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https://www.readbyqxmd.com/read/28735292/pathogenesis-of-hypertrophic-cardiomyopathy-is-mutation-rather-than-disease-specific-a-comparison-of-the-cardiac-troponin-t-e163r-and-r92q-mouse-models
#1
Cecilia Ferrantini, Raffaele Coppini, Josè Manuel Pioner, Francesca Gentile, Benedetta Tosi, Luca Mazzoni, Beatrice Scellini, Nicoletta Piroddi, Annunziatina Laurino, Lorenzo Santini, Valentina Spinelli, Leonardo Sacconi, Pieter De Tombe, Rachel Moore, Jil Tardiff, Alessandro Mugelli, Iacopo Olivotto, Elisabetta Cerbai, Chiara Tesi, Corrado Poggesi
BACKGROUND: In cardiomyocytes from patients with hypertrophic cardiomyopathy, mechanical dysfunction and arrhythmogenicity are caused by mutation-driven changes in myofilament function combined with excitation-contraction (E-C) coupling abnormalities related to adverse remodeling. Whether myofilament or E-C coupling alterations are more relevant in disease development is unknown. Here, we aim to investigate whether the relative roles of myofilament dysfunction and E-C coupling remodeling in determining the hypertrophic cardiomyopathy phenotype are mutation specific...
July 22, 2017: Journal of the American Heart Association
https://www.readbyqxmd.com/read/28734944/triple-negative-breast-cancer-next-generation-sequencing-for-target-identification
#2
REVIEW
Jonathan D Marotti, Francine B de Abreu, Wendy A Wells, Gregory J Tsongalis
Our ability to now study disease at the most fundamental molecular level has led to a reclassification of human cancers into numerous subtypes that vary in disease progression and response to therapy. Like most solid tumors, breast cancer is a heterogeneous disease with considerable variation in histological and biological features. Triple negative breast cancer (TNBC) is a subtype of breast cancer in which estrogen receptor and progesterone receptor are not expressed, and human epidermal growth factor receptor 2 is not amplified or overexpressed...
July 19, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28733906/the-advanced-diarem-score-improves-prediction-of-diabetes-remission-1%C3%A2-year-post-roux-en-y-gastric-bypass
#3
Judith Aron-Wisnewsky, Nataliya Sokolovska, Yuejun Liu, Doron S Comaneshter, Shlomo Vinker, Tal Pecht, Christine Poitou, Jean-Michel Oppert, Jean-Luc Bouillot, Laurent Genser, Dror Dicker, Jean-Daniel Zucker, Assaf Rudich, Karine Clément
AIMS/HYPOTHESIS: Not all people with type 2 diabetes who undergo bariatric surgery achieve diabetes remission. Thus it is critical to develop methods for predicting outcomes that are applicable for clinical practice. The DiaRem score is relevant for predicting diabetes remission post-Roux-en-Y gastric bypass (RYGB), but it is not accurate for all individuals across the entire spectrum of scores. We aimed to develop an improved scoring system for predicting diabetes remission following RYGB (the Advanced-DiaRem [Ad-DiaRem])...
July 21, 2017: Diabetologia
https://www.readbyqxmd.com/read/28733441/molecular-screening-for-cancer-treatment-optimization-moscato-01-in-pediatric-patients-a-single-institutional-prospective-molecular-stratification-trial
#4
Anne Catherine Harttrampf, Ludovic Lacroix, Marc Deloger, Frederic Deschamps, Stéphanie Puget, Nathalie Auger, Philippe Vielh, Pascale Varlet, Zsofia Balogh, Samuel Abbou, Adrien Allorant, Dominique Valteau-Couanet, Sabine Sarnacki, Louise Galmiche, Guillaume Meurice, Véronique Minard-Colin, Jacques Grill, Laurence Brugières, Christelle Dufour, Nathalie Gaspar, Stefan Michiels, Gilles Vassal, Jean-Charles Soria, Birgit Geoerger
This single institutional feasibility study prospectively characterized genomic alterations in recurrent or refractory solid tumors of pediatric patients in order to select a targeted therapy.<br /><br />Experimental Design: Following treatment failure patients with signed consent and aged above 6 months, underwent tumor biopsy or surgical resection of primary or metastatic tumor site.  These newly acquired samples were analyzed by comparative genomic hybridization array, next generation sequencing for 75 target genes, whole exome and RNA sequencing...
