© 1996 by Oxford University Press
Journal of the National Cancer Institute, Vol. 88, No. 16, 1110-1117,
August 21, 1996
© 1996 Oxford University Press
Clinicopathologic and Prognostic Significance of an Angiogenic Factor, Thymidine Phosphorylase, in Human Colorectal Carcinoma
Department of Cancer Chemotherapy, Institute for Cancer Research and First Department of Surgery, Faculty of Medicine, Kagoshima University Japan
Department of Cancer Chemotherapy, Institute for Cancer Research, Faculty of Medicine, Kagoshima University Japan
Department of Public Health, Faculty of Medicine, Kagoshima University Japan
First Department of Surgery, Faculty of Medicine, Kagoshima University Japan
Department of Cancer Chemotherapy, Institute for Cancer Research, Faculty of Medicine, Kagoshima University Japan
Second Department of Anatomy, Faculty of Medicine, Kagoshima University Japan
First Department of Surgery, Faculty of Medicine, Kagoshima University Japan
Department of Cancer Chemotherapy, Institute for Cancer Research. Kagoshima University and Taiho Pharmaceutical Co. Ltd. Saitama, Japan
Taiho Pharmaceutical Co. Ltd.
Correspondence to: Shin-ichi Akiyama, M.D., Department of Cancer Chemotherapy. Institute for Cancer Research. Faculty of Medicine. Kagoshima University, Sakuragaoka 8-35-1, Kagoshima 890, Japan.
BACKGROUND:: Platelet-derived endothelial cell growth factor (PD-ECGF) is known to promote the development of new blood vessels, which are fundamental to tumor growth and metastasis. We previously found that thymidine phosphorylase (dThdPase) and PD-ECGF are the same protein.
PURPOSE:: We retrospectively examined the expression of dThdPase in primary colorectal carcinomas, its association with angiogenesis and clinicopathologic findings, and its prognostic value.
METHODS:: Tissues were obtained from the tumors of 163 patients whose colorectal carcinomas were completely removed by surgery. Microvessels assessed by immunostaining endothelial cells for factor VIII were counted on a 400x field in the most active areas of neovascularization within the tumor. We purified the monoclonal antibody against dThdPase and studied the expression of dThdPase in the same serial sections used for the detection of factor VIII. Those who carried out microvessel counting and dThdPase expression assessment had no knowledge of clinicopathologic findings. The significance of dThdPase in the prognosis of patients with colorectal carcinomas was also examined in the survival analysis of mortality follow-up data covering the period between 1984 through 1991. Reported P values are from two-sided tests of statistical significance.
RESULTS:: The mean microvessel count (± standard deviation) in dThdPase-positive colorectal carcinoma specimens (17.5 ± 7.2) was higher (P<.001) than that in dThdPase-negative carcinoma specimens (9.3 ± 5.5). The dThdPase positivity was in accordance with the microvessel count. dThdPase positivity showed highly significant statistical associations with tumor size, extent of invasion, lymph node metastasis, lymphatic invasion, and venous invasion. Cox regression analysis revealed that dThdPase expression was prognostic for poor disease outcome after adjustment for Dukes' stage and microvessel count.
CONCLUSIONS:: These findings suggest that higher levels of dThdPase expression in colorectal carcinomas are associated with more extensive angiogenesis, poor clinical and laboratory findings, and unfavorable clinical outcome.
