Early dogs may have helped human hunters track and kill mammoths in Ice Age Europe and Asia. The fierce dogs may have then guarded the meat from their wolf relatives.

Penn State archeologist Pat Shipman recently calculated that the age ranges of mammoths found in these ancient boneyards suggest that the animals were hunted, not just scavenged after a catastrophe killed an entire herd.Shipman suggested that the domestication of wolves, along with improvements in projectile weapons, may have allowed people to successfully hunt large numbers of mammoths. The journal Quaternary International published her results.

From approximately 40,000 to 15,000 years ago, human campsites from Siberia to central Europe contained tremendous numbers of mammoth bones, sometimes from more than 100 individual pachyderms. In many cases, humans constructed buildings using the mammothbones, tusks and hides.

Shipman noted that high numbers of wild wolf and Arctic fox bones appear along with the mammoth bones. Dogs may have helped guard the mammoth meat by alerting people when other carnivores came sniffing around. The wolves and foxes were then killed and skinned for their pelts and meat.

Earlier archeological discoveries, published in the Journal of Archeological Sciences, described a breed of dog, or semi-domesticated wolf, from approximately 32,000 years ago in what is now Belgium, the Ukraine and Russia. Genetic and skeletal evidence show that the dog-like creature was different from known wolves, yet its genetic signature didnt survive in modern dog populations. This could mean the mammoth-hunting dogs either died out, or interbred with other dogs and wolves until they became indistinguishable.

Relatives of modern humans, including Neanderthals, likely hunted mammoths too. Chemical signatures in their bones suggest Neanderthals ate the extinct creatures. However, no known Neanderthal campsites contain the remains of hundreds of mammoth bones.

Photo: Wikipedia Commons

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Approach is designed to help families with particular genetic faults who want to avoid passing on devastating incurable diseases to their children Expert scientific panel today gave its backing to the controversial techniques Concluded they were 'potentially useful' and did not appear to be unsafe

By Anna Hodgekiss

Published: 11:00 EST, 3 June 2014 | Updated: 15:36 EST, 3 June 2014

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Controversial IVF techniques that see babies born with three genetic parents could be available in two years, scientists said today.

The 'three-parent' technique is designed to help families with particular genetic faults who want to avoid passing on devastating incurable diseases to their children.

Today, an expert scientific panel gave its backing to the approach, declaring it was 'potentially useful' and did not appear to be unsafe - despite fears the move might lead to designer babies.

Hope: The 'three-parent' technique is designed to help families with particular genetic faults who want to avoid passing on devastating incurable diseases to their children

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Molecular Genetics of Nodulation Control in Legumes
Professor Peter M. Gresshoff QAAFI Science Seminar -- 27 May 2014 http://www.uq.edu.au/agriculture/petergresshoff Most legume plants, such as soybean, are ca...

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Let #39;s Play The Sims 3 - Perfect Genetics Challenge - Episode 40
My Sims 3 Page: http://mypage.thesims3.com/mypage/Llandros2012 My Blog: http://Llandros09.blogspot.com My Facebook: https://www.facebook.com/Llandros09?

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SkunkHouse Genetics Day12
18 oger MMMP patient and caregiver in full compliance.

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Endoscopic Oncology Clinic: Nutrition and Genetics
Parkview Comprehensive Cancer Center #39;s Endoscopic Oncology Clinic takes a team approach to cancer care. The approach draws on the combined expertise and expe...

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Changing your "Six Pack" Genetics Stretches Part 2
Sequel to the Change your "six-pack" genetic video to help get rid of Anterior Pelvic Tilt.

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The Secret to a Perfect Body - Genetics
This Infomercial Parody Is the Perfect Answer to Every Weight Loss Ad See more http://www.collegehumor.com LIKE us on: http://www.facebook.com/collegehumor FOLLOW us on: http://www.twitter.com/col...

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Combining oncolytic adenovirus-mediated cytotoxic gene therapy (OAMCGT) with intensity modulated radiation therapy (IMRT) reduces the risk of having a positive prostate biopsy two years after treatment in intermediate-risk prostate cancer without affecting patients' quality of life, according to a study published in the June 1, 2014 edition of the International Journal of Radiation Oncology Biology Physics (Red Journal), the official scientific journal of the American Society for Radiation Oncology (ASTRO).

Previous prospective clinical trials in prostate cancer have shown that increasing the standard radiation dose of 70 Gy by 10 to 15 percent improves the biochemical disease-free survival in some prognostic risk groups; however, more than 25 percent of men with intermediate- or high-risk disease develop prostate-specific antigen (PSA) progression within 10 years, suggesting that radiation doses higher than 80 Gy may be necessary. This prospective randomized phase II trial examines the use of OAMCGT to improve the effectiveness of IMRT without increasing the radiation dose in intermediate-risk prostate cancer.

