Targeting platelet-derived endothelial cell growth factor/thymidine phosphorylase for cancer therapy

Biochemical Pharmacology

Volumn 74, Issue 11, 2007, Pages 1555-1567

  Liekens, Sandra ^a   Bronckaers, Annelies ^a   Pérez Pérez, Maria Jésus ^b   Balzarini, Jan ^a  

^a REGA INSTITUTE FOR MEDICAL RESEARCH   (Belgium)

^b INSTITUTO DE QUÍMICA MÉDICA   (Spain)

Author keywords

5 Fluorouracil; Angiogenesis; Metastasis; Nucleoside metabolism; PD ECGF; Thymidine phosphorylase

Indexed keywords

2 DEOXY LEVO RIBOSE; 2 DEOXYRIBOSE; 5 CHLORO 6 [1 (2 IMINOPYRROLIDINYL)METHYL]URACIL PLUS TRIFLUOROTHYMIDINE; 5 HALO 6 [(2' NITROIMIDAZOL 1' YL)METHYL]URACIL; 5' O TRITYLINOSINE; 7 DEAZAXANTHINE; ANGIOGENIC FACTOR; CAPECITABINE; CISPLATIN; CYCLOPHOSPHAMIDE; DOCETAXEL; DOXIFLURIDINE; ENZYME INHIBITOR; FLUOROPYRIMIDINE DERIVATIVE; FLUOROURACIL; FOLINIC ACID; INTERLEUKIN 10; INTERLEUKIN 1ALPHA; KIN 59; NUCLEOSIDE ANALOG; OXYGEN RADICAL; PACLITAXEL; PLATELET DERIVED ENDOTHELIAL CELL GROWTH FACTOR; PRODRUG; PYRIMIDINE NUCLEOSIDE; TAS 102; THYMIDINE PHOSPHORYLASE; THYMIDINE PHOSPHORYLASE INHIBITOR; TUMOR NECROSIS FACTOR ALPHA; UNCLASSIFIED DRUG; UNINDEXED DRUG;

ANGIOGENESIS; APOPTOSIS; ARTICLE; CANCER; CANCER COMBINATION CHEMOTHERAPY; CLINICAL TRIAL; DIARRHEA; DRUG ACTIVATION; DRUG EFFECT; DRUG EFFICACY; DRUG STRUCTURE; DRUG TARGETING; ENZYME ACTIVATION; ENZYME ACTIVITY; ENZYME SYNTHESIS; GENE MUTATION; HUMAN; IC 50; METASTASIS; NONHUMAN; PRIORITY JOURNAL; PROGNOSIS; PROTEIN EXPRESSION; PROTEIN FUNCTION; STROMA CELL; STRUCTURE ANALYSIS; TUMOR CELL; UPREGULATION;

EID: 35348944819     PISSN: 00062952     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bcp.2007.05.008     Document Type: Note

References (116)

1. Friedkin M., and Roberts D. The enzymatic synthesis of nucleosides. I. Thymidine phosphorylase in mammalian tissue. J Biol Chem 207 (1954) 245-256
2. Iltzsch M.H., El Kouni M.H., and Cha S. Kinetic studies of thymidine phosphorylase from mouse liver. Biochemistry 24 (1985) 6799-6807
3. Nakayama C., Wataya Y., Meyer Jr. R.B., Santi D.V., Saneyoshi M., and Ueda T. Thymidine phosphorylase. Substrate specificity for 5-substituted 2′-deoxyuridines. J Med Chem 23 (1980) 962-964
4. Desgranges C., Razaka G., Rabaud M., Bricaud H., Balzarini J., and De Clercq E. Phosphorolysis of (E)-5-(2-bromovinyl)-2′-deoxyuridine (BVDU) and other 5-substituted-2′-deoxyuridines by purified human thymidine phosphorylase and intact blood platelets. Biochem Pharmacol 32 (1983) 3583-3590
5. de Bruin M., van Capel T., Van der Born K., Kruyt F.A., Fukushima M., Hoekman K., et al. Role of platelet-derived endothelial cell growth factor/thymidine phosphorylase in fluoropyrimidine sensitivity. Br J Cancer 88 (2003) 957-964
6. Miyazono K., Okabe T., Urabe A., Takaku F., and Heldin C.H. Purification and properties of an endothelial cell growth factor from human platelets. J Biol Chem 262 (1987) 4098-4103
7. Ishikawa F., Miyazono K., Hellman U., Drexler H., Wernstedt C., Hagiwara K., et al. Identification of angiogenic activity and the cloning and expression of platelet-derived endothelial cell growth factor. Nature 338 (1989) 557-562
8. Moghaddam A., and Bicknell R. Expression of platelet-derived endothelial cell growth factor in Escherichia coli and confirmation of its thymidine phosphorylase activity. Biochemistry 31 (1992) 12141-12146
9. Usuki K., Saras J., Waltenberger J., Miyazono K., Pierce G., Thomason A., et al. Platelet-derived endothelial cell growth factor has thymidine phosphorylase activity. Biochem Biophys Res Commun 184 (1992) 1311-1316
10. Asai K., Nakanishi K., Isobe I., Eksioglu Y.Z., Hirano A., Hama K., et al. Neurotrophic action of gliostatin on cortical neurons. Identity of gliostatin and platelet-derived endothelial cell growth factor. J Biol Chem 267 (1992) 20311-20316
11. Stenman G., Sahlin P., Dumanski J.P., Hagiwara K., Ishikawa F., Miyazono K., et al. Regional localization of the human platelet-derived endothelial cell growth factor (ECGF1) gene to chromosome 22q13. Cytogenet Cell Genet 59 (1992) 22-23
12. Usuki K., Miyazono K., and Heldin C.H. Covalent linkage between nucleotides and platelet-derived endothelial cell growth factor. J Biol Chem 266 (1991) 20525-20531
13. Walter M.R., Cook W.J., Cole L.B., Short S.A., Koszalka G.W., Krenitsky T.A., et al. Three-dimensional structure of thymidine phosphorylase from Escherichia coli at 2.8 A resolution. J Biol Chem 265 (1990) 14016-14022
14. Pérez-Pérez M.J., Priego E.M., Hernández A.I., Camarasa M.J., Balzarini J., and Liekens S. Thymidine phosphorylase inhibitors: recent developments and potential therapeutic applications. Mini Rev Med Chem 5 (2005) 1113-1123
15. Norman R.A., Barry S.T., Bate M., Breed J., Colls J.G., Ernill R.J., et al. Crystal structure of human thymidine phosphorylase in complex with a small molecule inhibitor. Structure 12 (2004) 75-84
16. El Omari K., Bronckaers A., Liekens S., Pérez-Pérez M.J., Balzarini J., and Stammers D.K. Structural basis for non-competitive product inhibition in human thymidine phosphorylase: implications for drug design. Biochem J 399 (2006) 199-204
17. Liekens S., De Clercq E., and Neyts J. Angiogenesis: regulators and clinical applications. Biochem Pharmacol 61 (2001) 253-270
18. Carmeliet P. Angiogenesis in life, disease and medicine. Nature 438 (2005) 932-936
19. Ellis L.M. Mechanisms of action of bevacizumab as a component of therapy for metastatic colorectal cancer. Semin Oncol 33 (2006) S1-S7
20. Haraguchi M., Miyadera K., Uemura K., Sumizawa T., Furukawa T., Yamada K., et al. Angiogenic activity of enzymes. Nature 368 (1994) 198
21. Stevenson D.P., Milligan S.R., and Collins W.P. Effects of platelet-derived endothelial cell growth factor/thymidine phosphorylase, substrate, and products in a three-dimensional model of angiogenesis. Am J Pathol 152 (1998) 1641-1646
22. Moghaddam A., Zhang H.T., Fan T.P., Hu D.E., Lees V.C., Turley H., et al. Thymidine phosphorylase is angiogenic and promotes tumor growth. Proc Natl Acad Sci USA 92 (1995) 998-1002
23. Liekens S., Bilsen F., De Clercq E., Priego E.M., Camarasa M.J., Pérez-Pérez M.J., et al. Anti-angiogenic activity of a novel multi-substrate analogue inhibitor of thymidine phosphorylase. FEBS Lett 510 (2002) 83-88
24. Rofstad E.K., and Halsor E.F. Vascular endothelial growth factor, interleukin 8, platelet-derived endothelial cell growth factor, and basic fibroblast growth factor promote angiogenesis and metastasis in human melanoma xenografts. Cancer Res 60 (2000) 4932-4938
25. Matsukawa K., Moriyama A., Kawai Y., Asai K., and Kato T. Tissue distribution of human gliostatin/platelet-derived endothelial cell growth factor (PD-ECGF) and its drug-induced expression. Biochim Biophys Acta 1314 (1996) 71-82
26. Miyadera K., Sumizawa T., Haraguchi M., Yoshida H., Konstanty W., Yamada Y., et al. Role of thymidine phosphorylase activity in the angiogenic effect of platelet derived endothelial cell growth factor/thymidine phosphorylase. Cancer Res 55 (1995) 1687-1690
27. Brown N.S., Jones A., Fujiyama C., Harris A.L., and Bicknell R. Thymidine phosphorylase induces carcinoma cell oxidative stress and promotes secretion of angiogenic factors. Cancer Res 60 (2000) 6298-6302
28. Hotchkiss K.A., Ashton A.W., Klein R.S., Lenzi M.L., Zhu G.H., and Schwartz E.L. Mechanisms by which tumor cells and monocytes expressing the angiogenic factor thymidine phosphorylase mediate human endothelial cell migration. Cancer Res 63 (2003) 527-533
29. Brown N.S., Streeter E.H., Jones A., Harris A.L., and Bicknell R. Cooperative stimulation of vascular endothelial growth factor expression by hypoxia and reactive oxygen species: the effect of targeting vascular endothelial growth factor and oxidative stress in an orthotopic xenograft model of bladder carcinoma. Br J Cancer 92 (2005) 1696-1701
30. Tanikawa T., Waguri-Nagaya Y., Kusabe T., Aoyama M., Asai K., and Otsuka T. Gliostatin/thymidine phosphorylase-regulated vascular endothelial growth factor production in human fibroblast-like synoviocytes. Rheumatol Int 27 (2007) 553-559
31. Gotanda T., Haraguchi M., Tachiwada T., Shinkura R., Koriyama C., Akiba S., et al. Molecular basis for the involvement of thymidine phosphorylase in cancer invasion. Int J Mol Med 17 (2006) 1085-1091
32. Ueda M., Terai Y., Kumagai K., Ueki K., Kanemura M., and Ueki M. Correlation between thymidine phosphorylase expression and invasion phenotype in cervical carcinoma cells. Int J Cancer 91 (2001) 778-782
33. Muro H., Waguri-Nagaya Y., Mukofujiwara Y., Iwahashi T., Otsuka T., Matsui N., et al. Autocrine induction of gliostatin/platelet-derived endothelial cell growth factor (GLS/PD-ECGF) and GLS-induced expression of matrix metalloproteinases in rheumatoid arthritis synoviocytes. Rheumatology (Oxford) 38 (1999) 1195-1202
34. Shaw T., Smillie R.H., and MacPhee D.G. The role of blood platelets in nucleoside metabolism: assay, cellular location and significance of thymidine phosphorylase in human blood. Mutat Res 200 (1988) 99-116
35. Miyadera K., Dohmae N., Takio K., Sumizawa T., Haraguchi M., Furukawa T., et al. Structural characterization of thymidine phosphorylase purified from human placenta. Biochem Biophys Res Commun 212 (1995) 1040-1045
36. Osuga Y., Toyoshima H., Mitsuhashi N., and Taketani Y. The presence of platelet-derived endothelial cell growth factor in human endometrium and its characteristic expression during the menstrual cycle and early gestational period. Hum Reprod 10 (1995) 989-999
37. Fujimoto J., Ichigo S., Sakaguchi H., Hirose R., and Tamaya T. Expression of platelet-derived endothelial cell growth factor and its mRNA in uterine endometrium during the menstrual cycle. Mol Hum Reprod 41998 (1998) 509-513
38. Sivridis E., Giatromanolaki A., Koukourakis M.I., Bicknell R., Harris A.L., and Gatter K.C. Thymidine phosphorylase expression in normal and hyperplastic endometrium. J Clin Pathol 53 (2000) 704-708
39. Zhang L., Mackenzie I.Z., Rees M.C., and Bicknell R. Regulation of the expression of the angiogenic enzyme platelet-derived endothelial cell growth factor/thymidine phosphorylase in endometrial isolates by ovarian steroids and cytokines. Endocrinology 138 (1997) 4921-4930
40. Jackson M.R., Carney E.W., Lye S.J., and Ritchie J.W. Localization of two angiogenic growth factors (PDECGF and VEGF) in human placentae throughout gestation. Placenta 15 (1994) 341-353
41. Haraguchi M., Tsujimoto H., Fukushima M., Higuchi I., Kuribayashi H., Utsumi H., et al. Targeted deletion of both thymidine phosphorylase and uridine phosphorylase and consequent disorders in mice. Mol Cell Biol 22 (2002) 5212-5221
