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Cancer and radioresistance

Zhila Rajaee, Samideh Khoei, Seied Rabi Mahdavi, Marzieh Ebrahimi, Sakine Shirvalilou, Alireza Mahdavian
The aim of this study was to investigate the effect of hyperthermia, 6 MeV electron radiation and combination of these treatments on cancer cell line DU145 in both monolayer culture and spheroids enriched for prostate cancer stem cells (CSCs). Flowcytometric analysis of the expression of molecular markers CD133+ /CD44+ was carried out to determine the prostate CSCs in cell line DU145 grown as spheroids in serum-free medium. Following monolayer and spheroid culture, DU145 cells were treated with different doses of hyperthermia, electron beam and combination of them...
February 17, 2018: Radiation and Environmental Biophysics
Perla Marmolejo-León, Erika Patricia Azorín-Vega, Nallely Jiménez-Mancilla, Héctor Javier Mendoza-Nava, Eleni Mitsoura, Benjamín Pineda, Eugenio Torres-García
Glioblastoma contains self-renewing, tumorigenic cancer stem-like cells that contribute to tumor initiation and therapeutic resistance. The aim of this research was to estimate and compare the effectiveness ratio (α/β) of stem-like cells and differentiated glioma cells derived from the U87MG glioblastoma cell line. Cell survival experiments were obtained in a dose range of 0-20 Gy (13.52 ± 0.09 Gy/h) as a hyperfractionationated accelerated radiotherapy scheme. Biochemical characterization of the post-irradiated cells was performed by flow cytometry analysis and the percentage of stem-like cells that resisted irradiation was determined by the CD133 expression...
January 11, 2018: Applied Radiation and Isotopes
Jian Zhang, Xinyu Qiu, Kedi Xi, Wentao Hu, Hailong Pei, Jing Nie, Ziyang Wang, Jiahan Ding, Peng Shang, Bingyan Li, Guangming Zhou
Radiation therapy is one of the routine treatment modalities for cancer patients. Ionizing radiation (IR) can induce bone loss, and consequently increases the risk of fractures with delayed and nonunion of the bone in the cancer patients who receive radiotherapy. The orchestrated bone remodeling can be disrupted due to the affected behaviors of bone cells, including bone mesenchymal stem cells (BMSCs), osteoblasts and osteoclasts. BMSCs and osteoblasts are relatively radioresistant compared with osteoclasts and its progenitors...
February 15, 2018: Connective Tissue Research
Christopher B Sylvester, Jun-Ichi Abe, Zarana S Patel, K Jane Grande-Allen
Radiation therapy (RT) in the form of photons and protons is a well-established treatment for cancer. More recently, heavy charged particles have been used to treat radioresistant and high-risk cancers. Radiation treatment is known to cause cardiovascular disease (CVD) which can occur acutely during treatment or years afterward in the form of accelerated atherosclerosis. Radiation-induced cardiovascular disease (RICVD) can be a limiting factor in treatment as well as a cause of morbidity and mortality in successfully treated patients...
2018: Frontiers in Cardiovascular Medicine
Eva-Maria Birkman, Adam Elzagheid, Terhi Jokilehto, Tuulia Avoranta, Eija Korkeila, Jarmo Kulmala, Kari Syrjänen, Jukka Westermarck, Jari Sundström
Preoperative (chemo)radiotherapy, (C)RT, is an essential part of the treatment of rectal cancer patients, but tumor response to this therapy among patients is variable. Thus far, there are no clinical biomarkers that could be used to predict response to (C)RT or to stratify patients into different preoperative treatment groups according to their prognosis. Overexpression of cancerous inhibitor of protein phosphatase 2A (CIP2A) has been demonstrated in several cancers and is frequently associated with reduced survival...
February 14, 2018: Cancer Medicine
Xin Xie, Zhaoping Xu, Chenghe Wang, Chen Fang, Juping Zhao, Le Xu, Xiaoqiang Qian, Jun Dai, Fukang Sun, Danfeng Xu, Wei He
Tip60, an oncogene, accelerates cell growth by regulating androgen receptor translocation into the nucleus in prostate cancer. However, the mechanism of Tip60 in the response of prostate cancer to radiotherapy, and radioresistance, has not been studied. Using human prostate cancer samples and two human prostate cancer cell lines (LNCaP and DU145), Tip60 protein expression and the acetylation of ataxia telangiectasia mutant (ATM) were analysed by western blotting and immunoprecipitation. Tip60 was downregulated with small interfering RNA...
