|
Reports describe recent advances in Brain Cancer research
(Science Letter Via Thomson Dialog NewsEdge)
Data on Brain Cancer are outlined in reports from Netherlands, Japan and United States.
Study 1: Vessel cooptation supersedes angiogenesis in gliomatosis cerebri.
"Gliomas are the most common primary brain tumors, many of which (especially astrocytic and oligodendroglial neoplasms) are characterized by diffuse infiltrative growth in the preexisting brain tissue," scientists in the Netherlands report.
"Gliomatosis cerebri is a rare glial tumor and represents an extreme example of such diffuse infiltrative growth. This growth pattern not only hampers curative treatment but also allows for vessel cooptation rather than tumor angiogenesis as a way of vessel recruitment by the tumor tissue. The goal of this study was to establish the extent to which tumor angiogenesis occurs in gliomatosis cerebri," wrote H. Bernsen and colleagues, Radboud University Nijmegen.
"Computerized image analysis was performed to assess quantitatively two microvascular parameters (vessel density and diameter) in different areas of a brain harboring a gliomatosis cerebri."
According to the report, "these regions were the cerebral white and gray matter in which there was a diffuse infiltrative tumor, cerebral white and gray matter in which there was a more compact growth pattern of tumor cells, and normal cerebral white and gray matter. In addition, the authors performed immunohistochemical stainings for blood-brain barrier (BBB) characteristics (Glut-1 and PgP) on samples obtained in these different areas."
"The results of the quantitative analysis strongly indicated that in gliomatosis cerebri tumor, angiogenesis was completely absent, a finding that is corroborated by the fact that the microvasculature in gliomatosis cerebri persists in exhibiting immunohistochemical characteristics of the BBB."
"The results of this study may help resolve the difficulties in radiological detection and delineation of the diffuse infiltrative part of glial brain tumors and put the expectations for antiangiogenic treatment of such tumors into perspective," researchers concluded.
Bernsen and colleagues published their study in the Journal of Neurosurgery (Gliomatosis cerebri: quantitative proof of vessel recruitment by cooptation instead of angiogenesis. J Neurosurg, 2005;103(4):702-706).
For additional information, contact H. Bernsen, Radboud University of Nijmegen, Dept. Neurology, Center Med, Canisius Wilhelmina Hospital, Nijmegen, Netherlands.
Study 2: Cytokines maintain neovascular growth in gliomas subjected to hypoxia.
According to recent research from Japan, "angiogenesis is one of essential components for the growth of neoplasms, including malignant gliomas. However, tumor vascularization is often poorly organized and marginally functional due to tumor structural abnormalities, inducing regional or temporal hypoxic conditions and nutritional shortages in tumor tissues."
"We investigated how during angiogenesis migrating endothelial cells survive in these hypoxic and reduced nutritional conditions. Human brain microvascular endothelial cells (HBMECs) underwent apoptosis and necrosis after serum withdrawal. This endothelial cell death was blocked by recombinant vascular endothelial growth factor (VEGF) protein or the culture medium of U251 glioma cells exposed to hypoxia (H-CM)," wrote Y. Ueda and colleagues, Fukui University.
"Hypoxic treatment increased vascular endothelial growth factor (VEGF) and tumor necrosis factor alpha (TNF-alpha) expression in U251 glioma cells. H-CM activated nuclear factor-kappa B (NF kappa B) protein and increased the gene expression of antiapoptotic factors including Bcl-2, Bcl-X-L, survivin and X-chromosome-linked inhibitor of apoptosis protein (XIAP) in endothelial cells."
"The survival activity of H-CM for endothelial cells was abolished by two kinds of VEGF inhibitors [cyclopeptidic VEGF inhibitor and a VEGF receptor tyrosine kinase inhibitor (4-[(4'-chloro-2'-fluoro) phenylamino]-6, 7-dimethoxyquinazoline)] or NF kappa B inhibitors (ALLN and BAY 11-7082)."
