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https://www.readbyqxmd.com/read/29352998/two-weeks-of-variable-stress-increases-gamma-h2ax-levels-in-the-mouse-bed-nucleus-of-the-stria-terminalis
#1
Brendan D Hare, Tina M Thornton, Mercedes Rincon, Borivoj Golijanin, S Bradley King, Diane M Jaworski, William A Falls
Recent reports demonstrate that DNA damage is induced, and rapidly repaired, in circuits activated by experience. Moreover, stress hormones are known to slow DNA repair, suggesting that prolonged stress may result in persistent DNA damage. Prolonged stress is known to negatively impact physical and mental health; however, DNA damage as a factor in stress pathology has only begun to be explored. Histone H2A-X phosphorylated at serine 139 (γH2AX) is a marker of DNA double strand breaks (DSB), a type of damage that may lead to cell death if unrepaired...
January 15, 2018: Neuroscience
https://www.readbyqxmd.com/read/29346578/effect-of-daidzein-and-equol-on-dna-replication-in-mcf-7-cells
#2
Mako Tsuji, Tomoki Tanaka, Ryosuke Nagashima, Yuka Sagisaka, Yuko Tousen, Yoriko Nishide, Yoshiko Ishimi, Yukio Ishimi
It has been reported that daidzein and equol stimulate DNA replication and proliferation of MCF-7 cells. However, their molecular mechanisms of action are still unclear. We examined the effects of daidzein and equol on DNA replication of MCF-7 cells, focusing on MCM2-7 proteins, which function as the replicative helicase. In the presence of either 1 μM of daidzein or equol, the number of cells in S-phase, which was determined by detecting bromodeoxyuridine incorporated into replicated DNA, almost doubled...
January 15, 2018: Journal of Biochemistry
https://www.readbyqxmd.com/read/29340049/pharmacological-treatment-with-inhibitors-of-nuclear-export-enhances-the-antitumor-activity-of-docetaxel-in-human-prostate-cancer
#3
Giovanni Luca Gravina, Andrea Mancini, Alessandro Colapietro, Francesco Marampon, Roberta Sferra, Simona Pompili, Leda Assunta Biordi, Roberto Iorio, Vincenzo Flati, Christian Argueta, Yosef Landesman, Michael Kauffman, Sharon Shacham, Claudio Festuccia
Background and aims: Docetaxel (DTX) modestly increases patient survival of metastatic castration-resistant prostate cancer (mCRPC) due to insurgence of pharmacological resistance. Deregulation of Chromosome Region Maintenance (CRM-1)/ exportin-1 (XPO-1)-mediated nuclear export may play a crucial role in this phenomenon. Material and methods: Here, we evaluated the effects of two Selective Inhibitor of Nuclear Export (SINE) compounds, selinexor (KPT-330) and KPT-251, in association with DTX by using 22rv1, PC3 and DU145 cell lines with their...
December 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29340025/the-novel-atm-inhibitor-az31-enhances-antitumor-activity-in-patient-derived-xenografts-that-are-resistant-to-irinotecan-monotherapy
#4
Justin Greene, Anna Nguyen, Stacey M Bagby, Gemma N Jones, W M Tai, Kevin S Quackenbush, Anna Schreiber, Wells A Messersmith, Kalpana M Devaraj, Patrick Blatchford, S Gail Eckhardt, Elaine B Cadogan, Gareth D Hughes, Aaron Smith, Todd M Pitts, John J Arcaroli
Irinotecan, a standard of care therapy for CRC, elicits cytotoxic effects by generating double strand breaks resulting in DNA damage. The activation of the ATM pathway plays a fundamental role in regulating the cellular response and repair to DNA damage. The objective of this preclinical study was to determine whether ATM inhibition would enhance sensitivity to irinotecan treatment. Treatment effects of AZ31, irinotecan or AZ31 + irinotecan were investigated in CRC cell lines and CRC patient derived xenografts...
