Increased metabolizing activities of the tricarboxylic acid cycle and decreased drug metabolism in hepatocellular carcinoma.

The aim of this study was to determine the metabolizing activities in the liver of patients with hepatocellular carcinoma (HCC). Thin-layer chromatography autoradioluminography was used to measure metabolizing activities. Succinate-producing activity (SPA) was used as an indicator of metabolizing activity of the tricarboxylic acid (TCA) cycle in mitochondria, and diazepam-N-demethylating activity (DZ-DA), diazepam-3-hydroxylating activity (DZ-HA) and tolbutamide-methyl-hydroxylating activity (TB-HA) as indicators of drug metabolizing activities by P-450.

Viability of liver slices exhibiting absorption, metabolism, and elimination of substrates in culture medium.

In an attempt to improve liver slice culture for in vitro tests of newly developed drugs, we found that a relatively thick 2-mm slice was much more viable, long-lived, and metabolically functional than the conventionally used 300-microm-thick slices. Results revealed that some ionic and nonionic compounds (Na(125)I, [(14)C]Ala, and [(14)C]Xyl) dissolved in culture medium were absorbed into the slices, reaching from the cut edges deep into the inner part, in only a short period. Moreover, the slices could be observed for 24 h after incubation so that a normal histological image could be obtained.

Proposition for assessment of quantitative whole-body autoradiography.

To assess recent improvements in quantitative whole-body autoradioluminography (QWBA), the entire QWBA procedure was divided into five processes. Each process was then investigated carefully to determine whether there were any problems in defining a clear standard operating procedure. Results show that use of two instruments, Macro-Cut, Leica, Germany, and the Bioimaging Analyzer with IP, Fuji Photo Film, was essential to produce macroautoradiographs for QWBA data.

Pharmacokinetic analysis and antitumor efficacy of MKT-077, a novel antitumor agent.

MKT-077 (1-ethyl-2-[[3-ethyl-5-(3-methylbenzothiazolin-2-yliden)]-4- oxothiazolidin-2-ylidenemethyl] pyridinium chloride), a novel rhodacyanine dye in phase I/II clinical trials, may provide a new approach to cancer therapy based on the accumulation in the mitochondria of the cells of certain carcinomas, for example, those of the colon, breast and pancreas. To support the development of MKT-077 for clinical application as an intravenous (i.v.

Mechanism of initial distribution of blood-borne colon carcinoma cells in the liver.

Background/aims/methods: The distribution characteristics of a human colon carcinoma cell line, KM12-HX cells, were examined. After intraportal vein (i.p.