Biomedical subjects

Qin Ouyang

Publications and source records attributed to Qin Ouyang.

At least 19 recordsLinked to original sources

PubMed2026

Increased expression of Ribonucleic acid export 1 (RAE1) gene promotes gastric carcinogenesis and is associated with Hippo signaling pathway.

BACKGROUND: Ribonucleic acid export 1 (RAE1) autoantibody may have good potential for early detection of gastric cancer (GC). However, the carcinogenicity of RAE1 in GC remains unknown. We aimed to explore the role and the potential mechanism for RAE1 in the carcinogenesis of GC. METHODS: Immunohistochemical assay was applied to analyze the expression of RAE1 in GC and precancerous lesion (PL) tissues and its relationship with clinical characteristics. The effects of RAE1 on proliferation, migration, apoptosis, and cell cycle were explored by constructing RAE1 knockdown and overexpression in GC cells. The effects of RAE1 knockdown on tumor growth were observed in a murine xenograft model. The signaling pathways involved in GC development that may be affected by RAE1 were investigated by transcriptome sequencing and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. RESULTS: Immunohistochemical expression of RAE1 was significantly higher in early GC patients than in PL and normal tissues, and the RAE1 expression was correlated with clinical stage (P<0.001). In vitro, knockdown of RAE1 inhibited the proliferation and migration of GC cells with promoted apoptosis and arrested cell cycle in the S phase, while overexpression of RAE1 showed the opposite trend. In vivo, knockdown of RAE1 inhibited the growth of subcutaneous graft tumors in mice. Transcriptome sequencing and subsequent analysis of RAE1 knockdown cells revealed that the Hippo signaling pathway was activated by RAE1 knockdown. CONCLUSIONS: RAE1 promotes GC cells proliferation and migration and is associated with the inhibition of the Hippo signaling pathway, and may be a potential biomarker for early diagnosis and treatment of GC.

Gastric cancer (GC)↗

PubMed2006

Management consensus of inflammatory bowel disease for the Asia-Pacific region.

At the present there are no large-scale epidemiologic data on inflammatory bowel disease (IBD) in the Asia-Pacific region, but several studies have shown an increased incidence and prevalence of IBD in this region. Compared to the West, there appears to exist a time lag phenomenon. With regard to the two main forms of IBD, ulcerative colitis (UC) is more prevalent than Crohn's disease (CD). In addition to geographic differences, ethnic differences have been observed in the multiracial Asian countries. Moreover, the genetic backgrounds are different in the Asian compared to Western patients. For instance, NOD2/CARD15 variants have not been found in Asian CD patients. In general, the clinical course of IBD seems to be less severe in the Asia-Pacific region than in Western countries. Diagnosis of IBD in this region poses special problems. The lack of a gold standard for the diagnosis of IBD, and the existence of a variety of infectious enterocolitis with similar manifestations to those of IBD make the differential diagnosis particularly difficult. So far, Western diagnostic criteria have been introduced for the diagnosis of IBD. A stepwise approach to exclude non-IBD enterocolitis also must be introduced, and a definite diagnosis must include typical histological features. In some patients, follow up and therapeutic trials might be necessary to obtain a definitive diagnosis. A better understanding of the pathogenesis of IBD will allow the development of better diagnostic markers. The management of IBD also poses some special problems in the Asia-Pacific Region. There is often a delay in using proper medications for IBD, and alternative local remedies are still widely used. With a combination of Western guidelines and regional experiences, similar principles can be used for induction and maintenance of remission. A stepwise selection of medications is advocated depending on the extent, activity and severity of the disease. Comprehensive and individualized approaches are suggested for different IBD patients. Deeper understanding of disease pathogenesis and the unique characteristics of IBD in the Asia-Pacific region, combined with reasonable and practical guidelines for drug management and the future use of biological agents would improve the therapeutic outlook of IBD in this region.

Anti-Inflammatory Agents↗

PubMed2006

Combined histology and molecular biology for diagnosis of early stage gastric MALT lymphoma.

