UMLS:C0178874 - FACTA Search

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Query: UMLS:C0178874 (tumor progression)
40,807 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The angiogenic factor platelet-derived endothelial cell growth factor/thymidine phosphorylase (PD-ECGF/TP) is expressed at higher levels in a wide variety of solid tumors compared to adjacent normal tissues. Patients with PD-ECGF/TP-positive colon and esophageal tumors have a poorer prognosis than those with negative tumors. The expression of PD-ECGF/TP is a prognostic factor independent of microvessel density suggesting that TP has effects on tumor progression independent of its angiogenic activity. Evidence that hypoxia and apoptosis affect tumor growth prompted us to determine whether increased expression of PD-ECGF/TP prevents apoptosis induced by hypoxia. KB/TP cells transfected with a PD-ECGF/TP cDNA were resistant to hypoxia-induced apoptosis. Among the degradation products of thymidine produced by PD-ECGF/TP, 2-deoxy-D-ribose and thymine partially prevented hypoxia-induced apoptosis. The ability of 1 microM 2-deoxy-D-ribose in combination with the same concentration of thymine to prevent hypoxia-induced apoptosis was similar to that of the overexpressed TP in KB cells. A concentration of 1 microM 2-deoxy-L-ribose abrogated the effects of these degradation products of thymidine. These findings suggested that TP can confer resistance to apoptosis induced by hypoxia and the degradation products of thymidine are involved in this resistance. Expression of PD-ECGF/TP may play an important role in the progression of solid tumors, and inhibitors of TP and analogs of the degradation products of thymidine may suppress the growth of tumors by promoting apoptosis.
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PMID:Prevention of hypoxia-induced apoptosis by the angiogenic factor thymidine phosphorylase. 991 7

In this study, we obtained fresh samples of tissue (tumors, adjacent normal mucosas, and metastatic lymph nodes) from 64 patients (metastatic lymph nodes were obtained from 16 patients) with esophageal cancer who underwent esophagectomy between 1993 and 1998. The thymidine phosphorylase (dThdPase) levels of tumors as determined by the ELISA method were compared with clinicopathological findings of tumors and were evaluated for their usefulness as a prognostic parameter for these patients. The dThdPase levels of tumors (221 +/- 21 U/mg protein) and metastatic lymph nodes (253 +/- 51 U/mg protein) were significantly higher than the dThdPase level of normal mucosas (53 +/- 7 U/mg protein, p < 0. 001). The dThdPase levels of tumors did not correlate with the histopathological grading of tumors, the depth of tumor invasion, and lymph node metastasis. The 3-year survival rate of 32 patients with a high level of dThdPase (42%) was not different from that of 32 patients with a low level of dThdPase (52%, p = 0.267). Moreover, the dThdPase level of tumors was not an independent prognostic factor for patients with esophageal cancer. These findings suggest that the level of dThdPase activity in esophageal cancers may not correlate with tumor progression and may not be a useful prognostic marker for patients with esophageal squamous cell carcinoma.
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PMID:Clinical significance of the detection of thymidine phosphorylase activity in esophageal squamous cell carcinomas. 1044 95

The expression of thymidine phosphorylase (TP) in carcinoma of the papilla of Vater was studied to clarify its significance in tumor progression and in determining prognosis. Fifty-nine cases of surgically resected carcinoma of the papilla of Vater were studied. Immunohistochemical staining was performed to evaluate the expression of TP, microvessel count and p53 overexpression. TP expression was demonstrated in tumor cells in 62.7% (37/59) of the cases. A higher frequency of regional lymph node metastasis was found in TP-positive tumors than in TP-negative tumors (P = 0.006). TP-positive tumors were more advanced than TP-negative tumors with regard to clinical stage (P = 0.035). TP-positive tumors had significantly higher microvessel density (27.6 +/- 10.1) than TP-negative tumors (20.4 +/- 10.0, P = 0.01). Moreover, TP expression was significantly correlated with a poor prognosis (P = 0. 02). These suggest that in carcinoma of the papilla of Vater, TP production by tumor cells is correlated with tumor progression through its regulatory effect on neovascularization.
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PMID:Significance of thymidine phosphorylase/platelet-derived endothelial cell growth factor in carcinoma of the papilla of Vater. 1076 Jun 93

