Tobacco Articles: category genes

Researchers find important 'target' playing role in tobacco-related lung cancers: IKBKE induces tobacco carcinogens, determines chemotherapy sensitivity

Ferdinand.DeVega@moffitt.org — Thu, 09 Feb 2012 05:00:00 GMT

Researchers at Moffitt Cancer Center in Tampa, Fla., have discovered that the immune response regulator IKBKE (serine/threonine kinase) plays two roles in tobacco-related non-small cell lung cancers. Tobacco carcinogens induce IKBKE and, in turn, IKBKE induces chemotherapy resistance. The study was published in a recent issue of Oconogene. "IKBKE is a newly identified oconogene, a gene linked to cancer," said study lead author Jin Q. Cheng, Ph.D., M.D., who studies genetic alterations and their molecular mechanisms in cancer. "In our study, we demonstrated that IKBKE is a STAT 3 target gene and is induced by tobacco. STAT3 is a signaling and transcription gene that is activated in various types of cancer and is required for cell transformation." As a "transcription factor" STAT3 plays a key role in many cellular processes, such as cell growth and programmed cell death, or "apoptosis."

EDITORIAL: But me no 'butts' about your DNA

Mon, 06 Feb 2012 05:00:00 GMT

While Foster's is not particularly interested in taking a position on dog poop left on Cheney properties, we are interested stopping the disgusting habit of discarded cigarettes. Why is it that, despite decades of anti-liter campaigns, all too many smokers continue to believe their discarded butts somehow evaporate in thin air before they can liter the ground. Of course, we are not about to involve the DNA butt police, as been done in the case of DNA and dog poop. But, we will use this opportunity to ask smokers who still liter the back doors of businesses, the sidewalks of our cities and our beautiful beaches to clean up their act.

SUKEL: As If You Needed Another Reason to Quit : Nicotine may prime the brain for addiction.

Fri, 03 Feb 2012 05:00:00 GMT

A few months ago, I attended Neuroscience 2011, the largest neuroscience conference in the world. Imagine 30,000+ scientists exiting the lab, squinting at the daylight and coming together to share the latest and greatest findings in the neuroscience world. . . . One of the studies I wrote up after the conference was a landmark study demonstrating the molecular mechanisms of nicotine as a gateway drug. The long and the short was that researchers at Columbia University found that nicotine, when taken along with cocaine, increases the risk of addiction. And it showed how it did so very elegantly at both the cellular and epigenetic levels. Translation: nicotine changed the way animals learned, priming them for addiction. And it did so by changing the way an animal's genes were expressed. . . . Nora Volkow, the Director of the National Institute on Drug Abuse, hailed the study as "transformative." And when we spoke about it during Neuroscience 2011, she mentioned that it may reach much further than just cocaine addiction—if nicotine can make these kinds of epigenetic changes, literally changing the way genes are expressed, it could mean that it also has influence over many other diseases and disorders. "This a previously unknown pharmacological effect of nicotine," she said. "And the implications...there are many potential implications. We give nicotine patches to help pregnant women stop smoking. But if it works this way on the genes, then maybe we should not be giving them those patches." Then the conjecture started. . . . If nicotine can act on all these genes, I can see it potentially playing a role in anorexia and depression—perhaps even exacerbating diseases like schizophrenia or Parkinson's disease. I told Volkow that all these questions were going to keep me up at night for a while. "This is the difference between good science and not-so-good science. Good science makes you think," she said. "This paper raises a lot of questions that are extremely interesting. And we need to see them through."

Genetic analyses of smoking initiation, persistence, quantity, and age-at-onset of regular cigarette use in Brazilian families: the Baependi Heart Study: BMC Medical Genetics 2012, 13:9 doi:10.1186/1471-2350-13-9

Mon, 30 Jan 2012 05:00:00 GMT

Background The purpose of this study was to estimate the genetic influences on the initiation of cigarette smoking, the persistence, quantity and age-at-onset of regular cigarette use in Brazilian families. Methods The data set consisted of 1,694 individuals enrolled in the Baependi Heart Study. . . . Conclusions Significant heritabilities were observed in smoking phenotypes for both males and females from the Brazilian population. These data add to the literature and are concordant with the notion of significant biological determination in smoking behavior. Samples from the Baependi Heart Study may be valuable for the mapping of genetic loci that modulate this complex biological trait.

