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Cancer and radioresistance

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https://www.readbyqxmd.com/read/27935117/long-noncoding-rna-malat1-affects-the-efficacy-of-radiotherapy-for-esophageal-squamous-cell-carcinoma-by-regulating-cks1-expression
#1
Zhijun Li, Yang Zhou, Bo Tu, Yu Bu, Aqiu Liu, Conghua Xie
OBJECTIVE: Long noncoding RNA MALAT1 has been well-studied in the progression of many malignancies. However, its association with the radioresistance of tumors has not been well-understood yet. This study tried to explore the role of MALAT1 in regulating the radiosensitivity of esophageal cancer (EC), especially esophageal squamous cell carcinoma (ESCC), involving its regulation on Cks1 expression. METHODS: KYSE150 cells were subcutaneously inoculated into nude mice to establish ESCC xenografts...
December 9, 2016: Journal of Oral Pathology & Medicine
https://www.readbyqxmd.com/read/27926533/andrographolide-impedes-cancer-stemness-and-enhances-radio-sensitivity-in-oral-carcinomas-via-mir-218-activation
#2
Po-Yu Yang, Pei-Ling Hsieh, Tong Hong Wang, Cheng-Chia Yu, Ming-Yi Lu, Yi-Wen Liao, Tzu-Hsin Lee, Chih-Yu Peng
Current evidence suggests that oral cancer stem cells (OCSCs) possess high tumorigenic and metastatic properties as well as chemo- and radioresistance. In this study, we demonstrated that andrographolide, the main bioactive component in the medicinal plant Andrographis, significantly reduced oncogenicity and restored radio-sensitivity of ALDH1+CD44+ OCSCs. Mechanistic studies showed that andrographolide treatment increased the expression of microRNA-218 (miR-218), leading to the downregulation of Bmi1. We showed that knockdown of miR-218 in ALDH1-CD44- non-OCSCs enhanced cancer stemness, while silencing of Bmi1 significantly counteracted it...
December 1, 2016: Oncotarget
https://www.readbyqxmd.com/read/27913065/hpv-status-cancer-stem-cell-marker-expression-hypoxia-gene-signatures-and-tumour-volume-identify-good-prognosis-subgroups-in-patients-with-hnscc-after-primary-radiochemotherapy-a-multicentre-retrospective-study-of-the-german-cancer-consortium-radiation-oncology
#3
Annett Linge, Fabian Lohaus, Steffen Löck, Alexander Nowak, Volker Gudziol, Chiara Valentini, Cläre von Neubeck, Martin Jütz, Inge Tinhofer, Volker Budach, Ali Sak, Martin Stuschke, Panagiotis Balermpas, Claus Rödel, Anca-Ligia Grosu, Amir Abdollahi, Jürgen Debus, Ute Ganswindt, Claus Belka, Steffi Pigorsch, Stephanie E Combs, David Mönnich, Daniel Zips, Frank Buchholz, Daniela E Aust, Gustavo B Baretton, Howard D Thames, Anna Dubrovska, Jan Alsner, Jens Overgaard, Mechthild Krause, Michael Baumann
OBJECTIVE: To investigate the impact of the tumour volume, HPV status, cancer stem cell (CSC) marker expression and hypoxia gene signatures, as potential markers of radiobiological mechanisms of radioresistance, in a contemporary cohort of patients with locally advanced head and neck squamous cell carcinoma (HNSCC), who received primary radiochemotherapy (RCTx). MATERIALS AND METHODS: For 158 patients with locally advanced HNSCC of the oral cavity, oropharynx or hypopharynx who were treated at six DKTK partner sites, the impact of tumour volume, HPV DNA, p16 overexpression, p53 expression, CSC marker expression and hypoxia-associated gene signatures on outcome of primary RCTx was retrospectively analyzed...
