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May 2008 Molecular Cancer Therapeutics Highlights

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Selected Articles from the May 1, 2008 Issue

The articles referenced in this Highlights section will be available online in HTML and PDF formats to all interested users at no charge until the next issue of Molecular Cancer Therapeutics is published. Click on the article title to view the complete article.

View the Table of Contents for the May 2008 issue of Molecular Cancer Therapeutics

Grading and Survival Prediction of Astrocytic Brain Tumours

Petalidis et al.

Page 1013

Histopathological grading of astrocytic tumours based on current WHO criteria offers a valuable but simplified representation of oncological reality and is often insufficient to predict clinical outcome. Petalidis and colleagues reported a new astrocytic tumour microarray gene expression dataset using Artificial Neural Networks to address grading of human astrocytic tumours, to derive transcriptional signatures from histopathological subtypes and to assess whether these signatures define survival prognostic subclasses over numerous published datasets. A novel set of 59 classifier genes was identified that formed three distinct functional classes, each characterizing a molecular tumour subtype. Survival prognosis using the tumour subtypes outperformed histopathological grading as well as tumour subtypes reported in other studies. 

Stroma-leukemia Cell Interactions Protect Leukemia Cells

Weisberg et al.

Page 1121

Leukemic CD34+ cells can persist in small numbers in the marrow of CML patients following years of treatment with imatinib, making the exploration of this area important for a better understanding of drug resistance mechanisms. Research by Weisberg and colleagues revealed the highest tumor burden and residual disease were in vivo in stroma-associated tissues in imatinib/nilotinib-treated mice, suggesting that significant reservoirs for tumor growth appear to be tissues that are able to support normal hematopoietic and malignant stem cell development. Partial stromal-mediated protection of leukemic cells from nilotinib treatment involved the cooperative interaction of members of a select panel of stromal-secreted viability factors. 

MRP7/ABCC10 Expression Marks Paclitaxel Resistance in NSCLC

Oguri et al.

Page 1150

Members of the multidrug-resistance-associated protein (MRP/ABCC) superfamily are primary active transporters that confer drug resistance by effluxing anticancer agents. Recently identified MRP7/ABCC10 was shown to mediate the ATP-dependent transport of several anticancer agents including paclitaxel. Oguri and colleagues found that the expression levels of MRP7/ABCC10 gene showed a significant correlation with paclitaxel resistance in non-small cell lung cancer (NSCLC) cells, and that the decreased MRP7/ABCC10 expression enhanced paclitaxel cytotoxicity in NSCLC cells concomitant with increased intracellular paclitaxel accumulation. Thus, MRP7/ABCC10 expression may be one of the candidate biomarkers for paclitaxel resistance in NSCLC. 

Raina and colleagues evaluated the chemopreventive efficacy of gallic acid, a major constituent of grape seed extract, against prostate cancer (PCa) progression in transgenic adenocarcinoma of the mouse prostate (TRAMP) model. Results indicated that gallic acid feeding inhibits PCa growth and progression to advanced stage adenocarcinoma in TRAMP mice via strong suppression of cell cycle progression and cell proliferation, and an increase in apoptosis. Since the TRAMP model closely mimics the human type of PCa progression, these findings suggest that gallic acid could be a useful agent for PCa prevention and intervention. 

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