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Precision medicine

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https://www.readbyqxmd.com/read/29331859/development-of-a-method-to-determine-axitinib-lapatinib-and-afatinib-in-plasma-by-micellar-liquid-chromatography-and-validation-by-the-european-medicines-agency-guidelines
#1
Jaume Albiol-Chiva, Josep Esteve-Romero, Juan Peris-Vicente
A method based on micellar liquid chromatography to quantify the tyrosine kinase inhibitors axitinib, lapatinib and afatinib in plasma is reported. The sample pretreatment was a simple 1/5-dilution in a pure micellar solution, filtration and direct injection, without requiring extraction or purification steps. The three drugs were resolved from the matrix in 17min, using an aqueous solution of 0.07M sodium dodecyl sulfate - 6.0% 1-pentanol, buffered at pH7 with 0.01M phosphate salt as mobile phase, running under isocratic mode at 1mL/min through a C18 column...
January 2, 2018: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
https://www.readbyqxmd.com/read/29331645/realising-the-potential-of-various-inhaled-airway-challenge-agents-through-improved-delivery-to-the-lungs
#2
REVIEW
Anne J Lexmond, Dave Singh, Henderik W Frijlink, Graham W Clarke, Clive P Page, Ben Forbes, Maarten van den Berge
Inhaled airway challenges provoke bronchoconstriction in susceptible subjects and are a pivotal tool in the diagnosis and monitoring of obstructive lung diseases, both in the clinic and in the development of new respiratory medicines. This article reviews the main challenge agents that are in use today (methacholine, mannitol, adenosine, allergens, endotoxin) and emphasises the importance of controlling how these agents are administered. There is a danger that the optimal value of these challenge agents may not be realised due to suboptimal inhaled delivery; thus considerations for effective and reproducible challenge delivery are provided...
January 10, 2018: Pulmonary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/29331519/understanding-and-misunderstanding-randomized-controlled-trials
#3
Angus Deaton, Nancy Cartwright
Randomized Controlled Trials (RCTs) are increasingly popular in the social sciences, not only in medicine. We argue that the lay public, and sometimes researchers, put too much trust in RCTs over other methods of investigation. Contrary to frequent claims in the applied literature, randomization does not equalize everything other than the treatment in the treatment and control groups, it does not automatically deliver a precise estimate of the average treatment effect (ATE), and it does not relieve us of the need to think about (observed or unobserved) covariates...
December 25, 2017: Social Science & Medicine
https://www.readbyqxmd.com/read/29331065/component-resolved-diagnostics-to-direct-in-venom-immunotherapy-important-steps-towards-precision-medicine
#4
Simon Blank, Maria Beatrice Bilò, Markus Ollert
Stings of Hymenoptera can induce IgE-mediated systemic and even fatal allergic reactions. Venom-specific immunotherapy (VIT) is the only disease-modifying and curative treatment of venom allergy. However, choosing the correct venom for VIT represents a necessary prerequisite for efficient protection against further anaphylactic sting reactions after VIT. In the past, therapeutic decisions based on the measurement of specific IgE (sIgE) levels to whole venom extracts were not always straightforward, especially when the patient was not able to identify the culprit insect...
January 13, 2018: Clinical and Experimental Allergy: Journal of the British Society for Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/29330437/a-computational-assay-of-estrogen-receptor-%C3%AE-antagonists-reveals-the-key-common-structural-traits-of-drugs-effectively-fighting-refractory-breast-cancers
#5
Matic Pavlin, Angelo Spinello, Marzia Pennati, Nadia Zaffaroni, Silvia Gobbi, Alessandra Bisi, Giorgio Colombo, Alessandra Magistrato
Somatic mutations of the Estrogen Receptor α (ERα) occur with an up to 40% incidence in ER sensitive breast cancer (BC) patients undergoing prolonged endocrine treatments. These polymorphisms are implicated in acquired resistance, disease relapse, and increased mortality rates, hence representing a current major clinical challenge. Here, multi-microseconds (12.5 µs) molecular dynamics simulations revealed that recurrent ERα polymorphisms (i. e. L536Q, Y537S, Y537N, D538G) (mERα) are constitutively active in their apo form and that they prompt the selection of an agonist (active)-like conformation even upon antagonists binding...