OBJECTIVE: To establish a sequential diagnostic procedure of gastric mucosa-associated lymphoid tissue (MALT) lymphoma and provide evidence for selected optimal cases to be treated in the early stage. METHODS: Thirty-one cases of gastric lymphoid hyperplasia (GLH) were selected and multiple investigations including histology, protein level, DNA and chromosome levels, combined with clinical follow-up were performed. Histological grade was according to Isaacson's criteria of GLH; CD20, UCHL-1 (CD45RO), anti-kappa (kappa), anti-lambda (lambda) and Ki-67 were used for immunohistochemical staining; semi-nested polymerase chain reaction (PCR) was used to detect IgH gene rearrangement and reverse-transcription PCR (RT-PCR) was used to detect API2-MALT1 fusion of the chromosome translocation t(11;18)(q21;q21). Twenty-nine cases underwent eradication therapy for Helicobacter pylori. Changes in histological grade, endoscopic appearance, expression of Ki-67 and IgH gene rearrangement were compared after eradication treatment. RESULTS: Of the 31 cases of GLH with predominant chronic gastritis and gastric ulcer most were histological grade 2 and 3. Only one case had lambda light chain restriction and 10 cases had monoclonal IgH gene rearrangement. Expression of Ki-67 and monoclonal IgH gene rearrangement were significantly increased with increased lymphoid hyperplasia (P < 0.05). Two cases had API2-MALT1 fusion. Helicobacter pylori was eradicated in 25 cases and another course of treatment had to be given in 4 cases. All cases were followed up for 1.5-37 months. Of the 27 successful eradication cases, 18 showed complete regression both histologically and endoscopically, 4 had partial regression and 7 were unchanged. CONCLUSIONS: A sequential diagnostic procedure based on histology, expression of Ki-67 combined with clonality of IgH rearrangement and API2-MALT1 fusion helps to diagnosis of early stage gastric MALT lymphoma and choose the best treatment strategy.

Adolescent↗

PubMed2006

Recognition of HLA class I-restricted beta-cell epitopes in type 1 diabetes.

Type 1 diabetes results from the autoimmune destruction of insulin-producing pancreatic beta-cells by cytotoxic T-lymphocytes (CTLs). In humans, few beta-cell epitopes have been reported, thereby limiting the study of beta-cell-specific CTLs in type 1 diabetes. To identify additional epitopes, HLA class I peptide affinity algorithms were used to identify a panel of peptides derived from the beta-cell proteins islet amyloid polypeptide (IAPP), islet-specific glucose-6-phosphatase catalytic subunit-related protein (IGRP), insulin, insulinoma-associated antigen 2 (IA-2), and phogrin that were predicted to bind HLA-A*0201. Peripheral blood mononuclear cells from 24 HLA-A*0201 recent-onset type 1 diabetic patients and 11 nondiabetic control subjects were evaluated for gamma-interferon secretion in response to peptide stimulation in enzyme-linked immunospot assays. We identified peptides IAPP9-17, IGRP215-223, IGRP152-160, islet IA-2(172-180), and IA-2(482-490) as novel HLA-A*0201-restricted T-cell epitopes in type 1 diabetic patients. Interestingly, we observed a strong inverse correlation between the binding affinity of beta-cell peptides to HLA-A*0201 and CTL responses against those peptides in recent-onset type 1 diabetic patients. In addition, we found that self-reactive CTLs with specificity for an insulin peptide are frequently present in healthy individuals. These data suggest that many beta-cell epitopes are recognized by CTLs in recent-onset type 1 diabetic patients. These epitopes may be important in the pathogenesis of type 1 diabetes.

Amino Acid Sequence↗

PubMed2006

Identification of Novel HLA-A*0201-restricted epitopes in recent-onset type 1 diabetic subjects and antibody-positive relatives.

