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News Article | May 2, 2017
Site: www.eurekalert.org

A new study has found brain abnormalities in people with bipolar disorder. In the largest MRI study to date on patients with bipolar disorder, a global consortium published new research showing that people with the condition have differences in the brain regions that control inhibition and emotion. By revealing clear and consistent alterations in key brain regions, the findings published in Molecular Psychiatry on May 2 offer insight to the underlying mechanisms of bipolar disorder. "We created the first global map of bipolar disorder and how it affects the brain, resolving years of uncertainty on how people's brains differ when they have this severe illness," said Ole A. Andreassen, senior author of the study and a professor at the Norwegian Centre for Mental Disorders Research at the University of Oslo. Bipolar disorder affects about 60 million people worldwide, according to the World Health Organization. It is a debilitating psychiatric disorder with serious implications for those affected and their families. However, scientists have struggled to pinpoint neurobiological mechanisms of the disorder, partly due to the lack of sufficient brain scans. The study was part of an international consortium led by the USC Stevens Neuroimaging and Informatics Institute at the Keck School of Medicine of USC: ENIGMA (Enhancing Neuro Imaging Genetics Through Meta Analysis) spans 76 centers and includes 26 different research groups around the world. The researchers measured the MRI scans of 6,503 individuals, including 2,447 adults with bipolar disorder and 4,056 healthy controls. They also examined the effects of commonly used prescription medications, age of illness onset, history of psychosis, mood state, age and sex differences on cortical regions. The study showed thinning of gray matter in the brains of patients with bipolar disorder when compared with healthy controls. The greatest deficits were found in parts of the brain that control inhibition and motivation -- the frontal and temporal regions. Some of the bipolar disorder patients with a history of psychosis showed greater deficits in the brain's gray matter. The findings also showed different brain signatures in patients who took lithium, anti-psychotics and anti-epileptic treatments. Lithium treatment was associated with less thinning of gray matter, which suggests a protective effect of this medication on the brain. "These are important clues as to where to look in the brain for therapeutic effects of these drugs," said Derrek Hibar, first author of the paper and a professor at the USC Stevens Neuroimaging and Informatics Institute when the study was conducted. He was a former visiting researcher at the University of Oslo and is now a senior scientist at Janssen Research and Development, LLC. Future research will test how well different medications and treatments can shift or modify these brain measures as well as improve symptoms and clinical outcomes for patients. Mapping the affected brain regions is also important for early detection and prevention, said Paul Thompson, director of the ENIGMA consortium and co-author of the study. "This new map of the bipolar brain gives us a roadmap of where to look for treatment effects," said Thompson, an associate director of the USC Stevens Neuroimaging and Informatics Institute at the Keck School of Medicine. "By bringing together psychiatrists worldwide, we now have a new source of power to discover treatments that improve patients' lives." Founded in 1885, the Keck School of Medicine of USC is among the nation's leaders in innovative patient care, scientific discovery, education, and community service. It is part of Keck Medicine of USC, the University of Southern California's medical enterprise, one of only two university-owned academic medical centers in the Los Angeles area. This includes the Keck Medical Center of USC, composed of the Keck Hospital of USC and the USC Norris Cancer Hospital. The two world-class, USC-owned hospitals are staffed by more than 500 physicians who are faculty at the Keck School. The school today has approximately 1,650 full-time faculty members and voluntary faculty of more than 2,400 physicians. These faculty direct the education of approximately 700 medical students and 1,000 students pursuing graduate and post-graduate degrees. The school trains more than 900 resident physicians in more than 50 specialty or subspecialty programs and is the largest educator of physicians practicing in Southern California. Together, the school's faculty and residents serve more than 1.5 million patients each year at Keck Hospital of USC and USC Norris Cancer Hospital, as well as USC-affiliated hospitals Children's Hospital Los Angeles and Los Angeles County + USC Medical Center. Keck School faculty also conduct research and teach at several research centers and institutes, including the USC Norris Comprehensive Cancer Center, the Zilkha Neurogenetic Institute, the Eli and Edythe Broad Center for Stem Cell Research and Regenerative Medicine at USC, the USC Cardiovascular Thoracic Institute, the USC Roski Eye Institute and the USC Institute of Urology. In 2016, U.S. News & World Report ranked Keck School of Medicine among the Top 40 medical schools in the country. For more information, go to keck.usc.edu.


