02 BOOK OF ABSTRACTS .indd

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Cleavage of uPAR; mechanism and prognostic significance Gunilla Høyer-Hansen, Charlotte Almasi, Helle Pappot, Keld Danø Finsen Laboratory, Strandboulevarden 49, DK-2100 Copenhagen Ø, Denmark Urokinase (uPA) cleaves its receptor, uPAR, thereby inactivating the binding potential of this molecule both with regards to uPA and vitronectin. The N-terminal domain I, uPAR(I) is liberated and the cleaved uPAR(II-III) stays on the cell surface. The cleavage takes place in the linker region between domains I and II after R 83 and R 89 . The cleavage is greatly accelerated on the cell surface compared to in solution and this acceleration is dependent on the uPA-uPAR binding. uPA cleaves glycolipid anchored uPAR (GPI-uPAR) but not soluble uPAR (suPAR), which lacks the glycolipid anchor. This is due to a difference in the conformation of the linker region between domains I and II and not because of a general difference in proteolytic susceptibility, since GPI-uPAR and suPAR are cleaved with equal efficiency by plasmin. The collective amounts of all uPAR forms measured by ELISA in tumour lysates or blood correlates to prognosis in several forms of cancer. However, the amounts of uPAR(II-III) and uPAR(I) may be directly related to the uPA activity and therefore be even stronger prognostic markers. Using combinations of monoclonal antibodies we have designed 3 time-resolved fluoroimmunoassays for the specific measurements of uPAR(I-III), uPAR(I-III) + uPAR(II-III), and uPAR(I). The amounts of uPAR(II-III) can be calculated. Applying these assays on tumour extracts from 63 patients diagnosed with squamous cell lung carcinoma revealed a stronger prognostic impact of uPAR(I) compared to total uPAR as measured by ELISA. 28l14
Cathepsins and their inhibitors in head and neck cancer Primo` Strojan Department of Radiation Oncology, Institute of Oncology, Zalo{ka 2, SI-1000 Ljubljana, Slovenia (pstrojan@onko-i.si) Head and neck cancer comprises approximately 5% of newly diagnosed invasive malignancies. More than 95 % of tumors are of epithelial origins: histologically they belong to the group of squamous cell carcinomas. Alcohol and tobacco abuse are common etiologic factors for oral cavity, oropharyngeal, hypopharyngeal, and laryngeal cancers. Moreover, because the entire aerodigestive epithelium may be exposed to these carcinogens, patients with head and neck cancer are at risk for developing second primary neoplasms of the head and neck, lung, and esophagus. Successful treatment of head and neck cancer requires accurate risk stratification to determine the type and extent of therapy needed and the expected clinical outcome. Physical examination, diagnostic imaging studies, and pathologic review are aimed to determine the size and extent of the primary tumor (T-stage), the status of regional (cervical) lymph nodes (N-stage), and the likelihood of systemic metastases (Mstage). In addition to TNM staging, other clinical and pathological factors have been shown to influence response to therapy and outcome. Cathepsins are a group of lysosomal cysteine (cathepsins B, H, L and others) or aspartic proteases (cathepsin D) that are involved predominantly in phagolysosomal protein degradation. Most of the cathepsins are expressed ubiquitously, but a few demonstrate strict tissue specificity. Endogenous inhibitors of cysteine cathepsins belong to cystatins, which are subdivided into three families, i.e. stefins, cystatins, and kininogens, and thyropins, whereas the naturally occurring inhibitor of aspartic protease, cathepsin D, has not been found yet in men. l15 29 During the last decades it has been shown that pericellular proteolysis has multiple roles in virtually all aspects of the normal life of a cell, such as protein degradation, antigen presentation, bone resorption and hormone processing. The same process is involved in the degradation of extracellular matrix barriers during invasion and