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Biomedical subjects

H Okuda

Publications and source records attributed to H Okuda.

550 records · Page 31Linked to original sources
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Sonographic estimation of liver tumor development induced by oral administration of thioacetamide in rat.

Animal models for various types of cancer are of great help in the study of tumors and antitumor effects. Subcutaneous models have been widely utilized because they can be produced easily by subcutaneously implanting tumor cells into animals. Although subcutaneous models are very convenient for examining tumor development, they are definitely different from clinical manifestations of original tumors. In orthotopic animal models for internal tumors, however, it is difficult to examine tumor development without sacrificing animals. We demonstrate here that the occurrence and growth of liver tumors induced by oral administration of thioacetamide into rats were clearly observable by ultrasonography, and that the sonographic estimation was accurate. It was observed sonographically that the number and volume of liver tumors increased proportionately with TAA treatment periods. These results indicate that sonography is a useful and non-invasive method to investigate liver tumor development in rats.

Administration, Oral↗
PubMedDate not supplied

Inhibitory effects of active substances isolated from Cassia garrettiana heartwood on tumor growth and lung metastasis in Lewis lung carcinoma-bearing mice (Part 1).

A methanol extract (500 mg/kg x 2/day) of the heartwood of Cassia garrettiana inhibited the tumor growth and metastasis to the lung in Lewis lung carcinoma (LLC)-bearing mice. We isolated the two active substances from the methanol extract of C. garrettiana: compound 1 was identified as Cassigarol A and the determination of the structure of compound 2 is now in progress. We examined the effect of the active substance (compound 1, Cassigarol A) on tumor growth and lung metastasis in LLC-bearing and primary tumor-removed mice and found that Cassigarol A (50 mg and 100 mg/kg x 2/day) inhibited the tumor growth and metastasis to the lung. In addition, Cassigarol A inhibited the plasmin activity and the formation of capillary-like networks of human umbilical vein endothelial cells (HUVECs) at concentrations of 10 to 100 microM. Therefore, it is suggested that the antitumor and antimetastatic activities of Cassigarol A might be due to the inhibition of plasmin activity and formation of tubes (angiogenesis) from HUVECs.

Angiogenesis Inhibitors↗
PubMedDate not supplied

Inhibitory effects of active substances isolated from Cassia garrettiana heartwood on tumor growth and lung metastasis in Lewis lung carcinoma-bearing mice (Part 2).

Previously, we reported that a methanol extract (500 mg/kg x 2/day) of the heartwood of Cassia garrettiana inhibited the tumor growth and metastasis to the lung in Lewis lung carcinoma (LLC)-bearing mice. Furthermore, we isolated the two active substances from the methanol extract of C. garrettiana and identified compound 1 as cassigarol A. In the present study, compound 2 was identified as 3, 3', 4, 5'-tetrahydroxy stilbene (piceatannol) based on the 1H-NMR spectral data and products formed by oxidation with potassium permanganate. We examined the active substance (compound 2, piceatannol) and its acetylated derivative on the tumor growth and lung metastasis in LLC-bearing and carcinectomized mice. Piceatannol (50 mg and 100 mg/kg x 2/day) did not affect the tumor growth, while piceatannol acetate (50 mg and 100 mg/kg x 2/day) significantly inhibited the tumor growth. Piceatannol and its derivative piceatannol acetate inhibited the metastasis to the lung dose-dependently in carcinectomized mice. Moreover, piceatannol and piceatannol acetate prolonged the survival time and increased the survival rate in carcinectomized mice. In addition, piceatannol inhibited the formation of capillary-like networks of human umbilical vein endothelial cells (HUVECs) at the concentrations of 10 to 100 microM, but its acetylated derivative did not. Therefore, it is suggested that the antimetastatic activities of piceatannol might be due to the inhibition of tube formation (angiogenesis) of HUVECs.

Acetylation↗
PubMedDate not supplied

Thrombospondin-1 and -2 messenger RNA expression in epithelial ovarian tumor.

