| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Molecular Oncology, Markers, Clinical Correlates |
Departments of Medical Oncology [B. v. T., H. M. P., P. S. S., D. A. V., K. S., K. H., G. J. P.] and Pathology [P. J. v. D.], University Hospital Vrije Universiteit, 1007 MB, Amsterdam, and Departments of Pathology[J. L. G. B.] and Surgery [H. F. W. H.], Onze Lieve Vrouwe Gasthuis, 1090 HM, Amsterdam, the Netherlands
5-Fluorouracil (5FU)-based therapy is given to patients with advanced colorectal cancer and as adjuvant treatment. Thymidylate synthase (TS) is the target for 5FU, and may have a prognostic role for the outcome of 5FU-based therapy together with proliferation markers such as p53 and Ki67. Thymidine phosphorylase (TP, also known as platelet-derived endothelial cell growth factor) may be of importance both in the 5FU drug activation pathway and in tumor angiogenesis, similar to vascular endothelial growth factor (VEGF). TS and TP levels were determined biochemically in fresh-frozen tumor specimens of 32 untreated patients with colorectal cancer, whereas in paraffin-embedded tissue samples, immunohistochemistry was performed for TS, TP, and additional prognostic markers such as p53, Ki67, and VEGF as well as microvessel density. All factors were correlated with patient characteristics such as age, gender, Dukes’ stage, angio-invasion, and differentiation grade. TS and TP as measured by various assays were correlated with overall and disease-free survival in this patient group. TP enzyme activity and protein expression correlated with each other. A significant correlation was found between TP enzyme activity and 5-fluoro-2'-deoxyuridine-5'-monophosphate binding activity. VEGF expression correlated significantly with TP immunostaining and Ki67 index. Survival analysis revealed a significant relation of TS levels to the overall survival in this small patient group and a significant correlation between TP activity and disease-free survival. TS and TP both were of prognostic significance in these patients with colorectal cancer. The interesting relationship of TS and TP with angiogenesis and proliferation needs further investigation.
This article has been cited by other articles:
|
|
 |
|
  P. Ceppi, M. Volante, A. Ferrero, L. Righi, I. Rapa, R. Rosas, A. Berruti, L. Dogliotti, G. V. Scagliotti, and M. Papotti Thymidylate Synthase Expression in Gastroenteropancreatic and Pulmonary Neuroendocrine Tumors Clin. Cancer Res., February 15, 2008; 14(4): 1059 - 1064. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. N. Reske, S. Deisenhofer, G. Glatting, B. D. Zlatopolskiy, A. Morgenroth, A. T. J. Vogg, A. K. Buck, and C. Friesen 123I-ITdU-Mediated Nanoirradiation of DNA Efficiently Induces Cell Kill in HL60 Leukemia Cells and in Doxorubicin-, {beta}-, or {gamma}-Radiation-Resistant Cell Lines J. Nucl. Med., June 1, 2007; 48(6): 1000 - 1007. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. W. Suh, J. H. Kim, D. Y. Kim, Y. B. Kim, C. Lee, and S. Choi Which Gene is a Dominant Predictor of Response During FOLFOX Chemotherapy for the Treatment of Metastatic Colorectal Cancer, the MTHFR or XRCC1 Gene? Ann. Surg. Oncol., November 1, 2006; 13(11): 1379 - 1385. [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]
|
|
|
|
 |
|
 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]
|
|
|
|
|
|