Smoking Increases the Risk for Colorectal Adenomas in Patients With Lynch Syndrome: Gastroenterology Volume 142, Issue 2 , Pages 241-247, February 2012

ellen.kampman@wur.nl — Wed, 01 Feb 2012 05:00:00 GMT

Background & Aims Individuals with Lynch syndrome have a high risk of developing colorectal carcinomas and adenomas at a young age, due to inherited mutations in mismatch repair genes. We investigated whether modifiable lifestyle factors, such as smoking and alcohol intake, increase this risk. , , , Conclusions Among people with Lynch syndrome, current smokers have an increased risk of colorectal adenomas. Former smokers have a lower risk than current smokers, but greater risk than never smokers. Individuals with Lynch syndrome should be encouraged to avoid smoking.

Lead, Calcium Uptake, and Related Genetic Variants in Association with Renal Cell Carcinoma Risk in a Cohort of Male Finnish Smokers

Wed, 14 Dec 2011 05:00:00 GMT

Conclusions: Higher blood lead concentrations, below the 10 μg/dL level of concern, were associated with RCC, independent from serum calcium and CALB1 promoter polymorphism. Impact: Increased risk of RCC is associated with lower serum calcium and higher whole blood lead in smokers. The clinical prognostic value of serum calcium and vitamin D in RCC should be further investigated.

Smoke-Activated Cells Ravage Lungs in Emphysema

Sat, 21 Jan 2012 05:00:00 GMT

Action Points * Explain that the destruction of lung tissue in emphysema was mediated by antigen-presenting cells (APCs) that were activated by the smoke. * Point out that transfer of lung APCs from mice with emphysema showed that this population was capable of transferring disease even in the absence of tobacco smoke exposure, a process dependent on IL-17A expression. The destruction of lung tissue in emphysema was mediated by antigen-presenting cells (APCs) that were activated by the smoke, according to an experimental study. Four months of active smoke exposure in a chamber that mimicked smoking habits in humans significantly increased dendritic cells and neutrophils compared with controls. The exposed mice also showed significant increases in lung volume (417 ± 8 mm3 air-exposed mice versus 500 ± 9 mm3 smoke-exposed) and decreases in density (-428 ± 9 HU versus -478 ± 7 HU, P<0.05) reported Farrah Kheradmand, MD, from the Baylor College of Medicine in Houston, and colleagues, in Science Translational Medicine.

Smoke-Activated Cells Ravage Lungs in Emphysema

Sat, 21 Jan 2012 05:00:00 GMT

Cigarette Smoke Induction of Osteopontin (SPP1) Mediates TH17 Inflammation in Human and Experimental Emphysema: Science Translational Medicine Home > 18 January 2012 > Shan et al., 4:(117): 117ra9 Sci Transl Med 18 January 2012: Vol. 4, Issue 117, p. 117ra9

Wed, 18 Jan 2012 05:00:00 GMT

We have shown that CD1a+ antigen-presenting cells (APCs) from lungs of patients with emphysema can induce autoreactive T helper 1 (TH1) and TH17 cells. Similarly, the canonical cytokines interferon-γ (IFN-γ) and interleukin-17A (IL-17A) are specifically linked to lung destruction in smokers, but how smoke activates APCs to mediate emphysema remains unknown. Here, we show that, in addition to increasing IFN-γ expression, cigarette smoke increased the expression of IL-17A in both CD4+ and γδ T cells from mouse lung. IL-17A deficiency resulted in attenuation of, whereas lack of γδ T cells exacerbated, smoke-induced emphysema in mice. Adoptive transfer of lung APCs isolated from mice with emphysema revealed that this cell population was capable of transferring disease even in the absence of active smoke exposure, a process that was dependent on IL-17A expression. Spp1 (the gene for osteopontin) was highly expressed in the pathogenic lung APCs of smoke-exposed mice and was required for the TH17 responses and emphysema in vivo, in part through its inhibition of the expression of the transcription factor Irf7. Thus, the Spp1-Irf7 axis is critical for induction of pathological TH17 responses, revealing a major mechanism by which smoke activates lung APCs to induce emphysema and identifying a pathway that could be targeted for therapeutic purposes.

Study Maps Path From Smoking to Emphysema in Mice: Immune response to smoke causes the disease, researchers say

Wed, 18 Jan 2012 05:00:00 GMT

Smoking activates certain genes and portions of the immune system, which in turn causes inflammation that leads to emphysema. So say researchers who mapped the destructive path from smoking to the debilitating lung disease in mice. "Previously, emphysema was thought to be a nonspecific injurious response to long-term smoke exposure," study author Dr. Farrah Kheradmand, a professor of medicine and immunology at Baylor College of Medicine, said in a college news release. "These studies show for the first time that emphysema is caused by a specific immune response induced by smoke."

