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Radiosensitisers

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https://www.readbyqxmd.com/read/27875881/communication-position-does-matter-the-photofragmentation-of-the-nitroimidazole-isomers
#1
P Bolognesi, A R Casavola, A Cartoni, R Richter, P Markus, S Borocci, J Chiarinelli, S Tošić, H Sa'adeh, M Masič, B P Marinković, K C Prince, L Avaldi
A combined experimental and theoretical approach has been used to disentangle the fundamental mechanisms of the fragmentation of the three isomers of nitroimidazole induced by vacuum ultra-violet (VUV) radiation, namely, 4-, 5-, and 2-nitroimidazole. The results of mass spectrometry as well as photoelectron-photoion coincidence spectroscopy display striking differences in the radiation-induced decomposition of the different nitroimidazole radical cations. Based on density functional theory (DFT) calculations, a model is proposed which fully explains such differences, and reveals the subtle fragmentation mechanisms leading to the release of neutral species like NO, CO, and HCN...
November 21, 2016: Journal of Chemical Physics
https://www.readbyqxmd.com/read/27867425/gold-nanoparticles-for-cancer-radiotherapy-a-review
#2
REVIEW
Kaspar Haume, Soraia Rosa, Sophie Grellet, Małgorzata A Śmiałek, Karl T Butterworth, Andrey V Solov'yov, Kevin M Prise, Jon Golding, Nigel J Mason
Radiotherapy is currently used in around 50% of cancer treatments and relies on the deposition of energy directly into tumour tissue. Although it is generally effective, some of the deposited energy can adversely affect healthy tissue outside the tumour volume, especially in the case of photon radiation (gamma and X-rays). Improved radiotherapy outcomes can be achieved by employing ion beams due to the characteristic energy deposition curve which culminates in a localised, high radiation dose (in form of a Bragg peak)...
2016: Cancer Nanotechnology
https://www.readbyqxmd.com/read/27756009/magnetic-nanoparticle-induced-hyperthermia-with-appropriate-payloads-paul-ehrlich-s-magic-nano-bullet-for-cancer-theranostics
#3
N R Datta, S Krishnan, D E Speiser, E Neufeld, N Kuster, S Bodis, H Hofmann
Effective multimodal cancer management requires the optimal integration of diagnostic and therapeutic modalities. Radiation therapy, chemotherapy and immunotherapy, alone or in combination, are integral parts of various cancer treatment protocols. Hyperthermia at 39-45°C is a potent radiosensitiser and has been shown to improve therapeutic outcomes in various tumours through its synergy with chemotherapy. Gene silencing approaches, using small interfering RNAs and microRNAs, are also being explored in clinical trials in oncology...
October 3, 2016: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/27755996/treatment-de-intensification-strategies-for-head-and-neck-cancer
#4
REVIEW
Jacqueline R Kelly, Zain A Husain, Barbara Burtness
Increasingly, squamous cell carcinoma of the oropharynx (OPSCC) is attributable to transformation resulting from high-risk human papillomavirus (HPV) infection. Such cancers are significantly more responsive to treatment than traditional tobacco- and alcohol-associated squamous cell cancers of the head and neck. Conventional management with definitive chemoradiation, surgery and adjuvant radiation, or radiation given with altered fractionation schemes, while effective, incurs long-term morbidity that escalates with treatment intensity and significantly impairs quality of life...
November 2016: European Journal of Cancer
https://www.readbyqxmd.com/read/27744728/3d-radiobiological-evaluation-of-combined-radiotherapy-and-hyperthermia-treatments
#5
C M van Leeuwen, J Crezee, A L Oei, N A P Franken, L J A Stalpers, A Bel, H P Kok
PURPOSE: Currently, clinical decisions regarding thermoradiotherapy treatments are based on clinical experience. Quantification of the radiosensitising effect of hyperthermia allows comparison of different treatment strategies, and can support clinical decision-making regarding the optimal treatment. The software presented here enables biological evaluation of thermoradiotherapy plans through calculation of equivalent 3D dose distributions. METHODS: Our in-house developed software (X-Term) uses an extended version of the linear-quadratic model to calculate equivalent radiation dose, i...
October 17, 2016: International Journal of Hyperthermia
https://www.readbyqxmd.com/read/27722716/using-high-harmonic-radiation-to-reveal-the-ultrafast-dynamics-of-radiosensitiser-molecules
#6
Pierre Çarçabal, Dominique Descamps, Stéphane Petit, Yann Mairesse, Valérie Blanchet, Raluca Cireasa
5-Fluorouracil (5FU) is a radiosensitiser molecule routinely used in combined chemo- and radio-therapies to enhance and localize cancer treatments. We have employed ultra-short XUV pulses produced by high harmonic generation (HHG) as a pump pulse to study the dynamics underlying the photo-stability and the radiation damage of this molecule. This work shows that it is possible to resolve individual dynamics even when using unselected HH. By comparing the results with those obtained in the multiphoton absorption at 400 nm, we were able to identify the frequencies of the HH comb relevant to the recorded dynamics: HH5 and HH3...
