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https://www.readbyqxmd.com/read/29165875/4%C3%AE-hydroxywithanolide-e-selectively-induces-oxidative-dna-damage-for-selective-killing-of-oral-cancer-cells
#1
Jen-Yang Tang, Hurng-Wern Huang, Hui-Ru Wang, Ya-Ching Chan, Jo-Wen Haung, Chih-Wen Shu, Yang-Chang Wu, Hsueh-Wei Chang
Reactive oxygen species (ROS) induction had been previously reported in 4β-hydroxywithanolide (4βHWE)-induced selective killing of oral cancer cells, but the mechanism involving ROS and the DNA damage effect remain unclear. This study explores the role of ROS and oxidative DNA damage of 4βHWE in the selective killing of oral cancer cells. Changes in cell viability, morphology, ROS, DNA double strand break (DSB) signaling (γH2AX foci in immunofluorescence and DSB signaling in western blotting), and oxidative DNA damage (8-oxo-2'deoxyguanosine [8-oxodG]) were detected in 4βHWE-treated oral cancer (Ca9-22) and/or normal (HGF-1) cells...
November 22, 2017: Environmental Toxicology
https://www.readbyqxmd.com/read/29165219/porcine-circovirus-type-1-was-undetected-in-vaccine-but-could-be-cultured-in-the-cell-substrate-of-lanzhou-lamb-rotavirus-vaccine
#2
Qingchuan Yu, Yan Liu, Jialiang Du, Yueyue Liu, Lili Zhang, Tai Guo
In 2010, Rotarix was found to be contaminated with infectious porcine circovirus type 1 (PCV1). In China, the Lanzhou lamb rotavirus (LLR) vaccine is the only vaccine used to prevent rotavirus disease. From 2006 to September 2014, more than 54 million doses of LLR vaccines have been lot released. It is a safety issue whether PCV1 is present in the LLR vaccine. Although the cell substrate of LLR, bovine kidney (BK), is different from that of Rotarix, we have investigated the cell's permissivity for PCV1 by both infectivity and full-length PCR analysis...
November 22, 2017: Journal of General Virology
https://www.readbyqxmd.com/read/29163881/displacement-and-hybridization-reactions-in-aptamer-functionalized-hydrogels-for-biomimetic-protein-release-and-signal-transduction
#3
Jinping Lai, Shihui Li, Xuechen Shi, James Coyne, Nan Zhao, Fengping Dong, Yingwei Mao, Yong Wang
A variety of hydrogels have been synthesized for controlling the release of signaling molecules in applications such as drug delivery and regenerative medicine. However, it remains challenging to synthesize hydrogels with the ability to control the release of signaling molecules sequentially or periodically under physiological conditions as living cells do in response to the variation of metabolism. The purpose of this work was to study a novel biomimetic hydrogel system with the ability of recapitulating the procedure of cellular signal transduction and controlling the sequential release of signaling molecules under physiological conditions...
November 1, 2017: Chemical Science
https://www.readbyqxmd.com/read/29163793/rapid-ultra-low-coverage-copy-number-profiling-of-cell-free-dna-as-a-precision-oncology-screening-strategy
#4
Daniel H Hovelson, Chia-Jen Liu, Yugang Wang, Qing Kang, James Henderson, Amy Gursky, Scott Brockman, Nithya Ramnath, John C Krauss, Moshe Talpaz, Malathi Kandarpa, Rashmi Chugh, Missy Tuck, Kirk Herman, Catherine S Grasso, Michael J Quist, Felix Y Feng, Christine Haakenson, John Langmore, Emmanuel Kamberov, Tim Tesmer, Hatim Husain, Robert J Lonigro, Dan Robinson, David C Smith, Ajjai S Alva, Maha H Hussain, Arul M Chinnaiyan, Muneesh Tewari, Ryan E Mills, Todd M Morgan, Scott A Tomlins
Current cell-free DNA (cfDNA) next generation sequencing (NGS) precision oncology workflows are typically limited to targeted and/or disease-specific applications. In advanced cancer, disease burden and cfDNA tumor content are often elevated, yielding unique precision oncology opportunities. We sought to demonstrate the utility of a pan-cancer, rapid, inexpensive, whole genome NGS of cfDNA approach (PRINCe) as a precision oncology screening strategy via ultra-low coverage (~0.01x) tumor content determination through genome-wide copy number alteration (CNA) profiling...
