Immunomodulatory analogs of thalidomide inhibit growth of Hs Sultan cells and angiogenesis in vivo

被引:135
作者
Lentzsch, S
LeBlanc, R
Podar, K
Davies, F
Lin, B
Hideshima, T
Catley, L
Stirling, DI
Anderson, KC
机构
[1] Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr,Dept Adult Onc, Boston, MA 02115 USA
[2] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA
[3] Celgene Corp, Warren, NJ USA
[4] Humboldt Univ, Med Ctr, Charite, Robert Roessle Klin, Berlin, Germany
关键词
thalidomide; multiple myeloma; Hs Sultan;
D O I
10.1038/sj.leu.2402745
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
We have previously shown that thalidomide and its potent immunomodulatory derivatives (IMiDs) inhibit the in vitro growth of multiple myeloma (MM) cell lines and patient MM cells that are resistant to conventional therapy. In this study, we further characterize the effect of these drugs on growth of B cell malignancies and angiogenesis. We established a beige-nude-xid (BNX) mouse model to allow for simultaneous in vivo measurement of both anti-tumor and anti-angiogenic effects of thalidomide and its analogs. Daily treatment (50 mg/kg/d) with thalidomide or IMiDs was nontoxic. The IMiDs were significantly more potent than thalidomide in vivo in suppressing tumor growth, evidenced by decreased tumor volume and prolonged survival, as well as mediating anti-angiogenic effects, as determined by decreased microvessel density. Our results therefore show that the IMiDs have more potent direct antitumor and anti-angiogenic effects than thalidomide in vivo, providing the framework for clinical protocols evaluating these agents in MM and other B cell neoplasms.
引用
收藏
页码:41 / 44
页数:4
相关论文
共 17 条
[1]   Thalidomide: Therapeutic potential in hematologic malignancies [J].
Anderson, KC .
SEMINARS IN HEMATOLOGY, 2000, 37 (01) :1-4
[2]   Immunomodulation by thalidomide and thalidomide analogues [J].
Corral, LG ;
Kaplan, G .
ANNALS OF THE RHEUMATIC DISEASES, 1999, 58 :107-113
[3]  
Corral LG, 1999, J IMMUNOL, V163, P380
[4]   THALIDOMIDE IS AN INHIBITOR OF ANGIOGENESIS [J].
DAMATO, RJ ;
LOUGHNAN, MS ;
FLYNN, E ;
FOLKMAN, J .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1994, 91 (09) :4082-4085
[5]   Thalidomide and immunomodulatory derivatives augment natural killer cell cytotoxicity in multiple myeloma [J].
Davies, FE ;
Raje, N ;
Hideshima, T ;
Lentzsch, S ;
Young, G ;
Tai, YT ;
Lin, B ;
Podar, K ;
Gupta, D ;
Chauhan, D ;
Treon, SP ;
Richardson, PG ;
Schlossman, RL ;
Morgan, GJ ;
Muller, GW ;
Stirling, DI ;
Anderson, KC .
BLOOD, 2001, 98 (01) :210-216
[6]   Cross-contamination: HS-Sultan is not a myeloma but a Burkitt lymphoma cell line [J].
Drexler, HG ;
MacLeod, RAF ;
Dirks, WG .
BLOOD, 2001, 98 (12) :3495-3496
[7]   Adherence of multiple myeloma cells to bone marrow stromal cells upregulates vascular endothelial growth factor secretion: therapeutic applications [J].
Gupta, D ;
Treon, SP ;
Shima, Y ;
Hideshima, T ;
Podar, K ;
Tai, YT ;
Lin, B ;
Lentzsch, S ;
Davies, FE ;
Chauhan, D ;
Schlossman, RL ;
Richardson, P ;
Ralph, P ;
Wu, L ;
Payvandi, F ;
Muller, G ;
Stirling, DI ;
Anderson, KC .
LEUKEMIA, 2001, 15 (12) :1950-1961
[8]   Thalidomide and its analogs overcome drug resistance of human multiple myeloma cells to conventional therapy [J].
Hideshima, T ;
Chauhan, D ;
Shima, Y ;
Raje, N ;
Davies, FE ;
Tai, YT ;
Treon, SP ;
Lin, B ;
Schlossman, RL ;
Richardson, P ;
Muller, G ;
Stirling, DI ;
Anderson, KC .
BLOOD, 2000, 96 (09) :2943-2950
[9]   Amino-substituted thalidoimide analogs:: Potent inhibitors of TNF-α production [J].
Muller, GW ;
Chen, R ;
Huang, SY ;
Corral, LG ;
Wong, LM ;
Patterson, RT ;
Chen, YX ;
Kaplan, G ;
Stirling, DI .
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 1999, 9 (11) :1625-1630
[10]   Thalidomide - A revival story. [J].
Raje, N ;
Anderson, K .
NEW ENGLAND JOURNAL OF MEDICINE, 1999, 341 (21) :1606-1609