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https://www.readbyqxmd.com/read/28427237/oxidative-dna-double-strand-breaks-and-autophagy-in-the-antitumor-effect-of-sterically-hindered-platinum-ii-complexes-in-nsclcs
#1
Feihong Chen, Xinyi Wang, Xiufeng Jin, Jian Zhao, Shaohua Gou
A series of novel platinum(II) complexes with (1R,2R)-N1,N2-diisobutyl-1,2-diaminocyclohexane as a carrier ligand, while N1,N2-diisobutyl moiety serving as steric hindrance were designed, synthesized and characterized. The in vitro biological assays demonstrated that complex 3 had increased cytotoxicity against lung cancer cells, especially non-small-cell lung cancer (NSCLC) compared to its mono-substituted complex 3a, indicating that the sterically hindered alkyl moieties have significant influences on its antitumor property...
March 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/28425423/pathology-and-molecular-analysis-of-hapalotrema-mistroides-digenea-spirorchiidae-infecting-a-mediterranean-loggerhead-turtle-caretta-caretta
#2
M Santoro, F Di Nocera, D Iaccarino, S P Lawton, A Cerrone, B Degli Uberti, M D'Amore, A Affuso, S Hochscheid, F Maffucci, G Galiero
Turtle blood flukes belonging to the family Spirorchiidae (Digenea) represent a major threat for sea turtle health and are considered the most important parasitic cause of turtle stranding and mortality worldwide. Despite the large diversity of spirorchiid species found globally, there are only 2 records for free-ranging Mediterranean sea turtles that date back to the late 1800s involving just Hapalotrema mistroides Monticelli, 1896. This study describes the first fatal confirmed case of spirorchiidiasis in a free-ranging Mediterranean loggerhead turtle Caretta caretta (Linnaeus) and, owing to the complexities of taxonomic identification of these parasites, provides the first molecular characterization and phylogenetic analysis of H...
April 20, 2017: Diseases of Aquatic Organisms
https://www.readbyqxmd.com/read/28412778/parp-inhibitors-the-cornerstone-of-dna-repair-targeted-therapies
#3
REVIEW
Jaydira Del Rivero, Elise C Kohn
The activity and therapeutic licensing of poly(ADP-ribose) polymerase (PARP) inhibitors is the culmination of 50 years of research. However, the biology, mechanisms of action, adequate treatment combinations, and targeted populations for these agents need to be explored further. PARP activity is essential for the repair of single-strand DNA breaks via the base excision repair pathway. This pathway is the default repair pathway in cells with deficient high-fidelity double-strand break homologous recombination (HR) repair, such as occurs with loss of BRCA1 or BRCA2 function...
April 15, 2017: Oncology (Williston Park, NY)
https://www.readbyqxmd.com/read/28394347/new-factors-in-mammalian-dna-repair-the-chromatin-connection
#4
REVIEW
G Raschellà, G Melino, M Malewicz
In response to DNA damage mammalian cells activate a complex network of stress response pathways collectively termed DNA damage response (DDR). DDR involves a temporary arrest of the cell cycle to allow for the repair of the damage. DDR also attenuates gene expression by silencing global transcription and translation. Main function of DDR is, however, to prevent the fixation of debilitating changes to DNA by activation of various DNA repair pathways. Proper execution of DDR requires careful coordination between these interdependent cellular responses...
April 10, 2017: Oncogene
https://www.readbyqxmd.com/read/28394283/single-round-infectious-particle-antiviral-screening-assays-for-the-japanese-encephalitis-virus
#5
Chien-Yi Lu, Mann-Jen Hour, Ching-Ying Wang, Su-Hua Huang, Wen-Xiang Mu, Yu-Chun Chang, Cheng-Wen Lin
Japanese Encephalitis virus (JEV) is a mosquito-borne flavivirus with a positive-sense single-stranded RNA genome that contains a big open reading frame (ORF) flanked by 5'- and 3'- untranslated regions (UTRs). Nearly 30,000 JE cases with 10,000 deaths are still annually reported in East Asia. Although the JEV genotype III vaccine has been licensed, it elicits a lower protection against other genotypes. Moreover, no effective treatment for a JE case is developed. This study constructed a pBR322-based and cytomegaloviruses (CMV) promoter-driven JEV replicon for the production of JEV single-round infectious particles (SRIPs) in a packaging cell line expressing viral structural proteins...
