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Archive for the ‘Gene Therapy Research’ Category

Gene differences in tumors making cancer treatment difficult

A woman receives cancer treatment

(CBS/AP) BOSTON - Scientists are reporting what could be very bad news for efforts to customize cancer treatment based on each person's genes.

PICTURES: Got cancer? 10 secrets for better decisions

They have discovered big differences from place to place in the same tumor as to which genes are active or mutated. They also found differences in the genetics of the main tumor and places where the cancer has spread.

This means that the single biopsies that doctors rely on to choose drugs are probably not giving a true view of the cancer's biology. It also means that treating cancer won't be as simple as many had hoped.

New treatment for kidney transplant patients may reduce need for anti-rejection drugs

By analyzing tumors in unprecedented detail, "we're finding that the deeper you go, the more you find," said one study leader, Dr. Charles Swanton of the Cancer Research UK London Research Institute in England. "It's like going from a black-and-white television with four pixels to a color television with thousands of pixels."

Yet the result is a fuzzier picture of how to treat the disease.

The study is reported in Thursday's New England Journal of Medicine.

It is a reality check for "overoptimism" in the field devoted to conquering cancer with new gene-targeting drugs, Dr. Dan Longo, a deputy editor at the journal, wrote in an editorial.

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Gene differences in tumors making cancer treatment difficult

Gene Mutations Linked to Crohn's Disease in Ashkenazi Jews

THURSDAY, March 8 (HealthDay News) -- Researchers have identified five new genetic mutations associated with Crohn's disease in Jews of Eastern European descent (Ashkenazi Jews) and say their findings may help explain why Crohn's is nearly four times more prevalent in this group than in the general population.

Crohn's is an inflammatory bowel disease that causes swelling and irritation in the digestive tract. Symptoms include abdominal pain, diarrhea, rectal bleeding, weight loss, and fever.

Previous research pinpointed 71 genetic variants associated with Crohn's disease risk in people of European ancestry. In this new study, Mount Sinai School of Medicine researchers compared almost 2,000 Ashkenazi Jews with Crohn's disease to another 4,500 Ashkenazi Jews without the disease.

The team found 12 of the known risk variants and also discovered five new genetic risk regions on chromosomes 5q21.1, 2p15, 8q21.11, 10q26.3 and 11q12.1.

"This is the largest study to date, and the first to discover the unique risk factors of Crohn's disease in the Ashkenazi Jewish population," study leader Inga Peter, an associate professor of genetics and genomic sciences, said in a Mount Sinai news release.

"The prevalence of this disease is so much higher in Ashkenazi Jews, and the involvement of genetic variants predominant in this population might help understand why that is," she added.

The researchers also found that the genetic structure of the newly-identified regions associated with Crohn's disease risk in Ashkenazi Jews was much less diverse than that of non-Jewish Europeans.

"Not only did we discover different risk factors for Ashkenazi Jews, but we found that some previously known risk factors are more potent to this population," Peter said. "Armed with this new information, we can begin to analyze the specific signals in order to pinpoint causal genetic mutations, discover why they are malfunctioning, and eventually develop novel treatment approaches."

The study is published March 8 in the online edition of PLoS Genetics.

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Gene Mutations Linked to Crohn's Disease in Ashkenazi Jews

Researchers discover breakthrough with DNA testing

March 8, 2012 at 2:20 PM

As students start transitioning into spring, researchers are transitioning into a new era of gene research.

Dr. Frank Pugh, Willaman Chair in Molecular Biology, and his researchers have found a way to isolate proteins at the genes they regulate and to determine where exactly the protein bound to the gene.

Genes are the hereditary units that determine what traits, like eye and hair color, people have. They are composed of sequences of deoxyribose nucleic acid, or DNA.

These DNA sequences also are what determine which proteins bind where to control gene expression.

Pugh and his team began by isolating and purifying a particular protein using a technique called chromatin immunoprecipitation, otherwise known as ChIP. The technique uses antibodies to identify proteins associated with specific parts of a genome.

After purifying the protein they used an enzyme called exonuclease to destroy the DNA not involved in the gene they were examining, for the protein protected the DNA sequence to which it was bound.

This method, Pugh wrote in an email, reduced the noise that had interfered with previous methods, like extra DNA sequences that contaminated the samples that were being examined. He compared this noise to background noise that might interfere with someone listening to music.

These contaminations give the impression that there are additional binding sequences, Pugh wrote, and there is no way to distinguish between the actual binding sequences and the contaminations.

Once Pugh's team ran the tests, the results shocked them. They had expected the protein to bind to a few hundred places, but instead discovered that it bound to a few thousand locations - much more than they expected, even with the ChIP-exo method.

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Researchers discover breakthrough with DNA testing

Genetic changes make cancer deadly

London, March 8 (IANS) A single cancer can be dramatically different within one person, say experts. They discovered that different parts of a tumour can have different genes.

And a tumour that has spread to the chest can be genetically very different to the original tumour in the kidney, the Daily Mail reported Thursday.

The finding is important because cancer has traditionally been thought of as a disease in which a single cell starts dividing out of control, creating a tumour in which every cell is the same. Now it is clear that the disease is much more complex.