Cytotoxic T-lymphocytes (CTLs) are considered to be essential for beta-cell destruction in type 1 diabetes. However, few islet-associated peptides have been demonstrated to activate autoreactive CTLs from type 1 diabetic subjects. In an effort to identify novel epitopes, we used matrix-assisted algorithms to predict peptides of glial fibrillary acidic protein (GFAP), prepro-islet amyloid polypeptide (ppIAPP), and islet-specific glucose-6-phosphatase catalytic subunit-related protein (IGRP) that likely bind to HLA-A*0201 with a strong affinity and contain a COOH-terminal proteasomal cleavage site. Seven peptides stabilized HLA-A*0201 expression in binding assays and were used to stimulate peripheral blood mononuclear cells and were evaluated for granzyme B secretion. We found that 5 of 13 type 1 diabetic subjects and 4 of 6 antibody-positive relatives exhibited greater numbers of granzyme B-secreting cells in response to at least one putative epitope compared with healthy control subjects. The most prevalent responses in antibody-positive and type 1 diabetic subjects were to ppIAPP(9-17). Other peptides recognized by type 1 diabetic or antibody-positive subjects included GFAP(143-151), IGRP(152-160), and GFAP(214-222). These data implicate peptides of ppIAPP, GFAP, and IGRP as CTL epitopes for a heterogenous CD8(+) T-cell response in type 1 subjects and antibody-positive relatives.

Adolescent↗

PubMed2006

[Effects of selective and non-selective cyclooxygenase-2 inhibitor on the growth of colon cancer cells].

OBJECTIVE: To evaluate the effects of selective and non-selective cyclooxygenase-2 on the growth and apoptosis of colon cancer cell lines in vitro. METHODS: The proliferation of colon cancer cells was determined by MTT assay, and the cell cycle progression was analyzed by flow cytometric assay. Annexin V/PI staining in combination with flow cytometric assay was used to detect apoptosis induced by NSAIDs. RESULTS: It was found that celecoxib, meloxicam and aspirin could inhibit the growth of HT-29 or SW480 cell and showed a concentration dependent pattern. COX-2 protein was expressed in HT-29 and LS174-T, but not in SW480 cells. In addition, PCNA levels in both HT-29 cell and SW480 cells were reduced by aspirin and celecoxib. Both aspirin (10 mmol/ L) and celecoxib (50 micromol/L) induced apoptosis of HT-29 and SW480 colon cancer cells, the apoptosis rates were 4.8%, 17.7% and 5.1%, 20.4% respectively. CONCLUSION: Both COX-2 selective and non-selective inhibitors can potentially inhibit the growth of colon cell lines and such inhibitory effect on COX-2 negative colon cancer cells is also evident.

Apoptosis↗

PubMed2006

[A clinical trial of rosiglitazone and 5-aminosalicylate combination for ulcerative colitis].

OBJECTIVE: To investigate the therapeutic effects of the combination of rosiglitazone, which is peroxisome proliferators-activated receptor gamma (PPARgamma) ligands used to treat type 2 diabetes mellitus, and aminosalicylate on mildly or moderately active ulcerative colitis and on relevant cytokine expressions. METHODS: According to the national guideline of China for diagnosis and treatment of the inflammatory bowel disease (IBD), 42 patients with mild, moderately active ulcerative colitis were selected from the outpatient clinic of West China Hospital from July to November, 2004. Patients with infectious colitis, amoebiasis, or cardiac, renal or hepatic failure were excluded, as well as those who had received corticosteroid or immunosuppressant treatment within the last month. Following a quasi-randomization principle, patients were allocated alternatively into the treatment group with rosiglitazone 4 mg/d plus 5-aminosalicylic acid (5-ASA) 2 g/d or sulfasalazine 3 g/d and the control group with 5-ASA or sulfasalazine alone for 4 weeks. Clinical and histological changes were evaluated weekly by the Mayo scoring system for assessment of the activity of ulcerative colitis and the Truelove-Richards' grading system, respectively. PPARgamma and nuclear factor (NF)-kappaB p65 expressions in colonic mucosa were investigated before and after the treatment. RESULTS: Mayo scores decreased 4.01 in treatment group and 3.48 in control group respectively, with a remission rate 71.4% in treatment group and 57.1% in control group respectively. Along with the improvement of the Mayo score, the histological grade improvement was more significant in treatment group than in control group (P < 0.05). PPARgamma expression was higher, and NF-kappaB p65 positive rate was lower in treatment group than in control group after the treatment, and there was a good negative correlation between PPARgamma and NF-kappaB. CONCLUSIONS: Combined treatment with rosiglitazone and 5-ASA achieved better therapeutic effect than 5-ASA alone without any side effects. The PPARgamma expression was lower in active ulcerative colitis. Rosiglitazone alleviate colonic inflammation probably the through blockade of NF-kappaB, which can be a novel approach to the ulcerative colitis treatment.