April 10, 2017: Viruses
https://www.readbyqxmd.com/read/28392333/outcome-of-hematopoietic-cell-transplantation-for-dna-double-strand-breakage-repair-disorders
#6
James Slack, Michael H Albert, Dmitry Balashov, Bernd H Belohradsky, Alice Bertaina, Jack Bleesing, Claire Booth, Jochen Büchner, Rebecca H Buckley, Marie Ouachée-Chardin, Elena Deripapa, Katarzyna Drabko, Mary Eapen, Tobias Feuchtinger, Andrea Finocchi, H Bobby Gaspar, Sujal Ghosh, Alfred Gillio, Luis I Gonzalez-Granado, Eyal Grunebaum, Tayfun Güngör, Carsten Heilmann, Merja Helminen, Kohei Higuchi, Kohsuke Imai, Krzysztof Kalwak, Nubuo Kanazawa, Gülsün Karasu, Zeynep Y Kucuk, Alexandra Laberko, Andrzej Lange, Nizar Mahlaoui, Roland Meisel, D Moshous, Hideki Muramatsu, Suhag Parikh, Srdjan Pasic, Irene Schmid, Catharina Schuetz, Ansgar Schulz, Kirk R Schultz, Peter J Shaw, Mary A Slatter, Karl-Walter Sykora, Shinobu Tamura, Mervi Taskinen, Angela Wawer, Beata Wolska-Kus Nierz, Morton J Cowan, Alain Fischer, Andrew R Gennery
BACKGROUND: Rare DNA breakage-repair disorders predispose to infection and lympho-reticular malignancies. Hematopoietic cell transplantation (HCT) is curative but co-administered chemo- or radio-therapy is damaging due to systemic radio-sensitivity. We collected HCT outcome data for Nijmegen Breakage syndrome (NBS), DNA ligase IV deficiency (LIG4), Cernunnos-XLF deficiency and ataxia-telangiectasia. METHODS: Data from 38 centres worldwide, including indication, donor, conditioning regimen, graft-versus-host disease (GvHD) and outcome were analyzed...
April 6, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28378638/expression-signatures-of-dna-repair-genes-correlate-with-survival-prognosis-of-astrocytoma-patients
#7
Juliana Ferreira de Sousa, Raul Torrieri, Rodolfo Bortolozo Serafim, Luis Fernando Macedo Di Cristofaro, Fábio Dalbon Escanfella, Rodrigo Ribeiro, Dalila Lucíola Zanette, Maria Luisa Paçó-Larson, Wilson Araujo da Silva, Daniela Pretti da Cunha Tirapelli, Luciano Neder, Carlos Gilberto Carlotti, Valeria Valente
Astrocytomas are the most common primary brain tumors. They are very resistant to therapies and usually progress rapidly to high-grade lesions. Here, we investigated the potential role of DNA repair genes in astrocytoma progression and resistance. To this aim, we performed a polymerase chain reaction array-based analysis focused on DNA repair genes and searched for correlations between expression patters and survival prognoses. We found 19 genes significantly altered. Combining these genes in all possible arrangements, we found 421 expression signatures strongly associated with poor survival...
