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https://www.readbyqxmd.com/read/28334731/characterisation-of-cct271850-a-selective-oral-and-potent-mps1-inhibitor-used-to-directly-measure-in-vivo-mps1-inhibition-vs-therapeutic-efficacy
#1
Amir Faisal, Grace W Y Mak, Mark D Gurden, Cristina P R Xavier, Simon J Anderhub, Paolo Innocenti, Isaac M Westwood, Sébastien Naud, Angela Hayes, Gary Box, Melanie R Valenti, Alexis K De Haven Brandon, Lisa O'Fee, Jessica Schmitt, Hannah L Woodward, Rosemary Burke, Rob L M vanMontfort, Julian Blagg, Florence I Raynaud, Suzanne A Eccles, Swen Hoelder, Spiros Linardopoulos
BACKGROUND: The main role of the cell cycle is to enable error-free DNA replication, chromosome segregation and cytokinesis. One of the best characterised checkpoint pathways is the spindle assembly checkpoint, which prevents anaphase onset until the appropriate attachment and tension across kinetochores is achieved. MPS1 kinase activity is essential for the activation of the spindle assembly checkpoint and has been shown to be deregulated in human tumours with chromosomal instability and aneuploidy...
March 23, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28334093/association-between-mirna-binding-site-polymorphisms-in-double-strand-break-repair-genes-and-risk-of-recurrence-in-patients-with-squamous-cell-carcinomas-of-the-nonoropharynx
#2
Lijun Zhu, Erich M Sturgis, Zhongming Lu, Hua Zhang, Peng Wei, Qingyi Wei, Guojun Li
Genetic polymorphisms at miRNA-binding sites may affect miRNA-mediated gene regulation. Thus, miRNA-binding site polymorphisms in double-strand break (DSB) repair genes may affect DNA repair capacity, which in turn could affect cancer prognosis. To determine whether miRNA-binding site polymorphisms in DSB repair genes are associated with the risk of recurrence of squamous cell carcinoma of the nonoropharynx (SCCNOP), we used a log-rank test and multivariable Cox models to evaluate the associations between miRNA-binding site polymorphisms in DSB repair genes and SCCNOP recurrence...
February 18, 2017: Carcinogenesis
https://www.readbyqxmd.com/read/28333958/targeted-deep-sequencing-of-plasma-circulating-cell-free-dna-reveals-vimentin-and-fibulin-1-as-potential-epigenetic-biomarkers-for-hepatocellular-carcinoma
#3
Reetta Holmila, Athena Sklias, David C Muller, Davide Degli Esposti, Paule Guilloreau, James Mckay, Suleeporn Sangrajrang, Petcharin Srivatanakul, Pierre Hainaut, Philippe Merle, Zdenko Herceg, Andre Nogueira da Costa
Hepatocellular carcinoma (HCC) is the second most common cause of cancer death worldwide, but is still lacking sensitive and specific biomarkers for early diagnosis and prognosis. In this study, we applied targeted massively parallel semiconductor sequencing to assess methylation on a panel of genes (FBLN1, HINT2, LAMC1, LTBP1, LTBP2, PSMA2, PSMA7, PXDN, TGFB1, UBE2L3, VIM and YWHAZ) in plasma circulating cell-free DNA (cfDNA) and to evaluate the potential of these genes as HCC biomarkers in two different series, one from France (42 HCC cases and 42 controls) and one from Thailand (42 HCC cases, 26 chronic liver disease cases and 42 controls)...
2017: PloS One
https://www.readbyqxmd.com/read/28332580/clinical-impact-of-single-nucleotide-polymorphism-in-pd-l1-on-response-to-nivolumab-for-advanced-non-small-cell-lung-cancer-patients
#4
Takashi Nomizo, Hiroaki Ozasa, Takahiro Tsuji, Tomoko Funazo, Yuto Yasuda, Hironori Yoshida, Yoshitaka Yagi, Yuichi Sakamori, Hiroki Nagai, Toyohiro Hirai, Young Hak Kim
This study was intended to determine the efficacy of nivolumab, we evaluated treatment response with respect to PD-1/PD-L1 SNPs among patients with NSCLC. A total of 50 patients with NSCLC were treated with nivolumab and were also evaluated for PD-1/PD-L1 single nucleotide polymorphisms (SNPs) from plasma DNA. We investigated the association among PD-1/PD-L1 SNPs, objective response rate (ORR) and progression-free survival (PFS). Two of seven SNPs studied showed association with ORR and PFS, with maximum evidence at the marker rs2282055...
