The dual role of thymidine phosphorylase in cancer development and chemotherapy

Medicinal Research Reviews

Volumn 29, Issue 6, 2009, Pages 903-953

  Bronckaers, Annelies ^a   Gago, Federico ^b   Balzarini, Jan ^a   Liekens, Sandra ^a  

^a REGA INSTITUTE FOR MEDICAL RESEARCH   (Belgium)

^b UNIVERSITY OF ALCALÁ   (Spain)

Author keywords

Angiogenesis; Cancer chemotherapy; Fluoropyrimidines; Thymidine phosphorylase (TP); Thymidine phosphorylase inhibitors

Indexed keywords

5 CHLORO 6 [1 (2 IMINOPYRROLIDINYL)METHYL]URACIL; 5' O TRITYLINOSINE; 6 AMINO 5 BROMOURACIL; 6 AMINOTHYMINE; 7 DEAZAXANTHINE; ANTINEOPLASTIC AGENT; BEVACIZUMAB; CAPECITABINE; CEDIRANIB; CISPLATIN; CYCLOPHOSPHAMIDE; DOCETAXEL; DOXORUBICIN; ENZASTAURIN; FLOXURIDINE; FLUOROURACIL; FOLINIC ACID; GLYCOSYLTRANSFERASE INHIBITOR; KIN 59; MITOMYCIN C; OXALIPLATIN; PACLITAXEL; PLATELET DERIVED ENDOTHELIAL CELL GROWTH FACTOR; PRODRUG; RIBOSE; SORAFENIB; SUNITINIB; TEGAFUR; THYMIDINE PHOSPHORYLASE INHIBITOR; UFT; UNCLASSIFIED DRUG; UNINDEXED DRUG;

ADVANCED CANCER; ANGIOGENESIS; ANTIANGIOGENIC ACTIVITY; ANTIANGIOGENIC THERAPY; APOPTOSIS; BREAST CANCER; CANCER CHEMOTHERAPY; CANCER GRADING; CANCER GROWTH; CANCER RADIOTHERAPY; CANCER STAGING; CARCINOGENESIS; CELL MIGRATION; CLINICAL TRIAL; COLON CANCER; COLON CARCINOMA; COLORECTAL CANCER; CONTINUOUS INFUSION; DRUG ACTIVATION; DRUG BIOAVAILABILITY; DRUG EFFICACY; DRUG POTENTIATION; DRUG TARGETING; DRUG TOLERABILITY; ENDOTHELIUM CELL; ENZYME ACTIVITY; ENZYME STRUCTURE; EXPERIMENTAL NEOPLASM; GASTROINTESTINAL SYMPTOM; GASTROINTESTINAL TOXICITY; HUMAN; INFLAMMATORY DISEASE; LIVER METASTASIS; METASTASIS; METASTASIS INHIBITION; MICROMETASTASIS; MNGIE SYNDROME; MONOTHERAPY; NONHUMAN; PROTEIN EXPRESSION; PROTEIN FUNCTION; PROTEIN SECRETION; REVIEW; TUMOR VASCULARIZATION; UNSPECIFIED SIDE EFFECT;

ANTINEOPLASTIC AGENTS; FEMALE; HUMANS; MALE; MODELS, MOLECULAR; NEOPLASMS; PROTEIN CONFORMATION; THYMIDINE PHOSPHORYLASE;

EID: 70350446963     PISSN: 01986325     EISSN: None     Source Type: Journal    
DOI: 10.1002/med.20159     Document Type: Review

References (401)

1. Friedkin M, Roberts D. The enzymatic synthesis of nucleosides. I. Thymidine phosphorylase in mammalian tissue. J Biol Chem 1954;207:245-256.
2. Iltzsch MH, El Kouni MH, Cha S. Kinetic studies of thymidine phosphorylase from mouse liver. Biochemistry 1985;24:6799-6807. (Pubitemid 16170208)
3. Schwartz M. Thymidine phosphorylase from Escherichia coli. Properties and kinetics. Eur J Biochem 1971;21:191-198.
4. Desgranges C, Razaka G, Rabaud M, Bricaud H, Balzarini J, De Clercq E. Phosphorolysis of (E)-5-(2-bromovinyl)-20-deoxyuridine (BVDU) and other 5-substituted-20-deoxyuridines by purified human thymidine phosphorylase and intact blood platelets. Biochem Pharmacol 1983;32:3583-3590. (Pubitemid 14205368)
5. Heidelberger C, Anderson S. Fluorinated pyrimidines. XXI. The tumor-inhibitory activity of 5-triflyoromethyl-2′-deoxyuridine. Cancer Res 1964;24:1979-1985.
6. Schwartz EL, Baptiste N, Wadler S, Makower D. Thymidine phosphorylase mediates the sensitivity of human colon carcinoma cells to 5-fluorouracil. J Biol Chem 1995;270:19073-19077.
7. Walko CM, Lindley C. Capecitabine: A review. Clin Ther 2005;27:23-44.
8. Miyazono K, Okabe T, Urabe A, Takaku F, Heldin CH. Purification and properties of an endothelial cell growth factor from human platelets. J Biol Chem 1987;262:4098-4103. (Pubitemid 17102635)
9. Ishikawa F, Miyazono K, Hellman U, Drexler H, Wernstedt C, Hagiwara K, Usuki K, Takaku F, Risau W, Heldin CH. Identification of angiogenic activity and the cloning and expression of platelet-derived endothelial cell growth factor. Nature 1989;338:557-562. (Pubitemid 19102308)
10. Moghaddam A, Bicknell R. Expression of platelet-derived endothelial cell growth factor in Escherichia coli and confirmation of its thymidine phosphorylase activity. Biochemistry 1992;31:12141-12146. (Pubitemid 23011359)
11. Usuki K, Saras J, Waltenberger J, Miyazono K, Pierce G, Thomason A, Heldin CH. Platelet-derived endothelial cell growth factor has thymidine phosphorylase activity. Biochem Biophys Res Commun 1992;184:1311-1316.
12. Furukawa T, Yoshimura A, Sumizawa T, Haraguchi M, Akiyama S, Fukui K, Ishizawa M, Yamada Y. Angiogenic factor. Nature 1992;356:668.
13. Asai K, Hirano T, Kaneko S, Moriyama A, Nakanishi K, Isobe I, Eksioglu YZ, Kato T. A novel glial growth inhibitory factor, gliostatin, derived from neurofibroma. J Neurochem 1992;59:307-317.
14. Asai K, Nakanishi K, Isobe I, Eksioglu YZ, Hirano A, Hama K, Miyamoto T, Kato T. Neurotrophic action of gliostatin on cortical neurons. Identity of gliostatin and platelet-derived endothelial cell growth factor. J Biol Chem 1992;267:20311-20316.
15. Blank JG, Hoffee PA. Purification and properties of thymidine phosphorylase from Salmonella typhimurium. Arch Biochem Biophys 1975;168:259-265.
16. Voytek P. Purification of thymidine phosphorylase from Escherichia coli and its photoinactivation in the presence of thymine, thymidine, and some halogenated analogs. J Biol Chem 1975;250:3660-3665.
17. Kubilus J, Lee LD, Baden HP. Purification of thymidine phosphorylase from human amniochorion. Biochim Biophys Acta 1978;527:221-228. (Pubitemid 9055839)
18. Barton GJ, Ponting CP, Spraggon G, Finnis C, Sleep D. Human platelet-derived endothelial cell growth factor is homologous to Escherichia coli thymidine phosphorylase. Protein Sci 1992;1:688-690. (Pubitemid 23009203)
19. Schwartz M. Thymidine phosphorylase from Escherichia coli. Methods Enzymol 1978;51:442-445.
20. Desgranges C, Razaka G, Rabaud M, Bricaud H. Catabolism of thymidine in human blood platelets: Purification and properties of thymidine phosphorylase. Biochim Biophys Acta 1981;654:211-218. (Pubitemid 11058078)
21. Walter MR, Cook WJ, Cole LB, Short SA, Koszalka GW, Krenitsky TA, Ealick SE. Three-dimensional structure of thymidine phosphorylase from Escherichia coli at 2.8 A resolution. J Biol Chem 1990;265:14016-14022. (Pubitemid 20252271)
22. Pugmire MJ, Cook WJ, Jasanoff A, Walter MR, Ealick SE. Structural and theoretical studies suggest domain movement produces an active conformation of thymidine phosphorylase. J Mol Biol 1998;281:285-299. (Pubitemid 28360595)
23. Pugmire MJ, Ealick SE. The crystal structure of pyrimidine nucleoside phosphorylase in a closed conformation. Structure 1998;6:1467-1479.
24. Mendieta J, Martin-Santamaria S, Priego EM, Balzarini J, Camarasa MJ, Pérez-Pérez MJ, Gago F. Role of histidine-85 in the catalytic mechanism of thymidine phosphorylase as assessed by targeted molecular dynamics simulations and quantum mechanical calculations. Biochemistry 2004;43:405-414. (Pubitemid 38082562)
25. Norman RA, Barry ST, Bate M, Breed J, Colls JG, Ernill RJ, Luke RW, Minshull CA, McAlister MS, McCall EJ, McMiken HH, Paterson DS, Timms D, Tucker JA, Pauptit RA. Crystal structure of human thymidine phosphorylase in complex with a small molecule inhibitor. Structure 2004;12:75-84. (Pubitemid 38120276)
26. Spraggon G, Stuart D, Ponting C, Finnis C, Sleep D, Jones Y. Crystallization and X-ray diffraction study of recombinant platelet-derived endothelial cell growth factor. J Mol Biol 1993;234:879-880. (Pubitemid 24007807)
27. El Omari K, Bronckaers A, Liekens S, Pérez-Pérez MJ, Balzarini J, Stammers DK. Structural basis for non-competitive product inhibition in human thymidine phosphorylase: Implications for drug design. Biochem J 2006;399:199-204. (Pubitemid 44570281)
28. Fox SB, Moghaddam A, Westwood M, Turley H, Bicknell R, Gatter KC, Harris AL. Platelet-derived endothelial cell growth factor/thymidine phosphorylase expression in normal tissues: An immunohistochemical study. J Pathol 1995;176:183-190.
29. Yoshimura A, Kuwazuru Y, Furukawa T, Yoshida H, Yamada K, Akiyama S. Purification and tissue distribution of human thymidine phosphorylase; high expression in lymphocytes, reticulocytes and tumors. Biochim Biophys Acta 1990;1034:107-113. (Pubitemid 20114807)
30. Matsukawa K, Moriyama A, Kawai Y, Asai K, Kato T. Tissue distribution of human gliostatin/platelet-derived endothelial cell growth factor (PD-ECGF) and its drug-induced expression. Biochim Biophys Acta 1996;1314:71-82. (Pubitemid 26395501)
31. Shaw T, Smillie RH, MacPhee DG. The role of blood platelets in nucleoside metabolism: Assay, cellular location and significance of thymidine phosphorylase in human blood. Mutat Res 1988;200:99-116. (Pubitemid 18173995)
32. Jackson MR, Carney EW, Lye SJ, Ritchie JW. Localization of two angiogenic growth factors (PDECGF and VEGF) in human placentae throughout gestation. Placenta 1994;15:341-353.
33. Usuki K, Norberg L, Larsson E, Miyazono K, Hellman U, Wernstedt C, Rubin K, Heldin CH. Localization of platelet-derived endothelial cell growth factor in human placenta and purification of an alternatively processed form. Cell Regul 1990;1:577-584.
34. Zhang L, MacKenzie IZ, Rees MC, 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 1997;138:4921-4930. (Pubitemid 27460932)
35. Fujimoto J, Ichigo S, Sakaguchi H, Hirose R, Tamaya T. Expression of platelet-derived endothelial cell growth factor and its mRNA in uterine endometrium during the menstrual cycle. Mol Hum Reprod 1998;4:509-513. (Pubitemid 28253213)
36. Abbas MM, Evans JJ, Sykes PH, Benny PS. Modulation of vascular endothelial growth factor and thymidine phosphorylase in normal human endometrial stromal cells. Fertil Steril 2004;82:1048-1053. (Pubitemid 39335915)
37. Osuga Y, Toyoshima H, Mitsuhashi N, 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 1995;10:989-993.
38. Creamer D, Jaggar R, Allen M, Bicknell R, Barker J. Overexpression of the angiogenic factor platelet-derived endothelial cell growth factor/thymidine phosphorylase in psoriatic epidermis. Br J Dermatol 1997;137:851-855. (Pubitemid 28011123)
39. Hammerberg C, Fisher GJ, Voorhees JJ, Cooper KD. 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 1991;97:286-290.
40. Giatromanolaki A, Sivridis E, Maltezos E, Papazoglou D, Simopoulos C, Gatter KC, Harris AL, Koukourakis MI. Hypoxia inducible factor 1alpha and 2alpha overexpression in inflammatory bowel disease. J Clin Pathol 2003;56:209-213. (Pubitemid 36308037)
41. Saito S, Tsuno NH, Sunami E, Hori N, Kitayama J, Kazama S, Okaji Y, Kawai K, Kanazawa T, Watanabe T, Shibata Y, Nagawa H. Expression of platelet-derived endothelial cell growth factor in inflammatory bowel disease. J Gastroenterol 2003;38:229-237. (Pubitemid 36527125)
42. Wang EH, Goh YB, Moon IS, Park CH, Lee KH, Kang SH, Kang CS, Choi YJ. Upregulation of thymidine phosphorylase in chronic glomerulonephritis and its role in tubulointerstitial injury. Nephron Clin Pract 2006;102:c133-c142.
43. Boyle JJ, Wilson B, Bicknell R, Harrower S, Weissberg PL, Fan TP. Expression of angiogenic factor thymidine phosphorylase and angiogenesis in human atherosclerosis. J Pathol 2000;192:234-242. (Pubitemid 30768990)
44. Takeuchi M, Otsuka T, Matsui N, Asai K, Hirano T, Moriyama A, Isobe I, Eksioglu YZ, Matsukawa K, Kato T. Aberrant production of gliostatin/platelet- derived endothelial cell growth factor in rheumatoid synovium. Arthritis Rheum 1994;37:662-672. (Pubitemid 24145069)
45. Asai K, Hirano T, Matsukawa K, Kusada J, Takeuchi M, Otsuka T, Matsui N, Kato T. High concentrations of immunoreactive gliostatin/platelet-derived endothelial cell growth factor in synovial fluid and serum of rheumatoid arthritis. Clin Chim Acta 1993;218:1-4. (Pubitemid 23294509)
46. Waguri Y, Otsuka T, Sugimura I, Matsui N, Asai K, Moriyama A, Kato T. Gliostatin/platelet-derived endothelial cell growth factor as a clinical marker of rheumatoid arthritis and its regulation in fibroblast-like synoviocytes. Br J Rheumatol 1997;36:315-321. (Pubitemid 27352865)
47. Waguri-Nagaya Y, Otsuka T, Sugimura I, Matsui N, Asai K, Nakajima K, Tada T, Akiyama S, Kato T. Synovial inflammation and hyperplasia induced by gliostatin/platelet-derived endothelial cell growth factor in rabbit knees. Rheumatol Int 2000;20:13-19.
