PubMed Health⌕ Search

PubMed · 11740806

Angiogenesis-dependent diseases.

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.

Explore related subjects

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

J Folkman. 2001. Angiogenesis-dependent diseases.. https://doi.org/10.1016/s0093-7754(01)90021-1

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related citations

The immunosuppressant FTY720 inhibits tumor angiogenesis via the sphingosine 1-phosphate receptor 1.

FTY720, a sphingosine 1-phosphate (S1P) analog, acts as an immunosuppressant through trapping of T cells in secondary lymphoid tissues. FTY720 was also shown to prevent tumor growth and to inhibit vascular permeability. The MTT proliferation assay illustrated that endothelial cells are more susceptible to the anti-proliferative effect of FTY720 than Lewis lung carcinoma (LLC1) cells. In a spheroid angiogenesis model, FTY720 potently inhibited the sprouting activity of VEGF-A-stimulated endothelial cells even at concentrations that apparently had no anti-proliferative effect. Mechanistically, the anti-angiogenic effect of the general S1P receptor agonist FTY720 was mimicked by the specific S1P1 receptor agonist SEW2871. Moreover, the anti-angiogenic effect of FTY720 was abrogated in the presence of CXCR4-neutralizing antibodies. This indicates that the effect was at least in part mediated by the S1P1 receptor and involved transactivation of the CXCR4 chemokine receptor. Additionally, we could illustrate in a coculture spheroid model, employing endothelial and smooth muscle cells (SMCs), that the latter confer a strong protective effect regarding the action of FTY720 upon the endothelial cells. In a subcutaneous LLC1 tumor model, the anti-angiogenic capacity translated into a reduced tumor size in syngeneic C57BL/6 mice. Consistently, in the Matrigel plug in vivo assay, 10 mg/kg/d FTY720 resulted in a strong inhibition of angiogenesis as demonstrated by a reduced capillary density. Thus, in organ transplant patients, FTY720 may prove efficacious in preventing graft rejection as well as tumor development.

Angiogenesis Inhibitors↗