The genetic changes could help explain why cancer causes so many deaths, despite huge advances in medicine, and why a drug that has helped initially suddenly stops working.

Researchers funded by Cancer Research UK tested samples taken from kidney cancer patients being treated at London's Royal Marsden Hospital, the Mail said.

The research is still at an early stage, but, in future, doctors might take several biopsies from a patient, instead of just one. The genetic changes in the tumours accumulate over time, so early diagnosis will also be vital.

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Genetic changes make cancer deadly

Genetic manipulation boosts growth of brain cells linked to learning, enhances antidepressants

Public release date: 8-Mar-2012 [ | E-mail | Share ]

Contact: Deborah Wormser deborah.wormser@utsouthwestern.edu 214-648-3404 UT Southwestern Medical Center

DALLAS -- UT Southwestern Medical Center investigators have identified a genetic manipulation that increases the development of neurons in the brain during aging and enhances the effect of antidepressant drugs.

The research finds that deleting the Nf1 gene in mice results in long-lasting improvements in neurogenesis, which in turn makes those in the test group more sensitive to the effects of antidepressants.

"The significant implication of this work is that enhancing neurogenesis sensitizes mice to antidepressants meaning they needed lower doses of the drugs to affect 'mood' and also appears to have anti-depressive and anti-anxiety effects of its own that continue over time," said Dr. Luis Parada, director of the Kent Waldrep Center for Basic Research on Nerve Growth and Regeneration and senior author of the study published in the Journal of Neuroscience.

Just as in people, mice produce new neurons throughout adulthood, although the rate declines with age and stress, said Dr. Parada, chairman of developmental biology at UT Southwestern. Studies have shown that learning, exercise, electroconvulsive therapy and some antidepressants can increase neurogenesis. The steps in the process are well known but the cellular mechanisms behind those steps are not.

"In neurogenesis, stem cells in the brain's hippocampus give rise to neuronal precursor cells that eventually become young neurons, which continue on to become full-fledged neurons that integrate into the brain's synapses," said Dr. Parada, an elected member of the prestigious National Academy of Sciences, its Institute of Medicine, and the American Academy of Arts and Sciences.

The researchers used a sophisticated process to delete the gene that codes for the Nf1 protein only in the brains of mice, while production in other tissues continued normally. After showing that mice lacking Nf1 protein in the brain had greater neurogenesis than controls, the researchers administered behavioral tests designed to mimic situations that would spark a subdued mood or anxiety, such as observing grooming behavior in response to a small splash of sugar water.

The researchers found that the test group mice formed more neurons over time compared to controls, and that young mice lacking the Nf1 protein required much lower amounts of anti-depressants to counteract the effects of stress. Behavioral differences between the groups persisted at three months, six months and nine months. "Older mice lacking the protein responded as if they had been taking antidepressants all their lives," said Dr. Parada.

"In summary, this work suggests that activating neural precursor cells could directly improve depression- and anxiety-like behaviors, and it provides a proof-of-principle regarding the feasibility of regulating behavior via direct manipulation of adult neurogenesis," Dr. Parada said.

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Genetic manipulation boosts growth of brain cells linked to learning, enhances antidepressants

Detailed Genetic Tests Reveal Cancer's Complexity

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A study of kidney cancer patients finds the complexity of tumors may thwart simple attempts to personalize treatment.

A study of kidney cancer patients finds the complexity of tumors may thwart simple attempts to personalize treatment.

Cancer may be even more complicated than everybody already thought. And that's why a single tissue sample taken from a single tumor may not be the best way to figure out a course of treatment.

British researchers took multiple samples within kidney tumors (before and after drug treatment) and also got samples from tumors that had spread from the original cancers in four patients.

They performed all kinds of genetic tests, including detailed DNA sequencing, on the cancers and found wide variations in some key traits.

"We used every possible genomics technique available," senior author Charles Swanton told science blogger Ed Yong. "Even then we are only scratching the surface of the complexity within each cancer."

Even so, they found that some genetic variations that would be considered unfavorable for patients and others that would be good news for them were present in different parts of the same tumor.

Those results help explain why some treatments that seem like a good idea may not work. And they underscore the challenge in developing personalized tests and drugs for cancer therapy.

"It's a sobering finding," Andrew Futreal, a cancer geneticist and co-author of the study told The Wall Street Journal. The work was published in the latest New England Journal of Medicine.

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Detailed Genetic Tests Reveal Cancer's Complexity

Genetic Makeup of Tumors More Complex Than Thought

New Research Shows Personalized Treatment for Cancer Not So Simple

WebMD Health News

March 8, 2012 -- A small study that shows a surprising complexity of genetic changes within a single tumor has far-reaching implications for the march toward personalized cancer therapy, according to researchers.

A single biopsy from a tumor might not be sufficient to give a full picture of its genetic landscape, a team from the United Kingdom reports.

When the researchers examined 10 biopsies taken from a single kidney cancer tumor, they found "an extraordinary amount of diversity" in the genetic changes that had taken place in different parts of the tumor.

"There were more differences between biopsies from the same tumor at the genetic level than there were similarities," said researcher Charles Swanton, MD, PhD, from the Cancer Research UK, London Institute, and the University College London, United Kingdom.

