Heat-shock protein 90 (Hsp90) has a crucial role in both the stabilisation and regulation of various proteins, including those related to radioresistance. Inhibition Hsp90 may therefore provide strategy for enhancing radiosensitivity tumour cells. This study explores responses four cell lines (A549, GaMG, HT 1080 SNB19) combined treatment with ionising radiation (IR) two novel inhibitors Hsp90, NVP-AUY922 NVP-BEP800. The techniques used included colony counts, expression Hsp70, Akt,...

High expression of constitutive histone γ-H2AX, a sensitive marker DNA damage, might be indicative defective repair pathway or genomic instability. 53BP1 (p53-binding protein 1) is conserved checkpoint with properties double-strand breaks sensor. This study explores the relationship between clinical radiosensitivity tumor patients and expression/induction γ-H2AX in vitro. Using immunostaining, we assessed spontaneous radiation-induced foci 53 BP1 peripheral blood mononuclear cells derived...

Previous studies have shown that the dual phosphatidylinositide 3-kinase/mammalian target of rapamycin (PI3K/mTOR) inhibitor NVP-BEZ235 radiosensitizes tumor cells if added shortly before ionizing radiation (IR) and kept in culture medium thereafter. The present study explores impact IR schedule on radiosensitizing ability four human glioblastoma cell lines. Two different drug-IR treatment schedules were compared. In I, treated with for 24 hours drug was removed IR. II, exposed to 1 hour...

In the present study, we assessed, if novel dual phosphatidylinositol 3-kinase (PI3K)/mammalian target of rapamycin (mTOR) inhibitor NVP-BEZ235 radiosensitizes triple negative (TN) MDA-MB-231 and estrogen receptor (ER) positive MCF-7 cells to ionizing radiation under various oxygen conditions, simulating different microenvironments as occurring in majority breast cancers (BCs). Irradiation (IR) BC cultivated hypoxic conditions revealed increased radioresistance compared normoxic controls....

Glioblastoma multiforme (GBM) is characterized by rapid growth, invasion and resistance to chemo−/radiotherapy. The complex cell surface morphology with abundant membrane folds, microvilli, filopodia other extensions believed contribute the highly invasive behavior therapy of GBM cells. present study addresses mechanisms leading excessive area in five lines differing mutational status for PTEN p53. In addition scanning electron microscopy (SEM), folding were quantified dielectric...

Ketogenic diets (KDs) or short-term fasting are popular trends amongst supportive approaches for cancer patients. Beta-hydroxybutyrate (3-OHB) is the main physiological ketone body, whose concentration can reach plasma levels of 2–6 mM during KDs fasting. The impact 3-OHB on biology tumor cells described so far contradictory. Therefore, we investigated effect a 3 metabolism, proliferation, and viability breast (BC) in vitro. Seven different human BC cell lines (BT20, BT474, HBL100, MCF-7,...

// Simon Memmel 1 , Dmitri Sisario 1, 2 Caren Zöller Vanessa Fiedler Astrid Katzer Robin Heiden Nicholas Becker Lorenz Eing Fábio L.R. Ferreira Heiko Zimmermann 3, 4 Markus Sauer Michael Flentje Vladimir L. Sukhorukov 2, * and Cholpon S. Djuzenova Department of Radiation Oncology, University Hospital Würzburg, Germany Biotechnology Biophysics, 3 Fraunhofer-Institut für Biomedizinische Technik, Sulzbach, Molekulare und Zelluläre Biotechnologie/Nanotechnologie, Universität des Saarlandes,...

Most tumor cells show aberrantly activated Akt which leads to increased cell survival and resistance cancer radiotherapy. Therefore, targeting can be a promising strategy for radiosensitization. Here, we explore the impact of inhibitor MK-2206 alone in combination with dual PI3K mTOR PI-103 on radiation sensitivity glioblastoma cells. In addition, examine migration drug-treated Using single-cell tracking wound healing tests, colony-forming assay, Western blotting, flow cytometry...

