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https://www.readbyqxmd.com/read/29691397/non-invasive-detection-of-human-cardiomyocyte-death-using-methylation-patterns-of-circulating-dna
#1
Hai Zemmour, David Planer, Judith Magenheim, Joshua Moss, Daniel Neiman, Dan Gilon, Amit Korach, Benjamin Glaser, Ruth Shemer, Giora Landesberg, Yuval Dor
Detection of cardiomyocyte death is crucial for the diagnosis and treatment of heart disease. Here we use comparative methylome analysis to identify genomic loci that are unmethylated specifically in cardiomyocytes, and develop these as biomarkers to quantify cardiomyocyte DNA in circulating cell-free DNA (cfDNA) derived from dying cells. Plasma of healthy individuals contains essentially no cardiomyocyte cfDNA, consistent with minimal cardiac turnover. Patients with acute ST-elevation myocardial infarction show a robust cardiac cfDNA signal that correlates with levels of troponin and creatine phosphokinase (CPK), including the expected elevation-decay dynamics following coronary angioplasty...
April 24, 2018: Nature Communications
https://www.readbyqxmd.com/read/29689710/esr1-and-pik3ca-mutational-status-in-serum-and-plasma-from-metastatic-breast-cancer-patients-a-comparative-study
#2
Takashi Takeshita, Yutaka Yamamoto, Mutsuko Yamamoto-Ibusuki, Mai Tomiguchi, Aiko Sueta, Hirotaka Iwase
PURPOSE: Plasma and serum cell-free DNA (cfDNA) are useful sources of tumor DNA, but comparative investigations of the tumor mutational status between them are rare. METHODS: we performed droplet digital PCR assay for representative hotspot mutations in metastatic breast cancer (MBC) (ESR1 and PIK3CA) in serum and plasma cfDNA concurrently extracted from the blood of 33 estrogen receptor-positive MBC patients. RESULTS: ESR1 mutations in plasma cfDNA were found in 7 of the 33 patients; ESR1 mutations in serum cfDNA were detected in only one out of 7 patients with ESR1 mutations in plasma cfDNA...
April 7, 2018: Cancer Biomarkers: Section A of Disease Markers
https://www.readbyqxmd.com/read/29689598/correlation-between-circulating-cell-free-pik3ca-tumor-dna-levels-and-treatment-response-in-patients-with-pik3ca-mutated-metastatic-breast-cancer
#3
Annette R Kodahl, Sidse Ehmsen, Niels Pallisgaard, Anne Marie B Jylling, Jeanette Dupont Jensen, Anne-Vibeke Laenkholm, Ann S Knoop, Henrik J Ditzel
Liquid biopsies focusing on the analysis of circulating cell-free tumor DNA (ctDNA) may have important clinical implications for personalized medicine, including early detection of cancer, therapeutic guidance and monitoring of recurrence. Mutations in the oncogene, PIK3CA, are frequently observed in breast cancer and have been suggested as a predictive biomarker for PI3K-selective inhibitor treatment. In this study, we analyzed the presence of PIK3CA mutations in formalin-fixed, paraffin-embedded, metastatic tissue and corresponding ctDNA from serum of patients with advanced breast cancer using a highly-sensitive, optimized droplet digital PCR (ddPCR) assay...
April 24, 2018: Molecular Oncology
https://www.readbyqxmd.com/read/29688820/elucidating-differential-nano-bio-interactions-of-multi-walled-andsingle-walled-carbon-nanotubes-using-subcellular-proteomics
#4
Joseph D T Ndika, Jukka Sund, Harri Alenius, Anne Puustinen
Understanding the relationship between adverse exposure events and specific material properties will facilitate predictive classification of carbon nanotubes (CNTs) according to their mechanisms of action, and a safe-by-design approach for the next generation of CNTs. Mass-spectrometry-based proteomics is a reliable tool to uncover the molecular dynamics of hazardous exposures, yet challenges persist with regards to its limited dynamic range when sampling whole organisms, tissues or cell lysates. Here, the simplicity of the sub-cellular proteome was harnessed to unravel distinctive adverse exposure outcomes at the molecular level, between two CNT subtypes...
