Search results for "Radiation-Sensitizing Agents"
showing 10 items of 22 documents
Comparative analysis of the effects of a sphingosine kinase inhibitor to temozolomide and radiation treatment on glioblastoma cell lines.
2017
ABSTRACT Glioblastoma multiforme (GBM) exhibits high resistance to the standard treatment of temozolomide (TMZ) combined with radiotherapy, due to its remarkable cell heterogeneity. Accordingly, there is a need to target alternative molecules enhancing specific GBM autocrine or paracrine mechanisms and amplifying the effect of standard treatment. Sphingosine 1-phosphate (S1P) is such a lipid target molecule with an important role in cell invasion and proliferation. Sphingosine kinase inhibitors (SKI) prevent S1P formation and induce increased production of reactive oxygen species (ROS), which may potentiate radiation cytotoxicity. We analyzed the effect of SKI singular versus combined treat…
Clinical outcome of concomitant vs interrupted BRAF inhibitor therapy during radiotherapy in melanoma patients
2018
Background: Concomitant radiation with BRAF inhibitor (BRAFi) therapy may increase radiation-induced side effects but also potentially improve tumour control in melanoma patients. Methods: A total of 155 patients with BRAF-mutated melanoma from 17 European skin cancer centres were retrospectively analysed. Out of these, 87 patients received concomitant radiotherapy and BRAFi (59 vemurafenib, 28 dabrafenib), while in 68 patients BRAFi therapy was interrupted during radiation (51 vemurafenib, 17 dabrafenib). Overall survival was calculated from the first radiation (OSRT) and from start of BRAFi therapy (OSBRAFi). Results: The median duration of BRAFi treatment interruption prior to radiothera…
Curcumin and trans-resveratrol exert cell cycle-dependent radioprotective or radiosensitizing effects as elucidated by the PCC and G2-assay
2013
Curcumin and trans-resveratrol are well-known antioxidant polyphenols with radiomodulatory properties, radioprotecting non-cancerous cells while radiosensitizing tumor cells. This dual action may be the result of their radical scavenging properties and their effects on cell-cycle checkpoints that are activated in response to radiation-induced chromosomal damage. It could be also caused by their effect on regulatory pathways with impact on detoxification enzymes, the up-regulation of endogenous protective systems, and cell-cycle-dependent processes of DNA damage. This work aims to elucidate the mechanisms underlying the dual action of these polyphenols and investigates under which conditions…
Nicotinamide exerts different acute effects on microcirculatory function and tissue oxygenation in rat tumors
1993
Abstract Purpose : Nicotinamide has been reported to preferentially radiosensitize tumor tissue, supposedly through a reduction in tumor hypoxia. This may occur as a result of nicotinamide-induced changes in tumor blood flow and therefore the present study was undertaken to evaluate the effect of nicotinamide on circulatory parameters in skeletal muscle and tumor tissue (subcutaneously-implanted DS-sarcomas) of the rat. Methods and Materials : Mean arterial blood pressure (measured in the common carotid artery using a pressure transducer) and red blood cell flux (as measured by laser Doppler flowmetry) were continuously monitored for 120 min following a single intraperitoneal application of…
Elimination of Ehrlich tumours by ATP-induced growth inhibition, glutathione depletion and X-rays
1995
ATP-induced tumour growth inhibition is accompanied by a selective decrease in the content of the tripeptide glutathione (GSH) within the cancer cells in vivo. Depletion of cellular GSH sensitizes tumours to chemotherapy and radiation, but the usefulness of this depletion depends on whether the levels of GSH can be reduced in the tumour relative to normal tissues. We report here that administration of ATP in combination with diethylmaleate and X-rays leads to complete regression of 95% of Ehrlich ascites tumours in mice. This shows that an aggressive tumour can be eliminated by using a therapy based on modulation of GSH levels in cancer cells.
Co-localisation of hypoxia and perfusion markers with parameters of glucose metabolism in human squamous cell carcinoma (hSCC) xenografts
2009
Purpose: To examine relationships between tumour hypoxia, perfusion and metabolic microenvironment at themicroregional level in three different human squamous cell carcinomas (hSCC). Materials and methods: Nude mice bearing FaDu, UT-SCC-15, and UT-SCC-5 hSCC were injected with pimonidazole hypoxia and Hoechst perfusion markers. Bioluminescence imaging was used to determine spatial distribution of glucose and lactate content in serial tumour sections. Metabolite levels were grouped in 10 concentration ranges. Images were co-registered and at each concentration range the proportion of area stained for pimonidazole and Hoechst was determinedin 1113 tumours per tumour line. Results: The spatia…
Modulation of Spatial O2Tension Distribution in Experimental Tumors by Increasing Arterial O2Supply
1995
Tumor oxygenation has been measured polarographically in s.c. implanted DS-sarcomas on the dorsum of the hind foot of male Sprague-Dawley rats. pO2 was determined in all 3 spatial dimensions and 3-dimensional pO2 distributions as well as the mean extent of confluent areas with pO25 mmHg were calculated. Finally, the effect of elevating arterial pO2 (by carbogen breathing) as well as of increasing tumor blood flow (by angiotensin infusion) on the spatial pO2 distribution was analyzed. Depending on the tumor volume, the spatial pO2 distribution is more or less anisotropic. In smaller tumors, areas with physiological pO2 values are found adjacent to large hypoxic areas whereas larger tumors ar…
Comparison of the combined action of oxaliplatin or cisplatin and radiation in cervical and lung cancer cells
2007
To test the combined effects of oxaliplatin and radiation versus cisplatin and radiation using human cervical and lung cancer cell lines.CaSki cervical cancer cells, and A549 lung cancer cells were cultured under standard conditions. Cells were treated with escalating doses of gamma-irradiation (0-6 Gy), and with oxali- and cisplatin for 2 h or 24 h, or a combination of both. Cell survival was measured by a colony-forming assay. Survival curves were fitted to the data using the linear quadratic model. Sensitizer enhancement ratios (SER) were calculated at the 37% survival level, and isobologram analysis was applied to test for the drug-radiation interactions.Oxaliplatin as well as cisplatin…
Fludarabine combined with radiotherapy in patients with locally advanced NSCLC lung carcinoma: a phase I study
2011
Abstract Background and purpose Fludarabine is an adenine nucleoside analogue that has significant activity in hematological malignancies and has shown promising activity in combination with radiation in preclinical solid tumor models. We designed a phase I trial exploring concurrent fludarabine and radiotherapy in patients with advanced non-small cell lung cancer (NSCLC) to determine the maximum tolerated dose (MTD) of fludarabine given with concurrent irradiation. Materials and methods Thirteen patients with stage IIIB NSCLC received thoracic irradiation of 60 Gy. Fludarabine was administered during the 5th and 6th week of radiotherapy. Doses started at 10 mg/m2 per day and increased by s…
The combined effect of fludarabine monophosphate and radiation as well as gemcitabine and radiation on squamous carcinoma tumor cell lines in vitro.
2008
Despite proven antitumor activity of gemcitabine in chemoradiotherapy of advanced head and neck cancer, many authors refer to severe acute and late local and haematological toxicity. Fludarabine does imply nearly the same mechanisms of action as gemcitabine, inhibiting various enzymes involved in DNA replication. This investigation focuses on the combined effect of either fludarabine or gemcitabine and radiation on human squamous carcinoma cell lines in vitro, providing data for future decisions on head and neck chemoradiotherapy regimen.ZMK-1, A549, BW-225, GR-145, OH-65 and CaSki cell lines were incubated with either drug at defined schedules and irradiated at a single fraction dose of 2 …