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Hongxia Yang, Gang Zhang, Xiaolin Che, Shudong Yu
Slug is associated with the radioresistance of nasopharyngeal carcinoma (NPC) and the main current approach of treatment for NPC is radiotherapy. Hence, the aim of the current study was to determine the effect of Slug silencing on the radiosensitivity of NPC cells. Lentiviral-mediated transfection of Slug RNA interference (RNAi) in NPC cell line C666-1 was performed in vitro . Following Slug inhibition, its expression was detected using western blotting. A clonogenic survival assay and flow cytometry were then performed to evaluate the clonogenic cell survival, cell cycle distribution and apoptosis of C666-1 cells following irradiation...
April 2018: Experimental and Therapeutic Medicine
Ayushi Guleria, Neha Thukral, Sudhir Chandna
Sf9 lepidopteran insect cells are 100-200 times more radioresistant than mammalian cells. This distinctive feature thus makes them suitable for studies exploring radioprotective molecular mechanisms. It has been established from previous studies of our group that downstream mitochondrial apoptotic signaling pathways in Sf9 cells are quite similar to mammalian cells, implicating the upstream signaling pathways in their extensive radioresistance. In the present study, intracellular and mitochondrial calcium levels remained unaltered in Sf9 cells in response to radiation, in sharp contrast to human (HEK293T) cells...
March 10, 2018: Biochemical and Biophysical Research Communications
Mary Carroll Shapiro, Tien Tang, Atreyi Dasgupta, Lyazat Kurenbekova, Ryan Shuck, M Waleed Gaber, Jason T Yustein
PURPOSE: Radiation therapy (RT) is a viable therapeutic option for Ewing sarcoma (ES) patients. However, little progress has been made to elucidate the mechanisms of radioresistance. This study establishes a novel ES irradiation-adapted model designed to assess molecular and18 F fluorodeoxyglucose (FDG) positron emission tomography (PET) alterations secondary to RT. METHODS AND MATERIALS: Radiation-adapted cell lines (RACLs) were created in vitro by exposing ES human cell lines to fractionated doses of radiation...
February 5, 2018: International Journal of Radiation Oncology, Biology, Physics
Zhen-Wei Zou, Ting Liu, Yong Li, Peng Chen, Xin Peng, Charlie Ma, Wen-Jie Zhang, Pin-Dong Li
Thyroid cancer is the most common endocrine carcinoma with increasing incidence worldwide and anaplastic subtypes are frequently associated with cancer related death. Radioresistance of thyroid cancer often leads to therapy failure and cancer-related death. In this study, we found that melatonin showed potent suppressive roles on NF-κB signaling via inhibition of p65 phosphorylation and generated redox stress in thyroid cancer including the anaplastic subtypes. Our data showed that melatonin significantly decreased cell viability, suppressed cell migration and induced apoptosis in thyroid cancer cell lines in vitro and impaired tumor growth in the subcutaneous mouse model in vivo...
March 1, 2018: Redox Biology
Tian Zhang, Xiaojie Liu, Xiuli Chen, Jing Wang, Yuwen Wang, Dong Qian, Qingsong Pang, Ping Wang
Positive cofactor 4 (PC4) participates in DNA damage repair and involved in nonhomologous end joining (NHEJ). Our previous results demonstrated that knockdown of PC4 downregulated the expression of XRCC4-like factor (XLF) in esophageal squamous cell carcinoma. However, the mechanism how PC4 regulates the expression of XLF remains unclear. Here, we found that knockdown of PC4 increased radiosensitivity of non-small cell lung cancer (NSCLC) both in vivo and in vitro. Furthermore, we found that PC4 knockdown downregulated the expression of XLF, whereas recovering XLF expression restored radioresistance in the PC4-knockdown NSCLC cells...
March 9, 2018: Cancer Medicine
Simon P Keam, Twishi Gulati, Cristina Gamell, Franco Caramia, Cheng Huang, Ralf B Schittenhelm, Oded Kleifeld, Paul J Neeson, Ygal Haupt, Scott G Williams
INTRODUCTION: The development of radioresistance in prostate cancer (PCa) is an important clinical issue and is still largely uninformed by personalized molecular characteristics. The aim of this study was to establish a platform that describes the early oncoproteomic response of human prostate tissue to radiation therapy (RT) using a prospective human tissue cohort. METHODS: Fresh and fixed transperineal biopsies from eight men with clinically localized tumors were taken prior to and 14 days following a single fraction of high-dose-rate brachytherapy...
March 9, 2018: Prostate
Yuanjian Huang, Duxun Tan, Juan Xiao, Qiaoyun Li, Xianfeng Zhang, Zhiqiang Luo
Introduction: Radiotherapy has been the primary treatment for nasopharyngeal carcinoma (NPC), but the NPC radiocurability was severely limited with the radioresistance. The research suggested the important role of miRNAs in cancer therapeutic response. Materials and Methods: A radioresistant NPC cell line CNE-2R, we exposed CNE-2 cells to a range of radiation doses. Levels of miR-150 were measured by quantitative reverse-transcriptase polymerase chain reaction in CNE-2R and CNE-2 cells...
