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SAN DIEGO--(BUSINESS WIRE)--Celgene Corporation (NASDAQ:CELG), Dana-Farber Cancer Institute and the University of Arkansas for Medical Sciences today announced the creation of the Myeloma Genome Project, a collaborative initiative aimed at compiling the largest dataset of high-quality genomic and clinical data to identify distinct molecular disease segments within multiple myeloma to advance diagnosis, prognosis and treatment of multiple myeloma patients. The initiative seeks to develop clinically relevant tests. Details of the project and initial characterization and preliminary analyses of newly diagnosed myeloma patient data were presented today by Brian Walker, Ph.D., of the University of Arkansas for Medical Sciences at the 58th American Society of Hematology Annual Meeting in San Diego, Calif. “The Myeloma Genome Project is a really exciting initiative that may change the way we manage myeloma patients,” said Gareth Morgan, M.D., Ph.D., Director of the Myeloma Institute at the University of Arkansas for Medical Sciences. Current technologies have discovered five major translocation groups within myeloma patients and these mutations have demonstrated varying effects on prognosis. The Myeloma Genome Project is also looking at minor translocation and mutational groups that are often poorly described due to small sample numbers in limited data sets. The group has established a set of 2,161 patients for which whole exome sequencing (WES; n=1,436), whole genome sequencing (WGS; n=708), targeted panel sequencing (n=993) and expression data from RNA-sequencing and gene expression arrays (n=1,497) were available. The data were collected from the Myeloma XI trial (UK), Intergroupe Francophone du Myeloma/Dana-Farber Cancer Institute, Myeloma Institute at the University of Arkansas for Medical Sciences and the Multiple Myeloma Research Foundation. “Understanding the various subgroups within multiple myeloma that exhibit distinct pathogenesis and clinical behavior is critical when looking to advance new therapies, particularly when considering a targeted approach,” said Rob Hershberg, M.D., Ph.D., Executive Vice President and Chief Scientific Officer at Celgene. “We look forward to the insights that this collaboration will provide for research and for patients.” “The Myeloma Genome Project expects to lead the way towards developing personalized and targeted therapy to improve patient outcomes in myeloma,” said Nikhil Munshi, M.D., Director of Basic and Correlative Science at the Jerome Lipper Multiple Myeloma Center at Dana-Farber Cancer Institute. The Myeloma Genome Project has begun to integrate these diverse, large genomic data sets and is identifying genetic information that may inform clinical targets for therapy. While analyses are not completed, the current efforts clearly demonstrate the feasibility of this approach and the project leaders plan to expand collaboration to include additional investigators and institutions and present updates at future medical and scientific meetings including publications in peer-reviewed journals. Celgene Corporation, headquartered in Summit, New Jersey, is an integrated global biopharmaceutical company engaged primarily in the discovery, development and commercialization of innovative therapies for the treatment of cancer and inflammatory diseases through next-generation solutions in protein homeostasis, immuno-oncology, epigenetics, immunology and neuro-inflammation. For more information, please visit www.celgene.com. Follow Celgene on Social Media: @Celgene, Pinterest, LinkedIn, Facebook and YouTube. From achieving the first remissions in childhood cancer with chemotherapy in 1948, to developing the very latest new therapies, Dana-Farber Cancer Institute is one of the world’s leading centers of cancer research and treatment. It is the only center ranked in the top 4 of U.S. News and World Report’s Best Hospitals for both adult and pediatric cancer care. Dana-Farber sits at the center of a wide range of collaborative efforts to reduce the burden of cancer through scientific inquiry, clinical care, education, community engagement, and advocacy. Dana-Farber/Brigham and Women’s Cancer Center provides the latest in cancer care for adults; Dana-Farber/Boston Children's Cancer and Blood Disorders Center for children. The Dana-Farber/Harvard Cancer Center unites the cancer research efforts of five Harvard academic medical centers and two graduate schools, while Dana-Farber Community Cancer Care provides high quality cancer treatment in communities outside Boston’s Longwood Medical Area. Dana-Farber is dedicated to a unique, 50/50 balance between cancer research and care, and much of the Institute’s work is dedicated to translating the results of its discovery into new treatments for patients locally and around the world. About the University of Arkansas for Medical Sciences The University of Arkansas for Medical Sciences (UAMS) is Arkansas’ only comprehensive academic health center, with colleges of Medicine, Nursing, Pharmacy, Health Professions and Public Health; a graduate school; a hospital; a northwest Arkansas regional campus; a statewide network of regional centers; and seven institutes: the Winthrop P. Rockefeller Cancer Institute, the Jackson T. Stephens Spine & Neurosciences Institute, the Myeloma Institute, the Harvey & Bernice Jones Eye Institute, the Psychiatric Research Institute, the Donald W. Reynolds Institute on Aging and the Translational Research Institute. It is the only adult Level 1 trauma center in Arkansas. UAMS physicians and other professionals provide care to patients at UAMS, Arkansas Children’s Hospital, the VA Medical Center and UAMS regional centers throughout the state. The UAMS Myeloma Institute is the most comprehensive center in the world for research and clinical care related to multiple myeloma and related diseases, such as Castleman Disease and Waldenstrom Macroglobulemia. The institute’s team of scientists and clinicians has pioneered many advances that have become standards of care, leading to improved survival rates. The UAMS Myeloma Institute is known for its “bench to bedside” approach, continually translating advances in the laboratory into breakthrough clinical treatments. Visit www.uams.edu or www.uamshealth.com. Find us on Facebook, Twitter, YouTube or Instagram.


