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https://www.readbyqxmd.com/read/30343431/a-comparative-analysis-of-gut-microbiota-disturbances-in-the-gottingen-minipig-and-rhesus-macaque-models-of-acute-radiation-syndrome-following-bioequivalent-radiation-exposures
#1
Franck Carbonero, Alba C Mayta-Apaza, Jiang-Zhou Yu, Matt Lindeblad, Alex Lyubimov, Flavia Neri, Erzsebet Szilagyi, Amelia Bartholomew
In rodent studies, the gut microbiota has been implicated in facilitating both radioresistance, by protecting the epithelium from apoptotic responses and radiosensitivity, inducing endothelial apoptotic responses. Despite the observation that large animal models, such as the Chinese Rhesus macaque and the Gottingen Minipig, demonstrate similarity to human physiologic responses to radiation, little is known about radiation-induced changes of the gut microbiome in these models. To compare the two models, we used bioequivalent radiation doses which resulted in an LD50 for Gottingen Minipigs and Chinese Rhesus macaques, 1...
October 20, 2018: Radiation and Environmental Biophysics
https://www.readbyqxmd.com/read/30343341/ataxia-telangiectasia-alters-the-apob-and-reelin-pathway
#2
Júlia Canet-Pons, Ralf Schubert, Ruth Pia Duecker, Roland Schrewe, Sandra Wölke, Matthias Kieslich, Martina Schnölzer, Andreas Chiocchetti, Georg Auburger, Stefan Zielen, Uwe Warnken
Autosomal recessive ataxia telangiectasia (A-T) is characterized by radiosensitivity, immunodeficiency, and cerebellar neurodegeneration. A-T is caused by inactivating mutations in the ataxia telangiectasiamutated (ATM) gene, a serine-threonine protein kinase involved in DNA damage response and excitatory neurotransmission. The selective vulnerability of cerebellar Purkinje neurons (PN) to A-T is not well understood. Employing global proteomic profiling of cerebrospinal fluid from patients at ages around 15 years, we detected reduced calbindin, reelin, cerebellin-1, cerebellin-3, protocadherin fat 2, sempahorin 7A, and increased apolipoprotein B and J peptides...
October 21, 2018: Neurogenetics
https://www.readbyqxmd.com/read/30342967/influence-of-linear-energy-transfer-on-the-nucleo-shuttling-of-the-atm-protein-a-novel-biological-interpretation-relevant-for-particles-and-radiation
#3
Mira Maalouf, Adeline Granzotto, Clément Devic, Larry Bodgi, Mélanie Ferlazzo, Christophe Peaucelle, Marcel Bajard, Jean-Yves Giraud, Jacques Balosso, Joël Hérault, Marie-Claude Biston, Claude Malet, Nicolas Foray
PURPOSE: Linear energy transfer (LET) plays an important role in radiation response. Recently, the radiation-induced nucleo-shuttling of ATM from cytoplasm to the nucleus was shown to be a major event of the radiation response that permits a normal DNA double-strand breaks (DSB) recognition and repair. Here, we aimed to verify the relevance of the ATM nucleo-shuttling model for high-LET particles and various radiation types. METHODS AND MATERIALS: ATM- and H2AX-immunofluorescence was used to assess the number of recognized and unrepaired DSB in quiescent fibroblast cell lines exposed to X-rays, γ-rays, 9 and 12 MeV electrons, 3 and 65 MeV protons and 75 MeV/u carbon ions...
October 18, 2018: International Journal of Radiation Oncology, Biology, Physics
https://www.readbyqxmd.com/read/30342098/genome-damage-in-children-with-classical-ehlers-danlos-syndrome-an-in-vivo-and-in-vitro-study
#4
Anna Aghajanyan, Aleksandra Fucic, Leila Tskhovrebova, Olga Gigani, Pasko Konjevoda
Ehlers-Danlos syndrome (EDS) is a heritable connective tissue disorder characterized by skin hyperextensibility, abnormal wound healing, and joint hypermobility with prevalence 1:20 000. Its incidence is probably underestimated due to unknown number of subjects having mild symptoms who may have never been diagnosed through entire life time. Classical EDS is characterized by pathogenic variants of genes encoding type V collagen. The biological effects and health risks of patients with EDS exposure to low doses of ionizing radiation is poorly understood...
October 17, 2018: European Journal of Medical Genetics
https://www.readbyqxmd.com/read/30338747/synthesis-of-18f-faza-using-nosyl-and-iodo-precursors-for-nucleophilic-radiofluorination
#5
William Sun, Cheryl Falzon, Ebrahim Naimi, Ali Akbari, Leonard I Wiebe, Manju Tandon, Piyush Kumar
BACKGROUND: 1-α-D-(5-Deoxy-5-[18F]fluoroarabinofuranosyl)-2-nitroimidazole ([18F]FAZA) is manufactured by nucleophilic radiofluorination of 1-&alpha;-D-(2',3'-di-O-acetyl-5'-O-toluenesulfonylarabinofuranosyl)-2-nitroimidazole (DiAcTosAZA) and alkaline deprotection to afford [18F]FAZA. High yields (>60%) under optimized conditions frequently revert to low yields (<20%) in large scale, automated syntheses. Competing side reactions and concomitant complex reaction mixtures contribute to substantial loss of product during HPLC clean-up...
