The activity and expression of thymidine phosphorylase in human solid tumours

Takebayashi, Yuji; Yamada, Kazutaka; Miyadera, Kazutaka; Sumizawa, Tomoyuki; Furukawa, Tatsuhiko; Kinoshita, Fumiaki; Aoki, Dai; Okumura, Hiroshi; Yamada, Yuji; Akiyama, Shin–ichi; Aikou, Takashi

doi:10.1016/0959-8049(96)00061-5

Cited by 168 publications

(119 citation statements)

References 26 publications

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“…7 TP reactivity reportedly is increased considerably in tumor tissues relative to neighboring normal tissues in a variety of malignancies. 12,13 In human malignancies of various organs, different patterns of stromal and tumor cell-TP expression have been observed. 14 -24 In colorectal carcinoma, 14,15 , gastric carcinoma, 17 and breast carcinoma, 18,19 intensive TP expression has been observed in intratumoral macrophages.…”

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confidence: 99%

Thymidine phosphorylase and vascular endothelial growth factor in patients with Stage I lung adenocarcinoma

Kojima

Shijubo

Abe

2002

Cancer

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Sleeping giants: As a mimic of cell agglomeration to form tissues, a novel vesicle aggregation process with the characteristic advantages of being highly efficient, light‐responsive, reversible, large‐scale, and stable is reported. Giant hyperbranched polymer vesicles (5–10 μm) are used as the building blocks (see scheme), and the vesicle aggregates can assemble and disassemble with alternating UV and Vis irradiation.

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confidence: 99%

Thymidine phosphorylase and vascular endothelial growth factor in patients with Stage I lung adenocarcinoma

Kojima

Shijubo

Abe

2002

Cancer

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“…[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%

“…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%

“…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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“…Fluoropyrimidines have been shown to inhibit thymidylate synthase (TS), be detoxified by dihydropyrimidine dehydrogenase (DPD), and be activated by thymidine phosphorylase (TP), which is present in higher amounts in malignant tissue than non-neoplastic tissue [15,16]. Given the pivotal role that these enzymes play in regulating the cytotoxicity and metabolism of these agents, investigators have tested the hypothesis that these enzymes may be useful predictors of response and toxicity to a fluoropyrimidine-based therapy.…”

Section: Introductionmentioning

confidence: 99%

Phase II clinical trial of capecitabine in the treatment of advanced, persistent or recurrent squamous cell carcinoma of the cervix with translational research: A gynecologic oncology group study

García¹,

Blessing

Darcy

et al. 2007

Gynecologic Oncology

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Purpose-To evaluate the anti-tumor activity and adverse events of capecitabine in advanced, persistent or recurrent squamous cell carcinoma of the cervix, and to explore biomarkers with the potential to predict capecitabine response and toxicity. The following member institutions participated in this study: University of Mississippi Medical Center, Indiana University School of Medicine, Wake Forest University School of Medicine, University of California Medical Center at Irvine, University of Texas-Galveston.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. NIH Public Access NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author ManuscriptExperimental Design-Eligible, consenting patients were treated with a starting dose of 2500 mg/m 2 /day or 1800 mg/m 2 /day(divided into two doses given every 12 hours) for 14 days of each 21-day cycle. Prior chemotherapy was allowed only in the context of radiation "sensitization". Genotyping in the 5' and 3' ends of thymidylate synthase (TS) was performed in DNA from pretreatment blood. Relative gene expression of TS, dihydropyrimidine dehydrogenase (DPD) and thymidine phosphorylase (TP) was quantified in RNA extracted from paraffin-embedded tumor.Results-All patients had prior radiotherapy and 22 received a radiation sensitizer. A partial response was observed in 4 of 26 (15%) evaluable patients. An additional 35% of patients achieved stable disease while 42% experienced increasing disease. The most common serious non hematological toxicities were gastrointestinal and dermatologic. Exploratory analyses suggested that: a germline polymorphism in the 3' or the 5' end of TS was not associated with TS gene expression, relative tumor expression of TS, DPD and TP were not correlated, and relative tumor expression of TP may predict severe anemia.Conclusions-Based on the modest response rate, this trial was closed without a second stage of accrual; single agent capecitabine was not selected for further study in advanced persistent or recurrent squamous cell carcinoma of the cervix previously treated with radiation or chemoradiation.

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The activity and expression of thymidine phosphorylase in human solid tumours

Cited by 168 publications

References 26 publications

Thymidine phosphorylase and vascular endothelial growth factor in patients with Stage I lung adenocarcinoma

Thymidine phosphorylase and vascular endothelial growth factor in patients with Stage I lung adenocarcinoma

Expression of uridine and thymidine phosphorylase genes in human breast carcinoma

Phase II clinical trial of capecitabine in the treatment of advanced, persistent or recurrent squamous cell carcinoma of the cervix with translational research: A gynecologic oncology group study

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