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https://www.readbyqxmd.com/read/28432456/deregulated-bcl-2-family-proteins-impact-on-repair-of-dna-double-strand-breaks-and-are-targets-to-overcome-radioresistance-in-lung-cancer
#1
Sarah A Wieczorek, Frank Breitenbuecher, Aashish Soni, Katja Paul-Konietzko, Sophie Ziegler, Ali Sak, George Iliakis, Martin Schuler
PURPOSE: DNA damage-induced cell death is a major effector mechanism of radiotherapy. Aberrant expression of anti-apoptotic BCL-2 family proteins is frequently observed in lung cancers. Against this background, we studied radioresistance mediated by BCL-2 family proteins at the mechanistic level and its potential as target for radiochemotherapy. METHODS: Lung cancer models stably expressing BCL-xL or MCL-1 were irradiated to study cell death, clonogenic survival, and DNA repair kinetics in vitro, and growth suppression of established tumors in vivo...
April 21, 2017: Journal of Cancer Research and Clinical Oncology
https://www.readbyqxmd.com/read/28431753/eef2k-promotes-progression-and-radioresistance-of-esophageal-squamous-cell-carcinoma
#2
Hongcheng Zhu, Hongmei Song, Guangzong Chen, Xi Yang, Jia Liu, Yangyang Ge, Jing Lu, Qin Qin, Chi Zhang, Liping Xu, Xiaoke Di, Jing Cai, Jianxin Ma, Shu Zhang, Xinchen Sun
OBJECTIVES: To investigate the biological function of eEF2K in esophageal squamous cell carcinoma (ESCC). MATERIALS AND METHODS: Tissue microarrays containing 100 pairs of ESCC tumor and adjacent normal tissues were completed. Overexpression and knockdown of eEF2K were constructed in ECA-109 and TE-13 ESCC cells. DNA damage, cell viability, migration and invasion, radioresistance, apoptosis and autophagy were determined by immunofluorescence, CCK-8, transwell assay, colony formation assay, flow cytometry and western blot, respectively...
April 18, 2017: Radiotherapy and Oncology: Journal of the European Society for Therapeutic Radiology and Oncology
https://www.readbyqxmd.com/read/28428710/cma-down-regulates-p53-expression-through-degradation-of-hmgb1-protein-to-inhibit-irradiation-triggered-apoptosis-in-hepatocellular-carcinoma
#3
Jing-Hua Wu, Jia-Pei Guo, Jun Shi, Hui Wang, Lei-Lei Li, Bin Guo, Dian-Xing Liu, Qing Cao, Zhi-Yong Yuan
AIM: To investigate the mechanism of chaperone-mediated autophagy (CMA)-induced resistance to irradiation-triggered apoptosis through regulation of the p53 protein in hepatocellular carcinoma (HCC). METHODS: Firstly, we detected expression of lysosome-associated membrane protein 2a (Lamp-2a), which is the key protein of CMA, by western blot in HepG2 and SMMC7721 cells after irradiation. We further used shRNA Lamp-2a HCC cells to verify the radioresistance induced by CMA...
April 7, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/28427525/precision-medicine-for-early-breast-cancer-radiotherapy-opening-up-new-horizons
#4
REVIEW
Jacques Bernier
So far most efforts put forth to test the value of predictive and prognostic tools in the field of breast radiotherapy remained globally disappointing, or at least below the convincing levels reached for systemic therapy. Nevertheless the addition of predictive tools to the clinical armament tends to prevail over the use of the sole prognostic factors, also in radiotherapy. A number of predictive assays, clinically validated or not, have recently elicited significant associations between molecular profiles and tumor biological aggressiveness and/or radiosensitivity levels...
