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Autophagy and radioresistance

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https://www.readbyqxmd.com/read/28463025/autophagy-enhanced-the-radioresistance-of-non-small-cell-lung-cancer-by-regulating-ros-level-under-hypoxia-condition
#1
Xiaoyan Chen, Ping Wang, Fei Guo, Xiangdong Wang, Juan Wang, Jinping Xu, Dexiao Yuan, Jianghong Zhang, Chunlin Shao
PURPOSE: Tumor resistance towards radiation has been a big obstacle to patient's poor prognosis of lung cancer. It has been reported that hypoxia and autophagy are contributing to this resistance partly. However, there is controversy over whether autophagy plays positive role in cancer therapy or not. We aim to find out the specific mechanism of radiation resistance. MATERIALS AND METHODS: A549 cells were treated with conditioned medium (CM) under 12h hypoxia or normoxia before irradiation...
May 2, 2017: International Journal of Radiation Biology
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/28342984/hdac4-and-hdac6-sustain-dna-double-strand-break-repair-and-stem-like-phenotype-by-promoting-radioresistance-in-glioblastoma-cells
#4
Francesco Marampon, Francesca Megiorni, Simona Camero, Clara Crescioli, Heather P McDowell, Roberta Sferra, Antonella Vetuschi, Simona Pompili, Luca Ventura, Francesca De Felice, Vincenzo Tombolini, Carlo Dominici, Roberto Maggio, Claudio Festuccia, Giovanni Luca Gravina
The role of histone deacetylase (HDAC) 4 and 6 in glioblastoma (GBM) radioresistance was investigated. We found that tumor samples from 31 GBM patients, who underwent temozolomide and radiotherapy combined treatment, showed HDAC4 and HDAC6 expression in 93.5% and 96.7% of cases, respectively. Retrospective clinical data analysis demonstrated that high-intensity HDAC4 and/or HDAC6 immunostaining was predictive of poor clinical outcome. In vitro experiments revealed that short hairpin RNA-mediated silencing of HDAC4 or HDAC6 radiosensitized U87MG and U251MG GBM cell lines by promoting DNA double-strand break (DSBs) accumulation and by affecting DSBs repair molecular machinery...
March 23, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28302031/hif1a-is-overexpressed-in-medulloblastoma-and-its-inhibition-reduces-proliferation-and-increases-epas1-and-atg16l1-methylation
#5
Gustavo Alencastro Veiga Cruzeiro, Maristella Bergamo Dos Reis, Vanessa Silva Silveira, Régia Caroline Peixoto Lira, Carlos Gilberto Carlotti, Luciano Neder, Ricardo Santos Oliveira, José Andres Yunes, Silvia Regina Brandalise, Simone Aguiar, Agda Karina Eterovic, Luiz Gonzaga Tone, Carlos Alberto Scrideli, Elvis Terci Valera
BACKGROUND: Genetic and epigenetic modifications are closely related to tumor initiation and progression and can provide guidance for understanding tumor functioning, potentially leading to the discovery of new therapies. Studies have associated hypoxia-related genes to tumor progression and chemo/radioresistance in brain tumors. Information on the expression profile of hypoxia-related genes in pediatric medulloblastoma, although scarce, may reveal relevant information that could support treatment decisions...
March 15, 2017: Current Cancer Drug Targets
https://www.readbyqxmd.com/read/28216370/targeting-autophagy-in-cancer-stem-cells-as-an-anticancer-therapy
#6
Yuanyuan Lei, Dan Zhang, Jin Yu, Hui Dong, Jianwei Zhang, Shiming Yang
Cancer stem cells (CSCs), which comprise a small proportion of total cancer cells, have special capacities for self-renewal, differentiation and tumor formation. Currently, CSCs are regarded as the major cause of the failure in anticancer therapy, such as chemoresistance and/or radioresistance, tumor recurrence and metastasis. Autophagy, a process of cellular self-digestion and response to stress, has a role in tumor formation and progression, and it may play a dual role in CSCs-related resistance to anticancer therapy...
