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BIOMARKERS ADME

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https://www.readbyqxmd.com/read/27788482/reg-proteins-promote-acinar-to-ductal-metaplasia-and-act-as-novel-diagnostic-and-prognostic-markers-in-pancreatic-ductal-adenocarcinoma
#1
Qing Li, Hao Wang, George Zogopoulos, Qin Shao, Kun Dong, Fudong Lv, Karam Nwilati, Xian-Yong Gui, Adeline Cuggia, Jun-Li Liu, Zu-Hua Gao
Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive malignant tumor. Acinar-to-ductal metaplasia (ADM) and pancreatic intraepithelial neoplasia (PanIN) are both precursor lesions that lead to the development of PDAC. Reg family proteins (Reg1A, 1B, 3A/G, 4) are a group of calcium-dependent lectins that promote islet growth in response to inflammation and/or injuries. The aim of this study was to establish a role for Reg proteins in the development of PDAC and their clinical value as biomarkers. We found that Reg1A and Reg3A/G were highly expressed in the ADM tissues by immunohistochemistry...
October 24, 2016: Oncotarget
https://www.readbyqxmd.com/read/27713887/new-role-of-biomarkers-mid-regional-pro-adrenomedullin-the-biomarker-of-organ-failure
#2
Francisco Valenzuela-Sánchez, Blanca Valenzuela-Méndez, Juan Francisco Rodríguez-Gutiérrez, Ángel Estella-García, María Ángela González-García
Mid-regional pro-adrenomedullin (MR-proADM) has a good biomarker profile: its half-life is several hours, and its plasma concentrations can be determined in clinical practice, it is essentially irrelevant, but proportionally represents the levels and activity of adrenomedullin (ADM). ADM synthesis is widely distributed in tissues, including bone, adrenal cortex, kidney, lung, blood vessels and heart. Its fundamental biological effects include vasodilator, positive inotropic, diuretic, natriuretic and bronchodilator...
September 2016: Annals of Translational Medicine
https://www.readbyqxmd.com/read/27669316/osanalyzer-a-bioinformatics-tool-for-the-analysis-of-gene-polymorphisms-enriched-with-clinical-outcomes
#3
Giuseppe Agapito, Cirino Botta, Pietro Hiram Guzzi, Mariamena Arbitrio, Maria Teresa Di Martino, Pierfrancesco Tassone, Pierosandro Tagliaferri, Mario Cannataro
BACKGROUND: The identification of biomarkers for the estimation of cancer patients' survival is a crucial problem in modern oncology. Recently, the Affymetrix DMET (Drug Metabolizing Enzymes and Transporters) microarray platform has offered the possibility to determine the ADME (absorption, distribution, metabolism, and excretion) gene variants of a patient and to correlate them with drug-dependent adverse events. Therefore, the analysis of survival distribution of patients starting from their profile obtained using DMET data may reveal important information to clinicians about possible correlations among drug response, survival rate, and gene variants...
2016: Microarrays
https://www.readbyqxmd.com/read/27559615/synthesis-and-biological-evaluation-of-n-1-4-sulfonyl-piperazin-1-yl-cycloalkyl-methyl-benzamide-inhibitors-of-glycine-transporter-1
#4
Christopher L Cioffi, Shuang Liu, Mark A Wolf, Peter R Guzzo, Kashinath Sadalapure, Visweswaran Parthasarathy, David T J Loong, Jun-Ho Maeng, Edmund Carulli, Xiao Fang, Kalesh Karunakaran, Lakshman Matta, Sok Hui Choo, Shailijia Panduga, Ronald N Buckle, Randall N Davis, Samuel A Sakwa, Priya Gupta, Bruce J Sargent, Nicholas A Moore, Michele M Luche, Grant J Carr, Yuri L Khmelnitsky, Jiffry Ismail, Mark Chung, Mei Bai, Wei Yee Leong, Nidhi Sachdev, Srividya Swaminathan, Andrew J Mhyre
We previously disclosed the discovery of rationally designed N-((1-(4-(propylsulfonyl)piperazin-1-yl)cycloalkyl)methyl)benzamide inhibitors of glycine transporter-1 (GlyT-1), represented by analogues 10 and 11. We describe herein further structure-activity relationship exploration of this series via an optimization strategy that primarily focused on the sulfonamide and benzamide appendages of the scaffold. These efforts led to the identification of advanced leads possessing a desirable balance of excellent in vitro GlyT-1 potency and selectivity, favorable ADME and in vitro pharmacological profiles, and suitable pharmacokinetic and safety characteristics...