Based on encouraging results from a prior phase I trial, 44 patients were enrolled in this randomized phase II trial from January 2008 to July 2010. Patients were randomized to receive either OAMCGT with IMRT (21) or IMRT alone (23), and outcomes were focused on toxicity, quality of life and prostate biopsy findings at two years post-treatment. Eligible patients had newly diagnosed, clinically localized, intermediate-risk prostate cancer, defined as clinical stage T1/T2 with a Gleason score of 7 or a PSA of 10 to 20 ng/ml. Patients with a Gleason score of 5/6, a PSA <10 ng/ml and 50 percent positive biopsy cores were also eligible because it has been found that these patients tend to respond biochemically similar to patients with intermediate-risk disease. Of the 44 patients analyzed in this study, 82 percent (36) had stage T1 disease and 18 percent (8) had stage T2 disease. Sixteen percent (7) had a Gleason score of 6 and 84 percent (37) had a Gleason score of 7.

All patients were treated with IMRT (80 Gy in 2.0 Gy fractions over eight weeks). Patients who were treated with OAMCGT in addition to IMRT also received a single intraprostatic injection of 1 x 10^12 viral particles of the Ad5-yCD/mutTKSR39rep-ADP adenovirus on the first day of treatment. Two days later, patients in the OAMCGT arm began IMRT treatment and received 5-FC (150 mg/kg/day, four times per day) and vGCV (1,800 mg/kg/day, twice daily) orally five days a week for two weeks.

Toxicity was assessed once a week during treatment. After completion of treatment, follow-up was conducted every three months for the first year post-treatment, at 18 and 24 months and then annually thereafter. Quality of life (QOL) was assessed at six, 12, 24 and 36 months post-treatment using the validated Expanded Prostate Cancer Index Composite (EPIC) and EuroQol EQ-5D instruments. A 12-core prostate biopsy was taken at 24 months post-treatment. Biopsies were examined by two pathologists blinded to the study treatments.

Gastrointestinal (GI) and genitourinary (GU) toxicity are the most common side effects of prostate radiation therapy. In this study, 5 percent of men (1) in the OAMCGT arm and 9 percent (2) in the IMRT alone arm experienced grade 2 or higher acute (90 days) GI toxicity. Grade 2 or higher acute GU toxicity was more prevalent in both arms, with 43 percent (9) in the OAMCGT arm and 31 percent (7) in the IMRT alone arm; however, there was no statistical significance in acute GI or GU toxicity between the two arms. Men in the OAMCGT arm experienced a higher occurrence of influenza-like symptoms, which were expected and attributed to the oncolytic adenovirus.

The sole significant difference in QOL in the EPIC domains (urinary incontinence, unitary irritation/obstruction, bowel, sexual, hormonal and overall satisfaction) at six months post-treatment was the sexual domain, which was better in the OAMCGT arm. The only significant difference in the EQ-5D domains (mobility, self-care, usual activities, pain and discomfort, anxiety and depression, and health state) was self-care at 24 months post-treatment, which was better in the OAMCGT arm.

An important outcome was prostate biopsy at two years post-treatment, which is prognostic of long-term results. In this study, 84 percent (37) of patients had two-year biopsies. For men in the OAMCGT arm, there was a 42 percent relative reduction in positive biopsy at two years, and a 60 percent relative reduction in men with <50 percent positive biopsy cores at baseline. At the time of this study's findings, one patient in each arm had exhibited biochemical failure (4.8 percent in the OAMCGT arm and 4.3 percent in the IMRT alone arm). The events occurred 14.5 months post-treatment in the OAMCGT arm and 13.8 months post-treatment in the IMRT alone arm. No patients had developed hormone-refractory or metastatic disease, and no patients died from prostate cancer.

"The study's results demonstrate that gene therapy generated few noticeable side effects and did not diminish the patient's quality of life when combined with modern radiation therapy. Moreover, a greater percentage of men who received gene therapy and radiation had negative prostate biopsies two years after treatment relative to men who received radiation alone," said Svend O. Freytag, PhD, lead author of the study and division head of biology research in the department of radiation oncology at Henry Ford Hospital in Detroit. "Our findings suggest that gene therapy has a potential role as a strategy to enhance outcomes, along with radiation therapy, while maintaining quality of life for our patients. This research helps open the door for further studies of this novel combination therapy approach in prostate cancer and other disease sites."

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THE SPINAL INJURY PATIENT FILM
An award-winning film for people who are newly injured, or who are new to spinal cord injury. It was viewed over 22000 times on our previous YouTube channel where YouTube #39;s limitations meant...

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(2006-06) David Steenblock - Umbilical Cord Stem Cell Therapy
David Steenblock Umbilical cord stem cell therapy 2006-06-15 Visit the Silicon Valley Health Institute (aka Smart Life Forum) at http://www.svhi.com Silicon Valley Health Institute Smart...

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ABC Researcher Kaylene Younger is one of two inaugural recipients of the Metcalf Prize.

A Tasmanian researcher will use a $50,000 national prize for stem cell research which may help treat conditions like Alzheimer's disease and multiple sclerosis.

Dr Kaylene Young has won an inaugural Metcalf Prize from the National Stem Cell Foundation of Australia.

Her research has already uncovered that people have lazy or inactive brain cells and are common in people with multiple sclerosis, Alzheimer's and other degenerative diseases.

They are also found in people with a brain injury.

She has told ABC Local Radio her research will help improve the understanding of brain cell behaviour in order to treat disorders or damage.

She believes she can persuade cells to self repair and wake up, either by stimulation or electrically.

"[I'm] really trying to find what it is that controls their behaviours, what makes them divide, what makes them able to generate different types of brain cells in order to be able to use them for therapeutic treatments for things like Alzheimer's disease, multiple sclerosis and even brain cancers," Dr Young said.

"What I am really trying to do is push our endogenous stem cells, the stem cells that are already in our brain every day, to just work that little bit harder."

Dr Young says the award is a great honour.

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Scientists Grow Human Cartlilage Using Stem Cells

By: https://www.youtube.com/user/ReutersVideo Please like PigMine #39;s FaceBook page here: http://www.facebook.com/PigMineNews Subscribe to http://www.youtube.com/subscription_center?add_user=PigMi...

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A Littlestown resident went through a five-day procedure to give bone marrow stem cells to a man living in France

By Adam Michael

amichael@GameTimePA.com

@goodoletwonames on Twitter

John Sibirtzeff will never meet the man who used his stem cells to heal. He'll never know exactly what his affliction was, and he's OK with that.

A month ago, Sibirtzeff spent five days in Washington D.C. donating bone marrow stem cells that would be used to heal a 69-year-old man living in France.

"I'll never know who the recipient was," he said. "I'll never know if he was American or French, military or non."

When Sibirtzeff, of Littlestown, was in Navy boot camp in 2007, he opted into the C.W. Bill Young Department of Defense Marrow Donor Program. Naval doctors drew a vial of his blood and stored it after identifying his type. In 2011, Sibirtzeff finished his tour of duty, but his name remained on the donor list.

This past January, the program contacted Sibirtzeff requesting that he return for testing, as he was a potential match for a 69-year-old man living in France.

According to the program's website, salutetolife.org, 70 percent of patients are unable to find a match within their families. Sibirtzeff's receiver was among them.

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Everyday hero: Littlestown man donates bone marrow stem cells to stranger

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Perched on the end of the scientists green glove, the tiny oblong-shaped object looks like a small jewel. It is in fact artificially-grown human cartilage, developed from human stem cells in the laboratory for the first time.

Cartilage, which protects the bone ends in joints, does not have blood vessels or nerves and does not heal over time if damaged.

Scientists at Columbia University in New York took cells from adult bone marrow and developed them into cartilage as robust as the natural human tissue.

We do have technology. We do understand underlying principles. But we are not ready to go into patients. There is a lot of pre-clinical work that will need to be done to make this happen, said Gordana Vunjak-Novakovic, Professor of Biomedical Engineering at Columbia University, who led the study.

Until now, scientists have made cartilage from young animal cells but the resulting tissue was often weak.

In the new study stem cells were condensed via a process that imitates how the body produces the tissue naturally.

The research team now plans to test the cartilage grown from stem cells to examine its long-term effects.

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Regulated information 2 June, 2014

TiGenix completes the sale of its Dutch manufacturing facility to PharmaCell

TiGenix to receive a total consideration of Euro 5.75 million

PharmaCell will continue to manufacture ChondroCelect, which Sobi will market and distribute

TiGenix to focus on bringing its development pipeline to patients

Leuven, Belgium - 2 June, 2014 - TiGenix NV (Euronext Brussels: TIG), the European leader in cell therapy, announced today that it has completed the sale of its Dutch production facility to PharmaCell BV for a total consideration of Euro 5.75 million. PharmaCell, a leading European contract manufacturing organisation active in the areas of cell therapy and regenerative medicine, has acquired the shares of TiGenix' wholly-owned subsidiary,TiGenix BV, which holds the Dutch manufacturing facility.

