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Molecular cell biology

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https://www.readbyqxmd.com/read/29156792/liquid-biopsy-in-colon-cancer-comparison-of-different-circulating-dna-extraction-systems-following-absolute-quantification-of-kras-mutations-using-intplex-allele-specific-pcr
#1
Vera Kloten, Nadine Rüchel, Nadina Ortiz Brüchle, Janina Gasthaus, Nils Freudenmacher, Florian Steib, Jolein Mijnes, Julian Eschenbruch, Marcel Binnebösel, Ruth Knüchel, Edgar Dahl
Non-invasive molecular analysis of circulating tumor DNA (ctDNA) is a promising application in personalized cancer management, although there is still much to learn about the biological characteristics of ctDNA. The present study compared absolute amounts of KRAS mutated ctDNA and total circulating cell-free DNA (cfDNA) in colorectal cancer (CRC) patients (n=50) from various stages and healthy controls (n=8) by Intplex allele-specific and digital droplet PCR. In addition, the impact of two prominent extraction techniques (silica-based membrane vs...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29156678/epigenetic-silencing-of-tumor-suppressor-candidate-3-confers-adverse-prognosis-in-early-colorectal-cancer
#2
Elke Burgermeister, Patrick Höde, Johannes Betge, Tobias Gutting, Andreas Merkel, Wen Wu, Marc Tänzer, Maximilian Mossner, Daniel Nowak, Julia Magdeburg, Felix Rückert, Carsten Sticht, Katja Breitkopf-Heinlein, Nadine Schulte, Nicolai Härtel, Sebastian Belle, Stefan Post, Timo Gaiser, Barbara Ingold Heppner, Hans-Michael Behrens, Christoph Röcken, Matthias P A Ebert
Colorectal cancer (CRC) is a biologically and clinically heterogeneous disease. Even though many recurrent genomic alterations have been identified that may characterize distinct subgroups, their biological impact and clinical significance as prognostic indicators remain to be defined. The tumor suppressor candidate-3 (TUSC3/N33) locates to a genomic region frequently deleted or silenced in cancers. TUSC3 is a subunit of the oligosaccharyltransferase (OST) complex at the endoplasmic reticulum (ER) which catalyzes bulk N-glycosylation of membrane and secretory proteins...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29156384/targeting-fgfr-pathway-in-breast-cancer
#3
J Perez-Garcia, E Muñoz-Couselo, J Soberino, F Racca, J Cortes
Developments in breast cancer biology over the last years have permitted deconstructing the molecular profile of the most relevant breast cancer subtypes. This has led to an increase in therapeutic options, including more effective personalized therapy for breast cancer and substantial improvements in patient outcomes. Although currently there are only a few targeted therapies approved for metastatic breast cancer, the discovery of druggable kinase gene alterations has radically changed cancer treatment by providing novel and successfully actionable drug targets...
November 17, 2017: Breast: Official Journal of the European Society of Mastology
https://www.readbyqxmd.com/read/29156376/comparative-transcriptomic-analysis-of-endothelial-progenitor-cells-derived-from-umbilical-cord-blood-and-adult-peripheral-blood-implications-for-the-generation-of-induced-pluripotent-stem-cells
#4
Xiugong Gao, Jeffrey J Yourick, Robert L Sprando
Induced pluripotent stem cells (iPSCs) offer the potential to generate tissues with ethnic diversity enabling toxicity testing on selected populations. Recently, it has been reported that endothelial progenitor cells (EPCs) derived from umbilical cord blood (CB) or adult peripheral blood (PB) afford a practical and efficient cellular substrate for iPSC generation. However, differences between EPCs from different blood sources have rarely been studied. In the current study, we derived EPCs from blood mononuclear cells (MNCs) and reprogrammed EPCs into iPSCs...
November 7, 2017: Stem Cell Research
https://www.readbyqxmd.com/read/29156254/xenografted-tissue-models-for-the-study-of-human-endometrial-biology
#5
REVIEW
Satu Kuokkanen, Liyin Zhu, Jeffrey W Pollard
The human endometrium undergoes extensive morphological, biochemical and molecular changes under the influence of female sex steroid hormones. Besides the fact that estrogen stimulates endometrial cell proliferation and progesterone inhibits this proliferation and induces differentiation, there is limited knowledge about precise molecular mechanisms underlying human endometrial biology. The importance of paracrine signaling in endometrial physiology explains why in vitro culture of endometrial cells has been challenging...
