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Kai-Hua Chen, Ya Guo, Ling Li, Song Qu, Wei Zhao, Qi-Teng Lu, Qi-Yan Mo, Bin-Bin Yu, Lei Zhou, Guo-Xiang Lin, Yong-Chu Sun, Xiao-Dong Zhu
The radioresistance of nasopharyngeal carcinoma (NPC) may be related to cancer stem cells (CSCs), and the characteristics of CSCs may be maintained by telomerase activity. In this study, we explored the CSC-like characteristics and telomerase activity of the NPC radioresistant cell line CNE-2R. This work provides a foundation for future studies on stem cell-targeted therapies by targeting the radioresistance of NPC. The expression of stem cell-related genes/proteins and the hTERT gene/protein in CNE-2R and its parent radiosensitive cell line CNE-2 were detected using qPCR/Western Blot...
August 13, 2018: Cancer Medicine
Hyejin Park, Ye Ji Jeong, Na-Kyung Han, Joong Sun Kim, Hae-June Lee
Although many attempts have been made to improve the efficacy of radiotherapy to treat cancer, radiation resistance is still an obstacle in lung cancer treatment. Oridonin is a natural compound with promising antitumor efficacy that can trigger cancer cell death; however, its direct cellular targets, efficacy as a radiosensitizer, and underlying mechanisms of activity remain unclear. Herein, we report that oridonin exhibits additive cytotoxic and antitumor activity with radiation using the H460 non-small cell lung cancer cell lines...
August 13, 2018: International Journal of Molecular Sciences
Chao-Yuan Huang, Feng-Shu Hsieh, Cheng-Yi Wang, Li-Ju Chen, Shih-Shin Chang, Ming-Hsien Tsai, Man-Hsin Hung, Chiung-Wen Kuo, Chi-Ting Shih, Tzu-I Chao, Kuen-Feng Chen
AIM: Palbociclib is an oral cyclin-dependent kinase 4/6 inhibitor, which is efficacious in treating breast cancer. Currently, there are numerous active clinical trials testing palbociclib alone or in combination with other medications for treating various types of malignancies. Here, we evaluated the anti-cancer effect of palbociclib in combination with radiation therapy (RT) for treating human hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA) and addressed the molecular mechanism behind the combination therapy...
August 10, 2018: European Journal of Cancer
Andreea Nissenkorn, Tomer Erlich, Dorit E Zilberman, Ifat Sarouk, Alexander Krauthammer, Noam D Kitrey, Gali Heimer, Bruria BenZeev, Yoram Mor
BACKGROUND: Ataxia telangiectasia (AT) is a neurodegenerative cerebellar disorder, caused by mutations in the ATM gene, involved in DNA repair. Radiosensitivity, progressive ataxia, immune deficiency and malignancies, are well known symptoms, but urological manifestations are scarcely described. OBJECTIVE: To characterize urologic manifestations in a large cohort of AT patients. METHODS: Retrospective cross-sectional chart study comprising 52 AT patients followed at a National AT Center...
July 26, 2018: European Journal of Paediatric Neurology: EJPN
Taranga Jyoti Baruah, R N Sharan, Lakhan Kma
Non-small cell lung cancer (NSCLC) is a major form of cancer and is resistant to chemo- and radio-therapy. Vicenin-2 (VCN-2) is a flavonoid obtained from Ocimum sanctum L. and it has been reported to have radioprotective and anti-cancer properties. This study was conducted to check for the radiosensitizing potential of VCN-2 in the NSCLC cell line, NCI-H23. NCI-H23 cells were exposed to VCN-2 singularly, and to X-rays with and without prior VCN-2 treatment. Cytotoxicity assay, cell proliferation assay, caspase-3 activity assay, DNA fragmentation assay and Western blotting for Rad50, MMP-2 and p21 were performed to investigate the radiosensitizing properties of VCN-2...
