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November 15 Cancer Research Highlights

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Selected Articles from the November 15, 2007 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 Cancer Research is published. Click on the article title to view the complete article.

View the Table of Contents for the November 15 issue of Cancer Research.

Subtype of HER2+ Breast Cancers Identified

Alexe et al.

Page 10669

Most gene-expression–based classification schemes do not robustly cluster all HER2+ breast cancers, in part due to limitations and bias of clustering techniques used. Alexe and colleagues propose an alternate approach that first separates the HER2+ tumors using a gene amplification signal for Her2/neu amplicon genes and then applies consensus ensemble clustering separately to the HER2+ and HER2- clusters to look for further substructure. Their data suggest that early-stage HER2+ cancers associated with lymphocytic infiltration are a biologically distinct subtype with an improved natural history.

New Model Aids Detection of Colorectal Cancer

Santiago et al.

Page 10766

Santiago et al. Patients with colitis have an increased risk for developing colorectal cancer, but the mechanisms are still unknown. At present, the most commonly used marker for screening and prevention is dysplasia, which is subject to interphysician variability. Using the well established trinitrobenzene sulfonic acid model of colitis, Santiago and colleagues created a new rat model of colitis-associated colon cancer. This model will allow in-depth analysis of the transition from chronic inflammation to dysplasia, as well as provide a new tool to identify better potential markers for the detection and prevention of colorectal cancer.

Endostatin Inhibits Dissemination of Cancer

Yokoyama et al.

Page 10813

Yokoyama et al. During the early phase of ovarian cancer dissemination, tumor cells coopt and attach to preexisting vascular bed in the peritoneal cavity. Tumor cell seeding is mediated by the Integrin α5β1, which is also the major target for the angiogenesis inhibitor, endostatin. Yokoyama and colleagues investigated the ability of endostatin to inhibit tumor cell seeding of the peritoneum. Adenovirus-mediated expression of endostatin inside the peritoneum inhibited tumor cell seeding and vessel cooption. These studies demonstrate a paraendothelial mechanism by which endostatin can inhibit peritoneal dissemination of ovarian cancer.

Nitric oxide–donating nonsteroidal anti-inflammatory drugs (NO-NSAIDs) are an emergent class of pharmaceutical derivatives with promising utility as cancer chemopreventive agents. McIlhatton and colleagues found that the aspirin (ASA)- and NO-ASA–treated MMR-deficient cell lines displayed a dose-dependent suppression of microsatellite instability (MSI) that appeared as early as 8 weeks and gradually increased to include up to 67% of the microsatellite sequences. The doses required for stabilization by the ortho-NO-ASA and para-NO-ASA were 300- to 3000-fold lower than ASA. These results suggest that NO-ASA derivatives may be more effective at suppressing MSI in MMR-deficient cell lines than ASA and should be considered for chemopreventive trials with HNPCC carriers.

Silibinin Inhibits Prostate Tumor Progression in TRAMP Mice

Raina et al.

Page 11083

Silibinin is a flavonolignan isolated from milk thistle seeds. Raina and colleagues evaluated chemopreventive efficacy of silibinin against prostate cancer (PCa) growth and progression and associated molecular alterations in transgenic adenocarcinoma of the mouse prostate (TRAMP) model. Results indicated that dietary feeding of silibinin blocks PCa growth and progression at PIN stage in TRAMP mice by modulating IGF-IGFBP-3 axis and cell cycle regulators and via apoptosis induction. Because TRAMP model mimics human PCa progression, results suggest that silibinin has practical and translational potential in suppressing growth and neoplastic conversion of PIN to advanced stages of PCa in humans.

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