News Article | May 8, 2017
Site: www.eurekalert.org

Drug users born in the 1980s and 1990s are turning to injection drug more quickly than previous generations, a USC-led study suggests The prescription opioid epidemic is shrinking the time it used to take drug users to progress to drug injection, a new Keck School of Medicine of USC-led study suggests. The study may predict the next national public health threat related to prescription painkiller abuse, said Ricky Bluthenthal, lead author of the study and a professor of preventive medicine at the Keck School of Medicine. "The prescription opioid epidemic is creating a heroin epidemic, which will create an injection drug use epidemic," Bluthenthal said. "We've seen the first two. Now we're waiting to see the last emerge on the national level. I predict we'll see an uptick in injection-related diseases over the next couple of years." The study, published in April in the journal Drug and Alcohol Dependence, is based on 776 drug users in Los Angeles and San Francisco. Participants born in the 1980s or 1990s, on average, took six years to escalate from first illicit drug use to first drug injection. The average for participants born in the 1970s was nine years. "The more rapid transition to injection is an impact of the prescription opioid-to-heroin use phenomenon," Bluthenthal said. "Heroin is most efficiently used via injection as compared to other formerly popular drugs such as crack cocaine or even cocaine." Injection-related diseases can include HIV, which affects more than 1.2 million Americans, and hepatitis C, which affected an estimated 3.9 million Americans in 2014, according to the Centers for Disease Control and Prevention. People who inject drugs also are at elevated risk for sexually transmitted infections, abscesses and soft-tissue infections, mental health disorders, drug overdose and dying young, the study stated. Researchers found that the first drug injected changed in tandem with national drug use trends. In general, however, heroin and prescription opiate pills were the most common first drug injected. Drug users born in the 1980s and 1990s moved quicker from initial illicit drug use to syringe use than those born in the '70s. In California, 2,014 deaths were attributed to opioid-related poisoning or overdose, according to the state's Department of Public Health. Nationwide, the rate of overdose deaths involving opioids -- more than 165,000 deaths -- has nearly quadrupled since 1999, according to the U.S. Department of Health and Human Services. On an average day in America, some 3,900 people begin nonmedical use of prescription opioids, creating more than $55 billion in health and social costs each year. Prescription opioids are the current drug of choice and has been for nearly two decades, Bluthenthal said. Heroin was popular in the 1970s, crack cocaine in the 1980s and marijuana in the 1990s. For the past 20 years, people who inject drugs were considered an aging population. Long-acting opioid-based medications became available in the 1990s, Bluthenthal said. Once use of prescription opioid pain relievers and heroin skyrocketed, however, the downward trend changed, he noted. In the study, researchers divided the 776 individuals into birth cohorts: those born before the 1960s, in the 1960s, 1970s and 1980s or later. All participants had injected in the last month. About 33 percent were white, 30 percent were African-American and 25 percent were Latino. The adult participants completed a survey that asked if they had ever used a list of drugs, including crack cocaine, methamphetamine, speed, heroin, tranquilizers, nonmedical use of prescription opioids and buprenorphine. They reported when they first used that drug, the first time they injected and what drug they injected. More than half had injected heroin, powder cocaine and methamphetamine. More than 30 percent reported they had injected crack cocaine and opioid painkillers. Longer time until first injection was associated with drug treatment prior to first injection. This fact suggests that drug interventions may help keep drug users away from the needle. "We need to get ahead of a possible drug injection epidemic," Bluthenthal said. "What works for Latinos in East Los Angeles might not work for people in West Virginia. We need to come up with prevention activities responsive to specific cultures, generations and locales to combat the move to drug injection." USC researchers from multiple disciplines, including the USC Schaeffer Center for Health Policy and Economics, are trying to solve the intractable problem of unnecessary drug prescriptions. Previous USC-led research found that a "nudge" reduces doctors' unnecessary antibiotic prescriptions. Researchers ranked and shared a list of physicians most likely to give an unnecessary prescription and used pop-up boxes that required physicians to justify their pharmacy order. Interventions such as these potentially can prevent unnecessary opioid prescriptions and the negative effects that result from painkiller addiction. Bluthenthal is collecting more data from younger people using opioids to better understand the drug behaviors associated with younger generations. The research was supported by the National Institute on Drug Abuse and the National Cancer Institute via nearly $1.7 million in awards. Founded in 1885, the Keck School of Medicine of USC is among the nation's leaders in innovative patient care, scientific discovery, education, and community service. It is part of Keck Medicine of USC, the University of Southern California's medical enterprise, one of only two university-owned academic medical centers in the Los Angeles area. This includes the Keck Medical Center of USC, composed of the Keck Hospital of USC and the USC Norris Cancer Hospital. The two world-class, USC-owned hospitals are staffed by more than 500 physicians who are faculty at the Keck School. The school today has approximately 1,650 full-time faculty members and voluntary faculty of more than 2,400 physicians. These faculty direct the education of approximately 700 medical students and 1,000 students pursuing graduate and post-graduate degrees. The school trains more than 900 resident physicians in more than 50 specialty or subspecialty programs and is the largest educator of physicians practicing in Southern California. Together, the school's faculty and residents serve more than 1.5 million patients each year at Keck Hospital of USC and USC Norris Cancer Hospital, as well as USC-affiliated hospitals Children's Hospital Los Angeles and Los Angeles County + USC Medical Center. Keck School faculty also conduct research and teach at several research centers and institutes, including the USC Norris Comprehensive Cancer Center, the Zilkha Neurogenetic Institute, the Eli and Edythe Broad Center for Stem Cell Research and Regenerative Medicine at USC, the USC Cardiovascular Thoracic Institute, the USC Roski Eye Institute and the USC Institute of Urology. In 2016, U.S. News & World Report ranked Keck School of Medicine among the Top 40 medical schools in the country. For more information, go to keck.usc.edu.


