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Jie Yang, Lei Li, Yan Xi, Ruimei Sun, Hu Wang, Yanxin Ren, Liufang Zhao, Xiaoli Wang, Xiaojiang Li
This research aimed to analyze the effect of IFITM1 on the radioresistance of oral neoplasm. IFITM1 emerged using multi-group heat map from GSE9716 analysis of GEO database as the relevant radioresistance gene. IFITM1 was screened by TCGA database before its expression was analyzed. IFITM1 expression was quantified by qRT-PCR and immunohistochemistry in 19 paired oral neoplasm cases. The effects of time and dose of radiation on IFITM1 expression level in CAL27 and TSCC1 cell lines was tested via qRT-PCR. Oral neoplasm cells were transfected with siRNA after radiotherapy to disturb IFITM1 expression...
May 16, 2018: Cancer Science
Yonghong Fu, Sen Zhang, Dongjie Wang, Jing Wang
Icotinib hydrochloride is a small epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) that was developed by Chinese scientists. While clinical trials have revealed its efficacy in the treatment of lung cancer, very little is known about its role in enhancing radiosensitivity. In this study, we investigated the effectiveness of Icotinib in enhancing lung cancer cell radiosensitivity and have detailed its underlying molecular mechanism. The lung cancer cell line H1650 was pretreated with or without Icotinib for 24 hours before radiation, and clonogenic survival assay was performed...
May 16, 2018: Clinical and Experimental Pharmacology & Physiology
Prateek Kinra, Gaurav P S Gahlot, Rajni Yadav, Vandana Baloda, Govind K Makharia, Siddhartha Datta Gupta, Prasenjit Das
BACKGROUND: Histological assessment of dysplasia in Barrett's esophagus (BE) has high inter-observer variability. Hence, use of ancillary markers for early detection of dysplasia in BE is an important clinical question. METHODS: In this retrospective study consecutive cases of BE (n = 59), over a period of 4 years were included. Hematoxylin and eosin stained sections were reviewed independently by 3 senior qualified pathologists, who graded the dysplasia according to the Vienna Classification system and inter-observer agreement was analysed using the Kappa statistics...
May 13, 2018: Pathology, Research and Practice
Yan Huang, Ying Tian, Yuanyuan Zhao, Cong Xue, Jianhua Zhan, Lin Liu, Xiaobo He, Li Zhang
BACKGROUND: Tumor hypoxia is considered an important factor in metastasis and disease relapse. Evofosfamide is a hypoxia-activated prodrug that selectively targets the hypoxic regions of solid tumors. As hypoxia-inducible factor-1α (HIF-1α) is overexpressed in nasopharyngeal carcinoma (NPC) tissues, we performed the present study to evaluate the efficacy profile of evofosfamide in NPC. METHODS: We evaluated the efficacy of evofosfamide as a single agent or combined with cisplatin (DDP) in the NPC cell lines CNE-2, HONE-1 and HNE-1, and in nude mouse xenograft tumor models...
May 3, 2018: Cancer communications
Na Ma, Hai-Xia Zhao, Qian Chen, Gui-Fang Han, Zhen-Cai Liu, Ding Yuan, Chang-Cheng Zhang
To study the protective effect of Wuzi Yanzong recipe on testicular DNA damage and apoptosis in natural ageing rats, SPF grade 16-month-old SD male rats were randomly divided into three groups: ageing model group, low and high dose Wuzi Yanzong recipe groups (WZ, 1, 4 g·kg⁻¹). In addition, 2-month-old SD rats were used as adult control group (10 rats in each group). The ageing model group and the adult control group were fed with normal diet for 4 months. Wuzi Yanzong groups received medicated feed for 4 months...
April 2018: Zhongguo Zhong Yao za Zhi, Zhongguo Zhongyao Zazhi, China Journal of Chinese Materia Medica
Mengxia Li, Xiao Yang, Xianfeng Lu, Nan Dai, Shiheng Zhang, Yi Cheng, Lei Zhang, Yuxin Yang, Yie Liu, Zhenzhou Yang, Dong Wang, David M Wilson
Base excision repair (BER) handles many forms of endogenous DNA damage, and apurinic/apyrimidinic endonuclease 1 (APE1) is central to this process. Deletion of both alleles of APE1 (a.k.a. Apex1) in mice leads to embryonic lethality, and deficiency in cells can promote cell death. Unlike most other BER proteins, APE1 expression is inversely correlated with cellular senescence in primary human fibroblasts. Depletion of APE1 via shRNA induced senescence in normal human BJ fibroblasts, a phenotype that was not seen in counterpart cells expressing telomerase...
May 10, 2018: Nucleic Acids Research
Jeong-Yub Kim, Jeong-Chul Kim, Ji-Yun Lee, Myung-Jin Park
Breast cancer stem cells (BCSCs) are a small subpopulation of breast cancer cells that have been proposed to be a primary cause of failure of therapies, including ionizing radiation (IR). Their embryonic stem-like signature is associated with poor clinical outcome. In the present study, the function of octamer-binding transcription factor 4 (Oct4), an embryonic stem cell factor, in the resistance of BCSCs to IR was investigated. Mammosphere cells exhibited increased expression of stemness-associated genes, including Oct4 and sex‑determining region Y‑box 2 (Sox2), and were more resistant to IR compared with serum-cultured monolayer cells...