The prognostic value of histone γ-H2AX and 53BP1 proteins to predict the radiotherapy (RT) outcome patients with rectal carcinoma (RC) was evaluated in a prospective study. High expression constitutive is indicative defective DNA repair pathway and/or genomic instability, whereas (p53-binding protein 1) conserved checkpoint properties double-strand breaks sensor.Using fluorescence microscopy, we assessed spontaneous radiation-induced foci peripheral blood mononuclear cells derived from...

Abstract Background Phosphorylated histone H2AX, also known as γH2AX, forms μm-sized nuclear foci at the sites of DNA double-strand breaks (DSBs) induced by ionizing radiation and other agents. Due to their specificity sensitivity, γH2AX immunoassays have become gold standard for studying DSB induction repair. One these assays relies on immunofluorescent staining followed microscopic imaging counting. During last years, semi- fully automated image analysis, capable fast detection...

NVP-AUY922, a novel inhibitor of Hsp90, was shown to enhance the effect ionizing radiation (IR) on tumor cells under normoxic conditions. Since low oxygen tension is common feature solid tumors, we explore in present study impact hypoxia combined treatment lung carcinoma A549 and glioblastoma SNB19 cell lines with NVP-AUY922 IR. Cellular analysis included colony-forming ability, expression CAIX, Hsp70, Raf-1, Akt, cycle progression associated proteins, as well DNA damage measured by histone...

Inhibition of Hsp90 can increase the radiosensitivity tumor cells. However, inhibition alone induces anti-apoptotic Hsp70 and thereby decreases radiosensitivity. Therefore, preventing induction be a promising strategy for radiosensitization. PI-103, an inhibitor PI3K mTOR, has previously been shown to suppress up-regulation Hsp70. Here, we explore impact combining PI-103 with NVP-AUY922 in irradiated glioblastoma colon carcinoma We analyzed cellular response drug-irradiation treatments by...

Abstract The effects, of microsecond electropulses (1–kV/cm) on the viability murine B lymphocytes and their binding antibodies by surface immunoglobulin (Ig) were studied in relation to cell cycle. Before electropulsing, cultures given 48 h mitogenic stimulation showed at least two subpopulations, which distinguishable levels surface‐Ig expression as assessed with FITC‐labelled against mouse Ig. immunofluorescence intensity cells S G2/M phases was higher than that G0/G1 cells. After...

Targeting heat shock protein 90 (Hsp90) provides a promising therapeutic approach to enhance the sensitivity of tumor cells ionizing radiation (IR). To explore impact scheduling drug-IR administration, in present study, we analyzed response lung carcinoma A549 and glioblastoma SNB19 simultaneous treatment followed by long-term drug administration. Cellular was evaluated at different time intervals after IR-alone, drug-alone, or combined treatments colony counts expression profiles Hsp90 its...

Induction of DNA double-strand breaks (DSBs) by ionizing radiation leads to formation micrometer-sized DNA-repair foci, whose organization on the nanometer-scale remains unknown because diffraction limit (∼200 nm) conventional microscopy. Here, we applied diffraction-unlimited, direct stochastic optical-reconstruction microscopy ( dSTORM) with a lateral resolution ∼20 nm analyze focal nanostructure DSB marker histone γH2AX and protein kinase (DNA-PK) in irradiated glioblastoma multiforme...

About 5% of oncology patients treated by radiation therapy develop acute or late radiotoxic effects whose molecular mechanisms remain poorly understood. In this study, we evaluated the potential role DNA repair proteins in hypersensitivity cancer to therapy. The expression levels and focal nuclear distribution proteins, hMre11, Rad50 Rad51 were investigated skin fibroblasts strains derived from with adverse early reaction radiotherapy using Western blot foci immunofluorescence techniques,...

Abstract Nijmegen breakage syndrome (NBS) patients and carriers are predisposed to malignancy often treated with X‐irradiation. In the present study, single‐cell gel electrophoresis (Comet) assay was used examine radiation‐induced DNA damage repair in peripheral blood mononuclear cells from NBS ( n = 13) 36) of six unrelated families. Cells apparently healthy donors 10) breast cancer normal clinical radiosensitivity served as controls. were irradiated 5 Gy X‐rays assayed for initial residual...