January 15 2008 Clinical Cancer Research Highlights

Selected Articles from the January 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 Clinical Cancer Research is published. Click on the article title to view the complete article.

View the Table of Contents for the January 15 issue of Clinical Cancer Research.

Flavopiridol Inhibits the Growth of Rhabdoid Tumors

Smith et al.

Page 523

Aggressive and incurable pediatric malignancies, rhabdoid tumors depend on cyclin D1 for their genesis and survival. To therapeutically target the cyclin/cyclin dependent kinase (cdk) axis in rhabdoid tumors, Smith and colleagues investigated the effect of a pan-cdk inhibitor, flavopiridol, on rhabdoid tumors both in vitro and in vivo. Flavopiridol inhibited rhabdoid cell growth, arrested G1 and G2, and induced apoptosis in vitro. Using an in vivo model, the investigators showed that flavopiridol inhibits the growth of xenografted rhabdoid tumors and that this inhibition correlates with p21 induction and cyclin D1 down-modulation. These results indicate that flavopiridol is a potential new chemotherapeutic agent in fighting rhabdoid tumors.

MicroRNAs Predict Survival in Hepatocellular Carcinoma

Jiang et al.

Page 419

MicroRNA expression is known to be deregulated in a number of human cancers. To explore the relationship between microRNA expression and hepatocellular carcinoma (HCC), Jiang and colleagues used real-time PCR to profile microRNA expression in HCC specimens. They found that many microRNAs were upregulated in cirrhotic, hepatitis-positive liver specimens, compared with uninfected, noncirrhotic samples. By analyzing microRNA expression levels along with survival data in patients with HCC, Jiang and colleagues were able to identify two groups of patients: those with low microRNA expression and poor survival, and those with high microRNA expression and good survival. These results suggest that microRNA expression profiles may be a prognostic indicator of disease outcome in HCC.

The Role of Iron in Esophageal Adenocarcinoma

Boult et al.

Page 379

There is growing evidence that iron is important in regulating the development of esophageal adenocarcinoma, though how iron mediates carcinogenesis at the molecular level remains unclear. Boult and colleagues have shown that the cellular iron transport proteins transferin receptor 1 (TfR1) and divalent metal transporter 1 (DMT1), which are essential in the capture of circulating transferrin-bound iron, are overexpressed in esophageal adenocarcinoma. This suggests that these iron transport proteins are involved in the progression of Barrett’s metaplasia to esophageal adenocarcinoma. Overexpression of TfR1 and DMT1 was further associated with iron deposition in tumors, which may be crucial for mediating cellular proliferation. The results of these investigations suggest that strategies involving iron chelation may provide a platform for therapeutic intervention in managing patients with esophageal disease.

Diversity During DCIS Progression

Allred et al.

Page 370

Ductal carcinoma in situ (DCIS) is the immediate precursor of most human invasive breast cancers. Using conventional methodology, Allred and colleagues found a broad range of histological and biological diversity among cases of DCIS, which was nearly identical to the spectrum of diversity that exists in invasive breast cancers. Using more refined methods, the investigators found broad diversity within individual cases of DCIS (including luminal, basal, and erbB2-intrinsic subtypes) and discovered that this diversity was highly correlated with mutations in p53. These findings suggest that there is a great deal of plasticity during the gradual evolution of poorly differentiated tumors from well-differentiated tumors and that this progression is accelerated by genetic instability.

January 15 2008 Clinical Cancer Research Highlights

Selected Articles from the January 15, 2008 Issue

Flavopiridol Inhibits the Growth of Rhabdoid Tumors

MicroRNAs Predict Survival in Hepatocellular Carcinoma

The Role of Iron in Esophageal Adenocarcinoma

Diversity During DCIS Progression

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