Navigation Links
Defeating nicotine's double role in lung cancer
Date:6/8/2009

A lung cancer treatment that inhibits nicotine receptors was shown to double survival time in mice, according to Italian researchers.

The results of the early phase animal model study were reported in the June 15 issue of the American Journal of Respiratory and Critical Care Medicine.

Changes in genes encoding nicotine receptors are strongly associated not only with the tendency to smoke, but with susceptibility to lung cancer. Nicotine exposure also heightens the expression of the nicotine receptors, which leads to increased cell proliferation and inhibition of apoptosis, further setting the stage for cancer.

Patrizia Russo, Ph.D. and Laura Paleari, Ph.D. of the Lung Cancer Unit of the National Cancer Research Institute in Genoa, Italy and colleagues from San Raffaele Pisana Scientific Institute for Research, Hospitalization and Health Care (IRCCS), Catholic University, Campus Biomedico University in Rome, Mario Negri Institute in Milan and CEA Gyf sur Yvette in France showed in past research that an antagonist of nicotine acetylcholine receptors (nAChRs), may serve as an anticancer agent. The antagonist, called d-tubocurarine/α-Cobratoxin (α-CbT), specifically targeted the α7 subunit of nAChRs, the area primarily associated with increased cell proliferation.

In this study, the authors took the research a step further and showed that α-CbT could inhibit non-small cell lung carcinoma (NSCLC) growth and prolong life in non-obese/severe combined immunodeficient (NOD/SCID) mice that had human NSCLC grafted to their lungs. This study attempted to mimic human cancer conditions more closely by delaying treatment until the tumors were well-established. In addition to control mice that were untreated, the researchers randomized one third of the mice to receive standard chemotherapy.

They found that NOD/SCID mice treated with the standard chemotherapy agent, cisplatin, had a 16 percent longer median survival time than untreated mice (p= 0.05). Mice treated with α-CbT, however, had an increased median survival time of 1.7-fold over the cisplatin-treated mice and 2.1-fold over the no-treatment controls (p=0.0005).

"The results of this study show that α-CbT, a powerful, high-affinity α-7-nAChR inhibitor, induces antitumor activity against NSCLC by triggering apoptosis," wrote Dr. Russo. "The prolonged survival of α-CbT-treated animals in our mouse model of NSCLC is most likely the result of several mechanisms, including various antiproliferative and antiangiogenic effects."

The research also found that unaffected (i.e., noncancerous) cells showed no inhibition of proliferation when treated with α-CbT, suggesting that the treatment would have limited if any toxic effects. Dr. Russo and colleagues postulated that this finding may be due to the reduced number of receptor binding sites on normal cells as opposed to cancerous cells. Conversely, they reported that cancer cells with the greatest number of receptor binding sites seemed to respond with the greatest sensitivity to the treatment.

"The goal of this research line is to explore the widest range of possibilities of intervention on the α7-nAChRs. We hope to move further on towards the clinical setting experimentation phase for the assessment of potentially new treatment strategies for NSCLC," said Dr. Russo.

An editorial in the same issue of the journal asked if nicotine may be to lung cancer what estrogen is to breast cancer. Eliot R. Spindel, M.D., Ph.D., of Oregon Health & Science University, stated that estrogen can stimulate the development of breast cancer and estrogen-receptor antagonists, such as tamoxifen, provide therapeutic benefit. In support of a carcinogenic role for estrogen, the incidence of breast cancer appears to be decreasing as estrogen hormone replacement therapy is being used less often. Likewise, nicotine may promote lung cancer yet nicotine receptor antagonists may offer treatment options for patients with lung cancer.

John Heffner, M.D., past president of the ATS stated that "this research clearly has profound clinical implications regarding the role of nicotine in stimulating lung cancer and nicotine receptor antagonists in treating the disease. The highly addictive nature of nicotine, however, complicates patients' ability to quit smoking and avoid ongoing nicotine exposure."

"This [addictive nature of nicotine] underscores the importance of potential FDA regulation of nicotine in tobacco products to limit exposure to this drug that promotes tumor growth," wrote Dr. Spindel.


'/>"/>

Contact: Keely Savoie
ksavoie@thoracic.org
212-315-8620
American Thoracic Society
Source:Eurekalert

Related medicine news :

1. Kids Brain Trust: A New Nonprofit Gives Parents Hope of Defeating Autism
2. Komen Foundation Support of Planned Parenthood Self-Defeating
3. Tobacco Industry Puts Profits Before Kids in Defeating Oregon Ballot Initiative
4. Mayo Clinic finds new pathology tests double sensitivity to detect bile duct and pancreatic cancers
5. Obesity and diabetes double risk of HF -- patients with both conditions very difficult to treat
6. Indias Non-Small-Cell Lung Cancer Drug Market Will Almost Double by 2013
7. Decho Doubles Number of Mozy Healthcare Customers
8. Chinese Non-Small-Cell Lung Cancer Drug Market Will More Than Double by 2013
9. Demand for Outpatient Diagnostic Imaging Forecast to Increase by Double Digits Across All Modalities Through 2012
10. Double-Lung Transplant Better for Long-Term Survival
11. Abbott Reports 16 Percent Earnings Growth in First Quarter; Confirms Double-Digit Earnings Growth Outlook for 2009
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:5/27/2016)... ... May 27, 2016 , ... In response to ... who are unaware of the plight of aphasia. In collaboration with the American ... Awareness” campaign. , The link between stroke and aphasia is relatively unknown, but ...
(Date:5/27/2016)... NY (PRWEB) , ... May 27, 2016 , ... Aimed ... inspiring human interest stories, which come courtesy of leaders in the nursing and health ... industry, from leading advocates and associations—namely Abilene Christian University. , As the nursing ...
(Date:5/26/2016)... ... ... Despite last week’s media reports hinting at a June rate hike after ... 2017 for an interest rate increase, according to Rajeev Dhawan of the Economic Forecasting ... Open Market Committee (FOMC) dot charts are of interest to the press for their ...
(Date:5/26/2016)... , ... May 26, 2016 , ... ... discovery of thousands of defective respirators, according to court documents and SEC filings. ... of William and Becky Tyler v. American Optical Corporation, Case No. BC588866, Los ...
(Date:5/26/2016)... ... May 26, 2016 , ... Connor Sports, through its Connor ... for the Tamika Catchings Legacy Tour that will commemorate the Indiana Fever ... basketball surfaces in all forms and levels of the game, Connor Sports has committed ...
Breaking Medicine News(10 mins):
(Date:5/27/2016)... -- Hutchison China MediTech (Chi-Med) (HCM) ... highly lucrative global oncology and immunology markets. HCM ... or best-in-class tyrosine kinase inhibitor (TKI) drugs, some ... HCM,s profitable Chinese healthcare business continues to benefit ... of the mid-to-late-stage pipeline during 2016-17 (including US ...
(Date:5/26/2016)... ALBANY, New York , May 26, 2016 ... Transparency Market Research "Medical Waste Management Market - U.S. Industry ... the medical waste management market in the U.S. was valued ... expand at a CAGR of 3.4% from 2015 to 2023 ... report provides exhaustive analysis of current and emerging needle free ...
(Date:5/26/2016)... 2016 Since its commercial introduction ... essential life science tool for conducting genetic studies in ... reveals in its new report that the industry sits ... powered by a range of new applications in the ... http://photos.prnewswire.com/prnh/20140723/694805 ) , Since the ...
Breaking Medicine Technology: