Book of abstract 2008

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Delivery of meta-tetra(hydroxyphenyl)chlorine (mTHPC) in organicallymodified silica (ORMOSIL) nanoparticles to cancer cells C. Compagnin1, M. Mognato1, L. Baù2, F. Mancin2, L. Celotti1, E. Reddi1 1Dept. of Biology, University of Padova, Padova, Italy; 2Dept. of Chemical Sciences, University of Padova, Padova, Italy Nanoparticles, nanotubes, quantum dots and dendrimers are objects of intense investigations due to their potential application in many areas of biology and medicine. In particular these materials are receiving considerable attention because of their potential use for bioimaging, diagnostic technology and drug or gene delivery. The benefits offered by targeted nanoscale drug carriers could be an improvement of drug bioavailability, precision of drug targeting and reduced drug toxicity. For this reason the entrapment of anticancer agents in nanoparticles is considered an innovative method for drug delivery aimed at improving the efficacy of cancer therapies. We investigated the use of ORMOSIL nanoparticles (NPs) loaded non covalently with meta-tetra(hydroxyphenyl)chlorine (mTHPC) for its delivery to human oesophageal carcinoma cells (KYSE 510) in vitro. Silica nanoparticles are known for their compatibility in biological systems. mTHPC is a hydrophobic second generation PDT (Photodynamic Therapy) photosensitiser approved in Europe for the palliative treatment of advanced head and neck cancers and characterized by a high antitumoral activity. mTHPC loaded in NPs or delivered by the standard solvent ethanol/polyethyleneglycol 400/water (20:30:50, by vol.) was internalised by KYSE 510 cells very quickly and localized in the Golgi apparatus and endoplasmic reticulum. NP-entrapped mTHPC was taken up by the cells less efficiently than free mTHPC but this did not decrease the efficiency of cell photokilling. No cytotoxicity in the dark was observed when mTHPC was delivered in NPs with respect to free mTHPC. Irradiation with 0.12 J/cm2 of red light (600-700 nm) induced a complete p8 loss of cellular viability following 24 h incubation with 1 μM NP-entrapped or free mTHPC. The results show that ORMOSIL NPs can be used as nanosystems for the delivery of hydrophobic drug and may improve the selectivity of cancer therapy through their targeting with functional groups specifically recognised by receptors over-expressed in tumour cells. 90
Increased tumour hypoxia and morphological blood vessel changes in tumours after electrochemotherapy Andrej Cör1, Mateja Legan1, Simona Kranjc2, Maja Čemažar2, Gregor Serša2 1Institute of Histology and Embryology, Medical Faculty, University of Ljubljana, Korytkova 2, Ljubljana, Slovenia; 2Institute of Oncology Ljubljana, Zaloška 2, Ljubljana, Slovenia It is widely accepted that no solid tumour can grow larger than a critical size of ~ 1mm3 without developing a blood supply network. Tumour vascular networks are chaotic, featuring complex branching patterns and a lack of hierarchy. Vessel diameters are irregular and blood flow rates are low (1). Evidences has accumulated showing that up to 50-60% of locally advanced solid tumours may exhibit hypoxic and/or anoxic tissue areas, which are heterogeneously distributed within the tumour mass. The underlying mechanism of electrochemotherapy is electroporation of the cell membrane, which facilitates access of poorly or non-permeable molecules into the tumour cells. Additionally to the well-established direct cytotoxic effect on tumour cells, blood flow measurements showed an immediate reduction of tumour blood flow after application of electric pulses and electrochemotherapy (2). In our study, SA-1 solid subcutaneous sarcoma tumours in A/J mice were treated by bleomycin (BLM), the application of electric pulses (8 pulses, 1040V, 100 μs, 1Hz) or a combination of both – electrochemotherapy. At various time points after therapy, tumours were excised and analysed histochemically and immunohistochemically with antibodies against CD-31 as endothelial cell marker, Glut-1 as intrinsic hypoxic marker and active casapase-3 as apoptotic marker. After application of electric pulses alone, as well as after electrochemotherapy, the extent of tumour hypoxia, detected by Glut-1, reached its peak after 2h and lasted up to 8h after the treatment. After the application of electric pulses, the recovery to pre-treatment level lasted 14h, whereas p9 after electrochemotherapy the recovery to pre-treatment level did not occur