American Association for Cancer Research

August 1 Cancer Research Highlights

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

View the Table of Contents for the August 1 issue of Cancer Research.


Dietary COX-2 Inhibitor Delays Pancreatic Cancer Progression

Funahashi et al.

Page 7068

Cyclooxygenase-2 (COX-2) represents an intriguing target for cancer therapy and prevention. To evaluate the efficacy of a selective COX-2 inhibitor on the development of pancreatic cancer, Funahashi and colleagues used the conditional KrasG12D mouse model of pancreatic cancer. Dietary intake of the COX-2 inhibitor nimesulide delayed the progression of pancreatic intraepithelial neoplasias, designated pancreatic cancer precursor lesions, and was accompanied by a marked reduction of intrapancreatic prostaglandin E2 levels.


New Bioluminescence Resonance Energy Transfer Vector Uses a Single Live Cell

De et al.

Page 7175

Bioluminescence resonance energy transfer (BRET)–based assays are currently used for efficient and precision monitoring of various intracellular events including protein-protein interactions in normal and aberrant cellular pathways. De and coauthors described construction of a new BRET vector utilizing a photon-efficient mutant Renilla luciferase (Rluc-M or Rluc8) donor in combination with a GFP2 acceptor. The authors demonstrate the capacity of the new vector in an imaging-based drug screening protocol to measure in vivo protein functions directly from single living cells. Applications will include anticancer therapy screening in cell culture and in living small animals.


Monoclonal Antibody Inhibits Tumor Cell Growth via Potassium Current

Gómez-Varela et al.

Page 7343

The specific blockade of human Eag1 (hEag1), because of the implication of hEag1 in tumor biology, may offer an opportunity for the treatment of cancer. Gómez-Varela and coauthors described and validated the first rational design of a monoclonal antibody that selectively inhibits a potassium current in intact cells. Using this antibody specifically to block hEag1 function inhibits tumor cell growth both in vitro and in vivo. The particular antibody described, and the technique developed to make additional functional antibodies to Eag1, make it possible to evaluate the possibilities of the channel as a target for cancer therapy.


Dieli et al.γδ T cells protect animals against tumors, and readily enter tissues where they may be activated by “stress signals” (in humans) such as isoprenoid metabolites. However, γδ T cells are pleiotropic, requiring specific conditions to activate TRAIL and other antitumor effectors. Applying low-dose interleukin-2 with zoledronate (an antiresorptive osteoclast inhibitor that blocks protein isoprenylation) to hormone-refractory prostate cancer patients, Dieli and colleagues markedly increased effector/memory γδ T cells whose numbers correlated positively with objective clinical outcome over 12 months.


New Models for Elucidating Mechanisms of Prostate Cancer

Liao et al.

Page 7525

Liao et al.A spontaneous mouse model for prostate adenocarcinoma with simultaneous expression of a reporter gene like luciferase or EGFP should be valuable for monitoring growth, regression, or relapse of the tumor. Liao and colleagues described such a model in which the expression of a reporter gene in the tumor is not under the control of androgen, thus conferring the advantage in the scrutiny of different stages of prostate cancer irrespective of hormonal manipulations. These refined models should help to uncover mechanisms of prostate cancer progression and serve as convenient preclinical systems for evaluation of new regimens for prevention or treatment.

 


Estrogen Plus Progestin Lowers Colorectal Cancer Risk

Newcomb et al.

Page 7534

Current users of postmenopausal hormones have a 30–40% lower risk of colorectal cancer (CRC), although associations with specific types of hormones have been inconsistent and it is unclear whether some tumor types have a different risk. Newcomb and colleagues found that postmenopausal hormone preparations containing estrogen plus progestin, but not estrogen alone, were associated with a statistically significant reduction of CRC risk. A 40% reduction in microsatellite unstable–low or stable CRC risk associated with estrogen plus progestin use was observed, but there was no reduction in microsatellite unstable–high CRC risk.


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