March 1 Clinical Cancer Research Highlights

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Selected Articles from the March 1, 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 Clinical Cancer Research is published. Click on the article title to view the complete article.

View the Table of Contents for the March 1 issue of Clinical Cancer Research.

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Viral Tumor Imaging

Fu et al.
Page 1453

Epstein-Barr virus (EBV) is associated with a variety of malignancies. The EBV thymidine kinase (TK) is either not expressed or is expressed at very low levels in EBV-associated tumors. However, EBV-TK expression can be induced with several chemotherapeutic agents that promote viral lytic induction. Ex vivo biodistribution studies with [125I]FIAU showed that uptake and retention of radiolabeled FIAU was specific for cells that express EBV-TK. Planar gamma imaging of EBV(+) Burkitt’s lymphoma xenografts in mice demonstrated [125I]FIAU localization within tumors following treatment with one such induction agent, bortezomib. These results indicate the feasibility of imaging chemotherapy-mediated viral lytic induction by radiopharmaceutical-based techniques such as single photon emission computed tomography (SPECT) and positron emission tomography (PET).

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Bortezomib Trial for Pediatric Leukemia   

Horton et al.
Page 1516

Bortezomib, a proteasome inhibitor used in the treatment of multiple myeloma, inhibits NF-kappaB (NF-κB), a transactivating factor that is overexpressed in many cancers. Horton et al. performed a phase I pediatric bortezomib trial in children with relapsed leukemia. Bortezomib was administered twice weekly, every 2 weeks, and was well tolerated at 1.3 mg/m2. They examined apoptosis, IκB expression, and NF-κB activity in leukemia cells before and after bortezomib administration. Bortezomib inhibited NF-κB activity, with a maximum observed effect at 24 hours posttreatment. In contrast, apoptosis and capsase 9 activation were observed at 6-8 hours following bortezomib treatment.  These studies suggested that bortezomib-induced apoptosis in leukemia may be NF-κB independent.

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Oral Lactoferrin Promising for Head and Neck Cancers

Wolf et al.
Page 1601

The naturally occurring glycoprotein lactoferrin has been shown to inhibit the growth of human cancers. Wolf et al. designed experiments to determine the mechanism of lactoferrin-induced tumor inhibition on head and neck squamous cell carcinoma (HNSCCA). In vitro, the inhibition of HNSCCA was dose-dependent, and lactoferrin was found to induce G1/G0 cell arrest.  In murine models, lactoferrin inhibited tumor growth and increased the quantity of tumor-infiltrating lymphocytes.  When T-cells were depleted, all tumor effects were abrogated.  Because oral lactoferrin is associated with minimal toxicity, this compound shows promise as a possible therapeutic agent for HNSCCA.

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Green Tea and Cox-2 Inhibitors Against Prostate Cancer

Adhami et al.
Page 1611

COX-2 inhibitors hold promise for cancer chemoprevention, but recent toxicity concerns suggest that new strategies are needed. One approach to overcome this limitation is to use lower doses of COX-2 inhibitors in combination with other established agents with complementary mechanisms. Adhami et al. tested the effect of EGCG, a promising chemopreventive agent from green tea, alone and in combination with specific COX-2 inhibitors on growth of human prostate cancer (PCa) cells both in vitro and in vivo. Their data suggested synergistic and/or additive effects of combinatorial chemopreventive agents and underscored the need for rational design of human clinical trials.

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