Angiogenesis is essential for tumor growth and metastasis. It is regulated by numerous angiogenic factors, one of the most important being vascular endothelial growth factor (VEGF). Recently, VEGF-C, a new VEGF family member, has been identified that binds to the tyrosine kinase receptors flt-4 [VEGF receptor (VEGFR) 3] and KDR (VEGFR2). Although the importance of VEGF has been shown in many human tumor types, the contribution of VEGF-C and its primary receptor flt-4 to tumor progression is less well understood. We have therefore measured the level of VEGF-C, flt-4, and KDR mRNA by RNase protection assay and the pattern of VEGF-C expression by immunohistochemistry in 11 normal breast tissue samples and 61 invasive breast cancers. No significant difference in VEGF-C expression was observed between normal and neoplastic breast tissues (P = 0.11). There was a significant correlation between VEGF-C and both flt-4 (P = 0.02) and KDR (P = 0.0002), but no association was seen between VEGF-C and either lymph node status (P = 0.66) or number of involved nodes (P = 0.88), patient age (P = 0.83), tumor size (P = 0.20), estrogen receptor status (P = 0.67), or tumor grade (P = 0.35). No significant relationship was present between VEGF-C and vascular invasion (P = 0.30), tumor vascularity (P = 0.21), VEGF-A (P = 0.62), or thymidine phosphorylase expression (P = 1.00). VEGF-C was expressed predominantly in the cytoplasm of tumor cells, although occasional stromal components including fibroblasts were also positive. We could demonstrate no association between lymph node metastasis and either VEGF-C (P = 0.66) or flt-4 (P = 0.4). However, we did observe a significant loss of the long but not the short isoform of flt-4 in tumors compared with normal tissues (P = 0.02 and P = 0.25, respectively), and this difference was largely accounted for by the reduction of long flt-4 in node-positive tumors. These findings strongly support a role for VEGF-C/flt-4 signaling in tumor growth by enhancement of angiogenesis and/or lymphangiogenesis and suggest that differential regulation of these processes may be controlled via flt-4 isoform transcription. They further suggest that the measurement of flt-4 isoform expression may identify a patient group that is likely to have node-positive disease and therefore benefit from additional treatment and also emphasize an additional ligand interaction that could be exploited by anti-VEGFR therapy.
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PMID:The short form of the alternatively spliced flt-4 but not its ligand vascular endothelial growth factor C is related to lymph node metastasis in human breast cancers. 1110 44

We measured thymidine phosphorylase activity in colorectal cancer tissue and conducted immunostaining to investigate enzyme expression in the tumor tissue. The results showed a correlation between staining ratio of thymidine phosphorylase and cancer progression as well as a correlation between enzyme activity and staining ratios of cancer cells and stromal cells. Since enzyme activity levels can be judged by staining ratios, this method may be useful for assessing cancer malignancy.
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PMID:The significance of thymidine phosphorylase expression in colorectal cancer. 1111 83