G. J. Peters, P. Noordhuis, C. J. van Groeningen, G. Giaccone, U. Holwerda, D. Voorn, A. Schrijvers, J. H. Schornagel, J. H. Beijnen, P. Fumoleau, et al. The Effect of Food on the Pharmacokinetics of S-1 after Single Oral Administration to Patients with Solid Tumors Clin. Cancer Res., June 15, 2004; 10(12): 4072 - 4076. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Popat, A. Matakidou, and R. S. Houlston Thymidylate Synthase Expression and Prognosis in Colorectal Cancer: A Systematic Review and Meta-Analysis J. Clin. Oncol., February 1, 2004; 22(3): 529 - 536. [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]
|
|
|
|
|
|
J. R. Bertino and D. Banerjee Is the Measurement of Thymidylate Synthase to Determine Suitability for Treatment with 5-Fluoropyrimidines Ready for Prime Time? Clin. Cancer Res., April 1, 2003; 9(4): 1235 - 1239. [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]
|
|
|
|
|
|
C. J. Allegra, S. Paik, L. H. Colangelo, A. L. Parr, I. Kirsch, G. Kim, P. Klein, P. G. Johnston, N. Wolmark, and H. S. Wieand Prognostic Value of Thymidylate Synthase, Ki-67, and p53 in Patients With Dukes' B and C Colon Cancer: A National Cancer Institute-National Surgical Adjuvant Breast and Bowel Project Collaborative Study J. Clin. Oncol., January 15, 2003; 21(2): 241 - 250. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Derenzini, L. Montanaro, A. Chilla, E. Tosti, C. Ceccarelli, F. Dall'Olio, D. Ofner, and D. Trere Evaluation of Thymidylate Synthase Protein Expression by Western Blotting and Immunohistochemistry on Human Colon Carcinoma Xenografts in Nude Mice J. Histochem. Cytochem., December 1, 2002; 50(12): 1633 - 1640. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Shirota, W. Ichikawa, H. Uetake, H. Yamada, Z. Nihei, and K. Sugihara Intratumoral Dihydropyrimidine Dehydrogenase Messenger RNA Level Reflects Tumor Progression in Human Colorectal Cancer Ann. Surg. Oncol., July 1, 2002; 9(6): 599 - 603. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Edler, B. Glimelius, M. Hallstrom, A. Jakobsen, P. G. Johnston, I. Magnusson, P. Ragnhammar, and H. Blomgren Thymidylate Synthase Expression in Colorectal Cancer: A Prognostic and Predictive Marker of Benefit From Adjuvant Fluorouracil-Based Chemotherapy J. Clin. Oncol., April 1, 2002; 20(7): 1721 - 1728. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. J. Allegra, A. L. Parr, L. E. Wold, M. R. Mahoney, D. J. Sargent, P. Johnston, P. Klein, K. Behan, M. J. O'Connell, R. Levitt, et al. Investigation of the Prognostic and Predictive Value of Thymidylate Synthase, p53, and Ki-67 in Patients With Locally Advanced Colon Cancer J. Clin. Oncol., April 1, 2002; 20(7): 1735 - 1743. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C.S. Brock and S.M. Lee Anti-angiogenic strategies and vascular targeting in the treatment of lung cancer Eur. Respir. J., March 1, 2002; 19(3): 557 - 570. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Ciccolini, P. Cuq, A. Evrard, S. Giacometti, A. Pelegrin, C. Aubert, J.-P. Cano, and A. Iliadis Combination of Thymidine Phosphorylase Gene Transfer and Deoxyinosine Treatment Greatly Enhances 5-Fluorouracil Antitumor Activity in Vitro and in Vivo Mol. Cancer Ther., December 1, 2001; 1(2): 133 - 139. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Yao, T. Kubota, K. Sato, and R. Kitai Macrophage Infiltration-associated Thymidine Phosphorylase Expression Correlates with Increased Microvessel Density and Poor Prognosis in Astrocytic Tumors Clin. Cancer Res., December 1, 2001; 7(12): 4021 - 4026. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Cancer Research | Clinical Cancer Research |
| Cancer Epidemiology Biomarkers & Prevention | Molecular Cancer Therapeutics |
| Molecular Cancer Research | Cancer Prevention Research |
| Cancer Prevention Journals Portal | Cancer Reviews Online |
| Annual Meeting Education Book | Meeting Abstracts Online |
