Category Archives: Gene Medicine

UT Southwestern Medical Center researchers are developing a new predictive tool that could help patients with breast cancer and certain lung cancers decide whether follow-up treatments are likely to help.

Dr. Jerry Shay, Vice Chairman and Professor of Cell Biology at UT Southwestern, led a three-year study on the effects of irradiation in a lung cancer-susceptible mouse model. When his team looked at gene expression changes in the mice, then applied them to humans with early stage cancer, the results revealed a breakdown of which patients have a high or low chance of survival.

The findings, published online in Clinical Cancer Research, offer insight into helping patients assess treatment risk. Radiation therapy and chemotherapy that can destroy tumors also can damage surrounding healthy tissue. So with an appropriate test, patients could avoid getting additional radiation or chemotherapy treatment they may not need, Dr. Shay said.

"This finding could be relevant to the many thousands of individuals affected by these cancers and could prevent unnecessary therapy," said Dr. Shay, Associate Director for Education and Training for the Harold C. Simmons Comprehensive Cancer Center at UT Southwestern. "We're trying to find better prognostic indicators of outcomes so that only patients who will benefit from additional therapy receive it."

Dr. Shay's study closely monitored lung cancer development in mice after irradiation. His group found some types of irradiation resulted in an increase in invasive, more malignant tumors. He examined the gene expression changes in mice well before some of them developed advanced cancers. The genes in the mouse that correlated with poor outcomes were then matched with human genes. When Dr. Shay's team compared the predictive signatures from the mice with more than 700 human cancer patient signatures, the overall survivability of the patients correlated with his predictive signature in the mice. Thus, the classifier that predicted invasive cancer in mice also predicted poor outcomes in humans.

His study looked at adenocarcinoma, a type of lung cancer in the air sacks that afflicts both smokers and non-smokers. The findings also predicted overall survival in patients with early-stage breast cancer and thus offer the same helpful information to breast cancer patients; however the genes were not predictive of another type of lung cancer, called squamous cell carcinoma. Other types of cancers have yet to be tested.

The American Cancer Society estimates the risk of developing lung cancer to be 1 in 13 for men and 1 in 16 for women, including both smokers and non-smokers. Lung cancer is the second most common cancer in both men and women, accounting for about 13 percent of all new cancers, and about 27 percent of cancer deaths. The American Cancer Society estimates more than 224,210 new cases of lung cancer and nearly 160,000 deaths from lung cancer will occur in 2014. Survival statistics vary depending on the stage of the cancer and when it is diagnosed.

Dr. Shay's research is paid for in part by a five-year grant from NASA, which helps fund cancer research due to cancer risks faced by astronauts during space missions. The findings could lead to more individualized care and pave the way to better, more science-based care and decision making, he said.

"Personalized medicine is coming," Dr. Shay said. "I think this is the future -- patients looking at their risks of cancer recurrence and deciding what to do next. We can better tailor the treatment to fit the individual. That's the goal."

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Gene may predict if further cancer treatments are needed

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Newswise NEW ORLEANS, La. David Epstein, author of the New York Times bestseller, The Sports Gene, will deliver the Presidential Keynote at the 23rd Annual Meeting of the American Medical Society for Sports Medicine (AMSSM) at the Hyatt Regency in New Orleans next week. In his keynote, Epstein will address the following:

How "nature versus nurture" in sports is a false dichotomy. Why Major League Baseball players need both the right physical "hardware" and "software" to be able to hit 100-mph fastballs. Where the 10,000-hours rule comes from and what the data from that famous study says. How the body types of athletes have changed faster than the gene pool of humanity has changed, and how that provides new information to help people find the right sport. Why the push for increased youth sport specialization is bad both for the health of youth athletes and their athletic development.

Epstein is currently an investigative reporter at the nonprofit newsroom, ProPublica. Prior to that, he was a senior writer at Sports Illustrated, where he focused on sports science and medicine. Epstein is perhaps best known for co-authoring the story that exposed the steroid use of Yankees third baseman Alex Rodriguez. He has a Masters degree in environmental science and was All-East as an 800-meter runner at Columbia University.

