RESUMEN
While retrospective studies have compared the efficacy of anti-tumour necrosis factor (TNF) agents and tacrolimus (TAC) in ulcerative colitis (UC), information regarding first-time use of these agents is limited. The aim of our study was to investigate the short- and long-term efficacy of anti-TNF agents [adalimumab (ADA) and infliximab (IFX)] and TAC in anti-TNF agent- and TAC-naïve steroid-refractory UC patients. We evaluated 150 steroid-refractory UC patients receiving anti-TNF agents (IFX: n = 30, ADA: n = 41) or TAC (n = 79) at eight institutions in Japan. Clinical response rates at 8 weeks were 73.2% and 75.9% while remission rates were 30.1% and 25.3% in the anti-TNF and TAC groups, respectively. Logistic regression analysis showed the male sex and higher C-reactive protein to be independent factors for response to anti-TNF agents and TAC, respectively. Use of TAC was an independent factor for relapse. No differences in response to the treatment or relapse were observed between IFX and ADA. In conclusion, TAC and anti-TNF agents promoted similar short-term effects, but anti-TNF agents ensured better long-term outcomes at first-time treatment of steroid-refractory UC patients.
Asunto(s)
Colitis Ulcerosa/tratamiento farmacológico , Esteroides/uso terapéutico , Tacrolimus/uso terapéutico , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Adalimumab/uso terapéutico , Adulto , Proteína C-Reactiva/metabolismo , Femenino , Humanos , Infliximab/uso terapéutico , Modelos Logísticos , Masculino , Persona de Mediana Edad , Modelos de Riesgos Proporcionales , Resultado del Tratamiento , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
BACKGROUND AND AIMS: Chemokine CXC ligand 13 (CXCL13) and CXC receptor type 5 (CXCR5) are constitutively expressed in tertiary lymphoid follicles where the CXCL13/CXCR5 system regulates B lymphocytes homing. In this study, we sought to examine CXCL13 expression in the H. pylori-infected and -uninfected gastric mucosa and to elucidate the implication in the pathogenesis of HAG in humans. METHODS: Using endoscopic biopsies taken from the gastric antrum of 29 subjects infected with Helicobacter pylori and 22 uninfected subjects, mucosal CXCL13 mRNA and protein levels were measured by real-time polymerase chain reaction and enzyme-linked immunosorbent assay, respectively. RESULTS: The CXCL13 expression levels were significantly more elevated in H. pylori-positive patients than uninfected ones. The CXCL13 expression levels correlated with the degree of chronic gastritis and bacterial colonization. Immunohistochemistry and in vitro infection assay showed that CXCL13 was not produced by the gastric epithelium, but the α-smooth muscle antigen expressing mesenchymal cells were the possible source of CXCL13 within H. pylori-infected gastric mucosa. CXCR5 immunostaining was seen in the CD20-positive lymphoid aggregates. CONCLUSIONS: The enhanced induction of CXCL13 may be involved in the pathogenesis of H. pylori-associated gastritis.
