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)

Expression of platelet-derived endothelial cell growth factor/thymidine phosphorylase (PD-ECGF/TP), an angiogenic factor, was immunohistochemically analyzed in 117 specimens of invasive breast carcinoma (IBC). PD-ECGF/TP expression was observed in cancer cells and/or stromal cells; most of these stromal cells were activated macrophages. Therefore, we assessed the PD-ECGF/TP expression separately in cancer cells and stromal cells. Sixty-one (52.1%) cases were classified as PD-ECGF/TP-positive in cancer cells and 44 (37.6%) were classified as positive in stromal cells. The PD-ECGF/TP expression in cancer cells did not correlate with any prognostic factors. However, its expression in stromal cells positively correlated with both tumor size and microvessel count, and inversely correlated with estrogen receptor status. Relapse-free survival and overall survival (OS) were significantly worse in patients with PD-ECGF/TP-positive stromal cells than in patients with negative cells. A multivariate analysis using the Cox proportional hazards model showed that the PD-ECGF/TP expression in stromal cells independently predicted OS as well as nodal status and tumor size. In conclusion, PD-ECGF/TP expression in stromal cells correlates with tumor angiogenesis and can be used to predict the prognosis of patients with IBC.
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PMID:Platelet-derived endothelial cell growth factor/thymidine phosphorylase expression in macrophages correlates with tumor angiogenesis and prognosis in invasive breast cancer. 968 77

FdUrd was evaluated in vivo as a potential agent for intrathecal chemotherapy of meningeal carcinomatosis. Neurotoxicity was examined pathologically in normal mice after 4 consecutive intrathecal injections of FdUrd. Using mice models of meningeal carcinomatosis, antitumor activities were studied by evaluating survival time. Pathological examination showed none of the following abnormal findings: demyelination, degeneration and destruction of ependymal linings. FdUrd also had an effect on meningeal carcinomatosis of mice (203 glioma and MM46 transplantable ascitic mammary cancer). In causing FdUrd to exhibit its efficacy, it is necessary to take into consideration the balance between the activity of two key enzymes, thymidine phosphorylase (TPase) (anabolic enzyme) and thymidine kinase (TK) (metabolic enzyme), in tumor tissues as compared with their activity in normal tissues. TPase activity which results in conversion to 5-FU was much lower in malignant glioma and metastatic brain tumors compared with tumors in other extracranial organs. TPase activity in normal brain was much less than in normal tissues in extracranial organs and its activity in gray matter (cortex) was significantly lower than that in white matter. On the other hand, TK activity in malignant brain tumors was much less than that in extracranial organs, however, its activity in normal brain was almost equal to that in normal tissues in extracranial organs. These data obtained in vivo study showed FdUrd to be a possible agent for intrathecal chemotherapy.
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PMID:[In vivo study on intrathecal use of 5-fluoro-2'-deoxyuridine (FdUrd) in meningeal dissemination of malignant tumor]. 978 91