BACKGROUND: The role of thrombospondin (TSP) in tumor progression remains controversial. The association of TSP with clinicopathological features regarding prognostic significance was examined in patients with epithelial ovarian tumor. MATERIALS AND METHODS: Gene expression of TSP-1 and TSP-2 was assessed by reverse transcriptase-polymerase chain reaction in 6 borderline and 29 malignant epithelial ovarian tumors. RESULTS: TSP-1 mRNA expression was detected in 14 out of the 29 malignant epithelial ovarian tumors (48.3%), whereas TSP-2 mRNA expression was detected in 7 malignant epithelial ovarian tumors (24.1%). In contrast, no specimen from the borderline epithelial ovarian tumors expressed TSP mRNA. TSP-1 expression was significantly higher in tumors with advanced stage, massive ascites, positive peritoneal cytology and high grade. TSP-2 expression was significantly higher in tumors with massive ascites. Patients exhibiting TSP-1 and -2 mRNA expression demonstrated a markedly poorer prognosis than those lacking TSP-1 and -2 mRNA expression. CONCLUSION: These findings provide evidence that TSP expression may be associated with an aggressive phenotype in this class of neoplasm.

Adenocarcinoma, Clear Cell↗
PubMedDate not supplied

Dose-related effects of phenobarbital on hepatic glutathione-S-transferase activity and ligandin levels in the rat.

To determine which individual parameters contribute to the increased bilirubin clearance which follows phenobarbital administration in the rat, dose response studies are being conducted relating changes in various aspects of bilirubin transport to the dose of phenobarbital administered. The relationships between phenobarbital dose, immunoreactive ligandin concentrations, and cytosolic glutathione-S-transferase (GSHT) enzymatic activities were determined in the 100,000g liver cytosol obtained from non-fasted male Sprague-Dawley rats, treated for 6 days (ip) with either phenobarbital at various doses ranging from 1 to 125 mg/kg/day or distilled water. Ligandin levels were measured by radioimmunoassay employing an antiserum which reacts with both GSHT-1 (Ya) and -2 (Yc) subunits. Ligandin concentration increased in a dose-dependent fashion, achieving a maximal observed value of 278% of control at the highest administered phenobarbital dose. Values were significantly elevated compared to controls at doses as low as 3 mg/kg/day. GSH-dependent delta 5-3-ketosteroid isomerase (KSI) activity, which reflects predominantly GSH transferase subunit 1, and GSHT activity against 1-chloro-2,4-dinitrobenzene (CDNB) also increased over the entire range of phenobarbital doses administered. Both of these enzymatic activities were highly correlated with immunoreactive ligandin levels (KSI: r = 0.89, p less than 0.005; GSHT (CDNB): r = 0.92, p less than 0.001). By contrast, GSHT activity against 1,2-dichloro-4-nitrobenzene (DCNB), which resides principally on GSHT subunits not present in ligandin, did not correlate significantly with measured ligandin concentrations. These studies indicate that phenobarbital is capable of inducing immunoreactive ligandin concentrations and related enzymatic activities at doses as small as 5% of those commonly employed to demonstrate this effect.

Animals↗
PubMedDate not supplied

Analysis of intrahepatic invasion of hepatocellular carcinoma using fluorescent dye-labeled cells in mice.

Despite intensive efforts in the treatment of hepatocellular carcinoma (HCC), its prognosis remains poor, mainly because of intrahepatic metastasis. It is, therefore, important to investigate the invasive and metastatic behavior of HCC. To examine this, murine HCC cells were labeled with the fluorescent carbocyanine dye, DiI and implanted under the capsule of the liver of syngeneic mice. Optimal conditions are described for labeling HCC cells with DiI. Histological analysis using fluorescent and confocal microscopes revealed that HCC cells migrate to and invade the adjacent portal vein, but not the adjacent central vein. Conversely, DiI-labeled hepatocytes were shown not to migrate in the liver. These results suggest that intrahepatic metastasis of HCC occurs by invading the portal venous system. Furthermore, it is indicated that orthotopic implantation of fluorescent dye-labeled tumor cells may be a convenient and useful method to investigate the invasive and metastatic behavior of various types of cancer.

Animals↗