April 24, 2018: Nanotoxicology
https://www.readbyqxmd.com/read/29688721/nano-encapsulation-of-novel-inhibitors-of-pnkp-for-selective-sensitization-to-ionizing-radiation-and-irinotecan-and-induction-of-synthetic-lethality
#5
Zahra Shire, Mohammad Reza Vakili, Timothy D R Morgan, Dennis G Hall, Afsaneh Lavasanifar, Michael Weinfeld
There is increasing interest in developing and applying DNA repair inhibitors in cancer treatment to augment the efficacy of radiation and conventional genotoxic chemotherapy. However, targeting the inhibitor is required to avoid reducing the repair capacity of normal tissue. The aim of this study was to develop nano-delivery systems for the encapsulation of novel imidopiperidine-based inhibitors of the DNA 3'-phosphatase activity of polynucleotide kinase/phosphatase (PNKP), a DNA repair enzyme that plays a critical role in rejoining DNA single- and double-strand breaks...
April 24, 2018: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/29687943/plasma-cell-free-dna-and-qsofa-score-predict-7-day-mortality-in-481-emergency-department-bacteraemia-patients
#6
Juha Rannikko, Tapio Seiskari, Reetta Huttunen, Iina Tarkiainen, Juulia Jylhävä, Mikko Hurme, Jaana Syrjänen, Janne Aittoniemi
BACKGROUND: A few studies have shown that both quick Sequential Organ Failure Assessment (qSOFA) score and cell-free DNA (cfDNA) have potential use as a prognostic marker in patients with infection. We studied these two markers alone and in combination to identify those emergency department (ED) patients with the highest risk of death. METHODS: Plasma cfDNA level was studied on days 0 to 4 after admittance to the ED from 481 culture-positive bloodstream infection cases...
April 24, 2018: Journal of Internal Medicine
https://www.readbyqxmd.com/read/29687201/folate-promotes-s-adenosyl-methionine-reactions-and-the-microbial-methylation-cycle-and-boosts-ruminants-production-and-reproduction
#7
REVIEW
Imtiaz Hussain Raja Abbasi, Farzana Abbasi, Lamei Wang, Mohamed E Abd El Hack, Ayman A Swelum, Ren Hao, Junhu Yao, Yangchun Cao
Folate has gained significant attention due to its vital role in biological methylation and epigenetic machinery. Folate, or vitamin (B9 ), is only produced through a de novo mechanism by plants and micro-organisms in the rumen of mature animals. Although limited research has been conducted on folate in ruminants, it has been noted that ruminal synthesis could not maintain folate levels in high yielding dairy animals. Folate has an essential role in one-carbon metabolism and is a strong antiproliferative agent...
April 23, 2018: AMB Express
https://www.readbyqxmd.com/read/29686994/cell-free-dna-high-mobility-group-box-1-and-procalcitonin-concentrations-in-dogs-with-gastric-dilatation-volvulus-syndrome
#8
Roberta Troia, Massimo Giunti, Stefano Calipa, Robert Goggs
Canine gastric dilatation-volvulus (GDV) is a life-threatening disease characterized by extensive tissue ischemia, tissue hypoperfusion, and systemic inflammation. Biomarkers that better reflect the severity of gastric necrosis and systemic inflammation would aid clinicians in the management of these patients. This study aimed to investigate the prognostic significance of cell-free DNA (cfDNA), high-mobility group box-1 (HMGB1), and procalcitonin (PCT) in dogs with GDV. Concentrations of cfDNA, HMGB1, and PCT were measured in citrated plasma samples collected from 29 dogs with GDV at hospital admission...
