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https://www.readbyqxmd.com/read/29029481/cell-cycle-specific-radiosensitisation-by-the-disulfiram-and-copper-complex
#1
Mathias Tesson, Giorgio Anselmi, Caitlin Bell, Robert Mairs
The disulfiram and copper complex (DSF:Cu) has emerged as a potent radiosensitising anti-cancer agent. The ability of copper to stabilise DSF in a planar conformation and to inhibit DNA replication enzymes stimulated our investigation of the effect of DSF:Cu on cell cycle regulation. Flow cytometry and immunoblotting were used to assess the effect of DSF:Cu on cell cycle progression of the neuroblastoma cell line SK-N-BE(2c) and the glioma cell line UVW. Treatment with 0.1 and 0.3 μM DSF:Cu inhibited DNA synthesis in SK-N-BE(2c) and UVW cells, respectively...
September 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/28982844/clinical-potential-of-statins-in-prostate-cancer-radiation-therapy
#2
REVIEW
Jack Hutchinson, Laure Marignol
BACKGROUND/AIM: Statins are cholesterol- lowering drugs that have been shown to possess anti-tumour properties. Observational studies have shown that 3-hydroxy-3-methlyglutaryl coenzyme A reductase inhibitor (statin) use may be associated with reduced prostate cancer risk. Preclinical studies suggest that statins possess anticancer and radiosensitising properties. This review aims to determine the impact of statin use in the efficacy of radiation therapy and the therapeutic window in prostate cancer...
October 2017: Anticancer Research
https://www.readbyqxmd.com/read/28952430/gold-nanoparticles-promising-agent-to-improve-the-diagnosis-and-therapy-of-cancer
#3
Limin Ning, Benwei Zhu, Tao Gao
BACKGROUND: Gold nanoparticles have been exploited for nanobiotechnology applications for the last two decades. New insights of the nanomaterials as promising agent for cancer diagnosis and therapy have just started to emerge. Due to the size- and shape-dependent optical, electrical and thermal properties, gold nanoparticles are being developed as diagnostic reagents, drug carriers, contrast agents, photothermal agents and radiosensitisers. OBJECTIVE: This review aims to summarize the latest advances of gold nanoparticles in cancer treatment...
September 25, 2017: Current Drug Metabolism
https://www.readbyqxmd.com/read/28894897/peptide-receptor-radionuclide-therapy-prrt-in-european-neuroendocrine-tumour-society-enets-grade-3-g3-neuroendocrine-neoplasia-nen-a-single-institution-retrospective-analysis
#4
Sue Ping Thang, Mei Sim Lung, Grace Kong, Michael S Hofman, Jason Callahan, Michael Michael, Rodney J Hicks
PURPOSE: Grade 3 NENs are aggressive tumours with poor prognosis. PRRT+/- radiosensitising chemotherapy is a potential treatment for disease with high somatostatin receptor (SSTR) expression without spatially discordant FDG-avid disease. We retrospectively evaluated the efficacy of PRRT in G3 NEN. METHODS: Kaplan-Meier estimation was used to determine progression-free survival (PFS) and overall survival (OS) defined from start of PRRT. Subgroup analysis was performed for patients with Ki-67 ≤ 55% and >55%...
September 12, 2017: European Journal of Nuclear Medicine and Molecular Imaging
https://www.readbyqxmd.com/read/28873460/perfluorocarbon-emulsions-radiosensitise-brain-tumors-in-carbogen-breathing-mice-with-orthotopic-gl261-gliomas
#5
Lisa A Feldman, Marie-Sophie Fabre, Carole Grasso, Dana Reid, William C Broaddus, Gregory M Lanza, Bruce D Spiess, Joel R Garbow, Melanie J McConnell, Patries M Herst
BACKGROUND: Tumour hypoxia limits the effectiveness of radiation therapy. Delivering normobaric or hyperbaric oxygen therapy elevates pO2 in both tumour and normal brain tissue. However, pO2 levels return to baseline within 15 minutes of stopping therapy. AIM: To investigate the effect of perfluorocarbon (PFC) emulsions on hypoxia in subcutaneous and intracranial mouse gliomas and their radiosensitising effect in orthotopic gliomas in mice breathing carbogen (95%O2 and 5%CO2)...
