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https://www.readbyqxmd.com/read/28545088/transcriptional-activation-of-hif-1-by-a-ros-erk-axis-underlies-the-resistance-to-photodynamic-therapy
#1
María Julia Lamberti, María Florencia Pansa, Renzo Emanuel Vera, Martín Ernesto Fernández-Zapico, Natalia Belén Rumie Vittar, Viviana Alicia Rivarola
Photodynamic therapy (PDT), a promising treatment option for cancer, involves the activation of a photosensitizer (PS) by local irradiation with visible light. Excitation of the PS leads to a series of photochemical reactions and consequently the local generation of harmful reactive oxygen species (ROS) causing limited or none systemic defects. However, the development of resistance to this promising therapy has slowed down its translation into the clinical practice. Thus, there is an increase need in understanding of the molecular mechanism underlying resistance to PDT...
2017: PloS One
https://www.readbyqxmd.com/read/28544946/perceived-barriers-to-healthcare-and-receipt-of-recommended-medical-care-among-elderly-medicare-beneficiaries
#2
Jibby E Kurichi, Liliana Pezzin, Joel E Streim, Pui L Kwong, Ling Na, Hillary R Bogner, Dawei Xie, Sean Hennessy
PURPOSE: Many Medicare beneficiaries perceive barriers to receiving healthcare, although the consequences are unknown. Facilitators can aid in the receipt of healthcare services. The objective was to assess the relationship between perceived facilitators and barriers to healthcare and actual receipt of recommended medical care among elderly beneficiaries. METHODS: A cohort study using data from the 2001-2008 entry panels of the Medicare Current Beneficiary Survey that included 24,607 community-dwelling beneficiaries 65 years of age and older...
May 18, 2017: Archives of Gerontology and Geriatrics
https://www.readbyqxmd.com/read/28544600/effect-of-magnesium-on-arrhythmia-incidence-in-patients-undergoing-coronary-artery-bypass-grafting
#3
Alireza Mohammadzadeh, Farshad Towfighi, Naser Jafari
BACKGROUND: Cardiac arrhythmia after coronary artery bypass grafting (CABG) surgery is a common complication of cardiac surgery. The effect of serum magnesium, hypomagnesaemia treatment and prophylactic administration of magnesium in the development and prevention of arrhythmias is controversial and there are many different ideas. This study evaluates the therapeutic effects of magnesium in cardiac arrhythmia after CABG surgery. METHODS: The clinical trial enrolled 250 patients who underwent CABG...
May 22, 2017: ANZ Journal of Surgery
https://www.readbyqxmd.com/read/28544567/chemoproteomics-aided-medicinal-chemistry-for-the-discovery-of-epha2-inhibitors
#4
Stephanie Heinzlmeir, Jonas Lohse, Tobias Treiber, Denis Kudlinzki, Verena Linhard, Santosh Lakshmi Gande, Sridhar Sreeramulu, Krishna Saxena, Xiaofeng Liu, Mathias Wilhelm, Harald Schwalbe, Bernhard Kuster, Guillaume Médard
The receptor tyrosine kinase EPHA2 has gained interest as therapeutic drug target in cancer and infectious diseases. However, EPHA2 research and EPHA2-based therapies have been hampered by the lack of selective small molecule inhibitors. Here, we report on the synthesis and evaluation of dedicated EPHA2 inhibitors based on the clinical BCR-ABL/SRC inhibitor Dasatinib as a lead structure. We designed hybrid structures of Dasatinib and the previously known EPHA2 binders CHEMBL249097, PD-173955 and a known EPHB4 inhibitor in order to exploit both the ATP pocket entrance as well as the ribose pocket as binding epitopes in the kinase EPHA2...
May 24, 2017: ChemMedChem
https://www.readbyqxmd.com/read/28544386/skin-mucous-membrane-disorder-and-therapeutic-effect-of-pegylated-liposomal-doxorubicin-in-recurrent-ovarian-cancer
#5
Yuki Yamada, Ryuji Kawaguchi, Fuminori Ito, Kana Iwai, Emiko Niiro, Hiroshi Shigetomi, Yasuhito Tanase, Hiroshi Kobayashi
AIM: Hand-foot syndrome (HFS) induced by chemotherapy and molecule-targeting drugs is correlated with treatment efficacy. We conducted a retrospective analysis to evaluate the relationship between HFS and efficacy of pegylated liposomal doxorubicin (PLD) for recurrent ovarian cancer. METHODS: Patients were treated with PLD between July 2009 and May 2014. We evaluated patient characteristics, incidence of adverse events, clinical benefit (rate of complete response, partial response, and stable disease), progression-free survival, and overall survival...