The findings, published in the New England Journal of Medicine, were highlighted at a London news conference organized by Cancer Research UK, which funded the study.

The team also found differences in genetic changes between the primary tumor and places in the body where the cancer spread. Similar findings have been documented by other research groups.

But it is the extent of the genetic changes that is surprising, the researchers note.

The findings have far-reaching implications for the efforts currently being directed toward personalized cancer therapy, in which therapy is targeted at genetic changes identified in tumor tissue. Swanton cautioned that "if you take only one biopsy, you could be misled clinically."

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Genetic Makeup of Tumors More Complex Than Thought

Mr. Ludwig’s Gene Therapy Project – Video

06-03-2012 17:28 Baylie, Mason, and Sid on Gene Therapy

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Mr. Ludwig's Gene Therapy Project - Video

Nuvilex Points Toward Cell Encapsulation Technology Future to Expand Stem Cell Use for Late Stage Cancer Treatments

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Nuvilex Points Toward Cell Encapsulation Technology Future to Expand Stem Cell Use for Late Stage Cancer Treatments

Cancer gene mutation more complex than previously thought

Taking a sample or biopsy from just one part of a tumor might not give a full picture of its genetic diversity and may explain why doctors, despite using genetically targeted drugs, are often unable to save patients whose cancer has spread, scientists said.

A study by British researchers found there are more genetic differences than similarities between biopsies taken from separate areas of the same tumor, and yet further gene differences in samples taken from secondary tumors.

That might help explain why, despite recent development of a wave of highly targeted drugs designed to tackle cancers of specific genetic types, the prognosis remains poor for many patients with so-called solid-tumor disease like breast, lung, or kidney cancer that has spread to others parts of the body.

But the researchers, whose study was partly funded by charity Cancer Research UK and published in the New England Journal of Medicine, said it also pointed to a way forward.

The team carried out the first ever genome-wide analysis of the genetic changes or faults in different regions of the same tumor.

They looked at four patients with cancer in their kidneys, taking samples from different regions of the primary tumor and also from other organs where the tumor had spread.

They found that the majority of gene faults, around two-thirds, were not the same in one sample as in another, even when the biopsies were taken from the same tumor.

Samples taken from secondary tumors - which are a result of the disease spreading to other parts of the body - had yet more different genetic faults, suggesting that basing treatment decisions on just one primary tumor sample is not sufficient.

"We've known for some time that tumors are a patchwork of faults, but this is the first time we've been able to use cutting-edge genome sequencing technology to map out the genetic landscape of a tumor in such exquisite detail," said Charles Swanton, of University College London's cancer institute, who led the study and presented its results at a briefing in London on Tuesday.

He said they had uncovered "an extraordinary amount of diversity" at a genetic level both within tumors and within a single patient, with more differences between biopsies from the same tumor than similarities.

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Cancer gene mutation more complex than previously thought

2nd Antibody Engineering Summit 2012 to Open in Beijing This June

SHANGHAI--(BUSINESS WIRE)--

With the launch of Chinas 12th Five-year Plan for the biomedical industry, Chinas antibody drugs development will usher in a golden era. According to prediction of askci.com, by 2015, Chinas antibody drugs industry will record a total revenue of over RMB 40 billion, among which monoclonal antibody drugs will contribute over RMB 18 billion.

Under policy supports, Chinas antibodies R&D technology is constantly improving, with cancer and immune diseases as its main subjects, while therapeutic monoclonal antibodies also gained much progress. In addition, the enterprises have attached long-term importance to improving the protein expression in pilot trial and elevating the level of industrialization.

The 2nd Antibody Engineering Summit 2012 will discuss the policies, market, and R&D technologies, as well as arrange a GMP training session to interpret the latest standards and a factory tour to learn about the current technologies.

TOPICS:

PAST CHAIRMAN:

Ya-Jun Guo, Director of PLA General Hospital Cancer Center, Director of Cancer Research Institute of the Second Military Medical University and Chairman of National Engineering Research Center of Antibody Medicine and National Key Laboratory of Antibody Therapeutics.

PAST SPEAKERS/ATTENDEES:

ABOUT CBI

The medical conference team at CBI has long been committed to tracking the development and trend of medical industry, by adhering to the CBI principle of conducting in-depth study into the industry and keeping in close contact with industry players. The team takes a third-party perspective and regularly organizes summits on industrial hot issues. The ultimate goal is to serve professionals in the medical community by enhancing mutual understanding among domestic and overseas players, and by facilitating communication among research institutes, manufacturing enterprises and government institutions.

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2nd Antibody Engineering Summit 2012 to Open in Beijing This June

Scientists unlock genetic code for gorillas – and show the human link

Despite the evolutionary split with gorillas around 10 million years ago, we still share a remarkable number of genes with the great ape. Photo: AFP

HUMANS and gorillas last shared a common ancestor 10 million years ago, according to an analysis of the first full sequence of the gorilla genome. The gorilla is the last of the living great apes - humans, chimpanzees, gorillas and orangutans - to have its complete genetic code catalogued.

Scientists, led by researchers from the Wellcome Trust Sanger Institute near Cambridge, England, and Baylor College of Medicine in Houston, Texas, also found that 15 per cent of the gorilla's genetic code is closer between humans and gorillas than it is between humans and chimpanzees, our closest animal relative. The genomes of all three species are, in any case, highly similar: humans and chimpanzees share more than 98 per cent of their genes, while humans and gorillas share more than 96 per cent.