October 18, 2018: Current Radiopharmaceuticals
https://www.readbyqxmd.com/read/30337872/antidiabetic-biguanides-radiosensitize-hypoxic-colorectal-cancer-cells-through-a-decrease-in-oxygen-consumption
#6
Sven de Mey, Heng Jiang, Cyril Corbet, Hui Wang, Inès Dufait, Kalun Law, Estelle Bastien, Valeri Verovski, Thierry Gevaert, Olivier Feron, Mark De Ridder
Background and Purpose: The anti-diabetic biguanide drugs metformin and phenformin exhibit antitumor activity in various models. However, their radiomodulatory effect under hypoxic conditions, particularly for phenformin, is largely unknown. This study therefore examines whether metformin and phenformin as mitochondrial complex I blockades could overcome hypoxic radioresistance through inhibition of oxygen consumption. Materials and Methods: A panel of colorectal cancer cells (HCT116, DLD-1, HT29, SW480, and CT26) was exposed to metformin or phenformin for 16 h at indicated concentrations...
2018: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/30337664/stem-cell-enriched-epithelial-spheroid-cultures-for-rapidly-assaying-small-intestinal-radioprotectors-and-radiosensitizers-in-vitro
#7
Marimar de la Cruz Bonilla, Kristina M Stemler, Cullen M Taniguchi, Helen Piwnica-Worms
Radiation therapy is one of the main treatment options for many cancer patients. Although high doses of radiation may maximize tumor cell killing, dose escalation is limited by toxicity to neighboring normal tissues. This limitation applies particularly to the small intestine, the second most radiosensitive organ in the body. Identifying small intestinal (SI) radioprotectors could enable dose escalation in the treatment of abdominopelvic malignancies. However, the only assay currently available to identify effects of radiomodulating drugs on the regenerating capacity of SI stem cells is the Withers-Elkind microcolony assay, which requires large numbers of mice, making it a costly and low throughput method...
October 18, 2018: Scientific Reports
https://www.readbyqxmd.com/read/30337559/persistent-mrna-and-mirna-expression-changes-in-irradiated-baboons
#8
Matthias Port, Francis Hérodin, Marco Valente, Michel Drouet, Patrick Ostheim, Matthäus Majewski, Michael Abend
We examined the transcriptome/post-transcriptome for persistent gene expression changes after radiation exposure in a baboon model. Eighteen baboons were irradiated with a whole body equivalent dose of 2.5 or 5 Gy. Blood samples were taken before, 7, 28 and 75-106 days after radiation exposure. Stage I was a whole genome screening for mRNA combined with a qRT-PCR platform for detection of 667 miRNAs. Candidate mRNAs and miRNAs differentially up- or down-regulated in stage I were chosen for validation in stage II using the remaining samples...
October 18, 2018: Scientific Reports
https://www.readbyqxmd.com/read/30337244/artesunate-enhances-radiosensitivity-of-esophageal-cancer-cells-by-inhibiting-the-repair-of-dna-damage
#9
Zhenhua Fei, Wenyue Gu, Raoying Xie, Huafang Su, Yiyan Jiang
Radiotherapy plays an important therapeutic role in esophageal cancer (EC). However, acquired radioresistance impairs the efficacy of radiotherapy, often leading to treatment failure. Therefore, it is important to develop novel radiosensitizers to enhance the clinical treatment of EC. The purpose of this study was to investigate the role of artesunate (ART) on radiosensitivity of human EC cell line TE-1. We found that ART inhibited the proliferation of EC cells and enhanced the radiosensitivity of TE-1 cells (SER = 1...
September 29, 2018: Journal of Pharmacological Sciences
https://www.readbyqxmd.com/read/30336548/nafamostat-mesilate-enhances-the-radiosensitivity-and-reduces-the-radiation-induced-invasive-ability-of-colorectal-cancer-cells
#10
Hiroshi Sugano, Yoshihiro Shirai, Takashi Horiuchi, Nobuhiro Saito, Yohta Shimada, Ken Eto, Tadashi Uwagawa, Toya Ohashi, Katsuhiko Yanaga
Neoadjuvant chemoradiotherapy followed by radical surgery is the standard treatment for patients with locally advanced low rectal cancer. However, several studies have reported that ionizing radiation (IR) activates nuclear factor kappa B (NF-κB) that causes radioresistance and induces matrix metalloproteinase (MMP)-2/-9, which promote tumor migration and invasion. Nafamostat mesilate (FUT175), a synthetic serine protease inhibitor, enhances the chemosensitivity to cytotoxic agents in digestive system cancer cells by inhibiting NF-κB activation...
