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Cancer and radioresistance

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https://www.readbyqxmd.com/read/29042418/socs1-gene-therapy-improves-radiosensitivity-and-enhances-irradiation-induced-dna-damage-in-esophageal-squamous-cell-carcinoma
#1
Takahito Sugase, Tsuyoshi Takahashi, Satoshi Serada, Minoru Fujimoto, Kosuke Hiramatsu, Tomoharu Ohkawara, Koji Tanaka, Yasuhiro Miyazaki, Tomoki Makino, Yukinori Kurokawa, Makoto Yamasaki, Kiyokazu Nakajima, Tadamitsu Kishimoto, Masaki Mori, Yuichiro Doki, Tetsuji Naka
STAT3 has been implicated recently in radioresistance in cancer. In this study, we investigated the association between STAT3 and radioresistance in esophageal squamous cell carcinoma (ESCC). Strong expression of activated phospho-STAT3 (p-STAT3) was observed in 16/22 ESCC patients with preoperative chemoradiotherapy (CRT), compared to 9/24 patients with surgery alone, where the prognosis of those with CRT was poor. Expression of p-STAT3 and the anti-apoptotic proteins Mcl-1 and survivin was strongly induced in ESCC cells by irradiation...
October 17, 2017: Cancer Research
https://www.readbyqxmd.com/read/29039578/the-foxm1-bub1b-signaling-pathway-is-essential-for-the-tumorigenicity-and-radioresistance-of-glioblastoma
#2
Qing Ma, Yanmei Liu, Liang Shang, Jiao Yu, Qiumin Qu
Accumulating evidence indicates that mitotic checkpoint serine/threonine kinase B (BUB1B) plays a critical role in multiple types of cancer. However, the biological function and molecular regulatory mechanism of BUB1B in glioblastoma (GBM) remain unclear. In the present study, we identified that BUB1B expression was enriched in GBM tumors and was functionally required for tumor proliferation both in vitro and in vivo. Clinically, BUB1B expression was associated with poor prognosis in GBM patients and BUB1B‑dependent radioresistance in GBM was decreased by targeting BUB1B via shRNAs...
October 12, 2017: Oncology Reports
https://www.readbyqxmd.com/read/29036263/effects-of-12c6-heavy-ion-beam-irradiation-on-the-p53-signaling-pathway-in-hepg2-liver-cancer-cells
#3
Kai Liu, Xinke Zhao, Jing Gu, Jianjun Wu, Hong Zhang, Yingdong Li
The heavy ion beam is considered to be the ideal source for radiotherapy. The p53 tumor suppressor gene senses DNA damage and transducts intracellular apoptosis signals. Previous reports showed that the heavy ion beam can trigger complex forms of damage to cellular DNA, leading to cell cycle arrest and apoptosis of HepG2 human liver cancer cells; however, the mechanisms remains unclear fully. In order to explore whether the intrinsic or extrinsic pathway participates this process, HepG2 cells were treated with 12C6+ HIB irradiation at doses of 0 (control), 1, 2, 4, and 6 Gy with various methods employed to understand relevant mechanisms, such as detection of apoptosis, cell cycle, and Fas expression by flow cytometry, analysis of apoptotic morphology by electron microscopy and laser scanning confocal microscopy, and screening differentially expressed genes relating to p53 signaling pathway by PCR-array assay following with any genes confirmed by western blot analysis...
September 23, 2017: Acta Biochimica et Biophysica Sinica
https://www.readbyqxmd.com/read/29030460/hmg-coa-reductase-inhibition-delays-dna-repair-and-promotes-senescence-after-tumor-irradiation
#4
Elena V Efimova, Natalia Ricco, Edwardine Labay, Helena J Mauceri, Amy C Flor, Aishwarya Ramamurthy, Harold G Sutton, Ralph R Weichselbaum, Stephen J Kron
Despite significant advances in combinations of radiotherapy and chemotherapy, altered fractionation schedules and image-guided radiotherapy, many cancer patients fail to benefit from radiation. A prevailing hypothesis is that targeting repair of DNA double strand breaks (DSBs) can enhance radiation effects in the tumor and overcome therapeutic resistance without incurring off-target toxicities. Unrepaired DSBs can block cancer cell proliferation, promote cancer cell death and induce cellular senescence. Given the slow progress to date translating novel DSB repair inhibitors as radiosensitizers, we have explored drug repurposing, a proven route to improving speed, costs and success rates of drug development...