September 22, 2016: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/27533451/serum-protein-fingerprinting-by-pea-immunoassay-coupled-with-a-pattern-recognition-algorithms-distinguishes-mgus-and-multiple-myeloma
#5
Petra Schneiderova, Tomas Pika, Petr Gajdos, Regina Fillerova, Pavel Kromer, Milos Kudelka, Jiri Minarik, Tomas Papajik, Vlastimil Scudla, Eva Kriegova
Serum protein fingerprints associated with MGUS and MM and their changes in MM after autologous stem cell transplantation (MM-ASCT, day 100) remain unexplored. Using highly-sensitive Proximity Extension ImmunoAssay on 92 cancer biomarkers (Proseek Multiplex, Olink), enhanced serum levels of Adrenomedullin (ADM, Pcorr= .0004), Growth differentiation factor 15 (GDF15, Pcorr= .003), and soluble Major histocompatibility complex class I-related chain A (sMICA, Pcorr= .023), all prosurvival and chemoprotective factors for myeloma cells, were detected in MM comparing to MGUS...
August 12, 2016: Oncotarget
https://www.readbyqxmd.com/read/27363516/the-metabolome-of-2-14-c-epicatechin-in-humans-implications-for-the-assessment-of-efficacy-safety-and-mechanisms-of-action-of-polyphenolic-bioactives
#6
Javier I Ottaviani, Gina Borges, Tony Y Momma, Jeremy P E Spencer, Carl L Keen, Alan Crozier, Hagen Schroeter
Diet is a major life style factor affecting human health, thus emphasizing the need for evidence-based dietary guidelines for primary disease prevention. While current recommendations promote intake of fruit and vegetables, we have limited understanding of plant-derived bioactive food constituents other than those representing the small number of essential nutrients and minerals. This limited understanding can be attributed to some extent to a lack of fundamental data describing the absorption, distribution, metabolism and excretion (ADME) of bioactive compounds...
2016: Scientific Reports
https://www.readbyqxmd.com/read/27237819/the-role-of-cancer-biomarkers-in-hiv-infected-hosts
#7
REVIEW
Domenico Galati, Serena Zanotta
A higher incidence of cancer has been observed in Human Immunodeficiency Virus (HIV) infected individuals as compared with healthy people of the same age. A complex relationship between HIV-induced immune suppression, chronic antigenic stimulation, and oncogenic virus co-infections may promote carcinogenesis and increase the risk of developing tumors in these patients. Cancers in HIV subjects include the AIDS-defining malignancies (ADMs) and other non-AIDS-defining malignancies (NADMs). Antiretroviral therapy has reduced the incidence of ADMs whereas a concurrent increase of NADMs was observed in the last years...
2016: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/27137427/prediction-of-nonremission-to-antidepressant-therapy-using-diffusion-tensor-imaging
#8
Stuart M Grieve, Mayuresh S Korgaonkar, Evian Gordon, Leanne M Williams, A John Rush
OBJECTIVE: Over 50% of outpatients with nonpsychotic major depressive disorder (MDD) do not achieve remission with any single antidepressant medication (ADM). There are currently no clinically useful pretreatment measures that inform the decision to prescribe or select ADMs. This report examines whether a biomarker based on diffusion tensor imaging (DTI) measures of brain connectivity can identify a subset of nonremitting patients with a sufficiently high degree of specificity that use of a medication that is likely to fail could be avoided...
April 2016: Journal of Clinical Psychiatry
https://www.readbyqxmd.com/read/27073013/variable-effect-of-maternal-oral-glucose-load-on-circulating-cell-free-placental-mrnas
#9
Teresa Mary MacDonald, Tu'uhevaha Joy Kaitu'u-Lino, Susan Philippa Walker, Kirsten Margaret Dane, Elizabeth Beatrice Lockie, Stephen Tong, Clare Louise Whitehead, Lisa Hui
BACKGROUND: It is not known whether fasting affects levels of circulating placenta-specific transcripts. OBJECTIVE: To assess whether a glucose load affects circulating placenta-specific transcripts. METHOD: RNA was extracted from paired blood samples (fasting and 1-h post 75 g oral glucose) from 22 women. Placenta-specific genes were measured by RT-qPCR. RESULTS: There was no change in ADM, CSH1, PAPPA2, PSG1 or TAC3 expression between fasting and post-glucose states...
May 5, 2016: Journal of Maternal-fetal & Neonatal Medicine
https://www.readbyqxmd.com/read/26954182/computational-prediction-of-alzheimer-s-and-parkinson-s-disease-micrornas-in-domestic-animals
#10
Hai Yang Wang, Zi Li Lin, Xian Feng Yu, Yuan Bao, Xiang-Shun Cui, Nam-Hyung Kim
As the most common neurodegenerative diseases, Alzheimer's disease (AD) and Parkinson's disease (PD) are two of the main health concerns for the elderly population. Recently, microRNAs (miRNAs) have been used as biomarkers of infectious, genetic, and metabolic diseases in humans but they have not been well studied in domestic animals. Here we describe a computational biology study in which human AD- and PD-associated miRNAs (ADM and PDM) were utilized to predict orthologous miRNAs in the following domestic animal species: dog, cow, pig, horse, and chicken...
