Brain Tumors Research Today is a free monthly online journal that collates and summarizes the latest research about Brain Tumors, including details on symptoms, benign and malignant tumors, gliomas, screening, treatment.

Gli activity correlates with tumor grade in platelet-derived growth factor-induced gliomas.

Becher OJ, Hambardzumyan D, Fomchenko EI, Momota H, Mainwaring L, Bleau AM, Katz AM, Edgar M, Kenney AM, Cordon-Cardo C, Blasberg RG, Holland EC

Department of Cancer Biology and Genetics, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.

Gli signaling is critical for central nervous system development and is implicated in tumorigenesis. To monitor Gli signaling in gliomas in vivo, we created platelet-derived growth factor-induced gliomas in a Gli-luciferase reporter mouse. We find that Gli activation is found in gliomas and correlates with grade. In addition, we find that sonic hedgehog (SHH) is expressed in these tumors and also correlates with grade. We identify microvascular proliferation and pseudopalisades, elements that define high-grade gliomas as SHH-producing microenvironments. We describe two populations of SHH-producing stromal cells that reside in perivascular niche (PVN), namely low-cycling astrocytes and endothelial cells. Using the Ptc-LacZ knock-in mouse as a second Gli responsive reporter, we show beta-galactosidase activity in the PVN and in some tumors diffusely throughout the tumor. Lastly, we observe that SHH is similarly expressed in human gliomas and note that an intact tumor microenvironment or neurosphere conditions in vitro are required for Gli activity.

Published 2 April 2008 in Cancer Res, 68(7): 2241-9.
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Articles on Brain Tumors published 2 April 2008:

Identification of noninvasive imaging surrogates for brain tumor gene-expression modules.   Proc Natl Acad Sci U S A, 105(13): 5213-8.

Glioblastoma multiforme (GBM) is the most common and lethal primary brain tumor in adults. We combined neuroimaging and DNA microarray analysis to create a multidimensional map of gene-expression patterns in GBM that provided clinically relevant insights into tumor biology. Tumor contrast enhancement and mass effect predicted activation of specific hypoxia and proliferation gene-expression programs, respectively. Overexpression of EGFR, a receptor tyrosine kinase and potential therapeutic ... [Abstract] [Full-text]

Articles on Brain Tumors published 28 March 2008:

Low-grade gliomas: do changes in rCBV measurements at longitudinal perfusion-weighted MR imaging predict malignant transformation?   Radiology, 247(1): 170-8.

PURPOSE: To prospectively perform longitudinal magnetic resonance (MR) perfusion imaging of conservatively treated low-grade gliomas to determine whether relative cerebral blood volume (rCBV) changes precede malignant transformation as defined by conventional MR imaging and clinical criteria. MATERIALS AND METHODS: All patients gave written informed consent for this institutional ethics committee-approved study. Thirteen patients (seven men, six women; age range, 29-69 years) with biopsy-proved ... [Abstract] [Full-text]

Articles on Brain Tumors published 27 March 2008:

1p36 is a preferential target of chromosome 1 deletions in astrocytic tumours and homozygously deleted in a subset of glioblastomas.   Oncogene, 27(14): 2097-108.

Astrocytic, oligodendroglial and mixed gliomas are the commonest gliomas in adults. They have distinct phenotypes and clinical courses, but as they exist as a continuous histological spectrum, differentiating them can be difficult. Co-deletions of total 1p and 19q are found in the majority of oligodendrogliomas and considered as a diagnostic marker and a prognostic indicator. The 1p status of astrocytomas has not yet been thoroughly examined. Using a chromosome 1 tile path array, we ... [Abstract] [Full-text]

The genomic profile of human malignant glioma is altered early in primary cell culture and preserved in spheroids.   Oncogene, 27(14): 2091-6.

Screening of therapeutics relies on representative cancer models. The representation of human glioblastoma by in vitro cell culture models is questionable. We obtained genomic profiles by array comparative genomic hybridization of both short- and long-term primary cell and spheroid cultures, derived from seven glioblastomas and one anaplastic oligodendroglioma. Chromosomal copy numbers were compared between cell cultures and spheroids and related to the parental gliomas using unsupervised ... [Abstract] [Full-text]

Articles on Brain Tumors published 21 March 2008:

Ovarian hyperstimulation syndrome caused by an FSH-secreting pituitary adenoma.   Nat Clin Pract Endocrinol Metab, 4(4): 234-8.

BACKGROUND: A 40-year-old woman presented with galactorrhea and oligomenorrhea. She had a history of multiple ovarian cysts and pelvic pain. INVESTIGATIONS: Laboratory evaluation included measurements of the levels of estradiol, follicle-stimulating hormone, luteinizing hormone, prolactin, thyroid-stimulating hormone, free endogenous T4, the glycoprotein hormone alpha subunit, cortisol, adrenocorticotropic hormone, and insulin-like growth factor I. Radiological studies included MRI of the ... [Abstract] [Full-text]

Articles on Brain Tumors published 19 March 2008:

Therapeutic targets for medulloblastoma.   Expert Opin Ther Targets, 12(4): 449-61.

BACKGROUND: Present treatment of medulloblastoma, the most common malignant brain tumor in children, includes surgery, radiotherapy and chemotherapy. In spite of radical treatment, only about 70% of patients survive. Also side effects of the treatment are severe, mostly due to applied radiotherapy. OBJECTIVE: The following review highlights potential molecular targets for pharmacotherapy of medulloblastoma, as well as the directions in which, in the authors' opinion, the field will evolve in ... [Abstract] [Full-text]

Articles on Brain Tumors published 18 March 2008:

Bradykinin increases blood-tumor barrier permeability by down-regulating the expression levels of ZO-1, occludin, and claudin-5 and rearranging actin cytoskeleton.   J Neurosci Res, 86(5): 1153-68.

Bradykinin (BK) has been shown to open blood-tumor barrier (BTB) selectively and to increase permeability of the BTB transiently, but the mechanism is unclear. This study was performed to determine whether BK opens the BTB by affecting the tight junction (TJ)-associated proteins zonula occluden-1 (ZO-1), occludin, and caludin-5 and cytoskeleton protein filamentous actin (F-actin). In rat brain glioma model and BTB model in vitro, we find that the protein expression levels of ZO-1, occludin, and ... [Abstract] [Full-text]

Articles on Brain Tumors published 17 March 2008:

Transtemporal-transchoroidal approach and its transamygdala extension to the posterior chiasmatic cistern and diencephalo-mesencephalic lesions.   Acta Neurochir (Wien), 150(4): 317-27; discussion 327-8.

The aim of this report is to illustrate the successful surgical management of five patients with suprasellar retrochiasmatic and diencephalo-mesencephalic tumours, using a trans-amygdala extension of the trans-temporal/trans-choroidal fissure approach.The procedure is described for five surgically treated patients with such lesions that includes three retrochiasmatic craniopharyngiomas, one hypothalamic hamartoma, and one pilocytic astrocytoma in the left crus cerebri. The management procedure ... [Abstract] [Full-text]

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