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https://www.readbyqxmd.com/read/28088627/the-telomere-binding-protein-trf2-is-required-for-metronomic-therapeutic-effects-of-gemcitabine-and-capecitabine
#1
Wei-Ping Lee, Keng-Hsin Lan, Chung-Pin Li, Yee Chao, Ming-Chih Hou, Han-Chieh Lin, Shou-Dong Lee
Gemcitabine and capecitabine are two effective anticancer agents against solid tumors. The pharmacological mechanisms have been known as incorporation into DNA and thereby inhibition of DNA synthesis. When used as metronomic chemotherapy, they may inhibit angiogenesis and induce immunity. In our previous study, we showed that low-dose gemcitabine caused telomere shortening by stabilizing TRF2 that was required for XPF-dependent telomere loss. In this report, we established a SKOV3.ip1 ascites cell model. Tumor-bearing mice were treated with low-dose gemcitabine (GEM) or capecitabine (CAP)...
January 11, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28087363/membrane-restructuring-following-in-situ-sialidase-digestion-of-gangliosides-complex-model-bilayers-by-synchrotron-radiation-reflectivity
#2
Valeria Rondelli, Paola Brocca, Giovanna Fragneto, Jean Daillant, Cristina Tringali, Laura Cantu', Elena Del Favero
Synchrotron radiation reflectometry was used to access the transverse structure of model membranes under the action of the human sialidase NEU2, down to the Ångström length scale. Model membranes were designed to mimic the lipid composition of so-called Glycosphingolipids Enriched Microdomains (GEMs), which are membrane platforms specifically enriched in cholesterol and sphingolipids, where also typical signalling molecules are hosted. Gangliosides, glycosphingolipids containing one or more sialic acid residues, are asymmetrically embedded in GEMs, in the outer membrane leaflet...
January 10, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28078792/synthesis-of-1-difluoroalkylated-isoquinolines-via-palladium-catalyzed-radical-cascade-difluoroalkylation-cyclization-of-vinyl-isocyanides-with-bromodifluoroacetic-derivatives
#3
Yingle Liu, Ke Zhang, Weidong Jiang, Yi Yang, Yan Jiang, Xiaoqiang Liu, Ying Xie, Jincai Wu, Junjie Cai, Xiu-Hua Xu
A general method for the synthesis of 1-difluoroalkyl isoquinolines through a palladium-catalyzed radical cascade difluoroalkylation-cyclization of vinyl isocyanides with bromodifluoroacetic derivants is described.The difluoroalkylation-cyclization products can also be readily converted to more valuable gem-difluorocontaining compounds.
January 11, 2017: Chemistry, An Asian Journal
https://www.readbyqxmd.com/read/28076775/nutritional-programming-of-lifespan-by-foxo-inhibition-on-sugar-rich-diets
#4
Adam J Dobson, Marina Ezcurra, Charlotte E Flanagan, Adam C Summerfield, Matthew D W Piper, David Gems, Nazif Alic
Consumption of unhealthy diets is exacerbating the burden of age-related ill health in aging populations. Such diets can program mammalian physiology to cause long-term, detrimental effects. Here, we show that, in Drosophila melanogaster, an unhealthy, high-sugar diet in early adulthood programs lifespan to curtail later-life survival despite subsequent dietary improvement. Excess dietary sugar promotes insulin-like signaling, inhibits dFOXO-the Drosophila homolog of forkhead box O (FOXO) transcription factors-and represses expression of dFOXO target genes encoding epigenetic regulators...
