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https://www.readbyqxmd.com/read/28926421/a-novel-hydroxyphenyl-hydrazone-derivate-ycl0426-inhibits-cancer-cell-proliferation-through-sequestering-iron
#1
Feifei Li, Long Long, Junhai Xiao, Chen Wang, Wei Li, Song Li, Changqi Zhao, Lili Wang
Cancer cells have an increased requirement for iron than normal cells, and iron chelators are under active consideration for cancer treatment. The metal-sequestering potential and antiproliferative mechanisms of a novel hydroxyphenyl hydrazone derivate YCL0426 were investigated here. Antiproliferative activity of YCL0426 was detected by MTT assay. The iron-sequestering potential was evaluated by ferrozine-Fe(II) sequestering assay and Fe(II) titration assay. Cell-cycle-arresting profile was checked by flow cytometry and the DNA synthesis status was evaluated by BrdU incorporation assay...
September 18, 2017: Anti-cancer Drugs
https://www.readbyqxmd.com/read/28923112/cobalt-nanoparticles-induce-lung-injury-dna-damage-and-mutations-in-mice
#2
Rong Wan, Yiqun Mo, Zhenyu Zhang, Mizu Jiang, Shichuan Tang, Qunwei Zhang
BACKGROUND: We and other groups have demonstrated that exposure to cobalt nanoparticles (Nano-Co) caused oxidative stress and inflammation, which have been shown to be strongly associated with genotoxic and carcinogenic effects. However, few studies have reported Nano-Co-induced genotoxic effects in vivo. Here, we propose that Nano-Co may have high genotoxic effects due to their small size and high surface area, which have high capacity for causing oxidative stress and inflammation. METHODS: gpt delta transgenic mice were used as our in vivo study model...
September 18, 2017: Particle and Fibre Toxicology
https://www.readbyqxmd.com/read/28919752/zinc-oxide-nanoparticles-induce-apoptosis-and-autophagy-in-human-ovarian-cancer-cells
#3
Ding-Ping Bai, Xi-Feng Zhang, Guo-Liang Zhang, Yi-Fan Huang, Sangiliyandi Gurunathan
BACKGROUND: Zinc oxide nanoparticles (ZnO NPs) are frequently used in industrial products such as paint, surface coating, and cosmetics, and recently, they have been explored in biologic and biomedical applications. Therefore, this study was undertaken to investigate the effect of ZnO NPs on cytotoxicity, apoptosis, and autophagy in human ovarian cancer cells (SKOV3). METHODS: ZnO NPs with a crystalline size of 20 nm were characterized with various analytical techniques, including ultraviolet-visible spectroscopy, X-ray diffraction, transmission electron microscopy, Fourier transform infrared spectroscopy, and atomic force microscopy...
2017: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/28915668/nsc30049-inhibits-chk1-pathway-in-5-fu-resistant-crc-bulk-and-stem-cell-populations
#4
Satya Narayan, Aruna S Jaiswal, Ritika Sharma, Akbar Nawab, Lizette Vila Duckworth, Brian K Law, Maria Zajac-Kaye, Thomas J George, Jay Sharma, Arun K Sharma, Robert A Hromas
The 5-fluorouracil (5-FU) treatment induces DNA damage and stalling of DNA replication forks. These stalled replication forks then collapse to form one sided double-strand breaks, leading to apoptosis. However, colorectal cancer (CRC) stem cells rapidly repair the stalled/collapsed replication forks and overcome treatment effects. Recent evidence suggests a critical role of checkpoint kinase 1 (Chk1) in preventing the replicative stress. Therefore, Chk1 kinase has been a target for developing mono or combination therapeutic agents...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28915641/reevaluation-of-atr-signaling-in-primary-resting-chronic-lymphocytic-leukemia-cells-evidence-for-pro-survival-or-pro-apoptotic-function