March 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28331215/description-of-a-strong-relationship-among-total-cell-free-dna-levels-ldh-values-ast-values-and-platelet-count-in-patients-with-hellp-syndrome
#5
Pablo Stiefel, María L Miranda, Hada Macher, Luis M Beltran-Romero, Rocio Muñoz-Hernandez
No abstract text is available yet for this article.
March 23, 2017: Hypertension Research: Official Journal of the Japanese Society of Hypertension
https://www.readbyqxmd.com/read/28330468/tumor-burden-monitoring-using-cell-free-tumor-dna-could-be-limited-by-tumor-heterogeneity-in-advanced-breast-cancer-and-should-be-evaluated-together-with-radiographic-imaging
#6
José Angel García-Saenz, Patricia Ayllón, Marion Laig, Daniel Acosta-Eyzaguirre, Marta García-Esquinas, Myriam Montes, Julián Sanz, Miguel Barquín, Fernando Moreno, Vanesa Garcia-Barberan, Eduardo Díaz-Rubio, Trinidad Caldes, Atocha Romero
BACKGROUND: Accurate measurement of tumor burden in breast cancer disease is essential to improve the clinical management of patients. In this study, we evaluate whether the fluctuations in the fraction of PIK3CA mutant allele correlates with tumor response according to RECIST criteria and tumor markers quantification. METHODS: Eighty six plasma samples were analyzed by digital PCR using Rare Mutation Assays for E542K, E545K and H1047R. Mutant cfDNA and tumor markers CA15-3 and CEA were compared with radiographic imaging...
March 22, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28328955/treatment-monitoring-in-metastatic-colorectal-cancer-patients-by-quantification-and-kras-genotyping-of-circulating-cell-free-dna
#7
Andreas W Berger, Daniel Schwerdel, Hanna Welz, Ralf Marienfeld, Stefan A Schmidt, Alexander Kleger, Thomas J Ettrich, Thomas Seufferlein
Treatment of metastatic colorectal cancer (CRC) has continuously improved over the last decade. However, disease monitoring remains underdeveloped and mostly dependent on imaging e.g. RECIST 1.1 criteria. The genetic landscape of individual cancers and subsequently occurring treatment-induced evolution remain neglected in current surveillance strategies. Novel biomarkers demand minimally invasive and repetitive tracking of the cancer mutagenome for therapy stratification and to make prognostic predictions. Carcinoembryonic antigen (CEA), a routinely used tumor marker for CRC, does not meet these goals and thus prevents its use as a reliable monitoring tool...
2017: PloS One
https://www.readbyqxmd.com/read/28327951/hpv16-dna-and-integration-in-normal-and-malignant-epithelium-implications-for-the-etiology-of-laryngeal-squamous-cell-carcinoma
#8
X Chen, L Gao, E M Sturgis, Z Liang, Y Zhu, X Xia, X Zhu, X Chen, G Li, Z Gao
Background: Molecular evidence suggests that human papillomavirus (HPV) has a role in the etiology of oropharyngeal squamous cell carcinoma. However, the role of HPV in laryngeal squamous cell carcinoma (LSCC) is unclear. Patients and Methods: We conducted a case-control study using tumor tissue specimens from 300 LSCC patients and vocal cord polyp specimens from 300 cancer-free controls. HPV genotype, HPV16 viral load and viral integration status, and p16 expression were determined...
January 23, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28327944/a-phase-2-randomized-double-blind-placebo-%C3%A2-controlled-study-of-chemo-immunotherapy-combination-using-motolimod-with-pegylated-liposomal-doxorubicin-in-recurrent-or-persistent-ovarian-cancer-a-gynecologic-oncology-group-partners-study
#9
B J Monk, M F Brady, C Aghajanian, H A Lankes, T Rizack, J Leach, J M Fowler, R Higgins, P Hanjani, M Morgan, R Edwards, W Bradley, T Kolevska, P Foukas, E Swisher, K S Anderson, R Gottardo, J K Bryan, M Newkirk, K L Manjarrez, R S Mannel, R M Hershberg, G Coukos
Background: A phase 2, randomized, placebo-controlled trial was conducted in women with recurrent epithelial ovarian carcinoma to evaluate the efficacy and safety of motolimod-a Toll-like receptor 8 (TLR8) agonist that stimulates robust innate immune responses-combined with pegylated liposomal doxorubicin (PLD), a chemotherapeutic that induces immunogenic cell death. Patients and methods: Women with ovarian, fallopian tube, or primary peritoneal carcinoma were randomized 1 : 1 to receive PLD in combination with blinded motolimod or placebo...