November 29, 2016: Radiotherapy and Oncology: Journal of the European Society for Therapeutic Radiology and Oncology
https://www.readbyqxmd.com/read/27910734/targeting-the-akt-cyclin-d1-pathway-to-overcome-intrinsic-and-acquired-radioresistance-of-tumors-for-effective-radiotherapy
#4
Tsutomu Shimura
PURPOSE: Radiotherapy (RT) is a powerful tool in the treatment of cancer, having the advantage of preserving normal tissues. Clinical outcomes of RT are significantly improved by technological advances, enabling increased radiation doses directed very specifically to a tumor. However, tumor radioresistance remains a major impediment to effective RT. We have shown that human tumor cells surviving after repeated exposure to fractionated radiation (FR) of X-rays for 1 month have acquired radioresistance through constitutive activation of AKT and downstream cyclin D1 nuclear retention...
December 2, 2016: International Journal of Radiation Biology
https://www.readbyqxmd.com/read/27903972/gdf15-contributes-to-radioresistance-and-cancer-stemness-of-head-and-neck-cancer-by-regulating-cellular-reactive-oxygen-species-via-a-smad-associated-signaling-pathway
#5
Yan-Liang Li, Joseph T Chang, Li-Yu Lee, Kang-Hsing Fan, Ya-Ching Lu, Yi-Chen Li, Chang-Hsu Chiang, Guo-Rung You, Hsin-Ying Chen, Ann-Joy Cheng
Radiotherapy is an integral part for the treatment of head and neck cancer (HNC), while radioresistance is a major cause leads to treatment failure. GDF15, a member of the TGF-β superfamily, is hypothesized to participate in various types of homeostasis. However, the potential role of this molecule in regulation of radiosensitivity remains unclear. In this study, we demonstrated that GDF15 contributed to radioresistance of HNC, as determined by both gain- and lost-of-functional experiments. These results were achieved by the induction of mitochondrial membrane potential and suppression of intracellular reactive oxygen species (ROS)...
November 26, 2016: Oncotarget
https://www.readbyqxmd.com/read/27902466/long-non-coding-rna-urothelial-carcinoma-associated-1-uca1-mediates-radiation-response-in-prostate-cancer
#6
Alireza Fotouhi Ghiam, Samira Taeb, Xiaoyong Huang, Vincent Huang, Jessica Ray, Seville Scarcello, Christianne Hoey, Sahar Jahangiri, Emmanouil Fokas, Andrew Loblaw, Robert G Bristow, Danny Vesprini, Paul Boutros, Stanley K Liu
Radioresistance remains a significant obstacle in the treatment of Prostate Cancer (PCa). To simulate the clinical scenario of irradiation resistance (IRR), we created DU145-IRR PCa cell lines by treatment with 2 Gy daily IR for 59 fractions. DU145-IRR cells acquired an aggressive phenotype as evidenced by increased clonogenic survival, tumorigenic potential and invasiveness. We performed transcriptome profiling to discover dysregulated genes in DU145-IRR cells and identified the long non-coding RNA (lncRNA), Urothelial carcinoma-associated 1 (UCA1)...
November 24, 2016: Oncotarget
https://www.readbyqxmd.com/read/27899964/radiation-induces-the-generation-of-cancer-stem-cells-a-novel-mechanism-for-cancer-radioresistance
#7
Fengsheng Li, Kunming Zhou, Ling Gao, Bin Zhang, Wei Li, Weijuan Yan, Xiujun Song, Huijie Yu, Sinian Wang, Nan Yu, Qisheng Jiang
Radioresistance remains a major obstacle for the radiotherapy treatment of cancer. Previous studies have demonstrated that the radioresistance of cancer is due to the existence of intrinsic cancer stem cells (CSCs), which represent a small, but radioresistant cell subpopulation that exist in heterogeneous tumors. By contrast, non-stem cancer cells are considered to be radiosensitive and thus, easy to kill. However, recent studies have revealed that under conditions of radiation-induced stress, theoretically radiosensitive non-stem cancer cells may undergo dedifferentiation subsequently obtaining the phenotypes and functions of CSCs, including high resistance to radiotherapy, which indicates that radiation may directly result in the generation of novel CSCs from non-stem cancer cells...