His presidential keynote will be held from 10:40 a.m. to 11:10 a.m. on Sunday, April 6, 2014 at the Hyatt Regency New Orleans. Registration is required for admittance. Media interested in being credentialed for the 2014 AMSSM Annual Meeting must contact Jessica Torres-Sosa, AMSSM Communications Manager, at jtorres@amssm.org.

About the AMSSM Annual Meeting: More than 1,400 sports medicine physicians from the United States and abroad come together to address advances and challenges in sports medicine through lectures and research. Learn more at https://www.amssm.org/ConferencesDetails.php?IDconf=58&Past=.

About the AMSSM: AMSSM is a multi-disciplinary organization of 2,500 sports medicine physicians dedicated to education, research, advocacy and the care of athletes of all ages. The majority of AMSSM members are primary care physicians with fellowship training and added qualification in sports medicine who then combine their practice of sports medicine with their primary specialty. AMSSM includes members who specialize solely in non-surgical sports medicine and serve as team physicians at the youth level, NCAA, NFL, MLB, NBA, WNBA, MLS and NHL, as well as with Olympic teams. By nature of their training and experience, sports medicine physicians are ideally suited to provide comprehensive medical care for athletes, sports teams or active individuals who are simply looking to maintain a healthy lifestyle. http://www.amssm.org

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David Epstein, New York Times Best-Selling Author of 'The Sports Gene', to Deliver Presidential Keynote at 2014 AMSSM ...

Charlottesville, VA (PRWEB) March 27, 2014

Researchers at the University of Virginia School of Medicine have identified a key gene variation linked to an increased risk of stroke. The discovery comes as part of a breakthrough in the understanding of what causes some people to produce too much homocysteine, an amino acid associated with stroke, cancer, dementia, hardening of the arteries and other diseases.

As part of their work, the researchers have developed a genetic test that can predict which people are at risk for producing too much homocysteine, and their discovery could lead to new treatments for the associated diseases.

The findings also show that the conversion of the enzyme methionine into homocysteine the primary focus of the researchers investigation plays an important role in controlling the activity of genes. That discovery could have significant implications for understanding stroke, cardiovascular disease and other conditions.

Excess Homocysteine While high homocysteine levels have long been suspected as a culprit in diseases, efforts to lower homocysteine in scientific trials have not produced health benefits. The new UVA research explains what may be happening to produce the elevated levels, suggesting that one gene in particular, GNMT, is being stimulated to work too hard. The researchers found four other genes that appear to play a role as well, though to a lesser degree.

What we found was a really striking result for a genome association study, said Stephen R. Williams, PhD, a postdoctoral fellow at UVAs Cardiovascular Research Center and UVAs Center for Public Health Genomics. Its hard to find something thats significant, and its hard to find something biologically relevant, and we did that five times over.

Risk for Stroke The researchers set out to determine why certain people metabolize methionine into homocysteine differently than do others. To do so, they reviewed the genomes of nearly 5,000 participants in two studies: the Vitamin Intervention for Stroke Prevention, a trial that aimed to prevent people from suffering a second ischemic stroke, and the Framingham Heart Study, which has followed participants cardiovascular health for decades. It was through that review that the researchers were able to identify the five critical genes, including one form of the ALDH1L1 gene associated with ischemic stroke in the Framingham study.

The researchers then determined that differences in the regulation of the GNMT gene are the main reasons for the variations in methionine metabolism in people. To reach that conclusion, they created a test based on the DNA from a person who was a high methionine metabolizer and DNA from a low metabolizer, to see how the DNA reacted when treated with methionine. What turned out was that the individuals who had higher post-methionine load homocysteine had higher gene-promoter activity, Williams said. That was really interesting, because it gave us a functional cause that partially explains why this may be happening and the genetics of why people may metabolize methionine differently.

The researchers were able to devise a risk score evaluating the risk for developing excess homocysteine based on which gene variations people have. If you had all of them, you are in the highest risk category, said UVA researcher Michle Sale, PhD.

The risk score actually predicts how an overall population would perform in the post-methionine load test, Williams explained. Thats genetic relevance thats actually leading to clinical prediction. So thats really cool.

