1119 Long-term Results Treatment of Nasopharynx Malignant Tumors in Children and Teenagers
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Poster Sessions european journal of cancer 48, suppl. 5 (2012) S25–S288 S269 1116 Pulsed Magnetic Field and Ultraviolet C Radiation − Synergistic Effect During Cellular Ageing M.J. Ruiz-G´ omez 1 , S. Mercado-S´ aenz 1 , B. L´ opez-D´ ıaz 1 , L. Lumbreras 1 , L. Gil 1 , M. Mart´ ınez-Morillo 1 . 1 Universidad de M ´ alaga − Facultad de Medicina, Radiolog´ ıa y Medicina F´ ısica, M ´ alaga, Spain Background: A wide number of articles related to magnetic field effects have been reported during the last years, mainly to study the possible association with cancer risk. However, very few studies have been made using pulsed magnetic field (PMF) in co-exposure with other physical agents. The aim of this study was to investigate the synergistic effect of PMF and ultraviolet C (UVC) radiation during the aging phenomenon of cultured cells. Material and Methods: S. cerevisiae cells were cultured on YPD medium. They were exposed to PMF (25 Hz, 1.5 mT, 8 hours/day) during the aging process (40 days). In addition, UVC radiation (50 J/m 2 ) was applied on days 1, 20 and 40 of aging. Then, the surviving fraction was measured by clonogenic assay. Four treatment groups were considered: Unexposed control, samples exposed to PMF, samples exposed to UVC, and samples exposed to UVC+PMF. Results: The cell population experienced a gradual chronological aging from a 100% of survival in the early stages (day 0) until a survival rate of 15% in the latter stages (day 40). The cytotoxic effect of UVC radiation can be clearly seen that causes a decrease in cell survival, being the surviving fraction 0.01% at day 40 of aging. No significant differences were observed between cells exposed to PMF in relation to its relative non-exposed controls in the final stages. However, the surviving fraction obtained (0.001%) for the group treated with MF+UVC was smaller to that obtained for the group exposed only to UVC (0.01%). Conclusion: The aging cells are more sensible to UVC. The exposure of aging cells to PMF (25 Hz, 1.5 mT, 8 hours/day) sensitizes the population against UVC radiation (50 J/m 2 ). 1117 X-ray Irradiation Influences Eph Receptors and Cellular Properties in Human Melanoma Cells B. Mosch 1 , D. Pietzsch 1 , J. Pietzsch 1 . 1 Helmholtz-Zentrum Dresden- Rossendorf, Institute of Radiopharmacy, Dresden, Germany Introduction: There is experimental evidence that X-ray irradiation influences survival and metastatic properties of tumor cells. On the other hand, metastasis and cellular motility can be modified by EphA2 and EphA3, two members of the Eph receptor/ephrin family of receptor tyrosine kinases. The aim of this study was to analyze whether there is a molecular link between X-ray irradiation, Eph expression, and modification of metastasis-associated cell properties in human melanoma cells. Material and Methods: We irradiated one pre-metastatic and three metastatic human melanoma cells lines, including one self-generated metastatic variant, with X-rays (5 and 10Gy). At day 1 and day 7 post irradiation (p.i.) we analyzed cell proliferation, colony formation, adhesion, and migration. Additionally, selected Eph receptors and ephrin ligands were analyzed regarding irradiation- dependent changes in mRNA and protein content. For EphA2 and selected downstream signaling molecules we determined the phosphorylation status, representing protein activity. Results and Discussion: Irradiation resulted in decreased proliferation and colony formation. Colony formation showed partial recovery at 7 days p.i. with 5 Gy. Regarding cell adhesion, we detected an irradiation-induced increment paralleled by a decrease in migration of Mel-Juso and Mel-Juso-L3 cells and, in part, A375 cells. Thus, we assume that X-rays merely act anti-metastatic on the investigated melanoma cells. Expression of the ephrins A1 and A5 generally was very low and after Xray showed a substantial decrement for ephrin A5 in all cells, but a heterogenous behaviour for ephrin A1. For EphA2 we detected a decrease after irradiation both in expression and activity at 