 4, 1 was serotype 5 and in 2 was serotype 6; HCV serotypes in the remaining 17 patients could not determined. In Pegasys treatment group, the biochemical and virological response was not significantly different at the end of treatment between the patients with serotype 1 and non serotype 1 or serotype undetermined patients, but the sustained virological response rate of HCV serotype undetermined group (66.7 percent) was significantly higher than that of serotype 1 patients (27.3 percent) (p=0.035). In Roferon-A treatment group, the virological response rate at 24 weeks and sustained viral response rate at the end of follow-up was not significantly different between serotype 1 and non serotype 1 patients or serotype undetermined patients.

CONCLUSIONAfter the six months treatment course, the HCV serotype had some effects on the treatment response to Pegasys treatment for chronic hepatitic C.

Adult ; Antiviral Agents ; administration & dosage ; Drug Administration Schedule ; Female ; Hepacivirus ; drug effects ; immunology ; Hepatitis C Antibodies ; blood ; Hepatitis C, Chronic ; drug therapy ; immunology ; Humans ; Interferons ; administration & dosage ; Male ; Middle Aged ; Young Adult

Aged ; Female ; Humans ; Male ; Middle Aged ; Multiple Myeloma ; diagnosis ; immunology ; Prognosis ; T-Lymphocyte Subsets ; immunology

OBJECTIVETo investigate the relationship of hepatitis C virus (HCV) serotype with genotype.

METHODSThe serotypes of HCV in the serum of 104 patients with chronic hepatitis C from 14 cities in China for which HCV genotypes were available, were determined by ELISA using Murex HCV Serotyping 1-6 Assay.

RESULTSThe serotypes of 86 (82.69 percent) of the 104 serum specimens were determined, and HCV serotypes were determined for 91 strains. Overall the concordance between hepatitis C virus serotype and genotype was 62.1 percent, and the concordance of serotype, with genotypes 1, 2 and 3 were 69.4 percent, 51.2 percent and 70.0 percent, respectively. The false-negative rate and concordance of genotype 2b was lower (54.5 percent).

CONCLUSIONThe specificity of HCV serotyping was affected by HCV strains' genotype and sometimes HCV serotype was not in concordance with genotype.

Genotype ; Hepacivirus ; classification ; Hepatitis C, Chronic ; virology ; Humans ; Serotyping

OBJECTIVETo generate a gene delivery plasmid carrying the dominant negative form of the protein phosphatase 2A catalytic subunit a (DN-PP2Aca) driven by a hepatocellular carcinoma (HCC) tissue-specific promoter and investigate its ability to inhibit growth of cultured hepatoma cells.

METHODSThe gene delivery plasmid was constructed by PCR-amplifying DN-PP2Aca from wild-type PP2Aca using site-directed mutagenesis and then ligating the sequence-verified amplicon downstream of an alpha-fetoprotein enhancer and phosphoglycerate kinase promoter (AFpg) in the luciferase reporter vector pGL3-Basic. Following transfection into two AFP+ hepatoma cell lines (HepG2 and HepG3) and two AFP- hepatoma cell lines (SK-HEP-1 and L02), the transcriptional activity of the AFpg-driven DN-PP2Aca plasmid was tested using luciferase reporter gene assay and western blotting. The effect on cell growth was tested using MTT assay. Between group differences were assessed by t-test.

RESULTSThe AFpg-driven DN-PP2Aca plasmid showed high transcriptional activity and protein expression in both HepG2 and Hep3B cells. At 72 h after transfection, the proliferation capacities were repressed by 42.65%+/-3.99% (P = 0.0002) and 39.87%+/-3.91% (P = 0.0002) in AFP+ HepG2 and Hep3B cells, respectively (vs. untransfected). In contrast, the plasmid was transcriptionally inactive in and had no effect on proliferation of AFP- cells.

CONCLUSIONThe AFpg-driven DN-PP2Aca plasmid exhibits selective cytotoxicity against AFP+ hepatoma cells, and may represent a useful gene therapy strategy to treat HCC.

Carcinoma, Hepatocellular ; genetics ; metabolism ; Enhancer Elements, Genetic ; Genetic Therapy ; Genetic Vectors ; Hep G2 Cells ; Humans ; Liver Neoplasms ; genetics ; metabolism ; Mutation ; Promoter Regions, Genetic ; Protein Phosphatase 2 ; genetics ; alpha-Fetoproteins ; genetics

OBJECTIVETo evaluate whether the rapid viral response (RVR) to combinational therapy with interferon and rabavirin can be used to predict the sustained viral response (SVR) in chronic hepatitis C patients.

METHODSAccording to their clinical characteristics, all patients in this study were given pegylated or conventional interferon injection and different dose of ribavirin according to their weight. Patients were injected Pegasys (pegierferon alpha-2a) 180 microg or 135 microg once a week, or pegyintron 50-80 microg once a week, or conventional interferon 3-5 MU every two days, in combination with a dose of 600-1500 mg/d ribavirin. The serum HCV RNA load was determined at 0, 4, 12 week, and then every 12 weeks. After the viral response obtained, the patients were treated for another 24-72 weeks and followed up 24 weeks. The main parameter to evaluate the efficacy was SVR rate. The influence factors associated with rapid viral response were investigated.