April 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28364014/radium-223-inhibits-osseous-prostate-cancer-growth-by-dual-targeting-of-cancer-cells-and-bone-microenvironment-in-mouse-models
#8
Mari I Suominen, Katja M Fagerlund, Jukka P Rissanen, Yvonne M Konkol, Jukka P Morko, ZhiQi Peng, Esa J Alhoniemi, Salla K Laine, Eva Corey, Dominik Mumberg, Karl Ziegelbauer, Sanna-Maria Käkönen, Jussi Halleen, Robert L Vessella, Arne Scholz
Radium-223 dichloride (radium-223, Xofigo®), a targeted alpha therapy, is currently used for the treatment of patients with castration-resistant prostate cancer (CRPC) with bone metastases. This study examines the mode-of-action and antitumor efficacy of radium-223 in two prostate cancer xenograft models. <br /><br />Experimental Design: Mice bearing intratibial LNCaP or LuCaP 58 tumors were randomized to groups (n = 12-17) based on lesion grade and/or serum PSA level and administered with radium-223 (300 kBq/kg) or vehicle, twice at 4-week intervals...
March 31, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28362341/the-role-of-micrornas-in-myocardial-infarction-from-molecular-mechanism-to-clinical-application
#9
REVIEW
Teng Sun, Yan-Han Dong, Wei Du, Chun-Ying Shi, Kun Wang, Muhammad-Akram Tariq, Jian-Xun Wang, Pei-Feng Li
MicroRNAs (miRNAs) are a class of small single-stranded and highly conserved non-coding RNAs, which are closely linked to cardiac disorders such as myocardial infarction (MI), cardiomyocyte hypertrophy, and heart failure. A growing number of studies have demonstrated that miRNAs determine the fate of the heart by regulating cardiac cell death and regeneration after MI. A deep understanding of the pathophysiology of miRNA dependent regulatory pathways in these processes is required. The role of miRNAs as diagnostic, prognostic, and therapeutic targets also needs to be explored in order to utilize them in clinical settings...
March 31, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28362255/ribonuclease-l-mediates-the-cell-lethal-phenotype-of-the-double-stranded-rna-editing-enzyme-adar1-in-a-human-cell-line
#10
Yize Li, Shuvojit Banerjee, Stephen A Goldstein, Beihua Dong, Christina Gaughan, Sneha Rath, Jesse Donovan, Alexei V Korennykh, Robert H Silverman, Susan R Weiss
ADAR1 isoforms are adenosine deaminases that edit and destabilize double-stranded RNA reducing its immunostimulatory activities. Mutation of ADAR1 leads to a severe neurodevelopmental and inflammatory disease of children, Aicardi-Goutiéres syndrome. In mice, Adar1 mutations are embryonic lethal but are rescued by mutation of the Mda5 or Mavs genes, which function in IFN induction. However, the specific IFN regulated proteins responsible for the pathogenic effects of ADAR1 mutation are unknown. We show that the cell-lethal phenotype of ADAR1 deletion in human lung adenocarcinoma A549 cells is rescued by CRISPR/Cas9 mutagenesis of the RNASEL gene or by expression of the RNase L antagonist, murine coronavirus NS2 accessory protein...
March 31, 2017: ELife
https://www.readbyqxmd.com/read/28358361/tumor-treating-fields-elicit-a-conditional-vulnerability-to-ionizing-radiation-via-the-downregulation-of-brca1-signaling-and-reduced-dna-double-strand-break-repair-capacity-in-non-small-cell-lung-cancer-cell-lines
#11
Narasimha Kumar Karanam, Kalayarasan Srinivasan, Lianghao Ding, Brock Sishc, Debabrata Saha, Michael D Story
The use of tumor-treating fields (TTFields) has revolutionized the treatment of recurrent and newly diagnosed glioblastoma (GBM). TTFields are low-intensity, intermediate frequency, alternating electric fields that are applied to tumor regions and cells using non-invasive arrays. The predominant mechanism by which TTFields are thought to kill tumor cells is the disruption of mitosis. Using five non-small cell lung cancer (NSCLC) cell lines we found that there is a variable response in cell proliferation and cell killing between these NSCLC cell lines that was independent of p53 status...
