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https://www.readbyqxmd.com/read/28109167/cell-cycle-tailored-targeting-of-metastatic-melanoma-challenges-opportunities
#1
Nikolas K Haass, Brian Gabrielli
The advent of targeted therapies of metastatic melanoma, such as MAPK pathway inhibitors and immune checkpoint antagonists, has turned dermato-oncology from the 'bad guy' to the 'poster child' in oncology. Current targeted therapies are effective; although here is a clear need to develop combination therapies to delay the onset of resistance. Many anti-melanoma drugs impact on the cell cycle but are also dependent on certain cell cycle phases resulting in cell cycle phase-specific drug insensitivity. Here, we raise the question: Have combination trials been abandoned prematurely as ineffective possibly only because drug scheduling was not optimized? Firstly, if both drugs of a combination hit targets in the same melanoma cell, cell cycle-mediated drug insensitivity should be taken into account when planning combination therapies, timing of dosing schedules and choice of drug therapies in solid tumors...
January 21, 2017: Experimental Dermatology
https://www.readbyqxmd.com/read/28109133/the-prognostic-and-therapeutic-application-of-micrornas-in-breast-cancer-tissue-and-circulating-micrornas
#2
REVIEW
Afsane Bahrami, Seyed Amir Aledavoud, Kazem Anvari, Seyed Mahdi Hassanian, Mina Maftouh, Ali Yaghobzade, Omid Salarzaee, Soodabeh ShahidSales, Amir Avan
Breast cancer is the second most common malignancy diagnosed in women, supporting the need for identification of novel prognostic and diagnostic biomarkers. Recently, microRNAs have emerged as molecular regulators that can have key roles in pathogenesis and progression of different malignancies, including breast cancer. Micro-RNAs can be circulated in body fluid, suggesting their values as non-invasive marker. There is growing body of evidence showing the aberrant activation of some known circulating miRNAs, e...
January 21, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28109113/-effect-of-sodium-phenylbutyrate-on-the-sensitivity-of-pc3-dtx-resistant-prostate-cancer-cells-to-docetaxel
#3
Ya-Wen Xu, Shao-Bo Zheng, Bin-Sheng Chen, Yong Wen, Shan-Wen Zhu
OBJECTIVE: To investigate the effect of sodium phenylbutyrate (SPB) in modulating docetaxel resistance in human prostate cancer cells in vitro. METHODS: A PC3/docetaxel-resistant human prostate cancer cell line PC3/DTX was induced and examined for proliferation, viability, and cell inhibition rate in the presence of SPB. The concentration of concentration of docetaxel required to kill 50% of PC3/DTX cells incubated with 0, 1, 2, and 4 mmol/L SPB was determined using MTT assay...
2017: Nan Fang Yi Ke da Xue Xue Bao, Journal of Southern Medical University
https://www.readbyqxmd.com/read/28108978/treatment-of-complicated-urinary-tract-infection-and-acute-pyelonephritis-by-short-course-intravenous-levofloxacin-750%C3%A2-mg-day-or-conventional-intravenous-oral-levofloxacin-500%C3%A2-mg-day-prospective-open-label-randomized-controlled-multicenter-non-inferiority
#4
Hong Ren, Xiao Li, Zhao-Hui Ni, Jian-Ying Niu, Bin Cao, Jie Xu, Hong Cheng, Xiao-Wen Tu, Ai-Min Ren, Ying Hu, Chang-Ying Xing, Ying-Hong Liu, Yan-Feng Li, Jun Cen, Rong Zhou, Xu-Dong Xu, Xiao-Hui Qiu, Nan Chen
OBJECTIVE: To compare the efficacy and safety of short-course intravenous levofloxacin (LVFX) 750 mg with a conventional intravenous/oral regimen of LVFX 500 mg in patients from China with complicated urinary tract infections (cUTIs) and acute pyelonephritis (APN). METHODS: This was a prospective, open-label, randomized, controlled, multicenter, non-inferiority clinical trial. Patients with cUTI and APN were randomly assigned to a short-course therapy group (intravenous LVFX at750 mg/day for 5 days) or a conventional therapy group (intravenous/oral regimen of LVFX at 500 mg/day for 7-14 days)...
