Read by QxMD icon Read


Juan A Montero, Cristina Sanchez-Fernandez, Carlos I Lorda-Diez, Juan A Garcia-Porrero, Juan M Hurle
DNA damage independent of caspase activation accompanies programmed cell death in different vertebrate embryonic organs. We analyzed the significance of DNA damage during the regression of the interdigital tissue, which sculpts the digits in the embryonic limb. Interdigit remodeling involves oxidative stress, massive apoptosis and cell senescence. Phosphorylation of H2AX mediated by ATM precedes caspase dependent apoptosis and cell senescence during interdigit regression. The association of γH2AX with other downstream DNA repair factors, including MDC1, Rad50 and 53BP1 suggests a defensive response of cells against DNA damage...
October 18, 2016: Scientific Reports
Joohwee Kim, Vivek Vaish, Mingxiao Feng, Kevin Field, Ioulia Chatzistamou, Minsub Shim
Cyclooxygenase (COX) is a key enzyme in the biosynthesis of prostanoids, lipid signaling molecules that regulate various physiological processes. COX2, one of the isoforms of COX, is highly inducible in response to a wide variety of cellular and environmental stresses. Increased COX2 expression is thought to play a role in the pathogenesis of many age-related diseases. COX2 expression is also reported to be increased in the tissues of aged humans and mice, which suggests the involvement of COX2 in the aging process...
October 7, 2016: Aging
Chun-Yen Liu, Chang-Hung Hsieh, Seung-Hun Kim, Jing-Ping Wang, Yu-Lin Ni, Chun-Li Su, Ching-Fa Yao, Kang Fang
Human liver cancer is one of the most frequently diagnosed cancers worldwide. The development of resistance to therapy limits the application against the disease. To improve treatment, new effective anticancer agents are constantly pursued. Previously, we reported that an indolylquinoline, 3-((7-ethyl-1H-indol-3-yl)-methyl)-2-methylquinoline (EMMQ), is effective in suppressing the growth of human lung cancer by impairing mitochondria functions. The present study revealed that EMMQ inhibited cell growth and induced apoptosis in liver cancer cells, but not in normal cells...
October 5, 2016: International Journal of Oncology
Zhiqiang Wang, Wenya Xu, Ziying Lin, Chunyan Li, Yahong Wang, Lawei Yang, Gang Liu
Lung cancer is the leading cause of cancer-related deaths worldwide and is associated with a very poor outcome. Oxymatrine exerts antitumor effects by inducing apoptosis and inhibiting the proliferation of different cancer cells; however, the anticancer effects and mechanism of action of oxymatrine have not been evaluated sufficiently in human lung cancer cells. Thus, the present study aimed to investigate the anticancer effects of oxymatrine in human lung cancer cells and identify the molecular mechanisms underlying these effects...
October 14, 2016: International Journal of Oncology
Fei Lu, Xiaojun Wu, Feng Yin, Christina Chia-Fang Lee, Min Yu, Ivailo S Mihaylov, Jiekai Yu, Hong Sun, Hui Zhang
DNA replication licensing occurs on chromatin, but how the chromatin template is regulated for replication remains mostly unclear. Here, we have analyzed the requirement of histone methyltransferases for a specific type of replication: the DNA re-replication induced by the downregulation of either Geminin, an inhibitor of replication licensing protein CDT1, or the CRL4CDT2 ubiquitin E3 ligase. We found that siRNA-mediated reduction of essential components of the MLL-WDR5-RBBP5 methyltransferase complexes including WDR5 or RBBP5, which transfer methyl groups to histone H3 at K4 (H3K4), suppressed DNA re-replication and chromosomal polyploidy...
