Book of abstract 2008

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L41. Malcolm Reed: Genetic predisposition on breast cancer – clinical perspectives L42. Christian Schichor: Interaction of human adult mesenchymal stem cells and malignant gliomas L43. Manfred Schmitt: Kallikrein-related peptidases: novel therapeutic target molecules L44. R. Schulte Hermann: Pro-carcinogenic effects of non-genotoxic chemical carcinogens L45. Gregor Serša: Vascular disrupting action of electroporation and electrochemotherapy L46. Natalia P. Sharova: The role of the immune proteasomes in the anticancer defence L47. Bonnie F. Sloane: Cysteine cathepsins in tumors and their microenvironment L48. Primož Strojan: Cysteine cathepsins and stefins in head and neck cancer: an update of clinical studies L49. Youssef Tamzali: Electrochemotherapy in veterinary oncology L50. Justin Teissié: Time dependence of electric field effects on cell membranes L51. Gregor Tevž: IL-12 gene therapy of murine sarcoma tumors and metastases combined with radiotherapy L52. Jozef Tímár: Melanoma genomics and molecular targeting L53. Gillian M. Tozer: Response to VEGF receptor inhibition and vascular disrupting therapy of mouse tumours expressing only single isoforms of VEGF-A L54. Boris Turk: Lysosomal protease-mediated killing of cells: possible use in cancer therapy? L55. Engin Ulukaya: Chemotherapy-induced cell death and its assessment in vivo L56. Olga Vasiljeva: Reduced tumour cell proliferation and delayed development of high grade mammary carcinomas in cathepsin B deficient mice. L57. Boris Vojnović: Towards high throughput, high content, fluorescence lifetime imaging L58. Lisa Wiesmüller: Resveratrol induces fidelity control mechanisms of DNA doublestrand break repair via activation of ATM/ATR signalling pathways L59. Katarina Wolf: Mechanisms of proteolytic tumor invasion resulting in multicellular tumor patterning 14
Tyrosine kinase inhibitors increase the anti-tumour effect of chemotherapy drugs in malignant gliomas Paula Kinsella, Martin Clynes and Verena Amberger Murphy National Institute for Cellular Biotechnology, Dublin City University, Glasnevin, Dublin 9, Ireland Despite major improvements in the surgical management the prognosis for patients bearing malignant gliomas is still dismal. Traditional chemotherapy was unable to offer extended survival gain for a long period of time, until radiation and concurrent Temozolomide followed by adjuvant Temozolomide became the standard of care for newly diagnosed glioblastoma multiforme. The new understanding of cellular and molecular mechanisms of tumours has led to the development of targeted agents, which are aimed at the tumourspecific microenvironment and/or molecules. Taxanes are a group of chemotherapeutic drugs, which have proven to be very effective in the treatment of a variety of cancer types; however, were ruled out for the treatment of brain tumours, because of their inability to cross the blood brain barrier. New application techniques, like convection enhanced delivery, allow surpassing the blood brain barrier and delivering the drug directly to the tumour area. Therefore, we tested the effects of taxanes (Taxotere and Taxol) in combination with a tyrosine kinase inhibitor on proliferation and invasion activity of brain tumour cell lines. Taxotere or Taxol alone at nanomolar concentrations strongly inhibited proliferation and invasion of one astrocytoma grade III and 3 glioblastoma cell lines in vitro. However, after removing the drug, invasion activity resumed suggesting a reversible effect on the tumour cells. The combination of Imatinib, a tyrosine kinase inhibitor for e.g. platelet derived growth factor, c-kit and c-able, together with Taxotere inhibited tumour cell proliferation in a synergistic manner, which was even increased when drug application was scheduled. Invasion was also strongly inhibited by the drug combination and this effect was irreversible. We also tested this drug combination on newly developed cell cultures from biopsy tissue and found similar effects. These results demonstrate that, compared to single drug application, l1 the combination of tyrosine kinase inhibitors and classical chemotherapy drugs strongly increases the anti-tumour effects in vitro, which could have implications for the treatment of malignant gliomas in vivo. 15
Page 2 and 3: Co-chairs of the conference: Janko
Page 4 and 5: Table of Contents Conference Progra
Page 6 and 7: 12:40 - 12:55 Irina Kondakova: Matr
Page 8 and 9: 18:15 - 18:40 Ib Jarle Christensen:
Page 11 and 12: Abstracts of Lectures
Page 13: inhibitor of metalloproteinases-1 i
Page 17 and 18: Cancer gene therapy by electrotrans
Page 19 and 20: effect of tamoxifen. From a clinica
Page 21 and 22: Cox-2 is a target gene of Rho GDP d