42. Spinazzola A., Marti R., Nishino I., Andreu A.L., Naini A., Tadesse S., et al. Altered thymidine metabolism due to defects of thymidine phosphorylase. J Biol Chem 277 (2002) 4128-4133
43. Reynolds K., Farzaneh F., Collins W.P., Campbell S., Bourne T.H., Lawton F., et al. Association of ovarian malignancy with expression of platelet-derived endothelial cell growth factor. J Natl Cancer Inst 86 (1994) 1234-1238
44. Toi M., Inada K., Hoshina S., Suzuki H., Kondo S., and Tominaga T. Vascular endothelial growth factor and platelet-derived endothelial cell growth factor are frequently coexpressed in highly vascularized human breast cancer. Clin Cancer Res 1 (1995) 961-964
45. Takebayashi Y., Akiyama S., Akiba S., Yamada K., Miyadera K., Sumizawa T., et al. Clinicopathologic and prognostic significance of an angiogenic factor, thymidine phosphorylase, in human colorectal carcinoma. J Natl Cancer Inst 88 (1996) 1110-1117
46. Imazano Y., Takebayashi Y., Nishiyama K., Akiba S., Miyadera K., Yamada Y., et al. Correlation between thymidine phosphorylase expression and prognosis in human renal cell carcinoma. J Clin Oncol 15 (1997) 2570-2578
47. Takao S., Takebayashi Y., Che X., Shinchi H., Natsugoe S., Miyadera K., et al. Expression of thymidine phosphorylase is associated with a poor prognosis in patients with ductal adenocarcinoma of the pancreas. Clin Cancer Res 4 (1998) 1619-1624
48. Yao Y., Kubota T., Sato K., and Kitai R. Macrophage infiltration-associated thymidine phosphorylase expression correlates with increased microvessel density and poor prognosis in astrocytic tumors. Clin Cancer Res 7 (2001) 4021-4026
49. Sivridis E., Giatromanolaki A., Papadopoulos I., Gatter K.C., Harris A.L., and Koukourakis M.I. Thymidine phosphorylase expression in normal, hyperplastic and neoplastic prostates: correlation with tumour associated macrophages, infiltrating lymphocytes, and angiogenesis. Br J Cancer 86 (2002) 1465-1471
50. Morita T., Matsuzaki A., Suzuki K., and Tokue A. Role of thymidine phosphorylase in biomodulation of fluoropyrimidines. Curr Pharm Biotechnol 2 (2001) 257-267
51. O'Byrne K.J., Koukourakis M.I., Giatromanolaki A., Cox G., Turley H., Steward W.P., et al. Vascular endothelial growth factor, platelet-derived endothelial cell growth factor and angiogenesis in non-small-cell lung cancer. Br J Cancer 82 (2000) 1427-1432
52. Toi M., Ueno T., Matsumoto H., Saji H., Funata N., Koike M., et al. Significance of thymidine phosphorylase as a marker of protumor monocytes in breast cancer. Clin Cancer Res 5 (1999) 1131-1137
53. Fujimoto J., Sakaguchi H., Aoki I., and Tamaya T. The value of platelet-derived endothelial cell growth factor as a novel predictor of advancement of uterine cervical cancers. Cancer Res 60 (2000) 3662-3665
54. Shimada H., Takeda A., Shiratori T., Nabeya Y., Okazumi S., Matsubara H., et al. Prognostic significance of serum thymidine phosphorylase concentration in esophageal squamous cell carcinoma. Cancer 94 (2002) 1947-1954
55. Haraguchi M., Komuta K., Akashi A., Furui J., and Kanematsu T. Occurrence of hematogenous metastasis and serum levels of thymidine phosphorylase in colorectal cancer. Oncol Rep 10 (2003) 1207-1212
56. Nagaoka H., Iino Y., Takei H., and Morishita Y. Platelet-derived endothelial cell growth factor/thymidine phosphorylase expression in macrophages correlates with tumor angiogenesis and prognosis in invasive breast cancer. Int J Oncol 13 (1998) 449-454
