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https://www.readbyqxmd.com/read/28102676/novel-antitumor-platinum-ii-conjugates-containing-the-nonsteroidal-anti-inflammatory-agent-diclofenac-synthesis-and-dual-mechanisms-of-antiproliferative-effects
#1
Francesco Paolo Intini, Juraj Zajac, Vojtech Novohradsky, Teresa Saltarella, Concetta Pacifico, Viktor Brabec, Giovanni Natile, Jana Kasparkova
One concept how to improve anticancer effects of conventional metallodrugs consists in conjugation of these compounds with other biologically (antitumor) active agents, acting by a different mechanism. Here, we present synthesis, biological effects, and mechanisms of action of new Pt(II) derivatives containing one or two nonsteroidal anti-inflammatory diclofenac (DCF) ligands also known for their antitumor effects. The antiproliferative properties of these metallic conjugates show that these compounds are potent and cancer cell selective cytotoxic agents exhibiting activity in cisplatin resistant and the COX-2 positive tumor cell lines...
January 19, 2017: Inorganic Chemistry
https://www.readbyqxmd.com/read/28102322/size-selective-separation-and-overall-amplification-of-cell-free-fetal-dna-fragments-using-pcr-based-enrichment
#2
Qiwei Yang, Zhenwu Du, Yang Song, Sujie Gao, Shan Yu, He Zhu, Ming Ren, Guizhen Zhang
This study aimed to establish a method for the selective amplification of cell-free fetal DNA (cffDNA) in maternal plasma and preserve the integrity of DNA fragments during amplification, thereby providing a sufficient amount of cffDNA to meet the requirement of routine non-invasive prenatal testing. We amplified DNA molecules in a one-reaction system without considering their particular sequences and lengths (overall amplification) by using PCR-based enrichment. We then modified PCR conditions to verify the effect of denaturation temperature on DNA amplification on various lengths of DNA (selective overall amplification)...
January 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28101802/cold-pcr-technologies-in-the-area-of-personalized-medicine-methodology-and-applications
#3
REVIEW
Florence Mauger, Alexandre How-Kit, Jörg Tost
Somatic mutations bear great promise for use as biomarkers for personalized medicine, but are often present only in low abundance in biological material and are therefore difficult to detect. Many assays for mutation analysis in cancer-related genes (hotspots) have been developed to improve diagnosis, prognosis, prediction of drug resistance, and monitoring of the response to treatment. Two major approaches have been developed: mutation-specific amplification methods and methods that enrich and detect mutations without prior knowledge on the exact location and identity of the mutation...
January 18, 2017: Molecular Diagnosis & Therapy
https://www.readbyqxmd.com/read/28100495/probe-free-digital-pcr-quantitative-methodology-to-measure-donor-specific-cell-free-dna-after-solid-organ-transplantation
#4
Su Kah Goh, Vijayaragavan Muralidharan, Christopher Christophi, Hongdo Do, Alexander Dobrovic
BACKGROUND: Donor-specific cell-free DNA (dscfDNA) is increasingly being considered as a noninvasive biomarker to monitor graft health and diagnose graft rejection after solid-organ transplantation. However, current approaches used to measure dscfDNA can be costly and/or laborious. A probe-free droplet digital PCR (ddPCR) methodology using small deletion/insertion polymorphisms (DIPs) was developed to circumvent these limitations without compromising the quantification of dscfDNA. This method was called PHABRE-PCR (Primer to Hybridize across an Allelic BREakpoint-PCR)...
January 18, 2017: Clinical Chemistry
https://www.readbyqxmd.com/read/28099328/clinical-and-prognostic-significance-of-merkel-cell-polyomavirus-in-nonsmall-cell-lung-cancer
#5
Gun-Jik Kim, Jae-Ho Lee, Deok Heon Lee
Recently, an association between Merkel cell polyomavirus (MCPyV) and epidermal growth factor receptor (EGFR) mutations in nonsmall cell lung cancer (NSCLC) was reported. However, the underlying carcinogenic effects and the prognosis related to MCPyV are still unclear. The aim of this study was to clarify the incidence and prognosis related to MCPyV infections in NSCLC.Tissue samples from 167 NSCLC patients (92 with squamous cell carcinomas [SCCs] and 75 with adenocarcinomas) were analyzed for the presence of MCPyV and EGFR mutations...
