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Smokers with Stroke in the Family 6 Times More Likely to Have Stroke Too 

A new study shows that people who are smokers and have a family history of brain aneurysm appear to be significantly more likely to suffer a stroke from a brain aneurysm themselves. The research is published in the December 31, 2008, online issue of Neurology, the medical journal of the American Academy of Neurology and will appear in the January 6, 2009, print issue of Neurology.

The type of stroke, called subarachnoid hemorrhage, is one of the bleeding types of stroke and is deadly in about 35 to 40 percent of people. . . .

“While all people should be advised to quit smoking, our findings suggest that there is an interaction so that if you smoke and you have a family history of aneurysms, you are at an extremely high risk of suffering a stroke from a ruptured brain aneurysm,” says study author Daniel Woo, MD, with the University of Cincinnati in Ohio and member of the American Academy of Neurology.

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• Drug Might Protect Smokers From Lung Damage, Researchers Say  

Mice that inhaled cigarette smoke five hours daily avoided lung damage in a study by eating a chemical compound.

The mice were exposed to smoke in a laboratory to study emphysema, a progressive lung disease that causes shortness of breath and often is fatal. The compound, CDDO-imidazole, boosted the animals’ production of antioxidants that keep lung cells from dying and decrease inflammation, according to a report today in the Proceedings of the National Academy of Sciences.

Cigarette smoke is the most common cause of emphysema. The research, from the Bloomberg School of Public Health at Johns Hopkins University in Baltimore, may show drugmakers where to focus efforts to treat the malady, said James Kiley, the director of the division of lung diseases at the National Heart, Lung, and Blood Institute.

“Is it going to bring a new therapy tomorrow?” said Kiley, who wasn’t involved in the study. “Absolutely not. We don’t have any therapies that will cure the disease or halt the progression once it’s started, so it’s a step toward that.

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Drug shields mice from chronic lung disease: study  

An experimental drug protected mice exposed to tobacco smoke from developing chronic lung disease, raising hope for a treatment in humans, U.S. researchers said on Monday.

They said the chemical CDDO-Im helped activate a master gene called Nrf2 that bolsters the lung's ability to fight off chronic obstructive pulmonary disease, or COPD, a condition that includes emphysema, chronic bronchitis and some types of serious chronic asthma.

"COPD is the 4th-largest killer in the world with no effective drugs," Shyam Biswal of Johns Hopkins School of Medicine in Maryland, who worked on the study, said in an e-mail.

In prior research, Biswal and colleagues found that Nrf2 works as a "master gene," turning on genes involved in protecting the lungs from pollution and cigarette smoke.

"The Nrf2 pathway is the major antioxidant and detoxifying response in the lungs. Therapies targeting this pathway need to be developed and tested in patients," said Biswal, whose study was published in the Proceedings of the National Academy of Sciences.

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• Gene Variant Tied to Smokers' Risk of Lung Cancer  

People may face an increased risk of lung cancer if they have a gene variant that metabolizes the most potent of cigarette smoke carcinogens, a new study says.

The ABCB1 and ABCC1 genes normally help protect the lungs by removing inhaled toxins. Specifically, they act on tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) -- a cigarette smoke component shown to cause lung cancer in rodents.

Researchers at Fudan University in Shanghai, China, recently identified common variants in the ABCB1 and ABCC1 genes (ABCB1 rs3842 or ABCC1 rs212090) tied to people with lung cancer that might indicate a person's increased risk of developing the disease. In particular, women and people under age 60 with ABCB1 rs3842 showed an increased risk of cancer. The variant was also linked to adenocarcinoma, a major type of lung cancer. . . .

The findings were published online Dec. 22 in Cancer and will appear in the Feb. 1, 2009, print issue of the journal.

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Scientist studies effects of heavy smoking and drinking  

The party never stops for mice in Todd Wyatt's laboratory at the University of Nebraska Medical Center, where researchers hope to learn how chronic heavy drinking and smoking often inflicts a double whammy on lungs.

The drinking water for some mice there is 40 proof, raising blood alcohol to the point they can't legally be at the wheel. The mice also smoke the equivalent of a pack a day, based on blood cotinine levels.

They lack only some Texas hold 'em tables and a country western jukebox, but sacrifices must be made to serious science.

Wyatt, a Ph.D researcher, hopes the five-year, $1.5 million study will explain everybody's apocryphal uncle Joe -- the relative who smokes and drinks daily, even on his 87th birthday.

Wyatt said whenever he talks about his research, someone always brings up uncle Joe.

Understanding what makes Joe immune to lung disease could lead to better treatments for COPD -- chronic obstructive pulmonary disease, an incurable syndrome afflicting 40 million people and for which there are no good treatments.

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Large international study identifies genetic susceptibility to lung cancer 

In a paper to be published in Nature Genetics on 2nd November, a worldwide consortium of investigators present a major breakthrough for understanding the genetic basis of lung cancer.