The genetic sequence was taken from a female western lowland gorilla named Kamilah and published in the science journal Nature.

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''Gorillas are an interesting animal in their right but the main reason they are of particular interest is because of their evolutionary closeness to us,'' said Aylwyn Scally, an author of the research from the institute. ''They're our second-closest evolutionary cousins after chimpanzees and knowing the content of the gorilla genome enables us to say quite a lot about an important period in human evolution when we were diverging from chimpanzees.''

Studying the gorilla genome suggests that the divergence of gorillas from the common ancestor of humans and chimpanzees happened around 10 million years ago. Humans and chimpanzees last shared a common ancestor around 6 million years ago. Eastern and western gorillas split some time in the last million years.

One curious find was the evolution of genes associated with hearing, which seem very similar between humans and gorillas. ''Scientists had suggested that the rapid evolution of human hearing genes was linked to the evolution of language,'' said Chris Tyler-Smith, senior author from the Wellcome Trust Sanger Institute. ''Our results cast doubt on this, as hearing genes have evolved in gorillas at a similar rate to those in humans.''

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Scientists unlock genetic code for gorillas - and show the human link

Tumor's Genetic Identity Not Revealed By Single Biopsy

Featured Article Academic Journal Main Category: Cancer / Oncology Also Included In: Genetics;Urology / Nephrology Article Date: 08 Mar 2012 - 2:00 PST

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Professor Peter Johnson, chief clinician at Cancer Research UK said in a statement that the study highlights "important differences that exist within tumours and suggest a way to improve the success rate of personalised cancer medicines".

The lead author of the study is Professor Charles Swanton, who works at Cancer Research UK's London Research Institute and the UCL Cancer Institute. He and his colleagues analyzed the genetic variation among different regions of the same cancer tumor, using samples donated by patients with advanced kidney cancer.

This is the first time genome-wide analysis has been used for this.

Swanton told the press that scientists have known for a while that a tumor is a "patchwork" of faults, but this is the first time, thanks to cutting edge genomic sequencing technology, scientists have been able to map the genetic landscape of a tumor in such "exquisite detail".

For the study, he and his colleagues compared the genetic variations in samples taken from different regions of four separate kidney tumors. They also took samples from other organs the cancer had spread to.

They found that about two thirds of the genetic faults in a tumor were not repeated across other biopsy samples from the same tumor.

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Tumor's Genetic Identity Not Revealed By Single Biopsy

Circassia's Ragweed Allergy Therapy Achieves Positive Phase II Clinical Results

OXFORD, England, March 8, 2012 /PRNewswire/ --

Circassia Ltd, a specialty biopharmaceutical company focused on allergy, today announced that its ragweed allergy therapy has achieved positive results in a key phase II clinical trial. In the study, patients with more severe symptoms achieved a significantly greater improvement following treatment with the ToleroMune T-cell vaccine than those on placebo (p0.05). The results were presented at the 2012 Annual Meeting of the American Academy of Allergy, Asthma and Immunology*.

"The results of this key phase II study are highly encouraging, because they show our ToleroMune ragweed allergy vaccine can reduce patients' symptoms after just a short course of treatment and, most importantly, offers the greatest improvement to those who can benefit most," said Steve Harris, Circassia's CEO. "We have now achieved successful phase II results with four of our allergy T-cell vaccines, which validate our scientific approach and give us the confidence to progress our lead programmes into the final phase of development."

Circassia's latest phase II study was designed to assess the T-cell vaccine's efficacy and tolerability and to identify the optimal treatment regime. The trial was conducted in Canada in 275 ragweed allergy patients. During the randomised, double-blind, placebo-controlled trial, volunteers received one of four regimens of ToleroMune treatment over a three-month period. Patients were exposed to ragweed allergens in a validated exposure chamber, and investigators compared their nasal and ocular symptoms against the pre-treatment baseline. The results show that the T-cell vaccine's optimal regimen substantially reduced patients' symptoms, achieving a 97% greater reduction than placebo (p0.05) in subjects who had a moderate level of symptoms at baseline. The treatment was safe and well tolerated in all groups.

About Circassia's allergy T-cell vaccines

Circassia is developing a range of allergy treatments based on its proprietary ToleroMune technology, which utilises small sections of allergens (epitopes) to generate regulatory T cells that suppress allergic immune responses, and thereby desensitise patients. The company has successfully completed a number of phase II studies with its cat, house dust mite, ragweed and grass allergy therapies. Clinical results show that short treatment regimes with Circassia's T-cell vaccines can greatly reduce patients' allergic responses, without the need for adjuvants or other immune stimulators, while proving extremely well tolerated. As a result, the treatments offer major potential clinical benefits compared with existing therapies, and have significant market opportunities. More than 150 million people suffer from allergic rhinitis in the US and Europe, and over 25% of the population of the United States and a growing number of Europeans are sensitive to ragweed pollen. As a result, the current allergy treatment market is valued at approximately $12 billion per year.

