Effects of Thalidomide and Related Metabolites in a Mouse Corneal Model of Neovascularization

Kenyon, Bärbel M.; Browne, Fiona; D’Amato, Robert J.

doi:10.1006/exer.1997.0292

Cited by 407 publications

(257 citation statements)

References 30 publications

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“…The exact mechanism of action of thalidomide is unknown; however, data point to inhibition of angiogenesis for its anti-cancer role [9]. Thalidomide has been shown to reduce corneal neovascularization induced by bFGF in rabbit model and by VEGF in a mouse model [21]. It also reduces tumor necrosis factor-alpha (TNF-α) production by monocytes and macrophages.…”

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

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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.

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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

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“…7 The up-regulation of VEGF has been demonstrated in patients with ccRCC. 3,21,22 In a previous study of antiangiogenic intervention in patients with ccRCC using thalidomide, which inhibits VEGF-induced neovascularization and, in some tissue specimens, VEGF expression, [23][24][25] these tumors were shown to overcome the inhibitory effects of thalidomide treatment. 26 Strategies targeting a single angiogenic factor, such as VEGF, may be ineffectual because of redundancies or alternate pathways.…”

Section: Discussionmentioning

confidence: 99%

Endothelin axis expression is markedly different in the two main subtypes of renal cell carcinoma

Douglas

Richardson

Nicol

2004

Cancer

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BACKGROUNDThe endothelin axis has been implicated in cancer growth, angiogenesis, and metastasis, but to the authors' knowledge the expression of endothelin genes has not been defined in renal cell carcinoma (RCC).METHODSTissue specimens were harvested from both normal and tumor‐affected regions at the time of radical nephrectomy from 35 patients with RCC (22 with clear cell RCC [ccRCC] and 13 with papillary RCC [PRCC]). Real‐time reverse transcriptase‐polymerase chain reaction analysis determined the expression profile of the preproendothelins (PPET‐1, PPET‐2, and PPET‐3), the endothelin receptors (ETA and ETB), and the endothelin‐converting enzymes (ECE‐1 and ECE‐2).RESULTSPPET‐1 was found to be up‐regulated in ccRCC tumor specimens and down‐regulated in PRCC tumor specimens. ETA was significantly down‐regulated in PRCC tumor specimens. ECE‐1 was expressed in all tissue specimens at comparable levels, with moderate but significant elevation in normal tissue specimens associated with PRCC. Of the other genes, PPET‐2 and ETB were expressed in all tissue specimens and no differences were observed between tumor subtypes or tumor‐affected and normal tissue specimens, whereas PPET‐3 and ECE‐2 were present in all tissue specimens but were barely detectable.CONCLUSIONSThe endothelin axis was expressed differently in the two main subtypes of RCC and appeared to match macroscopic features commonly observed in these tumors (i.e., high expression of PPET‐1 in hypervascular ccRCC contrasted against low PPET‐1 and ETA expression in hypovascular PRCC). The presence of ECE‐1 mRNA in these tissue specimens suggested that active endothelin ligands were present, indicating endothelin axis activity was elevated in ccRCC compared with normal kidney, but impaired in PRCC. The current study provided further evidence that it is not appropriate to consider ccRCC and PRCC indiscriminately in regard to treatment. Cancer 2004. © 2004 American Cancer Society.

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“…These include rodent and rabbit corneal assays where blood vessels induced in response to a FGF soaked bead are destroyed following thalidomide application (D'Amato et al, 1994; Kenyon et al, 1997). Rat fetuses exposed to thalidomide in late gestation show blood vessel disruption in areas of the brain areas linked to causing autism (Hallene et al, 2006).…”

Section: Thalidomide Is Antiangiogenicmentioning

confidence: 99%

Thalidomide‐induced teratogenesis: History and mechanisms

Vargesson

2015

Birth Defects Research Pt C

710

557

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Nearly 60 years ago thalidomide was prescribed to treat morning sickness in pregnant women. What followed was the biggest man‐made medical disaster ever, where over 10,000 children were born with a range of severe and debilitating malformations. Despite this, the drug is now used successfully to treat a range of adult conditions, including multiple myeloma and complications of leprosy. Tragically, a new generation of thalidomide damaged children has been identified in Brazil. Yet, how thalidomide caused its devastating effects in the forming embryo remains unclear. However, studies in the past few years have greatly enhanced our understanding of the molecular mechanisms the drug. This review will look at the history of the drug, and the range and type of damage the drug caused, and outline the mechanisms of action the drug uses including recent molecular advances and new findings. Some of the remaining challenges facing thalidomide biologists are also discussed. Birth Defects Research (Part C) 105:140–156, 2015. © 2015 The Authors Birth Defects Research Part C: Embryo Today: Reviews Published by Wiley Periodicals, Inc.

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Effects of Thalidomide and Related Metabolites in a Mouse Corneal Model of Neovascularization

Cited by 407 publications

References 30 publications

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

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

Endothelin axis expression is markedly different in the two main subtypes of renal cell carcinoma

Thalidomide‐induced teratogenesis: History and mechanisms

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