January 20, 2017: International Urology and Nephrology
https://www.readbyqxmd.com/read/28108622/a-genome-wide-loss-of-function-screen-identifies-slc26a2-as-a-novel-mediator-of-trail-resistance
#5
Lina Dimberg, Christina G Towers, Kian Behbakht, Taylor Hotz, Jihye Kim, Susan P Fosmire, Christopher C Porter, Aik-Choon Tan, Andrew Thorburn, Heide L Ford
: TNF-related apoptosis inducing ligand (TRAIL) is a potent death-inducing ligand that mediates apoptosis through the extrinsic pathway and serves as an important endogenous tumor suppressor mechanism. Because tumor cells are often killed by TRAIL and normal cells are not, drugs that activate the TRAIL pathway have been thought to have potential clinical value. However, to date, most TRAIL-related clinical trials have largely failed due to the tumor cells having intrinsic or acquired resistance to TRAIL-induced apoptosis...
January 20, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28108275/benzofuran-2-acetic-ester-derivatives-induce-apoptosis-in-breast-cancer-cells-by-upregulating-p21-cip-waf1-gene-expression-in-p53-independent-manner
#6
Cinzia Giordano, Daniela Rovito, Ines Barone, Raffaella Mancuso, Daniela Bonofiglio, Francesca Giordano, Stefania Catalano, Bartolo Gabriele, Sebastiano Andò
Breast cancer is the most common malignancy and the leading cause of cancer-related death in women worldwide. High toxicity of used chemotherapeutics and resistance of cancer cells to treatments are a driving force for searching the new drug candidates for breast cancer therapy. In this study, we tested the antiproliferative effects of a series of benzofuran-2-acetic methyl ester derivatives, synthesized by a palladium-catalyzed carbonylative heterocyclization approach, on breast cancer cells. We observed that benzofuran compounds bearing a phenyl or tert-butyl substituent α to the methoxycarbonyl group significantly inhibited anchorage-dependent and -independent cell growth, and induced G0/G1 cell cycle arrest in human estrogen receptor alpha positive (MCF-7 and T47D) and in triple negative MDA-MB-231 breast cancer cells, without affecting growth of MCF-10A normal breast epithelial cells...
January 15, 2017: DNA Repair
https://www.readbyqxmd.com/read/28108242/evaluation-of-the-antimicrobial-activity-of-the-mastoparan-polybia-mpii-isolated-from-venom-of-the-social-wasp-pseudopolybia-vespiceps-testacea-vespidae-hymenoptera
#7
Juliana C Silva, Lázaro M Neto, Rogério C Neves, Jaqueline C Gonçalves, Monalisa M Trentini, Ricardo Mucury-Filho, Karina S Smidt, Isabel C Fensterseifer, Osmar N Silva, Lilian D Lima, Patricia B Clissa, Nathália Vilela, Fernanda Guilhelmelli, Luciano P Silva, Marisa Rangel, André Kipnis, Ildinete Silva-Pereira, Octavio L Franco, Ana P Junqueira-Kipnis, Anamelia L Bocca, Márcia R Mortari
Mastoparans, a class of peptides found in wasp venom, have significant effects following a sting as well as useful applications in clinical practice. Among these is their potential use in the control of micro-organisms that cause infectious diseases with a significant impact on society. Thus, the present study describes the isolation and identification of a mastoparan peptide from the venom of the social wasp Pseudopolybia vespiceps and evaluated its antimicrobial profile against bacteria (Staphylococcus aureus and Mycobacterium abscessus subsp...