October 13, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/29030353/rad50-expression-is-associated-with-poor-clinical-outcomes-after-radiotherapy-for-resected-non-small-cell-lung-cancer
#5
Yifan Wang, Jayanthi Gudikote, Uma Giri, Jun Yan, Weiye Deng, Rui Ye, Wen Jiang, Nan Li, Brian Hobbs, Jing Wang, Stephen G Swisher, Junya Fujimoto, Ignacio Ivan Wistuba, Ritsuko Komaki, John Heymach, Steven H Lin
PURPOSE: Although postoperative radiotherapy is often used to maintain local control after surgical resection and chemotherapy for locally advanced non-small cell lung cancer (NSCLC), both locoregional failure and distant metastasis remain problematic.  The mechanisms of therapeutic resistance remain poorly understood.    Experimental Design: We used reverse-phase protein arrays (RPPAs) to profile the baseline expression of 170 total and phosphorylated proteins in 70 NSCLC cell lines to categorize pathways that may contribute to radiation resistance...
October 13, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29029886/heterogeneity-in-treatment-response-of-spine-metastases-to-spine-stereotactic-radiosurgery-within-radiosensitive-subtypes
#6
Vincent Bernard, Andrew J Bishop, Pamela K Allen, Behrang Amini, Xin A Wang, Jing Li, Claudio E Tatsui, Laurence D Rhines, Paul D Brown, Amol J Ghia
PURPOSE: To characterize outcomes of metastatic colorectal and non-small cell lung cancer (NSCLC) histologies, compared with other radiosensitive histologies, treated with spine stereotactic radiosurgery with regard to local control, overall survival, and predictors of response. METHODS AND MATERIALS: A total of 127 patients with 148 spine stereotactic radiosurgery-treated metastatic lesions at our institution between 2003 and 2013 were reviewed. We assessed clinical endpoints in relation to histologic type, including local control (LC) and overall survival (OS), using univariate and multivariate analyses...
September 1, 2017: International Journal of Radiation Oncology, Biology, Physics
https://www.readbyqxmd.com/read/29028842/in-vitro-investigation-of-head-and-neck-cancer-stem-cell-proportions-and-their-changes-following-x-ray-irradiation-as-a-function-of-hpv-status
#7
Paul Reid, Puthenparampil Wilson, Yanrui Li, Loredana G Marcu, Alexander H Staudacher, Michael P Brown, Eva Bezak
INTRODUCTION: Some head and neck squamous cell carcinomas (HNSCC) have a distinct aetiology, which depends on the presence of oncogenic human papilloma virus (HPV). Also, HNSCC contains cancer stem cells (CSCs) that have greater radioresistance and capacity to change replication dynamics in response to irradiation compared to non-clonogenic cells. Since there is limited data on CSCs in HNSCC as a function of HPV status, better understanding of their radiobiology may enable improved treatment outcome...
2017: PloS One
https://www.readbyqxmd.com/read/29027959/radiation-induced-changes-of-microrna-expression-profiles-in-radiosensitive-and-radioresistant-leukemia-cell-lines-with-different-levels-of-chromosome-abnormalities
#8
Daria Liamina, Wladimir Sibirnyj, Anna Khokhlova, Viacheslav Saenko, Eugenia Rastorgueva, Aleksandr Fomin, Yury Saenko
In our study, we estimate an effect from chromosome aberrations and genome mutations on changes in microRNA expression profiles in cancer cell lines demonstrating different radiosensitivity. Here, cell viability and microRNA spectrum have been estimated 1, 4, and 24 h after irradiation. MiSeq high-throughput sequencing system (Illumina, San Diego, CA, USA) is employed to perform microRNA spectrum estimation. In the K562 cell line, the number of expressed microRNAs in chromosomes demonstrates a more pronounced variation...