January 10, 2017: Cell Reports
https://www.readbyqxmd.com/read/28073764/causal-effect-of-genetic-variants-associated-with-body-mass-index-on-multiple-sclerosis-susceptibility
#5
Milena A Gianfrancesco, M Maria Glymour, Stefan Walter, Brooke Rhead, Xiaorong Shao, Ling Shen, Hong Quach, Alan Hubbard, Ingileif Jónsdóttir, Kári Stefánsson, Pernilla Strid, Jan Hillert, Anna Hedström, Tomas Olsson, Ingrid Kockum, Catherine Schaefer, Lars Alfredsson, Lisa F Barcellos
Multiple sclerosis (MS) is an autoimmune disease with both genetic and environmental risk factors. Recent studies indicate that childhood and adolescent obesity double the risk of MS, but this association may reflect unmeasured confounders rather than causal effects of obesity. We used separate-sample Mendelian randomization to estimate the causal effect of body mass index (BMI) on susceptibility to MS. Using data from non-Hispanic white members of the Kaiser Permanente Medical Care Plan of Northern California (KPNC) (2006-2014; 1,104 cases of MS and 10,536 controls) and a replication data set from Sweden (the Epidemiological Investigation of MS (EIMS) and the Genes and Environment in MS (GEMS) studies, 2005-2013; 5,133 MS cases and 4,718 controls), we constructed a weighted genetic risk score using 97 variants previously established to predict BMI...
January 9, 2017: American Journal of Epidemiology
https://www.readbyqxmd.com/read/28072706/a-randomized-multicenter-phase-iii-study-of-gemcitabine-combined-with-capecitabine-versus-gemcitabine-alone-as-first-line-chemotherapy-for-advanced-pancreatic-cancer-in-south-korea
#6
Hee Seung Lee, Moon Jae Chung, Jeong Youp Park, Seungmin Bang, Seung Woo Park, Ho Gak Kim, Myung Hwan Noh, Sang Hyub Lee, Yong-Tae Kim, Hyo Jung Kim, Chang Duck Kim, Dong Ki Lee, Kwang Bum Cho, Chang Min Cho, Jong Ho Moon, Dong Uk Kim, Dae Hwan Kang, Young Koog Cheon, Ho Soon Choi, Tae Hyeon Kim, Jae Kwang Kim, Jieun Moon, Hye Jung Shin, Si Young Song
BACKGROUND: This phase III trial compared the efficacy and safety of gemcitabine plus capecitabine (GemCap) versus single-agent gemcitabine (Gem) in advanced pancreatic cancer as first-line chemotherapy. METHODS: A total of 214 advanced pancreatic cancer patients were enrolled from 16 hospitals in South Korea between 2007 and 2011. Patients were randomly assigned to receive GemCap (oral capecitabine 1660 mg/m plus Gem 1000 mg/m by 30-minute intravenous infusion weekly for 3 weeks followed by a 1-week break every 4 weeks) or Gem (by 30-minute intravenous infusion weekly for 3 weeks every 4 weeks)...
January 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28071891/dual-enzymatic-reaction-assisted-gemcitabine-delivery-systems-for-programmed-pancreatic-cancer-therapy
#7
Haijie Han, Daniel Valdeperez, Qiao Jin, Bin Yang, Zuhong Li, Yulian Wu, Beatriz Pelaz, Wolfgang J J Parak, Jian Ji
Dual enzymatic reactions were introduced to fabricate programmed gemcitabine (GEM) nanovectors for targeted pancreatic cancer therapy. Dual-enzyme sensitive GEM nanovectors were prepared by conjugation of matrix metalloproteinase-9 (MMP-9) detachable poly(ethylene glycol) (PEG), cathepsin B cleavable GEM, and targeting ligand CycloRGD to CdSe/ZnS quantum dots (QDs). The GEM nanovectors decorated with PEG corona could avoid nonspecific interactions and exhibit prolonged blood circulation time. After GEM nanovectors were accumulated in tumor tissue by the enhanced permeability and retention (EPR) effect, the PEG corona can be removed by overexpressed MMP-9 in tumor tissue and RGD would be exposed, which was capable of facilitating cellular internalization...