January 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28099078/prevalence-of-terrapene-herpesvirus-1-in-free-ranging-eastern-box-turtles-terrapene-carolina-carolina-in-tennessee-and-illinois
#6
Lauren P Kane, Matthew C Allender, Grace Archer, Elena Dzhaman, John Pauley, A Russell Moore, Marilyn O Ruiz, Rebecca L Smith, John Byrd, Christopher A Phillips
Diseases affecting the upper respiratory tract, such as herpesviruses, are well described in captive chelonians worldwide, but their importance in free-ranging populations is less well known. To characterize the disease epidemiology of terrapene herpesvirus 1 (TerHV1), 409 free-ranging eastern box turtles ( Terrapene carolina carolina) in Tennessee and Illinois were tested for TerHV1 in 2013 and 2014 using TaqMan quantitative PCR. Whole blood and swabs of the oral mucosa were collected from 365 adults (154 females, 195 males, 16 unknown sex) and 44 juveniles...
January 18, 2017: Journal of Wildlife Diseases
https://www.readbyqxmd.com/read/28098911/diagnosis-for-choroideremia-in-a-large-chinese-pedigree-by-next%C3%A2-generation-sequencing-ngs-and-non%C3%A2-invasive-prenatal-testing-nipt
#7
Li Zhu, Jingliang Cheng, Boxu Zhou, Chunli Wei, Weichan Yang, Dong Jiang, Iqra Ijaz, Xiaojun Tan, Rui Chen, Junjiang Fu
To develop an effective strategy to isolate and use cell‑free fetal DNA (cffDNA) for the combined use of next‑generation sequencing (NGS) for diagnosing choroideremia and non‑invasive prenatal testing (NIPT) for Y chromosome determination, a large Chinese family with an X‑linked recessive disease, choroideremia, was recruited. Cell‑free DNA was extracted from maternal plasma, and SRY polymerase chain reaction amplification was performed using NIPT. Sanger sequencing was subsequently used for fetal amniotic fluid DNA verification...
January 13, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28098143/efficient-dna-free-genome-editing-of-bread-wheat-using-crispr-cas9-ribonucleoprotein-complexes
#8
Zhen Liang, Kunling Chen, Tingdong Li, Yi Zhang, Yanpeng Wang, Qian Zhao, Jinxing Liu, Huawei Zhang, Cuimin Liu, Yidong Ran, Caixia Gao
Substantial efforts are being made to optimize the CRISPR/Cas9 system for precision crop breeding. The avoidance of transgene integration and reduction of off-target mutations are the most important targets for optimization. Here, we describe an efficient genome editing method for bread wheat using CRISPR/Cas9 ribonucleoproteins (RNPs). Starting from RNP preparation, the whole protocol takes only seven to nine weeks, with four to five independent mutants produced from 100 immature wheat embryos. Deep sequencing reveals that the chance of off-target mutations in wheat cells is much lower in RNP mediated genome editing than in editing with CRISPR/Cas9 DNA...
January 18, 2017: Nature Communications
https://www.readbyqxmd.com/read/28096542/liquid-biopsy-in-2016-circulating-tumour-cells-and-cell-free-dna-in-gastrointestinal-cancer
#9
Klaus Pantel, Catherine Alix-Panabières
No abstract text is available yet for this article.
January 18, 2017: Nature Reviews. Gastroenterology & Hepatology
https://www.readbyqxmd.com/read/28096488/novel-superspreader-bacteriophages-promote-horizontal-gene-transfer-by-transformation
#10
Eric C Keen, Valery V Bliskovsky, Francisco Malagon, James D Baker, Jeffrey S Prince, James S Klaus, Sankar L Adhya
: Bacteriophages infect an estimated 10(23) to 10(25) bacterial cells each second, many of which carry physiologically relevant plasmids (e.g., those encoding antibiotic resistance). However, even though phage-plasmid interactions occur on a massive scale and have potentially significant evolutionary, ecological, and biomedical implications, plasmid fate upon phage infection and lysis has not been investigated to date. Here we show that a subset of the natural lytic phage population, which we dub "superspreaders," releases substantial amounts of intact, transformable plasmid DNA upon lysis, thereby promoting horizontal gene transfer by transformation...
January 17, 2017: MBio
https://www.readbyqxmd.com/read/28096456/antibody-conjugated-dna-based-nanocarriers-intercalated-with-doxorubicin-eliminate-myofibroblasts-in-explants-of-human-lens-tissue
#11
Jacquelyn Gerhart, Marvin Greenbaum, Lou Casta, Anthony Clemente, Keith Mathers, Robert Getts, Mindy George-Weinstein
Posterior capsule opacification (PCO) occurs in some adults and most children following cataract surgery. The fibrotic form of PCO arises, in part, from migratory, contractile myofibroblasts that deform the lens capsule and impair vision. In short-term cultures of human anterior lens tissue, myofibroblasts emerge from Myo/Nog cells that are identified with the G8 monoclonal antibody and by their expression of the MyoD transcription factor and bone morphogenetic protein inhibitor noggin. In this study, we tested the hypothesis that targeted depletion of Myo/Nog cells with the G8 mAb conjugated to three-dimensional DNA nanocarriers intercalated with Doxorubicin (G8:3DNA:Dox) would prevent the accumulation of myofibroblasts in long-term, serum and growth factor free cultures of human lens tissue obtained by capsulorhexis...