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UVA Links Gene to Stroke Risk, Finds Clues to Genetics of Many Diseases

PUBLIC RELEASE DATE:

26-Mar-2014

Contact: Cathy Yarbrough press@genetics-gsa.org sciencematter@yahoo.com 858-243-1814 Genetics Society of America

Four years ago, University of Iowa scientists discovered that mutations in the prickle gene in Drosophila were responsible for much more than merely altering the bristles on the fly's body to point them in the wrong direction.

Prompted by a colleague's finding that PRICKLE gene mutations were responsible for triggering a form of epilepsy in humans, John Manak, Ph.D., who led the fly research team, took a closer look at the Drosophila prickle mutants. (PRICKLE refers to the human gene, while prickle is the Drosophila form of the gene.)

Through a series of experiments, Dr. Manak found that flies with prickle mutations had seizures with jerky movements of their wings and leg muscles that closely resembled the myoclonic form of epilepsy that affects patients with mutations in the human version of the gene. During myoclonic epileptic seizures, the patients' muscles involuntarily twitch and jerk.

In a 2011 paper about the discovery, the University of Iowa scientists also reported that valproic acid, the anti-convulsive drug, which has been used to effectively treat myoclonic epilepsy patients with PRICKLE gene mutations, also helped control seizures in the mutated flies. These findings suggested that the pathway responsible for seizures in flies and humans was conserved, and that flies with prickle mutations could now be used to screen new experimental therapeutic agents for this disorder. These experiments are now underway.

The scientists have continued to investigate Drosophila flies with the mutated prickle gene. They determined that the seizure threshold, the amount of electrical stimulation required to induce a seizure, was lower in flies with the prickle mutation than in the normal (control) Drosophila flies of the same age, demonstrating that these flies exhibited a classic characteristic of seizure susceptibility. In addition, muscle recordings after experimentally induced electric shock through the nervous system revealed that spiking activity, a measure of neuronal activity, was higher in the flies with the prickle mutations than in the control flies.

Using a technique that they developed for the study, the researchers also found that ataxia (or uncoordinated gait), which occurs in patients with myoclonic epilepsy, also occurs in flies with the prickle gene mutation. The ataxia was more severe in the Drosophila with two prickle gene mutations than in flies with one prickle gene mutated, suggesting that prickle dosage plays an important role in controlling seizures.

The University of Iowa researchers' most recent studies have identified the basic cellular mechanism that goes awry in the prickle mutant flies, leading to the epilepsy-like seizures, and these data will be presented at the GSA Drosophila Research Conference.

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Gene mutations in flies and humans produce similar epilepsy syndromes

(PRWEB) March 27, 2014

According to the new market research report, Gene Expression Analysis Market by Technology (DNA Microarray, Real-Time PCR, Next Generation Sequencing), Consumables (DNA Chips, Reagents), Services (Gene Profiling, Bioinformatics, Data Analysis Software) & Applications - Global Forecast to 2018, global gene expression analysis market estimated at $2.6 billion in 2013 and is expected to reach $4.3 billion by 2018, growing at a CAGR of 10.4% from 2013 to 2018.

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The Global Gene Expression Analysis Market (2013-2018) analyzes and studies the major market drivers and restraints in North America, Europe, Asia, and the Rest of the World (RoW).

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The global gene expression analysis market is witnessing a significant growth and will continue to do so in the next five years. The factors contributing to this growth are increased funding scenario worldwide, increased government involvement, developments in research for diseases like cancer, and the use of gene expression in drug discovery and personalized medicine. The Asian region is projected to have the highest growth rate with growth hinged at China, India, and Japan. Apart from Asia, countries such as Turkey, Brazil, and South Africa too have a high projected growth.

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Over the years, gene expression analysis techniques have evolved significantly and are being widely used in the areas of diagnostics, drug discovery, and treatment of certain diseases. In the past few years, the market has witnessed significant technological advancements, as companies have introduced new products in the market. This technologically driven market has witnessed a large number of offerings by big as well as small companies. In order to be competitive in this market, companies must be focused on delivering superior quality products that are technologically advanced.

