RESUMEN
Congenital infiltrating lipomatosis is a benign yet locally invasive lipomatous tumor. Current treatment involves surgical excision and reconstruction of craniofacial deformity. Invasion of vital structures often makes complete resection problematic and recurrence is common. We present the case of a 15-year-old female patient with extensive congenital infiltrating lipomatosis involving the left face. A broad treatment algorithm was devised involving surgical resection as well as targeted chemotherapy. At 18 month follow-up the patient demonstrated improved facial symmetry without evidence of disease progression. Combining surgical and medical intervention may allow for a synergistic approach to controlling this rare disease.
Asunto(s)
Neoplasias Faciales/congénito , Neoplasias Faciales/patología , Lipomatosis/congénito , Lipomatosis/patología , Receptores del Factor de Crecimiento Derivado de Plaquetas/administración & dosificación , Adolescente , Biopsia con Aguja , Quimioterapia Adyuvante , Neoplasias Faciales/tratamiento farmacológico , Neoplasias Faciales/cirugía , Femenino , Estudios de Seguimiento , Humanos , Inmunohistoquímica , Lipomatosis/tratamiento farmacológico , Lipomatosis/cirugía , Imagen por Resonancia Magnética/métodos , Enfermedades Raras , Medición de Riesgo , Tomografía Computarizada por Rayos X/métodos , Resultado del TratamientoRESUMEN
Although patients with advanced refractory solid tumors have poor prognosis, the clinical development of targeted protein kinase inhibitors offers hope for the future treatment of many cancers. In vivo and in vitro studies have shown that the oral multikinase inhibitor, sorafenib, inhibits tumor growth and disrupts tumor microvasculature through antiproliferative, antiangiogenic, and/or proapoptotic effects. Sorafenib has shown antitumor activity in phase II/III trials involving patients with advanced renal cell carcinoma and hepatocellular carcinoma. The multiple molecular targets of sorafenib (the serine/threonine kinase Raf and receptor tyrosine kinases) may explain its broad preclinical and clinical activity. This review highlights the antitumor activity of sorafenib across a variety of tumor types, including renal cell, hepatocellular, breast, and colorectal carcinomas in the preclinical setting. In particular, preclinical evidence that supports the different mechanisms of action of sorafenib is discussed.
Asunto(s)
Bencenosulfonatos/farmacología , Inhibidores de Proteínas Quinasas/farmacología , Piridinas/farmacología , Receptores del Factor de Crecimiento Derivado de Plaquetas/administración & dosificación , Receptores de Factores de Crecimiento Endotelial Vascular/antagonistas & inhibidores , Quinasas raf/antagonistas & inhibidores , Animales , Ensayos de Selección de Medicamentos Antitumorales , Humanos , Niacinamida/análogos & derivados , Compuestos de Fenilurea , SorafenibRESUMEN
Migration of adventitial fibroblasts contributes to vascular remodeling after angioplasty. This study has used perivascular gene transfer of a truncated platelet-derived growth factor PDGF receptor (PDGFXR) to investigate whether antagonism of PDGF signaling alters adventitial cell migration after balloon injury in rat carotid arteries. Adenoviruses coordinating expression of beta-galactosidase (LacZ) and PDGFXR or LacZ and green fluorescent protein (GFP) were applied to the perivascular surface of arteries and balloon injury performed 4 days later. Vessels were excised at 3, 7, and 14 days to determine morphology and gene expression. Uninjured arteries only expressed LacZ positive cells in the adventitial compartment; however, after injury in LacZ and GFP transfected arteries, LacZ positive cells contributed to the population of cells within the media and neointima at 7-14 days. Overexpression of PDGFXR and LacZ resulted in a significant reduction in the number of LacZ labeled cells in the neointima after vascular injury, concomitant with reduced remodeling, collagen content, expression of matrix metalloproteinase-2, and increased levels of tissue inhibitors of metalloproteinase-1 and -2. We provide evidence that perivascular antagonism of PDGF attenuates remodeling and contribution of adventitial fibroblasts to neointima formation after balloon angioplasty. Perivascular gene transfer may represent a therapeutic strategy to reduce the incidence of restenosis.
Asunto(s)
Traumatismos de las Arterias Carótidas/terapia , Movimiento Celular , Factor de Crecimiento Derivado de Plaquetas/antagonistas & inhibidores , Receptores del Factor de Crecimiento Derivado de Plaquetas/administración & dosificación , Transfección , Angioplastia de Balón/efectos adversos , Animales , Arteriopatías Oclusivas/prevención & control , Traumatismos de las Arterias Carótidas/patología , Fibroblastos/fisiología , Proteínas Fluorescentes Verdes/administración & dosificación , Proteínas Fluorescentes Verdes/genética , Proteínas Fluorescentes Verdes/farmacocinética , Operón Lac/genética , Ratas , Receptores del Factor de Crecimiento Derivado de Plaquetas/genética , Eliminación de Secuencia , Distribución TisularRESUMEN
We have shown that the genetically diabetic mouse (C57BLKS/J-m+/+Lepr(db)) has a wound healing and neovascularization deficit associated with an inability to recruit endothelial precursor cells (EPCs) to the wound. This may account for a fundamental mechanism in impaired diabetic wound healing. We hypothesized that the adenoviral mediated overexpression of platelet-derived growth factor-B (PDGF-B) would enhance wound healing, improve neovascularization, and recruit EPCs to the epithelial wound in three diabetic mouse models. Eight-mm full-thickness flank wounds were made in db/db, nonobese NOD/Ltj, streptozotocin, and C57BLKS/J mice. Wounds were treated with either 1 x 10(8) PFU Ad-PDGF-B or Ad LacZ or phosphate buffered saline solution. Wounds harvested at seven days were analyzed for epithelial gap, blood vessel density, granulation tissue area, and EPCs per high powered field. All three diabetic models have a significant wound healing and neovascularization defect compared to C57BLKS/J controls. Adenoviral-PDGF-B treatment significantly enhanced epithelial gap closure in db/db, streptozotocin, and nonobese NOD/Ltj mice as compared to diabetic phosphate buffered saline solution or Ad LacZ controls. A similar increase in the formation of granulation tissue and vessel density was also observed. All three models had reduced levels of GATA-2 positive EPCs in the wound bed that was corrected by the adenoviral mediated gene transfer of PDGF. EPC recruitment was positively correlated with neovascularization and wound healing. Three different diabetic models have a wound healing impairment and a decreased ability to recruit EPCs. The vulnerary effect of adenoviral mediated gene therapy with PDGF-B significantly enhanced wound healing and neovascularization in diabetic wounds. The PDGF-B mediated augmentation of EPC recruitment to the wound bed may be a fundamental mechanism of these results.