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View the Table of Contents for the August 1 issue of Cancer Research.
Page 7068
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.
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.
Page 7450
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.
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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.