2018: Frontiers in Veterinary Science
https://www.readbyqxmd.com/read/29686738/a-new-approach-to-epigenome-wide-discovery-of-non-invasive-methylation-biomarkers-for-colorectal-cancer-screening-in-circulating-cell-free-dna-using-pooled-samples
#9
María Gallardo-Gómez, Sebastian Moran, María Páez de la Cadena, Vicenta Soledad Martínez-Zorzano, Francisco Javier Rodríguez-Berrocal, Mar Rodríguez-Girondo, Manel Esteller, Joaquín Cubiella, Luis Bujanda, Antoni Castells, Francesc Balaguer, Rodrigo Jover, Loretta De Chiara
Background: Colorectal cancer is the fourth cause of cancer-related deaths worldwide, though detection at early stages associates with good prognosis. Thus, there is a clear demand for novel non-invasive tests for the early detection of colorectal cancer and premalignant advanced adenomas, to be used in population-wide screening programs. Aberrant DNA methylation detected in liquid biopsies, such as serum circulating cell-free DNA (cfDNA), is a promising source of non-invasive biomarkers...
2018: Clinical Epigenetics
https://www.readbyqxmd.com/read/29686400/electrochemical-affinity-biosensors-for-fast-detection-of-gene-specific-methylations-with-no-need-for-bisulfite-and-amplification-treatments
#10
Eloy Povedano, Eva Vargas, Víctor Ruiz-Valdepeñas Montiel, Rebeca M Torrente-Rodríguez, María Pedrero, Rodrigo Barderas, Pablo San Segundo-Acosta, Alberto Peláez-García, Marta Mendiola, David Hardisson, Susana Campuzano, José M Pingarrón
This paper describes two different electrochemical affinity biosensing approaches for the simple, fast and bisulfite and PCR-free quantification of 5-methylated cytosines (5-mC) in DNA using the anti-5-mC antibody as biorecognition element. One of the biosensing approaches used the anti-5-mC as capture bioreceptor and a sandwich type immunoassay, while the other one involved the use of a specific DNA probe and the anti-5-mC as a detector bioreceptor of the captured methylated DNA. Both strategies, named for simplicity in the text as immunosensor and DNA sensor, respectively, were implemented on the surface of magnetic microparticles and the transduction was accomplished by amperometry at screen-printed carbon electrodes by means of the hydrogen peroxide/hydroquinone system...
April 23, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29685176/atr-kinase-inhibitors-nvp-bez235-and-azd6738-effectively-penetrate-the-brain-after-systemic-administration
#11
Guido Fròsina, Aldo Profumo, Daniela Marubbi, Diana Marcello, Jean Louis Ravetti, Antonio Daga
Ataxia Telangiectasia and Rad3 related protein (ATR) is a central mediator of the response to DNA damage that may cause the quiescent resistance of cancer initiating cells to genotoxic radiotherapy. NVP-BEZ235 is a dual PI3K/mTOR inhibitor that also effectively targets ATR with IC50  = 21 × 10- 9  M in cells. AZD6738 does not target significantly PI3K/mTOR-related kinases but specifically inhibits ATR with IC50  = 74 × 10- 9  M in cells. Both drugs have been proposed as radiosensitizers of different tumors including glioblastoma (GB), the most malignant brain tumor...
April 23, 2018: Radiation Oncology
https://www.readbyqxmd.com/read/29684875/toxicoproteomic-analysis-of-human-lung-epithelial-cells-exposed-to-steel-industry-ambient-particulate-matter-pm-reveals-possible-mechanism-of-pm-related-carcinogenesis
#12
S Senthil Kumar, P Muthuselvam, V Pugalenthi, N Subramanian, K M Ramkumar, T Suresh, T Suzuki, P Rajaguru
Toxicoproteomic analysis of steel industry ambient particulate matter (PM) that contain high concentrations of PAHs and metals was done by treating human lung cancer cell-line, A549 and the cell lysates were analysed using quantitative label-free nano LC-MS/MS. A total of 18,562 peptides representing 1576 proteins were identified and quantified, with 196 proteins had significantly altered expression in the treated cells. Enrichment analyses revealed that proteins associated to redox homeostsis, metabolism, and cellular energy generation were inhibited while, proteins related to DNA damage and repair and other stresses were over expressed...
