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Genes related to inflammation found to be major risk factors for lung cancer

Scientists from the National Cancer Institute and the University of Texas M. D. Anderson Cancer Center found that two genes, related to inflammation, may be major risk factors for developing lung cancer. "Our findings help explain how heavy smoking, for example, combines with a genetic predisposition to create a besieged environment within the lungs," said lead author Eric Engels, researcher at the Viral Epidemiology Branch of the NCI's Division of Cancer Epidemiology and Genetics. "Essentially, sustained inflammation alters the microenvironment of the lung tissue, damaging cells and altering DNA." The study discovered the mechanism by which damage to the lung through smoking triggers an over zealous inflammatory response by the immune system that can lead to lung cancer. The researchers studied 1,500 lung cancer patients and 1,700 controls and found that some variants or polymorphisms in the genes for interleukin (IL) 1A and 1B are found more frequently in patients with lung cancer. The findings of this study increase the understanding of how some people are predisposed to developing cancer and may lead to potential therapies.

Researchers at UT Southwestern Medical Center discovered a substance from the bark of the lapacho tree that has anti-cancer properties and could be useful for treating lung cancer. The researchers found that in non-small cell lung cancer, the substance beta-lapachone is metabolized by the enzyme NQO1 and results in cell death without damaging non-cancerous tissues which do not express NQO1. "Future therapies based on beta-lapachone and NQO1 interaction have the potential to play a major role in treating devastating drug-resistant cancers such as non-small cell lung cancer," said Erik Bey, lead author of the study and a postdoctoral researcher at the Harold C. Simmons Comprehensive Cancer Center. "This is the first step in developing chemotherapeutic agents that exploit the proteins needed for a number of cellular processes, such as DNA repair and programmed cell death."

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Pre-treatment blood test could guide lung cancer therapy

A team of researchers led by Vanderbilt-Ingram Cancer Center, University of Colorado, Aurora, have discovered that certain types of protein present in the blood could predict the benefits of targeted cancer therapy in non-small lung cancer patients. “There’s a real clinical need to identify which patients will benefit from targeted therapies. If our findings are confirmed, we will be able to use a simple and inexpensive blood test to select the most beneficial therapy for each patient,” said Dr. David Carbone, professor at Cancer Research, Vanderbilt-Ingram. Targeted therapy with the drugs EGF receptor tyrosine kinase inhibitors (TKIs) can lead to a 30 to 40% survival benefit for some non-small lung cancer patients. Previously, it was unclear which patients would benefit from targeted therapy over chemotherapy. The researchers analyzed pre-treatment blood samples from patients and found that for patients with a "signature" of eight proteins, targeted therapy led to prolonged survival.

Researchers at the University of Florida have found that talcum powder stunts cancer growth by cutting blood flow to metastatic lung tumors. According to the research report, talc stimulates healthy cells to produce a hormone called endostatin, which enhances the treatment of metastatic lung cancer. “Talc is able to prevent the formation of blood vessels, thereby killing the tumor and choking off its growth,” said Veena Antony, professor of pulmonary medicine. The report, published in the European Respiratory Journal, also states that the effects of medical thoracoscopy with talc pleurodesis are immediate. The doctors observed that the patients who underwent medical thoracoscopy with talcum powder lived up to 18 months longer than expected.

Scientists at the University of California, Irvine, found that a drug used to treat cancer could enhance long-term memory and strengthen neural connections in the brain. According to the study, histone deacetylase (HDAC) inhibitors, currently used in the clinical treatment of cancerous tumors, could boost memory in humans and be therapeutic for Huntington’s disease, Alzheimer’s and Rubenstein-Taybi syndrome.

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Lung cancer studies make headway

Researchers from the New York State Department of Health have discovered that certain molecular signals in the blood or in the airways can help detect the early stages of lung cancer. Through a research study on 33 people, they found that exhaled breath carries DNA from cells in the lungs. They closely studied the methylation patterns of particular gene promoters in the subjects and identified a potential predictor of the cancer. Their conclusions suggest that a breath test can predict lung cancer risk. Early detection of lung cancer is extremely important since treatment at this time will be most effective.

Moreover, another study conducted at Harvard University found that marijuana could help combat lung cancer. The researchers carried out lab studies and discovered that delta-tetrahydrocannabinol (THC), the active component in the drug, halves tumor growth in cases of common lung cancer and also prevents the cancer from spreading. They injected mice with human lung cancer cells and THC. Three weeks later the tumors showed a 50 percent reduction. However, the mice displayed signs of clumsiness and being high. The studies may be at an early stage but the therapeutic potential of THC is now undeniable.

Another American research study associated excessive intake of cured meats with lung disease. Researchers studied the data from the Third National Health and Nutrition Examination, conducted from 1988 to 1994, which covered 7,352 people. They examined the lung function tests and saw that those consuming meat not less than 14 times a month had higher chances of suffering from chronic obstructive pulmonary disease (COPD). COPD includes several lung conditions such as bronchitis and emphysema. Rich in nitrites, cured meats produce nitrogen species, which may harm the lungs. However, further studies are essential to know the risk factor of such meats.

