Project description:RATIONALE: Beclomethasone may be an effective treatment for graft-versus-host disease.
PURPOSE: Phase I/II trial to study the effectiveness of beclomethasone in treating patients who have graft-versus-host disease of the esophagus, stomach, small intestine, or colon.
Project description:The macrolide rapamycin is known for its immunosuppressive properties since it inhibits mTOR (mammalian target of rapamycin), which activity affects differentiation and functions of various innate and adaptive immune cells involved in graft-versus-host disease development. Since rapamycin procures immunosuppressive effects on the immune response, rapamycin is an attractive candidate for graft-versus-host disease prevention after allogeneic bone marrow transplantation. Recently, an activating effect of rapamycin on the function of myeloid-derived suppressor cells (MDSCs), a subset of immune suppressive cells of myeloid origin was reported. However, the effect of rapamycin treatment on MDSCs induction and function in the management of graft-versus-host disease is largely unknown. We used an MHC class I and II mismatched parent into F1 bone marrow transplantation mouse model to elucidate the mechanisms of rapamycin on MDSCs in the context of graft-versus-host disease prevention. To define the impact of rapamycin therapy on MDSCs gene expression profile, we performed mircoarray analysis and compared gene expression profiles of ex vivo isolated MDSCs from rapamycin and PBS treated mice
Project description:The macrolide rapamycin is known for its immunosuppressive properties since it inhibits mTOR (mammalian target of rapamycin), which activity affects differentiation and functions of various innate and adaptive immune cells involved in graft-versus-host disease development. Since rapamycin procures immunosuppressive effects on the immune response, rapamycin is an attractive candidate for graft-versus-host disease prevention after allogeneic bone marrow transplantation We used an MHC class I and II mismatched parent into F1 bone marrow transplantation mouse model to elucidate the mechanisms of rapamycin on T cells in the context of graft-versus-host disease prevention. To define the impact of rapamycin therapy on T cells gene expression profile, we performed mircoarray analysis and compared gene expression profiles of sorted splenic T cells from rapamycin and PBS treated mice
Project description:Lethally irradiated C57Bl/6 Act-mOVA mice receiving allogeneic hematopoietic stem cell transplantation (aHSCT) from C57Bl/6 OT-I animals develop acute graft versus host disease (aGvHD) in a CD8+ T cell-dependent, reproducible manner, and succumb to the disease within 4-7 days. Tracking of UBC-GFP/OT-I graft CD8+ T cells discloses heavy infiltration of the GI tract, liver and lungs at the onset of the disease, and hallmark histologic features of acute gastrointestinal and hepatic GvHD, and aGVHD-associated lymphocytic bronchitis. This dataset describes gene expression patterns of CD45.1/OT-1 CD8+ T cells retrieved from the graft before (aHSCT + Day 0), and from various target organs of the host after (aHSCT + Day 4) grafting them into Act-mOVA recipients.
Project description:To assess if gene expression signatures could predict acute graft-versus-host disease, we examined the global gene expression profiles of peripheral blood mononuclear cells at day +14 post-transplantation from 94 patients undergoing allogeneic hematopoietic cell transplantation with nonmyeloablative conditioning.