May 2017: Critical Reviews in Oncology/hematology
https://www.readbyqxmd.com/read/28426747/metabolic-analysis-of-radioresistant-medulloblastoma-stem-like-clones-and-potential-therapeutic-targets
#5
Lue Sun, Takashi Moritake, Kazuya Ito, Yoshitaka Matsumoto, Hironobu Yasui, Hidehiko Nakagawa, Aki Hirayama, Osamu Inanami, Koji Tsuboi
Medulloblastoma is a fatal brain tumor in children, primarily due to the presence of treatment-resistant medulloblastoma stem cells. The energy metabolic pathway is a potential target of cancer therapy because it is often different between cancer cells and normal cells. However, the metabolic properties of medulloblastoma stem cells, and whether specific metabolic pathways are essential for sustaining their stem cell-like phenotype and radioresistance, remain unclear. We have established radioresistant medulloblastoma stem-like clones (rMSLCs) by irradiation of the human medulloblastoma cell line ONS-76...
2017: PloS One
https://www.readbyqxmd.com/read/28418703/radioresistance-of-adenine-to-cosmic-rays
#6
Gabriel S Vignoli Muniz, Christian F Mejía, Rafael Martinez, Basile Auge, Hermann Rothard, Alicja Domaracka, Philippe Boduch
The presence of nucleobases in carbonaceous meteorites on Earth is an indication of the existence of this class of molecules in outer space. However, space is permeated by ionizing radiation, which can have damaging effects on these molecules. Adenine is a purine nucleobase that amalgamates important biomolecules such as DNA, RNA, and ATP. Adenine has a unique importance in biochemistry and therefore life. The aim of this work was to study the effects of cosmic ray analogues on solid adenine and estimate its survival when exposed to corpuscular radiation...
April 2017: Astrobiology
https://www.readbyqxmd.com/read/28418119/endoplasmic-reticulum-stress-pathway-perk-eif2%C3%AE-confers-radioresistance-in-oropharyngeal-carcinoma-by-activating-nf-%C3%AE%C2%BAb
#7
Qiao Qiao, Chaonan Sun, Chuyang Han, Ning Han, Miao Zhang, Guang Li
Endoplasmic reticulum stress (ERS) plays an important role in the pathogenesis and development of malignant tumours, as well as in the regulation of radio- and chemoresistance in many malignancies. ERS signalling pathway protein kinase RNA-like endoplasmic reticulum kinase (PERK) -eukaryotic initiation factor-2 (eIF2α) may induce aberrant activation of nuclear factor-κB (NF-κB). Our previous study showed that NF-κB confered radioresistance in lymphoma cells. However, whether PERK-eIF2α regulates radioresistance in oropharyngeal carcinoma through NF-κB activation is unknown...
April 18, 2017: Cancer Science
https://www.readbyqxmd.com/read/28416140/ribonucleotide-reductase-requires-subunit-switching-in-hypoxia-to-maintain-dna-replication
#8
Iosifina P Foskolou, Christian Jorgensen, Katarzyna B Leszczynska, Monica M Olcina, Hanna Tarhonskaya, Bauke Haisma, Vincenzo D'Angiolella, William K Myers, Carmen Domene, Emily Flashman, Ester M Hammond
Cells exposed to hypoxia experience replication stress but do not accumulate DNA damage, suggesting sustained DNA replication. Ribonucleotide reductase (RNR) is the only enzyme capable of de novo synthesis of deoxyribonucleotide triphosphates (dNTPs). However, oxygen is an essential cofactor for mammalian RNR (RRM1/RRM2 and RRM1/RRM2B), leading us to question the source of dNTPs in hypoxia. Here, we show that the RRM1/RRM2B enzyme is capable of retaining activity in hypoxia and therefore is favored over RRM1/RRM2 in order to preserve ongoing replication and avoid the accumulation of DNA damage...