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Good news for lung cancer patients

Researchers from the Washington University School of Medicine have found an advanced method of radiation to measure lung motion. During radiation for lung cancer patients, a large area needs to be radiated, since the tumor moves with each breathing motion. Scientists have conducted extensive studies and found mathematical details of the lung’s chaotic movements. Using these patterns, they have invented a device, the 4D Phantom that reconstructs actual tissue motion. Studies conducted earlier considered the breathing patterns to be completely even and turning off the radiation beams at certain intervals had not worked in the past. The next step is to improve asthma and emphysema treatments after analyzing breathing patterns.

At the Dana Farber Institute, researchers have designed molecules that inhibit lung cancer cell growth. Using X-ray crystallography, they studied normal and mutated forms of epidermal growth factor receptor (EGFR) and identified the arrangement of two of its mutated forms in lung cancer cells. A defect in EGFR causes cancer development, which in certain cases could also be its weakness. They found two inhibitors, gefitinib and AEE788, which are highly effective in curbing cancer growth. The findings are likely to lead to better lung cancer therapies.

Another study has proven that a hormone used in blood pressure treatment is significant for lung cancer. Human cancer cells, taken from the American Tissue Culture Collection, were injected into mice. After 32 days, a random group of mice were infused with angiotensin (1-7) for 28 days, which led to a 30 per cent reduction in tumor volume. The blood levels in the mice had a likeness to those in humans given the angiotensin-converting enzyme. The control group was given saline treatment and their tumor volume doubled. This study combined with an earlier study on lung cancer cells in the lab has significant implications and may lead to a more effective cancer treatment.

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Battle against lung cancer continues

In separate studies, researchers have come up with possible treatment options for lung cancer.

Scientists are on their way to treating non-small cell lung cancer (NSCLC) with gene therapy and nanotechnology. Scientists from the University of Texas MD Anderson Cancer Center and the University of Texas Southwestern Medical Center conducted a study on mice to test whether gene therapy administered through lipid-based nanoparticles can successfully fight tumors. They sent positively charged nanoparticles to the negatively charged cancer cell membrane. When these nanoparticles are taken into the cell, the genes express the tumor suppressing p53 or FUS1 gene depending on the design. The scientists then found that while p53 and FUS1 individually fought well against cancer, they were most effective when combined. The two together bring about apoptosis, a process wherein the cancer cells self-destruct. Since FUS1 hinders the functioning of a gene that destroys p53, the combination therapy caused more cells to die. In the final analysis, the combination caused a 75 per cent reduction in the number of tumors per mouse and a decrease of 80 per cent in the weight of the tumors.

Meanwhile, the lung cancer vaccine Stimuvax that scientists from Cancer Research UK had prepared is now set to enter phase III of its clinical trial. Stimuvax is a therapeutic vaccine that will compel the immune system to kill MUC1, a molecule found in large quantities in tumor cells. This way, no harm will be done to the healthy cells. Merck KgaA will conduct this trial named START (Stimulating Targeted Antigenic Responses To NSCLC). The trial will evaluate the efficacy of Stimuvax in comparison to a placebo. It aims to involve over 1,300 patients across 30 countries. With lung cancer being the most common cancer worldwide, any progress towards its treatment is welcome news.


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Genes linked to cancer

In an important discovery, American scientists have zeroed in on a gene whose mutation is a probable cause of pediatric kidney cancer, also called Wilms tumor. Researchers from the Massachusetts General Hospital (MGH) Cancer Center came to this conclusion after studying the tumor samples from 82 patients. They found that nearly 30 per cent of them had abnormalities in the same gene of the X chromosome. The researchers named this gene WTX. Since this gene is on the X chromosome, a single mutation can stop the functioning of the gene and cause tumor formation in both males and females. The researchers are now looking at WTX’s normal function with the help of an animal model.

Meanwhile, researchers from the UK Institute of Cancer Research have linked a new gene to breast cancer. The study they conducted involved 923 women with breast cancer and 1084 healthy women. They were checked for abnormalities in the PALB2 gene, a DNA-repair gene. While 10 of the women with breast cancer had defects, none of the healthy women had them. It was concluded that inheriting a damaged copy of this gene could doubly increase the likelihood of developing breast cancer. The discovery will help in formulating personalized treatments for breast cancer.

Across the globe, in Taiwan, researchers have developed a test to predict the benefits of chemotherapy individually for lung cancer patients. On examining tumor samples from 125 lung cancer patients, the researchers from Taiwan University short-listed a cluster of five genes. A test targeting these genes was then formulated. This test is expected to be extremely beneficial for patients as it will help to differentiate between patients in the high or low risk categories and offer scope for personalized treatment.

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Lung cancer research renews hope

Researchers fighting lung cancer now have more weapons in their arsenal to do so.

American researchers have formulated a genetic test that could possibly predict whether patients with early stage lung cancer will need post-operative chemotherapy to survive or surgery alone will be adequate. Dr Anil Potti, lead author of the study and assistant professor at the Duke Institute for Genome Sciences, said that in this preliminary study, the researchers were investigating a group of genes in a way similar to fingerprinting. Based on that fingerprint, they will be able to identify the patients most likely to have a recurrence of lung cancer. The test is a major advancement in personalized medicine, where treatments are tailored to each patient’s genetic code.