July 21, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28733374/the-fallacy-of-average-how-using-hba1c-alone-to-assess-glycemic-control-can-be-misleading
#5
Roy W Beck, Crystal G Connor, Deborah M Mullen, David M Wesley, Richard M Bergenstal
HbA1c is a valuable metric for comparing treatment groups in a randomized trial, for assessing glycemic trends in a population over time, or for cross-sectional comparisons of glycemic control in different populations. However, what is not widely appreciated is that HbA1c may not be a good indicator of an individual patient's glycemic control because of the wide range of mean glucose concentrations and glucose profiles that can be associated with a given HbA1c level. To illustrate this point, we plotted mean glucose measured with continuous glucose monitoring (CGM) versus central laboratory-measured HbA1c in 387 participants in three randomized trials, showing that not infrequently HbA1c may underestimate or overestimate mean glucose, sometimes substantially...
August 2017: Diabetes Care
https://www.readbyqxmd.com/read/28733195/the-evolving-role-of-companion-diagnostics-for-breast-cancer-in-an-era-of-next-generation-omics
#6
REVIEW
Jason N Rosenbaum, Paul Weisman
A companion diagnostic is a test for a specific biomarker-approved by the United States Food and Drug Administration-qualifying a patient to receive a specific, associated therapy. As interest has grown in precision medicine over the last decade, the principle of companion diagnostics has gained increasing purchase among laboratory professionals, clinicians, regulators, and even patients. The evolution of the biomarkers used to stratify and treat breast cancer illustrates the history of companion diagnostics, and provides a lens through which to examine potential challenges...
July 18, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28731804/nuclear-medicine-and-molecular-imaging-an-impactful-decade-of-contributions-to-patient-care-and-driving-precision-medicine
#7
Rathan M Subramaniam
No abstract text is available yet for this article.
August 2017: AJR. American Journal of Roentgenology
https://www.readbyqxmd.com/read/28731449/cerebrospinal-fluid-neurogranin-as-a-biomarker-of-neurodegenerative-diseases-a-cross-sectional-study
#8
Simone Lista, Nicola Toschi, Filippo Baldacci, Henrik Zetterberg, Kaj Blennow, Ingo Kilimann, Stefan J Teipel, Enrica Cavedo, Antonio Melo Dos Santos, Stéphane Epelbaum, Foudil Lamari, Bruno Dubois, Robert Nisticò, Roberto Floris, Francesco Garaci, Harald Hampel
We investigated cerebrospinal fluid (CSF) concentrations of the postsynaptic biomarker neurogranin at baseline in cognitively healthy controls (HC) compared to individuals with mild cognitive impairment (MCI), patients with Alzheimer's disease (AD) dementia, and patients with frontotemporal dementia (FTD). CSF neurogranin was quantified using an in-house immunoassay in a cross-sectional multicenter study of 108 participants [AD dementia (n = 35), FTD (n = 9), MCI (n = 41), cognitively HC (n = 23)]...
July 18, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28730480/identification-and-validation-of-driver-kinases-from-next-generation-sequencing-data
#9
Andri Leonidou, Barrie Peck, Rachael Natrajan
It is well appreciated that activating mutations in kinase genes result in kinome reprogramming that leads to altered downstream signaling networks that drive tumor progression. Indeed small-molecule inhibition of activated kinases has heralded the wave of precision medicine in the past decade. The advent of next-generation sequencing has identified a plethora of potentially activating mutations and fusion genes in previously unreported kinase genes that can potentially be developed as targeted therapies. However, the bottleneck in the translation of these alterations into clinically useful therapies lies in their functional validation...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28730160/epigenetic-interactions-between-alcohol-and-cannabinergic-effects-focus-on-histone-modification-and-dna-methylation
#10
Tiyash Parira, Alejandra Laverde, Marisela Agudelo
Epigenetic studies have led to a more profound understanding of the mechanisms involved in chronic conditions. In the case of alcohol addiction, according to the National Institute on Alcohol Abuse and Alcoholism, 16 million adults suffer from Alcohol Use Disorders (AUDs). Even though therapeutic interventions like behavioral therapy and medications to prevent relapse are currently available, no robust cure exists, which stems from the lack of understanding the mechanisms of action of alcohol and the lack of development of precision medicine approaches to treat AUDs...
