Thymidine phosphorylase in human esophageal squamous cell carcinoma

Takebayashi, Yuji; Natsugoe, Shoji; Baba, Masamichi; Akiba, Suminori; Fukumoto, Toshitaka; Miyadera, Kazutaka; Yamada, Yuji; Takao, Sonshin; Akiyama, Shin–ichi; Aikou, Takashi

doi:10.1002/(sici)1097-0142(19990115)85:2<282::aid-cncr3>3.0.co;2-t

Cited by 49 publications

(44 citation statements)

References 41 publications

(64 reference statements)

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“…Thymidine phosphorylase (TP, EC 2.4.2.4), which is identical to platelet-derived endothelial cell growth factor, is also a potent angiogenic factor (Griffiths and Stratford, 1997). In oesophageal squamous-cell carcinoma (SCC), IHC studies indicated that high TP expression was associated with angiogenesis, tumour progression and poor prognosis (Igarashi et al, 1998;Takebayashi et al, 1999). In head and neck SCC, a low percentage of cancer cells with nuclear TP expression in pre-treatment biopsies was associated with a high rate of complete regression after combined CRT .…”

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confidence: 99%

Expression of angiogenic factors predicts response to chemoradiotherapy and prognosis of oesophageal squamous cell carcinoma

et al. 2002

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The ability to predict patients' responses to chemoradiotherapy by analyzing pre-treatment biopsy specimens would be valuable for managing oesophageal squamous-cell cancer. To this end, the expression of p53, thymidine phosphorylase and vascular endothelial cell growth factor was analyzed by immunohistochemistry in 52 patients with oesophageal squamous-cell cancer prior to chemoradiotherapy. Treatment consisted of radiotherapy (40 Gy) and 5 day-infusion of 5-Fluorouracil (500 mg m 72 per day) combined with cisplatin (10 mg m 72 per day). Following treatment, imaging and endoscopic reassessment was performed to establish treatment response. Thirty-one patients underwent radical surgery and 21 patients were treated with an additional 20 Gy of radiotherapy. Of the tumours studied, 58% were p53-positive, 40% thymidine phosphorylase-positive and 44% vascular endothelial cell growth factor-positive. A clinical response was observed in 36 patients (69%) and was negatively associated with thymidine phosphorylase expression (P=0.02) and vascular endothelial cell growth factor expression (P50.001). However, the 5-year survival rate was significantly lower only in patients with vascular endothelial cell growth factor-positive tumours (P=0.037). Multivariate analysis identified vascular endothelial cell growth factor as a significant independent prognostic factor (P=0.0147). These results suggest that expression of angiogenic factors has predictive value for the treatment response and outcome of patients with oesophageal cancer.

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confidence: 99%

Expression of angiogenic factors predicts response to chemoradiotherapy and prognosis of oesophageal squamous cell carcinoma

et al. 2002

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“…The local levels of each of these cytokines differs from tumor to tumor in human colon carcinomas. 26,27 We speculate that presence of different Immunohistochemical analysis has shown that dThdPase expression is an independent prognostic factor in colon, esophageal and renal cell carcinoma, 7,8,12 but not in breast carcinoma. 9 The present results confirm the lack of correlation between clinical outcome and expression of the gene at the mRNA level in breast cancer.…”

Section: Discussionmentioning

confidence: 82%

“…21 dThdPase is an angiogenic enzyme and its enzyme activity is indispensable for the angiogenesis in experimental models. 21,22 Furthermore, the relationship between dThdPase expression and angiogenesis has been verified in several types of human solid carcinomas, 7,11,12 including breast carcinoma. 9 The current study confirms these findings and shows that UPase in contrast does not correlate with microvessel numbers in the tumors.…”

Section: Discussionmentioning

confidence: 98%

“…[7][8][9]11,12 UPase activity has also been reported to be higher expression in several types of neoplastic tissues compared to non-neoplastic tissues and in 28 breast carcinomas, it was 2.5-fold higher than in normal breast tissues. 19 Liu et al 19 also reported that there was the high degree of variation in the ratio of dThdPase activity to UPase activity (an overall ratio ϭ 2) and that the ratio between these 2 enzyme activities was slightly lower in breast carcinoma.…”

