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https://www.readbyqxmd.com/read/27926889/precision-medicine-diabetes-and-the-u-s-food-and-drug-administration
#1
Robert J Meyer
The U.S. Food and Drug Administration (FDA) has long sought to achieve the broader use of personalized medicine, which is better targeting of FDA-approved therapies through incorporating precise knowledge of a patient's underlying condition to therapies optimally chosen to match those needs. While some strides have been made in precision medicine-particularly in oncology and rare genetic diseases-most of the standard general medicine indications have yet to realize the benefits of precision-guided therapies...
November 2016: Diabetes Care
https://www.readbyqxmd.com/read/27926828/harnessing-cancer-cell-metabolism-for-theranostic-applications-using-metabolic-glycoengineering-of-sialic-acid-in-breast-cancer-as-a-pioneering-example
#2
REVIEW
Haitham A Badr, Dina M M AlSadek, Motawa E El-Houseini, Christopher T Saeui, Mohit P Mathew, Kevin J Yarema, Hafiz Ahmed
Abnormal cell surface display of sialic acids - a family of unusual 9-carbon sugars - is widely recognized as distinguishing feature of many types of cancer. Sialoglycans, however, typically cannot be identified with sufficiently high reproducibility and sensitivity to serve as clinically accepted biomarkers and similarly, almost all efforts to exploit cancer-specific differences in sialylation signatures for therapy remain in early stage development. In this report we provide an overview of important facets of glycosylation that contribute to cancer in general with a focus on breast cancer as an example of malignant disease characterized by aberrant sialylation...
November 25, 2016: Biomaterials
https://www.readbyqxmd.com/read/27926778/met-tyrosine-kinase-receptor-expression-and-amplification-as-prognostic-biomarkers-of-survival-in-gastroesophageal-adenocarcinoma
#3
Daniel V T Catenacci, Agnes Ang, Wei-Li Liao, Jing Shen, Emily O'Day, Robert D Loberg, Fabiola Cecchi, Todd Hembrough, Annamaria Ruzzo, Francesco Graziano
BACKGROUND: MET gene amplification and Met protein overexpression may be associated with a poor prognosis. The MET/Met status is typically determined with fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC), respectively. Targeted proteomics uses mass spectrometry-based selected reaction monitoring (SRM) to accurately quantitate Met expression. FISH, IHC, and SRM analyses were compared to characterize the prognostic value of MET/Met in gastroesophageal adenocarcinoma (GEC)...
December 7, 2016: Cancer
https://www.readbyqxmd.com/read/27926736/structure-of-cc-chemokine-receptor-2-with-orthosteric-and-allosteric-antagonists
#4
Yi Zheng, Ling Qin, Natalia V Ortiz Zacarías, Henk de Vries, Gye Won Han, Martin Gustavsson, Marta Dabros, Chunxia Zhao, Robert J Cherney, Percy Carter, Dean Stamos, Ruben Abagyan, Vadim Cherezov, Raymond C Stevens, Adriaan P IJzerman, Laura H Heitman, Andrew Tebben, Irina Kufareva, Tracy M Handel
CC chemokine receptor 2 (CCR2) is one of 19 members of the chemokine receptor subfamily of human class A G-protein-coupled receptors. CCR2 is expressed on monocytes, immature dendritic cells, and T-cell subpopulations, and mediates their migration towards endogenous CC chemokine ligands such as CCL2 (ref. 1). CCR2 and its ligands are implicated in numerous inflammatory and neurodegenerative diseases including atherosclerosis, multiple sclerosis, asthma, neuropathic pain, and diabetic nephropathy, as well as cancer...
