RESUMO
A 54-year-old woman with peripheral T cell lymphoma in second complete remission (CR) received an autologous peripheral blood stem cell transplant (PBSCT). Antibiotic-resistant bloody diarrhea, and fever developed 110 days after transplant. Blood and stool cultures were negative. Skin rash was not observed. Barium enema and colonoscopy showed typical features of pancolonic-type ulcerative colitis (UC). Endoscopic biopsies confirmed the diagnosis of UC. Mesalazine and immunosuppressive therapy improved symptoms dramatically. We detected serum antibodies against synthetic tropomyosin (TM) peptide when UC was diagnosed. We postulate that autoimmunity including autoreactive anti-TM antibodies may be involved in the pathogenesis of UC after autologous PBSCT in this patient.
Assuntos
Colite Ulcerativa/etiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Linfoma não Hodgkin/complicações , Autoanticorpos/sangue , Autoimunidade/imunologia , Colite Ulcerativa/imunologia , Colite Ulcerativa/patologia , Feminino , Humanos , Linfoma não Hodgkin/terapia , Linfoma de Células T Periférico/complicações , Linfoma de Células T Periférico/terapia , Pessoa de Meia-Idade , Transplante Autólogo/efeitos adversos , Tropomiosina/imunologiaRESUMO
We have previously reported that superoxide stimulates the motility of tumor cells and the administration of Cu-Zn superoxide dismutase (SOD) significantly suppresses metastasis. However, ideally, anti-metastatic therapy should be long-lasting, systemically effective and have low toxicity. The half-life of Cu-Zn SOD in plasma is so short that it cannot provide long-lasting effects. Therefore, in this study we have developed a gene therapy in a mouse model utilizing extracellular SOD (EC-SOD), which is the most prevalent SOD isoenzyme in extracellular fluids. We retrovirally transfected fibroblasts (syngeneic) with the EC-SOD gene and established EC-SOD-secreting fibroblasts. Inoculation of EC-SOD-secreting fibroblasts suppressed both artificial and spontaneous metastatic lung nodules in mouse metastasis models. These data indicate the feasibility of anti-metastatic gene therapy utilizing the EC-SOD gene.
Assuntos
Terapia Genética/métodos , Neoplasias Pulmonares/secundário , Neoplasias Pulmonares/terapia , Superóxido Dismutase/genética , Transdução Genética , Animais , Carcinoma Pulmonar de Lewis/patologia , Carcinoma Pulmonar de Lewis/secundário , Carcinoma Pulmonar de Lewis/terapia , Técnicas de Cultura de Células , Divisão Celular , Meios de Cultura , DNA Complementar/genética , Estudos de Viabilidade , Fibroblastos/transplante , Expressão Gênica , Isoenzimas/genética , Isoenzimas/metabolismo , Neoplasias Pulmonares/patologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos , Transplante de Neoplasias , RNA Mensageiro/genética , Sarcoma Experimental/patologia , Sarcoma Experimental/secundário , Sarcoma Experimental/terapia , Superóxido Dismutase/metabolismoRESUMO
Acute graft-versus-host diseases (GVHD) is a major cause of morbidity and mortality in patients undergoing allogeneic bone marrow transplantation (BMT). T helper 1 (Th1)-type cytokines such as interferon-gamma or tumor necrosis factor-alpha have been implicated in the pathogenesis of acute GVHD. TAK-603 is a new quinoline derivative, which is now in clinical trials for use as a disease-modifying antirheumatic drug. In preclinical studies, it inhibited delayed-type hypersensitivity, but not Arthus-type reaction, in mice, and selectively suppressed Th1 cytokine production. Thus, the present study was designed to investigate whether the Th1 inhibitor (TAK-603) ameliorates lethal acute GVHD in a mouse model. Administration of TAK-603 into BALB/c mice given 10 Gy total body irradiation followed by transplantation of bone marrow and spleen cells from C57BL/6 mice markedly reduced the mortality in association with minimal signs of GVHD pathology in the liver, intestine, and skin. TAK-603 reduced not only the production of Th1-type cytokines, but also the proportion of Th1 cells in CD4(+) helper T cells in this GVHD mouse model. These results suggest that TAK-603 could be a potent therapeutic agent for acute lethal GVHD.