The results are based on the largest genetic study of lung cancer ever conducted, and was organised by the International Agency for Research on Cancer (IARC, Lyon, France), the Centre National de Génotypage (CNG, Evry, France), with support from the Institut National du Cancer (Paris, France).

The study brought together a research team from 18 countries who investigated DNA variants in more than 15,000 people: 6000 with lung cancer and 9000 without. The new lung cancer region is located on the 5th human chromosome and contains two known genes, TERT and CRR9, either of which might be the culprit. “We think TERT is the most likely candidate” CNG Director Mark Lathrop said. “It’s a gene that encodes part of telomerase, an enzyme critically linked to cancer development. It’s the stand out candidate”.

Two separate risk variants were found by the investigators, and they increased life time lung cancer risk by up to 60%, depending on the number of copies a person carries. The risk was also present in both smokers and never-smokers. Nevertheless, such a change in risk is dwarfed by the lung cancer risk that results from smoking tobacco. “So stopping smoking or never starting is still the best way to avoid lung cancer, irrespective of your genes” noted Dr Paul Brennan, head of the research group at IARC.

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• HORLEY: Could genes be a licence to smoke?  

Yet now the revolution in genetic science offers the chance to have treatments tailored to our personal DNA, and could soon identify those at least and greatest risk of certain diseases, such as smoking-related lung cancer. The consequences are not entirely benign, however; one leading oncologist goes so far as to claim that the tobacco industry could use such techniques to engineer a resurgence in smoking, and that it is just a matter of time before it succeeds in doing so.

The story starts eight years ago, when the 25,000 or so genes in human DNA were first identified by the Human Genome Project. . . .

The self-evident place to start would have been the genes known to metabolise tobacco, but as that has not yet borne fruit, the search will have to be broadened. "They will have to study the entire genome of large groups of people, which could take them five years. But the end result could be a gene-testing kit cheap enough to give as an 18th birthday present, so your children can find out how safe it is for them to start smoking."

The reason this would make sense for the tobacco companies is that, while the Government likes to tell smokers to quit or die, at least 80 per cent of them do not get lung cancer, and the precise mechanisms that link smoking and cancer are not well understood. . . .

Of course, the tobacco industry will never be able to claim outright that smoking could be made safe. Since 1998, when it was forced by a US court to cough up a quarter of a trillion dollars for the treatment of smoking-related diseases, it has been choosing its words carefully. Yet Dr David O'Reilly, the head of public health and scientific affairs at British American Tobacco, still foresees a day when BAT might sell a cigarette no more harmful than going out in the sun. . . .

In other words, just as we are now seeing personalised drugs tailored to our DNA in order to cure cancer, we can look forward to personalised cigarettes to help us avoid it.

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Probing Genetic Underpinnings Of Nicotine Addiction 

A new study from the Abramson Cancer Center and Department of Psychiatry in the University of Pennsylvania School of Medicine shows that smokers who carry a particular version of a gene for an enzyme that regulates dopamine in the brain may suffer from concentration problems and other cognitive deficits when abstaining from nicotine - a problem that puts them at risk for relapse during attempts to quit smoking.

The findings, newly published in the journal Molecular Psychiatry, pave the way to identify novel medications to treat nicotine addiction.

"These findings also provide an important step toward personalized therapy for nicotine addiction by clarifying the role of inherited genetic variation in smoking abstinence symptoms that promote relapse," says senior author Caryn Lerman, PhD, the Mary W. Calkins Professor in Penn's Department of Psychiatry and Scientific Director of Penn's Abramson Cancer Center.

"The new data identify a novel brain-behavior mechanism that plays a role in nicotine dependence and relapse during quitting attempts,"

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The chromosome 3p21.3-encoded gene, LIMD1, is a critical tumor suppressor involved in human lung cancer development 

Loss of heterozygosity (LOH) and homozygous deletions at chromosome 3p21.3 are common in both small and nonsmall cell lung cancers, indicating the likely presence of tumor suppressor genes (TSGs). . . .

Experimentally, LIMD1 is a bona fide TSG. Limd1−/− mice are predisposed to chemical-induced lung adenocarcinoma and genetic inactivation of Limd1 in mice heterozygous for oncogenic K-RasG12D markedly increased tumor initiation, promotion, and mortality. Thus, we conclude that LIMD1 is a validated chromosome 3p21.3 tumor-suppressor gene involved in human lung cancer development. LIMD1 is a LIM domain containing adapter protein that localizes to E-cadherin cell–cell adhesive junctions, yet also translocates to the nucleus where it has been shown to function as an RB corepressor. As such, LIMD1 has the potential to communicate cell extrinsic or environmental cues with nuclear responses.

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• Gene which protects against lung cancer identified 

A study led by researchers at The University of Nottingham has identified a gene that protects the body from lung cancer.

The research, published in the journal Proceedings of the National Academy of Sciences, USA and funded by a �72,000 grant from the British Lung Foundation, has found that the tumour suppressor gene, LIMD1, is responsible for protecting the body from developing lung cancer -- paving the way for possible new treatments and early screening techniques.