Page 23 and 24: Cancer preventive potential of xant
Page 25 and 26: Gene expression regulation by siRNA
Page 27 and 28: Aptamer-based capture molecular as
Page 29 and 30: The expression pattern of the uroki
Page 31 and 32: Tumour vascular disrupting agents:
Page 33 and 34: Matrix metalloproteinases, their ti
Page 35 and 36: Altered expression of cysteine cath
Page 37 and 38: l22 37 Adult stem cells: from bench
Page 39 and 40: l24 39 Specific laboratory animal h
Page 41 and 42: The pharmacogenetic basis for indiv
Page 43 and 44: Mechanisms in metastasis Ruth J. Mu
Page 45 and 46: The lymphatic ring assay: a new in
Page 47 and 48: The use of immuno-nanoparticles for
Page 49 and 50: after antiangiogenic strategies, su
Page 51 and 52: The role of integrative genomics/pr
Page 53 and 54: Effect of the tumour microenvironme
Page 55 and 56: Addressing the angiogenic switch by
Page 57 and 58: Genetic predisposition on breast ca
Page 59 and 60: Kallikrein-related peptidases: nove
Page 61 and 62: Vascular disrupting action of elect
Page 63 and 64: Cysteine cathepsins in tumors and t
Page 65 and 66:
Cysteine cathepsins and stefins in
Page 67 and 68:
l50 67 Time dependence of electric
Page 69 and 70:
Melanoma genomics and molecular tar
Page 71 and 72:
Response to VEGF receptor inhibitio
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l55 73 Chemotherapy-induced cell de
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Towards high throughput, high conte
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l59 77 Mechanisms of proteolytic tu
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List of Posters P1. Tina Batista Na
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P37. Geoffrey J. Pilkington: CD44 a
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Mistletoe extract triggers mitochon
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Glioma: combating the invasive cell
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Protease inhibitory and cytotoxic e
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Delivery of meta-tetra(hydroxypheny
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Platinum analogue trans-[PtCl 2 (3-
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Reduction of plasminogen activity i
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Cysteine cathepsins and their endog
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The influence of Mg ions on the eff
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Dimerization of endogenous MT1-MMP
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Chemical acylation improves membran
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Comparison of the results for the J
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Tumor blood flow modifying changes
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Sodium iodide method is suitable fo
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Gene transfer into solid tumors by
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Reversal of thiopurine cytotoxicity
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Quantification of viability in orga
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Electrochemotherapy of cutaneous me
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Cytotoxic and genotoxic influence o
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Antiproliferative and adhesion-stim
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Mushrooms as a source of antitumour
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Avoiding systemic toxicity of the T
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Advantage of nanoparticles to deliv
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The influence of hypoosmolar medium
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Xanthohumol may affect cancer progr
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List of participants Amberger Murph
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Genova Kalou Petia National Center
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Korolenko Tatiana Institute of Phys
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Opolon Paule Institut Gustave-Rouss
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Sedmak Bojan National Institute of
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Voulgari Angeliki National Hellenic
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E Edwards Dylan 20 Edwards Dylan R.
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Pavelić Krešimir 51 Pavlič Janez
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We believe in our future! Photo: Ma
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TANTUM VERDE 154
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