Anti-Factor VIII vessel immunostaining has been widely used in the detection of angiogenesis in non-small cell lung cancer and other tumors. Several new antibodies have shown a higher sensitivity, and anti-CD31 has recently been proposed to be the standard for microvessel study. In the present study, we comparatively evaluated the two antibodies in 134 cases of early operable non-small cell lung cancer. The F8/86 (anti-Factor VIII-associated antigen) and JC70 (anti-CD31) MoAbs were used in paraffin-embedded material. Eye appraisal of vascular grade (VG) and microvessel score (MS) was performed by three experienced pathologists. Different cutoff points were used for the analysis of VG and MS correlation with nodal involvement, overall survival, and thymidine phosphorylase expression. Intra- and interobserver variability was minimal for both antibodies. MS and VG were significantly correlated with each other. However, 54 and 22% of cases with high anti-CD31 VG or high MS, respectively, had low vascularization on anti-Factor VIII assessment. Anti-CD31 scoring was significantly associated with nodal involvement and overall survival for all cutoff points considered, which was not verified for anti-Factor VIII staining. VG was the most significant indicator of nodal involvement and survival for both antibodies. Tumors with high VG by anti-CD31 but low or medium VG by anti-Factor VIII behaved as tumors of high neoangiogenesis, defining a poor prognosis (P = 0.005) despite the failure of anti-factor VIII antibody to highlight intense neoangiogenesis. Anti-CD31 MS significantly associated with thymidine phosphorylase overexpression (P = 0.01), whereas no correlation was found for anti-Factor VIII counting. It was concluded that anti-CD31 microvessel immunostaining has several advantages over anti-Factor VIII, being a more sensitive method for highlighting small, immature microvessels or single endothelial cells. This could be of importance in revealing possible correlation of tumor angiogenesis with metastatic behavior, prognosis, or angiogenic factor overexpression. Vascular grading was the best method for neovascularization assessment, efficiently defining groups of tumors with aggressive clinical course.
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PMID:Comparative evaluation of angiogenesis assessment with anti-factor-VIII and anti-CD31 immunostaining in non-small cell lung cancer. 981 51

The activity of thymidine phosphorylase (TdR-Pase), which is identical to platelet-derived endothelial cell growth factor (a potent angiogenic factor), was analyzed in primary human bladder cancer tissues. TdR-Pase activity in tissues was determined from the conversion rate of 5'-deoxy-5-fluorouridine to 5-fluorouracil. The mean activity in 37 bladder cancers and in 8 samples of normal bladder epithelial tissue was 108.5 and 19.2 microgram 5-fluorouracil/mg protein/h, respectively, showing a statistically significant difference. Among the cancer tissues, differences in activity were seen according to the stage and grade of tumors. Low-grade (grade 1) tumors had significantly lower activities than high-grade tumors, and high-grade invasive tumors showed significantly higher activities than low-grade superficial tumors. These results demonstrate that a high TdR-Pase activity in bladder cancer is associated with the tumor characteristics of invasion and malignant potential. Our conclusions support the hypothesis that angiogenesis that is mediated by this molecule may be involved in the development of invasive human bladder cancer, as suggested by T. O'Brien et al. (Cancer Res., 55: 510-513, 1995), and also suggest that TdR-Pase is a potential therapeutic target in human bladder cancer.
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PMID:Thymidine phosphorylase activity in human bladder cancer: difference between superficial and invasive cancer. 981 73

It has been shown that human thymidine phosphorylase (TP) is identical to platelet-derived endothelial cell growth factor and has angiogenic activity. In the present study, the expression of TP was examined in 139 mammary carcinomas and 35 benign mammary disorders using biochemical and immunohistochemical methods. Moreover, in order to evaluate the significance of TP expression in mammary carcinomas, the relationship between vascular density and various clinicopathological factors, including age and menopausal status of patients with a mammary carcinoma, were compared with the size, nodal status, expression of estrogen receptor (ER), progesterone receptor (PgR), c-erbB-2, p53 and TP of a mammary carcinoma. Thymidine phosphorylase expression increased in both the nuclei and cytoplasm of mammary carcinoma cells in comparison to mammary benign disorder cells. The number of microvessels in mammary carcinomas was generally correlated to the number of tumor cells with TP expression in cytoplasm. The number of cells with TP expression in cytoplasm was significantly large in tumors that measured 3-4 cm in diameter, compared with tumors measuring 1-2 and 5-6 cm in diameter. In mammary tumors of 1-4 cm diameter, TP expression and vessel density were significantly high in tumors negative for ER or positive for c-erbB2 and in tumors positive for TP or c-erbB2, respectively; whereas tumors of 5-6 cm in diameter were not modified by any clinicopathological factors. The results indicated that TP plays an important angiogenetic role in mammary carcinomas, especially tumors with a certain progression.
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PMID:The expression of thymidine phosphorylase/platelet-derived endothelial cell growth factor is correlated to angiogenesis in breast cancer. 983 53