Several studies have supported the hypothesis that adrenocortical tumor formation is the result of a multistep process. The angiogenic switch has been proposed to be a key step in tumor progression from adenoma to carcinoma. In this study we measured the cytosolic concentrations of three proteins involved in angiogenesis [namely platelet-derived endothelial cell growth factor vascular endothelial cell growth factor A (VEGF-A), and thrombospondin-1 (TSP1)] in a series of 43 human sporadic adrenocortical tumors. The tumors were classified as adenomas (n = 18), transitional tumors (n = 12), or carcinomas (n = 13) according to the histological criteria defined by Weiss. Platelet-derived endothelial cell growth factor/thymidine phosphorylase levels were not significantly different among these three groups. One hundred percent of the adenomas and 73% of the transitional tumors showed VEGF-A concentrations under the threshold value of 107 ng/g protein, whereas 75% of the carcinomas had VEGF-A concentrations above this threshold value. Similarly, 89% of the adenomas showed TSP1 concentrations above the threshold value of 57 microg/g protein, whereas only 25% of the carcinomas and 33% of the transitional tumor samples did so. Insulin-like growth factor II overexpression, a common genetic alteration of adrenocortical carcinomas, was significantly correlated with higher VEGF-A and lower TSP1 concentrations. The tumors from the 6 patients with tumor recurrence after surgical ablation showed significantly higher VEGF-A values than the carcinomas and the transitional tumors from patients that did not relapse. Taken together, these data suggest that a decrease in TSP1 expression is an event that precedes an increase in VEGF-A expression during adrenocortical tumor progression. The population of premalignant tumors with low TSP1 and normal VEGF-A levels could represent a selective target for antiangiogenic therapies.
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PMID:Expression of the angiogenesis markers vascular endothelial growth factor-A, thrombospondin-1, and platelet-derived endothelial cell growth factor in human sporadic adrenocortical tumors: correlation with genotypic alterations. 1113 36

The aim of this study was to investigate whether angiogenic factors influence the occurrence of spontaneous apoptosis in advanced gastric cancer. The apoptotic indices (AIs) of 97 tumors from 97 patients with advanced gastric cancer (pT3, pN0, pM0, Stage II) were analyzed by the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate biotin nick end labeling (TUNEL) method. Intratumoral microvessel densities (IMVDs) of tumors stained with anti-CD34 monoclonal antibody were quantified under x 200 magnification using computer-assisted image analysis. The expressions of angiogenic factors, such as vascular endothelial growth factor (VEGF), thymidine phosphorylase (dThdPase), transforming growth factor-alpha (TGF-alpha), and p53 were analyzed immunohistochemically and compared with IMVDs and AIs. The mean IMVD of the 97 tumors was 365/mm2 (range 147-990/mm2). The mean AI of tumors was 2.1% (range 0-11.3%). A significant inverse correlation between the AIs and the IMVDs was shown (p = -0.278, P = 0.0064). The mean IMVDs of tumors with high expressions of dThdPase, TGF-alpha, or p53 were significantly higher than those of tumors with low expressions of these factors. The mean AI of tumors with high expressions of dThdPase was significantly lower than that of tumors with low expressions of dThdPase (P = 0.023). However, no significant correlations were detected between AIs and the expression levels of VEGF, TGF-alpha, or p53. In gastric cancer, dThdPase may play an important role in tumor progression by increasing microvessels and by suppressing apoptosis of cancer cells.
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PMID:Correlation between spontaneous apoptosis and the expression of angiogenic factors in advanced gastric adenocarcinoma. 1148 84