May 19, 2017: Journal of Obstetrics and Gynaecology Research
https://www.readbyqxmd.com/read/28544290/organic-co-prodrugs-structure-co-release-rate-relationship-studies
#6
Binghe Wang, Zhixiang Pan, Xingyue Ji, Vayou Chittavong, Wei Li, Kaili Ji, Mengyuan Zhu, Jun Zhang
Carbon monoxide (CO) is an endogenously produced gasotransmitter in mammals, and may have signaling roles in bacteria as well. It has many recognized therapeutic effects. A significant challenge in this field is the development of pharmaceutically acceptable forms of CO delivery with controllable and tunable release rates. Herein, we describe the structure-release rate studies of the first class of organic CO-prodrugs that release CO in aqueous solution at neutral pH.
May 25, 2017: Chemistry: a European Journal
https://www.readbyqxmd.com/read/28544151/the-emt-spectrum-and-therapeutic-opportunities
#7
REVIEW
Dominic Chih-Cheng Voon, Ruby Yun-Ju Huang, Rebecca A Jackson, Jean Paul Thiery
Carcinomas are phenotypically arrayed along an EMT spectrum, a developmental program currently exploited to understand the acquisition of drug resistance through a re-routing of growth factor signalling. This review collates the current approaches employed in developing therapeutics against cancer-associated EMT, and provides an assessment of their respective strengths and drawbacks. We reflect on the close relationship between EMT and chemoresistance against current targeted therapeutics, with a special focus on the epigenetic mechanisms that links these processes...
May 24, 2017: Molecular Oncology
https://www.readbyqxmd.com/read/28542596/progressive-mitochondrial-protein-lysine-acetylation-and-heart-failure-in-a-model-of-friedreich-s-ataxia-cardiomyopathy
#8
Amanda R Stram, Gregory R Wagner, Brian D Fogler, P Melanie Pride, Matthew D Hirschey, R Mark Payne
INTRODUCTION: The childhood heart disease of Friedreich's Ataxia (FRDA) is characterized by hypertrophy and failure. It is caused by loss of frataxin (FXN), a mitochondrial protein involved in energy homeostasis. FRDA model hearts have increased mitochondrial protein acetylation and impaired sirtuin 3 (SIRT3) deacetylase activity. Protein acetylation is an important regulator of cardiac metabolism and loss of SIRT3 increases susceptibility of the heart to stress-induced cardiac hypertrophy and ischemic injury...
2017: PloS One
https://www.readbyqxmd.com/read/28542136/pak4-regulates-g6pd-activity-by-p53-degradation-involving-colon-cancer-cell-growth
#9
Xiumei Zhang, Xia Zhang, Yang Li, Yangguang Shao, Jianying Xiao, Ge Zhu, Feng Li
The p21-activated kinase 4 (PAK4) is overexpressed in different cancers and promotes proliferation of cancer cells. Reprogramming of glucose metabolism is found in most cancer cells which in turn supports rapid proliferation. However, the relationship between PAK4 and glucose metabolism in cancer cells has not been explored. In this study, we reported that PAK4 promoted glucose intake, NADPH production and lipid biosynthesis, leading to an increased proliferation of colon cancer cells. Mechanistically, PAK4 interacted with glucose-6-phosphate dehydrogenase (G6PD), a rate-limiting enzyme of the pentose phosphate pathway and increased G6PD activity via enhancing Mdm2-mediated p53 ubiquitination degradation...
May 25, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28541554/activation-of-group-2-innate-lymphoid-cells-exacerbates-and-confers-corticosteroid-resistance-to-mouse-nasal-type-2-inflammation
#10
Taiyo Morikawa, Ayumi Fukuoka, Kazufumi Matsushita, Koubun Yasuda, Naruhito Iwasaki, Shoko Akasaki, Shigeharu Fujieda, Tomohiro Yoshimoto
Both Th2 cells and group 2 innate lymphoid cells (ILC2s) contribute to allergic diseases. However, their exact role and relationship in nasal allergic disorders is unclear. In this study, we investigated the cooperation of Th2 cells and ILC2s in a mouse model of nasal allergic disorder. To differentially activate Th2 cells and/or ILC2s in nasal mucosa, mice were intranasally administered ovalbumin (OVA) antigen, papain, an ILC2-activator, or both for 2 weeks. Epithelial thickness and number of eosinophils in the nasal mucosa were evaluated at 24 hours after the final challenge...
