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Fiona Griffin, Laure Marignol
Melatonin is an endogenous hormone primirarily known for its action on the circadian rhythms. But preclinical studies are reporting both its radioprotective and radiosensitising properties, possibly mediated through an interaction between melatonin and the regulation of estrogens. Melatonin pre-treatment prior to ionising 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...
March 9, 2018: International Journal of Radiation Biology
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
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...
January 18, 2018: British Journal of Cancer
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...
December 11, 2017: European Journal of Cancer
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...
December 2, 2017: Nanomedicine: Nanotechnology, Biology, and Medicine
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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