October 13, 2017: Cancers
https://www.readbyqxmd.com/read/29026318/rnai-mediated-knockdown-of-caix-enhances-the-radiosensitivity-of-nasopharyngeal-carcinoma-cell-line-cne-2
#9
Liji Jiang, Gang Xu, Zihuang Li, Xiaowei Zeng, Zhuangling Li, Jingwen Liu, Lin Mei, Xianming Li
Although radiotherapy remains the most powerful as well as the primary treatment modality for nasopharyngeal carcinoma (NPC), approximately 20% of NPC patients still have local recurrence. Carbonic anhydrase IX (CAIX)-related signaling pathways that mediate radioresistance have been found in various kinds of cancer. However, the role of CAIX in NPC radioresistance is still unknown. In this study, we investigated the effect of CAIX silencing on sensitization to ionizing radiation in NPC by using Lipofectamine 2000, which delivers small interfering ribonucleic acid (siRNA) that targets CAIX...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/29024383/down-regulation-of-lncrna-ccat1-enhances-radiosensitivity-via-regulating-mir-148b-in-breast-cancer
#10
Yong Lai, Yang Chen, Yuanhong Lin, Ling Ye
LncRNA colon-cancer-associated transcript-1 (CCAT1) was proved to be a potential prognostic biomarker for breast cancer progression. However, the role of CCAT1 in regulating radiosensitivity of breast cancer and its underlying mechanism have not been investigated. The present study showed that CCAT1 was up-regulated and miR-148b was down-regulated in radioresistant breast cancer tissues compared with radiosensitive breast cancer tissues. Radiation treatment triggered a significant increase in CCAT1 and an obvious decrease in miR-148b...
October 11, 2017: Cell Biology International
https://www.readbyqxmd.com/read/28993195/effect-of-trichostatin-a-on-radiation-induced-epithelial-mesenchymal-transition-in-a549%C3%A2-cells
#11
SunilGowda Sunnaghatta Nagaraja, Vishnuvarthan Krishnamoorthy, Raghavi Raviraj, Alagudinesh Paramasivam, Devipriya Nagarajan
Radiotherapy is used to treat tumors of different origins and nature, but often lead to development of radioresistance and metastasis of cells. Interestingly, radiation induces epithelial-mesenchymal transition (EMT), a process by which epithelial cells undergo mesenchymal phenotype and stimulates tumor progression capability. Our study investigated the effect of Trichostatin A (TSA), a natural derivate isolated from Streptomyces, upon radiation-induced lung EMT and we tried to understand the role of signaling molecules in irradiated lung cancer cells (A549)...
October 6, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28986892/tumor-tissue-analogs-for-the-assessment-of-radioresistance-in-cancer-stem-cells
#12
Meenakshi Upreti
Over the years, radiotherapy-related research has been based on local tumor control as an experimental endpoint, yielding a wealth of data demonstrating the importance of cancer stem cells in tumor reoccurrence after radiotherapy. Literature is replete with experimental and clinical evidence that the cancer stem cell population in a tumor affects its radiocurability. An important consideration for radiotherapy is the microenvironmental stimuli in the CSC niche that results from factors such as hypoxia, extracellular matrix (ECM) elements and their intercellular interaction with non-stem cells and other cell types that prevail in the tumor milieu...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28978144/targeting-the-pi3k-akt-mtor-signaling-pathway-as-an-effectively-radiosensitizing-strategy-for-treating-human-oral-squamous-cell-carcinoma-in-vitro-and-in-vivo
#13
Chih-Chia Yu, Shih-Kai Hung, Hon-Yi Lin, Wen-Yen Chiou, Moon-Sing Lee, Hui-Fen Liao, Hsien-Bin Huang, Hsu-Chueh Ho, Yu-Chieh Su
Radiation therapy (RT) is the current standard adjuvant approach for oral squamous cell carcinoma (OSCC) patients. Radioresistance is a major contributor to radiotherapy failure. In this study, we used patient-derived cells and a radiation-resistant cell line in vitro and in vivo for two purposes: evaluate the anti-tumor effects and understand the mechanisms in the dual PI3K/mTOR signaling pathway regulation of radiosensitization. Our findings indicate that in OML1-R cells, the radioresistance phenotype is associated with activation of the PI3K/AKT/mTOR signaling pathway...