April 20, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28415784/misregulation-of-dna-damage-repair-pathways-in-hpv-positive-head-and-neck-squamous-cell-carcinoma-contributes-to-cellular-radiosensitivity
#9
Catherine M Nickson, Parisa Moori, Rachel J Carter, Carlos P Rubbi, Jason L Parsons
Patients with human papillomavirus type 16 (HPV)-associated oropharyngeal squamous cell carcinomas (OPSCC) display increased sensitivity to radiotherapy and improved survival rates in comparison to HPV-negative forms of the disease. However the cellular mechanisms responsible for this characteristic difference are unclear. Here, we have investigated the contribution of DNA damage repair pathways to the in vitro radiosensitivity of OPSCC cell lines. We demonstrate that two HPV-positive OPSCC cells are indeed more radiosensitive than two HPV-negative OPSCC cells, which correlates with reduced efficiency for the repair of ionising radiation (IR)-induced DNA double strand breaks (DSB)...
March 16, 2017: Oncotarget
https://www.readbyqxmd.com/read/28415585/serum-cd166-a-novel-biomarker-for-predicting-nasopharyngeal-carcinoma-response-to-radiotherapy
#10
Huan Lin, Ze-Tan Chen, Xiao-Dong Zhu, Ling Li, Song Qu, Wei Zhao, Fang Su, Jing-Ni Wei, Zhong-Guo Liang, Qi-Yan Mo, Jiang-Bo Wu, Hui-Ling Meng
The present study aimed to identify whether CD166 can be used as a biomarker for predicting the response of nasopharyngeal carcinoma (NPC) to radiotherapy. The serum concentration of CD166 in patients with NPC were detected by enzyme-linked immunosorbent assay. The secreted level of CD166 with radioresistant NPC was significantly higher than that with radiosensitive NPC. In vitro, the CD166 positive rate in the CNE2 cell membrane was significantly lower than that in the CNE2R cell membrane. The magnetic-activated cell sorting technology was used to obtain CNE-2R-CD166(+) and CNE-2R-CD166(-) cell lines...
March 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/28414793/radiosensitizing-effect-of-diosmetin-on-radioresistant-lung-cancer-cells-via-akt-signaling-pathway
#11
Zhijie Xu, Yuanliang Yan, Lingfang Xiao, Shuang Dai, Shuangshuang Zeng, Long Qian, Lin Wang, Xue Yang, Yi Xiao, Zhicheng Gong
Radiotherapy is a powerful tool in the treatment of cancer that has the advantage of preserving normal tissues. However, tumor radioresistance currently remains a major impediment to effective RT. Thus, exploring effective radiation sensitizers is urgently needed. In this study, we have shown that diosmetin, the aglycone of the lavonoid glycoside from olive leaves, citrus fruits and some medicinal herbs, has a promising effect on radiotherapy sensitization. In our results, DIO could induce G1 phase arrest and thus enhance the radiosensitivity of radioresistant A549/IR lung cancer cells...
2017: PloS One
https://www.readbyqxmd.com/read/28410229/in-vivo-evaluation-of-the-effects-of-simultaneous-inhibition-of-glut-1-and-hif-1%C3%AE-by-antisense-oligodeoxynucleotides-on-the-radiosensitivity-of-laryngeal-carcinoma-using-micro-18f-fdg-pet-ct
#12
Li-Fang Shen, Xin Zhao, Shui-Hong Zhou, Zhong-Jie Lu, Kui Zhao, Jun Fan, Min-Li Zhou
PURPOSE: Hypoxia-inducible factor 1α (HIF-1α) and glucose transporter-1 (GLUT-1) are two important hypoxic markers associated with the radioresistance of cancers including laryngeal carcinoma. We evaluated whether the simultaneous inhibition of GLUT-1 and HIF-1α expression improved the radiosensitivity of laryngeal carcinoma. We explored whether the expression of HIF-1α and GLUT-1 was correlated with 2'-deoxy-2'-[18F]fluoro-D-glucose (18F-FDG) uptake and whether 18F-FDG positron emission tomography-computed tomography (PET/CT) was appropriate for early evaluation of the response of laryngeal carcinoma to targeted treatment in vivo...