48. Muro H, Waguri-Nagaya Y, Mukofujiwara Y, Iwahashi T, Otsuka T, Matsui N, Moriyama A, Asai K, Kato T. 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) 1999;38:1195-1202.
49. Ieda Y, Waguri-Nagaya Y, Iwahasi T, Otsuka T, Matsui N, Namba M, Asai K, Kato T. IL-1betainduced expression of matrix metalloproteinases and gliostatin/platelet-derived endothelial cell growth factor (GLS/PD-ECGF) in a chondrosarcoma cell line (OUMS-27). Rheumatol Int 2001;21:45-52.
50. Tanikawa T, Waguri-Nagaya Y, Kusabe T, Aoyama M, Asai K, Otsuka T. Gliostatin/thymidine phosphorylase-regulated vascular endothelial growth-factor production in human fibroblast-like synoviocytes. Rheumatol Int 2007;27:553-559. (Pubitemid 46411894)
51. Hirano M, Silvestri G, Blake DM, Lombes A, Minetti C, Bonilla E, Hays AP, Lovelace RE, Butler I, Bertorini TE. Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE): Clinical, biochemical, and genetic features of an autosomal recessive mitochondrial disorder. Neurology 1994;44:721-727. (Pubitemid 24130006)
52. Nishino I, Spinazzola A, Papadimitriou A, Hammans S, Steiner I, Hahn CD, Connolly AM, Verloes A, Guimaraes J, Maillard I, Hamano H, Donati MA, Semrad CE, Russell JA, Andreu AL, Hadjigeorgiou GM, Vu TH, Tadesse S, Nygaard TG, Nonaka I, Hirano I, Bonilla E, Rowland LP, DiMauro S, Hirano M. Mitochondrial neurogastrointestinal encephalomyopathy: An autosomal recessive disorder due to thymidine phosphorylase mutations. Ann Neurol 2000;47:792-800. (Pubitemid 30390200)
53. Spinazzola A, Marti R, Nishino I, Andreu AL, Naini A, Tadesse S, Pela I, Zammarchi E, Donati MA, Oliver JA, Hirano M. Altered thymidine metabolism due to defects of thymidine phosphorylase. J Biol Chem 2002;277:4128-4133. (Pubitemid 34968672)
54. Marti R, Nishigaki Y, Hirano M. Elevated plasma deoxyuridine in patients with thymidine phosphorylase deficiency. Biochem Biophys Res Commun 2003;303:14-18. (Pubitemid 36338200)
55. Valentino ML, Marti R, Tadesse S, Lopez LC, Manes JL, Lyzak J, Hahn A, Carelli V, Hirano M. Thymidine and deoxyuridine accumulate in tissues of patients with mitochondrial neurogastrointestinal encephalomyopathy (MNGIE). FEBS Lett 2007;581:3410-3414. (Pubitemid 47048186)
56. Haraguchi M, Tsujimoto H, Fukushima M, Higuchi I, Kuribayashi H, Utsumi H, Nakayama A, Hashizume Y, Hirato J, Yoshida H, Hara H, Hamano S, Kawaguchi H, Furukawa T, Miyazono K, Ishikawa F, Toyoshima H, Kaname T, Komatsu M, Chen ZS, Gotanda T, Tachiwada T, Sumizawa T, Miyadera K, Osame M, Yoshida H, Noda T, Yamada Y, Akiyama S. Targeted deletion of both thymidine phosphorylase and uridine phosphorylase and consequent disorders in mice. Mol Cell Biol 2002;22:5212-5221. (Pubitemid 34700710)
57. Lopez LC, Akman HO, Garcia-Cazorla A, Dorado B, Marti R, Nishino I, Tadesse S, Pizzorno G, Shungu D, Bonilla E, Tanji K, Hirano M. Unbalanced deoxynucleotide pools cause mitochondrial DNA instability in thymidine phosphorylase deficient mice. Hum Mol Genet 2009;18:714-722.
58. Hirano M, Nishigaki Y, Marti R. Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE): A disease of two genomes. Neurologist 2004;10:8-17. (Pubitemid 38140835)
59. Kumagai Y, Sugiura Y, Sugeno H, Takebayashi Y, Takenoshita S, Yamamoto T. Thymidine phosphorylase gene mutation is not a primary cause of mitochondrial neurogastrointestinal encephalomyopathy (MNGIE). Intern Med 2006;45:443-446. (Pubitemid 43676580)
60. Dickinson EK, Adams DL, Schon EA, Glerum DM. A human SCO2 mutation helps define the role of Sco1p in the cytochrome oxidase assembly pathway. J Biol Chem 2000;275:26780-26785.
61. Jaksch M, Ogilvie I, Yao J, Kortenhaus G, Bresser HG, Gerbitz KD, Shoubridge EA. Mutations in SCO2 are associated with a distinct form of hypertrophic cardiomyopathy and cytochrome c oxidase deficiency. Hum Mol Genet 2000;9:795-801. (Pubitemid 30162764)
62. Nishino I, Spinazzola A, Hirano M. Thymidine phosphorylase gene mutations in MNGIE, a human mitochondrial disorder. Science 1999;283:689-692. (Pubitemid 129506238)
63. Moghaddam A, Zhang HT, Fan TP, Hu DE, Lees VC, Turley H, Fox SB, Gatter KC, Harris AL, Bicknell R. Thymidine phosphorylase is angiogenic and promotes tumor growth. Proc Natl Acad Sci USA 1995;92:998-1002.
64. Arima J, Imazono Y, Takebayashi Y, Nishiyama K, Shirahama T, Akiba S, Furukawa T, Akiyama S, Ohi Y. Expression of thymidine phosphorylase as an indicator of poor prognosis for patients with transitional cell carcinoma of the bladder. Cancer 2000;88:1131-1138. (Pubitemid 30127675)
65. O'Brien TS, Fox SB, Dickinson AJ, Turley H, Westwood M, Moghaddam A, Gatter KC, Bicknell R, Harris AL. Expression of the angiogenic factor thymidine phosphorylase/ platelet-derived endothelial cell growth factor in primary bladder cancers. Cancer Res 1996;56:4799-4804. (Pubitemid 26338087)
66. Yoshikawa T, Suzuki K, Kobayashi O, Sairenji M, Motohashi H, Tsuburaya A, Nakamura Y, Shimizu A, Yanoma S, Noguchi Y. Thymidine phosphorylase/platelet- derived endothelial cell growth factor is upregulated in advanced solid types of gastric cancer. Br J Cancer 1999;79:1145-1150. (Pubitemid 29087888)
67. Takebayashi Y, Miyadera K, Akiyama S, Hokita S, Yamada K, Akiba S, Yamada Y, Sumizawa T, Aikou T. Expression of thymidine phosphorylase in human gastric carcinoma. Jpn J Cancer Res 1996;87:288-295. (Pubitemid 26117060)
68. Takebayashi Y, Yamada K, Miyadera K, Sumizawa T, Furukawa T, Kinoshita F, Aoki D, Okumura H, Yamada Y, Akiyama S, Aikou T. The activity and expression of thymidine phosphorylase in human solid tumours. Eur J Cancer 1996;32A:1227-1232. (Pubitemid 26231808)
69. O'Byrne KJ, Koukourakis MI, Giatromanolaki A, Cox G, Turley H, Steward WP, Gatter K, Harris AL. Vascular endothelial growth factor, platelet-derived endothelial cell growth factor and angiogenesis in non-small-cell lung cancer. Br J Cancer 2000;82:1427-1432. (Pubitemid 30175909)
70. Takebayashi Y, Natsugoe S, Baba M, Akiba S, Fukumoto T, Miyadera K, Yamada Y, Takao S, Akiyama S, Aikou T. Thymidine phosphorylase in human esophageal squamous cell carcinoma. Cancer 1999;85:282-289. (Pubitemid 29051280)
71. Fujimoto J, Sakaguchi H, Hirose R, Wen H, Tamaya T. Clinical implication of expression of platelet-derived endothelial cell growth factor (PD-ECGF) in metastatic lesions of uterine cervical cancers. Cancer Res 1999;59:3041-3044. (Pubitemid 29315997)
72. Yamamoto A, Dhar DK, El Assal ON, Igarashi M, Tabara H, Nagasue N. Thymidine phosphorylase (platelet-derived endothelial cell growth factor), microvessel density and clinical outcome in hepatocellular carcinoma. J Hepatol 1998;29:290-299. (Pubitemid 28352815)
73. Mainou-Fowler T, Angus B, Miller S, Proctor SJ, Taylor PR, Wood KM. Micro-vessel density and the expression of vascular endothelial growth factor (VEGF) and platelet-derived endothelial cell growth factor (PdEGF) in classical Hodgkin lymphoma (HL). Leuk Lymphoma 2006;47:223-230. (Pubitemid 43084560)
74. Slager EH, Honders MW, van der Meijden ED, Luxemburg-Heijs SA, Kloosterboer FM, Kester MG, Jedema I, Marijt WA, Schaafsma MR, Willemze R, Falkenburg JH. Identification of the angiogenic endothelial-cell growth factor-1/thymidine phosphorylase as a potential target for immunotherapy of cancer. Blood 2006;107:4954-4960. (Pubitemid 43882650)
75. Fujimoto J, Ichigo S, Sakaguchi H, Hirose R, Tamaya T. Expression of platelet-derived endothelial cell growth factor (PD-ECGF) and its mRNA in uterine endometrial cancers. Cancer Lett 1998;130:115-120. (Pubitemid 28425344)
76. Fujimoto K, Hosotani R, Wada M, Lee JU, Koshiba T, Miyamoto Y, Tsuji S, Nakajima S, Doi R, Imamura M. Expression of two angiogenic factors, vascular endothelial growth factor and platelet-derived endothelial cell growth factor in human pancreatic cancer, and its relationship to angiogenesis. Eur J Cancer 1998;34:1439-1447. (Pubitemid 28370938)
77. Fujioka S, Yoshida K, Yanagisawa S, KawakamiM, Aoki T, 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 2001;92:1788-1797. (Pubitemid 32952497)
78. Fujiwaki R, Hata K, Iida K, Koike M, Miyazaki K. Immunohistochemical expression of thymidine phosphorylase in human endometrial cancer. Gynecol Oncol 1998;68:247-252. (Pubitemid 28183494)
79. Fujiwaki R, Hata K, Iida K, Maede Y, Watanabe Y, Koike M, Miyazaki K. Co-expression of vascular endothelial growth factor and thymidine phosphorylase in endometrial cancer. Acta Obstet Gynecol Scand 1999;78:728-734. (Pubitemid 29392679)
80. Han HS, Hwang TS. Angiogenesis in gastric cancer: Importance of the thymidine phosphorylase expression of cancer cells as an angiogenic factor. Oncol Rep 2007;17:61-65.
81. Ikeda N, Adachi M, Taki T, Huang C, Hashida H, Takabayashi A, Sho M, Nakajima Y, Kanehiro H, Hisanaga M, Nakano H, Miyake M. Prognostic significance of angiogenesis in human pancreatic cancer. Br J Cancer 1999;79:1553-1563. (Pubitemid 29116820)
82. Ikeguchi M, Sakatani T, Ueta T, Fukuda K, Yamaguchi K, Tsujitani S, Kaibara N. The expression of thymidine phosphorylase suppresses spontaneous apoptosis of cancer cells in esophageal squamous cell carcinoma. Pathobiology 2001;69:36-43. (Pubitemid 32973982)
83. Jinfeng M, Kimura W, Sakurai F, Moriya T, Mizutani M, Hirai I. Prognostic role of angiogenesis and its correlations with thymidine phosphorylase and p53 expression in ductal adenocarcinoma of the pancreas. Hepatogastroenterology 2007;54:1635-1640. (Pubitemid 350068442)
84. Kakeji Y, Maehara Y, Tomoda M, Kabashima A, Oda S, Ooshiro T, Baba H, Kohnoe S, Sugimachi K. Thymidine phosphorylase activity and angiogenesis in gastric cancer. Oncol Rep 1999;6:995-999.
85. Kikuyama S, Inada T, Shimizu K, Miyakita M. Thymidine phosphorylase expression in gastric cancer in association with proliferative activity and angiogenesis. Anticancer Res 2000;20:2081-2086. (Pubitemid 30636187)
86. Kimura H, Konishi K, Nukui T, Kaji M, Maeda K, Yabushita K, Tsuji M, Miwa A. Prognostic significance of expression of thymidine phosphorylase and vascular endothelial growth factor in human gastric carcinoma. J Surg Oncol 2001;76:31-36. (Pubitemid 32128360)
87. Kimura H, Konishi K, Kaji M, Maeda K, Yabushita K, Miwa A. Correlation between expression levels of thymidine phosphorylase (dThdPase) and clinical features in human gastric carcinoma. Hepatogastroenterology 2002;49:882-886. (Pubitemid 34615371)
88. Konno S, Takebayashi Y, Aiba M, Akiyama S, Ogawa K. Clinicopathological and prognostic significance of thymidine phosphorylase and proliferating cell nuclear antigen in gastric carcinoma. Cancer Lett 2001;166:103-111. (Pubitemid 32274291)
89. Konno S, Takebayashi Y, Higashimoto M, Katsube T, Kanzaki A, Kawahara M, Takenoshita S, Aiba M, Ogawa K. Thymidine phosphorylase expression in gastric carcinoma as a marker for metastasis. Anticancer Res 2003;23:5011-5014. (Pubitemid 38182118)
90. Kuwahara K, Sasaki T, Kuwada Y, Murakami M, Yamasaki S, Chayama K. Expressions of angiogenic factors in pancreatic ductal carcinoma: A correlative study with clinicopathologic parameters and patient survival. Pancreas 2003;26:344-349. (Pubitemid 36529959)
91. Liakakos T, Troupis T, Ghiconti I, Triantafyllidis S, Macheras A, Karatzas G, Pavlakis K. Immunohistochemical localization of thymidine phosphorylase in gastric cancer: Is there a role of the differential expression in tumor cells and associated stromal cells? Anticancer Res 2006;26:3899-3903.
92. Mazurek A, Kuc P, Terlikowski S, Laudanski T. Evaluation of tumor angiogenesis and thymidine phosphorylase tissue expression in patients with endometrial cancer. Neoplasma 2006;53:242-246. (Pubitemid 43844384)
93. Mazurek A, Kuc P, Mazurek-Wadolkowska E, Laudanski T. A role of thymidine phosphorylase and P53 tissue protein expression in biology of endometrial cancer. Neoplasma 2008;55:261-265.