May 25, 2017: International Immunology
https://www.readbyqxmd.com/read/28541485/histologically-defined-intratumoral-sequencing-uncovers-evolutionary-cues-into-conserved-molecular-events-driving-gliomagenesis
#11
Antony Prabhu, Pravin Kesarwani, Shiva Kant, Stewart F Graham, Prakash Chinnaiyan
BACKGROUND: Glioblastoma represents an archetypal example of a heterogeneous malignancy. To understand the diverse molecular consequences of this complex tumor ecology, we analyzed RNA-seq data generated from commonly identified intra-tumoral structures in glioblastoma enriched using laser capture microdissection. METHODS: Raw gene-level fragments per kilobase of transcript per million reads mapped (FPKM) values and the associated clinical data were acquired from the publically available Ivy GAP database and analyzed using MetaboAnalyst (v...
May 25, 2017: Neuro-oncology
https://www.readbyqxmd.com/read/28540411/negative-symptoms-anxiety-and-depression-as-mechanisms-of-change-of-a-12-month-trial-of-assertive-community-treatment-as-part-of-integrated-care-in-patients-with-first-and-multi-episode-schizophrenia-spectrum-disorders-access-i-trial
#12
Stefanie J Schmidt, Matthias Lange, Daniel Schöttle, Anne Karow, Benno G Schimmelmann, Martin Lambert
Assertive community treatment (ACT) has shown to be effective in improving both functional deficits and quality of life (QoL) in patients with severe mental illness. However, the mechanisms of this beneficial effect remained unclear. We examined mechanisms of change by testing potential mediators including two subdomains of negative symptoms, i.e. social amotivation as well as expressive negative symptoms, anxiety, and depression within a therapeutic ACT model (ACCESS I trial) in a sample of 120 first- and multi-episode patients with a schizophrenia spectrum disorder (DSM-IV)...
May 24, 2017: European Archives of Psychiatry and Clinical Neuroscience
https://www.readbyqxmd.com/read/28538808/application-of-the-therapeutic-relationship-to-people-with-common-mental-disorder
#13
Maria do Perpétuo Socorro de Sousa Nóbrega, Marta Francisca Trigo Fernandes, Priscila de Freitas Silva
Objective: To report the results from applying a therapeutic relationship to people with common mental disorder. Method: Quantitative, descriptive, before and after study, conducted with 112 records accessed from an extension project in mental health in primary health care in Santo André, São Paulo. Screening was performed using a Self-Reporting Questionnaire. Data was collected in October 2014 and analyzed using simple frequency measures. Results: The entry score ranged between 7 and18 points, and the higher the frequency, the more relationship sessions were necessary...
May 18, 2017: Revista Gaúcha de Enfermagem
https://www.readbyqxmd.com/read/28538758/same-tt2r2-score-in-the-outpatient-anticoagulation-clinic-to-predict-time-in-therapeutic-range-and-adverse-events
#14
Fernando Pivatto, Rafael Selbach Scheffel, Lucas Ries, Ricardo Roitman Wolkind, Roberta Marobin, Sabrina Sigal Barkan, Luís Carlos Amon, Andréia Biolo
Background: The SAMe-TT2R2 score was developed to predict which patients on oral anticoagulation with vitamin K antagonists (VKAs) will reach an adequate time in therapeutic range (TTR) (> 65%-70%). Studies have reported a relationship between this score and the occurrence of adverse events. Objective: To describe the TTR according to the score, in addition to relating the score obtained with the occurrence of adverse events in patients with nonvalvular atrial fibrillation (AF) on oral anticoagulation with VKAs...
April 2017: Arquivos Brasileiros de Cardiologia
https://www.readbyqxmd.com/read/28537895/interaction-of-glycosphingolipids-gd3-and-gd2-with-growth-factor-receptors-maintains-breast-cancer-stem-cell-phenotype
#15
Yuh-Jin Liang, Chen-Yu Wang, I-An Wang, Yi-Wen Chen, Li-Tzu Li, Chuang-Yu Lin, Ming-Yi Ho, Tsung-Lung Chou, Ya-Hui Wang, Shih-Pin Chiou, Yu-Ju Lin, John Yu
Many studies have suggested that disialogangliosides, GD2 and GD3, are involved in the development of various tumor types. However, the functional relationships between ganglioside expression and cancer development or aggressiveness are not fully described. GD3 is upregulated in approximately half of all invasive ductal breast carcinoma cases, and enhanced expression of GD3 synthase (GD3S, alpha-N-acetylneuraminide alpha-2,8-sialyltransferase) in estrogen receptor-negative breast tumors, was shown to correlate with reduced overall patient survival...