"These VEGF inhibitors did not block the activation of NF kappa B induced by H-CM in endothelial cells. On the contrary, TNF-alpha antagonist WP9QY enhanced the survival activity of H-CM for endothelial cells and blocked NF kappa B activation induced by H-CM under serum-starved conditions," researchers indicated.
"Taken together, our data suggest that both the secretion of VEGF from glioma cells and activation of NF kappa B in endothelial cells induced by TNF-alpha are necessary for endothelial cell survival as they increase the expression of antiapoptotic genes in endothelial cells under conditions of serum starvation."
"These pathways may be one of the mechanisms by which angiogenesis is maintained in glioma tissues," scientists suggested.
Ueda and colleagues published their study in the Journal of Neurochemistry (Glioma cells under hypoxic conditions block the brain microvascular endothelial cell death induced by serum starvation. J Neurochem, 2005;95(1):99-110).
For additional information, contact T. Nakagawa, Fukui University, Dept. Neurosurgery, Shimoaizuki 23, Fukui 9101193, Japan.
Study 3: Scientists have identified novel tumor-specific isoforms of BEHAB/Brevican in human malignant gliomas.
"Malignant gliomas are deadly brain tumors characterized by diffuse invasion into the surrounding brain tissue. Understanding the mechanisms involved in glioma invasion could lead to new therapeutic strategies," scientists in the United States reported.
"We have previously shown that BEHAB/brevican, an extracellular matrix protein in the central nervous system, plays a role in the invasive ability of gliomas. The mechanisms that underlie BEHAB/brevican function are not yet understood, due in part to the existence of several isoforms that may have different functions," explained M.S. Viapiano and colleagues, Yale University.
"Here we describe for the first time the expression of BEHAB/brevican in human brain and characterize two novel glioma-specific isoforms, B/b(sia) and B/b(Delta g), which are generated by differential glycosylation and are absent from normal adult brain and other neuropathologies. B/b(sia) is an oversialylated isoform expressed by about half the high- and low-grade gliomas analyzed."
The investigators admitted, "B/b(Delta g) lacks most of the carbohydrates typically present on BEHAB/brevican and is the major up-regulated isoform of this protein in high-grade gliomas but is absent in a specific subset of low-grade, indolent oligodendrogliomas. B/b(Delta g) is detected on the extracellular surface, where it binds to the membrane by a mechanism distinct from the other BEHAB/brevican isoforms."
"The glioma-specific expression of B/b(Delta g), its restricted membrane localization, and its expression in all high-grade gliomas tested to date suggest that it may play a significant role in glioma progression and make it an important new potential therapeutic target."
The researchers concluded, "In addition, its absence from benign gliomas prompts its use as a diagnostic marker to distinguish primary brain tumors of similar histology but different pathologic course."
Viapiano and colleagues published their study in Cancer Research (Novel tumor-specific isoforms of BEHAB/Brevican identified in human malignant gliomas. Cancer Res, 2005;65(15):6726-6733).
For more information, contact M.S. Viapiano, Yale University, School of Medicine, Dept. Neurobiology, POB 208001, 333 Cedar St., SHM C405, New Haven, CT 06520, USA.
Keywords: New Haven, Connecticut, United States, BEHAB/Brevican, Brain Cancer, Brain Carcinoma, Central Nervous System, Central Nervous System Injury, Diagnostic Marker, Drug Development, Endocrinology, Neurology, Oncology, Tissue Engineering, Glioma Progression, Therapeutic Target.
This article was prepared by Science Letter editors from staff and other reports. Copyright 2006, Science Letter via NewsRx.com.
[ Back To TMCnet.com's Homepage ]
|
Find Solutions for Enterprises, SMBs & Service Providers at the INTERNET TELEPHONY Conference and EXPO West, September 16-18, 2008. Los Angeles, California.
