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https://www.readbyqxmd.com/read/28820749/surgical-pathology-of-gastrointestinal-stromal-tumors-practical-implications-of-morphologic-and-molecular-heterogeneity-for-precision-medicine
#1
Gregory W Charville, Teri A Longacre
Gastrointestinal stromal tumor (GIST), the most common mesenchymal neoplasm of the gastrointestinal tract, exhibits diverse histologic and clinical manifestations. With its putative origin in the gastrointestinal pacemaker cell of Cajal, GIST can arise in association with any portion of the tubular gastrointestinal tract. Morphologically, GISTs are classified as spindled or epithelioid, though each of these subtypes encompasses a broad spectrum of microscopic appearances, many of which mimic other histologic entities...
August 17, 2017: Advances in Anatomic Pathology
https://www.readbyqxmd.com/read/28820527/spatiotemporal-hydrogel-biomaterials-for-regenerative-medicine
#2
REVIEW
Tobin E Brown, Kristi S Anseth
Hydrogels mimic many of the physical properties of soft tissue and are widely used biomaterials for tissue engineering and regenerative medicine. Synthetic hydrogels have been developed to recapitulate many of the healthy and diseased states of native tissues and can be used as a cell scaffold to study the effect of matricellular interactions in vitro. However, these matrices often fail to capture the dynamic and heterogenous nature of the in vivo environment, which varies spatially and during events such as development and disease...
August 18, 2017: Chemical Society Reviews
https://www.readbyqxmd.com/read/28819565/genomic-and-immune-heterogeneity-are-associated-with-differential-responses-to-therapy-in-melanoma
#3
Alexandre Reuben, Christine N Spencer, Peter A Prieto, Vancheswaran Gopalakrishnan, Sangeetha M Reddy, John P Miller, Xizeng Mao, Mariana Petaccia De Macedo, Jiong Chen, Xingzhi Song, Hong Jiang, Pei-Ling Chen, Hannah C Beird, Haven R Garber, Whijae Roh, Khalida Wani, Eveline Chen, Cara Haymaker, Marie-Andrée Forget, Latasha D Little, Curtis Gumbs, Rebecca L Thornton, Courtney W Hudgens, Wei-Shen Chen, Jacob Austin-Breneman, Robert Szczepaniak Sloane, Luigi Nezi, Alexandria P Cogdill, Chantale Bernatchez, Jason Roszik, Patrick Hwu, Scott E Woodman, Lynda Chin, Hussein Tawbi, Michael A Davies, Jeffrey E Gershenwald, Rodabe N Amaria, Isabella C Glitza, Adi Diab, Sapna P Patel, Jianhua Hu, Jeffrey E Lee, Elizabeth A Grimm, Michael T Tetzlaff, Alexander J Lazar, Ignacio I Wistuba, Karen Clise-Dwyer, Brett W Carter, Jianhua Zhang, P Andrew Futreal, Padmanee Sharma, James P Allison, Zachary A Cooper, Jennifer A Wargo
Appreciation for genomic and immune heterogeneity in cancer has grown though the relationship of these factors to treatment response has not been thoroughly elucidated. To better understand this, we studied a large cohort of melanoma patients treated with targeted therapy or immune checkpoint blockade (n = 60). Heterogeneity in therapeutic responses via radiologic assessment was observed in the majority of patients. Synchronous melanoma metastases were analyzed via deep genomic and immune profiling, and revealed substantial genomic and immune heterogeneity in all patients studied, with considerable diversity in T cell frequency, and few shared T cell clones (<8% on average) across the cohort...
2017: NPJ Genomic Medicine
https://www.readbyqxmd.com/read/28818953/new-horizons-for-precision-medicine-in-biliary-tract-cancers
#4
REVIEW
Juan W Valle, Angela Lamarca, Lipika Goyal, Jorge Barriuso, Andrew X Zhu
Biliary tract cancers (BTC), including cholangiocarcinoma and gallbladder cancer, are poor-prognosis and low-incidence cancers, although the incidence of intrahepatic cholangiocarcinoma is rising. A minority of patients present with resectable disease but relapse rates are high; benefit from adjuvant capecitabine chemotherapy has been demonstrated. Cisplatin/gemcitabine combination chemotherapy has emerged as the reference first-line treatment regimen; there is no standard second-line therapy. Selected patients may be suitable for liver-directed therapy (e...