metastasizing. The predictive and prognostic value of individual cathepsins and their inhibitors was widely investigated in breast, lung, and colorectal carcinoma. Compared to these tumors, the squamous cell carcinoma of the head and neck fall into much less investigated group of cancers. Apart from the studies focused to the activity or level of cathepsins and their inhibitors as determined in matched pairs of tumor tissue and normal mucosa, there are only a limited number of reports in the literature assessing their predictive or prognostic value in this H&N cancer. There are several reasons, the two most important being: • head and neck cancers appear to be a heterogeneous group of tumors consisting of multiple primary sites inside the upper aerodigestive tract, each with its own natural history and treatment outcome
Page 2 and 3: Co-chairs of the conference: Scient
Page 4 and 5: Contents Conference programme 5 Lis
Page 6 and 7: Differential effects of Cathepsin L
Page 8 and 9: 17.25 - 17.50 Golzio Muriel, IPBS C
Page 10 and 11: List of lectures: L1. Teissiè Just
Page 13 and 14: Abstracts of lectures 13
Page 15 and 16: Proteases and their inhibitors duri
Page 17 and 18: Biochemical characterization and cl
Page 19 and 20: Assessment of cathepsin B activity
Page 21 and 22: Differential effects of Cathepsin L
Page 23 and 24: anecdotally and within a clinical t
Page 25 and 26: Tumor cell- and macrophage-derived
Page 27: The selection of serological marker
Page 31 and 32: Matrix metalloproteinase expression
Page 33 and 34: l18 33 Complement resistance impair
Page 35 and 36: Classical tumor vaccine potently st
Page 37 and 38: CpG oligonucleotides admixed with i
Page 39 and 40: Electrochemotherapy in veterinary o
Page 41 and 42: studies were able to provide a deta
Page 43 and 44: threshold and electric field intens
Page 45 and 46: Gene delivery systems in cancer gen
Page 47 and 48: Electropermeabilization: a non vira
Page 49 and 50: Visible light microscopy, efficient
Page 51 and 52: Progress in tumour vascular targeti
Page 53 and 54: The Fer kinas: a novel target for p
Page 55 and 56: Targeting of plasminogen activation
Page 57 and 58: Functional interdependence of natur
Page 59 and 60: Antiprotease therapy in cancer: hot
Page 61 and 62: Functional genomics and systems bio
Page 63 and 64: Tumor proteolysis: a multidimension
Page 65 and 66: Stem cell therapy for liver insuffi
Page 67 and 68: Increased plasma DNA concentration
Page 69 and 70: List of poster presentations P1. Ab
Page 71 and 72: Abstracts of posters 71
Page 73 and 74: Tumor VEGF modulates host proteolyt
Page 75 and 76: New inhibitors of human hydroxyster
Page 77 and 78: Cytotoxicity and antitumour effecti
Page 79 and 80:
Quantification of lysosomal fusion
Page 81 and 82:
Spatiotemporal relevance of tumor c
Page 83 and 84:
Electrogene therapy with p53 alone
Page 85 and 86:
Do organophosphorous pesticides pla
Page 87 and 88:
Molecular analysis of lymphoprolife
Page 89 and 90:
Humoral response in pleural space t
Page 91 and 92:
In conclusion, this study shows tha
Page 93 and 94:
Angiogenesis correlates with cycloo
Page 95 and 96:
Inhibition of mouse uPA activity by
Page 97 and 98:
Cathepsin X interacts with integrin
Page 99 and 100:
Annexin-V apoptosis analysis of hum
Page 101 and 102:
Tissue swelling at the site of elec
Page 103 and 104:
p30103 The Bcl-2 family members: me
Page 105 and 106:
p32105 Proteomics of astrocytic neo
Page 107 and 108:
Correlation of chromosomal abnormal
Page 109 and 110:
Optimization of treatment parameter
Page 111 and 112:
The effect of xantohumol on normal
Page 113 and 114:
Cappabianca Lucia University of Aqu
Page 115 and 116:
Jevnikar Zala University of Ljublja
Page 117 and 118:
Mesojednik Suzana Institute of Onco
Page 119 and 120:
Rols Marie-Pierre Institute of Phar
Page 121 and 122:
Author Index Abramovi} Zrinka 72 Ak
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Paridaens R. 31 Parker Katharine 99
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