April 15 Highlights: CR

November 15, 2008 Cancer Research Highlights

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

View the Table of Contents for the November 15 issue of Cancer Research.

CHRNA Variants and Nicotine and NNAL Levels

Le Marchand et al.

Page 9137

The long arm of chromosome 15, which includes the nicotinic acetylcholine receptor A subunits 3 and 5 (CHRNA3 and CHRNA5) genes, has recently been identified as a susceptibility locus for lung cancer. It is not clear whether the link to lung cancer is direct or mediated through differences in smoking behavior. Le Marchand and colleagues used urinary biomarkers to show that carriers of the risk variants in CHRNA3 and CHRNA5 smoke more intensively and are exposed to a higher internal dose of a carcinogenic tobacco-specific nitrosamine per cigarette dose than noncarriers, suggesting that number of cigarettes per day is not an adequate measure of smoking dose.

Leptin-Related Tumor Response in Colon Cancer

Alonlon et al. Page 9413

Abolhassani et al. Page 9423

Tumor progression is governed by genetic events intrinsic to cancer cells as well as epigenetic and environmental factors such as nutrition. Leptin, a cytokine-like peptide, plays a role in regulating food intake and has been proposed as a link between nutrition uptake and colon tumor growth. Aloulou and colleagues report that higher expression of the leptin receptor isoform ObRb in tumors compared with homologous normal mucosa, but not leptin serum levels, was associated with patients’ progression-free survival. ObRb was also found to be more strongly expressed in tumors with high-level microsatellite instability, which is associated with good prognosis, than in tumors with microsatellite stability. In a related paper, Abolhassani and colleagues report that leptin triggers an inflammatory response in tumor tissue by directly stimulating colonocytes, which can then recruit T cytotoxic cells in the tumor microenvironment. These studies suggest that leptin receptor expression in tumors is involved in adaptive immune response in sporadic colon and rectal cancers and are the first to describe pathways by which factors involved in nutrient uptake may stimulate the tumor immune response in these cancers.

A Garlic Constituent Inhibits Prostate Cancer in a Mouse Model

Singh et al.

Page 9503

Identification of agents that are safe but can delay onset and/or progression of prostate cancer is highly desirable. Epidemiologic studies have shown that Allium vegetables such as garlic may lower the risk of various malignancies including prostate cancer. Singh and colleagues demonstrate that oral gavage of garlic constituent diallyl trisulfide (DATS), at doses that can be generated through dietary intake of Allium vegetables, significantly inhibits development of poorly-differentiated prostate cancer and pulmonary metastasis multiplicity in TRAMP mice without causing weight loss or any other side effects. These results merit clinical investigations to determine efficacy of DATS against prostate carcinogenesis in humans.

Fenretinide, Low-Dose Tamoxifen, and Insulin Sensitivity

Johansson et al.

Page 9512

The prevalence of metabolic syndrome is increasing worldwide and evidence indicates a link to breast cancer incidence. Because fenretinide, a synthetic retinoid, improves insulin action and glucose tolerance in obese mice and because tamoxifen regulates markers of metabolic syndrome, Johannson and colleagues investigated the effect of fenretinide and low-dose tamoxifen on insulin resistance in premenopausal women at risk for breast cancer. Overweight women had a seven-fold greater probability of normalizing HOMA, an index of insulin sensitivity, after two years of fenretinide, whereas tamoxifen had an opposite effect. These results support a role for fenretinide in improving metabolic syndrome, which may favorably affect breast cancer risk. In addition, the features of metabolic syndrome should be incorporated in the decision-making process regarding the use of tamoxifen as a breast cancer preventive agent.

Splicing Markers for Breast Cancer

Venables et al.

Page 9525
Venables et al.

Venables and colleagues describe a new approach for the identification of breast cancer markers that uses the ratio of alternatively spliced mRNAs as the indicator, rather than gene expression levels. The authors used a high-throughput reverse transcription-PCR–based system to monitor the alternative splicing profiles of 600 cancer-associated genes. In a blind screen, a classifier based on the 12 best cancer-associated splicing events correctly identified cancer tissues with 96% accuracy and a subset of these alternative splicing events could order tissues according to histopathologic grade. These results provide a simple alternative for the classification of normal and cancerous breast tumor tissues and underscore the putative role of alternative splicing in the biology of cancer.

November 15, 2008 Cancer Research Highlights

Selected Articles from the November 15, 2008 Issue

CHRNA Variants and Nicotine and NNAL Levels

Leptin-Related Tumor Response in Colon Cancer

A Garlic Constituent Inhibits Prostate Cancer in a Mouse Model

Fenretinide, Low-Dose Tamoxifen, and Insulin Sensitivity

Splicing Markers for Breast Cancer

Highlights

Highlights: Cancer Research

Highlights: CCR

Highlights: CEBP

Highlights: MCR

Highlights: MCT

AACR Journals

Cancer Research Home

Clinical Cancer Research Home

CEBP Home

Cancer Prevention Research Home

Molecular Cancer Research Home

Molecular Cancer Therapeutics Home

Cancer Reviews Online Home

Prevention Portal Home