February 21, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28327522/isolation-and-characterization-of-a-shewanella-phage-host-system-from-the-gut-of-the-tunicate-ciona-intestinalis
#10
Brittany Leigh, Charlotte Karrer, John P Cannon, Mya Breitbart, Larry J Dishaw
Outnumbering all other biological entities on earth, bacteriophages (phages) play critical roles in structuring microbial communities through bacterial infection and subsequent lysis, as well as through horizontal gene transfer. While numerous studies have examined the effects of phages on free-living bacterial cells, much less is known regarding the role of phage infection in host-associated biofilms, which help to stabilize adherent microbial communities. Here we report the cultivation and characterization of a novel strain of Shewanella fidelis from the gut of the marine tunicate Ciona intestinalis, inducible prophages from the S...
March 22, 2017: Viruses
https://www.readbyqxmd.com/read/28326560/sex-chromosome-aneuploidy-detection-by-non-invasive-prenatal-testing-helpful-or-hazardous
#11
Rosemary E Reiss, Marie Discenza, Judith Foster, Lori Dobson, Louise Wilkins-Haug
OBJECTIVES: To assess the incidence of sex chromosome aneuploidy (SCA) predicted by non-invasive prenatal testing (NIPT), assess test performance, and compare it with nuchal translucency (NT) screening among patients seen in our prenatal diagnosis center. METHODS: We identified suspected cases of SCA by reviewing results from all NIPT samples sent from our center to commercial laboratories offering analysis by cell-free DNA between December 1, 2012 to July 31, 2015...
March 21, 2017: Prenatal Diagnosis
https://www.readbyqxmd.com/read/28325688/current-and-emerging-molecular-tests-for-human-papillomavirus-related-neoplasia-in-the-genomic-era
#12
REVIEW
Sixto M Leal, Margaret L Gulley
Laboratory tests have a key role in preventing human papillomavirus (HPV)-driven carcinomas and in guiding therapeutic interventions. An understanding of the virology, immunology, and carcinogenesis of HPV is essential for choosing appropriate diagnostic test modalities and developing new and even more effective cancer prevention strategies. HPV infects basal epithelial cells on multiple surfaces and induces carcinoma primarily in the cervix and the oropharynx. HPV types are stratified as high risk or low risk based on their carcinogenic potential, driven largely by viral interference with cell cycle regulation and the DNA damage response to promote continuous cell division while thwarting apoptosis, which enables mutation accumulation...
March 18, 2017: Journal of Molecular Diagnostics: JMD
https://www.readbyqxmd.com/read/28325102/building-up-and-breaking-down-mechanisms-controlling-recombination-during-replication
#13
Dana Branzei, Barnabas Szakal
The complete and faithful duplication of the genome is an essential prerequisite for proliferating cells to maintain genome integrity. This objective is greatly challenged by DNA damage encountered during replication, which causes fork stalling and in certain cases, fork breakage. DNA damage tolerance (DDT) pathways mitigate the effects on fork stability induced by replication fork stalling by mediating damage-bypass and replication fork restart. These DDT mechanisms, largely relying on homologous recombination (HR) and specialized polymerases, can however contribute to genome rearrangements and mutagenesis...
March 22, 2017: Critical Reviews in Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/28323177/biodegradable-cationic-poly-carbonates-effect-of-varying-side-chain-hydrophobicity-on-key-aspects-of-gene-transfection
#14
Zhan Yuin Ong, Chuan Yang, Wei Cheng, Zhi Xiang Voo, Willy Chin, James L Hedrick, Yi Yan Yang
The degree of hydrophobicity in cationic polymers plays an important but often underappreciated role in the safety and efficacy of gene delivery processes. In order to further elucidate structure-activity relationships of biodegradable cationic poly(carbonate) gene carriers, we synthesized a series of narrowly dispersed homo-polymers via metal-free organocatalytic living ring-opening polymerization (ROP) of cyclic carbonate monomers bearing either alkyl (propyl, hexyl or nonyl) or 4-methyl benzyl halide side chains...