April 20, 2018: Environmental Pollution
https://www.readbyqxmd.com/read/29684862/antioxidant-effects-of-lycium-barbarum-polysaccharides-on-photoreceptor-degeneration-in-the-light-exposed-mouse-retina
#13
Liujiu Tang, Shuyin Bao, Yu Du, Zengyan Jiang, A O Wuliji, Xiang Ren, Chenghong Zhang, Haiying Chu, Li Kong, Haiying Ma
We assessed the neuroprotective effects of Lycium barbarum Polysaccharides (LBP) on photoreceptor degeneration and the mechanisms involved in oxidative stress in light-exposed mouse retinas. Mice were given a gavage of LBP (150 mg/kg or 300 mg/kg) or phosphate buffered saline (PBS) for 7 days before exposure to light (5000 lx for 24 h). We found that LBP significantly improved the electroretinography (ERG) amplitudes of the a- and b-waves that had been attenuated by light exposure. In addition, changes caused by light exposure including photoreceptor cell loss, nuclear condensation, an increased number of mitochondria vacuoles, outer membrane disc swelling and cristae fractures were distinctly ameliorated by LBP...
April 20, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29684744/the-role-of-circulating-tumour-cells-and-nucleic-acids-in-blood-for-the-detection-of-bladder-cancer-a-systematic-review
#14
REVIEW
Pramit Khetrapal, Matthew Wei Liang Lee, Wei Shen Tan, Liqin Dong, Patricia de Winter, Andrew Feber, John D Kelly
BACKGROUND: Blood-based biomarkers are a neglected resource in bladder cancer, where the mainstay of focus has been on urinary biomarkers. However, blood-based biomarkers are gaining popularity in other solid cancers, particularly circulating tumour cells (CTCs) and circulating nucleic acids. In this systematic review, we identify and discuss the diagnostic value of CTC, cell-free DNA and RNA based biomarkers in bladder cancer. METHODS: A MEDLINE/Pubmed systematic search was performed using the following keywords: (bladder cancer) AND (blood OR plasma OR serum) AND biomarker AND (DNA OR RNA OR cfDNA OR cell-free DNA OR RNA OR CTC)...
April 17, 2018: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/29684697/new-arene-ruthenium-ii-complexes-of-4%C3%A2-aryl%C3%A2-4h%C3%A2-naphthopyrans-with-anticancer-and-anti-vascular-activities
#15
Florian Schmitt, Jana Kasparkova, Viktor Brabec, Gerrit Begemann, Rainer Schobert, Bernhard Biersack
A series of four 2‑amino‑3‑cyano‑4‑(3/4‑pyridyl)‑4H‑benzo[h]chromenes 2a-d and their dichlorido(p‑cymene)ruthenium(II) complexes 3a-d were tested for antiproliferative, vascular-disruptive, anti-angiogenic and DNA-binding activity. The coordination of the 4‑pyridyl‑4H‑naphthopyrans 2 to ruthenium led to complexes with pleiotropic effects. Unlike the free ligands 2a-d, their ruthenium complexes 3a-d showed a significant affinity for DNA as demonstrated by electrophoretic mobility shift assays (EMSA) and ethidium bromide assays...
April 5, 2018: Journal of Inorganic Biochemistry
https://www.readbyqxmd.com/read/29684456/radioprotective-effect-of-orally-administered-beta-d-glucan-derived-from-saccharomyces-cerevisiae
#16
Fang Liu, Zhuanzi Wang, Jia Liu, Wenjian Li
The present study was to evaluate the in vivo radioprotective effect of oral administration of Saccharomyces cerevisiae-derived-beta-d-glucan (S. cerevisiae-BG) and to investigate the protective mechanism. The results demonstrated that oral pretreatment with 350 mg/kg S. cerevisiae-BG once daily for 14 consecutive days significantly increased the survival rate of mice from 6 Gy X-rays irradiation. At the 30th day after irradiation, cellularity and the percentage of hematopoietic stem/progenitor cells in bone marrow (BM) of surviving mice were increased by S...