January 12, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29330417/high-stap1-expression-in-dux4-rearranged-cases-is-not-suitable-as-therapeutic-target-in-pediatric-b-cell-precursor-acute-lymphoblastic-leukemia
#6
Elisabeth M P Steeghs, Marjolein Bakker, Alex Q Hoogkamer, Judith M Boer, Quirine J Hartman, Femke Stalpers, Gabriele Escherich, Valerie de Haas, Hester A de Groot-Kruseman, Rob Pieters, Monique L den Boer
Approximately 25% of the pediatric B-cell precursor acute lymphoblastic leukemia (BCP-ALL) cases are genetically unclassified. More thorough elucidation of the pathobiology of these genetically unclassified ('B-other') cases may identify novel treatment options. We analyzed gene expression profiles of 572 pediatric BCP-ALL cases, representing all major ALL subtypes. High expression of STAP1, an adaptor protein downstream of the B-cell receptor (BCR), was identified in BCR-ABL1-like and non-BCR-ABL1-like B-other cases...
January 12, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29329368/discovering-personalized-driver-mutation-profiles-of-single-samples-in-cancer-by-network-control-strategy
#7
Wei-Feng Guo, Shao-Wu Zhang, Li-Li Liu, Fei Liu, Qian-Qian Shi, Lei Zhang, Ying Tang, Tao Zeng, Luonan Chen
Motivation: It is a challenging task to discover personalized driver genes that provide crucial information on disease risk and drug sensitivity for individual patients. However, few methods have been proposed to identify the personalized-sample driver genes from the cancer omics data due to the lack of samples for each individual. To circumvent this problem, here we present a novel single-sample controller strategy (SCS) to identify personalized driver mutation profiles from network controllability perspective...
January 10, 2018: Bioinformatics
https://www.readbyqxmd.com/read/29329296/identification-and-in-silico-analysis-of-functional-snps-of-human-tagap-protein-a-comprehensive-study
#8
Maria Arshad, Attya Bhatti, Peter John
Genetic polymorphisms in TAGAP gene have been associated with many diseases including rheumatoid arthritis, multiple sclerosis and other autoimmune disorders. Identifying functional SNPs in such disease associated genes is an uphill task hence before planning larger population study, it is better to scrutinize putative functional SNPs. In this study we used various computational approaches to identify nsSNPs which are deleterious to the structure and/or function of TAGAP protein that might be causing these diseases...
2018: PloS One
https://www.readbyqxmd.com/read/29328927/alzheimer-s-disease-biomarker-guided-diagnostic-workflow-using-the-added-value-of-six-combined-cerebrospinal-fluid-candidates-a%C3%AE-1-42-total-tau-phosphorylated-tau-nfl-neurogranin-and-ykl-40
#9
Harald Hampel, Nicola Toschi, Filippo Baldacci, Henrik Zetterberg, Kaj Blennow, Ingo Kilimann, Stefan J Teipel, Enrica Cavedo, Antonio Melo Dos Santos, Stéphane Epelbaum, Foudil Lamari, Remy Genthon, Bruno Dubois, Roberto Floris, Francesco Garaci, Simone Lista
INTRODUCTION: The diagnostic and classificatory performances of all combinations of three core (amyloid β peptide [i.e., Aβ1-42], total tau [t-tau], and phosphorylated tau) and three novel (neurofilament light chain protein, neurogranin, and YKL-40) cerebrospinal fluid biomarkers of neurodegeneration were compared among individuals with mild cognitive impairment (n = 41), Alzheimer's disease dementia (ADD; n = 35), frontotemporal dementia (FTD; n = 9), and cognitively healthy controls (HC; n = 21), using 10-fold cross-validation...
January 9, 2018: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
https://www.readbyqxmd.com/read/29328498/an-uplc-ms-ms-method-for-simultaneous-determination-of-five-flavonoids-from-stellerachamaejasme-l-in-rat-plasma-and-its-application-to-a-pharmacokinetic-study
#10
Yun-Qing Li, Cheng-Jian Li, Lei Lv, Qing-Qing Cao, Xian Qian, Si Wei Li, Hui Wang, Liang Zhao
Stellerachamaejasme L. has been used as a Traditional Chinese Medicine for the treatment of scabies, tinea, stubborn skin ulcers, chronic tracheitis, cancer and tuberculosis. A sensitive and selective ultra-high liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was developed and validated for the simultaneous determination of five flavonoids (stelleranol, chamaechromone, neochamaejasmin A, chamaejasmine and isochamaejasmin) of Stellerachamaejasme L. in rat plasma. Chromatographic separation was accomplished on an Agilent Poroshell 120 EC-C18 column (2...