Asunto(s)
Quimiocina CXCL13/metabolismo , Gastritis/metabolismo , Gastritis/microbiología , Infecciones por Helicobacter/metabolismo , Helicobacter pylori , Anciano , Anciano de 80 o más Años , Biopsia , Estudios de Casos y Controles , Células Epiteliales/metabolismo , Células Epiteliales/microbiología , Células Epiteliales/patología , Femenino , Mucosa Gástrica/metabolismo , Mucosa Gástrica/microbiología , Mucosa Gástrica/patología , Gastritis/patología , Infecciones por Helicobacter/complicaciones , Helicobacter pylori/aislamiento & purificación , Humanos , Masculino , Persona de Mediana Edad , Antro Pilórico/metabolismo , Antro Pilórico/microbiología , Antro Pilórico/patología , ARN Mensajero/metabolismo , Receptores CXCR5/metabolismo , Estudios RetrospectivosRESUMEN
BACKGROUND: Helicobacter pylori vacuolating cytotoxin, VacA, stimulates apoptosis via a mitochondria-dependent pathway. VacA induces apoptosis via activation of the pro-apoptotic B-cell lymphoma (Bcl)-2 family proteins, Bcl-2-associated X protein (Bax) and Bcl-2 homologous antagonist/killer (Bak), while the implication of such pro-survival Bcl-2 family members as Bcl-2 and Bcl-XL in the VacA-induced apoptosis remains unknown. Signal transduction and activator of transcription 3 (STAT3) is a pivotal transcription factor that upregulates Bcl-2 and Bcl-XL. AIMS: This study was conducted to elicit the implication of STAT3 and pro-survival Bcl-2 and Bcl-XL in the intrinsic apoptosis. METHODS: Immunoblot and reverse transcriptase real-time polymerase chain reaction (RT-PCR) were employed to assess the cellular expression of STAT3, Bcl-2, and Bcl-XL in response to purified VacA in gastric adenocarcinoma cell lines. VacA-induced apoptosis was quantitated morphologically following knockdown by each specific small interfering RNA (siRNA) or in the presence of pharmacological inhibitors. RESULTS: VacA reduced STAT3, Bcl-2, and Bcl-XL expression in a dose-dependent manner. Knockdown of STAT3, Bcl-2, and Bcl-XL by siRNA induced apoptosis to a similar extent in the case of sufficient VacA inoculation. The VacA-mediated reduction of STAT3 expression was independent of cellular vacuolization, since a vacuolar-type ATPase inhibitor, bafilomycin A1, did not inhibit VacA-induced reduction of STAT3, Bcl-2, and Bcl-XL expression. Instead, a c-JUN NH2-terminal kinase (JNK) inhibitor, SP600125, restored the VacA-induced reduction of STAT3 expression to the basal level. CONCLUSIONS: VacA-induced apoptosis may be, in part, implicated in the reduction of STAT3 linking to the downregulation of Bcl-2 and Bcl-XL, in association with JNK activity.
Asunto(s)
Apoptosis , Proteínas Bacterianas/fisiología , Mucosa Gástrica/microbiología , Helicobacter pylori/fisiología , Proteínas Proto-Oncogénicas c-bcl-2/biosíntesis , Factor de Transcripción STAT3/biosíntesis , Antracenos/farmacología , Proteínas Bacterianas/farmacología , Línea Celular Tumoral , Regulación hacia Abajo/efectos de los fármacos , Inhibidores Enzimáticos/farmacología , Mucosa Gástrica/efectos de los fármacos , Mucosa Gástrica/metabolismo , Humanos , Proteínas Quinasas JNK Activadas por Mitógenos/antagonistas & inhibidores , Macrólidos/farmacología , ARN Interferente Pequeño/farmacologíaRESUMEN
AIM: Barrett's esophagus (BE) with specialized intestinal metaplasia (SIM) is at high risk of esophageal adenocarcinoma. Magnified endoscopy with narrow band imaging (ME-NBI) can be useful for detecting this condition. In addition to pit patterns, light blue crests (LBC), blue-whitish patchy areas on the metaplastic epithelia of the stomach, can predict SIM in BE under ME-NBI observation. METHODS: A total of 54 patients with BE underwent ME-NBI to identify IM pits (tubular and villous pits) and LBC. Biopsy samples were taken for histological evaluation of IM, immunohistochemical staining for CD10, MUC2 and MUC5AC antigen, transmission electron microscopy and real-time polymerase chain reaction (RT-PCR) analysis of CD10 mRNA expression. RESULTS: IM pit pattern with ME-NBI for the diagnosis of IM yielded acceptable sensitivity, specificity and accuracy at 92%, 77% and 83%, respectively. However, the sensitivity, specificity and accuracy of LBC with ME-NBI for IM were comparably high at 79%, 97% and 89%, respectively. Upon immunohistochemistry, all 19 metaplastic epithelia of LBC-positive BE showed immunoreactivity against anti-MUC2 antibody, whereas CD10 antigen was identified in 11 of the 19 LBC-positive BE. Brush borders were seen on IM epithelia using electron microscopy. On real-time PCR analysis, CD10 mRNA levels in the LBC-positive BE were higher compared to those in the LBC-negative BE. CONCLUSION: The appearance of LBC can be an accurate sign to predict SIM in BE and may be associated with high CD10 expression, possibly along with brush borders.