October 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/29163150/targeting-dna-repair-through-podophyllotoxin-and-rutin-formulation-in-hematopoietic-radioprotection-an-in-silico-in-vitro-and-in-vivo-study
#5
M H Yashavarddhan, Sandeep K Shukla, Pankaj Chaudhary, Nitya N Srivastava, Jayadev Joshi, Mrutyunjay Suar, Manju L Gupta
Drug discovery field has tremendously progressed during last few decades, however, an effective radiation countermeasure agent for the safe administration to the victims of radiation exposure is still unavailable. This multi-model study is aimed at elucidating the mechanistic aspects of a novel podophyllotoxin and rutin combination (henceforth referred as G-003M) in the hematopoietic radioprotection and its involvement in the DNA damage and repair signaling pathways. Using in silico study, we identified the binding sites and structural components of G-003M and validated in vitro...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29162979/association-of-tissue-specific-dna-methylation-alterations-with-%C3%AE-thalassemia-southeast-asian-deletion
#6
Tanapat Pangeson, Phanchana Sanguansermsri, Torpong Sanguansermsri, Teerapat Seeratanachot, Narutchala Suwanakhon, Metawee Srikummool, Worasak Kaewkong, Khwanruedee Mahingsa
In the wild-type allele, DNA methylation levels of 10 consecutive CpG sites adjacent to the upstream 5'-breakpoint of α-thalassemia Southeast Asian (SEA) deletion are not different between placenta and leukocytes. However, no previous study has reported the map of DNA methylation in the SEA allele. This report aims to show that the SEA mutation is associated with DNA methylation changes, resulting in differential methylation between placenta and leukocytes. Methylation-sensitive high-resolution analysis was used to compare DNA methylation among placenta, leukocytes, and unmethylated control DNA...
2017: Genetics & Epigenetics
https://www.readbyqxmd.com/read/29161279/whole-exome-sequencing-for-determination-of-tumor-mutation-load-in-liquid-biopsy-from-advanced-cancer-patients
#7
Florence Koeppel, Steven Blanchard, Cécile Jovelet, Bérengère Genin, Charles Marcaillou, Emmanuel Martin, Etienne Rouleau, Eric Solary, Jean-Charles Soria, Fabrice André, Ludovic Lacroix
Tumor mutation load (TML) has been proposed as a biomarker of patient response to immunotherapy in several studies. TML is usually determined by tumor biopsy DNA (tDNA) whole exome sequencing (WES), therefore TML evaluation is limited by informative biopsy availability. Circulating cell free DNA (cfDNA) provided by liquid biopsy is a surrogate specimen to biopsy for molecular profiling. Nevertheless performing WES on DNA from plasma is technically challenging and the ability to determine tumor mutation load from liquid biopsies remains to be demonstrated...
2017: PloS One
https://www.readbyqxmd.com/read/29159804/antibodies-against-human-papillomaviruses-as-diagnostic-and-prognostic-biomarker-in-patients-with-neck-squamous-cell-carcinoma-from-unknown-primary
#8
Lea Schroeder, Gunnar Wichmann, Maria Willner, Angelika Michel, Manuel Wiesenfarth, Christa Flechtenmacher, Tanja Gradistanac, Michael Pawlita, Andreas Dietz, Tim Waterboer, Dana Holzinger
Treatment of patients with neck lymph node metastasis of squamous cell carcinoma (SCC) from unknown primary tumor (NSCCUP) is challenging due to the risk of missing occult tumors or inducing toxicity to unaffected sites. Human papillomavirus (HPV) is a promising biomarker given its causal link to oropharyngeal SCC and superior survival of patients with HPV-driven oropharyngeal SCC and NSCCUP. Identification of HPV-driven NSCCUP could focus diagnostic work-up and treatment on the oropharynx. For the first time, we assessed HPV antibodies and their prognostic value in NSCCUP patients...
November 21, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/29158830/sustained-release-talazoparib-implants-for-localized-treatment-of-brca1-deficient-breast-cancer
#9
Jodi E Belz, Rajiv Kumar, Paige Baldwin, Noelle Castilla Ojo, Ana S Leal, Darlene B Royce, Di Zhang, Anne L van de Ven, Karen T Liby, Srinivas Sridhar
Talazoparib, a potent PARP inhibitor, has shown promising clinical and pre-clinical activity by inducing synthetic lethality in cancers with germline Brca1/2 mutations. Conventional oral delivery of Talazoparib is associated with significant off-target effects, therefore we sought to develop new delivery systems in the form of an implant loaded with Talazoparib for localized, slow and sustained release of the drug at the tumor site in Brca1-deficient breast cancer. Poly(lactic-co-glycolic acid) (PLGA) implants (0...