News Article | February 16, 2017
Site: www.eurekalert.org

What if you could lose weight and reduce your risk of life-threatening disease without any changes in what you eat -- other than a five-day special diet once every few months? That's what happened for 71 adults who were placed on three cycles of a low-calorie, "fasting-mimicking" diet. The phase II trial, conducted by researchers at the USC Leonard Davis School of Gerontology, demonstrated a host of benefits from the regimen. The diet reduced cardiovascular risk factors including blood pressure, signs of inflammation (measured by C-reactive protein levels), as well as fasting glucose and reduced levels of IGF-1, a hormone that affects metabolism. It also shrank waistlines and resulted in weight loss, both in total body fat and trunk fat, but not in muscle mass. In effect, the diet reduced the study participants' risks for cancer, diabetes, heart disease and other age-related diseases, according to the findings published Feb. 15 in Science Translational Medicine. "This study provides evidence that people can experience significant health benefits through a periodic, fasting-mimicking diet that is designed to act on the aging process," said Valter Longo, director of the USC Longevity Institute and a professor of biological sciences for USC Davis and Dornsife. "Prior studies have indicated a range of health benefits in mice, but this is the first randomized clinical trial with enough participants to demonstrate that the diet is feasible, effective and safe for humans. "Larger FDA studies are necessary to confirm its effects on disease prevention and treatment," he added. One hundred people participated in the trial from April 2013 to July 2015. The participants, ages 20 to 70 and all generally healthy, were divided into two groups for the randomized trial. Participants in the first group, the control group, were asked to continue their normal eating habits for three months. People in the second group were placed on a three-month test of the fasting-mimicking diet. Those on the special diet were required to eat food products supplied by the nutrition company L-Nutra during the fasting periods of five days each month. The diet, which was designed to mimic the results of a water-only fast, allowed for participants to consume between 750 and 1,100 calories per day. The meals for the fast-mimicking diet contained precise proportions of proteins, fats and carbohydrates. After three months, participants in the control group were moved onto the special diet. The researchers found that participants on the fasting-mimicking diet lost an average of about 6 pounds. Their waistlines shrank by 1 to 2 inches. Their systolic blood pressure, which was in the normal range when the study began, dropped by 4.5 mmHG, while their diastolic blood pressure dropped by 3.1 mmHg. Also, their levels of IGF-1 dropped to between 21.7 ng/mL and 46.2 ng/mL, reaching a range associated with lower cancer risk. "After the first group completed their three months on the fasting diet, we moved over participants in the control group to see if they also would experience similar results," Longo said. "We saw similar outcomes, which provides further evidence that a fasting-mimicking diet has effects on many metabolic and disease markers. Our mouse studies using a similar fasting-mimicking diet indicate that these beneficial effects are caused by multi-system regeneration and rejuvenation in the body at the cellular and organ levels. "Our participants retained those effects, even when they returned to their normal daily eating habits," he added. The researchers also noted that participants considered "at risk" because they had risk factors such as high IGF-1, cholesterol, blood pressure or blood sugar levels, made significant progress toward better health. For example, baseline fasting glucose levels for participants with high blood sugar levels (putting them at risk for diabetes) dropped into the healthy range, below 99 mg/dl -- but these levels didn't drop among participants who already had healthy levels at the beginning of the study. Cholesterol was reduced by 20 mg/dl in those with high cholesterol levels, and by about 5 mg/dl in all participants. "Fasting seems to be the most beneficial for patients who have the great risk factors for disease, such as those who have high blood pressure or pre-diabetes or who are obese," Longo said. The researchers had invited participants in the study for one last set of tests three months later, at the end of the diet. The research team found that the beneficial effects -- from weight loss, smaller waistlines and lower glucose, blood pressure and IGF-1 levels -- were sustained. The next step for researchers is a large, FDA phase III clinical trial to test the FMD on patients diagnosed with age-related diseases or at high risk for them. The researchers said further investigation will determine whether the benefits of the diet can continue for several months. The work was funded by the USC Edna M. Jones Chair in Gerontology fund, as well as through a National Institutes of Health grant to co-author Wendy Mack at the Keck School of Medicine of USC, through the Southern California Clinical and Translational Science Institute. Study co-authors from USC Davis were Min Wei and Sebastian Brandhorst (lead co-authors) and Mahshid Shelehchi, Hamed Mirzaei, Chia Wei Cheng, Julia Budniak, Esra Guen, Stefano Di Biase, Pinchas Cohen and Todd Morgan. Others were Tanya Dorff of USC Norris Comprehensive Cancer Center; Kurt Hong, of the Keck School of Medicine; Andreas Michalsen of Charité University Medical Center in Germany; and Alessandro Laviano at IFOM, the FIRC Institute of Molecular Oncology. Longo is the founder of L-Nutra, whose food products were used in the study. His interest in L-Nutra has been disclosed and managed per USC's conflicts of interest policies to assure objectivity and a lack of bias in the conduct and reporting of his research. USC also has an ownership interest in L-Nutra, and the potential to receive royalty payments from L-Nutra. USC's financial interest in the company has been disclosed and managed under USC's institutional conflict of interest policies.