About Circassia

Circassia was founded in 2006 by a team of highly experienced biotechnology scientists and entrepreneurs, and is chaired by the former Chairman of GlaxoSmithKline, Sir Richard Sykes. The company is based in the UK on the Oxford Science Park, and in Hamilton, Canada, where its joint venture Adiga Life Sciences is located. Its ToleroMune technology was developed originally by scientists at Imperial College, London. Having successfully completed four fundraising rounds, Circassia has raised approximately 93 million ($159 million) and is backed by a syndicate of world-class institutional investors, including Imperial Innovations and Invesco Perpetual.

* Hafner R et al. Validation of peptide immunotherapy as a new approach in the treatment of allergic rhinoconjunctivitis: The clinical benefits of treatment with Amb a 1 derived T cell epitopes.

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Circassia's Ragweed Allergy Therapy Achieves Positive Phase II Clinical Results

Can Genes Keep You From Learning How to Jump Higher | Jump workout – Video

07-03-2012 03:35 jumpmanual.howtojumphigher.us There are lots of people out there that struggle with obesity, depression and the lack of athletic ability. Most, if not all, of these people blame their genes for these difficult times. While genes can play a role in making our lives more difficult, personal trainers, coaches and other health specialist are learning that genes do not determine the outcome of our lives. Genetic testing has come a very long way. Geneticists are getting closer every year to completing the gene mapping system for the human body. Recently researchers have found out that the ACTN3 gene, or the ""sprinting gene"" is common in Olympic athletes, giving them the conclusion that this gene (or variants of it) is what causes some athletes to be faster than others. They have also found that determining factors of your endurance such as your VO2max and Muscle Fiber Composition are directly related to your genes as well. Findings like these are giving people false confirmation that you are what you are because of your genes. But more and more people are finding that having the mental desire to be a better athlete, or to be better at anything, is the first step in overcoming gene challenges. Yet, people are starting to ask is athleticism (the desire to be an athlete) and personality inherited genetics? In other words, is the determination, drive, and will to overcome genetic traits, actually a genetic trait in of itself? Possibly. Geneticists are still learning about humans ...

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Can Genes Keep You From Learning How to Jump Higher | Jump workout - Video

Cost of Gene Sequencing Falls, Raising Hopes for Medical Advances

MOUNTAIN VIEW, Calif. -- In Silicon Valley, the line between computing and biology has begun to blur in a way that could have enormous consequences for human longevity.

Bill Banyai, an optical physicist at Complete Genomics, has helped make that happen. When he began developing a gene sequencing machine, he relied heavily on his background at two computer networking start-up companies. His digital expertise was essential in designing a factory that automated and greatly lowered the cost of mapping the three billion base pairs that form the human genome.

The promise is that low-cost gene sequencing will lead to a new era of personalized medicine, yielding new approaches for treating cancers and other serious diseases. The arrival of such cures has been glacial, however, although the human genome was originally sequenced more than a decade ago.

Now that is changing, in large part because of the same semiconductor industry manufacturing trends that opened up consumer devices like the PC and the smartphone: exponential increases in processing power and transistor density are accompanied by costs that fall at an accelerating rate.

As a result, both new understanding and new medicines will arrive at a quickening pace, according to the biologists and computer scientists.

"For all of human history, humans have not had the readout of the software that makes them alive," said Larry Smarr, director of the California Institute of Telecommunications and Information Technology, a research center that is jointly operated by the University of California, San Diego, and the University of California, Irvine, who is a member of the Complete Genomics scientific advisory board. "Once you make the transition from a data poor to data rich environment, everything changes."

Complete Genomics, based in Mountain View, is one of more than three dozen firms hastening to push the cost of sequencing an entire human genome below $1,000. The challenge is part biology, part chemistry, part computing, and in Complete Genomics' case, part computer networking.

Complete Genomics is a classic Silicon Valley start-up story. Even the gene sequencing machines, which are housed in a 4,000-square-foot room bathed in an eerie blue light, appear more like a traditional data center than a biology lab.

In 2005 ,when Clifford Reid, a successful Silicon Valley software entrepreneur, began to assemble his team, he approached Dr. Banyai and asked if he was interested in joining a gene sequencing start-up. Dr. Reid, who was also trained in physics and math, had spent a year as an entrepreneur-in-residence at the Massachusetts Institute of Technology, where he had become a convert to bioinformatics, the application of computer science and information technologies to biology and medicine.

Dr. Banyai had even less experience in biology.

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Cost of Gene Sequencing Falls, Raising Hopes for Medical Advances

Gene-based cancer research suffers setback, scientists say

BOSTON Scientists are reporting what could be very bad news for efforts to customize cancer treatment based on each persons genes.

They have discovered big differences from place to place in the same tumor as to which genes are active or mutated. They also found differences in the genetics of the main tumor and places where the cancer has spread.

This means that the single biopsies on which doctors rely to choose drugs are probably not giving a true view of the cancers biology. It also means that treating cancer wont be as simple as many had hoped.

By analyzing tumors in unprecedented detail, Were finding that the deeper you go, the more you find, said one study leader, Dr. Charles Swanton of the London Research Institutes Cancer Research UK. Its like going from a black-and-white television with four pixels to a color television with thousands of pixels.

Yet the result is a fuzzier picture of how to treat the disease.