IMPLICATIONS:: Inhibition of dThdPase in human colorectal carcinomas might improve prognosis for some patients.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  J. S. Brockenbrough, J. K. Morihara, S. E. Hawes, J. E. Stern, J. S. Rasey, L. W. Wiens, Q. Feng, and H. Vesselle Thymidine Kinase 1 and Thymidine Phosphorylase Expression in Non-Small-cell Lung Carcinoma in Relation to Angiogenesis and Proliferation J. Histochem. Cytochem., November 1, 2009; 57(11): 1087 - 1097. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Andreetta, C. Puppin, A. Minisini, F. Valent, E. Pegolo, G. Damante, C. Di Loreto, S. Pizzolitto, M. Pandolfi, G. Fasola, et al. Thymidine phosphorylase expression and benefit from capecitabine in patients with advanced breast cancer Ann. Onc., February 1, 2009; 20(2): 265 - 271. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J Heidemann, D G Binion, W Domschke, and T Kucharzik Antiangiogenic therapy in human gastrointestinal malignancies. Gut, October 1, 2006; 55(10): 1497 - 1511. [Full Text] [PDF]
|
|
|
|
 |
|
 A. M. Jubb, H. I. Hurwitz, W. Bai, E. B. Holmgren, P. Tobin, A. S. Guerrero, F. Kabbinavar, S. N. Holden, W. F. Novotny, G. D. Frantz, et al. Impact of Vascular Endothelial Growth Factor-A Expression, Thrombospondin-2 Expression, and Microvessel Density on the Treatment Effect of Bevacizumab in Metastatic Colorectal Cancer J. Clin. Oncol., January 10, 2006; 24(2): 217 - 227. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Tsuzuki, H. Sunaga, T. Ito, N. Narita, C. Sugimoto, and S. Fujieda Reliability of Platelet-Derived Endothelial Cell Growth Factor as a Prognostic Factor for Oral and Oropharyngeal Carcinomas Arch Otolaryngol Head Neck Surg, December 1, 2005; 131(12): 1071 - 1078. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. de Bruin, G. J. Peters, R. Oerlemans, Y. G. Assaraf, A. J. Masterson, A. D. Adema, B. A. C. Dijkmans, H. M. Pinedo, and G. Jansen 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., October 1, 2004; 66(4): 1054 - 1060. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. A. Rich, R. C. Shepard, and S. T. Mosley Four Decades of Continuing Innovation With Fluorouracil: Current and Future Approaches to Fluorouracil Chemoradiation Therapy J. Clin. Oncol., June 1, 2004; 22(11): 2214 - 2232. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y.-L. Chung, H. Troy, I. R. Judson, R. Leek, M. O. Leach, M. Stubbs, A. L. Harris, and J. R. Griffiths Noninvasive Measurements of Capecitabine Metabolism in Bladder Tumors Overexpressing Thymidine Phosphorylase by Fluorine-19 Magnetic Resonance Spectroscopy Clin. Cancer Res., June 1, 2004; 10(11): 3863 - 3870. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Boyer, E. G. McLean, S. Aroori, P. Wilson, A. McCulla, P. D. Carey, D. B. Longley, and P. G. Johnston Characterization of p53 Wild-Type and Null Isogenic Colorectal Cancer Cell Lines Resistant to 5-Fluorouracil, Oxaliplatin, and Irinotecan Clin. Cancer Res., March 15, 2004; 10(6): 2158 - 2167. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Nakajima, T. Gotanda, H. Uchimiya, T. Furukawa, M. Haraguchi, R. Ikeda, T. Sumizawa, H. Yoshida, and S.-i. Akiyama Inhibition of Metastasis of Tumor Cells Overexpressing Thymidine Phosphorylase by 2-Deoxy-L-Ribose Cancer Res., March 1, 2004; 64(5): 1794 - 1801. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Sivridis, A. Giatromanolaki, and M. I. Koukourakis "Stromatogenesis" and Tumor Progression International Journal of Surgical Pathology, January 1, 2004; 12(1): 1 - 9. [Abstract] [PDF]
|
|
|
|
|
|