#5
Maxime Beyaert, Eliza Starczewska, Ana Cristina González Pérez, Nicolas Vanlangendonck, Pascale Saussoy, Gaëlle Tilman, Anne De Leener, Marie-Christiane Vekemans, Eric Van Den Neste, Françoise Bontemps
ATM, primarily activated by DNA double-strand breaks, and ATR, activated by single-stranded DNA, are master regulators of the cellular response to DNA damage. In primary chronic lymphocytic leukemia (CLL) cells, ATR signaling is considered to be switched off due to ATR downregulation. Here, we hypothesized that ATR, though expressed at low protein level, could play a role in primary resting CLL cells after genotoxic stress. By investigating the response of CLL cells to UV-C irradiation, a prototypical activator of ATR, we could detect phosphorylation of ATR at Thr-1989, a marker for ATR activation, and also observed that selective ATR inhibitors markedly decreased UV-C-induced phosphorylation of ATR targets, including H2AX and p53...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28914798/genome-instability-and-%C3%AE-h2ax
#6
REVIEW
Anastasios Georgoulis, Constantinos E Vorgias, George P Chrousos, Emmy P Rogakou
γH2AX has emerged in the last 20 years as a central player in the DDR (DNA damage response), with specificity for DSBs (double-strand breaks). Upon the generation of DSBs, γ-phosphorylation extends along megabase-long domains in chromatin, both sides of the damage. The significance of this mechanism is of great importance; it depicts a biological amplification mechanism where one DSB induces the γ-phosphorylation of thousands of H2AX molecules along megabaselong domains of chromatin, that are adjusted to the sites of DSBs...
September 15, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28902347/measuring-the-response-of-human-head-and-neck-squamous-cell-carcinoma-to-irradiation-in-a-microfluidic-model-allowing-customized-therapy
#7
Ramsah Cheah, Rishi Srivastava, Nicholas D Stafford, Andrew W Beavis, Victoria Green, John Greenman
Radiotherapy is the standard treatment for head and neck squamous cell carcinoma (HNSCC), however, radioresistance remains a major clinical problem despite significant improvements in treatment protocols. Therapeutic outcome could potentially be improved if a patient's tumour response to irradiation could be predicted ex vivo before clinical application. The present study employed a bespoke microfluidic device to maintain HNSCC tissue whilst subjecting it to external beam irradiation and measured the responses using a panel of cell death and proliferation markers...
October 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28900036/polo-like-kinase-1-plk1-overexpression-enhances-ionizing-radiation-induced-cancer-formation-in-mice
#8
Zhiguo Li, Jinghui Liu, Jie Li, Yifan Kong, George Sandusky, Xi Rao, Yunlong Liu, Jun Wan, Xiaoqi Liu
Polo-like kinase 1 (Plk1), a serine/threonine protein kinase normally expressed in mitosis, is frequently upregulated in multiple types of human tumors regardless of the cell cycle stage. However, the causal relationship between Plk1 upregulation and tumorigenesis is incompletely investigated. To this end, using a conditional expression system, here we generated Plk1 transgenic mouse lines to examine Plk1 role in tumorigenesis. Plk1 overexpression in mouse embryonic fibroblasts prepared from the transgenic mice led to aberrant mitosis followed by aneuploidy and apoptosis...