News Article | March 1, 2017
Site: www.prweb.com

Breast Surgeon, Dr. Dennis Holmes of 90210 Surgery Medical Center will review minimally invasive cryoablation for the treatment of early stage breast cancer and where it fits in the treatment paradigm at Susan G. Komen San Diego’s Annual Dinner Symposium, “Screens, Genes & The Choices We Make.” The event brings together leading cancer and wellness experts to share the latest innovations in breast cancer research, treatment and holistic well-being. The symposium will take place on Thursday, March 16, 2017 at the San Diego Del Mar Marriott. Dr. Holmes is an internationally renowned breast surgeon and cancer researcher currently serving as Interim Director of the Margie Petersen Breast Center at Providence St. John’s Health Center and Interim Director, John Wayne Cancer Institute Breast Surgery Fellowship Program. Formerly, Dr. Holmes held the positions of Chief Breast Surgeon and Medical Director of the Los Angeles Center for Women’s Health, and Chief Breast Cancer Surgeon, and Breast Cancer Research Committee Co-Chair at the University of Southern California Kenneth Norris Comprehensive Cancer Center. Dr. Holmes has been a pioneer in the field of minimally invasive breast surgery, including intraoperative radiotherapy, lymph node-sparing surgery and cryoablation “I am thrilled to partner with Komen San Diego, as we share similar goals - to save lives and pursue the best breast cancer treatments,” said Dr. Holmes. Currently, the standard of care for early stage breast cancer is surgery (e.g. lumpectomy, mastectomy) and sentinel node biopsy followed by breast radiotherapy and adjuvant endocrine and/or chemotherapy. Although surgery offers tumor removal and margin verification, a major drawback of surgery is the cosmetic and functional impairment of the breast resulting from volume changes, scar formation, nipple displacement, sensation changes, skin/scar retraction, and re-excision rate. Dr. Holmes was an investigator in the National Cancer Institute Z1072 Clinical Trial sponsored by the Alliance for Clinical Trials in Oncology. The trial examined cryoablation for the treatment of early stage breast cancer. In a 5-year multicenter study, cryoablation was shown to be 92% effective for complete ablation of invasive breast tumors ≤2 cm and 100% effective for complete ablation of invasive ductal breast cancer tumors <1.0 cm. Results from this breast cancer study (ACOSOG Z1072), which included a 5-year follow-up, were published in the Annals of Surgical Oncology. The Visica® 2 Treatment System developed by Sanarus Technologies, was the exclusive device used in the Z1072 study. “Cryoablation is a very promising alternative to traditional surgery for early stage breast cancer. Cryoablation minimizes changes in breast volume and nipple position, and avoids prominent scars,” explained Dr. Holmes. “The outstanding results of Z0172 inspired me to start the FROST Clinical Study, for which I now serve as Principal Investigator.” The FROST Clinical Study is the evolution of data from Z1072, which examines the rate of successful tumor ablation in patients treated with cryoablation of the primary tumor instead of surgical removal of early stage breast cancer. The FROST Clinical Study is currently enrolling women age 50 and older with core needle biopsy proven clinical stage I, T1, (≤1.5 cm) clinically node negative (N0), unifocal, hormone receptor positive and HER2/neu-negative invasive ductal carcinoma. Cryoablation with the Visica 2 Treatment System is a nonsurgical option for patients that have been diagnosed with early stage breast cancer, is visible on sonogram, and has been confirmed with a biopsy. This procedure has many benefits including: under 30-minutes, local anesthesia, in-office, excellent cosmesis, cost efficient, and quick patient recovery. Cryoablation is a viable option to surgery that results in complete early stage tumor ablation. About Dr. Holmes Dr. Holmes serves in the leadership of several national surgical societies and is a frequent lecturer at national conferences. He is a member of the education committee of the American Society of Breast Surgeons. Dr. Holmes is a Fellow of the American College of Surgeons and was also recently selected as Board Chair and President of the TARGIT Collaborative Group, a national research and education organization. Widely respected by colleagues for his innovative approach to breast cancer care, Dr. Holmes has gained worldwide acclaim for his pioneering research in targeted intraoperative radiotherapy. Dr. Holmes believes wholeheartedly that, with proper treatment, most women diagnosed with breast cancer will live a long, fulfilling life—a life both richer and more meaningful than they could have ever imagined. Find out more at http://www.drholmesmd.com About Sanarus Technologies In 2001, the Visica® 2 Treatment System was the first device available for cryoablation of fibroadenomas. Since then, our system has been used to successfully treat thousands of patients. The Visica 2 Treatment System is FDA-cleared for the ablation of cancerous or malignant tissue and benign tumors. At Sanarus, we develop innovative solutions for the nonsurgical treatment of breast tumors. We are headquartered in Pleasanton, CA, and all our products are manufactured in the USA. Find out more at http://www.sanarus.com ABOUT SUSAN G. KOMEN SAN DIEGO®: Since its inception in 1995, Komen San Diego has granted more than $18 million to research and local non-profits who provide everything from free diagnostic mammograms, meal delivery, temporary financial aid, transportation and more. Seventy-five percent of every dollar raised in San Diego stays in San Diego County to fund breast health services for uninsured and underinsured women and their families. The remaining 25 percent funds international breast cancer research. In fact, next to the U.S. government, Susan G. Komen® is the largest funder of breast cancer research in the world. For more information, please visit http://www.komensandiego.org. Connect with us on Facebook and Twitter and Instagram.