Asunto(s)
Adenocarcinoma/patología , Esófago de Barrett/patología , Endoscopía Gastrointestinal/métodos , Neoplasias Intestinales/patología , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Cohortes , Femenino , Humanos , Masculino , Metaplasia , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Reproducibilidad de los Resultados , Estudios RetrospectivosRESUMEN
BACKGROUND: Adenoma of the major papilla carries a relatively high risk of malignant transformation to carcinoma, the leading cause of death in patients with familiar adenomatous polyposis (FAP) after colectomy. CASE REPORT: A 35-year-old man had undergone prophylactic colectomy for FAP 3 years earlier. On the forward-viewing and side-viewing endoscopy done for surveillance, the overlying mucosa of the major papilla showed even granularity. On magnifying duodenoscopy using a narrow-band system (NBI), which uses modified optical filters and yields clear images of fine surface structures on the mucosal layer, a compact formation of round pits was seen in the affected ampulla. The microvascular architecture on NBI magnification showed no abnormalities, such as dilated, tortuous or network-like vessels, suggestive of malignancy. On endoscopic retrograde pancreaticocholangiography there was no intraductal growth, and endoscopic ultrasonography showed confinement to the mucosal layer. The ampullary lesion was completely resected using endoscopic snare papillectomy. Histopathological examination of the removed specimen showed tubular adenoma without malignant foci. The patient's post-treatment course was uneventful and without complications, and no local recurrence was noted on repeat endoscopy. CONCLUSIONS: Thus, endoscopic surveillance and removal of ampullary adenomas appear to be justified.
Asunto(s)
Adenoma/diagnóstico , Poliposis Adenomatosa del Colon/diagnóstico , Ampolla Hepatopancreática/patología , Neoplasias del Conducto Colédoco/diagnóstico , Duodenoscopía/métodos , Adenoma/patología , Adenoma/cirugía , Poliposis Adenomatosa del Colon/cirugía , Adulto , Ampolla Hepatopancreática/cirugía , Colectomía , Neoplasias del Conducto Colédoco/patología , Neoplasias del Conducto Colédoco/cirugía , Humanos , MasculinoRESUMEN
CC chemokine ligand 20 (CCL20) attracts CC chemokine receptor 6 (CCR6)-expressing cells. Using endoscopic biopsies taken from the gastric antrum of 42 subjects infected with H. pylori and 42 uninfected subjects, mucosal CCL20 mRNA and protein levels were measured by real-time polymerase chain reaction and enzyme-linked immunosorbent assay, respectively. CCL19 mRNA and protein levels, as well as CCL21 mRNA levels, were also measured. The CCL20 mRNA and protein levels were significantly elevated in H. pylori-positive patients and substantially decreased after successful eradication. CCL19 and CCL21 expression levels were comparable in the H. pylori-infected and the uninfected groups. The CCL20 concentrations correlated with the degree of chronic gastritis. Immunohistochemistry and the in vitro infection assay showed that CCL20 was principally produced by the gastric epithelium. CCR6-expressing cells, including CD45RO(+) memory T lymphocytes and fascin(+)-CD1a(+) immature dendritic cells, infiltrated close to the CCL20-expressing epithelial cells. The CCL20/CCR6 interaction may be involved in the development of H. pylori-associated gastritis.