20% improvement in 4/7 primary indices.Sharp declines in several parameters were noticed during 3 to 6 months.Pain in 9 patients disappeared.There was also a statistically significant decrease in TNF ? transcripts in the PBMC.Conclusion Thalidomide is a reasonably promising drug for treating resistant ankylosing spondylitis and its biological mechanism is related to the gene expression suppression of proinflammatory cytokine TNF ?.

Objective To study the macrophage colony-stimulating factor(M-CSF)expression levels of serum and synovial fluids from patients with spondyloarthropathy(SPA)and its contribution to the pathogen- esis of SpA.Methods Eleven SpA synovial tissue samples were compared to those from peripheral blood mononuclear cells(PBMC)of 10 normal subjects using a 1176 gene array.M-CSF was detected in both serum samples and synovial fluids by enzyme linked immunosorbent assay(ELISA).Two groups of AS subjects were tested.The first group consisted of 41 ankylosing spondylitis(AS)patients who had not been treated with bio- logics.The second group consisted of 13 subjects whose serum samples were collected before and 14 weeks af- ter initiation of infliximab.These were compared to serum samples from 28 normal subjects,and synovial fluid samples from 15 SpA patients.Results Expression of M-CSF could be detected in both serum samples and synovial fluids.The concentration of M-CSF in the group of 41 AS patients not treated with biologics correlated with the Bath Ankylosing Spondylitis Disease Activity Index(BASDAI)values(r=0.41,P=0.004).Treatment of infliximab in AS patients led to a significant decrease in the values of BASDAI(P=0.000 07),but no signif- icant change in the serum M-CSF values.Conclusion M-CSF is a promising candidate for research on the mechanisms of SpA and its signaling on pathway in SpA is different from tumor necrosis factor(TNF)-?,and it may provide new basis for developing new anti-biologics for SpA.

BACKGROUNDOur previous studies demonstrated that mutant IkappaBalpha (IkappaBalphaM) inhibited the occurrence, growth and angiogenesis of human glioblastoma multiform (GBM). However, the specific mechanism by which IkappaBalphaM regulates protein-degrading enzymes secreted from GBM to inhibit invasion and metastasis has remained unclear. The aim of the present study was to investigate the regulatory role and significance of IkappaBalphaM genes in the expression of tissue inhibitor of metalloproteinase (TIMP)-2 and matrix metalloproteinase (MMP)-9 in human GBM.

METHODSWe established the following four GBM cell lines stably expressing IkappaBalphaM by plasmid construction, gene transfection and screening for IkappaBalphaM protein expression: mutant IkappaBalpha-transfected cells (G36Delta-M), wild-type IkappaBalpha-transfected cells (G36Delta-W), empty plasmid transfected cells (G36Delta-P) and untransfected cells (G36Delta). The TIMP-2 and MMP-9 expression was detected by RT-PCR and Western blotting. Tumor cells were then implanted subcutaneously into nude mice to establish an animal model of ectopic tumor growth, and TIMP-2 and MMP-9 expression was determined by immunohistochemical methods.

RESULTSThe results showed that there was a significant increase in TIMP-2 expression and a significant decrease in MMP-9 expression in the G36Delta-M group at both the RNA and protein levels compared with the G36Delta-W group, G36Delta-P group and G36Delta group. Similar results were observed in the immunohistochemical staining analysis of tumor tissues. In the G36Delta-M group, TIMP-2 expression was significantly higher while MMP-9 expression was significantly lower than in the other three groups.

CONCLUSIONSOur findings indicate that IkappaBalphaM inhibits the activation of NF-kappaB. It significantly up-regulates TIMP-2 expression in human malignant glioma cells and down-regulates the expression of MMP-9. Thus, IkappaBalphaM maintains the integrity of the extracellular matrix and further inhibits the growth and metastasis of tumor tissues.

Animals ; Blotting, Western ; Cell Line, Tumor ; Glioblastoma ; genetics ; metabolism ; Humans ; I-kappa B Proteins ; genetics ; physiology ; Immunohistochemistry ; Matrix Metalloproteinase 2 ; genetics ; metabolism ; Matrix Metalloproteinase 9 ; genetics ; metabolism ; Mice ; Mice, Nude ; NF-KappaB Inhibitor alpha ; Reverse Transcriptase Polymerase Chain Reaction

OBJECTIVETo investigate the effect of T-cell vaccination in murine experimental autoimmune hepatitis (EAH).