94. Miyake K, Imura S, Yoshizumi T, Ikemoto T, Morine Y, Shimada M. Role of thymidine phosphorylase and orotate phosphoribosyltransferase mRNA expression and its ratio to dihydropyrimidine dehydrogenase in the prognosis and clinicopathological features of patients with pancreatic cancer. Int J Clin Oncol 2007;12:111-119. (Pubitemid 46632459)
95. Noguchi T, Fujiwara S, Takeno S, Kai S, Mizuta A, Nagao Y, Uchida Y. Clinical impact of thymidine phosphorylase expression in gastric cancer. Oncol Rep 2003;10:561-566.
96. Ogawa K, Konno S, Takebayashi Y, Miura K, Katsube T, Kajiwara T, Aiba M, Aikou T, Akiyama S. Clinicopathological and prognostic significance of thymidine phosphorylase expression in gastric carcinoma. Anticancer Res 1999;19:4363-4367. (Pubitemid 30042791)
97. Sakamoto H, Shirakawa T, Izuka S, Igarashi T, Kinoshita K, Ohtani K, Takami T, Nakayama Y, Teramoto K, Satoh K. Thymidine phosphorylase expression is predominantly observed in stroma of well-differentiated adenocarcinoma of endometrium and correlates with a frequency of vascular involvement. Gynecol Oncol 1999;72:298-305. (Pubitemid 29118185)
98. Seki N, Kodama J, Hongo A, Miyagi Y, Yoshinouchi M, Kudo T. Angiogenesis and platelet-derived endothelial cell growth factor/thymidine phosphorylase expression in endometrial cancer. Int J Oncol 1999;15:781-786.
99. Seki N, Kodama J, Hongo A, Miyagi Y, Yoshinouchi M, Kudo T. Vascular endothelial growth factor and platelet-derived endothelial cell growth factor expression are implicated in the angiogenesis of endometrial cancer. Eur J Cancer 2000;36:68-73. (Pubitemid 30035346)
100. Shimaoka S, Matsushita S, Nitanda T, Matsuda A, Nioh T, Suenaga T, Nishimata Y, Akiba S, Akiyama S, Nishimata H. The role of thymidine phosphorylase expression in the invasiveness of gastric carcinoma. Cancer 2000;88:2220-2227. (Pubitemid 30247120)
101. Sivridis E, Giatromanolaki A, Koukourakis MI, Bicknell R, Harris AL, Gatter KC. Thymidine phosphorylase expression in endometrial carcinomas. Clin Exp Metastasis 1999;17:445-450. (Pubitemid 30020003)
102. Suda Y, Kuwashima Y, Tanaka Y, Uchida K, Sakamoto H, Hashiguchi Y, Sekine T. Expression of thymidylate synthase and thymidine phosphorylase in recurrence and survival rates of advanced gastric cancer. Gastric Cancer 1999;2:165-172.
103. Takao S, Takebayashi Y, Che X, Shinchi H, Natsugoe S, Miyadera K, Yamada Y, Akiyama S, Aikou T. Expression of thymidine phosphorylase is associated with a poor prognosis in patients with ductal adenocarcinoma of the pancreas. Clin Cancer Res 1998;4:1619-1624. (Pubitemid 28304722)
104. Tanaka Y, Kobayashi H, Suzuki M, Kanayama N, Suzuki M, Terao T. Thymidine phosphorylase expression in tumor-infiltrating macrophages may be correlated with poor prognosis in uterine endometrial cancer. Hum Pathol 2002;33:1105-1113. (Pubitemid 35416708)
105. Tokumo K, Kodama J, Seki N, Nakanishi Y, Miyagi Y, Kamimura S, Yoshinouchi M, Okuda H, Kudo T. Different angiogenic pathways in human cervical cancers. Gynecol Oncol 1998;68:38-44. (Pubitemid 28109821)
106. Tsujitani S, Saito H, Maeta Y, Yamaguchi K, Tatebe S, Kondo A, Kaibara N. Neoangiogenesis in patients with gastric carcinoma in relation to the expression of vascular endothelial growth factor and thymidine phosphorylase. Anticancer Res 2004;24:1853-1859. (Pubitemid 38954599)
107. Giatromanolaki A, Koukourakis MI, Kakolyris S, Kaklamanis L, Barbatis K, O'Byrne KJ, Theodosssiou D, Harris AL, Gatter KC. Focal expression of thymidine phosphorylase associates with CD31 positive lymphocytic aggregation and local neo-angiogenesis in non-small cell lung cancer. Anticancer Res 1998;18:71-76. (Pubitemid 28174687)
108. Fujimoto J, Ichigo S, Sakaguchi H, Hirose R, Tamaya T. Expression of platelet-derived endothelial cell growth factor (PD-ECGF) and its mRNA in ovarian cancers. Cancer Lett 1998;126:83-88. (Pubitemid 28142975)
109. Igarashi M, Dhar DK, Kubota H, Yamamoto A, El Assal O, Nagasue N. The prognostic significance of microvessel density and thymidine phosphorylase expression in squamous cell carcinoma of the esophagus. Cancer 1998;82:1225-1232. (Pubitemid 28155382)
110. Nakayama Y, Sueishi K, Oka K, Kono S, Tomonaga M. Stromal angiogenesis in human glioma: A role of platelet-derived endothelial cell growth factor. Surg Neurol 1998;49:181-187. (Pubitemid 28068424)
111. Maeda K, Kang SM, Ogawa M, Onoda N, Sawada T, Nakata B, Kato Y, Chung YS, Sowa M. Combined analysis of vascular endothelial growth factor and platelet-derived endothelial cell growth factor expression in gastric carcinoma. Int J Cancer 1997;74:545-550. (Pubitemid 27486514)
112. Saeki T, Tanada M, Takashima S, Saeki H, Takiyama W, Nishimoto N, Moriwaki S. Correlation between expression of platelet-derived endothelial cell growth factor (thymidine phosphorylase) and microvessel density in early-stage human colon carcinomas. Jpn J Clin Oncol 1997;27:227-230. (Pubitemid 127516769)
113. Engels K, Fox SB, Whitehouse RM, Gatter KC, Harris AL. Up-regulation of thymidine phosphorylase expression is associated with a discrete pattern of angiogenesis in ductal carcinomas in situ of the breast. J Pathol 1997;182:414-420. (Pubitemid 27317206)
114. Imazano Y, Takebayashi Y, Nishiyama K, Akiba S, Miyadera K, Yamada Y, Akiyama S, Ohi Y. Correlation between thymidine phosphorylase expression and prognosis in human renal cell carcinoma. J Clin Oncol 1997;15:2570-2578. (Pubitemid 27289887)
115. Kubota Y, Miura T, Moriyama M, Noguchi S, Matsuzaki J, Takebayashi S, Hosaka M. Thymidine phosphorylase activity in human bladder cancer: Difference between superficial and invasive cancer. Clin Cancer Res 1997;3:973-976. (Pubitemid 27252946)
116. Fox SB, Engels K, Comley M, Whitehouse RM, Turley H, Gatter KC, Harris AL. Relationship of elevated tumour thymidine phosphorylase in node-positive breast carcinomas to the effects of adjuvant CMF. Ann Oncol 1997;8:271-275. (Pubitemid 27153494)
117. Relf M, LeJeune S, Scott PA, Fox S, Smith K, Leek R, Moghaddam A, Whitehouse R, Bicknell R, Harris AL. Expression of the angiogenic factors vascular endothelial cell growth factor, acidic and basic fibroblast growth factor, tumor growth factor beta-1, platelet-derived endothelial cell growth factor, placenta growth factor, and pleiotrophin in human primary breast cancer and its relation to angiogenesis. Cancer Res 1997;57:963-969. (Pubitemid 27098025)
118. Toi M, Gion M, Biganzoli E, Dittadi R, Boracchi P, Miceli R, Meli S, Mori K, Tominaga T, Gasparini G. Co-determination of the angiogenic factors thymidine phosphorylase and vascular endothelial growth factor in node-negative breast cancer: Prognostic implications. Angiogenesis 1997;1:71-83. (Pubitemid 127505703)
119. Koukourakis MI, Giatromanolaki A, O'Byrne KJ, Comley M, Whitehouse RM, Talbot DC, Gatter KC, Harris AL. Platelet-derived endothelial cell growth factor expression correlates with tumour angiogenesis and prognosis in non-small-cell lung cancer. Br J Cancer 1997;75:477-481. (Pubitemid 27085285)
120. Tanigawa N, Amaya H, Matsumura M, Katoh Y, Kitaoka A, Aotake T, Shimomatsuya T, Rosenwasser OA, Iki M. Tumor angiogenesis and expression of thymidine phosphorylase/platelet derived endothelial cell growth factor in human gastric carcinoma. Cancer Lett 1996;108:281-290. (Pubitemid 26413534)
121. Takebayashi Y, Akiyama S, Akiba S, Yamada K, Miyadera K, Sumizawa T, Yamada Y, Murata F, Aikou T. Clinicopathologic and prognostic significance of an angiogenic factor, thymidine phosphorylase, in human colorectal carcinoma. J Natl Cancer Inst 1996;88:1110-1117. (Pubitemid 26274605)
122. Maeda K, Chung YS, Ogawa Y, Takatsuka S, Kang SM, Ogawa M, Sawada T, Onoda N, Kato Y, Sowa M. Thymidine phosphorylase/platelet-derived endothelial cell growth factor expression associated with hepatic metastasis in gastric carcinoma. Br J Cancer 1996;73:884-888. (Pubitemid 26116738)
123. Fox SB, Westwood M, Moghaddam A, Comley M, Turley H, Whitehouse RM, Bicknell R, Gatter KC, Harris AL. The angiogenic factor platelet-derived endothelial cell growth factor/thymidine phosphorylase is up-regulated in breast cancer epithelium and endothelium. Br J Cancer 1996;73:275-280. (Pubitemid 26047503)
124. Toi M, Hoshina S, Taniguchi T, Yamamoto Y, Ishitsuka H, Tominaga T. Expression of platelet-derived endothelial cell growth factor/thymidine phosphorylase in human breast cancer. Int J Cancer 1995;64:79-82.
125. Sugamoto T, Tanji N, Nishio S, Yokoyama M. Expression of platelet-derived endothelial cell growth factor in prostatic adenocarcinoma. Oncol Rep 1999;6:519-522.
126. Yamagata M, Mori M, Mimori K, Mafune KI, Tanaka Y, Ueo H, Akiyoshi T. Expression of pyrimidine nucleoside phosphorylase mRNA plays an important role in the prognosis of patients with oesophageal cancer. Br J Cancer 1999;79:565-569. (Pubitemid 29046237)
127. Mimori K, Ueo H, Shirasaka C, Shiraishi T, Yamagata M, Haraguchi M, Mori M. Up-regulated pyrimidine nucleoside phosphorylase in breast carcinoma correlates with lymph node metastasis. Ann Oncol 1999;10:111-113. (Pubitemid 29090600)
128. Mizutani Y, Okada Y, Yoshida O. Expression of platelet-derived endothelial cell growth factor in bladder carcinoma. Cancer 1997;79:1190-1194. (Pubitemid 27118614)
129. Alcalde RE, Terakado N, Otsuki K, Matsumura T. Angiogenesis and expression of platelet-derived endothelial cell growth factor in oral squamous cell carcinoma. Oncology 1997;54:324-328. (Pubitemid 27252729)
130. Kodama J, Seki N, Tokumo K, Hongo A, Miyagi Y, Yoshinouchi M, Okuda H, Kudo T. Platelet-derived endothelial cell growth factor is not implicated in progression of cervical cancer. Oncol Rep 1999;6:617-620. (Pubitemid 29151950)
131. Fujimoto J, Sakaguchi H, Hirose R, Ichigo S, Tamaya T. Expression of platelet-derived endothelial cell growth factor (PD-ECGF) and its mRNA in uterine cervical cancers. Br J Cancer 1999;79:1249-1254. (Pubitemid 29087906)
132. Hata K, Nagami H, Iida K, Miyazaki K, Collins WP. Expression of thymidine phosphorylase in malignant ovarian tumors: Correlation with microvessel density and an ultrasound-derived index of angiogenesis. Ultrasound Obstet Gynecol 1998;12:201-206. (Pubitemid 28474928)
133. Volm M, Mattern J, Koomagi R. Expression of platelet-derived endothelial cell growth factor in nonsmall cell lung carcinomas: Relationship to various biological factors. Int J Oncol 1998;13:975-979. (Pubitemid 28506067)
134. Sawase K, Nomata K, Kanetake H, Saito Y. The expression of platelet-derived endothelial cell growth factor in human bladder cancer. Cancer Lett 1998;130:35-41. (Pubitemid 28425335)
135. Nagaoka H, Iino Y, Takei H, 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 1998;13:449-454. (Pubitemid 28372665)
136. Fujieda S, Sunaga H, Tsuzuki H, Tanaka N, Saito H. Expression of platelet-derived endothelial cell growth factor in oral and oropharyngeal carcinoma. Clin Cancer Res 1998;4:1583-1590. (Pubitemid 28304717)
137. Matsumura M, Chiba Y, Lu C, Amaya H, Shimomatsuya T, Horiuchi T, Muraoka R, Tanigawa N. Platelet-derived endothelial cell growth factor/thymidine phosphorylase expression correlated with tumor angiogenesis and macrophage infiltration in colorectal cancer. Cancer Lett 1998;128:55-63. (Pubitemid 28279365)
138. Koukourakis MI, Giatromanolaki A, Kakolyris S, O'Byrne KJ, Apostolikas N, Skarlatos J, Gatter KC, Harris AL. Different patterns of stromal and cancer cell thymidine phosphorylase reactivity in non-small-cell lung cancer: Impact on tumour neoangiogenesis and survival. Br J Cancer 1998;77:1696-1703. (Pubitemid 28230477)
139. Leek RD, Landers R, Fox SB, Ng F, Harris AL, Lewis CE. Association of tumour necrosis factor alpha and its receptors with thymidine phosphorylase expression in invasive breast carcinoma. Br J Cancer 1998;77:2246-2251. (Pubitemid 28263948)
140. Takahashi Y, Bucana CD, Akagi Y, Liu W, Cleary KR, Mai M, Ellis LM. Significance of platelet-derived endothelial cell growth factor in the angiogenesis of human gastric cancer. Clin Cancer Res 1998;4:429-434. (Pubitemid 28122759)
141. Aikawa H, Takahashi H, Fujimura S, Sato M, Endo C, Sakurada A, Kondo T, Tanita T, Matsumura Y, Ono S, Saito Y, Sagawa M. Immunohistochemical study on tumor angiogenic factors in non-small cell lung cancer. Anticancer Res 1999;19:4305-4309.