February 2018: FEBS Open Bio
Maxim Sorokin, Roman Kholodenko, Anna Grekhova, Maria Suntsova, Margarita Pustovalova, Natalia Vorobyeva, Irina Kholodenko, Galina Malakhova, Andrew Garazha, Artem Nedoluzhko, Raif Vasilov, Elena Poddubskaya, Olga Kovalchuk, Leila Adamyan, Vladimir Prassolov, Daria Allina, Denis Kuzmin, Kirill Ignatev, Andreyan Osipov, Anton Buzdin
Acquired resistance to chemotherapy and radiation therapy is one of the major obstacles decreasing efficiency of treatment of the oncologic diseases. In this study, on the two cell lines (ovarian carcinoma SKOV-3 and neuroblastoma NGP-127), we modeled acquired resistance to five target anticancer drugs. The cells were grown on gradually increasing concentrations of the clinically relevant tyrosine kinase inhibitors (TKIs) Sorafenib, Pazopanib and Sunitinib, and rapalogs Everolimus and Temsirolimus, for 20 weeks...
January 12, 2018: Oncotarget
Wei Chen, Xiaohua Ren, Jiashun Wu, Xiaolei Gao, Xiao Cen, Shasha Wang, Surui Sheng, Qianming Chen, Ya-Jie Tang, Xin-Hua Liang, Ya-Ling Tang
Epithelial-mesenchymal transition (EMT) has been shown to associate with cancer stem cells and radioresistance. However, it is obscure whether EMT itself or specific EMT regulators play causal roles in these properties of salivary adenoid cystic carcinoma (SACC). Here, we exhibited that overexpression of HSP27 drove the migration and invasion, induced EMT, as well as mediated TGF-β1-induced EMT in SACC cells, accompanying the up-regulation of Snail1 and Prrx1. Conversely, HSP27 silencing reduced the migration and invasion and contributed to MET of SACC cells...
February 9, 2018: Journal of Cellular and Molecular Medicine
Teresa Bernadette Steinbichler, Abdelmoez Alshaimaa, Metzler Veronika Maria, Dejaco Daniel, Riechelmann Herbert, Dudas Jozsef, Skvortsova Ira-Ida
Objective: Epithelial-mesenchymal crosstalk (EMC) contributes to tumor progression, chemoresistance and acquisition of a mesenchymal phenotype (EMT) of cancer cells. This study aims to investigate the effects of EMC on radioresistance in head and neck squamous cell carcinoma (HNSCC) cells. Methods: In tumor cell lines, the response of HNSCC cells, stimulated with EMC conditioned medium (CM), to irradiation was evaluated with viability and clonogenic assays. Dose modifying factors (DMF) were calculated from the results of clonogenic assays...
January 9, 2018: Oncotarget
Yanling Wang, Haineng Xu, Tianrun Liu, Menggui Huang, Param-Puneet Butter, Chunsheng Li, Lin Zhang, Gary D Kao, Yanqing Gong, Amit Maity, Constantinos Koumenis, Yi Fan
Cancer stem cells (CSCs) - known to be resistant to genotoxic radiation and chemotherapy - are fundamental to therapy failure and cancer relapse. Here, we reveal that glioma CSCs are hypersensitive to radiation, but a temporal DNA repair mechanism converts the intrinsic sensitivity to genomic instability and treatment resistance. Transcriptome analysis identifies DNA-dependent protein kinase (DNA-PK) as a predominant DNA repair enzyme in CSCs. Notably, DNA-PK activity is suppressed after irradiation when ROS induce the dissociation of DNA-PKcs with Ku70/80, resulting in delayed DNA repair and radiosensitivity; subsequently, after ROS clearance, the accumulated DNA damage and robust activation of DNA-PK induce genomic instability, facilitated by Rad50-mediated cell-cycle arrest, leading to enhanced malignancy, CSC overgrowth, and radioresistance...