The study is reported in Thursdays New England Journal of Medicine.

It is a reality check for overoptimism in the field devoted to conquering cancer with new gene-targeting drugs, Dr. Dan L. Longo, a deputy editor at the journal, wrote in an editorial.

About 15 of these medicines are on the market now and hundreds more are in testing, but they have had only limited success. And the new study may help explain why.

The scientists used gene sequencing to a degree that has not been done before to study primary tumors and places where they spread in four patients with advanced kidney cancer. They found that two-thirds of gene mutations they detected were not present in all areas of the same tumor. They also were stunned to see different mutations in the same gene from one part of a tumor to another.

That means a single biopsy would reveal only a minority of mutations. Still, its not clear whether doing more biopsies would improve accuracy, or how many or how often they should be done.

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Gene-based cancer research suffers setback, scientists say

The 'macho' gene that makes men aggressive has been found

By Tamara Cohen

Last updated at 12:49 AM on 8th March 2012

Scientists believe they have found the macho gene which makes men behave more aggressively than women under stress.

They say this one gene could explain why men have a fight or flight response while women are more likely to try and defuse the situation, a response known as tend and befriend.

Australian researchers have studied the chemicals secreted by men when they react to stress and how this influences their behaviour.

Rage against the machine: Anger in men is the fault of the SRY gene, say researchers (file picture)

And they propose that the SRY gene only found on the Y chromosome and the proteins it activates in the body, are the key.

This gene was previously thought just to be involved in the development of male characteristics in the womb.

Good spread: The SRY proteins were found all over the body

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The 'macho' gene that makes men aggressive has been found

Complicated cancer: New research shows how genetic changes make the disease so deadly

By Fiona Macrae

Last updated at 11:55 PM on 7th March 2012

British scientists have begun to unlock one of cancers most deadly secrets.

In a breakthrough likened to going from watching TV in black and white to colour, theyve discovered that a single cancer can be dramatically different within one person.

Different parts of a single tumour can have different genes. And a tumour that has spread to the chest can be genetically very different to the original tumour in the kidney.

Difference: Scientists have found that different parts of a single cancer tumour have different genes, possibly explaining why cancer can be so difficult to treat

The finding is important because cancer has traditionally been thought of as a disease in which a single cell starts dividing out of control, creating a tumour in which every cell is the same.

Now it is clear that the disease is much more complex.

The genetic changes could help explain why cancer causes so many deaths, despite huge advances in medicine, and why a drug that has helped initially suddenly stops working.

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Complicated cancer: New research shows how genetic changes make the disease so deadly

Transplant without lifetime of drugs?

Lindsay Porter's kidneys weighed 16 pounds before her transplant.

STORY HIGHLIGHTS

(CNN) -- By the time Lindsay Porter had her kidneys removed two years ago, they were bulging -- covered in cysts -- and together weighed 16 pounds.

Her abdominal area was so distended, "I looked nine months pregnant, and people regularly asked when I was due," Porter said.

As she prepared for a transplant to address her polycystic kidney disease, Porter, 47, had mixed feelings -- relief to have found a donor, tinged with resignation. She was looking forward to both a new kidney, and a lifetime on immune system-suppressing drugs.

"You get this brand new shiny kidney, and then they give you drugs that eventually destroy it," said Porter.

But that scenario may eventually change, if results of a new pilot study are replicated in a larger group of patients. The study, published Wednesday in the journal Science Translational Medicine, describes eight kidney transplant patients, including Porter, who received a stem cell therapy that allowed donor and recipient immune cells to coexist in the same body.

The effect, in a handful of those patients, was to trick the recipient's immune system into recognizing the donated kidney as its own.

When it works, patients become a sort of medical rarity called a chimera.

"Chimerism is a condition wherein two different genetic cell populations are present in the body, and both cell types are tolerated," said Dr. Anthony Atala, director of the Institute for Regenerative Medicine at Wake Forest Baptist Medical Center, who was not involved in the study, via e-mail.

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Transplant without lifetime of drugs?

Bio-firm research jobs go

Bio-firm research jobs go

7:00pm Wednesday 7th March 2012 in News

SIXTEEN research jobs have gone at gene therapy company Oxford BioMedica, but its workforce has been boosted after it opened a new drug manufacturing plant in Cowley.

A total of 83 staff are now based at Oxford Science Park in Littlemore after two jobs went at the companys US office in San Diego and 14 in Oxford.

BioMedica, which has its headquarters at the science park, paid 1.9m last February for a building in Transport Way, Cowley, left vacant by RecipharmCobra Biologics.

Another 1.7m has been spent on recommissioning the building with clean rooms that exclude microscopic impurities.

Chief executive John Dawson said: We very much regret the redundancies, but to ensure the long-term future of the company we have had to move the culture towards manufacturing and commercialisation.

There are some areas of long-term research which we have needed to trim back on.

He added: Until we reach sustainable profitability, we continue to strike a balance between growing the company while being careful with costs.

The company raised 20m from investors to fund the Cowley plant and enough cash to last until 2013. Its newly-released half-year results showed an 11m pre-tax loss.