Adolescent↗

PubMed2005

Features of intestinal T-cell lymphomas in Chinese population without evidence of celiac disease and their close association with Epstein-Barr virus infection.

BACKGROUND: Intestinal T-cell lymphoma (ITCL) is a heterogeneous lymphoid neoplastic group with variable clinical and pathological features. ITCL in oriental countries is different from enteropathy-type intestinal T-cell lymphoma (ETCL) in relation to celiac disease and Epstein-Barr virus (EBV). The objective of this study was to investigate the clinicopathological features, immunophenotype, expression of cytotoxic molecule (TIA-1), T-cell receptor (TCR)-gamma gene rearrangement, and Epstein-Barr virus (EBV) latent infection in primary ITCL without celiac disease in Chinese. METHODS: The clinical data of 42 patients were analyzed, and the patients were followed up. Compared with human reactive lymphoid tissues, in situ hybridization for EBER1/2, polymerase chain reaction for TCR-gamma gene rearrangement, and immunohistochemical staining for immunophenotypes, TIA-1 and EBV latent membrane proteins (LMP-1) were investigated. Survival curves of different clinicopathological features, immuno-phenotypes, expression of LMP1, TCR-gamma gene rearrangement and therapy were analyzed. RESULTS: Three fourths of the patients suffered from ITCL in China were men with a peak age incidence in the 4th decade. Common presenting features included fever and hemotochezia. The prognosis was poor with a median survival of 3.0 months. The lesions were mostly localized in the ileocecum and colon. About 38/42 (90.5%) patients demonstrated pleomorphic medium-sized on large cells. Histological features of celiac disease were rarely seen. All 42 patients with ITCL revealed CD45RO positive. Neoplastic cells partially expressed T-cell differentiated antigens (CD3epsilon, CD4, CD8) and NK cell associated antigen (CD56). The positive frequency of CD3epsilon, CD4, CD8 and CD56 was 28/42 (66.7%), 7/42 (16.7%), 10/42 (23.8%) and 12/42 (28.6%) respectively. Thirty-nine cells (92.9%) expressed TIA-1, but none expressed CD20 and CD68. More than half of the patients (64.3%, 64.3% and 59.5%) revealed TCR-gamma gene rearrangement by three different TCR-gamma primers respectively. EBER1/2 was detected in 41 (97.6%) of the 42 patients. The expression frequency of LMP-1 was 38.1% (16/42). CONCLUSIONS: Primary ITCL without celiac disease in Chinese is a special highly EBV-associated clinicopathological entity. There are few similarities in patients with celiac disease in western countries. A small proportion of primary ITCLs in Chinese and extranodal NK/T-cell lymphoma of nasal type belong to the same spectrum.

Adolescent↗

PubMed2005

Identification and functional characterization of 2 variant alleles of the telomerase RNA template gene (TERC) in a patient with dyskeratosis congenita.