7 days p.i. In contrast, EphA3 was found to be up-regulated in 3 of 4 analyzed cell lines, raising the question, if there is a counter-regulation between EphA2 and EphA3. Analyzing downstream signaling, we detected decreased Src kinase and focal adhesion kinase (FAK) phosphorylation in A375, A2058, and Mel-Juso cells at 10 Gy for Src and both 5 Gy and 10 Gy for FAK at 7 days p.i. Conclusion: Our findings indicate that irradiation-induced downregulation of EphA2 and up-regulation of EphA3 in human melanoma cells is associated with anti-metastatic effects. The observed effects are assumed partly to be mediated by regulation of Src and FAK through EphA2. 1118 Potential Role of Lymphocytes During DNA Damage-induced Pneumopathy F. Cappuccini 1 , F. Wirsd¨ orfer 1 , E. Maniati 2 , T. Hagemann 2 , M. Stuschke 3 , V. Jendrossek 1 . 1 University Hospital Essen, Institute of Cell Biology, Essen, Germany, 2 Queen Mary University of London, Barts Cancer Institute, London, United Kingdom, 3 University Hospital Essen, Department of Radiation Oncology, Essen, Germany Introduction: Pneumopathy still represents a limiting side effect in the radiotherapy of thorax-associated neoplasms. It is suggested that radiation- induced injury disturbs the equilibrium of lung resident cells and their interactions with the extracellular matrix and infiltrating immune cells. The contribution of the inflammatory cells in the extensive lung changes and in fibrosis development is controversial and needs to be further elucidated. Aim of the present study was to gain more insight into the role of immune cells in DNA damage-induced pneumopathy by using mouse models of whole thorax irradiation and treatment with the radiomimetic drug bleomycin (BLM). Materials and Methods: C57BL/6 wild type mice (WT) or immunodeficient RAG-2 −/− mice received a single dose of whole thorax irradiation with 15 Gray (Gy), or were treated with intraperitoneal injections of BLM. Immune cells were isolated from lung tissue, spleen and cervical lymph nodes at defined time points and characterized via flow cytometry. Moreover, lung tissue samples were used for histological and immunohistochemical analyses. Results and Discussion: In WT mice, ionizing radiation and BLM-treatment induced time-dependant changes in leukocyte levels and characteristic alterations in the expression of specific surface molecules and other phenotypic markers (e.g. CD73, FOXP3) on distinct immune cell subsets in lung tissue and in lymphoid organs. Moreover, whole thorax irradiation and BLM treatment led to collagen deposition in the lung tissue of WT mice, whereas no such changes were observed in control mice (0 Gy or PBS treated). Fibrosis development after irradiation was associated with tissue hypoxia and increased levels of TGF-b and a-SMA. Of note, irradiated RAG-2 −/− mice showed an increased number of fibrotic foci in the lung 168 days after irradiation, when compared to WT mice. Conclusions: Our data indicate that, in WT mice, whole thorax irradiation and BLM treatment alter composition and activation/surface expression pattern of immune cell subpopulations in the lung and lymphoid organs, followed by tissue hypoxia and increased collagen deposition in the lung. The intensification of radiation-induced fibrosis in RAG-2 −/− mice suggests a role of mature B and /or T lymphocytes in the suppression of fibrotic changes. The role of specific immune cell subpopulations for DNA damage-induced tissue injury and fibrosis is under current investigation. 1119 Long-term Results Treatment of Nasopharynx Malignant Tumors in Children and Teenagers N.M. Karimova 1 , D.A. Abdurakhmonov 2 , F.E. Khayitov 1 , S.H.T. Nematov 1 , A.T. Shukullaev 1 , K.Z. Iskandarov 1 . 