August 17, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28818916/a-pathology-atlas-of-the-human-cancer-transcriptome
#5
Mathias Uhlen, Cheng Zhang, Sunjae Lee, Evelina Sjöstedt, Linn Fagerberg, Gholamreza Bidkhori, Rui Benfeitas, Muhammad Arif, Zhengtao Liu, Fredrik Edfors, Kemal Sanli, Kalle von Feilitzen, Per Oksvold, Emma Lundberg, Sophia Hober, Peter Nilsson, Johanna Mattsson, Jochen M Schwenk, Hans Brunnström, Bengt Glimelius, Tobias Sjöblom, Per-Henrik Edqvist, Dijana Djureinovic, Patrick Micke, Cecilia Lindskog, Adil Mardinoglu, Fredrik Ponten
Cancer is one of the leading causes of death, and there is great interest in understanding the underlying molecular mechanisms involved in the pathogenesis and progression of individual tumors. We used systems-level approaches to analyze the genome-wide transcriptome of the protein-coding genes of 17 major cancer types with respect to clinical outcome. A general pattern emerged: Shorter patient survival was associated with up-regulation of genes involved in cell growth and with down-regulation of genes involved in cellular differentiation...
August 18, 2017: Science
https://www.readbyqxmd.com/read/28818298/enhancing-the-pediatric-drug-development-framework-to-deliver-better-pediatric-therapies-tomorrow
#6
Christina Bucci-Rechtweg
Health care professionals involved in the clinical management of children have long appreciated the limited number of therapies suitably evaluated for their optimal use in the pediatric population. In the past century, advances in regulatory policy significantly evolved adult drug evaluation. The scarcity of available patient populations, practical complexities of drug development research, and minimal financial returns have hampered pharmaceutical investment in the study of therapies for children. More recently, pediatric policy and legislation in the United States and Europe have instituted a system of obligations and incentives to stimulate investment in pediatric drug development...
August 14, 2017: Clinical Therapeutics
https://www.readbyqxmd.com/read/28818163/evaluation-of-ckd-epi-pakistan-equation-for-estimated-glomerular-filtration-rate-egfr-acomparison-of-egfr-prediction-equations-in-pakistani-population
#7
Sibtain Ahmed, Lena Jafri, Aysha Habib Khan
OBJECTIVE: To evaluate the results of 24-hour urinary creatinine clearance (CrCl) with estimated glomerular filtration rate (eGFR) using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI), CKD-EPI Pakistan (CKD-EPI Pak), Cockcroft Gault (CG) and 4-variable Modification of Diet in Renal Disease (MDRD) equations. STUDY DESIGN: Descriptive, cross-sectional study. PLACE AND DURATION OF STUDY: Section of Clinical Chemistry, Department of Pathology and Laboratory Medicine, The Aga Khan University, Karachi, from June to October 2013...
July 2017: Journal of the College of Physicians and Surgeons—Pakistan: JCPSP
https://www.readbyqxmd.com/read/28818039/the-impact-of-rna-sequence-library-construction-protocols-on-transcriptomic-profiling-of-leukemia
#8
Ashwini Kumar, Matti Kankainen, Alun Parsons, Olli Kallioniemi, Pirkko Mattila, Caroline A Heckman
BACKGROUND: RNA sequencing (RNA-seq) has become an indispensable tool to identify disease associated transcriptional profiles and determine the molecular underpinnings of diseases. However, the broad adaptation of the methodology into the clinic is still hampered by inconsistent results from different RNA-seq protocols and involves further evaluation of its analytical reliability using patient samples. Here, we applied two commonly used RNA-seq library preparation protocols to samples from acute leukemia patients to understand how poly-A-tailed mRNA selection (PA) and ribo-depletion (RD) based RNA-seq library preparation protocols affect gene fusion detection, variant calling, and gene expression profiling...
August 17, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28817531/bias-confounding-and-interaction-lions-and-tigers-and-bears-oh-my
#9
Thomas R Vetter, Edward J Mascha
Epidemiologists seek to make a valid inference about the causal effect between an exposure and a disease in a specific population, using representative sample data from a specific population. Clinical researchers likewise seek to make a valid inference about the association between an intervention and outcome(s) in a specific population, based upon their randomly collected, representative sample data. Both do so by using the available data about the sample variable to make a valid estimate about its corresponding or underlying, but unknown population parameter...
September 2017: Anesthesia and Analgesia
https://www.readbyqxmd.com/read/28817233/evaluation-and-quantitative-analysis-of-11-compounds-in-morinda-officinalis-using-ultra-high-performance-liquid-chromatography-and-photodiode-array-detection-coupled-with-chemometrics
#10
Xiangsheng Zhao, Weijun Kong, Yakui Zhou, Jianhe Wei, Meihua Yang
Morinda officinalis (Rubiaceae) is a traditional Chinese medicine widely used for the treatment of impotence and osteoporosis in clinical therapy. In the present study, a rapid and simple ultra high performance liquid chromatography with photodiode array detection method was developed and validated for the simultaneous determination of 11 bioactive compounds in M. officinalis. This assay method was validated with respect to linearity (R(2)( ) > 0.9991), precision, repeatability, limit of detection, limit of quantification, and accuracy (with observed recovery rates between 94...