June 2016: Asian-Australasian Journal of Animal Sciences
https://www.readbyqxmd.com/read/26874931/pharmacogenomic-or-epigenomic-biomarkers-in-drug-treatment-two-sides-of-the-same-medal
#11
M Ingelman-Sundberg, I Cascorbi
Interindividual differences in expression of ADME genes are controlled by both genetic and epigenetic factors. Much emphasis has been made to describe the genetic influence, whereas the epigenetic part is not fully understood. Currently, we utilize mainly genetic biomarkers for optimization of drug therapy, although many rare genetic variants are not taken into consideration. Now, also epigenomic biomarkers are at hand and together genetic and epigenetic biomarkers can indeed improve the predictability of drug treatment...
May 2016: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/26622614/expression-and-clinical-significance-of-focal-adhesion-kinase-and-adrenomedullin-in-epithelial-ovarian-cancer
#12
Mingqun Li, L I Hong, Meimei Liao, Guanglin Guo
The aim of the present study was to investigate the expression of focal adhesion kinase (FAK) and adrenomedullin (ADM) and determine their clinical significance and cooperative role in human epithelial ovarian cancer. The expression of FAK and ADM was investigated in epithelial ovarian cancer, benign ovarian tumors and normal control tissues by immunohistochemical staining and optical microscopy. The FAK and ADM expression and correlation with clinicopathological parameters was analyzed using SPSS 13.0 software...
August 2015: Oncology Letters
https://www.readbyqxmd.com/read/26577429/plasma-bioactive-adrenomedullin-as-a-prognostic-biomarker-in-acute-heart-failure
#13
MULTICENTER STUDY
Wesley H Self, Alan B Storrow, Oliver Hartmann, Tyler W Barrett, Gregory J Fermann, Alan S Maisel, Joachim Struck, Andreas Bergmann, Sean P Collins
OBJECTIVE: The objective was to evaluate the prognostic performance of a new biomarker, plasma bioactive adrenomedullin (bio-ADM), for short-term clinical outcomes in acute heart failure. METHODS: A multicenter prospective cohort study of adult emergency department (ED) patients suspected of having acute heart failure was conducted to evaluate the association between plasma bio-ADM concentration and clinical outcomes. The primary outcome was a composite of the following within 30 days: death, cardiac arrest with resuscitation, respiratory failure, emergency dialysis, acute coronary syndrome, hospitalization >5 days, and repeat ED visit or hospitalization...
February 2016: American Journal of Emergency Medicine
https://www.readbyqxmd.com/read/26233324/imaging-predictors-of-remission-to-anti-depressant-medications-in-major-depressive-disorder
#14
REVIEW
Kee F Chi, Mayuresh Korgaonkar, Stuart M Grieve
BACKGROUND: We review what is currently known about neuroimaging predictors of remission in major depressive disorder (MDD) after antidepressant medication (ADM) treatment. METHODS: A systematic literature search found a total of twenty-seven studies comparing baseline neuroimaging findings in depressed patients who achieved remission with non-remitters following treatment with ADMs. RESULTS: Eighteen of these studies utilised structural magnetic resonance imaging (MRI)...
November 1, 2015: Journal of Affective Disorders
https://www.readbyqxmd.com/read/26207746/discovery-of-nct-501-a-potent-and-selective-theophylline-based-inhibitor-of-aldehyde-dehydrogenase-1a1-aldh1a1
#15
Shyh-Ming Yang, Adam Yasgar, Bettina Miller, Madhu Lal-Nag, Kyle Brimacombe, Xin Hu, Hongmao Sun, Amy Wang, Xin Xu, Kimloan Nguyen, Udo Oppermann, Marc Ferrer, Vasilis Vasiliou, Anton Simeonov, Ajit Jadhav, David J Maloney
Aldehyde dehydrogenases (ALDHs) metabolize reactive aldehydes and possess important physiological and toxicological functions in areas such as CNS, metabolic disorders, and cancers. Increased ALDH (e.g., ALDH1A1) gene expression and catalytic activity are vital biomarkers in a number of malignancies and cancer stem cells, highlighting the need for the identification and development of small molecule ALDH inhibitors. A new series of theophylline-based analogs as potent ALDH1A1 inhibitors is described. The optimization of hits identified from a quantitative high throughput screening (qHTS) campaign led to analogs with improved potency and early ADME properties...