The TiGenix state-of-the-art manufacturing facility is located in Sittard Geleen in the Netherlands. In 2012, the site passed a cGMP (current Good Manufacturing Practice) inspection by the Dutch authorities, and obtained approval from the European Medicines Agency for the production of ChondroCelect, the company's cell therapy product for cartilage repair in the knee.

TiGenix has received an upfront payment of Euro 3.5 million, and will receive a final payment of Euro 0.75 million in 2017. ChondroCelect will continue to be manufactured at the facility under a long-term manufacturing agreement, under the terms of which TiGenix will benefit from a cost relief of Euro 1.5 million during the first three years, the largest portion of which comes in the first year.

"The sale of the Dutch manufacturing facility together with the agreement to license the marketing and distribution rights of ChondroCelect to Sobi, which was signed in April, have transformed TiGenix," said Eduardo Bravo, CEO of TiGenix. "The combination of these two deals brings an immediate cash inflow of Euro 3.5 million to TiGenix, and a reduction in annual opeRating costs for manufacturing, sales and marketing of at least Euro 5 million. The broader geographical reach for ChondroCelect offered by Sobi will give TiGenix the potential for greater value generation in the long-term. TiGenix itself can now fully focus on progressing its promising advanced clinical stage pipeline to patients with high unmet medical need."

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TiGenix completes the sale of its Dutch manufacturing facility to PharmaCell

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An experimental gene-based diet helped a group of slimming volunteers increase their weight loss by a third, research has shown.

Tailoring nutrition to individual genetic profiles could revolutionise dieting and improve peoples health, scientists who carried out the study claim.

Personalised diets were prepared for 87 obese individuals based on an analysis of 19 genes known to affect metabolism and taste.

After two years the volunteers had lost 33% more weight than a matched group of 104 participants whose diets were not adjusted to suit their genes.

Lead researcher Nicola Pirastu, from the University of Trieste in Italy, said: Although there were no significant differences in age, sex and BMI [Body Mass Index] between the two groups at the beginning of the trial, we found that people in the group who had followed the gene-based diet lost 33% more weight than the controls over two years, and the percentage of lean body mass also increased more in this group.

By uncovering the genetic bases of taste and food preferences, we will be able to increase not only the effectiveness of nutritional interventions, but also compliance with them.

Another study conducted by Dr Pirastu involved an analysis of DNA samples from 4,000 European and Asian volunteers which uncovered 17 genes associated with liking certain foods. The range of foods was wide, including bacon, dark chocolate, white wine, and coffee.

Surprisingly, none of the genes played an active role in taste or smell perception.

We found a strong correlation between the HLA- DOA gene and white wine liking, but we have no idea which of the characteristics of white wine this gene influences, said Dr Pirastu, who presented his findings at the annual meeting of the European Society of Human Genetics in Milan.

Meanwhile, parents who are concerned their children may become obese should ensure they join them for breakfast and dinner but not lunch, a study found.

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Gene-based diet boosts weight loss, study finds

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Hawaii County set itself apart from much of the rest of the state in December by effectively banning the large biotech seed companies that have become a major, though controversial, part of Hawaii agriculture.

But with a ban also on the outdoor testing of transgenic crops, can the Big Island, home to genetically modified papaya, still be a place for genetic research?

Six months later, the answer might be clearly no for some researchers while a bit hazy for others.

Because of the law, Russell Nagata, Hawaii County administrator for the University of Hawaiis College of Tropical Agriculture and Human Resources, said his staff will not pursue genetic engineering.

It will prevent us from using biotech as a solution to agricultural issues, he said following a panel discussion on genetic modification Thursday evening.

It forces us to look at it in a different manner. It may be slow, it may not be as effective.

Scientists interviewed say growing modified crops, that are still under development, in open fields is necessary to test their effectiveness.

While they say they take steps to prevent the spread of genes, including the removal of plants before flowering, critics of genetic modification believe outdoor testing presents too much risk. They also question the approval process.

We are looking at the precautionary principle, said Kohala Councilwoman Margaret Wille during the panel discussion sponsored by the Hilo chapter of the American Association of University Women. Wille introduced the bill restricting the use of transgenic crops.

Under the countys law, testing can occur but it must be done indoors.

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GMO ban, research at odds?

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Newswise PHILADELPHIATeenage girls with a familial or genetic risk for breast cancer worry more about getting the disease, even when their mother has no history, compared to girls their age with no known high risks, according to new data presented today by researchers from Penn Medicines Abramson Cancer Center at the annual meeting of the American Society of Clinical Oncology (ASCO) in Chicago (Abstract #9527). Early analyses suggest that such worry may increase risk behavior, such as smoking and potentially alcohol use, but does not appear to influence positive behavior, such as exercise.

