Vitamin K Contents in Liver Tissue of Hepatocellular Carcinoma Patients

Serum protein induced in vitamin K absence‐II (PIVKA‐II) is used as a tumor marker because it increases at a notably higher rate in patients with hepatocellular carcinoma. To clarify the mechanism causing the elevation of serum PIVKA‐II, we measured the contents of vitamins K1 (phylloquinone, PK) and K2 (menaquinone, MK) (MK‐4, MK‐5, MK‐6, MK‐7, MK‐8, MK‐9, MK‐10) in liver tissue resected from 21 hepatic cancer patients (12 patients with hepatocellular carcinoma and 9 patients with metastatic hepatic cancer), using HPLC combined with coulometric reduction and fluorometric detection. In the cancerous tissue of hepatocellular carcinoma patients, PK, MK‐7, MK‐8, and MK‐10 in the cancerous tissue of hepatocellular carcinoma patients were significantly lower than that in the cancerous tissue of metastatic hepatic cancer patients. These data suggested that one of the mechanisms of the elevation of serum PIVKA‐II levels in hepatocellular carcinoma patients is a vitamin K deficiency in the local cancerous tissue.

[1]  J. Suttie,et al.  Comparative Distribution, Metabolism, and Utilization of Phylloquinone and Menaquinone-9 in Rat Liver , 1995, Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine.

[2]  H. Obata,et al.  Levels of vitamin K, immunoreactive prothrombin, des‐γ‐carboxy prothrombin and γ‐glutamyl carboxylase activity in hepatocellular carcinoma tissue , 1995 .

[3]  J. Suttie.  The importance of menaquinones in human nutrition. , 1995, Annual review of nutrition.

[4]  J. Belghiti,et al.  Mechanism of the abnormal vitamin k‐dependent γ‐carboxylation process in human hepatocellular carcinomas , 1994 .

[5]  A. Bach,et al.  Vitamin K-dependent carboxylase activity, prothrombin mRNA, and prothrombin production in two cultured rat hepatoma cell lines. , 1993, Thrombosis research.

[6]  M. Omata,et al.  Nucleotide sequence of prothrombin gene in abnormal prothrombin‐producing hepatocellular carcinoma cell lines , 1992, Cancer.

[7]  H. Ohta,et al.  Measurement of immunoreactive prothrombin, des-gamma-carboxy prothrombin, and vitamin K in human liver tissues: overproduction of immunoreactive prothrombin in hepatocellular carcinoma. , 1990, The American journal of gastroenterology.

[8]  C. Vermeer,et al.  Comparison of the vitamins K1, K2 and K3 as cofactors for the hepatic vitamin K-dependent carboxylase. , 1990, Biochimica et biophysica acta.

[9]  Ding‐Shinn Chen,et al.  Plasma des‐γ‐carboxyprothrombin in the early stage of hepatocellular carcinoma , 1990 .

[10]  K. Ozawa,et al.  Measurement of vitamin K in human liver by gradient elution high-performance liquid chromatography using platinum-black catalyst reduction and fluorimetric detection. , 1989, Journal of chromatography.

[11]  Y. Suzuki,et al.  Measurement of K vitamins in animal tissues by high-performance liquid chromatography with fluorimetric detection. , 1989, Journal of chromatography.

[12]  S. Fujiyama,et al.  Plasma abnormal prothrombin (Des‐γ‐carboxy prothrombin) as a marker of hepatocellular carcinoma , 1988 .

[13]  A. Morimoto,et al.  Simultaneous determination of vitamin K1, vitamin K1 2,3-epoxide and menaquinone-4 in human plasma by high-performance liquid chromatography with fluorimetric detection. , 1988, Journal of chromatography.

[14]  J. Lefrère,et al.  A New Method to Assay Des-γ-carboxyprothrombin , 1986 .

[15]  K. Sagara,et al.  Clinical evaluation of plasma abnormal prothrombin (PIVKA-II) in patients with hepatocellular carcinoma. , 1986, Hepato-gastroenterology.

[16]  A. Morimoto,et al.  Measurement of K vitamins in human and animal feces by high-performance liquid chromatography with fluorometric detection. , 1986, Chemical & pharmaceutical bulletin.

[17]  A. Morimoto,et al.  Measurement of K vitamins in human and animal plasma by high-performance liquid chromatography with fluorometric detection. , 1986, Chemical & pharmaceutical bulletin.

[18]  F. Endo,et al.  Detection of vitamin K deficiency by use of an enzyme-linked immunosorbent assay for circulating abnormal prothrombin. , 1985, Pediatric research.

[19]  Shou-Dong Lee,et al.  Des-γ-Carboxy (Abnormal) Prothrombin as a Serum Marker of Primary Hepatocellular Carcinoma , 1984 .

[20]  D. Mack,et al.  Solubilized Rat Liver Vitamin K Carboxylase Demonstrates Little Selectivity between Vitamin K1 and the Menaquinones , 1980, Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine.

[21]  E. Gardner,et al.  Effect of vitamin K homologues on the conversion of preprothrombin to prothrombin in rat liver microsomes. , 1976, Biochemical and biophysical research communications.

[22]  M. Shia,et al.  Some characteristics of a vitamin K-dependent carboxylating system from rat liver microsomes. , 1976, Biochemical and biophysical research communications.

[23]  P. Fernlund,et al.  Vitamin K dependent modifications of glutamic acid residues in prothrombin. , 1974, Proceedings of the National Academy of Sciences of the United States of America.

[24]  G. Nelsestuen,et al.  The purification and properties of an abnormal prothrombin protein produced by dicumarol-treated cows. A comparison to normal prothrombin. , 1972, The Journal of biological chemistry.

[25]  H. Hemker,et al.  Kinetic aspects of the interaction of blood clotting enzymes , 2007 .

[26]  P. O. Ganrot,et al.  Plasma prothrombin during treatment with Dicumarol. II. Demonstration of an abnormal prothrombin fraction. , 1968, Scandinavian journal of clinical and laboratory investigation.