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https://www.readbyqxmd.com/read/28445968/usp22-knockdown-enhanced-chemosensitivity-of-hepatocellular-carcinoma-cells-to-5-fu-by-up-regulation-of-smad4-and-suppression-of-akt
#1
Jing Zhang, Nan Luo, Yu Tian, Jiazhi Li, Xiaozhou Yang, Huimin Yin, Congshu Xiao, Jie Sheng, Yang Li, Bo Tang, Rongkuan Li
USP22, a member of the deubiquitinases (DUBs) family, is known to be a key subunit of the human Spt-Ada-Gcn5 acetyltransferase (hSAGA) transcriptional cofactor complex. Within hSAGA, USP22 removes ubiquitin from histone proteins, thus regulating the transcription and expression of downstream genes. USP22 plays important roles in many cancers; however, its effect and the mechanism underlying HCC chemoresistance remain unclear. In the present study, we found that USP22 was highly expressed in chemoresistant HCC tissues and cells and was correlated with the prognosis of HCC patients who received chemotherapy...
April 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28445961/azilsartan-ameliorates-apoptosis-of-dopaminergic%C3%A2-neurons-and-rescues-characteristic-parkinsonian-behaviors-in-a-rat-model-of-parkinson-s-disease
#2
Qing Gao, Zhou Ou, Teng Jiang, You-Yong Tian, Jun-Shan Zhou, Liang Wu, Jian-Quan Shi, Ying-Dong Zhang
Loss of dopaminergic neurons within the substantia nigra (SN) is a pathological hallmark of Parkinson's disease (PD), which leads to the onset of motor symptoms. Previously, our in vitro studies revealed that Angiotensin II (Ang II) induced apoptosis of dopaminergic neurons through its type 1 receptor (AT1R), but these findings needed to be confirmed via animal experiments. Here, using a rotenone-induced rat model of PD, we observed an overactivation of Ang II/AT1R axis in the SN, since Ang II level and AT1R expression were markedly increased...
April 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28445958/repressing-cd147-is-a-novel-therapeutic-strategy-for-malignant-melanoma
#3
REVIEW
Xing Hu, Juan Su, Youyou Zhou, Xiaoyun Xie, Cong Peng, Zhimin Yuan, Xiang Chen
CD147/basigin, a transmembrane protein, is a member of the immunoglobulin super family. Accumulating evidence has revealed the role of CD147 in the development and progression of various cancers, including malignant melanoma (MM). MM is a malignancy of pigment-producing cells that causes the greatest number of skin cancer-related deaths worldwide. CD147 is overexpressed in MM and plays an important role in cell viability, apoptosis, proliferation, invasion, and metastasis, probably by mediating vascular endothelial growth factor (VEGF) production, glycolysis, and multi-drug resistance (MDR)...
April 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28445868/suppressionof-pyruvate-dehydrogenase-kinase-2-re-sensitizes-paclitaxel-resistant-human-lung-cancer-cells-to-paclitaxel
#4
Hong Sun, Anyou Zhu, Xiang Zhou, Fengchao Wang
Despite impressive initial clinical responses, the majority of lung cancer patients treated with paclitaxel eventually develop resistance to the drug. Pyruvate dehydrogenase kinase-2 (PDK2) is a key regulator of glycolysis and oxidative phosphorylation, and its expression is increased in a variety of tumors. In this study, the role of PDK2 in mediating paclitaxel resistance in lung cancer cells was investigated using biochemical and isotopic tracing methods. Increased expression of PDK2 was observed in paclitaxel-resistant cells ascompared totheir parental cells...
April 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/28445864/tumor-antigen-glycosaminoglycan-modification-regulates-antibody-drug-conjugate-delivery-and-cytotoxicity
#5
Helena C Christianson, Julien A Menard, Vineesh Indira Chandran, Erika Bourseau-Guilmain, Dmitry Shevela, Jon Lidfeldt, Ann-Sofie Månsson, Silvia Pastorekova, Johannes Messinger, Mattias Belting
Aggressive cancers are characterized by hypoxia, which is a key driver of tumor development and treatment resistance. Proteins specifically expressed in the hypoxic tumor microenvironment thus represent interesting candidates for targeted drug delivery strategies. Carbonic anhydrase (CAIX) has been identified as an attractive treatment target as it is highly hypoxia specific and expressed at the cell-surface to promote cancer cell aggressiveness. Here, we find that cancer cell internalization of CAIX is negatively regulated by post-translational modification with chondroitin or heparan sulfate glycosaminoglycan chains...
