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https://www.readbyqxmd.com/read/29148554/modelling-direct-dna-damage-for-gold-nanoparticle-enhanced-proton-therapy
#1
Marios Sotiropoulos, Nicholas T Henthorn, John W Warmenhoven, Ranald I Mackay, Karen J Kirkby, Michael J Merchant
Gold nanoparticles have been proven as potential radiosensitizer when combined with protons. Initially the radiosensitization effect was attributed to the physical interactions of radiation with the gold and the production of secondary electrons that induce DNA damage. However, emerging data challenge this hypothesis, supporting the existence of alternative or supplementary radiosensitization mechanisms. In this work we incorporate a realistic cell model with detailed DNA geometry and a realistic gold nanoparticle biodistribution based on experimental data...
November 17, 2017: Nanoscale
https://www.readbyqxmd.com/read/29147434/acute-radiation-induced-changes-in-sprague-dawley-rat-submandibular-glands-a-histomorphometric-analysis
#2
Manu Krishnan, Aatish Tennavan, Seema Saraswathy, Tarun Sekhri, Ajay Kumar Singh, Velu Nair
Background: Radiation-induced xerostomia is a distressing clinical condition that starts appearing from the initial stages of radiotherapy in head and neck cancer patients. Though submandibular glands contribute to maximum of the "resting salivary" secretions, most of the acute xerostomia experiments so far reported have been on animal parotid glands. Therefore, we assessed and quantified the histologic changes in submandibular glands of Sprague-Dawley (SD) rats using histomorphometry, 24 hours after radiation...
April 2017: World Journal of Oncology
https://www.readbyqxmd.com/read/29141565/radio-modulatory-potential-ofcaffeic-acid-phenethyl-ester-a-therapeutic-perspective
#3
Km Anjaly, Ashu Tiku
Use of natural agents is an upcoming area of research in cancer biology. Caffeic acid phenethyl ester has received great attention because of its therapeutic potential in various conditions including cancer. It is an active/abundant component of propolis. Propolis is a honey bee hive product produced by bees using their enzyme-rich digestive secretions on resinous mix, bee wax and pollen from plants. It is used to protect the beehive against bacteria and other infections.Although a lot of work has been done on chemotherapeutic aspects of CAPE, its role as a radiomodulator is yet to be delineated...
November 13, 2017: Anti-cancer Agents in Medicinal Chemistry
https://www.readbyqxmd.com/read/29141555/evaluation-of-antineoplastic-effects-of-nf-%C3%AE%C2%BAb-inhibition-by-dhmeq-dehydroxymethylepoxyquinomicin-in-medulloblastoma-cell-lines
#4
Priscila Maria Manzini Ramos, Julia Alejandra Pezuk, Angel Mauricio Castro-Gamero, Harley Francisco de Oliveira, Carlos Alberto Scrideli, Kazuo Umezawa, Luiz Gonzaga Tone
PURPOSE: NF-κB is a transcription factor involved in the transcriptional regulation of a large number of genes related to tumorigenesis in several cancer cell types, and it's inhibition have been related to anticancer effect. DHMEQ (Dehydroxymethylepoxyquinomicin) is a compound that blocks the translocation of NF-κB from the cytoplasm to the nucleus, thus inhibiting its activity as a transcriptional activator. Several studies have shown the antineoplastic effects of DHMEQ in numerous tumor types, however, there are no surveys that tested their effects in MB...
November 13, 2017: Anti-cancer Agents in Medicinal Chemistry
https://www.readbyqxmd.com/read/29137372/microrna-33a-5p-increases-radiosensitivity-by-inhibiting-glycolysis-in-melanoma
#5
Ke Cao, Jingjing Li, Jia Chen, Li Qian, Aijun Wang, Xiang Chen, Wei Xiong, Jintian Tang, Shijie Tang, Yong Chen, Yao Chen, Yan Cheng, Jianda Zhou
Glycolysis was reported to have a positive correlation with radioresistance. Our previous study found that the miR-33a functioned as a tumor suppressor in malignant melanoma by targeting hypoxia-inducible factor1-alpha (HIF-1α), a gene known to promote glycolysis. However, the role of miR-33a-5p in radiosensitivity remains to be elucidated. We found that miR-33a-5p was downregulated in melanoma tissues and cells. Cell proliferation was downregulated after overexpression of miR-33a-5p in WM451 cells, accompanied by a decreased level of glycolysis...
