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Cancer and radioresistance

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https://www.readbyqxmd.com/read/28209968/activating-akt1-mutations-alter-dna-double-strand-break-repair-and-radiosensitivity
#1
S Oeck, K Al-Refae, H Riffkin, G Wiel, R Handrick, D Klein, G Iliakis, V Jendrossek
The survival kinase Akt has clinical relevance to radioresistance. However, its contributions to the DNA damage response, DNA double strand break (DSB) repair and apoptosis remain poorly defined and often contradictory. We used a genetic approach to explore the consequences of genetic alterations of Akt1 for the cellular radiation response. While two activation-associated mutants with prominent nuclear access, the phospho-mimicking Akt1-TDSD and the clinically relevant PH-domain mutation Akt1-E17K, accelerated DSB repair and improved survival of irradiated Tramp-C1 murine prostate cancer cells and Akt1-knockout murine embryonic fibroblasts in vitro, the classical constitutively active membrane-targeted myrAkt1 mutant had the opposite effects...
February 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28208648/n-butylidenephthalide-regulated-tumor-stem-cell-genes-ezh2-axl-and-reduced-its-migration-and-invasion-in-glioblastoma
#2
Ssu-Yin Yen, Hong-Meng Chuang, Mao-Hsuan Huang, Shinn-Zong Lin, Tzyy-Wen Chiou, Horng-Jyh Harn
Glioblastoma (GBM) is one of the most common and aggressive types of brain tumor. Due to its highly recurrent rate and poor prognosis, the overall survival time with this type of tumor is only 20-21 months. Recent knowledge suggests that its recurrence is in part due to the presence of cancer stem cells (CSCs), which display radioresistant, chemoresistant, self-renewal and tumorigenic potential. Enhancers of Zeste 2 (EZH2) and AXL receptor tyrosine kinase (AXL) are both highly expressed in GBM. Additionally, they are an essential regulator involved in CSCs maintenance, migration, invasion, epithelial-to-mesenchymal transition (EMT), stemness, metastasis and patient survival...
February 10, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28205588/hypoxia-induced-angiotensin-ii-by-the-lactate-chymase-dependent-mechanism-mediates-radioresistance-of-hypoxic-tumor-cells
#3
Guozhu Xie, Ying Liu, Qiwei Yao, Rong Zheng, Lanfang Zhang, Jie Lin, Zhaoze Guo, Shasha Du, Chen Ren, Quan Yuan, Yawei Yuan
The renin-angiotensin system (RAS) is a principal determinant of arterial blood pressure and fluid and electrolyte balance. RAS component dysregulation was recently found in some malignancies and correlated with poor patient outcomes. However, the exact mechanism of local RAS activation in tumors is still unclear. Here, we find that the local angiotensin II predominantly exists in the hypoxic regions of tumor formed by nasopharyngeal carcinoma CNE2 cells and breast cancer MDA-MB-231 cells, where these tumor cells autocrinely produce angiotensin II by a chymase-dependent rather than an angiotensin converting enzyme-dependent mechanism...
February 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28180110/assessing-tumor-oxygenation-for-predicting-outcome-in-radiation-oncology-a-review-of-studies-correlating-tumor-hypoxic-status-and-outcome-in-the-preclinical-and-clinical-settings
#4
REVIEW
Florence Colliez, Bernard Gallez, Bénédicte F Jordan
Tumor hypoxia is recognized as a limiting factor for the efficacy of radiotherapy, because it enhances tumor radioresistance. It is strongly suggested that assessing tumor oxygenation could help to predict the outcome of cancer patients undergoing radiation therapy. Strategies have also been developed to alleviate tumor hypoxia in order to radiosensitize tumors. In addition, oxygen mapping is critically needed for intensity modulated radiation therapy (IMRT), in which the most hypoxic regions require higher radiation doses and the most oxygenated regions require lower radiation doses...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/28147323/the-dna-repair-function-of-cux1-contributes-to-radioresistance
#5
Zubaidah M Ramdzan, Vasudeva Ginjala, Jordan B Pinder, Dudley Chung, Caroline M Donovan, Simran Kaur, Lam Leduy, Graham Dellaire, Shridar Ganesan, Alain Nepveu
Ionizing radiation generates a broad spectrum of oxidative DNA lesions, including oxidized base products, abasic sites, single-strand breaks and double-strand breaks. The CUX1 protein was recently shown to function as an auxiliary factor that stimulates enzymatic activities of OGG1 through its CUT domains. In the present study, we investigated the requirement for CUX1 and OGG1 in the resistance to radiation. Cancer cell survival following ionizing radiation is reduced by CUX1 knockdown and increased by higher CUX1 expression...