Mapping the destructive path from cigarette to emphysema

pathak@bcm.edu — Wed, 18 Jan 2012 05:00:00 GMT

From the cherry red tip of a lighted cigarette through the respiratory tract to vital lung cells, the havoc created by tobacco smoke seems almost criminal, activating genes and portions of the immune system to create inflammation that results in life-shortening emphysema, said researchers led by those at Baylor College of Medicine and the Michael E. DeBakey Veterans Affairs Medical Center. In a report online in the journal Science Translational Medicine, the scientists, including two from The University of Texas MD Anderson Cancer Center, described the track the toxic smoke takes through the tissues and how they accomplish their destructive work. "It's like walking into a crime scene," said Dr. Farrah Kheradmand, professor of medicine and immunology at BCM and a senior author of the report. In their current work, the scientists took cells present in the "crime scene" apart, piece by piece to elucidate what occurred when, and how. It is a complicated story that took more than four years for her, her co-senior author Dr. David Corry and members of their laboratories and colleagues in the Dan L. Duncan Cancer Center at BCM to unravel, she said. Corry is professor and chief of the section of immunology, allergy and rheumatology in the department of medicine at BCM and a member of the faculty at the Michael E. DeBakey VA Medical Center. "Previously, emphysema was thought to be a non-specific injurious response to long-term smoke exposure," she said. "These studies show for the first time that emphysema is caused by a specific immune response induced by smoke." "It is a combination of little genes affected by an epigenetic factor," she said. Epigenetics are factors that affect the way genes are expressed after DNA forms. Cigarette smoke is an environmental epigenetic factor.

Mutations Offer Clues to Lung Cancer in Nonsmokers

Fri, 13 Jan 2012 05:00:00 GMT

Lung cancer in nonsmokers has distinct mutation patterns that might provide clues into the origin and pathogenesis of the disease, ongoing laboratory studies have suggested. Tumors from patients who had never smoked had fewer alterations in genes commonly associated with lung cancer, such as EGFR, KRAS, and EML/ALK translocations. . . . Action Points * Note that this study was published as an abstract and presented at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal. * This study found that lung cancer in nonsmokers has distinct mutation patterns that might provide clues into the origin and pathogenesis of the disease.

Fighting cancer in the lab and at the bedside

Sun, 15 Jan 2012 05:00:00 GMT

In Gelmon’s private practice in Vancouver, the cancers of 93 percent of the women she sees do not stem from mutations, she says, but rather from hormones, obesity and even smoking if one starts as a teen. “In Israel, about 10% [of cases] are inherited,” she says. Thus the added risk is not very significant. “We are gradually learning more about inherited factors that cause higher risk.”

New Therapies for Non-Smoking Lung Cancer Patients

Fri, 06 Jan 2012 05:00:00 GMT

(Ivanhoe Newswire) Smoking is a well-known risk factor for lung cancer, but about 25% of all lung cancer patients have never smoked. According to this study, a gene fusion event could explain a significant proportion of these lung cancer cases, and may serve as a target for new therapies. Recent strides have been made to identify gene mutation events driving cases of lung adenocarcinoma in never-smokers, but the underlying genetic events leading to these lung cancers still remain unknown in a large number of cases. In this report, using a combination of genome sequencing and RNA sequencing, a team of researchers in South Korea has characterized a previously unknown gene fusion event in a case of lung adenocarcinoma striking a 33-year-old Korean male with no history of smoking or cancer within his family.

Mixed News on Tough-to-Treat Lung Cancer: One drug made little difference, another showed promise in mice with genetic mutation

Tue, 10 Jan 2012 05:00:00 GMT

Dutch researchers report disappointing results from an early clinical trial of the drug Nexavar (sorafenib) in fighting a tough-to-treat form of lung cancer. But, in better news, an experimental drug known as ganetespib showed promise in laboratory and animal experiments. The results of both studies were to be presented Tuesday at an American Association for Cancer Research/International Association for the Study of Lung Cancer meeting in San Diego. In recent years, researchers have made some headway in finding treatments to combat lung cancer, which often doesn't respond well to chemotherapy, explained Dr. Len Lichtenfeld, deputy chief medical officer of the American Cancer Society. Those treatments include drugs such as crizotinib (Xalkori) and erlotinib (Tarceva), which are most effective in tumors that contain certain genetic mutations. However, those drugs tend to not work well in people with tumors that contain a particular type of mutation in the KRAS gene. KRAS is the most common molecular mutation, present in about 25 percent of people with non-small cell lung cancers such as adenocarcinoma, particularly smokers, said Dr. Paul Bunn, a professor of lung cancer research at the University of Colorado and executive director of the International Association for the Study of Lung Cancer.