for at least 48h. To discover the cause of the increased hypoxia in the tumours after therapy, the morphological characteristics of small tumour blood vessels were analysed. Changes in the endothelial cells’ shape were observed 1h after the application of electric pulses. Endothelial cells were rounded up and swollen, and the lumens of blood vessels were narrowed. The same blood vessel morphological changes were also found after electrochemotherapy, although at later times, approximately 14h after electrochemotherapy, some endothelial cells with apoptotic characteristics and immunohistochemical active caspase-3 positivity were found. Apoptotic endothelial cells were not observed in tumours treated with electric pulses alone. Our results demonstrate that electrochemotherapy also has a vascular disrupting action, which can greatly increase the hypoxia in the tumours. References: 1. Tozer GM, Kanthou C, Baguley BC. Disrupting tumour blood vesels. Nat Rev Cancer 2005; 5: 423-33. 2. Sersa G, Jarm T, Kotnik T, et al. Vascular disrupting action of electroporation and electrochemotherapy with bleomycin in murine sarcoma. Br J Cancer 2008; 98: 388-98. 91
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Co-chairs of the conference: Janko
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Table of Contents Conference Progra
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12:40 - 12:55 Irina Kondakova: Matr
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18:15 - 18:40 Ib Jarle Christensen:
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Abstracts of Lectures
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inhibitor of metalloproteinases-1 i
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Tyrosine kinase inhibitors increase
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Cancer gene therapy by electrotrans
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effect of tamoxifen. From a clinica
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Cox-2 is a target gene of Rho GDP d
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Cancer preventive potential of xant
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Gene expression regulation by siRNA
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Aptamer-based capture molecular as
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The expression pattern of the uroki
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Tumour vascular disrupting agents:
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Matrix metalloproteinases, their ti
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Altered expression of cysteine cath
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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
Page 73 and 74: l55 73 Chemotherapy-induced cell de
Page 75 and 76: Towards high throughput, high conte
Page 77: l59 77 Mechanisms of proteolytic tu
Page 80 and 81: List of Posters P1. Tina Batista Na
Page 82 and 83: P37. Geoffrey J. Pilkington: CD44 a
Page 84 and 85: Mistletoe extract triggers mitochon
Page 86 and 87: Glioma: combating the invasive cell
Page 88 and 89: Protease inhibitory and cytotoxic e
Page 92 and 93: Platinum analogue trans-[PtCl 2 (3-
Page 94 and 95: Reduction of plasminogen activity i
Page 96 and 97: Cysteine cathepsins and their endog
Page 98 and 99: The influence of Mg ions on the eff
Page 100 and 101: Dimerization of endogenous MT1-MMP
Page 102 and 103: Chemical acylation improves membran
Page 104 and 105: Comparison of the results for the J
Page 106 and 107: Tumor blood flow modifying changes
Page 108 and 109: Sodium iodide method is suitable fo
Page 110 and 111: Gene transfer into solid tumors by
Page 112 and 113: Reversal of thiopurine cytotoxicity
Page 114 and 115: Quantification of viability in orga
Page 116 and 117: Electrochemotherapy of cutaneous me
Page 118 and 119: Cytotoxic and genotoxic influence o
Page 120 and 121: Antiproliferative and adhesion-stim
Page 122 and 123: Mushrooms as a source of antitumour
Page 124 and 125: Avoiding systemic toxicity of the T
Page 126 and 127: Advantage of nanoparticles to deliv
Page 128 and 129: The influence of hypoosmolar medium
Page 130 and 131: Xanthohumol may affect cancer progr
Page 132 and 133: List of participants Amberger Murph
Page 134 and 135: Genova Kalou Petia National Center
Page 136 and 137: Korolenko Tatiana Institute of Phys
Page 138 and 139: 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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