January 2018: Journal of Cancer Research and Therapeutics
Xiaojing Chang, Xiaoying Xue, Yafang Zhang, Ge Zhang, Huandi Zhou, Yanling Yang, Yuge Ran, Zhiqing Xiao, Xiaohui Ge, Huizhi Liu
Background: Neurotrophin receptor-interacting MAGE homolog (NRAGE) has been considered as a tumor suppressor. In the previous study, we established human esophageal carcinoma resistance cell line TE13R120 and found the difference of NRAGE expression between TE13 and TE13R120 cells by gene microarray. Herein, we further discuss the possible molecular mechanism of NRAGE on participating the radiation sensitivity of esophageal carcinoma cells. Materials and Methods: We used colony formation assay to measure the surviving fraction and relevant radiobiological parameters...
January 2018: Journal of Cancer Research and Therapeutics
Stéphane Supiot, Caroline Rousseau, Mélanie Dore, Catherine Cheze-Le-Rest, Christine Kandel-Aznar, Vincent Potiron, Stéphane Guerif, François Paris, Ludovic Ferrer, Loïc Campion, Philippe Meingan, Gregory Delpon, Mathieu Hatt, Dimitris Visvikis
Purpose: Hypoxia is a major factor in prostate cancer aggressiveness and radioresistance. Predicting which patients might be bad candidates for radiotherapy may help better personalize treatment decisions in intermediate-risk prostate cancer patients. We assessed spatial distribution of18 F-Misonidazole (FMISO) PET/CT uptake in the prostate prior to radiotherapy treatment. Materials and Methods: Intermediate-risk prostate cancer patients about to receive high-dose (>74 Gy) radiotherapy to the prostate without hormonal treatment were prospectively recruited between 9/2012 and 10/2014...
February 9, 2018: Oncotarget
Elodie Melsens, Elly De Vlieghere, Benedicte Descamps, Christian Vanhove, Ken Kersemans, Filip De Vos, Ingeborg Goethals, Boudewijn Brans, Olivier De Wever, Wim Ceelen, Piet Pattyn
BACKGROUND: Esophageal cancer is an aggressive disease with poor survival rates. A more patient-tailored approach based on predictive biomarkers could improve outcome. We aimed to predict radiotherapy (RT) response by imaging tumor hypoxia with18 F-FAZA PET/CT in an esophageal adenocarcinoma (EAC) mouse model. Additionally, we investigated the radiosensitizing effect of the hypoxia modifier nimorazole in vitro and in vivo. METHODS: In vitro MTS cell proliferation assays (OACM5 1...
March 7, 2018: Radiation Oncology
Rui Yang, Ze-Zhang Tao, Mao-Ling Huang, Yong-Fa Zheng, Meng-Yuan Dai, You Zou, Shi-Ming Chen
The present study investigated the radiosensitizing effect of placenta specific 8 (PLAC8) in nasopharyngeal carcinoma (NPC) cells. A PLAC8-knockout CNE2 cell line was constructed using the CRISPR/Cas9 system. The CCK-8 assay demonstrated knockout of PLAC8 significantly reduced cell proliferation and cell survival after irradiation compared to both control cells and non-irradiated PLAC8-knockout cells. The clonogenic assay showed knockout of PLAC8 enhanced the radiosensitivity of NPC cells. Flow cytometry revealed knockout of PLAC8 increased apoptosis and G2/M phase arrest after irradiation...
2018: American Journal of Translational Research
Seyed Jalal Hosseinimehr
: Background: Radiotherapy is an important protocol in the treatment of cancers, but radioresistance of cancerous cells is a challenge in cancer treatment. OBJECTIVE: The aim of this study was to evaluate the radiosensitizing effect of cerium oxide nanoparticles (CNPs) on human promyelocytic leukemia cells (HL-60). METHOD: HL-60 cells were treated with CNPs at different concentrations (10-100 µg/ml) and exposed to ionizing radiation (IR). The genotoxicity effects of CNPs or/and IR were assessed by micronuclei assay in HL-60 cells...
March 6, 2018: Pharmaceutical Nanotechnology
Yumei Huang, Kaishun Hu, Sheng Zhang, Xiaorong Dong, Zhongyuan Yin, Rui Meng, Yingchao Zhao, Xiaofang Dai, Tao Zhang, Kunyu Yang, Li Liu, Kai Huang, Shaojun Shi, Yu Zhang, Junjie Chen, Gang Wu, Shuangbing Xu
Rationale: Mxi1 is regarded as a potential tumor suppressor protein that antagonizes the transcriptional activity of proto-oncogene Myc. However, the clinical significances and underlying mechanisms by which Mxi1 is regulated in lung cancer remain poorly understood. Methods: Mass spectrometry analysis and immunoprecipitation assay were utilized to detect the protein-protein interaction. The phosphorylation of Mxi1 was evaluated by in vitro kinase assays. Poly-ubiquitination of Mxi1 was examined by in vivo ubiquitination assay...
