Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The antitumor activity of cytostatic 5'-deoxy-5-fluorouridine (5'-dFUrd) depends on its being converted to 5-fluorouracil (5-FUra) by the enzyme thymidine phosphorylase (dThdPase, EC 2.42.4). We prepared mouse anti-human dThdPase monoclonal antibodies to serve as tools for clinical studies with this drug. Partially purified dThdPase obtained form HCT116 human colon cancer cells grown in athymic mice was used as and antigen for the immunization of mice. Six hybridomas were cloned which produced anti-human dThdPase antibodies, as detected by Western blot analysis with human dThdPase. With these antibodies, we developed an ELISA method sensitive enough to measure dThdPase levels, even in tumor tissue samples weighing as little as 10 mg. In addition, one monoclonal antibody was suitable for immunologically staining the enzyme in tumor tissues. Thus, these anti-human dThdPase monoclonal antibodies could be used to measure levels of the enzyme in tumor cells, which is essential for the activation of 5'-dFUrd.
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PMID:Preparation of anti-human thymidine phosphorylase monoclonal antibodies useful for detecting the enzyme levels in tumor tissues. 895 Nov 54

We report that hypoxia regulates and influences the level of the angiogenic enzyme platelet-derived endothelial cell growth factor (PD-ECGF), also called thymidine phosphorylase, in vitro and in vivo. Levels of PD-ECGF protein increased 6-fold in the breast cancer cell line MDA 231 after 16 h of growth in 0.3% oxygen. A simultaneous increase in enzyme activity was observed. Immunohistochemical staining of MDA 231 tumors grown in nu/nu mice showed increased expression of PD-ECGF in those parts of the tumor that are proximal to the areas of necrosis. In addition, increased and widespread staining for PD-ECGF protein was obtained when the tumor vascular supply was occluded for 2 h by clamping. Lowering the media pH to 6.3-6.7 in vitro also resulted in an increase in PD-ECGF protein levels. This study demonstrates that tumor microenvironmental factors can result in the specific up-regulation of an angiogenic enzyme that can also activate 5-fluorouracil prodrugs and hence is exploitable therapeutically.
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PMID:The influence of oxygen tension and pH on the expression of platelet-derived endothelial cell growth factor/thymidine phosphorylase in human breast tumor cells grown in vitro and in vivo. 904 26

Studies have shown that thymidine phosphorylase (TdRPase) activity in various tumors is higher than that in normal tissues. We studied the immunohistochemical localization of TdRPase in uterine cervical intraepithelial neoplasia (CIN) using monoclonal antibody against TdRPase. Sixty-nine patients were studied: CIN 1, 14; CIN 2, 15; CIN 3 (severe dysplasia), 23; CIN 3 (carcinoma in situ), 17. Immunoreactivity for TdRPase was found in 29% of CIN 1, 40% of CIN 2, 70% of CIN 3 (severe dysplasia), and 88% of CIN 3 (carcinoma in situ), showing increasing incidence with the progression of tumor grade. Furthermore, in higher grade tumor, more immunoreactive cells were found with increased intensity of immunoreaction. Both nucleus and cytoplasm of atypical cells showed immunoreactivity in most TdRPase positive cases, while either nucleus or cytoplasm was positive in a few cases. The stromal tissues were negative for the antibody except 3 cases of CIN 3 (carcinoma in situ) in which the stromal tissues adjacent to the tumor was positive. Our data suggest that immunoreactivity of TdRPase in CIN may correlate with the grade of CIN.
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PMID:[Immunohistochemical study of thymidine phosphorylase in uterine cervical intraepithelial neoplasia]. 917 Sep 77

The aim of this study was to determine whether the expression of thymidine phosphorylase (TP) by uterine sarcoma and leiomyoma cells is associated with the density of microvessels within the tumor, and with Doppler ultrasound-derived peak systolic velocity (PSV) of blood flow. Sections of tissue from four uterine sarcomas and 41 uterine leiomyomas which had been used in a previous study to determine intratumoral peak systolic velocity were analyzed for the cellular expression of TP and the intratumoral density of microvessels by immunohistochemistry, using monoclonal antibody to TP and factor VIII-related antigen, respectively. The main outcome measures were whether or not the tumor cells were TP-positive or TP-negative, and the microvessel count within each tumor type. Uterine sarcomata were classified as TP-positive and uterine leiomyomata as TP-negative. The microvessel count in uterine sarcomas was significantly higher than that in uterine leiomyomas (p = 0.002, Mann-Whitney U test). We concluded that the expression of TP by uterine sarcoma cells is associated with an increase in microvessel density and with a higher peak systolic velocity.
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PMID:Expression of thymidine phosphorylase in uterine sarcoma and uterine leiomyoma: association with microvessel density and Doppler blood flow analysis. 926 24

Recent studies on angiogenesis in human solid tumors have underlined its importance as therapeutic target. In particular, of interest is to suppress the function of several positive regulators including vascular endothelial growth factors (VEGF), basic fibroblast growth factor and thymidine phosphorylase, because they are evident to be responsible for the promotion of neovascularization in a variety of tumor types. In this review, we picked up VEGF, probably one of most promising target, and discuss about the therapeutic tools for controlling VEGF function in human tumors.
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PMID:[New molecular target of cancer therapy--angiogenesis regulator VEGF]. 942 62

