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Cancer and radioresistance

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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/28427525/precision-medicine-for-early-breast-cancer-radiotherapy-opening-up-new-horizons
#2
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
#3
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/28416140/ribonucleotide-reductase-requires-subunit-switching-in-hypoxia-to-maintain-dna-replication
#4
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/28414793/radiosensitizing-effect-of-diosmetin-on-radioresistant-lung-cancer-cells-via-akt-signaling-pathway
#5
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
#6
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/28402230/downregulation-of-lncrna-anril-inhibits-proliferation-induces-apoptosis-and-enhances-radiosensitivity-in-nasopharyngeal-carcinoma-cells-through-regulating-mir-125a
#7
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
#8
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
#9
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/28367244/mrna-and-methylation-profiling-of-radioresistant-esophageal-cancer-cells-the-involvement-of-sall2-in-acquired-aggressive-phenotypes
#10
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
#11
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/28358668/evolution-of-18-f-fluorodeoxyglucose-and-18-f-fluoroazomycin-arabinoside-pet-uptake-distributions-in-lung-tumours-during-radiation-therapy
#12
Dario Di Perri, John A Lee, Anne Bol, François-Xavier Hanin, Guillaume Janssens, Daniel Labar, Annie Robert, Edmond Sterpin, Xavier Geets
BACKGROUND: Dose painting (DP) aims to improve radiation therapy (RT) outcome by targeting radioresistant tumour regions identified through functional imaging, e.g., positron emission tomography (PET). Importantly, the expected benefit of DP relies on the ability of PET imaging to identify tumour areas which could be consistently targeted throughout the treatment. In this study, we analysed the spatial stability of two potential DP targets in lung cancer patients undergoing RT: the tumour burden surrogate [(18)F]fluorodeoxyglucose (FDG) and the hypoxia surrogate [(18)F]fluoroazomycin arabinoside (FAZA)...
April 2017: Acta Oncologica
https://www.readbyqxmd.com/read/28356955/ursolic-acid-sensitizes-radioresistant-nsclc-cells-expressing-hif-1%C3%AE-through-reducing-endogenous-gsh-and-inhibiting-hif-1%C3%AE
#13
Bing Song, Qian Zhang, Maohu Yu, Xinrong Qi, Gang Wang, Linlin Xiao, Qiyi Yi, Wensen Jin
In previous studies, the present authors demonstrated that effective sensitization of ionizing radiation-induced death of tumor cells, including non-small cell lung cancer (NSCLC) cells, could be produced by oleanolic acid (OA), a pentacyclic triterpenoid present in plants. In the present study, it was investigated whether ursolic acid (UA), an isomer of OA, had also the capacity of sensitizing radioresistant NSCLC cells. The radioresistant cell line H1299/M-hypoxia inducible factor-1α (HIF-1α) was established by transfection with a recombinant plasmid expressing mutant HIF-1α (M-HIF-1α)...
February 2017: Oncology Letters
https://www.readbyqxmd.com/read/28351566/micrornas-in-human-tongue-squamous-cell-carcinoma-from-pathogenesis-to-therapeutic-implications
#14
REVIEW
Omer Faruk Karatas, Muhammet Oner, Alican Abay, Ali Diyapoglu
Being one of the most aggressive cancers of oral cavity, tongue squamous cell carcinoma (TSCC) constitutes 41% of all oral carcinomas. Despite considerable improvements in multimodal diagnosis and treatment techniques, TSCC still remains to be one of the most lethal cancer types in the head and neck region. MicroRNAs are endogenously synthesized, small, non-coding RNAs, which are responsible for post-transcriptional regulation of mRNA expression. They are involved in regulation of almost all biological processes through their spatial and temporal expression...
April 2017: Oral Oncology
https://www.readbyqxmd.com/read/28351325/intracellular-calcium-promotes-radioresistance-of-non-small-cell-lung-cancer-a549-cells-through-activating-akt-signaling
#15
Yiling Wang, Jiantao He, Shenghui Zhang, Qingbo Yang
Radiotherapy is a major therapeutic approach in non-small cell lung cancer but is restricted by radioresistance. Although Akt signaling promotes radioresistance in non-small cell lung cancer, it is not well understood how Akt signaling is activated. Since intracellular calcium (Ca(2+)) could activate Akt in A549 cells, we investigated the relationship between intracellular calcium (Ca(2+)) and Akt signaling in radioresistant A549 cells by establishing radioresistant non-small cell lung cancer A549 cells. The radioresistant cell line A549 was generated by dose-gradient irradiation of the parental A549 cells...