September 12, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28898696/a-dual-role-of-caspase-8-in-triggering-and-sensing-proliferation-associated-dna-damage-a-key-determinant-of-liver-cancer-development
#9
Yannick Boege, Mohsen Malehmir, Marc E Healy, Kira Bettermann, Anna Lorentzen, Mihael Vucur, Akshay K Ahuja, Friederike Böhm, Joachim C Mertens, Yutaka Shimizu, Lukas Frick, Caroline Remouchamps, Karun Mutreja, Thilo Kähne, Devakumar Sundaravinayagam, Monika J Wolf, Hubert Rehrauer, Christiane Koppe, Tobias Speicher, Susagna Padrissa-Altés, Renaud Maire, Jörn M Schattenberg, Ju-Seong Jeong, Lei Liu, Stefan Zwirner, Regina Boger, Norbert Hüser, Roger J Davis, Beat Müllhaupt, Holger Moch, Henning Schulze-Bergkamen, Pierre-Alain Clavien, Sabine Werner, Lubor Borsig, Sanjiv A Luther, Philipp J Jost, Ricardo Weinlich, Kristian Unger, Axel Behrens, Laura Hillert, Christopher Dillon, Michela Di Virgilio, David Wallach, Emmanuel Dejardin, Lars Zender, Michael Naumann, Henning Walczak, Douglas R Green, Massimo Lopes, Inna Lavrik, Tom Luedde, Mathias Heikenwalder, Achim Weber
Concomitant hepatocyte apoptosis and regeneration is a hallmark of chronic liver diseases (CLDs) predisposing to hepatocellular carcinoma (HCC). Here, we mechanistically link caspase-8-dependent apoptosis to HCC development via proliferation- and replication-associated DNA damage. Proliferation-associated replication stress, DNA damage, and genetic instability are detectable in CLDs before any neoplastic changes occur. Accumulated levels of hepatocyte apoptosis determine and predict subsequent hepatocarcinogenesis...
September 11, 2017: Cancer Cell
https://www.readbyqxmd.com/read/28891354/brca2-protects-mammalian-cells-from-heat-shock
#10
Yosuke Nakagawa, Atsuhisa Kajihara, Akihisa Takahashi, Akiho S Murata, Masaya Matsubayashi, Soichiro S Ito, Ichiro Ota, Takahiko Nakagawa, Masatoshi Hasegawa, Tadaaki Kirita, Takeo Ohnishi, Eiichiro Mori
PURPOSE: Heat shock induces DNA double-strand breaks (DSBs) in mammalian cells. Mammalian cells are capable of repairing DSBs by utilising the homologous recombination (HR) pathway. Breast cancer susceptibility gene 2 (BRCA2) is known to regulate the HR pathway. Here, we investigate the role of BRCA2 in repairing DNA damage induced by heat shock. MATERIALS AND METHODS: Chinese hamster lung fibroblast cell lines and human tongue squamous cell carcinoma SAS cells were used...
September 10, 2017: International Journal of Hyperthermia
https://www.readbyqxmd.com/read/28889235/genotoxic-potential-of-diesel-exhaust-particles-from-the-combustion-of-first-and-second-generation-biodiesel-fuels-the-fuelhealth-project
#11
Magdalena Kowalska, Aneta Wegierek-Ciuk, Kamil Brzoska, Maria Wojewodzka, Sylwia Meczynska-Wielgosz, Joanna Gromadzka-Ostrowska, Remigiusz Mruk, Johan Øvrevik, Marcin Kruszewski, Anna Lankoff
Epidemiological data indicate that exposure to diesel exhaust particles (DEPs) from traffic emissions is associated with higher risk of morbidity and mortality related to cardiovascular and pulmonary diseases, accelerated progression of atherosclerotic plaques, and possible lung cancer. While the impact of DEPs from combustion of fossil diesel fuel on human health has been extensively studied, current knowledge of DEPs from combustion of biofuels provides limited and inconsistent information about its mutagenicity and genotoxicity, as well as possible adverse health risks...
September 9, 2017: Environmental Science and Pollution Research International
https://www.readbyqxmd.com/read/28887524/selective-uptake-of-epidermal-growth-factor-conjugated-gold-nanoparticle-egf-gnp-facilitates-non-thermal-plasma-ntp-mediated-cell-death
#12
Wanil Kim, Kyung-Yoon Na, Kyung-Ha Lee, Hyun Wook Lee, Jae Koo Lee, Kyong-Tai Kim
Non-thermal atmospheric pressure plasma (NTP) has been shown to induce cell death in various mammalian cancer cells. Accumulated evidence also shows that NTP could be clinically used in cancer therapy. However, the current NTP-based applications lack target specificity. Here, a novel method in NTP-mediated cancer therapeutics was described with enhanced target specificity by treating EGF (epidermal growth factor)-conjugated GNP (gold nanoparticle). The treatment with EGF-conjugated GNP complex, followed by NTP irradiation showed selective apoptosis of cells having receptor-mediated endocytosis...
