Originally published as JCO Early Release 10.1200/JCO.2005.03.723 on June 6 2005

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Thalidomide Downregulates Angiogenic Genes in Bone Marrow Endothelial Cells of Patients With Active Multiple Myeloma

Angelo Vacca, Claudio Scavelli, Vittorio Montefusco, Giulia Di Pietro, Antonino Neri, Michela Mattioli, Silvio Bicciato, Beatrice Nico, Domenico Ribatti, Franco Dammacco, Paolo Corradini

From the Department of Internal Medicine and Clinical Oncology, and Department of Human Anatomy and Histology, University of Bari Medical School, I-70124 Bari; Hematology Operative Unit 2, Ospedale Maggiore, I-20122; Department of Hematology and Bone Marrow Transplantation, Istituto Nazionale dei Tumori, I-20133 Milan; and the Department of Chemical Engineering Processes, University of Padua, I-35131 Padua, Italy

Address reprint requests to Angelo Vacca, MD, Text: 4024, Department of Internal Medicine and Clinical Oncology, Policlinico—Piazza Giulio Cesare, 11 I-70124 BARI, Italy; e-mail: a.vacca{at}dimo.uniba.it.

PURPOSE: To study the antiangiogenic effect of thalidomide.

PATIENTS AND METHODS: The expression of key angiogenic genes was studied in bone marrow endothelial cells (ECs) of patients with active and nonactive multiple myeloma (MM), monoclonal gammopathies unattributed/unassociated (MG[u]), diffuse large B-cell non-Hodgkin's lymphoma, in a Kaposi's sarcoma (KS) cell line, and in healthy human umbilical vein ECs (HUVECs) following exposure to therapeutic doses of thalidomide.

RESULTS: Thalidomide markedly downregulates the genes in a dose-dependent fashion in active MMECs and KS cell line, but upregulates them or is ineffective in nonactive MMECs, MG(u)ECs, NHL-ECs, and in HUVECs. Secretion of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF) and hepatocyte growth factor also diminishes according to the dose in culture conditioned media (CM) of active MMECs and KS, whereas it does not change in the other CM.

CONCLUSION: Inhibition by thalidomide is probably confined to the genes of active MMECs and KS. This would account for its higher efficacy in these diseases.

Supported by Associazione Italiana per la Ricerca sul Cancro (AIRC), Milan, Ministry for Education, the Universities and Research (Project CARSO No. 72/2), and Ministry for Health - Regione Puglia (grant BS2), Rome, Italy.

A.V. and C.S. contributed equally to this work.

Terms in blue are defined in the glossary, found at the end of this issue and online at www.jco.org.

Authors' disclosures of potential conflicts of interest are found at the end of this article.

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