Lead researcher Dr Tyson Sharp and his University of Nottingham team, together with US collaborator Dr Greg Longmore, set out to examine if loss of the LIMD1 gene correlated with lung cancer development.

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Proteomics of Human Lung Tissue Identifies Surfactant Protein A as a Marker of Chronic Obstructive Pulmonary Disease  

Chronic Obstructive Pulmonary Disease (COPD), a lung disease related to smoking, is one of the leading causes of chronic morbidity and mortality around the world. One goal in COPD research is the identification of biomarkers for early diagnosis of the disease. Here, we sought COPD-specific changes in the proteome from human lung tissue. This revealed increased levels of surfactant protein A (SP-A) in COPD but not in the normal or fibrotic lung. The results were confirmed by immunohistochemistry, morphometry and Western blotting. Furthermore, elevated SP-A protein levels were detected from the induced sputum supernatants of COPD patients. The levels of other surfactant proteins (SP-B, SP-C, SP-D) were not altered. Our results suggest that SP-A is linked to the pathogenesis of COPD and could be considered as a potential COPD biomarker.

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• Genetic Link to Likely Tobacco Addiction Identified 

Scientists say they have pinpointed a genetic link that makes people more likely to get hooked on tobacco, causing them to smoke more cigarettes, making it harder to quit, and leading more often to deadly lung cancer.

The discovery by three separate teams of scientists makes the strongest case so far for the biological underpinnings of the addiction of smoking and sheds light on how genetics and cigarettes join forces to cause cancer, experts said. The findings also lay the groundwork for more tailored quit-smoking treatments. . . .

The three studies, funded by governments in the U.S. and Europe, is being published Thursday in the journals Nature and Nature Genetics.

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• Smoking, Teens and Their Parents: New Research 

A new study found that adolescents were at the greatest risk of smoking when their parents began smoking at an early age and the parents' smoking quickly reached high levels and persisted over time.

The study, published in the November issue of Health Psychology, draws from the long-running Indiana University Smoking Survey and builds on previous research that suggests smoking behavior is influenced by both genetics and the environment.

"This particular study focuses more on the genetic influence in the specific case of a parent's smoking behavior impacting a teenage son or daughter's smoking," said Jon Macy, project director of the IU Smoking Survey in the Department of Psychological and Brain Sciences.

"The study findings suggest that the characteristics of early onset and high levels of long-term smoking are great candidates for behavioral and molecular genetic studies of the causes of smoking and how smoking behavior is passed from one generation to the next. . . .

The IU Smoking Survey, a 28-year longitudinal study of the natural history of cigarette smoking, is the longest running study of its kind. Researchers began collecting data in 1980 from middle and high school students in Monroe County, Ind.

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• Link Between Nicotine Addiction And Autism 

Scientists have identified a relationship between two proteins in the brain that has links to both nicotine addiction and autism. The finding has led to speculation that existing drugs used to curb nicotine addiction might serve as the basis for potential therapies to alleviate the symptoms of autism.

The discovery identified a defining role for a protein made by the neurexin-1 gene, which is located in brain cells and assists in connecting neurons as part of the brain's chemical communication system. The neurexin-1 beta protein's job is to lure another protein, a specific type of nicotinic acetylcholine receptor, to the synapses, where the receptor then has a role in helping neurons communicate signals among themselves and to the rest of the body.

This function is important in autism because previous research has shown that people with autism have a shortage of these nicotinic receptors in their brains. Meanwhile, scientists also know that people who are addicted to nicotine have too many of these receptors in their brains.

"If we were to use drugs that mimic the actions of nicotine at an early time in human brain development, would we begin to help those and other circuits develop properly and thus significantly mitigate the deficits in autism? This is a novel way of thinking about how we might be able to use drugs to approach autism treatment," said Rene Anand, associate professor of pharmacology in Ohio State University's College of Medicine and principal investigator of the research.

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• Smoking May Harm the Egg, Embryo Study in mice points to real damage, scientists say  

In research that might have implications for human reproduction, U.S. and Chinese scientists have found that cigarette smoke damages mouse eggs and embryos.

The study was designed to examine whether cigarette smoke causes oxidative stress, cell death and dysfunction, and the shortening of telomeres (DNA at the ends of chromosomes that protect them from degradation). Two groups of female mice were exposed to cigarette smoke or cigarette smoke condensate for four weeks and compared to a control group of mice.

The mice exposed to cigarette smoke or the condensate were more likely than the unexposed mice to show increased fragmentation and delayed fertilization, resulting in impaired embryo development, the study found.

The fragmented eggs also showed oxidative stress, and embryos from mice exposed to cigarette smoke or condensate for four weeks before fertilization were more likely to contain dead cells and altered expression of the protein Oct4, which plays an important role in the formation of viable blastocysts (a stage of embryonic development).

The association between cigarette smoke or condensate and embryo development was dependent on the length of exposure

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