January 17, 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/28096270/mutation-enrichment-next-generation-sequencing-for-quantitative-detection-of-kras-mutations-in-urine-cell-free-dna-from-patients-with-advanced-cancers
#12
Takeo Fuji, Afsaneh Barzi, Andrea Sartore-Bianchi, Andrea Cassingena, Giulia Siravegna, Daniel Karp, Sarina Piha-Paul, Vivek Subbiah, Apostolia M Tsimberidou, Helen Huang, Sillvio Veronese, Federica Di Nicolantonio, Sandeep C Pingle, Cecile Rose T Vibat, Saege Hancock, David Berz, Vladislava O Melnikova, Mark G Erlander, Rajyalakshmi Luthra, Scott Kopetz, Funda Meric-Bernstam, Salvatore Siena, Heinz-Josef Lenz, Alberto Bardelli, Filip Janku
PURPOSE: Tumor-derived cell-free DNA (cfDNA) from urine of patients with cancer offers non-invasive biologic material for detection of cancer-related molecular abnormalities such as mutations in Exon 2 of KRAS. EXPERIMENTAL DESIGN: A quantitative, mutation-enrichment next-generation sequencing test for detecting KRASG12/G13 mutations in urine cfDNA was developed and results were compared to clinical testing of archival tumor tissue and plasma cfDNA from patients with advanced cancer...
January 17, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28096087/diffuse-large-b-cell-lymphoma-genotyping-on-the-liquid-biopsy
#13
Davide Rossi, Fary Diop, Elisa Spaccarotella, Sara Monti, Manuela Zanni, Silvia Rasi, Clara Deambrogi, Valeria Spina, Alessio Bruscaggin, Chiara Favini, Roberto Serra, Antonio Ramponi, Renzo Boldorini, Robin Foa', Gianluca Gaidano
Accessible and real-time genotyping for diagnostic, prognostic or treatment purposes is increasingly impelling in diffuse large B-cell lymphoma (DLBCL). Cell-free DNA (cfDNA) is shed into the blood by tumor cells undergoing apoptosis and can be used as source of tumor DNA for the identification of DLBCL mutations, clonal evolution, and genetic mechanisms of resistance. Here we aimed at tracking the basal DLBCL genetic profile and its modification upon treatment using plasma cfDNA. Ultra-deep targeted next generation sequencing of pre-treatment plasma cfDNA from DLBCL patients correctly discovered DLBCL-associated mutations that were represented in >20% of the alleles of the tumor biopsy with a >90% sensitivity and a ~100% specificity...
January 17, 2017: Blood
https://www.readbyqxmd.com/read/28095613/xenopus-egg-extract-to-study-regulation-of-genome-wide-and-locus-specific-dna-replication
#14
REVIEW
Erica Raspelli, Lucia Falbo, Vincenzo Costanzo
Faithful DNA replication, coupled with accurate repair of DNA damage, is essential to maintain genome stability and relies on different DNA metabolism genes. Many of these genes are involved in the assembly of replication origins, in the coordination of DNA repair to protect replication forks progression in the presence of DNA damage and in the replication of repetitive chromatin regions. Some DNA metabolism genes are essential in higher eukaryotes, suggesting the existence of specialized mechanisms of repair and replication in organisms with complex genomes...
January 17, 2017: Genesis: the Journal of Genetics and Development
https://www.readbyqxmd.com/read/28093244/novel-mutations-on-egfr-leu792-potentially-correlate-to-acquired-resistance-to-osimertinib-in-advanced-nsclc
#15
Kai Chen, Fei Zhou, Wenxiang Shen, Tao Jiang, Xue Wu, Xiaoling Tong, Yang W Shao, Songbing Qin, Caicun Zhou
Osimertinib is an irreversible third generation EGFR tyrosine kinase inhibitor (TKI) and has shown outstanding performances in treating EGFR T790M-positive advanced non-small cell lung cancer (NSCLC) patients, but acquired resistance is inevitable. EGFR C797S is the most notable resistance mechanism to this drug, but other EGFR mutations may also exist. In three lung adenocarcinoma patients resistant to osimertinib, we identified recurrent novel mutations at EGFR Leu792 codon by targeted next generation sequencing (NGS) of cell free DNA (cfDNA) from plasma or pleural effusion...