September 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28978005/bazedoxifene-enhances-the-anti-tumor-effects-of-cisplatin-and-radiation-treatment-by-blocking-il-6-signaling-in-head-and-neck-cancer
#14
Arti Yadav, Bhavna Kumar, Theodoros N Teknos, Pawan Kumar
Recent studies have shown that IL-6 signaling plays an important role in the aggressive and metastatic phenotype of head and neck squamous cell carcinoma (HNSCC). Therefore, we hypothesized that targeting of IL-6 signaling in HNSCC could enhance the therapeutic efficacy of standard chemoradiation treatment. We used both in vitro and in vivo models to test the efficacy of Bazedoxifene (BZA), a drug that was originally developed as a newer-generation selective estrogen receptor modulator (SERM) for the treatment of postmenopausal osteoporosis...
September 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28972962/igf-1r-associates-with-adverse-outcomes-after-radical-radiotherapy-for-prostate-cancer
#15
Tamara Aleksic, Clare Verrill, Richard J Bryant, Cheng Han, Andrew Ross Worrall, Laurent Brureau, Stephane Larré, Geoff S Higgins, Fahad Fazal, Ahmad Sabbagh, Syed Haider, Francesca M Buffa, David Cole, Valentine M Macaulay
BACKGROUND: Activated type 1 insulin-like growth factor receptors (IGF-1Rs) undergo internalisation and nuclear translocation, promoting cell survival. We previously reported that IGF-1R inhibition delays DNA damage repair, sensitising prostate cancer cells to ionising radiation. Here we tested the clinical relevance of these findings. METHODS: We assessed associations between IGF-1R and clinical outcomes by immunohistochemistry in diagnostic biopsies of 136 men treated with 55-70 Gy external beam radiotherapy for prostate cancer, comparing results with publicly available transcriptional data in surgically treated patients...
October 3, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28962138/radioresistance-of-chordoma-cells-is-associated-with-the-atm-atr-pathway-in-which-rad51-serves-as-an-important-downstream-effector
#16
Chao Zhang, Bing Wang, Lei Li, Yawei Li, Pengzhi Li, Guohua Lv
Surgery followed by radiotherapy is the standard treatment for chordomas, which are a rare but low-grade type of bone cancer arising from remnants of the embryonic notochord. However, disease recurrence following radiotherapy is common, most likely due to endogenous DNA repair mechanisms that promote cell survival upon radiation strikes. The ataxia telangiectasia mutated/ataxia telangiectasia mutated and Rad3 related (ATM/ATR)-mediated pathway has a critical role in DNA repair mechanisms; however, it has rarely been investigated in chordomas...