April 2017: Journal of Alcoholism and Drug Dependence
https://www.readbyqxmd.com/read/28729958/mutational-analysis-of-driver-genes-with-tumor-suppressive-and-oncogenic-roles-in-gastric-cancer
#11
Tianfang Wang, Yining Liu, Min Zhao
Gastric cancer (GC) is a complex disease with heterogeneous genetic mechanisms. Genomic mutational profiling of gastric cancer not only expands our knowledge about cancer progression at a fundamental genetic level, but also could provide guidance on new treatment decisions, currently based on tumor histology. The fact that precise medicine-based treatment is successful in a subset of tumors indicates the need for better identification of clinically related molecular tumor phenotypes, especially with regard to those driver mutations on tumor suppressor genes (TSGs) and oncogenes (ONGs)...
2017: PeerJ
https://www.readbyqxmd.com/read/28729428/fluorine-18-labeled-carboplatin-derivative-for-pet-imaging-of-platinum-drug-distribution
#12
Narottam Lamichhane, Gajanan K Dewkar, Sundaresan Gobalakrishnan, Li Wang, Purnima Jose, Muhammad Otabashi, Jean-Luc Morelle, Nicholas Farrell, Jamal Zweit
Increasing evidence indicates that reduced intracellular drug accumulation is the parameter most consistently associated with platinum drug resistance, and emphasizes the need to directly measure intra-tumor drug concentration. In the era of precision medicine and with the advent of powerful imaging and proteomics technologies, there is an opportunity to better understand drug resistance, by exploiting these techniques to provide new knowledge on drug-target interactions. Here, we are contributing to this endeavor by reporting on the development of a fluorine-18 labeled carboplatin derivative ((18)F-FCP) that can be used to potentially image drug uptake and retention, including intra-tumoral distribution, by positron emission tomography (PET)...
July 20, 2017: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
https://www.readbyqxmd.com/read/28729406/tumor-evolution-as-a-therapeutic-target
#13
REVIEW
Nabil Amirouchene-Angelozzi, Charles Swanton, Alberto Bardelli
Recent technological advances in the field of molecular diagnostics (including blood-based tumor genotyping) allow the measurement of clonal evolution in patients with cancer, thus adding a new dimension to precision medicine: time. The translation of this new knowledge into clinical benefit implies rethinking therapeutic strategies. In essence, it means considering as a target not only individual oncogenes but also the evolving nature of human tumors. Here, we analyze the limitations of targeted therapies and propose approaches for treatment within an evolutionary framework...
July 20, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28728997/sepsis-reconsidered-identifying-novel-metrics-for-behavioral-landscape-characterization-with-a-high-performance-computing-implementation-of-an-agent-based-model
#14
Chase Cockrell, Gary An
OBJECTIVES: Sepsis affects nearly 1 million people in the United States per year, has a mortality rate of 28-50% and requires more than $20 billion a year in hospital costs. Over a quarter century of research has not yielded a single reliable diagnostic test or a directed therapeutic agent for sepsis. Central to this insufficiency is the fact that sepsis remains a clinical/physiological diagnosis representing a multitude of molecularly heterogeneous pathological trajectories. Advances in computational capabilities offered by High Performance Computing (HPC) platforms call for an evolution in the investigation of sepsis to attempt to define the boundaries of traditional research (bench, clinical and computational) through the use of computational proxy models...