2018: Theranostics
Natalie A Lockney, T Jonathan Yang, David Barron, Emily Gelb, Daphna Y Gelblum, Ellen Yorke, Weiji Shi, Zhigang Zhang, Andreas Rimner, Abraham J Wu
Objectives: Hyperactivation of the phosphatidylinositol-3-kinase (PI3K) pathway has been associated with radioresistance. It is unclear whether such mutations confer suboptimal local control for patients who receive lung stereotactic body radiation therapy (SBRT). Our objective was to examine whether mutations in the EGFR/AKT/PIK3CA signaling pathway are associated with local failure (LF) after lung SBRT. Methods: We retrospectively reviewed 166 patients who underwent SBRT to primary or metastatic lung lesions from 2007-2015 for whom genetic testing data was available for EGFR, AKT, and PIK3CA genes...
December 2017: Clinical and Translational Radiation Oncology
Katsuya Satoh, Hiroki Arai, Toshihiko Sanzen, Yuko Kawaguchi, Hidenori Hayashi, Shin-Ichi Yokobori, Akihiko Yamagishi, Yutaka Oono, Issay Narumi
Deinococcus aerius strain TR0125 is a bacterium isolated from the high atmosphere above Japan that shows strong resistance to desiccation, UV-C, and gamma radiation. Here, we report the draft genome sequence of D. aerius (4.5 Mb), which may provide useful genetic information supporting its biochemical features.
March 1, 2018: Genome Announcements
Myung Woul Han, In Sun Ryu, Jong Cheol Lee, Song Hee Kim, Hyo Won Chang, Yoon Sun Lee, Seulkina Lee, Seong Who Kim, Sang Yoon Kim
OBJECTIVES: PI3K/Akt/mTOR pathway is commonly activated in most cancers and is correlated with resistance to anticancer therapies such as radiotherapy. Therefore, PI3K is an attractive target for treating PI3K-associated cancers. MATERIAL AND METHODS: We investigated the basal expression and the expression after treatment of PI3K inhibitor or Src inhibitor of PI3K/Akt pathway-related proteins in AMC-HN3, AMC-HN3R, HN30 and HN31 cells by performing immunoblotting analysis...
March 2018: Oral Oncology
Song Qu, Ya Guo, Shi-Ting Huang, Xiao-Dong Zhu
Radioresistance remains a major obstacle for clinicians in the treatment of nasopharyngeal carcinoma (NPC). Others and we have reported that signal transducer and activator of transcription 1 (STAT1) may be as an important gene for resistance to radiation. However, the relationship between STAT1 and radioresistance is still elusive. In this study, by constitutive silencing STAT1 in human radioresistant nasopharyngeal carcinoma CNE-2R cell line, we showed that inhibition of STAT1 enhanced radiosensitivity of CNE-2R...
February 2, 2018: Oncotarget
Lisa Walter, Lucie Heinzerling
BACKGROUND/AIM: Recent evidence suggests that melanoma patients treated with BRAF inhibitors experience radiosensitization with an increased frequency of side-effects. This could also imply increased effectiveness when treating melanoma. MATERIALS AND METHODS: To test whether the BRAF inhibitors dabrafenib and vemurafenib together with ionizing radiation more effectively inhibit melanoma cells, primary human melanoma tumor cell lines expressing wild-type (WT) or mutant V600E BRAF were analyzed by cell survival, cell death, and cell-cycle testing...
March 2018: Anticancer Research
You Quan Li, Eu Tiong Chua, Kevin L M Chua, Melvin L K Chua
Intracranial hemangiopericytomas (HPC) are chemotherapy- and radiotherapy (RT)-resistant. Here, we report on a novel stereotactic radiosurgery (SRS) technique-"Cor Occidere" (Latin), as a potential strategy of overcoming radioresistance of HPC. A 36-year old female presented to our clinic for consideration of a 3rd-course of RT for her recurrent cavernous sinus HPC, following previous cranial RT at 13 and 5 years prior, and a failed 9 months trial of bevacizumab/temozolomide. The tumor-adjacent brain stem and carotid artery risked substantial damage given the cumulative RT doses to these organs...
February 2018: Chinese Clinical Oncology
James E Bates, Christopher G Morris, Nicole M Iovino, Michael Rutenberg, Robert A Zlotecki, C Parker Gibbs, Mark Scarborough, Daniel J Indelicato
PURPOSE: Radiation therapy (RT) is often used in the treatment of unresectable or recurrent aggressive fibromatosis (also known as desmoid tumor) typically with excellent local control. Prior reports have suggested that local control in pediatric patients with aggressive fibromatosis is poor. We aimed to report a long-term single-institution experience with the radiotherapeutic treatment of these tumors with a focus on age-dependent outcomes. METHODS AND MATERIALS: A total of 101 patients treated with RT for aggressive fibromatosis between 1975 and 2015 at a single institution were identified...
March 15, 2018: International Journal of Radiation Oncology, Biology, Physics
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