RESUMO
INTRODUCTION: Surgical resection and systemic chemotherapy with temozolomide remain the mainstay for treatment of glioblastoma. However, many patients are not candidates for surgical resection given inaccessible tumor location or poor health status. Furthermore, despite being first line treatment, temozolomide has only limited efficacy. METHODS: The development of injectable hydrogel-based carrier systems allows for the delivery of a wide range of chemotherapeutics that can achieve high local concentrations, thus potentially avoiding systemic side effects and wide-spread neurotoxicity. To test this modality in a realistic environment, we developed a diblock copolypeptide hydrogel (DCH) capable of carrying and releasing paclitaxel, a compound that we found to be highly potent against primary gliomasphere cells. RESULTS: The DCH produced minimal tissue reactivity and was well tolerated in the immune-competent mouse brain. Paclitaxel-loaded hydrogel induced less tissue damage, cellular inflammation and reactive astrocytes than cremaphor-taxol (typical taxol-carrier) or hydrogel alone. In a deep subcortical xenograft model of glioblastoma in immunodeficient mice, injection of paclitaxel-loaded hydrogel led to local tumor control and improved survival. However, the tumor cells were highly migratory and were able to eventually escape the area of treatment. CONCLUSIONS: These findings suggest this technology may be ultimately applicable to patients with deep-seated inoperable tumors, but as currently formulated, complete tumor eradication would be highly unlikely. Future studies should focus on targeting the migratory potential of surviving cells.
Assuntos
Antineoplásicos Fitogênicos/uso terapêutico , Glioblastoma/tratamento farmacológico , Hidrogéis/química , Paclitaxel/uso terapêutico , Peptídeos/química , Animais , Antineoplásicos Fitogênicos/química , Linhagem Celular Tumoral , Sistema Nervoso Central/patologia , Portadores de Fármacos/química , Glioblastoma/mortalidade , Glioblastoma/patologia , Humanos , Camundongos , Camundongos Endogâmicos NOD , Camundongos SCID , Paclitaxel/química , Taxa de Sobrevida , Temozolomida/química , Temozolomida/uso terapêutico , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
BACKGROUND: Supratentorial hemangioblastomas are rare tumors, most commonly occurring in the sellar/suprasellar region, cerebrum, and ventricle. They are generally found in patients with von Hippel Lindau disease but have infrequently been reported in patients without this syndrome. CASE DESCRIPTION: A 35-year-old woman with a history of neurofibromatosis type 1 presented to our care with visual loss and headaches. Magnetic resonance imaging of the brain demonstrated an 8-mm cystic, contrast-enhancing lesion abutting the optic chiasm and optic tracts. The patient's endocrine profile was unremarkable. The tumor was resected using an endoscopic expanded transsphenoidal approach. Pathologic evaluation was consistent with hemangioblastoma. Postoperatively, the patient experienced an improvement in her visual symptoms. CONCLUSIONS: Hemangioblastoma should be included in the differential of sellar/suprasellar mass lesions, particularly in patients with von Hippel Lindau disease. Small suprasellar lesions may be safely and effectively removed using an expanded transsphenoidal approach.