January 10, 2017: ACS Nano
https://www.readbyqxmd.com/read/28065383/molecular-alterations-contributing-to-pancreatic-cancer-chemoresistance
#8
REVIEW
Azam Rajabpour, Farzad Rajaei, Ladan Teimoori-Toolabi
Pancreatic ductal adenocarcinoma (PDAC) is one of the most common causes of cancer-related death all over the world. This disease is difficult to treat and patients have an overall 5-year survival rate of less than 5%. Although two drugs, gemcitabine (GEM) and 5-fluorouracil (5-FU) have been shown to improve the survival rate of patients systematically, they do not increase general survival to a clinically acceptable degree. Lack of ideal clinical response of pancreatic cancer patients to chemotherapy is likely to be due to intrinsic and acquired chemoresistance of tumor cells...
December 28, 2016: Pancreatology: Official Journal of the International Association of Pancreatology (IAP) ... [et Al.]
https://www.readbyqxmd.com/read/28060420/multimetallic-hierarchical-aerogels-shape-engineering-of-the-building-blocks-for-efficient-electrocatalysis
#9
Bin Cai, Arezoo Dianat, René Hübner, Wei Liu, Dan Wen, Albrecht Benad, Luisa Sonntag, Thomas Gemming, Gianaurelio Cuniberti, Alexander Eychmüller
A new class of multimetallic hierarchical aerogels composed entirely of interconnected Ni-Pdx Pty nano-building blocks with in situ engineered morphologies and compositions is demonstrated. The underlying mechanism of the galvanic shape-engineering is elucidated in terms of nanowelding of intermediate nanoparticles. The hierarchical aerogels integrate two levels of porous structures, leading to improved electrocatalysis performance.
January 6, 2017: Advanced Materials
https://www.readbyqxmd.com/read/28055291/metuzumab-enhanced-chemosensitivity-and-apoptosis-in-non-small-cell-lung-carcinoma
#10
Fei Feng, Bin Wang, Xiuxuan Sun, Yumeng Zhu, Hao Tang, Gang Nan, Lijuan Wang, Bo Wu, Muren Huhe, Shuangshuang Liu, Tengyue Diao, Rong Hou, Yang Zhang, Zheng Zhang
Targeted therapeutics is used as an alternative treatment for non-small cell lung cancer (NSCLC); however, treatment effect is far from being satisfactory, and therefore identification of new targets is needed. We have previously shown that metuzumab inhibit tumor growth in vivo. The present study was performed to investigate the anti-tumor efficacy of metuzumab combined with gemcitabine and cisplatin (GP), paclitaxel and cisplatin (TP) or navelbine and cisplatin (NP) regimens in multiple NSCLC cell lines. Our results demonstrate that, in comparison to single agent metuzumab or GP treated cells, metuzumab combined with GP display inhibitory effects on tumor growth...
January 5, 2017: Cancer Biology & Therapy
https://www.readbyqxmd.com/read/28053958/inducible-mouse-models-for-cancer-drug-target-validation
#11
REVIEW
Joseph H Jeong
Genetically-engineered mouse (GEM) models have provided significant contributions to our understanding of cancer biology and developing anticancer therapeutic strategies. The development of GEM models that faithfully recapitulate histopathological and clinical features of human cancers is one of the most pressing needs to successfully conquer cancer. In particular, doxycycline-inducible transgenic mouse models allow us to regulate (induce or suppress) the expression of a specific gene of interest within a specific tissue in a temporal manner...
December 2016: Journal of Cancer Prevention
https://www.readbyqxmd.com/read/28045649/cost-effectiveness-of-pemetrexed-in-combination-with-cisplatin-as-first-line-treatment-for-patients-with-advanced-non-squamous-non-small-cell-lung-cancer-in-spain
#12
Jonathan González García, Fernando Gutiérrez Nicolás, Gloria Julia Nazco Casariego, Cristina Valcárcel Nazco, Jose Norberto Batista López, Juana Oramas Rodríguez
INTRODUCTION: Lung cancer is the third most frequent neoplastic tumour in Spain, with around 27 000 new cases diagnosed per year; 80-95% of these are non-small-cell cancer (NSCLC), and the majority of cases are diagnosed in advanced stages of the disease, and for this reason it is one of the oncologic conditions with higher mortality rates (21.4% mean survival at 5 years). The main treatment regimens used for first-line treatment of NSCLC are: cisplatin/pemetrexed (cis/pem), cisplatin/gemcitabine/ bevacizumab (cis/gem/bev), and carboplatin/paclitaxel/ bevacizumab (carb/pac/bev)...
