Orotate phosphoribosyltransferase levels measured by a newly established enzyme-linked immunosorbent assay in gastric carcinoma

Yoichi Sakurai, Kazuki Sakamoto, Yoshikazu Sugimoto, Ikuo Yoshida, Toshihiko Masui, Shuhei Tonomura, Kazuki Inaba, Mitsutaka Shoji, Yasuko Nakamura, Ichiro Uyama, Yoshiyuki Komori, Masahiro Ochiai, Shiro Matsuura, Hideyuki Tanaka, Toshinori Oka, Masakazu Fukushima

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

A number of enzymes have been shown to be involved in the process of activation and/or degradation of 5-fluorouracil (5-FU), and are potential candidates for predicting chemosensitivity to 5-FU. Among these, orotate phosphoribosyltransferase (OPRT EC 2.4.2.10) is a key enzyme related to the first-step activation process of 5-FU and has been shown to be an important enzyme that helps to predict sensitivity to 5-FU and its related derivatives. We developed a new enzyme-linked immunosorbent assay (ELISA) to accurately assess intratumoral activity of OPRT. A new sandwich ELISA was established using anti-OPRT polyclonal antibodies obtained from the rabbit immunized with the recombinant human peptides of the OPRT molecule. OPRT levels were measured in eight human cancer xenografts and in 75 gastric cancer tissues using both a newly established ELISA and a conventional enzyme assay, using radiolabeled 5-FU as a substrate. There was a significant correlation between OPRT levels measured by this ELISA and OPRT enzyme activity the in eight human cancer xenografts (r2 = 0.782) and gastric carcinoma tissue (r2 = 0.617). The ELISA system for OPRT requires a minimal amount of carcinoma tissue, making it an easy-to-use assay system to predict sensitivity to 5-FU and its derivatives in gastric carcinoma. There was a significant correlation between tumor growth inhibition rates against the oral administration of oral-uracil/tegafur (UFT) and OPRT enzyme activity in the human cancer xenografts (r2 = 0.574). These results suggest that this newly developed sandwich ELISA system for the quantification of OPRT levels is technically simple, feasible and a useful tool to predict sensitivity to fluoropyrimidine-based anticancer chemotherapy in patients with gastric carcinoma and other cancers.

Original languageEnglish
Pages (from-to)492-498
Number of pages7
JournalCancer Science
Volume97
Issue number6
DOIs
Publication statusPublished - 2006 Jun
Externally publishedYes

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Orotate Phosphoribosyltransferase
Fluorouracil
Stomach
Enzyme-Linked Immunosorbent Assay
Carcinoma
Heterografts
Enzymes
Neoplasms
Tegafur
Uracil
Enzyme Assays
Human Activities
Stomach Neoplasms
Oral Administration
Rabbits
Drug Therapy
Peptides
Antibodies
Growth

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Orotate phosphoribosyltransferase levels measured by a newly established enzyme-linked immunosorbent assay in gastric carcinoma. / Sakurai, Yoichi; Sakamoto, Kazuki; Sugimoto, Yoshikazu; Yoshida, Ikuo; Masui, Toshihiko; Tonomura, Shuhei; Inaba, Kazuki; Shoji, Mitsutaka; Nakamura, Yasuko; Uyama, Ichiro; Komori, Yoshiyuki; Ochiai, Masahiro; Matsuura, Shiro; Tanaka, Hideyuki; Oka, Toshinori; Fukushima, Masakazu.

In: Cancer Science, Vol. 97, No. 6, 06.2006, p. 492-498.

Research output: Contribution to journalArticle

Sakurai, Y, Sakamoto, K, Sugimoto, Y, Yoshida, I, Masui, T, Tonomura, S, Inaba, K, Shoji, M, Nakamura, Y, Uyama, I, Komori, Y, Ochiai, M, Matsuura, S, Tanaka, H, Oka, T & Fukushima, M 2006, 'Orotate phosphoribosyltransferase levels measured by a newly established enzyme-linked immunosorbent assay in gastric carcinoma', Cancer Science, vol. 97, no. 6, pp. 492-498. https://doi.org/10.1111/j.1349-7006.2006.00200.x
Sakurai, Yoichi ; Sakamoto, Kazuki ; Sugimoto, Yoshikazu ; Yoshida, Ikuo ; Masui, Toshihiko ; Tonomura, Shuhei ; Inaba, Kazuki ; Shoji, Mitsutaka ; Nakamura, Yasuko ; Uyama, Ichiro ; Komori, Yoshiyuki ; Ochiai, Masahiro ; Matsuura, Shiro ; Tanaka, Hideyuki ; Oka, Toshinori ; Fukushima, Masakazu. / Orotate phosphoribosyltransferase levels measured by a newly established enzyme-linked immunosorbent assay in gastric carcinoma. In: Cancer Science. 2006 ; Vol. 97, No. 6. pp. 492-498.
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