January 12, 2018: Biomedical Chromatography: BMC
https://www.readbyqxmd.com/read/29326075/use-of-crispr-cas9-gene-editing-tools-for-developing-models-in-drug-discovery
#11
REVIEW
Gulzar Ahmad, Mansoor Amiji
Clustered regularly interspaced short palindromic repeat/CRISPR-associated 9 (CRISPR/Cas9) enables targeted genome engineering. The simplicity of this system, its facile engineering, and amenability to multiplex genes make it the system of choice for many applications. This system has revolutionized our ability to carry out gene editing, transcription regulation, genome imaging, and epigenetic modification. In this review, we discuss the discovery of CRISPR/Cas9, its mechanism of action, its application in medicine and animal model development, and its delivery...
January 8, 2018: Drug Discovery Today
https://www.readbyqxmd.com/read/29325810/current-and-future-initiatives-for-radiation-oncology-at-the-national-cancer-institute-in-the-era-of-precision-medicine
#12
EDITORIAL
Charles A Kunos, C Norman Coleman
No abstract text is available yet for this article.
January 8, 2018: International Journal of Radiation Oncology, Biology, Physics
https://www.readbyqxmd.com/read/29325731/pharmacogenomic-testing-in-child-and-adolescent-psychiatry-an-evidence-based-review
#13
Anna M Wehry, Laura Ramsey, Shane E Dulemba, Sarah A Mossman, Jeffrey R Strawn
Significant advances have been made in the application of pharmacogenomic testing for the treatment of patients with psychiatric disorders. Over the past decade, a number of studies have evaluated the utility of pharmacogenomic testing in pediatric patients with psychiatric disorders. The evidence base for pharmacogenomic testing in youth with depressive and anxiety disorders as well as attention/deficit hyperactivity disorder (ADHD) is reviewed in this article. General pharmacogenomic principles are summarized and functional polymorphisms in P450 enzymes (and associated metabolizer phenotypes), the serotonin transporter promoter polymorphisms, serotonin 2 A receptor genes (e...
January 8, 2018: Current Problems in Pediatric and Adolescent Health Care
https://www.readbyqxmd.com/read/29325707/successful-creation-of-pancreatic-cancer-organoids-by-means-of-eus-guided-fine-needle-biopsy-for-personalized-cancer-treatment
#14
Herve Tiriac, Juan Carlos Bucobo, Demetrios Tzimas, Suman Grewel, Joseph F Lacomb, Leahana M Rowehl, Satish Nagula, Maoxin Wu, Joseph Kim, Aaron Sasson, Shivakumar Vignesh, Laura Martello, Maria Munoz-Sagastibelza, Jonathan Somma, David A Tuveson, Ellen Li, Jonathan M Buscaglia
BACKGROUND AND AIMS: Pancreatic cancer organoids are tumor models of individualized human pancreatic ductal adenocarcinoma (PDA), created from surgical specimens and used for personalized treatment strategies. Unfortunately the vast majority of patients with PDA are not operative candidates. Creation of human PDA organoids at the time of initial tumor diagnosis is therefore critical. Our aim was to assess the feasibility of creating human PDA organoids by EUS fine-needle biopsy (EUS-FNB) in patients with PDA...
January 8, 2018: Gastrointestinal Endoscopy
https://www.readbyqxmd.com/read/29325630/towards-precision-medicine
#15
Tanya Bardakjian, Pedro Gonzalez-Alegre
The concept of precision medicine, also referred to as individualized or personalized medicine, has recently gained traction in scientific, medical, and public spheres, and is frequently mentioned as the next model of healthcare delivery. Its goal is to integrate unique information obtained from a given patient to customize the care provided to achieve the best possible outcome. Although precision medicine is not fully implemented yet, its application is slowly infiltrating clinical practice, and the dream of individualizing healthcare to each patient is now closer to being fulfilled...
