Nicotine Patch, Gum May Undermine Chemo

John (Gold)
John (Gold)

April 3rd, 2006, 3:16 am #1

Nicotine Patch, Gum
May Undermine Chemo
April 2, 2006

By RANDOLPH E. SCHMID

The Associated Press
Filed at 1:12 p.m. EST

WASHINGTON (AP) -- Lung-cancer patients who use nicotine supplements such as patch or gum to help them quit smoking may undermine their chemotherapy.

Nicotine is not known to cause cancer, but it can protect cancer cells from some of the most widely used chemotherapy drugs, researchers reported Sunday at a cancer meeting.

Srikumar Chellappan of the University of South Florida and colleagues studied the effects of nicotine on lung cancer cells that were treated with three commonly used drugs in cancer therapy -- gemcitabine, cisplatin and taxol.

The laboratory research focused on human nonsmall cell lung cancer, which accounts for 80 percent of all lung cancers. In chemotherapy, exposure to the chemicals causes cancer cells to self-destruct in a process called apoptosis.

When nicotine was present, the cells increased production of a pair or proteins, XIAP and survivin, that protected the cells from apoptosis.

"Our findings are in agreement with clinical studies showing that patients who continue to smoke have worse survival profiles than those who quit before treatment," the researchers said.

"They also raise the possibility that nicotine supplementation for smoking cessation might reduce the response to chemotheraputic agents," they added in a report appearing in next week's online edition of Proceedings of the National Academy of Sciences.

The findings also were being presented at the annual meeting of the American Association for Cancer Research in Washington.

For smokers with lung cancer, "the best thing is to stop as soon as they can," Chellappan said in a telephone interview. They should avoid nicotine in all forms, not just smoking, he said, adding "that is easier said than done."

"There are a lot of smoking cessation programs, behavioral rather than chemical based," he noted. "That would be the best thing to quit smoking."

Dr. John Stevens, a vice president of the American Cancer Society, said if there were anyway that someone "could be induced to quit without using nicotine substitutes, then that would be my suggestion."

"However, if there is no other way, I would opt for the lesser of two evils, and the lesser is to quit smoking by whatever means," Stevens, who was not part of the research team, said in a telephone interview.

Dr. Nithya Ramnath, a lung-cancer specialist at the Roswell Park Cancer Institute in Buffalo, N.Y., agreed on the need for lung-cancer patients to stop smoking. But Ramnath stopped short of saying they should avoid using things such as a nicotine patch to help them do so.

The research was done in a laboratory and it can be a leap of faith to assume that it would work the same in humans, said Ramnath, who was not part of Chellappan's team.

"At this point we tell patients we do know that treatment effects are going to be worse if they continue to smoke," she said in a telephone interview. "We tell them absolutely to stop smoking."

Chellappan's research adds detail to earlier findings by Dr. Phillip A. Dennis of the National Cancer Institute.
Copyright 2006 Associated Press. All rights reserved.
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Thanks Sallie for this important find!
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John (Gold)
John (Gold)

April 11th, 2006, 1:56 am #2

Nicotine inhibits apoptosis induced by chemotherapeutic drugs by up-regulating XIAP and survivin.

Proceedings of the National Academy of Sciences of the United States of America (PNAS), 2006 April 6;

Dasgupta P, Kinkade R, Joshi B, Decook C, Haura E, Chellappan S.

Department of Interdisciplinary Oncology, H. Lee Moffitt Cancer Center and Research Institute, University of South Florida, 12902 Magnolia Drive, Tampa, FL 33647.

Non-small cell lung cancer (NSCLC) demonstrates a strong etiologic association with smoking. Although nicotine is not carcinogenic, it can induce cell proliferation and angiogenesis and suppress apoptosis induced by certain agents. Here we show that nicotine inhibits apoptosis induced by the drugs gemcitabine, cisplatin, and taxol, which are used to treat NSCLCs. This protection correlated with the induction of XIAP and survivin by nicotine in a panel of human NSCLC cell lines, and depletion of XIAP and survivin ablated the protective effects of nicotine.

The antiapoptotic effects of nicotine were mediated by dihydro beta-erythroidine-sensitive alpha3-containing nicotinic acetylcholine receptors and required the Akt pathway. Chromatin immunoprecipitation assays demonstrated that nicotine stimulation caused an increased recruitment of E2F1 and concomitant dissociation of retinoblastoma tumor suppressor protein (Rb) from survivin promoter in A549 cells. Moreover, ablation of E2F1 levels caused abrogation of the protective effects of nicotine against cisplatin-induced apoptosis in A549 cells whereas ablation of signal transducer and activator of transcription 3 levels had no effect.

These studies suggest that exposure to nicotine might negatively impact the apoptotic potential of chemotherapeutic drugs and that survivin and XIAP play a key role in the antiapoptotic activity of nicotine.