March 30, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28351923/differences-in-integron-cassette-excision-dynamics-shape-a-trade-off-between-evolvability-and-genetic-capacitance
#12
Céline Loot, Aleksandra Nivina, Jean Cury, José Antonio Escudero, Magaly Ducos-Galand, David Bikard, Eduardo P C Rocha, Didier Mazel
Integrons ensure a rapid and "on demand" response to environmental stresses driving bacterial adaptation. They are able to capture, store, and reorder functional gene cassettes due to site-specific recombination catalyzed by their integrase. Integrons can be either sedentary and chromosomally located or mobile when they are associated with transposons and plasmids. They are respectively called sedentary chromosomal integrons (SCIs) and mobile integrons (MIs). MIs are key players in the dissemination of antibiotic resistance genes...
March 28, 2017: MBio
https://www.readbyqxmd.com/read/28347154/-circulating-micrornas-in-the-diagnostics-of-endocrine-neoplasms
#13
Ábel Decmann, Pál Perge, Zoltán Nagy, Henriett Butz, Attila Patócs, Péter Igaz
MicroRNAs (miRNA, miR) are short - 19-25 nucleotide long - single stranded (in their mature form), non-coding RNA molecules that regulate gene expression mostly at the posttranscriptional level. microRNAs are involved in the regulation of various physiological processes such as cell differentiation and proliferation, development, haematopoesis, cell death, while their aberrant expression is observed in numerous diseases, like autoimmune disorders, inflammations, vascular diseases or tumorigenesis. microRNAs are expressed in a tissue specific fashion...
April 2017: Orvosi Hetilap
https://www.readbyqxmd.com/read/28342984/hdac4-and-hdac6-sustain-dna-double-strand-break-repair-and-stem-like-phenotype-by-promoting-radioresistance-in-glioblastoma-cells
#14
Francesco Marampon, Francesca Megiorni, Simona Camero, Clara Crescioli, Heather P McDowell, Roberta Sferra, Antonella Vetuschi, Simona Pompili, Luca Ventura, Francesca De Felice, Vincenzo Tombolini, Carlo Dominici, Roberto Maggio, Claudio Festuccia, Giovanni Luca Gravina
The role of histone deacetylase (HDAC) 4 and 6 in glioblastoma (GBM) radioresistance was investigated. We found that tumor samples from 31 GBM patients, who underwent temozolomide and radiotherapy combined treatment, showed HDAC4 and HDAC6 expression in 93.5% and 96.7% of cases, respectively. Retrospective clinical data analysis demonstrated that high-intensity HDAC4 and/or HDAC6 immunostaining was predictive of poor clinical outcome. In vitro experiments revealed that short hairpin RNA-mediated silencing of HDAC4 or HDAC6 radiosensitized U87MG and U251MG GBM cell lines by promoting DNA double-strand break (DSBs) accumulation and by affecting DSBs repair molecular machinery...
March 23, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28340172/repositioning-disulfiram-as-a-radiosensitizer-against-atypical-teratoid-rhabdoid-tumor
#15
Young Eun Lee, Seung Ah Choi, Pil Ae Kwack, Hak Jae Kim, Il Han Kim, Kyu-Chang Wang, Ji Hoon Phi, Ji Yeoun Lee, Sangjoon Chong, Sung-Hye Park, Kyung Duk Park, Do Won Hwang, Kyeung Min Joo, Seung-Ki Kim
Background.: Atypical teratoid/rhabdoid tumor (AT/RT) is one of the most common malignant brain tumors in infants. Although cancer stem cells of AT/RT express aldehyde dehydrogenase (ALDH), effective chemotherapies against AT/RT have not been established. Here, we examined radiosensitizing effects of disulfiram (DSF), an irreversible inhibitor of ALDH against AT/RT for a novel therapeutic method. Methods.: Patient-derived primary cultured AT/RT cells (SNU.AT/RT-5 and SNU...