May 1, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28134935/egr-1-regulates-irradiation-induced-autophagy-through-atg4b-to-promote-radioresistance-in-hepatocellular-carcinoma-cells
#7
W-X Peng, Y-Y Wan, A-H Gong, L Ge, J Jin, M Xu, C-Y Wu
Although hepatocellular carcinoma (HCC) is usually response to radiation therapy, radioresistance is still the major obstacle that limits the efficacy of radiotherapy for HCC patients. Therefore, further investigation of underlying mechanisms in radioresistant HCC cells is warranted. In this study, we determined the effect of early growth response factor (Egr-1) on irradiation-induced autophagy and radioresistance in HCC cell lines SMMC-7721 and HepG2. We showed that autophagy-related gene 4B (Atg4B) is induced by Egr-1 upon ionizing radiation (IR) in HCC cells...
January 30, 2017: Oncogenesis
https://www.readbyqxmd.com/read/28117625/autophagy-influences-the-low-dose-hyper-radiosensitivity-of-human-lung-adenocarcinoma-cells-by-regulating-mlh1
#8
Qiong Wang, Zhuya Xiao, Zhenyu Lin, Jie Zhou, Weihong Chen, Wuyun Jie, Xing Cao, Zhongyuan Yin, Jing Cheng
Purpose To investigate the impact of autophagy on the low-dose hyper-radiosensitivity (HRS) of human lung adenocarcinoma cells via MLH1 regulation. Materials and methods Immunofluorescent staining, Western blotting, and electron microscopy were utilized to detect autophagy in A549 and H460 cells. shRNA was used to silence MLH1 expression. The levels of MLH1, mTOR, p-mTOR, BNIP3, and Beclin-1 were measured by real-time polymerase chain reaction (PCR) and Western blotting. Results A549 cells, which have low levels of MLH1 expression, displayed HRS/induced radioresistance (IRR)...
January 24, 2017: International Journal of Radiation Biology
https://www.readbyqxmd.com/read/28099922/pafr-selectively-mediates-radioresistance-and-irradiation-induced-autophagy-suppression-in-prostate-cancer-cells
#9
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...
February 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/27793904/pulsed-electromagnetic-field-with-temozolomide-can-elicit-an-epigenetic-pro-apoptotic-effect-on-glioblastoma-t98g-cells
#10
Francesca Pasi, Lorenzo Fassina, Maria Evelina Mognaschi, Giuseppe Lupo, Franco Corbella, Rosanna Nano, Enrica Capelli
Treatment with pulsed electromagnetic fields (PEMFs) is emerging as an interesting therapeutic option for patients with cancer. The literature has demonstrated that low-frequency/low-energy electromagnetic fields do not cause predictable effects on DNA; however, they can epigenetically act on gene expression. The aim of the present work was to study a possible epigenetic effect of a PEMF, mediated by miRNAs, on a human glioblastoma cell line (T98G). We tested a PEMF (maximum magnetic induction, 2 mT; frequency, 75 Hz) that has been demonstrated to induce autophagy in glioblastoma cells...
2016: Anticancer Research
https://www.readbyqxmd.com/read/27708237/proteomic-identification-of-the-lactate-dehydrogenase-a-in-a-radioresistant-prostate-cancer-xenograft-mouse-model-for-improving-radiotherapy
#11
Jingli Hao, Peter Graham, Lei Chang, Jie Ni, Valerie Wasinger, Julia Beretov, Junli Deng, Wei Duan, Joseph Bucci, David Malouf, David Gillatt, Yong Li
Radioresistance is a major challenge for prostate cancer (CaP) metastasis and recurrence after radiotherapy. This study aimed to identify potential protein markers and signaling pathways associated with radioresistance using a PC-3 radioresistant (RR) subcutaneous xenograft mouse model and verify the radiosensitization effect from a selected potential candidate. PC-3RR and PC-3 xenograft tumors were established and differential protein expression profiles from two groups of xenografts were analyzed using liquid chromatography tandem-mass spectrometry...