September 22, 2016: Faraday Discussions
https://www.readbyqxmd.com/read/27711083/radvan-a-randomised-phase-2-trial-of-wbrt-plus-vandetanib-for-melanoma-brain-metastases-results-and-lessons-learnt
#7
Avinash Gupta, Corran Roberts, Finn Tysoe, Matthew Goff, Jenny Nobes, James Lester, Ernie Marshall, Carie Corner, Virginia Wolstenholme, Charles Kelly, Adelyn Wise, Linda Collins, Sharon Love, Martha Woodward, Amanda Salisbury, Mark R Middleton
BACKGROUND: Brain metastases occur in up to 75% of patients with advanced melanoma. Most are treated with whole-brain radiotherapy (WBRT), with limited effectiveness. Vandetanib, an inhibitor of vascular endothelial growth factor receptor, epidermal growth factor receptor and rearranged during transfection tyrosine kinases, is a potent radiosensitiser in xenograft models. We compared WBRT with WBRT plus vandetanib in the treatment of patients with melanoma brain metastases. METHODS: In this double-blind, multi-centre, phase 2 trial patients with melanoma brain metastases were randomised to receive WBRT (30 Gy in 10 fractions) plus 3 weeks of concurrent vandetanib 100 mg once daily or placebo...
November 8, 2016: British Journal of Cancer
https://www.readbyqxmd.com/read/27678267/high-clinical-and-morphologic-response-using-90-y-dota-octreotate-sequenced-with-177-lu-dota-octreotate-induction-peptide-receptor-chemoradionuclide-therapy-prcrt-for-bulky-neuroendocrine-tumours
#8
Grace Kong, Jason Callahan, Michael S Hofman, David A Pattison, Tim Akhurst, Michael Michael, Peter Eu, Rodney J Hicks
PURPOSE: Bulky disease is an adverse prognostic factor for (177)Lu-DOTA-octreotate ((177)Lu-DOTATATE) peptide receptor radionuclide therapy (PRRT). (90)Y-DOTA-octreotate ((90)Y-DOTATATE) has theoretical advantages in this setting but may less effectively treat co-existent smaller deposits and have higher toxicity than (177)Lu-DOTATATE. The aim of this study was to assess the efficacy and safety of using these agents sequentially. METHODS: We reviewed patients (pts) with at least one lesion of a transaxial diameter >4 cm who completed 1-2 cycles of (90)Y-DOTATATE followed by 2-3 cycles of (177)Lu-DOTATATE, with treatment empirically adapted to disease size and burden in individual patients...
September 27, 2016: European Journal of Nuclear Medicine and Molecular Imaging
https://www.readbyqxmd.com/read/27659007/review-of-geant4-dna-applications-for-micro-and-nanoscale-simulations
#9
S Incerti, M Douglass, S Penfold, S Guatelli, E Bezak
Emerging radiotherapy treatments including targeted particle therapy, hadron therapy or radiosensitisation of cells by high-Z nanoparticles demand the theoretical determination of radiation track structure at the nanoscale. This is essential in order to evaluate radiation damage at the cellular and DNA level. Since 2007, Geant4 offers physics models to describe particle interactions in liquid water at the nanometre level through the Geant4-DNA Package. This package currently provides a complete set of models describing the event-by-event electromagnetic interactions of particles with liquid water, as well as developments for the modelling of water radiolysis...
September 19, 2016: Physica Medica: PM
https://www.readbyqxmd.com/read/27599042/hypoxia-independent-gene-expression-signature-associated-with-radiosensitisation-of-prostate-cancer-cell-lines-by-histone-deacetylase-inhibition
#10
Marte Jonsson, Harald Bull Ragnum, Cathinka Halle Julin, Andree Yeramian, Trevor Clancy, Kari-Anne Myrum Frikstad, Therese Seierstad, Trond Stokke, Xavier Matias-Guiu, Anne Hansen Ree, Kjersti Flatmark, Heidi Lyng
BACKGROUND: Histone deacetylase inhibitors (HDACis) like vorinostat are promising radiosensitisers in prostate cancer, but their effect under hypoxia is not known. We investigated gene expression associated with radiosensitisation of normoxic and hypoxic prostate cancer cells by vorinostat. METHODS: Cells were exposed to vorinostat under normoxia or hypoxia and subjected to gene expression profiling before irradiation and clonogenic survival analysis. RESULTS: Pretreatment with vorinostat led to radiosensitisation of the intrinsically radioresistant DU 145 cells, but not the radiosensitive PC-3 and 22Rv1 cells, and was independent of hypoxia status...