For the study, Angela Bradbury, MD, assistant professor of Medicine in the division of Hematology-Oncology at the Perelman School of Medicine at the University of the Pennsylvania, and colleagues from Penn Medicine and Fox Chase Cancer Center, evaluated psychosocial adjustments (cancer specific worry, anxiety and depression) and health behaviors in 320 girls aged 13 to 19 (208 were classified as high risk and 112 were classified as being at the general population risk). Girls were considered high risk if they had a parent with a BRCA1/2 mutation or at least one relative with a history of breast cancer. Girls were classified as population risk if they had a parent who tested true negative for a BRCA1/2 mutation or no family breast cancer history.

The study found that high-risk girls have significantly more worry around the disease than population-risk girls, even if mom has no history of the disease. There was no difference between the groups for general anxiety and depression. High-risk girls were also more likely to perceive their lifetime risk as higher than other girls their age at population risk (73 v. 32 percent). Interestingly, some population-risk girls also believe themselves to be at increased risk for breast cancer, particularly as they get older.

Breast cancer worry in daughters who have mothers with breast cancer is well reported. But one of the most surprising findings from this study is that living within the context of a breast cancer family, regardless of whether mom has breast cancer or not, has an impact on these girls, said Bradbury. Another key finding was that a mothers worry and anxiety are strongly associated with her daughters worry and anxiety. More needs to be understood about this impact on psychosocial adjustment and health behaviors as girls transition to adulthood. The more we understand what young girls know about breast cancer risklow or high riskand how they perceive that information, the more likely we can help correct any misconceptions they may have and address their worry to benefit their development.

The study also revealed some differences in health behavior among both groups of girls (aged 13 to 19). High-risk girls were significantly more likely to smoke cigarettes. High risk girls were also more likely to try alcohol, although this difference was not statistically significant. Conversely, the analysis did not reveal significant differences in preventive behaviors, like exercise or self-exams among the girls. Though, high-risk girls were more likely to perform a self-breast exam and less likely to have ever had a clinical breast exam.

Whether worry translates into greater risk-taking behaviors is a concern and the data suggests this possibility. This is a crucial time for development of behavior and a better understanding of the impact of awareness of breast cancer risk on development of health behaviors could provide opportunities to promote cancer preventive behaviors earlier, said Bradbury. We need more research in order to fully understand how this knowledge affects these girls and their families in order to tailor interventions so we can optimize care and promote adaptive responses to breast cancer risk in girls and their mothers.

Bradbury presented the teams findings at ASCO on Monday, June 2, 2014 in the Patient and Survivor Care poster session from 8 a.m. to 11 a.m. in McCormick Place S102.

##

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Penn Medicine Researchers Investigate Worry and Behavior Among Teens at Higher Risk for Breast Cancer

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When the Food and Drug Administration recently approved a promising new lung cancer drug named Zykadia four months ahead of schedule, it heralded the medication as a breakthrough therapy.

The drug isnt meant for everyone with the devastating disease, which kills an estimated 160,000 Americans each year. Or even for the majority of patients with its most common form, non-small-cell lung cancer.

Rather, Zykadia is designed for a sliver of patients about 5percent who have advanced non-small-cell lung cancer and have a specific gene mutation that causes tumors to become resistant to existing treatment. For them, and only them, the drug has the proven potential to shrink tumors and extend lives.

The FDAs speedy approval of Zykadia offered the latest evidence that the age of personalized medicine, while long predicted, is increasingly becoming reality. For reasons scientific and economic, one-size-fits-all blockbuster drugs are giving way to treatments tailored to individuals genetic makeups and aimed at narrow subsets of broader diseases.

Its a new world, said Wendy Selig, president of the Melanoma Research Alliance, the largest private funder of research on the disease, which this year is expected to kill nearly 10,000 Americans. Were segmenting what we thought of as large diseases into smaller populations of patients that are defined by genetic distinctions. ... The goal is to match the right therapy to the right patient, and to do it with minimal collateral damage.

Since 2011, the FDA has approved numerous new treatments for melanoma patients with certain types of genetic mutations. The agency also has given the green light to many drugs for other specific cancers, and to a revolutionary treatment for a small proportion of people with cystic fibrosis. Companion diagnostic tests often help identify which patients might benefit from the targeted treatments.

Pharmaceutical companies have ramped up investment in personalized medicine in recent years, and the number of targeted therapies in the development pipeline reflect that evolution. For example, the FDA said about 80percent of the nearly 50 drugs it has designated as potential breakthrough drugs involve targeted therapies.