October 17, 2018: Cancers
https://www.readbyqxmd.com/read/30335243/flow-cytometry-in-peripheral-blood-reticulocytes-as-a-marker-of-chromosome-instability-in-highgrade-glioma-patients
#11
Lina Marcela Barrera, León Darío Ortiz, Hugo Grisales, Mauricio Rojas, Mauricio Camargo
Introduction: The quantification of chromosomal instability is an important parameter to assess genotoxicity and radiosensitivity. Most conventional techniques require cell cultures or laborious microscopic analyses of chromosomes or nuclei. However, a flow cytometry that selects the reticulocytes has been developed as an alternative for in vivo studies, which expedites the analytical procedures and increases up to 20 times the number of target cells to be analyzed. Objectives: To standardize the flow cytometry parameters for selecting and quantifying the micronucleated reticulocytesCD71+ (MN-RET) from freshly drawn peripheral blood and to quantify the frequency of this abnormal cell subpopulation as a measure of cytogenetic instability in populations of healthy volunteers (n =25), and patients (n=25), recently diagnosed with high-grade gliomas before the onset of treatment...
September 1, 2018: Biomédica: Revista del Instituto Nacional de Salud
https://www.readbyqxmd.com/read/30334677/as1411-aptamer-targeted-gold-nanoclusters-effect-on-the-enhancement-of-radiation-therapy-efficacy-in-breast-tumor-bearing-mice
#12
Fatemeh Ghahremani, Amirhosein Kefayat, Daryoush Shahbazi-Gahrouei, Hasan Motaghi, Masoud A Mehrgardi, Shaghayegh Haghjooy-Javanmard
AIM: Herein, the AS1411 aptamer-targeted ultrasmall gold nanoclusters (GNCs) were assessed at different aspects as a radiosensitizer. MATERIALS & METHODS: AS1411 aptamer-conjugated gold nanoclusters (Apt-GNCs) efficacy was evaluated at cancer cells targeting, radiosensitizing effect, tumor targeting, and biocompatibility in breast tumor-bearing mice. RESULTS: Flow cytometry and fluorescence microscopy exhibited more cellular uptake for Apt-GNCs in comparison with GNCs...
October 18, 2018: Nanomedicine
https://www.readbyqxmd.com/read/30334352/radioprotective-effects-of-roxadustat-fg-4592-in-haematopoietic-system
#13
Pei Zhang, Jicong Du, Hainan Zhao, Ying Cheng, Suhe Dong, Yanyong Yang, Bailong Li, Fu Gao, Xuejun Sun, Jianming Cai, Cong Liu
BACKGROUND: Ionizing radiation often causes severe injuries to radiosensitive tissues, especially haematopoietic system. Novel radioprotective drugs with low toxicity and high effectiveness are required. Prolyl hydroxylases domain (PHD) inhibitors have been reported to protect against radiation-induced gastrointestinal toxicity. In this study, we demonstrated the protective effects of a PHD inhibitor, roxadustat (FG-4592), against radiation-induced haematopoietic injuries in vitro and in vivo...
October 18, 2018: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/30328366/exo1-overexpression-is-associated-with-poor-prognosis-of-hepatocellular-carcinoma-patients
#14
Yaoyao Dai, Zuxiong Tang, Zongguo Yang, Lan Zhang, Qing Deng, Xiaofeng Zhang, Yongchun Yu, Xing Liu, Junfeng Zhu
BACKGROUND/AIM: The roles of exonuclease 1 (EXO1) in hepatocellular carcinoma (HCC) tumorigenesis and progression remain unclear. This study aimed to assess the prognostic value and therapeutic potential of EXO1 in HCC. METHODS: Exo1 gene copy numbers were obtained from three Oncomine microarray datasets (n=447). EXO1 mRNA expression was validated by semi-quantitative PCR and QuantiGene® 2.0 assays. Cell growth curve and colony formation were performed to asses the cell proliferation...
October 17, 2018: Cell Cycle
https://www.readbyqxmd.com/read/30326943/temozolomide-perillyl-alcohol-conjugate-impairs-mitophagy-flux-by-inducing-lysosomal-dysfunction-in-non-small-cell-lung-cancer-cells-and-sensitizes-them-to-irradiation
#15
Minghui Chang, Xingguo Song, Xinran Geng, Xingwu Wang, Weijun Wang, Thomas C Chen, Li Xie, Xianrang Song
BACKGROUND: Temozolomide-perillyl alcohol conjugate (TMZ-POH), a novel Temozolomide (TMZ) analog developed based on the conjugation of TMZ and perillyl alcohol (POH), displayed strong anticancer potency in multiple cancer types. In this study, we aimed to clarify the relationship between TMZ-POH and autophagy, and explore the underlying mechanisms involved in. METHODS: The proteins involved in autophagy, mitochondrial fission, lysosomal function and membrane traffic were detected by western blots; Autophagosome, mitochondria and lysosome were visualized by transmission electron microscope (TEM) and immunostaining; Apoptosis analysis and fluorescence probe detection were applied by flow cytometry...
