Despite improved knowledge and advanced treatments of gliomas, the overall survival rate for glioma patients remains low. Gliomas comprise of significant cell heterogeneity that contains a large number of multidrug resistant (MDR) phenotypes and cancer stem cells (CSCs), a combination that may contribute to the resistance to treatment. This article reviews the MDR related genes, major-vault protein (MVP), anti-apoptotic protein (Bcl-2) and the molecular mechanisms that may contribute to chemoresistance, in addition to the upregulated MDR phenotypes present in CSCs that has recently been identified in gliomas. Moreover, future potential therapies that modulate MDR phenotypes and CSCs are also reviewed. An improved understanding of MDR may lead to a combined treatment, targeting both CSCs and their protective MDR phenotypes leading eventually to attractive strategies for the treatment of gliomas.

CD133 (stem marker) and drug resistant gene (mdr1 and bcl-2) expression were detected in human glioblastoma and normal brain tissues. Glioma tissues contained higher ratio of CD133+ cells compared to normal tissues ( approximately 10 fold increase). The chemosensitivity assay showed that GOS-3 and NHA CD133+ possess greater resistance towards drugs compared to CD133- fractions. This study revealed for the first time that: a) serum deprivation enriched CD133 expression and demonstrated a direct co-expression between CD133 and drug resistant in GOS-3 cells and b) higher expression of CD133 and drug resistance were found in glioblastoma tissues in comparison to normal brain tissues.

This study investigated the effects of cholecystokinin-octapeptide (CCK-8) on pancreatic juice flow and its contents, and on cytosolic calcium (Ca2+) and magnesium (Mg2+) levels in streptozotocin (STZ)-induced diabetic rats compared to healthy age-matched controls. Animals were rendered diabetic by a single injection of STZ (60 mg kg(-1), I.P.). Age-matched control rats obtained an equivalent volume of citrate buffer. Seven weeks later, animals were either anaesthetised (1 g kg(-1) urethane; IP) for the measurement of pancreatic juice flow or humanely killed and the pancreas isolated for the measurements of cytosolic Ca2+ and Mg2+ levels. Non-fasting blood glucose levels in control and diabetic rats were 92.40 +/- 2.42 mg dl(-1) (n = 44) and >500 mg dl(-1) (n = 27), respectively. Resting (basal) pancreatic juice flow in control and diabetic anaesthetised rats was 0.56 +/- 0.05 ul min(-1) (n = 10) and 1.28 +/- 0.16 ul min(-1) (n = 8). CCK-8 infusion resulted in a significant (p < 0.05) increase in pancreatic juice flow in control animals compared to a much larger increase in diabetic rats. In contrast, CCK-8 evoked significant (p < 0.05) increases in protein output and amylase secretion in control rats compared to much reduced responses in diabetic animals. Basal [Ca2+]i in control and diabetic fura-2-loaded acinar cells was 109.40 +/- 15.41 nM (n = 15) and 130.62 +/- 17.66 nM (n = 8), respectively. CCK-8 (10(-8)M) induced a peak response of 436.55 +/- 36.54 nM (n = 15) and 409.31 +/- 34.64 nM (n = 8) in control and diabetic cells, respectively. Basal [Mg2+]i in control and diabetic magfura-2-loaded acinar cells was 0.96 +/- 0.06 nM (n = 18) and 0.86 +/- 0.04 nM (n = 10). In the presence of CCK-8 (10(-8)) [Mg2+]i in control and diabetic cells was 0.80 +/- 0.05 nM (n = 18) and 0.60 +/- 0.02 nM (n = 10), respectively. The results indicate that diabetes-induced pancreatic insufficiency may be associated with derangements in cellular Ca2+ and Mg2+ homeostasis.

The continuous advancements in cancer research have contributed to the overwhelming evidence of the presence of telomerase in primary and secondary tumours together with hsp90 and c-Myc. This review will discuss the important role of telomerase together with hsp90 and c-Myc within the initiation and progression of gliomas. Also it will review the differential expression of these genes in the different grades of gliomas and the possibility of new treatments targeting these specific genes.

Hsp90alpha's vital role in cell cycle progression and apoptosis together with its presence in gliomas and absence in normal tissue, make it a credible target for cancer therapy. Three sets of dsRNA oligos designed to align different regions of the hsp90alpha sequence were used to downregulate hsp90alpha. SiRNA 1, 2, and 3 resulted in significant levels of silencing of hsp90alpha after 48 hr treatment (p < .0001). Concurrent treatment of the glioma cell line U87-MG with siRNA 1 and temozolomide (TMZ) resulted in a 13-fold reduction in the dose of TMZ required to achieve a similar effect if TMZ was used alone.