May 2, 2018: International Journal of Oncology
Laetitia Marzi, Keli Agama, Junko Murai, Simone Difilippantonio, Amy James, Cody J Peer, William D Figg, Daniel Beck, Mohamed S A Elsayed, Mark Cushman, Yves Pommier
Contrary to other anticancer targets, topoisomerase I (TOP1) is targeted by only one chemical class of FDA-approved drugs: topotecan and irinotecan, the derivatives of the plant alkaloid, camptothecin. The indenoisoquinolines LMP400, LMP744 and LMP776 are novel non-camptothecin TOP1 inhibitors in clinical trial, which overcome the limitations of camptothecins. To further improve metabolic stability, their methoxy groups have been replaced by a fluorine, as in the fluoroindenoisoquinolines NSC 781517 (LMP517), NSC 779135 (LMP135) and NSC 779134 (LMP134)...
May 10, 2018: Molecular Cancer Therapeutics
Cameron J Koch
Hypoxia in tumors has many well-characterized effects that are known to prevent optimal cancer treatment. Despite the existence of a large number of assays that have supported hypoxia as an important diagnostic, there is no routine clinical assay in use, and anti-hypoxia therapies have often not included parallel hypoxia measurements. Even with a functioning hypoxia assay, it is difficult to match the oxygen dependence of treatment resistance to that of the assay, and this mismatch can vary substantially from assay to assay and even from tumor to tumor [e...
May 10, 2018: Radiation Research
Jordan R Becker, David Gallo, Wendy Leung, Taylor Croissant, Yee Mon Thu, Hai Dang Nguyen, Timothy K Starr, Grant W Brown, Anja-Katrin Bielinsky
Overexpression of the flap endonuclease FEN1 has been observed in a variety of cancer types and is a marker for poor prognosis. To better understand the cellular consequences of FEN1 overexpression we utilized a model of its Saccharomyces cerevisiae homolog, RAD27. In this system, we discovered that flap endonuclease overexpression impedes replication fork progression and leads to an accumulation of cells in mid-S phase. This was accompanied by increased phosphorylation of the checkpoint kinase Rad53 and histone H2A-S129...
May 7, 2018: Nucleic Acids Research
Ye-Xing Xu, Man-Li Zeng, Di Yu, Jie Ren, Fen Li, Anyuan Zheng, Yong-Ping Wang, Chen Chen, Ze-Zhang Tao
The present study aimed to investigate the antitumor efficacy of di-2-pyridylketone-4-cyclohexyl-4-methyl-3-thiosemicarbazone (DpC) and di-2-pyridylketone-4,4,-dimethyl-3-thiosemicarbazone (Dp44mT) on head and neck squamous cell carcinoma (HNSCC) cells. The proliferation and apoptosis of HNSCC cells treated with the iron chelators DpC and Dp44mT were detected. The mechanism of DpC-induced apoptosis on HNSCC cells was investigated. The human HNSCC cell lines FaDu, Cal-27 and SCC-9 were cultured in vitro and exposed to gradient concentrations of DpC and Dp44mT...
May 2018: Oncology Letters
Jiyeon Leem, Jae-Sung Kim, Jeong Su Oh
Maternal DNA damage during meiosis causes genetic abnormalities that can lead to infertility, birth defects, and abortion. While DNA damage can rapidly halt cell cycle progression and promote DNA repair in somatic cells, mammalian oocytes are unable to mount a robust G2/prophase arrest in response to DNA damage unless damage levels are severe. Here we show that inhibition of WIP1 phosphatase enhances the ability of oocytes to respond to DNA damage. We found that WIP1 was expressed constantly during meiotic maturation, and that inhibition of WIP1 activity did not impair meiotic maturation...
May 3, 2018: Biology of Reproduction
Samir Attoub, Kholoud Arafat, Tamam Khalaf, Shahrazad Sulaiman, Rabah Iratni
Over recent years, we have demonstrated that Frondoside A, a triterpenoid glycoside isolated from an Atlantic sea cucumber, has potent in vitro and in vivo anti-cancer effects against human pancreatic, breast, and lung cancer. We have also demonstrated that Frondoside A is able to potentiate and/or synergize the anti-cancer effects of major classical cytotoxic agents, namely, gemcitabine, paclitaxel, and cisplatin, in the treatment of pancreatic, breast, and lung cancer, respectively. This study evaluates the impact of Frondoside A alone and in combination with the standard cytotoxic drugs oxaliplatin and 5-fluorouracil (5-FU) in the treatment of colon cancer using three human colon cancer cell lines, namely, HT-29, HCT-116, and HCT8/S11...