November 8, 2016: Oncotarget
https://www.readbyqxmd.com/read/27694690/suppression-of-pc-1-prlz-sensitizes-prostate-cancer-cells-to-ionizing-radiation-by-attenuating-dna-damage-repair-and-inducing-autophagic-cell-death
#12
Zeng-Fu Shang, Qiang Wei, Lan Yu, Fang Huang, Bei-Bei Xiao, Hongtao Wang, Man Song, Li Wang, Jianguang Zhou, Jian Wang, Shanhu Li
Radiotherapy is promising and effective for treating prostate cancer but the addition of a tumor cell radiosensitizer would improve therapeutic outcomes. PC-1/PrLZ, a TPD52 protein family member is frequently upregulated in advanced prostate cancer cells and may be a biomarker of aggressive prostate cancer. Therefore, we investigated the potential role of PC-1/PrLZ for increasing radioresistance in human prostate cancer cell lines. Growth curves and survival assays after g-ray irradiation confirmed that depletion of endogenous PC-1/PrLZ significantly increased prostate cancer cell radiosensitivity...
September 20, 2016: Oncotarget
https://www.readbyqxmd.com/read/27644442/chloroquine-an-autophagy-inhibitor-potentiates-the-radiosensitivity-of-glioma-initiating-cells-by-inhibiting-autophagy-and-activating-apoptosis
#13
Hongxing Ye, Mantao Chen, Fei Cao, Hongguang Huang, Renya Zhan, Xiujue Zheng
BACKGROUND: Glioblastoma is refractory to conventional treatment, which is combined of surgery, chemotherapy and radiotherapy. Recent studies have shown that glioma initiating cells (GICs) contribute to tumorigenesis and radioresistance. Recently, other studies showed that the GICs use the autophagy as the major pathway to survive. Chloroquine, an anti-malarial chemical, is an autophagic inhibitor which blocks autophagosome fusion with lysosome and slows down lysosomal acidification. The aim of this study was to explore the mechanisms of chloroquine on the radiosensitivity of GICs...
September 20, 2016: BMC Neurology
https://www.readbyqxmd.com/read/27626497/artesunate-enhances-the-therapeutic-response-of-glioma-cells-to-temozolomide-by-inhibition-of-homologous-recombination-and-senescence
#14
Nancy Berte, Stefanie Lokan, Marcus Eich, Ella Kim, Bernd Kaina
Glioblastoma multiforme (GBM), a malignant brain tumor with a dismal prognosis, shows a high level of chemo- and radioresistance and, therefore, attempts to sensitize glioma cells are highly desired. Here, we addressed the question of whether artesunate (ART), a drug currently used in the treatment of malaria, enhances the killing response of glioblastoma cells to temozolomide (TMZ), which is the first-line therapeutic for GBM. We measured apoptosis, necrosis, autophagy and senescence, and the extent of DNA damage in glioblastoma cells...
October 11, 2016: Oncotarget
https://www.readbyqxmd.com/read/27335774/hypoxia-induced-autophagy-as-an-additional-mechanism-in-human-osteosarcoma-radioresistance
#15
Helin Feng, Jin Wang, Wei Chen, Baoen Shan, Yin Guo, Jianfa Xu, Ling Wang, Peng Guo, Yingze Zhang
Osteosarcoma (OS) responds poorly to radiotherapy, but the mechanism is unclear. We found OS tumor tissues expressed high level of protein HIF-1α, a common biological marker indicative of hypoxia. It is known that hypoxic cells are generally radioresistant because of reduced production of irradiation-induced DNA-damaging reactive oxygen species (ROS) in the anaerobic condition. Here we report another mechanism how hypoxia induces radioresistance. In MG-63 human osteosarcoma cells, hypoxic pretreatment increased the cellular survival in irradiation...
