Toxicopathology and Carcinogenesis - Research Groups

Toxicopathology I (Luigi Terracciano, co-applicant)
The Institute for Pathology has specialists for the investigation of organ systems with clinical and toxicological relevance, including brain, heart, lung, liver, kidney, gastrointestinal tract, endocrine organs, urinary tract, prostate, bone marrow and lymphatic system, breast, ovary, bone and skin. Immunohistochemical analysis, electron microscopy and techniques in molecular pathology are used routinely. Yearly, the Institute analyses approximately 50,000 human tissue samples and 10,000 cytological smears from the above-mentioned organs. Based on a more than 50 years old tradition, there is precious knowledge about toxico-pathological problems such as toxicity of analgesics (so-called “Phenacetinniere”), calcineurin inhibitors (calcineurin inhibitor toxicity [CIN]) and others (23b, 23c). The Molecular Pathology Division of the Institute of Pathology has recently constructed tissue microarrays from more than 25’000 different tumors (23d). TMA technology has been extensively used in our Laboratory in cancer research, particularly for biomarker validation. It is obvious that this technique should also be applicable for toxicological studies early in drug development.

Toxicopathology II (Laura Rubbia-Brandt, Solange Moll, Pierre Lescuyer, co-applicants)
Drug-induced liver injury accounts for more than 40% of cases of hepatitis among patients > 50 years and up to 25% of cases of fulminant hepatic failure. Adverse reactions can occur also with herbal remedies and dietary supplements (mixtures of ingredients of uncertain purity and doses). Several chemotherapeutic drugs display major liver toxicity. Currently, oxaliplatin (OX) -based neoadjuvant chemotherapy is largely used because of its high rate of both radiological and histological responses in hepatic colorectal metastasis (HCRM) and its beneficial effect on survival. Preliminary data pointed out to further increase in these response rates when OX is associated to a targeted biologic therapy as with bevacizumab (avastin), a recombinant human monoclonal antibody to vascular endothelial growth factor-A (VEGF-A). We have recently reported development of sinusoidal lesion in non-tumorous liver mostly associated to OX-based chemotherapy. The lesion corresponds to sinusoidal obstruction syndrome (SOS) and nodular regenerative hyperplasia (NRH) (76-77).

Last Updated on Thursday, 25 March 2010 15:40 Created: Tuesday, 07 April 2009 11:57