Heterozygous mutations of the human telomerase RNA template gene (TERC) have been described in patients with acquired aplastic anemia and the autosomal dominant form of dyskeratosis congenita (DKC). Patients with mutations in both TERC alleles have not yet been reported. Here, we report a patient with DKC who inherited 2 distinct TERC sequence variants from her parents; a deletion (216_229del) in one and a point mutation (37A>G) in the other allele of the TERC gene. Her marrow was hypocellular and showed an abnormal clone [46, XX t(7;21)(q34;q22)]. The telomere lengths in leukocytes of the patient and her relatives were shorter than those of the age-matched controls and were progressively shorter in subsequent generations of family members with the 216_229del allele. Telomerase enzymatic levels in lymphocytes from the patient were approximately half of those measured in healthy controls. The 216_229del mutation failed to reconstitute telomerase activity in transfected cells, but, when coexpressed with the 37A>G variant, telomerase activity was only modestly suppressed. These clinical and laboratory findings support the concept that telomerase levels in human hematopoietic stem cells are tightly controlled as even moderately reduced levels result in accelerated telomere shortening and eventual marrow failure.

Adolescent↗

PubMed2005

Significance of glucocorticoid receptor expression in colonic mucosal cells of patients with ulcerative colitis.

AIM: Glucocorticoid (GC) resistant ulcerative colitis (UC) remains a serious disease and is difficult to manage. Although the molecular basis of GC insensitivity is still unknown, GC receptors (GRalpha and GRbeta) may play an important role in it. This study was aimed to investigate the relationship between the expression of GRalpha and GRbeta in colonic mucosal cells of patients with UC, the efficacy of GC therapy and the intensity of inflammation. METHODS: Twenty-five cases of UC were classified into: GC sensitive (n = 16) and GC resistant (n = 9) cases. Patients consisted of mild (n = 6), moderate (n = 8) and severe (n = 11) cases. GRalpha and GRbeta expression in colonic mucosal specimens were investigated by immunohistochemistry, and compared between GC resistant and sensitive groups, and also among various degrees of inflammation. RESULTS: All cases were positive for GRalpha and GRbeta expression. Both positive association between GRalpha expression and the response of UC to GC and strong negative association between GRbeta expression and the response of UC to GC were identified. There was no significant association between GRalpha/GRbeta expression and the degree of inflammation of UC. CONCLUSION: These findings suggest that both GRalpha and GRbeta may play an important role in the action of GC, and that GRbeta functions as a dominant negative inhibitor of GRalpha. Expression of GRalpha and GRbeta in colonic mucosal cells of patients with UC may serve as predictors of glucocorticoid response, but can not function as markers of inflammatory intensity.

Adolescent↗

PubMed2005

Diallyl trisulfide inhibits tumor necrosis factor-alpha expression in inflammed mucosa of ulcerative colitis.

The present study aimed to investigate the effect of diallyl trisulfide (DATS) on tumor necrosis factor (TNF)-alpha expression in inflammed mucosa of ulcerative colitis and its possible mechanism. Colonic biopsies from ulcerative colitis were treated with 0, 1, 5, and 10 microM DATS for 24 hr. Lactate dehydrogenase (LDH) activities and concentrations of TNF-alpha in supernatants were measured. mRNA expressions of TNF-alpha in biopsies were analyzed by RT-PCR. The expression of NF-kappaB P65 in tissues was studied by immunohistochemistry. Concentrations of TNF-alpha in supernatants of biopsies treated with 5 and 10 microM DATS were lower than those of untreated biopsies. There were fewer lamina propria mononuclear cells whose NF-kappaB P65 expression in nuclei was positive, and less mRNA expression of TNF-alpha in biopsies treated with 10 microM DATS than in untreated biopsies. There were no differences in LDH activities in supernatants between tissues treated with DATS and untreated tissues. DATS could downregulate TNF-alpha production and inhibit NF-kappaB activation in lamina propria mononuclear cells of inflammed mucosa, without any effect on the viability of colonic tissue cells.

