Tumores experimentais do sistema nervoso central: padronização de modelo em roedores utilizando a linhagem 9L

Michailowsky, Custódio; Niura, Flavio Key; Valle, Angela C.; Sonohara, Shigueko; Meneguin, Thales Dalessandro; Tsanaclis, Ana Maria Crous

doi:10.1590/s0004-282x2003000200013

Cited by 5 publications

(2 citation statements)

References 14 publications

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“…Para que o paciente diagnosticado com esse tipo de tumor apresente mais que um ano de sobrevida, é preciso muito conhecimento sobre a patogênese e a etiologia dos tumores malignos primários do Sistema Nervoso Central (SNC) como o glioma, para encaminhar para o melhor tratamento (Michailowsky et al, 2003).…”

Section: Tumores Cerebraisunclassified

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Estudo da marcação e biodistribuição da substância P utilizando Lutécio-177 como radiotraçador

Lima¹

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Aos meus pais que sempre acreditaram e confiaram em mim e pelo total apoio para concluir mais esta etapa. AGRADECIMENTOSA Deus, pela vida, pela saúde, por minha família e por mais uma vez não ter me desamparado em toda a preparação para este trabalho. À minha orientadora pela grande oportunidade que me concedeu, pela confiança, pela paciência, dedicação e por sua simplicidade em transmitir seus conhecimentos.Aos bolsistas por me acolherem com tanto carinho e atenção, por cada ajuda recebida, cada ensinamento, pela troca de conhecimento, pela paciência e pela amizade construída neste período, em especial: Adriana Vidal, Akin, Camila, Priscilla e Renata. À Dra. Maria Tereza Colturato e à Dra. Tatiana Lavinias pelo apoio. A Dra. Josefina pelos seus ensinamentos e esclarecimentos. À Diretoria de Radiofarmácia -DIRF onde todos os experimentos deste trabalho foram realizados. À Miriam Suzuki pela ajuda sempre que possível para realização dos experimentos com células. À Marcela e Raquel do Centro de Desenvolvimento da Tecnologia Nuclear (CDTN-MG) pela doação das células tumorais U-87 MG. À Neide do Biotério por disponibilizar os animais para os ensaios. À colaboração dos colegas da DIRF em especial: Idelí, Nathanael e Vivian. A toda minha família por todo o estímulo recebido, em especial: Claudionor e Patrícia, Claudia e Rubens, Claudete, sobrinhos, Tio Geraldo e Tia Margarida. Às minhas amigas: em especial Adriana Siqueira, por sempre me apoiar, acreditar nos meus sonhos e por sua amizade incondicional e Marcela pelas aulas de inglês. Aos colegas de trabalho: RESUMO Gliomas malignos são tumores cerebrais primários, resistentes a vários tratamentos, como quimioterapia, radioterapia, indução de apoptose e cirurgia. Uma alternativa para o tratamento dos gliomas malignos é a terapia radionuclídea. Essa técnica ABSTRACT Malignant gliomas are primary brain tumors, resistant to various treatments, as chemotherapy, radiotherapy, induction of apoptosis and surgery. An alternative for the treatment of malignant gliomas is the radionuclide therapy. This technique apply radiolabeled molecules that selectively bind to tumor cells producing cytotoxic effect by dose irradiation, and resulting in death of tumor cells. Most protocols for radionuclide therapy of malignant brain tumors involve the administration of peptides labeled with β emitting radioisotopes. The Substance P (SP) is an 11-amino acid neuropeptide, characterized by the C-terminal sequence Phe-X-Gly-Leu-Met-NH 2 . The use of SP labeled with different radionuclides including 177 Lu, have been proposed for in vivo treatment of tumors. SP is the most important target of neurokinin 1 receptors, overexpressed in malignant gliomas. The objective of this work was to study conditions of radiolabeling DOTA-SP with 177 Lu, the stability of labeled compound and in vivo and in vitro, to develop a protocol production and evaluate the potential of the radiopharmaceutical in the therapy of gliomas. The labeling conditions were optimized varying the temperature, reaction time, activity ...