1 National Cancer Centre, Pediatric Oncology, Tashkent, Uzbekistan, 2 National Cancer Centre, Chemotherapy, Tashkent, Uzbekistan Background: To study long-term results treatment of nasopharynx malignant tumors in children and teenagers. Materials and Methods: In research were 74 patients with nasopahrynx malignant tumors, age from 0 to 18 years. Histologic undifferentiated cancer revealed in 44 patients, planocellular cancer in 15 patients, lumphosarcoma in 6, esthesioneuroblastoma in 7, Hodjkin lymphoma in 1, neuroblastoma in 1. In patients performed clinic-roentgenolgic, endoscopic, computer tomography and magneto resonance tomography examinations. Level spreading of tumor process estimated by TNM: T 2 N 0−2 M 0 − 2 patients; T3N 0−2 M 0 − 36; T 3 N 0−2 M 1 − 1; T 4 N 0−2 M 0 − 17 and T 4 N 1 M 0−1 − 6. Main treatment method was chemo-padiotherapy with using twice scheme of VCAP (vincristin + cyclophasphan + docsorubicin + cysplatin) then followed radiotherapy and four time chemotherapy. There were two radiotherapy methods: in 28 patients (37.8%) radiotherapy performed by method ‘semi-semi’ worked out in National Cancer Center of Uzbekistan and in 46 (62.2%) used standard methods. In standard radiotherapy used 2 gray single dose, total dose was 55−60 gray. In exposure by scheme ‘semi-semi’ radiotherapy curried out multifractionation method with 1.2 gray single dose a day, total dose was on primary area − 66−72 gray, on lyph outflow − 36−40 gray. Results: Patients controled from 6 month to 4 years. In group of malignant tumor patients with using standard radiotherapy and chemotherapy 3 years survival rate was 60.6%, but using method ‘semi-semi’ telegammatherapy survival rate was 89.3%. Conclusion: Chemo-radio therapy is method of election in treatment of nasopharynx malignant tumors, especially with using radio therapy by scheme ‘semi-semi’. 1120 Analysis of Clinical Manifestations and Diagnostic Signs of Osteosarcoma With Lung Metastases D. Polatova 1 , M. Gafur-Akhunov 2 , K. Abdikarimov 1 , S. Urunbaev 1 . 1 National Research Center of Oncoclogy, General oncology, Tashkent, Uzbekistan, 2 Tashkent Institute of Postgraduate Medical Education, Oncology, Tashkent, Uzbekistan Background: To study clinical manifestations and diagnostic signs of pulmonary metastating process of osteosarcoma. Material and Methods: We had analyzed 33 patients with lung metastases osteosarcoma, which had been treated in the National Research Center of Oncology of Uzbekistan, during 2007–2010 years. Females − 19 (58%),
Transcript of 1119 Long-term Results Treatment of Nasopharynx Malignant Tumors in Children and Teenagers
Poster Sessions european journal of cancer 48, suppl. 5 (2012) S25–S288 S269
1116 Pulsed Magnetic Field and Ultraviolet C Radiation − Synergistic
Effect During Cellular Ageing
M.J. Ruiz-Gomez1, S. Mercado-Saenz1, B. Lopez-Dıaz1, L. Lumbreras1,L. Gil1, M. Martınez-Morillo1. 1Universidad de Malaga − Facultad deMedicina, Radiologıa y Medicina Fısica, Malaga, Spain
Background: A wide number of articles related to magnetic field effects havebeen reported during the last years, mainly to study the possible associationwith cancer risk. However, very few studies have been made using pulsedmagnetic field (PMF) in co-exposure with other physical agents. The aim ofthis study was to investigate the synergistic effect of PMF and ultraviolet C(UVC) radiation during the aging phenomenon of cultured cells.Material and Methods: S. cerevisiae cells were cultured on YPD medium.They were exposed to PMF (25 Hz, 1.5mT, 8 hours/day) during the agingprocess (40 days). In addition, UVC radiation (50 J/m2) was applied ondays 1, 20 and 40 of aging. Then, the surviving fraction was measured byclonogenic assay. Four treatment groups were considered: Unexposed control,samples exposed to PMF, samples exposed to UVC, and samples exposed toUVC+PMF.Results: The cell population experienced a gradual chronological aging froma 100% of survival in the early stages (day 0) until a survival rate of 15%in the latter stages (day 40). The cytotoxic effect of UVC radiation can beclearly seen that causes a decrease in cell survival, being the surviving fraction0.01% at day 40 of aging. No significant differences were observed betweencells exposed to PMF in relation to its relative non-exposed controls in thefinal stages. However, the surviving fraction obtained (0.001%) for the grouptreated with MF+UVC was smaller to that obtained for the group exposed onlyto UVC (0.01%).Conclusion: The aging cells are more sensible to UVC. The exposure of agingcells to PMF (25 Hz, 1.5mT, 8 hours/day) sensitizes the population againstUVC radiation (50 J/m2).