February 8, 2018: JCI Insight
You Quan Li, Yun Ming Tian, Sze Huey Tan, Ming Zhu Liu, Grace Kusumawidjaja, Enya H W Ong, Chong Zhao, Terence W K Tan, Kam Weng Fong, Kiattisa Sommat, Yoke Lim Soong, Joseph T S Wee, Fei Han, Melvin L K Chua
Purpose To investigate for a prognostic index (PI) to personalize recommendations for salvage intensity-modulated radiotherapy (IMRT) in patients with locally recurrent nasopharyngeal carcinoma (lrNPC). Methods Patients with lrNPC from two academic institutions (Sun Yat-Sen University Cancer Center [SYSUCC-A; n = 251 (training cohort)] and National Cancer Centre Singapore [NCCS; n = 114] and SYSUCC-B [n = 193 (validation cohorts)]) underwent salvage treatment with IMRT from 2001 to 2015. Primary and secondary clinical end points were overall survival (OS) and grade 5 toxicity-free rate (G5-TFR), respectively...
February 7, 2018: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
Abraham Pedroza-Torres, Alma D Campos-Parra, Oliver Millan-Catalan, Yahir A Loissell-Baltazar, Horacio Zamudio-Meza, David Cantú de León, Gonzalo Montalvo-Esquivel, David Isla-Ortiz, Luis A Herrera, Óscar Ángeles-Zaragoza, Guadalupe Robelo-Romero, Ángel Herrera-Gómez, Carlos Pérez-Plasencia
Cervical cancer (CC) is one of the most common cancers diagnosed in women worldwide, and it is estimated that ~500,000 new patients are diagnosed with cervical cancer annually and that ~270,000 deaths occur each year. Patients with cervical cancer are treated with different radiotherapy schedules, either alone or with adjuvant chemotherapy. Unfortunately, nearly 50% of all patients with cervical cancer do not respond to standard treatment due to tumor radioresistance. In this scenario, several microRNAs (miRNAs) have been associated with the acquisition of the radioresistance phenotype...
January 18, 2018: Oncology Reports
Satoshi Endo, Mayumi Fujita, Shigeru Yamada, Kaori Imadome, Fumiaki Nakayama, Tetsuro Isozaki, Takeshi Yasuda, Takashi Imai, Hisahiro Matsubara
Fos‑related antigen 1 (Fra‑1) has roles in a variety of cell functions, including cell proliferation, differentiation, transformation, and invasiveness, and it is upregulated in various cancers. We investigated the role of Fra‑1 in cellular radioresistance using cells of two human colorectal cancer cell lines, SW620 and SW480. We found that SW620 cells are more sensitive than SW480 cells at doses greater than 6 Gy for X‑ray or 3 Gy for carbon‑ion (C‑ion) radiation. Fra‑1 expression tended to be decreased by the radiation in a dose‑dependent manner in both cell lines; of note, a greater reduction of Fra‑1 expression was observed in SW620 cells, especially at 6 Gy of X‑ray or 3 Gy of C‑ion irradiation, than in SW480 cells, indicating a possible association between Fra‑1 downregulation and cellular radiosensitivity...
January 19, 2018: Oncology Reports
Jia Ma, Yanwei Lu, Sheng Zhang, Yan Li, Jing Huang, Zhongyuan Yin, Jinghua Ren, Kai Huang, Li Liu, Kunyu Yang, Gang Wu, Shuangbing Xu
Aberrant expression of FOXN2, a member of the Forkhead box transcription factors, has been found in several types of cancer. However, the underlying mechanisms of FOXN2 deregulation in tumorigenesis remain largely unknown. Here, we find that FOXN2 binds to and is ubiquitinated by β-Trcp ubiquitin ligase and RSK2 kinase for degradation. Furthermore, we demonstrate that the Ser365 and Ser369 sites in a conserved DSGYAS motif are critical for the degradation of FOXN2 by β-Trcp and RSK2. Moreover, gain-of-function and loss-of-function studies show that FOXN2 impairs cell proliferation in vitro and in vivo and enhances the radiosensitivity of lung cancer...
February 2, 2018: Cell Death and Differentiation
Shan-Tong Jiang, Shu-Yan Han, Li-Na Pang, Yan-Na Jiao, Xi-Ran He, Ping-Ping Li
Human apurinic/apyrimidinic endonuclease 1 (APE1) is a ubiquitous multifunctional protein, which possesses DNA repair and redox activities. High levels of APE1 are associated with chemo‑ and radioresistance, and poor prognosis in various types of cancer, including non‑small cell lung cancer (NSCLC). Bu‑Fei decoction (BFD) is a traditional Chinese herbal formula, which is believed to supplement Qi, clear away heat and nourish the lungs. BFD and modified Bu‑Fei decoction (MBFD) have been used in China to treat patients with lung cancer...