142. Saito S, Tsuno N, Nagawa H, Sunami E, Zhengxi J, Osada T, Kitayama J, Shibata Y, Tsuruo T, Muto T. Expression of platelet-derived endothelial cell growth factor correlates with good prognosis in patients with colorectal carcinoma. Cancer 2000;88:42-49. (Pubitemid 30027677)
143. Ueda M, Terai Y, Kumagai K, Ueki K, Okamoto Y, Ueki M. Correlation between tumor angiogenesis and expression of thymidine phosphorylase, and patient outcome in uterine cervical carcinoma. Hum Pathol 1999;30:1389-1394. (Pubitemid 29534305)
144. Matsuura T, Kuratate I, Teramachi K, Osaki M, Fukuda Y, Ito H. Thymidine phosphorylase expression is associated with both increase of intratumoral microvessels and decrease of apoptosis in human colorectal carcinomas. Cancer Res 1999;59:5037-5040. (Pubitemid 29472912)
145. Saito H, Tsujitani S, Oka S, Kondo A, Ikeguchi M, Maeta M, Kaibara N. The expression of thymidine phosphorylase correlates with angiogenesis and the efficacy of chemotherapy using fluorouracil derivatives in advanced gastric carcinoma. Br J Cancer 1999;81:484-489. (Pubitemid 29458803)
146. Shomori K, Sakatani T, Goto A, Matsuura T, Kiyonari H, Ito H. Thymidine phosphorylase expression in human colorectal mucosa, adenoma and carcinoma: Role of p53 expression. Pathol Int 1999;49:491-499. (Pubitemid 29411163)
147. Ikeguchi M, Oka S, Saito H, Kondo A, Tsujitani S, Maeta M, Kaibara N. Clinical significance of the detection of thymidine phosphorylase activity in esophageal squamous cell carcinomas. Eur Surg Res 1999;31:357-363. (Pubitemid 29381172)
148. Yamashita J, Ogawa M, Abe M, Nishida M. Platelet-derived endothelial cell growth factor/ thymidine phosphorylase concentrations differ in small cell and non-small cell lung cancer. Chest 1999;116:206-211. (Pubitemid 29340284)
149. Kodama J, Yoshinouchi M, Seki N, Hongo A, Miyagi Y, Kudo T. Angiogenesis and platelet-derived endothelial cell growth factor/thymidine phosphorylase expression in cervical cancer. Int J Oncol 1999;15:149-154.
150. Koide N, Watanabe H, Yazawa K, Adachi W, Amano J. Immunohistochemical expression of thymidine phosphorylase/platelet-derived endothelial cell growth factor in squamous cell carcinoma of the esophagus. Hepatogastroenterology 1999;46:944-951. (Pubitemid 29224770)
151. Toi M, Ueno T, Matsumoto H, Saji H, Funata N, Koike M, Tominaga T. Significance of thymidine phosphorylase as a marker of protumor monocytes in breast cancer. Clin Cancer Res 1999;5:1131-1137. (Pubitemid 29233229)
152. Hata K, Takebayashi Y, Iida K, Fujiwaki R, Fukumoto M, Miyazaki K. Expression of thymidine phosphorylase in human cervical cancer. Anticancer Res 1999;19:709-716. (Pubitemid 29168320)
153. Volm M, Koomagi R, Mattern J. PD-ECGF, bFGF, and VEGF expression in non-small cell lung carcinomas and their association with lymph node metastasis. Anticancer Res 1999;19:651-655. (Pubitemid 29168310)
154. Hata K, Kamikawa T, Arao S, Tashiro H, Katabuchi H, Okamura H, Fujiwaki R, Miyazaki K, Fukumoto M. Expression of the thymidine phosphorylase gene in epithelial ovarian cancer. Br J Cancer 1999;79:1848-1854. (Pubitemid 29132314)
155. Tanioka K, Takeshima H, Hirano H, Kimura T, Nagata S, Akiyama S, Kuratsu J. Biological role of thymidine phosphorylase in human astrocytic tumors. Oncol Rep 2001;8:491-496. (Pubitemid 33758442)
156. Hata K, Fujiwaki R, Nakayama K, Maede Y, Fukumoto M, Miyazaki K. Expression of thymidine phosphorylase and vascular endothelial growth factor in epithelial ovarian cancer: Correlation with angiogenesis and progression of the tumor. Anticancer Res 2000;20:3941-3949. (Pubitemid 32002302)
157. Okada K, Yokoyama K, Okihara K, Ukimura O, Kojima M, Miki T, Takamatsu T. Immunohistochemical localization of platelet-derived endothelial cell growth factor expression and its relation to angiogenesis in prostate. Urology 2001;57:376-381. (Pubitemid 32140835)
158. Matsumoto Y, Ishiko O, Deguchi M, Ogita S, Haba T, Wakasa K. Platelet-derived endothelial cell growth factor in keratinizing-type squamous cell uterine cervical cancer. Oncol Rep 2001;8:93-97. (Pubitemid 33758207)
159. Terai Y, Ueda M, Kumagai K, Ueki K, Ueki M. Tumor angiogenesis and thymidine phosphorylase expression in ovarian carcinomas including serous surface papillary adenocarcinoma of the peritoneum. Int J Gynecol Pathol 2000;19:354-360. (Pubitemid 30842154)
160. Fujiwaki R, Hata K, Nakayama K, Fukumoto M, Miyazaki K. Gene expression for dihydropyrimidine dehydrogenase and thymidine phosphorylase influences outcome in epithelial ovarian cancer. J Clin Oncol 2000;18:3946-3951.
161. Dobbs SP, Brown LJ, Ireland D, Abrams KR, Murray JC, Gatter K, Harris A, Steward WP, O'Byrne KJ. Platelet-derived endothelial cell growth factor expression and angiogenesis in cervical intraepithelial neoplasia and squamous cell carcinoma of the cervix. Ann Diagn Pathol 2000;4:286-292. (Pubitemid 30818619)
162. Li Z, Shimada Y, Uchida S, Maeda M, Kawabe A, Mori A, Itami A, Kano M, Watanabe G, Imamura M. TGF-alpha as well as VEGF, PD-ECGF and bFGF contribute to angiogenesis of esophageal squamous cell carcinoma. Int J Oncol 2000;17:453-460.
163. Fujimoto J, Sakaguchi H, Aoki I, Tamaya T. The value of platelet-derived endothelial cell growth factor as a novel predictor of advancement of uterine cervical cancers. Cancer Res 2000;60:3662-3665. (Pubitemid 30482191)
164. Sakatani T, Okamoto E, Tsujitani S, Ikeguchi M, Kaibara N, Ito H. Expressions of thymidine phosphorylase (dThdPase) and vascular endothelial growth factor on angiogenesis in intestinaltype gastric carcinoma. Oncol Rep 2000;7:831-836.
165. Takano S, Tsuboi K, Matsumura A, Tomono Y, Mitsui Y, Nose T. Expression of the angiogenic factor thymidine phosphorylase in human astrocytic tumors. J Cancer Res Clin Oncol 2000;126:145-152. (Pubitemid 30140214)
166. Van Triest B, Pinedo HM, Blaauwgeers JL, van Diest PJ, Schoenmakers PS, Voorn DA, Smid K, Hoekman K, Hoitsma HF, Peters GJ. Prognostic role of thymidylate synthase, thymidine phosphorylase/platelet-derived endothelial cell growth factor, and proliferation markers in colorectal cancer. Clin Cancer Res 2000;6:1063-1072. (Pubitemid 30159368)
167. Tang W, Wang X, Utsunomiya H, Nakamuta Y, Yang Q, Zhang Q, Zhou G, Tsubota Y, Mabuchi Y, Li L, Kakudo K. Thymidine phosphorylase expression in tumor stroma of uterine cervical carcinomas: Histological features and microvessel density. Cancer Lett 2000;148:153-159. (Pubitemid 30047102)
168. Tanaka T, Yoshiki T, Arai Y, Higuchi K, Kageyama S, Ogawa Y, Isono T, Okada Y. Expression of platelet-derived endothelial cell growth factor/thymidine phosphorylase in human bladder cancer. Jpn J Cancer Res 1999;90:1344-1350. (Pubitemid 30032073)
169. Fujiwaki R, Hata K, Iida K, Maede Y, Koike M, Miyazaki K. Thymidine phosphorylase expression in progression of cervical cancer: Correlation with microvessel count, proliferating cell nuclear antigen, and apoptosis. J Clin Pathol 1999;52:598-603. (Pubitemid 29371905)
170. Hirano Y, Takayama T, Kageyama S, Ushiyama T, Suzuki K, Fujita K. Thymidine phosphorylase and dihydropyrimidine dehydrogenase in renal cell carcinoma: Relationship between histological parameters and chemosensitivity to 5-fluorouracil. Eur Urol 2003;43:45-51. (Pubitemid 36134315)
171. Hirano Y, Kageyama S, Ushiyama T, Suzuki K, Fujita K. Clinical significance of thymidine phosphorylase and dihydropyrimidine dehydrogenase expression in transitional cell cancer. Cancer Chemother Pharmacol 2003;51:29-35. (Pubitemid 36057020)
172. Kaio E, Tanaka S, Kitadai Y, Sumii M, Yoshihara M, Haruma K, Chayama K. Clinical significance of angiogenic factor expression at the deepest invasive site of advanced colorectal carcinoma. Oncology 2003;64:61-73. (Pubitemid 35477956)
173. Ranieri G, Labriola A, Achille G, Florio G, Zito AF, Grammatica L, Paradiso A. Microvessel density, mast cell density and thymidine phosphorylase expression in oral squamous carcinoma. Int J Oncol 2002;21:1317-1323.
174. Aoki T, Katsumata K, Tsuchida A, Tomioka H, Koyanagi Y. Correlation between malignancy grade and p53 gene in relation to thymidine phosphorylase activity in colorectal cancer patients. Oncol Rep 2002;9:1267-1271.
175. Yao L, Itoh S, Furuta I. Thymidine phosphorylase expression in oral squamous cell carcinoma. Oral Oncol 2002;38:584-590. (Pubitemid 34880119)
176. Kanzaki A, Takebayashi Y, Bando H, Eliason JF, Watanabe SS, Miyashita H, Fukumoto M, Toi M, Uchida T. Expression of uridine and thymidine phosphorylase genes in human breast carcinoma. Int J Cancer 2002;97:631-635. (Pubitemid 34087802)
177. Yang Q, Barbareschi M, Mori I, Mauri F, Muscara M, Nakamura M, Nakamura Y, Yoshimura G, Sakurai T, Caffo O, Galligioni E, Dalla PP, Kakudo K. Prognostic value of thymidine phosphorylase expression in breast carcinoma. Int J Cancer 2002;97:512-517. (Pubitemid 34027812)
178. Yao Y, Kubota T, Sato K, Kitai R. Macrophage infiltration-associated thymidine phosphorylase expression correlates with increased microvessel density and poor prognosis in astrocytic tumors. Clin Cancer Res 2001;7:4021-4026. (Pubitemid 34044622)
179. Makoto O, Takeda A, Ting-Leig L, Shinnichi O, Hisahiro M, Yutaka F, Yoshihiro N, Kobayashi S, Gunji Y, Suzuki T, Takenori O, Hideaki S. Prognostic significance of thymidine phosphorylase and p53 co-expression in esophageal squamous cell carcinoma. Oncol Rep 2002;9:23-28.
180. Yano T, Takeo S. Thymidine phosphorylase activity in nonsmall cell lung carcinoma tissues. Cancer 2001;92:2658-2661. (Pubitemid 33049450)
181. Li S, Nomata K, Sawase K, Noguchi M, Kanda S, Kanetake H. Prognostic significance of platelet-derived endothelial cell growth factor/thymidine phosphorylase expression in stage pT1 G3 bladder cancer. Int J Urol 2001;8:478-482. (Pubitemid 32953818)
182. Hirano H, Tanioka K, Yokoyama S, Akiyama S, Kuratsu J. Angiogenic effect of thymidine phosphorylase on macrophages in glioblastoma multiforme. J Neurosurg 2001;95:89-95. (Pubitemid 32799777)
183. van Halteren HK, Peters HM, van Krieken JH, Coebergh JW, Roumen RM, van der WE, Wagener JT, Vreugdenhil G. Tumor growth pattern and thymidine phosphorylase expression are related with the risk of hematogenous metastasis in patients with Astler Coller B1/B2 colorectal carcinoma. Cancer 2001;91:1752-1757. (Pubitemid 32377962)
184. Okamoto E, Osaki M, Kase S, Adachi H, Kaibara N, Ito H. Thymidine phosphorylase expression causes both the increase of intratumoral microvessels and decrease of apoptosis in human esophageal carcinomas. Pathol Int 2001;51:158-164. (Pubitemid 32337064)
185. Suzuki K, Morita T, Hashimoto S, Tokue A. Thymidine phosphorylase/ platelet-derived endothelial cell growth factor (PD-ECGF) associated with prognosis in renal cell carcinoma. Urol Res 2001;29:7-12. (Pubitemid 32216721)
186. Ioachim E. Thymidine phoshorylase expression in breast cancer: The prognostic significance and its association with other angiogenesis related proteins and extracellular matrix components. Histol Histopathol 2008;23:187-196.
187. Kobayashi Y, Wada Y, Ohara T, Okuda Y, Suzuki N, Hasegawa K, Kiguchi K, Ishizuka B. Enzymatic activities of uridine and thymidine phosphorylase in normal and cancerous uterine cervical tissues. Hum Cell 2007;20:107-110. (Pubitemid 47628567)
188. Nonomura N, Nakai Y, Nakayama M, Inoue H, Nishimura K, Hatanaka E, Arima R, Kishimoto T, Miki T, Kuroda H, Okuyama A. The expression of thymidine phosphorylase is a prognostic predictor for the intravesical recurrence of superficial bladder cancer. Int J Clin Oncol 2006;11:297-302. (Pubitemid 44306213)
189. Takayama T, Mugiya S, Sugiyama T, Aoki T, Furuse H, Liu H, Hirano Y, Kai F, Ushiyama T, Ozono S. High levels of thymidine phosphorylase as an independent prognostic factor in renal cell carcinoma. Jpn J Clin Oncol 2006;36:564-569. (Pubitemid 44593899)
190. Aoki S, Yamada Y, Nakamura K, Taki T, Tobiume M, Honda N. Thymidine phosphorylase expression as a prognostic marker for predicting recurrence in primary superficial bladder cancer. Oncol Rep 2006;16:279-284.
191. Nomiya T, Nemoto K, Nakata E, Takai Y, Yamada S. Expression of thymidine phosphorylase and VEGF in esophageal squamous cell carcinoma. Oncol Rep 2006;15:1497-1501.