2017: Theranostics
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
#10
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/29156777/patients-with-nsclc-may-display-a-low-ratio-of-p-t790m-vs-activating-egfr-mutations-in-plasma-at-disease-progression-implications-for-personalised-treatment
#11
Marzia Del Re, Paola Bordi, Iacopo Petrini, Eleonora Rofi, Francesca Mazzoni, Lorenzo Belluomini, Enrico Vasile, Giuliana Restante, Francesco Di Costanzo, Alfredo Falcone, Antonio Frassoldati, Ron H N van Schaik, Christi M J Steendam, Antonio Chella, Marcello Tiseo, Riccardo Morganti, Romano Danesi
Introduction: NSCLC harboring activating mutations of EGFR is highly sensitive to first-line EGFR-tyrosine kinase inhibitors (TKIs), but drug resistance depending on the EGFR mutation p.T790M will occur in about 50-60% of patients. Detailed information on the amount of p.T790M plasmatic level associated with resistance to EGFR-TKIs and guidance to treatment with p.T790M-effective TKI depending on these levels, is lacking. Methods: This study enrolled p.T790M-positive patients (n=49) affected by EGFR-mutated NSCLC at progression to first-line EGFR-TKIs and, in selected cases (n=5), after second-line treatment with osimertinib...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29156753/candidate-tumor-suppressor-znf154-suppresses-invasion-and-metastasis-in-npc-by-inhibiting-the-emt-via-wnt-%C3%AE-catenin-signalling
#12
Ying Hu, Min-Fang Qi, Qian-Lan Xu, Xiang-Yun Kong, Rui Cai, Qiu-Qiu Chen, Hua-Ying Tang, Wei Jiang
Background: Nasopharyngeal carcinoma (NPC) is especially prevalent in southeast Asia and southern China, but its molecular mechanisms remain poorly characterized. DNA methylation is associated with initiation and progression of tumors, including NPC. Through a genome-wide DNA methylation screening approach, we discovered ZNF154, but its methylation status and roles in NPC have not been investigated. Methods: The methylation status of ZNF154 in NPC was detected with Methylation specific-PCR (MSP) and Quantitative Sequenom MassARRAY...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29156716/using-droplet-digital-pcr-to-analyze-mycn-and-alk-copy-number-in-plasma-from-patients-with-neuroblastoma
#13
Marco Lodrini, Annika Sprüssel, Kathy Astrahantseff, Daniela Tiburtius, Robert Konschak, Holger N Lode, Matthias Fischer, Ulrich Keilholz, Angelika Eggert, Hedwig E Deubzer
The invasive nature of surgical biopsies deters sequential application, and single biopsies often fail to reflect tumor dynamics, intratumor heterogeneity and drug sensitivities likely to change during tumor evolution and treatment. Implementing molecular characterization of cell-free neuroblastoma-derived DNA isolated from blood plasma could improve disease assessment for treatment selection and monitoring of patients with high-risk neuroblastoma. We established droplet digital PCR (ddPCR) protocols for MYCN and ALK copy number status in plasma from neuroblastoma patients...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29155953/max-mutations-in-endometrial-cancer-clinicopathologic-associations-and-recurrent-max-p-his28arg-functional-characterization
#14
Christopher J Walker, Craig M Rush, Paola Dama, Matthew J O'Hern, Casey M Cosgrove, Jessica L Gillespie, Roman A Zingarelli, Blair Smith, Maggie E Stein, David G Mutch, Reena Shakya, Chia-Wen Chang, Karuppaiyah Selvendiran, Jonathan W Song, David E Cohn, Paul J Goodfellow
Background: Genomic studies have revealed that multiple genes are mutated at varying frequency in endometrial cancer (EC); however, the relevance of many of these mutations is poorly understood. An EC-specific recurrent mutation in the MAX transcription factor p.His28Arg was recently discovered. We sought to assess the functional consequences of this hotspot mutation and determine its association with cancer-relevant phenotypes. Methods: MAX was sequenced in 509 endometrioid ECs, and associations between mutation status and clinicopathologic features were assessed...
November 15, 2017: Journal of the National Cancer Institute
https://www.readbyqxmd.com/read/29155394/label-free-and-dynamic-monitoring-of-cytotoxicity-to-the-blood-brain-barrier-cells-treated-with-nanometre-copper-oxide
#15
Duan Lian, Zhang Chonghua, Gu Wen, Zhang Hongwei, Bai Xuetao
A cytotoxicity study was conducted with a primary culture of the nervous system cells, including brain microvascular endothelial cells (BMECs) and astrocytes, which are important components of the blood-brain barrier. The real-time cell analysis (RTCA) was used to determine the cytotoxicity of copper-oxide nanoparticles (CuO NPs). The IC50 values of CuO NPs in astrocytes and BMECs were determined by the RTCA at different exposure times and were used as base values for further research. DNA damage after exposure to CuO NPs for 3 and 24 h was assessed using comet assay at the IC50 obtained from RTCA...
