title: Mdr1 gene-expression in a multidrug-resistant human non-hodgkins-lymphoma xenograft model.
abstract: In order to investigate the biology of tumor cells which express MDR1 gene and to test the activity of different P-glycoprotein blocking agents in vivo, we established a nude mice model. Five Non Hodgkin's Lymphoma (NHL) tumor specimens were xenografted to nude mice. One of them, obtained from a chemotherapy-refractory patient gave rise to a mice transplantable model. This tumor xenograft model, IGR-NHL-90, showed overexpression of the human MDR1 gene. In this tumor model, histology, mitotic index, phenotypic and karyotypic traits remained stable at subsequent passages. The in vitro resistance of vincristine was reversed by verapamil for these NHL tumor cells, suggesting that the MDR1 resistance is a relevant mechanism in this model. In the absence of chemotherapy a higher biological aggressivity of the heterotransplanted NHL was noted in subsequent nude mice passages. This was associated with decreased passage time and higher MDR1 m-RNA transcript levels. Thus IGR-NHL-90 may represent a suitable material to study regulation of MDR1 gene transcription in vivo and also to test the activity of various P-glycoprotein reversing agents with concurrent chemotherapy.
authors.affiliation: INST GUSTAVE ROUSSY,PHARMACOL CLIN & MOLEC LAB,39 RUE CAMILLE DESMOULINS,F-94805 VILLEJUIF,FRANCE. INST GUSTAVE ROUSSY,DEPT INTERNAL MED,DIV HEMATOL,F-94805 VILLEJUIF,FRANCE. INST GUSTAVE ROUSSY,EXPTL THERAPEUT SECT,F-94805 VILLEJUIF,FRANCE. INST GUSTAVE ROUSSY,CYTOGENET LAB,F-94805 VILLEJUIF,FRANCE. INST GUSTAVE ROUSSY,DEPT HISTOPATHOL,F-94805 VILLEJUIF,FRANCE. HARVARD UNIV,SCH MED,JOINT CTR RADIAT THERAPY,BOSTON,MA 02115.
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authors.lastname: Pico
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authors.lastname: Hayat