April 20, 2018: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/29683790/multicenter-phase-ib-trial-of-carboxyamidotriazole-orotate-and-temozolomide-for-recurrent-and-newly-diagnosed-glioblastoma-and-other-anaplastic-gliomas
#17
Antonio Omuro, Kathryn Beal, Katharine McNeill, Robert J Young, Alissa Thomas, Xuling Lin, Robert Terziev, Thomas J Kaley, Lisa M DeAngelis, Mariza Daras, Igor T Gavrilovic, Ingo Mellinghoff, Eli L Diamond, Andrew McKeown, Malbora Manne, Andrew Caterfino, Krishna Patel, Linda Bavisotto, Greg Gorman, Michael Lamson, Philip Gutin, Viviane Tabar, Debyani Chakravarty, Timothy A Chan, Cameron W Brennan, Elizabeth Garrett-Mayer, Rashida A Karmali, Elena Pentsova
Purpose Carboxyamidotriazole orotate (CTO) is a novel oral inhibitor of non-voltage-dependent calcium channels with modulatory effects in multiple cell-signaling pathways and synergistic effects with temozolomide (TMZ) in glioblastoma (GBM) models. We conducted a phase IB study combining CTO with two standard TMZ schedules in GBM. Methods In cohort 1, patients with recurrent anaplastic gliomas or GBM received escalating doses of CTO (219 to 812.5 mg/m2 once daily or 600 mg fixed once-daily dose) combined with TMZ (150 mg/m2 5 days during each 28-day cycle)...
April 23, 2018: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/29683524/fetal-sex-determination-in-twin-pregnancies-using-cell-free-fetal-dna-analysis
#18
Miguel Milan, Emilia Mateu, David Blesa, Monica Clemente-Ciscar, Carlos Simon
OBJECTIVE(S): We sought to develop an accurate sex classification method in twin pregnancies using data obtained from a standard commercial non-invasive prenatal test. STUDY DESIGN: A total of 706 twin pregnancies were included in this retrospective analytical data study. Normalized chromosome values for chromosomes X and Y were used and adapted into a sex-score to predict fetal sex in each fetus and results were compared to the clinical outcome at birth. RESULTS: Outcome information at birth for sex chromosomes was available for 232 twin pregnancies...
April 23, 2018: Prenatal Diagnosis
https://www.readbyqxmd.com/read/29683453/a-blood-based-test-for-the-detection-of-ros1-and-ret-fusion-transcripts-from-circulating-ribonucleic-acid-using-digital-polymerase-chain-reaction
#19
Hestia S Mellert, Kristin E Alexander, Leisa P Jackson, Gary A Pestano
We have developed novel methods for the isolation and characterization of tumor-derived circulating ribonucleic acid (cRNA) for blood-based liquid biopsy. Robust detection of cRNA recovered from blood represents a solution to a critical unmet need in clinical diagnostics. The test begins with the collection of whole blood into blood collection tubes containing preservatives that stabilize cRNA. Cell-free, exosomal, and platelet-associated RNA is isolated from plasma in this test system. The cRNA is reverse transcribed to complementary DNA (cDNA) and amplified using digital polymerase chain reaction (dPCR)...
April 5, 2018: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/29683451/production-and-purification-of-baculovirus-for-gene-therapy-application
#20
Md Nasimuzzaman, Johannes C M van der Loo, Punam Malik
Baculovirus has traditionally been used for the production of recombinant protein and vaccine. However, more recently, baculovirus is emerging as a promising vector for gene therapy application. Here, baculovirus is produced by transient transfection of the baculovirus plasmid DNA (bacmid) in an adherent culture of Sf9 cells. Baculovirus is subsequently expanded in Sf9 cells in a serum-free suspension culture until the desired volume is obtained. It is then purified from the culture supernatant using heparin affinity chromatography...
April 9, 2018: Journal of Visualized Experiments: JoVE
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