October 11, 2016: British Journal of Cancer
https://www.readbyqxmd.com/read/27573059/in-silico-modelling-of-a-cancer-stem-cell-targeting-agent-and-its-effects-on-tumour-control-during-radiotherapy
#11
Loredana G Marcu, David Marcu
Head and neck cancers (HNC), like most solid tumours, contain a subpopulation of cancer stem cells (CSC) that are commonly responsible for treatment failure. Conventional therapies are unsuccessful in controlling CSCs, thus novel, targeting therapies are needed. A promising agent is ATRA (All-trans-retinoic acid) that was shown to induce CSC differentiation, cell cycle redistribution and CSCs radiosensitisation. To add to the limited data, this work simulated the effects of ATRA on a virtual HNC and evaluated tumour response to radiotherapy...
2016: Scientific Reports
https://www.readbyqxmd.com/read/27515310/an-evaluation-in-vitro-of-parp-1-inhibitors-rucaparib-and-olaparib-as-radiosensitisers-for-the-treatment-of-neuroblastoma
#12
Donna L Nile, Colin Rae, Iain J Hyndman, Mark N Gaze, Robert J Mairs
BACKGROUND: The radiopharmaceutical (131)I-meta-iodobenzylguanidine ((131)I-MIBG) is an effective treatment for neuroblastoma. However, maximal therapeutic benefit from (131)I-MIBG is likely to be obtained by its combination with chemotherapy. We previously reported enhanced antitumour efficacy of (131)I-MIBG by inhibition of the poly(ADP-ribose) polymerase-1 (PARP-1) DNA repair pathway using the phenanthridinone derivative PJ34. Recently developed alternative PARP-1 inhibitors have greater target specificity and are expected to be associated with reduced toxicity to normal tissue...
2016: BMC Cancer
https://www.readbyqxmd.com/read/27488871/induction-of-apoptosis-in-intestinal-toxicity-to-a-histone-deacetylase-inhibitor-in-a-phase-i-study-with-pelvic-radiotherapy
#13
Erta Kalanxhi, Karianne Risberg, Imon S Barua, Svein Dueland, Stein Waagene, Solveig Norheim Andersen, Solveig J Pettersen, Jessica M Lindvall, Kathrine Røe Redalen, Kjersti Flatmark, Anne Hansen Ree
Purpose: When integrating molecularly targeted compounds in radiotherapy, synergistic effects of the systemic agent and radiation may extend the limits of patient tolerance, increasing the demand for understanding the pathophysiological mechanisms of treatment toxicity. In this Pelvic Radiation and Vorinostat (PRAVO) study, we investigated mechanisms of adverse effects in response to the histone deacetylase (HDAC) inhibitor vorinostat (suberoylanilide hydroxamic acid; SAHA) when administered as a potential radiosensitiser...
July 28, 2016: Cancer Research and Treatment: Official Journal of Korean Cancer Association
https://www.readbyqxmd.com/read/27422809/chk1-inhibition-radiosensitizes-head-and-neck-cancers-to-paclitaxel-based-chemoradiotherapy
#14
Holly E Barker, Radhika Patel, Martin McLaughlin, Ulrike Schick, Shane Zaidi, Christopher M Nutting, Katie L Newbold, Shreerang Bhide, Kevin J Harrington
Head and neck squamous cell carcinoma (HNSCC) is a leading cause of cancer-related deaths, with increasingly more cases arising due to high-risk human papillomavirus (HPV) infection. Cisplatin-based chemoradiotherapy is a standard-of-care for locally advanced head and neck cancer but is frequently ineffective. Research into enhancing radiation responses as a means of improving treatment outcomes represents a high priority. Here, we evaluated a CHK1 inhibitor (CCT244747) as a radiosensitiser and investigated whether a mechanistically rational triple combination of radiation/paclitaxel/CHK1 inhibitor delivered according to an optimized schedule would provide added benefit...
