Angiogenesis-dependent diseases

doi:10.1016/S0093-7754(01)90021-1

Seminars in Oncology

Volume 28, Issue 6, December 2001, Pages 536-542

https://doi.org/10.1016/S0093-7754(01)90021-1 Get rights and content

Abstract

There is accumulating evidence that leukemias and other hematologic diseases are angiogenesis-dependent. Therefore, angiogenesis inhibitors may be useful adjuncts to conventional therapies in the treatment of these diseases. When all conventional therapy has failed, an angiogenesis inhibitor may be successfully used alone, as has been demonstrated in the treatment of multiple myeloma by thalidomide. The experimental and clinical evidence that the efficacy of thalidomide against multiple myeloma is mediated in part by its antiangiogenic activity is presented here. In current clinical trials throughout the United States, angiogenesis inhibitors are being used against cancer in combination with conventional chemotherapy or radiotherapy. Angiogenesis inhibitors are also being used in combination with each other. This practice may increase as different angiogenesis inhibitors become more widely available.

References (42)

G Brunner et al.
Basic fibroblast growth factor expression in human bone marrow and peripheral blood cells
Blood
(1993)
A Vacca et al.
Bone marrow neovascularization, plasma cell angiogenic potential, and matrix metalloproteinase-2 secretion, parallel progression of human multiple myeloma
Blood
(1999)
A Aguayo et al.
Cellular vascular endothelial growth factor is a predictor of outcome in patients with acute myeloid leukemia
Blood
(1999)
LG Lundberg et al.
Bone marrow in polycythemia vera, chronic myelocytic leukemia, and myelofibrosis has an increased vascularity
Am J Pathol
(2000)
FA Scappaticci et al.
Combination angiostatin and endostatin gene transfer induces synergistic antiangiogenic activity in vitro and antitumor efficacy in leukemia and solid tumors in mice
Mol Ther
(2001)
MS O'Reilly et al.
Angiostatin: A novel angiogenesis inhibitor that mediates the suppression of metastases by a Lewis lung carcinoma
Cell
(1994)
MS O'Reilly et al.
Endostatin: An endogenous inhibitor of angiogenesis and tumor growth
Cell
(1997)
SV Rajkumar et al.
A review of angiogenesis and antiangiogenic therapy with thalidomide in multiple myeloma
Cancer Treat Rev
(2000)
T Hideshima et al.
Thalidomide and its analogs overcome drug resistance of human multiple myeloma cells to conventional therapy
Blood
(2000)
SV Rajkumar et al.
Thalidomide in the treatment of relapsed multiple myeloma

K Kondo et al.

The von Hippel-Lindau tumor suppressor gene

Exp Cell Res

(2001)

F Bertolini et al.

Thalidomide in multiple myeloma, myelodysplastic syndromes and histiocytosis. Analysis of clinical results and of surrogate angiogenesis markers

Ann Oncol

(2001)

X Xin et al.

Peroxisome proliferator-activated receptor gamma ligands are potent inhibitors of angiogenesis in vitro and in vivo

J Biol Chem

(1999)

GJ Roboz et al.

Arsenic trioxide induces dose- and time-dependent apoptosis of endothelium and may exert an antileukemic effect via inhibition of angiogenesis

Blood

(2000)

J Folkman

Tumor angiogenesis

J Folkman

Angiogenesis

J Folkman

Regulation of angiogenesis

M Nguyen et al.

Elevated levels of an angiogenic peptide, basic fibroblast growth factor, in the urine of patients with a wide spectrum of cancers

J Natl Cancer Inst

(1994)

A Vacca et al.

Bone marrow angiogenesis and progression in multiple myeloma

Br J Haematol

(1994)

N Weidner et al.

Tumor angiogenesis and metastasis-correlation in invasive breast carcinoma

N Engl J Med

(1991)

D Ribatti et al.

Bone marrow angiogenesis and mast cell density increase simultaneously with progression of human multiple myeloma

Br J Cancer

(1999)

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^☆: Update on “Angiogenesis-Dependent Diseases” presented at the Expert's Roundtable on Angiogenesis, Boston, MA, October 4, 2000.

^☆☆: Supported in part by US Public Health Service Grant No. 2 P01 CA45548 from the National Cancer Institute, and by a grant to Children's Hospital from EntreMed Inc, Rockville, MD.

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Angiogenesis-dependent diseases☆,☆☆

Abstract

Blood

Blood

Blood

Am J Pathol

Mol Ther

Cell

Cell

Cancer Treat Rev

Blood

Exp Cell Res

Ann Oncol

J Biol Chem

Blood

Tumor angiogenesis

Angiogenesis

Regulation of angiogenesis

Elevated levels of an angiogenic peptide, basic fibroblast growth factor, in the urine of patients with a wide spectrum of cancers

J Natl Cancer Inst

Bone marrow angiogenesis and progression in multiple myeloma

Br J Haematol

Tumor angiogenesis and metastasis-correlation in invasive breast carcinoma

N Engl J Med

Bone marrow angiogenesis and mast cell density increase simultaneously with progression of human multiple myeloma

Br J Cancer