October 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/29135311/atm-bcl2-and-tgf%C3%AE-gene-polymorphisms-as-radiotherapy-outcome-biomarkers-in-head-and-neck-squamous-cell-carcinoma-patients
#6
Lidiane P Agostini, Elaine Stur, Fernanda M Garcia, Diego P Ventorim, Raquel S Dos Reis, Raquel S Dettogni, Eldamária V W Dos Santos, Gabriela T Peterle, Lucas L Maia, Suzanny O Mendes, Marcos B de Carvalho, Eloiza H Tajara, Flavia de Paula, Marcelo Dos Santos, Adriana M A da Silva, Iúri Drumond Louro
AIMS: Polymorphisms in cell cycle genes are considered prognostic and radiosensitivity markers in patients with head and neck squamous cell carcinoma. Therefore, we have aimed to investigate the relationship of ATM 5557G>A, ATM IVS62 + 60G>A, TP53 215G>C, BCL2-938C>A, TGFβ-509C>T, and TGFβ 29C>T with radiotherapy response. MATERIALS AND METHODS: Genotyping was performed by polymerase chain reaction followed by restriction fragment length polymorphism in 210 patients with oral cavity/oropharynx carcinoma and 101 patients with larynx tumors...
November 14, 2017: Genetic Testing and Molecular Biomarkers
https://www.readbyqxmd.com/read/29134684/enhanced-radiosensitization-of-enzalutamide-via-schedule-dependent-administration-to-androgen-sensitive-prostate-cancer-cells
#7
Maryam Ghashghaei, Miltiadis Paliouras, Mitra Heravi, Hamed Bekerat, Mark Trifiro, Tamim M Niazi, Thierry Muanza
BACKGROUND: Prostate cancer (PCa) is a progressive disease and the most diagnosed cancer in men. The current standard of care for high-risk localized PCa is a combination of androgen deprivation therapy (ADT) and radiation (XRT). The majority of these patients however become resistant due to incomplete responses to ADT as a result of selective cells maintaining androgen receptor (AR) activity. Improvement can be made if increasing radiosensitivity is realized. Therefore, the aim of this study is to investigate the efficacy of the next-generation PCa drug Enzalutamide (ENZA), as a radiosensitizer in XRT therapy...
November 14, 2017: Prostate
https://www.readbyqxmd.com/read/29133592/parp1-trapping-and-dna-replication-stress-enhance-radiosensitization-with-combined-wee1-and-parp-inhibitors
#8
Leslie A Parsels, David Karnak, Joshua Parsels, Qiang Zhang, Jonathan Vélez-Padilla, Zachery Reichert, Daniel R Wahl, Jonathan Maybaum, Mark J O'Connor, Theodore S Lawrence, Meredith A Morgan
KRAS mutations in non-small cell lung cancer (NSCLC) cause increased levels of DNA damage and replication stress, suggesting that inhibition of the DNA damage response (DDR) is a promising strategy for radiosensitization of NSCLC. This study investigates the ability of a WEE1 inhibitor (AZD1775) and a PARP inhibitor (olaparib) to radiosensitize KRAS mutant NSCLC cells and tumors. In addition to inhibiting the DDR, these small-molecule inhibitors of WEE1 and PARP induce DNA replication stress via nucleotide exhaustion and PARP trapping, respectively...
November 13, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/29132682/-biomarkers-of-radiation-induced-dna-repair-processes
#9
REVIEW
Alexis Vallard, Chloé Rancoule, Jean-Baptiste Guy, Sophie Espenel, Sylvie Sauvaigo, Claire Rodriguez-Lafrasse, Nicolas Magné
The identification of DNA repair biomarkers is of paramount importance. Indeed, it is the first step in the process of modulating radiosensitivity and radioresistance. Unlike tools of detection and measurement of DNA damage, DNA repair biomarkers highlight the variations of DNA damage responses, depending on the dose and the dose rate. The aim of the present review is to describe the main biomarkers of radiation-induced DNA repair. We will focus on double strand breaks (DSB), because of their major role in radiation-induced cell death...
November 10, 2017: Bulletin du Cancer
https://www.readbyqxmd.com/read/29130566/cisplatin-conjugated-gold-nanoparticles-as-a-theranostic-agent-for-head-and-neck-cancer
#10
Erez Shmuel Davidi, Tamar Dreifuss, Menachem Motiei, Eliezer Shai, Dimitri Bragilovski, Leon Lubimov, Marc Jose Jonathan Kindler, Aron Popovtzer, Jeremy Don, Rachela Popovtzer
BACKGROUND: The purpose of this study was to develop a nanoplatform, which simultaneously acts as radiosensitizer, drug carrier, and tumor imaging agent for head and neck cancer. METHODS: We synthesized 20 nm gold nanoparticles, coated with glucose and cisplatin (CG-GNPs). Their penetration into tumor cells and their cellular toxicity were evaluated in vitro. In vivo experiments were conducted to evaluate their impact on tumor growth and their imaging capabilities...
