© Oxford University Press 2006.
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WINS Trial of Fat Reduction in Breast Cancer PatientsEpidemiology studies have suggested that dietary fat intake might be associated with breast cancer incidence or recurrence, although findings have been inconsistent. The Women's Intervention Nutrition Study (WINS) randomized trial was designed to test whether a dietary intervention to reduce fat intake would increase relapse-free survival in women with resected early-stage breast cancer. Chlebowski et al. (p. 1767) report that women who received a low-fat eating plan and dietary counseling did reduce their intake of dietary fat. After a median follow-up of 5 years, women in this intervention group had a slightly lower risk of relapse than women in the control group, although the difference was of borderline statistical significance. In exploratory secondary analyses, the effect was stronger in women with hormone receptor–negative cancer.
In an editorial, Thiébaut et al. (p. 1753) discuss several factors that complicate interpretation of the WINS results, including the higher frequency of mastectomy and the greater weight loss in the intervention group. Nevertheless, they write that the trial made several important contributions, including demonstrating that it is possible to implement a complex lifestyle intervention.
Cost Analysis of Palliative Radiotherapy for NSCLC
Radiotherapy is used to alleviate the symptoms of poor-prognosis patients with non–small-cell lung cancer (NSCLC), but it is unclear whether a short- or long-course radiotherapy schedule provides better value for the money. Van den Hout et al. (p. 1786) conducted a cost–utility analysis of a Dutch randomized trial of 297 patients with inoperable non–small-cell lung cancer, which found that long-course radiotherapy provided prolonged palliation and better survival than short-course radiotherapy. The analysis showed that, during their remaining lifetime, patients who received long-course radiotherapy had a quality of life that was more highly valued than patients who received short-course radiotherapy. This difference was due mainly to longer survival rather than to improved quality of life. The authors conclude that long-course palliative radiotherapy provides an acceptable value for the money by current economic benchmarks.
Breast Cancer Initiating Cells and Radiation Treatment
To determine how breast cancer initiating cells respond to radiation treatment, Phillips et al. (p. 1777) propagated cancer initiating cells from several breast cancer cell lines as spherical colonies, or mammospheres. They compared the responses of the mammospheres and of monolayer cultures of the same cell lines to a radiation treatment regimen similar to that given to breast cancer patients. The authors found that, after radiation treatment, fewer cells of the monolayer cultures than mammospheres survived. In addition, irradiated monolayer cultures had higher levels of reactive oxygen species and higher amounts of phosphorylated histone H2AX than irradiated mammospheres. The authors conclude that the relative resistance of breast cancer initiating cells to short courses of radiation treatment may partially explain the accelerated repopulation of breast cancer cells during gaps in radiotherapy.
In an editorial, Diehn and Clarke (p. 1755) provide an overview of the stem cell model of tumorigenesis and discuss how the findings of Phillips et al. contribute to current efforts to determine how stem and initiating cells affect the response of tumors to radiation and chemotherapy. They point out questions that the results raise, highlight limitations of the study design, and make suggestions for future studies on this topic.
Risk Model for Radiation-Induced Leukemia
Second cancers induced by radiation therapy are a clinically important issue. Shuryak et al. (p. 1794) extended an earlier model of the risk of radiation-induced solid tumors to leukemia by including the effect of repopulation by undamaged hematopoietic stem cells that have migrated to the irradiation site through the bloodstream. They found that the new model provided risk estimates for radiation-induced leukemia that were consistent with published values over a wide range of therapeutic radiation doses. The authors conclude that their model predicts the risk of radiation-induced leukemia with reasonable accuracy.
Cromolyn, S100P, and Growth of Pancreatic Cancer Cells
S100P, a member of the S100 protein family that interacts with the receptor for advanced glycation end-products (RAGE), is expressed in more than 90% of pancreatic tumors and is associated with pancreatic tumor growth and metastasis. Arumugam et al. (p. 1806) used mouse models of invasive pancreatic cancer to determine whether cromolyn, an anti-allergy drug that is known to bind to other members of the S100 protein family, could inhibit S100P activity and block the growth and invasiveness of pancreatic cancer cells. The authors found that, in vitro, cromolyn blocked the S100–RAGE interaction and inhibited S100P-stimulated pancreatic tumor cell proliferation and invasion. In vivo, cromolyn inhibited the growth of xenograft pancreatic tumors and increased the efficacy of gemcitabine, a drug that is currently used to treat pancreatic cancer. The authors conclude that cromolyn inhibits tumor growth and improves the effectiveness of gemcitabine in tumor models by binding to S100P and blocking its interaction with RAGE.
Statin Use and Risk of Prostate Cancer
The cholesterol-lowering drugs known as statins have both pro-apoptotic and antimetastatic activity. Some observational studies have yielded inverse associations between statin use and a number of different cancer types, including prostate cancer, but others have not shown such associations. Platz et al. (p. 1819) examined statin use and risk of both total and advanced prostate cancer in a large prospective cohort study of nearly 35,000 men. Current statin users had lower risks of both advanced and metastatic prostate cancer than past or never users of statins, and the risk of advanced disease was lower with longer statin use. However, there was no association between statin use and the risk of all forms of prostate cancer.
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