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https://www.readbyqxmd.com/read/29054569/cause-specific-mortality-in-endometrioid-endometrial-cancer-patients-with-type-2-diabetes-using-metformin-or-other-types-of-antidiabetic-medication
#1
R Arima, A Hautakoski, M Marttila, M Arffman, R Sund, P Ilanne-Parikka, J Kangaskokko, M Hinkula, U Puistola, E Läärä
AIM: To obtain further evidence of the association between metformin or other types of antidiabetic medication (ADM) and mortality from endometrial cancer (EC) and other causes of death in patients with endometrioid EC and type 2 diabetes (T2D). MATERIALS AND METHODS: A retrospective cohort of women with existing T2D and diagnosed with endometrioid EC from 1998 to 2011, obtained from a nationwide diabetes database (FinDM), were included in the study. Cumulative mortality from EC and that from other causes was described by using the Aalen-Johansen estimator...
October 17, 2017: Gynecologic Oncology
https://www.readbyqxmd.com/read/29050217/triterpenoids-from-aglaia-abbreviata-exert-cytotoxicity-and-multidrug-resistant-reversal-effect-in-mcf-7-adm-cells-via-reactive-oxygen-species-induction-and-p-glycoprotein-inhibition
#2
Juan Cen, Beibei Zheng, Rubing Bai, Li Zhang, Feng Zhang, Xia Zhang
Triterpenoids from the Aglaia have been shown cytotoxicity on a broad spectrum of human tumor cells. In the present study, we extracted triterpenoids AA-5 (1) and AA-6 (2) from stems of Aglaia abbreviata, and studied their cytotoxicity in multidrug resistant (MDR) MCF-7/ADM cells. After 48 h treatment, AA-5 (1) and AA-6 (2) significantly increased mitochondrial-mediated apoptosis by enhancing reactive oxygen species (ROS) with depressed mitochondrial membrane potential and caspase-9 activities. The drug efflux transporter P-glycoprotein (P-gp) and the intracellular antioxidant systems, involving Glutathione S-Transferase π, Glutathione and heme oxygenase-1, were also inhibited via the ROS-depressed Akt/NF-E2-related factor 2 pathway...
September 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29050213/serum-protein-fingerprinting-by-pea-immunoassay-coupled-with-a-pattern-recognition-algorithms-distinguishes-mgus-and-multiple-myeloma
#3
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...
September 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29048889/lipoyl-homotaurine-derivative-adm_12-reverts-oxaliplatin-induced-neuropathy-and-reduces-cancer-cells-malignancy-by-inhibiting-carbonic-anhydrase-ix-caix
#4
Marco Fragai, Giuseppina Comito, Lorenzo Di Cesare Mannelli, Roberta Gualdani, Vito Calderone, Alexandra Louka, Barbara Richichi, Oscar Francesconi, Andrea Angeli, Alessio Nocentini, Paola Gratteri, Paola Chiarugi, Carla Ghelardini, Francesco Tadini-Buoninsegni, Claudiu T Supuran, Cristina Nativi
Oxaliplatin (OXA) is a valuable and largely used cancer drug, which induces a serious and intractable neuropathy. The lipoyl-homotaurine derivative, ADM_12, reverts in vivo OXA-induced neuropathy and it is an effective antagonist of the nociceptive sensor channel TRPA1. Unprecedentedly, this safe analgesic showed a synergy with OXA in vitro and proved to inhibit CA IX, a relevant therapeutic target, clearly interfering with pancreatic cancer cells aggressiveness.
October 19, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29046011/-biomarkers-in-diagnosis-treatment-and-prognosis-of-infectious-lung-diseases
#5
M Unnewehr, M Kolditz, W Windisch, B Schaaf
Biomarkers play an important role in the management of infectious pulmonary diseases, even though there is only limited evidence that biomarker-guided therapies are superior to clinical strategies.Well-established indications for the use of biomarkers are the guidance of the duration of antibiotic therapy in community-acquired pneumonia (CAP) by PCT, the decision against the use of antibiotics by CRP or PCT in ambulatory settings, and the evaluation of CAP treatment by CRP or PCT kinetics.In the prognostic assessment of CAP, the standard biomarkers of acute organ dysfunction should be given priority, e...