News Article | December 19, 2016
Site: www.eurekalert.org

Funding will support the development of an off-the-shelf stem cell therapy that could be cheaper and less invasive than joint replacement surgery LOS ANGELES - Keck School of Medicine of the University of Southern California (USC) is one of four institutions to receive a multi-million dollar grant from the California Institute for Regenerative Medicine (CIRM) for translational research projects. The $2.5 million grant will support potential osteoarthritis therapies that could significantly impact standards of care for the disease. Arthritis affects approximately 52 million adults in the United States, with that number conservatively expected to grow to 78 million by the year 2040. Grant recipient Denis Evseenko, MD, PhD, associate professor of orthopaedic surgery, and stem cell biology and regenerative medicine, is working towards this therapy by using pluripotent stem cells to regenerate cartilage. While scientists have used these cells to create a cartilage-like tissue, they have not been able to generate cells that develop new cartilage. Evseenko proposes a unique approach to storing pluripotent stem cell-derived chondrocytes, which are the cells that can become cartilage, and implanting those chondrocytes into the joint. If successful on a large scale, this therapy would be a cheaper, minimally invasive, off-the-shelf alternative to joint replacement surgery as a treatment for osteoarthritis. "The rapidly growing prevalence and staggering costs of osteoarthritis demand a solution that can benefit both patients and providers," Evseenko said. "My team is working diligently to provide this solution by expanding on our previous stem cell research, and we are grateful for CIRM's support of our endeavor." Osteoarthritis, more commonly known as arthritis, is a chronic disease caused by injury and wear and tear of the joints. It affects 23 percent of adults nationwide, and costs the U.S. $100 billion annually. Those numbers are expected to grow exponentially due to longer lifespans and rising obesity. There is no cure for osteoarthritis. Some patients with severe arthritis will require a total joint replacement. Although total joint replacement is a successful operation, the prosthesis may wear out over time in younger patients, requiring revision surgery. Evseenko hopes his research will reduce the need for these types of surgeries, mitigating the burden of osteoarthritis on patients and physicians. "Bridging the gap between scientific innovation and clinical application is critical for our mission to provide the best quality of patient care," said Jay Lieberman, MD, professor and chair of the Department of Orthopaedic Surgery at Keck School of Medicine of USC. "We are delighted for Denis and are eagerly anticipating his contributions made possible through CIRM's support." CIRM, the California agency charged with dispensing $3 billion in voter-approved dollars to researchers throughout the state, accelerates stem cell treatments for patients with urgent medical needs without a current solution. This grant is part of CIRM's Translational Award program, which supports the most promising scientific projects with the potential for human clinical trials. In addition to Keck School, this year's recipients also include two biotech institutes studying Alzheimer's disease and osteonecrosis, and one other academic medical center researching pediatric therapies for sickle cell disease. "CIRM has made a wise investment in Denis and Denis's research. He's an outstanding young scientist, developing innovative approaches to bridge the gap between basic understanding and clinical application. Developing new approaches will be essential to combat osteoarthritis, a prevalent disabling disease," said Andy McMahon, PhD, FRS, professor and chair of the Department of Stem Cell Biology and Regenerative Medicine. ABOUT THE KECK SCHOOL OF MEDICINE OF USC Founded in 1885, the Keck School of Medicine of USC is among the nation's leaders in innovative patient care, scientific discovery, education, and community service. It is part of Keck Medicine of USC, the University of Southern California's medical enterprise, one of only two university-owned academic medical centers in the Los Angeles area. This includes the Keck Medical Center of USC, composed of the Keck Hospital of USC and the USC Norris Cancer Hospital. The two world-class, USC-owned hospitals are staffed by more than 500 physicians who are faculty at the Keck School. The school today has more than 1,500 full-time faculty members and voluntary faculty of more than 2,400 physicians. These faculty direct the education of approximately 700 medical students and 1,000 students pursuing graduate and post-graduate degrees. The school trains more than 900 resident physicians in more than 50 specialty or subspecialty programs and is the largest educator of physicians practicing in Southern California. Together, the school's faculty and residents serve more than 1.5 million patients each year at Keck Hospital of USC and USC Norris Cancer Hospital, as well as USC-affiliated hospitals Children's Hospital Los Angeles and Los Angeles County + USC Medical Center. Keck School faculty also conduct research and teach at several research centers and institutes, including the USC Norris Comprehensive Cancer Center, the Zilkha Neurogenetic Institute, the Eli and Edythe Broad Center for Stem Cell Research and Regenerative Medicine at USC, the USC Cardiovascular Thoracic Institute, the USC Roski Eye Institute and the USC Institute of Urology. In 2016, U.S. News & World Report ranked Keck School of Medicine among the Top 40 medical schools in the country. For more information, go to keck.usc.edu.