January 13, 2017: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/28089353/cerebrospinal-fluid-mitochondrial-dna-in-the-alzheimer-s-disease-continuum
#16
Laura Cervera-Carles, Daniel Alcolea, Ainara Estanga, Mirian Ecay-Torres, Andrea Izagirre, Montserrat Clerigué, Maite García-Sebastián, Jorge Villanúa, Clàudia Escalas, Rafael Blesa, Pablo Martínez-Lage, Alberto Lleó, Juan Fortea, Jordi Clarimón
Low levels of cell-free mitochondrial DNA (mtDNA) in the cerebrospinal fluid (CSF) of Alzheimer's disease (AD) patients have been identified and proposed as a novel biomarker for the disease. The lack of validation studies of previous results prompted us to replicate this finding in a comprehensive series of patients and controls. We applied droplet digital polymerase chain reaction in CSF specimens from 124 patients representing the AD spectrum and 140 neurologically healthy controls. The following preanalytical and analytical parameters were evaluated: the effect of freeze-thaw cycles on mtDNA, the linearity of mtDNA load across serial dilutions, and the mtDNA levels in the diagnostic groups...
December 22, 2016: Neurobiology of Aging
https://www.readbyqxmd.com/read/28081343/the-combined-effects-of-proteasome-inhibitor-bortezomib-with-topoisomerase-i-and-ii-inhibitors-on-topoisomerase-enzymes
#17
Emine Öksüzoğlu, Çiydem Tırınoğlu, Barış Kerimoğlu
BACKGROUND/AIM: DNA topoisomerases are ubiquitous enzymes that regulate conformational changes in DNA topology during essential cellular processes, and, for this reason, have been characterized as the cellular targets of a number of anticancer drugs. Bortezomib is a powerful proteasome inhibitor used in the treatment of hematological malignancies. In this study, we investigated the inhibitory effects of bortezomib on human topoisomerase I and II enzymes both alone and in combination modes with camptothecin and etoposide...
December 20, 2016: Turkish Journal of Medical Sciences
https://www.readbyqxmd.com/read/28081183/circulating-cell-free-dna-in-dogs-with-mammary-tumors-short-and-long-fragments-and-integrity-index
#18
Giorgia Beffagna, Alessandro Sammarco, Chiara Bedin, Chiara Romualdi, Marta Mainenti, Antonio Mollo, Laura Cavicchioli, Silvia Ferro, Davide Trez, Raffaella De Maria, Donato Nitti, Andrea Saccani, Michelangelo Campanella, Marco Agostini, Valentina Zappulli
Circulating cell-free DNA (cfDNA) has been considered an interesting diagnostic/prognostic plasma biomarker in tumor-bearing subjects. In cancer patients, cfDNA can hypothetically derive from tumor necrosis/apoptosis, lysed circulating cells, and some yet unrevealed mechanisms of active release. This study aimed to preliminarily analyze cfDNA in dogs with canine mammary tumors (CMTs). Forty-four neoplastic, 17 non-neoplastic disease-bearing, and 15 healthy dogs were recruited. Necrosis and apoptosis were also assessed as potential source of cfDNA on 78 CMTs diagnosed from the 44 dogs...
2017: PloS One
https://www.readbyqxmd.com/read/28079901/the-clinical-utility-of-dna-based-screening-for-fetal-aneuploidy-by-primary-obstetrical-care-providers-in-the-general-pregnancy-population
#19
Glenn E Palomaki, Edward M Kloza, Barbara M O'Brien, Elizabeth E Eklund, Geralyn M Lambert-Messerlian
OBJECTIVE: To assess the clinical utility of cell-free DNA (cfDNA)-based screening for aneuploidies offered through primary obstetrical care providers to a general pregnancy population. METHODS: Patient educational materials were developed and validated and providers were trained. Serum was collected for reflexive testing of cfDNA failures. Providers and patients were surveyed concerning knowledge, decision making, and satisfaction. Pregnancy outcome was determined by active or passive ascertainment...
January 12, 2017: Genetics in Medicine: Official Journal of the American College of Medical Genetics
https://www.readbyqxmd.com/read/28078820/improvement-of-the-in-vivo-cellular-repopulation-of-decellularized-cardiovascular-tissues-by-a-detergent-free-non-proteolytic-actin-disassembling-regimen
#20
Alexander Assmann, Marc Struß, Franziska Schiffer, Friederike Heidelberg, Hiroshi Munakata, Elena V Timchenko, Pavel E Timchenko, Tim Kaufmann, Khon Huynh, Yukiharu Sugimura, Quentin Leidl, Antonio Pinto, Volker R Stoldt, Artur Lichtenberg, Payam Akhyari
Low immunogenicity and high repopulation capacity are crucial determinants for the functional and structural performance of acellular cardiovascular implants. The present study evaluates a detergent-free, non-proteolytic, actin-disassembling regimen (BIO) for decellularization of heart valve and vessel grafts, particularly focusing on their bio-functionality. Rat aortic conduits (rAoC; n = 89) and porcine aortic valve samples (n = 106) are decellularized using detergents (group DET) or the BIO regimen...
January 11, 2017: Journal of Tissue Engineering and Regenerative Medicine
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