March 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28402936/lysophosphatidic-acid-lpa-as-a-pro-fibrotic-and-pro-oncogenic-factor-a-pivotal-target-to-improve-the-radiotherapy-therapeutic-index
#13
REVIEW
Chloé Rancoule, Sophie Espenel, Jane-Chloé Trone, Julien Langrand-Escure, Alexis Vallard, Amel Rehailia-Blanchard, Anis El Meddeb Hamrouni, Yaxiong Xia, Jean-Baptiste Guy, Majed Ben-Mrad, Nicolas Magné
Radiation-induced fibrosis is widely considered as a common but forsaken phenomenon that can lead to clinical sequela and possibly vital impairments. Lysophosphatidic acid is a bioactive lipid involved in fibrosis and probably in radiation-induced fibrosis as suggested in recent studies. Lysophosphatidic acid is also a well-described pro-oncogenic factor, involved in carcinogenesis processes (proliferation, survival, angiogenesis, invasion, migration). The present review highlights and summarizes the links between lysophosphatidic acid and radiation-induced fibrosis, lysophosphatidic acid and radioresistance, and proposes lysophosphatidic acid as a potential central actor of the radiotherapy therapeutic index...
March 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28402230/downregulation-of-lncrna-anril-inhibits-proliferation-induces-apoptosis-and-enhances-radiosensitivity-in-nasopharyngeal-carcinoma-cells-through-regulating-mir-125a
#14
Xigang Hu, Huijuan Jiang, Xiaojun Jiang
Increasing evidence demonstrated that long non-coding RNA ANRIL serves as a fatal oncogene in many cancers, including nasopharyngeal carcinoma (NPC). However, little is known whether ANRIL regulated NPC cell radioresistance. Quantitative real-time PCR (qRT-PCR) was performed to examine the expression of lncRNA ANRIL and miR-125a in NPC tissues and cell lines. MTT assay was conducted to measure the cell viability of CNE2 and HONE1 cells. The apoptotic rate of CNE2 and HONE1 cells was determined by flow cytometry analysis...
April 12, 2017: Cancer Biology & Therapy
https://www.readbyqxmd.com/read/28389334/loss-of-dusp3-activity-radiosensitizes-human-tumor-cell-lines-via-attenuation-of-dna-repair-pathways
#15
Thompson E P Torres, Lilian C Russo, Alexsandro Santos, Gabriela R Marques, Yuli T Magalhaes, Sartaj Tabassum, Fabio L Forti
BACKGROUND: Radiotherapy causes the regression of many human tumors by increasing DNA damage, and the novel molecular mechanisms underlying the genomic instability leading to cancer progression and metastasis must be elucidated. Atypical dual-specificity phosphatase 3 (DUSP3) has been shown to down-regulate mitogen-activated protein kinases (MAPKs) to control the proliferation and apoptosis of human cancer cells. We have recently identified novel molecular targets of DUSP3 that function in DNA damage response and repair; however, whether DUSP3 affects these processes remains unknown...
April 4, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28376901/down-regulation-of-lncrna-tug1-enhances-radiosensitivity-in-bladder-cancer-via-suppressing-hmgb1-expression
#16
Huijuan Jiang, Xigang Hu, Hongzhi Zhang, Wenbo Li
BACKGROUND: Long non-coding RNAs (lncRNAs) have been reported to regulate the sensitivity of different cancer cells to chemoradiotherapy. Aberrant expression of lncRNA Taurine-upregulated gene 1 (TUG1) has been found to be involved in the development of bladder cancer, however, its function and underlying mechanism in the radioresistance of bladder cancer remains unclear. METHODS: Quantitative real-time PCR (qRT-PCR) was conducted to measure the expression of TUG1 and HMGB1 mRNA in bladder cancer tissues and cell lines...