August 11, 2018: Molecular Biology Reports
Xin Zhang, Xuehai Wang, Shujun Xu, Xingang Li, Xiangyu Ma
Resistance to adjuvant radiotherapy is a major cause of treatment failure in patients with glioblastoma (GBM). Recently, the role of lysosome, especially lysosomal proteases, in radioresistance is being paid more and more attention to. Here, we investigated the radioresistant role of Cathepsin B (CTSB), one important member of cysteine proteases, in GBM cell lines. A protease array kit was used to test GBM cells before and after irradiation. Nude mice were implanted with GBM cells to generate orthotopic xenografts for in vivo studies...
August 9, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Wei Yin, Ming Qiang, Wendong Ke, Yu Han, Jean Felix Mukerabigwi, Zhishen Ge
Radiosensitizers play an important role in the clinical radiotherapy of hypoxic solid tumors to improve therapeutic efficacy. However, the in vivo performance of clinically used small-molecule radiosensitizers is commonly compromised by low bioavailability in hypoxic tumor regions. Herein, amphiphilic block copolymer radiosensitizers are prepared from clinically approved poly(ethylene glycol)-block-poly(l-glutamic acid) (PEG-b-PLG) and metronidazole (MN) to obtain MN-grafted PEG-b-PLG (PEG-b-P(LG-g-MN)) via condensation reaction, which can self-assemble into core-shell micelles as nanoparticle-formulated radiosensitizers in aqueous solution...
August 4, 2018: Biomaterials
Hoang Quy Nguyen, Nhu Hanh To, Patricia Zadigue, Stéphane Kerbrat, Alexandre De La Taille, Sabine Le Gouvello, Yazid Belkacemi
Ionizing radiation-exposure induces a variety of cellular reactions, such as senescence and apoptosis. Senescence is a permanent arrest state of the cell division, which can be beneficial or detrimental for normal tissue via an inflammatory response and senescence-associated secretion phenotype. Damage to healthy cells and their microenvironment is considered as an important source of early and late complications with an increased risk of morbidity in patients after radiotherapy (RT). In addition, the benefit/risk ratio may depend on the radiation technique/dose used for cancer eradication and the irradiated volume of healthy tissues...
September 2018: Critical Reviews in Oncology/hematology
Evagelia C Laiakis, Tytus D Mak, Steven J Strawn, Yi-Wen Wang, Bo-Hyun Moon, Pelagie Ake, Albert J Fornace
Exposures to ionizing radiation (IR) may either be accidental or intentional, for medical purposes or even through terrorist actions. As certain populations emerge to be more radiosensitive than others, it is imperative to assess those individuals and treat them accordingly. To demonstrate the feasibility of rapid identification of such cases, we utilized the highly radiosensitive mouse model Atm-/- in the C57BL/6 background, and evaluated the urinary responses in 8-10 week old male mice at early time points (4, 24, and 72 h) after exposure to their respective LD50/30 doses [4 Gy for Atm-/- , and 8 Gy for wild type (WT)]...
August 10, 2018: Environmental and Molecular Mutagenesis
Sarah May, Cordula Hirsch, Alexandra Rippl, Nils Bohmer, Jean-Pierre Kaiser, Liliane Diener, Adrian Wichser, Alexander Bürkle, Peter Wick
Due to their interesting physicochemical properties, gold nanoparticles (Au-NPs) are the focus of increasing attention in the field of biomedicine and are under consideration for use in drug delivery and bioimaging, or as radiosensitizers and nano-based vaccines. Thorough evaluation of the genotoxic potential of Au-NPs is required, since damage to the genome can remain undetected in standard hazard assessments. Available genotoxicity data is either limited or contradictory. Here, we examined the influence of three surface modified 3-4 nm Au-NPs on human A549 cells, according to the reactive oxygen species (ROS) paradigm...