December 7, 2016: Nature
https://www.readbyqxmd.com/read/27926691/on-treatment-blood-pressures-of-older-hypertensive-patients-in-canada-implications-for-systolic-blood-pressure-intervention-trial
#5
Jiri George Fodor, Penelope Baker, Li Chen, Frans H H Leenen
OBJECTIVE: The therapeutic target level for the blood pressure (BP) on antihypertensive drug treatment in older hypertensive patients is still extensively debated. We assessed the achieved BP levels in older treated hypertensive patients in a representative sample of the population. DESIGN: During the 2006 Ontario Survey on the Prevalence and Control of Hypertension, BP (using the SPRINT protocol) and treatment data were collected in 2551 respondents from a random and representative sample of the adult (20-79 years) population...
December 6, 2016: Journal of Hypertension
https://www.readbyqxmd.com/read/27926541/major-unanswered-questions-in-the-clinical-gout-field
#6
Lisa K Stamp
PURPOSE OF REVIEW: Although gout is one of the most common forms of inflammatory arthritis, it has been relatively neglected until recently. Despite progress in many areas of pathophysiology and genetics of gout and the development of new urate lowering therapies, there remain a number of unanswered clinical questions. With the resurgence of interest in gout it is important to recognize key aspects of gout management that remain challenging and require further research. RECENT FINDINGS: The unanswered clinical issues outlined in this review are basic aspects of gout management that clinicians treating people with gout face on a daily basis and include when urate lowering therapy should be commenced, the most appropriate target serum urate, use of prophylaxis when starting urate lowering therapy and the most appropriate urate lowering therapy, particularly for those with chronic kidney disease...
December 6, 2016: Current Opinion in Rheumatology
https://www.readbyqxmd.com/read/27926532/novel-parp1-2-inhibitor-mefuparib-hydrochloride-elicits-potent-in-vitro-and-in-vivo-anticancer-activity-characteristic-of-high-tissue-distribution
#7
Jin-Xue He, Meng Wang, Xia-Juan Huan, Chuan-Huizi Chen, Shan-Shan Song, Ying-Qing Wang, Xue-Mei Liao, Cun Tan, Qian He, Lin-Jiang Tong, Yu-Ting Wang, Xiao-Hua Li, Yi Su, Yan-Yan Shen, Yi-Ming Sun, Xin-Ying Yang, Yi Chen, Zhi-Wei Gao, Xiao-Yan Chen, Bing Xiong, Xiu-Lian Lu, Jian Ding, Chun-Hao Yang, Ze-Hong Miao
The approval of poly(ADP-ribose) polymerase (PARP) inhibitor AZD2281 in 2014 marked the successful establishment of the therapeutic strategy targeting homologous recombination repair defects of cancers in the clinic. However, AZD2281 has poor water solubility, low tissue distribution and relatively weak in vivo anticancer activity, which appears to become limiting factors for its clinical use. In this study, we found that mefuparib hydrochloride (MPH) was a potent PARP inhibitor, possessing prominent in vitro and in vivo anticancer activity...
December 1, 2016: Oncotarget
https://www.readbyqxmd.com/read/27926525/apoptosis-linked-gene-2-promotes-breast-cancer-growth-and-metastasis-by-regulating-the-cytoskeleton
#8
Juan Qin, Dengwen Li, Yunqiang Zhou, Songbo Xie, Xin Du, Ziwei Hao, Ruming Liu, Xinqi Liu, Min Liu, Jun Zhou
Breast cancer is the most prevalent cancer in women. Although it begins as local disease, breast cancer frequently metastasizes to the lymph nodes and distant organs. Therefore, novel therapeutic targets are needed for the management of this disease. Apoptosis-linked gene 2 (ALG-2) is a calcium-binding protein crucial for diverse physiological processes and has recently been implicated in cancer development. However, it remains unclear whether this protein is involved in the pathogenesis of breast cancer. Here, we demonstrate that the expression of ALG-2 is significantly upregulated in breast cancer tissues and is correlated with clinicopathological characteristics indicative of tumor malignancy...
December 1, 2016: Oncotarget
https://www.readbyqxmd.com/read/27926512/depression-of-oncogenecity-by-dephosphorylating-and-degrading-bcr-abl
#9
Miao Gao, Zheng-Lan Huang, Kun Tao, Qing Xiao, Xin Wang, Wei-Xi Cao, Min Xu, Jing Hu, Wen-Li Feng
Aberrant phosphorylation and overexpression of BCR-ABL fusion protein are responsible for the main pathogenesis in chronic myeloid leukemia (CML). Phosphorylated BCR-ABL Y177 recruits GRB2 adaptor and triggers leukemic RAS-MAPK and PI3K-AKT signals. In this study, we engineered a SPOA system to dephosphorylate and degrade BCR-ABL by targeting BCR-ABL Y177. We tested its effect on BCR-ABL phosphorylation and expression, as well as cell proliferation and apoptosis in CML cells. We found that SPOA remarkably dephosphorylated BCR-ABL Y177, prevented GRB2 recruitment, and uncoupled RAS-MAPK and PI3K-AKT signals...
December 1, 2016: Oncotarget
https://www.readbyqxmd.com/read/27926500/the-association-between-clinical-prognostic-factors-and-epidermal-growth-factor-receptor-tyrosine-kinase-inhibitor-egfr-tki-efficacy-in-advanced-non-small-cell-lung-cancer-patients-a-retrospective-assessment-of-94-cases-with-egfr-mutations
#10
Jing-Hui Lin, Dong Lin, Ling Xu, Qiang Wang, Hui-Hua Hu, Hai-Peng Xu, Zhi-Yong He
OBJECTIVE: This study aimed to examine the association of clinical prognostic factors with epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) efficacy in advanced non-small-cell lung cancer (NSCLC) patients. METHODS: The demographic and clinical characteristics of 94 patients with stage IV NSCLC were retrospectively reviewed, and the association between clinical factors and EGFR-TKIs efficacy was evaluated. RESULTS: Of the 94 stage IV NSCLC patients enrolled in this study, a 74...
December 3, 2016: Oncotarget
https://www.readbyqxmd.com/read/27926493/developmental-therapeutics-for-inflammatory-breast-cancer-biology-and-translational-directions
#11
REVIEW
Ricardo Costa, Cesar A Santa-Maria, Giovanna Rossi, Benedito A Carneiro, Young Kwang Chae, William J Gradishar, Francis J Giles, Massimo Cristofanilli
Inflammatory breast cancer (IBC) is a rare and aggressive form of breast cancer, which accounts for approximately 3% of cases of breast malignancies. Diagnosis relies largely on its clinical presentation, and despite a characteristic phenotype, underlying molecular mechanisms are poorly understood. Unique clinical presentation indicates that IBC is a distinct clinical and biological entity when compared to non-IBC. Biological understanding of non-IBC has been extrapolated into IBC and targeted therapies for HER2 positive (HER2+) and hormonal receptor positive non-IBC led to improved patient outcomes in the recent years...
December 2, 2016: Oncotarget
https://www.readbyqxmd.com/read/27926485/axitinib-induces-senescence-associated-cell-death-and-necrosis-in-glioma-cell-lines-the-proteasome-inhibitor-bortezomib-potentiates-axitinib-induced-cytotoxicity-in-a-p21-waf-cip1-dependent-manner
#12
Maria Beatrice Morelli, Consuelo Amantini, Massimo Nabissi, Claudio Cardinali, Matteo Santoni, Giovanni Bernardini, Angela Santoni, Giorgio Santoni
Glioblastoma is associated with a poor overall survival despite new treatment advances. Antiangiogenic strategies targeting VEGF based on tyrosine kinase inhibitors (TKIs) are currently undergoing extensive research for the treatment of glioma.Herein we demonstrated that the TKI axitinib induces DNA damage response (DDR) characterized by γ-H2AX phosphorylation and Chk1 kinase activation leading to G2/M cell cycle arrest and mitotic catastrophe in U87, T98 and U251 glioma cell lines. Moreover, we found that p21(Waf1/Cip1) increased levels correlates with induction of ROS and senescence-associated cell death in U87 and T98 cell lines, which are reverted by N-acetyl cysteine pretreatment...