192. Lassmann S, Hennig M, Rosenberg R, Nahrig J, Schreglmann J, Krause F, Poignee-Heger M, Nekarda H, Hofler H, Werner M. Thymidine phosphorylase, dihydropyrimidine dehydrogenase and thymidylate synthase mRNA expression in primary colorectal tumors-correlation to tumor histopathology and clinical follow-up. Int J Colorectal Dis 2006;21:238-247. (Pubitemid 43280331)
193. Stavropoulos NE, Bouropoulos C, Ioachim E, Michael M, Hastazeris K, Tsimaris I, Kalogeras D, Liamis Z, Kafarakis V, Stefanaki S, Malamou-Mitsi V. Prognostic significance of thymidine phosphorylase in superficial bladder carcinoma. Int Urol Nephrol 2005;37:55-60. (Pubitemid 41236243)
194. Nakamura T, Ozawa S, Kitagawa Y, Shih CH, Ueda M, Kitajima M. Expression of basic fibroblast growth factor is associated with a good outcome in patients with squamous cell carcinoma of the esophagus. Oncol Rep 2005;14:617-623.
195. Li C, Shintani S, Terakado N, Klosek SK, Ishikawa T, Nakashiro K, Hamakawa H. Microvessel density and expression of vascular endothelial growth factor, basic fibroblast growth factor, and platelet-derived endothelial growth factor in oral squamous cell carcinomas. Int J Oral Maxillofac Surg 2005;34:559-565. (Pubitemid 40790355)
196. Kataoka A, Yuasa T, Kageyama S, Iwaki H, Higuchi K, Tanaka T, Okada Y, Yoshiki T. Expression of thymidine phosphorylase correlates with microvessel density in prostate cancer. Oncol Rep 2005;13:597-600.
197. Yasuno M, Mori T, Koike M, Takahashi K, Toi M, Takizawa T, Shimizu S, Yamaguchi T, Matsumoto H. Importance of thymidine phosphorylase expression in tumor stroma as a prognostic factor in patients with advanced colorectal carcinoma. Oncol Rep 2005;13:405-412.
198. Miszczak-Zaborska E, Wojcik-Krowiranda K, Kubiak R, Bienkiewicz A, Bartkowiak J. The activity of thymidine phosphorylase as a new ovarian tumor marker. Gynecol Oncol 2004;94:86-92. (Pubitemid 38950503)
199. Li H, Suo Z, Zhang Y, Risberg B, Karlsson MG, Villman K, Nesland JM. The prognostic significance of thymidine phosphorylase, thymidylate synthase and dihydropyrimidine dehydrogenase mRNA expressions in breast carcinomas. Histol Histopathol 2004;19:129-136. (Pubitemid 38111257)
200. Watanabe Y, Nakai H, Ueda H, Nozaki K, Hoshiai H, Noda K. Platelet-derived endothelial cell growth factor predicts of progression and recurrence in primary epithelial ovarian cancer. Cancer Lett 2003;200:173-176. (Pubitemid 38366099)
201. Morita T, Matsuzaki A, Tokue A. Quantitative analysis of thymidine phosphorylase and dihydropyrimidine dehydrogenase in renal cell carcinoma. Oncology 2003;65:125-131. (Pubitemid 37025973)
202. Sato J, Sata M, Nakamura H, Inoue S, Wada T, Takabatake N, Otake K, Tomoike H, Kubota I. Role of thymidine phosphorylase on invasiveness and metastasis in lung adenocarcinoma. Int J Cancer 2003;106:863-870. (Pubitemid 37071664)
203. Mizutani Y, Wada H, Yoshida O, Fukushima M, Kawauchi A, Nakao M, Miki T. The significance of thymidine phosphorylase/platelet-derived endothelial cell growth factor activity in renal cell carcinoma. Cancer 2003;98:730-736. (Pubitemid 36959268)
204. Kikuno N, Yoshino T, Urakami S, Shigeno K, Kishi H, Hata K, Shiina H, Igawa M. The role of thymidine phosphorylase (TP) mRNA expression in angiogenesis of prostate cancer. Anticancer Res 2003;23:1305-1312. (Pubitemid 36754092)
205. Wada S, Yoshimura R, Naganuma T, Yoshida N, Narita K, Ikemoto S. Thymidine phosphorylase levels as a prognostic factor in renal cell carcinoma. BJU Int 2003;91:105-108. (Pubitemid 36098806)
206. Morita T, Matsuzaki A, Suzuki K, Tokue A. Role of thymidine phosphorylase in biomodulation of fluoropyrimidines. Curr Pharm Biotechnol 2001;2:257-267. (Pubitemid 32798800)
207. Ono M. Molecular links between tumor angiogenesis and inflammation: Inflammatory stimuli of macrophages and cancer cells as targets for therapeutic strategy. Cancer Sci 2008;99:1501-1506.
208. Torisu-Itakura H, Furue M, Kuwano M, Ono M. Co-expression of thymidine phosphorylase and heme oxygenase-1 in macrophages in human malignant vertical growth melanomas. Jpn J Cancer Res 2000;91:906-910. (Pubitemid 30774565)
209. Zhang JM, Mizoi T, Shiiba K, Sasaki I, Matsuno S. Expression of thymidine phosphorylase by macrophages in colorectal cancer tissues. World J Gastroenterol 2004;10:545-549. (Pubitemid 38325312)
210. Sivridis E, Giatromanolaki A, Papadopoulos I, Gatter KC, Harris AL, Koukourakis MI. Thymidine phosphorylase expression in normal, hyperplastic and neoplastic prostates: Correlation with tumour associated macrophages, infiltrating lymphocytes, and angiogenesis. Br J Cancer 2002;86:1465-1471. (Pubitemid 34548071)
211. Poon RT, Fan ST, Wong J. Clinical implications of circulating angiogenic factors in cancer patients. J Clin Oncol 2001;19:1207-1225. (Pubitemid 32176299)
212. Shimada H, Hoshino T, Okazumi S, Matsubara H, Funami Y, Nabeya Y, Hayashi H, Takeda A, Shiratori T, Uno T, Ito H, Ochiai T. Expression of angiogenic factors predicts response to chemoradiotherapy and prognosis of oesophageal squamous cell carcinoma. Br J Cancer 2002;86:552-557. (Pubitemid 34185091)
213. Pauly JL, Schuller MG, Zelcer AA, Kirss TA, Gore SS, Germain MJ. Identification and comparative analysis of thymidine phosphorylase in the plasma of healthy subjects and cancer patients. J Natl Cancer Inst 1977;58:1587-1590.
214. Pauly JL, Paolini NS, Ebarb RL, Germain MJ. Elevated thymidine phosphorylase activity in the plasma and ascitis fluids of tumor-bearing animals. Proc Soc Exp Biol Med 1978;157:262-267.
215. Shimada H, Takeda A, Shiratori T, Nabeya Y, Okazumi S, Matsubara H, Funami Y, Hayashi H, Gunji Y, Kobayashi S, Suzuki T, Ochiai T. Prognostic significance of serum thymidine phosphorylase concentration in esophageal squamous cell carcinoma. Cancer 2002;94:1947-1954. (Pubitemid 34270047)
216. Haraguchi M, Komuta K, Akashi A, Furui J, Kanematsu T. Occurrence of hematogenous metastasis and serum levels of thymidine phosphorylase in colorectal cancer. Oncol Rep 2003;10:1207-1212.
217. Ferrara N, Kerbel RS. Angiogenesis as a therapeutic target. Nature 2005;438:967-974.
218. Carmeliet P. Angiogenesis in life, disease and medicine. Nature 2005;438:932-936.
219. Folkman J. Angiogenesis: An organizing principle for drug discovery? Nat Rev Drug Discov 2007;6:273-286.
220. Bergers G, Benjamin LE. Tumorigenesis and the angiogenic switch. Nat Rev Cancer 2003;3:401-410.
221. Haraguchi M, Miyadera K, Uemura K, Sumizawa T, Furukawa T, Yamada K, Akiyama S, Yamada Y. Angiogenic activity of enzymes. Nature 1994;368:198.
222. Liekens S, Bilsen F, De Clercq E, Priego EM, Camarasa MJ, Pérez-Pérez MJ, Balzarini J. Antiangiogenic activity of a novel multi-substrate analogue inhibitor of thymidine phosphorylase. FEBS Lett 2002;510:83-88. (Pubitemid 34084888)
223. Uchimiya H, Furukawa T, Okamoto M, Nakajima Y, Matsushita S, Ikeda R, Gotanda T, Haraguchi M, Sumizawa T, Ono M, Kuwano M, Kanzaki T, Akiyama S. Suppression of thymidine phosphorylase-mediated angiogenesis and tumor growth by 2-deoxy-L-ribose. Cancer Res 2002;62:2834-2839. (Pubitemid 34525768)
224. Miyadera K, Sumizawa T, Haraguchi M, Yoshida H, Konstanty W, Yamada Y, Akiyama S. Role of thymidine phosphorylase activity in the angiogenic effect of platelet derived endothelial cell growth factor/thymidine phosphorylase. Cancer Res 1995;55:1687-1690.
225. Pula G, Mayr U, Evans C, Prokopi M, Vara DS, Yin X, Astroulakis Z, Xiao Q, Hill J, Xu Q, Mayr M. Proteomics identifies thymidine phosphorylase as a key regulator of the angiogenic potential of colony-forming units and endothelial progenitor cell cultures. Circ Res 2009;104:32-40.
226. Asahara T, Murohara T, Sullivan A, Silver M, van der ZR, Li T, Witzenbichler B, Schatteman G, Isner JM. Isolation of putative progenitor endothelial cells for angiogenesis. Science 1997;275:964-967. (Pubitemid 27087709)
227. Asahara T, Masuda H, Takahashi T, Kalka C, Pastore C, Silver M, Kearne M, Magner M, Isner JM. Bone marrow origin of endothelial progenitor cells responsible for postnatal vasculogenesis in physiological and pathological neovascularization. Circ Res 1999;85:221-228. (Pubitemid 29377293)
228. Marsboom G, Janssens S. Endothelial progenitor cells: New perspectives and applications in cardiovascular therapies. Expert Rev Cardiovasc Ther 2008;6:687-701.
229. Debatin KM, Wei J, Beltinger C. Endothelial progenitor cells for cancer gene therapy. Gene Ther 2008;15:780-786. (Pubitemid 351627362)
230. Hotchkiss KA, Ashton AW, Klein RS, Lenzi ML, Zhu GH, Schwartz EL. Mechanisms by which tumor cells and monocytes expressing the angiogenic factor thymidine phosphorylase mediate human endothelial cell migration. Cancer Res 2003;63:527-533.
231. Sengupta S, Sellers LA, Matheson HB, Fan TP. Thymidine phosphorylase induces angiogenesis in vivo and in vitro: An evaluation of possible mechanisms. Br J Pharmacol 2003;139:219-231. (Pubitemid 36760354)
232. Stevenson DP, Milligan SR, Collins WP. Effects of platelet-derived endothelial cell growth factor/thymidine phosphorylase, substrate, and products in a three-dimensional model of angiogenesis. Am J Pathol 1998;152:1641-1646. (Pubitemid 28275022)
233. Stevenson DP, Collins WP, Farzaneh F, Hata K, Miyazaki K. Thymidine phosphorylase activity and prodrug effects in a three-dimensional model of angiogenesis: Implications for the treatment of ovarian cancer. Am J Pathol 1998;153:1573-1578. (Pubitemid 28509914)
234. Brown NS, Jones A, Fujiyama C, Harris AL, Bicknell R. Thymidine phosphorylase induces carcinoma cell oxidative stress and promotes secretion of angiogenic factors. Cancer Res 2000;60:6298-6302. (Pubitemid 30952126)
235. de Bruin M, Smid K, Laan AC, Noordhuis P, Fukushima M, Hoekman K, Pinedo HM, Peters GJ. Rapid disappearance of deoxyribose-1-phosphate in platelet derived endothelial cell growth factor/thymidine phosphorylase overexpressing cells. Biochem Biophys Res Commun 2003;301:675-679. (Pubitemid 36268944)
236. Usuki K, Miyazono K, Heldin CH. Covalent linkage between nucleotides and platelet-derived endothelial cell growth factor. J Biol Chem 1991;266:20525-20531. (Pubitemid 21908492)
237. Brown NS, Bicknell R. Thymidine phosphorylase, 2-deoxy-D-ribose and angiogenesis. Biochem J 1998;334:1-8.
238. Groarke JM, Mahoney WC, Hope JN, Furlong CE, Robb FT, Zalkin H, Hermodson MA. The amino acid sequence of D-ribose-binding protein from Escherichia coli K12. J Biol Chem 1983;258:12952-12956.
239. Wolanin PM, Thomason PA, Stock JB. Histidine protein kinases: Key signal transducers outside the animal kingdom. Genome Biol 2002;3:REVIEWS3013.
240. Hotchkiss KA, Ashton AW, Schwartz EL. 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 2003;278:19272-19279.
241. Seeliger H, Guba M, Koehl GE, Doenecke A, Steinbauer M, Bruns CJ, Wagner C, Frank E, Jauch KW, Geissler EK. Blockage of 2-deoxy-D-ribose-induced angiogenesis with rapamycin counteracts a thymidine phosphorylase-based escape mechanism available for colon cancer under 5-fluorouracil therapy. Clin Cancer Res 2004;10:1843-1852. (Pubitemid 38435576)
242. Seeliger H, Guba M, Kleespies A, Jauch KW, Bruns CJ. Role of mTOR in solid tumor systems: A therapeutical target against primary tumor growth, metastases, and angiogenesis. Cancer Metastasis Rev 2007;26:611-621. (Pubitemid 350115107)
243. Malik RK, Parsons JT. Integrin-dependent activation of the p70 ribosomal S6 kinase signaling pathway. J Biol Chem 1996;271:29785-29791. (Pubitemid 26389608)
244. Gan B, Yoo Y, Guan JL. Association of focal adhesion kinase with tuberous sclerosis complex 2 in the regulation of s6 kinase activation and cell growth. J Biol Chem 2006;281:37321-37329. (Pubitemid 46042036)
245. Tenhunen R, Marver HS, Schmid R. Microsomal heme oxygenase. Characterization of the enzyme. J Biol Chem 1969;244:6388-6394.
246. Bussolati B, Ahmed A, Pemberton H, Landis RC, Di Carlo F, Haskard DO, Mason JC. Bifunctional role for VEGF-induced heme oxygenase-1 in vivo: Induction of angiogenesis and inhibition of leukocytic infiltration. Blood 2004;103:761-766. (Pubitemid 38129530)
247. Deshane J, Chen S, Caballero S, Grochot-Przeczek A, Was H, Li CS, Lach R, Hock TD, Chen B, Hill-Kapturczak N, Siegal GP, Dulak J, Jozkowicz A, Grant MB, Agarwal A. Stromal cell-derived factor 1 promotes angiogenesis via a heme oxygenase 1-dependent mechanism. J Exp Med 2007;204:605-618. (Pubitemid 46457083)
248. Loboda A, Jazwa A, Grochot-Przeczek A, Rutkowski AJ, Cisowski J, Agarwal A, Jozkowicz A, Dulak J. Heme oxygenase-1 and the vascular bed: From molecular mechanisms to therapeutic opportunities. Antioxid Redox Signal 2008;10:1767-1812.