September 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28887153/the-eya-phosphatase-its-unique-role-in-cancer
#13
REVIEW
Hengbo Zhou, Lingdi Zhang, Rebecca L Vartuli, Heide L Ford, Rui Zhao
The Eya proteins were originally identified as essential transcriptional co-activators of the Six family of homeoproteins. Subsequently, the highly conserved C-terminal domains of the Eya proteins were discovered to act as a Mg(2+)-dependent Tyr phosphatases, making Eyas the first transcriptional activators to harbor intrinsic phosphatase activity. Only two direct targets of the Eya Tyr phosphatase have been identified: H2AX, whose dephosphorylation directs cells to the DNA repair instead of the apoptotic pathway upon DNA damage, and ERβ, whose dephosphorylation inhibits its anti-tumor transcriptional activity...
September 5, 2017: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/28886471/dna-damage-by-2-3-7-8-tetrachlorodibenzo-p-dioxin-induced-p53-mediated-apoptosis-through-activation-of-cytochrome-p450-aryl-hydrocarbon-receptor
#14
Durgesh Nandini Das, Prashanta Kumar Panda, Niharika Sinha, Subhadip Mukhopadhyay, Prajna Parimita Naik, Sujit K Bhutia
2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD; polycyclic aromatic hydrocarbon) is a persistent and ubiquitous environmental contaminant that causes a wide variety of deleterious effects. In this study, the DNA damage and apoptotic activity induced by TCDD was examined using in silico and in vitro approaches. In silico study showed that conformational changes and energies involved in the binding of TCDD to cytochrome P450 1B1 (CYP1B1) were crucial for its target proteins. Moreover, activated TCDD had high affinity to bind with aryl hydrocarbon receptor (AhR), with a binding energy of -564...
August 18, 2017: Environmental Toxicology and Pharmacology
https://www.readbyqxmd.com/read/28882572/identification-of-essential-transcription-factors-for-adequate-dna-damage-response-after-benzo-a-pyrene-and-aflatoxin-b1-exposure-by-combining-transcriptomics-with-functional-genomics
#15
Evelyn Smit, Terezinha Souza, Danyel G J Jennen, Jos C S Kleinjans, Twan van den Beucken
DNA damage mediates widespread changes in transcription through activation or repression of transcription factors (TFs). However, the consequences of regulating specific TFs for the outcome of the DNA repair process remain incompletely understood. Here, we combined transcriptomics and TF binding prediction with functional genomics to identify TFs essential for adequate DNA repair in HepG2 liver cells after a non-cytotoxic dose of carcinogens benzo(a)pyrene (BaP) (2μM) and aflatoxin B1 (AFB1) (5μM). BaP and AFB1 induced a largely common transcriptional response, mediated by similar TFs...
September 4, 2017: Toxicology
https://www.readbyqxmd.com/read/28882183/mir-22-suppresses-tumorigenesis-and-improves-radiosensitivity-of-breast-cancer-cells-by-targeting-sirt1
#16
Xia Zhang, Yuehua Li, Dan Wang, Xiaoer Wei
BACKGROUND: miR-22 has been shown to be frequently downregulated and act as a tumor suppressor in multiple cancers including breast cancers. However, the role of miR-22 in regulating the radioresistance of breast cancer cells, as well as its underlying mechanism is still not well understood. METHODS: The expressions of miR-22 and sirt1 at mRNA and protein levels were examined by qRT-PCR and Western Blot. The effects of miR-22 overexpression and sirt1 knockdown on cell viability, apoptosis, radiosensitivity, γ-H2AX foci formation were evaluated by CCK-8 assay, flow cytometry, colony formation assay, and γ-H2AX foci formation assay, respectively...