December 1, 2016: Oncotarget
https://www.readbyqxmd.com/read/27926382/prediction-of-anti-cancer-drug-response-by-kernelized-multi-task-learning
#13
Mehmet Tan
MOTIVATION: Chemotherapy or targeted therapy are two of the main treatment options for many types of cancer. Due to the heterogeneous nature of cancer, the success of the therapeutic agents differs among patients. In this sense, determination of chemotherapeutic response of the malign cells is essential for establishing a personalized treatment protocol and designing new drugs. With the recent technological advances in producing large amounts of pharmacogenomic data, in silico methods have become important tools to achieve this aim...
October 2016: Artificial Intelligence in Medicine
https://www.readbyqxmd.com/read/27925850/metallic-taste-in-cancer-patients-treated-with-systemic-therapy-a-questionnaire-based-study
#14
Irene IJpma, Erik R Timmermans, Remco J Renken, Gert J Ter Horst, Anna K L Reyners
A metallic taste is reported by cancer patients as a side effect of systemic therapy. Despite the high prevalence, this taste alteration has received limited attention. The present study investigated: 1) the prevalence of metallic taste in cancer patients treated with systemic therapy; 2) possible predictors of metallic taste; and 3) characteristics of metallic taste. A heterogeneous population of 127 cancer patients, who had received systemic treatment in the past year or were still on treatment, completed a questionnaire developed for this study...
December 7, 2016: Nutrition and Cancer
https://www.readbyqxmd.com/read/27925796/a-severe-asthma-disease-signature-from-gene-expression-profiling-of-peripheral-blood-from-u-biopred-cohorts
#15
Jeannette Bigler, Michael Boedigheimer, James P R Schofield, Paul J Skipp, Julie Corfield, Anthony Rowe, Ana R Sousa, Martin Timour, Lori Twehues, Xuguang Hu, Graham Roberts, Andrew A Welcher, Wen Yu, Kian F Chung, Ian M Adcock, Peter J Sterk, Ratko Djukanović
RATIONALE: Stratification of asthma at the molecular level, especially using accessible biospecimens, could greatly enable patient selection for targeted therapy. OBJECTIVES: To determine the value of blood to identify transcriptional differences between clinically defined asthmatic and non-asthmatic groups, identify potential patient subgroups based on gene expression, and explore biological pathways associated with identified differences. METHODS: Transcriptomics profiles were generated by microarray analysis of blood from 610 asthmatic and control participants in U-BIOPRED...
December 7, 2016: American Journal of Respiratory and Critical Care Medicine
https://www.readbyqxmd.com/read/27925609/a-comparison-of-virological-suppression-and-rebound-between-indigenous-and-non-indigenous-persons-initiating-combination-antiretroviral-therapy-in-a-multisite-cohort-of-individuals-living-with-hiv-in-canada
#16
Anita C Benoit, Jaime Younger, Kerrigan Beaver, Randy Jackson, Mona Loutfy, Renée Masching, Tony Nobis, Earl Nowgesic, Doe O'Brien-Teengs, Wanda Whitebird, Art Zoccole, Mark Hull, Denise Jaworsky, Anita Rachlis, Sean Rourke, Ann N Burchell, Curtis Cooper, Robert Hogg, Marina B Klein, Nima Machouf, Julio Montaner, Chris Tsoukas, Janet Raboud, Building Bridges
BACKGROUND: This study compared time to virologic suppression and rebound between Indigenous and non-Indigenous individuals living with HIV in Canada initiating combination antiretroviral therapy (cART). METHODS: Data were from the Canadian Observational Cohort collaboration; 8 studies of treatment-naïve persons with HIV initiating cART after 1/1/2000. Fine and Gray models were used to estimate the effect of ethnicity on 1) time to virologic suppression (two consecutive viral loads (VLs) <50 copies/mL at least three months apart) after adjusting for the competing risk of death and 2) time until virologic rebound (two consecutive VLs >200 copies/mL at least three months apart) following suppression...