November 10, 2017: Differentiation; Research in Biological Diversity
https://www.readbyqxmd.com/read/29155750/ground-state-depletion-super-resolution-imaging-in-mammalian-cells
#6
Rose E Dixon, Oscar Vivas, Karen I Hannigan, Eamonn J Dickson
Advances in fluorescent microscopy and cell biology are intimately correlated, with the enhanced ability to visualize cellular events often leading to dramatic leaps in our understanding of how cells function. The development and availability of super-resolution microscopy has considerably extended the limits of optical resolution from ~250-20 nm. Biologists are no longer limited to describing molecular interactions in terms of colocalization within a diffraction limited area, rather it is now possible to visualize the dynamic interactions of individual molecules...
November 5, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/29155710/dna-nanotubes-as-a-versatile-tool-to-study-semiflexible-polymers
#7
Jörg Schnauß, Martin Glaser, Jessica S Lorenz, Carsten Schuldt, Christin Möser, Martin Sajfutdinow, Tina Händler, Josef A Käs, David M Smith
Mechanical properties of complex, polymer-based soft matter, such as cells or biopolymer networks, can be understood in neither the classical frame of flexible polymers nor of rigid rods. Underlying filaments remain outstretched due to their non-vanishing backbone stiffness, which is quantified via the persistence length (lp), but they are also subject to strong thermal fluctuations. Their finite bending stiffness leads to unique, non-trivial collective mechanics of bulk networks, enabling the formation of stable scaffolds at low volume fractions while providing large mesh sizes...
October 25, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/29155091/dynamic-molecular-events-associated-to-plasmodium-berghei-gametogenesis-through-proteomic-approach
#8
Carlos H S Garcia, Delphine Depoix, Rayner M L Queiroz, Jaques M F Souza, Wagner Fontes, Marcelo V de Sousa, Marlon D M Santos, Paulo C Carvalho, Philippe Grellier, Sébastien Charneau
Plasmodium mature sexual cycle occurs in the vector mosquitoes and ensures the transmission to a new host. Gametogenesis takes place within minutes in the vector midgut. Gametocytes have to complete a deep nuclear reorganization, quick differentiation, and in the case of male gametocytes, intracytoplasmic flagellum assembly that results in free-swimming microgametes required for macrogamete fertilization. In efforts to improve our knowledge of molecular mechanisms involved in gamete morphogenesis, we carried out a nanoLC/MSMS based quantitative proteomic analysis throughout the xanthurenic acid-induced gametogenesis of the rodent parasite P...
November 15, 2017: Journal of Proteomics
https://www.readbyqxmd.com/read/29155028/chitosan-oligosaccharides-with-degree-of-polymerization-2-6-induces-apoptosis-in-human-colon-carcinoma-hct116%C3%A2-cells
#9
Pan Zou, Shoujun Yuan, Xin Yang, Xingchen Zhai, Jing Wang
Colon cancer is the third most common cancer, and yet there is a lack of effective therapeutic methods with low side effects. Chitosan oligosaccharides (COS) is derived from chitosan after chitin deacetylation, and attracts more interests due to smaller molecular weight and soluble property. Previously, COS, mainly absorbed through intestinal epithelia, has been reported to exhibit many bioactivities, especially its anti-tumor effect. Recent references pay little attention to molecular weight distribution which is crucial for understanding its biological behavior...
November 16, 2017: Chemico-biological Interactions
https://www.readbyqxmd.com/read/29154952/in-vitro-mechanisms-of-beauvericin-toxicity-a-review
#10
REVIEW
Beatriz Mallebrera, Alessandra Prosperini, Guillermina Font, Maria-Jose Ruiz
Beauvericin (BEA) is a mycotoxin produced by many species of fungus Fusarium and by Beauveria bassiana; BEA is a natural contaminant of cereals and cereals based products and possesses a wide variety of biological properties. The mechanism of action seems to be related to its ionophoric activity, that increases ion permeability in biological membranes. As a consequence, BEA causes cytotoxicity in several cell lines and is capable to produce oxidative stress at molecular level. Moreover, BEA is genotoxic (produces DNA fragmentation, chromosomal aberrations and micronucleus) and causes apoptosis with the involvement of mitochondrial pathway...
November 15, 2017: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/29154875/optimization-of-pegylation-reaction-time-and-molar-ratio-of-rhg-csf-toward-increasing-bioactive-potency-of-monopegylated-protein
#11
Jamila Behi, RymHassiki, Nadia Ben Said, Balkiss Bouhaouala-Zahar, Mohamed Lamine Benkhoud
PEGylation is one of the strategies used for enhancing in vivo residence time of recombinant human Granulocyte Colony-Stimulating Factor (rhG-CSF) and therefore reducing in dose frequency to better fit with patient comfort treatment. In this study, three methoxy polyethylene glycol propionaldehydes (mPEG- ALD) of 10, 20 and 30kDa MW were utilized to produce biologically active monoPEGylated rhG-CSF with enhanced molecular weight. PEGylation reactions were carried out at room temperature and pH 5.0 in the presence of cyanoborohydride and two mPEG-ALD: protein molar ratios (3:1 and 5:1)...
