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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/28108780/cement-augmented-screws-in-a-cervical-two-level-corpectomy-with-anterior-titanium-mesh-cage-reconstruction-a-biomechanical-study
#2
Sebastian Hartmann, Claudius Thomé, Anja Tschugg, Johannes Paesold, Pujan Kavakebi, Werner Schmölz
STUDY DESIGN: Biomechanical investigation. PURPOSE: Cervical two-level corpectomies with anterior-only instrumentation are associated with a high rate of implant-related complications. These procedures, therefore, often require an additional dorsal instrumentation to prevent screw loosening. Cement augmentation of the anterior screws in two-level corpectomies might stabilize the construct, so that a second dorsal procedure could be avoided. To evaluate the screw anchorage in cervical anterior-only procedures, an ex vivo evaluation of the range of motion (ROM) in two-level corpectomies (C4 and C5), with and without cement augmentation of the anterior screws, was carried out in this study...
January 21, 2017: European Spine Journal
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
#3
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/28107995/multivariate-optimization-of-headspace-trap-for-furan-and-furfural-simultaneous-determination-in-sponge-cake
#4
Mayela Cepeda-Vázquez, David Blumenthal, Valérie Camel, Barbara Rega
Furan, a possibly carcinogenic compound to humans, and furfural, a naturally occurring volatile contributing to aroma, can be both found in thermally treated foods. These process-induced compounds, formed by close reaction pathways, play an important role as markers of food safety and quality. A method capable of simultaneously quantifying both molecules is thus highly relevant for developing mitigation strategies and preserving the sensory properties of food at the same time. We have developed a unique reliable and sensitive headspace trap (HS trap) extraction method coupled to GC-MS for the simultaneous quantification of furan and furfural in a solid processed food (sponge cake)...
March 1, 2017: Talanta
https://www.readbyqxmd.com/read/28107977/ultrasensitive-detection-of-mucin-1-biomarker-by-immuno-loop-mediated-isothermal-amplification
#5
Hongmei Cao, Xueen Fang, Haipeng Li, Hua Li, Jilie Kong
Mucin 1 (MUC-1), a glycoprotein over-expressed on most malignant epithelial cell surfaces, such as colorectal, lung, prostate, pancreatic, ovarian, and bladder carcinomas, has been confirmed as a useful biomarker for the diagnosis of early cancers. Therefore, it is very important for early cancer diagnoses to develop the sensitive and specific detection approach of MUC-1. In this paper, we report a novel technique of aptamer-based Immuno-Loop-Mediated Isothermal Amplification (Im-LAMP) for the quantitative detection of MUC-1 by MUC-1 aptamer with high affinity for MUC-1...
March 1, 2017: Talanta
https://www.readbyqxmd.com/read/28107968/towards-perylenequinonoid-effective-application-to-reversible-fluorescent-probe-for-monitoring-hydrogen-persulfide-in-solvents-and-living-cells
#6
Tiancheng Qiu, Haipeng Wei, Dan Cheng, Liyan Zhang, Chuanglin Jiang, Shenglian Luo, Lin Yuan, Zebing Zeng
Hydrogen persulfide (H2S2), as a direct redox form of H2S, may have its own physiological processes in maintaining intracellular redox homeostasis. The research on hydrogen persulfide was rapidly growing. As it is the actual signalling molecules derived from hydrogen sulfide, reversible detection of hydrogen persulfide changes in cells is of great significance. To address this critical need, we present a reversible fluorescent switch-on H2S2 probe, the tautomeric of 6, 7-dihydroxyperylene-1, 12-quinone (DHPQ), capable of tracking H2S2 in solvents and living cells...
March 1, 2017: Talanta
https://www.readbyqxmd.com/read/28107938/nucleotide-base-analog-pyrrolo-deoxycytidine-as-fluorescent-probe-signal-for-enzyme-free-and-signal-amplified-nucleic-acids-detection
#7
Zhijuan Duan, Zhuo Li, Jianyuan Dai, Hongfei He, Dan Xiao
In the present work, an enzyme-free and signal amplified nucleic acids detection method based on the fluorescent nucleotide base analog pyrrolo-deoxycytidine (P-dC) and catalyzed hairpin assembly (CHA) has been developed. In the CHA signal amplification system, two hairpin auxiliary probes, H1 and H2, which containing a fluorescent P-dC at the end of the stem, respectively, were used as the fluorescent probes. The fluorescence of P-dC in H1 and H2 was quenched owing to the stacking interaction among the bases in the stem...
