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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
#1
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 22, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28340172/repositioning-disulfiram-as-a-radiosensitizer-against-atypical-teratoid-rhabdoid-tumor
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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
https://www.readbyqxmd.com/read/28299324/micrornas-and-cardiovascular-disease-in-diabetes-mellitus
#8
REVIEW
Yue Ding, Xue Sun, Peng-Fei Shan
Cardiovascular disease (CVD) is the major macrovascular complication of diabetes mellitus. Recently, although CVD morbidity and mortality have decreased as a result of comprehensive control of CVD risk factors, CVD remains the leading cause of death of patients with diabetes in many countries, indicating the potential underlying pathophysiological mechanisms. MicroRNAs are a class of noncoding, single-stranded RNA molecules that are involved in β-cell function, insulin secretion, insulin resistance, skeletal muscle, and adipose tissue and which play an important role in glucose homeostasis and the pathogenesis of diabetic complications...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28299201/lyssaviruses-and-rabies-current-conundrums-concerns-contradictions-and-controversies
#9
REVIEW
Charles Rupprecht, Ivan Kuzmin, Francois Meslin
Lyssaviruses are bullet-shaped, single-stranded, negative-sense RNA viruses and the causative agents of the ancient zoonosis rabies. Africa is the likely home to the ancestors of taxa residing within the Genus Lyssavirus, Family Rhabdoviridae. Diverse lyssaviruses are envisioned as co-evolving with bats, as the ultimate reservoirs, over seemingly millions of years. In terms of relative distribution, overt abundance, and resulting progeny, rabies virus is the most successful lyssavirus species today, but for unknown reasons...
2017: F1000Research
https://www.readbyqxmd.com/read/28296564/azd1775-induces-toxicity-through-double-stranded-dna-breaks-independently-of-chemotherapeutic-agents-in-p53-mutated-colorectal-cancer-cells
#10
Peter John Webster, Anna Tiffany Littlejohns, Hannah Jane Gaunt, K Raj Prasad, David John Beech, Dermot Anthony Burke
AZD1775 is a small molecule WEE1 inhibitor used in combination with DNA-damaging agents to cause premature mitosis and cell death in p53-mutated cancer cells. Here we sought to determine the mechanism of action of AZD1775 in combination with chemotherapeutic agents in light of recent findings that AZD1775 can cause double-stranded DNA (DS-DNA) breaks. AZD1775 significantly improved the cytotoxicity of 5-FU in a p53-mutated colorectal cancer cell line (HT29 cells), decreasing the IC50 from 9.3 μM to 3.5 μM...
March 15, 2017: Cell Cycle
https://www.readbyqxmd.com/read/28285495/pharmacological-interventions-for-acute-hepatitis-c-infection-an-attempted-network-meta-analysis
#11
REVIEW
Maria Kalafateli, Elena Buzzetti, Douglas Thorburn, Brian R Davidson, Emmanuel Tsochatzis, Kurinchi Selvan Gurusamy
BACKGROUND: Hepatitis C virus (HCV) is a single-stranded RNA (ribonucleic acid) virus that has the potential to cause inflammation of the liver. The traditional definition of acute HCV infection is the first six months following infection with the virus. Another commonly used definition of acute HCV infection is the absence of HCV antibody and subsequent seroconversion (presence of HCV antibody in a person who was previously negative for HCV antibody). Approximately 40% to 95% of people with acute HCV infection develop chronic HCV infection, that is, have persistent HCV RNA in their blood...
March 13, 2017: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/28284865/total-synthesis-and-antileukemic-evaluations-of-the-phenazine-5-10-dioxide-natural-products-iodinin-myxin-and-their-derivatives
#12
Elvar Örn Viktorsson, Bendik Melling Grøthe, Reidun Aesoy, Misbah Sabir, Simen Snellingen, Anthony Prandina, Ove Alexander Høgmoen Åstrand, Tore Bonge-Hansen, Stein Ove Døskeland, Lars Herfindal, Pål Rongved
A new efficient total synthesis of the phenazine 5,10-dioxide natural products iodinin and myxin and new compounds derived from them was achieved in few steps, a key-step being 1,6-dihydroxyphenazine di-N-oxidation. Analogues prepared from iodinin, including myxin and 2-ethoxy-2-oxoethoxy derivatives, had fully retained cytotoxic effect against human cancer cells (MOLM-13 leukemia) at atmospheric and low oxygen level. Moreover, iodinin was for the first time shown to be hypoxia selective. The structure-activity relationship for leukemia cell death induction revealed that the level of N-oxide functionality was essential for cytotoxicity...