Adult↗

PubMed2005

Sulfasalazine inhibits activation of nuclear factor-kappaB in patients with ulcerative colitis.

BACKGROUND: Although sulfasalazine is widely used to treat inflammatory bowel disease, its mechanisms of action remain unclear. Activation of transcription factor nuclear factor (NF)-kappaB, which controls transcription of various pro-inflammatory cytokine genes, has been shown to play a critical role in the pathogenesis of inflammatory bowel disease. The purpose of the present study was to determine whether sulfasalazine therapy affected NF-kappaB activation and the expression of pro-inflammatory cytokines in patients with ulcerative colitis. METHODS: A total of 38 patients with moderate ulcerative colitis were investigated. Twenty-one patients received sulfasalazine. Seventeen patients did not receive any medication. Biopsy specimens were obtained from inflamed mucosa and analyzed for NF-kappaB DNA binding activity, NF-kappaBp65/IkappaBalpha protein expression and the levels of pro-inflammatory cytokine mRNA using electrophoretic mobility shift assay, western blot analysis, immunohistochemical staining and reverse transcription-polymerase chain reaction (RT-PCR) analysis, respectively. RESULTS: Increased activation of NF-kappaB and high levels of the expression of interleukin (IL)-1beta mRNA and IL-8 mRNA were detected in biopsy specimens from patients with ulcerative colitis. Therapeutic administration of sulfasalazine effectively downregulated the activation of NF-kappaB and the expression of IL-1beta mRNA and IL-8 mRNA while IkappaBalpha levels were stable. CONCLUSION: The therapeutic benefits for ulcerative colitis of sulfasalazine might at least in part be attributed to its ability to inhibit NF-kappaB activation, resulting in the downregulation of pro-inflammatory cytokine mRNA expression.

Adult↗

PubMed2005

Expansion of peripheral CD8+ CD28- T cells in response to Epstein-Barr virus in patients with rheumatoid arthritis.

OBJECTIVE: To investigate control of Epstein-Barr virus (EBV) infection in rheumatoid arthritis (RA) by comparing the frequency phenotypes and function of peripheral CD8+ EBV-peptide antigen-specific T cells in patients with RA and healthy longterm carriers of EBV. METHODS: The frequency of interferon-g (IFN-g)-producing HLA-A2 or HLA-B8-restricted EBV-reactive CD8+ T cells in peripheral blood mononuclear cells (PBMC) from 49 RA patients and 26 healthy EBV carriers was evaluated in Elispot assays with 12 lytic/latent peptide epitopes. Direct staining with HLA-peptide tetramers containing 3 of these peptides was performed for comparison. The phenotype and function of these T cells was determined by FACS and cytotoxicity testing. RESULTS: IFN-g production patterns in Elispot assays revealed that EBV-specific CD8+ T cells were directed predominantly against the lytic epitopes A2/GLC and B8/RAK and to a minor extent to all the other lytic and latent epitopes tested, with no significant differences of the frequencies in patients and controls. However, although similar frequencies of CD8+ T cells stained with A2/GLC or B8/RAK tetramers in both groups, the fraction of A2/GLC or B8/RAK-reactive T cells producing IFN-g in response to specific peptide antigen was significantly lower in RA patients than controls. The A2/GLC or B8/RAK tetramer-positive T cells were also substantially enriched in CD28-CD27- T cells of a late-differentiated phenotype in RA patients but not in controls. CONCLUSION: RA patients show clonal expansion of dysfunctional, terminally differentiated CD8+ EBV-specific T cells in their T cell responses to immunodominant lytic peptide EBV epitopes, which could be a sign of specific impairment of virus-host interactions in RA.

Adult↗

PubMed2005

[Expression with TGFbeta1 in the patients with ulcerative colitis].