September 2016: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/27380135/repression-of-the-autophagic-response-sensitises-lung-cancer-cells-to-radiation-and-chemotherapy
#15
Ilias V Karagounis, Dimitra Kalamida, Achilleas Mitrakas, Stamatia Pouliliou, Maria V Liousia, Alexandra Giatromanolaki, Michael I Koukourakis
BACKGROUND: The cellular autophagic response to radiation is complex. Various cells and tissues respond differentially to radiation, depending on both the dose of exposure and the time post irradiation. In the current study, we determined the autophagosomal and lysosomal response to radiation in lung cancer cell lines by evaluating the expression of the associated proteins, as well as the effect of relevant gene silencing in radio and chemosensitisation. Furthermore, tumour sensitisation was evaluated in in vivo autophagic gene silencing model after irradiation...
July 26, 2016: British Journal of Cancer
https://www.readbyqxmd.com/read/27325273/efficient-protocol-for-the-identification-of-hypoxic-cell-radiosensitisers
#16
Cho Rong Hong, Jingli Wang, Kevin O Hicks, Michael P Hay
An evolution in radiotherapy practice is leading to greater use of stereotactic body radiotherapy (SBRT), raising the prospect of increased hypoxic cell radioresistance. New clinical interest in nitroimidazole radiosensitisers, combined with appropriate biomarkers, signals a revival for radiosensitisers in the context of SBRT. Our interest in modifiers of radiation therapy led us to revisit this area and we have identified a new class of nitroimidazole radiosensitiser. We have developed an abbreviated screening protocol suitable for an academic drug discovery laboratory which allows expeditious triage of compounds with poor physicochemical and in vitro properties and combines in vitro radiosensitisation data with tumour pharmacokinetic data to efficiently select candidates for further evaluation...
2016: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/27318679/dna-repair
#17
Kerstin Borgmann, Sabrina Köcher, Malte Kriegs, Wael Yassin Mansour, Ann Christin Parplys, Thorsten Rieckmann, Kai Rothkamm
Cellular chromosomal DNA is the principal target through which ionising radiation exerts it diverse biological effects. This chapter summarises the relevant DNA damage signalling and repair pathways used by normal and tumour cells in response to irradiation. Strategies for tumour radiosensitisation are reviewed which exploit tumour-specific DNA repair deficiencies or signalling pathway addictions, with a special focus on growth factor signalling, PARP, cancer stem cells, cell cycle checkpoints and DNA replication...
2016: Recent Results in Cancer Research
https://www.readbyqxmd.com/read/27139157/preliminary-evaluation-of-prostate-targeted-radiotherapy-using-131-i-mip-1095-in-combination-with-radiosensitising-chemotherapeutic-drugs
#18
Mathias Tesson, Colin Rae, Colin Nixon, John W Babich, Robert J Mairs
OBJECTIVES: Despite recent advances in the treatment of metastatic prostate cancer, survival rates are low and treatment options are limited to chemotherapy and hormonal therapy. (131) I-MIP-1095 is a recently developed prostate-specific membrane antigen (PSMA)-targeting, small molecular weight radiopharmaceutical which has anti-tumour activity as a single agent. Our purpose was to determine in vitro the potential benefit to be gained by combining (131) I-MIP-1095 with cytotoxic drug treatments...
July 2016: Journal of Pharmacy and Pharmacology
https://www.readbyqxmd.com/read/27080849/protein-disulphide-isomerase-as-a-target-for-nanoparticle-mediated-sensitisation-of-cancer-cells-to-radiation
#19
L E Taggart, S J McMahon, K T Butterworth, F J Currell, G Schettino, K M Prise
Radiation resistance and toxicity in normal tissues are limiting factors in the efficacy of radiotherapy. Gold nanoparticles (GNPs) have been shown to be effective at enhancing radiation-induced cell death, and were initially proposed to physically enhance the radiation dose deposited. However, biological responses of GNP radiosensitization based on physical assumptions alone are not predictive of radiosensitisation and therefore there is a fundamental research need to determine biological mechanisms of response to GNPs alone and in combination with ionising radiation...
May 27, 2016: Nanotechnology
https://www.readbyqxmd.com/read/27002558/review-of-ultrasound-image-guidance-in-external-beam-radiotherapy-part-ii-intra-fraction-motion-management-and-novel-applications
#20
Tuathan O'Shea, Jeffrey Bamber, Davide Fontanarosa, Skadi van der Meer, Frank Verhaegen, Emma Harris
Imaging has become an essential tool in modern radiotherapy (RT), being used to plan dose delivery prior to treatment and verify target position before and during treatment. Ultrasound (US) imaging is cost-effective in providing excellent contrast at high resolution for depicting soft tissue targets apart from those shielded by the lungs or cranium. As a result, it is increasingly used in RT setup verification for the measurement of inter-fraction motion, the subject of Part I of this review (Fontanarosa et al 2015 Phys...
April 21, 2016: Physics in Medicine and Biology
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