57. Okada K., Yokoyama K., Okihara K., Ukimura O., Kojima M., Miki T., et al. Immunohistochemical localization of platelet-derived endothelial cell growth factor expression and its relation to angiogenesis in prostate. Urology 57 (2001) 376-381
58. Fujioka S., Yoshida K., Yanagisawa S., Kawakami M., Aoki T., and Yamazaki Y. Angiogenesis in pancreatic carcinoma: thymidine phosphorylase expression in stromal cells and intratumoral microvessel density as independent predictors of overall and relapse-free survival. Cancer 92 (2001) 1788-1797
59. Zhu G.H., Lenzi M., and Schwartz E.L. The Sp1 transcription factor contributes to the tumor necrosis factor-induced expression of the angiogenic factor thymidine phosphorylase in human colon carcinoma cells. Oncogene 21 (2002) 8477-8485
60. Zhu G.H., and Schwartz E.L. Expression of the angiogenic factor thymidine phosphorylase in THP-1 monocytes: induction by autocrine tumor necrosis factor-alpha and inhibition by aspirin. Mol Pharmacol 64 (2003) 1251-1258
61. Schwartz E.L., Wan E., Wang F.S., and Baptiste N. Regulation of expression of thymidine phosphorylase/platelet-derived endothelial cell growth factor in human colon carcinoma cells. Cancer Res 58 (1998) 1551-1557
62. Goto H., Kohno K., Sone S., Akiyama S., Kuwano M., and Ono M. Interferon gamma-dependent induction of thymidine phosphorylase/platelet-derived endothelial growth factor through gamma-activated sequence-like element in human macrophages. Cancer Res 61 (2001) 469-473
63. Sawada N., Ishikawa T., Fukase Y., Nishida M., Yoshikubo T., and Ishitsuka H. Induction of thymidine phosphorylase activity and enhancement of capecitabine efficacy by taxol/taxotere in human cancer xenografts. Clin Cancer Res 4 (1998) 1013-1019
64. Blanquicett C., Gillespie G.Y., Nabors L.B., Miller C.R., Bharara S., Buchsbaum D.J., et al. Induction of thymidine phosphorylase in both irradiated and shielded, contralateral human U87MG glioma xenografts: implications for a dual modality treatment using capecitabine and irradiation. Mol Cancer Ther 1 (2002) 1139-1145
65. de Bruin M., Peters G.J., Oerlemans R., Assaraf Y.G., Masterson A.J., Adema A.D., et al. Sulfasalazine down-regulates the expression of the angiogenic factors platelet-derived endothelial cell growth factor/thymidine phosphorylase and interleukin-8 in human monocytic-macrophage THP1 and U937 cells. Mol Pharmacol 66 (2004) 1054-1060
66. Kikuno N., Moriyama-Gonda N., Yoshino T., Yoneda T., Urakami S., Terashima M., et al. Blockade of paclitaxel-induced thymidine phosphorylase expression can accelerate apoptosis in human prostate cancer cells. Cancer Res 64 (2004) 7526-7532
67. Griffiths L., Dachs G.U., Bicknell R., Harris A.L., and Stratford I.J. 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. Cancer Res 57 (1997) 570-572
68. Fukuiwa T., Takebayashi Y., Akiba S., Matsuzaki T., Hanamure Y., Miyadera K., et al. Expression of thymidine phosphorylase and vascular endothelial cell growth factor in human head and neck squamous cell carcinoma and their different characteristics. Cancer 85 (1999) 960-969
69. Kabuubi P., Loncaster J.A., Davidson S.E., Hunter R.D., Kobylecki C., Stratford I.J., et al. No relationship between thymidine phosphorylase (TP, PD-ECGF) expression and hypoxia in carcinoma of the cervix. Br J Cancer 94 (2006) 115-120
70. Hagiwara K., Stenman G., Honda H., Sahlin P., Andersson A., Miyazono K., et al. Organization and chromosomal localization of the human platelet-derived endothelial cell growth factor gene. Mol Cell Biol 11 (1991) 2125-2132