October 18, 2017: Pneumologie
https://www.readbyqxmd.com/read/29045053/ensamble-based-adme-tox-profiling-and-virtual-screening-for-the-discovery-of-new-inhibitors-of-the-leishmania-mexicana-cysteine-protease-cpb2-8%C3%AE-cte
#6
Angela Scala, Antonio Rescifina, Nicola Micale, Anna Piperno, Tanja Schirmeister, Louis Maes, Giovanni Grassi
In an effort to identify novel molecular warheads able to inhibit Leishmania mexicana cysteine protease CPB2.8ΔCTE, fused benzo[b]thiophenes and β,β'-triketones emerged as covalent inhibitors binding the active site cysteine residue. Enzymatic screening showed a moderate to excellent activity (12-90% inhibition of the target enzyme at 20 μM). The most promising compounds were selected for further profiling including in vitro cell-based assays and docking studies. Computational data suggest that benzo[b]thiophenes act immediately as non-covalent inhibitors and then as irreversible covalent inhibitors, whereas a reversible covalent mechanism emerged for the 1,3,3'-triketones with a Y-topology...
October 17, 2017: Chemical Biology & Drug Design
https://www.readbyqxmd.com/read/29043024/validating-distribution-models-for-twelve-endemic-bird-species-of-tropical-dry-forest-in-western-mexico
#7
Miguel A Ortega-Huerta, Jorge H Vega-Rivera
Considering the high biodiversity and conservation concerns of the tropical dry forest, this study aim is to predict and evaluate the potential and current distributions of twelve species of endemic birds which distribute along the western slope of Mexico. The main goal is to evaluate altogether different methods for predicting actual species distribution models (ADMs) of the twelve species including the identification of key environmental potential limiting factors. ADMs for twelve endemic Mexican birds were generated and validated by means of applying: (1) three widely used species niche modeling approaches (ENFA, Garp, and Maxent); (2) two thresholding methods, based on ROC curves and Kappa Index, for transforming continuous models to presence/absence (binary) models; (3) documented habitat-species associations for reducing species potential distribution models (PDMs); and (4) field occurrence data for validating final ADMs...
October 2017: Ecology and Evolution
https://www.readbyqxmd.com/read/29041842/identifying-novel-small-molecule-antagonists-for-mlst8-protein-using-computational-approaches
#8
Tuleshwori Devi Sapam, Anbumani Velmurugan Ilavarasi, Bhagath Kumar Palaka, Elakkiya Elumalai, Nirmala Devi Kanika, Dinakara Rao Ampasala
Mammalian lethal with SEC13 protein 8 (mLST8), is an indispensable protein subunit of mammalian target of rapamycin (mTOR) signaling pathway that interacts with the kinase domain of mTOR protein, thereby stabilizing its active site. Experimental studies reported the over expression of mLST8 in human colon and prostate cancers by activation of both mTORC1/2 complexes and subsequent downstream substrates leading to tumor progression. Considering its role, targeting mLST8 protein would be a therapeutic approach against tumor progression in colon and prostate cancers...
October 17, 2017: Journal of Receptor and Signal Transduction Research
https://www.readbyqxmd.com/read/29039601/vasohibin2-promotes-adriamycin-resistance-of-breast-cancer-cells-through-regulating-abcg2-via-akt-signaling-pathway
#9
Deliang Ma, Liang Wu, Shuangjie Li, Zhigang Sun, Kai Wang
As a well‑known angiogenic factor in different histology and pathological conditions, the pro‑progressive role of vasohibin2 (VASH2) has been reported in various types of tumors. However, its role in drug resistance of breast cancer has not been reported so far. The present study demonstrated that MCF‑7 cells with increased expression of VASH2 demonstrate stronger adriamycin (ADM) resistance compared with MDA‑MB‑231 cells with decreased expression of VASH2. Overexpression of VASH2 in MDA‑MB‑231 cells increased ADM resistance and silencing VASH2 in MCF‑7 cells inhibited ADM resistance...
October 13, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29037750/environmental-toxicology-and-omics-a-question-of-sex
#10
Xuefang Liang, April Feswick, Denina Simmons, Christopher J Martyniuk
Molecular initiating events and downstream transcriptional/proteomic responses provide valuable information for adverse outcome pathways, which can be used predict the effects of chemicals on physiological systems. There has been a paucity of research that addresses sex-specific expression profiling in toxicology and due to cost, time, and logistical considerations, sex as a variable has not been widely considered. In response to this deficiency, federal agencies in the United States, Canada, and Europe have highlighted the importance of including sex as a variable in scientific investigations...