For patients who benefit, the advantages are striking: Earlier and better diagnoses, more effective treatments and even possible cures, or at least more time, for people who previously had little hope.

But the trend toward targeted medicine also is forcing hard questions on regulators, drug makers, insurers and patients alike: Who should pay for the growing number of specialized drugs, which can cost hundreds of thousands of dollars a year? How does society ensure that everyone who might benefit rich or poor can receive treatment? What about patients whose specific conditions or mutations have not attracted investment dollars or the attention of researchers, leaving them to watch and hope from the sidelines?

Were heading for some kind of reckoning, said Barry Werth, an author and journalist who has spent decades writing about the pharmaceutical industry. I dont know that anybody has thought through how thats going to play out.

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Drugmakers find breakthroughs in medicine tailored to individuals genetic makeups

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PUBLIC RELEASE DATE:

2-Jun-2014

Contact: Robin Dutcher Robin.dutcher@hitchcock.org 603-653-9056 The Geisel School of Medicine at Dartmouth

New research confirms a vulnerability to lung cancer can be inherited and implicates the BRCA2 gene as harboring one of the involved genetic mutations. An international consortium of scientists including investigators at the Institute for Cancer Research in London, the International Agency for Research on Cancer in Lyon, the National Cancer Institute in Bethesda, Harvard, and Dartmouth used integrated results from the 1000 Genomes Project with genetics studies of lung cancer to complete the investigation published on June 1, 2014 in Nature Genetics.

The study scanned the genomes of more than 11 thousand individuals of European descent to look for common variations associated with non-small cell carcinoma, a common form of lung cancer. The analysis showed that variations in the BRCA2 and CHEK2 genes can significantly increase an individual's risk for lung cancer. A smoker's chances of developing lung cancer may be doubled if he or she carries the BRCA2 variation. In addition, the TP63 gene, which previously was only associated with lung cancer risk in Asian populations, was associated with risk for adenocarcinoma, a form of non-small cell carcinoma, in those of European descent.

The study used four genome-wide association (GWA) studies from the U.T. M.D. Anderson Cancer Center, the Institute of Cancer Research, the National Cancer Institute, and the International Agency for Research on Cancer. Scientists used imputation, a statistical form of inference, in which data from a reference set of individuals who have been sequenced is used to fill in missing values on the genome for the study participants. The study validated the use of this approach in finding common genetic variations between multiple sets of data and by extensively genotyping additional participants from Harvard, the International Agency for Research in Cancer, the University of Toronto, the Institute of Cancer Research, and the German Cancer Research Institute.

Chris Amos, PhD, senior author of the paper and director of the Center for Genomic Medicine at Dartmouth said, "This variant confers one the strongest associations found to date for cancer among those identified by genome-wide association studies, and identifies a subset of people who are particularly susceptible to harm associated with smoking."

The BRCA2 gene codes for a very large protein that functions primarily for coordinating activities of many different genes involved in DNA repair. Cells accumulate DNA damage as a result of environmental toxins such as those contained in tobacco smoke. Mutations in BRCA2 may affect the ability of cells to respond to DNA damage, increasing the chance that a cell will become a cancer.

Previous studies did not detect a connection between BRCA2 and lung cancer. All four GWA data set analyses in this study showed significant association of the BRCA2 gene (rs11571833) with non-small cell carcinoma, specifically squamous cell carcinoma. In addition, results validated previous studies connecting CHEK2 (rs17879961) with squamous cell carcinoma. The findings of the TP63 (rs13314271) variation in individuals in European ancestry provides robust evidence for its connection to adenocarcinoma.

"Our study showed that mutations to two genes, BRCA2 and CHEK2, have a very large effect on lung cancer risk in the context of smoking. Mutated BRCA2 in particular seems to increase risk by around 1.8 times," said study leader Richard Houlston, professor of Molecular and Population Genetics at The Institute of Cancer Research (ICR). "Smokers in general have nearly a 15 per cent chance of developing lung cancer, far higher than in non-smokers. Our results show that some smokers with BRCA2 mutations are at an enormous risk of lung cancer somewhere in the region of 25 per cent over their lifetime. Lung cancer claims more than a million lives a year worldwide and is by far the biggest cancer killer in the UK. We know that the single biggest thing we can do to reduce death rates is to persuade people not to smoke, and our new findings make plain that this is even more critical in people with an underlying genetic risk."

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BRCA2 gene now connected to lung cancer, doubling a smoker's risk

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The Boy with amazing genetics
The Boy with amazing genetics Please Read: The Better Aesthetics YouTube channel is dedicated to providing the viewer with relevant, informative videos that ...