January 1, 2017: Farmacia Hospitalaria
https://www.readbyqxmd.com/read/28039362/defining-the-temporal-course-of-murine-neurofibromatosis-1-optic-gliomagenesis-reveals-a-therapeutic-window-to-attenuate-retinal-dysfunction
#13
Joseph A Toonen, Yu Ma, David H Gutmann
BACKGROUND: Optic gliomas arising in the neurofibromatosis type 1 (NF1) cancer predisposition syndrome cause reduced visual acuity in 30%-50% of affected children. Since human specimens are rare, genetically engineered mouse (GEM) models have been successfully employed for preclinical therapeutic discovery and validation. However, the sequence of cellular and molecular events that culminate in retinal dysfunction and vision loss has not been fully defined relevant to potential neuroprotective treatment strategies...
December 29, 2016: Neuro-oncology
https://www.readbyqxmd.com/read/28029789/gem-diprenylation-of-acylphloroglucinols-by-a-fungal-prenyltransferase-of-the-dimethylallyltryptophan-synthase-superfamily
#14
Kang Zhou, Carsten Wunsch, Jungui Dai, Shu-Ming Li
Aspergillus terreus aromatic prenyltransferase (AtaPT) catalyzes predominantly C-monoprenylation of acylphloroglucinols in the presence of different prenyl diphosphates. With dimethylallyl diphosphate (DMAPP) as prenyl donor, gem-diprenylated products 1D3, 2D3, and 3D3 were also detected. High conversion of 1D1 to 1D3, 2D1 to 2D3, and 3D1 to 3D3 was demonstrated by incubation with AtaPT and DMAPP. The first example of gem-diprenylation by a member of the dimethylallyltryptophan synthase superfamily is provided...
December 28, 2016: Organic Letters
https://www.readbyqxmd.com/read/28029039/stimuli-sensitive-biodegradable-and-amphiphilic-block-copolymer-gemcitabine-conjugates-self-assemble-into-a-nanoscale-vehicle-for-cancer-therapy
#15
Zhenyu Duan, Yanhong Zhang, Hongyan Zhu, Ling Sun, Hao Cai, Bijin Li, Qiyong Gong, Zhongwei Gu, Kui Luo
The availability and the stability of current anticancer agents, particularly water-insoluble drugs, are still far from satisfactory. A widely used anticancer drug, gemcitabine (GEM), is so poorly stable in circulation that some polymeric drug-delivery systems have been under development for sometimes to improve its therapeutic indexes. Herein, we designed, prepared and characterized a biodegradable amphiphilic block N-(2-hydroxypropyl) methacrylamide (HPMA) copolymer-GEM conjugate-based nanoscale and stimuli-responsive drug delivery vehicle...
December 28, 2016: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28027677/do-prerecorded-lecture-vodcasts-affect-lecture-attendance-of-first-yearpre-clinical-graduate-entry-to-medicine-students
#16
Mark G Rae, Dervla O'Malley
BACKGROUND: There is increasing concern amongst educators that the provision of recorded lectures may reduce student attendance of live lectures. We therefore sought to determine if the provision of prerecorded lecture video podcasts (VODcasts) to first-year Graduate Entry to Medicine (GEM) students, affected attendance at 21 Physiology lectures within three separate pre-clinical modules. METHODS: Data on lecture attendance, utilization of VODcasts, and whether VODcasts should replace live lectures were drawn from three surveys conducted in academic years 2014-2015 and 2015-2016 on all first-year GEM students in two first-year pre-clinical modules where prerecorded Physiology VODcasts were available for viewing or downloading prior to scheduled live lectures...