January 30, 2018: International Journal of Molecular Medicine
Richard Smith, Jiaxi Wang, Colin Seymour, Cristian Fernandez-Palomo, Jennifer Fazzari, Elisabeth Schültke, Elke Bräuer-Krisch, Jean Laissue, Christian Schroll, Carmel Mothersill
To evaluate microbeam radiation therapy (MRT), for brain tumor treatment, the bystander effect in nonirradiated companion animals was investigated. Adult rats were irradiated with 35 or 350 Gy at the European Synchrotron Research Facility using homogenous irradiation (HR) or MRT to the right brain hemisphere. The irradiated rats were housed with nonirradiated rats. After 48 hours, all rats were euthanized and the frontal lobe proteome was analyzed using 2-dimensional electrophoresis and mass spectrometry. Proteome changes were determined by analysis of variance ( P < ...
January 2018: Dose-response: a Publication of International Hormesis Society
Shang-Yu Chou, Shao-Lun Yen, Chao-Cheng Huang, Eng-Yen Huang
BACKGROUND: Galectin-1, a radioresistance marker, was found in our previous study to be a prognostic factor for cervical cancer. The aim of current study is to determine the prognostic significance of the galectin-1 expression level in patients with glioblastoma multiforme (GBM) undergoing adjuvant radiotherapy (RT). METHODS: We included 45 patients with GBM who were treated with maximal safe surgical resection or biopsy alone followed by adjuvant RT of EQD2 (equivalent dose in 2-Gy fractions) > or = 60 Gy for homogeneous treatment...
January 30, 2018: BMC Cancer
Wanyeon Kim, HyeSook Youn, Sungmin Lee, EunGi Kim, Daehoon Kim, Jung Sub Lee, Jae-Myung Lee, BuHyun Youn
An interaction between ribosomal protein S3 (rpS3) and nuclear factor kappa B or macrophage migration inhibitory factor in non-small-cell lung cancer is responsible for radioresistance. However, the role of rpS3 in glioblastoma (GBM) has not been investigated to date. Here we found that in irradiated GBM cells, rpS3 translocated into the nucleus and was subsequently ubiquitinated by ring finger protein 138 (RNF138). Ubiquitin-dependent degradation of rpS3 consequently led to radioresistance in GBM cells. To elucidate the apoptotic role of rpS3, we analyzed the interactome of rpS3 in ΔRNF138 GBM cells...
January 26, 2018: Experimental & Molecular Medicine
Chao Xiao, Yupeng Wang, Miao Zheng, Jian Chen, Guohe Song, Zhijie Zhou, Chongzhi Zhou, Xing Sun, Lin Zhong, Erxun Ding, Yi Zhang, Liu Yang, Gang Wu, Shifeng Xu, Hong Zhang, Xiaoliang Wang
Radiotherapy (RT) can be used as preoperative treatment to downstage initially unresectable locally rectal carcinoma, but the radioresistance and recurrence remain significant problems. Retinoblastoma binding protein 6 (RBBP6) has been implicated in the regulation of cell cycle, apoptosis and chemoresistance both in vitro and in vivo. This study investigated whether the inhibition of RBBP6 expression would improve radiosensitivity in human colorectal cancer cells. After SW620 and HT29 cells were exposed to radiation, the levels of RBBP6 mRNA and protein increased over time in both two cells...
January 25, 2018: Cancer Science
Francesco Jacopo Romano, Elia Guadagno, Domenico Solari, Giorgio Borrelli, Sara Pignatiello, Paolo Cappabianca, Marialaura Del Basso De Caro
Glioblastoma is one of the most malignant cancers, with a distinguishing dismal prognosis: surgery followed by chemo- and radiotherapy represents the current standard of care, and chemo- and radioresistance underlie disease recurrence and short overall survival of patients suffering from this malignancy. ATM is a kinase activated by autophosphorylation upon DNA doublestrand breaks arising from errors during replication, byproducts of metabolism, chemotherapy or ionizing radiations; TP53 is one of the most popular tumor suppressor, with a preeminent role in DNA damage response and repair...
January 25, 2018: Journal of Cellular Biochemistry
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