January 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28143717/the-bet-bromodomain-inhibitor-jq1-radiosensitizes-non-small-cell-lung-cancer-cells-by-upregulating-p21
#6
Jian Wang, Ye Wang, Hong Mei, Zhongyuan Yin, Yuanyuan Geng, Tao Zhang, Gang Wu, Zhenyu Lin
Radiotherapy is an important treatment modality in the management of locally advanced non-small cell lung cancer (NSCLC). However, radioresistance markedly impairs its efficacy in clinic. Bromodomain and extra-terminal (BET) bromodomain inhibitors have demonstrated dramatic antitumor activity in several preclinical human cancer models. In this study, we investigated for the first time the effect of JQ1, a novel BET bromodomain inhibitor, on tumor cell radiosensitivity of NSCLC in vitro and in vivo. Our results demonstrated that JQ1 significantly enhanced the effect of irradiation in NSCLC cell lines through a c-myc-independent mechanism...
January 29, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28138801/mir-668-enhances-the-radioresistance-of-human-breast-cancer-cell-by-targeting-i%C3%AE%C2%BAb%C3%AE
#7
Ming Luo, Ling Ding, Qingjian Li, Herui Yao
BACKGROUND: A large proportion of breast cancer patients are resistant to radiotherapy, which is a mainstay treatment for this malignancy, but the mechanisms of radioresistance remain unclear. METHODS AND MATERIALS: To evaluate the role of miRNAs in radioresistance, we established two radioresistant breast cancer cell lines MCF-7R and T-47DR derived from parental MCF-7 and T-47D. Moreover, miRNA microarray, quantitative RT-PCR analysis, luciferase reporter assay and western blotting were used...
January 30, 2017: Breast Cancer: the Journal of the Japanese Breast Cancer Society
https://www.readbyqxmd.com/read/28137309/induction-of-metastasis-cancer-stem-cell-phenotype-and-oncogenic-metabolism-in-cancer-cells-by-ionizing-radiation
#8
REVIEW
Su Yeon Lee, Eui Kyong Jeong, Min Kyung Ju, Hyun Min Jeon, Min Young Kim, Cho Hee Kim, Hye Gyeong Park, Song Iy Han, Ho Sung Kang
Radiation therapy is one of the major tools of cancer treatment, and is widely used for a variety of malignant tumours. Radiotherapy causes DNA damage directly by ionization or indirectly via the generation of reactive oxygen species (ROS), thereby destroying cancer cells. However, ionizing radiation (IR) paradoxically promotes metastasis and invasion of cancer cells by inducing the epithelial-mesenchymal transition (EMT). Metastasis is a major obstacle to successful cancer therapy, and is closely linked to the rates of morbidity and mortality of many cancers...
January 30, 2017: Molecular Cancer
https://www.readbyqxmd.com/read/28110706/corrigendum-to-role-of-cancer-stem-cell-in-radioresistant-head-and-neck-cancer-auris-nasus-larynx-43-october-5-2016-556-561
#9
Young Min Park, Sei Young Lee, Suk Won Park, Se-Heon Kim
No abstract text is available yet for this article.
February 2017: Auris, Nasus, Larynx
https://www.readbyqxmd.com/read/28108736/long-non-coding-rnas-a-rising-biotarget-in-colorectal-cancer
#10
Jian Luo, Jian Qu, Dong-Kai Wu, Zhi-Li Lu, Yue-Sheng Sun, Qiang Qu
Colorectal cancer (CRC) is a common gastrointestinal cancer, with a high incidence and high mortality. Long non-coding RNAs (lncRNAs) are involved in the development, invasion and metastasis, early diagnosis, prognosis, the chemoresistance and radioresistance of CRC through interference with mRNA activity, directly combining with proteins to regulate their activity or alter their localization, influencing downstream gene expression by inhibiting RNA polymerase and regulating gene expression as competing endogenous RNAs...
January 18, 2017: Oncotarget
https://www.readbyqxmd.com/read/28105205/microrna-320-regulates-the-radiosensitivity-of-cervical-cancer-cells-c33ar-by-targeting-%C3%AE-catenin
#11
Chun-Xu Yang, Shi-Min Zhang, Jie Li, Bo Yang, Wen Ouyang, Zi-Jie Mei, Jing Chen, Jing Dai, Su Ke, Fu-Xiang Zhou, Yun-Feng Zhou, Cong-Hua Xie
Cervical cancer is the second most common malignancy in women worldwide and always has recurrence owing to radioresistance. MicroRNA (miRNA or miR) has been identified to relate to the sensitivity of cancer radiotherapy. Here, we investigated the potential of miRNA-320 as a biomarker for radiosensitivity by targeting β-catenin in cervical cancer. A radioresistant cervical cancer cell line, C33AR, was established, and the radioresistance of C33AR cells was confirmed by a colony-formation assay. The expression of miRNA-320 was detected by reverse transcription-quantitative polymerase chain reaction, and compared between C33A and C33AR...
December 2016: Oncology Letters
https://www.readbyqxmd.com/read/28099922/pafr-selectively-mediates-radioresistance-and-irradiation-induced-autophagy-suppression-in-prostate-cancer-cells
#12
Bing Yao, Bingqian Liu, Lei Shi, Xiang Li, Chuanchuan Ren, Mingbo Cai, Wen Wang, Jianhua Li, Yongde Sun, Yudong Wu, Jianguo Wen
Platelet-activating factor receptor (PAFR) promotes tumorigenesis, angiogenesis and metastasis. Here, we defined the PAFR as a yielding new inhibiting target to selectively enhance the sensitivity of prostate cancer (PCa) cells to radiation. The selective responding to PAFR inhibiter may be caused by the differential expression pattern of PAFR in PCa cells. In this study, we also determined PAFR as a molecular basis by which the radiation induces autophagy suppression independent of activating mTOR pathway...
January 14, 2017: Oncotarget
https://www.readbyqxmd.com/read/28094252/a-signature-motif-in-lim-proteins-mediates-binding-to-checkpoint-proteins-and-increases-tumour-radiosensitivity
#13
Xiaojie Xu, Zhongyi Fan, Chaoyang Liang, Ling Li, Lili Wang, Yingchun Liang, Jun Wu, Shaohong Chang, Zhifeng Yan, Zhaohui Lv, Jing Fu, Yang Liu, Shuai Jin, Tao Wang, Tian Hong, Yishan Dong, Lihua Ding, Long Cheng, Rui Liu, Shenbo Fu, Shunchang Jiao, Qinong Ye
Tumour radiotherapy resistance involves the cell cycle pathway. CDC25 phosphatases are key cell cycle regulators. However, how CDC25 activity is precisely controlled remains largely unknown. Here, we show that LIM domain-containing proteins, such as FHL1, increase inhibitory CDC25 phosphorylation by forming a complex with CHK2 and CDC25, and sequester CDC25 in the cytoplasm by forming another complex with 14-3-3 and CDC25, resulting in increased radioresistance in cancer cells. FHL1 expression, induced by ionizing irradiation in a SP1- and MLL1-dependent manner, positively correlates with radioresistance in cancer patients...
January 17, 2017: Nature Communications
https://www.readbyqxmd.com/read/28089483/patterns-of-failure-after-radiotherapy-for-pediatric-patients-with-intracranial-ependymoma
#14
Fatima Tensaouti, Anne Ducassou, Léonor Chaltiel, Stéphanie Bolle, Xavier Muracciole, Bernard Coche-Dequeant, Claire Alapetite, Valérie Bernier, Line Claude, Stéphane Supiot, Aymeri Huchet, Christine Kerr, Elisabeth le Prisé, Anne Laprie
PURPOSE: To investigate the patterns of failure after radiotherapy for pediatric intracranial ependymoma and their correlation with dose parameters. METHODS: Between 2000 and 2013, 206 patients were treated in France. MRI scans at relapse were registered to the original planning CTs for topographic analysis of failure patterns. To compare relapse patients (RP) with non relapse patients (NRP), several dose parameters were derived from dose volume histograms. RESULTS: Over a median follow-up of 53...
January 12, 2017: Radiotherapy and Oncology: Journal of the European Society for Therapeutic Radiology and Oncology
https://www.readbyqxmd.com/read/28087741/14-3-3sigma-contributes-to-radioresistance-by-regulating-dna-repair-and-cell-cycle-via-parp1-and-chk2
#15
Yifan Chen, Zhaomin Li, Zizheng Dong, Jenny Beebe, Ke Yang, Liwu Fu, Jian-Ting Zhang
: 14-3-3sigma has been implicated in the development of chemo and radiation resistance and in poor prognosis of multiple human cancers. While it has been postulated that 14-3-3sigma contributes to these resistances via inhibiting apoptosis and arresting cells in G2/M phase of the cell cycle, the molecular basis of this regulation is currently unknown. In this study, we tested the hypothesis that 14-3-3sigma causes resistance to DNA-damaging treatments by enhancing DNA repair in cells arrested in G2/M phase following DNA-damaging treatments...