August 10, 2018: Nanoscale
Clément Devic, Mélanie L Ferlazzo, Nicolas Foray
The adaptive response (AR) phenomenon generally describes a protective effect caused by a "priming" low dose ( d AR ) delivered after a period of time (Δ t AR ) before a higher "challenging" dose ( D AR ). The AR is currently observed in human cells if d AR , Δ t AR , and D AR belong to (0.001-0.5 Gy), (2-24 hours), (0.1-5 Gy), respectively. In order to investigate the molecular mechanisms specific to AR in human cells, we have systematically reviewed the experimental AR protocols, the cellular models, and the biological endpoints used from the 1980s...
July 2018: Dose-response: a Publication of International Hormesis Society
Hai-Yan Chen, Lei Xu, Lin-Feng Li, Xiao-Xing Liu, Jian-Xin Gao, Yong-Rui Bai
Endogenous immune response participates in tumor control, and radiotherapy has immune modulatory capacity, but the role of immune modulation in the tumor microenvironment invoked by radiotherapy in radiosensitivity is poorly defined. In the present study, a radio-resistant melanoma cell line was obtained after repeated irradiation to the parental tumor in C57BL/6 mice. Radiotherapy resulted in aggregation of CD8+ and CD3+ T cells, and decrease of myeloid-derived suppressor cells and dendritic cells in the parental tumor, but not in the resistant tumors...
August 9, 2018: Scientific Reports
Chuan Sun, Xiaoxia Wei, Aziguli Yimaer, Zhengping Xu, Guangdi Chen
Extremely low frequency magnetic field (ELF-MF) has been classified as a possible carcinogen to humans by the International Agency for Research on Cancer [2002]. However, debate on the genotoxic effects of ELF-MF has continued due to lack of sufficient experimental evidence. Ataxia telangiectasia mutated (ATM) plays a central role in DNA damage repair; its deficiency can result in cellular sensitivity to DNA-damaging agents. To evaluate the genotoxicity of ELF-MF, we investigated the effects of 50 Hz MF on DNA damage in ATM-proficient (Atm+/+ ) mouse embryonic fibroblasts (MEFs) and ATM-deficient (Atm-/- ) MEFs, a radiosensitive cell line...
August 9, 2018: Bioelectromagnetics
Chuanyi Zhang, Xinzhou Deng, Li Qiu, Feng Peng, Shanshan Geng, Li Shen, Zhiguo Luo
Radiotherapy has played a limited role for the treatment of human esophageal cancer owing to the risk of tumor radioresistance. Core 1 β1, 3-galactosyltransferase (C1GalT1), which catalyzes the formation of core 1 O-glycan structures, is frequently overexpressed during tumorigenesis. However, the exact effects and mechanisms of C1GalT1 in the radioresistance of esophageal cancer remain unclear. In this study, Public databases and our data revealed that C1GalT1 expression was up-regulated in esophageal cancer tissues and was associated with poor survival...
2018: Journal of Cancer
Soojeong Cho, Byeongdu Lee, Wooram Park, Xiaoke Huang, Dong-Hyun Kim
To enhance localization and precision of therapeutic radiation delivery, nano-radiosensitizers have been developed. A specific volume of comprising surface atoms is known to be the radiosensitizing region. However, the shape dependent local dose enhancement of nanoparticles is often underestimated and rarely reported. Here, a noble metal nanostructure, inspired by the photoperiodic day-flowers, was synthesized by metal reduction with bile acid molecules. The impact of high surface area of day-flower like nanoparticles (D-NP) on radiosensitizing effect was demonstrated with assays for ROS generation, cellular apoptosis, and clonogenic survival of human liver cancer cells (HepG2) cells...
