RESUMEN
Malignant mesothelioma (MM) is a lethal tumor linked with a prior exposure to asbestos in which limited progress has been made so far using conventional therapies. MM is an example of a "nonimmunogenic" tumor characterized by a fibrous stroma and an absence of infiltrating T lymphocytes. High levels of transforming growth factor-beta (TGF-beta) produced by mesothelioma cells have been related to the immune tolerance towards the tumor. In order to evaluate the effect of local delivery of cytokines such as interferon gamma (IFN-gamma) by gene transfer, we characterized and used a murine model, AK7, which appeared very similar to human mesothelioma. AK7 cells expressed low levels of major histocompatibility class I and class II antigens and secreted high levels of latent TGF-beta. The TGF-beta pathway in AK7 cells is operative but inefficient because endogenous TGF-beta is predominantly inactive. Treatment of pre-established AK7 tumors by direct intratumoral injection of an adenovirus vector expressing murine IFN-gamma, Ad.mIFN-gamma, led to significant tumor regression. Peripheral tumor infiltration by CD4+ and CD8+ T lymphocytes in the treated tumors appeared to be because of the induction of an immune response. Tumor relapse was observed, which could be due to local TGF-beta secretion by remaining tumor cells.
Asunto(s)
Técnicas de Transferencia de Gen , Terapia Genética/métodos , Interferón gamma/genética , Mesotelioma/terapia , Adenoviridae/genética , Animales , Apoptosis , Western Blotting , Caspasa 3 , Caspasas/metabolismo , Línea Celular Tumoral , Separación Celular , Citocinas/metabolismo , ADN Complementario/metabolismo , Regulación hacia Abajo , Femenino , Citometría de Flujo , Inmunohistoquímica , Interferón gamma/metabolismo , Mesotelioma/metabolismo , Mesotelioma/patología , Ratones , Ratones Endogámicos C57BL , Trasplante de Neoplasias , Fosforilación , Reacción en Cadena de la Polimerasa , ARN/metabolismo , Linfocitos T/metabolismo , Factores de Tiempo , Factor de Crecimiento Transformador beta/metabolismo , Regulación hacia ArribaAsunto(s)
Enfermedades del Pie/diagnóstico , Granuloma Piogénico/diagnóstico , Mancha Vino de Oporto/diagnóstico , Enfermedades de la Piel/diagnóstico , Adulto , Anciano , Diagnóstico Diferencial , Femenino , Enfermedades del Pie/complicaciones , Granuloma Piogénico/complicaciones , Humanos , Masculino , Mancha Vino de Oporto/complicaciones , Enfermedades de la Piel/complicaciones , MuñecaRESUMEN
The association between antiphospholipid syndrome (APS) and vasculitis is rare and continues to evoke great interest. We report a case with neurological manifestations of polyarteritis nodosa (PAN) and concurrent APS. Electromyography and neuromuscular biopsy of the limb showed an axonal polyneuropathy following obliteration and necrosis of medium sized arteries, initially suggesting PAN. This vasculitis was confirmed on visceral selective arteriography, with the presence of numerous aneurysms. Cerebral MRI revealed multiple cortical and subcortical signals in the fronto-parietal areas, corresponding to ischemic microvascular lesions of APS. This association was confirmed by the presence IgG anticardiolipid, the past medical history of skin necrotic lesions and central retinal obliteration. Pulse intravenous cyclophosphamide, oral prednisolone and curative anticoagulation led to stabilization for 8 months.
Asunto(s)
Síndrome Antifosfolípido/complicaciones , Enfermedades del Sistema Nervioso/etiología , Poliarteritis Nudosa/complicaciones , Adulto , Humanos , MasculinoRESUMEN
BACKGROUND: Imatinib is a new major treatment in chronic myeloid leukemia. OBJECTIVE: To study the cutaneous reactions induced by imatinib. METHODS: All inpatients and outpatients with Philadelphia chromosome-positive leukemia treated by imatinib were included in this prospective study. Clinical features, pathologic findings, evolution of each case, and analysis of potential risk factors were recorded. RESULTS: A total of 54 patients were included, 48 of whom experienced at least 1 cutaneous reaction. These reactions consisted of 36 rashes, 35 edemas, and 22 pruritus. The rash was severe in 5 patients, resulting in temporary interruption of treatment in 3. Highly significant relationships were observed between the daily dose of imatinib and both rashes and edema. In a multivariate analysis, female sex and the daily dose of imatinib were independent risk factors for the development of rashes. CONCLUSION: Adverse cutaneous reactions induced by imatinib are frequent, generally moderate, and dose-dependent.