January 13, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28081154/sensitization-of-radioresistant-prostate-cancer-cells-by-resveratrol-isolated-from-arachis-hypogaea-stems
#16
Yu-An Chen, Hsiu-Man Lien, Min-Chuan Kao, U-Ging Lo, Li-Chiung Lin, Chun-Jung Lin, Sheau-Jiun Chang, Chia-Chang Chen, Jer-Tsong Hsieh, Ho Lin, Chih-Hsin Tang, Chih-Ho Lai
Resveratrol (RV, 3,4',5-trihydroxystilbene) is naturally produced by a wide variety of plants including grapes and peanuts (Arachis hypogaea). However, the yield of RV from peanut stem and its potential radiosensitizing effects in prostate cancer (PCa) have not been well investigated. In this study, we characterized RV in peanut stem extract (PSE) for the first time and showed that both RV and PSE dose-dependently induced cell death in DOC-2/DAB2 interactive protein (DAB2IP)-deficient PCa cells with the radioresistant phenotype...
2017: PloS One
https://www.readbyqxmd.com/read/28068245/ku70-ku80-and-sclusterin-a-cluster-of-predicting-factors-for-response-to-neoadjuvant-chemoradiation-therapy-in-patients-with-locally-advanced-rectal-cancer
#17
Sabina Pucci, Chiara Polidoro, Alessandro Joubert, Francesca Mastrangeli, Barbara Tolu, Michaela Benassi, Valeria Fiaschetti, Laura Greco, Roberto Miceli, Roberto Floris, Giuseppe Novelli, Augusto Orlandi, Riccardo Santoni
PURPOSE: The identification of predictive biomarkers for neoadjuvant chemoradiation therapy (CRT) is a current clinical need. The heterodimer Ku70/80 plays a critical role in DNA repair and cell death induction after damage. The aberrant expression and localization of these proteins fail to control DNA repair and apoptosis. sClusterin is the Ku70 partner that sterically inhibits Bax-dependent cell death after damage in some pathologic conditions. This study sought to evaluate the molecular relevance of Ku70-Ku80-Clu as a molecular cluster predicting the response to neoadjuvant CRT in patients with locally advanced rectal cancer (LARC)...
February 1, 2017: International Journal of Radiation Oncology, Biology, Physics
https://www.readbyqxmd.com/read/28066633/the-kinome-pathways-in-radioresistance-breast-cancer-stem-cells
#18
COMMENT
AbdulFattah Fararjeh, Yuan-Soon Ho
No abstract text is available yet for this article.
November 2016: Journal of Thoracic Disease
https://www.readbyqxmd.com/read/28063356/nanoparticles-for-radiooncology-mission-vision-challenges
#19
REVIEW
Leoni A Kunz-Schughart, Anna Dubrovska, Claudia Peitzsch, Alexander Ewe, Achim Aigner, Samuel Schellenburg, Michael H Muders, Silke Hampel, Giuseppe Cirillo, Francesca Iemma, Rainer Tietze, Christoph Alexiou, Holger Stephan, Kristof Zarschler, Orazio Vittorio, Maria Kavallaris, Wolfgang J Parak, Lutz Mädler, Suman Pokhrel
Cancer is one of the leading non-communicable diseases with highest mortality rates worldwide. About half of all cancer patients receive radiation treatment in the course of their disease. However, treatment outcome and curative potential of radiotherapy is often impeded by genetically and/or environmentally driven mechanisms of tumor radioresistance and normal tissue radiotoxicity. While nanomedicine-based tools for imaging, dosimetry and treatment are potential keys to the improvement of therapeutic efficacy and reducing side effects, radiotherapy is an established technique to eradicate the tumor cells...
December 14, 2016: Biomaterials
https://www.readbyqxmd.com/read/28061440/il-6-stat3-twist-inhibition-reverses-ionizing-radiation-induced-emt-and-radioresistance-in-esophageal-squamous-carcinoma
#20
Chunbao Zang, Xujie Liu, Bing Li, Yanqiong He, Shen Jing, Yujia He, Wenli Wu, Bingqian Zhang, Shuhong Ma, Weiwei Dai, Shaolin Li, Zhiping Peng
The acquisition of radioresistance by esophageal squamous carcinoma (ESC) cells during radiotherapy may lead to cancer recurrence and poor survival. Previous studies have demonstrated that ionizing radiation (IR) induces epithelial-mesenchymal transition (EMT) of ESC cells accompanied by increased migration, invasion, and radioresistance. However, the underlying molecular mechanisms of IR-induced EMT and radioresistance are not well established, hampering the development of potential solutions. To address this issue, we investigated the role of the IL-6/STAT3/TWIST signaling pathway in IR-induced EMT...
January 4, 2017: Oncotarget
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