October 13, 2017: Journal of Proteomics
https://www.readbyqxmd.com/read/29029979/immunoaffinity-capture-coupled-with-capillary-electrophoresis-mass-spectrometry-to-study-protein-therapeutic-stability-in-vivo
#11
Mei Han, Josh T Pearson, Yunan Wang, Dwight Winters, Marcus Soto, Dan A Rock, Brooke M Rock
Protein engineering is at an all-time high in biopharmaceutics. As a result, absorption, distribution, metabolism and excretion (ADME) of proteins has become more important to understand in the context of engineering strategies to optimize therapeutic properties of potential lead constructs. Immunoaffinity capture coupled with a newly developed capillary electrophoresis - mass spectrometry (CE-MS) system was used to characterize intact protein mass analysis of a wildtype Fc-FGF21 construct and a sequence re-engineered Fc-FGF21 construct from an in vivo study...
October 10, 2017: Analytical Biochemistry
https://www.readbyqxmd.com/read/29029933/highly-potent-and-selective-nav1-7-inhibitors-for-use-as-intravenous-agents-and-chemical-probes
#12
R Ian Storer, Andy Pike, Nigel A Swain, Aristos J Alexandrou, Bruce M Bechle, David C Blakemore, Alan D Brown, Neil A Castle, Matthew S Corbett, Neil J Flanagan, David Fengas, M Scott Johnson, Lyn H Jones, Brian E Marron, C Elizabeth Payne, David Printzenhoff, David J Rawson, Colin R Rose, Thomas Ryckmans, Jianmin Sun, Jonathan W Theile, Rubben Torella, Elaine Tseng, Joseph S Warmus
The discovery and selection of a highly potent and selective NaV1.7 inhibitor PF-06456384, designed specifically for intravenous infusion, is disclosed. Extensive in vitro pharmacology and ADME profiling followed by in vivo preclinical PK and efficacy model data are discussed. A proposed protein-ligand binding mode for this compound is also provided to rationalise the high levels of potency and selectivity over inhibition of related sodium channels. To further support the proposed binding mode, potent conjugates are described which illustrate the potential for development of chemical probes to enable further target evaluation...
November 1, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/29028080/roles-of-hypoxia-inducible-factor-1%C3%AE-and-its-target-genes-in-neonatal-hypoxic-pulmonary-hypertension
#13
C-F Han, Z-Y Li, T-H Li
OBJECTIVE: To investigate the role of hypoxia-inducible factor-1α and its target genes in hypoxic pulmonary hypertension in neonates. PATIENTS AND METHODS: A total of 117 newborns were selected and divided into two groups for clinical experiments: 85 cases in the hypoxic pulmonary hypertension (HPH) group, including mild, moderate and severe subgroups, and 32 cases in the case-control group. ELISA was used to detect the serum HIF-1α, endothelin-1 (ET-1) and adrenomedullin (ADM) levels, and echocardiography was used to detect the dynamic changes in pulmonary artery systolic pressure (PASP), right ventricular ejection fraction (RVEF), tricuspid E peak and A peak ratio (E/A) and right ventricular Tei index...
September 2017: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/29017761/adm-guidance-ceramics-fatigue-principles-and-testing
#14
REVIEW
J R Kelly, P F Cesar, S S Scherrer, A Della Bona, R van Noort, M Tholey, A Vichi, U Lohbauer
BACKGROUND: Clinical failure of dental ceramics is usually reported as partial fracture of the restoration (chipping) or as catastrophic fracture of the whole structure. In contrast to metals, ceramics are linear-elastic, brittle materials exhibiting extremely low damage tolerance to failure. Well documented clinical and lab reports have shown this fracture event often occurs at loads far below their fracture strength due to intrinsic fatigue degradation via slow crack growth or cyclic fatigue mechanisms...
October 7, 2017: Dental Materials: Official Publication of the Academy of Dental Materials
https://www.readbyqxmd.com/read/29016549/depressive-symptoms-antidepressant-medication-use-and-inflammatory-markers-in-the-diabetes-prevention-program
#15
Mary de Groot, David Marrero, Lisa Mele, Todd Doyle, Frank Schwartz, Kieren J Mather, Ronald Goldberg, David W Price, Yong Ma, William C Knowler
OBJECTIVE: Antidepressant medication use (ADM) has been shown to predict diabetes. This paper assessed the role of inflammatory markers in this relationship within the Diabetes Prevention Program (DPP). METHODS: DPP participants randomized to Metformin (MET), Lifestyle Intervention (ILS) or placebo (PLB) were assessed for depression (BDI; Beck Depression Inventory) annually; ADM use semi-annually; serum inflammatory markers (CRP, IL-6) at baseline and Year 1; and diagnosis of T2DM semi-annually (over 3...