July 17, 2017: Journal of Theoretical Biology
https://www.readbyqxmd.com/read/28726855/cyclodextrin-based-biological-stimuli-responsive-carriers-for-smart-and-precision-medicine
#15
Rongqiang Liao, Pin Lv, Qian Wang, Jiaoni Zheng, Bing Feng, Bo Yang
Spurred on by recent progress in nanotechnology and precision medicine, smart drug carriers are entering an entirely new era. Smart drug carriers have been widely studied in recent years as a result of their ability to control drug release under different microenvironments (such as pH, redox, and enzyme) in vivo. Host-guest interactions based on cyclodextrins have proven to be an efficient tool for fabricating smart drug carriers. Because of the application of host-guest interactions, many kinds of biological molecules or supramolecular building blocks can combine into an organic whole at the molecular level...
July 20, 2017: Biomaterials Science
https://www.readbyqxmd.com/read/28725790/biobanking-budgets-and-the-role-of-pathology-biobanks-in-precision-medicine
#16
Chris Andry, Elizabeth Duffy, Christopher A Moskaluk, Shannon McCall, Michael H A Roehrl, Daniel Remick
Biobanks have become an important component of the routine practice of pathology. At the 2016 meeting of the Association of Pathology Chairs, a series of presentations covered several important aspects of biobanking. An often overlooked aspect of biobanking is the fiscal considerations. A biobank budget must address the costs of consenting, procuring, processing, and preserving high-quality biospecimens. Multiple revenue streams will frequently be necessary to create a sustainable biobank; partnering with other key stakeholders has been shown to be successful at academic institutions which may serve as a model...
January 2017: Acad Pathol
https://www.readbyqxmd.com/read/28723506/biomarkers-for-metastatic-castration-resistant-prostate-cancer-mcrpc-yes-or-no-predictive-and-response-biomarkers-towards-precision-medicine-in-mcrpc
#17
Joaquin Mateo
Advances in drug development and molecular studies for castration-resistant prostate cancer (CRPC) render the possibility of more efficient and precise patient care through the use of predictive, response, and resistance biomarkers. Thorough scrutiny of assay validation and clinical qualification processes for biomarkers in development, ideally in parallel with clinical trials, is critical for the success of personalised medicine in CRPC management.
December 2016: European Urology Focus
https://www.readbyqxmd.com/read/28723287/advanced-renal-cell-carcinoma-role-of-the-radiologist-in-the-era-of-precision-medicine
#18
Atul B Shinagare, Katherine M Krajewski, Marta Braschi-Amirfarzan, Nikhil H Ramaiya
For the past decade, advanced renal cell carcinoma (RCC) has been at the forefront of oncologic innovation. Our rapidly evolving understanding of the molecular and genetic basis of RCC has revolutionized the management of advanced RCC; 10 novel molecular targeted agents and immune checkpoint inhibitor have received U.S. Food and Drug Administration approval for treatment of advanced RCC in a little over a decade. Amid this progress, imaging has assumed a central role in metastatic surveillance and follow-up of advanced RCC...
August 2017: Radiology
https://www.readbyqxmd.com/read/28719907/tumor-heterogeneity-in-lymphomas-a-different-breed
#19
Christian M Schürch, Birgit Federmann, Leticia Quintanilla-Martinez, Falko Fend
The facts that cancer represents tissues consisting of heterogeneous neoplastic, as well as reactive, cell populations and that cancers of the same histotype may show profound differences in clinical behavior have long been recognized. With the advent of new technologies and the demands of precision medicine, the investigation of tumor heterogeneity has gained much interest. An understanding of intertumoral heterogeneity in patients with the same disease entity is necessary to optimally guide personalized treatment...
July 19, 2017: Pathobiology: Journal of Immunopathology, Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28718902/pluripotent-stem-cell-based-platforms-in-cardiac-disease-modeling-and-drug-testing
#20
N Shaheen, A Shiti, L Gepstein
The ability to generate patient/disease-specific human pluripotent stem cell (hPSC)-derived cardiomyocytes (hPSC-CMs) brings a unique value to the fields of cardiac disease modeling, drug testing, drug discovery, and precision medicine. Further integration of emerging innovative technologies such as developmental-biology inspired differentiation into chamber-specific cardiomyocyte subtypes, genome-editing, tissue-engineering, and novel functional phenotyping methodologies should facilitate even more advanced investigations...
August 2017: Clinical Pharmacology and Therapeutics
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