Various key growth strategies such as new product launches, acquisitions, expansions, agreements, partnerships, collaborations, and joint ventures were mainly adopted by key players such as QIAGEN N.V. (Netherlands), Agilent Technologies (U.S.), Illumina, Inc. (U.S.), Life Technologies Corporation (U.S.), and Roche Diagnostics Corporation (Switzerland). These players adopted these strategies to increase their market shares. For instance, in October 2013, QIAGEN acquired CLC bio, a leading bioinformatics analysis software provider. This acquisition will position QIAGEN as a leader in next-generation bioinformatics, with a focus on biological analysis and interpretation/reporting. Thus, companies are investing efforts and resources in these strategies to help them gain a competitive advantage in the gene expression analysis market.

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Gene Expression Analysis Market (Gene Profiling, Bioinformatics, Data Analysis Software) worth $4.3 Billion by 2018 ...

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Newswise March 26, 2014 (BRONX, NY) From uncovering the role nerve cells play in metastasis to identifying new cancer-causing genes, researchers at Albert Einstein College of Medicine of Yeshiva University made notable advances in the understanding and potential treatment of cancer during the past year.

Several Einstein faculty members and students will present their recent research at the American Association for Cancer Research (AACR) Annual Meeting, taking place in San Diego April 5-9, 2014. Among the presentations are those during major and mini symposia:

Gene Regulation and Transcription Factors Ujunwa Cynthia Okoye-Okafor, M.D./Ph.D. student Ms. Okoye-Okafor, who will be receiving the AACRs 2014 AACR Minority Scholar in Cancer Research Award during the Annual Meeting, will present Characterization of novel protein-coding gene named TIHL (Translocated in Hodgkins Lymphoma). Ms. Okoye-Okafor discovered this gene as a student in the lab of Ulrich Steidl, M.D., Ph.D., who focuses on transcriptional and epigenetic regulation of hematopoiesis and leukemia. Dr. Steidl is associate professor of cell biology and of medicine at Einstein and associate chair, translational research in oncology at Montefiore Medical Center, the University Hospital for Einstein. Monday, April 7, 3:00-5:00 pm (3:20-3:35 pm), Room 33, San Diego Convention Center

Neural Regulation of Prostate Cancer Paul Frenette, M.D. Dr. Frenette will present at the major symposium titled Complexity in the Tumor Microenvironment. He will discuss his research, including his recent Science paper that showed nerves play a key role in triggering prostate cancer and influencing its spread. Dr. Frenette is chair and director of Einsteins Ruth L. and David S. Gottesman Institute for Stem Cell and Regenerative Medicine. Tuesday, April 8, 10:30 am-12:30 pm, Ballroom 20D, San Diego Convention Center

EGFR Family, P13K, AKT and NF-kB Signaling Antonio Di Cristofano, Ph.D. Dr. Di Cristofano will chair and present during the minisymposium. The central focus of his laboratory is the identification and characterization of the specific biological processes and signaling pathways that are controlled by the PI3K/PTEN/AKT cascade. His research is centered on tumors originating in the thyroid gland and he was recently honored by the American Thyroid Association for his work. Dr. Di Cristofano is professor of developmental & molecular biology at Einstein. Tuesday, April 8, 3:00-5:00 pm, Room 6CF, San Diego Convention Center

Epigenetics 4 Orsolya Giricz, Ph.D. Dr. Giricz will be presenting Integrated epigenomic profiling reveals widespread demethylation in melanoma and reveals CSF-1 receptor as an aberrant regulator of malignant growth and invasion. She received an AACR Millennium Scholar in Training Award for this work. Dr. Giricz is an associate in the medicine department at Einstein and works in the lab of Amit Verma, M.B.B.S., whose research focuses on epigenomic profiling of tumors. Dr. Verma is associate professor of medicine and of developmental & molecular biology at Einstein and director of hematologic malignancies at Montefiore Einstein Center for Cancer Care, Tuesday, April 8, 3:00-5:00 pm (3:35-3:50 pm), Room 6A, San Diego Convention Center

In addition to the symposium presentations, faculty members will lead two methods workshops and present 19 posters on a variety of topics, including imaging tumor cells, evaluating cancer subtypes in epidemiological studies, and identifying potential biomarkers and drug targets for breast, colon, thyroid, head and neck, and lung cancers.