71. Hotchkiss K.A., Ashton A.W., and Schwartz E.L. Thymidine phosphorylase and 2-deoxyribose stimulate human endothelial cell migration by specific activation of the integrins alpha 5 beta 1 and alpha V beta 3. J Biol Chem 278 (2003) 19272-19279
72. Kojima H., Shijubo N., and Abe S. Thymidine phosphorylase and vascular endothelial growth factor in patients with Stage I lung adenocarcinoma. Cancer 94 (2002) 1083-1093
73. Sivridis E., Giatromanolaki A., Gatter K.C., Harris A.L., and Koukourakis M.I. Association of hypoxia-inducible factors 1alpha and 2alpha with activated angiogenic pathways and prognosis in patients with endometrial carcinoma. Cancer 95 (2002) 1055-1063
74. Akiyama S., Furukawa T., Sumizawa T., Takebayashi Y., Nakajima Y., Shimaoka S., et al. The role of thymidine phosphorylase, an angiogenic enzyme, in tumor progression. Cancer Sci 95 (2004) 851-857
75. Jeung H.C., Che X.F., Haraguchi M., Furukawa T., Zheng C.L., Sumizawa T., et al. Thymidine phosphorylase suppresses apoptosis induced by microtubule-interfering agents. Biochem Pharmacol 70 (2005) 13-21
76. Jeung H.C., Che X.F., Haraguchi M., Zhao H.Y., Furukawa T., Gotanda T., et al. Protection against DNA damage-induced apoptosis by the angiogenic factor thymidine phosphorylase. FEBS Lett 580 (2006) 1294-1302
77. Hammerberg C., Fisher G.J., Voorhees J.J., and Cooper K.D. Elevated thymidine phosphorylase activity in psoriatic lesions accounts for the apparent presence of an epidermal "growth inhibitor," but is not in itself growth inhibitory. J Invest Dermatol 97 (1991) 286-290
78. Kasugai K., Joh T., Kataoka H., Sasaki M., Tada T., Asai K., et al. Evidence for participation of gliostatin/platelet-derived endothelial cell growth factor in gastric ulcer healing. Life Sci 61 (1997) 899-1906
79. Ignatescu M.C., Gharehbaghi-Schnell E., Hassan A., Rezaie-Majd S., Korschineck I., Schleef R.R., et al. Expression of the angiogenic protein, platelet-derived endothelial cell growth factor, in coronary atherosclerotic plaques: In vivo correlation of lesional microvessel density and constrictive vascular remodeling. Arterioscler Thromb Vasc Biol 19 (1999) 2340-2347
80. Saito S., Tsuno N.H., Sunami E., Hori N., Kitayama J., Kazama S., et al. Expression of platelet-derived endothelial cell growth factor in inflammatory bowel disease. J Gastroenterol 38 (2003) 229-237
81. Takeuchi M., Otsuka T., Matsui N., Asai K., Hirano T., Moriyama A., et al. Aberrant production of gliostatin/platelet-derived endothelial cell growth factor in rheumatoid synovium. Arthritis Rheum 37 (1994) 662-672
82. Muro H., Waguri-Nagaya Y., Otsuka T., Matsui N., Asai K., and Kato T. Serum gliostatin levels in patients with rheumatoid factor-negative and-positive rheumatoid arthritis and changes of these levels after surgical treatments. Clin Rheumatol 20 (2001) 331-336
83. Waguri Y., Otsuka T., Sugimura I., Matsui N., Asai K., Moriyama A., et al. Gliostatin/platelet-derived endothelial cell growth factor as a clinical marker of rheumatoid arthritis and its regulation in fibroblast-like synoviocytes. Br J Rheumatol 36 (1997) 315-321
84. Kusabe T., Waguri-Nagaya Y., Tanikawa T., Aoyama M., Fukuoka M., Kobayashi M., et al. The inhibitory effect of disease-modifying anti-rheumatic drugs and steroids on gliostatin/platelet-derived endothelial cell growth factor production in human fibroblast-like synoviocytes. Rheumatol Int 25 (2005) 625-630