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Bio-firm research jobs go

Cancer gene mutation more complex than previously thought -study

LONDON (Reuters) - Taking a sample or biopsy from just one part of a tumour might not give a full picture of its genetic diversity and may explain why doctors, despite using genetically targeted drugs, are often unable to save patients whose cancer has spread, scientists said.

A study by British researchers found there are more genetic differences than similarities between biopsies taken from separate areas of the same tumour, and yet further gene differences in samples taken from secondary tumours.

That might help explain why, despite recent development of a wave of highly targeted drugs designed to tackle cancers of specific genetic types, the prognosis remains poor for many patients with so-called solid-tumour disease like breast, lung, or kidney cancer that has spread to others parts of the body.

But the researchers, whose study was partly funded by charity Cancer Research UK and published in the New England Journal of Medicine, said it also pointed to a way forward.

The team carried out the first ever genome-wide analysis of the genetic changes or faults in different regions of the same tumour.

They looked at four patients with cancer in their kidneys, taking samples from different regions of the primary tumour and also from other organs where the tumour had spread.

They found that the majority of gene faults, around two-thirds, were not the same in one sample as in another, even when the biopsies were taken from the same tumour.

Samples taken from secondary tumours - which are a result of the disease spreading to other parts of the body - had yet more different genetic faults, suggesting that basing treatment decisions on just one primary tumour sample is not sufficient.

"We've known for some time that tumours are a patchwork of faults, but this is the first time we've been able to use cutting-edge genome sequencing technology to map out the genetic landscape of a tumour in such exquisite detail," said Charles Swanton, of University College London's cancer institute, who led the study and presented its results at a briefing in London on Tuesday.

He said they had uncovered "an extraordinary amount of diversity" at a genetic level both within tumours and within a single patient, with more differences between biopsies from the same tumour than similarities.

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Cancer gene mutation more complex than previously thought -study

From 'Refrigerator Mothers' to untangling the genetic roots of autism

Public release date: 7-Mar-2012 [ | E-mail | Share ]

Contact: Michael Bernstein m_bernstein@acs.org 202-872-6042 American Chemical Society

With the "Refrigerator Mother" notion about the cause of autism a distant and discredited memory, scientists are making remarkable progress in untangling the genetic roots of the condition, which affects millions of children and adults, according to an article in the current edition of Chemical & Engineering News. C&EN is the weekly newsmagazine of the American Chemical Society, the world's largest scientific society.

In the story, C&EN Associate Editor Lauren K. Wolf points out that most people in the 1960s believed autism resulted from a lack of maternal warmth and emotional attachment. It was a hypothesis popularized by Austrian-born American child psychologist and writer Bruno Bettelheim. Now scientists around the globe are focusing on genes that have been implicated in autism and related conditions, collectively termed "autism spectrum disorders." That research may solve mysteries about autism, which affects 1 in 110 children in the U.S. Among them: what causes autism, why does it affect more boys than girls and what can be done to prevent and treat it?

C&EN explains that scientists now have solidly implicated certain genes as being involved in autism. Most of those genes play a role in the transmission of signals through the junctions or "synapses" between nerve cells. Synapses are the territory where one nerve releases a chemical signal that hands off messages to an adjoining nerve. The human brain has an estimated 1,000 trillion synapses, and they are hot spots for miscommunications that underpin neurological disorders like autism. Scientists now are gleaning information on what those genes do, what brain circuits they affect and how the proteins they produce function. In doing so, they are paving the way for future medications for autism spectrum disorders.

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The American Chemical Society is a nonprofit organization chartered by the U.S. Congress. With more than 164,000 members, ACS is the world's largest scientific society and a global leader in providing access to chemistry-related research through its multiple databases, peer-reviewed journals and scientific conferences. Its main offices are in Washington, D.C., and Columbus, Ohio.

To automatically receive news releases from the American Chemical Society contact newsroom@acs.org.

AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert! system.

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From 'Refrigerator Mothers' to untangling the genetic roots of autism

More effective treatments urgently needed for adolescent depression

Public release date: 7-Mar-2012 [ | E-mail | Share ]

Contact: Cathia Falvey cfalvey@liebertpub.com 914-740-2100 Mary Ann Liebert, Inc./Genetic Engineering News

New Rochelle, NY, Mar 07, 2012--More than 2 million teenagers suffer from depression in the U.S. Recent drug warnings and study results have led to increased controversy surrounding the treatment of adolescent depression. A state-of-the-art issue reporting on the latest research findings on antidepressant medications combined with appropriate therapeutic strategies has been published by Journal of Child and Adolescent Psychopharmacology, a peer-reviewed journal from Mary Ann Liebert, Inc. The special issue on psychopharmacology of adolescent depression is available free on the Journal of Child and Adolescent Psychopharmacology website.

"There are no radically new treatments on the horizon for the treatment of depression, and so we have to do better with the treatments we have available," says Graham J. Emslie, MD, Guest Editor of the issue and Director of Child Psychiatry at University of Texas Southwestern Medical Center, Dallas. "Few youths with depression receive adequate treatment."