2017: PloS One
https://www.readbyqxmd.com/read/28839000/radiosensitisation-in-vivo-by-histone-deacetylase-inhibition-with-no-increase-in-early-normal-tissue-radiation-toxicity
#6
Blaz Groselj, Jia-Ling Ruan, Helen Scott, Jessica Gorrill, Judith Nicholson, Jacqueline Kelly, Selvakumar Anbalagan, James Thompson, Michael Rl Stratford, Sarah J Jevons, Ester M Hammond, Cheryl L Scudamore, Martin Kerr, Anne E Kiltie
As the population ages, more elderly patients require radiotherapy-based treatment for their pelvic malignancies, including muscle-invasive bladder cancer, as they are unfit for major surgery. Therefore, there is an urgent need to find radiosensitising agents minimally toxic to normal tissues, including bowel and bladder, for such patients. We developed methods to determine normal tissue toxicity severity in intestine and bladder in vivo, using novel radiotherapy techniques on a small animal radiation research platform (SARRP)...
August 24, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28756902/bevacizumab-for-advanced-cervical-cancer-final-overall-survival-and-adverse-event-analysis-of-a-randomised-controlled-open-label-phase-3-trial-gynecologic-oncology-group-240
#7
Krishnansu S Tewari, Michael W Sill, Richard T Penson, Helen Huang, Lois M Ramondetta, Lisa M Landrum, Ana Oaknin, Thomas J Reid, Mario M Leitao, Helen E Michael, Philip J DiSaia, Larry J Copeland, William T Creasman, Frederick B Stehman, Mark F Brady, Robert A Burger, J Tate Thigpen, Michael J Birrer, Steven E Waggoner, David H Moore, Katherine Y Look, Wui-Jin Koh, Bradley J Monk
BACKGROUND: On Aug 14, 2014, the US Food and Drug Administration approved the antiangiogenesis drug bevacizumab for women with advanced cervical cancer on the basis of improved overall survival (OS) after the second interim analysis (in 2012) of 271 deaths in the Gynecologic Oncology Group (GOG) 240 trial. In this study, we report the prespecified final analysis of the primary objectives, OS and adverse events. METHODS: In this randomised, controlled, open-label, phase 3 trial, we recruited patients with metastatic, persistent, or recurrent cervical carcinoma from 81 centres in the USA, Canada, and Spain...
October 7, 2017: Lancet
https://www.readbyqxmd.com/read/28700660/cancer-selective-single-agent-chemoradiosensitising-gold-nanoparticles
#8
Sophie Grellet, Konstantina Tzelepi, Meike Roskamp, Phil Williams, Aquila Sharif, Richard Slade-Carter, Peter Goldie, Nicky Whilde, Małgorzata A Śmiałek, Nigel J Mason, Jon P Golding
Two nanometre gold nanoparticles (AuNPs), bearing sugar moieties and/or thiol-polyethylene glycol-amine (PEG-amine), were synthesised and evaluated for their in vitro toxicity and ability to radiosensitise cells with 220 kV and 6 MV X-rays, using four cell lines representing normal and cancerous skin and breast tissues. Acute 3 h exposure of cells to AuNPs, bearing PEG-amine only or a 50:50 ratio of alpha-galactose derivative and PEG-amine resulted in selective uptake and toxicity towards cancer cells at unprecedentedly low nanomolar concentrations...
2017: PloS One
https://www.readbyqxmd.com/read/28677687/topk-modulates-tumour-specific-radiosensitivity-and-correlates-with-recurrence-after-prostate-radiotherapy
#9
Giacomo Pirovano, Thomas M Ashton, Katharine J Herbert, Richard J Bryant, Clare L Verrill, Lucia Cerundolo, Francesca M Buffa, Remko Prevo, Iona Harrap, Anderson J Ryan, Valentine Macaulay, William G McKenna, Geoff S Higgins
BACKGROUND: Tumour-specific radiosensitising treatments may enhance the efficacy of radiotherapy without exacerbating side effects. In this study we determined the radiation response following depletion or inhibition of TOPK, a mitogen-activated protein kinase kinase family Ser/Thr protein kinase that is upregulated in many cancers. METHODS: Radiation response was studied in a wide range of cancer cell lines and normal cells using colony formation assays. The effect on cell cycle progression was assessed and the relationship between TOPK expression and therapeutic efficacy was studied in a cohort of 128 prostate cancer patients treated with radical radiotherapy...
August 8, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28638277/titanium-dioxide-nanoparticles-as-radiosensitisers-an-in-vitro-and-phantom-based-study
#10
Esho Qasho Youkhana, Bryce Feltis, Anton Blencowe, Moshi Geso
Objective: Radiosensitisation caused by titanium dioxide nanoparticles (TiO2-NPs) is investigated using phantoms (PRESAGE(®) dosimeters) and in vitro using two types of cell lines, cultured human keratinocyte (HaCaT) and prostate cancer (DU145) cells. Methods: Anatase TiO2-NPs were synthesised, characterised and functionalised to allow dispersion in culture-medium for in vitro studies and halocarbons (PRESAGE(®) chemical compositions). PRESAGE(®) dosimeters were scanned with spectrophotometer to determine the radiation dose enhancement...