News Article | December 13, 2016
Site: www.eurekalert.org

For years, scientists have puzzled over what prompts the intertwined double-helix DNA to open its two strands and then start replication. Knowing this could be the key to understanding how organisms - from healthy cells to cancerous tumors - replicate and multiply for their survival. A group of USC scientists believe they have solved the mystery. Replication is prompted by a ring of proteins that bond with the DNA at a special location known as "origin DNA." The ring tightens around the strands and melts them to open up the DNA, initiating replication. This all takes place at a nano level that is impossible to see with the naked eye. A strand of DNA is only about one nanometer in size - not even close to the width of a human hair which is roughly equivalent to 100,000 DNA strands. The researchers made their discovery by studying a cancerous virus, SV40. The virus hijacked the DNA replication process with a ring of proteins, called a "helicase" that mimicked the rings of proteins that prompt genetic replication in healthy cells. The findings were published on Dec. 6 in the journal eLife. "Understanding the mechanisms of origin DNA opening or melting allows us to learn this fundamental process of genetic duplication," said corresponding author Xiaojiang Chen, a professor of biological sciences and chemistry in the USC Dornsife College of Letters, Arts and Sciences and director of the college's Center of Excellence in NanoBiophysics. "The knowledge we have gained may be applicable for future intervention of this process to block the replication of viral pathogens and cancer cells." When the origin DNA melts, the double helix divides into separate strands, Chen explained. Those DNA strands then become the template for faithful duplication of other strands - a Xerox copy of their parental DNA. As soon as replication is complete, one double helix DNA now becomes two exact copies of the same double helix. "DNA replication is critical for heredity and survival," said Chen, who also is affiliated with the Norris Comprehensive Cancer Center at the Keck School of Medicine at USC. "The origin DNA's opening is an essential step for DNA replication in our cells and for some tumor viral pathogens to replicate and spread." Why is origin DNA so special? Regular DNA sequences contain the A, T, G and C nucleotides, more or less in equal ratio. But origin DNA sequences contain more A and T nucleotides than usual. To prompt replication, the scientists used a helicase from a "Large Tumor Antigen" or Large T. The antigen comes from a virus, SV40, linked to human cancers such as brain and bone cancers, mesothelioma and lymphoma. The six proteins from Large T comprise a "helicase" that mimics the structure of the healthy cells' helicases. The scientists obtained a 3-D view of the atomic structure of the helicase using X-ray crystallography, a technique for examining nano-biomolecules and their structures at the atomic level that has been refined over centuries. Chen said the images revealed that the proteins which surrounded the DNA had attached to it, then tightened like a vice until the bonds between the two strands of the double helix broke - or melted - the origin DNA. Although the scientists used a cancerous virus to study replication, healthy cells replicate in a similar way, Chen said. Other co-authors were Dahai Gai, also of USC Dornsife, Damian Wang of the Keck School of Medicine at USC, and Shu-Xing Li of USC Dornsife's Center for Excellence in NanoBiophysics. The study was funded by an NIH grant, A1055926.