October 16, 2018: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/30326253/stabilization-of-mirnas-in-esophageal-cancer-contributes-to-radioresistance-and-limits-efficacy-of-therapy
#16
REVIEW
Akshay Malhotra, Uttam Sharma, Shyamly Puhan, Naga Chandra Bandari, Anjali Kharab, P P Arifa, Lovlesh Thakur, Hridayesh Prakash, Karen M Vasquez, Aklank Jain
The five-year survival rate of esophageal cancer patients is less than 20%. This may be due to increased resistance (acquired or intrinsic) of tumor cells to chemo/radiotherapies, often caused by aberrant cell cycle, deregulated apoptosis, increases in growth factor signaling pathways, and/or changes in the proteome network. In addition, deregulation in non-coding RNA-mediated signaling pathways may contribute to resistance to therapies. At the molecular level, these resistance factors have now been linked to various microRNA (miRNAs), which have recently been shown to control cell development, differentiation and neoplasia...
October 13, 2018: Biochimie
https://www.readbyqxmd.com/read/30324833/trimodal-therapy-for-muscle-invasive-bladder-cancer
#17
Joachim Mathes, Steffen Rausch, Tilman Todenhöfer, Arnulf Stenzl
Radical cystectomy is the standard therapy for patients with muscle-invasive bladder cancer. Organ-preserving surgical procedures have been established as alternatives to radical surgery for localized malignancies in other anatomic sites. Trimodal therapy consisting of radiation therapy, chemotherapy, and either transurethral resection of the bladder or partial cystectomy is an effective treatment for selected patients with muscle-invasive bladder cancer that allows for preservation of the urinary bladder. Areas covered: This review provides an overview of the value of trimodal therapy in the treatment of muscle-invasive bladder cancer...
October 17, 2018: Expert Review of Anticancer Therapy
https://www.readbyqxmd.com/read/30324190/energy-dependent-photochromism-at-room-temperature-for-visually-detecting-and-distinguishing-x-rays
#18
Yi-Bo Su, Yong-Qin Wei, Li-Zhen Cai, Pei-Xin Li, Ming-Sheng Wang, Guo-Cong Guo
A radiochromic material with energy-dependent X-ray-induced photochromism was obtained by incorporating a radiosensitive glycolate ligand into an electron-transfer photochromic metalloviologen system. It is highly promising for detecting soft X-rays with energies less than 2 keV and may find application in qualitatively and visually distinguishing the energy range of X-rays.
October 16, 2018: Chemical Communications: Chem Comm
https://www.readbyqxmd.com/read/30323668/the-role-of-autophagy-in-the-radiosensitivity-of-the-radioresistant-human-nasopharyngeal-carcinoma-cell-line-cne-2r
#19
Zhong-Guo Liang, Guo-Xiang Lin, Bin-Bin Yu, Fang Su, Ling Li, Song Qu, Xiao-Dong Zhu
Purpose: The present study aimed to study the role of autophagy in the radiosensitivity of the radioresistant human nasopharyngeal carcinoma cell line CNE-2R. Methods: Before being irradiated, CNE-2R cells were treated with the autophagy inhibitor chloroquine diphosphate (CDP) or the autophagy inducer rapamycin (RAPA). Microtubule-associated protein light chain 3 (LC3-II) and p62 were assessed using Western blotting analysis 48 hours after CNE-2R cells were irradiated...
2018: Cancer Management and Research
https://www.readbyqxmd.com/read/30323167/sensitivity-of-cd3-cd28-stimulated-versus-non-stimulated-lymphocytes-to-ionizing-radiation-and-genotoxic-anticancer-drugs-key-role-of-atm-in-the-differential-radiation-response
#20
Daniel Heylmann, Jennifer Badura, Huong Becker, Jörg Fahrer, Bernd Kaina
Activation of T cells, a major fraction of peripheral blood lymphocytes (PBLCS), is essential for the immune response. Genotoxic stress resulting from ionizing radiation (IR) and chemical agents, including anticancer drugs, has serious impact on T cells and, therefore, on the immune status. Here we compared the sensitivity of non-stimulated (non-proliferating) vs. CD3/CD28-stimulated (proliferating) PBLC to IR. PBLCs were highly sensitive to IR and, surprisingly, stimulation to proliferation resulted in resistance to IR...
October 15, 2018: Cell Death & Disease
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