249. Dulak J, Deshane J, Jozkowicz A, Agarwal A. Heme oxygenase-1 and carbon monoxide in vascular pathobiology: Focus on angiogenesis. Circulation 2008;117:231-241.
250. Deramaudt BM, Braunstein S, Remy P, Abraham NG. Gene transfer of human heme oxygenase into coronary endothelial cells potentially promotes angiogenesis. J Cell Biochem 1998;68:121-127. (Pubitemid 27520116)
251. Jazwa A, Loboda A, Golda S, Cisowski J, Szelag M, Zagorska A, Sroczynska P, Drukala J, Jozkowicz A, Dulak J. Effect of heme and heme oxygenase-1 on vascular endothelial growth factor synthesis and angiogenic potency of human keratinocytes. Free Radic Biol Med 2006;40:1250-1263.
252. Li W, Tanaka K, Morioka K, Uesaka T, Yamada N, Takamori A, Handa M, Tanabe S, Ihaya A. Thymidine phosphorylase gene transfer inhibits vascular smooth muscle cell proliferation by upregulating heme oxygenase-1 and p27KIP1. Arterioscler Thromb Vasc Biol 2005;25:1370-1375. (Pubitemid 40923354)
253. Carmeliet P. VEGF as a key mediator of angiogenesis in cancer. Oncology 2005;69:4-10. (Pubitemid 41680947)
254. Brown NS, Streeter EH, Jones A, Harris AL, 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 2005;92:1696-1701. (Pubitemid 40756481)
255. Hu J, Van den Steen PE, Sang QX, Opdenakker G. Matrix metalloproteinase inhibitors as therapy for inflammatory and vascular diseases. Nat Rev Drug Discov 2007;6:480-498. (Pubitemid 47064570)
256. Ueda M, Terai Y, Kumagai K, Ueki K, Kanemura M, Ueki M. Correlation between thymidine phosphorylase expression and invasion phenotype in cervical carcinoma cells. Int J Cancer 2001;91:778-782. (Pubitemid 32178644)
257. Nakajima Y, Haraguchi M, Furukawa T, Yamamoto M, Nakanishi H, Tatematsu M, Akiyama S. 2-Deoxy-L-ribose inhibits the invasion of thymidine phosphorylase-overexpressing tumors by suppressing matrix metalloproteinase-9. Int J Cancer 2006;119:1710-1716. (Pubitemid 44258781)
258. Gotanda T, Haraguchi M, Tachiwada T, Shinkura R, Koriyama C, Akiba S, Kawahara M, Nishiyama K, Sumizawa T, Furukawa T, Mimata H, Nomura Y, Akiyama S, Nakagawa M. Molecular basis for the involvement of thymidine phosphorylase in cancer invasion. Int J Mol Med 2006;17:1085-1091.
259. Kurizaki T, Toi M, Tominaga T. Relationship between matrix metalloproteinase expression and tumor angiogenesis in human breast carcinoma. Oncol Rep 1998;5:673-677. (Pubitemid 28189326)
260. Gunningham SP, Currie MJ, Morrin HR, Tan EY, Turley H, Dachs GU, Watson AI, Frampton C, Robinson BA, Fox SB. The angiogenic factor thymidine phosphorylase up-regulates the cell adhesion molecule P-selectin in human vascular endothelial cells and is associated with P-selectin expression in breast cancers. J Pathol 2007;212:335-344. (Pubitemid 47010067)
261. Borsig L, Wong R, Feramisco J, Nadeau DR, Varki NM, Varki A. Heparin and cancer revisited: Mechanistic connections involving platelets, P-selectin, carcinoma mucins, and tumor metastasis. Proc Natl Acad Sci USA 2001;98:3352-3357. (Pubitemid 32220849)
262. Morbidelli L, Brogelli L, Granger HJ, Ziche M. Endothelial cell migration is induced by soluble P-selectin. Life Sci 1998;62:L7-11. (Pubitemid 28132978)
263. Currie MJ, Gunningham SP, Han C, Scott PA, Robinson BA, Harris AL, Fox SB. Angiopoietin-1 is inversely related to thymidine phosphorylase expression in human breast cancer, indicating a role in vascular remodeling. Clin Cancer Res 2001;7:918-927. (Pubitemid 32708730)
264. Davis S, Aldrich TH, Jones PF, Acheson A, Compton DL, Jain V, Ryan TE, Bruno J, Radziejewski C, Maisonpierre PC, Yancopoulos GD. Isolation of angiopoietin-1, a ligand for the TIE2 receptor, by secretion-trap expression cloning. Cell 1996;87:1161-1169. (Pubitemid 27010100)
265. Papapetropoulos A, Garcia-Cardena G, Dengler TJ, Maisonpierre PC, Yancopoulos GD, Sessa WC. Direct actions of angiopoietin-1 on human endothelium: Evidence for network stabilization, cell survival, and interaction with other angiogenic growth factors. Lab Invest 1999;79:213-223. (Pubitemid 29110651)
266. Suri C, Jones PF, Patan S, Bartunkova S, Maisonpierre PC, Davis S, Sato TN, Yancopoulos GD. Requisite role of angiopoietin-1, a ligand for the TIE2 receptor, during embryonic angiogenesis. Cell 1996;87:1171-1180. (Pubitemid 27010101)
267. Kwak HJ, So JN, Lee SJ, Kim I, Koh GY. Angiopoietin-1 is an apoptosis survival factor for endothelial cells. FEBS Lett 1999;448:249-253. (Pubitemid 29168496)
268. Li W, Tanaka K, Ihaya A, Fujibayashi Y, Takamatsu S, Morioka K, Sasaki M, Uesaka T, Kimura T, Yamada N, Tsuda T, Chiba Y. Gene therapy for chronic myocardial ischemia using platelet-derived endothelial cell growth factor in dogs. Am J Physiol Heart Circ Physiol 2005;288:H408-H415. (Pubitemid 40023873)
269. Li W, Tanaka K, Morioka K, Takamori A, Handa M, Yamada N, Ihaya A. Long-term effect of gene therapy for chronic ischemic myocardium using platelet-derived endothelial cell growth factor in dogs. J Gene Med 2008;10:412-420.
270. Deng YM, Wu BJ, Witting PK, Stocker R. Probucol protects against smooth muscle cell proliferation by upregulating heme oxygenase-1. Circulation 2004;110:1855-1860. (Pubitemid 39299229)
271. Handa M, Li W, Morioka K, Takamori A, Yamada N, Ihaya A. Adventitial delivery of platelet-derived endothelial cell growth factor gene prevented intimal hyperplasia of vein graft. J Vasc Surg 2008;48:1566-1574.
272. Takao S, Akiyama SI, Nakajo A, Yoh H, Kitazono M, Natsugoe S, Miyadera K, Fukushima M, Yamada Y, Aikou T. Suppression of metastasis by thymidine phosphorylase inhibitor. Cancer Res 2000;60:5345-5348. (Pubitemid 30761238)
273. Nakajima Y, Gotanda T, Uchimiya H, Furukawa T, Haraguchi M, Ikeda R, Sumizawa T, Yoshida H, Akiyama S. Inhibition of metastasis of tumor cells overexpressing thymidine phosphorylase by 2-deoxy-L-ribose. Cancer Res 2004;64:1794-1801. (Pubitemid 38428704)
274. Rofstad EK, Halsor EF. 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 2000;60:4932-4938. (Pubitemid 30701511)
275. Matsushita S, Nitanda T, Furukawa T, Sumizawa T, Tani A, Nishimoto K, Akiba S, Miyadera K, Fukushima M, Yamada Y, Yoshida H, Kanzaki T, Akiyama S. The effect of a thymidine phosphorylase inhibitor on angiogenesis and apoptosis in tumors. Cancer Res 1999;59:1911-1916. (Pubitemid 29186165)
276. Ikeguchi M, Cai J, Fukuda K, Oka S, Katano K, Tsujitani S, Maeta M, Kaibara N. Correlation between spontaneous apoptosis and the expression of angiogenic factors in advanced gastric adenocarcinoma. J Exp Clin Cancer Res 2001;20:257-263. (Pubitemid 32641070)
277. Hata K, Fujiwaki R, Maede Y, Nakayama K, Fukumoto M, Miyazaki K. Expression of thymidine phosphorylase in epithelial ovarian cancer: Correlation with angiogenesis, apoptosis, and ultrasound-derived peak systolic velocity. Gynecol Oncol 2000;77:26-34. (Pubitemid 30217301)
278. Kitazono M, Takebayashi Y, Ishitsuka K, Takao S, Tani A, Furukawa T, Miyadera K, Yamada Y, Aikou T, Akiyama S. Prevention of hypoxia-induced apoptosis by the angiogenic factor thymidine phosphorylase. Biochem Biophys Res Commun 1998;253:797-803. (Pubitemid 29039222)
279. Ikeda R, Furukawa T, Kitazono M, Ishitsuka K, Okumura H, Tani A, Sumizawa T, Haraguchi M, Komatsu M, Uchimiya H, Ren XQ, Motoya T, Yamada K, Akiyama S. Molecular basis for the inhibition of hypoxia-induced apoptosis by 2-deoxy-D-ribose. Biochem Biophys Res Commun 2002;291:806-812. (Pubitemid 34694347)
280. Ikeda R, Che XF, Ushiyama M, Yamaguchi T, Okumura H, Nakajima Y, Takeda Y, Shibayama Y, Furukawa T, Yamamoto M, Haraguchi M, Sumizawa T, Yamada K, Akiyama S. 2-Deoxy-D-ribose inhibits hypoxia-induced apoptosis by suppressing the phosphorylation of p38 MAPK. Biochem Biophys Res Commun 2006;342:280-285. (Pubitemid 43247388)
281. Ikeda R, Tajitsu Y, Iwashita K, Che XF, Yoshida K, Ushiyama M, Furukawa T, Komatsu M, Yamaguchi T, Shibayama Y, Yamamoto M, Zhao HY, Arima J, Takeda Y, Akiyama S, Yamada K. Thymidine phosphorylase inhibits the expression of proapoptotic protein BNIP3. Biochem Biophys Res Commun 2008;370:220-224.
282. Ikeda R, Furukawa T, Mitsuo R, Noguchi T, Kitazono M, Okumura H, Sumizawa T, Haraguchi M, Che XF, Uchimiya H, Nakajima Y, Ren XQ, Oiso S, Inoue I, Yamada K, Akiyama S. Thymidine phosphorylase inhibits apoptosis induced by cisplatin. Biochem Biophys Res Commun 2003;301:358-363. (Pubitemid 36279246)
283. Jeung HC, Che XF, Haraguchi M, Furukawa T, Zheng CL, Sumizawa T, Rha SY, Roh JK, Akiyama S. Thymidine phosphorylase suppresses apoptosis induced by microtubule-interfering agents. Biochem Pharmacol 2005;70:13-21. (Pubitemid 40797866)
284. Jeung HC, Che XF, Haraguchi M, Zhao HY, Furukawa T, Gotanda T, Zheng CL, Tsuneyoshi K, Sumizawa T, Roh JK, Akiyama S. Protection against DNA damage-induced apoptosis by the angiogenic factor thymidine phosphorylase. FEBS Lett 2006;580:1294-1302. (Pubitemid 43221991)
285. Mori S, Takao S, Ikeda R, Noma H, Mataki Y, Wang X, Akiyama S, Aiko T. Role of thymidine phosphorylase in Fas-induced apoptosis. Hum Cell 2001;14:323-330.
286. Mori S, Takao S, Ikeda R, Noma H, Mataki Y, Wang X, Akiyama S, Aikou T. Thymidine phosphorylase suppresses Fas-induced apoptotic signal transduction independent of its enzymatic activity. Biochem Biophys Res Commun 2002;295:300-305. (Pubitemid 34785833)
287. Stenman G, Sahlin P, Dumanski JP, Hagiwara K, Ishikawa F, Miyazono K, Collins VP, Heldin CH. Regional localization of the human platelet-derived endothelial cell growth factor (ECGF1) gene to chromosome 22q13. Cytogenet Cell Genet 1992;59:22-23.
288. Hagiwara K, Stenman G, Honda H, Sahlin P, Andersson A, Miyazono K, Heldin CH, Ishikawa F, Takaku F. Organization and chromosomal localization of the human platelet-derived endothelial cell growth factor gene. Mol Cell Biol 1991;11:2125-2132. (Pubitemid 21895584)
289. Zhu GH, Lenzi M, Schwartz EL. The Sp1 transcription factor contributes to the tumor necrosis factor-induced expression of the angiogenic factor thymidine phosphorylase in human colon carcinoma cells. Oncogene 2002;21:8477-8485. (Pubitemid 36054888)
290. Rohlff C, Ahmad S, Borellini F, Lei J, Glazer RI. Modulation of transcription factor Sp1 by cAMP-dependent protein kinase. J Biol Chem 1997;272:21137-21141. (Pubitemid 27373973)
291. Finkenzeller G, Sparacio A, Technau A, Marme D, Siemeister G. Sp1 recognition sites in the proximal promoter of the human vascular endothelial growth factor gene are essential for platelet-derived growth factor-induced gene expression. Oncogene 1997;15:669-676. (Pubitemid 27389929)
292. Toi M, Inada K, Hoshina S, Suzuki H, Kondo S, 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 1995;1:961-964.
293. Amaya H, Tanigawa N, Lu C, Matsumura M, Shimomatsuya T, Horiuchi T, Muraoka R. Association of vascular endothelial growth factor expression with tumor angiogenesis, survival and thymidine phosphorylase/platelet-derived endothelial cell growth factor expression in human colorectal cancer. Cancer Lett 1997;119:227-235. (Pubitemid 27478108)
294. Fukuiwa T, Takebayashi Y, Akiba S, Matsuzaki T, Hanamure Y, Miyadera K, Yamada Y, Akiyama S. Expression of thymidine phosphorylase and vascular endothelial cell growth factor in human head and neck squamous cell carcinoma and their different characteristics. Cancer 1999;85:960-969. (Pubitemid 29077575)
295. Kojima H, Shijubo N, Abe S. Thymidine phosphorylase and vascular endothelial growth factor in patients with Stage I lung adenocarcinoma. Cancer 2002;94:1083-1093. (Pubitemid 34150864)
296. Fujiwaki R, Hata K, Iida K, Maede Y, Miyazaki K. Vascular endothelial growth factor expression in progression of cervical cancer: Correlation with thymidine phosphorylase expression, angiogenesis, tumor cell proliferation, and apoptosis. Anticancer Res 2000;20:1317-1322. (Pubitemid 30240721)
297. Harino Y, Imura S, Kanemura H, Morine Y, Fujii M, Ikegami T, Uehara H, Shimada M. Role of tumor angiogenesis in gallbladder carcinoma: With special reference to thymidine phosphorylase. Int J Clin Oncol 2008;13:452-457.
