TGF-β, Neuronal Stem Cells and Glioblastoma

Golestaneh, Nady; Mishra, Bibhuti

doi:10.1038/sj.onc.1208925

Cited by 86 publications

(60 citation statements)

References 125 publications

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“…All three isoforms TGFβ1, TGFβ2 and TGFβ3 are expressed in neurons and glial cells 36 . The respective TGFβ receptors are expressed in almost every mammalian cells, including cancer cells 40,41 . In adult healthy CNS, TGFβ2 and TGFβ3 are ubiquitous and usually co-expressed in the CNS 42 .…”

Section: Molecular Pathways and Tumorigenesismentioning

confidence: 99%

Aberrant signaling pathways in medulloblastomas: a stem cell connection

Rodini

Suzuki

Nakahata

et al. 2010

Arq. Neuro-Psiquiatr.

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Medulloblastoma is a highly malignant primary tumor of the central nervous system. It represents the most frequent type of solid tumor and the leading cause of death related to cancer in early childhood. Current treatment includes surgery, chemotherapy and radiotherapy which may lead to severe cognitive impairment and secondary brain tumors. New perspectives for therapeutic development have emerged with the identification of stem-like cells displaying high tumorigenic potential and increased radio-and chemoresistance in gliomas. Under the cancer stem cell hypothesis, transformation of neural stem cells and/or granular neuron progenitors of the cerebellum are though to be involved in medulloblastoma development. Dissecting the genetic and molecular alterations associated with this process should significantly impact both basic and applied cancer research. Based on cumulative evidences in the fields of genetics and molecular biology of medulloblastomas, we discuss the possible involvement of developmental signaling pathways as critical biochemical switches determining normal neurogenesis or tumorigenesis. From the clinical viewpoint, modulation of signaling pathways such as TGFb, regulating neural stem cell proliferation and tumor development, might be attempted as an alternative strategy for future drug development aiming at more efficient therapies and improved clinical outcome of patients with pediatric brain cancers. Key words: medulloblastoma, neurobiology, signal transduction, stem cells, transforming growth factor beta, biological therapy.Vias de sinalização aberrantes no meduloblastoma: uma conexão com célula-tronco RESUMO Meduloblastoma é um tumor maligno do sistema nervoso central (SNC). Na infância, representa o tumor sólido mais frequente e a principal causa de morte relacionada ao câncer. Tratamentos atuais incluem cirurgia, quimioterapia e radioterapia, que podem trazer prejuízos cognitivos e desenvolvimento de tumores secundários. Novas perspectivas terapêuticas surgem com a identificação de células-tronco em gliomas, as quais apresentam alto potencial tumorigênico e maior resistência à radioterapia e quimioterapia. A hipótese das células-tronco tumorais sugere que a transformação de células-tronco e/ou progenitores neurais do cerebelo está envolvida no desenvolvimento do meduloblastoma. Portanto, analisar alterações genéticas e moleculares envolvidas nesse processo é de grande importância na pesquisa básica e aplicada ao câncer. Nesse sentido, discutimos o possível envolvimento de vias de sinalização bioquímica críticas a ambos os processos de

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Section: Molecular Pathways and Tumorigenesismentioning

confidence: 99%

Aberrant signaling pathways in medulloblastomas: a stem cell connection

Rodini

Suzuki

Nakahata

et al. 2010

Arq. Neuro-Psiquiatr.

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“…4,6,7 Furthermore, altered or aberrant signaling is frequently observed in key developmental or differentiation pathways involving EGFR, PTEN, transforming growth factor b and Notch. 5,[8][9][10] Therefore, the identification of aberrant components of developmental pathways may reveal new prognostic factors and/or novel therapeutic targets.…”

mentioning

confidence: 99%

Polypyrimidine tract binding protein and Notch1 are independently re-expressed in glioma

et al. 2006

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“…Moreover, in sharp contrast with DOX, JI-34 elicited a downregulation of two important glial growth factors (42,43), FGF basic and TGFβ. This may also reflect stem cell maturation and a tendency to increased cellular mortality, because growth promoting cytokines (42) are able to stimulate the survival cascades (44).…”

Section: Discussionmentioning

confidence: 90%

“…This may also reflect stem cell maturation and a tendency to increased cellular mortality, because growth promoting cytokines (42) are able to stimulate the survival cascades (44). The decrease in TGFβ is especially important, because this cytokine not only stimulates malignant transformation and growth (43), but also promotes angiogenesis, epithelial-mesenchymal transition (EMT), invasion, and suppresses peritumoral immune responses (45). Further, deprivation of growth factors (2) may suspend the constitutive stimulatory activity of extracellular signal-regulated kinases/mitogen activated protein kinases (ERK/ MAPKs) over Bcl-2 (37).…”

Section: Discussionmentioning

confidence: 99%

Potentiation of cytotoxic chemotherapy by growth hormone-releasing hormone agonists

Jászberényi

Rick

Popovics

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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The dismal prognosis of malignant brain tumors drives the development of new treatment modalities. In view of the multiple activities of growth hormone-releasing hormone (GHRH), we hypothesized that pretreatment with a GHRH agonist, JI-34, might increase the susceptibility of U-87 MG glioblastoma multiforme (GBM) cells to subsequent treatment with the cytotoxic drug, doxorubicin (DOX). This concept was corroborated by our findings, in vivo, showing that the combination of the GHRH agonist, JI-34, and DOX inhibited the growth of GBM tumors, transplanted into nude mice, more than DOX alone. In vitro, the pretreatment of GBM cells with JI-34 potentiated inhibitory effects of DOX on cell proliferation, diminished cell size and viability, and promoted apoptotic processes, as shown by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide proliferation assay, ApoLive-Glo multiplex assay, and cell volumetric assay. Proteomic studies further revealed that the pretreatment with GHRH agonist evoked differentiation decreasing the expression of the neuroectodermal stem cell antigen, nestin, and up-regulating the glial maturation marker, GFAP. The GHRH agonist also reduced the release of humoral regulators of glial growth, such as FGF basic and TGFβ. Proteomic and geneexpression (RT-PCR) studies confirmed the strong proapoptotic activity (increase in p53, decrease in v-myc and Bcl-2) and antiinvasive potential (decrease in integrin α3) of the combination of GHRH agonist and DOX. These findings indicate that the GHRH agonists can potentiate the anticancer activity of the traditional chemotherapeutic drug, DOX, by multiple mechanisms including the induction of differentiation of cancer cells.peptide analogs | targeted therapy

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TGF-β, Neuronal Stem Cells and Glioblastoma

Cited by 86 publications

References 125 publications

Aberrant signaling pathways in medulloblastomas: a stem cell connection

Aberrant signaling pathways in medulloblastomas: a stem cell connection

Polypyrimidine tract binding protein and Notch1 are independently re-expressed in glioma

Potentiation of cytotoxic chemotherapy by growth hormone-releasing hormone agonists

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