2018: Handbook of Clinical Neurology
https://www.readbyqxmd.com/read/29325607/genetic-and-genomic-testing-for-neurologic-disease-in-clinical-practice
#16
Brent L Fogel
The influence of genetics on neurologic disease is broad and it is becoming more common that clinicians are presented with a patient whose disease is likely of genetic origin. In the search for mutations causing Mendelian disorders, advances in genetic testing methodology have propelled modern neurologic practice beyond single-gene testing into the realm of genomic medicine, where routine evaluations encompass hundreds or thousands of genes, or even the entire exome, representing all protein-coding genes in the genome...
2018: Handbook of Clinical Neurology
https://www.readbyqxmd.com/read/29325210/a-new-co-p-nanocomposite-with-ultrahigh-relaxivity-for-in-vivo-magnetic-resonance-imaging-guided-tumor-eradication-by-chemo-photothermal-synergistic-therapy
#17
Jianhua Liu, Longhai Jin, Yinghui Wang, Xing Ding, Songtao Zhang, Shuyan Song, Daguang Wang, Hongjie Zhang
Design of new nanoagents that intrinsically have both diagnostic imaging and therapeutic capabilities is highly desirable for personalized medicine. In this work, a novel nanotheranostic agent is fabricated based on polydopamine (PDA)-functionalized Co-P nanocomposites (Co-P@PDA) for magnetic resonance imaging (MRI)-guided combined photothermal therapy and chemotherapy. The ultrahigh relaxivity of 224.61 mm-1 s-1 can enable Co-P@PDA to be applied as an excellent contrast agent for MRI in vitro and in vivo, providing essential and comprehensive information for tumor clinical diagnosis...
January 11, 2018: Small
https://www.readbyqxmd.com/read/29324928/individual-kidney-depth-determination-is-mandatory-to-assess-split-renal-function-in-nephrography-irrespective-of-age
#18
Helmut Sinzinger, Lindsay Brammen
Nephrography having been introduced more than 60 years ago still now is one of the most frequently used and informative procedures in Nuclear Medicine. Although being considered a well standardized method, a worldwide study in 34 centers in 21 countries revealed that determination of split kidney function shows unacceptable high variation, particularly in patients with a relative kidney function below 30%. Furthermore, kidney depth usually is not considered. The calculation of kidney depth by various formulas available, each claiming to be more predictive, is different in races and does not allow individual information, which particularly in patients with a diseased kidney may become unreliable...
September 2017: Hellenic Journal of Nuclear Medicine
https://www.readbyqxmd.com/read/29324546/applying-precision-medicine-to-ovarian-cancer-proof-of-principle-for-a-molecular-second-look
#19
Melissa Schwartz, Olga Camacho-Vanegas, Ashley M Wood, Matthew Dashkoff, Courtney Whitelock, Timothy T Harkins, Carmel J Cohen, Ann Marie Beddoe, Peter Dottino, John A Martignetti
OBJECTIVES: The objectives of this study were to assess if targeted investigation for tumor-specific mutations by ultradeep DNA sequencing of peritoneal washes of ovarian cancer patients after primary surgical debulking and chemotherapy, and clinically diagnosed as disease free, provides a more sensitive and specific method to assess actual treatment response and tailor future therapy and to compare this "molecular second look" with conventional cytology and histopathology-based findings...
January 10, 2018: International Journal of Gynecological Cancer
https://www.readbyqxmd.com/read/29321555/fourier-transform-infrared-microscopy-enables-guidance-of-automated-mass-spectrometry-imaging-to-predefined-tissue-morphologies
#20
Jan-Hinrich Rabe, Denis A Sammour, Sandra Schulz, Bogdan Munteanu, Martina Ott, Katharina Ochs, Peter Hohenberger, Alexander Marx, Michael Platten, Christiane A Opitz, Daniel S Ory, Carsten Hopf
Multimodal imaging combines complementary platforms for spatially resolved tissue analysis that are poised for application in life science and personalized medicine. Unlike established clinical in vivo multimodality imaging, automated workflows for in-depth multimodal molecular ex vivo tissue analysis that combine the speed and ease of spectroscopic imaging with molecular details provided by mass spectrometry imaging (MSI) are lagging behind. Here, we present an integrated approach that utilizes non-destructive Fourier transform infrared (FTIR) microscopy and matrix assisted laser desorption/ionization (MALDI) MSI for analysing single-slide tissue specimen...
January 10, 2018: Scientific Reports
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