Meanwhile, researchers from the University of Pennsylvania have devised an innovative method to exchange gas through the abdominal cavity. The technique involves recirculating a gas-carrying liquid through the abdomen to deliver oxygen. When the test was tried out on adult pigs ventilated with low concentrations of oxygen to simulate lung failure, it was found that arterial oxygen saturation increased from 73 per cent to 89 per cent. Joseph Friedberg, MD, Associate Professor of Surgery and principal investigator of this study, believes that if this technique could be transferred to a critical care setting, it could help those reversible lung failure patients who need more time and support to heal than what a ventilator can provide.

Besides, Roche Holding AG has filed an application with the European Medicines Agency for using its cancer drug Avastin in addition to platinum-based chemotherapy in the first-line treatment of non-small cell lung cancer in patients with a certain cell type. Also, the US Food and Drug Administration has granted fast track status to Novelos Therapeutics’ possible lung cancer drug.

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Roche introduces anti-cancer in India

Roche Scientific Company has launched its anti-cancer drug ‘Tarceva' (erlotinib) in India. This drug can prolong lung cancer patient’s life by 6-9 months and also reduce the symptoms denoting the advanced stage of the disease. Tarceva has remarkable survival benefit (42.5 per cent) in advanced non-small cell lung cancer (NSCLC), the most common form of the disease. Traceva, unlike chemotherapy, specifically targets tumor cells and inhibits their growth. Roche claims that ‘Tarceva’ is especially helpful for advanced or metastatic NSCLC patients for whom at least one prior chemotherapy treatment has failed. The US has approved this drug since November 2004 and the European Union, since September 2005.  The company has applied for a patent in India.

With a potential to treat many types of solid tumors, this tablet is to be taken orally, once a day, but Tarceva comes at a high price. Only 3-5 per cent of India's 1,69,000 cancer patients can afford this drug. There is a likelihood of other Indian companies making cheaper versions of the medicine. Currently, Roche imports almost all the products to India from its manufacturing facilities abroad. The company is hopeful that the government will reduce the import duties, which can significantly reduce the cost.

Roche Group is exploring possibilities of partnering with Indian biotechnology companies for product manufacturing, research outsourcing and other pharma service outsourcing. Industry sources said Roche had preliminary discussions with leading Indian companies in the biotechnology space including Shantha Biotech, Biocon, Bharat Biotech etc.

Anesthetic radiation comes to the rescue of lung cancer patients

Lung cancer, one of the major causes of cancer deaths linked to smoking may be treated with small doses of radiation. A recent Australian study reports that palliative or sedative radiation, normally administered to ease the pain caused by cancer symptoms, may be effective enough to significantly escalate the lifespan of the patient by 5 years or more after diagnosis of advanced lung cancer.

The study conducted at Peter Mac Callum Cancer Center, Melbourne, Australia, by a research team under the leadership of radiation oncologist, Dr Michael Mac Manus, focused on 2337 patients suffering from incurable lung cancer. All the victims were treated with low doses of radiation therapy for a maximum of 68 days following which, they were continuously monitored through either physical examinations or chest radiographs. The results revealed that a little more than one per cent survived the 5-year landmark. About one-third of these survivors were considered ‘cured’ after their cancer stopped progressing on reaching the 5-year juncture. There was a 43 per cent chance of them surviving the 5-year timeline and a 78 per cent probability of reaching a cancer-arrested or ‘progression-free’ state.

According to the Global Lung Cancer Coalition, globally 10 million people are detected with lung cancer each year out of which half of the patients succumb to the deadly disease within a year of diagnosis. While unusual treatments or faith healings were used as explanations for some cases of survival, this study is believed to render some hope among the newly detected cases of lung cancer.

Tomatoes may act as rescue agents for lung cancer

Japanese scientists predict that tomatoes may work as protective mechanism for smokers to prevent lung diseases. A study conducted on mice revealed that tomato juice mixed in their drinking water prevented them from suffering emphysema, predominantly a smokers’ condition, which prevents the lungs from functioning properly, resulting in breathlessness and wheezing. This accidental discovery was accomplished while searching for a good animal model for studying the effects of smoking. However, it’s a long way before this fact can be proved to have a similar reactional effect on humans.

The research team at Juntendo University School of Medicine in Tokyo experimented on two groups of mice containing normal breed and an ageing breed whose lungs were made susceptible to developing emphysema by exposure to tobacco smoke for eight weeks. Thereafter, regular water supply of one group was replaced with 50 per cent tomato juice. The ageing breed in the group not fed on tomato juice developed emphysema while the other group was unaffected by the disease. The test led to a conclusion that the antioxidant lycopene probably reversed the effects of tissue-destroying oxidant molecules present in tobacco smoke.

Meanwhile, there is a dispute revolving around the effectiveness of lycopene as a preventative agent. Recently, the US Food and Drug Administration found that lycopene was not likely to reduce the risk of cancer whereas studies by Harvard University established that one serving of tomato-based foods per day could reduce the risk of heart disease by up to 30 per cent.

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