Search results for "radiation tolerance"
showing 10 items of 39 documents
Knockdown of hnRNPK leads to increased DNA damage after irradiation and reduces survival of tumor cells.
2017
Radiotherapy is an important treatment option in the therapy of multiple tumor entities among them head and neck squamous cell carcinoma (HNSCC). However, the success of radiotherapy is limited by the development of radiation resistances. Heterogeneous nuclear ribonucleoprotein K (hnRNPK) is a cofactor of p53 and represents a potential target for radio sensitization of tumor cells. In this study, we analyzed the impact of hnRNPK on the DNA damage response after gamma irradiation. By yH2AX foci analysis, we found that hnRNPK knockdown increases DNA damage levels in irradiated cells. Tumor cells bearing a p53 mutation showed increased damage levels and delayed repair. Knockdown of hnRNPK appl…
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…
Cytokine profile of breast cell lines after different radiation doses
2017
Purpose: Ionizing radiation (IR) treatment activates inflammatory processes causing the release of a great amount of molecules able to affect the cell survival. The aim of this study was to analyze the cytokine signature of conditioned medium produced by non-tumorigenic mammary epithelial cell line MCF10A, as well as MCF7 and MDA-MB-231 breast cancer cell lines, after single high doses of IR in order to understand their role in high radiation response. Materials and methods: We performed a cytokine profile of irradiated conditioned media of MCF10A, MCF7 and MDA-MB-231 cell lines treated with 9 or 23 Gy, by Luminex and ELISA analyses. Results: Overall, our results show that both 9 Gy and 23 …
Synthetic antioxidants: biochemical actions and interference with radiation, toxic compounds, chemical mutagens and chemical carcinogens.
1984
Abstract Biological actions of 4 commonly used synthetic antioxidants — butylated hydroxyanisole, butylated hydroxytoluene, ethoxquin and propul gallate — on the molecular, cellular and organ level are compiled. Such actions may be divided into modulation of growth, macromolecule synthesis and differentiation, modulation of immune response, interference with oxygen activation and miscellaneous. Moreover, an overview of beneficial and adverse interactions of these antioxidants with exogenous noxae is given. Beneficial interactions include radioprotection, protection against acute toxicity of chemicals, antimutagenic activity and antitumorigenic action. Possible mechanisms of the antitumorige…
Blood supply, oxygenation status and metabolic micromilieu of breast cancers: characterization and therapeutic relevance.
2000
The metabolic microenvironment of a tumor is predominantly determined by the efficacy of blood flow, flux parameters (such as diffusion and convective currents in the interstitial space) and metabolic rates. The most important factors in this context include oxygen and nutrient supply, tissue pH and the bioenergetic status. It is now widely accepted that the metabolic microenvironment of a tumor can dramatically influence a range of factors such as proliferation rate, cell cycle position, growth rate and the development of apoptosis and necrosis. At the same time, these parameters can have an impact on tumor detection, therapeutic response to conventional irradiation, some chemotherapy agen…
Overexpression of p63 is associated with radiation resistance and prognosis in oral squamous cell carcinoma
2010
Summary Background : The tumor suppressor homologue p63 is expressed in basal and parabasal layers of intraoral mucosa. Full length transcripts with transactivational domain (TA forms) present with homology to p53 and implicate functions governing cell proliferation, differentiation and apoptosis control. To date studies show an increase of p63 expression in oral dysplasia and additionally high expression levels correlated with poor prognosis for patients with OSCC, whereas a possible link to radiation resistance of tumors has not been investigated yet. In the present study we tested the hypothesis for p63 being a marker of radioresistance and overall survival in OSCC. Methods : p63 Express…
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…
Biodosimetry Based on γ-H2AX Quantification and Cytogenetics after Partial- and Total-Body Irradiation during Fractionated Radiotherapy
2015
The aim of this current study was to quantitatively describe radiation-induced DNA damage and its distribution in leukocytes of cancer patients after fractionated partial- or total-body radiotherapy. Specifically, the impact of exposed anatomic region and administered dose was investigated in breast and prostate cancer patients receiving partial-body radiotherapy. DNA double-strand breaks (DSBs) were quantified by γ-H2AX immunostaining. The frequency of unstable chromosomal aberrations in stimulated lymphocytes was also determined and compared with the frequency of DNA DSBs in the same samples. The frequency of radiation-induced DNA damage was converted into dose, using ex vivo generated ca…
Overexpression of GLUT-1 is associated with resistance to radiotherapy and adverse prognosis in squamous cell carcinoma of the oral cavity
2006
This study tested the hypothesis that GLUT-1 is a marker of radioresistance in oral squamous cell carcinomas (OSCC). A GLUT-1 labeling index (LI) was determined by immunohistochemistry in 40 pretreatment OSCC biopsies. Radiation responses were categorized by histopathology of the resection specimens. Associations between the LI and radiation response, Kaplan-Meier survival estimates and Cox regression analysis for the variables GLUT-1, T-stage, N-stage and chemotherapy were examined. The median LI was 64.2% (range 14-100%). Tumors with65% of GLUT-1+cells were more resistant to radiation (p=0.023). Overall survival was higher (p=0.044) for subjects with low LI (median value) than those with …
Primary mouse fibroblasts deficient for c-Fos, p53 or for both proteins are hypersensitive to UV light and alkylating agent-induced chromosomal break…
2000
The important regulatory proteins, c-Fos and p53 are induced by exposure of cells to a variety of DNA damaging agents. To investigate their role in cellular defense against genotoxic compounds, we comparatively analysed chromosomal aberrations and apoptosis induced by ultraviolet (UV-C) light and the potent alkylating agent methyl methanesulfonate (MMS) in primary diploid mouse fibroblasts knockout for either c-Fos or p53, or double knockout for both genes. We show that c-Fos and p53 deficient fibroblasts are more sensitive than the corresponding wild-type cells as to the induction of chromosomal aberrations and apoptosis. Double knockout fibroblasts lacking both c-Fos and p53 are viable an…