The activity of thymidine phosphorylase (dThdPase) in the myometrium and uterine myomas has been investigated in perimenopausal women. Differences in the activity of dThdPase have been found depending on the myoma type, menopause stage and the phase of the menstrual cycle in which the surgery was performed. The enzyme in the cytoplasmatic soluble fraction obtained at 50,000 x g was the most active in cellular leiomyomas of the follicular phase, the least in adenomyomas of the luteal phase of the menstrual cycle, whereas its activity in myometrium was always unchanged. Greater differences can be observed in the activity of dThdPase after a partial purification of the enzyme from myomas. It seems that the increase in dThdPase activity may point to its correlation with transient, premalignant tumor which may later transform into malignant forms.
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PMID:The activity of thymidine phosphorylase in the uterine myomas and the myometrium in perimenopausal women. 946 43

Capecitabine (N4-pentyloxycarbonyl-5'-deoxy-5-fluorocytidine) is a new fluoropyrimidine carbamate, which is converted to 5-fluorouracil (5-FUra) selectively in tumors through the intermediate metabolite 5'-deoxy-5-fluorouridine (5'-dFUrd, doxifluridine). 5'-dFUrd is metabolized to 5-FUra by thymidine phosphorylase (dThdPase) located in high levels in various types of solid tumors from patients, whereas 5-FUra generated is catabolized to dihydrofluorouracil by dihydropyrimidine dehydrogenase (DPD). The present study investigated whether the efficacy of capecitabine and its intermediate metabolite 5'-dFUrd correlates with levels of these enzymes in various human cancer xenograft models. Capecitabine and 5'-dFUrd were highly effective and inhibited tumor growth by more than 50% in 18 of 24 xenograft lines (75%) and 15 of 24 xenograft lines (63%), respectively, whereas 5-FUra and a mixture of tegafur and uracil were effective only in 1 of 24 (4.2%) and 5 of 24 (21%), respectively. The efficacy of capecitabine correlated with dThdPase activity. However, capecitabine was effective even in tumors with lower levels of dThdPase if DPD levels were also lower. In contrast, it was not as effective even in tumors with sufficient levels of dThdPase if DPD levels were very high. The efficacy of capecitabine consequently correlated very well with and depended on the ratio of these two enzymes in tumors. These results indicate that capecitabine might exert its efficacy through 5-FUra generated in tumor tissues but not through that generated in normal organs. On the other hand, there was no correlation between the efficacy of a mixture of tegafur and uracil and these enzyme activities in tumors. The efficacy of capecitabine would be optimized by selecting patients who have tumors with a high ratio of dThdPase to DPD activities.
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PMID:Positive correlation between the efficacy of capecitabine and doxifluridine and the ratio of thymidine phosphorylase to dihydropyrimidine dehydrogenase activities in tumors in human cancer xenografts. 948 21

Intratumoral proteases are known to be involved in not only tumor cell invasion but also a variety of stromal reactions including neovascularization. In this study, we have examined the expression of matrix metalloproteinases (MMPs) by gelatin gel zymography and compared its expression with angiogenesis activities including the expression of several endothelial growth regulators and intratumoral microvessel density (MVD) in human breast cancer tissues. There was a significant correlation between activated MMP-2 expression and vascular endothelial growth factor (VEGF) expression (p=0.045). In addition, the expression of activated MMP-9 expression was significantly correlated with thymidine phosphorylase (TP) expression (p=0.0044). Pro MMP-9 expression tended to correlated with the increment of MVD (p=0.063). MMP-2 and MMP-9 expressions were frequently co-upregulated with endothelial growth regulators in human breast cancer tissues, which underlines the cooperative function of MMPs in neovascularization.
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PMID:Relationship between matrix metalloproteinase expression and tumor angiogenesis in human breast carcinoma. 953 74

Inhibitors of thymidine phosphorylase (dThdPase) are expected to suppress the growth and metastasis of tumor cells by inhibition of angiogenesis and were designed by utilizing the three dimensional structure of the enzyme. 5-Substituted 6-aminouracils (5) and 7-substituted pyrrolo[2,3-d]pyrimidine-2,4-diones (6) were synthesized and tested for inhibition of human placenta thymidine phosphorylase. 5-Bromo-6-aminouracil (5d), 5-cyano-6-[3-(methylamino)propyl]-uracil (5e), and 7-(2-aminoethyl)-pyrrolo[2,3-d]pyrimidine-2,4-dione (6c) inhibited dThdPase with IC50s of 7.6, 3.8 and 44.0 microM, respectively.
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PMID:Synthesis of 6-aminouracils and pyrrolo[2,3-d]pyrimidine-2,4-diones and their inhibitory effect on thymidine phosphorylase. 958 98

To clarify whether platelet-derived endothelial cell growth factor/thymidine phosphorylase (PD-ECGF/TP) expression in both tumor cells and stromal cells has independent or synergistic effects on tumor angiogenesis and progression and to explore a possible regulator for PD-ECGF/TP expression, immunohistochemical staining was conducted on 148 specimens of colorectal cancer. The microvessel count was significantly correlated with the extent of PD-ECGF/TP expression. Macrophage infiltration in tumors with positive TP was significantly higher than in tumors with negative TP (P < 0.001). The Cox model showed that PD-ECGF/TP expression was an independent prognostic factor, although the microvessel count had a stronger value in determining the patient prognosis.
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PMID:Platelet-derived endothelial cell growth factor/thymidine phosphorylase expression correlated with tumor angiogenesis and macrophage infiltration in colorectal cancer. 965 93


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