August 7, 2018: ACS Applied Materials & Interfaces
Yaqi Wang, Lifeng Yang, Jing Zhang, Menglong Zhou, Lijun Shen, Weijuan Deng, Liping Liang, Ran Hu, Wang Yang, Ye Yao, Hui Zhang, Zhen Zhang
Irinotecan, an analog of camptothecin, which is an inhibitor of topoisomerase I, is currently used in the treatment of metastatic colorectal cancer. Camptothecin derivatives have been demonstrated to exert radiosensitizing effects on several types of cancer cells. However, to date, at least to the best of our knowledge, few studies have examined these effects in colorectal cancer cell lines. In the present study, we examined the radiosensitizing effects of irinotecan on the p53-mutant colorectal cancer cell lines, HT29 and SW620, and explored the potential underlying mechanisms...
October 2018: International Journal of Oncology
Qibin Fu, Jing Wang, Tuchen Huang
Hyperthermia (HT) acts as a cancer treatment by direct cell killing, radiosensitization, and promotion of tumor reoxygenation. The sensor proteins of the DNA damage response (DDR) are the direct targets of HT. However, the spatiotemporal properties of sensor proteins under HT are still unclear. Therefore, investigating the impact of HT on sensor proteins is of great importance. In the present study, the human fibrosarcoma cell line HT1080 stably transfected with 53BP1-GFP [the DDR protein 53BP1 fused to green fluorescent protein (GFP)] was used to investigate the real-time cellular response to DNA double-strand breaks (DSBs) induced by γ-rays...
July 30, 2018: Journal of Radiation Research
Francesca Polito, Maria Cucinotta, Rosaria V Abbritti, Anna Brogna, Stefano Pergolizzi, Chiara Tomasello, Flavio F Angileri, Rosa Maria Di Giorgio, Alfredo Conti, Domenico La Torre, Antonino Germanò, M'hammed Aguennouz
Adrenocortical dysplasia (ACD) is a shelterin protein involved in the maintenance of telomere length and in cancer radioresistance. This study investigated the expression profile of ACD in human gliomas and its role in radioresistance of glioma cells. The expression of ACD was analyzed in 62 different grades of glioma tissues and correlated with prognosis. A radioresistant cell line was generated from U87MG cells. For mechanistic studies, ACD was inhibited by small interfering RNA-targeting ACD and the effect on cell radioresistance, telomerase activity, cyclinD1, caspase-3, hTERT, and BIRC1 was evaluated...
July 20, 2018: Translational Research: the Journal of Laboratory and Clinical Medicine
Vahid Hosseini, Mehri Mirrahimi, Ali Shakeri-Zadeh, Fereshteh Koosha, Behafarid Ghalandari, Shayan Maleki, Ali Komeili, S Kamran Kamrava
In this study, gold coated iron oxide nanoparticle (Au@Fe2 O3 NP) was synthesized in a core-shell structure. Photothermal and radiosensitization effects of Au@Fe2 O3 NPs were investigated on KB human mouth epidermal carcinoma cell line. Cell death and apoptosis were measured to study the effects of nanoparticles in combination with both radiotherapy (RT) and photothermal therapy (PTT). The KB cells were treated with Au@Fe2 O3 NPs (20 μg/ml; 4 h) and then received different treatment regimens of PTT and/or RT using laser (808 nm, 6 W/cm2 , 10 min) and/or 6 MV X-ray (single dose of 2 Gy)...
August 2, 2018: Photodiagnosis and Photodynamic Therapy
Liangzhu Feng, Ziliang Dong, Chao Liang, Muchao Chen, Danlei Tao, Liang Cheng, Kai Yang, Zhuang Liu
Owing to the existence of severe tumor hypoxia and limited X-ray absorption of solid tumors, the therapeutic efficacy of radiotherapy is far from satisfactory. Herein, ultrasmall iridium nanocrystals (IrNCs) with homogeneous size distribution are successfully synthesized. The obtained IrNCs show catalase-like catalytic activity towards hydrogen peroxide (H2 O2 ) with great temperatures/pH stability. As free IrNCs are prone to be toxified by thiol-containing biomolecules, we encapsulate as-prepared IrNCs within stealth liposomal carriers, obtaining Ir@liposome with well-protected catalytic activity in physiological conditions...
July 30, 2018: Biomaterials
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