January 9, 2017: International Journal of Antimicrobial Agents
https://www.readbyqxmd.com/read/28108199/freedom-from-infection-confirming-interruption-of-malaria-transmission
#8
REVIEW
Gillian Stresman, Angus Cameron, Chris Drakeley
The global reductions in disease burden and the continued spread of drug and insecticide resistance make malaria elimination both viable and imperative, although this may be more easily achieved in some settings compared to others. Whilst the focus has been on optimal approaches to achieve elimination, less attention has been paid to how to measure the absence of malaria. Measuring the absence of transmission poses a specific challenge in that it involves proving a negative. The concept of freedom from infection, routinely used in veterinary epidemiology, can provide quantitative and reproducible estimates that, if infections were present above a predefined (low) threshold, they would be detected with a known uncertainty...
January 17, 2017: Trends in Parasitology
https://www.readbyqxmd.com/read/28108151/a-functional-genetic-screen-identifies-the-phosphoinositide-3-kinase-pathway-as-a-determinant-of-resistance-to-fibroblast-growth-factor-receptor-inhibitors-in-fgfr-mutant-urothelial-cell-carcinoma
#9
Liqin Wang, Tonći Šuštić, Rodrigo Leite de Oliveira, Cor Lieftink, Pasi Halonen, Marieke van de Ven, Roderick L Beijersbergen, Michel M van den Heuvel, René Bernards, Michiel S van der Heijden
Activating mutations and translocations of the FGFR3 gene are commonly seen in urothelial cell carcinoma (UCC) of the bladder and urinary tract. Several fibroblast growth factor receptor (FGFR) inhibitors are currently in clinical development and response rates appear promising for advanced UCC. A common problem with targeted therapeutics is intrinsic or acquired resistance of the cancer cells. To find potential drug targets that can act synergistically with FGFR inhibition, we performed a synthetic lethality screen for the FGFR inhibitor AZD4547 using a short hairpin RNA library targeting the human kinome in the UCC cell line RT112 (FGFR3-TACC3 translocation)...
January 17, 2017: European Urology
https://www.readbyqxmd.com/read/28108098/comparative-efficacies-of-daptomycin-vancomycin-and-linezolid-in-experimental-enterococcal-peritonitis
#10
Toshiki Kajihara, Shigeki Nakamura, Naoki Iwanaga, Kazuhiro Oshima, Katsuji Hirano, Taiga Miyazaki, Koichi Izumikawa, Katsunori Yanagihara, Yoshitsugu Miyazaki, Noboru Hattori, Nobuoki Kohno, Shigeru Kohno, Hiroshi Mukae
Enterococci have become increasingly important pathogens for nosocomial infection (e.g. bacteremia, intra-abdominal infection, endocarditis, etc.), related to their intrinsic resistance to many antibiotics. Although the in vitro susceptibility of daptomycin (DAP) against Enterococci is well established, the Food and Drug Administration has only approved its use for complicated skin and skin structure infections induced by Enterococcus faecalis. In this study we evaluated the potential therapeutic application of DAP in a murine model of enterococcal experimental peritonitis...
January 17, 2017: Journal of Infection and Chemotherapy: Official Journal of the Japan Society of Chemotherapy
https://www.readbyqxmd.com/read/28108091/implementation-of-a-simple-innovative-system-for-postprescription-antibiotic-review-based-on-computerized-tools-with-shared-access
#11
F Bouchand, A Dinh, A L Roux, B Davido, H Michelon, M Lepainteur, B Legendre, F El Sayed, I Pierre, J Salomon, C Lawrence, C Perronne, M Villart, A-C Crémieux
BACKGROUND: Controlling antibiotic use in healthcare establishments limits their consumption and the emergence of bacterial resistance. AIM: To evaluate the efficiency of an innovative antibiotic stewardship strategy implemented over three years in a university hospital. METHODS: An antimicrobial multi-disciplinary team (AMT) [pharmacist, microbiologist and infectious disease specialist (IDS)] conducted a postprescription review. Specific coding of targeted antibiotics (including broad-spectrum β-lactams, glycopeptides, lipopeptides, fluoroquinolones and carbapenems) in the computerized physician order entry allowed recording of all new prescriptions...