September 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28954285/phase-ii-study-of-proton-based-stereotactic-body-radiation-therapy-for-liver-metastases-importance-of-tumor-genotype
#17
Theodore S Hong, Jennifer Y Wo, Darrell R Borger, Beow Y Yeap, Erin I McDonnell, Henning Willers, Lawrence S Blaszkowsky, Eunice L Kwak, Jill N Allen, Jeffrey W Clark, Shyam Tanguturi, Lipika Goyal, Janet E Murphy, John A Wolfgang, Lorraine C Drapek, Ronald S Arellano, Harvey J Mamon, John T Mullen, Kenneth K Tanabe, Cristina R Ferrone, David P Ryan, A John Iafrate, Thomas F DeLaney, Andrew X Zhu
Background: We evaluated the efficacy and safety of risk-adapted, proton-based stereotactic body radiation therapy (SBRT) for liver metastases from solid tumors. Methods: This single-arm phase II single institutional study (NCT01239381) included patients with limited extrahepatic disease, 800 mL or greater of uninvolved liver, and no cirrhosis or Child-Pugh A, who had received proton-based SBRT to one to four liver metastases from solid tumors. Treatment comprised 30 to 50 Gray equivalent (GyE) in five fractions based on the effective volume of liver irradiated...
September 1, 2017: Journal of the National Cancer Institute
https://www.readbyqxmd.com/read/28945826/genomic-alterations-and-radioresistance-in-breast-cancer-an-analysis-of-the-profiler-protocol
#18
E Bernichon, A Vallard, Q Wang, V Attignon, D Pissaloux, T Bachelot, P E Heudel, I Ray-Coquard, E Bonnet, A de la Fouchardière, C Faure, N Chopin, F Beurrier, S Racadot, M P Sunyach, C Rancoule, D Perol, V Corset, V Agrapart, F Tinquaut, J Y Blay, N Magné, O Trédan
Background: Breast cancer (BC) patients with comparable prognostic features have heterogeneous outcomes, party related to a possible radiotherapy resistance leading to local-regional recurrences (LRR). The objective of the present study was to identify predictive molecular biomarkers of LRR of BC. Patients and Methods: Genetic profile of 146 BC patients' tumours included in the ProfiLER clinical trial (NC01774409) between 2013 and 2016 were analysed using Next-Generation-Sequencing and Comparative-Genomic-Hybridization tests...
September 1, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28943930/downregulation-of-cytochrome-c-oxidase-1-induced-radioresistance-in-esophageal-squamous-cell-carcinoma
#19
Tomoko Takesue, Hirofumi Kawakubo, Tetsu Hayashida, Mai Tsutsui, Kazuhiro Miyao, Kazumasa Fukuda, Rieko Nakamura, Tsunehiro Takahashi, Norihito Wada, Hiroya Takeuchi, Yuko Kitagawa
Comprehensive gene screening with transposons is a novel procedure for the systematic identification of resistant genes. The present study aimed to use this technique to identify candidate radioresistant genes in esophageal squamous cell carcinoma. A transposon is a base sequence that can translocate to another location in the genome at random. By inserting the cytomegalovirus promotor as a transcriptional activator in the transposon, the following gene in the new location becomes overexpressed and the gene located at the transposon insertion site is downregulated...
October 2017: Oncology Letters
https://www.readbyqxmd.com/read/28939847/dual-mab-her-family-blockade-in-head-and-neck-cancer-human-cell-lines-combined-with-photon-therapy
#20
Jean-Baptiste Guy, Benoîte Méry, Edouard Ollier, Sophie Espenel, Alexis Vallard, Anne-Sophie Wozny, Stéphanie Simonet, Alexandra Lauret, Priscillia Battiston-Montagne, Dominique Ardail, Gersende Alphonse, Chloé Rancoule, Claire Rodriguez-Lafrasse, Nicolas Magné
Head and neck cancer stem cells (CSCs) are highly resistant to treatment. When EGFR is overexpressed in head and neck squamous cell carcinoma (HNSCC), HER2 and HER3 are also expressed. The aim of the present study was to investigate the effect of HER1/2/3 blockade through a combination of cetuximab and pertuzumab, with or without photon irradiation, on the proliferation and migration/invasion capabilities of an HNSCC chemo- and radioresistant human cell line (SQ20B) and its corresponding stem cell subpopulation...
September 22, 2017: Scientific Reports
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