November 11, 2017: Head & Neck
https://www.readbyqxmd.com/read/29126793/inhibition-of-notch1-hes1-signaling-pathway-improves-radiosensitivity-of-colorectal-cancer-cells
#11
Hongzhi Zhang, Huijuan Jiang, Lei Chen, Juncai Liu, Xigang Hu, Huixiang Zhang
Notch signaling pathway has been demonstrated to mediate radioresistance of several tumors. Our study aims to explore the function of Notch1/HES1 pathway in the radioresistance of colorectal cancer (CRC). The results demonstrated that expressions of Notch1 and Hes1 were up-regulated with the increasing irradiation dose. DAPT (N-[(3,5-difluorophenacetyl)acety1]-L-alanyl-2-phenyl]glycine-1,1-dimethylethyl ester) or si-Notch1 reduced expressions of Notch1 and Hes1, exacerbated irradiation-induced cell proliferation inhibition, and improved radiosensitivity of CRC cells...
November 8, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29120816/tumor-targeted-stealthy-and-degradable-bismuth-nanoparticles-for-enhanced-x-ray-radiation-therapy-of-breast-cancer
#12
Junjie Deng, Shandong Xu, Weike Hu, Xiaojie Xun, Liyuan Zheng, Ming Su
Nanoparticles of heavy elements can be used as radiosensitizers to enhance X-ray radiation therapy, but a major roadblock in translating nanoparticle radiosensitizers into clinical practice of cancer treatment is related to the non-degradable nature of the nanoparticles, which can cause accumulation inside body and long-term toxicity. This paper reports the use of a folate-inserted, red blood cell membrane-modified bismuth (i.e., F-RBC bismuth) nanoparticles in X-ray radiation therapy for breast cancer, where cell membrane coating provides long blood circulation time, folate acts as tumor targeting agent, X-ray and bismuth nanoparticles interaction generates more free radicals for cancer cells damage, and physiological condition helps dissolve bismuth nanoparticles after treatment...
October 30, 2017: Biomaterials
https://www.readbyqxmd.com/read/29118323/valproic-acid-sensitizes-hepatocellular-carcinoma-cells-to-proton-therapy-by-suppressing-nrf2-activation
#13
Jeong Il Yu, Changhoon Choi, Sung-Won Shin, Arang Son, Ga-Haeng Lee, Shin-Yeong Kim, Hee Chul Park
Although efficacy of combined histone deacetylase (HDAC) inhibitors and conventional photon radiotherapy is being tested in clinical trials, their combined effect with proton beam radiotherapy has yet to be determined. Here, we compared combined effect of valproic acid (VPA), a class I and II HDAC inhibitor and antiepileptic drug with proton and photon irradiation in hepatocellular carcinoma (HCC) cells in vitro and in vivo. We found that VPA sensitized more Hep3B cells to proton than to photon irradiation...
November 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29117674/dominant-pathways-of-adenosyl-radical-induced-dna-damage-revealed-by-qm-mm-metadynamics
#14
Paweł Wityk, Miłosz Wieczór, Samanta Makurat, Lidia Chomicz-Mańka, Jacek Czub, Janusz Rak
Brominated nucleobases sensitize double stranded DNA to hydrated electrons, one of the dominant genotoxic species produced in hypoxic cancer cells during radiotherapy. Such radiosensitizers can therefore be administered locally to enhance treatment efficiency within the solid tumor while protecting the neighboring tissue. When a solvated electron attaches to 8-bromoadenosine, a potential sensitizer, the dissociation of bromide leads to a reactive C8 adenosyl radical known to generate a range of DNA lesions...
November 9, 2017: Journal of Chemical Theory and Computation
https://www.readbyqxmd.com/read/29116014/quantitative-assessment-of-radiation-dose-and-fractionation-effects-on-normal-tissue-by-utilizing-a-novel-lung-fibrosis-index-model
#15
Cheng Zhou, Bleddyn Jones, Mahmoud Moustafa, Christian Schwager, Julia Bauer, Bing Yang, Liji Cao, Min Jia, Andrea Mairani, Ming Chen, Longhua Chen, Juergen Debus, Amir Abdollahi
BACKGROUND: Normal lung tissue tolerance constitutes a limiting factor in delivering the required dose of radiotherapy to cure thoracic and chest wall malignancies. Radiation-induced lung fibrosis (RILF) is considered a critical determinant for late normal tissue complications. While RILF mouse models are frequently approached e.g., as a single high dose thoracic irradiation to investigate lung fibrosis and candidate modulators, a systematic radiobiological characterization of RILF mouse model is urgently needed to compare relative biological effectiveness (RBE) of particle irradiation with protons, helium-, carbon and oxygen ions now available at HIT...