298. O'Brien T, Cranston D, Fuggle S, Bicknell R, Harris AL. Different angiogenic pathways characterize superficial and invasive bladder cancer. Cancer Res 1995;55:510-513.
299. Schwartz EL, Wan E, Wang FS, Baptiste N. Regulation of expression of thymidine phosphorylase/platelet-derived endothelial cell growth factor in human colon carcinoma cells. Cancer Res 1998;58:1551-1557. (Pubitemid 28193623)
300. Goto H, Kohno K, Sone S, Akiyama S, Kuwano M, 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 2001;61:469-473. (Pubitemid 32128599)
301. Yao Y, Kubota T, Sato K, Takeuchi H, Kitai R, Matsukawa S. Interferons upregulate thymidine phosphorylase expression via JAK-STAT-dependent transcriptional activation and mRNA stabilization in human glioblastoma cells. J Neurooncol 2005;72:217-223. (Pubitemid 40867403)
302. Fukushima M, Okabe H, Takechi T, Ichikawa W, Hirayama R. Induction of thymidine phosphorylase by interferon and taxanes occurs only in human cancer cells with low thymidine phosphorylase activity. Cancer Lett 2002;187:103-110. (Pubitemid 35279338)
303. Eda H, Fujimoto K, Watanabe S, Ura M, Hino A, Tanaka Y, Wada K, Ishitsuka H. Cytokines induce thymidine phosphorylase expression in tumor cells and make them more susceptible to 50-deoxy-5-fluorouridine. Cancer Chemother Pharmacol 1993;32:333-338. (Pubitemid 23207988)
304. Zhu GH, Schwartz EL. Expression of the angiogenic factor thymidine phosphorylase in THP-1 monocytes: Induction by autocrine tumor necrosis factor-alpha and inhibition by aspirin. Mol Pharmacol 2003;64:1251-1258.
305. de Bruin M, Peters GJ, Oerlemans R, Assaraf YG, Masterson AJ, Adema AD, Dijkmans BA, Pinedo HM, Jansen G. 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 2004;66:1054-1060. (Pubitemid 39319478)
306. Kusabe T, Waguri-Nagaya Y, Tanikawa T, Aoyama M, Fukuoka M, Kobayashi M, Otsuka T, Asai K. 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 2005;25:625-630. (Pubitemid 41414061)
307. Blanquicett C, Gillespie GY, Nabors LB, Miller CR, Bharara S, Buchsbaum DJ, Diasio RB, Johnson MR. 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 2002;1:1139-1145.
308. Sawada N, Ishikawa T, Fukase Y, Nishida M, Yoshikubo T, Ishitsuka H. Induction of thymidine phosphorylase activity and enhancement of capecitabine efficacy by taxol/taxotere in human cancer xenografts. Clin Cancer Res 1998;4:1013-1019. (Pubitemid 28183404)
309. Sawada N, Ishikawa T, Sekiguchi F, Tanaka Y, Ishitsuka H. X-ray irradiation induces thymidine phosphorylase and enhances the efficacy of capecitabine (Xeloda) in human cancer xenografts. Clin Cancer Res 1999;5:2948-2953. (Pubitemid 29493974)
310. Guarcello V, Blanquicett C, Naguib FN, El Kouni MH. Suppression of thymidine phosphorylase expression by promoter methylation in human cancer cells lacking enzyme activity. Cancer Chemother Pharmacol 2008;62:85-96. (Pubitemid 351537849)
311. Griffiths L, Dachs GU, Bicknell R, Harris AL, Stratford IJ. 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 1997;57:570-572. (Pubitemid 27085632)
312. Folkman J. Tumor angiogenesis: Therapeutic implications. N Engl J Med 1971;285:1182-1186.
313. Bergers G, Hanahan D. Modes of resistance to anti-angiogenic therapy. Nat Rev Cancer 2008;8:592-603.
314. Fernando NT, Koch M, Rothrock C, Gollogly LK, D'Amore PA, Ryeom S, Yoon SS. Tumor escape from endogenous, extracellular matrix-associated angiogenesis inhibitors by up-regulation of multiple proangiogenic factors. Clin Cancer Res 2008;14:1529-1539.
315. Batchelor TT, Sorensen AG, di Tomaso E, Zhang WT, Duda DG, Cohen KS, Kozak KR, Cahill DP, Chen PJ, Zhu M, Ancukiewicz M, Mrugala MM, Plotkin S, Drappatz J, Louis DN, Ivy P, Scadden DT, Benner T, Loeffler JS, Wen PY, Jain RK. AZD2171, a pan-VEGF receptor tyrosine kinase inhibitor, normalizes tumor vasculature and alleviates edema in glioblastoma patients. Cancer Cell 2007;11:83-95. (Pubitemid 46075199)
316. Pérez-Pérez MJ, Priego EM, Hernandez AI, Camarasa MJ, Balzarini J, Liekens S. Thymidine phosphorylase inhibitors: Recent developments and potential therapeutic applications. Mini Rev Med Chem 2005;5:1113-1123. (Pubitemid 41723568)
317. Langen P, Etzold G, Barwolff D, Preussel B. Inhibition of thymidine phosphorylase by 6-aminothymine and derivatives of 6-aminouracil. Biochem Pharmacol 1967;16:1833-1837.
318. Fukushima M, Suzuki N, Emura T, Yano S, Kazuno H, Tada Y, Yamada Y, Asao T. Structure and activity of specific inhibitors of thymidine phosphorylase to potentiate the function of antitumor 20-deoxyribonucleosides. Biochem Pharmacol 2000;59:1227-1236. (Pubitemid 30157885)
319. Balzarini J, Gamboa AE, Esnouf R, Liekens S, Neyts J, De Clercq E, Camarasa MJ, Pérez-Pérez MJ. 7-Deazaxanthine, a novel prototype inhibitor of thymidine phosphorylase. FEBS Lett 1998;438:91-95. (Pubitemid 28517841)
320. Balzarini J, Degreve B, Esteban-Gamboa A, Esnouf R, De Clercq E, Engelborghs Y, Camarasa MJ, Pérez-Pérez MJ. Kinetic analysis of novel multisubstrate analogue inhibitors of thymidine phosphorylase. FEBS Lett 2000;483:181-185. (Pubitemid 30782648)
321. Esteban-Gamboa A, Balzarini J, Esnouf R, De Clercq E, Camarasa MJ, Pérez-Pérez MJ. Design, synthesis, and enzymatic evaluation of multisubstrate analogue inhibitors of Escherichia coli thymidine phosphorylase. J Med Chem 2000;43:971-983. (Pubitemid 30152302)
322. Liekens S, Hernandez AI, Ribatti D, De Clercq E, Camarasa MJ, Pérez-Pérez MJ, Balzarini J. The nucleoside derivative 50-O-trityl-inosine (KIN59) suppresses thymidine phosphorylase-triggered angiogenesis via a noncompetitive mechanism of action. J Biol Chem 2004;279:29598-29605. (Pubitemid 38915842)
323. Liekens S, Bronckaers A, Hernandez AI, Priego EM, Casanova E, Camarasa MJ, Pérez-Pérez MJ, Balzarini J. 50-O-tritylated nucleoside derivatives: Inhibition of thymidine phosphorylase and angiogenesis. Mol Pharmacol 2006;70:501-509. (Pubitemid 44092311)
324. Cole C, Reigan P, Gbaj A, Edwards PN, Douglas KT, Stratford IJ, Freeman S, Jaffar M. Potential tumor-selective nitroimidazolylmethyluracil prodrug derivatives: Inhibitors of the angiogenic enzyme thymidine phosphorylase. J Med Chem 2003;46:207-209. (Pubitemid 36078140)
325. Reigan P, Edwards PN, Gbaj A, Cole C, Barry ST, Page KM, Ashton SE, Luke RW, Douglas KT, Stratford IJ, Jaffar M, Bryce RA, Freeman S. Aminoimidazolylmethyluracil analogues as potent inhibitors of thymidine phosphorylase and their bioreductive nitroimidazolyl prodrugs. J Med Chem 2005;48:392-402. (Pubitemid 40139782)
326. Reigan P, Gbaj A, Stratford IJ, Bryce RA, Freeman S. Xanthine oxidase-activated prodrugs of thymidine phosphorylase inhibitors. Eur J Med Chem 2008;43:1248-1260. (Pubitemid 351734545)
327. Heidelberger C, Chaudhuri N, Danneberg P, Mooren D, Griesbach L, Duschinsky R, Schnitzer R, Pleven E, Scheiner J. Fluorinated pyrimidines, a new class of tumour-inhibitory compounds. Nature 1957;179:663-666.
328. Longley DB, Harkin DP, Johnston PG. 5-fluorouracil: Mechanisms of action and clinical strategies. Nat Rev Cancer 2003;3:330-338. (Pubitemid 37328853)
329. Peters GJ, Laurensse E, Leyva A, Pinedo HM. Purine nucleosides as cell-specific modulators of 5-fluorouracil metabolism and cytotoxicity. Eur J Cancer Clin Oncol 1987;23:1869-1881. (Pubitemid 18013328)
330. Schwartz EL, Baptiste N, O'Connor CJ, Wadler S, Otter BA. Potentiation of the antitumor activity of 5-fluorouracil in colon carcinoma cells by the combination of interferon and deoxyribonucleosides results from complementary effects on thymidine phosphorylase. Cancer Res 1994;54:1472-1478. (Pubitemid 24106408)
331. Ciccolini J, Cuq P, Evrard A, Giacometti S, Pelegrin A, Aubert C, Cano JP, Iliadis A. Combination of thymidine phosphorylase gene transfer and deoxyinosine treatment greatly enhances 5-fluorouracil antitumor activity in vitro and in vivo. Mol Cancer Ther 2001;1:133-139.
332. Santi DV, McHenry CS, Sommer H. Mechanism of interaction of thymidylate synthetase with 5-fluorodeoxyuridylate. Biochemistry 1974;13:471-481.
333. Sommer H, Santi DV. Purification and amino acid analysis of an active site peptide from thymidylate synthetase containing covalently bound 5-fluoro-2′-deoxyuridylate and methylenetetrahydrofolate. Biochem Biophys Res Commun 1974;57:689-695.
334. Di Paolo A, Lencioni M, Amatori F, Di Donato S, Bocci G, Orlandini C, Lastella M, Federici F, Iannopollo M, Falcone A, Ricci S, Del Tacca M, Danesi R. 5-fluorouracil pharmacokinetics predicts disease-free survival in patients administered adjuvant chemotherapy for colorectal cancer. Clin Cancer Res 2008;14:2749-2755.
335. Modulation of fluorouracil by leucovorin in patients with advanced colorectal cancer: Evidence in terms of response rate. Advanced colorectal cancer meta-analysis project. J Clin Oncol 1992;10:896-903.
336. Douillard JY, Bennouna J, Senellart H. Is XELOX equivalent to FOLFOX or other continuous-infusion 5-fluorouracil chemotherapy in metastatic colorectal cancer? Clin Colorectal Cancer 2008;7:206-211.
337. Takechi T, Nakano K, Uchida J, Mita A, Toko K, Takeda S, Unemi N, Shirasaka T. Antitumor activity and low intestinal toxicity of S-1, a new formulation of oral tegafur, in experimental tumor models in rats. Cancer Chemother Pharmacol 1997;39:205-211. (Pubitemid 26414256)
338. Kanamitsu SI, Ito K, Okuda H, Ogura K, Watabe T, Muro K, Sugiyama Y. Prediction of in vivo drug-drug interactions based on mechanism-based inhibition from in vitro data: Inhibition of 5-fluorouracil metabolism by (E)-5-(2-bromovinyl)uracil. Drug Metab Dispos 2000;28:467-474. (Pubitemid 30185686)
339. Ogura K, Nishiyama T, Takubo H, Kato A, Okuda H, Arakawa K, Fukushima M, Nagayama S, Kawaguchi Y, Watabe T. Suicidal inactivation of human dihydropyrimidine dehydrogenase by (E)-5-(2-bromovinyl)uracil derived from the antiviral, sorivudine. Cancer Lett 1998;122:107-113. (Pubitemid 28058624)
340. Porter DJ, Chestnut WG, Merrill BM, Spector T. Mechanism-based inactivation of dihydropyrimidine dehydrogenase by 5-ethynyluracil. J Biol Chem 1992;267:5236-5242.
341. Heslin MJ, Yan J, Weiss H, Shao L, Owens J, Lucas VS, Diasio RB. Dihydropyrimidine dehydrogenase (DPD) rapidly regenerates after inactivation by eniluracil (GW776C85) in primary and metastatic colorectal cancer. Cancer Chemother Pharmacol 2003;52:399-404. (Pubitemid 37363613)
342. Hoff PM. Practical considerations in the use of oral fluoropyrimidines. Semin Oncol 2003;30:88-92. (Pubitemid 36712863)
343. Sugata S, Kono A, Hara Y, Karube Y, Matsushima Y. Partial purification of a thymidine phosphorylase from human gastric cancer. Chem Pharm Bull (Tokyo) 1986;34:1219-1222.
344. de Bruin M, van Capel T, van der BK, Kruyt FA, Fukushima M, Hoekman K, Pinedo HM, Peters GJ. Role of platelet-derived endothelial cell growth factor/thymidine phosphorylase in fluoropyrimidine sensitivity. Br J Cancer 2003;88:957-964. (Pubitemid 36520887)
345. Yu LJ, Matias J, Scudiero DA, Hite KM, Monks A, Sausville EA, Waxman DJ. P450 enzyme expression patterns in the NCI human tumor cell line panel. Drug Metab Dispos 2001;29:304-312. (Pubitemid 32179532)
346. Komatsu T, Yamazaki H, Shimada N, Nakajima M, Yokoi T. Roles of cytochromes P450 1A2, 2A6, and 2C8 in 5-fluorouracil formation from tegafur, an anticancer prodrug, in human liver microsomes. Drug Metab Dispos 2000;28:1457-1463.
347. Yoshisue K, Masuda H, Matsushima E, Ikeda K, Nagayama S, Kawaguchi Y. Tissue distribution and biotransformation of potassium oxonate after oral administration of a novel antitumor agent (drug combination of tegafur, 5-chloro-2,4-dihydroxypyridine, and potassium oxonate) to rats. Drug Metab Dispos 2000;28:1162-1167. (Pubitemid 30747323)
348. Poorter RL, Bakker PJ, Veenhof CH. Continuous infusion of chemotherapy: Focus on 5-fluorouracil and fluorodeoxyuridine. Pharm World Sci 1998;20:45-59. (Pubitemid 28228434)
349. Mocellin S, Pilati P, Lise M, Nitti D. Meta-analysis of hepatic arterial infusion for unresectable liver metastases from colorectal cancer: The end of an era? J Clin Oncol 2007;25:5649-5654.