May 1, 2018: Nutrients
Tatsushi Toyooka, Yukie Yanagiba, Yuko Ibuki, Rui-Sheng Wang
Trichloroethylene (TCE), a chlorinated hydrocarbon, was recently reclassified as a human carcinogen by the International Agency for Research on Cancer. Genotoxic events are known to be crucial steps in the initiation of cancer. The genotoxic properties of TCE have been examined in many studies using a standard battery of genotoxicity tests both in vitro and in vivo. However, consistent results have not been obtained, and studies investigating the mechanism behind the genotoxicity of this compound are lacking...
May 3, 2018: Journal of Applied Toxicology: JAT
Sarwat Naz, Anastasia L Sowers, Rajani Choudhuri, Maria F Wissler, Janet Gamson, Askale Mathias, John A Cook, James B Mitchell
PURPOSE: To characterize the ionizing radiation (IR) enhancing effects and underlying mechanisms of CDK4/6 inhibitor, Abemaciclib in Non-Small Cell Lung Cancer cells (NSCLC) in vitro and in vivo Experimental Design: IR enhancement by Abemaciclib in a variety of NSCLC cell lines was assessed by in vitro clonogenic assay, flow cytometry, and target inhibition verified by immunoblotting. IR-induced DNA damage repair was evaluated by γ-H2AX analysis. Global metabolic alterations by Abemaciclib and IR combination was evaluated by LC/MS mass spectrometry and YSI-Bioanalyzer...
May 1, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Silvia Diaz-Perez, Nathanael Kane, Alexis A Kurmis, Fei Yang, Nicolas T Kummer, Peter B Dervan, Nicholas G Nickols
Pyrrole-imidazole (Py-Im) polyamides are synthetic non-genotoxic minor groove-binding small molecules. We hypothesized that Py-Im polyamides can modulate the cellular response to ionizing radiation. Pre-treatment of cells with a Py-Im polyamide prior to exposure to ionizing radiation resulted in a delay in resolution of phosphorylated γ-H2AX foci, increase in XRCC1 foci, and reduced cellular replication potential. RNA-sequencing of cell lines exposed to the polyamide showed induction of genes related to the ultraviolet radiation response...
2018: PloS One
Saravanabavaan Suntharalingam, Emil Mladenov, Theresia Sarabhai, Axel Wetter, Oliver Kraff, Harald H Quick, Michael Forsting, Georg Iliakis, Kai Nassenstein
Purpose To investigate the relationship between abdominopelvic magnetic resonance (MR) imaging and formation of DNA double-strand breaks (DSBs) in peripheral blood lymphocytes among a cohort of healthy volunteers. Materials and Methods Blood samples were obtained from 40 healthy volunteers (23 women and 17 men; mean age, 27.2 years [range, 21-37 years]) directly before and 5 and 30 minutes after abdominopelvic MR imaging performed at 1.5 T (n = 20) or 3.0 T (n = 20). The number of DNA DSBs in isolated blood lymphocytes was quantified after indirect immunofluorescent staining of a generally accepted DSB marker, γ-H2AX, by means of high-throughput automated microscopy...
May 1, 2018: Radiology
Natalia Fernández-Bertólez, Carla Costa, Fátima Brandão, Gözde Kiliç, José Alberto Duarte, Joao Paulo Teixeira, Eduardo Pásaro, Vanessa Valdiglesias, Blanca Laffon
Iron oxide nanoparticles (ION) have great potential for an increasing number of medical and biological applications, particularly those focused on nervous system. Although ION seem to be biocompatible and present low toxicity, it is imperative to unveil the potential risk for the nervous system associated to their exposure, especially because current data on ION effects on human nervous cells are scarce. Thus, in the present study potential toxicity associated with silica-coated ION (S-ION) exposure was evaluated on human A172 glioblastoma cells...
April 27, 2018: Food and Chemical Toxicology
Mohammad Sabbir Siddiqui, Maxime Francois, Jane Hecker, Jeffrey Faunt, Michael F Fenech, Wayne R Leifert
An early cellular response to DNA double-strand breaks is the phosphorylation of histone H2AX to form γH2AX. Although increased levels of γH2AX have been reported in neuronal nuclei of Alzheimer's disease (AD) patients, γH2AX responses in the lymphocytes of individuals with mild cognitive impairment (MCI) and AD remain unexplored. In this study, the endogenous γH2AX level was measured, using laser scanning cytometry (LSC) and visual scoring, in lymphocyte nuclei from MCI (n = 18), or AD (n = 20) patients and healthy controls (n = 40)...
May 2018: Mutation Research
Yuichiro Hatano, Shinya Fukuda, Hiroshi Makino, Hiroyuki Tomita, Ken-Ichirou Morishige, Akira Hara
BACKGROUND: Although p53 signature, benign-appearing epithelial cells with p53 diffuse expression, is frequently found in the fallopian tubes, the clinical and pathological significance of this lesion in the case of high-grade serous carcinoma (HGSC) patients still remains unclear. CASE PRESENTATION: A 56-year-old woman was referred to the gynecologist on account of abdominal distention. Since radiological and serological workup suggested that her illness was due to advanced ovarian cancer (FIGO Stage IVB), she received neoadjuvant chemotherapy, and the clinical evaluation of the chemotherapeutic response was a partial response...
April 27, 2018: Diagnostic Pathology
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