The expression of platelet-derived endothelial cell growth factor in human bladder cancer

Sawase, Kenji; Nomata, Koichiro; Kanetake, Hiroshi; Saito, Yutaka

doi:10.1016/s0304-3835(98)00097-4

Cited by 11 publications

(4 citation statements)

References 14 publications

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“…The 'angiogenic enzyme' thymidine phosphorylase (TP) is commonly upregulated in many solid tumours including TCC (O'Brien et al, 1996), and overexpression has been shown to correlate with increased tumour invasion (O'Brien et al, 1996;Sawase et al, 1998) and poor prognosis (Arima et al, 2000) in bladder carcinoma. While TP has been known to be angiogenic for many years (Ishikawa et al, 1989), the precise mechanism has remained elusive.…”

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confidence: 99%

Cooperative stimulation of vascular endothelial growth factor expression by hypoxia and reactive oxygen species: the effect of targeting vascular endothelial growth factor and oxidative stress in an orthotopic xenograft model of bladder carcinoma

et al. 2005

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Elevated thymidine phosphorylase has been shown to correlate with increased angiogenesis and poor prognosis in many cancers including transitional cell carcinoma of the bladder. In vitro studies have demonstrated that thymidine phosphorylase activity causes cellular oxidative stress and increases secretion of vascular endothelial growth factor. In this study, we show that thymidine phosphorylase activity also augments levels of the hypoxia-inducible factor-1a during in vitro hypoxia, and that thymidine phosphorylase activity and hypoxia act in concert to increase vascular endothelial growth factor (VEGF) secretion. We also demonstrate that thymidine phosphorylase overexpression confers tumorigenicity on an orthotopically implanted transitional cell carcinoma cell line. Administration of the antioxidant N-acetylcysteine together with a blocking anti-VEGF antibody abrogates the increase in tumorigenicity. Our results support the increased efficacy of combination approaches to antiangiogenic therapy.

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confidence: 99%

Cooperative stimulation of vascular endothelial growth factor expression by hypoxia and reactive oxygen species: the effect of targeting vascular endothelial growth factor and oxidative stress in an orthotopic xenograft model of bladder carcinoma

et al. 2005

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“…However, Sawase et al demonstrated that the tumor-free interval of PD-ECGF/TP-positive superficial bladder cancer patients was significantly shorter than that seen in the negative patients. 8) In that particular study, all patients with superficial tumors were treated with intravesicular chemotherapy following transurethral resection. This therapeutic method may have great significance.…”

Section: Discussionmentioning

confidence: 99%

“…9) Sense and antisense primers for PD-ECGF/TP mRNA were: 5′-AGGGAGCCAGGGACTTCCCGA-3′ (in exon 2) and 5′-TGGAATGCTTGTCCACAAGCTGC-3′ (in exon 3), respectively. They were synthesized according to published information 8) and amplified a 290 bp fragment. Sense and antisense primers for glyceraldehyde-3-phosphate dehydrogenase (GAPDH) mRNA were: 5′-GGATTTGGTCGTATTGGGCGCCT-3′ (in exon 2) and 5′-AGTGAGCTTCCCGTCTAGCTCAG-3′ (in exon 7), respectively.…”

Section: Analysis Of Pd-ecgf/tp Mrna Expression By Rt-pcrmentioning

confidence: 99%

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Expression of Platelet‐derived Endothelial Cell Growth Factor/Thymidine Phosphorylase in Human Bladder Cancer

Tanaka¹,

Tokura²,

Arai³

et al. 1999

Japanese Journal of Cancer Research

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We investigated the expression of platelet-derived endothelial cell growth factor/thymidine phosphorylase (PD-ECGF/TP) in primary bladder cancer, its association with clinicopathologic findings, and their prognostic value. mRNA was extracted from 20 bladder cancer specimens and 6 normal bladder mucosal tissues. Relative amounts of PD-ECGF/TP mRNA were evaluated by reverse transcriptase-polymerase chain reaction (RT-PCR) and compared with the level of glyceraldehyde-3-phosphate dehydrogenase mRNA (used as an internal standard). PD-ECGF/TP expression was examined by immunohistochemistry in 85 patients who underwent cystectomy for bladder cancer. Serum PD-ECGF/TP levels were measured in 23 patients using a sandwich-type enzymelinked immunosorbent assay. By RT-PCR analysis, expression of PD-ECGF/TP was found to be 7-fold higher in invasive tumors than in superficial tumors (P < < < <0.01) and 9-fold higher than in normal bladder (P < < < <0.01).

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The dual role of thymidine phosphorylase in cancer development and chemotherapy

Bronckaers¹,

Gago²,

Balzarini³

et al. 2009

Medicinal Research Reviews

177

176

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Thymidine phosphorylase (TP), also known as "platelet-derived endothelial cell growth factor" (PD-ECGF), is an enzyme, which is upregulated in a wide variety of solid tumors including breast and colorectal cancers. TP promotes tumor growth and metastasis by preventing apoptosis and inducing angiogenesis. Elevated levels of TP are associated with tumor aggressiveness and poor prognosis. Therefore, TP inhibitors are synthesized in an attempt to prevent tumor angiogenesis and metastasis. TP is also indispensable for the activation of the extensively used 5-fluorouracil prodrug capecitabine, which is clinically used for the treatment of colon and breast cancer. Clinical trials that combine capecitabine with TP-inducing therapies (such as taxanes or radiotherapy) suggest that increasing TP expression is an adequate strategy to enhance the antitumoral efficacy of capecitabine. Thus, TP plays a dual role in cancer development and therapy: on the one hand, TP inhibitors can abrogate the tumorigenic and metastatic properties of TP; on the other, TP activity is necessary for the activation of several chemotherapeutic drugs. This duality illustrates the complexity of the role of TP in tumor progression and in the clinical response to fluoropyrimidine-based chemotherapy.

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The expression of platelet-derived endothelial cell growth factor in human bladder cancer

Cited by 11 publications

References 14 publications

Cooperative stimulation of vascular endothelial growth factor expression by hypoxia and reactive oxygen species: the effect of targeting vascular endothelial growth factor and oxidative stress in an orthotopic xenograft model of bladder carcinoma

Cooperative stimulation of vascular endothelial growth factor expression by hypoxia and reactive oxygen species: the effect of targeting vascular endothelial growth factor and oxidative stress in an orthotopic xenograft model of bladder carcinoma

Expression of Platelet‐derived Endothelial Cell Growth Factor/Thymidine Phosphorylase in Human Bladder Cancer

The dual role of thymidine phosphorylase in cancer development and chemotherapy

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