Uridine phosphorylase (UPase) catalyzes the reversible phosphorolysis of uridine to uracil. We purified the enzyme from the murine colon 26 tumor using a two-step procedure through 5-amino-benzylacyclouridine affinity chromatography. Antibodies raised in rabbits against the purified protein revealed single bands in Western blots of normal human tissue and tumor extracts. The polyclonal antibody used to screen a human liver expression library allowed the isolation of a 1.2-kb clone that contained the entire open reading frame of the human UPase. The UPase cDNA has been expressed as a fusion protein in Escherichia coli using the pMal-C2 vector. The kinetic analysis demonstrated that the recombinant UPase preferentially uses uridine, 5-fluorouracil, and uracil as substrates, although lower levels of activity were observed with 2-deoxyuridine and thymidine. Clinical samples of human tumors and adjacent normal tissues were assayed for phosphorolytic activity and sensitivity to 5-benzylacyclouridine (BAU), a potent inhibitor of the enzyme presently in Phase I-II clinical trial. Activity in normal tissues appeared to be low but very sensitive to BAU (approximately 90% inhibition at 10 microM). Tumors had generally 2-3-fold greater activity compared with adjacent normal tissues. In breast cancer specimens and head-neck squamous carcinomas, however, uridine cleavage was only partially inhibited (40-60%) by 10 or 100 microM BAU. The BAU-insensitive activity requires phosphate and pH conditions similar to the normal enzyme, and the new phosphorolytic activity was independent from thymidine phosphorylase. The BAU-insensitive phosphorolytic activity in selected tumors, coupled with the potent inhibitory activity of BAU against the "classical" uridine phosphorylase in normal human tissues, provides the rationale for combining BAU with 5-fluorouracil in the treatment of breast and head-neck tumors.
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PMID:Expression, characterization, and detection of human uridine phosphorylase and identification of variant uridine phosphorolytic activity in selected human tumors. 985 74

The prognostic influence of post-operative adjuvant chemotherapy on stage I b or II gastric cancer was studied retrospectively. The immunohistochemical expressions of p53 protein and thymidine phosphorylase (TP) were also examined; the relations between these protein expressions and clinicopathological features along with the effect of adjuvant chemotherapy were also investigated. The 5-year survival rate of the patients who received adjuvant chemotherapy was 95.5%, which was better than that (89.8%) of those who did not, although the difference did not reach significance (p = 0.09). The venous invasion of tumor was slight frequently observed in p53 or TP positive cases than negative cases, respectively (p < 0.1), but no significant associations were found between the t-, n- or ly-factor, and p53 or TP expression. Moreover p53 and TP expression had no significant influence on post-operative survival. But, among the patients with p53- or TP-positive tumor, adjuvant chemotherapy conferred survival benefits, although the difference did not reach significance. The 5-year survival rate was 100% with adjuvant chemotherapy, 84.3% without chemotherapy in p53-positive patients (p = 0.137), 97.0% with adjuvant chemotherapy, and 90.8% without chemotherapy in TP-positive tumors (p = 0.326).
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PMID:[Preliminary evaluation of adjuvant chemotherapy against stage Ib or II gastric cancer]. 1006 94

Growth, progression, and metastasis of breast cancer, as well as of most of the other tumors, are angiogenesis-dependent processes. Several pro-angiogenic growth factors and endogenous inhibitors of angiogenesis have been identified and sequenced, and experimental studies suggest that angiogenic activity of a tumor may result from downregulation of inhibitors of angiogenesis or up-regulation of endothelial growth factors. The mechanisms leading to the alteration of the balance between positive and negative modulators of angiogenesis are only partially known. We are at the beginning of research to identify the more active angiogenic factors in human breast cancer, and little information is presently available on their clinical significance. Preliminary results suggest that among the known angiogenic peptides, both vascular endothelial growth factor (VEGF) and platelet-derived endothelial cell growth factor / thymidine phosphorylase (PD-ECGF/TP) have promising prognostic and, perhaps, predictive value. No data are available on the clinical value of co-determination of positive and negative regulators of angiogenesis to look at the angiogenic balance of each single tumor. Only a few studies have assessed the role of endogenous inhibitors of angiogenesis in human breast cancer, with results available only on thrombospondin-1 and -2 (TSP-1, -2). Finally, the determination of some integrins such as alpha6 and alphavbeta3 and of some other endothelial-adhesion molecules seems to be of potential prognostic value. Recognizing which are the more biologically active positive and negative angiogenic factors is the key for the identification not only of new prognostic markers but also of targets for antiangiogenic therapy in human breast cancer.
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PMID:Clinical significance of angiogenic factors in breast cancer. 1006 80