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PUBLIC RELEASE DATE:

2-Jun-2014

Contact: Brittany Ashcroft press@astro.org 703-839-7336 American Society for Radiation Oncology

Fairfax, Va., June 2, 2014Combining oncolytic adenovirus-mediated cytotoxic gene therapy (OAMCGT) with intensity modulated radiation therapy (IMRT) reduces the risk of having a positive prostate biopsy two years after treatment in intermediate-risk prostate cancer without affecting patients' quality of life, according to a study published in the June 1, 2014 edition of the International Journal of Radiation Oncology Biology Physics (Red Journal), the official scientific journal of the American Society for Radiation Oncology (ASTRO).

Previous prospective clinical trials in prostate cancer have shown that increasing the standard radiation dose of 70 Gy by 10 to 15 percent improves the biochemical disease-free survival in some prognostic risk groups; however, more than 25 percent of men with intermediate- or high-risk disease develop prostate-specific antigen (PSA) progression within 10 years, suggesting that radiation doses higher than 80 Gy may be necessary. This prospective randomized phase II trial examines the use of OAMCGT to improve the effectiveness of IMRT without increasing the radiation dose in intermediate-risk prostate cancer.

Based on encouraging results from a prior phase I trial, 44 patients were enrolled in this randomized phase II trial from January 2008 to July 2010. Patients were randomized to receive either OAMCGT with IMRT (21) or IMRT alone (23), and outcomes were focused on toxicity, quality of life and prostate biopsy findings at two years post-treatment. Eligible patients had newly diagnosed, clinically localized, intermediate-risk prostate cancer, defined as clinical stage T1/T2 with a Gleason score of 7 or a PSA of 10 to 20 ng/ml. Patients with a Gleason score of 5/6, a PSA <10 ng/ml and 50 percent positive biopsy cores were also eligible because it has been found that these patients tend to respond biochemically similar to patients with intermediate-risk disease. Of the 44 patients analyzed in this study, 82 percent (36) had stage T1 disease and 18 percent (8) had stage T2 disease. Sixteen percent (7) had a Gleason score of 6 and 84 percent (37) had a Gleason score of 7.

All patients were treated with IMRT (80 Gy in 2.0 Gy fractions over eight weeks). Patients who were treated with OAMCGT in addition to IMRT also received a single intraprostatic injection of 1 x 1012 viral particles of the Ad5-yCD/mutTKSR39rep-ADP adenovirus on the first day of treatment. Two days later, patients in the OAMCGT arm began IMRT treatment and received 5-FC (150 mg/kg/day, four times per day) and vGCV (1,800 mg/kg/day, twice daily) orally five days a week for two weeks.

Toxicity was assessed once a week during treatment. After completion of treatment, follow-up was conducted every three months for the first year post-treatment, at 18 and 24 months and then annually thereafter. Quality of life (QOL) was assessed at six, 12, 24 and 36 months post-treatment using the validated Expanded Prostate Cancer Index Composite (EPIC) and EuroQol EQ-5D instruments. A 12-core prostate biopsy was taken at 24 months post-treatment. Biopsies were examined by two pathologists blinded to the study treatments.

Gastrointestinal (GI) and genitourinary (GU) toxicity are the most common side effects of prostate radiation therapy. In this study, 5 percent of men (1) in the OAMCGT arm and 9 percent (2) in the IMRT alone arm experienced grade 2 or higher acute (90 days) GI toxicity. Grade 2 or higher acute GU toxicity was more prevalent in both arms, with 43 percent (9) in the OAMCGT arm and 31 percent (7) in the IMRT alone arm; however, there was no statistical significance in acute GI or GU toxicity between the two arms. Men in the OAMCGT arm experienced a higher occurrence of influenza-like symptoms, which were expected and attributed to the oncolytic adenovirus.

The sole significant difference in QOL in the EPIC domains (urinary incontinence, unitary irritation/obstruction, bowel, sexual, hormonal and overall satisfaction) at six months post-treatment was the sexual domain, which was better in the OAMCGT arm. The only significant difference in the EQ-5D domains (mobility, self-care, usual activities, pain and discomfort, anxiety and depression, and health state) was self-care at 24 months post-treatment, which was better in the OAMCGT arm.

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Newswise Fairfax, Va., June 2, 2014Combining oncolytic adenovirus-mediated cytotoxic gene therapy (OAMCGT) with intensity modulated radiation therapy (IMRT) reduces the risk of having a positive prostate biopsy two years after treatment in intermediate-risk prostate cancer without affecting patients quality of life, according to a study published in the June 1, 2014 edition of the International Journal of Radiation Oncology Biology Physics (Red Journal), the official scientific journal of the American Society for Radiation Oncology (ASTRO).