August 17, 2017: Journal of Separation Science
https://www.readbyqxmd.com/read/28816646/chronic-cigarette-smoke-mediated-global-changes-in-lung-mucoepidermoid-cells-a-phosphoproteomic-analysis
#11
Hitendra S Solanki, Jayshree Advani, Aafaque Ahmad Khan, Aneesha Radhakrishnan, Nandini A Sahasrabuddhe, Sneha M Pinto, Xiaofei Chang, Thottethodi Subrahmanya Keshava Prasad, Premendu Prakash Mathur, David Sidransky, Harsha Gowda, Aditi Chatterjee
Proteomics analysis of chronic cigarette smoke exposure is a rapidly emerging postgenomics research field. While smoking is a major cause of lung cancer, functional studies using proteomics approaches could enrich our mechanistic understanding of the elusive lung cancer global molecular signaling and cigarette smoke relationship. We report in this study on a stable isotope labeling by amino acids in cell culture-based quantitative phosphoproteomic analysis of a human lung mucoepidermoid carcinoma cell line, H292 cells, chronically exposed to cigarette smoke...
August 2017: Omics: a Journal of Integrative Biology
https://www.readbyqxmd.com/read/28816643/pharmacometabolomics-informs-quantitative-radiomics-for-glioblastoma-diagnostic-innovation
#12
Theodora Katsila, Minos-Timotheos Matsoukas, George P Patrinos, Dimitrios Kardamakis
Applications of omics systems biology technologies have enormous promise for radiology and diagnostics in surgical fields. In this context, the emerging fields of radiomics (a systems scale approach to radiology using a host of technologies, including omics) and pharmacometabolomics (use of metabolomics for patient and disease stratification and guiding precision medicine) offer much synergy for diagnostic innovation in surgery, particularly in neurosurgery. This synthesis of omics fields and applications is timely because diagnostic accuracy in central nervous system tumors still challenges decision-making...
August 2017: Omics: a Journal of Integrative Biology
https://www.readbyqxmd.com/read/28816146/quality-assessment-of-stereotactic-radiosurgery-of-a-melanoma-brain-metastases-model-using-a-mouselike-phantom-and-the-small-animal-radiation-research-platform
#13
Cheng-Chia Wu, Kunal R Chaudhary, Yong Hum Na, David Welch, Paul J Black, Adam M Sonabend, Peter Canoll, Yvonne M Saenger, Tony J C Wang, Cheng-Shie Wuu, Tom K Hei, Simon K Cheng
PURPOSE: To establish a novel preclinical model for stereotactic radiosurgery (SRS) with combined mouselike phantom quality assurance in the setting of brain metastases. METHODS AND MATERIALS: C57B6 mice underwent intracranial injection of B16-F10 melanoma cells. T1-weighted postcontrast magnetic resonance imaging (MRI) was performed on day 11 after injection. The MRI images were fused with cone beam computed tomography (CBCT) images using the Small Animal Radiation Research Platform (SARRP)...
September 1, 2017: International Journal of Radiation Oncology, Biology, Physics
https://www.readbyqxmd.com/read/28815633/the-gas-that-fuels-the-engine-individuals-motivations-for-medicalisation
#14
Ann V Bell
It is well established that the drivers of medicalisation have shifted alongside changes in the institution of medicine. The process of medicalisation is no longer incited by macro processes of institutional prestige or control; rather, individual patients/consumers are pushing the process forward. The present study complicates this neat transition and examines the relationship between structure and agency using the case of assisted reproductive technology (ART), specifically the medicalisation of lesbian reproduction in the US...
August 16, 2017: Sociology of Health & Illness
https://www.readbyqxmd.com/read/28815129/sdt-a-tree-method-for-detecting-patient-subgroups-with-personalized-risk-factors
#15
Xiangrui Li, Dongxiao Zhu, Ming Dong, Milad Zafar Nezhad, Alexander Janke, Phillip D Levy
Eradicating health disparity is a new focus for precision medicine research. Identifying patient subgroups is an effective approach to customized treatments for maximizing efficiency in precision medicine. Some features may be important risk factors for specific patient subgroups but not necessarily for others, resulting in a potential divergence in treatments designed for a given population. In this paper, we propose a tree-based method, called Subgroup Detection Tree (SDT), to detect patient subgroups with personalized risk factors...