May 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28536328/-microrna-in-various-aspects-of-cancer-development
#16
Sho Nambara, Koshi Mimori
MicroRNAs(miRNAs)are small(18-25 nucleotides)noncoding RNA molecules that bind to partially complementary mRNA sequences, resulting in target degradation or translation inhibition. A single miRNA can influence the expression of hundreds of target genes, and miRNAs have been implicated as key molecules in various diseases, including cancer. Many studies have shown that the miRNAs play an important role in cancer cells and tumor microenvironment and may be biomarkers for early detection and therapeutic targets for various cancers...
May 2017: Gan to Kagaku Ryoho. Cancer & Chemotherapy
https://www.readbyqxmd.com/read/28535646/-the-research-advances-in-the-relationship-between-visfatin-and-cancer
#17
W Y Tian, Y M Wang, Y F Zhang, F X Xue
Visfatin is a cytokine secreted by visceral adipose tissue, which plays an important role in obesity, diabetes, insulin resistance, atherosclerosis and polycystic ovarian syndrome. Additionally, visfatin is also involved in the metabolic syndrome-associated malignancies such as breast, colon, gastric and endometrial cancers. Visfatin inhibitor might be a potential antitumor therapeutic strategy for inhibiting the growth of many cancers.
May 23, 2017: Zhonghua Zhong Liu za Zhi [Chinese Journal of Oncology]
https://www.readbyqxmd.com/read/28535629/-association-between-sorcs1-rs1416406-and-therapeutic-effect-of-exenatide
#18
L M Zhou, W Xu, X M Yan, M X Y Li, H Liang, J P Weng
Objective: To study the relationship between SORCS1 gene rs1416406 and efficiency of exenatide. Methods: Between August 2010 and August 2012, a hundred and one newly diagnosed patients with type 2 diabetes mellitus (T2DM) were from CONFIDENCE study covering 25 university-affiliated hospitals in 13 provinces of China. All patients received exenatide treatment for 48 weeks. Hemoglobin A1c (HbA1c), fasting plasma glucose (FPG), body mass index (BMI), oral glucose tolerance test (OGTT) glucose and insulin levels were measured before and after therapy...
May 16, 2017: Zhonghua Yi Xue za Zhi [Chinese medical journal]
https://www.readbyqxmd.com/read/28535625/-expression-and-clinical-significance-of-ser10-phosphorylated-p27-kip1-protein-in-human-breast-carcinoma
#19
Z Q Guo, Q S Lü, Z Wang, L H Lu, N Lu, X W Wen, W X Wu, M Yao
Objective: To explore the expression and clinicopathological significance of Ser10 phosphorylated p27(kip1)(P-p27Ser10) protein in human breast carcinoma tissue. Methods: Tissue specimens were obtained from 111 cases with breast carcinoma from January 2004 to December 2005. And the expression of P-p27Ser10 protein for each specimen was detected by immunohistochemical (EnVision) analysis. Six representative paired samples of cancerous and paired adjacent normal tissues were collected and detected by Western blot...
May 16, 2017: Zhonghua Yi Xue za Zhi [Chinese medical journal]
https://www.readbyqxmd.com/read/28535045/bet-bromodomain-inhibitors-with-one-step-synthesis-discovered-from-virtual-screen
#20
Alex M Ayoub, Laura M L Hawk, Ryan J Herzig, Jiewei Jiang, Andrea J Wisniewski, Clifford T Gee, Peiliang Zhao, Jin-Yi Zhu, Norbert Berndt, Nana K Offei-Addo, Thomas G Scott, Jun Qi, James E Bradner, Timothy R Ward, Ernst Schönbrunn, Gunda I Georg, William C K Pomerantz
Chemical inhibition of epigenetic regulatory proteins BrdT and Brd4 is emerging as a promising therapeutic strategy in contraception, cancer, and heart disease. We report an easily synthesized dihydropyridopyrmidine pan-BET inhibitor scaffold, which was uncovered via a virtual screen followed by testing in a fluorescence anisotropy assay. Dihydropyridpyimidine 3 was subjected to further characterization and is highly selective for the BET family of bromodomains. Structure-activity relationship data and ligand deconstruction highlight the importance of the substitution of the uracil moiety for potency and selectivity...
May 23, 2017: Journal of Medicinal Chemistry
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