OBJECTIVE: To elucidate the differences in expression of TGFbeta1 and TGFbeta1 mRNA between ulcerative colitis (UC), infectious colitis (IC) and normal control. METHODS: TGFbeta1 in colonic mucosa was detected by immunohistochemistry (IHC). TGFbeta1 mRNA was detected by hybridization in situ. RESULTS: There was no difference in detecting TGFbeta1 expression and TGFbeta1 mRNA expression in colonic mucosa between UC group and IC group (P>0.05), but the expression rates for the two groups were significantly higher than those for normal control (P<0.001). The expression of TGFbeta1 in colonic mucosa of UC group was noted to have a positive correlation with UC histological grade (r=0.462, P=0.002). CONCLUSION: Enhanced TGFbeta1 production in the colonic mucosa of UC patients can not inhibit proinflammatory cytokine production and hence can not get control of inflammation; this finding suggests the possible presence of TGFbeta1 signaling defects in the cases of UC. TGFbeta1 may serve as a disease activity marker of ulcerative colitis.

Adult↗

PubMed2005

[The clinical, pathological features and expression of Ki-67 and COX-2 in severe reflux esophagitis and Barrett's esophagus].

OBJECTIVE: To study the clinical, pathological features of severe reflux esophagitis (SRE) and Barrett's esophagus (BE) and search for expression and significance of Ki-67 and COX-2 in their tissues. METHODS: Both SRE (n = 15) and BE (n = 25) cases were retrospectively analyzed for clinical manifestations, endoscopic findings and pathological features. The expression levels of Ki-67 and COX-2 of esophageal epithelium in the two groups were compared with that of normal esophageal (NE) epithelium (n = 10) by immunoperoxidase staining. RESULTS: It was found that the positivity and staining intensity of Ki-67 expression in SRE and BE were higher than those in normal esophageal epithelium (P<0.01), but there were no statistical differences between these two groups (P>0.05); COX-2 was selectively expressed in some BE epithelium, but not in SRE and normal esophageal epithelium. CONCLUSION: There were intensified Ki-67 expressions in the epithelium of SRE and BE, which could help us to evaluate the prognosis of gastroesophageal reflux disease (GERD) patients clinically by surveillance of Ki-67. COX-2 was selectively expressed in BE epithelium, so COX-2 inhibitors may have the potential for treatment of BE and for chemoprevention of its malignant change.

Aged↗

PubMed2005

The emergence of inflammatory bowel disease in the Asian Pacific region.

PURPOSE OF REVIEW: Inflammatory bowel disease has been traditionally considered rare in the Asian Pacific region, but recent evidence indicates that both Crohn disease and ulcerative colitis are becoming increasingly common among local populations. This review will validate this significant epidemiological and clinical observation using data published in the current Asian literature and information presented at the 2004 Asian Pacific Digestive Week in Beijing, China. RECENT FINDINGS: A progressive rise in the incidence and prevalence of inflammatory bowel disease is discernible is most Asian Pacific countries, more so for ulcerative colitis than Crohn disease. Some ethnic differences are notably evident, as Indians suffer more inflammatory bowel disease than Chinese or Malays. Age of onset and gender are similar to those of Western patients, as are the distribution and extent of disease which, however, tends to be clinically less severe than in European and North American patients. A family history is occasionally elicited, whereas smoking and appendectomy appear to have the same impact on inflammatory bowel disease as seen in the West. A remarkable difference is the absence of any association of Asian Crohn disease with NOD2/CARD15 mutations, as repeatedly observed in white and Jewish populations. Intestinal tuberculosis is still common in the Asian Pacific region, and poses major diagnostic and therapeutic hurdles, often delaying the diagnosis of true Crohn disease. SUMMARY: Investigation of inflammatory bowel disease in the Asian Pacific region offers the unprecedented opportunity to study the 'early stages' of the disease, and may provide new clues to its pathophysiology by identifying key environmental factors and distinct genetic make-ups.

Asia↗

PubMed2005

[Study the effect and mechanism of thalidomide in model of inflammatory bowed disease].