April 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28445850/simultaneous-quantification-of-busulfan-clofarabine-and-f-ara-a-using-isotope-labelled-standards-and-standard-addition-in-plasma-by-lc-ms-ms-for-exposure-monitoring-in-hematopoietic-cell-transplantation-conditioning
#6
Arjen M Punt, Jurgen B Langenhorst, Annelies C Egas, Jaap Jan Boelens, Charlotte van Kesteren, Erik M van Maarseveen
In allogeneic hematopoietic cell transplantation (HCT) it has been shown that over- or underexposure to conditioning agents have an impact on patient outcomes. Conditioning regimens combining busulfan (Bu) and fludarabine (Flu) with or without clofarabine (Clo) are gaining interest worldwide in HCT. To evaluate and possibly adjust full conditioning exposure a simultaneous analysis of Bu, F-ARA-A (active metabolite of Flu) and Clo in one analytical run would be of great interest. However, this is a chromatographical challenge due to the large structural differences of Bu compared to F-ARA-A and Clo...
April 15, 2017: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
https://www.readbyqxmd.com/read/28445815/lc-ms-ms-determination-of-tranexamic-acid-in-human-plasma-after-phospholipid-clean-up
#7
Nicolas Fabresse, Fanta Fall, Isabelle Etting, Philippe Devillier, Jean-Claude Alvarez, Stanislas Grassin-Delyle
Tranexamic acid is a widely used antifibrinolytic drug but its pharmacology and pharmacokinetics remains poorly understood. Owing to the recent knowledge on phospholipid-induced matrix effects during human plasma analysis, our aim was to develop a liquid chromatography-mass spectrometry method for the quantitation of tranexamic acid after efficient sample clean-up. Sample preparation consisted in phospholipid removal and protein precipitation. Hydrophilic interaction liquid chromatography was used and the detection was achieved with multiple reaction monitoring...
April 19, 2017: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/28445768/polymer-free-electrospun-nanofibers-from-sulfobutyl-ether7-beta-cyclodextrin-sbe7-%C3%AE-cd-inclusion-complex-with-sulfisoxazole-fast-dissolving-and-enhanced-water-solubility-of-sulfisoxazole
#8
Zehra Irem Yildiz, Asli Celebioglu, Tamer Uyar
In this study, our aim was to develop solid drug-cyclodextrin inclusion complex system having nanofibrous morphology in order to have fast-dissolving property and enhanced water-solubility of poorly water-soluble drug. Here, we prepared a highly concentrated aqueous solution of inclusion complex between sulfisoxazole and sulfobutyl ether7-beta-cyclodextrin (SBE7-β-CD, Captisol(®)), and then, without using any polymeric matrix, the electrospinning of sulfisoxazole/SBE7-β-CD-IC nanofibers was performed in order to obtain free-standing and handy nanofibrous web...
April 23, 2017: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/28445766/inhibitory-effect-of-emulsifiers-in-sedds-on-protease-activity-just-an-illusion
#9
Noemi Lupo, Una Fidahic, Gergely Hetényi, Janine Griesser, Andreas Bernkop-Schnürch
AIM: Evaluation of inhibitory effect of emulsifiers on pancreatic trypsin and α-chymotrypsin. METHODS: The inhibitory effect of Cremophor EL, Cremophor RH 40, Brij O10, Tween 20, polyethylene glycol 8000, polyethylene glycol 400, Carbitol, Pemulen TR-1, Pemulen TR-2, Carbopol Ultrez 20 and Carbopol Ultrez 21 on pancreatic trypsin and α-chymotrypsin was tested. BAEE (Nα-Benzoyl-L-arginine ethyl ester), BTEE (N-Benzoyl-L-tyrosine ethyl ester), casein and insulin were used as substrates for trypsin and α-chymotrypsin...
April 23, 2017: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/28445764/development-of-light-driven-gas-forming-liposomes-for-efficient-tumor-treatment
#10
Jae Min Lee, Yu Seok Youn, Eun Seong Lee
In this study, we report a gas-forming liposome containing 1H-1H-2H-perfluoro-1-hexene (PFH) and gold nanoparticles (AuNPs). These liposomes were rapidly destabilized by external near-infrared (NIR) light, as a result of the vaporization of PFH influenced by an AuNPs-mediated photothermal event. In particular, these liposomes showed the triggered release of the encapsulated D-(KLAKLAK)2 peptide drug. The experimental results demonstrated that the light-irradiated liposomes significantly enhanced in vitro photothermal and D-(KLAKLAK)2 peptide-mediated cell death of CAOV-3 tumor cells...