CHARLESTON, S.C.--(BUSINESS WIRE)--Aeterna Zentaris Inc. (NASDAQ: AEZS)(TSX: AEZ) (the “Company”) today announced that a poster entitled, “A phase II trial of zoptarelin doxorubicin in castration-and taxane-resistant prostate cancer”, will be presented during the 2017 Genitourinary Cancers Symposium’s “Translating Research to Value-based and Patient-centric Care” by lead investigator, and co-author of the presentation, Jacek Pinski, MD, PhD, USC Norris Comprehensive Cancer Center, in Orlando, Florida on Thursday, February 16, 2017 at 11:30am-1:00pm ET and 5:15pm-6:15pm ET. The event is a co-sponsored by the American Society of Clinical Oncology – ASCO; Society of Urologic Oncology – SUO; and Targeting Cancer Care – ASTRO. The address for the sessions is Rosen Shingle Creek Hotel, 9939 Universal Blvd, Orlando, FL 32819. On December 14, 2010, the Company announced the initiation of the Phase 1/2 trial. On February 3, 2012, updated results for the Phase 1 portion of the study were reported. The results were based on 13 patients who had been previously treated with androgen-deprivation therapy (LHRH agonist) and at least one taxane-based chemotherapy regimen, who were treated on three dose levels of Zoptrex™: three at 160 mg/m2, three at 210 mg/m2, and seven at 267 mg/m2. Overall, Zoptrex™ was well tolerated among this group of heavily pretreated older patients. There were two dose-limiting toxicities, each of which having been a case of asymptomatic Grade 4 neutropenia at the 267 mg/m2 dose level and both patients fully recovered. The Grade 3 and 4 toxicities were primarily hematologic. There was minimal non- hematologic toxicity, most frequently fatigue and alopecia. Despite the low doses of Zoptrex™ in the first cohorts, there was indication of antitumor activity. One patient received eight cycles (at 210 mg/m2) due to continued benefit. Among the five evaluable patients with measurable disease, four achieved stable disease. At the time of submission of the abstract, a decrease in prostate specific antigen (“PSA”) was noted in six patients. Six of 13 (46%) treated patients received at least five cycles of therapy with no evidence of disease progression at twelve weeks. On November 12, 2012, we announced the initiation of the Phase 2 portion of Dr. Pinski’s Phase 1/2 study of Zoptrex™ in prostate cancer. This was a single-arm Simon Optimum Design Phase 2 study of Zoptrex™ in 25 patients with castrate-resistant prostate cancer (CRPC). Patients received Zoptrex™ (210 mg/m2) intravenously over two hours, every three weeks. The primary endpoint was clinical benefit (“CB”), defined as remaining progression-free by RECIST and PSA after treatment for 12+ weeks. Secondary endpoints were progression free survival (PFS), best overall response, toxicity, pain and overall survival (OS). On June 3, 2013, we announced that final data for the Phase 1 portion of Dr. Pinski’s Phase 1/2 trial with Zoptrex™ in prostate cancer demonstrated the compound's promising anti-tumor activity. Results were presented by Dr. Pinski during a poster session at the ASCO Annual Meeting in Chicago. The results of the study were published in an article by Liu et al in the journal Clinical Cancer Research (Clin. Cancer Res. (2014) 20:6277). Eighteen men were treated at three dose levels: (160 mg/m2; (ii) 210 mg/m2; and (iii) 267 mg/m2). Overall Zoptrex™ was well tolerated among this group of heavily pretreated patients. There were two dose-limiting toxicities (grade four neutropenia and grade three febrile neutropenia), prompting de- escalation to 210 mg/m2 and establishing it as the Maximum Tolerated Dose. Among the 15 evaluable patients with measurable disease, ten achieved stable disease (SD), and a drop in PSA was noted in three patients. On September 28, 2015, Dr. Pinski announced during a poster session at the 18th ECCO - 40th ESMO European Cancer Congress in Vienna, Austria, that among the 25 patients in the Phase 2 portion of the trial, 11 patients experienced CB as the primary endpoint and 13 patients achieved SD. Maximal PSA response was stable in 20 patients. Pain assessment improved for 11 patients. Zoptrex™ was well tolerated in this heavily pretreated patient population with hematological toxicities, usually limited to grade three, as the most common adverse events. Dr. Pinski concluded that Zoptrex™ was well tolerated and met the primary efficacy endpoint in castration- and taxane-resistant prostate cancer patients. Zoptarelin doxorubicin represents a new targeting concept in oncology using a hybrid molecule composed of a synthetic peptide carrier and a well-known chemotherapy agent, doxorubicin. Zoptarelin doxorubicin is the first intravenous drug in advanced clinical development that directs the chemotherapy agent specifically to LHRH-receptor expressing tumors, resulting in a more targeted treatment with less damage to healthy tissue. The Company recently concluded a Phase 3 trial in women with advanced, recurrent or metastatic endometrial cancer called ZoptEC (Zoptarelin doxorubicin in Endometrial Cancer). Aeterna Zentaris owns the worldwide rights to this compound. The Company believes that Zoptrex™ may be useful in treating other cancers, including breast cancer, bladder cancer and prostate cancer. We terminated early clinical trials of the compound as a treatment for triple-negative breast cancer and bladder cancer as part of our ongoing review of our development activities to ensure the most effective use of our resources. The Company assisted Dr. Jacek Pinski, Associate Professor of Medicine at the Norris Comprehensive Cancer Center of the University of Southern California, to conduct a Phase 1/2 study in refractory prostate cancer with Zoptrex™. Dr. Pinski received a $1.6 million grant from The National Institutes of Health (“NIH”) to conduct the study. The study, entitled “A Phase I/II Trial of AN-152 [AEZS-108] in Castration-and Taxane-Resistant Prostate Cancer,” was conducted in two portions: an abbreviated dose-escalation study followed by a single arm, Simon Optimum two-stage design Phase 2 study, using the dose selected in the Phase 1 portion. Aeterna Zentaris is a specialty biopharmaceutical company engaged in developing and commercializing novel treatments in oncology, endocrinology and women’s health. We are engaged in drug development activities and in the promotion of products for others. We recently completed Phase 3 studies of two internally developed compounds. The focus of our business development efforts is the acquisition of licenses to products that are relevant to our therapeutic areas of focus. We also intend to license out certain commercial rights of internally developed products to licensees in non-US territories where such out-licensing would enable us to ensure development, registration and launch of our product candidates. Our goal is to become a growth-oriented specialty biopharmaceutical company by pursuing successful development and commercialization of our product portfolio, achieving successful commercial presence and growth, while consistently delivering value to our shareholders, employees and the medical providers and patients who will benefit from our products. For more information, visit www.aezsinc.com.


News Article | April 19, 2016
Site: www.biosciencetechnology.com

A simple blood test could have the potential to replace an invasive biopsy in breast cancer patients, according to positive results from a University of Southern California study presented Monday at The American Association for Cancer Research Annual Meeting 2016. The so called “liquid biopsy”, Parsoritx, developed by specialist medical diagnostic company Angle plc, was put through a head to head comparison of the results of the invasive metastatic biopsy by researchers at the USC Norris Comprehensive Cancer Center. For the study researchers analyzed CTCs (circulating tumor cells) collected from a simple blood test, as well as tissue from an invasive biopsy of a secondary cancer site, and found the blood test demonstrated a statistically significant correlation between the expression signature of 192 genes, with similar analysis of the tissue from the invasive procedure. Both the tissue and the CTCs were subjected to whole-transcriptome analysis using total RNA sequencing. Through this technique scientists can measure thousands of genes simultaneously to pull a fuller picture of cellular function into focus. Tissue samples were taken from numerous metastatic sites, including skin, fluid around the heart, breast, and bone tissue.  According to the company, for all of the different sites the CTCs showed a similar gene expression compared to the metastatic biopsy, suggesting that the same clinically relevant information can be attained from a blood test as from an invasive biopsy regardless of its location. Some of the main advantages to using a liquid biopsy to harvest cancer cells for analysis are that it could reduce the time it takes to make treatment decisions, and avoid delays in treatment because of recovery after an invasive procedure.  The company said this technique also enables researchers to receive information on all cancer sites at once, rather than a single site, and allows for continued assessment of tumor biology over time. “As a breast cancer surgeon, I am very enthusiastic about the potential of liquid biopsy to gain information to guide the treatment of breast cancer patients based on the specific tumor biology for each patient,” Julie E. Lang, M.D., director of USC Breast Cancer Program and associate Professor of Surgery at the Norris Comprehensive Cancer Center said in prepared statement. “Our pilot data shows that potentially the same information can be obtained from a simple blood test using Parsortix as from an invasive tissue biopsy and indeed may be advantageous over invasive tissue biopsies in regards to the diverse sites of metastatic disease, thus providing a compelling rationale for use in clinical practice after further validation.” Next, Angle plans to work with USC to run clinical studies to confirm the pilot data of using the Parsortix system as a clinical application for biopsy of metastatic breast cancer patients. Establish your company as a technology leader! For more than 50 years, the R&D 100 Awards have showcased new products of technological significance. You can join this exclusive community! Learn more.