March 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28349820/efficient-killing-of-radioresistant-breast-cancer-cells-by-cytokine-induced-killer-cells
#16
Qingming Guo, Danni Zhu, Xiaocui Bu, Xiaofang Wei, Changyou Li, Daiqing Gao, Xiaoqiang Wei, Xuezhen Ma, Peng Zhao
Recurrence of breast cancer after radiotherapy may be partly explained by the presence of radioresistant cells. Thus, it would be desirable to develop an effective therapy against radioresistant cells. In this study, we demonstrated the intense antitumor activity of cytokine-induced killer cells against MCF-7 and radioresistant MCF-7 cells, as revealed by cytokine-induced killer-mediated cytotoxicity, tumor cell proliferation, and tumor invasion. Radioresistant MCF-7 cells were more susceptible to cytokine-induced killer cell killing...
March 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28345453/tumor-suppressor-mir-29c-regulates-radioresistance-in-lung-cancer-cells
#17
Elena Arechaga-Ocampo, Cesar Lopez-Camarillo, Nicolas Villegas-Sepulveda, Claudia H Gonzalez-De la Rosa, Isidro X Perez-Añorve, Reynalda Roldan-Perez, Ali Flores-Perez, Omar Peña-Curiel, Oscar Angeles-Zaragoza, Rosalva Rangel Corona, Juan A Gonzalez-Barrios, Raul Bonilla-Moreno, Oscar Del Moral-Hernandez, Luis A Herrera, Alejandro Garcia-Carranca
Radiotherapy is an important treatment option for non-small cell lung carcinoma patients. Despite the appropriate use of radiotherapy, radioresistance is a biological behavior of cancer cells that limits the efficacy of this treatment. Deregulation of microRNAs contributes to the molecular mechanism underlying resistance to radiotherapy in cancer cells. Although the functional roles of microRNAs have been well described in lung cancer, their functional roles in radioresistance are largely unclear. In this study, we established a non-small cell lung carcinoma Calu-1 radioresistant cell line by continuous exposure to therapeutic doses of ionizing radiation as a model to investigate radioresistance-associated microRNAs...
March 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28344198/radiosensitizing-effect-of-p2x7-receptor-antagonist-on-melanoma-in-vitro-and-in-vivo
#18
Keisuke Tanamachi, Keisuke Nishino, Natsuki Mori, Toshihiro Suzuki, Sei-Ichi Tanuma, Ryo Abe, Mitsutoshi Tsukimoto
Melanoma is highly malignant, and generally exhibits radioresistance, responding poorly to radiation therapy. We previously reported that activation of P2X7, P2Y6, and P2Y12 receptors is involved in the DNA damage response after γ-irradiation of human lung adenocarcinoma A549 cells. However, it is not clear whether these receptors are also involved in the case of melanoma cells, although P2X7 receptor is highly expressed in various cancers, including melanoma. Here, we show that P2X7 receptor antagonist enhances radiation-induced cytotoxicity in B16 melanoma cells in vitro and in vivo...
March 24, 2017: Biological & Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/28339028/2-methoxyestradiol-enhances-radiosensitivity-in-radioresistant-melanoma-mda-mb-435r-cells-by-regulating-glycolysis-via-hif-1%C3%AE-pdk1-axis
#19
Hong Zhao, Huangang Jiang, Zheng Li, Yafei Zhuang, Yinyin Liu, Shuliang Zhou, Youde Xiao, Conghua Xie, Fuxiang Zhou, Yunfeng Zhou
HIF-1α overexpression is associated with radio-resistance of various cancers. A radioresistant human melanoma cell model MDA-MB-435R (435R) was established by us previously. Compared with the parental cells MDA-MB‑435 (435S), an elevated level of HIF-1α expression in 435R cells was demonstrated in our recent experiments. Therefore, in the current study, we sought to determine whether selective HIF-1α inhibitors could radiosensitize the 435R cells to X-ray, and to identify the potential mechanisms. Our data demonstrated that inhibition of HIF-1α with 2-methoxyestradiol (2-MeOE2) significantly enhanced radiosensitivity of 435R cells...
March 22, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28327297/first-proof-of-bismuth-oxide-nanoparticles-as-efficient-radiosensitisers-on-highly-radioresistant-cancer-cells
#20
Callum Stewart, Konstantin Konstantinov, Sally McKinnon, Susanna Guatelli, Michael Lerch, Anatoly Rosenfeld, Moeava Tehei, Stéphanie Corde
This study provides the first proof of the novel application of bismuth oxide as a radiosensitiser. It was shown that on the highly radioresistant 9L gliosarcoma cell line, bismuth oxide nanoparticles sensitise to both kilovoltage (kVp) or megavoltage (MV) X-rays radiation. 9L cells were exposed to a concentration of 50μg.mL(-1) of nanoparticle before irradiation at 125kVp and 10MV. Sensitisation enhancement ratios of 1.48 and 1.25 for 125kVp and 10MV were obtained in vitro, respectively. The radiation enhancement of the nanoparticles is postulated to be a combination of the high Z nature of the bismuth (Z=83), and the surface chemistry...
November 2016: Physica Medica: PM
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