The issue focuses on the controversy, the data, and the challenges and opportunities in the care of adolescents with major depressive illness. The articles cover a wide range of issues that all contribute to the goal of improving outcomes. Included in the issue, Greg Clarke, PhD et al., Kaiser Permanente Center for Health Research (Portland, OR), present an evaluation of new and refill antidepressant prescribing practices among physicians before and after warnings related to teen suicide risk were issued. Kenneth Wells, MD, MPH and colleagues from University of California, Los Angeles, and Stony Brook University (NY), explore the effectiveness of appropriate care delivered in a primary care setting. Dr. Emslie and colleagues from UT Southwestern Medical Center examine the common problem of insomnia in youths with depression and its impact on treatment.

"Depression is a major public health concern among young people, particularly teens, but many people have a hard time talking about it," says Harold S. Koplewicz, MD, Editor-in-Chief of Journal of Child and Adolescent Psychopharmacology, and President, Child Mind Institute, New York, NY. "Advancing research is one way we can work to change a culture of denial that too often stands in the way of effective and sometimes life-saving treatment."

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About the Journal

Journal of Child and Adolescent Psychopharmacology is an authoritative peer-reviewed journal published bimonthly in print and online. The journal is dedicated to child and adolescent psychiatry and behavioral pediatrics, covering clinical and biological aspects of child and adolescent psychopharmacology and developmental neurobiology. Complete tables of content and a sample issue may be viewed online at the Journal of Child and Adolescent Psychopharmacology website.

About the Company

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More effective treatments urgently needed for adolescent depression

New England Journal of Medicine Publishes Data from Phase 2 Study of Asfotase Alfa in Life-Threatening Hypophosphatasia

CHESHIRE, Conn.--(BUSINESS WIRE)--

Alexion Pharmaceuticals, Inc. (Nasdaq: ALXN - News) today announced that asfotase alfa (formerly known as ENB-0040), a highly innovative investigational targeted enzyme replacement therapy, was shown to improve skeletal abnormalities, pulmonary and physical function, and cognitive development in a Phase 2 study of infants and young children with life-threatening hypophosphatasia (HPP). Alexion is developing asfotase alfa as a potential treatment for patients with HPP, an ultra-rare, genetic, life-threatening metabolic disease for which there are currently no approved or effective treatment options. Findings from the study are published in the March 8th issue of the New England Journal of Medicine.

Due to a genetic enzyme deficiency, symptomatic patients with HPP face progressive damage to multiple vital organs including destruction and deformity of bones, profound muscle weakness, seizures, impaired renal function, and respiratory failure.1,2,3,4 About half of newborns with HPP do not survive past one year of age.1

This inborn error of metabolism can cause progressive skeletal deterioration and muscle weakness in severely affected infants and very young children with HPP, leading to respiratory insufficiency and significant mortality, said lead study author Michael P. Whyte, M.D., Medical-Scientific Director, Center for Metabolic Bone Disease and Molecular Research, Shriners Hospitals for Children, St. Louis. In this study of patients with severe perinatal and infantile forms of HPP, we saw in nearly all patients striking skeletal healing that included improved bone formation and reduced deformity, as well as improved pulmonary function and motor development. These findings are remarkable given the historically grim outlook for patients with life-threatening HPP.

About the Study

The multinational, open-label Phase 2 study of asfotase alfa enrolled 11 patients with HPP ages 3 years or younger whose symptoms began before the age of 6 months. Patients in the study received asfotase alfa for six months and then had the opportunity to enroll in an open-label extension study.

The primary efficacy endpoint was change in the skeletal manifestations of HPP, as assessed by radiography. Response to treatment was defined as a mean improvement of two or more points, as rated by a panel of three independent radiologists, on a seven-point scale known as the radiographic global impression of change (RGI-C). Skeletal changes were also assessed using a 10-point scale that measured skeletal abnormalities at the wrists and knees. Additional efficacy assessments included evaluations of respiratory status, gross motor function, and cognitive development (Bayley-III scale).

Ten patients completed the six-month study and nine patients are currently participating in the extension study. All patients treated with asfotase alfa demonstrated an improvement in two key biochemical indicators of HPP: blood levels of PPi (inorganic pyrophosphate) and PLP (pyridoxal 5 phosphate). For the primary efficacy endpoint, nine of 10 patients (90%) met the criterion for treatment response by week 24, and eight of nine (89%) achieved treatment response by week 48. Skeletal healing became apparent as early as week 3.

Respiratory function improved in all patients. These improvements were evident as early as week 12. Compared to the 10 of 11 patients who required respiratory support at baseline, at week 48 only three of nine patients required any respiratory support and only one patient remained on full mechanical ventilation. In addition to the improvements in bone mineralization and respiratory function, there were improvements in fine motor, gross motor and cognitive development, as assessed by the Bayley-III instrument, for seven of the eight patients who were evaluated. Whereas at baseline, no patients were able to bear weight through their legs owing to skeletal abnormalities and muscle weakness, at 48 weeks of treatment, seven of nine patients were able to bear weight through their legs.

The most common treatment-related adverse event observed in the study was mild injection-site reaction. Severe adverse events observed in the study were generally consistent with the symptoms expected of patients with severe HPP, including infection, respiratory disorders, and nervous-system complications. One patient died, and this was determined to not be related to study drug.

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New England Journal of Medicine Publishes Data from Phase 2 Study of Asfotase Alfa in Life-Threatening Hypophosphatasia

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