December 2017: IET Nanobiotechnology
https://www.readbyqxmd.com/read/29155161/extracellular-vesicles-compartment-in-liquid-biopsies-clinical-application
#16
REVIEW
Noemi Garcia-Romero, Susana Esteban-Rubio, Gorjana Rackov, Josefa Carrión-Navarro, Cristobal Belda-Iniesta, Angel Ayuso-Sacido
Liquid biopsy is becoming a new source of biomarkers that complement and resolve some of the most important limitations of surgical biopsy, which are the accessibility to the diseased tissue and its heterogeneity, especially relevant for tumors. The diseased tissues release their molecule content to the bloodstream in free form, inside a cell or within extracellular vesicles (EVs). While the identification of molecular alterations in total DNA isolated from peripheral blood is already in use for some tumors that secrete large amounts of DNA, it is challenging to assay those secreting lower amounts of molecules as well as for many other non-tumoral pathologies like immunological and cardiovascular diseases...
November 16, 2017: Molecular Aspects of Medicine
https://www.readbyqxmd.com/read/29155091/dynamic-molecular-events-associated-to-plasmodium-berghei-gametogenesis-through-proteomic-approach
#17
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/29154976/microneedle-arrays-coated-with-charge-reversal-ph-sensitive-copolymers-improve-antigen-presenting-cells-homing-dna-vaccine-delivery-and-immune-responses
#18
Huu Thuy Trang Duong, Nak Won Kim, Thavasyappan Thambi, V H Giang Phan, Min Sang Lee, Yue Yin, Ji Hoon Jeong, Doo Sung Lee
Successful delivery of a DNA vaccine to antigen-presenting cells and their subsequent stimulation of CD4(+) and CD8(+) T cell immunity remains an inefficient process. In general, the delivery of prophylactic vaccines is mainly mired by low transfection efficacy, poor immunogenicity, and safety issues from the materials employed. Currently, several strategies have been exploited to improve immunogenicity, but an effective strategy for safe and pain-free delivery of DNA vaccines is complicated. Herein, we report the rapid delivery of polyplex-based DNA vaccines using microneedle arrays coated with a polyelectrolyte multilayer assembly of charge reversal pH-responsive copolymer and heparin...
November 15, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/29154831/detection-of-mycobacterium-tuberculosis-derived-dna-in-circulating-cell-free-dna-from-a-patient-with-disseminated-infection-with-digital-pcr
#19
Masaki Yamamoto, Ryota Ushio, Hiroki Watanabe, Takayoshi Tachibana, Masatsugu Tanaka, Tomoyuki Yokose, Jun Tsukiji, Hideaki Nakajima, Takeshi Kaneko
Mycobacterium tuberculosis (MTB) can disseminate to extra-pulmonary organs, particularly in severely immunosuppressed patients. Confirmation of active MTB infection is often difficult in subjects with contraindication for invasive procedures. We herein report a case of disseminated MTB infection after hematopoietic stem cell transplantation. Circulating cell free DNA of the patient showed positive amplification for a MTB complex specific sequence using digital PCR technique. MTB infection could be confirmed with positive acid fast stain and approved quantitative PCR assay using the liver tissue obtained at an autopsy...
November 14, 2017: International Journal of Infectious Diseases: IJID
https://www.readbyqxmd.com/read/29154198/evaluation-of-antioxidant-dna-targeting-antimicrobial-and-cytotoxic-studies-of-imine-capped-copper-and-nickel-nanoparticles
#20
P Adwin Jose, J Dhaveethu Raja, M Sankarganesh, J Rajesh
In this work, we have synthesized pyrimidine derivatives of Schiff base ligand 2-(4,6-dimethoxypyrimidin-2-ylimino)methyl)-6-methoxyphenol (DPMM) stabilized copper nanoparticles (DPMM-CuNPs) and nickel nanoparticles (DPMM-NiNPs) by modified Brust-Schiffrin technique as two step phase transfer assisted method and confirmed by UV-Visible, SEM and TEM analysis. The free radical scavenging activity of DPMM, DPMM-CuNPs &DPMM-NiNPs with 2, 2'-diphenylpicryl hydrazyl (DPPH), hydrogen peroxide (H2O2) super oxide dismutase (SOD) and nitric oxide (NO) shows that the antioxidant activity of DPMM-CuNPs is higher than DPMM &DPMM-NiNPs...
November 6, 2017: Journal of Photochemistry and Photobiology. B, Biology
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