December 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29338178/dna-damage-and-apoptosis-induction-in-cancer-cells-by-chemically-engineered-thiolated-riboflavin-gold-nanoassembly
#5
Abhishek Sau, Sulagna Sanyal, Kallol Bera, Sabyasachi Sen, Amrit Krishna Mitra, Uttam Pal, Prabal Kumar Chakraborty, Sayantan Ganguly, Biswarup Satpati, Chandrima Das, Samita Basu
Herein we have engineered a smart nuclear targeting thiol-modified riboflavin-gold nano assembly, RfS@AuNPs, which accumulates selectively in nucleus without any nuclear-targeting peptides (NLS/RGD) and shows photophysically in vitro DNA intercalation. A theoretical model using Molecular Dynamics has been developed to probe the mechanism of formation and stability as well as dynamics of the RfS@AuNPs in aqueous solution and within DNA microenvironment. The RfS@AuNPs facilitate the binucleated cell formation that is reflected in the significant increase of DNA damage marker, γ-H2AX as well as the arrest of most of the HeLa cells at pre-G1 phase indicating cell death...
January 16, 2018: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/29331678/microrna-320-enhances-radiosensitivity-of-glioma-through-down-regulation-of-sirtuin-type-1-by-directly-targeting-forkhead-box-protein-m1
#6
Tengfei Li, Ji Ma, Xinwei Han, Yongxu Jia, Huifeng Yuan, Shaofeng Shui, Dong Guo
Glioma is the most common cancer in human brain system and seriously threatens human health. miRNA-320 has been demonstrated to be closely correlated with the development of glioma. However, its effect and molecular mechanism underlying radioresistance have not been fully elucidated in glioma. Here, RT-qPCR assay was used to assess the expressions of miR-320 and forkhead box protein M1 (FoxM1) mRNA in glioma tumor tissues and cells. The effects of miR-320, FoxM1 and sirtuin type 1 (Sirt1) on radiosensitivity in glioma cells were evaluated by clone formation assay, apoptosis assay, histone H2AX phosphorylation level (γH2AX) detection and caspase 3 activity analysis, respectively...
January 10, 2018: Translational Oncology
https://www.readbyqxmd.com/read/29324381/comparative-study-of-diesel-and-biodiesel-exhausts-on-lung-oxidative-stress-and-genotoxicity-in-rats
#7
Thierry Douki, Cécile Corbière, David Preterre, Perrine J Martin, Valérie Lecureur, Véronique André, Yann Landkocz, Ivannah Pottier, Veronika Keravec, Olivier Fardel, Silvestre Moreira-Rebelo, Didier Pottier, Cathy Vendeville, Frédéric Dionnet, Pierre Gosset, Sylvain Billet, Christelle Monteil, François Sichel
The contribution of diesel exhaust to atmospheric pollution is a major concern for public health, especially in terms of occurrence of lung cancers. The present study aimed at addressing the toxic effects of a repeated exposure to these emissions in an animal study performed under strictly controlled conditions. Rats were repeatedly exposed to the exhaust of diesel engine. Parameters such as the presence of a particle filter or the use of gasoil containing rapeseed methyl ester were investigated. Various biological parameters were monitored in the lungs to assess the toxic and genotoxic effects of the exposure...
January 8, 2018: Environmental Pollution
https://www.readbyqxmd.com/read/29321089/silencing-of-e3-ubiquitin-ligase-rnf8-enhances-ionizing-radiation-sensitivity-of-5-medulloblastoma-cells-by-promoting-the-deubiquitination-of-pcna
#8
Fei Li, Bin Liu, Xiaolan Zhou, Quan Xu
DNA damage response induced by ionizing radiation (IR) is an important event that involved in the sensitivity and efficiency of radiotherapy in human medulloblastoma. RNF8 is a E3 ubiquitin ligase and has key roles in the process of DNA damage and repair. Our study aimed to evaluate the effect of RNF8 in the DNA damage repair induced by IR exposure in medulloblastoma cells. We found that the levels of RNF8 were significantly up-regulated by γ-ray irradiation in a dose-dependent manner in medulloblastoma cells, and colocalized with γ-H2AX, a sensitive marker of DNA double strand break induced by γ-ray radiation...