November 26, 2016: Journal of Hospital Infection
https://www.readbyqxmd.com/read/28107918/bismuth-nanoparticles-carbon-nanotubes-modified-sensor-for-sulfasalazine-analysis
#12
Biljana Nigović, Sandra Jurić, Iva Mitrović
Nanocomposite of bismuth nanoparticles and carbon nanotubes in Nafion matrix was used as modifier for glassy carbon electrode in analysis of anti-inflamatory drug sulfasalazine. The nanocomposite surface exhibited exceptional synergy and remarkable enhancement effect to the voltammetric response of drug. The surface morphology and structure characterization of the modified electrodes was characterized by scanning electron microscopy, energy dispersive X-ray spectroscopy and cyclic voltammetry. The sensor exhibited excellent electroanalytical performance for drug determination in comparison with bismuth film electrode...
March 1, 2017: Talanta
https://www.readbyqxmd.com/read/28107870/identifications-of-drug-resistance-mutations-among-antiretroviral-treatment-naive-hiv-1-patients-in-peninsular-malaysia
#13
Rozainanee Mohd Zain, Nabila Ibrahim, Suriani Ismail, Jeyanthi Suppiah, Nor Aziyah Mat Rahim, Ravindran Thayan
OBJECTIVE: To determine drug resistance mutations and the HIV-1 subtypes among antiretroviral treatment naive HIV-1 patients in Peninsular Malaysia. METHODS: A total of 45 samples from four hospitals that provide HIV viral load services were subjected to the amplification of the protease and two third of reverse transcriptase regions of the pol gene by RT-PCR and Sanger sequencing. Drug resistance mutation (DRM) interpretation reports the presence of mutations related to protease inhibitors (PIs), Nucleoside reverse-transcriptase inhibitors (NRTI) and Non-nucleoside reverse-transcriptase inhibitors (NNRTI) based on analysis using Stanford HIV database program...
January 2017: Asian Pacific Journal of Tropical Medicine
https://www.readbyqxmd.com/read/28107698/the-natural-flavonoid-apigenin-sensitizes-human-cd44-prostate-cancer-stem-cells-to-cisplatin-therapy
#14
Suat Erdogan, Kader Turkekul, Rıza Serttas, Zeynep Erdogan
Prostate cancer (PCa) is the second most common type of cancer and the fifth leading cause of cancer-related death among men. Development of chemoresistance, tumor relapse and metastasis remain major barriers to effective treatment and all been identified to be associated with cancer stem cells (CSCs). Natural flavonoids such as apigenin have been shown to have the ability to improve the therapeutic efficacy of common chemotherapy agents through CSCs sensitization. Thus, the aim of this study was to evaluate the combination of apigenin with cisplatin on CD44(+) PCa stem cell growth and migration...
January 17, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28107695/antibacterial-activity-computational-analysis-and-host-toxicity-study-of-thymol-sulfonamide-conjugates
#15
Shasank S Swain, Sudhir K Paidesetty, Rabindra N Padhy
Methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin resistant Enterococcus faecalis (VRE) are notorious pathogenic multidrug resistant (MDR) bacteria in both hospital and community sectors, and today the first antibacterial drug sulfamethoxazole is ineffective. The monoterpene phenol, thymol was conjugated with seven sulfa drug derivatives individually, adopting the dye-azo synthesis protocol, and conjugates were characterized using spectral analysis techniques such as, UV, FTIR, MS, HPLC, (1)H NMR, (13)C NMR and SEM...
January 17, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28107674/mitochondrial-serine-hydroxymethyltransferase-2-is-a-potential-diagnostic-and-prognostic-biomarker-for-human-glioma
#16
Bo Wang, Wei Wang, ZhiZhong Zhu, XueBin Zhang, Fan Tang, Dong Wang, Xi Liu, XiaoLing Yan, Hao Zhuang
OBJECTIVE: Scholars have gradually come to appreciate the relevance of serine and glycine metabolism. Recently, researchers have discovered that mitochondrial serine hydroxymethyltransferase 2 (SHMT2) is overexpressed in various types of cancer. However, the function of SHMT2 in glioma is not clear. In this study, we sought to examine the expression of SHMT2 in glioma, the association between SHMT2 expression and clinicopathological characteristics, and the association of SHMT2 expression with prognosis in glioma patients...
