ESTRO 38 Abstract book

S603 ESTRO 38

Ltd, Switzerland). Animals: mice BALB/c and nude mice. Lines of the human (KB oral mucosa carcinoma) and murine (C26 colon carcinoma) tumor cells . Irradiation of the animals was performed once in a single focal dose (RPM) of 5 Gy for every mouse using Elekta Precise linear accelerator ( nude mice, KB tumor) or Theratron Equinox gamma-therapeutic apparatus (60Co, γ-radiation, BALB / c mice, C26 tumor) after its intratumoral injection GTC. The efficacy of the combined gene and radiotherapy was evaluated by the grade of tumor growth inhibition (T/C, u), and the treatment was considered to be efficient (synergistic effect) at T/С[combined therapy] < T/С[GENE THERAPY] x T/С[RADIOTHERAPY] . Statistical analysis was performed using Statistica ver. 10.0 programme. Results The combined treatment using GTC and the local irradiation in a single dose of 5 Gy on the model of subсutaneous KB xenograft or on the transplanted C26 murine tumor demonstrated a pronounced antitumor effect. The indices of efficiency of the combined therapy demonstrated the synergism of GTC/GCV and radiation impacts. The obtained synergism of the experimental therapeutic effects of the suicide gene therapy and radiotherapy opens up good prospects of further study of the combined therapy with the inclusion of these components of treatment. Conclusion The revealed spectrum of the anti-tumor activity of GTC/GCV systems may be used as the basis for choice of cancer diseases in early clinical trials. The synergy between suicidal gene therapy and radiation therapy proves to be prospective for further study of the combined therapy with an inclusion of these components of treatment. The reported study was funded by RFBR according to the research project No. 16-34-60185. PO-1087 The interaction between miR-221 overexpression and radiosensitivity in mamma carcinoma cell lines E. Hirmer 1,2,3 , R. Kell 3 , S. Winkler 3 , K. Winkler 3 , L. Mutschelknaus 3 , S. Mörtl 3 , M. Atkinson 1,2,3 , S. Combs 1,2 , T. Schmid 1,2 , N. Anastasov 3 1 Klinikum rechts der Isar, Radiooncology, München, Germany ; 2 Helmholtz Zentrum München, Institute of innovative Radiotherapy, Neuherberg, Germany ; 3 Helmholtz Zentrum München, Department of Radiation Sciences, Neuherberg, Germany Purpose or Objective Despite the steady improvement of breast cancer therapy, the prognosis for certain subgroups like triple negative breast cancer (TNBC) remains poor. In order to identify new therapeutic targets, it is important to analyze the pathogenesis of TNBC on a molecular level. TNBC shows significant overexpression of miR-221, which is associated with poor prognosis. By regulating cellular processes like proliferation, migration and cell survival, miR-221 is heavily involved in tumor pathogenesis. The interaction of miR-221 overexpression with radiation and its influence on migration, proliferation and colony formation were The mammary carcinoma cell lines SKBR3 and MDA-MB-231 were transduced with lentiviral vectors to ensure miR-221 overexpression in SKBR3 cells or miR-221 knock-down in MDA-MB-231, naturally overexpressing miR-221. In order to analyze the interaction between radiation and miR-221 expression, the miR-221 or anti-miR-221 cells were compared to the empty vector controls (EV co-expressing further investigated. Material and Methods Poster: Radiobiology track: Radiation response biomarkers

CIN-, Ras wt, BRAF wt, p53 wt) and CaCo2 (MSS, CIN+, Ras wt, BRAF wt, p53 mut) colorectal cancer cells were analysed for cell viability (beta-hexosaminidase assay), trifluridine incorporation (anti-BrdU immunofluorescence), DNA damage induction (H2AX phosphorylation), cell cycle dynamics (5-ethynyl-2'- deoxyuridine pulse labelling & flow cytometry) and colony formation following treatment with TFTD and/or X-rays. Results While treatment with 1-10 µM TFTD for three days only moderately affected cellular metabolic activity, 5-day treatments showed significant effects at all concentrations in all cell lines except CaCo2. All cell lines incorporated similar amounts of trifluridine during S phase, irrespective of TFTD concentration and duration of treatment. Cells arrested in S phase and appeared to undergo endoreplication, resulting in polyploidy. TFTD treatment for 2, 6 and 24 h induced gamma-H2AX mainly in S/G2, while G1 phase cells remained mostly unaffected. Interestingly, levels subsided close to controls at 6 h in TFTD-resistant CaCo2 cells. Colony assays performed for 4 µM TFTD and X-rays alone as well as in four different treatment combination schedules demonstrated purely additive effects when cells were treated with X-rays and TFTD within 6 hours of each other. However, 24 h TFTD treatment prior to irradiation caused marked radiosensitisation in all cell lines analysed so far, with dose enhancement factors of 1.5-3. Corresponding xenograft studies using the same cell lines are underway. Conclusion Cell cycle arrest and endoreplication resulting in polyploidy may contribute to the cytotoxicity of TFTD. The observation of a strong radiosensitising effect after prolonged treatment with TFTD provides a robust argument for a daily fractionated combined regime of TFTD and RT in rectal cancer treatment. PO-1086 Antitumor Efficacy of Combined Gene and Radio – Therapy in Animals O. Bezborodova 1 , I. Alexeenko 2 , A. Gevorkov 3 , E. Nemtsova 1 , A. Boyko 3 , E. Khmelevskiy 3 , R. Yakubovskaya 1 , A. Pankratov 1 , A. Kaprin 4 , E. Sverdlov 5 1 Moscow Research Gerzen Oncology Institut, Laboratory of Modifiers and Protective Agents in Anti-Cancer Therapy, Moscow, Russian Federation ; 2 Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry Institute of Molecular Genetics, Laboratory of Structure and Functions of Human Genes, Moscow, Russian Federation ; 3 Moscow Research Gerzen Oncology Institut, Radiation oncology, Moscow, Russian Federation ; 4 Moscow Research Gerzen Oncology Institut, Director of the Institute, Moscow, Russian Federation ; 5 Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry Institute of Molecular Genetics, Laboratory of Structure and Functions of Human Genes, Moscow, Russian Federation Purpose or Objective Objective of the research was to study the anti-tumor activity of gene therapeutic constructs (GTC) used in combination with radiotherapy. Material and Methods Gene therapeutic constructs : bicistronic constructs of HSVtk-hGM-CSF plasmid DNA with HSVtk (thymidine kinase of herpes simple virus) and human hGM- CSF (granulocyte-macrophage colony stimulating factor) genes and HSVtk-mGM-CSF plasmid DNA with HSVtk and murine mGM-CSF genes. Every construct is included into a non-viral vector of PPT (Polyethylene glycol- Polyethylenimine-TAT peptide) block-copolymer. Prodrug: ganciclovir (GCV) (Cymeven, Roche Products Poster: Radiobiology track: Biological therapies (e.g. viruses, vaccines)