RESUMO
Four patients with metastatic primary small bowel adenocarcinoma associated with Crohn's disease were successfully treated with low dose combination chemotherapy consisting of 5-fluorouracil, leucovorin and irinotecan with or without gemcitabine. Benefits included prolonged survival, objective responses, response of resistant tumors, downstaging, and a successful secondary complete resection (Ro) with a durable remission.
Assuntos
Adenocarcinoma/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Doença de Crohn/complicações , Neoplasias Duodenais/tratamento farmacológico , Neoplasias do Íleo/tratamento farmacológico , Neoplasias do Jejuno/tratamento farmacológico , Adenocarcinoma/complicações , Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Camptotecina/administração & dosagem , Camptotecina/análogos & derivados , Doença de Crohn/tratamento farmacológico , Neoplasias Duodenais/complicações , Neoplasias Duodenais/mortalidade , Neoplasias Duodenais/patologia , Feminino , Humanos , Neoplasias do Íleo/complicações , Neoplasias do Íleo/mortalidade , Neoplasias do Íleo/patologia , Intestino Delgado/patologia , Irinotecano , Neoplasias do Jejuno/complicações , Neoplasias do Jejuno/mortalidade , Neoplasias do Jejuno/patologia , Leucovorina/administração & dosagem , Masculino , Indução de Remissão , Análise de SobrevidaRESUMO
Intravascular introduction of replication-deficient adenoviral vectors (Advectors) provides an ideal model of delivery of transgenes for the treatment of various vascular abnormalities. On the basis of the knowledge that Advectors can induce inflammatory responses after intravascular administration, we speculated that cellular activation by Advector infection could directly modulate the endothelial cell (EC) adhesion molecule/chemokine expression repertoire. Infection of human umbilical vein ECs or bone marrow microvascular ECs with an E1(-)E4(+) Advector resulted in the upregulation of intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and CD34, but not E-selectin, P-selectin, CD36, CD13, CD44, HLA-DR or PECAM. Upregulation of ICAM-1, VCAM-1, and CD34 was apparent 12 hours after infection and persisted for weeks after infection. Selective induction of adhesion molecules was mediated by the presence of the E4 gene in the Advector, because infection of ECs with an E1(-)E4(-) Advector had no effect on adhesion molecule expression. ECs infected with E1(-)E4(+) Advector, but not those infected with E1(-)E4(-) Advector, supported the adhesion of leukocytes. Monoclonal antibodies to ICAM-1 and VCAM-1 inhibited adhesion of leukocytes to E1(-)E4(+)-infected ECS: Infection of the ECs with E1(-)E4(+) Advector, but not E1(-)E4(-) Advector, resulted in downregulation of expression of chemocytokines, including interleukin-8, MCP-1, RANTES, and GM-CSF. Nonetheless, a large number of leukocytes migrated through ECs infected with E1(-)E4(+), but not those infected with E1(-)E4(l-), in response to exogenous chemokines. These results demonstrate that infection of ECs with E1(-)E4(+) Advectors, but not E1(-)E4(-) Advectors, may directly augment inflammatory responses by upregulating expression of adhesion molecules and enhancing migration through Advector-infected ECs and suggest that E1(-)E4(-) Advectors may be a better choice for gene-transfer strategies directed to the ECS:
