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Archive for the ‘Population Health Management, Genetics & Pharmaceutical’ Category

Reporter and Curator: Dr. Sudipta Saha, Ph.D.

WC 10

WordCloud by Zach Day; Article Title: Interaction of enzymes and hormones

The majority of living forms depend for their functioning upon two classes of biocatalysts, the enzymes and the hormones. These biocatalysts permit the diverse chemical reactions of the organism to proceed at 38°C with specificity and at rates frequently unattainable in vitro at elevated temperatures with similar reactants. The physiologic importance of enzymes and hormones is evident not only under normal circumstances, but is reflected clinically in the diverse descriptions of errors of metabolism, due to lack or deficiency of one or more enzymes, and the numerous hypo and hyper functioning states resulting from imbalance of hormonal supply.

In as much as both enzymes and hormones function, with rare exception, to accelerate the rates of processes in cells, investigators have sought possible interrelationships and interactions of enzymes and hormones, particularly as a basis for the mechanism of hormonal action. It has seemed logical to hypothesize that hormones, while not essential for reactions to proceed but never the less affecting the rates of reactions, may function by altering either the concentration or activity of the prime cellular catalysts, the enzymes. This proposed influence of hormones on enzymatic activity might be a primary, direct effect achieved by the hormone participating as an integral part of an enzyme system, or an indirect influence based upon the hormone altering the concentration of available enzyme and/or substrate utilized by a particular enzyme. Many publications have described alterations in the activity of enzymes in various tissues following administration in vivo of diverse hormonal preparations. However, it is not possible to judge, in the in vivo experiments, whether the reported effects are examples of direct enzyme-hormone interaction, or an indirect influence of the hormone mediated via one or more metabolic pathways, and therefore other enzyme systems whose activities are not being measured. Data from in-vivo studies of this type are thus not pertinent to a discussion of direct hormone-enzyme interaction.

Enzyme hormone interaction, as seen, for example, in the profound role of the enzymes of the liver in the metabolism of certain hormones, is of paramount importance in determining the effectiveness of these hormones. The ability of the organic chemist to prepare synthetic hormonal derivatives which are relatively resistant to enzymatic processes in the liver has been of outstanding value for approaches to oral hormonal therapy. Largely unexplored as yet is the possibility that enzyme-hormone interactions may lead to the production of physiologically more active substances from compounds normally synthesized and secreted by a particular endocrine gland. It may be said at the outset that in no instance has a hormone been demonstrated to influence the rate of a cellular reaction by functioning as a component of an enzyme system.

It is plausible that enzymes in a pathway might be structurally conserved because of their similar substrates and products for linked metabolic steps. However, this is not typically observed, and sequence analysis confirms the lack of convergent or divergent evolution. One might postulate that, if the folds or overall structures of the enzymes in a pathway are not conserved, then perhaps at least pathway-related active site similarities would exist. It is true that metal-binding sites and nucleotide-binding sites are structurally conserved. For example, cofactor-binding motifs for zinc, ATP, biopterin and NAD have been observed and biochemically similar reactions appear to maintain more structural similarity than pathway-related structural motifs. In general, ‘horizontal’ structural equivalency is prevalent in that chemistry-related structural similarities exist, but ‘vertical’ pathway-related structural similarities do not hold.

For metabolic pathways, protein fold comparisons and corresponding active site comparisons are sometimes possible if structural and functional homology exists. Unfortunately, with the current structural information available, the majority of active sites that can be structurally characterized are not similar within a metabolic pathway. Other examples exist of nearly completed pathways, for example, the tricarboxylic acid (TCA) cycle, and similar observations are observed. Situations in which different metals are incorporated in enzyme active sites lead to inherently different catalytic portions of the active sites. Slight differences in the ligand-binding portions of the respective active sites must lead to the observed differences in pathway-related enzyme specificities. These modifications in enzymatic activity are similar to what Koshland and co-workers previously observed. They showed that very minor active site perturbations to isocitrate dehydrogenase had drastic effects on catalysis.

Molecular level understanding of chemical and biological processes requires mechanistic details and active site information. The current knowledge regarding enzyme active sites is incomplete. Even in situations in which ATP-, ADP- or NAD(P)+-binding domains are observed or in situations in which similar folds are found (e.g. even for related kinases or for proteins involved in the immune system), structural comparisons do not yield specific details about active sites and it is not possible to predict where the substrate binds or to identify determinants of active site substrate specificity. Therefore, in this era of structural genomics, there should be major continued emphasis on completing structural information for important metabolic pathways. This will require improved efforts to obtain structures for enzyme complexes with appropriate cofactors, substrates or substrate analogs, as well as with inhibitors and regulators of activity. Then and only then will we have complete structural knowledge and facilitated structure-based drug design efforts. Structural genomics efforts promise to provide structural data in a high-throughput mode. However, we need to ensure that much of this focus is placed on completing the picture of metabolic pathways and enzyme active sites.

The availability of the human genomic sequence is changing the way in which biological questions are addressed. Based on the prediction of genes from nucleotide sequences, homologies among their encoded amino acids can be analyzed and used to place them in distinct families. This serves as a first step in building hypotheses for testing the structural and functional properties of previously uncharacterized paralogous genes. As genomic information from more organisms becomes available, these hypotheses can be refined through comparative genomics and phylogenetic studies. Instead of the traditional single-gene approach in endocrine research, we are beginning to gain an understanding of entire mammalian genomes, thus providing the basis to reveal subfamilies and pathways for genes involved in ligand signaling. The present review provides selective examples of postgenomic approaches in the analysis of novel genes involved in hormonal signaling and their chromosomal locations, polymorphisms, splicing variants, differential expression, and physiological function. In the postgenomic era, scientists will be able to move from a gene-by-gene approach to a reconstructionistic one by reading the encyclopedia of life from a global perspective. Eventually, a community-based approach will yield new insights into the complexity of intercellular communications, thereby offering us an understanding of hormonal physiology and pathophysiology. Many cellular signaling pathways ultimately control specific patterns of gene expression in the nucleus through a variety of signal-regulated transcription factors, including nuclear hormone receptors. The advent of genomic technologies for examining signal-regulated transcriptional responses and transcription factor binding on a genomic scale has dramatically increased our understanding of the cellular programs that control hormonal signaling and gene regulation. Studies of transcription factors, especially nuclear hormone receptors, using genomic approaches have revealed novel and unexpected features of hormone-regulated transcription, and a global view is beginning to emerge.

Source References:

http://pediatrics.aappublications.org/content/26/3/476.abstract

http://www.ncbi.nlm.nih.gov/pubmed/13499378

http://endo.endojournals.org/content/54/5/591.long

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC528661/

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1196745/

http://www.ncbi.nlm.nih.gov/pubmed/11114510

http://www.ncbi.nlm.nih.gov/pubmed/23516625

http://www.annualreviews.org/doi/abs/10.1146/annurev.bi.50.070181.002341

http://www.sciencedirect.com/science/article/pii/S0016648098971258#

http://www.interactive-biology.com/3931/basics-of-hormone-classification/

http://en.wikipedia.org/wiki/Category:Hormones_by_chemical_structure

http://www.annualreviews.org/doi/abs/10.1146/annurev-physiol-021909-135840

http://www.ncbi.nlm.nih.gov/pubmed/16423812

http://edrv.endojournals.org/content/23/3/381.full.pdf

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Reporter: Aviva Lev-Ari, PhD, RN

The Consumer Genetics Conference (CGC) is a one-of-a-kind event that draws together a dynamic community of scientists, clinicians, technology innovators, and patients to discuss the burning issues around the analysis and delivery of genomics results directly to patients and consumers. Over three days, attendees will hear about disruptive diagnostic technologies, cognitive barriers to patients (and medical professionals), ethical/regulatory/privacy issues, the thorny issue of reimbursement, and the challenges of building relationships to realize the potential of personal genomics and individualized medicine. CGC provides an opportunity for all stakeholders to come together at one venue, share viewpoints and engage in an honest dialogue, and together learn how to move the elephant of change. Program topics will include:
  • Whole Genome Debates
  • Translational Genomics
  • Clinical & Third-Generation Sequencing
  • Personal Genome Analysis & Interpretation
  • Empowering Patients: Companies & Technologies
  • Molecular Diagnostics & Point-of-Care
  • Investment & Funding Opportunities
  • Reimbursement Models
  • Five-Year Plan for Consumer Genomics
  • Data Analysis & Management
  • Ethics, Privacy & Regulation
  • Digital Health Tracking Apps

SPEAKERS

2013 Distinguished Faculty

Bonnie Ancone, Vice President, Molecular Diagnostics, XIFIN, Inc.
Bonnie Ancone has 25 years experience in the medical industry of which 15 years have been directly related to medical billing and collections. Prior to coming to XIFIN, Ms. Ancone worked in Anatomic Pathology Reference laboratory settings for 10 years. She held multiple positions including Billing Supervisor, Billing Manager and Director of Billing & Collections. She was also a partner in a medical billing company. Ms. Ancone’s prior experience includes 10 years in outpatient substance abuse clinics as a nurse and Assistant Director. In this capacity, she interacted with regulatory bodies such as DEA, FDA and multiple state behavioral health agencies dealing with licensing, auditing and regulations. She participated in the development of state methadone regulations and the state methadone coalition for Arizona and Nevada. She started her career on the operations side of banking.

Nazneen Aziz, Ph.D., Director, Molecular Medicine, Transformation Program Office, College of American Pathologists
Nazneen Aziz is the Director of Molecular Medicine at the College of American Pathologists. In this role, Dr. Aziz is guiding strategies and leading projects related to genomic medicine at CAP. Currently, she leads a committee that focuses on critical issues surrounding next generation sequencing. She is a member of the Association for Molecular Pathology Workgroup for Whole Genome Analysis and the Center for Disease Control Nex-StoCT-II Workgroup on next generation sequencing bioinformatics and the Interpretation of Sequence Variant Work Group at the College of American College of Medical Genetics. In her prior positions, Dr. Aziz was Vice President of Research and Development at Interleukin Genetics, Vice President of External Research at Point Therapeutics and Director of Translational Research at Novartis Institute of Biomedical Research. In her industry career, she has focused on personalized medicine, biomarkers, genetic tests, and development of drugs in cancer and diabetes. Prior to joining the biotechnology industry Dr. Aziz was an Assistant Professor at Harvard Medical School and Children’s Hospital in Boston where she discovered and characterized the function of novel genes involved in recessive polycystic kidney disease. Nazneen received her Ph.D. in molecular genetics and Masters Degree in biochemistry at the Massachusetts Institute of Technology and her Bachelor’s Degree from Wellesley College.

Pam Baker, Senior Director, Market Access, CardioDx
Ms. Pam Baker is Senior Director of Market Access & Policy with Cardio Dx. She is a life sciences professional with 17 years of experience in pharma, biotech and diagnostics in a series of commercial roles across marketing, new product commercialization, reimbursement, pipeline and sales management. She started her healthcare career 17 years ago, beginning with Johnson & Johnson (Janssen, Ortho and Mc Neil), followed by Genentech. Ms Baker started out in sales, then moved into sales training, sales leadership and to multiple marketing roles, from product launch, to in-line marketing. She then moved into the reimbursement arena, leading the Program Strategy & Management team for Genentech Access Solutions, and has recently joined a molecular diagnostics company in Palo Alto, CA called CardioDx. Ms Baker received a Bachelor of Arts, Political Science and Asian Studies from Northwestern University and a Master, International Management from Thunderbird School of Global Management. She is a mom of 5 year old twin girls.

Shawn C. Baker, Ph.D., CSO, BlueSEQ
Dr. Shawn C. Baker is the Chief Science Officer and co-founder of BlueSEQ, an independent guide for researchers outsourcing their DNA sequencing. Having received his Ph.D. at the University of California – Davis, he started his career as a Research Scientist at Illumina when it was a 15-person startup. After spending several years at the bench developing gene expression array products, he transitioned to Product Marketing where he led a team in charge of Illumina’s Expression and Regulation sequencing portfolio. Dr. Baker started working with BlueSEQ in 2011, helping to establish an online marketplace for life science researchers to gain access to the best sequencing technology for their projects. In addition, BlueSEQ has created the Knowledge Bank, a neutral source of information on the various sequencing technologies, platforms and applications.

Cinnamon S. Bloss, Ph.D., Director, Social Sciences & Bioethics, Assistant Professor, Scripps Translational Science Institute

Dr. Bloss is an Assistant Professor, as well as Director of Social Sciences and Bioethics at the Scripps Translational Science Institute. Her research is funded by the National Institutes of Health and is focused on investigating individuals’ behavioral and psychological responses to disclosure of personal genomic information. She is the lead researcher on STSI’s Scripps Genomic Health Initiative, and her work on this project was recently published in the New England Journal of Medicine and has been highlighted at a number of national and international scientific meetings. She has also presented invited testimony on consumer genomics before the Food and Drug Administration Advisory Panel. Dr. Bloss’ other research interests include developing ways of combining genomics with traditional disease risk factors to make predictions about disease development, progression and response to treatment, as well as designing effective health interventions that leverage genomic information. She also conducts genetic association studies and has several collaborations to investigate the genetic underpinnings of neurological, behavioral, and other health-related phenotypes. Dr. Bloss received her B.A. in Psychology from Smith College, her Ph.D. in Clinical Psychology from the University of California, San Diego, and completed a predoctoral internship in clinical neuropsychology at the University of Florida. Dr. Bloss completed a post-doctoral fellowship in statistical genetics and genomic medicine at The Scripps Research Institute. At STSI, Dr. Bloss directs the Summer Undergraduate Research Internship and is an instructor in the TSRI Graduate Program. She is also a California-licensed clinical psychologist and has worked with adults and children with a wide range of neurological and psychiatric conditions.
John Boyce, President and CEO, GnuBIO
John Boyce is President, CEO and Co-Founder of GnuBIO. Prior to starting GnuBIO, John co-founded Delphi Bio, LLC, a strategic consulting company that serves startup and fortune 500 companies within the life sciences market. Using his proven ability to drive companies to commercial success, John served as the Business Development head for a number of clients, including Affomix. Over a two year period, John developed the business plan for Affomix, oversaw all commercial activities, as well as initiated and drove the sale of the company to a multi-billion dollar sequencing corporation in July 2010. Prior to Delphi and Affomix, John served as Head of Business Development for Helicos BioSciences (HLCS), where he was responsible for identifying new market opportunities. Prior to Helicos, John was the Senior Director of Commercial Development for Parallele Biosciences, Inc. where he played an integral role of building the company leading to an acquisition of the company by Affymetrix (AFFY). He was the Senior Director of Business Development for Genomics Collaborative where he was responsible for putting in place and building the Sales, Marketing, and Business Development infrastructure. John executed several key deals and played a key role in the acquisition by SeraCare Life Sciences, Inc. Prior to Genomics Collaborative, John led the successful expansion of Sequenom’s MassARRAY system as Director, United States Sales at Sequenom Inc. (SQNM), from 2000 to 2003.

Catherine Brownstein, Ph.D., Project Manager, The Gene Partnership, Boston Children’s Hospital; Instructor, Pediatrics, Harvard Medical School
Catherine Brownstein, PhD, MPH is the Project Manager for The Gene Partnership at Boston Children’s Hospital and an Instructor in Pediatrics at Harvard Medical School. For the last two years, Catherine has worked to establish and develop new sequencing and pharmacogenomics programs at the hospital. Before coming to BCH and HMS, Catherine was a toxicologist at the Massachusetts Department of Public Health, and spent four years in the world of Health 2.0, creating online patient communities for individuals with chronic and terminal diseases. Catherine’s interests and expertise lie with the intersection of genotype and phenotype, and the integration of patient-reported outcomes with genomics and medicine.

Kenneth Chahine, Ph.D., J.D., Senior Vice President and General Manager, DNA, ancestry.com
Ken Chahine has served as Senior Vice President and General Manager for Ancestry DNA, LLC since 2011. Prior to joining us he held several positions, including as Chief Executive Officer of Avigen, a biotechnology company, in the Department of Human Genetics at the University of Utah, and at Parke-Davis Pharmaceuticals (currently Pfizer). Mr. Chahine also teaches a course focused on new venture development, intellectual property, and licensing at the University of Utah’s College of Law. He earned a Ph.D. in Biochemistry from the University of Michigan, a J.D. from the University of Utah College of Law, and a B.A. in Chemistry from Florida State University.

Mick Correll, COO, Genospace
Mick Correll is the Co-Founder and Chief Operating Officer of GenoSpace, a Cambridge, Massachusetts-based company that is pioneering a bold and innovative software platform for advancing 21st-century genomic medicine. Prior to launching GenoSpace, Mick was the Associate Director of the Center for Cancer Computational Biology (CCCB) at the Dana-Farber Cancer Institute, overseeing the Center’s next-generation sequencing facility, bioinformatics consulting service and software development efforts.Mick started his career as a Bioinformatician at Lion Bioscience Research Inc, where he was the principle architect of a globally distributed gene annotation and analysis platform, and subsequently served asHead of Professional Services for Lion Bioscience Inc in North America, and Director of Healthcare Product Management at InforSense LLC.

Steven Dickman, President & Owner, CBT Advisors
Steven Dickman is President & Owner of CBT Advisors, a boutique life sciences consulting firm in Cambridge, Massachusetts. CBT Advisors works with over 20 clients a year on product positioning and corporate strategy; communications and fund-raising materials; and market analysis based on research and expert interviews. Clients include public and private biotech companies and life science venture funds. Before founding CBT Advisors in 2003, Mr. Dickman spent four years in venture capital with TVM Capital. There, Mr. Dickman’s deals included Sirna Therapeutics, sold to Merck in 2006 for $1.1 billion. Earlier, he was a Knight Science Journalism Fellow at MIT, a freelance contributor to The Economist, Discover, Science, GEO and Die Zeit and the founding bureau chief for Nature in Munich, Germany. Fluent in German, Mr. Dickman received his biochemistry degree cum laude from Princeton University.
Lynn Doucette-Stamm, Ph.D., Vice President, Development and Clinical Operations, Interleukin Genetics, Inc.
Lynn Doucette-Stamm has served as Vice President of Development and Clinical Operations at Interleukin Genetics since 2011. Prior to joining Interleukin she has worked in numerous capacities in Life Sciences for greater than 25 years. Key positions she has held prior to Interleukin include Vice President of Business Development at Beckman Coulter Genomics and Agencourt Bioscience, and Vice President and General Manager of the GenomeVisionTM Services Business Unit at Genome Therapeutics. She earned a Ph.D. in Cell Biology and Genetics from Cornell University Graduate School of Medical Sciences and a B.S. in Biology from McMaster University.
Yaniv Erlich, Ph.D., Principal Investigator and Whitehead Fellow, Whitehead Institute for Biomedical Research 
Dr. Yaniv Erlich is Andria and Paul Heafy Family Fellow and Principal Investigator at the Whitehead Institute for Biomedical Research at the Massachusetts Institute of Technology. He received a bachelor’s degree from Tel-Aviv University at Israel and his PhD from the Watson School of Biological Sciences at Cold Spring Harbor Laboratory. Dr. Erlich’s research interests are computational human genetics. He has extensive experience in developing new algorithms for high throughputs sequencing and to detect disease genes. In two of his studies, he identified the genetic basis of devastating genetic disorders. His lab works on a wide range of topics including developing compressed sensing approach to identify rare genetic variations, devising new algorithms for personal genomics, and using Web 2.0 information for genetic studies. Dr. Erlich is the recipient of the Harold M. Weintraub award, the IEEE/ACM-CS HPC award, Goldberg-Lindsay Fellowship, Wolf foundation scholarship for Excellence in exact science, and Emmanuel Ax scholarship, and he was selected as one of 2010 Tomorrow’s PIs team of Genome Technology.

Kyle Fetter, Associate Vice President, Molecular Diagnostics, XIFIN, Inc.
Kyle Fetter has overseen the commercialization, billing, and reimbursement processes for more than 10 molecular diagnostic companies releasing new high complexity laboratory testing services into the healthcare market. He currently manages billing processes for more than 10 companies at various stages of commercialization and third party payer contracting. In addition to overseeing a large molecular diagnostic billing department, Mr. Fetter consults with molecular diagnostic companies on projecting cash flow for non-covered services, implementing successful appeals strategies, and the relationship between sales and reimbursement for new medical technology. He came to the healthcare industry with a background in private equity and technology commercialization. Mr. Fetter has a B.A. in History and Journalism from the University of Southern California and an M.B.A from the University of Utah.
Birgit Funke, Ph.D., FACMG, Assistant Molecular Pathologist and Director of Clinical Research and Development, Laboratory for Molecular Medicine, Massachusetts General Hospital; Assistant Professor in Pathology, Harvard Medical School
Birgit Funke, Ph.D., FACMG is an Associate Laboratory Director of the Laboratory for Molecular Medicine (LMM) at PCPGM and is an Instructor in Pathology at Harvard Medical School. She currently oversees genetic testing and test development in the area of cardiovascular disease at the LMM. She has authored and co-authored many publications focusing on a wide array of topics, most recently incentive learning and memory in mice. Currently, Dr. Funke focuses on genetic testing with emphasis on genetically heterogeneous cardiovascular diseases, with the goal of defining the genetic basis for these disorders and developing comprehensive tests using new emerging molecular technologies. In addition, she is interested in developing genetic tests for common, complex disorders, working to understand the genetic variants that have been linked with psychotic and affective disorders.

Amanda Gammon, MS, CGC, Licensed Genetic Counselor, Huntsman Cancer Institute, University of Utah 
Amanda Gammon is a board-certified genetic counselor with a master’s degree in genetic counseling from University of Colorado at Denver Health Sciences Center. She received her bachelor’s degree from the University of Colorado at Boulder in molecular, cellular, and developmental biology and English literature. While completing her education, Amanda worked at Rocky Mountain Cancer Centers. She began working at Huntsman Cancer Institute in July 2007. She provides genetic counseling to patients in the Family Cancer Assessment Clinic and the research-oriented High Risk Breast Cancer Clinic. She also provides counseling for two National Institutes of Health-funded studies. For one study, she discusses familial colorectal cancer risk with individuals by telephone in rural Utah and Idaho to assess effectiveness of telephone intervention versus written risk information in encouraging individuals to pursue colonoscopy. In the other, she provides hereditary breast and ovarian cancer counseling to women in rural Utah both by phone and in-person to assess equivalency. Her main research interests include hereditary breast cancer and provision of genetic counseling through alternative modes for individuals with limited access to genetic counseling centers.

Manuel L. Gonzalez-Garay, Ph.D., Assistant Professor, The University of Texas Health Science Center at Houston
Dr. Gonzalez-Garay obtained his B.S. from the University of Nuevo Leon, Mexico in 1988. He wrote a bachelor’s research dissertation “Papillomavirus and cervical cancer in Mexican population” under the supervision of Dr. Barrera-Saldana and Dr. Gariglio. After a pre-doctoral fellowship at University of Texas, he joined the doctoral program in 1990. In 1996, Dr. Gonzalez-Garay completed his Ph.D. at the University of Texas, writing a dissertation about the regulation of the stoichiometry of tubulin. After a two-year Post-Doctoral Fellowship in the lab of Dr. Fernando Cabral, he joined Lexicon Genetics as a Bioinformatician. He was subsequently promoted to manager of Bioinformatics Group. During his stay at Lexicon Genetics, Dr. Gonzalez-Garay developed a large number of proprietary software and databases to support the gene knockout and drug discovery pipelines. During 2002, Dr. Gonzalez-Garay moved to Baylor College of Medicine, Human Genome Sequencing Center (HGSC) where he working as a Senior Scientific Programmer and team leader. During his stay at the HGSC he developed “Genboree discovery system” and participated as a bioinformatician in a large number of sequencing projects including the sequencing of the Human chromosome 3 and 12, the complete genomes of Rat and Sea Urchin. Dr. Gonzalez-Garay was instrumental in the development of pipelines for the re-sequencing of candidate genes at HGSC. From 2007 to 2009 he actively participated in the Tumor Sequencing Project (TSP) and the cancer genome atlas (TCGA) project. In January, 2010, The IMM recruited Dr. Gonzalez-Garay as Research Assistant Professor for The Brown Foundation Institute of Molecular Medicine for the Prevention of Human Diseases. Dr. Gonzalez-Garay is currently developing the pipelines to analyze whole genome and exome sequences and he is currently participating in three main projects: The identification of the causal mutations for tuberous sclerosis, cardiomyopathy and schizophrenia.

Robert Green, M.D., M.P.H., Associate Professor of Medicine, Division of Genetics, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School 
Robert C. Green, MD, MPH is a medical geneticist and a clinical researcher who directs the G2P research program (genomes2people.org) in translational genomics and health outcomes in the Division of Genetics at Brigham and Women’s Hospital and Harvard Medical School. Dr. Green is principal investigator of the NIH-funded REVEAL Study, in which a cross-disciplinary team has conducted 4 separate multi-center randomized clinical trials collectively enrolling 1100 individuals to disclose a genetic risk factor for Alzheimer’s disease in order to explore emerging themes in translational genomics. Dr. Green also co-directs the NIH-funded PGen Study, the first prospective study of direct-to-consumer genetic testing services and leads the MedSeq Project, the first NIH-funded research study to explore the use of whole genome sequencing in preventive medicine. Dr. Green is currently Associate Director for Research of the Partners Center for Personalized Genetic Medicine, a Board Member of the Council for Responsible Genetics and a member of the Informed Cohort Oversight Boards for both the Children’s Hospital Boston Gene Partnership Program and the Coriell Personalized Medicine Collaborative. He co-chairs the ACMG working group that is currently developing recommendations for management of incidental findings in clinical sequencing.

Steve Gullans, Managing Director, Excel Venture Management
Dr. Gullans is an experienced investor, entrepreneur and scientist. At Excel, he focuses on life science technology companies with a particular interest in disruptive platforms that can impact multiple industries. Steve is currently a Director at Tetraphase Pharmaceuticals, PathoGenetix, nanoMR, Cleveland HeartLab, and Catch.com. He was previously a board member of Activate Networks as well as BioTrove which was acquired by Life Technologies (LIFE) in 2009 and Biocius Life Sciences which was acquired by Agilent Technologies (A) in 2011. Prior to Excel, Steve co-founded RxGen, Inc., a pharma services company where he served as CEO from 2004-2008. In 2002, Steve stepped in as a senior executive at U.S. Genomics to direct operations, recruit a new CEO, and assist with fundraising. In the 1990s, he co-developed the technology that launched CellAct Pharma GmbH, a drug development company. Steve’s experience with venture investing began in the late 1980s when he became an active advisor to small biotechs and venture investors, including being a Senior Advisor to CB Health Ventures for 10 years. Dr. Gullans is an expert in advanced life science technologies and was a faculty member at Harvard Medical School and Brigham and Women’s Hospital for nearly 20 years. He has published more than 130 scientific papersin many leading journals, lectured internationally, and co-invented numerous patents. He recently co-authored with Juan Enriquez an eBook entitled, Homo evolutis: A Short Tour of Our New Species, and a comment in Nature entitled, “Genetically Enhanced Olympics Are Coming,” which describe a world where humans increasingly shape their environment, themselves, and other species. Steve received his B.S. at Union College, Ph.D. at Duke University, and postdoctoral training at the Yale School of Medicine. He is a Fellow of the AAAS and the AHA.

Tina Hambuch, Senior Scientist, Illumina, Inc.
Tina Hambuch earned her Bachelor’s degree from UC Riverside and her doctorate from UC Berkeley, focusing on genetic analyses of genes that control the immune system. She continued her studies of genetic variation as a post-doctoral fellow at the Centers for Disease Control and an assistant professor at the Ludwig Maximillians University in Munich. After her academic career, Tina used her understanding of genetics and genetic variation to help identify and design diagnostic sequencing tests for clinical application at Ambry Genetics. Tina joined Illumina in 2008 where she combined her experience in genetics, genomics, and clinical diagnostics to contribute to the development of the CLIA-certified, CAP-accredited Illumina Clinical Services Laboratory (ICSL). In 2010, she launched a California-certified Clinical Genetic Molecular Biologist Scientist training program in which she serves as the Education Coordinator and Director. Tina is currently active in the development and validation of genetic testing, as well as clinical tools for doctor support and education. Tina is a member of the American College of Medical Genetics and the American Society of Human Genetics.

Michael Hawley, Chief Design Officer, Mad*Pow

As leader of the Mad*Pow Experience Design team, Michael leverages expertise in usability and user experience to help clients achieve their goals through design. Michael holds his MS in Human Factors in Information Design from Bentley College McCallum Graduate School of Business, and BA in Cellular and Molecular Biology from the University of Michigan. He is an active member of the professional design community, serving as an officer in the User Experience Professional’s Association and contributing ideas as a speaker and author, exploring trends within the UX discipline as a published columnist in publications such as UXMatters, iMedia, TMCNet and CPWire.
Caleb J Kennedy, Ph.D., Lead Scientist, Good Start Genetics, Inc.
Caleb currently leads an amazing group of scientist-engineers developing high-performance analytical tools for next-generation advances in genetic testing and research. He holds a Ph.D. in genetics from Harvard University, as well as M.S. and B.S. degrees in molecular and cellular biology from Texas A&M University. Caleb has two beautiful boys, one with Down syndrome.
Ayub Khattak, CEO, ruubix
Ayub Khattak, CEO or ruubix inc., uses his background in biochemistry, programming and electronics in the development of the ruubix digital diagnostic platform. He has his degree in Mathematics from UCLA and developed a NSF funded project in the genetic engineering of RNAi systems before founding ruubix.

Wendy Kohlmann, MS, CGC, Licensed Genetic Counselor, Huntsman Cancer Institute, University of Utah 
Wendy Kohlmann is a board-certified genetic counselor with a master’s degree in genetic counseling from the University of Cincinnati and a bachelor’s degree in zoology from the University of Wisconsin. She has worked as a genetic counselor at the University of Texas-M.D. Anderson Cancer Center in Houston and the University of Michigan Comprehensive Cancer Center in Ann Arbor. She began working at Huntsman Cancer Institute as a research associate in 2006. Wendy Kohlmann’s research interests include the inherited basis of melanoma and pancreatic cancer, psychosocial and behavioral outcomes of genetic counseling, and issues for children and adolescents with hereditary cancer syndromes.

Antoinette F. Konski, J.D., Partner, Foley & Lardner LLP
Antoinette F. Konski is a partner with Foley & Lardner LLP where her practice focuses on intellectual property. She works with life science clients, creating and optimizing value in intellectual property portfolios encompassing technologies that include personalized medicine, regenerative and stem cell biology, antibodies, immunology, gene therapy, nanotechnology, diagnostics, small molecules and drug delivery. She represents public and private companies and universities. Ms. Konski currently serves as the firm’s Silicon Valley IP office chairperson and co-chair of the Life Sciences Industry Team.

Gary J. Kurtzman, MD, Managing Director, Healthcare, Safeguard
Gary has 25+ years of experience in operations and investments, leveraging his medical expertise to enable businesses to enhance their products and grow their services, as well as to discover new partnering potential in developing entrepreneurial companies. Gary joined Safeguard in 2006, where he is responsible for identifying, deploying capital in and supporting emerging healthcare companies in molecular and point-of-care diagnostics, medical devices and healthcare IT. He targets companies with solutions that address the high cost of medical care, and safer and more effective treatments. Gary is a board member of Safeguard partner companies Alverix, Crescendo Bioscience, Good Start Genetics, Medivo, and PixelOptics. Gary has realized value for companies through a series of successful IPOs, M&A and turnaround transactions—most recently Shire’s acquisition of Safeguard’s partner company Advanced BioHealing for $750 million, in cash, representing a 13x cash-on-cash return for Safeguard; and Eli Lilly’s acquisition of Safeguard’s partner company Avid Radiopharmaceuticals for $300 million, up front, with an additional $500 million payout dependent upon the achievement of future regulatory and commercial milestones, representing an initial 3x cash-on-cash return for Safeguard with the potential to realize up to 8x. Gary joined Safeguard from BioAdvance, a state initiative committed to funding early-stage life sciences companies, where he served as Managing Director and Chief Operating Officer. Previously, he was Chief Executive Officer at Pluvita Corporation, a company developing biological and bioinformatic solutions for drug and diagnostic development. Gary also previously served as Chief Operating Officer at Genovo, Inc., a gene therapy start-up company. He was also employed as head of research & development by Avigen, Inc., an early-stage gene therapy company located in San Francisco. Gary began his career with Gilead Sciences, Inc.—at the time, a pre-IPO biotechnology company—as virology group leader. A board-certified internist from Barnes Hospital in St. Louis, MO, with a hematology sub-specialty, Gary has authored more than 40 research articles, book chapters and reviews, and is credited as inventor on twelve issued United States patents. Presently, Gary serves on various academic and biomedical committees and boards along with the editorial board of Biotechnology Healthcare. Presently, Gary is a lecturer in the Health Care Systems Department at the Wharton School at the University of Pennsylvania where he teaches entrepreneurship in life sciences.

Gholson Lyon, M.D., Ph.D., Assistant Professor of Human Genetics, Cold Spring Harbor Laboratory; Research Scientist, Utah Foundation for Biomedical Research
Gholson Lyon is an assistant professor in human genetics at Cold Spring Harbor Laboratory and a research scientist at the Utah Foundation for Biomedical Research. He is also a board-certified child, adolescent and adult psychiatrist. He earned an M.Phil. in Genetics at the University of Cambridge, England, then received a Ph.D. and M.D. through the combined Cornell/Sloan-Kettering/Rockefeller University training program. He started his independent research career in 2009, after finishing clinical residencies in child, adolescent and adult psychiatry. In addition to his research on the genetics of neuropsychiatric illnesses, Dr. Lyon is focusing on the genetic basis of rare Mendelian diseases.

Daniel MacArthur, Ph.D., Assistant Professor, Massachusetts General Hospital; Co-founder, Genomes Unzipped 
Daniel MacArthur is a group leader at the Analytic and Translational Genetics Unit at Massachusetts General Hospital, an assistant professor at Harvard Medical School, and a research affiliate at the Broad Institute of Harvard and MIT. His research focuses on understanding the functional impact of genetic variation using genome sequencing data. His writing on personal genomics is archived at Wired Science, and his research is described on his lab page at http://www.macarthurlab.org/.

Ellen T. Matloff, M.S., Research Scientist, Department of Genetics and Director, Cancer Genetic Counseling, Yale Cancer Center
Ellen T. Matloff, M.S., C.G.C., received her Bachelor’s degree in Biology from Union College, her Master’s degree in Genetic Counseling from Northwestern University, and her board certification from the American Board of Genetic Counseling. She specializes in hereditary breast and ovarian cancer syndrome (BRCA1, BRCA2), hereditary colon cancer syndromes (HNPCC, FAP), and rare cancer syndromes. Her interests include patient and provider issues in genetic counseling, sexuality and cancer patients, and the impact of patents on clinical practice.

Martin Mendiola, M.D., MPH, Director, Clinical Program Development, Happtique
Martin Mendiola is responsible for clinical needs assessments of mHealth technology for the purposes of enhancing the provision of care and patient engagement and satisfaction. He is involved in the clinical implementation of Happtique’s solutions within client health systems while serving as a liaison to its healthcare providers. He has also created the medical, health, and wellness library intellectual property offered to Happtique’s members. Prior to joining Happtique, Martin worked in the direct delivery of care within several hospital systems and through international humanitarian relief efforts, and has conducted extensive clinical research. He earned his MD from the Ponce School of Medicine and MPH in Health Policy from Columbia University Mailman School of Public Health.

Peter S. Miller, COO, Genomic Healthcare Strategies
Peter Miller is Chief Operating Officer of Genomic Healthcare Strategies, a company focused on the changes in healthcare resulting from advances in molecular medicine. Peter spent his career building companies which have operated in expanding markets driven by new technology. He has a track record of spotting trends and successful implementation. He did his undergraduate work at MIT. While working on his MBA at MIT’s Sloan School, he was a founding member of Abt Associates Inc, and over a period of 17 years worked as COO and Board member as the company grew from 3 people to 800. Peter has been a key advisor to firms facing a variety of transitional events (external or internal), entering new markets, and facing choices around mergers/acquisitions/going public. He has helped build successful companies in software and professional services, three of which were sold to public companies. He has served on a number of boards of innovative technology companies, helping build their success, both organizationally and in their markets. He has a long term interest in health care. He established the original health care research group at Abt Associates. He has helped teach a course at Harvard School of Public Health, working with Dr. John Bryant, later Dean of Columbia’s School of Public Health. He has worked on physician education with the American Association of Medical Colleges and has been a board member of several health care services firms. He has extensive experience with entrepreneurial companies, having successfully worked with firms raising money seven times, both as an employee and as a business plan quarterback. He is involved in M&A activities on both the buy and sell sides. In addition he has been a licensed (NASD) broker/dealer. Peter is a frequent invited speaker on the changing healthcare landscape, writing and speaking on Personalized Medicine for many years as a thought leader. He has been invited to speak at the Molecular Medicine Tri-Conference, LabCompete, the University of California at Santa Barbara’s Technology Management Program, among others. Peter is co-author with Keith Batchelder of GHS of an invited Nature Biotechnology commentary: “A Change in the Market – Investing in Diagnostics.” He is active with his alma mater, having been Board Chairman of the Global MIT Enterprise Forum, a past board member of the MIT Alumni Association, and currently helps fledgling startups as Co-Director of the MIT Venture Mentoring Service.

Georgia Mitsi, MSc, Ph.D., MBA, Founder and CEO, Apptomics LLC 
Georgia Mitsi MSc, PhD, MBA is the Founder and CEO of Apptomics LLC ,a health technology firm specializing in the design and validation of quality medical mobile applications for selected conditions with high unmet need focusing primarily in CNS. Georgia received her PhD in Health Sciences and MSc in Applied Medical Sciences from University of Patras, Greece and her MBA from University of Miami. She has extensive experience in Pharmaceutical Industry and Healthcare Consulting where she has been involved in positions of increased responsibility in areas such as Clinical Research, Health Outcomes and Health Economics. She often played an instrumental role in uncovering and fostering new business opportunities and developing a strategic roadmap for product’s value proposition. Georgia also worked at the Health Services Research Center (HSRC), a joint venture between Humana and University of Miami and among other responsibilities she led the scientific effort for Games for Health initiative. She has completed successfully many research projects of high complexity and has collaborated with pharmaceutical companies as well as academic institutions. She has co-authored several scientific publications and presented in conferences such as ISPOR and DIA. Georgia is also a published novelist in her native language, Greek.

David Mittelman, Ph.D., Associate Professor, Virginia Bioinformatics Institute, Virginia Tech Department of Biological Sciences, and VTC School of Medicine
Dr. Mittelman is an Associate Professor at the Virginia Bioinformatics Institute, the Virginia Tech Department of Biological Sciences, and the VTC School of Medicine. David Mittelman holds a PhD in Molecular Biophysics through the Department of Biochemistry at Baylor College of Medicine (BCM). Dr. Mittelman completed his postdoctoral training in the Department of Molecular and Human Genetics at BCM. In 2009, Dr. Mittelman was awarded the Ruth L. Kirschstein National Research Service Award, and began an independent research program in population-scale genomics at BCM’s Human Genome Sequencing Center (HGSC). Currently, Dr. Mittelman leads the Genetics and Genomic Medicine Laboratory at Virginia Tech, combining experimental and computational approaches to characterizing personal genomes.

Anne Morriss, Founder and CEO, Genepeeks
Anne is the founder and CEO of Genepeeks, a genetic information company that helps families to protect their future children. She has helped to launch and grow multiple technology companies, and is the best-selling co-author of Uncommon Service: How to Win By Putting Customers at the Core of Your Business (Harvard Business Review Press). Anne received her B.A in American Studies from Brown University and an M.B.A from Harvard Business School.

Julia Oh, Chief Science Officer, 1eq

Heidi L. Rehm, Ph.D., FACMG, Chief Laboratory Director, Molecular Medicine, Partners HealthCare Center for Personalized Genetic Medicine (PCPGM); Assistant Professor of Pathology, Harvard Medical School
Heidi Rehm, Ph.D. was recruited in 2001 to build the Laboratory for Molecular Medicine at PCPGM and serves as its Laboratory Director. She is a board-certified clinical molecular geneticist and Assistant Professor of Pathology at Harvard Medical School with appointments at BWH, MGH and Children’s Hospital Boston. Her undergraduate degree is from Middlebury College, her graduate degree in Genetics is from Harvard University and her postdoctoral and fellowship training was at HMS. Heidi has served as the Director of the ABMG Clinical Molecular Genetics Training Program at HMS since 2006. In addition to running the LMM and the molecular training program, she also conducts research in hearing loss, Usher syndrome, cardiomyopathy and the use of IT in enabling personalized medicine.
Jessica Richman, CEO and Co-Founder, uBiome

Gabe Rudy, Vice President, Product Development, Golden Helix and Author “A Hitchhikers Guide to Next Generation Sequencing”
Gabe Rudy has been GHI’s Vice President of Product Development and team member since 2002. Gabe thrives in the dynamic and fast-changing field of bioinformatics and genetic analysis. Leading a killer team of Computer Scientists and Statisticians in building powerful products and providing world-class support, Gabe puts his passion into enabling Golden Helix’s customers to accelerate their research. When not reading or blogging, Gabe enjoys the outdoor Montana lifestyle. But most importantly, Gabe truly loves spending time with his sons and wife.

Meredith Salisbury, Senior Consultant, Bioscribe
Prior to becoming a consultant for Bioscribe, Meredith was CEO and Editor-in-Chief of GenomeWeb, the leading news and information service for scientists in the systems biology field. During her 11 years with the company, Meredith honed her knowledge of the genomics market, with a particular focus on next-gen DNA sequencing. She is the co-founder of the Consumer Genetics Conference held annually in Boston. Before joining GenomeWeb, Meredith had an extended internship in the busy newsroom at Newsweek in New York City. Meredith brings her industry knowledge and connections to oversee editorial strategy for Bioscribe clients. Meredith enjoys hot-air ballooning and is based in the NYC metropolitan area.

Anish Sebastian, Co-Founder and CEO, 1eq

Juhan Sonin, Creative Director, Involution Studios, MIT
Juhan Sonin is an emeritus of some of the finest software organizations in the world: Apple, the National Center for Supercomputing Applications (NCSA) and the Massachusetts Institute of Technology (MIT). He has been a creative director for almost two decades with his work being featured in the New York Times, Newsweek, BBC International, Billboard Magazine and National Public Radio (NPR). He is also a lecturer on design and rapid prototyping at the Massachusetts Institute of Technology (MIT).

Vasisht Tadigotla, Ph.D., Senior Bioinformatics Scientist, Courtagen Life Sciences, Inc.
Vasisht is currently working as a Senior Bioinformatics Scientist at Courtagen Life Sciences. Previously, he has worked as a Staff Scientist at Life Technologies helping develop the SOLiD and Ion Torrent sequencing technologies and at the Department of Physics at Boston University. Vasisht earned a Ph.D. in Biophysics and Computational Biology from Rutgers University and a B.Tech. in Biochemical Engineering from Indian Institute of Technology, New Delhi.

Spencer Wells, Ph.D., Explorer-in-Residence and Director, The Genographic Project, National Geographic Society
Spencer Wells is a leading population geneticist and director of the Genographic Project from National Geographic and IBM. His fascination with the past has led the scientist, author, and documentary filmmaker to the farthest reaches of the globe in search of human populations who hold the history of humankind in their DNA. By studying humankind’s family tree he hopes to close the gaps in our knowledge of human migration. A National Geographic explorer-in-residence, Wells is spearheading the Genographic Project, calling it “a dream come true.” His hope is that the project, which builds on Wells’s earlier work (featured in his book and television program, The Journey of Man) and is being conducted in collaboration with other scientists around the world, will capture an invaluable genetic snapshot of humanity before modern-day influences erase it forever. Wells’s own journey of discovery began as a child whose zeal for history and biology led him to the University of Texas, where he enrolled at age 16, majored in biology, and graduated Phi Beta Kappa three years later. He then pursued his Ph.D. at Harvard University under the tutelage of distinguished evolutionary geneticist Richard Lewontin. Beginning in 1994, Wells conducted postdoctoral training at Stanford University’s School of Medicine with famed geneticist Luca Cavalli-Sforza, considered the “father of anthropological genetics.” It was there that Wells became committed to studying genetic diversity in indigenous populations and unraveling age-old mysteries about early human migration. Wells’s field studies began in earnest in 1996 with his survey of Central Asia. In 1998 Wells and his colleagues expanded their study to include some 25,000 miles of Asia and the former Soviet republics. His landmark research findings led to advances in the understanding of the male Y chromosome and its ability to trace ancestral human migration. Wells then returned to academia where, at Oxford University, he served as director of the Population Genetics Research Group of the Wellcome Trust Centre for Human Genetics at Oxford. Following a stint as head of research for a Massachusetts-based biotechnology company, Wells made the decision in 2001 to focus on communicating scientific discovery through books and documentary films. From that was born The Journey of Man: A Genetic Odyssey, an award-winning book and documentary that aired on PBS in the U.S. and National Geographic Channel internationally. Written and presented by Wells, the film chronicled his globe-circling, DNA-gathering expeditions in 2001-02 and laid the groundwork for the Genographic Project. Since the Genographic Project began, Wells’s work has taken him to over three dozen countries, including Chad, Tajikistan, Morocco, Papua New Guinea, and French Polynesia, and he recently published his second book, Deep Ancestry: Inside the Genographic Project. He lives with his wife, a documentary filmmaker, in Washington, D.C.
Eric P. Williams, Ph.D., Senior Bioinformatics Scientist, National Marrow Donor Program
Dr. Eric Williams is Senior Bioinformatics Scientist at the National Marrow Donor Program (NMDP) which is entrusted to operate the C.W. Bill Young Cell Transplantation Program, including the Be The Match Registry. Eric has 9 years of experience working in research related to aspects of biology, histocompatibility and population genetics associated with finding matching donors for patients needing stem cell therapies. His interests include the utilization of genetic information to further medicine, infer ancestry, and aid in family history research. He has led development of systems utilized by worldwide transplant centers to access population HLA frequency and ancestry information critical to the process of finding matching, unrelated donors for patients. Other activities have included utilizing Geographic Information Systems to map global frequencies of HLA haplotypes and a US market area capacity analysis resulting in increased funding to develop facilities at medical institutions supporting stem cell therapy programs. Prior to his work with the NMDP, Eric has 18 years experience supporting marker assisted plant breeding programs at Pioneer Hi-Bred, Mycogen Seeds and Syngenta Seeds. Dr. Williams received a Ph.D. in Plant Breeding and Genetics and a MS in Plant Physiology from the University of Nebraska-Lincoln and a BA in Agronomy from Brigham Young University.
Rina Wolf, Vice President, Commercialization Strategies, XIFIN, Inc.
Rina Wolf is a nationally recognized expert in the field of laboratory commercialization and reimbursement, with over 20 years of experience in the diagnostic laboratory industry, specializing in Molecular Diagnostic Laboratories. She lectures extensively on these topics and has consulted for major laboratories and laboratory associations throughout the U.S.. She is a former President and board member of the California Clinical Laboratory Association and is an active participant with the ACLA (American Clinical Laboratory Association) and the Personalized Medicine Coalition. Ms. Wolf also advises and presents to investor audiences, recent speaking engagements include Piper Jaffray, Cowen Group and Bloomberg’s G2 Intelligence Lab Investment Forum. Most recently Ms. Wolf held the position of Vice President of Reimbursement and Regulatory Affairs at Axial Biotech, Inc. where she was responsible for creating and implementing their successful reimbursement strategies. Prior to joining Axial Biotech, Inc., Ms. Wolf held executive positions in the area of commercialization and reimbursement at RedPath Integrated Pathology, Inc., Genomic Health, Inc., and Esoterix (now LabCorp). Ms. Wolf has a Bachelor of Arts degree from UCLA and a Masters of HealthCare Administration.

http://www.consumergeneticsconference.com/cgc_content.aspx?id=116061
 

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Treatment for Endocrine Tumors and Side Effects

Reporter and Curator: Dr. Sudipta Saha, Ph.D.

Surgery

The purpose of surgery is typically to remove the entire tumor, along with some of the healthy tissue around it, called the margin. If the tumor cannot be removed entirely, “debulking” surgery may be performed. Debulking surgery is a procedure in which the goal is to remove as much of the tumor as possible. Side effects of surgery include weakness, fatigue, and pain for the first few days following the procedure.

Chemotherapy

Chemotherapy is the use of drugs to kill tumor cells, usually by stopping the cells’ ability to grow and divide. Systemic chemotherapy is delivered through the bloodstream to reach tumor cells throughout the body. A chemotherapy regimen (schedule) usually consists of a specific number of cycles given over a set period of time. A patient may receive one drug at a time or combinations of different drugs at the same time. The side effects of chemotherapy depend on the individual and the dose used, but they can include fatigue, risk of infection, nausea and vomiting, loss of appetite, and diarrhea. These side effects usually go away once treatment is finished.

Radiation therapy

Radiation therapy is the use of high-energy x-rays or other particles to kill tumor cells. The most common type of radiation treatment is called external-beam radiation therapy, which is radiation given from a machine outside the body. When radiation treatment is given using implants, it is called internal radiation therapy or brachytherapy. A radiation therapy regimen usually consists of a specific number of treatments given over a set period of time. Side effects from radiation therapy may include fatigue, mild skin reactions, upset stomach, and loose bowel movements. Most side effects go away soon after treatment is finished.

Hormone therapy

The goal of hormone therapy is often to lower the levels of hormones in the body. Hormone therapy may be given to help stop the tumor from growing or to relieve symptoms caused by the tumor. In addition, for thyroid cancer, hormone therapy will be given if the thyroid gland has been removed, to replace the hormone that is needed by the body to function properly.

Immunotherapy

Immunotherapy (also called biologic therapy) is designed to boost the body’s natural defenses to fight the tumor. It uses materials made either by the body or in a laboratory to bolster, target, or restore immune system function. Examples of immunotherapy include cancer vaccines, monoclonal antibodies, and interferons. Alpha interferon is a form of biologic therapy given as an injection under the skin. This is sometimes used to help relieve symptoms caused by the tumor, but it can have severe side effects including fatigue, depression, and flu-like symptoms.

Targeted therapy

Targeted therapy is a treatment that targets the tumor’s specific genes, proteins, or the tissue environment that contributes to cancer growth and survival. This type of treatment blocks the growth and spread of tumor cells while limiting damage to normal cells, usually leading to fewer side effects than other cancer medications.

Recent studies show that not all tumors have the same targets. To find the most effective treatment, the doctor may run tests to identify the genes, proteins, and other factors in the tumor. As a result, doctors can better match each patient with the most effective treatment whenever possible.

Depending on the type of endocrine tumor, targeted therapy may be a possible treatment option. For instance, targeted therapies, such as sunitinib (Sutent) and everolimus (Afinitor), have been approved for treating advanced islet cell tumors. Early results of clinical trials (research studies) with targeted therapy drugs for other types of endocrine tumors are promising, but more research is needed to prove they are effective.

Recurrent endocrine tumor

Once the treatment is complete and there is a remission (absence of symptoms; also called “no evidence of disease” or NED). Many survivors feel worried or anxious that the tumor will come back. If the tumor does return after the original treatment, it is called a recurrent tumor. It may come back in the same place (called a local recurrence), nearby (regional recurrence), or in another place (distant recurrence). When this occurs, a cycle of testing will begin again to learn as much as possible about the recurrence. Often the treatment plan will include the therapies described above (such as surgery, chemotherapy, and radiation therapy) but may be used in a different combination or given at a different pace. People with a recurrent tumor often experience emotions such as disbelief or fear. Patients are encouraged to talk with their health care team about these feelings and ask about support services to help them cope.

Metastatic endocrine tumor

If a cancerous tumor has spread to another location in the body, it is called metastatic cancer. A treatment plan that includes a combination of surgery, chemotherapy, radiation therapy, hormone therapy, immunotherapy, or targeted therapy may be recommended if required.

In addition to treatment to slow, stop, or eliminate the cancer (also called disease-directed treatment), an important part of cancer care is relieving a person’s symptoms and side effects. It includes supporting the patient with his or her physical, emotional, and social needs, an approach called palliative or supportive care. People often receive disease-directed therapy and treatment to ease symptoms at the same time.

Source References:

http://www.cancer.net/cancer-types/endocrine-tumor/treatment

 

http://www.macmillan.org.uk/Cancerinformation/Cancertypes/Endocrine/Endocrinetumours.aspx

 

http://cancer.osu.edu/patientsandvisitors/cancerinfo/cancertypes/endocrine/Pages/index.aspx

 

http://cancer.northwestern.edu/cancertypes/cancer_type.cfm?category=8

 

http://www.cancervic.org.au/about-cancer/cancer_types/endocrine_cancer

 

http://www.oncolink.org/types/types1.cfm?c=4

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“The SILENCE of the Lambs” Introducing The Power of Uncoded RNA

Curator: Demet Sag, PhD

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Word Cloud By Danielle Smolyar

An illustration of the central dogma of molecu...