November 2016: Oncology Letters
https://www.readbyqxmd.com/read/27898411/radioprotective-effects-of-heat-killed-mycobacterium-tuberculosis-in-cultured-cells-and-radiosensitive-tissues
#8
Yuanyuan Chen, Yang Xu, Jicong Du, Jiaming Guo, Xiao Lei, Jianguo Cui, Cong Liu, Ying Cheng, Bailong Li, Fu Gao, Jintao Ju, Jianming Cai, Yanyong Yang
BACKGROUND: Exposure to ionizing radiation (IR) often causes severe damage to radiosensitive tissues, which limits the use of radiotherapy in cancer patients. Novel safe and effective radioprotectant is urgently required. It has been reported toll like receptor 2 (TLR2) plays a critical role in radioresistance. In this study, we demonstrated the protective effects of Heat-Killed Mycobacterium tuberculosis (HKMT), a potent TLR2 agonist, against IR. METHODS: Cell survival and apoptosis were determined by CCK-8 assay and Annexin V assay, respectively...
November 30, 2016: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/27877235/x-ray-induced-photodynamic-therapy-a-combination-of-radiotherapy-and-photodynamic-therapy
#9
Geoffrey D Wang, Ha T Nguyen, Hongmin Chen, Phillip B Cox, Lianchun Wang, Koichi Nagata, Zhonglin Hao, Andrew Wang, Zibo Li, Jin Xie
Conventional photodynamic therapy (PDT)'s clinical application is limited by depth of penetration by light. To address the issue, we have recently developed X-ray induced photodynamic therapy (X-PDT) which utilizes X-ray as an energy source to activate a PDT process. In addition to breaking the shallow tissue penetration dogma, our studies found more efficient tumor cell killing with X-PDT than with radiotherapy (RT) alone. The mechanisms behind the cytotoxicity, however, have not been elucidated. In the present study, we investigate the mechanisms of action of X-PDT on cancer cells...
2016: Theranostics
https://www.readbyqxmd.com/read/27871924/mir-335-regulates-the-chemo-radioresistance-of-small-cell-lung-cancer-cells-by-targeting-parp-1
#10
Yingshan Luo, Lihua Tong, Hui Meng, Weiliang Zhu, Linlang Guo, Ting Wei, Jian Zhang
The role of miR-335 in the regulation of chemosensitivity and radiosensitivity of small cell lung cancer (SCLC) was investigated. miR-335 was significantly downregulated in multi-drug-resistant SCLC H69AR and H446DDP cells compared with parental cells as detected by qRT-PCR. Then, we demonstrated the negative correlation between miR-335 expression and the chemo-radiosensitivity of SCLC cells, including cell proliferation, cell clonality and cell apoptosis. In addition, miR-335 overexpression inhibited cell migration in vitro and tumor growth in vivo, whereas inhibition of miR-335 promoted cell migration and tumor growth...
November 18, 2016: Gene
https://www.readbyqxmd.com/read/27847320/inhibition-of-cdk9-induces-apoptosis-and-potentiates-the-effect-of-cisplatin-in-hypopharyngeal-carcinoma-cells
#11
Shengda Cao, Yingyi Yu, Shangren Chen, Dapeng Lei, Shudong Wang, Xinliang Pan, Jun Peng
Myeloid cell leukemia-1 (Mcl-1) plays an important role in survival, chemo- and radioresistance of head and neck squamous cell carcinoma (HNSCC). Cyclin-dependent kinase 9/cyclin T (CDK9) promotes excessive production of multiple pro-survival proteins including Mcl-1, leading to impaired apoptosis of cancer cells. As such, CDK9 is an emerging therapeutic target in cancer therapy. We herein report the first study of targeting CDK9 as a treatment strategy for hypopharyngeal squamous cell carcinoma (HSCC), an aggressive malignancy associated with one of the worst prognoses within HNSCC...