1117 X-ray Irradiation Influences Eph Receptors and Cellular
Properties in Human Melanoma Cells
B. Mosch1, D. Pietzsch1, J. Pietzsch1. 1Helmholtz-Zentrum Dresden-Rossendorf, Institute of Radiopharmacy, Dresden, Germany
Introduction: There is experimental evidence that X-ray irradiation influencessurvival and metastatic properties of tumor cells. On the other hand, metastasisand cellular motility can be modified by EphA2 and EphA3, two members of theEph receptor/ephrin family of receptor tyrosine kinases. The aim of this studywas to analyze whether there is a molecular link between X-ray irradiation,Eph expression, and modification of metastasis-associated cell properties inhuman melanoma cells.Material and Methods: We irradiated one pre-metastatic and three metastatichuman melanoma cells lines, including one self-generated metastatic variant,with X-rays (5 and 10Gy). At day 1 and day 7 post irradiation (p.i.) we analyzedcell proliferation, colony formation, adhesion, and migration. Additionally,selected Eph receptors and ephrin ligands were analyzed regarding irradiation-dependent changes in mRNA and protein content. For EphA2 and selecteddownstream signaling molecules we determined the phosphorylation status,representing protein activity.Results and Discussion: Irradiation resulted in decreased proliferation andcolony formation. Colony formation showed partial recovery at 7 days p.i. with5 Gy. Regarding cell adhesion, we detected an irradiation-induced incrementparalleled by a decrease in migration of Mel-Juso and Mel-Juso-L3 cells and,in part, A375 cells. Thus, we assume that X-rays merely act anti-metastaticon the investigated melanoma cells. Expression of the ephrins A1 and A5generally was very low and after Xray showed a substantial decrement forephrin A5 in all cells, but a heterogenous behaviour for ephrin A1. For EphA2we detected a decrease after irradiation both in expression and activity at7 days p.i. In contrast, EphA3 was found to be up-regulated in 3 of 4 analyzedcell lines, raising the question, if there is a counter-regulation between EphA2and EphA3. Analyzing downstream signaling, we detected decreased Srckinase and focal adhesion kinase (FAK) phosphorylation in A375, A2058, andMel-Juso cells at 10 Gy for Src and both 5 Gy and 10Gy for FAK at 7 days p.i.Conclusion: Our findings indicate that irradiation-induced downregulation ofEphA2 and up-regulation of EphA3 in human melanoma cells is associatedwith anti-metastatic effects. The observed effects are assumed partly to bemediated by regulation of Src and FAK through EphA2.
1118 Potential Role of Lymphocytes During DNA Damage-induced
Pneumopathy
F. Cappuccini1, F. Wirsdorfer1, E. Maniati2, T. Hagemann2, M. Stuschke3,V. Jendrossek1. 1University Hospital Essen, Institute of Cell Biology, Essen,Germany, 2Queen Mary University of London, Barts Cancer Institute,London, United Kingdom, 3University Hospital Essen, Department ofRadiation Oncology, Essen, Germany
Introduction: Pneumopathy still represents a limiting side effect in theradiotherapy of thorax-associated neoplasms. It is suggested that radiation-
induced injury disturbs the equilibrium of lung resident cells and theirinteractions with the extracellular matrix and infiltrating immune cells. Thecontribution of the inflammatory cells in the extensive lung changes and infibrosis development is controversial and needs to be further elucidated. Aimof the present study was to gain more insight into the role of immune cells inDNA damage-induced pneumopathy by using mouse models of whole thoraxirradiation and treatment with the radiomimetic drug bleomycin (BLM).Materials and Methods: C57BL/6 wild type mice (WT) or immunodeficientRAG-2−/− mice received a single dose of whole thorax irradiation with 15 Gray(Gy), or were treated with intraperitoneal injections of BLM. Immune cells wereisolated from lung tissue, spleen and cervical lymph nodes at defined timepoints and characterized via flow cytometry. Moreover, lung tissue sampleswere used for histological and immunohistochemical analyses.Results and Discussion: In WT mice, ionizing radiation and BLM-treatmentinduced time-dependant changes in leukocyte levels and characteristicalterations in the expression of specific surface molecules and other phenotypicmarkers (e.g. CD73, FOXP3) on distinct immune cell subsets in lung tissue andin lymphoid organs. Moreover, whole thorax irradiation and BLM treatment ledto collagen deposition in the lung tissue of WT mice, whereas no such changeswere observed in control mice (0 Gy or PBS treated). Fibrosis developmentafter irradiation was associated with tissue hypoxia and increased levels ofTGF-b and a-SMA. Of note, irradiated RAG-2−/− mice showed an increasednumber of fibrotic foci in the lung 168 days after irradiation, when comparedto WT mice.Conclusions: Our data indicate that, in WT mice, whole thorax irradiationand BLM treatment alter composition and activation/surface expression patternof immune cell subpopulations in the lung and lymphoid organs, followedby tissue hypoxia and increased collagen deposition in the lung. Theintensification of radiation-induced fibrosis in RAG-2−/− mice suggests a roleof mature B and /or T lymphocytes in the suppression of fibrotic changes. Therole of specific immune cell subpopulations for DNA damage-induced tissueinjury and fibrosis is under current investigation.