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Albert Einstein College of Medicine Researchers Present at AACR Annual Meeting Symposia

PUBLIC RELEASE DATE:

24-Mar-2014

Contact: Andrea Grossman 617-636-3728 Tufts University, Health Sciences Campus

Boston, MA [March 24, 2014, 3:00 p.m. EDT] A single gene appears to play a crucial role in coordinating the immune system and metabolism, and deleting the gene in mice reduces body fat and extends lifespan, according to new research by scientists at the Jean Mayer USDA Human Nutrition Research Center (USDA HNRCA) on Aging at Tufts University and Yale University School of Medicine. Their results are reported online today in the Proceedings of the National Academy of Sciences.

Based on gene expression studies of fat tissue conducted at the USDA HNRCA, the Tufts University researchers initiated studies of the role of FAT10 in adipose tissue and metabolism. "No one really knew what the FAT10 gene did, other than it was 'turned on' by inflammation and that it seemed to be increased in gynecological and gastrointestinal cancers." said co-author Martin S. Obin, Ph.D., an adjunct scientist in the Functional Genomics Core Unit at the USDA HNRCA at Tufts University. "Turning off the FAT10 gene produces a variety of beneficial effects in the mice, including reduced body fat, which slows down aging and extends lifespan by 20 percent."

Typically, mice gain fat as they age. The authors observed that activation of the FAT10 gene in normal mice increases in fat tissue with age. Mice lacking FAT10 consume more food, but burn fat at an accelerated rate. As a result, they have less than half of the fat tissue found in normal, aged mice. At the same time their skeletal muscle ramps up production of an immune molecule that increases their response to insulin, resulting in reduced circulating insulin levels, protection against type 2 diabetes and longer lifespan.

The authors note that eliminating FAT10 will not fully address the dilemma of aging and weight gain. "Laboratory mice live in a lab under ideal, germ-free conditions," said Obin, who is also an associate professor at the Friedman School of Nutrition Science and Policy at Tufts University. "Fighting infection requires energy, which can be provided by stored fat. Mice without the FAT10 gene might be too lean to fight infection effectively outside of the laboratory setting. More research is needed to know how to achieve that balance in mice and then hopefully, at some point, people."

The possibilities for future research of FAT10 are exciting. Recent high-profile studies reported that FAT10 interacts with hundreds of other proteins in cells. Now the Tufts and Yale researchers have demonstrated that it impacts immune response, lipid and glucose metabolism, and mitochondrial function.

"Now there is dramatic road map for researchers looking at all of the proteins that FAT10 gets involved with," said co-first and corresponding author Allon Canaan, Ph.D., an associate scientist in the Department of Genetics at Yale. "Blocking what FAT10 does to coordinate immunity and metabolism could lead to new therapies for metabolic disease, metabolic syndrome, cancer and healthy aging, because when we knock it out the net result is mice live longer."

Canaan and colleagues initially developed the FAT10-deficient mouse to study the role of FAT10 in sepsis. In an attempt to increase sensitivity for sepsis, Canaan aged the FAT10 knockout mice and made the discovery that mice lacking the gene were lean and aged more slowly. The mice appear younger and more robust than comparably-aged normal mice, have better muscle tone, and do not develop age-related tumors.

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Deletion of FAT10 gene reduces body fat, slows down aging in mice

Scientists from Weill Cornell Medical College and Houston Methodist have found that a gene previously unassociated with breast cancer plays a pivotal role in the growth and progression of the triple negative form of the disease, a particularly deadly strain that often has few treatment options. Their research, published in this week's Nature, suggests that targeting the gene may be a new approach to treating the disease.

About 42,000 new cases of triple negative breast cancer (TNBC) are diagnosed in the United States each year, about 20 percent of all breast cancer diagnoses. Patients typically relapse within one to three years of being treated.

Senior author Dr. Laurie H. Glimcher, the Stephen and Suzanne Weiss Dean of Weill Cornell Medical College, wanted to know whether the gene -- already understood from her prior work to be a critical regulator of immune and metabolic functions -- was important to cancer's ability to adapt and thrive in the oxygen- and nutrient-deprived environments inside of tumors. Using cells taken from patients' tumors and transplanted into mice, Dr. Glimcher's team found that the gene, XBP1, is especially active in triple negative breast cancer, particularly in the progression of malignant cells and their resurgence after treatment.