News Article | December 13, 2016
Site: phys.org

A group of USC scientists believe they have solved the mystery. Replication is prompted by a ring of proteins that bond with the DNA at a special location known as "origin DNA." The ring tightens around the strands and melts them to open up the DNA, initiating replication. This all takes place at a nano level that is impossible to see with the naked eye. A strand of DNA is only about one nanometer in size - not even close to the width of a human hair which is roughly equivalent to 100,000 DNA strands. The researchers made their discovery by studying a cancerous virus, SV40. The virus hijacked the DNA replication process with a ring of proteins, called a "helicase" that mimicked the rings of proteins that prompt genetic replication in healthy cells. The findings were published on Dec. 6 in the journal eLife. "Understanding the mechanisms of origin DNA opening or melting allows us to learn this fundamental process of genetic duplication," said corresponding author Xiaojiang Chen, a professor of biological sciences and chemistry in the USC Dornsife College of Letters, Arts and Sciences and director of the college's Center of Excellence in NanoBiophysics. "The knowledge we have gained may be applicable for future intervention of this process to block the replication of viral pathogens and cancer cells." When the origin DNA melts, the double helix divides into separate strands, Chen explained. Those DNA strands then become the template for faithful duplication of other strands - a Xerox copy of their parental DNA. As soon as replication is complete, one double helix DNA now becomes two exact copies of the same double helix. "DNA replication is critical for heredity and survival," said Chen, who also is affiliated with the Norris Comprehensive Cancer Center at the Keck School of Medicine at USC. "The origin DNA's opening is an essential step for DNA replication in our cells and for some tumor viral pathogens to replicate and spread." Why is origin DNA so special? Regular DNA sequences contain the A, T, G and C nucleotides, more or less in equal ratio. But origin DNA sequences contain more A and T nucleotides than usual. To prompt replication, the scientists used a helicase from a "Large Tumor Antigen" or Large T. The antigen comes from a virus, SV40, linked to human cancers such as brain and bone cancers, mesothelioma and lymphoma. The six proteins from Large T comprise a "helicase" that mimics the structure of the healthy cells' helicases. The scientists obtained a 3-D view of the atomic structure of the helicase using X-ray crystallography, a technique for examining nano-biomolecules and their structures at the atomic level that has been refined over centuries. Chen said the images revealed that the proteins which surrounded the DNA had attached to it, then tightened like a vice until the bonds between the two strands of the double helix broke - or melted - the origin DNA. Although the scientists used a cancerous virus to study replication, healthy cells replicate in a similar way, Chen said. More information: Dahai Gai et al. The structure of SV40 large T hexameric helicase in complex with AT-rich origin DNA, eLife (2016). DOI: 10.7554/eLife.18129


News Article | November 21, 2016
Site: www.eurekalert.org

The American Association for the Advancement of Science recognizes the researchers for their distinguished efforts to advance science or its applications Five USC scientists have been elected fellows of the American Association for the Advancement of Science, an honor bestowed upon AAAS members by their academic peers. AAAS, the world's largest general scientific society and publisher of the journal Science, began the AAAS Fellows tradition in 1874. The nonprofit organization was founded in 1848. This year 391 AAAS members will be made fellows because of their scientifically or socially distinguished efforts to advance science or its applications. The USC fellows are: Wendy Cozen, a professor of preventive medicine and pathology at the Keck School of Medicine of USC, for contributions to the understanding of the epidemiology, etiology and immunology of Hodgkin's disease and non-Hodgkin's lymphoma. Cozen is also co-director of the Translational Pathology Core at the USC Norris Comprehensive Cancer Center. Roger Ghanem, the Gordon S. Marshall Professor of Engineering Technology and a professor of civil and environmental engineering at the USC Viterbi School of Engineering, for outstanding contributions to practical, mathematical and computational aspects of uncertainty quantification. His research spans a wide spectrum of applications across science and engineering. Robert Guralnick, a professor of mathematics at USC Dornsife College of Letters, Arts and Sciences, for being one of the central figures at the moment in the very broad domain of group theory. Michael Paine, a professor and director of the master's and doctorate program in craniofacial biology at the Herman Ostrow School of Dentistry of USC, for distinguished contributions to the field of biomineralization, for identifying protein-to-protein self assembly and for linking systemic disease of solute transport to enamel formation. D. Brent Polk, a professor of pediatrics, biochemistry and molecular medicine at the Keck School, for distinguished contributions to the field of gastroenterology, particularly in understanding signal transduction mechanisms regulating intestinal growth and repair related to inflammatory bowel disease. Polk is also vice dean for clinical affairs (Children's Hospital Los Angeles). A steering group, three fellows or the association's CEO nominates new fellows from among the organization's membership pool. Fellows must have been continuous members of AAAS for four years.

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