METHODSTo induce the EAH model, the syngeneic S-100 antigen emulsified in complete Freud's adjuvant was injected intraperitoneally to C57Bl/6 at day 1 and day 7. For T-cell vaccination, splenocytes were removed from animal 2 weeks after induction of EAH and from control animals, and activated in vitro by mitogen stimulation with Concanavalin A (Con A), then inactivated by mitomycin and injected at 5 10(7) cells per animal as T-cell vaccination at 14 and 7 days before first induction of EAH.

RESULTSThe histological grade and serum ALT level of the mice who received T-cell vaccination were decrease significantly, compared with that of model group (1.44+/-0.88 vs. 2.33+/-0.87, t=2.24, P<0.05; 63.0U/L+/-23.4U/L vs. 115.0U/L1+/-39.6U/L, t=2.37, P<0.01, respectively); there was no significant change in mice who received irrelevant T-cell vaccination.

CONCLUSIONT-cell vaccination with T cells from EAH animals, but not with irrelevant T cells, was able to protect animals from EAH.

Animals ; Hepatitis, Autoimmune ; prevention & control ; Male ; Mice ; Mice, Inbred C57BL ; T-Lymphocytes ; immunology ; Vaccination

Adult ; Brain Neoplasms ; diagnosis ; secondary ; Female ; Humans ; Lymphomatoid Granulomatosis ; complications ; diagnosis ; Male ; Young Adult

OBJECTIVETo explore the operation indication and safety of presacral tumor.

METHODSClinical data of 36 patients with presacral tumor from November 1990 to May 2006 treated in our hospital, in whom 23 patients underwent trans-sacral operation, were analyzed retrospectively.

RESULTSThe operation time was from 43 to 210 min (average 94 min). The volume of blood loss was from 30 to 2000 ml (average 350 ml). Hospital stay was from 8 to 16 days (average 10.7 days). There were 13 different pathology types of tumors in the 36 patients including 26.4% of malignancy. Complications of trans-sacral operation included 1 case of ureteral damage, 1 case of sacral wound hernia, 1 case of presacral abscess who was healed by sigmoid stoma and wound drainage.

CONCLUSIONTrans-sacral resection of low presacral tumor is safe and effective with less trauma, less bleeding and quick recovery.

Adolescent ; Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Pelvic Neoplasms ; surgery ; Retrospective Studies ; Sacrum ; surgery ; Treatment Outcome ; Young Adult

BACKGROUNDChemotherapy is the most frequently adopted adjuvant therapy of pancreatic ductal adenocarcinoma (PDAC), but the development of drug resistance reduces its effectiveness. Clarification of the mechanism of multidrug resistance (MDR) development in PDAC is needed to improve the therapeutic effect of chemotherapy. This study was aimed to investigate the molecular mechanism of MDR of PDAC and to identify genes associated with MDR development.

METHODSThe gene expression profiles of cell line SW1990 and three drug-selected pancreatic chemoresistant sub-lines, SW1990/5-Fu, SW1990/ADM and SW1990/GEM, were obtained using an oligonucleotide microarray (Affymetrix HG U133 2.0 plus) that contained approximately 38,000 human genes. The microarray results were validated by real-time quantitative polymerase chain reaction and Western blot analysis.

RESULTSThere were 165 genes and expressed sequence tags, some of which have never been linked to drug resistance, that were up- or down-regulated at least 2-fold in all resistant sub-lines when compared with SW1990. According to Gene Ontology annotation, differentially expressed genes related to MDR in pancreatic cancer belong to many functional families and with diverse biological processes. Genes related to antioxidant activity, apoptosis, the cell cycle, signal transduction and intracellular adhesion may undergo epigenetic changes preceding MDR development. A hierarchical clustering was conducted and several interesting clusters were discovered that may be primarily related to cell cycle and developmental regulation. A prediction rule was built from the expression profiles of 117 genes after support vector machine (SVM) analysis, and the prediction result was examined by cytotoxic testing. As a result, a differential gene expression pattern was constructed in multidrug resistant pancreatic cancer cells.

CONCLUSIONSThe findings of this study prove that construction of a chemoresistance prediction rule, based on gene expression patterns, is practical. These data provide new insights into the molecular mechanism of pancreatic cancer MDR development and may be useful for the detection and treatment of MDR in pancreatic cancer patients.