December 7, 2016: Antiviral Therapy
https://www.readbyqxmd.com/read/27925473/the-role-of-cancer-stem-cells-in-tumor-heterogeneity-and-resistance-to-therapy
#17
Christina Valbirk Konrad, Reshma Murali, Binitha Anu Varghese, Radhika Nair
Cancer is a heterogenous disease displaying marked inter- and intra-tumoral diversity. The existence of cancer stem cells (CSCs) has been experimentally demonstrated in a number of cancer types as a subpopulation of tumor cells that drives the tumorigenic and metastatic properties of the entire cancer. Thus, eradication of the CSC population is critical for the complete ablation of a tumor. This is, however, confounded by the inherent resistance of CSCs to standard anticancer therapies, eventually leading to the outgrowth of resistant tumor cells and relapse in patients...
September 3, 2016: Canadian Journal of Physiology and Pharmacology
https://www.readbyqxmd.com/read/27925407/population-level-decline-in-bmi-and-systolic-blood-pressure-following-mass-hiv-treatment-evidence-from-rural-kwazulu-natal
#18
Pascal Geldsetzer, Andrea B Feigl, Frank Tanser, Dickman Gareta, Deenan Pillay, Till Bärnighausen
OBJECTIVE: Clinic-based studies have shown that patients with human immunodeficiency virus (HIV) gain weight after initiation of antiretroviral therapy (ART). This study aimed to determine whether the scale-up of ART was associated with a population-level increase in body mass index (BMI) and blood pressure (BP) in a community with high HIV and obesity prevalence. METHODS: A household survey was conducted in rural KwaZulu-Natal before ART scale-up (in 2004) and when ART coverage had reached 25% (in 2010)...
December 7, 2016: Obesity
https://www.readbyqxmd.com/read/27925310/prognostic-factors-in-patients-with-stemi-undergoing-primary-pci-in-the-clopidogrel-era-role-of-dual-antiplatelet-therapy-at-admission-and-the-smoking-paradox-on-long-term-outcome
#19
Giovanni Ciccarelli, Emanuele Barbato, Marco Golino, Giovanni Cimmino, Jozef Bartunek, Luigi Di Serafino, Domenico Di Girolamo, Bernard De Bruyne, William Wijns, Paolo Golino
BACKGROUND: Several clinical and laboratory variables have an impact on the prognosis of STEMI patients undergoing PPCI; however, little is known about the role of ongoing DAPT at the time of the event and the smoking status as prognostic factors affecting the outcome of these patients. METHODS AND RESULTS: Seven-hundred and thirteen consecutive STEMI patients undergoing PPCI, admitted to the S. Anna and S. Sebastiano Hospital (Caserta, Italy) and to the OLV Clinic (Aalst, Belgium), between March 2009 and December 2011, were retrospectively enrolled...
December 7, 2016: Journal of Interventional Cardiology
https://www.readbyqxmd.com/read/27925201/vascular-inter-regulation-of-inflammation-molecular-and-cellular-targets-for-cns-therapy
#20
REVIEW
Marta Machado-Pereira, Tiago Santos, Liliana Bernardino, Raquel Ferreira
Angiogenesis and inflammation are clearly interconnected and interdependent processes that are dysregulated in a series of systemic and brain pathologies. Herein, key aspects regarding endothelial cell function and tissue remodelling that are particularly affected or aggravated by inflammation are presented. Most importantly, the cellular and molecular mechanisms involved in the vascular regulation of the inflammatory processes occurring in several brain disorders and how they impact on disease/injury progression are detailed, highlighting potential targets for therapy...
December 7, 2016: Journal of Neurochemistry
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