February 28, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28280600/structural-basis-of-a-novel-pd-l1-nanobody-for-immune-checkpoint-blockade
#13
Fei Zhang, Hudie Wei, Xiaoxiao Wang, Yu Bai, Pilin Wang, Jiawei Wu, Xiaoyong Jiang, Yugang Wang, Haiyan Cai, Ting Xu, Aiwu Zhou
The use of antibodies to target immune checkpoints, particularly PD-1/PD-L1, has made a profound impact in the field of cancer immunotherapy. Here, we identified KN035, an anti-PD-L1 nanobody that can strongly induce T-cell responses and inhibit tumor growth. The crystal structures of KN035 complexed with PD-L1 and free PD-L1, solved here at 1.7 and 2.7 Å resolution, respectively, show that KN035 competes with PD-1 (programmed death protein 1) for the same flat surface on PD-L1, mainly through a single surface loop of 21 amino acids...
2017: Cell Discovery
https://www.readbyqxmd.com/read/28273084/vitamin-d-deficiency-predicts-infections-in-young-north-indian-children-a-secondary-data-analysis
#14
Ranadip Chowdhury, Sunita Taneja, Nita Bhandari, Bireshwar Sinha, Ravi Prakash Upadhyay, Maharaj Kishan Bhan, Tor A Strand
BACKGROUND: Recent studies have demonstrated a relationship between poor vitamin D status and respiratory infections and diarrhea among young children. Acute lower respiratory infections (ALRI) and diarrhea are among the two most important causes of death in under-5 children. In this paper, we examined the extent to which vitamin-D deficiency (<10 ng/ml) predicts ALRI, clinical pneumonia and diarrhea among 6 to 30 months old children. METHODS: We used data from a randomized controlled trial (RCT) of daily folic acid and/or vitamin B12 supplementation for six months in 6 to 30 months old children conducted in Delhi, India...
2017: PloS One
https://www.readbyqxmd.com/read/28270495/the-checkpoint-kinase-1-inhibitor-prexasertib-induces-regression-of-preclinical-models-of-human-neuroblastoma
#15
Caitlin D Lowery, Alle B VanWye, Michele Dowless, Wayne Blosser, Beverly L Falcon, Julie Stewart, Jennifer Stephens, Richard P Beckmann, Aimee Bence Lin, Louis F Stancato
PURPOSE: Checkpoint kinase 1 (CHK1) is a key regulator of the DNA damage response and a mediator of replication stress through modulation of replication fork licensing and activation of S and G2/M cell cycle checkpoints. We evaluated prexasertib (LY2606368), a small molecule CHK1 inhibitor currently in clinical testing, in multiple preclinical models of pediatric cancer. Following an initial assessment of prexasertib activity, this study focused on preclinical models of neuroblastoma...
March 7, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28270450/ssb1-and-ssb2-cooperate-to-regulate-mouse-hematopoietic-stem-and-progenitor-cells-by-resolving-replicative-stress
#16
Wei Shi, Therese Vu, Didier Boucher, Anna Biernacka, Jules Nde, Raj K Pandita, Jasmin Straube, Glen M Boyle, Fares Al-Ejeh, Purba Nag, Jessie Jeffery, Janelle L Harris, Amanda L Bain, Marta Grzelak, Magdalena Skrzypczak, Abhishek Mitra, Norbert Dojer, Nicola Crosetto, Nicole Cloonan, Olivier J Becherel, John Finnie, Jeffrey R Skaar, Carl R Walkley, Tej K Pandita, Maga Rowicka, Krzysztof Ginalski, Steven W Lane, Kum Kum Khanna
Hematopoietic stem and progenitor cells (HSPCs) are vulnerable to endogenous damage and defects in DNA repair can limit their function. The two single-stranded DNA binding proteins SSB1 and SSB2 are crucial regulators of the DNA damage response; however their overlapping roles during normal physiology are incompletely understood. We generated mice where both Ssb1 and Ssb2 were constitutively or conditionally deleted. Constitutive Ssb1/Ssb2 double knockout (DKO) caused early embryonic lethality, while conditional Ssb1/Ssb2 double knockout (cDKO) in adult mice resulted in acute lethality due to bone marrow failure and intestinal atrophy featuring stem and progenitor cell depletion, a phenotype unexpected from the previously reported single knockout models of Ssb1 or Ssb2 Mechanistically, cDKO HSPCs showed altered replication fork dynamics, massive accumulation of DNA damage, genome-wide double strand breaks (DSBs) enriched at Ssb binding regions and CpG islands, together with the accumulation of R-loops and cytosolic ssDNA...