Cell Cycle Proteins ; genetics ; Cell Line, Tumor ; Computational Biology ; Drug Resistance, Multiple ; Drug Resistance, Neoplasm ; Gene Expression Profiling ; Glutathione Peroxidase ; genetics ; Glutathione Transferase ; genetics ; Humans ; Microtubule-Associated Proteins ; genetics ; Oligonucleotide Array Sequence Analysis ; methods ; Pancreatic Neoplasms ; drug therapy ; genetics ; Tankyrases ; genetics

Adult ; Aged ; Female ; Humans ; Magnetic Resonance Imaging ; Male ; Meningeal Neoplasms ; pathology ; surgery ; Meningioma ; pathology ; surgery ; Middle Aged ; Postoperative Care ; methods ; Tomography, X-Ray Computed ; Treatment Outcome

Insulin-like growth factor binding-protein-7 (IGFBP7) was obtained from our previous colonic adenocarcinoma (CRC) and normal mucosa suppression subtraction hybridization (SSH) cDNA libraries. By RT-PCR and immunohistochemistry, we found that IGFBP7 was overexpressed in CRC tissue compared to normal tissue. However, our in vitro experiments performed in 10 CRC cell lines showed that IGFBP7 expressed only in SW480 and Caco2 cell lines, which implied an underlying reversible regulatory mechanism. Using methylation-specific PCR (MSP) and bisulfite sodium PCR (BSP), we found that its expression was associated with DNA hypomethylation of exon1. This was further supported by the in vitro study which showed restored IGFBP7 expression after demethylation agent 5-aza-2'-deoxycytidine treatment. Correlation analysis between IGFBP7 expression and prognosis indicated that overexpression of IGFBP7 in CRC tissue correlated with favourable survival. Investigation of the functional role of IGFBP7 through transfection studies showed that IGFBP7 protein could inhibit growth rate, decrease colony formation activity, and induce apoptosis in RKO and SW620 cells, suggesting it a potential tumor suppressor protein in colorectal carcinogenesis. In conclusion, our study clearly demonstrated that IGFBP7 plays a potential tumor suppressor role against colorectal carcinogenesis and its expression is associated with DNA hypomethylation of exon 1.
Adenocarcinoma ; genetics ; metabolism ; Apoptosis ; genetics ; Cell Line, Tumor ; Colorectal Neoplasms ; genetics ; metabolism ; DNA Methylation ; Exons ; Gene Expression Regulation, Neoplastic ; genetics ; Humans ; Insulin-Like Growth Factor Binding Proteins ; genetics ; metabolism ; Transfection ; Tumor Suppressor Proteins ; genetics ; metabolism

OBJECTIVETo study the prevalence of hepatitis C virus (HCV) infection and characteristics on molecular biology related to HCV among patients who were enrolled in a Methadone maintenance clinic in Wuhan.

METHODSSerum samples from 332 injection drug users (IDUs) were obtained and anti-HCV IgG was detected by enzyme linked immunosorbrent assay(ELISA), together with 86 anti-HCV positive specimens genotyped. A reverse transcriptase-polymerase chain reaction (RT-nPCR) assay using conserved primers deduced from the core-envelopel (C-E1) region of the HCV genome was employed to amplify a 474 bp fragment. Phylogenetic analysis of the C-E1 sequences was conducted by direct sequencing of the RT-nPCR products and alignment with determined by nucleotide sequencing followed by composition of a phylogenetic tree.

RESULTSThere were 313 cases (94.3%) appeared positive anti-HCV IgG in the 332 patients from a Methadone maintenance clinic in Wuhan. It was demonstrated that there were four different subtypes of HCV in that clinic in Wuhan, including 6a--71 cases (82.5%), 3b--7 cases (8.2%), 1a--5 cases (5.8%) and 1b--3 cases (3.5%).

CONCLUSIONInfection of 6a genotype HCV was predominant in patients from the Methadone maintenance clinic in Wuhan, followed by HCV 3b, 1a and 1b.

Adult ; Antibodies, Viral ; analysis ; China ; Enzyme-Linked Immunosorbent Assay ; Female ; Genotype ; Hepacivirus ; classification ; genetics ; Humans ; Male ; Methadone ; therapeutic use ; Middle Aged ; Phylogeny ; Reverse Transcriptase Polymerase Chain Reaction ; Substance Abuse Treatment Centers ; Substance-Related Disorders ; drug therapy ; rehabilitation ; Young Adult