Effects of sex steroids (estradiol-17 beta, E2; progesterone, Prog) and growth factors (epidermal growth factor, EGF; transforming growth factor-alpha, TGF-alpha) on invasive activity and 5'-deoxy-5-fluorouridine (5'-dFUrd) sensitivity of ovarian adenocarcinoma OMC-3 cells were investigated. Tumor cell migration along a gradient of substratum-bound fibronectin and invasion into reconstituted basement membrane were inhibited by 10 microM Prog, but stimulated by 0.1-10 nM EGF and TGF-alpha in a concentration-dependent manner. E2 did not have any effect on tumor cell migration or invasion. The zymography of tumor conditioned medium showed that the treatment of OMC-3 cells with EGF and TGF-alpha resulted in increases of type IV collagenase, stromelysin and urokinase-type plasminogen activator (uPA). EGF and TGF-alpha up-regulated thymidine phosphorylase (dThdPase) expression of tumor cells and consequently enhanced the antiproliferative action of 5'-dFUrd, which is converted to 5-fluorouracil by dThdPase. E2 and Prog did not have significant effects on the expression of proteolytic enzymes and dThdPase, or on the 5'-dFUrd sensitivity of tumor cells. The inhibitory effect of Prog on tumor cell invasion may depend on its inhibitory action on the motility of tumor cells. These results suggest that EGF and TGF-alpha simultaneously up-regulate the potential of ovarian adenocarcinoma cells to invade extracellular matrices and their dThdPase expression, both of which are associated with the specific action of 5'-dFUrd selectively to kill tumor cells with high invasive and metastatic potential.
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PMID:Effects of sex steroids and growth factors on invasive activity and 5'-deoxy-5-fluorouridine sensitivity in ovarian adenocarcinoma OMC-3 cells. 1008 95

Tumor-associated monocytic cells (TAMs) are a major component of the stroma responsible for tumor formation. TAMs generate various kinds of mediators for their function, one of which is thymidine phosphorylase (TP). TP is an angiogenic enzyme that is known to be up-regulated in tumor tissues. Here, we focused on the clinical implication of TP expression in TAMs by studying 229 primary breast carcinoma tissues. Immunohistochemical analysis demonstrated that monocytic TP+ tumors had a significantly worse prognosis than did monocytic TP- tumors (P < 0.01, log-rank test). A multivariate analysis confirmed that monocytic TP status provided an independent prognostic value (P < 0.0001). Furthermore, of interest was that monocytic TP status could categorize the CD68+ patients, who had an extensive accumulation of CD68+ TAMs, into two subgroups with strikingly contrasting prognoses: a good prognostic monocytic TP- group and a poor prognostic monocytic TP+ group. This indicates that there are both antitumor and protumor types of TAM. Subanalysis showed that microvessel density was significantly increased in CD68+/monocytic TP+ tumors compared with CD68+/monocytic TP- tumors. Experimentally, TAMs are known to function in diverse manners, antitumor and protumor; however, little is known about clinically recognizable markers to characterize the TAMs in histological sections. TP might be such a marker, which would be useful for identifying the character of TAMs, particularly the protumor phenotype.
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PMID:Significance of thymidine phosphorylase as a marker of protumor monocytes in breast cancer. 1035 48


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