Purification and characterization of vascular endothelial cell proliferation factor from platelets.

Miyazono, Kohei; Okabe, Tetsuro; Urabe, Akio; Takaku, Fumimaro

doi:10.2491/jjsth1970.17.254

Cited by 83 publications

(108 citation statements)

References 7 publications

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“…Platelet-derived endothelial cell growth factor (PD-ECGF) is an angiogenic factor discovered in the late 1980s (Miyazono et al, 1987;Ishikawa et al, 1989). Sequence analysis of the gene revealed a stretch of 120 amino acids to be identical to thymidine phosphorylase (TP), an enzyme catalysing the reversible phosphorolysis of thymidine to thymine and 2-deoxyribose-1-phosphate (dR-1-P) (Furukawa et al, 1992).…”

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Role of platelet-derived endothelial cell growth factor/thymidine phosphorylase in fluoropyrimidine sensitivity

et al. 2003

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Platelet-derived endothelial cell growth factor (PD-ECGF)/thymidine phosphorylase (TP) catalyses the reversible phosphorolysis of thymidine to thymine and 2-deoxyribose-1-phosphate and is involved in the metabolism of fluoropyrimidines. It can also activate 5 0 -deoxyfluorouridine (5 0 DFUR) and possibly 5-fluorouracil (5FU) and Ftorafur (Ft), but inactivates trifluorothymidine (TFT). We studied the contribution of TP activity to the sensitivity for these fluoropyrimidines by modulating its activity and/or expression level in colon and lung cancer cells using a specific inhibitor of TP (TPI) or by overproduction of TP via stable transfection of human TP. Expression was analysed using competitive template-RT -PCR (CT-RT -PCR), Western blot and an activity assay. TP activity ranged from nondetectable to 70678 pmol h À1 10 À6 cells, in Colo320 and a TP overexpressing clone Colo320TP1, respectively. We found a good correlation between TP activity and mRNA expression (r ¼ 0.964, Po0.01) in our cell panel. To determine the role of TP in the sensitivity to 5FU, 5 0 DFUR, Ft and TFT, cells were cultured with the various fluoropyrimidines with or without TPI and differences in IC 50 's were established. TPI modified 5 0 DFUR, increasing the IC 50 's 2.5-to 1396-fold in WiDR and Colo320TP1, respectively. 5-Fluorouracil could be modified by inhibiting TP but to a lesser extent than 5 0 DFUR: IC 50 's increased 1.9-to 14.7-fold for WiDR and Colo320TP1, respectively. There was no effect on TFT or Ft. There appears to be a threshold level of TP activity to influence the 5 0 DFUR and 5FU sensitivity, which is higher for 5FU. Even high levels of TP overexpression only had a moderate effect on 5FU sensitivity.

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confidence: 99%

Role of platelet-derived endothelial cell growth factor/thymidine phosphorylase in fluoropyrimidine sensitivity

et al. 2003

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“…PD-ECGF stimulates chemotaxis of endothelial cells in vitro and has an angiogenic activity in vivo (Ishikawa et al, 1989;Miyazono et al, 1987). Experimental evidence has shown that angiogenesis plays a significant role in tumour growth and metastasis (Folkman, 1990;Folkman and Klagsbrun, 1987).…”

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Thymidine phosphorylase/platelet-derived endothelial cell growth factor is upregulated in advanced solid types of gastric cancer

et al. 1999

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Summary Previous studies demonstrated that the immunohistochemical expression of thymidine phosphorylase (dThdPase) was related with distant metastasis and disease progression. In this study we investigated the production of dThdPase/platelet-derived endothelial cell growth factor in gastric cancer quantitatively. In a total of 75 tumour tissues and 60 normal gastric mucosa specimens, dThdPase protein concentrations were determined by ELISA. The amount of dThdPase was significantly higher in the tumour tissue than in the normal tissue. Intratumoural dThdPase concentrations were significantly higher in Borrmann types I and II macroscopically, in poorly differentiated and solid type histologically, in the medullary type of the tumour stroma, and in the tumour-invading serosa. In the medullary type of the amount of tumour stroma, protein levels of dThdPase were positively correlated with the vertical diameter of the tumour (r = 0.580, P = 0.019). By immunohistochemical study, dThdPase expression on tumour cells was observed in all seven specimens with high dThdPase protein levels, but not in all 14 cases with low dThdPase protein levels (P < 0.05). In summary, these data indicated that dThdPase is up-regulated in advanced solid types of gastric cancer, suggesting that dThdPase production in carcinoma cells might be induced by the microenvironment.

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“…It is also known as platelet derived endothelial cell growth factor, and has been shown to promote angiogenesis (Miyazono et al, 1987). High tumour TP levels have been shown to correlate with poor prognosis (van Triest et al, 2000), and response to 5-FU (Metzger et al, 1998) in CRC patients.…”

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confidence: 99%

The impact of surgically induced ischaemia on protein levels in patients undergoing rectal cancer surgery

et al. 2006

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The goal of targeted therapy has driven a search for markers of prognosis and response to adjuvant therapy. The surgical resection of a solid tumour induces tissue ischaemia and acidosis, both potent mediators of gene expression. This study investigated the impact of colorectal cancer (CRC) surgery on prognostic and predictive marker levels. Tumour expression of thymidylate synthase, thymidine phosphorylase, cyclin A, vascular endothelial growth factor (VEGF), carbonic anhydrase-9, hypoxia inducible factor-1a, and glucose transporter-1 (GLUT-1) proteins was determined before and after rectal cancer surgery. Spectral imaging of tissue sections stained by immunohistochemistry provided quantitative data. Surgery altered thymidylate synthase protein expression (P ¼ 0.02), and this correlated with the change in the proliferation marker cyclin A. The expression of hypoxia inducible factor-1a, VEGF, and GLUT-1 proteins was also different following surgery. Colorectal cancer surgery significantly impacts on intratumoral gene expression, suggesting archival specimens may not accurately reflect in situ marker levels. Although rectal cancer was the studied model, the results may be applicable to any solid tumour undergoing extirpation in which molecular markers have been proposed to guide patient therapy.

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Purification and characterization of vascular endothelial cell proliferation factor from platelets.

Cited by 83 publications

References 7 publications

Role of platelet-derived endothelial cell growth factor/thymidine phosphorylase in fluoropyrimidine sensitivity

Role of platelet-derived endothelial cell growth factor/thymidine phosphorylase in fluoropyrimidine sensitivity

Thymidine phosphorylase/platelet-derived endothelial cell growth factor is upregulated in advanced solid types of gastric cancer

The impact of surgically induced ischaemia on protein levels in patients undergoing rectal cancer surgery

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