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https://www.readbyqxmd.com/read/30018737/an-evaluation-in-vitro-of-the-efficacy-of-nutlin-3-and-topotecan-in-combination-with-177-lu-dotatate-for-the-treatment-of-neuroblastoma
#1
Mathias Tesson, Richa Vasan, Andreas Hock, Colin Nixon, Colin Rae, Mark Gaze, Robert Mairs
Targeted radiotherapy of metastatic neuroblastoma using the somatostatin receptor (SSTR)-targeted octreotide analogue DOTATATE radiolabelled with lutetium-177 (177 Lu-DOTATATE) is a promising strategy. This study evaluates whether its effectiveness may be enhanced by combination with radiosensitising drugs. The growth rate of multicellular tumour spheroids, derived from the neuroblastoma cell lines SK-N-BE(2c), CHLA-15 and CHLA-20, was evaluated following treatment with 177 Lu-DOTATATE, nutlin-3 and topotecan alone or in combination...
June 26, 2018: Oncotarget
https://www.readbyqxmd.com/read/29979089/clinical-trials-targeting-hypoxia
#2
Hannah Tharmalingham, Peter Hoskin
The concept of tumour hypoxia as a cause of radiation resistance has been prevalent for over 100 years. During this time, our understanding of tumour hypoxia has matured with the recognition that oxygen tension within a tumour is influenced by both diffusion and perfusion mechanisms. In parallel, clinical strategies to modify tumour hypoxia with the expectation that this will improve response to radiation have been developed and tested in clinical trials. Despite many disappointments, meta-analysis of the data on hypoxia modification confirms a significant impact on both tumour control and survival...
July 6, 2018: British Journal of Radiology
https://www.readbyqxmd.com/read/29871812/outcomes-of-radiosensitisation-in-elderly-patients-with-advanced-bladder-cancer
#3
Marianna Christodoulou, Kimberley J Reeves, Clare Hodgson, Anthi Zeniou, Finbar Slevin, Jason Kennedy, Peter J Hoskin, Ann Henry, Ananya Choudhury
INTRODUCTION: There is little evidence to guide treatment in elderly patients with muscle invasive bladder cancer (MIBC). We evaluated the efficacy and tolerability of concurrent radical radiotherapy with gemcitabine radiosensitisation (GemX) in elderly patients with MIBC and compared outcomes to those from the bladder carbogen and nicotinamide (BCON) phase III trial. MATERIALS AND METHODS: Data were retrospectively analysed for patients who received GemX from two oncology centres in the UK...
June 2, 2018: Radiotherapy and Oncology: Journal of the European Society for Therapeutic Radiology and Oncology
https://www.readbyqxmd.com/read/29773816/experimental-investigation-of-radiobiology-in-head-and-neck-cancer-cell-lines-as-a-function-of-hpv-status-by-mtt-assay
#4
Paul Reid, Puthenparampil Wilson, Yanrui Li, Loredana G Marcu, Alexander H Staudacher, Michael P Brown, Eva Bezak
Head and neck cancers (HNCs) are aggressive epithelial tumours frequently treated using radiation. HNC biology shows distinctions dependent on the oncologic involvement of the human papilloma virus (HPV). Clinically, HPV positive HNCs respond better to radiotherapy but few in vitro data demonstrate radiobiological differences explaining differences in clinical outcomes. This pilot study examined radiobiological responses to irradiation and subsequent regeneration in two HNC cell lines (HPV positive and negative)...
May 17, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29609813/metallic-nanoparticle-radiosensitisation-of-ion-radiotherapy-a-review
#5
REVIEW
Dylan Peukert, Ivan Kempson, Michael Douglass, Eva Bezak
The use of gold nanoparticle (GNP) and other metal nanoparticle (MNP) radiosensitisers to enhance radiotherapy offers the potential of improved treatment outcomes. Originally intended for use with X-ray therapy, the possibility of enhanced hadron therapy is desirable due to the superior sparing of healthy tissue in hadron therapy compared to conventional X-ray therapy. While MNPs were not expected to be effective radiosensitisers for hadron therapy due to the limited Z dependence of interactions, recent experimental measurements have contradicted this expectation...
March 2018: Physica Medica: PM
https://www.readbyqxmd.com/read/29521142/therapeutic-potential-of-melatonin-for-breast-cancer-radiation-therapy-patients
#6
Fiona Griffin, Laure Marignol
Melatonin is an endogenous hormone primarily known for its action on the circadian rhythms. But pre-clinical studies are reporting both its radioprotective and radiosensitizing properties, possibly mediated through an interaction between melatonin and the regulation of estrogens. Melatonin pre-treatment prior to ionizing radiation was associated with a decrease in cell proliferation and an increase in p53 mRNA expression, leading to an increase in the radiosensitivity of breast cancer cells. At the same time, a decrease in radiation-induced side effects was described in breast cancer patients and in rodent models...
