Glioblastomas

Temozolomide crosses the blood brain barrier and can be used for the treatment of brain tumors (e.g., glioblastoma multiforme). The most common side effects are nausea and vomiting. 

Cancer Elevated levels of AEA in glioblastomas, increased levels of 2-AG in meningiomas, elevated levels of both AEA and 2-AG in colorectal carcinoma, with possible anti-tumour action Inhibitors of degradation (both FAAH and cellular re-uptake)... 

In addition to their inherent self-sustaining properties, brain tumor stem cells may be more resistant to chemotherapy and radiation therapy than other tumor cells. Bao et al. (2006) found glioma stem cells (CD133+) were relatively radioresistant compared to CD133- tumor cells and preferentially activated the DNA damage checkpoint response. This relative resistance to standard treatment approaches of tumor stem cells compared to the majority of other cells within a tumor may underlie our current inability to cure patients with aggressive brain tumors such as glioblastoma. 

Desbaillets 1, Tada M, de Tribolet N, Diserens AC, Hamou ME, Van Meir EG (1994) Human astrocytomas and glioblastomas express monocyte chemoattractant protein-1 (MCP-1) in vivo and in vitro. Int J Cancer 58 240-247... 

GaUi R, Binda E, OrfaneUi U, CipeUetti B, Gritti A, De Vitis S, Eiocco R, Foroni C, Dimeco F Vescovi A (2004) Isolation and characterization of tumorigenic, stem-hke neural precursors from human glioblastoma. Cancer Res 64 7011-7021... 

Rempel SA, Dudas S, Ge S, Gutierrez JA (2000) Identification and localization of the cytokine SDFl and its receptor, CXC chemokine receptor 4, to regions of necrosis and angiogenesis in human glioblastoma. Chn Cancer Res 6 102-111 Reya T, Morrison SJ, Clarke ME, Weissman IL (2001) Stem cells, cancer, and cancer stem cells. Nature 414 105-111... 

Tang Y, Shah K, Messerli SM, Snyder E, Breakefield X, Weissleder R (2003) In vivo tracking of neural progenitor cell migration to glioblastomas. Hum Gene Ther 14 1247-1254... 

Zagzag D, Lukyanov Y, Lan L, Ah MA, Esencay M, Mendez O, Yee H, Voura EB, Newcomb EW (2006) Hypoxia-inducible factor 1 and VEGF upregulate CXCR4 in glioblastoma implications for angiogenesis and glioma cell invasion. Lab Invest 86 1221-1232... 

EGFR or ERB-BI Codes for epidermal growth factor (EGFR) receptor Glioblastoma, breast cancer, squamous carcinoma... 

N-MYC Neuroblastoma, small cell lung cancer, and glioblastoma... 

Barbero S, Bonavia R, Bajetto A, et al. Stromal cell-derived factor la stimulates human glioblastoma cell growth through the activation of both extracellular signal-regulated kinases 1/2 and AKT. Cancer Res 2003 63 1969-1974. 

S9788. Comparison with 11 other MDR-modulating agents in a model of doxorubicin-resistant rat glioblastoma cells, Eur. J. Cancer 1993, 30, 1377-1383. 

Shir A, Ogris M, Wagner E, Levitzki A (2006) EGF receptor-targeted synthetic double-stranded RNA eliminates glioblastoma, breast cancer, and adenocarcinoma tumors in mice. PLoS Med 3 e6... 

P. Manning, C.J. McNeil, J.M. Cooper, and E.W. Hillhouse, Direct, real-time sensing of free radical production by activated human glioblastoma cells. Free Radical Bio. Med. 24, 1304-1309 (1998). 

BCNU-Loaded Polyanhydride Discs for Treatment of Glioblastoma Multiforma... 

The ability of 3-phosphoinositides to stimulate cell proliferation/survival via activation of Akt is countered by the 3-phosphatase PTEN, which hydrolyzes PI(3,4)P2 and PI(3,4,5)P3. A link between PTEN activity and 3-phosphoinositide content in cells is evident from the observations that (a) overexpression of PTEN results in a dramatic reduction in the cellular content of these lipids, and (b) 3-phosphoinositide concentrations are greatly elevated in mammalian PTEN-null cell lines [28]. Cells in which PTEN activity is reduced have increased tumori-genic properties, since Akt inhibits apoptosis and promotes cell survival. Conversely, PTEN activity programs the fate of the cell toward apoptosis. Mutations of PTEN have been shown to occur in a wide range of tumor types, but with a particularly high frequency in glioblastomas. 

PDGFR Overexpression and autocrine stimulation. Activation of blood vessel smooth muscle cells in the media Glioblastomas, Restenosis, Atherosclerosis... 

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