January 16, 2017: Clinical Neurology and Neurosurgery
https://www.readbyqxmd.com/read/28107651/one-ring-to-fight-them-all-the-sulfazecin-story
#17
Daniel Braga, Gerald Lackner
In this issue of Cell Chemical Biology, Li et al. (2017) report on the biosynthesis of the monobactam sulfazecin by Pseudomonas acidophila and hypothesize a novel mechanism of β-lactam ring formation. As monobactam antibiotics are unaffected by some emerging resistance mechanisms (particularly metallo-β-lactamases), this discovery opens prospects to engineer β-lactam antibiotics against multi-drug resistant pathogens.
January 19, 2017: Cell Chemical Biology
https://www.readbyqxmd.com/read/28107434/anti-mrka-monoclonal-antibodies-reveal-distinct-structural-and-antigenic-features-of-mrka
#18
Qun Wang, Yan Chen, Romana Cvitkovic, Meghan E Pennini, Chew Shun Chang, Mark Pelletier, Jessica Bonnell, Adem C Koksal, Herren Wu, William F Dall'Acqua, C Kendall Stover, Xiaodong Xiao
Antibody therapy against antibiotics resistant Klebsiella pneumoniae infections represents a promising strategy, the success of which depends critically on the ability to identify appropriate antibody targets. Using a target-agnostic strategy, we recently discovered MrkA as a potential antibody target and vaccine antigen. Interestingly, the anti-MrkA monoclonal antibodies isolated through phage display and hybridoma platforms all recognize an overlapping epitope, which opens up important questions including whether monoclonal antibodies targeting different MrkA epitopes can be generated and if they possess different protective profiles...
2017: PloS One
https://www.readbyqxmd.com/read/28107423/characterization-of-the-drug-resistance-profiles-of-patients-infected-with-crf07_bc-using-phenotypic-assay-and-ultra-deep-pyrosequencing
#19
Szu-Wei Huang, Wei-You Li, Wen-Hung Wang, Yu-Ting Lin, Chih-Hung Chou, Marcelo Chen, Hsien-Da Huang, Yen-Hsu Chen, Po-Liang Lu, Sheng-Fan Wang, Shinichi Oka, Yi-Ming Arthur Chen
The usefulness of ultra-deep pyrosequencing (UDPS) for the diagnosis of HIV-1 drug resistance (DR) remains to be determined. Previously, we reported an explosive outbreak of HIV-1 circulating recombinant form (CRF) 07_BC among injection drug users (IDUs) in Taiwan in 2004. The goal of this study was to characterize the DR of CRF07_BC strains using different assays including UDPS. Seven CRF07_BC isolates including 4 from early epidemic (collected in 2004-2005) and 3 from late epidemic (collected in 2008) were obtained from treatment-naïve patient's peripheral blood mononuclear cells...
2017: PloS One
https://www.readbyqxmd.com/read/28107379/experimental-and-in-silico-investigation-of-anti-microbial-activity-of-1-chloro-2-isocyanatoethane-derivatives-of-thiomorpholine-piperazine-and-morpholine
#20
Charles O Nwuche, Oguejiofo T Ujam, Akachukwu Ibezim, Ifeoma B Ujam
The Antibiogram properties of 1-chloro-2-isocyanatoethane derivatives of thiomorpholine (CTC), piperazine (CPC) and morpholine (CMC) were evaluated by the approved agar well diffusion, the minimum inhibitory concentration (MIC) and in silico techniques. A total of fourteen microbial cultures consisting of ten bacteria and four yeast strains were used in the biological study while affinity of the compounds for DNA gyrase, a validated antibacterial drug target, was investigated by docking method. Results indicate that both thiomorpholine and piperazine had zero activity against the Gram negative organisms tested...
2017: PloS One
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