November 12, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27834104/upregulating-dab2ip-expression-via-egr-1-inhibition-a-new-approach-for-overcoming-fractionated-irradiation-induced-cross-tolerance-to-ionizing-radiation-and-mitomycin-c-in-tumor-cells
#12
Rulve Chang, Hui He, Guangmin Mao, Zhaolu Kong
PURPOSE: In this study, we evaluated the effect of fractionated irradiation (FI) on tumor cells sensitivity to ionizing radiation (IR) and antineoplastic drugs, and examined the potential of early growth response-1 (EGR-1) inhibition to sensitize tumor cells to IR. MATERIALS AND METHODS: PC3 and HepG2 cells were subjected to γ-rays at 2 Gy for ten times. Survived cells were named PC3/R and HepG2/R, respectively. Cells sensitivity to irradiation and chemotherapeutic drugs, including cisplatin (PT), doxorubicin (DOX), mitomycin C (MMC) and 5-fluorouracil (5-FU) were identified by colony formation assay and MMT method, respectively...
November 11, 2016: International Journal of Radiation Biology
https://www.readbyqxmd.com/read/27824512/hypoxia-a-double-edged-sword-in-cancer-therapy
#13
Hamed Manoochehri Khoshinani, Saeid Afshar, Rezvan Najafi
Hypoxia is a common feature of malignant tumors. There is an interactive connection between hypoxia and chemoresistance, radioresistance, invasiveness, and angiogenesis. Therefore, tumor hypoxia has been considered as a validated target for treating cancer. This review focuses on the role of hypoxia on chemoresistance and radioresistance. In addition, we address several approaches targeting tumor hypoxia, known as hypoxia-targeted therapy.
November 25, 2016: Cancer Investigation
https://www.readbyqxmd.com/read/27815359/antibody-targeting-grp78-enhances-the-efficacy-of-radiation-therapy-in-human-glioblastoma-and-non-small-cell-lung-cancer-cell-lines-and-tumor-models
#14
David Ya Dadey, Vaishali Kapoor, Kelly Hoye, Arpine Khudanyan, Andrea Collins, Dinesh Thotala, Dennis E Hallahan
PURPOSE: Non-small-cell lung cancer (NSCLC) and glioblastoma multiforme (GBM) have poor median survival. NSCLC and GBM overexpress glucose regulated protein 78 (GRP78), which has a role in radioresistance and recurrence. In this study, we determined the effect of anti-GRP78 antibody and the combined effect of the anti-GRP78 antibody with ionizing radiation (XRT) on NSCLC and GBM cell lines both in vitro and in vivo. EXPERIMENTAL DESIGN: NSCLC and GBM cancer cell lines were treated with anti-GRP78 antibodies and evaluated for proliferation, colony formation, cell death and PI3K/Akt/mTOR signaling...
November 4, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/27793904/pulsed-electromagnetic-field-with-temozolomide-can-elicit-an-epigenetic-pro-apoptotic-effect-on-glioblastoma-t98g-cells
#15
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...
November 2016: Anticancer Research
https://www.readbyqxmd.com/read/27788958/upregulation-of-long-noncoding-rna-small-nucleolar-rna-host-gene-18-promotes-radioresistance-of-glioma-by-repressing-semaphorin-5a
#16
Rong Zheng, Qiwei Yao, Chen Ren, Ying Liu, Hongli Yang, Guozhu Xie, Shasha Du, Kaijun Yang, Yawei Yuan
PURPOSE: Although increasing evidence has shown that long noncoding RNAs play an important regulatory role in carcinogenesis and tumor progression, little is known about the role of small nucleolar RNA host gene 18 (SNHG18) in cancer. The goal of this study was to investigate the expression of SNHG18 and its clinical significance in glioma. METHODS AND MATERIALS: Differences in the lncRNA expression profile between M059K and M059J cells were assessed by lncRNA expression microarray analysis...