August 13, 2015: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/26136912/plasma-concentrations-of-adrenomedullin-and-natriuretic-peptides-in-patients-with-essential-hypertension
#16
Wei Hu, Pang-Hu Zhou, Xiao-Bin Zhang, Chang-Geng Xu, Wei Wang
This study was designed to assess any changes in the plasma concentrations of adrenomedullin (ADM) and atrial and brain natriuretic peptide (ANP and BNP, respectively), and to investigate their pathophysiological roles in patients with essential hypertension (EH). The plasma ADM, ANP and BNP concentrations were measured in 64 patients with untreated EH and 35 normotensive control subjects. After 4 weeks of effective antihypertensive therapy with oral drugs for the hypertensive patients, the plasma concentrations of ADM, ANP and BNP in the hypertensive patients were measured again...
May 2015: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/25965825/slc15a2-genomic-variation-is-associated-with-the-extraordinary-response-of-sorafenib-treatment-whole-genome-analysis-in-patients-with-hepatocellular-carcinoma
#17
Yeon-Su Lee, Bo Hyun Kim, Byung Chul Kim, Aesun Shin, Jin Sook Kim, Seung-Hyun Hong, Jung-Ah Hwang, Jung Ahn Lee, Seungyoon Nam, Sung Hoon Lee, Jong Bhak, Joong-Won Park
Reliable biomarkers are required to predict the response to sorafenib. We investigated genomic variations associated with responsiveness to sorafenib for patients with unresectable hepatocellular carcinoma (HCC). Blood samples from 2 extreme, 2 strong and 3 poor responders to sorafenib were subjected to whole-genome analysis. Then, we validated candidate genomic variations with another 174 HCC patients, and performed in vitro functional analysis and in silico analyses. Genomic data of >96 gigabases/sample was generated at average of ~34X sequencing depth...
June 30, 2015: Oncotarget
https://www.readbyqxmd.com/read/25868038/the-evaluation-of-the-clinical-utility-of-urocortin-1-and-adrenomedullin-versus-probnp-in-systolic-heart-failure
#18
Erkan Yıldırım, Mahir Cengiz, Nilgün Yıldırım, Kürşat Aslan, Emrah İpek, Ali Fuat Korkmaz, Fatih Rıfat Ulusoy, Engin Hatem
OBJECTIVE: Urocortin 1 (UCN1) has vasodilator, diuretic, and natriuretic effects, and its expression increases in heart failure (HF). Adrenomedullin (ADM) increases cardiac output and lowers blood pressure in healthy men and in patients with heart failure. The aim of the study was to determine UCN1 and ADM levels in patients with HF, to evaluate the relationship of UCN1 and ADM with various clinical parameters, and to assess UCN1 and ADM as diagnostic markers in HF, in comparison with pro-brain natriuretic peptide (pro-BNP)...
December 25, 2014: Anatolian Journal of Cardiology
https://www.readbyqxmd.com/read/25766241/studies-for-development-of-novel-quinazolinones-new-biomarker-for-egfr
#19
Swati Aggarwal, Deepa Sinha, Anjani Kumar Tiwari, Pooja Pooja, Ankur Kaul, Gurmeet Singh, Anil Kumar Mishra
The binding capabilities of a series of novel quinazolinone molecules were established and stated in a comprehensive computational methodology as well as by in vitro analysis. The main focus of this work was to achieve more insight of the interactions with crystal structure of PDB ID: 1M17 and predict their binding mode to EGFR. Three molecules were screened for further examination, which were synthesized and characterized using spectroscopic techniques. The persuasive affinity of these molecules towards EGFR inhibition (IC50 for QT=45nM) was established and validated from specific kinase assay including the cell viability spectrophotometric assay (QT=12nM)...
May 15, 2015: Spectrochimica Acta. Part A, Molecular and Biomolecular Spectroscopy
https://www.readbyqxmd.com/read/25699098/small-sized-egfr1-and-her2-specific-bifunctional-antibody-for-targeted-cancer-therapy
#20
Li Ding, Caiping Tian, Song Feng, Guissi Fida, Congying Zhang, Yuxiang Ma, Guanhua Ai, Samuel Achilefu, Yueqing Gu
Targeting tumors using miniature antibodies is a novel and attractive therapeutic approach, as these biomolecules exhibit low immunogenicity, rapid clearance, and high targeting specificity. However, most of the small-sized antibodies in existence do not exhibit marked anti-tumor effects, which limit their use in targeted cancer immunotherapy. To overcome this difficulty in targeting multiple biomarkers by combination therapies, we designed a new bifunctional antibody, named MaAbNA (multivalent antibody comprised of nanobody and affibody moieties), capable of targeting EGFR1 and HER2, which are widely overexpressed in a variety of tumor types...
2015: Theranostics
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