"Patients with the triple negative form of breast cancer are those who most desperately need new approaches to treat their disease," said Dr. Glimcher, who is also a professor of medicine at Weill Cornell. "This pathway was activated in about two-thirds of patients with this type of breast cancer. Now that we better understand how this gene helps tumors proliferate and then return after a patient's initial treatment, we believe we can develop more effective therapies to shrink their growth and delay relapse."

The group, which included investigators from nine institutions, examined several types of breast cancer cell lines. They found that XBP1 was particularly active in basal- like breast cancer cells cultivated in the lab and in triple negative breast cancer cells from patients. When they suppressed the activity of the gene in laboratory cell cultures and animal models, however, the researchers were able to dramatically reduce the size of tumors and the likelihood of relapse, especially when these approaches were used in conjunction with the chemotherapy drugs doxorubicin or paclitexel. The finding suggests that XBP1 controls behaviors associated with tumor-initiating cells that have been implicated as the originators of tumors in a number of cancers, including that of the breast, supporting the hypothesis that combination therapy could be an effective treatment for triple negative breast cancer.

The scientists also found that interactions between XBP1 and another transcriptional regulator, HIF1-alpha, spurs the cancer-driving proteins. Silencing XBP1 in the TNBC cell lines reduced the tumor cells' growth and other behaviors typical of metastasis.

"This starts to demonstrate how cancer cells co-opt the endoplasmic reticulum stress response pathway to allow tumors to grow and survive when they are deprived of nutrients and oxygen," said lead author Dr. Xi Chen, a postdoctoral associate at Weill Cornell, referring to the process by which healthy cells maintain their function. "It shows the interaction between two critical pathways to make the cells better able to deal with a hostile microenvironment, and in that way offers new strategies to target triple negative breast cancer."

Scientists still need to study how those strategies would help women with the disease.

"Obviously we need to know now whether what our group saw in models is what we'll see in patients," said coauthor Dr. Jenny Chang, professor of medicine at Weill Cornell and director of the Houston Methodist Cancer Center. "We are very excited about the prospect of moving this research forward as soon as possible for the benefit of patients."

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Gene implicated in progression, relapse of deadly breast cancer finding points to potential Achilles' heel in triple ...

PUBLIC RELEASE DATE:

24-Mar-2014

Contact: Jen Gundersen jeg2034@med.cornell.edu 646-317-7402 Weill Cornell Medical College

NEW YORK (March 24, 2014) Scientists from Weill Cornell Medical College and Houston Methodist have found that a gene previously unassociated with breast cancer plays a pivotal role in the growth and progression of the triple negative form of the disease, a particularly deadly strain that often has few treatment options. Their research, published in this week's Nature, suggests that targeting the gene may be a new approach to treating the disease.

About 42,000 new cases of triple negative breast cancer (TNBC) are diagnosed in the United States each year, about 20 percent of all breast cancer diagnoses. Patients typically relapse within one to three years of being treated.

Senior author Dr. Laurie H. Glimcher, the Stephen and Suzanne Weiss Dean of Weill Cornell Medical College, wanted to know whether the gene already understood from her prior work to be a critical regulator of immune and metabolic functions was important to cancer's ability to adapt and thrive in the oxygen- and nutrient-deprived environments inside of tumors. Using cells taken from patients' tumors and transplanted into mice, Dr. Glimcher's team found that the gene, XBP1, is especially active in triple negative breast cancer, particularly in the progression of malignant cells and their resurgence after treatment.

"Patients with the triple negative form of breast cancer are those who most desperately need new approaches to treat their disease," said Dr. Glimcher, who is also a professor of medicine at Weill Cornell. "This pathway was activated in about two-thirds of patients with this type of breast cancer. Now that we better understand how this gene helps tumors proliferate and then return after a patient's initial treatment, we believe we can develop more effective therapies to shrink their growth and delay relapse."

