Search results for "Radiosensitivity"
showing 10 items of 23 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…
A Putatively Functional Haplotype in the Gene Encoding Transforming Growth Factor Beta-1 as a Potential Biomarker for Radiosensitivity
2011
Purpose To determine whether genetic variability in TGFB1 is related to circulating transforming growth factor-β1 (TGF-β1) plasma concentrations after radiotherapy and to radiosensitivity of lymphoid cells. Patients and Methods Transforming growth factor-β1 plasma concentrations ( n = 79) were measured in patients 1 year after radiotherapy and chromosomal aberrations ( n = 71) ex vivo before therapy start. Furthermore, TGF-β1 secretion and apoptosis were measured in isolated peripheral blood mononuclear cells of 55 healthy volunteers. These phenotypes were analyzed in relation to five germline polymorphisms in the 5′ region of the TGFB1 gene. Because of high linkage disequilibrium, these fi…
Blood Flow and Tissue Oxygenation of Human Tumors: An Update
1992
It is generally accepted that tumor microcirculation, blood flow, oxygen and nutrient supply, tissue pH distribution, and the bioenergetic status (factors which are usually closely linked and which define the so-called cellular microenvironment) can markedly influence the therapeutic response of malignant tumors. Tumor blood flow is the major determinant for intra-tumor pharmacokinetics and (through modulation of the cellular microenvironment) of pharmacody-namics. The oxygen supply greatly determines the radiosensitivity of the tumors to be treated. The oxygen enhancement ratio, i.e., the ratio of doses with and without oxygen to produce the same biological effect is 2.7 to 3.0. O2 partial…
Erythropoietin restores the anemia-induced reduction in radiosensitivity of experimental human tumors in nude mice
2003
Abstract Purpose The effect of recombinant human erythropoietin (rhEPO) on the radiosensitivity of human tumor xenografts growing in anemic and nonanemic nude mice was studied. Methods and materials Anemia was induced by total body irradiation ([TBI], 2 × 4 Gy) of mice before tumor implantation into the subcutis of the hind leg. The development of anemia was prevented by rhEPO (750 U/kg s.c.) given 3 times weekly starting 2 weeks before TBI. Fourteen days after fractionated TBI (tumor volume of approx. 40 mm 3 ), single-dose irradiation of the tumor with varying doses was performed so that in full dose–response relationship for the probability of tumor cure was obtained. Results Radiation-i…
Growth rates or radiobiological hypoxia are not correlated with local metabolite content in human melanoma xenografts with similar vascular network.
1995
Investigations were carried out on two lines of human melanomas (MF; n = 12 and EE; n = 13) xenografted in nude mice. The tumours were characterised by a similar vascular supply but showed a pronounced difference in the rate of volume growth and in the radiobiologically hypoxic fraction. The distribution of ATP, glucose and lactate in the tumours was investigated using quantitative bioluminescence and single photon imaging. Concentrations of the metabolites were obtained as global values for the entire tumour mass, in regions with densely packed, structurally intact tumour cells ('viable zones'), in areas with necrosis, stromal cells and fibrous material ('necrotic zones') and in adjacent n…
A bioluminescence technique for quantitative and structure-associated imaging of pyruvate
2006
A novel bioluminescence assay has been developed for measuring pyruvate within sections of snap-frozen tissue in a quantitative manner as well as with a spatial resolution on a microscopical level. The assay was verified via HPLC and two independent photometric tests. The novel assay makes it possible to determine pyruvate concentrations in cryosections in the range of 0-5.0 micromol/g tissue (dry weight). Based on the analysis of samples of given pyruvate concentrations, the assay exhibits a recovery with a deviationor =15%. The minimal detectable amount was 0.02 pmol based on a 20 microm thick tissue section with an area of 1 cm(2). Combination of the already established imaging biolumine…
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…
Effect of Cell Line and Differentiation on the Oxygenation Status of Experimental Sarcomas
1997
Since the measurement of tumor oxygenation status and the fraction of hypoxia within tumor tissue by computerized pO2-histography [10] has become increasingly im-portant in the clinical setting, many studies on tumor oxygenation in different experimental malignancies as well as in various human tumors have been carried out. Because pO2-histography is an invasive technique, this method has been used in humans mostly in superficial primary tumors and lymph node metastases [1,3,10] (for a review see [9]). Experimental studies in animals have been carried out on a wide range of isotransplanted rodent sarcomas or carcinomas [2,4,6–8,11] and of xenotransplanted human tumors [6]. The results obtai…
Microcirculatory and pH Alterations in Isotransplanted Rat and Xenotransplanted Human Tumors Associated with Hyperthermia
1988
The rationale for considering the use of hyperthermia as an antitumor agent is based on three different mechanisms of action depending on the hyperthermia levels chosen: At moderate hyperthermia levels (40°–42.5° C) heat can increase the radiosensitivity and/or the chemosensitivity. At higher tissue temperatures ( > 42.5° C) hyperthermia acts as a cytotoxic agent since mammalian cells die after heating in a temperature-, time-, and cell cycle-dependent manner. Besides direct effects on the cell membranes, on the cytoskeleton, on metabolic processes, on DNA replication, and on RNA and protein synthesis, indirect effects distinctly modulating the anticancer action of heat have to be considere…
Increased radioresistance via G12S K-Ras by compensatory upregulation of MAPK and PI3K pathways in epithelial cancer
2011
Background Irradiation-induced signaling via the 2 pathways, Raf-MEK-ERK and PI3K-Akt, is known to be closely associated with a limited response to radiotherapy. In the present study we analyzed the relevance of constitutively active K-Ras for postradiogenic pathway stimulation and the option of coordinated inhibition to overcome these rescue mechanisms. Methods We used 2 epithelial tumor cell lines as a model system, one of them harboring a G12S K-Ras mutation. Cells were irradiated and the effect of combined treatment with ionizing radiation and inhibitors on the expression of pERK and pAkt was determined by Western blotting. Additionally, clonogenic assays were performed to functionally …