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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
#1
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)...
May 24, 2017: Oncotarget
https://www.readbyqxmd.com/read/28605448/efficacy-of-peptide-receptor-radionuclide-therapy-prrt-for-functional-metastatic-paraganglioma-and-phaeochromocytoma
#2
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)/Phaeochromocytoma (PCC), especially with uncontrolled secondary hypertension (HTN) are limited. Preliminary studies with PRRT suggest efficacy but data on HTN control and survival are lacking. We assessed PRRT outcomes in such patients from 2 referral centres. Methods: 20 consecutive patients (M:F=13:7; 21-77y.o.) with high somatostatin receptor (SSTR) expression treated with 177Lu-DOTA-octreotate, 9 with radiosensitising chemotherapy, were retrospectively reviewed...
June 9, 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
#3
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
#4
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
#5
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
#6
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
#7
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
#8
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...
March 31, 2017: Cancer Research
https://www.readbyqxmd.com/read/28327297/first-proof-of-bismuth-oxide-nanoparticles-as-efficient-radiosensitisers-on-highly-radioresistant-cancer-cells
#9
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
#10
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
https://www.readbyqxmd.com/read/28217175/a-local-effect-model-based-interpolation-framework-for-experimental-nanoparticle-radiosensitisation-data
#11
Jeremy M C Brown, Fred J Currell
A local effect model (LEM)-based framework capable of interpolating nanoparticle-enhanced photon-irradiated clonogenic cell survival fraction measurements as a function of nanoparticle concentration was developed and experimentally benchmarked for gold nanoparticle (AuNP)-doped bovine aortic endothelial cells (BAECs) under superficial kilovoltage X-ray irradiation. For three different superficial kilovoltage X-ray spectra, the BAEC survival fraction response was predicted for two different AuNP concentrations and compared to experimental data...
2017: Cancer Nanotechnology
https://www.readbyqxmd.com/read/28055251/opportunities-for-research-in-molecular-radiotherapy
#12
REVIEW
Glenn D Flux, Joe O'Sullivan, Mark N Gaze, Kevin M Prise
Cancer has been treated with radiopharmaceuticals for 80 years. A recent National Cancer Research Institute report from the Clinical and Translational Radiotherapy Research Working Group reviews the current status of molecular radiotherapy and has highlighted the barriers to and opportunities for increased research activities. The report recommends a number of actions to promote this field, which in the dawning age of personalized medicine and theragnostics is of increasing importance, particularly with the clinical introduction of a range of new commercial radiotherapeutics at costs in line with those seen for conventional chemotherapeutics...
March 2017: British Journal of Radiology
https://www.readbyqxmd.com/read/27919339/the-role-of-gene-mutations-and-gene-products-in-intestinal-tissue-reactions-from-ionising-radiation
#13
REVIEW
Jolyon H Hendry, Kensuke Otsuka
The response of the intestine to (low linear-energy-transfer) ionising radiation is reviewed regarding the cellular basis to the reactions, the regenerative processes which restore the tissue, and external agents which aid its recovery. In the steady-state, it is generally considered that the crypt cell lineages in both small and large intestine are maintained by a small number of stem cells, but there are differences for example in the composition of their niche residence and in the numbers of transit cell generations...
October 2016: Mutation Research
https://www.readbyqxmd.com/read/27875881/communication-position-does-matter-the-photofragmentation-of-the-nitroimidazole-isomers
#14
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
#15
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
#16
REVIEW
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...
November 2016: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/27755996/treatment-de-intensification-strategies-for-head-and-neck-cancer
#17
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
#18
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
#19
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...
December 16, 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
#20
RANDOMIZED CONTROLLED TRIAL
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
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