Purification and tissue distribution of human thymidine phosphorylase; high expression in lymphocytes, reticulocytes and tumors

Yoshimura, Akihiko; Kuwazuru, Yasuo; Furukawa, Tatsuhiko; Yoshida, Hiroki; Yamada, Kazutaka; Akiyama, Shin Ichi

doi:10.1016/0304-4165(90)90160-x

Cited by 163 publications

(131 citation statements)

References 29 publications

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“…45 PD-ECGF expression is assumed to be elevated in areas of interstitial fibrosis in scarred kidneys because local oxygen supply is most likely to be diminished in these areas owing to obliteration of the postglomerular capillary network, and tubules, fibroblasts, and mononuclear infiltrates are able to produce PD-ECGF. [22][23][24] Immunostaining of PD-ECGF increased remarkably on tubular cells, including the atrophic tubules located in fibrotic areas of the scarred kidneys. In addition, a significant correlation was noted between the number of PD-ECGF ϩ tubular cells and microvessel count.…”

Section: Discussionmentioning

confidence: 95%

“…Immunostaining of PD-ECGF was observed in both the cytoplasm and nucleus as previously reported. 22 The mean numbers of PD-ECGF ϩ tubular cells were significantly increased in scarred kidneys with grade 1 (89.1 Ϯ 20.94), grade 2 (193.7 Ϯ 35.37), and grade 3 fibrosis (162.8 Ϯ 28.07), compared with normal kidneys (6.9 Ϯ 3.95) (P Ͻ 0.005, P Ͻ 0.0001, and P Ͻ 0.0001, respectively; Figure 4A). Significant increases were noted in grade 2 or grade 3 fibrosis compared with grade 1 (P Ͻ 0.0001 and P ϭ 0.0002, respectively), but no significant difference was found between grade 2 and grade 3 (P Ͼ 0.5).…”

Section: Immunohistochemical Staining For Pd-ecgfmentioning

confidence: 99%

“…18,24,29 -31 Immunostained PD-ECGF has been observed in fibroblasts, macrophages, differentiated lymphocytes, and renal tubules. [22][23][24] Renal scarring secondary to a variety of urinary tract diseases, such as reflux nephropathy and obstructive nephropathy, is characterized by primary tubulointerstitial pathology with subsequent involvement of the glomerular structure. 12,32,33 This type of renal disease is thought to progress via the formation of atubular glomeruli that have open capillaries but are not connected to normal proximal tubules.…”

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confidence: 99%

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Expression of Platelet-Derived Endothelial Cell Growth Factor and its Potential Role in Up-Regulation of Angiogenesis in Scarred Kidneys Secondary to Urinary Tract Diseases

Konda

Sato

Sakai

et al. 1999

The American Journal of Pathology

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Section: Discussionmentioning

confidence: 95%

Section: Immunohistochemical Staining For Pd-ecgfmentioning

confidence: 99%

mentioning

confidence: 99%

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Expression of Platelet-Derived Endothelial Cell Growth Factor and its Potential Role in Up-Regulation of Angiogenesis in Scarred Kidneys Secondary to Urinary Tract Diseases

Konda

Sato

Sakai

et al. 1999

The American Journal of Pathology

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“…The TP enzyme activity was assayed using the method published by Yoshimura et al (1990) with minor modification. Briefly, 10 ml of total protein extracted in RIPA buffer containing 25 mM TrisHCl, 0.1% SDS, 1% Triton X-100, 0.15 M NaCl, 1 mM EDTA and 1 Â protease inhibitor mixture (Roche, East Sussex, UK) was mixed with 90 ml of reaction buffer consisting of 10 mM thymidine, 10 mM KH 2 PO 4 (pH 7.4).…”

Section: Tp-activity Assaymentioning

confidence: 99%

In vitro evaluation of cancer-specific NF-κB-CEA enhancer–promoter system for 5-fluorouracil prodrug gene therapy in colon cancer cell lines