November 14, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/29154838/tp-0903-inhibits-neuroblastoma-cell-growth-and-enhances-the-sensitivity-to-conventional-chemotherapy
#12
Sanja Aveic, Diana Corallo, Elena Porcù, Marcella Pantile, Daniele Boso, Carlo Zanon, Giampietro Viola, Viktoryia Sidarovich, Elena Mariotto, Alessandro Quattrone, Giuseppe Basso, Gian Paolo Tonini
Neuroblastoma (NB) is an embryonal tumor with low cure rate for patients classified as high-risk. This class of NB tumors shows a very complex genomic background and requires aggressive treatment strategies. In this work we evaluated the efficacy of the novel multi-kinase inhibitor TP-0903 in impairing NB cells' growth, proliferation and motility. In vitro studies were performed using cell lines with different molecular background, and in vivo studies were done using the zebrafish experimental model. Our results confirmed a strong cytotoxicity of TP-0903 already at the sub-micro molar concentrations...
November 14, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29154193/fundamentals-on-the-biochemistry-of-peroxynitrite-and-protein-tyrosine-nitration
#13
REVIEW
Silvina Bartesaghi, Rafael Radi
In this review we provide an analysis of the biochemistry of peroxynitrite and tyrosine nitration. Peroxynitrite is the product of the diffusion-controlled reaction between superoxide (O2(•)(-)) and nitric oxide ((•)NO). This process is in competition with the enzymatic dismutation of O2(•-) and the diffusion of (•)NO across cells and tissues and its reaction with molecular targets (e.g. guanylate cyclase). Understanding the kinetics and compartmentalization of the O2(•-) / (•)NO interplay is critical to rationalize the shift of (•)NO from a physiological mediator to a cytotoxic intermediate...
September 19, 2017: Redox Biology
https://www.readbyqxmd.com/read/29153976/image-based-ex-vivo-drug-screening-for-patients-with-aggressive-haematological-malignancies-interim-results-from-a-single-arm-open-label-pilot-study
#14
Berend Snijder, Gregory I Vladimer, Nikolaus Krall, Katsuhiro Miura, Ann-Sofie Schmolke, Christoph Kornauth, Oscar Lopez de la Fuente, Hye-Soo Choi, Emiel van der Kouwe, Sinan Gültekin, Lukas Kazianka, Johannes W Bigenzahn, Gregor Hoermann, Nicole Prutsch, Olaf Merkel, Anna Ringler, Monika Sabler, Georg Jeryczynski, Marius E Mayerhoefer, Ingrid Simonitsch-Klupp, Katharina Ocko, Franz Felberbauer, Leonhard Müllauer, Gerald W Prager, Belgin Korkmaz, Lukas Kenner, Wolfgang R Sperr, Robert Kralovics, Heinz Gisslinger, Peter Valent, Stefan Kubicek, Ulrich Jäger, Philipp B Staber, Giulio Superti-Furga
BACKGROUND: Patients with refractory or relapsed haematological malignancies have few treatment options and short survival times. Identification of effective therapies with genomic-based precision medicine is hampered by intratumour heterogeneity and incomplete understanding of the contribution of various mutations within specific cancer phenotypes. Ex-vivo drug-response profiling in patient biopsies might aid effective treatment identification; however, proof of its clinical utility is limited...
November 15, 2017: Lancet Haematology
https://www.readbyqxmd.com/read/29153588/azole-hydrazone-derivatives-design-synthesis-in-vitro-biological-evaluation-dual-egfr-her2-inhibitory-activity-cell-cycle-analysis-and-molecular-docking-study-as-anticancer-agents
#15
Madlen B Labib, John N Philoppes, Phoebe F Lamie, Esam R Ahmed
In this research, three series of azole-hydrazone derivatives namely, benzimidazole, benzoxazole and benzothiazole were designed and synthesized. Their structures were confirmed by elemental analysis and spectroscopic techniques. Stereochemical configuration of the synthesized compounds (Z/E) was determined. The new derivatives were tested in vitro against both human breast adenocarcinoma (MCF-7) and human hepatic adenocarcinoma (HepG2) cell lines. The most active compounds 3h (IC50 = 0.067 μM against MCF-7) and 3l (IC50 = 0...