J. Zhou, Z.-Y. Tang, J. Fan, Z.-Q. Wu, Y. Ji, Y.-S. Xiao, Y.-H. Shi, X.-M. Li, Q.-M. Sun, Y.-K. Liu, et al. Capecitabine Inhibits Postoperative Recurrence and Metastasis after Liver Cancer Resection in Nude Mice with Relation to the Expression of Platelet-Derived Endothelial Cell Growth Factor Clin. Cancer Res., December 1, 2003; 9(16): 6030 - 6037. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. H. Zhu and E. L. Schwartz Expression of the Angiogenic Factor Thymidine Phosphorylase in THP-1 Monocytes: Induction by Autocrine Tumor Necrosis Factor-{alpha} and Inhibition by Aspirin Mol. Pharmacol., November 1, 2003; 64(5): 1251 - 1258. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. A. Hotchkiss, A. W. Ashton, and E. L. Schwartz 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., May 23, 2003; 278(21): 19272 - 19279. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. A. Hotchkiss, A. W. Ashton, R. S. Klein, M. L. Lenzi, G. H. Zhu, and E. L. Schwartz Mechanisms by Which Tumor Cells and Monocytes Expressing the Angiogenic Factor Thymidine Phosphorylase Mediate Human Endothelial Cell Migration Cancer Res., January 15, 2003; 63(2): 527 - 533. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. D. Seidman and M. Aapro Introduction Oncologist, December 1, 2002; 7(90006): 1 - 3. [Full Text] [PDF]
|
|
|
|
 |
|
 M. Haraguchi, H. Tsujimoto, M. Fukushima, I. Higuchi, H. Kuribayashi, H. Utsumi, A. Nakayama, Y. Hashizume, J. Hirato, H. Yoshida, et al. Targeted Deletion of Both Thymidine Phosphorylase and Uridine Phosphorylase and Consequent Disorders in Mice Mol. Cell. Biol., July 15, 2002; 22(14): 5212 - 5221. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Frickhofen, F.-J. Beck, B. Jung, H.-G. Fuhr, H. Andrasch, and M. Sigmund Capecitabine can induce acute coronary syndrome similar to 5-fluorouracil Ann. Onc., May 1, 2002; 13(5): 797 - 801. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Uchimiya, T. Furukawa, M. Okamoto, Y. Nakajima, S. Matsushita, R. Ikeda, T. Gotanda, M. Haraguchi, T. Sumizawa, M. Ono, et al. Suppression of Thymidine Phosphorylase-mediated Angiogenesis and Tumor Growth by 2-Deoxy-L-ribose Cancer Res., May 1, 2002; 62(10): 2834 - 2839. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. M. Borner, D. Dietrich, R. Stupp, R. Morant, H. Honegger, M. Wernli, R. Herrmann, B. C. Pestalozzi, P. Saletti, S. Hanselmann, et al. Phase II Study of Capecitabine and Oxaliplatin in First- and Second-Line Treatment of Advanced or Metastatic Colorectal Cancer J. Clin. Oncol., April 1, 2002; 20(7): 1759 - 1766. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. L. Schilsky, D. Bertucci, N. J. Vogelzang, H. L. Kindler, and M. J. Ratain Dose-Escalating Study of Capecitabine Plus Gemcitabine Combination Therapy in Patients With Advanced Cancer J. Clin. Oncol., January 15, 2002; 20(2): 582 - 587. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Osanai, W. Ichikawa, Y. Takagi, H. Uetake, Z. Nihei, and K. Sugihara Expression of Pyrimidine Nucleoside Phosphorylase (PyNPase) in Colorectal Cancer Jpn. J. Clin. Oncol., October 1, 2001; 31(10): 500 - 505. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. T.-P. Poon, S.-T. Fan, and J. Wong Clinical Implications of Circulating Angiogenic Factors in Cancer Patients J. Clin. Oncol., February 15, 2001; 19(4): 1207 - 1225. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Kono, M. Nishida, N. Inagaki, Y. Tanaka, M. Yoneda, and S. Kasai Development and Characterization of 1C6-203, a New Monoclonal Antibody Specific to Human Thymidine Phosphorylase J. Histochem. Cytochem., January 1, 2001; 49(1): 131 - 138. [Abstract] [Full Text]
|
|
|
|
|
|