News Article | March 31, 2016
Site: www.cemag.us

A research team led by University of Arkansas chemist Jingyi Chen and University of Arkansas for Medical Sciences microbiologist Mark Smeltzer has developed an alternative therapeutic approach to fighting antibiotic-resistant infections. The novel method uses a targeted, light-activated nanodrug consisting of antibiotic-loaded nanoconstructs, which are nanoscale cages made of gold and coated with polydopamine. The antibiotic is loaded into the polydopamine coating. The gold nanocages convert laser irradiation to heat, resulting in the photothermal effect and simultaneously releasing the antibiotic from the polydopamine coating. “We believe that this approach could facilitate the effective treatment of infections caused by antibiotic-resistant bacteria, including those associated with bacterial biofilms, which are involved in a wide variety of bacterial infections,” says Chen, assistant professor in the Department of Chemistry and Biochemistry in the J. William Fulbright College of Arts and Sciences. Microbial resistance to antibiotics has become a growing public health concern in hospitals and the community at large, so much so that the Infectious Diseases Society of America has designated six bacterial species as “ESKAPE pathogens” — Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species. This designation reflects the limited availability of antibiotics that can be used to treat infections caused by these species. “It is also estimated that 80 percent of all bacterial infections involve formation of a biofilm, and all of these infections share the common characteristic of intrinsic resistance to conventional antibiotic therapy,” says Smeltzer, professor in the Department of Microbiology and Immunology at UAMS and director of the Center for Microbial Pathogenesis and Host Inflammatory Responses. “Intrinsic resistance refers to the fact that bacteria within a biofilm exhibit a therapeutically relevant level of resistance to essentially all antibiotics.” Researchers in Smeltzer’s laboratory study the ESKAPE pathogen Staphylococcus aureus. They focus on how the pathogen causes biofilm-associated bone infection and infections associated with orthopaedic implants. But, as Smeltzer explains, there are many other examples in infections — intravenous catheters and vascular grafts, for example — caused by Staphylococcus aureus. The team used Staphylococcus aureus as the proof-of-principle pathogen to demonstrate the potency of their nanodrug. The combination of achieving a photothermal effect and controlled release of antibiotics directly at the site of infection was achieved by laser irradiation at levels within the current safety standard for use in humans. The therapeutic effects of this approach were validated using planktonic bacterial cultures — bacterial cells that are free-floating rather than contained with a biofilm — of both methicillin-sensitive and methicillin-resistant Staphylococcus aureus strains. However, the method was subsequently shown to be effective even in the context of an intrinsically resistant biofilm. “The even better news is that the technology we developed would be readily adaptable to other bacterial pathogens that cause such infections, including the other ESKAPE pathogens,” Smeltzer says. The researchers’ work was recently published in ACS Infectious Diseases, a publication of the American Chemical Society (ACS) and “the first journal to highlight chemistry and its role in the multidisciplinary and collaborative field of infectious disease research.” Participating in the research were first authors Daniel Meeker, an M.D./Ph.D. student in Smeltzer’s lab, and Samir Jenkins, who obtained his doctoral degree in the Chen lab and is now a postdoctoral fellow at UAMS. Other participants included Karen Beenken, senior researcher in Smeltzer’s lab; Allister Loughran at UAMS; Timothy Muldoon, assistant professor of biomedical engineering at the U of A; Amy Powless, doctoral student in biomedical engineering at the U of A; Emily Miller, a U of A undergraduate and Honors College student; Vladimir Zharov, director of the Arkansas Nanomedicine Center at the UAMS Winthrop P. Rockefeller Cancer Institute and professor of otolaryngology, head and neck surgery at UAMS; and Ekaterina Galanzha, associate research professor of otolaryngology, head and neck surgery at UAMS.


