Combination oral antiangiogenic therapy with thalidomide and sulindac inhibits tumour growth in rabbits

Verheul, Henk M.W.; Panigrahy, Dipak; Yuan, Jing; D’Amato, Robert J.

doi:10.1038/sj.bjc.6690020

Cited by 76 publications

(40 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Our study on preclinical trial addresses the efficiency of thalidomide in lung adenocarcinoma, a subtype of non -small cell lung cancer. Several studies have reported that thalidomide reduces vascular endothelial growth factor expression in tumor tissues, leading to a dramatic decrease in vascular density and permeability, and an increase in tumor cell apoptosis (38). Our results also showed that thalidomide inhibits the overexpression of vascular endothelial growth factor in tumors excised from nude mice.…”

Section: Discussionsupporting

confidence: 73%

A Novel Anticancer Effect of Thalidomide: Inhibition of Intercellular Adhesion Molecule-1–Mediated Cell Invasion and Metastasis through Suppression of Nuclear Factor-κB

Lin

Shun²,

et al. 2006

Clinical Cancer Research

127

103

View full text Add to dashboard Cite

Purpose: Thalidomide has been reported to have antiangiogenic and antimetastatic effects.Intercellular adhesion molecule-1 (ICAM-1) was shown to be involved in monocyte adherence to epithelial cells and cancer cell invasion. In this study, we further investigated the role of ICAM-1 in tumorigenesis, including tumor formation and metastasis. ICAM-1 as a molecular target for cancer and the anticancer effect of thalidomide were investigated. Experimental Design: Expression of ICAM-1 protein in human lung cancer specimens was assessed by immunohistochemistry. ICAM-1 overexpressing A549 cells (A549/ICAM-1) were established to investigate the direct effect of ICAM-1 on in vitro cell invasion and in vivo tumor metastasis. Transient transfection and luciferase assay, electrophoretic mobility shift assay, and chromatin immunoprecipitation were done to assess the activity and binding of nuclear factor-nB to the ICAM-1 promoter. A xenograft model in nude mice was conducted to evaluate the anticancer effect of thalidomide. Results: High expression of ICAM-1 in human lung cancer specimens was correlated with a greater risk of advanced cancers (stages III and IV). A549/ICAM-1 cells were shown to induce in vitro cell invasion and in vivo tumor metastasis. Anti-ICAM-1 antibody and thalidomide had inhibitory effect on these events. Thalidomide also suppressed tumor necrosis factor-a^induced ICAM-1 expression through inhibition of nuclear factor-nB binding to the ICAM-1 promoter. The in vivo xenograft model showed the effectiveness of thalidomide on tumor formation. Conclusion: These studies provide a framework for targeting ICAM-1 as a biologically based therapy for cancer, and thalidomide might be effective in human lung cancer.

show abstract

Section: Discussionsupporting

confidence: 73%

A Novel Anticancer Effect of Thalidomide: Inhibition of Intercellular Adhesion Molecule-1–Mediated Cell Invasion and Metastasis through Suppression of Nuclear Factor-κB

Lin

Shun²,

et al. 2006

Clinical Cancer Research

127

103

View full text Add to dashboard Cite

show abstract

“…These observations concur with reports that in mice, thalidomide is not teratogenic, 30 is unable to oxidize DNA, 18,31 and has no antitumor nor antiangiogenic effects in mice bearing several types of tumors. [32][33][34] Others reported that thalidomide had an antiangiogenic effect in V2 carcinoma growing in rabbits, 29 but that human or rabbit microsomes were required for in vitro inhibition of microvessel formation in a rat aorta system and for inhibiting proliferation of human aortic endothelial cells by thalidomide, 26 supporting the notion that active metabolites of thalidomide are responsible, at least in part, for its antiangiogenic properties. None of these studies reports measurement of thalidomide metabolism or the presence of its metabolites.…”