R. Fujiwaki, K. Hata, K. Nakayama, M. Fukumoto, and K. Miyazaki Gene Expression for Dihydropyrimidine Dehydrogenase and Thymidine Phosphorylase Influences Outcome in Epithelial Ovarian Cancer J. Clin. Oncol., December 1, 2000; 18(23): 3946 - 3951. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Van Cutsem, M. Findlay, B. Osterwalder, W. Kocha, D. Dalley, R. Pazdur, J. Cassidy, L. Dirix, C. Twelves, D. Allman, et al. Capecitabine, an Oral Fluoropyrimidine Carbamate With Substantial Activity in Advanced Colorectal Cancer: Results of a Randomized Phase II Study J. Clin. Oncol., March 13, 2000; 18(6): 1337 - 1345. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. van Triest, H. M. Pinedo, J. L. G. Blaauwgeers, P. J. van Diest, P. S. Schoenmakers, D. A. Voorn, K. Smid, K. Hoekman, H. F. W. Hoitsma, and G. J. Peters Prognostic Role of Thymidylate Synthase, Thymidine Phosphorylase/ Platelet-derived Endothelial Cell Growth Factor, and Proliferation Markers in Colorectal Cancer Clin. Cancer Res., March 1, 2000; 6(3): 1063 - 1072. [Abstract] [Full Text]
|
|
|
|
 |
|
 R. Konda, H. Sato, K. Sakai, M. Sato, S. Orikasa, and N. Kimura Expression of Platelet-Derived Endothelial Cell Growth Factor and its Potential Role in Up-Regulation of Angiogenesis in Scarred Kidneys Secondary to Urinary Tract Diseases Am. J. Pathol., November 1, 1999; 155(5): 1587 - 1597. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Matsuura, I. Kuratate, K. Teramachi, M. Osaki, Y. Fukuda, and H. Ito Thymidine Phosphorylase Expression Is Associated with Both Increase of Intratumoral Microvessels and Decrease of Apoptosis in Human Colorectal Carcinomas Cancer Res., October 1, 1999; 59(19): 5037 - 5040. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J.-i. Yamashita, M. Ogawa, M. Abe, and M. Nishida Platelet-Derived Endothelial Cell Growth Factor/Thymidine Phosphorylase Concentrations Differ in Small Cell and Non-small Cell Lung Cancer Chest, July 1, 1999; 116(1): 206 - 211. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Fujimoto, H. Sakaguchi, R. Hirose, H. Wen, and T. Tamaya Clinical Implication of Expression of Platelet-derived Endothelial Cell Growth Factor (PD-ECGF) in Metastatic Lesions of Uterine Cervical Cancers Cancer Res., July 1, 1999; 59(13): 3041 - 3044. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Twelves, R. Glynne-Jones, J. Cassidy, J. Schuller, T. Goggin, B. Roos, L. Banken, M. Utoh, E. Weidekamm, and B. Reigner Effect of Hepatic Dysfunction due to Liver Metastases on the Pharmacokinetics of Capecitabine and Its Metabolites Clin. Cancer Res., July 1, 1999; 5(7): 1696 - 1702. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. A. Villalona-Calero, G. R. Weiss, H. A. Burris, M. Kraynak, G. Rodrigues, R. L. Drengler, S. G. Eckhardt, B. Reigner, J. Moczygemba, H. U. Burger, et al. Phase I and Pharmacokinetic Study of the Oral Fluoropyrimidine Capecitabine in Combination With Paclitaxel in Patients With Advanced Solid Malignancies J. Clin. Oncol., June 1, 1999; 17(6): 1915 - 1915. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Toi, T. Ueno, H. Matsumoto, H. Saji, N. Funata, M. Koike, and T. Tominaga Significance of Thymidine Phosphorylase as a Marker of Protumor Monocytes in Breast Cancer Clin. Cancer Res., May 1, 1999; 5(5): 1131 - 1137. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Matsushita, T. Nitanda, T. Furukawa, T. Sumizawa, A. Tani, K. Nishimoto, S. Akiba, K. Miyadera, M. Fukushima, Y. Yamada, et al. The Effect of a Thymidine Phosphorylase Inhibitor on Angiogenesis and Apoptosis in Tumors Cancer Res., April 1, 1999; 59(8): 1911 - 1916. [Abstract] [Full Text] [PDF]
|
|