Deshmukh A.,UAMS | Kumar G.,Medical College of Wisconsin | Pant S.,UAMS | Rihal C.,Mayo Medical School | And 2 more authors.
American Heart Journal | Year: 2012

Background: The aim of this study was to describe the prevalence of Takotsubo cardiomyopathy (TTC), age-gender interaction, and various comorbidities associated with it based on nationwide hospitalization records. Takotsubo cardiomyopathy is an increasingly reported clinical syndrome; however, there are no data on its prevalence in the general US population. Methods: The Nationwide Inpatient Sample discharge records were queried for the year 2008 using the International Classification of Diseases, Ninth Revision, code 429.83. Results: There were 6,837 patients diagnosed with TTC among 33,506,402 hospitalizations in the Nationwide Inpatient Sample database. Women were found to have higher odds of developing TTC (odds ratio 8.8). Women > 55 years old had 4.8 times higher odds for developing TTC when compared with women < 55 years old. Smoking, alcohol abuse, anxiety states, and hyperlipidemia were commonly associated with TTC. The peak incidence of hospitalization for TTC was in summer. Conclusion: Takotsubo cardiomyopathy was diagnosed in about 0.02% of all hospitalizations in the United States, mostly in elderly women with history of smoking, alcohol abuse, anxiety states, and hyperlipidemia. © 2012 Mosby, Inc. All rights reserved.


O'Connell C.M.,Childrens Hospital of Pittsburgh | AbdelRahman Y.M.,University of Tennessee Health Science Center | Green E.,Childrens Hospital of Pittsburgh | Darville H.K.,Childrens Hospital of Pittsburgh | And 6 more authors.
Infection and Immunity | Year: 2011

We previously demonstrated that plasmid-deficient Chlamydia muridarum retains the ability to infect the murine genital tract but does not elicit oviduct pathology because it fails to activate Toll-like receptor 2 (TLR2). We derived a plasmid-cured derivative of the human genital isolate Chlamydia trachomatis D/UW-3/Cx, strain CTD153, which also fails to activate TLR2, indicating this virulence phenotype is associated with plasmid loss in both C. trachomatis and C. muridarum. As observed with plasmid-deficient C. muridarum, CTD153 displayed impaired accumulation of glycogen within inclusions. Transcriptional profiling of the plasmid-deficient strains by using custom microarrays identified a conserved group of chromosomal loci, the expression of which was similarly controlled in plasmid-deficient C. muridarum strains CM972 and CM3.1 and plasmid-deficient C. trachomatis CTD153. However, although expression of glycogen synthase, encoded by glgA, was greatly reduced in CTD153, it was unaltered in plasmid-deficient C. muridarum strains. Thus, additional plasmid-associated factors are required for glycogen accumulation by this chlamydial species. Furthermore, in C. trachomatis, glgA and other plasmid-responsive chromosomal loci (PRCLs) were transcriptionally responsive to glucose limitation, indicating that additional regulatory elements may be involved in the coordinated expression of these candidate virulence effectors. Glucose-limited C. trachomatis displayed reduced TLR2 stimulation in an in vitro assay. During human chlamydial infection, glucose limitation may decrease chlamydial virulence through its effects on plasmid-responsive chromosomal genes. Copyright © 2011, American Society for Microbiology. All Rights Reserved.


Eid J.F.,Urologic | Wilson S.K.,Urologic | Cleves M.,UAMS | Salem E.A.,Zagazig University
Urology | Year: 2012

Objective: To explore whether a "no touch" enhancement to the surgical technique of inflatable penile prosthesis (IPPs) implantaion will further decrease infection rates. Materials and Methods: A single surgeon performed 2347 IPPs between January 2002 and June 2011. Patients receiving each manufacturer's implants were stratified for age and diabetes. Since 2003, infection retardant-coated IPPs were implanted through the standardized penoscrotal approach. Since 2006, the "no touch" enhancement was added to the surgical procedure. Infection rates in the noncoated IPP, coated IPP with standard technique, and coated IPP implanted with "no touch" enhancement were calculated and subjected to statistical analysis. The two company's implants were scrutinized for their individual infection rates in each group. Results: Patients in all the groups were similar for age and diabetes. 132 noncoated implants had an infection rate of 5.3%. In the years 2003-2005, 704 coated devices had a statistically significant improvement in incidence of infection to 2%. In the years 2006-2010, the "no touch" technique enhanced the standard surgical procedure in 1511 patients. Only 7 infections were seen yielding an infection incidence of 0.46%. There was no difference in the two manufacturer's infection rates. Differentiation between virgin and revision operation displayed no bias in the infection rate. Conclusion: Infection-retardant coatings lower the risk of infection from 5.3% to 2%. The "no touch" enhancement to the surgical procedure further decreases the rate of infection to 0.46%. Neither manufacturer showed statistical superiority in survival from revision for infection. © 2012 Elsevier Inc. All Rights Reserved.