November 15, 2017: Bioorganic Chemistry
https://www.readbyqxmd.com/read/29153034/advances-in-maldi-mass-spectrometry-within-drug-discovery
#16
Dale S Cornett, Michael D Scholle
Inhibition of NK and effector T-cell functions and activation of regulatory cell populations are the main immunosuppressive effects of indoleamine-2,3-dioxygenase1 (IDO1). By converting tryptophan (Trp) into kynurenine (Kyn), IDO1 is involved in the immune response homeostasis, and its dysregulated expression is described in immune-related pathologies, as tumors that hijack it to evade immune destruction. Thereby, IDO1 inhibitors are being developed to stimulate antitumor immune responses. Existing and standard quantitation methods of IDO1 substrate and metabolite(s) are based on the total level of Trp and its metabolites determined by liquid chromatography tandem mass spectrometry analysis in human plasma, cerebrospinal fluid, and brain...
December 2017: SLAS Discovery
https://www.readbyqxmd.com/read/29152378/zinc-finger-proteins-in-health-and-disease
#17
REVIEW
Matteo Cassandri, Artem Smirnov, Flavia Novelli, Consuelo Pitolli, Massimiliano Agostini, Michal Malewicz, Gerry Melino, Giuseppe Raschellà
Zinc-finger proteins (ZNFs) are one of the most abundant groups of proteins and have a wide range of molecular functions. Given the wide variety of zinc-finger domains, ZNFs are able to interact with DNA, RNA, PAR (poly-ADP-ribose) and other proteins. Thus, ZNFs are involved in the regulation of several cellular processes. In fact, ZNFs are implicated in transcriptional regulation, ubiquitin-mediated protein degradation, signal transduction, actin targeting, DNA repair, cell migration, and numerous other processes...
2017: Cell Death Discovery
https://www.readbyqxmd.com/read/29152232/recent-therapeutic-advances-in-chronic-lymphocytic-leukemia
#18
REVIEW
Prithviraj Bose, Varsha Gandhi
The last several years have witnessed a paradigm shift in the management of patients with chronic lymphocytic leukemia (CLL). The course of this very heterogeneous disease, traditionally treated with chemotherapeutic agents usually in combination with rituximab, typically has been characterized by remissions and relapses, and survival times vary greatly, depending on intrinsic biological attributes of the leukemia. The developments of the last few years have been transformative, ushering in an era of novel, molecularly targeted therapies, made possible by extensive efforts to elucidate the biology of the disease that predated the new targeted drugs...
2017: F1000Research
https://www.readbyqxmd.com/read/29152094/xenotransplantation-of-pediatric-low-grade-gliomas-confirms-the-enrichment-of-braf-v600e-mutation-and-preservation-of-cdkn2a-deletion-in-a-novel-orthotopic-xenograft-mouse-model-of-progressive-pleomorphic-xanthoastrocytoma
#19
Mari Kogiso, Lin Qi, Holly Lindsay, Yulun Huang, Xiumei Zhao, Zhigang Liu, Frank K Braun, Yuchen Du, Huiyuan Zhang, Goeun Bae, Sibo Zhao, Sarah G Injac, Mary Sobieski, David Brunell, Vidya Mehta, Diep Tran, Jeffrey Murray, Patricia A Baxter, Xiao-Jun Yuan, Jack M Su, Adekunle Adesina, Laszlo Perlaky, Murali Chintagumpala, D Williams Parsons, Ching C Lau, Clifford C Stephan, Xinyan Lu, Xiao-Nan Li
To identify cellular and molecular changes that driver pediatric low grade glioma (PLGG) progression, we analyzed putative cancer stem cells (CSCs) and evaluated key biological changes in a novel and progressive patient-derived orthotopic xenograft (PDOX) mouse model. Flow cytometric analysis of 22 PLGGs detected CD133(+) (<1.5%) and CD15(+) (20.7 ± 28.9%) cells, and direct intra-cranial implantation of 25 PLGGs led to the development of 1 PDOX model from a grade II pleomorphic xanthoastrocytoma (PXA). While CSC levels did not correlate with patient tumor progression, neurosphere formation and in vivo tumorigenicity, the PDOX model, IC-3635PXA, reproduced key histological features of the original tumor...
October 20, 2017: Oncotarget
https://www.readbyqxmd.com/read/29152050/consequences-of-depsipeptide-substitution-on-the-clpp-activation-activity-of-antibacterial-acyldepsipeptides
#20
Yangxiong Li, Nathan P Lavey, Jesse A Coker, Jessica E Knobbe, Dat C Truong, Hongtao Yu, Yu-Shan Lin, Susan L Nimmo, Adam S Duerfeldt
The acyldepsipeptide (ADEP) antibiotics operate through a clinically unexploited mechanism of action and thus have attracted attention from several antibacterial development groups. The ADEP scaffold is synthetically tractable, and deep-seated modifications have produced extremely potent antibacterial leads against Gram-positive pathogens. Although newly identified ADEP analogs demonstrate remarkable antibacterial activity against bacterial isolates and in mouse models of bacterial infections, stability issues pertaining to the depsipeptide core remain...
November 9, 2017: ACS Medicinal Chemistry Letters
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