October 15, 2016: Biology Open
Michael M Im, Sheryl A Flanagan, Jeffrey J Ackroyd, Brendan Knapp, Aaron Kramer, Donna S Shewach
Gemcitabine (dFdCyd) shows broad antitumor activity in solid tumors in chemotherapeutic regimens or when combined with ionizing radiation (radiosensitization). While it is known that mismatches in DNA are necessary for dFdCyd radiosensitization, the critical event resulting in radiosensitization has not been identified. Here we hypothesized that late DNA damage (≥24 h after drug washout/irradiation) is a causal event in radiosensitization by dFdCyd, and that homologous recombination repair (HRR) is required for this late DNA damage...
October 14, 2016: Radiation Research
Ameer L Elaimy, Aarif Ahsan, Katherine Marsh, William B Pratt, Dipankar Ray, Theodore S Lawrence, Mukesh K Nyati
Heat shock protein 90 is a chaperone that plays an essential role in the stabilization of a large number of signal transduction molecules, many of which are associated with oncogenesis. An Hsp90 isoform (Hsp90α) has been shown to be selectively phosphorylated on two N-terminal threonine residues (threonine 5 and 7) and is involved in the DNA damage response and apoptosis. However, the kinase that phosphorylates Hsp90α after ionizing radiation (IR) and its role in post-radiation DNA repair remains unclear...
October 11, 2016: Oncotarget
Xuefeng Deng, Peng Xu, Wei Zou, Weiran Shen, Jianxin Peng, Kaiyu Liu, John F Engelhardt, Ziying Yan, Jianming Qiu
: Human bocavirus 1 (HBoV1), an emerging human pathogenic respiratory virus, is a member of the genus Bocaparvovirus of the Parvoviridae family. In human airway epithelia air-liquid interface (HAE-ALI) cultures, HBoV1 infection initiates a DNA damage response (DDR), activating all three phosphatidylinositol 3-kinase-related kinases (PI3KKs): ATM, ATR and DNA-PKcs. In this context, activation of PI3KKs is a requirement for amplification of the HBoV1 genome (PLoS Pathog., 2016; 12:e1005399), and HBoV1 replicates only in terminally differentiated, non-dividing cells...
October 12, 2016: Journal of Virology
Hiroyuki Moriyama, Mariko Moriyama, Kiyofumi Ninomiya, Toshio Morikawa, Takao Hayakawa
Human malignant melanomas remain associated with dismal prognosis due to their resistance to apoptosis and chemotherapy. There is growing interest in plant oligostilbenoids owing to their pleiotropic biological activities, including anti-inflammatory, antioxidant, and anticancer effects. Recent studies have demonstrated that resveratrol, a well-known stilbenoid from red wine, exhibits cell cycle-disrupting and apoptosis-inducing activities on melanoma cells. The objective of our study was to evaluate the anti-melanoma effect of oligostilbenoids isolated from the bark of Shorea roxburghii...
2016: Biological & Pharmaceutical Bulletin
Peizhou Jiang, Peng Huang, Shu-Hui Yen, Abba C Zubair, Dennis W Dickson
BACKGROUND AIMS: Aberrant production of reactive oxygen species (ROS) and its impact on the integrity of genomic DNA have been considered one of the major risk factors for the loss of dopaminergic neurons in Parkinson's disease (PD). Stem cell transplantation as a strategy to replenish new functional neurons has great potential for PD treatment. However, limited survival of stem cells post-transplantation has always been an obstacle ascribed to the existence of neurotoxic environment in PD patients...
October 6, 2016: Cytotherapy
L S E P W Castro, M R Kviecinski, F Ourique, E B Parisotto, V M A S Grinevicius, J F G Correia, D Wilhelm Filho, R C Pedrosa
This work evaluated the antitumor effects of albendazole (ABZ) and its relationship with modulation of oxidative stress and induction of DNA damage. The present results showed that ABZ causes oxidative cleavage on calf-thymus DNA suggesting that this compound can break DNA. ABZ treatment decreased MCF-7 cell viability (EC50=44.9 for 24h) and inhibited MCF-7 colony formation (~67.5% at 5μM). Intracellular ROS levels increased with ABZ treatment (~123%). The antioxidant NAC is able to revert the cytotoxic effects, ROS generation and loss of mitochondrial membrane potential of MCF-7 cells treated with ABZ...
