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Métodos Terapêuticos e Terapias MTCI
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1.
BMC Med Genet ; 19(1): 10, 2018 01 17.
Artigo em Inglês | MEDLINE | ID: mdl-29343221

RESUMO

BACKGROUND: Extraneural metastases are relatively rare manifestations of medulloblastoma. CASE PRESENTATION: We present the case of a young boy with group three MYCN-amplified medulloblastoma. He received multimodal chemotherapy consisting of gross total resection followed by postoperative craniospinal radiation and adjuvant chemotherapy. The patient developed extraneural metastases 4 months after the end of therapy. Literature review identifies the poor prognosis of MYCN-amplified medulloblastomas as well as extraneural metastases; we review the current limitations and future directions of medulloblastoma treatment options. CONCLUSION: To the best of our knowledge, this is the first molecularly characterized report of extraneural metastases of medulloblastoma in a child.


Assuntos
Meduloblastoma/genética , Proteína Proto-Oncogênica N-Myc/genética , Quimioterapia Adjuvante , Pré-Escolar , Radiação Cranioespinal , Ciclofosfamida/uso terapêutico , Relação Dose-Resposta à Radiação , Etoposídeo/uso terapêutico , Regulação Neoplásica da Expressão Gênica , Humanos , Isotretinoína/uso terapêutico , Imageamento por Ressonância Magnética , Masculino , Meduloblastoma/tratamento farmacológico , Meduloblastoma/radioterapia , Período Pós-Operatório , Proteínas Proto-Oncogênicas c-myc/genética , Vincristina/uso terapêutico
2.
Immunotherapy ; 8(6): 721-31, 2016 06.
Artigo em Inglês | MEDLINE | ID: mdl-27197540

RESUMO

Meningiomas are increasingly appreciated to share similar features with other intra-axial central nervous system neoplasms as well as systemic cancers. Immune checkpoint inhibition has emerged as a promising therapy in a number of cancers, with durable responses of years in a subset of patients. Several lines of evidence support a role for immune-based therapeutic strategies in the management of meningiomas, especially high-grade subtypes. Meningiomas frequently originate juxtaposed to venous sinuses, where an anatomic conduit for lymphatic drainage resides. Multiple populations of immune cells have been observed in meningiomas. PD-1/PD-L1 mediated immunosuppression has been implicated in high-grade meningiomas, with association between PD-L1 expression with negative prognostic outcome. These data point to the promise of future combinatorial therapeutic strategies in meningioma.


Assuntos
Antineoplásicos/uso terapêutico , Neoplasias do Sistema Nervoso Central/terapia , Neoplasias Hematológicas/terapia , Imunoterapia/métodos , Meningioma/terapia , Animais , Neoplasias do Sistema Nervoso Central/imunologia , Terapia Combinada , Receptores Coestimuladores e Inibidores de Linfócitos T/antagonistas & inibidores , Neoplasias Hematológicas/imunologia , Humanos , Meningioma/imunologia
4.
Eur J Endocrinol ; 174(4): R139-44, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26563980

RESUMO

Papillary craniopharyngioma (PCP) is an intracranial tumor that results in high levels of morbidity. We recently demonstrated that the vast majority of these tumors harbor the oncogenic BRAF V600E mutation. The pathologic diagnosis of PCP can now be confirmed using mutation specific immunohistochemistry and targeted genetic testing. Treatment with targeted agents is now also a possibility in select situations. We recently reported a patient with a multiply recurrent PCP in whom targeting both BRAF and MEK resulted in a dramatic therapeutic response with a marked anti-tumor immune response. This work shows that activation of the MAPK pathway is the likely principal oncogenic driver of these tumors. We will now investigate the efficacy of this approach in a multicenter phase II clinical trial. Post-treatment resection samples will be monitored for the emergence of resistance mechanisms. Further advances in the non-invasive diagnosis of PCP by radiologic criteria and by cell-free DNA testing could someday allow neo-adjuvant therapy for this disease in select patient populations.


Assuntos
Carcinoma Papilar/genética , Craniofaringioma/genética , Neoplasias Hipofisárias/genética , Mutação Puntual , Proteínas Proto-Oncogênicas B-raf/genética , Carcinoma Papilar/diagnóstico , Carcinoma Papilar/patologia , Ensaios Clínicos Fase II como Assunto , Craniofaringioma/diagnóstico , Craniofaringioma/patologia , Neoplasias das Glândulas Endócrinas/diagnóstico , Neoplasias das Glândulas Endócrinas/genética , Neoplasias das Glândulas Endócrinas/patologia , Ácido Glutâmico/genética , Humanos , Sistema de Sinalização das MAP Quinases/genética , Neoplasias Hipofisárias/diagnóstico , Neoplasias Hipofisárias/patologia , Valina/genética
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