March 17, 2017: Acta Biomaterialia
https://www.readbyqxmd.com/read/28323123/circumventing-intratumoral-heterogeneity-to-identify-potential-therapeutic-targets-in-hepatocellular-carcinoma
#15
Ao Huang, Xin Zhao, Xin-Rong Yang, Fu-Qiang Li, Xin-Lan Zhou, Kui Wu, Xin Zhang, Qi-Man Sun, Ya Cao, Hong-Mei Zhu, Xiang-Dong Wang, Huan-Ming Yang, Jian Wang, Zhao-You Tang, Yong Hou, Jia Fan, Jian Zhou
BACKGROUND AND AIMS: Intratumoral heterogeneity (ITH) challenges identifying mutations with target therapy potential whereas circulating cell-free DNAs (cfDNAs) in blood could possibly reflect the entire mutation spectrum in certain tumors. We investigated how to minimize the limit of ITH for profiling hepatocellular carcinoma (HCC). METHODS: Thirty-two multi-regional tumor samples from five patients were subjected to whole exome sequencing (WES) and targeted deep sequencing (TDS); matched preoperative cfDNAs were sequenced accordingly...
March 17, 2017: Journal of Hepatology
https://www.readbyqxmd.com/read/28323104/cytotoxicity-and-genotoxicity-of-lipid-nanocapsules
#16
Gaël Le Roux, Hélène Moche, Alejandro Nieto, Jean-Pierre Benoit, Fabrice Nesslany, Frédéric Lagarce
Lipid nanocapsules (LNCs) offer a promising method for the entrapment and nanovectorisation of lipophilic molecules. This new type of nanocarrier, formulated according to a solvent-free process and using only regulatory-approved components, exhibits many prerequisites for being well tolerated. Although toxicological reference values have already been obtained in mice, interaction of LNCs at the cell level needs to be elucidated. LNCs, measuring from 27.0±0.1nm (25nm LNCs) and 112.1±1.8nm (100nm LNCs) and with a zeta potential between -38...
March 17, 2017: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/28323041/quantitative-analyses-of-the-3d-nuclear-landscape-recorded-with-super-resolved-fluorescence-microscopy
#17
Volker J Schmid, Marion Cremer, Thomas Cremer
Recent advancements of super-resolved fluorescence microscopy have revolutionized microscopic studies of cells, including the exceedingly complex structural organization of cell nuclei in space and time. In this paper we describe and discuss tools for (semi-) automated, quantitative 3D analyses of the spatial nuclear organization. These tools allow the quantitative assessment of highly resolved different chromatin compaction levels in individual cell nuclei, which reflect functionally different regions or sub-compartments of the 3D nuclear landscape, and measurements of absolute distances between sites of different chromatin compaction...
March 18, 2017: Methods: a Companion to Methods in Enzymology
https://www.readbyqxmd.com/read/28322855/reconstitutions-of-plasmid-partition-systems-and-their-mechanisms
#18
REVIEW
Adam C Brooks, Ling Chin Hwang
Bacterial plasmid and chromosome segregation systems ensure that genetic material is efficiently transmitted to progeny cells. Cell-based studies have shed light on the dynamic nature and the molecular basis of plasmid partition systems. In vitro reconstitutions, on the other hand, have proved to be an invaluable tool for studying the minimal components required to elucidate the mechanism of DNA segregation. This allows us to gain insight into the biological and biophysical processes that enable bacterial cells to move and position DNA...
March 16, 2017: Plasmid
https://www.readbyqxmd.com/read/28322111/hpv-in-larynx-squamous-cell-carcinoma-new-serotypes-and-survival-study-within-10-year-follow-up
#19
Alvaro Sánchez Barrueco, Fernando González Galán, David Lora Pablos, José Miguel Villacampa Aubá, Claudio Ballestín Carcavilla, Carlos Cenjor Español, Carlos Almodóvar Álvarez
Objective To determine the presence of human papillomavirus (HPV) in head and neck squamous cell carcinoma, specifically in the larynx without the bias of other sublocations, and to describe the different serotypes of HPV and their impact on overall and disease-free survival after 10-year follow-up. Study Design Retrospective case series with chart review of ear, nose, and throat oncologic database. Setting Academic tertiary care hospital. Subjects A total of 123 samples of larynx squamous cell carcinoma were included, only from the glottis and treated only with surgery between 1977 and 2005...
March 1, 2017: Otolaryngology—Head and Neck Surgery
https://www.readbyqxmd.com/read/28321969/the-pangenome-of-the-genus-clostridium
#20
Zulema Udaondo, Estrella Duque, Juan Luis Ramos
We present the pangenome for the genus Clostridium sensu stricto, which was obtained using highly curated and annotated genomes from 16 species, some of these cause disease, while others are used for the production of added-value chemicals. Multilocus sequencing analysis revealed that species of this genus group into at least two clades that include non-pathogenic and pathogenic strains, suggesting that pathogenicity is dispersed across the phylogenetic tree. The core genome of the genus includes 546 protein families, which mainly comprise those involved in protein translation and DNA repair...
March 21, 2017: Environmental Microbiology
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