March 17, 2017: Neuro-oncology
https://www.readbyqxmd.com/read/28336131/modulating-the-dna-damage-response-to-improve-treatment-response-in-cervical-cancer
#16
L H Cossar, A G Schache, J M Risk, J J Sacco, N J Jones, R Lord
Cervical cancer is the fourth most common cause of cancer-related death in women worldwide and new therapeutic approaches are needed to improve clinical outcomes for this group of patients. Current treatment protocols for locally advanced and metastatic disease consist of ionising radiation and chemotherapy. Chemoradiation induces cytotoxic levels of DNA double-strand breaks, which activates programmed cell death via the DNA damage response (DDR). Cervical cancers are unique given an almost exclusive association with human papillomavirus (HPV) infection; a potent manipulator of the DDR, with the potential to alter tumour sensitivity to DNA-damaging agents and influence treatment response...
March 20, 2017: Clinical Oncology: a Journal of the Royal College of Radiologists
https://www.readbyqxmd.com/read/28334597/intramyocardial-bronchogenic-cyst-histological-appearance-and-a-review-of-the-literature
#17
Naoki Nishida, Yukiko Hata, Kazuhiro Nomoto
We report histological appearance of a bronchogenic cyst that was incidentally found in a 78-year-old man who died from drowning related to a traumatic accident. The cyst was found in the posterior edge of the interventricular septum and was monolocular with a 5-mm diameter. The cystic wall was not associated with cartilage or the smooth muscle layer, and was lined by ciliated respiratory epithelium. Immunohistochemistry showed that many of these epithelial cells were positive for cytokeratin 7 and thyroid transcription factor-1...
March 12, 2017: Cardiovascular Pathology: the Official Journal of the Society for Cardiovascular Pathology
https://www.readbyqxmd.com/read/28333135/bre-modulates-granulosa-cell-death-to-affect-ovarian-follicle-development-and-atresia-in-the-mouse
#18
Cheung Kwan Yeung, Guang Wang, Yao Yao, Jianxin Liang, Cheuk Yiu Tenny Chung, Manli Chuai, Kenneth Ka Ho Lee, Xuesong Yang
The BRE (brain and reproductive expression) gene, highly expressed in nervous and reproductive system organs, plays an important role in modulating DNA damage repair under stress response and pathological conditions. Folliculogenesis, a process that ovarian follicle develops into maturation, is closely associated with the interaction between somatic granulosa cell and oocyte. However, the regulatory role of BRE in follicular development remains undetermined. In this context, we found that BRE is normally expressed in the oocytes and granulosa cells from the primordial follicle stage...
March 23, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28331802/molecular-epidemiology-and-pathology-of-spirorchiid-infection-in-green-sea-turtles-chelonia-mydas
#19
Phoebe A Chapman, Helen Owen, Mark Flint, Ricardo J Soares Magalhães, Rebecca J Traub, Thomas H Cribb, Myat T Kyaw-Tanner, Paul C Mills
Spirorchiid blood fluke infections affect endangered turtle populations globally, and are reported as a common cause of mortality in Queensland green sea turtles. Both the flukes and their ova are pathogenic and can contribute to the stranding or death of their host. Of particular interest are ova-associated brain lesions, which have been associated with host neurological deficits. Accurate estimations of disease frequency and the relative effect of infection relating to different spirorchiid species are made difficult by challenges in morphological identification of adults of some genera, and a lack of species-level identifying features for ova...
April 2017: International Journal for Parasitology. Parasites and Wildlife
https://www.readbyqxmd.com/read/28323334/the-emerging-role-of-homologous-recombination-repair-and-parp-inhibitors-in-genitourinary-malignancies
#20
REVIEW
Kalen J Rimar, Phuoc T Tran, Richard S Matulewicz, Maha Hussain, Joshua J Meeks
As cells age and are exposed to genotoxic stress, preservation of the genomic code requires multiple DNA repair pathways to remove single-strand or double-strand breaks. Loss of function somatic genomic aberrations or germline deficiency in genes involved in DNA repair can result in acute cell death or, after a latency period, cellular transformation. Therapeutic exploitation of DNA repair by inhibition of poly (adenosine diphosphate [ADP]) ribose polymerases (PARP), a family of enzymes involved in the repair of single-strand and in some cases double-strand breaks, has become a novel cancer treatment...
March 21, 2017: Cancer
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