1119 Long-term Results Treatment of Nasopharynx Malignant Tumors
in Children and Teenagers
N.M. Karimova1, D.A. Abdurakhmonov2, F.E. Khayitov1, S.H.T. Nematov1,A.T. Shukullaev1, K.Z. Iskandarov1. 1National Cancer Centre, PediatricOncology, Tashkent, Uzbekistan, 2National Cancer Centre, Chemotherapy,Tashkent, Uzbekistan
Background: To study long-term results treatment of nasopharynx malignanttumors in children and teenagers.Materials and Methods: In research were 74 patients with nasopahrynxmalignant tumors, age from 0 to 18 years. Histologic undifferentiated cancerrevealed in 44 patients, planocellular cancer in 15 patients, lumphosarcoma in6, esthesioneuroblastoma in 7, Hodjkin lymphoma in 1, neuroblastoma in 1.In patients performed clinic-roentgenolgic, endoscopic, computer tomographyand magneto resonance tomography examinations. Level spreading of tumorprocess estimated by TNM: T2N0−2M0 − 2 patients; T3N0−2M0 − 36;T3N0−2M1 − 1; T4N0−2M0 − 17 and T4N1M0−1 − 6. Main treatment methodwas chemo-padiotherapy with using twice scheme of VCAP (vincristin +cyclophasphan + docsorubicin + cysplatin) then followed radiotherapy andfour time chemotherapy.There were two radiotherapy methods: in 28 patients (37.8%) radiotherapyperformed by method ‘semi-semi’ worked out in National Cancer Center ofUzbekistan and in 46 (62.2%) used standard methods.In standard radiotherapy used 2 gray single dose, total dose was 55−60 gray.In exposure by scheme ‘semi-semi’ radiotherapy curried out multifractionationmethod with 1.2 gray single dose a day, total dose was on primary area −66−72 gray, on lyph outflow − 36−40 gray.Results: Patients controled from 6 month to 4 years. In group of malignanttumor patients with using standard radiotherapy and chemotherapy 3 yearssurvival rate was 60.6%, but using method ‘semi-semi’ telegammatherapysurvival rate was 89.3%.Conclusion: Chemo-radio therapy is method of election in treatment ofnasopharynx malignant tumors, especially with using radio therapy by scheme‘semi-semi’.
1120 Analysis of Clinical Manifestations and Diagnostic Signs of
Osteosarcoma With Lung Metastases
D. Polatova1, M. Gafur-Akhunov2, K. Abdikarimov1, S. Urunbaev1. 1NationalResearch Center of Oncoclogy, General oncology, Tashkent, Uzbekistan,2Tashkent Institute of Postgraduate Medical Education, Oncology, Tashkent,Uzbekistan
Background: To study clinical manifestations and diagnostic signs ofpulmonary metastating process of osteosarcoma.Material and Methods: We had analyzed 33 patients with lung metastasesosteosarcoma, which had been treated in the National Research Centerof Oncology of Uzbekistan, during 2007–2010 years. Females − 19 (58%),