June 2016: Journal of Bone Oncology
https://www.readbyqxmd.com/read/27327120/hypoxia-responsive-mir-301a-and-mir-301b-promote-radioresistance-of-prostate-cancer-cells-via-downregulating-ndrg2
#16
Wei Wang, Mingbo Liu, Yawei Guan, Qingwu Wu
BACKGROUND MiR-301a and miR-301b are 2 oncomiRs involved in multiple types of cancer. In this study, we explored the expression change of miR-301a and miR-301b in prostate cancer cells in hypoxia and studied their regulation of autophagy and radiosensitivity of prostate cancer cells. MATERIAL AND METHODS QRT-PCR was performed to quantify the expression change of miR-301a and miR-301b in hypoxia. Their effects on autophagy were measured by Western blot analysis, and their effects on radiosensitivity were measured by clonogenic assay and flow cytometry...
June 21, 2016: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/27220494/mir-21-modulates-radiosensitivity-of-cervical-cancer-through-inhibiting-autophagy-via-the-pten-akt-hif-1%C3%AE-feedback-loop-and-the-akt-mtor-signaling-pathway
#17
Lili Song, Shikai Liu, Liang Zhang, Hairong Yao, Fangyuan Gao, Dongkui Xu, Qian Li
MiR-21 is an important microRNA (miRNA) modulating radiosensitivity of cervical cancer cells. However, the underlying mechanism of miR-21 upregulation in radioresistant cervical cancer has not been fully understood. In addition, autophagy may either promote or alleviate radioresistance, depending on the types of cancer and tumor microenvironment. How autophagy affects radiosensitivity in cervical cancer and how miR-21 is involved in this process has not been reported. This study showed that miR-21 upregulation in radioresistant cervical cancer is related to HIF-1α overexpression...
September 2016: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/27199567/stathmin1-increases-radioresistance-by-enhancing-autophagy-in-non-small-cell-lung-cancer-cells
#18
Xi Zhang, Jingfen Ji, Yu Yang, Juan Zhang, Liangfang Shen
Radioresistance has been demonstrated to be involved in the poor prognosis of patients with non-small-cell lung cancer (NSCLC). However, the underlying mechanism remains largely unclear. Investigation on special therapeutic targets associated with radioresistance shows promises for the enhancement of clinical radiotherapy effect toward NSCLC. This study aimed to reveal the role of Stathmin1 (STMN1) in radioresistance in NSCLC as well as the underlying mechanism. Our data showed that the protein levels of STMN1 were significantly upregulated in NSCLC cells subjected to radiation, accompanied with the activation of autophagy...
2016: OncoTargets and Therapy
https://www.readbyqxmd.com/read/27135967/different-roles-of-chop-and-jnk-in-mediating-radiation-induced-autophagy-and-apoptosis-in-breast-cancer-cells
#19
Feifei Li, Xiaogang Zheng, Yan Liu, Ping Li, Xiongxiong Liu, Fei Ye, Ting Zhao, Qingfeng Wu, Xiaodong Jin, Qiang Li
Unfolded protein response (UPR) is comprised of complex and conserved stress pathways that function as a short-term adaptive mechanism to reduce levels of unfolded or misfolded proteins and maintain homeostasis in the endoplasmic reticulum (ER). UPR can be triggered by prolonged or persistent ER stress under many physiological or pathological conditions, including radiation exposure. Radiation-induced ER stress elicits autophagy and apoptosis in cancer cells, where C/EBP homologous protein (CHOP) and c-Jun NH2-terminal kinase (JNK) may play crucial roles...
May 2016: Radiation Research
https://www.readbyqxmd.com/read/27109915/radiation-induced-autophagy-promotes-esophageal-squamous-cell-carcinoma-cell-survival-via-the-lkb1-pathway
#20
Chi Lu, Conghua Xie
Radiotherapy is an important treatment modality for esophageal cancer; however, the clinical efficacy of radiotherapy is limited by tumor radioresistance. In the present study, we explored the hypothesis that radiation induces tumor cell autophagy as a cytoprotective adaptive response, which depends on liver kinase B1 (LKB1) also known as serine/threonine kinase 11 (STK11). Radiation-induced Eca-109 cell autophagy was found to be dependent on signaling through the LKB1 pathway, and autophagy inhibitors that disrupted radiation-induced Eca-109 cell autophagy increased cell cycle arrest and cell death in vitro...
June 2016: Oncology Reports
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