350. Patterson AV, Zhang H, Moghaddam A, Bicknell R, Talbot DC, Stratford IJ, Harris AL. Increased sensitivity to the prodrug 50-deoxy-5-fluorouridine and modulation of 5-fluoro- 2′-deoxyuridine sensitivity in MCF-7 cells transfected with thymidine phosphorylase. Br J Cancer 1995;72:669-675.
351. Kato Y, Matsukawa S, Muraoka R, 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 1997;75:506-511. (Pubitemid 27085290)
352. Haraguchi M, Furukawa T, Sumizawa T, Akiyama S. Sensitivity of human KB cells expressing platelet-derived endothelial cell growth factor to pyrimidine antimetabolites. Cancer Res 1993;53:5680-5682. (Pubitemid 23360271)
353. Evrard A, Cuq P, Robert B, Vian L, Pelegrin A, Cano JP. Enhancement of 5-fluorouracil cytotoxicity by human thymidine-phosphorylase expression in cancer cells: In vitro and in vivo study. Int J Cancer 1999;80:465-470.
354. Bajetta E, Colleoni M, Rosso R, Sobrero A, Amadori D, Comella G, Marangolo M, Scanni A, Lorusso V, Calabresi F. Prospective randomised trial comparing fluorouracil versus doxifluridine for the treatment of advanced colorectal cancer. Eur J Cancer 1993;29A:1658-1663. (Pubitemid 23275864)
355. Bollag W, Hartmann HR. Tumor inhibitory effects of a new fluorouracil derivative: 50-deoxy-5-fluorouridine. Eur J Cancer 1980;16:427-432. (Pubitemid 10145102)
356. Temmink OH, de Bruin M, Turksma AW, Cricca S, Laan AC, Peters GJ. Activity and substrate specificity of pyrimidine phosphorylases and their role in fluoropyrimidine sensitivity in colon cancer cell lines. Int J Biochem Cell Biol 2007;39:565-575. (Pubitemid 46096794)
357. Cao D, Russell RL, Zhang D, Leffert JJ, Pizzorno G. Uridine phosphorylase (-/-) murine embryonic stem cells clarify the key role of this enzyme in the regulation of the pyrimidine salvage pathway and in the activation of fluoropyrimidines. Cancer Res 2002;62:2313-2317. (Pubitemid 34411710)
358. Schuller J, Cassidy J, Dumont E, Roos B, Durston S, Banken L, Utoh M, Mori K, Weidekamm E, Reigner B. Preferential activation of capecitabine in tumor following oral administration to colorectal cancer patients. Cancer Chemother Pharmacol 2000;45:291-297. (Pubitemid 30151522)
359. Van Cutsem E, Twelves C, Cassidy J, Allman D, Bajetta E, Boyer M, Bugat R, Findlay M, Frings S, Jahn M, McKendrick J, Osterwalder B, Perez-Manga G, Rosso R, Rougier P, Schmiegel WH, Seitz JF, Thompson P, Vieitez JM, Weitzel C, Harper P. Oral capecitabine compared with intravenous fluorouracil plus leucovorin in patients with metastatic colorectal cancer: Results of a large phase III study. J Clin Oncol 2001;19:4097-4106. (Pubitemid 33049527)
360. Hoff PM, Ansari R, Batist G, Cox J, Kocha W, Kuperminc M, Maroun J, Walde D, Weaver C, Harrison E, Burger HU, Osterwalder B, Wong AO, Wong R. Comparison of oral capecitabine versus intravenous fluorouracil plus leucovorin as first-line treatment in 605 patients with metastatic colorectal cancer: Results of a randomized phase III study. J Clin Oncol 2001;19:2282-2292. (Pubitemid 32366981)
361. Lamberti C, Sauerbruch T, Glasmacher A. Adjuvant capecitabine is at least as effective as fluorouracil plus leucovorin for survival in people with resected stage III colon cancer. Cancer Treat Rev 2005;31:648-652. (Pubitemid 41662892)
362. Twelves C, Wong A, Nowacki MP, Abt M, Burris III H, Carrato A, Cassidy J, Cervantes A, Fagerberg J, Georgoulias V, Husseini F, Jodrell D, Koralewski P, Kroning H, Maroun J, Marschner N, McKendrick J, Pawlicki M, Rosso R, Schuller J, Seitz JF, Stabuc B, Tujakowski J, Van Hazel G, Zaluski J, Scheithauer W. Capecitabine as adjuvant treatment for stage III colon cancer. N Engl J Med 2005;352:2696-2704. (Pubitemid 41007824)
363. Tripathy D. Capecitabine in combination with novel targeted agents in the management of metastatic breast cancer: Underlying rationale and results of clinical trials. Oncologist 2007;12:375-389. (Pubitemid 46698715)
364. Dal Lago L, D'Hondt V, Awada A. Selected combination therapy with sorafenib: A review of clinical data and perspectives in advanced solid tumors. Oncologist 2008;13:845-858.
365. Camidge DR, Gail ES, Gore L, O'Bryant CL, Leong S, Basche M, Holden SN, Musib L, Baldwin J, Darstein C, Thornton D, Finn RS, Britten CD. A phase I safety, tolerability, and pharmacokinetic study of enzastaurin combined with capecitabine in patients with advanced solid tumors. Anticancer Drugs 2008;19:77-84. (Pubitemid 350190970)
366. Meropol NJ, Gold PJ, Diasio RB, Andria M, DhamiM, Godfrey T, Kovatich AJ, Lund KA, Mitchell E, Schwarting R. Thymidine phosphorylase expression is associated with response to capecitabine plus irinotecan in patients with metastatic colorectal cancer. J Clin Oncol 2006;24:4069-4077. (Pubitemid 46622281)
367. Han JY, Hong EK, Lee SY, Yoon SM, Lee DH, Lee JS. Thymidine phosphorylase expression in tumour cells and tumour response to capecitabine plus docetaxel chemotherapy in non-small cell lung cancer. J Clin Pathol 2005;58:650-654.
368. Honda J, Sasa M, Moriya T, Bando Y, Hirose T, Takahashi M, Nagao T, Tangoku A. Thymidine phosphorylase and dihydropyrimidine dehydrogenase are predictive factors of therapeutic efficacy of capecitabine monotherapy for breast cancer-preliminary results. J Med Invest 2008;55:54-60. (Pubitemid 351643594)
369. Koizumi W, Okayasu I, Hyodo I, Sakamoto J, Kojima H. Prediction of the effect of capecitabine in gastric cancer by immunohistochemical staining of thymidine phosphorylase and dihydropyrimidine dehydrogenase. Anticancer Drugs 2008;19:819-824.
370. O'Shaughnessy J, Miles D, Vukelja S, Moiseyenko V, Ayoub JP, Cervantes G, Fumoleau P, Jones S, Lui WY, Mauriac L, Twelves C, Van Hazel G, Verma S, Leonard R. Superior survival with capecitabine plus docetaxel combination therapy in anthracycline-pretreated patients with advanced breast cancer: Phase III trial results. J Clin Oncol 2002;20:2812-2823. (Pubitemid 34651510)
371. Comella P, Casaretti R, Sandomenico C, Avallone A, Franco L. Capecitabine, alone and in combination, in the management of patients with colorectal cancer: A review of the evidence. Drugs 2008;68:949-961. (Pubitemid 351652923)
372. Heidelberger C, Parsons D, Remy D. Syntheses of 5-trifluoromethyluracil and 5-trifluoromethyl- 2′-deoxyuridine. J Med Chem 1964;7:1-5.
373. Reyes P, Heidelberger C. Fluorinated pyrimidines. XXVI. Mammalian thymidylate synthetase: Its mechanism of action and inhibition by fluorinated nucleotides. Mol Pharmacol 1965;1:14-30.
374. Eckstein JW, Foster PG, Finer-Moore J, Wataya Y, Santi DV. Mechanism-based inhibition of thymidylate synthase by 5-(trifluoromethyl)- 2′-deoxyuridine 5′-monophosphate. Biochemistry 1994;33:15086-15094.
375. Emura T, Suzuki N, Yamaguchi M, Ohshimo H, Fukushima M. A novel combination antimetabolite, TAS-102, exhibits antitumor activity in FU-resistant human cancer cells through a mechanism involving FTD incorporation in DNA. Int J Oncol 2004;25:571-578.
376. De Clercq E. Antiviral drugs in current clinical use. J Clin Virol 2004;30:115-133. (Pubitemid 38582018)
377. Ansfield FJ, Ramirez G. Phase I and II studies of 20-deoxy-5- (trifluoromethyl)-uridine (NSC-75520). Cancer Chemother Rep 1971;55:205-208.
378. Dexter DL, Wolberg WH, Ansfield FJ, Helson L, Heidelberger C. The clinical pharmacology of 5-trifluoromethyl-2′-deoxyuridine. Cancer Res 1972;32:247-253.
379. Emura T, Nakagawa F, Fujioka A, Ohshimo H, Kitazato K. Thymidine kinase and thymidine phosphorylase level as the main predictive parameter for sensitivity to TAS-102 in a mouse model. Oncol Rep 2004;11:381-387.
380. Emura T, Murakami Y, Nakagawa F, Fukushima M, Kitazato K. A novel antimetabolite, TAS-102 retains its effect on FU-related resistant cancer cells. Int J Mol Med 2004;13:545-549.
381. Temmink OH, Emura T, de Bruin M, Fukushima M, Peters GJ. Therapeutic potential of the dual-targeted TAS-102 formulation in the treatment of gastrointestinal malignancies. Cancer Sci 2007;98:779-789. (Pubitemid 46691813)
382. Overman MJ, Varadhachary G, Kopetz S, Thomas MB, Fukushima M, Kuwata K, Mita A, Wolff RA, Hoff PM, Xiong H, Abbruzzese JL. Phase 1 study of TAS-102 administered once daily on a 5-day-per-week schedule in patients with solid tumors. Invest New Drugs 2008;26:445-454.
383. Temmink OH, Hoebe EK, van der BK, Ackland SP, Fukushima M, Peters GJ. Mechanism of trifluorothymidine potentiation of oxaliplatin-induced cytotoxicity to colorectal cancer cells. Br J Cancer 2007;96:231-240. (Pubitemid 46160627)
384. Neale GA, Mitchell A, Finch LR. Enzymes of pyrimidine deoxyribonucleotide metabolism in Mycoplasma mycoides subsp. mycoides. J Bacteriol 1983;156:1001-1005. (Pubitemid 14216320)
385. Tham TN, Ferris S, Kovacic R, Montagnier L, Blanchard A. Identification of Mycoplasma pirum genes involved in the salvage pathways for nucleosides. J Bacteriol 1993;175:5281-5285. (Pubitemid 23232595)
386. Razin S, Yogev D, Naot Y. Molecular biology and pathogenicity of Mycoplasmas. Microbiol Mol Biol Rev 1998;62:1094-1156.
387. Krause D, Yogev D, Naot Y. In: McElhaney RN, Finch LR, Baseman JB, editors. Mycoplasmas: Molecular biology and pathogenesis. Washington, DC: American Society for Microbiology; 1992.
388. Cimolai N. Do mycoplasmas cause human cancer? Can J Microbiol 2001;47:691-697.
389. Liekens S, Bronckaers A, Balzarini J. Purine and pyrimidine antimetabolite-based anti-cancer treatment may be significantly improved by selective suppression of mycoplamsa-encoded catabolic enzymes during therapy. Lancet Oncol 2009; in press.
390. Kidder M, Chan PJ, Seraj IM, Patton WC, King A. Assessment of archived paraffin-embedded cervical condyloma tissues for mycoplasma-conserved DNA using sensitive PCR-ELISA. Gynecol Oncol 1998;71:254-257. (Pubitemid 28550809)
391. Hayflick L, Koprowski H. Direct agar isolation of mycoplasmas from human leukaemic bone marrow. Nature 1965;205:713-714.
392. Chan PJ, Seraj IM, Kalugdan TH, King A. Prevalence of mycoplasma conserved DNA in malignant ovarian cancer detected using sensitive PCR-ELISA. Gynecol Oncol 1996;63:258-260. (Pubitemid 26398609)
393. Huang S, Li JY, Wu J, Meng L, Shou CC. Mycoplasma infections and different human carcinomas. World J Gastroenterol 2001;7:266-269. (Pubitemid 32377482)
394. Feng SH, Tsai S, Rodriguez J, Lo SC. Mycoplasmal infections prevent apoptosis and induce malignant transformation of interleukin-3-dependent 32D hematopoietic cells. Mol Cell Biol 1999;19:7995-8002. (Pubitemid 30413994)
395. Zhang S, Tsai S, Wu TT, Li B, Shih JW, Lo SC. Mycoplasma fermentans infection promotes immortalization of human peripheral blood mononuclear cells in culture. Blood 2004;104:4252-4259. (Pubitemid 39620180)
396. Tsai S, Wear DJ, Shih JW, Lo SC. Mycoplasmas and oncogenesis: Persistent infection and multistage malignant transformation. Proc Natl Acad Sci USA 1995;92:10197-10201.
397. Ketcham CM, Anai S, Reutzel R, Sheng S, Schuster SM, Brenes RB, Agbandje-McKenna M, McKenna R, Rosser CJ, Boehlein SK. p37 Induces tumor invasiveness. Mol Cancer Ther 2005;4:1031-1038.
398. Goodison S, Nakamura K, Iczkowski KA, Anai S, Boehlein SK, Rosser CJ. Exogenous mycoplasmal p37 protein alters gene expression, growth and morphology of prostate cancer cells. Cytogenet Genome Res 2007;118:204-213. (Pubitemid 350125258)
399. Gong M, Meng L, Jiang B, Zhang J, Yang H, Wu J, Shou C. p37 From Mycoplasma hyorhinis promotes cancer cell invasiveness and metastasis through activation of MMP-2 and followed by phosphorylation of EGFR. Mol Cancer Ther 2008;7:530-537.
400. Bronckaers A, Balzarini J, Liekens S. The cytostatic activity of pyrimidine nucleosides is strongly modulated by Mycoplasma hyorhinis infection: Implications for cancer therapy. Biochem Pharmacol 2008;76:188-197.
401. Jette L, Bissoon-Haqqani S, Le Francois B, Maroun JA, Birnboim HC. Resistance of colorectal cancer cells to 5-FUdR and 5-FU caused by Mycoplasma infection. Anticancer Res 2008;28:2175-2180.