RESULTSRVR was obtained at week 4 in 84.2% of the 120 patients. The HCV RNA baseline of RVR group was (5.883+/-1.246) lg copies/ml, which was significantly lower than that of the group without RVR [(6.502+/-0.693) lg copies/ml, t=2.15, P=0.034]. 97 patients with RVR who finished treatment and follow-up, 90.7% of these patients obtained SVR, but the SVR rate in patients (82.4%) without RVR was lower than that in patients with RVR (x2=0.371, P=0.543). In this study, RVR rate was not associated with HCV genotype and the dose of interferon used. In the naive patients, the RVR to pegylated interferon was 87.8%, which was significantly higher than that in retreat patients (x2=4.651, P=0.031).

CONCLUSIONHigh RVR rate could be obtained in chronic hepatitis C patients treated combined with interferon and ribavirin. RVR rate is associated with the HCV RNA baseline load in both naive and retreat patients but not correlated to HCV genotype. RVR could predict the SVR.

Administration, Cutaneous ; Adolescent ; Adult ; Aged ; Antiviral Agents ; administration & dosage ; therapeutic use ; Child ; Drug Therapy, Combination ; Female ; Genotype ; Hepacivirus ; drug effects ; genetics ; Hepatitis C, Chronic ; blood ; drug therapy ; pathology ; Humans ; Interferon-alpha ; administration & dosage ; therapeutic use ; Male ; Middle Aged ; Polyethylene Glycols ; administration & dosage ; therapeutic use ; Predictive Value of Tests ; RNA, Viral ; blood ; Recombinant Proteins ; Recurrence ; Ribavirin ; administration & dosage ; therapeutic use ; Time Factors ; Treatment Outcome ; Viral Load ; Young Adult

OBJECTIVETo investigate the effect of Deferasirox on the micro-angiogenesis in narrow pedicle flap through Epithelial-Mesenchymal Transition.

METHODS32 male rats were randomly divided into group I and II which were subdivided into Ia and Ib, IIa and IIb, 8 rats in each group. The rats were administrated intragastrically for 7 days with Deferasirox 100 mg/kg in group Ia and IIa, with the same dose of N. S. in group Ib and IIb. After that, narrow pedicle flaps were formed on the rats back. In group I, the subcutaneous vascular network was observed intraoperatively. The flap survival rate was recorded. In group II , specimens were collected at the distal end of flaps 3 days after operation. IHC and Western Blot were done to examine the expression of CD34, E-cadherin, Vimentin. The microvessel density was also calculated.

RESULTSThe subcutaneous micro-angiogenesis in group Ia was more exuberant than that in group Ib. The narrow pedicle flaps in group Ia survived completely, while the survival rate was 62.5% in group Ib (P < 0.05). The percentage of flap survival area for Ia and Ib was (100 +/- 0.00) % and (84.06 +/- 4.42)% (P < 0.05). The expression of E-cadherin in IIa was lower than that in IIb, while the expression of Vimentin and CD34 were higher in IIa, showing statistically difference (P < 0.05).

CONCLUSIONDeferasirox can improve the flap micro-angiogenesis through inducing epithelial-mesenchymal transition, so as to improve the survival rate of narrow pedicle flap.

Animals ; Benzoates ; pharmacology ; Epithelial-Mesenchymal Transition ; drug effects ; Male ; Rats ; Rats, Sprague-Dawley ; Surgical Flaps ; blood supply ; Triazoles ; pharmacology

Objective To learn the current situation of knowledge,attitude and practice (KAP)about tuberculosis prevention and treatment among close contacts of tuberculosis patients in Yangzhou City and to explore the influencing factors and relationship of KAP.Methods A total of 460 TB(tuberculosis)patients'families in Yangzhou were randomly selected by means of cluster random sampling.And 746 close contacts of tuberculosis patients were investigated by face - to - face interview.Their basic information,knowledge ,belief and behavior of TB were analyzed by descriptive analysis and multivariable logistic regression analysis.Results The overall awareness rate of tuberculosis prevention and control was 58.30% ,and the rate of positive belief was 50.19%,and the behavior holding rate was 59.25%.The multivariable logistic regression analysis showed that diagnostic types,degree of education and location were the major influencing factors. Conclusion Close contacts with low education level and with smear positive patients in the family should be paid more attention.

Adult ; Antiviral Agents ; therapeutic use ; Female ; Hepatitis C, Chronic ; drug therapy ; Humans ; Interferon-alpha ; therapeutic use ; Male ; Polyethylene Glycols ; therapeutic use ; Recombinant Proteins

To investigate the relationship between the single nucleotide polymorphism (SNPs) of the bcr and abl gene and chronic myelogeous leukemia (CML), the 9 sequence-tagged sites (STS) in bcr and abl gene were screened by DNA pooling and denaturing high performance liquid chromatography (dHPLC), and the results were varified by sequencing. The results showed that the polymorphism sites were detected in 4 out of the 9 STS fragments and there were 3 bases different from the reference sequence found in 3 fragments. In conclusion, the novel SNP in U07000 fragment shows significantly different frequencies between CML and controled people.
Chromatography, High Pressure Liquid ; methods ; Fusion Proteins, bcr-abl ; genetics ; Genes, abl ; genetics ; Humans ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive ; genetics ; Polymorphism, Single Nucleotide ; Proto-Oncogene Proteins c-bcr ; genetics ; Sequence Analysis, DNA ; Sequence Tagged Sites