April 23, 2017: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/28445704/development-of-standard-methods-for-zika-virus-propagation-titration-and-purification
#11
Sharton Vinicius Antunes Coelho, Rômulo Leão Silva Neris, Michelle Premazzi Papa, Laila Castro Schnellrath, Lana Monteiro Meuren, Diogo A Tschoeke, Luciana Leomil, Brunno Renato Farias Verçoza, Milene Miranda, Fabiano L Thompson, Andrea Thompson Da Poian, Thiago Moreno L Souza, Fabiana Avila Carneiro, Clarissa R Damaso, Iranaia Assunção-Miranda, Luciana Barros de Arruda
The emergence of Zika virus (ZIKV) infection has stimulated several research groups to study and collaborate to understand virus biology and pathogenesis. These efforts may assist with the development of antiviral drugs, vaccines and diagnostic tests, as well as to promote advancements in public health policies. Here, we aim to develop standard protocols for propagation, titration, and purification of Asian and Brazilian ZIKV strains, by systematically testing different cell types, kinetics, multiplicity of infection and centrifugation protocols...
April 23, 2017: Journal of Virological Methods
https://www.readbyqxmd.com/read/28445699/journey-of-cystatins-from-being-mere-thiol-protease-inhibitors-to-at-heart-of-many-pathological-conditions
#12
REVIEW
Anas Shamsi, Bilqees Bano
Cystatins are thiol proteinase inhibitors (TPI), present ubiquitously in animals, plants and micro-organisms. These are not merely inhibitors rather they are at heart of many pathological conditions ranging from diabetes to renal failure. These are essential for maintenance of protein balance of the cell; once this balance gets disturbed, it may lead to cell death. Thus, cystatins cannot be merely regarded as TPI's as these have been found to play a pivotal role in tumorigenesis and neurodegenerative diseases...
April 23, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/28445649/high-serum-stability-of-collagen-hybridizing-peptides-and-their-fluorophore-conjugates
#13
Lucas L Bennink, Daniel J Smith, Catherine A Foss, Martin G Pomper, Yang Li, S Michael Yu
Collagen hybridizing peptides (CHPs) have a great potential for use in targeted drug delivery, diagnostics, and regenerative medicine due to their ability to specifically bind to denatured collagens associated with many pathologic conditions. Since peptides generally suffer from poor enzymatic stability resulting in rapid degradation and elimination in vivo, CHP's serum stability is a critical parameter that may dictate its pharmacokinetic behavior. Here, we report the serum stability of a series of monomeric CHP derivatives and establish how peptide length, amino acid composition, terminal modification, and linker chemistry influence their availability in serum...
April 26, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28445611/equivalence-of-complex-drug-products-advances-in-and-challenges-for-current-regulatory-frameworks
#14
Leonie Hussaarts, Stefan Mühlebach, Vinod P Shah, Scott McNeil, Gerrit Borchard, Beat Flühmann, Vera Weinstein, Sesha Neervannan, Elwyn Griffiths, Wenlei Jiang, Elena Wolff-Holz, Daan J A Crommelin, Jon S B de Vlieger
Biotechnology and nanotechnology provide a growing number of innovator-driven complex drug products and their copy versions. Biologics exemplify one category of complex drugs, but there are also nonbiological complex drug products, including many nanomedicines, such as iron-carbohydrate complexes, drug-carrying liposomes or emulsions, and glatiramoids. In this white paper, which stems from a 1-day conference at the New York Academy of Sciences, we discuss regulatory frameworks in use worldwide (e.g., the U...
April 26, 2017: Annals of the New York Academy of Sciences
https://www.readbyqxmd.com/read/28445474/cost-effectiveness-of-a-transitional-pharmaceutical-care-program-for-patients-discharged-from-the-hospital
#15
Fatma Karapinar-Çarkıt, Ronald van der Knaap, Fatiha Bouhannouch, Sander D Borgsteede, Marjo J A Janssen, Carl E H Siegert, Toine C G Egberts, Patricia M L A van den Bemt, Marieke F van Wier, Judith E Bosmans
BACKGROUND: To improve continuity of care at hospital admission and discharge and to decrease medication errors pharmaceutical care programs are developed. This study aims to determine the cost-effectiveness of the COACH program in comparison with usual care from a societal perspective. METHODS: A controlled clinical trial was performed at the Internal Medicine department of a general teaching hospital. All admitted patients using at least one prescription drug were included...