The group, which included investigators from nine institutions, examined several types of breast cancer cell lines. They found that XBP1 was particularly active in basal-like breast cancer cells cultivated in the lab and in triple negative breast cancer cells from patients. When they suppressed the activity of the gene in laboratory cell cultures and animal models, however, the researchers were able to dramatically reduce the size of tumors and the likelihood of relapse, especially when these approaches were used in conjunction with the chemotherapy drugs doxorubicin or paclitexel. The finding suggests that XBP1 controls behaviors associated with tumor-initiating cells that have been implicated as the originators of tumors in a number of cancers, including that of the breast, supporting the hypothesis that combination therapy could be an effective treatment for triple negative breast cancer.

The scientists also found that interactions between XBP1 and another transcriptional regulator, HIF1-alpha, spurs the cancer-driving proteins. Silencing XBP1 in the TNBC cell lines reduced the tumor cells' growth and other behaviors typical of metastasis.

"This starts to demonstrate how cancer cells co-opt the endoplasmic reticulum stress response pathway to allow tumors to grow and survive when they are deprived of nutrients and oxygen," said lead author Dr. Xi Chen, a postdoctoral associate at Weill Cornell, referring to the process by which healthy cells maintain their function. "It shows the interaction between two critical pathways to make the cells better able to deal with a hostile microenvironment, and in that way offers new strategies to target triple negative breast cancer."

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Gene implicated in progression and relapse of deadly breast cancer finding points to potential Achilles' heel in ...

One in a thousand children in the United States is deaf, and one in three adults will experience significant hearing loss after the age of 65. Whether the result of genetic or environmental factors, hearing loss costs billions of dollars in healthcare expenses every year, making the search for a cure critical.

Now a team of researchers led by Karen B. Avraham of the Department of Human Molecular Genetics and Biochemistry at Tel Aviv University's Sackler Faculty of Medicine and Yehoash Raphael of the Department of Otolaryngology-Head and Neck Surgery at University of Michigan's Kresge Hearing Research Institute have discovered that using DNA as a drug -- commonly called gene therapy -- in laboratory mice may protect the inner ear nerve cells of humans suffering from certain types of progressive hearing loss.

In the study, doctoral student Shaked Shivatzki created a mouse population possessing the gene that produces the most prevalent form of hearing loss in humans: the mutated connexin 26 gene. Some 30 percent of American children born deaf have this form of the gene. Because of its prevalence and the inexpensive tests available to identify it, there is a great desire to find a cure or therapy to treat it.

"Regenerating" neurons

Prof. Avraham's team set out to prove that gene therapy could be used to preserve the inner ear nerve cells of the mice. Mice with the mutated connexin 26 gene exhibit deterioration of the nerve cells that send a sound signal to the brain. The researchers found that a protein growth factor used to protect and maintain neurons, otherwise known as brain-derived neurotrophic factor (BDNF), could be used to block this degeneration. They then engineered a virus that could be tolerated by the body without causing disease, and inserted the growth factor into the virus. Finally, they surgically injected the virus into the ears of the mice. This factor was able to "rescue" the neurons in the inner ear by blocking their degeneration.

"A wide spectrum of people are affected by hearing loss, and the way each person deals with it is highly variable," said Prof. Avraham. "That said, there is an almost unanimous interest in finding the genes responsible for hearing loss. We tried to figure out why the mouse was losing cells that enable it to hear. Why did it lose its hearing? The collaborative work allowed us to provide gene therapy to reverse the loss of nerve cells in the ears of these deaf mice."

Although this approach is short of improving hearing in these mice, it has important implications for the enhancement of sound perception with a cochlear implant, used by many people whose connexin 26 mutation has led to impaired hearing.

Embryonic hearing?

Inner ear nerve cells facilitate the optimal functioning of cochlear implants. Prof. Avraham's research suggests a possible new strategy for improving implant function, particularly in people whose hearing loss gets progressively worse with time, such as those with profound hearing loss as well as those with the connexin gene mutation. Combining gene therapy with the implant could help to protect vital nerve cells, thus preserving and improving the performance of the implant.

More research remains. "Safety is the main question. And what about timing? Although over 80 percent of human and mouse genes are similar, which makes mice the perfect lab model for human hearing, there's still a big difference. Humans start hearing as embryos, but mice don't start to hear until two weeks after birth. So we wondered, do we need to start the corrective process in utero, in infants, or later in life?" said Prof. Avraham.

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From mouse ears to human's? Gene therapy to address progressive hearing loss