et al. 2007

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Nuclear factor-kappa B (NF-kB) is a transcription factor with high transcriptional activity in cancer cells. In this study, we developed a novel enhancer -promoter system, kB4-CEA205, in which the basal carcinoembryonic antigen (CEA) promoter sequence (CEA205) was placed downstream of the four tandem-linked NF-kB DNA-binding sites (kB4). In combination with a kB4 enhancer, the transcriptional activity of the CEA promoter was significantly enhanced (three-to eight-fold) in cancer cell lines but not in normal cells. In cancer cell lines, the transcriptional activity of kB4-CEA205 was comparable with that of the SV40 promoter. We also constructed vectors in which the thymidine phosphorylase (TP) cDNA was under the control of CEA205, kB4, kB4-CEA205 and CMV promoters, respectively. TP protein and enzyme activity were detected at comparable levels in kB4-CEA205-and CMV-driven TP cDNAtransfected cancer cell lines (H630 and RKO). The kB4-TP and CEA205-TP-transfected cell lines, respectively, only demonstrated negligible and low levels of TP protein and enzyme activity. Both CMV-and kB4-CEA205-driven TP cDNA transiently transfected cells were 8-to 10-fold sensitised to 5-fluorouracil (5-FU) prodrug, 5 0 -deoxy-5-fluorouradine (5 0 -DFUR), in contrast to only 1.5-to 2-fold sensitised by the kB4-and CEA205-driven TP cDNA-transfected cells. The bystander killing effect of CMV-and kB4-CEA205-driven TP cDNA-transfected cells was comparable. This is the first report that indicates that the NF-kB DNA-binding site could be used as a novel cancer-specific enhancer to improve cancer-specific promoter activity in gene-directed enzyme prodrug therapy. Lack of selectivity for malignant cells leading to dose-limiting toxicity is one of the major obstacles for the success of cancer chemotherapy. Gene-directed enzyme prodrug therapy (GDEPT) is potentially an elegant way to improve the therapeutic index of active anticancer drugs, but one of the major limitations for the clinical application of this approach is the lack of strong cancerspecific promoters (Aghi et al, 2000;Rooseboom et al, 2004).Carcinoembryonic antigen (CEA) is not expressed in normal and overexpressed in epithelial cancer cells (Shively and Beatty, 1985). Four cis-acting DNA-binding elements mapped on the CEA promoter region within 300 bp upstream of CEA translation starting point, especially, the first three elements are essential for specific CEA transcription (Hauck and Stanners, 1995;Richards et al, 1995a). Utilisation of the CEA promoter in an adenovirus vector for cytosine deaminase (CD) gene expression improves the selectivity of 5 0 -deoxy-5-fluorocytidine (5-DFCR)/5-fluorouracil (5-FU) conversion in CEA-expressing tumours (Richards et al, 1995a;Lan et al, 1996a). However, the transcriptional activity of CEA in most cancer cell lines is 10-to 300-fold lower than that of CMV and RSV viral promoters (Lan et al, 1996b;Ueda et al, 2001).Even when using adenovirus to deliver CEA promoter-driven suicide gene in vivo, few reports have demonstrated sufficient antitumou...

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“…In humans, areas of increased blood flow as a measure of angiogenesis are associated with elevated TP expression in ovarian tumours (Reynolds et al, 1994). High levels of TP are not limited to this tumour type but are also observed in liver, gastrointestinal, genitourinary and haematopoietic malignancies (Zimmerman and Seidenberg, 1964;Kono et al, 1984;Vertongen et al, 1984;Yoshimura et al, 1990). Indeed a significant increase in TP has been detected in serum from cancer patients (Pauly et al, 1977(Pauly et al, , 1978.…”

mentioning

confidence: 98%

The angiogenic factor platelet-derived endothelial cell growth factor/thymidine phosphorylase is up-regulated in breast cancer epithelium and endothelium

Fox

Westwood²,

Moghaddam³

et al. 1996

Br J Cancer

140

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Summary Tumour angiogenesis is a complex multistep process regulated by a number of angiogenic factors. One such factor, platelet-derived endothelial cell growth factor has recently been shown to be thymidine phosphorylase (TP). TP catalyses the reversible phosphorylation of thymidine to deoxyribose-1 -phosphate and thymine. Although known to be generally elevated in tumours, the expression of this enzyme in breast carcinomas is unknown. Therefore, we used ribonuclease protection assays and immunohistochemistry to examine the expression of TP in 240 primary breast carcinomas. Nuclear and/or cytoplasmic TP expression was observed in the neoplastic tumour epithelium in 53% of tumours. Immunoreactivity was also often present in the stromal, inflammatory and endothelial cell elements. Although endothelial cell staining was usually focal, immunoreactivity was observed in 61 % of tumours and was prominent at the tumour periphery, an area where tumour angiogenesis is most active. Tumour cell TP expression was significantly inversely correlated with grade (P = 0.05) and size (P = 0.003) but no association was observed with other tumour variables. These findings suggest that TP is important for remodelling the existing vasculature early in tumour development, consistent with its chemotactic non-mitogenic properties, and that additional angiogenic factors are more important for other angiogenic processes like endothelial cell proliferation. Relapse-free survival was higher in node-positive patients with elevated TP (P = 0.05) but not in other patient groups. This might be due to the potentiation of chemotherapeutic agents like methotrexate by TP. Therefore, this enzyme might be a prediction marker for response to chemotherapy.

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Purification and tissue distribution of human thymidine phosphorylase; high expression in lymphocytes, reticulocytes and tumors

Cited by 163 publications

References 29 publications

Expression of Platelet-Derived Endothelial Cell Growth Factor and its Potential Role in Up-Regulation of Angiogenesis in Scarred Kidneys Secondary to Urinary Tract Diseases

Expression of Platelet-Derived Endothelial Cell Growth Factor and its Potential Role in Up-Regulation of Angiogenesis in Scarred Kidneys Secondary to Urinary Tract Diseases

In vitro evaluation of cancer-specific NF-κB-CEA enhancer–promoter system for 5-fluorouracil prodrug gene therapy in colon cancer cell lines

The angiogenic factor platelet-derived endothelial cell growth factor/thymidine phosphorylase is up-regulated in breast cancer epithelium and endothelium

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