2017: PloS One
https://www.readbyqxmd.com/read/28445472/unsuspected-osteochondroma-like-outgrowths-in-the-cranial-base-of-hereditary-multiple-exostoses-patients-and-modeling-and-treatment-with-a-bmp-antagonist-in-mice
#16
Sayantani Sinha, Christina Mundy, Till Bechtold, Federica Sgariglia, Mazen M Ibrahim, Paul C Billings, Kristen Carroll, Eiki Koyama, Kevin B Jones, Maurizio Pacifici
Hereditary Multiple Exostoses (HME) is a rare pediatric disorder caused by loss-of-function mutations in the genes encoding the heparan sulfate (HS)-synthesizing enzymes EXT1 or EXT2. HME is characterized by formation of cartilaginous outgrowths-called osteochondromas- next to the growth plates of many axial and appendicular skeletal elements. Surprisingly, it is not known whether such tumors also form in endochondral elements of the craniofacial skeleton. Here, we carried out a retrospective analysis of cervical spine MRI and CT scans from 50 consecutive HME patients that included cranial skeletal images...
April 26, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28445455/structural-insight-into-allosteric-modulation-of-protease-activated-receptor-2
#17
Robert K Y Cheng, Cédric Fiez-Vandal, Oliver Schlenker, Karl Edman, Birte Aggeler, Dean G Brown, Giles A Brown, Robert M Cooke, Christoph E Dumelin, Andrew S Doré, Stefan Geschwindner, Christoph Grebner, Nils-Olov Hermansson, Ali Jazayeri, Patrik Johansson, Louis Leong, Rudi Prihandoko, Mathieu Rappas, Holly Soutter, Arjan Snijder, Linda Sundström, Benjamin Tehan, Peter Thornton, Dawn Troast, Giselle Wiggin, Andrei Zhukov, Fiona H Marshall, Niek Dekker
Protease-activated receptors (PARs) are a family of G-protein-coupled receptors (GPCRs) that are irreversibly activated by proteolytic cleavage of the N terminus, which unmasks a tethered peptide ligand that binds and activates the transmembrane receptor domain, eliciting a cellular cascade in response to inflammatory signals and other stimuli. PARs are implicated in a wide range of diseases, such as cancer and inflammation. PARs have been the subject of major pharmaceutical research efforts but the discovery of small-molecule antagonists that effectively bind them has proved challenging...
April 26, 2017: Nature
https://www.readbyqxmd.com/read/28445403/detection-of-hepatitis-b-virus-m204i-mutation-by-quantum-dot-labeled-dna-probe
#18
Cheng Zhang, Yiping Chen, Xinmiao Liang, Guanhua Zhang, Hong Ma, Leng Nie, Yu Wang
Quantum dots (QDs) are semiconductor nanoparticles with a diameter of less than 10 nm, which have been widely used as fluorescent probes in biochemical analysis and vivo imaging because of their excellent optical properties. Sensitive and convenient detection of hepatitis B virus (HBV) gene mutations is important in clinical diagnosis. Therefore, we developed a sensitive, low-cost and convenient QDs-mediated fluorescent method for the detection of HBV gene mutations in real serum samples from chronic hepatitis B (CHB) patients who had received lamivudine or telbivudine antiviral therapy...
April 26, 2017: Sensors
https://www.readbyqxmd.com/read/28445397/radiation-and-thyroid-cancer
#19
REVIEW
Elisabetta Albi, Samuela Cataldi, Andrea Lazzarini, Michela Codini, Tommaso Beccari, Francesco Saverio Ambesi-Impiombato, Francesco Curcio
Radiation-induced damage is a complex network of interlinked signaling pathways, which may result in apoptosis, cell cycle arrest, DNA repair, and cancer. The development of thyroid cancer in response to radiation, from nuclear catastrophes to chemotherapy, has long been an object of study. A basic overview of the ionizing and non-ionizing radiation effects of the sensitivity of the thyroid gland on radiation and cancer development has been provided. In this review, we focus our attention on experiments in cell cultures exposed to ionizing radiation, ultraviolet light, and proton beams...
April 26, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28445390/prevention-of-colorectal-cancer-by-targeting-obesity-related-disorders-and-inflammation
#20
REVIEW
Yohei Shirakami, Masaya Ohnishi, Hiroyasu Sakai, Takuji Tanaka, Masahito Shimizu
Colorectal cancer is a major healthcare concern worldwide. Many experimental and clinical studies have been conducted to date to discover agents that help in the prevention of this disease. Chronic inflammation in colonic mucosa and obesity, and its related metabolic abnormalities, are considered to increase the risk of colorectal cancer. Therefore, treatments targeting these factors might be a promising strategy to prevent the development of colorectal cancer. Among a number of functional foods, various phytochemicals, including tea catechins, which have anti-inflammatory and anti-obesity properties, and medicinal agents that ameliorate metabolic disorders, might also be beneficial in the prevention of colorectal cancer...
April 26, 2017: International Journal of Molecular Sciences
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