March 7, 2017: Blood
https://www.readbyqxmd.com/read/28268249/the-turn-of-the-gradient-educational-differences-in-breast-cancer-mortality-in-18-european-populations-during-the-2000s
#17
S Gadeyne, G Menvielle, I Kulhanova, M Bopp, P Deboosere, T A Eikemo, R Hoffmann, K Kovács, M Leinsalu, P Martikainen, E Regidor, J Rychtarikova, T Spadea, B H Strand, C Trewin, B Wojtyniak, J P Mackenbach
This study aims to investigate the association between educational level and breast cancer mortality in Europe in the 2000s. Unlike most other causes of death, breast cancer mortality tends to be positively related to education, with higher educated women showing higher mortality rates. Research has however shown that the association is changing from being positive over non-existent to negative in some countries. To investigate these patterns, data from national mortality registers and censuses were collected and harmonized for 18 European populations...
March 7, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28265620/glycine-functionalized-copper-ii-hydroxide-nanoparticles-with-high-intrinsic-superoxide-dismutase-activity
#18
Karsten Korschelt, Ruben Ragg, Carmen S Metzger, Martin Kluenker, Michael Oster, Bastian Barton, Martin Panthöfer, Dennis Strand, Ute Kolb, Mihail Mondeshki, Susanne Strand, Jürgen Brieger, M Nawaz Tahir, Wolfgang Tremel
Superoxide dismutases (SOD) are a group of enzymes that catalyze the dismutation of superoxide (O2(-)) radicals into molecular oxygen (O2) and H2O2 as a first line of defense against oxidative stress. Here, we show that glycine-functionalized copper(ii) hydroxide nanoparticles (Gly-Cu(OH)2 NPs) are functional SOD mimics, whereas bulk Cu(OH)2 is insoluble in water and catalytically inactive. In contrast, Gly-Cu(OH)2 NPs form water-dispersible mesocrystals with a SOD-like activity that is larger than that of their natural CuZn enzyme counterpart...
March 7, 2017: Nanoscale
https://www.readbyqxmd.com/read/28258182/annealing-of-complementary-dna-sequences-during-double-strand-break-repair-in-drosophila-is-mediated-by-the-ortholog-of-smarcal1
#19
Julie Korda Holsclaw, Jeff Sekelsky
DNA double-strand breaks (DSBs) pose a serious threat to genomic integrity. If unrepaired, they can lead to chromosome fragmentation and cell death. If repaired incorrectly, they can cause mutations and chromosome rearrangements. DSBs are repaired using end-joining or homology-directed repair strategies, with the predominant form of homology-directed repair being synthesis-dependent strand annealing (SDSA). SDSA is the first defense against genomic rearrangements and information loss during DSB repair, making it a vital component of cell health and an attractive target for chemotherapeutic development...
March 3, 2017: Genetics
https://www.readbyqxmd.com/read/28254358/specific-killing-of-dna-damage-response-deficient-cells-with-inhibitors-of-poly-adp-ribose-glycohydrolase
#20
Polly Gravells, Emma Grant, Kate M Smith, Dominic I James, Helen E Bryant
Poly(ADP-ribosylation) of proteins following DNA damage is well studied and the use of poly(ADP-ribose) polymerase (PARP) inhibitors as therapeutic agents is an exciting prospect for the treatment of many cancers. Poly(ADP-ribose) glycohydrolase (PARG) has endo- and exoglycosidase activities which can cleave glycosidic bonds, rapidly reversing the action of PARP enzymes. Like addition of poly(ADP-ribose) (PAR) by PARP, removal of PAR by PARG is also thought to be required for repair of DNA strand breaks and for continued replication at perturbed forks...
February 17, 2017: DNA Repair
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