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GBM Cells (gbm + cell)
Selected AbstractsInhibition of telomerase in the endothelial cells disrupts tumor angiogenesis in glioblastoma xenograftsINTERNATIONAL JOURNAL OF CANCER, Issue 6 2008Maria Laura Falchetti Abstract Tumor angiogenesis is a complex process that involves a series of interactions between tumor cells and endothelial cells (ECs). In vitro, glioblastoma multiforme (GBM) cells are known to induce an increase in proliferation, migration and tube formation by the ECs. We have previously shown that in human GBM specimens the proliferating ECs of the tumor vasculature express the catalytic component of telomerase, hTERT, and that telomerase can be upregulated in human ECs by exposing these cells to GBM in vitro. Here, we developed a controlled in vivo assay of tumor angiogenesis in which primary human umbilical vascular endothelial cells (HUVECs) were subcutaneously grafted with or without human GBM cells in immunocompromised mice as Matrigel implants. We found that primary HUVECs did not survive in Matrigel implants, and that telomerase upregulation had little effect on HUVEC survival. In the presence of GBM cells, however, the grafted HUVECs not only survived in Matrigel implants but developed tubule structures that integrated with murine microvessels. Telomerase upregulation in HUVECs enhanced such effect. More importantly, inhibition of telomerase in HUVECs completely abolished tubule formation and greatly reduced survival of these cells in the tumor xenografts. Our data demonstrate that telomerase upregulation by the ECs is a key requisite for GBM tumor angiogenesis. © 2007 Wiley-Liss, Inc. [source] Telomerase inhibition by stable RNA interference impairs tumor growth and angiogenesis in glioblastoma xenograftsINTERNATIONAL JOURNAL OF CANCER, Issue 9 2006Roberto Pallini Abstract Telomerase is highly expressed in advanced stages of most cancers where it allows the clonal expansion of transformed cells by counteracting telomere erosion. Telomerase may also contribute to tumor progression through still undefined cell growth-promoting functions. Here, we inhibited telomerase activity in 2 human glioblastoma (GBM) cell lines, TB10 and U87MG, by targeting the catalytic subunit, hTERT, via stable RNA interference (RNAi). Although the reduction in telomerase activity had no effect on GBM cell growth in vitro, the development of tumors in subcutaneously and intracranially grafted nude mice was significantly inhibited by antitelomerase RNAi. The in vivo effect was observed within a relatively small number of population doublings, suggesting that telomerase inhibition may hinder cancer cell growth in vivo prior to a substantial shortening of telomere length. Tumor xenografts that arose from telomerase-inhibited GBM cells also showed a less-malignant phenotype due both to the absence of massive necrosis and to reduced angiogenesis. © 2005 Wiley-Liss, Inc. [source] The natural compound n -butylidenephthalide derived from Angelica sinensis inhibits malignant brain tumor growth in vitro and in vivo3JOURNAL OF NEUROCHEMISTRY, Issue 4 2006Nu-Man Tsai Abstract The naturally-occurring compound, n -butylidenephthalide (BP), which is isolated from the chloroform extract of Angelica sinensis (AS-C), has been investigated with respect to the treatment of angina. In this study, we have examined the anti-tumor effects of n -butylidenephthalide on glioblastoma multiforme (GBM) brain tumors both in vitro and in vivo. In vitro, GBM cells were treated with BP, and the effects of proliferation, cell cycle and apoptosis were determined. In vivo, DBTRG-05MG, the human GBM tumor, and RG2, the rat GBM tumor, were injected subcutaneously or intracerebrally with BP. The effects on tumor growth were determined by tumor volumes, magnetic resonance imaging and survival rate. Here, we report on the potency of BP in suppressing growth of malignant brain tumor cells without simultaneous fibroblast cytotocixity. BP up-regulated the expression of Cyclin Kinase Inhibitor (CKI), including p21 and p27, to decrease phosphorylation of Rb proteins, and down-regulated the cell-cycle regulators, resulting in cell arrest at the G0/G1 phase for DBTRG-05MG and RG2 cells, respectively. The apoptosis-associated proteins were dramatically increased and activated by BP in DBTRG-05MG cells and RG2 cells, but RG2 cells did not express p53 protein. In vitro results showed that BP triggered both p53-dependent and independent pathways for apoptosis. In vivo, BP not only suppressed growth of subcutaneous rat and human brain tumors but also, reduced the volume of GBM tumors in situ, significantly prolonging survival rate. These in vitro and in vivo anti-cancer effects indicate that BP could serve as a new anti-brain tumor drug. [source] Review: On TRAIL for malignant glioma therapy?NEUROPATHOLOGY & APPLIED NEUROBIOLOGY, Issue 3 2010J. M. A. Kuijlen J. M. A. Kuijlen, E. Bremer, J. J. A. Mooij, W. F. A. den Dunnen and W. Helfrich (2010) Neuropathology and Applied Neurobiology36, 168,182 On TRAIL for malignant glioma therapy? Glioblastoma (GBM) is a devastating cancer with a median survival of around 15 months. Significant advances in treatment have not been achieved yet, even with a host of new therapeutics under investigation. Therefore, the quest for a cure for GBM remains as intense as ever. Of particular interest for GBM therapy is the selective induction of apoptosis using the pro-apoptotic tumour necrosis factor-related apoptosis-inducing ligand (TRAIL). TRAIL signals apoptosis via its two agonistic receptors TRAIL-R1 and TRAIL-R2. TRAIL is normally present as homotrimeric transmembrane protein, but can also be processed into a soluble trimeric form (sTRAIL). Recombinant sTRAIL has strong tumouricidal activity towards GBM cells, with no or minimal toxicity towards normal human cells. Unfortunately, GBM is a very heterogeneous tumour, with multiple genetically aberrant clones within one tumour. Consequently, any single agent therapy is likely to be not effective enough. However, the anti-GBM activity of TRAIL can be synergistically enhanced by a variety of conventional and novel targeted therapies, making TRAIL an ideal candidate for combinatorial strategies. Here we will, after briefly detailing the biology of TRAIL/TRAIL receptor signalling, focus on the promises and pitfalls of recombinant TRAIL as a therapeutic agent alone and in combinatorial therapeutic approaches for GBM. [source] | ||||||||||