September 22, 2016: Redox Biology
Yi-Shu Wang, Jianfeng Chen, Fengmei Cui, Huibo Wang, Shuai Wang, Wei Hang, Qinghua Zeng, Cheng-Shi Quan, Ying-Xian Zhai, Jian-Wei Wang, Xiang-Feng Shen, Yong-Ping Jian, Rui-Xun Zhao, Kaitlin D Werle, Rutao Cui, Jiyong Liang, Yu-Lin Li, Zhi-Xiang Xu
Liver kinase B1 (LKB1) functions as a tumor suppressor encoded by STK11, a gene that mutated in Peutz-Jeghers syndrome and in sporadic cancers. Previous studies showed that LKB1 participates in IR- and ROS-induced DNA damage response (DDR). However, the impact of LKB1 mutations on targeted cancer therapy remains unknown. Herein, we demonstrated that LKB1 formed DNA damage-induced nuclear foci and co-localized with ataxia telangiectasia mutated kinase (ATM), γ-H2AX, and breast cancer susceptibility 1 (BRCA1)...
September 29, 2016: Oncotarget
Pavel Lobachevsky, Trevor Leong, Patricia Daly, Jai Smith, Nickala Best, Ella R Thompson, Na Li, Ian G Campbell, Roger F Martin, Olga A Martin
A small percentage of cancer radiotherapy patients develop abnormally severe side effects as a consequence of intrinsic radiosensitivity. We analysed the γ-H2AX response to ex-vivo irradiation of peripheral blood lymphocytes (PBL) and plucked eyebrow hair follicles from 16 patients who developed severe late radiation toxicity following radiotherapy, and 12 matched control patients. Longer retention of the γ-H2AX signal and lower colocalization efficiency of repair factors in over-responding patients confirmed that DNA repair in these individuals was compromised...
September 28, 2016: Cancer Letters
Omar Nasser Rahal, Maamoun Fatfat, Carla Hankache, Bassam Osman, Hala Khalife, Khaled Machaca, Hala-Gali Muhtasib
Recently, we showed that the metal chelator TPEN targets colon cancer cells through redox cycling of copper. Here, we studied the DNA damage potential of TPEN and deciphered the role of Chk1, ATM and DNA-PK in TPEN-induced toxicity in three human colon cancer cell lines, HCT116, SW480 and HT29. We also investigated the role of reactive oxygen species (ROS) in TPEN-induced DNA damage. TPEN reduced cell viability in a dose- and time-dependent manner. Cytotoxicity was associated with significant DNA damage and higher expression of ɣ-H2AX protein and activation of ATM/ATR signaling pathway...
October 3, 2016: Cancer Biology & Therapy
Kathleen A Bridges, Xingxing Chen, Huifeng Liu, Crosby Rock, Thomas A Buchholz, Stuart D Shumway, Heath D Skinner, Raymond E Meyn
Radiotherapy is commonly used to treat a variety of solid tumors but improvements in the therapeutic ratio are sorely needed. The aim of this study was to assess the Chk1 kinase inhibitor, MK-8776, for its ability to radiosensitize human tumor cells. Cells derived from NSCLC and HNSCC cancers were tested for radiosensitization by MK-8776. The ability of MK-8776 to abrogate the radiation-induced G2 block was determined using flow cytometry. Effects on repair of radiation-induced DNA double strand breaks (DSBs) were determined on the basis of rad51, γ-H2AX and 53BP1 foci...