Section: Discussionmentioning

confidence: 61%

Antimyeloma efficacy of thalidomide in the SCID-hu model

Yaccoby

Johnson

Mahaffey

et al. 2002

Blood

View full text Add to dashboard Cite

To determine the mechanism of thalidomide's antimyeloma efficacy, we studied the drug's activity in our severe combined immunodeficiency-human (SCIDhu) host system for primary human myeloma. In this model, tumor cells interact with the human microenvironment to produce typical myeloma manifestations in the hosts, including stimulation of neoangiogenesis. Because mice are not able to metabolize thalidomide efficiently, SCID-hu mice received implants of fetal human liver fragments under the renal capsule in addition to subcutaneous implants of the fetal human bone. Myeloma cell growth in these mice was similar to their growth in hosts without liver implant, as assessed by change in levels of circulating human immunoglobulins and by histologic examinations. Thalidomide given daily by peritoneal injection significantly inhibited myeloma growth in 7 of 8 experiments, each with myeloma cells from a different patient, in hosts implanted with human liver. In contrast, thalidomide exerted an antimyeloma effect only in 1 of 10 mice without liver implants. Microvessel density in the untreated controls was higher than in thalidomide-responsive hosts but not different from nonresponsive ones. Expression of vascular endothelial growth factor by myeloma cells and by other cells in the human bone, determined immunohistochemically, was not affected by thalidomide treatment in any experiment. Our study suggests that thalidomide metabolism is required for its antimyeloma efficacy. Although response to thalidomide was strongly associated with decreased microvessel density, we were unable to conclude whether reduced microvessel density is a primary result of thalidomide's antiangiogenic activity or is secondary to a lessened tumor burden. (Blood. 2002;100:4162-4168)

show abstract

“…It also reduces tumor necrosis factor-alpha (TNF-α) production by monocytes and macrophages. Animal models demonstrated thalidomide activity against solid tumors in rabbits and nude mice, and it produced apoptosis in established tumors [22][23]. Singhal and colleagues were among the first to report significant activity of thalidomide in a population of patients with advanced, previously treated multiple myeloma [11].…”

Section: Discussionmentioning

confidence: 99%

A phase II trial of thalidomide in patients with refractory endometrial cancer and correlation with angiogenesis biomarkers: A Gynecologic Oncology Group study

McMeekin

Sill

Benbrook

et al. 2007

Gynecologic Oncology

View full text Add to dashboard Cite

Objectives-A phase II trial was conducted to evaluate the anti-tumor activity and adverse effects of thalidomide in persistent or recurrent endometrial cancer refractory to cytotoxic chemotherapy, and to correlate angiogenesis biomarker expression with clinical outcome.Methods-Consenting patients were treated until progression or intolerable toxicity with an oral starting dose of 200 mg thalidomide/day that was to increase by 200 mg every 2 weeks to a target dose of 1000 mg/day. Vascular endothelial growth factor (VEGF), basic fibroblastic growth factor (bFGF), and soluble endothelial protein C receptor (sEPCR) were analyzed by ELISA in pre and post-treatment specimens.Results-Twenty-four of 27 patients enrolled in the study were eligible, of whom 2 reached the target dose, 8 progressed before achieving the target dose and 14 refused or had toxicity that prohibited escalation. Two patients (8.3%) remained progression-free ≥ 6 months. There were 3 (12.5%) with partial responses, 2 (8.3%) with stable disease, 15 (62.5%) with increasing disease, and 4 (16.7%) who were inevaluable for response. Median progression-free survival and overall survival Précis: Thalidomide has minimal activity in chemo-refractory endometrial cancer as judged by the ability to prolong progression-free survival greater than 6 months.Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

show abstract

Combination oral antiangiogenic therapy with thalidomide and sulindac inhibits tumour growth in rabbits

Cited by 76 publications

References 27 publications

A Novel Anticancer Effect of Thalidomide: Inhibition of Intercellular Adhesion Molecule-1–Mediated Cell Invasion and Metastasis through Suppression of Nuclear Factor-κB

A Novel Anticancer Effect of Thalidomide: Inhibition of Intercellular Adhesion Molecule-1–Mediated Cell Invasion and Metastasis through Suppression of Nuclear Factor-κB

Antimyeloma efficacy of thalidomide in the SCID-hu model

A phase II trial of thalidomide in patients with refractory endometrial cancer and correlation with angiogenesis biomarkers: A Gynecologic Oncology Group study

Contact Info

Product

Resources

About