December 27, 2016: Medical Teacher
https://www.readbyqxmd.com/read/28007448/bioreductively-activatable-prodrug-conjugates-of-phenstatin-designed-to-target-tumor-hypoxia
#17
Blake A Winn, Zhe Shi, Graham J Carlson, Yifan Wang, Benson L Nguyen, Evan M Kelly, R David Ross, Ernest Hamel, David J Chaplin, Mary L Trawick, Kevin G Pinney
A variety of solid tumor cancers contain significant regions of hypoxia, which provide unique challenges for targeting by potent anticancer agents. Bioreductively activatable prodrug conjugates (BAPCs) represent a promising strategy for therapeutic intervention. BAPCs are designed to be biologically inert until they come into contact with low oxygen tension, at which point reductase enzyme mediated cleavage releases the parent anticancer agent in a tumor-specific manner. Phenstatin is a potent inhibitor of tubulin polymerization, mimicking the chemical structure and biological activity of the natural product combretastatin A-4...
December 1, 2016: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28003712/preliminary-results-of-btdf-calibration-of-transmissive-solar-diffusers-for-remote-sensing
#18
Georgi T Georgiev, James J Butler, Kurt Thome, Catherine Cooksey, Leibo Ding
Satellite instruments operating in the reflected solar wavelength region require accurate and precise determination of the optical properties of their diffusers used in pre-flight and post-flight calibrations. The majority of recent and current space instruments use reflective diffusers. As a result, numerous Bidirectional Reflectance Distribution Function (BRDF) calibration comparisons have been conducted between the National Institute of Standards and Technology (NIST) and other industry and university-based metrology laboratories...
2016: Proceedings of SPIE
https://www.readbyqxmd.com/read/28001233/candida-arthritis-in-a-patient-diagnosed-with-spondyloarthritis
#19
Remzi Çevik, Recep Tekin, Mehmet Gem
Candida arthritis is an unusual manifestation that usually affects the knees. A 35-year-old man presented with a 2-month history of pain and swelling in the right knee. Swelling persisted after anti-inflammatory treatment. Peripheric spondyloarthritis was considered, but methotrexate, sulfasalazine, and methylprednisolone did not reduce the swelling. Direct examination of synovial fluid and a culture were positive for Candida albicans. Intravenous and intra-articular amphotericin-B were administered. The arthritis regressed and a culture and direct staining showed negative results...
November 2016: Revista da Sociedade Brasileira de Medicina Tropical
https://www.readbyqxmd.com/read/28000865/pi3k-inhibitor-ly294002-as-opposed-to-wortmannin-enhances-akt-phosphorylation-in-gemcitabine-resistant-pancreatic-cancer-cells
#20
Yufeng Wang, Yasuhiro Kuramitsu, Byron Baron, Takao Kitagawa, Kazuhiro Tokuda, Junko Akada, Shin-Ichiro Maehara, Yoshihiko Maehara, Kazuyuki Nakamura
LY294002 and wortmannin are chemical compounds that act as potent inhibitors of phosphoinositide 3-kinases (PI3Ks). Both of them are generally used to inhibit cell proliferation as cancer treatment by inhibiting the PI3K/protein kinase B (AKT) signaling pathway. In this study, LY294002 (but not wortmannin) showed an abnormal ability to enhance AKT phosphorylation (at Ser472) specifically in gemcitabine (GEM)-resistant pancreatic cancer (PC) cell lines PK59 and KLM1-R. LY294002 was shown to activate AKT and accumulate phospho-AKT at the intracellular membrane in PK59, which was abolished by treatment with AKTi-1/2 or wortmannin...
December 14, 2016: International Journal of Oncology
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