PMID: 16601104 [PubMed - as supplied by publisher]
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John (Gold)
John (Gold)

April 11th, 2006, 2:04 am #3

Imagine being a smoker and bombarded by two decades of pharmaceutical industry marketing that has brain washed you into believing that pharmaceutical nicotine is the key to quitting, that it doubles your chances. Now try to imagine the catch-22 of being told your treatment battle against lung cancer probably won't be effective unless you first battle and arrest your chemical dependency upon nicotine.

Frightened by hair curling statistics such as one-third of all deaths during middle-age being attributable to smoking nicotine,that it causes half of all middle-age cancer deaths, or that each middle-age victim is loses an average of 20 to 25 years of life, sadly, each new study revelation drives nicotine addicts deeper into denial and despair.

Although few dependent upon nicotine understand the scientific harm jargon it can't sound good. According to the PANS study "previous studies have implied that nicotine may be genotoxic, forming adducts with DNA ... thereby causing mutations in vital genes leading to neoplastic transformation." "However recent evidence has shown that nicotine can also lead to sustained activation of mitogenic pathways, promote angiogenesis, and accelerate tumor growth rates and atherosclerosis."

Words like antiapoptotic, genotoxic, angiogenesis and atherosclerosis have little meaning when the chemical you are addicted is so captivating that despite more than 40% of smokers attempting to quit each year, half of all adult smokers are smoking themselves to death.

I wish we could bring them "all" here to spend a few hours with each of you. Instead I fear that it's getting harder to get through to them.

John (Gold x6)
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Kristie
Kristie

April 11th, 2006, 2:27 am #4

It seems to me that physicians saying things like this just affirm people's fears and gives them more excuses not to quit. Why do they do this?

For smokers with lung cancer, "the best thing is to stop as soon as they can," Chellappan said in a telephone interview. They should avoid nicotine in all forms, not just smoking, he said, adding "that is easier said than done."

"There are a lot of smoking cessation programs, behavioral rather than chemical based," he noted. "That would be the best thing to quit smoking."

Dr. John Stevens, a vice president of the American Cancer Society, said if there were anyway that someone "could be induced to quit without using nicotine substitutes, then that would be my suggestion."

"However, if there is no other way, I would opt for the lesser of two evils, and the lesser is to quit smoking by whatever means," Stevens, who was not part of the research team, said in a telephone interview.

Dr. Nithya Ramnath, a lung-cancer specialist at the Roswell Park Cancer Institute in Buffalo, N.Y., agreed on the need for lung-cancer patients to stop smoking. But Ramnath stopped short of saying they should avoid using things such as a nicotine patch to help them do so.

I think this gives the impression that it is impossible for some people to quit. Rubbish!

Kristie, nicotine free for 52 days
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John (Gold)
John (Gold)

October 26th, 2006, 5:56 pm #5

Nicotine patches may
boost intensive care risk
  • 19:30 25 October 2006
  • NewScientist.com news service
  • Roxanne Khamsi
Nicotine given to intensive care patients to ease their withdrawal from cigarettes may put them at a greater risk of death than going "cold turkey", researchers say.

A preliminary study of more than 200 smokers placed in intensive care suggests they are better off simply enduring withdrawal symptoms than receiving nicotine replacement therapy (NRT).

Nicotine replacement therapy has become common in hospitals' intensive care units (ICUs) in the last five to 10 years. The drug reduces withdrawal symptoms, such as headache and irritability, among smokers in these units, who are too sick to go to an area where they can smoke.

Bekele Afessa at the Mayo Clinic College of Medicine in Rochester, Minnesota, US, and colleagues expected to find that patients comforted by (NRT) fare better than smokers who do not receive it.

Heart power The team examined the intensive care records of 224 smokers, half of which received NRT, mostly via skin patches.

Surprisingly, they found that 18 of the patients on NRT died, compared with just three of the smokers that did not receive nicotine. Also, the average duration of an ICU stay for patients given nicotine was 24.4 hours, about 2 hours longer than their cold-turkey counterparts.

"We have to be aware that we may be doing some harm [by giving patients NRT]," Afessa warns.

He notes that many of the patients in the study had been admitted to the ICU because they had gone into sepsis due to an infection. Sepsis can cause the body to release myocardial depressant factor, a molecule that reduces the pumping power of the heart.

Nicotine may further weaken the hearts of these patients by causing the coronary artery feeding the heart, to narrow, he suggests. This would reduce the amount of oxygen being pumped to other organs in the body. Many of the ICU patients in the trial died of multiple organ failure.

Wake-up call Nicotine is known to cause a narrowing of the coronary artery in chronic smokers, but remains unknown whether short-term doses of the drug can have the same effect.

Experts say the results of the new study should encourage more research on how NRT affects hospital patients. "This is a wake-up call that we really need to study this," says Mark Rosen, president of the American College of Chest Physicians.

He adds, however, that a large prospective study is necessary to establish whether nicotine definitely causes an increased risk of death among patients.

Afessa presented the findings at the annual meeting of the American College of Chest Physicians (ACCP) in Salt Lake City, Utah, US, on Wednesday.
© Copyright Reed Business Information Ltd.
Source Link: http://www.newscientist.com/article/dn1 ... -risk.html
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