March 1, 2017: Talanta
https://www.readbyqxmd.com/read/28107748/tracing-the-sources-and-cycling-of-phosphorus-in-river-sediments-using-oxygen-isotopes-methodological-adaptations-and-first-results-from-a-case-study-in-france
#8
Chiara Pistocchi, Federica Tamburini, Gerard Gruau, André Ferhi, Dominique Trevisan, Jean-Marcel Dorioz
An essential aspect of eutrophication studies is to trace the ultimate origin of phosphate ions (P-PO4) associated with the solid phase of river sediments, as certain processes can make these ions available for algae. However, this is not a straightforward task because of the diversity of allochthonous and autochthonous sources that can supply P-PO4 to river sediments as well as the existence of in-stream processes that can change the speciation of these inputs and obscure the original sources. Here, we present the results of a study designed to explore the potentials, limitations and conditions for the use of the oxygen isotope composition of phosphate (δ(18)Op) extracted from river sediments for this type of tracing...
December 26, 2016: Water Research
https://www.readbyqxmd.com/read/28107698/the-natural-flavonoid-apigenin-sensitizes-human-cd44-prostate-cancer-stem-cells-to-cisplatin-therapy
#9
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/28107167/activity-of-the-liver-enzyme-ornithine-carbamoyltransferase-otc-in-blood-lc-ms-ms-assay-for-non-invasive-diagnosis-of-ornithine-carbamoyltransferase-deficiency
#10
Jakub Krijt, Jitka Sokolová, Pavel Ješina, Lenka Dvořáková, Martin Řeboun, Katarína Brennerová, Martin Mistrík, Jiří Zeman, Tomáš Honzík, Viktor Kožich
BACKGROUND: Liver enzymes are released from hepatocytes into circulation and their activity can be measured in the blood. We examined whether the plasma activity of the liver enzyme ornithine carbamoyltransferase, determined by a novel liquid chromatography-mass spectrometry (LC-MS/MS) assay, could be utilized for the detection of OTC deficiency (OTCD), an X-linked inborn error of the urea cycle. METHODS: The plasma ornithine carbamoyltransferase (OTC) activity was assayed in the reverse reaction using isotopically labeled citrulline-d4 as a substrate and by determination of the product, ornithine-d4, by LC-MS/MS analysis...
January 20, 2017: Clinical Chemistry and Laboratory Medicine: CCLM
https://www.readbyqxmd.com/read/28107059/age-dependent-modulation-of-songbird-summer-feather-molt-by-temporal-and-functional-constraints
#11
Yosef Kiat, Nir Sapir
Time constraints influence various ecological, life-history, and demographic properties of individuals and populations of many species throughout the annual cycle. Feather molt is a timely undertaking that is considered among the three most energy-demanding processes in the life cycle of birds. To deal with time pressure, passerines may shorten their molt duration, using three non-mutually exclusive mechanisms: (1) replacing only part of the plumage, (2) increasing the speed of molt, and (3) postponing the renewal of some or all the plumage to a later season (i...
February 2017: American Naturalist
https://www.readbyqxmd.com/read/28106981/controlling-multi-cycle-replication-of-live-attenuated-hiv-1-using-an-unnatural-genetic-switch
#12
Zhe Yuan, Nanxi Wang, Guobin Kang, Wei Niu, Qingsheng Li, Jiantao Guo
A safe and effective human immunodeficiency virus type 1 (HIV-1) vaccine is urgently needed, but remains elusive. While HIV-1 live-attenuated vaccine can provide potent protection as demonstrated in rhesus macaque-simian immunodeficiency virus model, the potential pathogenic consequences associated with the uncontrolled virus replication preclude such vaccine from clinical applications. We investigated a novel approach to address this problem by controlling live-attenuated HIV-1 replication through an unnatural genetic switch that was based on the amber suppression strategy...
January 20, 2017: ACS Synthetic Biology
https://www.readbyqxmd.com/read/28106643/imaging-and-the-infertility-evaluation
#13
Roohi Jeelani, Elizabeth E Puscheck
Ultrasound (US) has transformed the fertility evaluation. With 1 consultation, blood work and 1 to 2 USs, the female fertility status can be fully evaluated. The initial US is best done early in the follicular cycle to evaluate the pelvic anatomy and ovarian reserve. A three-dimensional US is important to evaluate for uterine anomalies and color Doppler for any masses. A mid-cycle saline infusion sonohysterogram assesses the endometrial cavity better than a hysterosalpingogram as it identifies the cause of any filling defects...
March 2017: Clinical Obstetrics and Gynecology
https://www.readbyqxmd.com/read/28106296/pten-plays-dual-roles-as-a-tumor-suppressor-in-osteosarcoma-cells
#14
Yongming Xi, Yan Chen
Osteosarcoma (OS) is the most common primary bone cancer, which occurs primarily in children and adolescents. Functional loss of the tumor suppressor PTEN has been demonstrated in bone malignancies including OS. We have recently reported that Pten expression inversely correlates with OS aggressiveness in mouse models. However, the mechanism whereby PTEN exerts its anti-tumor effect remains unknown. In this study, we first examined the expression of PTEN in human OS cell lines including U2OS, MG63 and Saos-2, and found that PTEN expression is reduced as compared to normal human osteoblasts...