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Section: Tumores Cerebraisunclassified

“…Glioblastoma multiforme (GBM) ou astrocitoma de grau IV é a forma mais (Michailowsky et al, 2003;Laks et al, 2010;National Cancer Institute, 2011).…”

Section: Gliomaunclassified

Estudo da marcação e biodistribuição da substância P utilizando Lutécio-177 como radiotraçador

Lima¹

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Immunophenotypic and Ultrastructural Validation of a New Human Glioblastoma Cell Line

et al. 2005

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1. A human glioma cell line, NG97, was established by Grippo et al. in 2001 from tissue obtained from a grade III astrocytoma (WHO, 2000). In this first study, the cell line grew as two morphologically distinct subpopulations: dendritic/spindle cells and small round cells. The injection of NG97 cells into nude mice induced an aggressive tumor characterized by: severe cytological atypia, vascular proliferation and pseudopalisading necrosis (glioblastoma multiforme features). 2. The purpose of the present study was to characterize the immunophenotype and ultrastructural aspects of this cell line, using the parental tumor, cultured cells and the xenotransplant, in order to assess its glial nature and possible divergent differentiation. 3. NG97 cells and xenotransplant expressed the main neuroglial markers (GFAP, S-100 protein, NSE and Leu-7) and showed no aberrant expression of other histogenetic markers. GFAP was similarly expressed in the parental tumor and in the cells in culture, but decreased in the xenotransplant. NSE expression was reduced in NG97 cells, but substantially recovered in the xenotransplant. This variability in expression of GFAP and NSE was interpreted as either a phenomenon of dedifferentiation or to microenvironmental selection of specific subclones. S-100 was equally expressed in the three contexts. The xenotransplant's ultrastructural features were those of a highly undifferentiated tumor. No significant immunophenotypic or ultrastructural differences between the two morphologically distinct populations were found. 4. Thus, our data demonstrate that NG97 cells constitute a pure glial-committed cell line, which may prove useful as a malignant glioma model in studies addressing pathophysiological, diagnostic and therapeutic issues.

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Standardization and Detailed Characterization of the Syngeneic Fischer/F98 Glioma Model

Mathieu

Lecomte

Tsanaclis

et al. 2007

Can. j. neurol. sci.

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296Malignant gliomas are aggressive brain tumors with a particularly poor prognosis. The standard treatment, consisting of maximal resective surgery followed by radiation and chemotherapy at recurrence, offers at best palliative control. Survival generally ranges from a few months to about 15 months for glioblastoma multiforme, the most aggressive of these lesions. 1 Many therapeutic strategies are currently under ABSTRACT: Introduction: Adequate animal glioma models are mandatory for the pursuit of preclinical research in neuro-oncology. Many implantation models have been described, but none perfectly emulate human malignant gliomas. This work reports our experience in standardizing, optimizing and characterizing the Fischer/F98 glioma model on the clinical, pathological, radiological and metabolic aspects. Materials and methods: F98 cells were implanted in 70 Fischer rats, varying the quantity of cells and volume of implantation solution, and using a micro-infusion pump to minimize implantation trauma, after adequate coordinates were established. Pathological analysis consisted in hematoxylin and eosin (H&E) staining and immunohistochemistry for GFAP, vimentin, albumin, TGF-b1, TGFb2, CD3 and CD45. Twelve animals were used for MR imaging at 5, 10, 15 and 20 days. Corresponding MR images were compared with pathological slides. Two animals underwent 18 F-FDG and 11 C-acetate PET studies for metabolic characterization of the tumors. Results: Implantation with 1x10 4 cells produced a median survival of 26 days and a tumor take of 100%. Large infiltrative neoplasms with a necrotic core were seen on H&E. Numerous mitosis, peritumoral infiltrative behavior, and neovascular proliferation were also obvious. GFAP and vimentin staining was positive inside the tumor cells. Albumin staining was observed in the extracellular space around the tumors. CD3 staining was negligible. The MR images correlated the pathologic findings.18 F-FDG uptake was strong in the tumors. Conclusion: The standardized model described in this study behaves in a predictable and reproducible fashion, and could be considered for future pre-clinical studies. It adequately mimics the behavior of human malignant astrocytomas. Can. J. Neurol. Sci.

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Tumores experimentais do sistema nervoso central: padronização de modelo em roedores utilizando a linhagem 9L

Cited by 5 publications

References 14 publications

Estudo da marcação e biodistribuição da substância P utilizando Lutécio-177 como radiotraçador

Estudo da marcação e biodistribuição da substância P utilizando Lutécio-177 como radiotraçador

Immunophenotypic and Ultrastructural Validation of a New Human Glioblastoma Cell Line

Standardization and Detailed Characterization of the Syngeneic Fischer/F98 Glioma Model

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