85. Ieda Y., Waguri-Nagaya Y., Iwahasi T., Otsuka T., Matsui N., Namba M., et al. IL-1beta-induced expression of matrix metalloproteinases and gliostatin/platelet-derived endothelial cell growth factor (GLS/PD-ECGF) in a chondrosarcoma cell line (OUMS-27). Rheumatol Int 21 (2001) 45-52
86. Tanikawa T., Waguri-Nagaya Y., Kusabe T., Aoyama M., Asai K., and Otsuka T. Gliostatin/thymidine phosphorylase-regulated vascular endothelial growth-factor production in human fibroblast-like synoviocytes. Rheumatol Int 27 (2007) 553-559
87. Waguri-Nagaya Y., Otsuka T., Sugimura I., Matsui N., Asai K., Nakajima K., et al. Synovial inflammation and hyperplasia induced by gliostatin/platelet-derived endothelial cell growth factor in rabbit knees. Rheumatol Int 20 (2000) 13-19
88. Bouis D., Boelens M.C., Peters E., Koolwijk P., Stob G., Kema I.P., et al. combination of vascular endothelial growth factor (VEGF) and thymidine phosphorylase (TP) to improve angiogenic gene therapy. Angiogenesis 6 (2003) 185-192
89. Li W., Tanaka K., Ihaya A., Fujibayashi Y., Takamatsu S., Morioka K., et al. Gene therapy for chronic myocardial ischemia using platelet-derived endothelial cell growth factor in dogs. Am J Physiol Heart Circ Physiol 288 (2005) H408-H415
90. Nishino I., Spinazzola A., and Hirano M. Thymidine phosphorylase gene mutations in MNGIE, a human mitochondrial disorder. Science 283 (1999) 689-692
91. Kumagai Y., Sugiura Y., Sugeno H., Takebayashi Y., Takenoshita S., and Yamamoto T. Thymidine phosphorylase gene mutation is not a primary cause of mitochondrial neurogastrointestinal encephalomyopathy (MNGIE). Intern Med 45 (2006) 443-446
92. Fukushima M., Suzuki N., Emura T., Yano S., Kazuno H., Tada Y., et al. Structure and activity of specific inhibitors of thymidine phosphorylase to potentiate the function of antitumor 2′-deoxyribonucleosides. Biochem Pharmacol 59 (2000) 1227-1236
93. Langen P., Etzold G., Barwolff D., and Preussel B. Inhibition of thymidine phosphorylase by 6-aminothymine and derivatives of 6-aminouracil. Biochem Pharmacol 16 (1967) 1833-1837
94. Takao S., Akiyama S.I., Nakajo A., Yoh H., Kitazono M., Natsugoe S., et al. Suppression of metastasis by thymidine phosphorylase inhibitor. Cancer Res 60 (2000) 5345-5348
95. Matsushita S., Nitanda T., Furukawa T., Sumizawa T., Tani A., Nishimoto K., et al. The effect of a thymidine phosphorylase inhibitor on angiogenesis and apoptosis in tumors. Cancer Res 59 (1999) 1911-1916
96. Hong D.S., Abbruzzese J.L., Bogaard K., Lassere Y., Fukushima M., Mita A., et al. Phase I study to determine the safety and pharmacokinetics of oral administration of TAS-102 in patients with solid tumors. Cancer 107 (2006) 1383-1390
97. Emura T., Suzuki N., Fujioka A., Ohshimo H., and Fukushima M. Potentiation of the antitumor activity of alpha, alpha, alpha-trifluorothymidine by the co-administration of an inhibitor of thymidine phosphorylase at a suitable molar ratio in vivo. Int J Oncol 27 (2005) 449-455
98. Reigan P., Edwards P.N., Gbaj A., Cole C., Barry S.T., Page K.M., et al. Aminoimidazolylmethyluracil analogues as potent inhibitors of thymidine phosphorylase and their bioreductive nitroimidazolyl prodrugs. J Med Chem 48 (2005) 392-402
99. Esteban-Gamboa A., Balzarini J., Esnouf R., De Clercq E., Camarasa M.J., and Pérez-Pérez M.J. Design, synthesis, and enzymatic evaluation of multisubstrate analogue inhibitors of Escherichia coli thymidine phosphorylase. J Med Chem 43 (2000) 971-983