April 4, 2017: Radiation Oncology
https://www.readbyqxmd.com/read/28371526/development-of-a-hypoxic-radiosensitizer-prodrug-liposome-delivery-dna-repair-inhibitor-dbait-combination-with-radiotherapy-for-glioma-therapy
#17
Hongmei Liu, Yifan Cai, Yafei Zhang, Yandong Xie, Hui Qiu, Lei Hua, Xuejiao Liu, Yuling Li, Jun Lu, Longzhen Zhang, Rutong Yu
Gliomas are highly radioresistant tumors, mainly due to hypoxia in the core region of the gliomas and efficient DNA double-strand break repair. However, the design of a radiosensitizer incorporating the two above mechanisms is difficult and has rarely been reported. Thus, this study develops a hypoxic radiosensitizer-prodrug liposome (MLP) to deliver the DNA repair inhibitor Dbait (MLP/Dbait) to achieve the simultaneous entry of radiosensitizers with two different mechanisms into the glioma. MLP/Dbait effectively sensitizes glioma cells to X-ray radiotherapy (RT)...
March 30, 2017: Advanced Healthcare Materials
https://www.readbyqxmd.com/read/28367244/mrna-and-methylation-profiling-of-radioresistant-esophageal-cancer-cells-the-involvement-of-sall2-in-acquired-aggressive-phenotypes
#18
Judong Luo, Wenjie Wang, Yiting Tang, Dandan Zhou, Yi Gao, Qi Zhang, Xifa Zhou, Hui Zhu, Ligang Xing, Jinming Yu
Esophageal squamous cell carcinoma (ESCC) is one of the deadliest malignancies worldwide. Radiotherapy plays a critical role in the curative management of inoperable ESCC patients. However, radioresistance restricts the efficacy of radiotherapy for ESCC patients. The molecules involved in radioresistance remain largely unknown, and new approaches to sensitize cells to irradiation are in demand. Technical advances in analysis of mRNA and methylation have enabled the exploration of the etiology of diseases and have the potential to broaden our understanding of the molecular pathways of ESCC radioresistance...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/28362167/adipocyte-secretome-increases-radioresistance-of-malignant-melanocytes-by-improving-cell-survival-and-decreasing-oxidative-status
#19
Pedro Coelho, Liliana Silva, Isabel Faria, Mónica Vieria, Armanda Monteiro, Gabriela Pinto, Cristina Prudêncio, Rúben Fernandes, Raquel Soares
Radiotherapy is a treatment option for the majority of malignancies. However, because melanoma is known to be radioresistant, the use of ionizing radiation as an adjuvant therapy in cutaneous melanoma patients is ineffective. Obesity has now been recognized as a risk factor for melanoma. High adiposity is generally associated with a more pro-oxidative status. Oxidative stress is a major player in radiation therapy and also a common link between obesity and cancer. Several adipocyte-released proteins are known to have a role in controlling cellular growth and pro-survival signaling...
March 31, 2017: Radiation Research
https://www.readbyqxmd.com/read/28360821/combined-ephb2-receptor-knockdown-with-radiation-decreases-cell-viability-and-invasion-in-medulloblastoma
#20
Shilpa Bhatia, Kellen Hirsch, Sanjana Bukkapatnam, Nimrah A Baig, Ayman Oweida, Anastacia Griego, Dylan Calame, Jaspreet Sharma, Andrew Donson, Nicholas Foreman, Christopher Albanese, Sujatha Venkataraman, Rajeev Vibhakar, Sana D Karam
BACKGROUND: Medulloblastoma is one of the most common types of pediatric brain tumor characterized by the subpopulation of cells that exhibit high invasive potential and radioresistant properties. In addition, dysregulated function and signaling by Eph family of receptors have been shown to impart pro-tumorigenic characteristics in this brain malignancy. In the current study, we investigated whether EphB2 knockdown in combination with radiation can alter invasiveness and decrease medulloblastoma tumor growth or viability in vitro...
2017: Cancer Cell International
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