September 28, 2016: Oncotarget
Garren M Low, David S Thylur, Vicky N Yamamoto, Uttam K Sinha
Much of the current literature regarding the molecular pathophysiology of human papillomavirus (HPV) in head and neck squamous cell carcinoma (HNSCC) has focused on the virus's effect on cell cycle modulation and cell proliferation. A second mechanism of pathogenicity employed by HPV, dysregulation of cellular DNA repair processes, has been more sparsely studied. The purpose of this review is to describe current understanding about the effect of HPV on DNA repair in HNSCC, taking cues from cervical cancer literature...
October 2016: Oral Oncology
Zhi-Yong He, Wen-Yue Wang, Wei-Yan Hu, Lu Yang, Yan Li, Wei-Yuan Zhang, Ya-Shu Yang, Si-Cheng Liu, Feng-Lan Zhang, Rong Mei, Da Xing, Zhi-Cheng Xiao, Ming Zhang
The PP2C family member Wild-type p53-induced phosphatase 1 (Wip1) critically regulates DNA damage response (DDR) under stressful situations. In the present study, we investigated whether Wip1 expression was involved in the regulation of DDR-induced and depression-related cellular senescence in mouse hippocampus. We found that Wip1 gene knockout (KO) mice showed aberrant elevation of hippocampal cellular senescence and of γ-H2AX activity, which is known as a biomarker of DDR and cellular senescence, indicating that the lack of Wip1-mediated γ-H2AX dephosphorylation facilitates cellular senescence in hippocampus...
September 30, 2016: Scientific Reports
Jayne Moquet, Stephen Barnard, Albena Staynova, Carita Lindholm, Octávia Monteiro Gil, Vanda Martins, Ute Rößler, Anne Vral, Charlot Vandevoorde, Maria Wojewódzka, Kai Rothkamm
PURPOSE: Within the EU RENEB project, seven laboratories have taken part in training and harmonisation activities to strengthen triage gamma-H2AX-based radiation exposure assessment. This has culminated in a second triage biodosimetry exercise. MATERIALS AND METHODS: Whole blood and separated lymphocyte samples were homogenously irradiated with (60)Co gamma rays at 0.5, 2.5 (blind samples), 0 and 2 Gy (reference samples). Following post-exposure incubations of 4 and 24 h, 16 samples were shipped on ice packs to each partner...
August 15, 2016: International Journal of Radiation Biology
Jianmin Wu, Yimin Sun, Pei-Ying Zhang, Mengyao Qian, Hengchao Zhang, Xiao Chen, Di Ma, Yunsheng Xu, Xiaoming Chen, Kai-Fu Tang
The Fra-1 transcription factor is frequently upregulated in multiple types of tumors. Here we found that Fra-1 promotes miR-134 expression. miR-134 activates JNK and ERK by targeting SDS22, which in turn induces Fra-1 expression and leads to miR-134 upregulation. In addition, miR-134 augmented H2AX S139 phosphorylation by activating JNK and promoted non-homologous end joining (NHEJ)-mediated DNA repair. Therefore, ectopic miR-134 expression reduced chemosensitivity in ovarian cancer cells. Furthermore, miR-134 promotes cell proliferation, migration and invasion of ovarian cancer cells, and enhances tumor growth in vivo...
2016: Cell Death & Disease
Yoshikazu Kuwahara, Mehryar Habibi Roudkenar, Masatoshi Suzuki, Yusuke Urushihara, Motoi Fukumoto, Yohei Saito, Manabu Fukumoto
PURPOSE: To understand the molecular mechanisms underlying cancer cell radioresistance, clinically relevant radioresistant (CRR) cells that continue to proliferate during exposure to 2 Gy/day X-rays for more than 30 days were established. A modified high-density survival assay for anticancer drug screening revealed that CRR cells were resistant to an antimicrotubule agent, docetaxel (DTX). The involvement of reactive oxygen species (ROS) from mitochondria (mtROS) in the cross-resistance to X-rays and DTX was studied...
November 1, 2016: International Journal of Radiation Oncology, Biology, Physics
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"