May 2018: International Journal of Radiation Biology
https://www.readbyqxmd.com/read/29365347/whole-brain-radiotherapy-for-the-treatment-of-newly-diagnosed-multiple-brain-metastases
#7
REVIEW
May N Tsao, Wei Xu, Rebecca Ks Wong, Nancy Lloyd, Normand Laperriere, Arjun Sahgal, Eileen Rakovitch, Edward Chow
BACKGROUND: This is an update to the review published in the Cochrane Library (2012, Issue 4).It is estimated that 20% to 40% of people with cancer will develop brain metastases during the course of their illness. The burden of brain metastases impacts quality and length of survival. OBJECTIVES: To assess the effectiveness and adverse effects of whole brain radiotherapy (WBRT) given alone or in combination with other therapies to adults with newly diagnosed multiple brain metastases...
January 25, 2018: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/29348487/h1-phgfk1-nanoparticles-exert-anti-tumoural-and-radiosensitising-effects-by-inhibition-of-met-in-glioblastoma
#8
Wenyan Zhang, Rui Duan, Jian Zhang, William K C Cheung, Xiaoge Gao, Raymond Zhang, Qing Zhang, Mengxue Wei, Gang Wang, Qian Zhang, Peng-Jin Mei, Hong-Lin Chen, Hsiangfu Kung, Marie C Lin, Zan Shen, Junnian Zheng, Longzhen Zhang, Hong Yao
BACKGROUND: The therapeutic resistance to ionising radiation (IR) and anti-angiogenesis mainly impair the prognosis of patients with glioblastoma. The primary and secondary MET aberrant activation is one crucial factor for these resistances. The kringle 1 domain of hepatocyte growth factor (HGFK1), an angiogenic inhibitor, contains a high-affinity binding domain of MET; however, its effects on glioblastoma remain elusive. METHODS: We formed the nanoparticles consisting of a folate receptor-targeted nanoparticle-mediated HGFK1 gene (H1/pHGFK1) and studied its anti-tumoural and radiosensitive activities in both subcutaneous and orthotopic human glioma cell-xenografted mouse models...
February 20, 2018: British Journal of Cancer
https://www.readbyqxmd.com/read/29241084/neoadjuvant-radiotherapy-combined-with-capecitabine-and-sorafenib-in-patients-with-advanced-kras-mutated-rectal-cancer-a-phase-i-ii-trial-sakk-41-08
#9
Roger von Moos, Dieter Koeberle, Sabina Schacher, Stefanie Hayoz, Ralph C Winterhalder, Arnaud Roth, György Bodoky, Panagiotis Samaras, Martin D Berger, Daniel Rauch, Piercarlo Saletti, Ludwig Plasswilm, Daniel Zwahlen, Urs R Meier, Pu Yan, Paola Izzo, Dirk Klingbiel, Daniela Bärtschi, Kathrin Zaugg
BACKGROUND: KRAS mutation occurs in ∼40% of locally advanced rectal cancers (LARCs). The multitarget tyrosine kinase inhibitor sorafenib has radiosensitising effects and might improve outcomes for standard preoperative chemoradiotherapy in patients with KRAS-mutated LARC. METHODS: Adult patients with KRAS-mutated T3/4 and/or N1/2M0 LARC were included in this phase I/II study. The phase I dose-escalation study of capecitabine plus sorafenib and radiotherapy was followed by a phase II study assessing efficacy and safety...
January 2018: European Journal of Cancer
https://www.readbyqxmd.com/read/29196180/unraveling-the-cell-type-dependent-radiosensitizing-effects-of-gold-through-the-development-of-a-multifunctional-gold-nanoparticle
#10
James R Nicol, Emma Harrison, Shannon M O'Neill, Dorian Dixon, Helen O McCarthy, Jonathan A Coulter
The radiosensitizing efficacy of gold is well established, however, there remain several significant barriers to the successful clinical translation of nano-sized gold particles (AuNPs). These barriers include: retaining stability in relevant biological sera, demonstrating effectiveness at clinically relevant AuNP concentrations and identifying the biological context where significant benefit is most likely to be achieved. Herein we have developed a AuNP preparation, stress-tested to provide effective protection from salt and serum mediated agglomeration...
February 2018: Nanomedicine: Nanotechnology, Biology, and Medicine
https://www.readbyqxmd.com/read/29029481/cell-cycle-specific-radiosensitisation-by-the-disulfiram-and-copper-complex
#11
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
#12
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
#13
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. This review aims to summarize the latest advances of gold nanoparticles in cancer treatment...
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
#14
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%...
February 2018: 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
#15
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/radiosensitization-in-vivo-by-histone-deacetylase-inhibition-with-no-increase-in-early-normal-tissue-radiation-toxicity
#16
EDITORIAL
Blaz Groselj, Jia-Ling Ruan, Helen Scott, Jessica Gorrill, Judith Nicholson, Jacqueline Kelly, Selvakumar Anbalagan, James Thompson, Michael R L 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 radiosensitizing 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)...
February 2018: 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
#17
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
#18
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
#19
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
#20
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
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