An illustration of the central dogma of molecular biology annotated with the processes ncRNAs are involved in. (Photo credit: Wikipedia)

X-ray structure of the tRNA Phe from yeast. Da...

X-ray structure of the tRNA Phe from yeast. Data was obtained by PDB 1ehz and rendered with PyMOL. violet: acceptor stem wine red: D-loop blue: anticodon loop orange: variable loop green: TPsiC-loop yellow: CCA-3′ of the acceptor stem grey: anticodon (Photo credit: Wikipedia)

 Our genome must be packed tightly to fit into the nucleus. Genome is the blue print of a living organism whether made up off a single or multiple cell.   Recently, the genome seen as a functional network of physical contacts within (cis) and between (trans) chromosomes.  It became necessary to map these physical DNA contacts at high-resolution with technologies such as the “chromosome conformation capture” (3C) and other 3C-related methods including 3C-Carbon Copy (5C) and Hi-C.  Yet, we all know that in vivo conformation, gene to gene interactions from a long distance, histones and 3D have an impact on gene regulation and expression.  The game is not just a sequence but functional genomics with a correct translation of sequence for development so that proper molecular diagnostics can be applied not only for prevention but also for monitoring the efficacy of the intervention. Thus, we can provide a targeted therapy for personalized medicine.

On the other hand, we still know very little about genome organization at the molecular level, although spatial genome organization can critically affect gene expression.  It is important to recognize who is there to be present and who is there to create the functional impact for regulation in a specific tissue and time.  In addition, mediation of these chromatin contacts based on a specific tissue is quite essential.  For example, during long-range control mechanism specific enhancers and distal promoters needed to be invited to a close physical proximity to each other by transcription factors that has been found at other loci.  Furthermore, chromatin-binding proteins such as the CCCTC-binding factor (CTCF) and cohesin seem to have critical roles in genome organization and gene expression.  Let’s not forget about epigenetics, since there are so many methods to regulate chromatin interactions like cytosine methylation, maternal gene, gradient level, post-translational modifications and non-coding RNAs.

The non-coding RNAs (ncRNAs) are silent but they have the 99% power because ncRNAs are a broad class of transcripts consisting of structural (rRNAs, tRNAs, snRNAs, snoRNAs, etc.), regulatory (miRNAs, piRNAs, etc.), and of sense/antisense transcripts.  Among these an interesting class is the latter group.   This class includes transcriptional “features” (eRNAs, tiRNAs), and a very large number of long non-coding RNAs (lncRNAs), length from 200 nt to 100 kb.  The magnificent future of lncRNAs comes from their production, as they can be transcribed nearby known protein-coding genes or from their introns. As a result, because of their intergenical production they are also called as “lincRNAs (long intergenical non-coding RNAs).  They are abundant and specific as microRNAs.  Hence, their inclusion into the biomarker list and assuming their roles during targeted therapy don’t require us to be a wizard but a functional genomicist knowing evolution, development and molecular genetics and plus signaling.

lincRNA can both activate and repress the gene either cis or trans acting to effect gene regulation will be discussed next.

As a result, one gene expression regulation needs from twenty to several hundred genes. As they say raising a child needs a village.

References:

“Functional demarcation of active and silent chromatin domains in human HOX loci by noncoding RNAs”.

Rinn JL, Kertesz M, Wang JK, Squazzo SL, Xu X, Brugmann SA, Goodnough LH, Helms JA, Farnham PJ, Segal E, Chang HY.  Cell. 2007 Jun 29; 129(7):1311-23.

“Long noncoding RNA as modular scaffold of histone modification complexes”

Tsai MC, Manor O, Wan Y, Mosammaparast N, Wang JK, Lan F, Shi Y, Segal E, Chang HYScience. 2010 Aug 6; 329(5992):689-93.

“Capturing Chromosome Conformation”.

Dekker J, Rippe K, Dekker M, Kleckner N.Science.2002;295:1306–1311.

“Chromosome Conformation Capture Carbon Copy (5C): a massively parallel solution for mapping interactions between genomic elements”.

Dostie J, Richmond TA, Arnaout RA, Selzer RR, Lee WL, Honan TA, Rubio ED, Krumm A, Lamb J, Nusbaum C, Green RD, Dekker J.Genome Res. 2006;16:1299–1309.

“Chromosome conformation capture carbon copy technology”.

Dostie J, Zhan Y, Dekker J. Curr. Protoc. Mol. Biol. 2007 Chapter 21, Unit 21 14.

“Comprehensive mapping of long-range interactions reveals folding principles of the human genome”.

Lieberman-Aiden E, van Berkum NL, Williams L, Imakaev M, Ragoczy T, Telling A, Amit I, Lajoie BR, Sabo PJ, Dorschner MO, Sandstrom R, Bernstein B, Bender MA, Groudine M, Gnirke A, Stamatoyannopoulos J, Mirny LA, Lander ES, Dekker J.  Science. 2009;326:289–293.

“Chromatin conformation signatures: ideal human disease biomarkers?”

Crutchley JL, Wang XQ, Ferraiuolo MA, Dostie J.Biomark. Med. 2010;4:611–629.

“Relationship between CAD risk genotype in the chromosome 9p21 locus and gene expression. Identification of eight new ANRIL splice variants”.

Folkersen L, Kyriakou T, Goel A, Peden J, Mälarstig A, Paulsson-Berne G, Hamsten A, Hugh Watkins, Franco-Cereceda A, Gabrielsen A, Eriksson P, PROCARDIS consortia

PLoS One. 2009 Nov 2; 4(11):e7677.

” A myelopoiesis-associated regulatory intergenic noncoding RNA transcript within the human HOXA cluster”.

Zhang X, Lian Z, Padden C, Gerstein MB, Rozowsky J, Snyder M, Gingeras TR, Kapranov P, Weissman SM, Newburger PE.  Blood. 2009 Mar 12; 113(11):2526-34.

Monk M.   Genes Dev. 1988 Aug; 2(8):921-5.

Hox genes specify vertebral types in the presomitic mesoderm

Marta Carapuço,1 Ana Nóvoa,1 Nicoletta Bobola,2 and Moisés Mallo1,3 .  Genes Dev. 2005 September 15; 19(18): 2116–2121.

Krumlauf R.  Cell. 1994 Jul 29; 78(2):191-201.

“Noncoding RNA synthesis and loss of Polycomb group repression accompanies the colinear activation of the human HOXA cluster”.

Sessa L, Breiling A, Lavorgna G, Silvestri L, Casari G, Orlando V.  RNA. 2007 Feb; 13(2):223-39.

“Functional demarcation of active and silent chromatin domains in human HOX loci by noncoding RNAs”.

Rinn JL, Kertesz M, Wang JK, Squazzo SL, Xu X, Brugmann SA, Goodnough LH, Helms JA, Farnham PJ, Segal E, Chang HY.  Cell. 2007 Jun 29; 129(7):1311-23.

“Long noncoding RNAs with enhancer-like function in human cells”.

Ørom UA, Derrien T, Beringer M, Gumireddy K, Gardini A, Bussotti G, Lai F, Zytnicki M, Notredame C, Huang Q, Guigo R, Shiekhattar R

“Histone modifications at human enhancers reflect global cell-type-specific gene expression”.

Heintzman ND, Hon GC, Hawkins RD, Kheradpour P, Stark A, Harp LF, Ye Z, Lee LK, Stuart RK, Ching CW, Ching KA, Antosiewicz-Bourget JE, Liu H, Zhang X, Green RD, Lobanenkov VV, Stewart R, Thomson JA, Crawford GE, Kellis M, Ren B.   Nature. 2009 May 7; 459(7243):108-12.

“Tiny RNAs associated with transcription start sites in animals”.

Taft RJ, Glazov EA, Cloonan N, Simons C, Stephen S, Faulkner GJ, Lassmann T, Forrest AR, Grimmond SM, Schroder K, Irvine K, Arakawa T, Nakamura M, Kubosaki A, Hayashida K, Kawazu C, Murata M, Nishiyori H, Fukuda S, Kawai J, Daub CO, Hume DA, Suzuki H, Orlando V, Carninci P, Hayashizaki Y, Mattick JS.  Nat Genet. 2009 May; 41(5):572-8.

“Chromatin modifications and their function”.

Kouzarides T.   Cell. 2007 Feb 23; 128(4):693-705.

Tripathi V, Ellis JD, Shen Z, Song DY, Pan Q, Watt AT, Freier SM, Bennett CF, Sharma A, Bubulya PA, Blencowe BJ, Prasanth SG, Prasanth KV.   Mol Cell. 2010 Sep 24; 39(6):925-38.

Selected Further Reading

“Small and long non-coding RNAs in cardiac homeostasis and regeneration”

Ounzain, S.; Crippa, S.; Pedrazzini, T.  BBA – Molecular Cell Research vol. 1833 issue 4 April, 2013. p. 923-933

“Regulatory mechanisms of long noncoding RNAs in vertebrate central nervous system development and function.” 

Knauss, J.L.; Sun, T.  “Neuroscience vol. 235 April 3, 2013. p. 200-214

“Comparative genomics reveals ‘novel’ Fur regulated sRNAs and coding genes in diverse proteobacteria.”

Sridhar, J.; Sabarinathan, R.; Gunasekaran, P.; Sekar, K.   Gene vol. 516 issue 2 March 10, 2013. p. 335-344 DOI: 10.1016/j.gene.2012.12.057. ISSN: 0378-1119.

miRNAs Regulate Expression and Function of Extracellular Matrix Molecules”

Rutnam, Z.J.; Wight, T.N.; Yang,  B.B.Matrixixix Biology vol. 32 issue 2 March 11, 2013. p. 74-85 DOI: 10.1016/j.matbio.2012.11.003. ISSN: 0945-053X.

Transcript profiling of microRNAs during the early development of the maize brace root via Solexa sequencing

Liu, P.; Yan, K.; Lei, Y.x.; Xu, R.; Zhang, Y.m.; Yang, G.d.; Huang, J.g.; Wu, C.A.; Zheng, C.C.Genomics vol. 101 issue 2 February, 2013. p. 149-156 DOI: 10.1016/j.ygeno.2012.11.004. ISSN: 0888-7543.

Regulatory mechanisms of long noncoding RNAs in vertebrate central nervous system development and function

Knauss, J.L.; Sun, T.  Neuroscience vol. 235 April 3, 2013. p. 200-214 DOI: 10.1016/j.neuroscience.2013.01.022. ISSN: 0306-4522.

“The dynamic biliary epithelia: Molecules, pathways, and disease”

O’Hara, Steven P.; Tabibian, James H.; Splinter, Patrick L.; LaRusso, Nicholas F. Journal of Hepatology vol. 58 issue 3 March, 2013. p. 575-582 DOI: 10.1016/j.jhep.2012.10.011. ISSN: 0168-8278

ABBREVIATIONS

3C = Chromosome conformation capture

rRNAs = Ribosomal RNAs

tRNAs = Transfer RNAs

snRNAs = Small nuclear RNAs

snoRNAs = Small nucleolar RNAs

miRNAs = MicroRNAs

piRNAs = Piwi-interacting RNAs

eRNAs = Enhancer RNAs

tiRNAs = Transcription initiation RNAs

spliRNAs = Splice-site RNAs

lincRNAs = Long intergenic non-coding RNAs

lncRNPs = Long non-coding ribonucleoprotein complexes

Igf2r = Insulin-like growth factor II receptor

HMTs = Histone methyl transferases

TSSs = Transcriptional start sites

TFs = Transcription factors

RNAi = RNA interference

PTMs = Post-translational modifications

  • Patent. (postdocstreet.wordpress.com)

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High Risk of Transmissible Disease and Mortality in Cancer, Advanced Cardiovascular Disease, and Hemodialysis Patients

Curator: Larry H Bernstein, MD, FCAP

This contribution is aimed at three situations of special concern with respect to transmission and handling of episodic bacteria or virus spread in hospital and ambulatory healthcare settings, where healthcare workers may be exposed and either become ill or are potential carriers of the disease.  Not discussed is a report in the last week of an association between human papilloma virus (HPV), known to be associated with cervical cancer, and oropharyngeal cancer.   In all of these situations, the patients at highest risk of death are immune compromized, carry a heavy burden of unbalanced oxidative stress, and have mitcochondrial dysfunction from unbalanced ubiquitination and repair.

Clostridium Difficile Colitis

Faten N Aberra, MD, MSCE; Chief Editor: Julian Katz, MD
Medscape – Practice Essentials

Clostridium difficile colitis results from a disturbance of the normal bacterial flora of the colon, colonization by C difficile, and the release of toxins that cause mucosal inflammation and damage. Antibiotic therapy is the key factor that alters the colonic flora. C difficile infection primarily occurs in hospitalized patients.

Essential update: Fidaxomicin superior to vancomycin for cancer patients with C difficile

In a multicenter study including 1105 subjects with C difficile – associated diarrhea, 183 of whom had solid tumors or hematologic malignancies, fidaxomicin treatment was superior to vancomycin treatment in cancer patients, resulting in higher cure and sustained response rates, shorter time to resolution of diarrhea (TTROD), and fewer recurrences.  Cure rates were lower overall in cancer patients than in others (79.2% vs 88.6%; P < 0.001).[2Whereas cure rates for noncancer patients were approximately the same with fidaxomicin as with vancomycin (88.5% vs 88.7%), those for cancer patients were higher with fidaxomicin than with vancomycin (85.1% vs 74.0%), though the difference was not statistically significant. Median TTRODs in noncancer patients were 54 hours with fidaxomicin and 58 with vancomycin; those in cancer patients were 74 and 123 hours, respectively.  The risk of recurrence was approximately twice as high with vancomycin as with fidaxomicin, regardless of whether patients had cancer or not, but because both cure and recurrence outcomes were better with fidaxomicin than with vacomycin in cancer patients, the relative odds of sustained response at 28 days in these patients were more than 2.5-fold higher for fidaxomicin than for vancomycin.

Background

Clostridium difficile is a gram-positive, anaerobic, spore-forming bacillus that is responsible for the development of antibiotic-associated diarrhea and colitis. C difficile was first described in 1935 as a component of the fecal flora of healthy newborns and was initially not thought to be a pathogen. It was named difficile because it grows slowly and is difficult to culture. While early investigators noted that the bacterium produced a potent toxin, the role of C difficile in antibiotic-associated diarrhea and pseudomembranous colitis was not elucidated until the 1970s.
Approximately 20% of individuals who are hospitalized acquire C difficile during hospitalization, and more than 30% of these patients develop diarrhea. Thus, C difficile colitis is currently one of the most common nosocomial infections.
The diagnosis of C difficile colitis should be suspected in any patient with diarrhea who has received antibiotics within the previous 2 months and/or when diarrhea occurs 72 hours or more after hospitalization.

Pathophysiology

Colonization occurs by the fecal-oral route. C difficile forms heat-resistant spores that can persist in the environment for several months to years. Outbreaks of C difficile diarrhea may occur in hospitals and other outpatient facilities where contamination with spores is prevalent. Normal gut flora resists colonization and overgrowth with C difficile. Antibiotic use, which suppresses the normal flora, allows proliferation of C difficile.
Pathogenic strains of C difficile produce 2 distinct toxins. Toxin A is an enterotoxin, and toxin B is a cytotoxin. Both are high–molecular weight proteins capable of binding to specific receptors on the intestinal mucosal cells. Receptor-bound toxins gain intracellular entry where they catalyze a specific alteration of Rho proteins, small glutamyl transpeptidase (GTP)–binding proteins that assist in actin polymerization, cytoskeletal architecture, and cell movement. Both toxin A and toxin B appear to play a role in the pathogenesis of C difficile colitis in humans.

Epidemiology

Although the incidence of other nosocomial infections declined from 2000-2009, the number of hospitalized patients with any C difficile infection discharge diagnosis more than doubled, from approximately 139,000 to 336,600. The number of patients with a primary C difficile infection diagnosis more than tripled, from 33,000 to 111,000.
Among C difficile infections identified in the Centers for Disease Control and Prevention’s (CDC’s) Emerging Infections Program data in 2010, 94% were associated with receiving health care; of these, 75% had onset among persons not currently hospitalized, including recently discharged patients, outpatients, and nursing home residents

Diagnosis

http://img.medscape.com/pi/emed/ckb/gastroenterology/169972-186458-3532tn.jpg

Physical examination may reveal the following in patients with the disorder:
  • Fever: Especially in more severe cases
  • Dehydration
  • Lower abdominal tenderness
  • Rebound tenderness: Raises the possibility of colonic perforation and peritonitis

Laboratory studies

  • Lab tests for evaluating patients with C difficile infection include the following:
  • Electrolytes: Dehydration and electrolyte imbalance may accompany severe disease
  • Albumin: Hypoalbuminemia and anasarca may accompany severe disease
    • Transthyretin is the serum protein of choice for a rapid onset diarrhea with dehydration leading to weight loss, dehydration, anasarca and sarcopenia, as it has a serum half-life of ~ 48 hrs rather than 21 days, and it is an accurate measure of lean body mass.
  • Complete blood count: Leukocytosis may be present
  • Stool examination: Stool may be Hemoccult positive in severe colitis, but grossly bloody stools are unusual; fecal leukocytes are present in about half of cases
  • Stool assays for C difficile, from the most to the least sensitive, include the following:
  1. Stool culture: The most sensitive test (sensitivity, 90-100%; specificity, 84-100%), but the results are slow and may lead to a delay in the diagnosis if used alone
  2. Glutamate dehydrogenase enzyme immunoassay (EIA): Very sensitive (sensitivity, 85-100%; specificity, 87-98%); this test detects the presence of glutamate dehydrogenase produced by C difficile
  3. Real-time polymerase chain reaction (PCR) assay: May be used to detect C difficile gene toxin
  4. The stool cytotoxin test: Has a sensitivity of 70-100% and a specificity of 90-100%; a positive test result is the demonstration of a cytopathic effect that is neutralized by a specific antiserum
  5. Enzyme immunoassay for detecting toxins A and B: Used in most labs; the sensitivity is moderate (79-80%), and the specificity is excellent (98%)
  6. Latex agglutination technique: Another means of detecting glutamate dehydrogenase; the sensitivity of this test is poor (48-59%), although the specificity is 95-96%

Management

Treatment for C difficile infection varies according to its severity. Interventions include the following:
  • Asymptomatic carriers: No treatment necessary
  • Mild, antibiotic-associated diarrhea without fever, abdominal pain, or leukocytosis: Cessation may be the only treatment necessary
  • Mild to moderate diarrhea or colitis: Metronidazole (oral or intravenous) or vancomycin (oral) for 10 days
Severe disease: Vancomycin is considered to produce faster symptom resolution and fewer treatment failures than metronidazole; in fulminant cases, combined therapy with intravenous metronidazole and oral vancomycin may be considered

Relapse

Relapse occurs in 20-27% of patients treated with metronidazole or vancomycin. Once a patient has one relapse, the risk for a second relapse is 45%. Relapses should be treated as follows:
  • First relapse: The choice of antibiotic should be based on the severity of C difficile diarrhea/colitis
  • Subsequent relapses: For every relapse beyond the first, vancomycin (prolonged taper/pulsed regimen) is recommended to help clear persistent spores
Among various investigational therapies, fecal transplantation (fecal enemas or infusion of donor feces through a nasoduodenal tube) has been reported to repopulate the colonic flora and treat recurrent C difficile infection.

Staphylococcus Aureus Infection

Robert W Tolan Jr, MD; Chief Editor: Russell W Steele, MD
http://emedicine.medscape.com/article/971358-overview?src=wnl_ref_prac_infd&uac=62859DN

Rise of methicillin and vancomycin-resistance

Both community-associated and hospital-acquired infections with Staphylococcus aureus have increased in the past 20 years, and the rise in incidence has been accompanied by a rise in antibiotic-resistant strains—in particular, methicillin-resistant S aureus (MRSA) and, more recently, vancomycin-resistant strains.

Essential update: Universal decolonization more effective than screening and isolation in reducing rates of MRSA

Daily washing of ICU patients with chlorhexidine-impregnated cloths reduced positive cultures of MRSA by 37% and reduced bloodstream infection by any pathogen by 44%, according to a study of 74,256 patients in 74 adult ICUs.
In the study, hospitals were randomized to 18 months of either screening for MRSA followed by isolation of positive patients, targeted decolonization of MRSA-positive patients and isolation, or universal decolonization of all ICU patients without screening. Decolonization was achieved via daily cleansing with chlorhexidine-impregnated cloths and 5 days of twice-daily intranasal mupirocin treatments. At baseline, there was no significant difference in the rate of MRSA infections between the 3 groups.  However, patients who underwent universal decolonization showed a significantly larger decline between baseline and intervention periods than those in either of the targeted interventions. Universal decolonization led to a 37% drop in the rate of MRSA infections, while targeted decolonization led to a 25% decline and no significant change was seen in the screening and isolation group. There was no significant difference in outcomes between the targeted decolonization and the screening and isolation groups, while the difference between the universal decolonization and the screening and isolation groups was significant (P = .003). Universal decolonization also significantly reduced ICU-attributed bloodstream infections from any pathogen.

Management

Antibiotic regimens include the following:
  • Empiric therapy with penicillins or cephalosporins may be inadequate because of community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA)
  • Combination therapy with a penicillinase-resistant penicillin or cephalosporin (in case the organism is methicillin-sensitive S aureus [MSSA]) and clindamycin or a quinolone
  • Clindamycin, trimethoprim-sulfamethoxazole (TMP-SMX), rifampin, doxycycline, or a quinolone
  • TMP-SMX and rifampin in combination, rather than singly
Clindamycin (rather than TMP-SMX) may become the preferred outpatient antibiotic therapy in regions with a relatively low incidence of clindamycin resistance
The Infectious Diseases Society of America has published treatment guidelines for MRSA infection

Bacteremia

Daptomycin, with or without beta-lactams, controls S aureus bacteremia without worsening renal dysfunction. In a cohort of patients with mild or moderate renal insufficiency, more than 80% responded to treatment, with no detrimental effect on their kidneys. Currently, the combination of daptomycin with beta-lactams is recommended only as salvage therapy for refractory MRSA bacteremia. 

New Coronavirus ‘Eerily’ Like SARS

By Michael Smith, North American Correspondent, MedPage   June 19, 2013
Reviewed by Robert Jasmer, MD; Associate Clinical Professor of Medicine, University of California, San Francisco
http://www.medpagetoday.com/InfectiousDisease/GeneralInfectiousDisease/39972?xid=nl_mpt_DHE_2013-06-20

The novel coronavirus outbreak in the Middle East is eerily similar to SARS, according to Trish Perl, MD, of the Johns Hopkins University School of Medicine, part of an international team, led by Ziad Memish, MD, of the World Health Organization in Riyadh, that looked into a cluster of 23 cases in hospitals in the east of Saudi Arabia. . “The illness pattern, the incubation period — there are a lot of eerie similarities,” Perl told MedPage Today. They reported online in the New England Journal of Medicine, that the virus, MERS-CoV, is related to the virus that caused the 2002-2003 SARS outbreak.  The viruses both are coronaviruses and both lead to severe respiratory illness. Further, person-to-person transmission can take place in healthcare settings and can do so with “considerable morbidity.”  One key difference, Perl and colleagues noted, is that — at least in the cluster they investigated — the fatality rate was 65%, markedly higher than the 8% or so seen in the SARS outbreak. On the other hand, that rate may fall if a large number of milder cases is detected, they noted.  An outside expert, David Freedman, MD, of the University of Alabama at Birmingham, told MedPage Today that an open question has been whether MERS could spread within hospitals as easily as did SARS.  The current study, he said, shows “unequivocally” that it can.
The report comes as the World Health Organization is reporting a total of 64 laboratory-confirmed cases of infection with MERS-CoV, including 38 deaths. Most reported cases have either occurred in the Middle East or have involved recent travel to the region.  SARS was contained and eventually controlled by identifying cases vigorously and then isolating them to prevent transmission, Perl noted, and similar tactics — when they were applied in Saudi Arabia — appeared to have the same effect. The key in the epidemiological chain may have been Patient C, who had been undergoing long-term hemodialysis, and was admitted to hospital April 6 in the room next to Patient A.  When Patient A developed a fever April 8, Patient C was still in the same room and developed fever himself 3 days later. He also had dialysis in the hospital’s outpatient hemodialysis unit twice after the onset of symptoms. Between April 14 and April 30, MERS was confirmed in nine more patients who were undergoing hemodialysis, including six who did so at times overlapping those of Patient C. All told, Patient C appears to have transmitted MERS directly to seven people, six in the dialysis unit and one in the intensive care unit, the researchers reported, while other infected people had more limited transmission and some did not pass on the disease at all.

Related articles

Clostridium Difficile

Clostridium Difficile (Photo credit: fjbengoat)

English: Low mag. Image:Colonic pseudomembrane...

English: Low mag. Image:Colonic pseudomembranes intermed mag.jpg (Photo credit: Wikipedia)

Obtained after an outbreak this micrograph dep...

Obtained after an outbreak this micrograph depicts Gram-positive Clostridium difficile bacteria. These C. difficile organisms were cultured from a stool sample obtained during an outbreak of gastrointestinal illness, and extracted using a .1µm filter. (Photo credit: Wikipedia)

English: Clostridium difficile toxin B rendere...

English: Clostridium difficile toxin B rendered from PDB 2BVM (Photo credit: Wikipedia)

Pseudomembranous Colitis, Colectomy (Gross)

Pseudomembranous Colitis, Colectomy (Gross) (Photo credit: euthman)

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Copy Number Variants (CNV) Alleles to be Detected by a Complete Recessive Carrier Screening Diagnostics

Reporter: Aviva Lev-Ari, PhD, RN

 

Using array comparative genomic hybridization data for 21,470 individuals, Baylor College of Medicine‘s James Lupski and colleagues considered the frequency with which deletions or other disruptive copy number variants appear in genes known for roles in recessive disease. As they report in Genome Research, the investigators unearthed more than 3,200 instances in which deletions affected one allele of a recessive disease gene, affecting 419 different recessive disease genes in all. The CNVs — which render individuals potential carriers of recessive disease — tended to occur in long genes and genes falling far from those contributing to dominant disease risk, study authors note. Based on their findings, they argue that “a complete recessive carrier screening method or diagnostic test should detect CNV alleles.”

Deletions of recessive disease genes: CNV contribution to carrier states and disease-causing alleles

Abstract

Over 1,200 recessive disease genes have been described in humans. The prevalence, allelic architecture, and per-genome load of pathogenic alleles in these genes remain to be fully elucidated, as does the contribution of DNA copy-number variants (CNVs) to carrier status and recessive disease. We mined CNV data from 21,470 individuals obtained by array comparative genomic hybridization in a clinical diagnostic setting to identify deletions encompassing or disrupting recessive disease genes. We identified 3,212 heterozygous potential carrier deletions affecting 419 unique recessive disease genes. Deletion frequency of these genes ranged from one occurrence to 1.5%. When compared with recessive disease genes never deleted in our cohort, the 419 recessive disease genes affected by at least one carrier deletion were longer and were located farther from known dominant disease genes, suggesting that the formation and/or prevalence of carrier CNVs may be affected by both local and adjacent genomic features and by selection. Some subjects had multiple carrier CNVs (307 subjects) and/or carrier deletions encompassing more than one recessive disease gene (206 deletions). Heterozygous deletions spanning multiple recessive disease genes may confer carrier status for multiple single-gene disorders, for complex syndromes resulting from the combination of two or more recessive conditions, or may potentially cause clinical phenotypes due to a multiply heterozygous state. In addition to carrier mutations, we identified homozygous and hemizygous deletions potentially causative for recessive disease. We provide further evidence that CNVs contribute to the allelic architecture of both carrier and recessive disease-causing mutations. Thus, a complete recessive carrier screening method or diagnostic test should detect CNV alleles.

  • Received February 7, 2013.
  • Accepted May 6, 2013.

© 2013, Published by Cold Spring Harbor Laboratory Press

 

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Reporter and Curator: Dr. Sudipta Saha, Ph.D.

Abbreviations:

 

Kinase inhibitors (KIs)

Adenosine triphosphate (ATP)

Mitogen-activated protein kinases (MAPK)

Tyrosine kinase (TK)

Papillary thyroid carcinomas (PTC)

Radioiodine (RAI)

Medullary thyroid carcinoma (MTC)

Mammalian target of rapamycin (mTOR)

Neuroendocrine tumors (NETs)

Adrenocortical carcinoma (ACC)

Kinase inhibitors (KIs) are a group of small organic molecules that interfere with the interaction between the kinase domain and adenosine triphosphate (ATP) or other mechanisms such as allosteric inhibitors, thereby inhibiting phosphorylation of the kinase and activation of downstream signaling pathways. The majority of KIs available in clinical practice are non-selective, being active against several molecular targets. They exhibit anticancer activity by targeting molecules that activate signalling pathways which promote cellular survival, proliferation and growth. Besides, KIs act as anti-angiogenic agents by halting the activation of specific receptors of angiogenic factors, thus inhibiting intracellular pathways that stimulate angiogenesis. In the last 15 years, several KIs have been developed and introduced into anticancer clinical trials. Aggressive forms of endocrine cancer are not uniformly responsive to cytotoxic chemotherapies while radiotherapy has mainly a palliative role. To date, therapeutic approach of endocrine tumors which persist after surgery and are not responsive to cytotoxic chemotherapies is challenging. Treatment with KIs is gaining a growing role in this clinical context. The present review focuses state-of-theart role of KIs for the treatment of advanced endocrine neoplasms. The protein kinases transfer the g-phosphate of ATP to the hydroxyl group of a serine, threonine or tyrosine residue on a target protein. Phosphorylation results in a number of diverse conformational and/or functional modifications in different proteins, thus initiating a downstream cascade of reactions. Thereby, the protein kinases act as effectors of intracellular cascades, such as the mitogen-activated protein kinases (MAPK) and the PI3K/Akt pathways, which regulate crucial cellular processes including proliferation, differentiation and survival. Abnormal activation of these pathways is strikingly involved in the process of human oncogenesis. Moreover, activity of angiogenic factors with a demonstrated role in survival and spread of cancer cells are mediated by receptors with tyrosine kinase (TK) function. To date, treatment with KIs is considered the most promising frontier in the field of oncology, especially in cases where the role of a particular protein kinase has a direct causal relevance to cancer through its inappropriate activation. Activating mutations of protein kinases genes have been associated with several types of endocrine cancer. About 70% of papillary thyroid carcinomas (PTC), the most common type (80-85%) of thyroid cancer, arise as a result of single activating somatic mutations of protein kinases genes. These involve single point mutations of BRAF and RAS and rearrangements of RET named RET/ PTC oncogenes. Furthermore, BRAF mutations are associated with radioiodine (RAI) unresponsiveness and increased rates of disease recurrence and mortality. The prominent role of the protein kinase RET in the pathogenesis of medullary thyroid carcinoma (MTC) has been widely demonstrated. RET proto-oncogene encodes a cell membrane TK receptor which regulates activation of the MAPK and PI3K/Akt pathways. Germline RET point mutations are responsible of hereditary forms of MTC, while approximately 50% of sporadic MTCs harbor activating RET mutations. Furthermore, there is a clear correlation between genotype and tumor behavior. A recent study performed by Moura et al. demonstrated that the majority of sporadic RET-negative MTC harbor mutations of HRAS, thus confirming that abnormal activation of the MAPK and PI3K/Akt pathways is a crucial step for MTC tumorigenesis. The mammalian target of rapamycin (mTOR) is a serine/threonine kinase that plays an important role in cellular growth and homeostasis. mTOR is activated by both phosphorylation through PI3K/Akt pathway and autophosphorylation at specific serine residues. As hyperactivation of the mTOR pathway has been detected in many human cancers, mTOR has become one of the most promising targets in anticancer therapy. Recent studies found that mTOR pathway is involved in the pathogenesis of neuroendocrine tumors (NETs) and adrenocortical carcinoma (ACC), thus stimulating trials with selective mTOR inhibitors for the treatment of these endocrine cancers.

Several retrospective and Phase II studies have been published about efficacy and safety of KIs in endocrine cancer but only few randomized Phase III clinical trials have been completed. To date, the largest experience has been gained in the treatment of advanced forms of MTC and NETs. Vandetanib and cabozantinib have been recently approved by the FDA for the treatment of advanced, progressive MTC. Given the toxicity related to the long-term administration, some authors suggest a selective use of these compounds in MTC patients having a wide disease burden and/or a strong progression of disease. Nevertheless, MTC usually exhibits an indolent behavior with just a slow progression of disease even in metastatic patients. Therefore, further studies are needed to identify therapeutic approaches which could improve the risk/benefit ratio in this kind of patients. Treatment with the mTOR inhibitor everolimus, alone or in combination with somatostatin analogs, should be considered in this field. In 2011, sunitinib and everolimus have been definitively approved for the treatment of advanced pancreatic NET. Given the slowly progressing nature of NET, even in advanced cases, patients are likely to be treated with these agents for many months and possibly years. Therefore, issues of long-term safety and compliance will require special attention in the future. Unfortunately, lack of available comparative studies between these targeted therapies makes it difficult to suggest the optimal sequence of treatments. Currently, treatment with TKIs represents the only feasible approach in patients with advanced RAI-refractory DTC. Nevertheless, none of these agents has been approved yet. Two randomized Phase III clinical trials evaluating activity of sorafenib and lenvatinib have recently completed patient accrual, but results are not available yet. Use of KIs has shown promising but still anecdotal results in the treatment of other types of endocrine cancers such as ATC, PGL/PCC and ACC and Phase II/III trials are needed to assess feasibility and activity of KIs in these fields. Finally, a better understanding of the molecular pathogenesis of other endocrine malignancies such as aggressive pituitary tumors and parathyroid carcinoma would be crucial for providing the rationale to the use of KIs.

Source References:

http://www.ncbi.nlm.nih.gov/pubmed/23675883

http://www.ncbi.nlm.nih.gov/pubmed/23450053

http://www.ncbi.nlm.nih.gov/pubmed/17993229

http://www.ncbi.nlm.nih.gov/pubmed/17253488

http://www.ncbi.nlm.nih.gov/pubmed/20605972

http://www.ncbi.nlm.nih.gov/pubmed/10387987

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Curator: Aviva Lev-Ari, PhD, RN

We covered the Elevated Blood Pressure and High Adult Arterial Stiffness in the following articles on this Open Access Online Scientific Journal:

Pearlman, JD and A. Lev-Ari 5/24/2013 Imaging Biomarker for Arterial Stiffness: Pathways in Pharmacotherapy for Hypertension and Hypercholesterolemia Management

http://pharmaceuticalintelligence.com/2013/05/24/imaging-biomarker-for-arterial-stiffness-pathways-in-pharmacotherapy-for-hypertension-and-hypercholesterolemia-management/

Lev-Ari, A. 5/17/2013 Synthetic Biology: On Advanced Genome Interpretation for Gene Variants and Pathways: What is the Genetic Base of Atherosclerosis and Loss of Arterial Elasticity with Aging

http://pharmaceuticalintelligence.com/2013/05/17/synthetic-biology-on-advanced-genome-interpretation-for-gene-variants-and-pathways-what-is-the-genetic-base-of-atherosclerosis-and-loss-of-arterial-elasticity-with-aging/

Bernstein, HL and A. Lev-Ari 5/15/2013 Diagnosis of Cardiovascular Disease, Treatment and Prevention: Current & Predicted Cost of Care and the Promise of Individualized Medicine Using Clinical Decision Support Systems

http://pharmaceuticalintelligence.com/2013/05/15/diagnosis-of-cardiovascular-disease-treatment-and-prevention-current-predicted-cost-of-care-and-the-promise-of-individualized-medicine-using-clinical-decision-support-systems-2/

Pearlman, JD and A. Lev-Ari 5/11/2013 Hypertension and Vascular Compliance: 2013 Thought Frontier – An Arterial Elasticity Focus

http://pharmaceuticalintelligence.com/2013/05/11/arterial-elasticity-in-quest-for-a-drug-stabilizer-isolated-systolic-hypertension-caused-by-arterial-stiffening-ineffectively-treated-by-vasodilatation-antihypertensives/

Pearlman, JD and A. Lev-Ari 5/7/2013 On Devices and On Algorithms: Arrhythmia after Cardiac Surgery Prediction and ECG Prediction of Paroxysmal Atrial Fibrillation Onset

http://pharmaceuticalintelligence.com/2013/05/07/on-devices-and-on-algorithms-arrhythmia-after-cardiac-surgery-prediction-and-ecg-prediction-of-paroxysmal-atrial-fibrillation-onset/

Pearlman, JD and A. Lev-Ari 5/4/2013 Cardiovascular Diseases: Decision Support Systems for Disease Management Decision Making

http://pharmaceuticalintelligence.com/2013/05/04/cardiovascular-diseases-decision-support-systems-for-disease-management-decision-making/

Lev-Ari, A. 5/29/2012 Triple Antihypertensive Combination Therapy Significantly Lowers Blood Pressure in Hard-to-Treat Patients with Hypertension and Diabetes

http://pharmaceuticalintelligence.com/2012/05/29/445/

Lev-Ari, A. 12/31/2012 Renal Sympathetic Denervation: Updates on the State of Medicine

http://pharmaceuticalintelligence.com/2012/12/31/renal-sympathetic-denervation-updates-on-the-state-of-medicine/

Manuela Stoicescu, MD, PhD, 2/9/2013 An Important Marker of Hypertension in Young Adults

http://pharmaceuticalintelligence.com/2013/02/09/an-important-marker-of-hypertension-in-young-adults/

Manuela Stoicescu, MD, PhD, 2/9/2013 Arterial Hypertension in Young Adults: An Ignored Chronic Problem

http://pharmaceuticalintelligence.com/2013/02/09/arterial-hypertension-in-young-adults-an-ignored-chronic-problem/

We present below, a new study on whether elevated pediatric BP could predict high PWV in adulthood and if there is a difference in the predictive ability between the standard BP definition endorsed by the National High Blood Pressure Education Program and the recently proposed 2 simplified definitions.

Simplified Definitions of ElevatedPediatric Blood Pressure and High Adult Arterial Stiffness

  1. Heikki Aatola, MDa,
  2. Costan G. Magnussen, PhDb,c,
  3. Teemu Koivistoinen, MD, MSca,
  4. Nina Hutri-Kähönen, MD, PhDd,
  5. Markus Juonala, MD, PhDb,e,
  6. Jorma S.A. Viikari, MD, PhDe,
  7. Terho Lehtimäki, MD, PhDf,
  8. Olli T. Raitakari, MD, PhDb,g, and
  9. Mika Kähönen, MD, PhDa

+Author Affiliations


  1. aDepartments of Clinical Physiology,

  2. dPediatrics, and

  3. fClinical Chemistry, Fimlab Laboratories, University of Tampere and Tampere University Hospital, Tampere, Finland;

  4. eDepartments of Medicine, and

  5. gClinical Physiology and Nuclear Medicine, and

  6. bthe Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku and Turku University Hospital, Turku, Finland; and

  7. cMenzies Research Institute Tasmania, University of Tasmania, Tasmania, Australia

ABSTRACT

OBJECTIVE: The ability of childhood elevated blood pressure (BP) to predict high pulse wave velocity (PWV), a surrogate marker for cardiovascular disease, in adulthood has not been reported. We studied whether elevated pediatric BP could predict high PWV in adulthood and if there is a difference in the predictive ability between the standard BP definition endorsed by the National High Blood Pressure Education Program and the recently proposed 2 simplified definitions.

METHODS: The sample comprised 1241 subjects from the Cardiovascular Risk in Young Finns Study followed-up 27 years since baseline (1980, aged 6–15 years). Arterial PWV was measured in 2007 by whole-body impedance cardiography.

RESULTS: The relative risk for high PWV was 1.5 using the simple 1 (age-specific) definition, 1.6 using the simple 2 (age- and gender-specific) definition, and 1.7 using the complex (age-, gender-, and height-specific) definition (95% confidence interval: 1.1–2.0, P = .007; 1.2–2.2, P = .001; and 1.2–2.2, P = .001, respectively). Predictions of high PWV were equivalent for the simple 1 or simple 2 versus complex definition (P = .25 and P = .68 for area under the curve comparisons, P = .13 and P = .35 for net reclassification indexes, respectively).

CONCLUSIONS: Our results support the previous finding that elevated BP tracks from childhood to adulthood and accelerates the atherosclerotic process. The simplified BP tables could be used to identify pediatric patients at increased risk of high arterial stiffness in adulthood and hence to improve the primary prevention of cardiovascular diseases.

Key Words:

  • blood pressure
  • pediatrics
  • prehypertension
  • screening
  • stiffness
  • Abbreviations:
    AUC —
    area under receiver-operating characteristic curve
    BP —
    blood pressure
    CVD —
    cardiovascular diseases
    NHBPEP —
    National High Blood Pressure Education Program
    NPV —
    negative predictive value
    NRI —
    net reclassification improvement
    PPV —
    positive predictive value
    PWV —
    pulse wave velocity
  • Accepted March 12, 2013.

http://pediatrics.aappublications.org/content/early/2013/06/05/peds.2012-3426.abstract?sid=1755f2a0-4e03-4bc8-a563-23458d9dc988

Kids’ High BP Tied to Arterial Stiffness as Adults

By Todd Neale, Senior Staff Writer, MedPage Today

Published: June 10, 2013

Reviewed by Robert Jasmer, MD; Associate Clinical Professor of Medicine, University of California, San Francisco and Dorothy Caputo, MA, BSN, RN, Nurse Planner

High blood pressure in childhood defined in three different ways was associated with high pulse wave velocity — a surrogate marker for cardiovascular disease — 27 years later, researchers found.

The relationship remained significant whether high blood pressure was identified using a complex definition that incorporated age, sex, and height or one of two simplified definitions (relative risk 1.5 to 1.7), according to Mika Kähönen, MD, PhD, of Tampere University Hospital in Finland, and colleagues.

The predictive ability of the two simplified definitions was comparable to that of the more complex definition, the researchers reported online in Pediatrics.

In guidelines published in 2004, the National High Blood Pressure Education Program recommended screening blood pressure at all pediatric visits starting at age 3. The document provides definitions for normal, prehypertensive, and hypertensive blood pressure levels according to age, sex, and height. But including all three of those factors results in hundreds of blood pressure thresholds for patients up to age 17.

Recently, two simplified definitions have been proposed — one that relies only on age and sex and reduces the number of blood pressure thresholds to 64 and another that relies on age alone and reduces the number of thresholds to 10.

“Our results support the previous finding that elevated blood pressure tracks from childhood to adulthood and accelerates the atherosclerotic process,” they wrote. “The simplified blood pressure tables could be used to identify pediatric patients at increased risk of high arterial stiffness in adulthood and hence to improve the primary prevention of cardiovascular diseases.”

“This complex definition could at least partly explain the poor diagnosis of prehypertension and hypertension in children and adolescents reported previously,” Kähönen and colleagues wrote.

The researchers explored the relationship between high blood pressure in childhood and high pulse wave velocity, which is a measure of arterial stiffness, in adulthood, as well as whether the definition of high blood pressure mattered, using 1,241 participants from the Cardiovascular Risk in Young Finns Study.

The participants were 6- to 15-years-old (mean age 10.7) at baseline in 1980. The researchers followed them for 27 years, at which point arterial pulse wave velocity was measured using whole-body impedance cardiography.

At baseline, the percentage of participants who had high blood pressure was 53.9% according to the definition based on age, 57.8% according to the definition based on age and sex, and 43.2% according to the more complex definition recommended in the guidelines.

At the 27-year follow-up assessment, 20% of the participants had a high pulse wave velocity. Compared with those with a low pulse wave velocity, these individuals had significantly higher blood pressure values and higher rates of elevated blood pressure at baseline. The differences widened at the adult follow-up.

Elevated pediatric blood pressure was associated with a greater risk of having a high pulse wave velocity for all three definitions used in the study:

  • Age-based: RR 1.5, 95% CI 1.1-2.0
  • Age- and sex-based: RR 1.6, 95% CI 1.2-2.2
  • Age-, sex-, and height-based: RR 1.7, 95% CI 1.2-2.2

The predictive ability of the definitions were not different from one another, as illustrated by a lack of significant differences when comparing area under the receiving-operating characteristic curves and net reclassification indexes (P>0.1 for all comparisons).

“This finding is clinically meaningful because both these simplified tables could be more easily implemented as a screening tool in pediatric healthcare settings and outside of a physician’s office when the height percentile required for the complex definition may not be obtainable,” the authors wrote.

They acknowledged that their study was potentially limited in that the method for measuring pulse wave velocity is not commonly used in epidemiologic settings. In addition, there could have been bias stemming from participants dropping out during follow-up and generalizability of the findings may be limited to white European individuals.

The study was supported by the Academy of Finland, the Social Insurance Institution of Finland, the Turku University Foundation, the Medical Research Fund of Kuopio University Hospital, the Medical Research Fund of Tampere University Hospital, the Turku University Hospital Medical Fund, the Emil Aaltonen Foundation, the Juha Vainio Foundation, the Finnish Foundation of Cardiovascular Research, the Finnish Cultural Foundation, and The Tampere Tuberculosis Foundation.

The authors reported no conflicts of interest.

From the American Heart Association:

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FUNDING: Supported by the Academy of Finland (grants 77841, 117832, 201888, 121584, and 126925); the Social Insurance Institution of Finland; the Turku University Foundation; the Medical Research Fund of Kuopio University Hospital; the Medical Research Fund of Tampere University Hospital; the Turku University Hospital Medical Fund; the Emil Aaltonen Foundation (T. Lehtimäki); the Juha Vainio Foundation; the Finnish Foundation of Cardiovascular Research; the Finnish Cultural Foundation; and The Tampere Tuberculosis Foundation.

Aatola H, et al “Simplified definitions of elevated pediatric blood pressure and high adult arterial stiffness” Pediatrics2013; DOI: 10.1542/peds.2012-3426.

 

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Reporter and Curator: Dr. Sudipta Saha, Ph.D.

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Word Cloud By Danielle Smolyar

Cancer is one of the most devastating and widespread diseases today. The development of cancer is a multi-step process involving genetic or epigenetic changes often occurring over a longer period of time. Moreover, cancer occurs in more or less all organs and tissues and is characterized by extensive heterogeneity both concerning the type and aggressiveness of the disease. Although some substantial progress in some areas has been made, there are still huge unmet needs in treatment methods and the efficacy of currently available drugs. The pharmaceutical industry has struggled with the ever increasing costs in drug development and unfortunately novel drugs have not seldom demonstrated only marginal improvement in efficacy often at the cost of quality of life of the patients. For these reasons, new approaches are focusing on disease prevention instead of only treating the symptoms. Recently, much attention has been paid to prevention of the disease in parallel to continuous drug discovery.

Intervention in food intake has been demonstrated to play an enormous role in both prevention as well as treatment of diseases. Numerous studies indicate a clear link between cancer and diet. The substantial development of sequencing technologies has resulted in access to enormous amounts of genomics information, which resulted in the establishment of nutrigenomics as an emerging approach to link genomics research to studies on nutrition. Increased understanding has demonstrated how nutrition can influence human health both at genetic and epigenetic levels. It investigates the effects of nutrition and bioactive food compounds on gene expression. This approach has allowed the investigation of the effect on nutrition on individuals with specific genetic features. Moreover, it has provided the basis for nutritional intervention in prevention and treatment of disease and the inauguration of personalized nutrition. However, differences in types of cancer, the level of aggressiveness, and their occurrence at different stages of life have seriously complicated the understanding of the effect of nutrition on cancer prevention and treatment. Other individual variations such as the amounts of food consumed, digestion, metabolism and other factors like geographical, ethnic and sociological diversity has hampered the identification of which food components are most important for human health. Dramatic dietary modifications have proven essential in reducing risk and even prevention of cancer. Moreover, intense revision of diet in cancer patients has revealed significant changes in gene expression and also has provided therapeutic efficacy even after short-term application.

Obviously, a multitude of diets have been evaluated, but probably the common factor for achieving both prophylactic and therapeutic responses is to consume predominantly diets rich in fruits, vegetables, fish and fibers and reduced quantities of especially red meat. There are numerous examples of how dietary intake can promote health on both a preventive as well as therapeutic level. Radical change in diet has resulted in dramatic changes in gene expression in prostate cancer patients revealing that many of those genes involved in cancer development were down-regulated. The importance of nutrigenomics as a multi-task approach involving genomics, proteomics, metabolomics, et cetera has further provided novel possibilities to address the effect of nutrition on human health. Despite encouraging findings on how dietary modifications can prevent disease and restore health, there are a number of factors which complicate the outcome. There are variations in response to dietary changes depending on age and gender. However, the vast amount of accumulated nutrigenomics data should not overshadow the needs to take into account other important factors such as lifestyle, social, geographical and economic factors affecting diet and health.

Source References:

http://www.lifescienceglobal.com/home/cart?view=product&id=121

http://www.frontiersin.org/Nutrigenomics/10.3389/fgene.2011.00091/abstract

http://www.sciencedirect.com/science/article/pii/S0002822308021871

http://ajcn.nutrition.org/content/89/5/1553S

http://www.sciencedirect.com/science/article/pii/S030438350800390X

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Reporter: Aviva Lev-Ari, PhD, RN

Genome.gov National Human Genome Research Institute National Institutes of Health

Online Research Resources

Contents

From NHGRI
Online Research Resources Developed at NHGRI
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The NHGRI Genome Sequencing Program (GSP)
Beyond NHGRI
The Completed Human Sequence
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Model Organism Genome Projects
Archaea and Bacteria
Eukaryotes
Databases
National Center for Biotechnology Information (NCBI) Databases and Tools
Nucleotide Sequence Databases
Trace Archives (Raw Sequence Data Repositories)
Single Nucleotide Polymorphisms (SNPs)
cDNAs and Expressed Sequence Tags (ESTs)
Model Organism Databases
Additional Sequence, Gene and Protein Databases
Ethical, Legal and Social Implications (ELSI) Information
Funding Agencies
Additional Genome Resources
Biology Resources
Selected Journals

From NHGRI

Online Research Resources Developed at NHGRI
Software, databases and research project Web sites from NHGRI’s Division of Intramural Research (DIR).

NHGRI Reports and Publications

The NHGRI Genome Sequencing Program (GSP) 
Genome sequencing projects currently in production and funded by NHGRI.

Beyond NHGRI

The Completed Human Sequence:
Other Federal Agencies Involved in Genomics
Human Genome Sequence Assemblies and Other Genomic Data Resources

 

Underlying Map Information
Sequencing Centers of the International Human Genome Sequencing Consortium

(Listed in order of total sequence contributed to the draft human sequence published February 15, 2001, Nature, 409:860-921)

Model Organism Genome Projects

Archaea and Bacteria

Eukaryotes

Databases

National Center for Biotechnology Information (NCBI) Databases and Tools

Nucleotide Sequence Databases

Trace Archives (Raw Sequence Data Repositories)

Single Nucleotide Polymorphisms (SNPs)

cDNAs and Expressed Sequence Tags (ESTs)

Model Organism Databases

Additional Sequence, Gene and Protein Databases

  • InterPro protein sequence analysis & classification [ebi.ac.uk]
    An integrated database of predictive protein signatures used for the classification and automatic annotation of proteins and genomes.
  • Eukaryotic Promoter Database [epd.isb-sib.ch]
  • PROSITE [expasy.org]
    A database of protein families and domains.
  • SWISS-PROT [web.expasy.org]
    A protein knowledgebase.
  • BioMagResBank [bmrb.wisc.edu]
    NMR spectroscopy data on proteins, peptides, and nucleic acids.
  • Protein Data Bank (PDB) [rcsb.org]
    The repository for 3-D biological macromolecular structure data.
  • DSSP [swift.cmbi.ru.nl]
    A database of secondary structure protein assignments.
  • FSSP [biocenter.helsinki.fi]
    A database of fold classifications based on structure-structure alignment of proteins.
  • HSSP [cmbi.kun.nl]
    A database of homology-derived secondary structure of proteins.
  • Nucleic Acid Database Project (NDB) [ndbserver.rutgers.edu]
    Structural information about nucleic acids.
  • The I.M.A.G.E. Consortium [image.hudsonalpha.org]
    A public collection of genes.
Ethical, Legal and Social Implications (ELSI) Research Program
Funding Agencies
Additional Genome Resources
Biology Resources
Selected Journals

Last Updated: October 16, 2012

SOURCE:

http://www.genome.gov/10000375

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