November 7, 2017: Radiation Oncology
https://www.readbyqxmd.com/read/29115478/torin2-enhances-the-radiosensitivity-of-mcf%C3%A2-7-breast-cancer-cells-by-downregulating-the-mtor-signaling-pathway-and-atm-phosphorylation
#16
Jia Luo, Guocheng Pi, He Xiao, Yunfei Ye, Qing Li, Lianhua Zhao, Huan Huang, Hong Luo, Qin Zhang, Dong Wang, Ge Wang
Radiotherapy has an important role in the comprehensive treatment of breast cancer. However, the clinical outcome of adjuvant radiotherapy may be limited due to intrinsic radioresistance, it is necessary to explore efficient radiosensitization methods that improve the clinical outcome of patients undergoing radiotherapy. The present study aimed to investigate whether the novel mechanistic target of rapamycin (mTOR) inhibitor Torin2 enhances the radiosensitivity of MCF‑7 breast cancer cells. A Cell Counting Kit‑8 (CCK‑8) assay was performed to measure the effect of Torin2 on cell proliferation, while clonogenic assays were employed to determine the effect of Torin2 in combination with radiation on the proliferation of MCF‑7 cells...
October 20, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29115437/simvastatin-enhances-the-radiosensitivity-of-p53%C3%A2-deficient-cells-via-inhibition-of-mouse-double-minute-2-homolog
#17
Ji Young Lee, Mi-Sook Kim, Jae Eun Ju, Mi So Lee, Namhyun Chung, Youn Kyoung Jeong
Simvastatin exhibits anticancer activities, but its molecular mechanisms and radiosensitizing effects relative to p53 status remain unclear. In this study, we investigated whether the combination of simvastatin and ionizing radiation (IR) would enhance the antitumor effects of IR alone in HCT116 p53+/+ and p53‑/- colon cancer cells. Using colony formation assays and a xenograft mouse model, we found that simvastatin potently stimulated radiosensitization of HCT116 p53‑/- cells and xenograft tumors. The combination of simvastatin with IR decreased G2/M arrest and delayed the repair of IR-induced DNA damage; however, no differences between the HCT116 p53+/+ and p53‑/- cells were evident...
November 6, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/29113987/bap1-is-a-novel-target-in-hpv-negative-head-and-neck-cancer
#18
Xiyou Liu, Liangpeng Yang, David P Molkentine, David Valdacanas, Shiying Yu, Manish Kumar, Raymond E Meyn, John Heymach, Heath D Skinner
PURPOSE: This study examined the potential role of the nuclear deubiquitinating enzyme BRCA1-associated protein-1 (BAP1) in radioresistance in head and neck squamous cell cancer (HNSCC). EXPERIMENTAL DESIGN: We overexpressed, knocked down, and rescued BAP1 expression in six HNSCC cell lines, three human papillomavirus (HPV) -negative and HPV-positive, and examined the effects on radiosensitivity in vitro and in HNSCC mouse xenograft models. Radiosensitivity was assessed by clonogenic cell survival and tumor growth delay assays; changes in protein expression were analyzed by immunofluorescence staining and western blotting...
November 7, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29113342/overexpression-of-microrna-132-enhances-the-radiosensitivity-of-cervical-cancer-cells-by-down-regulating-bmi-1
#19
Gui-Feng Liu, Shu-Hua Zhang, Xue-Feng Li, Li-Yan Cao, Zhan-Zhao Fu, Shao-Nan Yu
We examined the effects of microRNA-132 (miR-132) on Bmi-1 expression and radiosensitivity in HeLa, SiHa, and C33A cervical cancer (CC) cells and 104 CC patients. MiR-132 expression was decreased and Bmi-1 expression was increased in tumor tissues compared to adjacent normal tissues and in radiotherapy-resistant patients compared to radiotherapy-sensitive patients. MiR-132 expression and Bmi-1 mRNA expression were also negatively correlated in tumor tissues. HeLa, SiHa, and C33A cells were divided into blank, miR-132 negative control (NC), miR-132 inhibitor, miR-132 mimics, siBmi-1, and miR-132 inhibitor + siBmi-1 groups, after which expression of miR-132 and Bmi-1, and the interaction between them and cell survival, proliferation, and apoptosis were examined...
October 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/29113232/inhibition-of-cyclooxygenase-2-sensitizes-lung-cancer-cells-to-radiation-induced-apoptosis
#20
Zhi-Qiang Han, Hongwei Liao, Feng Shi, Xiao-Ping Chen, Hua-Cheng Hu, Ming-Qing Tian, Li-Hua Wang, Songmin Ying
Radiotherapy resistance is an enduring major setback in lung cancer therapy, and is responsible for a large proportion of treatment failures. In previous years, cyclooxygenase-2 (COX-2) has frequently been reported to promote tumor occurrence and development, suggesting a potential role in radiotherapy resistance. To investigate whether COX-2 inhibitors can be applied in radiosensitization, an MTT assay was performed to examine cell viability after X-ray radiation in the presence or absence of the specific COX-2 inhibitor Celecoxib...
November 2017: Oncology Letters
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