October 10, 2017: Psychosomatic Medicine
https://www.readbyqxmd.com/read/28990518/click-reactions-in-chemistry-of-triterpenes-advances-towards-development-of-potential-therapeutics
#16
Jan Pokorný, Lucie Borková, Milan Urban
Triterpenoids are natural compounds with a large variety of biological activities such as anticancer, antiviral, antibacterial, antifungal, antiparazitic, antiinflammatory and others. Despite their low toxicity and simple availability from the natural resources, their clinical use is still severely limited by their higher IC50 and worse pharmacological properties than in the currently used therapeutics. This fact encouraged a number of researchers to develop new terpenic derivatives more suitable for the potential clinical use...
October 9, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28988506/in-silico-adme-tox-modeling-progress-and-prospects
#17
Saeed Alqahtani
Although significant progress has been made in high-throughput screening of absorption, distribution, metabolism and excretion, and toxicity (ADME-Tox) properties in drug discovery and development, in silico ADME-Tox prediction continues to play an important role in facilitating the appropriate selection of candidate drugs by pharmaceutical companies prior to expensive clinical trials. Areas covered: This review provides an overview of the available in silico models that have been used to predict the ADME-Tox properties of compounds...
October 9, 2017: Expert Opinion on Drug Metabolism & Toxicology
https://www.readbyqxmd.com/read/28986815/effects-of-compound-zhebei-granule-combined-with-doxorubicin-on-expression-of-specific-surface-antigens-in-mice-with-transplanted-kg-1a-cells
#18
Yu Zhang, Li Hou, Xin-Yi Chen
OBJECTIVE: To investigate the effects of Compound Zhebei Granule (, CZG) combined with doxorubicin hydrochloride (adriamycin, ADM) on specific surface antigens in mice with KG-1a transplanted cells. METHODS: A subcutaneous tumor xenograft model was established by injection of the acute myeloid leukemia cell line KG-1a into the axillary flanks of BALB/c-nude mice. Twenty-four tumor bearing mice were divided into 4 groups according to a random number table, including normal saline control group, ADM group, high-dose CZG group, and mid-dose CZG group, with 6 mice in each group...
October 6, 2017: Chinese Journal of Integrative Medicine
https://www.readbyqxmd.com/read/28986582/assessing-inhibitors-of-mutant-isocitrate-dehydrogenase-using-a-suite-of-pre-clinical-discovery-assays
#19
Daniel J Urban, Natalia J Martinez, Mindy I Davis, Kyle R Brimacombe, Dorian M Cheff, Tobie D Lee, Mark J Henderson, Steven A Titus, Rajan Pragani, Jason M Rohde, Li Liu, Yuhong Fang, Surendra Karavadhi, Pranav Shah, Olivia W Lee, Amy Wang, Andrew McIver, Hongchao Zheng, Xiaodong Wang, Xin Xu, Ajit Jadhav, Anton Simeonov, Min Shen, Matthew B Boxer, Matthew D Hall
Isocitrate dehydrogenase 1 and 2 (IDH1 and IDH2) are key metabolic enzymes that are mutated in a variety of cancers to confer a gain-of-function activity resulting in the accumulation of an oncometabolite, D-2-hydroxyglutarate (2-HG). Accumulation of 2-HG can result in epigenetic dysregulation and a block in cellular differentiation, suggesting these mutations play a role in neoplasia. Based on its potential as a cancer target, a number of small molecule inhibitors have been developed to specifically inhibit mutant forms of IDH (mIDH1 and mIDH2)...
October 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28985730/clinical-utility-of-the-low-density-infinium-qc-genotyping-array-in-a-genomics-based-diagnostics-laboratory
#20
Petr Ponomarenko, Alex Ryutov, Dennis T Maglinte, Ancha Baranova, Tatiana V Tatarinova, Xiaowu Gai
BACKGROUND: With 15,949 markers, the low-density Infinium QC Array-24 BeadChip enables linkage analysis, HLA haplotyping, fingerprinting, ethnicity determination, mitochondrial genome variations, blood groups and pharmacogenomics. It represents an attractive independent QC option for NGS-based diagnostic laboratories, and provides cost-efficient means for determining gender, ethnic ancestry, and sample kinships, that are important for data interpretation of NGS-based genetic tests. METHODS: We evaluated accuracy and reproducibility of Infinium QC genotyping calls by comparing them with genotyping data of the same samples from other genotyping platforms, whole genome/exome sequencing...
October 6, 2017: BMC Medical Genomics
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