American Association for Cancer Research

March 15 Cancer Research Highlights

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

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


Lipid Bodies Implicated in Colon Cancer 

Accioly et al.

Page 1732

Increased lipid body numbers have been described in tumor cells; however, their functional significance in cancer has never been addressed. Accioly and colleagues demonstrated increased number of lipid bodies in tumor tissues from patients with adenocarcinoma of the colon when compared with adjacent normal tissue. Treatment with either aspirin or the fatty acid synthase inhibitor C75 significantly reduced the number of lipid bodies and PGE2 production in CACO-2 and in IEC-6 H-rasV12 cells, impacting cell proliferation. The authors’ results demonstrate that lipid bodies in colon cancer cells are dynamic and functional active organelles centrally involved in PGE2 synthesis and may potentially have implications for the pathogenesis of adenocarcinoma of colon. 
 

High Medulloblastoma Incidence in the Smo/Smo Mouse Model

Hatton et al.

Page 1768

Hatton et al. Towards the goal of developing an efficient mouse medulloblastoma model for preclinical studies, Hatton and colleagues developed the Smo/Smo medulloblastoma model, in which 94% of mice develop cerebellar tumors by two months of age. Tumor onset is thus predictable prior to symptom onset, which generally occurs at 4–5 months. These characteristics are ideal for preclinical studies and create a substantial window for monitoring tumor response to therapeutic agents. Additionally, the Smo/Smo model is the first mouse model to demonstrate tumor cells disseminating through the leptomeningeal membranes to the brain and spine, a feature common in human medulloblastoma cases. 


shRNA Treatment Inhibits Metastasis Development in Lung Cancer

Bulk et al.

Page 1896

Bulk and colleagues studied the metastasis inducer S100P as a novel target for antimetastatic therapy using RNAi. Plasmid-derived RNAi against S100P significantly decreased S100P protein expression in xenograft tumors and inhibited tumor angiogenesis in vivo. Importantly, development of lung metastasis after tumor resection was reduced by 50% in mice treated with shRNA against S100P. These findings suggest that RNAi can be an effective therapy to inhibit metastasis development. 


Roberts et al.PF-562,271 is a highly selective and potent inhibitor of focal adhesion kinase (FAK). The molecule is an ATP-competitive inhibitor, as demonstrated by the co-crystallization of the compound in the ATP-binding pocket. Unlike previous approaches that disrupt FAK function by perturbing FAK localization to the focal adhesions, PF-562,271 uniquely allows the elucidation of the role of FAK activity in the study of FAK function. Roberts and colleagues found the compound was exceptionally potent in preventing tumor growth in multiple animal models, resulting in repeated regressions. The antitumor activity can, in part, be attributed to an apoptotic and antiangiogenesis mechanism of action in vivo. This molecule was well tolerated in Phase I clinical testing, resulting in multiple metabolic responses. 


Silymarin Prevents Hepatocellular Carcinoma in Mice

Wu et al.

Page 2033

Wu et al.Silymarin is an herbal medicine and dietary supplement very widely used in the treatment of chronic liver diseases. As such, the effectiveness of silymarin as a chemopreventive agent for hepatocellular carcinoma is highly important. Wu and colleagues provided in vivo evidence demonstrating that silymarin exerts beneficial effects on the early stages of liver pathogenesis, preventing and delaying liver carcinogenesis. The effectiveness of silymarin on hepatocellular carcinoma prevention, as modeled in this study using HBV X protein transgenic mice, is an important step forward in identifying how and why silymarin works.  


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