September 7, 2017: Biological Research
https://www.readbyqxmd.com/read/28881656/brd4-facilitates-dna-damage-response-and-represses-cbx5-heterochromatin-protein-1-hp1
#17
Georgios Pongas, Marianne K Kim, Dong J Min, Carrie D House, Elizabeth Jordan, Natasha Caplen, Sirisha Chakka, Joyce Ohiri, Michael J Kruhlak, Christina M Annunziata
Ovarian cancer (OC) is a heterogeneous disease characterized by defective DNA repair. Very few targets are universally expressed in the high grade serous (HGS) subtype. We previously identified that CHK1 was overexpressed in most of HGSOC. Here, we sought to understand the DNA damage response (DDR) to CHK1 inhibition and increase the anti-tumor activity of this pathway. We found BRD4 suppression either by siRNA or BRD4 inhibitor JQ1 enhanced the cytotoxicity of CHK1 inhibition. Interestingly, BRD4 was amplified and/or upregulated in a subset of HGSOC with statistical correlation to overall survival...
August 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/28877067/diagnostic-and-prognostic-biomarkers-of-adrenal-cortical-carcinoma
#18
Ozgur Mete, Hasan Gucer, Mehmet Kefeli, Sylvia L Asa
The diagnosis of low-grade adrenal cortical carcinoma (ACC) confined to the adrenal gland can be challenging. Although there are diagnostic and prognostic molecular tests for ACC, they remain largely unutilized. We examined the diagnostic and prognostic value of altered reticulin framework and the immunoprofile of biomarkers including IGF-2, proteins involved in cell proliferation and mitotic spindle regulation (Ki67, p53, BUB1B, HURP, NEK2), DNA damage repair (PBK, γ-H2AX), telomere regulation (DAX, ATRX), wnt-signaling pathway (beta-catenin) and PI3K signaling pathway (PTEN, phospho-mTOR) in a tissue microarray of 50 adenomas and 43 carcinomas that were characterized for angioinvasion as defined by strict criteria, Weiss score, and mitotic rate-based tumor grade...
September 4, 2017: American Journal of Surgical Pathology
https://www.readbyqxmd.com/read/28873435/tgf-%C3%AE-signaling-is-an-effective-target-to-impair-survival-and-induce-apoptosis-of-human-cholangiocarcinoma-cells-a-study-on-human-primary-cell-cultures
#19
Anna Maria Lustri, Sabina Di Matteo, Alice Fraveto, Daniele Costantini, Alfredo Cantafora, Chiara Napoletano, Maria Consiglia Bragazzi, Felice Giuliante, Agostino M De Rose, Pasquale B Berloco, Gian Luca Grazi, Guido Carpino, Domenico Alvaro
Cholangiocarcinoma (CCA) and its subtypes (mucin- and mixed-CCA) arise from the neoplastic transformation of cholangiocytes, the epithelial cells lining the biliary tree. CCA has a high mortality rate owing to its aggressiveness, late diagnosis and high resistance to radiotherapy and chemotherapeutics. We have demonstrated that CCA is enriched for cancer stem cells which express epithelial to mesenchymal transition (EMT) traits, with these features being associated with aggressiveness and drug resistance. TGF-β signaling is upregulated in CCA and involved in EMT...
2017: PloS One
https://www.readbyqxmd.com/read/28866013/contrasting-cellular-damage-after-blue-iris-and-femto-lasik-in-cat-cornea
#20
Kaitlin T Wozniak, Noah Elkins, Daniel R Brooks, Daniel E Savage, Scott MacRae, Jonathan D Ellis, Wayne H Knox, Krystel R Huxlin
Blue-intra-tissue refractive index shaping (Blue-IRIS) is a new approach to laser refractive correction of optical aberrations in the eye, which alters the refractive index of the cornea rather than changing its shape. Before it can be implemented in humans, it is critical to establish whether and to what extent, Blue-IRIS damages the cornea. Here, we contrasted the impact of -1.5 D cylinder refractive corrections inscribed using either Blue-IRIS or femtosecond laser in-situ keratomileusis (femto-LASIK) on corneal cell viability...
August 31, 2017: Experimental Eye Research
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