Section: Discussionmentioning

confidence: 98%

“…10 Higher levels of dThdPase expression are associated with more extensive angiogenesis, tumor progression and poor clinical outcome in some types of human solid carcinoma. 7,11,12 In contrast, little is known about the relationship between the level of UPase gene expression and clinicopathological significance in human solid tumors, although it has long been known that UPase plays a role in 5-FU activation. [13][14][15][16][17][18] Several human solid tumors including breast carcinoma have 2-to 3-fold increased UPase enzymatic activities compared to those of adjacent non-neoplastic tissues as measured by phosphorolytic activity and sensitivity to benzylacyclouridine, a potent inhibitor of this enzyme.…”

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Expression of uridine and thymidine phosphorylase genes in human breast carcinoma

Kanzaki

Takebayashi

Bando

et al. 2001

Intl Journal of Cancer

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Uridine phosphorylase (UPase) and an angiogenic enzyme, thymidine phosphorylase (dThdPase) are involved in degradation of the pyrimidine nucleosides through phosphorolysis. The expression levels of UPase and dThdPase are higher in human solid tumors including breast carcinomas than in normal tissues. To clarify the correlation between the expression levels of UPase and dThdPase genes and the clinicopathological factors, mRNA levels of these enzymes were examined by RT-PCR in 43 breast carcinomas. UPase gene expression was not correlated with dThdPase gene expression (regression coefficient R ‫؍‬ 0.032). Although the expression level of the dThdPase gene was correlated with angiogenesis, detected by immunostaining endothelial cells (R ‫؍‬ 0.66), that of UPase gene was not (R ‫؍‬ 0.044). These results suggest that UPase does not have a strong angiogenic activity. The UPase gene expression levels in tumors of patients who relapsed were significantly higher than in those from patients who did not (p ‫؍‬ 0.039). Although the expression levels of neither UPase or dThdPase were associated with age, pT, pN, pM, estrogen or progesterone receptor positivity, the patients with the higher levels of UPase gene expression had worse survival (p ‫؍‬ 0.0038) than those with lower levels. In contrast, the expression of dThdPase gene was not related to relapse or survival of these patients with breast carcinoma. Our findings suggest that the expression level of UPase gene may be an independent prognostic marker in human breast carcinoma.

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Expression of thymidine phosphorylase as an indicator of poor prognosis for patients with transitional cell carcinoma of the bladder

Arima

Imazono

Takebayashi

et al. 2000

Cancer

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BACKGROUND Thymidine phosphorylase (TP), which is identical to platelet‐derived endothelial cell growth factor (PD‐ECGF), stimulates chemotaxis of endothelial cells and is involved in the angiogenesis of human solid tumors. METHODS The activity and expression of TP were examined in human transitional cell carcinomas (TCCs) of the bladder, and their association with clinicopathologic findings was determined. The activity of the enzyme in 37 TCCs and 12 adjacent nonneoplastic tissues was measured spectrophotometrically. The expression of TP was also examined by immunoblotting. Immunohistochemical analysis was performed on 108 TCCs. RESULTS TP activity in the carcinomas was higher than that in adjacent normal tissues (P = 0.002). TP activity in Grade 3 tumors or those classified as pT2–4 was higher than in Grade 1 and 2 tumors (P = 0.017) or those classified as pT1 (P = 0.007). The level of expression of TP detected by immunoblotting correlated well with TP activity. Immunohistochemical analyses showed that 62 of 108 cases (57.4%) were TP positive. There was a significant correlation between TP expression and histologic grade, infiltration pattern, local invasion, and lymph node metastasis. TP expression as a prognostic variable was studied using the Cox proportional hazards model. TP overexpression was an independent prognostic factor, as were lymph node metastasis and local invasion. CONCLUSIONS These findings suggest that TP activity and its level of expression influence the progression of TCC and the prognoses of patients with this disease. Cancer 2000;88:1131–8. © 2000 American Cancer Society.

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Thymidine phosphorylase in human esophageal squamous cell carcinoma

Cited by 49 publications

References 41 publications

Expression of angiogenic factors predicts response to chemoradiotherapy and prognosis of oesophageal squamous cell carcinoma

Expression of angiogenic factors predicts response to chemoradiotherapy and prognosis of oesophageal squamous cell carcinoma

Expression of uridine and thymidine phosphorylase genes in human breast carcinoma

Expression of thymidine phosphorylase as an indicator of poor prognosis for patients with transitional cell carcinoma of the bladder

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