100. Liekens S., Hernández A.I., Ribatti D., De Clercq E., Camarasa M.J., Pérez-Pérez M.J., et al. The nucleoside derivative 5′-O-trityl-inosine (KIN59) suppresses thymidine phosphorylase-triggered angiogenesis via a noncompetitive mechanism of action. J Biol Chem 279 (2004) 29598-29605
101. Liekens S., Bronckaers A., Hernández A.I., Priego E.M., Casanova E., Camarasa M.J., et al. 5′-O-tritylated nucleoside derivatives: inhibition of thymidine phosphorylase and angiogenesis. Mol Pharmacol 70 (2006) 501-509
102. Nakajima Y., Gotanda T., Uchimiya H., Furukawa T., Haraguchi M., Ikeda R., et al. Inhibition of metastasis of tumor cells overexpressing thymidine phosphorylase by 2-deoxy-l-ribose. Cancer Res 64 (2004) 1794-1801
103. Nakajima Y., Haraguchi M., Furukawa T., Yamamoto M., Nakanishi H., Tatematsu M., et al. 2-Deoxy-L-ribose inhibits the invasion of thymidine phosphorylase-overexpressing tumors by suppressing matrix metalloproteinase-9. Int J Cancer 119 (2006) 1710-1716
104. Longley D.B., Harkin D.P., and Johnston P.G. 5-Fluorouracil: mechanisms of action and clinical strategies. Nat Rev Cancer 3 (2003) 330-338
105. Miwa M., Ura M., Nishida M., Sawada N., Ishikawa T., Mori K., et al. Design of a novel oral fluoropyrimidine carbamate, capecitabine, which generates 5-fluorouracil selectively in tumours by enzymes concentrated in human liver and cancer tissue. Eur J Cancer 34 (1998) 1274-1281
106. Ishikawa T., Utoh M., Sawada N., Nishida M., Fukase Y., Sekiguchi F., et al. Tumor selective delivery of 5-fluorouracil by capecitabine, a new oral fluoropyrimidine carbamate, in human cancer xenografts. Biochem Pharmacol 55 (1998) 1091-1097
107. Walko C.M., and Lindley C. Capecitabine: a review. Clin Ther 27 (2005) 23-44
108. Schmoll H.J., and Arnold D. Update on capecitabine in colorectal cancer. Oncologist 11 (2006) 1003-1009
109. Haraguchi M., Furukawa T., Sumizawa T., and Akiyama S. Sensitivity of human KB cells expressing platelet-derived endothelial cell growth factor to pyrimidine antimetabolites. Cancer Res 53 (1993) 5680-5682
110. Patterson A.V., Zhang H., Moghaddam A., Bicknell R., Talbot D.C., Stratford I.J., et al. Increased sensitivity to the prodrug 5′-deoxy-5-fluorouridine and modulation of 5-fluoro-2′-deoxyuridine sensitivity in MCF-7 cells transfected with thymidine phosphorylase. Br J Cancer 72 (1995) 669-675
111. Kato Y., Matsukawa S., Muraoka R., and Tanigawa N. Enhancement of drug sensitivity and a bystander effect in PC-9 cells transfected with a platelet-derived endothelial cell growth factor thymidine phosphorylase cDNA. Br J Cancer 75 (1997) 506-511
112. Toi M., Atiqur Rahman M., Bando H., and Chow L.W. Thymidine phosphorylase (platelet-derived endothelial-cell growth factor) in cancer biology and treatment. Lancet Oncol 6 (2005) 158-166
113. Gelmon K., Chan A., and Harbeck N. The role of capecitabine in first-line treatment for patients with metastatic breast cancer. Oncologist 11 (2006) 42-51
114. Kindwall-Keller T., Otterson G.A., Young D., Neki A., Criswell T., Nuovo G., et al. Phase II evaluation of docetaxel-modulated capecitabine in previously treated patients with non-small cell lung cancer. Clin Cancer Res 11 (2005) 1870-1876
115. Ajani J. Review of capecitabine as oral treatment of gastric, gastroesophageal, and esophageal cancers. Cancer 107 (2006) 221-231
116. Saif M.W., Kang S.P., and Chu E. Treatment of metastatic colorectal cancer: from cytotoxic agents to molecular agents and multitargeted strategies. Oncology 20 (2006) 11-19