2017: International Journal of Medical Sciences
https://www.readbyqxmd.com/read/28624789/pediatric-and-adult-glioblastoma-radiosensitization-induced-by-pi3k-mtor-inhibition-causes-early-metabolic-alterations-detected-by-nuclear-magnetic-resonance-spectroscopy
#11
Alice Agliano, Geetha Balarajah, Daniela M Ciobota, Jasmin Sidhu, Paul A Clarke, Chris Jones, Paul Workman, Martin O Leach, Nada M S Al-Saffar
Poor outcome for patients with glioblastomas is often associated with radioresistance. PI3K/mTOR pathway deregulation has been correlated with radioresistance; therefore, PI3K/mTOR inhibition could render tumors radiosensitive. In this study, we show that NVP-BEZ235, a dual PI3K/mTOR inhibitor, potentiates the effects of irradiation in both adult and pediatric glioblastoma cell lines, resulting in early metabolic changes detected by nuclear magnetic resonance (NMR) spectroscopy. NVP-BEZ235 radiosensitises cells to X ray exposure, inducing cell death through the inhibition of CDC25A and the activation of p21cip1(CDKN1A)...
July 18, 2017: Oncotarget
https://www.readbyqxmd.com/read/28605448/efficacy-of-peptide-receptor-radionuclide-therapy-for-functional-metastatic-paraganglioma-and-pheochromocytoma
#12
COMPARATIVE STUDY
Grace Kong, Simona Grozinsky-Glasberg, Michael S Hofman, Jason Callahan, Amichay Meirovitz, Ofra Maimon, David A Pattison, David J Gross, Rodney J Hicks
Purpose: Treatment options for unresectable paraganglioma (PGL)/pheochromocytoma (PCC), especially with uncontrolled secondary hypertension (HTN), are limited. Preliminary studies with peptide receptor radionuclide therapy (PRRT) suggest efficacy, but data on HTN control and survival are lacking. We assessed PRRT outcomes in such patients from two referral centers. Methods: Twenty consecutive patients (13 men; age range, 21 to 77 years) with high somatostatin receptor (SSTR) expression treated with 177Lu-DOTA-octreotate, nine with radiosensitizing chemotherapy, were retrospectively reviewed...
September 1, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28540821/enhancing-radiosensitisation-of-brca2-proficient-and-brca2-deficient-cell-lines-with-hyperthermia-and-parp1-i
#13
Arlene L Oei, Vidhula R Ahire, C M van Leeuwen, Rosemarie Ten Cate, Lukas J A Stalpers, Johannes Crezee, H Petra Kok, Nicolaas A P Franken
Poly(ADP-ribose)polymerase1 (PARP1) is an important enzyme in regulating DNA replication. Inhibition of PARP1 can lead to collapsed DNA forks which subsequently causes genomic instability, making DNA more susceptible in developing fatal DNA double strand breaks. PARP1-induced DNA damage is generally repaired by homologous recombination (HR), in which BRCA2 proteins are essential. Therefore, BRCA2-deficient tumour cells are susceptible to treatment with PARP1-inhibitors (PARP1-i). Recently, BRCA2 was shown to be down-regulated by hyperthermia (HT) temporarily, and this consequently inactivated HR for several hours...
May 19, 2017: International Journal of Hyperthermia
https://www.readbyqxmd.com/read/28448462/targeting-the-atr-chk1-axis-in-cancer-therapy
#14
REVIEW
Stuart Rundle, Alice Bradbury, Yvette Drew, Nicola J Curtin
Targeting the DNA damage response (DDR) is a new therapeutic approach in cancer that shows great promise for tumour selectivity. Key components of the DDR are the ataxia telangiectasia mutated and Rad3 related (ATR) and checkpoint kinase 1 (CHK1) kinases. This review article describes the role of ATR and its major downstream target, CHK1, in the DDR and why cancer cells are particularly reliant on the ATR-CHK1 pathway, providing the rationale for targeting these kinases, and validation of this hypothesis by genetic manipulation...
April 27, 2017: Cancers
https://www.readbyqxmd.com/read/28399491/metformin-and-improved-treatment-outcomes-in-radiation-therapy-a-review
#15
REVIEW
Nur Atiqah Binte Samsuri, Michelle Leech, Laure Marignol
BACKGROUND: Metformin, a primary treatment for diabetes mellitus (DM) patients, is associated with improved outcomes for diabetic cancer patients fuelling further investigation on its mechanisms of action. The radiosensitising properties of metformin are increasingly reported in pre-clinical studies. This review discusses whether metformin should be offered to radiotherapy (RT) cancer patients as a means to improve their treatment outcomes. MATERIALS AND METHODS: A database search was conducted for articles published with metformin as the main intervention between 2010 and 2016...
