RESUMO
BACKGROUND: Mycosis fungoides (MF) classically presents from patch stage to plaque stage over a number of years and finally progresses to tumour stage with nodal or visceral involvement. The mechanism of progression remains incompletely elucidated. Chemokines and their receptors are known to be involved in disease mechanisms, with CXCL12 and CXCR4 playing a critical role in carcinogenesis, invasion and cancer cell migration in various carcinomas. OBJECTIVES: To investigate the expression of CXCL12 and CXCR4 in different cutaneous stages of MF. METHODS: Formalin-fixed, paraffin-embedded skin samples from 40 patients with MF (21 patch stage, 10 plaque stage, nine tumour stage) and 30 non-neoplastic control skin samples were analysed. CXCL12 and CXCR4 were assessed by quantitative reverse-transcription polymerase chain reaction and immunohistochemical staining. RESULTS: The expression level of mRNA for CXCL12 in plaque-stage MF was significantly higher than in control skin (P = 0.0035), or patch-stage (P = 0.0108) or tumour-stage disease (P = 0.0089). The CXCR4 mRNA expression level in plaque-stage disease was significantly higher than in control skin (P = 0.0090) or patch-stage disease (P = 0.0387). CXCL12- and CXCR4-positive cell rates in patch-stage and plaque-stage MF were significantly higher than those in control skin (P < 0.0001). CXCL12- and CXCR4-positive cell rates in tumour-stage MF were significantly lower than those in patch- and plaque-stage disease (P = 0.0274 and P = 0.0492, respectively). CONCLUSIONS: Our data suggest that neoplastic T cells in MF are exposed to the microenvironment, given the abundance of CXCL12 during its progression, and also that neoplastic T cells express CXCR4, especially in the pretumour stage. We reveal that the CXCL12-CXCR4 axis plays a critical role in MF progression.
Assuntos
Quimiocina CXCL12/metabolismo , Progressão da Doença , Micose Fungoide/metabolismo , Receptores CXCR4/metabolismo , Neoplasias Cutâneas/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Feminino , Humanos , Imuno-Histoquímica , Macrófagos/metabolismo , Masculino , Pessoa de Meia-Idade , RNA Mensageiro/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Pele/metabolismo , Linfócitos T/metabolismoRESUMO
We have generated a mouse model for hepatic ischemia in which surgical subcutaneous transposition of the spleen allows hepatic ischemia to be applied without affecting other tissues. Using this mouse model we investigated the relationship between the length of ischemic periods in the liver and subsequent liver function; furthermore, we assayed the activation of c-Jun N-terminal kinase (JNK) during ischemia and reperfusion. Although prior to this study only the activated form of JNK was known to be translocated to the nucleus, we found that JNK translocates to the nucleus during ischemia without activation and is then activated during reperfusion. These results suggest a novel mechanism of JNK activation.
Assuntos
Proteínas Quinases Dependentes de Cálcio-Calmodulina/metabolismo , Isquemia/metabolismo , Proteínas Quinases Ativadas por Mitógeno , Reperfusão , Animais , Apoptose/fisiologia , Proteínas Quinases Dependentes de Cálcio-Calmodulina/análise , Núcleo Celular/metabolismo , Modelos Animais de Doenças , Ativação Enzimática/fisiologia , Imuno-Histoquímica , Proteínas Quinases JNK Ativadas por Mitógeno , Fígado/citologia , Fígado/metabolismo , Testes de Função Hepática , Camundongos , Camundongos Endogâmicos , Testes de Precipitina , Baço/cirurgia , Fatores de TempoRESUMO
The effect of an orally administered glutamine-enriched elemental diet was examined following orthotopic small bowel allotransplantation using Brown Norway rats as donors and Lewis rats as recipients. The recipients was treated with FK 506 and randomized to receive glutamine-free elemental enteral diet solution (glutamine-free group), glutamine-enriched elemental diet solution containing 7500 mg of glutamine per 100 g diet (glutamine-enriched group) or standard chow (chow group) ad libitum for 7 d. There were no histological changes due to resection. Weight loss in the glutamine-enriched group was significantly less than that of the chow group. Both plasma glutamine levels and the ratio of glutamine to total amino acids in the homogenate of the graft mucosa of the glutamine-enriched group were significantly higher than those of the glutamine-fee group. Villous height and crypt depth were significantly decreased in the glutamine-free group. The BrdU labeling index in the graft epithelium and alkaline phosphatase activity in the homogenate of the graft mucosa of the glutamine-enriched group were significantly higher than those of the glutamine-free group. Therefore, orally administered glutamine-enriched elemental diet appears to promote the regeneration and differentiation of the graft mucosa following small bowel allotransplantation.