Willett R.,UAMS | Kudlyk T.,UAMS | Pokrovskaya I.,UAMS | Schonherr R.,University of Lübeck | And 3 more authors.
Nature Communications | Year: 2013

Vesicular tethers and SNAREs (soluble N-ethylmalemide-sensitive fusion attachment protein receptors) are two key protein components of the intracellular membrane-trafficking machinery. The conserved oligomeric Golgi (COG) complex has been implicated in the tethering of retrograde intra-Golgi vesicles. Here, using yeast two-hybrid and co-immunoprecipitation approaches, we show that three COG subunits, namely COG4, 6 and 8, are capable of interacting with defined Golgi SNAREs, namely STX5, STX6, STX16, GS27 and SNAP29. Comparative analysis of COG8-STX16 and COG4-STX5 interactions by a COG-based mitochondrial relocalization assay reveals that the COG8 and COG4 proteins initiate the formation of two different tethering platforms that can facilitate the redirection of two populations of Golgi transport intermediates to the mitochondrial vicinity. Our results uncover a role for COG sub-complexes in defining the specificity of vesicular sorting within the Golgi. © 2013 Macmillan Publishers Limited. All rights reserved.


News Article | October 29, 2016
Site: www.prweb.com

The Center for Vein Restoration (CVR), the nation’s largest, physician-led, vein treatment medical organization, is proud to announce expansion to Rosedale, MD. CVR's newest location has just begun seeing patients and is located at 9110 Philadelphia Road, Suite 306, Rosedale, MD 21237. Dr. Dov Frankel is proud to now serve on the team at the Center for Vein Restoration, where physicians have rededicated their careers to bringing relief to patients coping with venous disease. "I have always been fascinated by the human anatomy. As an emergency medicine physician, I take pride in the numerous medical procedures I perform on a daily basis. I was trained in the era of Ultrasound and have always had a passion for US guided procedures." Dr. Frankel continues, "Treating venous insufficiency combines my talents in medicine to best care for my patients in a safe and comfortable environment." Dr. Frankel’s dedication to providing state-of-the-art treatments comes at an important time. He states, "Venous disease is very prevalent in the US affecting nearly 40% of all individuals. The disease process ranges from mild discomfort with aesthetic un-pleasantries to significant morbidity." He continues, "The ability to treat patients with minimally invasive procedures using local anesthetics and giving patients significant relief and cure if very interesting to me." A native of Montreal, Canada, Dr. Dov Frankel obtained his Master of Science from McGill University in 1999, then went on to receive his MD at Ben Gurion University. Dr. Frankel completed his Emergency Medicine Residency at UAMS – Arkansas and during his last year, served as Chief Resident of the Emergency Medicine Department in 2005. He then joined Sinai Hospital in Baltimore, MD as an attending Emergency Physician and was appointed Associate Chief of the Emergency Department from 2007-2014. Dr. Frankel is a published author of scientific literature and has received multiple awards including "Best Poster Presentation Award" from McGill University and two-time winner of Baltimore Magazine's Top Doctors, to name a few. Venous insufficiency, the cause of varicose veins and spider veins, indiscriminately affects between 30–40 million Americans. Numerous factors including age, weight, prolonged sitting or standing, genetics or a history of DVT (blood clots) can increase the risk of developing this all-­to-­common and often under-diagnosed disorder. Treatment options range from lifestyle changes like exercising or taking regular breaks from prolonged sitting or standing to an array of minimally-­invasive, outpatient procedures that close problem veins, redirecting blood flow to healthier ones. Having performed its first procedure in 2007 under President and CEO Dr. Sanjiv Lakhanpal, Center for Vein Restoration (CVR) has since become a nationally recognized leader in the treatment of varicose and spider veins. Dedicated to relieving leg pain, treating the vascular cause of severe leg wounds, and eliminating unsightly veins, CVR’s minimally invasive procedures allow patients to look better, feel better, and live better. With 60 locations and counting, they have assembled the most qualified and experienced team of physicians, researchers, and staff to serve patients across Alabama, Connecticut, Indiana, Maryland, Michigan, New Jersey, New York, Pennsylvania, Virginia, and Washington, DC. For more information, visit http://www.centerforvein.com. You may also contact Nicole McMillan at nicole(dot)mcmillan(at)centerforvein(dot)com or 240-965-3277.