April 2017: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/28398879/parthenolide-selectively-sensitizes-prostate-tumor-tissue-to-radiotherapy-while-protecting-healthy-tissues-in-vivo
#16
Katherine L Morel, Rebecca J Ormsby, Eva Bezak, Christopher J Sweeney, Pamela J Sykes
Radiotherapy is widely used in cancer treatment, however the benefits can be limited by radiation-induced damage to neighboring normal tissues. Parthenolide (PTL) exhibits anti-inflammatory and anti-tumor properties and selectively induces radiosensitivity in prostate cancer cell lines, while protecting primary prostate epithelial cell lines from radiation-induced damage. Low doses of radiation have also been shown to protect from subsequent high-dose-radiation-induced apoptosis as well as DNA damage. These properties of PTL and low-dose radiation could be used to improve radiotherapy by killing more tumor cells and less normal cells...
May 2017: Radiation Research
https://www.readbyqxmd.com/read/28365670/the-impact-of-concentration-and-administration-time-on-the-radiomodulating-properties-of-undecylprodigiosin-in-vitro
#17
Sandra Petrović, Vesna Vasić, Tatjana Mitrović, Saša Lazović, Andreja Leskovac
Undecylprodigiosin pigment (UPP) is reported to display cytotoxic activity towards various types of tumours. Nevertheless, its efficacy in modifying the cellular response to ionising radiation is still unknown. In this study, the radiomodulating effects of UPP were investigated. The effects of UPP were assessed in vitro by treating cultures of human peripheral blood with UPP and ionising radiation using two treatment regimens, the UPP pre-irradiation treatment and UPP post-irradiation treatment. The activity of UPP was investigated evaluating its effects on the radiation-induced micronuclei formation, cell proliferation, and induction of apoptosis...
March 1, 2017: Arhiv za Higijenu Rada i Toksikologiju
https://www.readbyqxmd.com/read/28363998/e3-ligase-ciap2-mediates-downregulation-of-mre11-and-radiosensitization-in-response-to-hdac-inhibition-in-bladder-cancer
#18
Judith Nicholson, Sarah J Jevons, Blaz Groselj, Sophie Ellermann, Rebecca Konietzny, Martin Kerr, Benedikt M Kessler, Anne E Kiltie
The MRE11/RAD50/NBS1 (MRN) complex mediates DNA repair pathways, including double-strand breaks induced by radiotherapy. Meiotic recombination 11 homolog (MRE11) is downregulated by histone deacetylase inhibition (HDACi), resulting in reduced levels of DNA repair in bladder cancer cells and radiosensitization. In this study, we show that the mechanism of this downregulation is posttranslational and identify a C-terminally truncated MRE11, which is formed after HDAC inhibition as full-length MRE11 is downregulated...
June 1, 2017: Cancer Research
https://www.readbyqxmd.com/read/28327297/first-proof-of-bismuth-oxide-nanoparticles-as-efficient-radiosensitisers-on-highly-radioresistant-cancer-cells
#19
Callum Stewart, Konstantin Konstantinov, Sally McKinnon, Susanna Guatelli, Michael Lerch, Anatoly Rosenfeld, Moeava Tehei, Stéphanie Corde
This study provides the first proof of the novel application of bismuth oxide as a radiosensitiser. It was shown that on the highly radioresistant 9L gliosarcoma cell line, bismuth oxide nanoparticles sensitise to both kilovoltage (kVp) or megavoltage (MV) X-rays radiation. 9L cells were exposed to a concentration of 50μg.mL(-1) of nanoparticle before irradiation at 125kVp and 10MV. Sensitisation enhancement ratios of 1.48 and 1.25 for 125kVp and 10MV were obtained in vitro, respectively. The radiation enhancement of the nanoparticles is postulated to be a combination of the high Z nature of the bismuth (Z=83), and the surface chemistry...
November 2016: Physica Medica: PM
https://www.readbyqxmd.com/read/28300190/a-mechanistic-study-of-gold-nanoparticle-radiosensitisation-using-targeted-microbeam-irradiation
#20
Mihaela Ghita, Stephen J McMahon, Laura E Taggart, Karl T Butterworth, Giuseppe Schettino, Kevin M Prise
Gold nanoparticles (GNPs) have been demonstrated as effective radiosensitizing agents in a range of preclinical models using broad field sources of various energies. This study aimed to distinguish between these mechanisms by applying subcellular targeting using a soft X-ray microbeam in combination with GNPs. DNA damage and repair kinetics were determined following nuclear and cytoplasmic irradiation using a soft X-ray (carbon K-shell, 278 eV) microbeam in MDA-MB-231 breast cancer and AG01522 fibroblast cells with and without GNPs...
March 16, 2017: Scientific Reports
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