Previous prospective clinical trials in prostate cancer have shown that increasing the standard radiation dose of 70 Gy by 10 to 15 percent improves the biochemical disease-free survival in some prognostic risk groups; however, more than 25 percent of men with intermediate- or high-risk disease develop prostate-specific antigen (PSA) progression within 10 years, suggesting that radiation doses higher than 80 Gy may be necessary. This prospective randomized phase II trial examines the use of OAMCGT to improve the effectiveness of IMRT without increasing the radiation dose in intermediate-risk prostate cancer.

Based on encouraging results from a prior phase I trial, 44 patients were enrolled in this randomized phase II trial from January 2008 to July 2010. Patients were randomized to receive either OAMCGT with IMRT (21) or IMRT alone (23), and outcomes were focused on toxicity, quality of life and prostate biopsy findings at two years post-treatment. Eligible patients had newly diagnosed, clinically localized, intermediate-risk prostate cancer, defined as clinical stage T1/T2 with a Gleason score of 7 or a PSA of 10 to 20 ng/ml. Patients with a Gleason score of 5/6, a PSA <10 ng/ml and 50 percent positive biopsy cores were also eligible because it has been found that these patients tend to respond biochemically similar to patients with intermediate-risk disease. Of the 44 patients analyzed in this study, 82 percent (36) had stage T1 disease and 18 percent (8) had stage T2 disease. Sixteen percent (7) had a Gleason score of 6 and 84 percent (37) had a Gleason score of 7.

All patients were treated with IMRT (80 Gy in 2.0 Gy fractions over eight weeks). Patients who were treated with OAMCGT in addition to IMRT also received a single intraprostatic injection of 1 x 10^12 viral particles of the Ad5-yCD/mutTKSR39rep-ADP adenovirus on the first day of treatment. Two days later, patients in the OAMCGT arm began IMRT treatment and received 5-FC (150 mg/kg/day, four times per day) and vGCV (1,800 mg/kg/day, twice daily) orally five days a week for two weeks.

Toxicity was assessed once a week during treatment. After completion of treatment, follow-up was conducted every three months for the first year post-treatment, at 18 and 24 months and then annually thereafter. Quality of life (QOL) was assessed at six, 12, 24 and 36 months post-treatment using the validated Expanded Prostate Cancer Index Composite (EPIC) and EuroQol EQ-5D instruments. A 12-core prostate biopsy was taken at 24 months post-treatment. Biopsies were examined by two pathologists blinded to the study treatments.

Gastrointestinal (GI) and genitourinary (GU) toxicity are the most common side effects of prostate radiation therapy. In this study, 5 percent of men (1) in the OAMCGT arm and 9 percent (2) in the IMRT alone arm experienced grade 2 or higher acute (90 days) GI toxicity. Grade 2 or higher acute GU toxicity was more prevalent in both arms, with 43 percent (9) in the OAMCGT arm and 31 percent (7) in the IMRT alone arm; however, there was no statistical significance in acute GI or GU toxicity between the two arms. Men in the OAMCGT arm experienced a higher occurrence of influenza-like symptoms, which were expected and attributed to the oncolytic adenovirus.

The sole significant difference in QOL in the EPIC domains (urinary incontinence, unitary irritation/obstruction, bowel, sexual, hormonal and overall satisfaction) at six months post-treatment was the sexual domain, which was better in the OAMCGT arm. The only significant difference in the EQ-5D domains (mobility, self-care, usual activities, pain and discomfort, anxiety and depression, and health state) was self-care at 24 months post-treatment, which was better in the OAMCGT arm.

An important outcome was prostate biopsy at two years post-treatment, which is prognostic of long-term results. In this study, 84 percent (37) of patients had two-year biopsies. For men in the OAMCGT arm, there was a 42 percent relative reduction in positive biopsy at two years, and a 60 percent relative reduction in men with <50 percent positive biopsy cores at baseline. At the time of this studys findings, one patient in each arm had exhibited biochemical failure (4.8 percent in the OAMCGT arm and 4.3 percent in the IMRT alone arm). The events occurred 14.5 months post-treatment in the OAMCGT arm and 13.8 months post-treatment in the IMRT alone arm. No patients had developed hormone-refractory or metastatic disease, and no patients died from prostate cancer.

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Gene Therapy Combined with IMRT Found to Reduce the Rate of Positive Prostate Biopsy After Treatment for Intermediate ...

Recommendation and review posted by Bethany Smith

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