2017: AMIA Summits on Translational Science Proceedings
https://www.readbyqxmd.com/read/28815127/a-knowledge-based-system-for-intelligent-support-in-pharmacogenomics-evidence-assessment-ontology-driven-evidence-representation-and-retrieval
#16
Chia-Ju Lee, Beth Devine, Peter Tarczy-Hornoch
Pharmacogenomics holds promise as a critical component of precision medicine. Yet, the use of pharmacogenomics in routine clinical care is minimal, partly due to the lack of efficient and effective use of existing evidence. This paper describes the design, development, implementation and evaluation of a knowledge-based system that fulfills three critical features: a) providing clinically relevant evidence, b) applying an evidence-based approach, and c) using semantically computable formalism, to facilitate efficient evidence assessment to support timely decisions on adoption of pharmacogenomics in clinical care...
2017: AMIA Summits on Translational Science Proceedings
https://www.readbyqxmd.com/read/28815117/systematic-analysis-of-free-text-family-history-in-electronic-health-record
#17
Yanshan Wang, Liwei Wang, Majid Rastegar-Mojarad, Sijia Liu, Feichen Shen, Hongfang Liu
Family history is an important component in modern clinical care especially in the era of precision medicine. Family history information in the Electronic Health Record (EHR) system is usually stored in structured format as well as in free-text format. In this study, we systematically analyzed a family history text corpus from 3 million clinical notes for the patients receiving their primary care at Mayo Clinic. Family members, medical problems, and their associations were analyzed and reported. Our findings showed a great agreement between positive/negated medical problems mentioned in the diagnosis report and the family history, as measured by observed agreement and random agreement...
2017: AMIA Summits on Translational Science Proceedings
https://www.readbyqxmd.com/read/28815101/characterizing-the-strength-of-evidence-in-fda-labels-for-pharmacogenomic-biomarker-guided-medication-use
#18
Lauren Chin, Beth Devine, Sarah Baradaran, Katelyn Keyloun, William Canestaro, Jonathan Pham
There is great heterogeneity in drug treatment response that is thought to be due to individual-level allelic variation in pharmacogenomic biomarkers. FDA Drug Labels provide information to guide pharmacogenomic biomarker use. Yet, the strength of evidence for clinical validity and clinical utility is lacking. We characterized the strength of evidence and treatment recommendations contained in FDA Drug Labels as of December 2015. Pharmacogenomic biomarker information was provided for 137 drugs, involving 49 pharmacogenomic biomarkers, constituting 166 drug-biomarker pairs...
2017: AMIA Summits on Translational Science Proceedings
https://www.readbyqxmd.com/read/28815099/enabling-comprehension-of-patient-subgroups-and-characteristics-in-large-bipartite-networks-implications-for-precision-medicine
#19
Suresh K Bhavnani, Tianlong Chen, Archana Ayyaswamy, Shyam Visweswaran, Gowtham Bellala, Divekar Rohit, Bassler Kevin E
A primary goal of precision medicine is to identify patient subgroups based on their characteristics (e.g., comorbidities or genes) with the goal of designing more targeted interventions. While network visualization methods such as Fruchterman-Reingold have been used to successfully identify such patient subgroups in small to medium sized data sets, they often fail to reveal comprehensible visual patterns in large and dense networks despite having significant clustering. We therefore developed an algorithm called ExplodeLayout, which exploits the existence of significant clusters in bipartite networks to automatically "explode" a traditional network layout with the goal of separating overlapping clusters, while at the same time preserving key network topological properties that are critical for the comprehension of patient subgroups...
2017: AMIA Summits on Translational Science Proceedings
https://www.readbyqxmd.com/read/28813679/the-tumor-suppressor-p53-limits-ferroptosis-by-blocking-dpp4-activity
#20
Yangchun Xie, Shan Zhu, Xinxin Song, Xiaofang Sun, Yong Fan, Jinbao Liu, Meizuo Zhong, Hua Yuan, Lin Zhang, Timothy R Billiar, Michael T Lotze, Herbert J Zeh, Rui Kang, Guido Kroemer, Daolin Tang
Ferroptosis is a form of regulated cell death that may facilitate the selective elimination of tumor cells. The tumor suppressor p53 (TP53) has been demonstrated to promote ferroptosis via a transcription-dependent mechanism. Here, we show that TP53 limits erastin-induced ferroptosis by blocking dipeptidyl-peptidase-4 (DPP4) activity in a transcription-independent manner. Loss of TP53 prevents nuclear accumulation of DPP4 and thus facilitates plasma-membrane-associated DPP4-dependent lipid peroxidation, which finally results in ferroptosis...
August 15, 2017: Cell Reports
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