November 15, 2016: International Journal of Radiation Oncology, Biology, Physics
https://www.readbyqxmd.com/read/27779109/methylation-of-promoter-of-rbl1-enhances-the-radioresistance-of-three-dimensional-cultured-carcinoma-cells
#17
Dong Pan, Yaxiong Chen, Yarong Du, Zhenxin Ren, Xiaoman Li, Burong Hu
Three dimensional (3D) culture in vitro is a new cell culture model that more closely mimics the physiology features of the in vivo environment and is being used widely in the field of medical and biological research. It has been demonstrated that cancer cells cultured in 3D matrices are more radioresistant compared with cells in monolayer (2D). However, the mechanisms causing this difference remain largely unclear. Here we found that the cell cycle distribution and expression of cell cycle regulation genes in 3D A549 cells are different from the 2D...
October 13, 2016: Oncotarget
https://www.readbyqxmd.com/read/27769049/mir-424-acts-as-a-tumor-radiosensitizer-by-targeting-aprataxin-in-cervical-cancer
#18
Xia Wang, Qing Li, Hua Jin, Hua Zou, Wei Xia, Nan Dai, Xiao-Yan Dai, Dong Wang, Cheng-Xiong Xu, Yi Qing
Previous studies have shown that some dysregulated miRNAs are involved in radioresistance of tumor cells. Here, we identified significantly decreased miR-424 expression in radioresistant cervical cancer cells and specimens from cervical cancer patients with radioresistance compared to their radiosensitive parental cells and specimens from radiosensitive patients, respectively. Ectopic expression of miR-424 significantly increased radiation-induced DNA damage, cell apoptosis and G2/M cell cycle arrest in radioresistant cervical cancer cells...
October 18, 2016: Oncotarget
https://www.readbyqxmd.com/read/27757426/tie2-mediated-tyrosine-phosphorylation-of-h4-regulates-dna-damage-response-by-recruiting-abl1
#19
Mohammad B Hossain, Rehnuma Shifat, David G Johnson, Mark T Bedford, Konrad R Gabrusiewicz, Nahir Cortes-Santiago, Xuemei Luo, Zhimin Lu, Ravesanker Ezhilarasan, Erik P Sulman, Hong Jiang, Shawn S C Li, Frederick F Lang, Jessica Tyler, Mien-Chie Hung, Juan Fueyo, Candelaria Gomez-Manzano
DNA repair pathways enable cancer cells to survive DNA damage induced after genotoxic therapies. Tyrosine kinase receptors (TKRs) have been reported as regulators of the DNA repair machinery. TIE2 is a TKR overexpressed in human gliomas at levels that correlate with the degree of increasing malignancy. Following ionizing radiation, TIE2 translocates to the nucleus, conferring cells with an enhanced nonhomologous end-joining mechanism of DNA repair that results in a radioresistant phenotype. Nuclear TIE2 binds to key components of DNA repair and phosphorylates H4 at tyrosine 51, which, in turn, is recognized by the proto-oncogene ABL1, indicating a role for nuclear TIE2 as a sensor for genotoxic stress by action as a histone modifier...
April 2016: Science Advances
https://www.readbyqxmd.com/read/27752766/kca3-1-ik-modulates-pancreatic-cancer-cell-migration-invasion-and-proliferation-anomalous-effects-on-tram-34
#20
B Bonito, D R P Sauter, A Schwab, M B A Djamgoz, I Novak
In the recent decades, ion channels became the focus of cancer biologists, as many channels are overexpressed in tumour tissue and functionally they are linked to abnormal cell behaviour with processes including apoptosis, chemo- and radioresistance, proliferation and migration. KCa3.1 is a Ca(2+)-activated K(+) channel that plays a central role in tumour progression in many cancer types. Therefore, the aim of the present study was to investigate KCa3.1 expression in pancreatic cancer cells and assess possible implications to disease progression...
November 2016: Pflügers Archiv: European Journal of Physiology
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