Stack Jr. B.C.,University of Arkansas for Medical Sciences | Stack Jr. B.C.,Thyroid Center | Moore E.,University of Arkansas for Medical Sciences | Spencer H.,UAMS | And 2 more authors.
Otolaryngology - Head and Neck Surgery (United States) | Year: 2013

Objective. Describe data from patients undergoing outpatient thyroid surgeries for benign and malignant disease at academic medical centers in the United States. Study Design. Retrospective database search. Setting. The University Health System Consortium (UHC), Oak Brook, Illinois, data compiled from discharge summaries. Subjects and Methods. Discharge data were collected from the first quarter of 2005 through the fourth quarter of 2010. Searching strategy was based on diagnosis of thyroid disease and patients undergoing thyroid surgery across all UHC facilities. Demographic information was collected as well as charges. Complications were also evaluated in this analysis. Results. During the study period, 38,362 outpatient thyroidectomies were performed from our sample, 32% for thyroid cancer. More total thyroidectomies (43%) and fewer hemithyroidectomies (36%) were being performed overall; 64.1% of patients stayed 23 hours. Conclusion. This is one of the largest series reporting outcomes for outpatient thyroid surgery. Since these surgeries appear to be shifting to an outpatient setting, this report reflects the experience with the majority of endocrine surgeries from the UHC database being performed presently. These results are derived from teaching hospitals and their affiliates and may not reflect the entirety of thyroid surgery in the United States. © 2013 American Academy of Otolaryngology-Head and Neck Surgery Foundation.


Marino M.,University of Arkansas for Medical Sciences | Spencer H.,UAMS | Hohmann S.,University of Chicago | Bodenner D.,Thyroid Center | And 2 more authors.
Otolaryngology - Head and Neck Surgery (United States) | Year: 2014

Objective. To compare the cost of same-day vs 23-hour observation outpatient thyroidectomy at US academic medical centers. Study Design. Cross-sectional analysis of a national database. Setting. The University HealthSystem Consortium (UHC) data collected from discharge summaries. Subjects and Methods. Discharge data were collected from the first quarter of 2009 through the second quarter of 2013. The UHC database, compiled from more than 200 affiliated hospitals, was searched based on diagnosis codes for outpatient thyroid procedures. Cost data, calculated based on reported charges, were collected in addition to demographics. Comparisons were made between same-day vs 23-hour observation based on cost. Additional stratification was performed based on the extent of thyroidectomy. Results. During the study period, 49,936 outpatient thyroidectomies were performed. Overnight observation (63%) was more common than same-day discharge (37%). The overall mean cost of outpatient thyroidectomy was $5617, with a mean cost of same-day surgery of $4642 compared with $6101 for overnight observation (P <.0001). When stratifying by extent of thyroidectomy, the cost of same-day surgery was consistently lower than that for overnight observation. Conclusion. Outpatient thyroidectomy is commonly performed in the United States. It is most commonly performed on a 23-hour overnight observation basis. Overnight stay and complications were chief among other factors associated with higher cost, independent of the type of thyroid procedure performed. In appropriately selected patients, same-day thyroidectomy is a safe and cost-effective alternative to overnight observation or inpatient thyroid procedures. © American Academy of Otolaryngology-Head and Neck Surgery Foundation 2014.


Todorova V.K.,UAMS | Kaufmann Y.,UAMS | Klimberg V.S.,UAMS
Anticancer Research | Year: 2011

Background/Aim: It has been reported that continuous low-dose (metronomic) administration of cytotoxic drugs may be better tolerated and may have greater antitumor effects than a single high-dose chemotherapy. The aim of this study was to examine the efficacy and cardiotoxicity of metronomic administration of two of the most commonly used anticancer agents, cyclophosphamide (CPA) and doxorubicin (DOX), on an experimental breast cancer of rats. Materials and Methods: Breast tumors were induced in Fisher 344 female rats by implanting Mat B III cells. Rats with tumors were randomized into three groups and were treated with a total dose of 160 mg/kg CPA and a total dose of 12 mg/kg DOX, administered twice per week for four weeks. Control rats were injected with saline according to the same schedule. Echocardiography was performed before the start of treatment and before sacrifice, which took place two weeks after the last injection, when plasma troponin was also measured. Results: The metronomic CPA eradicated the tumors and preserved body weight and echocardiographic parameters. The metronomic DOX slowed tumor growth, but was not able to prevent DOX-induced cardiotoxicity. Conclusion: These results suggest that the success of a metronomic chemotherapy in terms of both efficacy and toxicity depends on the target, the class and the route of administration of the anticancer agent.

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