OBJECTIVE: To assess the effect of thalidomide on Trinitrobenzensulphonic acid (TNBS)-induced or oxazolone-induced colitis and discuss the possible mechanism of its action. METHODS: Transmural colitis was induced by TNBS in three groups of rats (n=6 each), and distal colitis was induced by oxazolone in three groups of rats (n=6 each). Then the rats of the groups were treated with thalidomide [200 mg/(kg x d)], prednisone [5 mg/(kg x d)] or vehicle (olive oil) respectively by oral gavage. The colitis was allowed to run its course for 7 d after gavage and at that time the following endpoints were assessed. Colitis was evaluated by macroscopic and microscopic score; the expression of NF-kappaB P65 was examined by immunohistchemical (IHC); the expression of TNF-alpha mRNA was assayed by hybridization in situ (ISH); the cytokine TNF-alpha, IL-4, IFN-gamma were estimated by enzyme-linked immunoadsordent assay (ELISA). RESULTS: With respect to TNBS model, in the control, prednisone-treatment and thalidomide-treatment groups, the macroscopic and microscopic scores were 6.33 +/- 1.03, 1.67 +/- 0.82, 2.00 +/- 0.89 and 7.33 +/- 1.03, 2.67s +/- 0.82, 3.17 +/- 0.75 respectively; the expression levels of NF-kappaB P65 and TNF-alpha mRNA in the three groups were 62.45 +/- 12.38, 23.62 +/- 8.54, 34.18 +/- 9.65 and 12.42 +/- 4.63, 9.86 +/- 3.29, 4.35 +/- 1.74 respectively; the levels of TNF-alpha, IL-4, IFN-gamma were 540.32 +/- 80.76, 94.58 +/- 14.45, 486.18 +/- 68.47; 396.53 +/- 92.42, 78.45 +/- 12.69, 347.56 +/- 82.94; and 385.68 +/- 88.57, 123.68 +/- 38.15, 378.27 +/- 90.65 respectively. The results indicated that thalidomide treatment significantly reduced colonic inflammation, suppressed NF-kappaB activation,enhanced TNF-alpha mRNA degradation, inhibited the synthesis of the TNF-alpha, IEN-gamma and increased the production of IL-4. However, with respect to oxazolone model, the macroscopic score and microscopic score were 2.00 +/- 0.89, 0.33 +/- 0.52, 1.83 +/- 0.75 and 7.83 +/- 1.47, 3.33 +/- 0.82, 6.50 +/- 1.22 respectively. Thalidomide appeared not to be effective in reducing the oxazolone-induced chronic colitis. CONCLUSION: Thalidomide may be proposed as a useful drug for Crohn's disease, but further work is needed to clarify whether it is an efficacious agent for ulcerative colitis.

Animals↗

PubMed2004

Prediction of survival in follicular lymphoma based on molecular features of tumor-infiltrating immune cells.

BACKGROUND: Patients with follicular lymphoma may survive for periods of less than 1 year to more than 20 years after diagnosis. We used gene-expression profiles of tumor-biopsy specimens obtained at diagnosis to develop a molecular predictor of the length of survival. METHODS: Gene-expression profiling was performed on 191 biopsy specimens obtained from patients with untreated follicular lymphoma. Supervised methods were used to discover expression patterns associated with the length of survival in a training set of 95 specimens. A molecular predictor of survival was constructed from these genes and validated in an independent test set of 96 specimens. RESULTS: Individual genes that predicted the length of survival were grouped into gene-expression signatures on the basis of their expression in the training set, and two such signatures were used to construct a survival predictor. The two signatures allowed patients with specimens in the test set to be divided into four quartiles with widely disparate median lengths of survival (13.6, 11.1, 10.8, and 3.9 years), independently of clinical prognostic variables. Flow cytometry showed that these signatures reflected gene expression by nonmalignant tumor-infiltrating immune cells. CONCLUSIONS: The length of survival among patients with follicular lymphoma correlates with the molecular features of nonmalignant immune cells present in the tumor at diagnosis.

Adult↗