http://repub.eur.nl/res/aut/10932/ List of Publications en http://repub.eur.nl/static-eur/img/logo.png http://repub.eur.nl http://repub.eur.nl/res/pub/18151/ 1997-06-04T00:00:00Z Cancer is a disease of all ages and even though cancer is not a common disease in younger people, cancer is recognized as one of the most imp0l1ant causes of death at any age. In fact, when considering the main death causes in people younger than thirty years, cancer is second only to accidents. Beyond the age of thirty years, the number of deaths from cancer increases upon aging, gradually at first, rising simply later on. Apm1 from cancer causing death, the disease is fem'ed because patients who suffer from cancer are often condemned to a long and painful terminal illness. Based on their frequency of occurrence, cancers are traditionally categorized as either epithelial cancers (approximately 85% of all human cancers) or non-epithelial cancers (approximately 15% of all human cancers). Cancers arising from epithelial cells (i.e. cells lining the body cavities and skin) are called cm'Cinomas (Latin: km'kinos - crab or lobster; oma - swelling), while those arising from non-epithelial cells are further subdivided according to the tissue and cell type from which they originate. Thus, sarcomas are derived from connective tissue or muscle cells (Greek: sarx - meat), while leukemias are derived from hematopoietic cells (Greek: leucos - white; haimablood). Other non-epithelial cancers include the ones deJived fi'Om cells ofthe nervous system and germinal or embryonal cells. http://repub.eur.nl/res/pub/8670/ 1997-01-01T00:00:00Z In the murine thymus, the stroma forms microenvironments that control different steps in T cell development. To study the architecture of such microenvironments and more particularly the nature of communicative signals in lympho-stromal interaction during T cell development, we have employed the phage antibody display technology, with the specific aim of isolating thymic stromal cell-specific single-chain antibodies from a semisynthetic phage library. A subtractive approach using intact, mildly fixed thymic fragments as target tissue and lymphocytes as absorber cells generated monoclonal phages (MoPhabs) detecting subsets of murine thymic stromal cells. In the present paper we report on the reactivity of single-chain antibodies derived from three MoPhabs, TB4-4, TB4-20, and TB4-28. While TB4-4 and TB4-20 are both epithelium specific, TB4-28 detects an epitope expressed on both epithelial- and mesenchymal-derived stromal cells. TB4-4 reacts with all cortical epithelial cells and with other endoderm-derived epithelia, but this reagent leaves the majority of medullary epithelial cells unstained. In contrast, MoPhab TB4-20 detects both cortical and medullary thymic epithelial cells, as well as other endoderm- and ectoderm-derived epithelial cells. Cross-reaction of single-chain antibodies to human thymic stromal cells shows that our semisynthetic phage antibody display library, in combination with the present subtractive approach, permits detection of evolutionary conserved epitopes expressed on subsets of thymic stromal cells.