"Stromatogenesis" is the formation of new stroma occurring, in parallel with the neoplastic process, at sites of active tumor invasion, i.e., at the free surface of a developing exophytic tumor, at the invading tumor front of an advancing endophytic tumor, and at sites of tumor metastasis, wherein the newly formed stroma disrupts the continuity of normal structures, cleaving paths for the invading tumor cells. Stroma is also present at the heart of the tumor, but only as a secondary event following tumor advancement and subsequent incorporation of its periphery into inner tumor areas. The new stroma, composed of stromal cells and extracellular matrix (ECM), is loose and edematous at the expanding tumor fronts, and rather dense in central tumor areas and sites of tumor metastasis. The stromal cells facing tumor invasion are intensely proliferating (high MIB-1 index) spindle-shaped cells, alpha-smooth muscle actin positive, and loaded with thymidine phosphorylase (TP) and SPARC (secreted protein acidic and rich in cysteine). The associated ECM is rich in collagen III, SPARC, and new blood vessels (CD31) but is depleted of collagen I and fibronectin. These constitutional changes render stromatogenesis amenable to tumor cell invasion and are, in cases of incipient neoplasia, a prospective criterion of early stromal invasion. Other stromal cell or ECM constituents, such as the lactate dehydrogenase-5 (LDH-5), the acidic fibroblast growth factor (aFGF), the basic FGF (bFGF), and the collagens II and IV, remain unchanged, and others are negative: myosin, desmin, S-100 protein and epidermal growth factor receptor (EGFR). The mechanism of stromatogenesis is obscure but is probably stimulated by specific stromatogenic growth factors, released by neoplastic and inflammatory cells. It appears that the process is neither neoplastic nor reactive, but rather is a, hereto unexplained, phenomenon of host's complicity in tumor progression.
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PMID:"Stromatogenesis" and tumor progression. 1476 66

Cyclooxygenase-2 (COX-2) has been found to be up-regulated in several types of human malignant tumors and proposed to have a role in the angiogenic process. This study examined the expression of COX-2 in two human malignant fibrous histiocytoma (MFH) cell lines by Western blotting, which showed a specific single band at 72 kDa. Immunohistochemistry was conducted in 35 MFHs and 30 benign fibrohistiocytic tumors (BFHTs), comparing the expression of vascular endothelial growth factor (VEGF) and thymidine phosphorylase (TP), as well as intratumoral microvessel density (IMVD). COX-2 expression was noted in 22 (62.9%) MFHs, but in no BFHT. IMVD values were significantly higher in the MFHs (90.6+/-8.0) than BFHTs (27.9+/-3.1), and also in the COX-2 positive (104.5+/-11.3) than negative (67.2+/-5.8) MFHs. VEGF and TP expression was also associated with a significantly higher level of COX-2, as well as greater IMVD. The highest IMVD values were noted in the 17 MFHs (120.8+/-11.5) expressing all three factors. Clinical analysis demonstrated poorer survival in the 18 COX-2 positive MFHs than in the 10 negative ones, although the small number of cases did not reveal a significant difference. The results overall indicated that COX-2 expression is associated with intratumoral angiogenesis, which might provide favorable conditions for tumor progression in human MFHs.
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PMID:Cyclooxygenase-2 in human malignant fibrous histiocytoma: correlations with intratumoral microvessel density, expression of vascular endothelial growth factor and thymidine phosphorylase. 1537 82

An angiogenic factor, platelet-derived endothelial cell growth factor/thymidine phosphorylase (TP), stimulates the chemotaxis of endothelial cells and confers resistance to apoptosis induced by hypoxia. 2-Deoxy-d-ribose, a degradation product of thymidine generated by TP enzymatic activity, partially prevented hypoxia-induced apoptosis. 2-Deoxy-d-ribose inhibited hypoxia-induced phosphorylation of p38 mitogen-activated protein kinase (MAPK) but not c-jun NH(2)-terminal kinase/stress-activated protein kinase in human leukemia HL-60 cells. 2-Deoxy-d-ribose also suppressed the levels of Bax attached to mitochondria under hypoxic conditions. SB203580, a specific inhibitor of the p38 MAPK, suppressed the hypoxia-induced apoptosis of HL-60 cells. These findings suggest that one of the molecular bases for resistance to hypoxia-induced apoptosis conferred by 2-deoxy-d-ribose is the inhibition of the p38 signaling pathway. The expression levels of TP are elevated in many malignant solid tumors and thus the 2-deoxy-d-ribose generated by TP in these tumors may play an important role in tumor progression by preventing hypoxia-induced apoptosis.
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PMID:2-Deoxy-D-ribose inhibits hypoxia-induced apoptosis by suppressing the phosphorylation of p38 MAPK. 1648 Sep 51

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