January 10, 2018: Oncology Research
https://www.readbyqxmd.com/read/29317830/quercetin-suppresses-dna-double-strand-break-repair-and-enhances-the-radiosensitivity-of-human-ovarian-cancer-cells-via-p53-dependent-endoplasmic-reticulum-stress-pathway
#9
Cheng Gong, Zongyuan Yang, Lingyun Zhang, Yuehua Wang, Wei Gong, Yi Liu
Quercetin is proven to have anticancer effects for many cancers. However, the role of tumor suppressor p53 on quercetin's radiosensitization and regulation of endoplasmic reticulum (ER) stress response in this process remains obscure. Here, quercetin exposure resulted in ER stress, prolonged DNA repair, and the expression of p53 protein; phosphorylation on serine 15 and 20 increased in combination with X-irradiation. Quercetin pretreatment could potentiate radiation-induced cell death. The combination of irradiation and quercetin treatment aggravated DNA damages and caused typical apoptotic cell death; as well the expression of Bax and p21 elevated and the expression of Bcl-2 decreased...
2018: OncoTargets and Therapy
https://www.readbyqxmd.com/read/29317649/synchrotron-generated-microbeams-induce-hippocampal-transections-in-rats
#10
Erminia Fardone, Benoît Pouyatos, Elke Bräuer-Krisch, Stefan Bartzsch, Hervè Mathieu, Herwig Requardt, Domenico Bucci, Giacomo Barbone, Paola Coan, Giuseppe Battaglia, Geraldine Le Duc, Alberto Bravin, Pantaleo Romanelli
Synchrotron-generated microplanar beams (microbeams) provide the most stereo-selective irradiation modality known today. This novel irradiation modality has been shown to control seizures originating from eloquent cortex causing no neurological deficit in experimental animals. To test the hypothesis that application of microbeams in the hippocampus, the most common source of refractory seizures, is safe and does not induce severe side effects, we used microbeams to induce transections to the hippocampus of healthy rats...
January 9, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29316551/chloroquine-enhances-the-radiosensitivity-of-bladder-cancer-cells-by-inhibiting-autophagy-and-activating-apoptosis
#11
Feng Wang, Jinyuan Tang, Pengchao Li, Shuhui Si, Hao Yu, Xiao Yang, Jun Tao, Qiang Lv, Min Gu, Haiwei Yang, Zengjun Wang
BACKGROUND/AIMS: Chloroquine was formerly used as an anti-malarial agent drug but has now been proven to be useful for various diseases. This study aimed to investigate the radiosensitizing effect of chloroquine in bladder cancer, with an emphasis on autophagy inhibition and apoptosis induction. METHODS: Bladder cancer cell lines were irradiated with or without chloroquine. Cell proliferation was determined by a Cell Counting Kit 8 assay. The radiosensitization effect of chloroquine was evaluated by clonogenic survival and progression of xenograft tumors...
December 22, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29312595/pyruvate-kinase-m2-phosphorylates-h2ax-and-promotes-genomic-instability-in-human-tumor-cells
#12
Li Xia, Kang Qin, Xin-Ran Wang, Xiao-Ling Wang, Ai-Wu Zhou, Guo-Qiang Chen, Ying Lu
Pyruvate kinase (PK) catalyzes the conversion of phosphoenolpyruvate and ADP to pyruvate and ATP, a rate-limiting reaction in glycolysis. M2 isoform of PK (PKM2) is the predominant form of PK expressed in tumors. In addition to its well established cytosolic functions as a glycolytic enzyme, PKM2 displays nuclear localization and important nonmetabolic functions in tumorigenesis. Herein, we report that nuclear PKM2 interacts with histone H2AX under DNA damage conditions. Depletion of PKM2 decreased the level of serine 139-phosphorylated H2AX (γ-H2AX) in response to DNA damage...