January 20, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28106048/simulating-the-hydrologic-cycle-in-coal-mining-subsidence-areas-with-a-distributed-hydrologic-model
#15
Jianhua Wang, Chuiyu Lu, Qingyan Sun, Weihua Xiao, Guoliang Cao, Hui Li, Lingjia Yan, Bo Zhang
Large-scale ground subsidence caused by coal mining and subsequent water-filling leads to serious environmental problems and economic losses, especially in plains with a high phreatic water level. Clarifying the hydrologic cycle in subsidence areas has important practical value for environmental remediation, and provides a scientific basis for water resource development and utilisation of the subsidence areas. Here we present a simulation approach to describe interactions between subsidence area water (SW) and several hydrologic factors from the River-Subsidence-Groundwater Model (RSGM), which is developed based on the distributed hydrologic model...
January 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28106010/models-of-life-epigenetics-diversity-cycles
#16
Kim Sneppen
This review emphasize aspects of biology that can be understood through repeated applications of simple causal rules. The selected topics include perspectives on gene regulation, phage lambda development, epigenetics, microbial ecology, as well as model approaches to diversity and punctuated equilibrium in evolution. Two outstanding features are repeatedly described. One is minimal rules to sustain specific states of a complex systems for a long time. The other is the collapse of such states and the subsequent dynamical cycle of situations that later return to new metastable states...
January 20, 2017: Reports on Progress in Physics
https://www.readbyqxmd.com/read/28105936/pathways-of-aging-comparative-analysis-of-gene-signatures-in-replicative-senescence-and-stress-induced-premature-senescence
#17
Kamil C Kural, Neetu Tandon, Mikhail Skoblov, Olga V Kel-Margoulis, Ancha V Baranova
BACKGROUND: In culturing normal diploid cells, senescence may either happen naturally, in the form of replicative senescence, or it may be a consequence of external challenges such as oxidative stress. Here we present a comparative analysis aimed at reconstruction of molecular cascades specific for replicative (RS) and stressinduced senescence (SIPS) in human fibroblasts. RESULTS: An involvement of caspase-3/keratin-18 pathway and serine/threonine kinase Aurora A/ MDM2 pathway was shared between RS and SIPS...
December 28, 2016: BMC Genomics
https://www.readbyqxmd.com/read/28105843/adaptive-pcr-based-on-hybridization-sensing-of-mirror-image-l-dna
#18
Nicholas M Adams, William E Gabella, Austin N Hardcastle, Frederick R Haselton
Polymerase chain reaction (PCR) is dependent on two key hybridization events during each cycle of amplification, primer annealing and product melting. To ensure that these hybridization events occur, current PCR approaches rely on temperature set points and reaction contents that are optimized and maintained using rigid thermal cycling programs and stringent sample preparation procedures. This report describes a fundamentally simpler and more robust PCR design that dynamically controls thermal cycling by more directly monitoring the two key hybridization events during the reaction...
January 3, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/28105811/palladium-catalyzed-denitrogenative-synthesis-of-aryl-ketones-from-arylhydrazines-and-nitriles-using-o2-as-sole-oxidant
#19
Xu Wang, Yubing Huang, Yanli Xu, Xiaodong Tang, Wanqing Wu, Huanfeng Jiang
An efficient and simple palladium-catalyzed approach for the synthesis of aryl ketones from low-cost nitriles and arylhydrazines using molecular oxygen (O2) as sole oxidant via C-N bond cleavage is reported. Various aryl ketones were synthesized in moderate to good yields under mild conditions. A possible mechanism involving the PdII/Pd0 catalytic cycle process is depicted, and a cationic palladium intermediate was detected by ESI-MS.
January 20, 2017: Journal of Organic Chemistry
https://www.readbyqxmd.com/read/28105486/immobilization-of-alkaline-polygalacturonate-lyase-from-bacillus-subtilis-on-the-surface-of-bacterial-polyhydroxyalkanoate-nano-granules
#20
GanQiao Ran, Dan Tan, WeiEr Dai, XinLiang Zhu, JiPing Zhao, Qi Ma, XiaoYun Lu
Alkaline polygalacturonate lyase (PGL), one of the pectinolytic enzymes, has been widely used for the bioscouring of cotton fibers, biodegumming, and biopulp production. In our study, PGL from Bacillus subtilis was successfully immobilized on the surface of polyhydroxyalkanoate (PHA) nanogranules by fusing PGL to the N-terminal of PHA synthase from Ralstonia eutropha via a designed linker. The PGL-decorated PHA beads could be simply achieved by recombinant fermentation and consequent centrifugation. The fused PGL occupied 0...
January 20, 2017: Applied Microbiology and Biotechnology
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