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October 13th, 2008:

Success Of Nicotine Replacement Therapy Unproven

13 Oct 2008

As smokers spend millions of dollars purchasing over-the-counter nicotine replacement therapy, a Hunter researcher has revealed the treatments are of uncertain effectiveness when used alone.

Associate Professor Raoul Walsh from the Centre for Health Research and Psycho-oncology (CHeRP) reviewed 12 studies relating to the effectiveness of over-the-counter nicotine replacement therapy. He discovered that the results of the studies did not convincingly demonstrate that the therapy, when used alone without additional support, was effective in helping smokers to quit.

Associate Professor Walsh said his review revealed that the methods used in nicotine replacement therapy trials were very different from real life. Based on the results, people cannot make valid assumptions on the effectiveness of the therapies.

“Nicotine replacement therapies, such as nicotine gum, lozenges or patches, purchased at the local supermarket can be effective as part of an overall strategy to help people stop smoking. However we do not really know the long term success of over-the-counter nicotine replacement therapy when used alone without additional support.

“Many smokers regard patches as magic bullets in their quest to stop smoking. This may be misleading because minimal support, such as medical advice or telephone counselling, in addition to the patches may be the necessary ingredients for achieving modest success rates.”

Associate Professor Walsh said it was important that over-optimistic assumptions were not made about the effectiveness of the therapy when purchased over the counter.

“To gain realistic measures of success, future research must involve more innovative, rigorous controlled trials where nicotine dependence is adequately assessed.”

Associate Professor Walsh’s review findings are published in the latest edition of the journal Drug and Alcohol Review. He hopes the review will result in education programs that emphasise the need for people to use over-the-counter nicotine replacement therapy in conjunction with other strategies.

(Source: Drug and Alcohol Review: University of Newcastle: October 2008)

Signaling Pathway Through Which Nicotine Promotes Breast Cancer Migration Discovered

GEN News Highlights – 13 Oct 08

Researchers at the Beth Israel Deaconess Medical Center determined that breast epithelial-like MCF10A cells and cancerous MCF7 cells both express four subunits of nicotine receptor nAChR. When bound, it initiates a signaling process that promotes migration in mammary epithelial or tumor cells.

The treatment of these cells with nicotine enhanced the activity of protein kinase C (PKC)   without changing its expression level, the scientists reports. Nicotine also stimulated [3H]thymidine incorporation into the genome of these cells as well as forces serum-starved cells to enter S phase of the cell cycle, resulting in growth promotion.

Also on nicotine treatment, the mobility of MCF10A and MCF7 cells was enhanced, which could be blocked by the addition of nAChR or PKC inhibitor, the research team adds. Experiments using siRNA knockdown or ectopic expression of cdc42 showed that cdc42 functions as a downstream effector of PKC and is crucial in the regulation of nicotine-mediated migratory activity in the cells.

“The best known role of nAChR is in the nerve system,” according to Chang Yan Chen, Ph.D., M.D., lead author of the study. “Although cells from various tissue origins express different subunits of nAChR, we know very little about the functions of nAChR in nonneuronal cells and tissues, in particular in mammary cells.”

When injected into the tail of a mouse, the cancerous MCF7 cells migrated to the lungs. In vivo and in vitro studies indicated that nicotine is not a conventional carcinogen, thus no metastasis occurs with nicotine alone, according to the researchers. Rather, they say that it combines with other factors to enable tumorigenesis.

Scientists say the next step is to explore the effects of nicotine in relation to first- and second-hand exposure on breast cancer initiation and development. In particular, they want to study genetic backgrounds with loss or defect of different tumor suppressors.

The paper appears in Cancer Research.