December 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/29301945/modulation-of-glutathione-promotes-apoptosis-in-triple-negative-breast-cancer-cells
#13
Tara Miran, Andreas T J Vogg, Natascha Drude, Felix M Mottaghy, Agnieszka Morgenroth
Triple-negative breast cancer has an extremely high rate of relapse. This is particularly due to the existence and survival of cancer stem cells (CSCs) characterized by increased amounts of glutathione (GSH). In this study, we evaluated the potential of pharmacological GSH depletion to sensitize CSCs to ionizing radiotherapy with an I-125-labeled nucleoside analog, 5-iodo-4'-thio-2'-deoxyuridine (ITdU). CSCs were isolated using CD24-- and CD44+-specific microbeads. GSH and reactive oxygen species (ROS) were evaluated by fluorescence-activated cell sorting...
January 4, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29298756/adct-402-a-pbd-dimer-containing-antibody-drug-conjugate-targeting-cd19-expressing-malignancies
#14
Francesca Zammarchi, Simon Corbett, Lauren Adams, Peter C Tyrer, Konstantinos Kiakos, Narinder Janghra, Teresa Marafioti, Charles E Britten, Carin E G Havenith, Simon Chivers, Francois D'Hooge, David G Williams, Arnaud Tiberghien, Philip W Howard, John A Hartley, Patrick H van Berkel
Human CD19 antigen is a 95-kDa type I membrane glycoprotein in the immunoglobulin superfamily whose expression is limited to the various stages of B-cell development and differentiation and is maintained in the majority of B-cell malignancies, including leukemias and non-Hodgkin lymphomas of B-cell origin. Coupled with its differential and favourable expression profile, CD19 has rapid internalization kinetics and it is not shed into the circulation, making it an ideal target for the development of antibody-drug conjugates (ADCs) to treat B-cell malignancies...
January 3, 2018: Blood
https://www.readbyqxmd.com/read/29298652/astragalin-attenuates-uvb-radiation-induced-actinic-keratosis-formation
#15
Jian Zhang, Na Li, Kun Zhang, Ping Pan, Hui Zhang, Ning Li, Qiong Tian, Li Zhang, Wenli Liu, Tianyuan Gao, Xin Mu, Dengchao Feng, Wei Guo, Xiaona Ma
Actinic keratosis (AK), is the most common precancerous skin lesion induced by the excessive ultraviolet B (UVB) and is a significant threat to the public health. UVB exposure causes oxidative DNA damage and is considered to be a significant contributor to AK and subsequent development of skin cancer. Besides, activation of p38 MAPK also plays a significant role in the development of AK. In our clinical findings revealed that p38 MAPK, phospho-MSK1, and γ-H2AX were significantly highly expressed in human AK tissue than the normal healthy skin tissue...
December 29, 2017: Anti-cancer Agents in Medicinal Chemistry
https://www.readbyqxmd.com/read/29297932/inhibition-of-novel-gcn5-atm-axis-restricts-the-onset-of-acquired-drug-resistance-in-leukemia
#16
Sameer Salunkhe, Saket V Mishra, Jyothi Nair, Samadri Ghosh, Neha Choudhary, Ekjot Kaur, Sanket Shah, Ketaki Patkar, Dev Anand, Navin Khattry, Syed K Hasan, Shilpee Dutt
Leukemia is majorly treated by topoisomerase inhibitors that induce DNA double strand breaks (DSB) resulting in cell death. Consequently, modulation of DSB repair pathway renders leukemic cells resistant to therapy. Since we do not fully understand the regulation of DSB repair acquired by resistant cells, targeting these cells has been a challenge. Here we investigated the regulation of DSB repair pathway in Early Drug Resistant Population (EDRP) and Late Drug Resistant Population (LDRP). We found that doxorubicin induced equal DSBs in parent and EDRP cells however; cell death is induced only in the parent cells...