Assuntos
Glutamina/farmacologia , Terapia de Imunossupressão/métodos , Intestino Delgado/efeitos dos fármacos , Intestino Delgado/transplante , Envelhecimento/metabolismo , Alanina/análise , Alanina/sangue , Alanina/metabolismo , Fosfatase Alcalina/análise , Fosfatase Alcalina/metabolismo , Amônia/análise , Amônia/sangue , Amônia/metabolismo , Animais , Peso Corporal/efeitos dos fármacos , Peso Corporal/fisiologia , Bromodesoxiuridina/análise , Divisão Celular/fisiologia , Dieta , Células Epiteliais/citologia , Células Epiteliais/efeitos dos fármacos , Ácido Glutâmico/sangue , Ácido Glutâmico/metabolismo , Glutamina/administração & dosagem , Glutamina/sangue , Imunossupressores/farmacologia , Mucosa Intestinal/química , Mucosa Intestinal/citologia , Mucosa Intestinal/efeitos dos fármacos , Intestino Delgado/química , Masculino , Microvilosidades/ultraestrutura , Distribuição Aleatória , Ratos , Ratos Endogâmicos BN , Ratos Endogâmicos Lew , Tacrolimo/farmacologia , Fatores de Tempo , Transplante HomólogoRESUMO
A case of an unresected, advanced gastric cancer with Sister Mary Joseph nodule was presented. It was treated with new combination chemotherapy of low-dose S-1 and cisplatin producing complete response of periumbilical metastasis. Few treatments are efficacious for umbilical invasion of peritoneal dissemination. A complete response for Sister Mary Joseph nodule from gastric adenocarcinoma has not been ever reported.
Assuntos
Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/patologia , Antimetabólitos Antineoplásicos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Ácido Oxônico/administração & dosagem , Piridinas/administração & dosagem , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/patologia , Tegafur/administração & dosagem , Adenocarcinoma/diagnóstico por imagem , Idoso , Cisplatino/administração & dosagem , Combinação de Medicamentos , Humanos , Masculino , Radiografia , Neoplasias Gástricas/diagnóstico por imagem , Resultado do TratamentoRESUMO
The authors present the results of a clinical and endoscopic controlled trial of outpatients with duodenal ulcer treated with carbenoxolone (CBX) and carbenoxolone plus antacids (CBX + AA). They observed complete healing of the duodenal ulcer in 77%-83,3% in both groups of patients. They concluded that CBX is important in the treatment of duodenal ulcer been equally effective alone or in association with antacids.
Assuntos
Antiácidos/uso terapêutico , Carbenoxolona/uso terapêutico , Úlcera Duodenal/tratamento farmacológico , Ácido Glicirretínico/análogos & derivados , Avaliação de Medicamentos , Quimioterapia Combinada , Úlcera Duodenal/diagnóstico , Endoscopia , Tecnologia de Fibra Óptica , Humanos , ComprimidosRESUMO
Biweekly intravenous infusions of low-dose cisplatin (CDDP) and 5-fluorouracil (5-FU) were evaluated in 80 patients with advanced or recurrent gastric, colorectal, pancreatic or gallbladder adenocarcinoma. CDDP was given biweekly at a dose of 15 mg/m2 infused for 30 minutes, and 5-FU 375 mg/m2 was infused for 2 hours as many times as possible. The response rate among patients with gastric cancer was 26%, colorectal cancer 10%, pancreatic cancer 7.7%, and gallbladder cancer 42.9%. The response rates were not so high, but the median survival time of patients with recurrent gastric cancer was 17.3 months, pancreatic cancer 6.7 months, and gallbladder cancer 10.7 months. A patient with unresected advanced pancreatic head cancer with liver and para-aortic lymph node metastases received this therapy 38 times, and lived for 54 months. No severe side effects occurred in any of these cases. Thus, this chemotherapy could well be effective for the outcome of cases of advanced gastrointestinal carcinoma.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Neoplasias do Colo/tratamento farmacológico , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Gástricas/tratamento farmacológico , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/mortalidade , Idoso , Idoso de 80 Anos ou mais , Cisplatino/administração & dosagem , Neoplasias do Colo/mortalidade , Esquema de Medicação , Fluoruracila/administração & dosagem , Neoplasias da Vesícula Biliar/tratamento farmacológico , Neoplasias da Vesícula Biliar/mortalidade , Humanos , Metástase Linfática , Pessoa de Meia-Idade , Neoplasias Pancreáticas/mortalidade , Prognóstico , Neoplasias Gástricas/mortalidade , Taxa de SobrevidaRESUMO
TS-1, a novel oral formation of 5-fluorouracil, consists of tegafur (5-FU), CDHP and Oxo. Low-dose cisplatin (CDDP) and TS-1 was evaluated in 12 patients with advanced or recurrent gastric cancer. CDDP was given biweekly at a dose of 15 mg/m2 infused for 30 minutes, and 80 mg/body of TS-1 was orally administered as many times as possible. The response rate was 41.7%. Median survival time was 13.3 months. In one case, an adverse reaction of grade 3 leucopenia was observed. Thus, thought it is necessary to watch for leucopenia, this chemotherapy could well be effective for patients with advanced or recurrent gastric cancer.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Ácido Oxônico/administração & dosagem , Piridinas/administração & dosagem , Neoplasias Gástricas/tratamento farmacológico , Tegafur/administração & dosagem , Administração Oral , Adulto , Idoso , Cisplatino/administração & dosagem , Esquema de Medicação , Combinação de Medicamentos , Feminino , Humanos , Infusões Intravenosas , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Neoplasias Gástricas/mortalidade , Taxa de SobrevidaRESUMO
Veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS) occurring after liver transplantation is a relatively rare complication but it often takes a life-threatening course. However, the detailed etiology and mechanism of VOD/SOS after liver transplantation (LT) remains unclear. We report two cases with rapidly progressive VOD/SOS after ABO-identical LT resistant to various therapies. In case 1, in which the patient underwent deceased-donor LT, the first episode of acute allograft rejection was triggered VOD/SOS, and the presence of donor non-specific anti-HLA antibodies was confirmed. The recipient died with graft failure on day 46 after transplantation. Case 2, in which the patient underwent living-donor LT from the mother, had neither rejection nor mechanical venous obstruction, but condition of the patient rapidly worsened and he died on day 13 after transplantation. This recipient's direct cross-match test for the donor's B lymphocyte was strongly positive, but that for T lymphocyte was negative. In both cases, neither stenosis of hepatic vein outflow tract nor C4d deposition in post-transplantation liver biopsy specimens and autopsy specimen was found. On the other hand, in both cases, the patient was transfusion unresponsive thrombocytopenia and hyperbilirubinemia persisted postoperatively, and glycoprotein â bα was strongly stained in the neighboring centrilobular area (zone 3), especially in the space of Disse, and platelet phagocytosis was observed in Kupffer cells and hepatocytes around zone 3 such as clinical xenotransplantation of the liver in post-transplantation liver biopsy specimens. From the viewpoint of graft injury, VOD/SOS was considered that sustained sinusoidal endothelial cells injury resulted in bleeding in the space of Disse and led to around centrilobular hemorrhagic necrosis, and the fundamental cause was damage around centrilobular area including sinusoid by acute cellular rejection, antibody-mediated rejection or ischemic reperfusion injury. The extrasinusoidal platelet activation, aggregation, and phagocytosis of platelets were some of the main reasons for VOD/SOS and transfusion-resistant thrombocytopenia.
Assuntos
Rejeição de Enxerto/complicações , Hepatopatia Veno-Oclusiva/etiologia , Transplante de Fígado/efeitos adversos , Doadores de Tecidos , Adulto , Biópsia , Feminino , Rejeição de Enxerto/diagnóstico , Hepatopatia Veno-Oclusiva/diagnóstico , Humanos , Masculino , Índice de Gravidade de Doença , Transplante HomólogoAssuntos
Apoptose , Proteínas Quinases Dependentes de Cálcio-Calmodulina/metabolismo , Isquemia/patologia , Fígado/irrigação sanguínea , Proteínas Quinases Ativadas por Mitógeno , Animais , Apoptose/efeitos dos fármacos , Ativação Enzimática , Isquemia/fisiopatologia , Proteínas Quinases JNK Ativadas por Mitógeno , Fígado/enzimologia , Fígado/patologia , Masculino , Camundongos , Camundongos Endogâmicos , Reperfusão , Fatores de Tempo , Vitamina E/farmacologiaAssuntos
Precondicionamento Isquêmico , Fígado/irrigação sanguínea , Traumatismo por Reperfusão/prevenção & controle , Alanina Transaminase/sangue , Animais , Interleucina-6/sangue , Isquemia/patologia , Isquemia/fisiopatologia , Fígado/patologia , Circulação Hepática , Masculino , Camundongos , Camundongos Endogâmicos , Necrose , Fatores de Tempo , Fator de Necrose Tumoral alfa/análiseRESUMO
A persistent photoinduced metal-to-insulator transition has been confirmed in a manganite thin film, Pr_(0.55)(Ca_(0.75)Sr_(0.25))_(0.45)MnO3, near a multicritical point by monitoring with transport measurements and x-ray photoemission spectroscopy. Together with the previously reported reverse effect, the photoinduced insulator-to-metal transition, it is found that the relative stability of the metallic and insulating phases interchanges around 80 K in the middle of a very wide hysteresis loop, which is a manifestation of the large potential barrier due to the long-range elastic energy. It is shown that photons are much more effective in overcoming the barrier via the electronically excited intermediate states than via the heat mode.
RESUMO
Wegener's granulomatosis is a disease characterized by necrotizing vasculitis and granulomatous inflammation. Gastrointestinal (GI) involvement is uncommon in this disorder. Only a few cases of perforation of GI tract have been reported, but vasculitis has not been demonstrated to be a cause of perforation in these cases. We report a case of Wegener's granulomatosis in which a single perforation in the terminal ileum was disclosed on laparotomy and active necrotizing vasculitis was found in the submucosal layer of the resected specimen.