January 3, 2018: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/29291159/dual-radiosensitization-and-anti-stat3-anti-proliferative-strategy-based-on-delivery-of-gold-nanoparticle-oligonucleotide-nanoconstructs-to-head-and-neck-cancer-cells
#17
Surong Zhang, Suresh Gupta, Thomas J Fitzgerald, Alexei A Bogdanov
Constitutively activated signal transducer and activator of transcription 3 (STAT3) factor is an important therapeutic target in head and neck cancer (HNC). Despite early promising results, a reliable systemic delivery system for STAT3- targeted oligonucleotide (ODN) drugs is still needed for future clinical translation of anti-STAT3 therapies. We engineered and tested a novel ODN duplex/gold nanoparticle (AuNP)-based system carrying a therapeutic STAT3 decoy (STAT3d) payload. This strategy is two-pronged because of the additive STAT3 antagonism and radiosensitizing properties of AuNP...
2018: Nanotheranostics
https://www.readbyqxmd.com/read/29285984/tetrandrine-enhances-radiosensitivity-through-the-cdc25c-cdk1-cyclin-b1-pathway-in-nasopharyngeal-carcinoma-cells
#18
Jun Wang, Lihong Chang, Xiaoping Lai, Xia Li, Zhiyuan Wang, Zizhen Huang, Jiancong Huang, Gehua Zhang
The increasing resistance of nasopharyngeal carcinoma to irradiation makes the exploration of effective radiosensitizers necessary. Tetrandrine is known to be an antitumor drug, but little is known regarding its radiosensitization effect on nasopharyngeal carcinoma. We investigated the effect of combined treatment of irradiation and maximum non-cytotoxic doses of tetrandrine on the nasopharyngeal carcinoma cell lines CNE1 and CNE2. The maximum non-cytotoxic doses of tetrandrine in CNE1 and CNE2 cells were assessed using the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay...
December 29, 2017: Cell Cycle
https://www.readbyqxmd.com/read/29285240/molecular-basis-for-the-dna-damage-induction-and-anticancer-activity-of-asymmetrically-substituted-anthrapyridazone-pdz-7
#19
Majus Misiak, Mateusz Heldt, Marlena Szeligowska, Stefania Mazzini, Leonardo Scaglioni, Grzegorz J Grabe, Marcin Serocki, Jan Lica, Marta Switalska, Joanna Wietrzyk, Giovanni L Beretta, Paola Perego, Dominik Zietkowski, Maciej Baginski, Edward Borowski, Andrzej Skladanowski
Anthrapyridazones, imino analogues of anthraquinone, constitute a family of compounds with remarkable anti-cancer activity. To date, over 20 derivatives were studied, of which most displayed nanomolar cytotoxicity towards broad spectrum of cancer cells, including breast, prostate and leukemic ones. BS-154, the most potent derivative, had IC50 values close to 1 nM, however, it was toxic in animal studies. Here, we characterize another anthrapyridazone, PDZ-7, which retains high cytotoxicity while being well tolerated in mice...
December 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/29249653/replication-stress-shapes-a-protective-chromatin-environment-across-fragile-genomic-regions
#20
Jeongkyu Kim, David Sturgill, Robin Sebastian, Simran Khurana, Andy D Tran, Garrett B Edwards, Alex Kruswick, Sandra Burkett, Eri K Hosogane, William W Hannon, Urbain Weyemi, William M Bonner, Karolin Luger, Philipp Oberdoerffer
Recent integrative epigenome analyses highlight the importance of functionally distinct chromatin states for accurate cell function. How these states are established and maintained is a matter of intense investigation. Here, we present evidence for DNA damage as an unexpected means to shape a protective chromatin environment at regions of recurrent replication stress (RS). Upon aberrant fork stalling, DNA damage signaling and concomitant H2AX phosphorylation coordinate the FACT-dependent deposition of macroH2A1...
December 11, 2017: Molecular Cell
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