Trabeculated adenoma of the thyroid gland and its malignant transformation.
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Biomedical subjects
Publications and source records attributed to S Otani.
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Diisobutyl-, dibutyl-, and dioctyl phthalates, at a concentration of 50 microM, markedly inhibited the incorporation of [3H]thymidine into DNA in tumor cells and also cell proliferation. The inhibitions were synergistically enhanced by hyperthermia at 42 degrees C for 1 h. In contrast, dimethyl-, and diethyl phthalates induced almost no inhibition. The effective phthalates were detected in the cells by gas-liquid chromatography, whereas the non-effective drugs were not or were little detected, suggesting involvement of permeability through cell membrane in cytotoxic effects. Combination of the cytotoxic phthalic acid esters and hyperthermia is suggested to be an advantageous treatment for cancer.
Ornithine decarboxylase (ODC) activity and polyamine levels in mucosal specimens obtained by endoscopic biopsy from the stomal portion and greater curvature of the gastric remnant mucosa taken from 181 patients were determined and compared with the histopathological findings. The results obtained can be summarized as follows. (a) The ODC activity was significantly higher in the stomal portion [455 +/- 340 (mean +/- SD)] of the gastric remnant than in the greater curvature (148 +/- 107). The ODC activity of the stomal portion was significantly higher following a Billroth's II method (599 +/- 417) than following any other operative method that consists of a Billroth's I method (327 +/- 172) and a Roux-en Y (341 +/- 191). (b) The levels of total polyamine, putrescine, spermidine, and spermine were also significantly higher in the stomal portion of the gastric remnant than in the greater curvature. There were no significant differences in the stomal tissue level of any of these substances among operative procedures used. (c) Histopathological changes consisting of glandular dilatation and an irregular glandular structure were detected more frequently in the stomal mucosal specimens, especially following a Billroth's II method. In summary, the present findings suggest that the measurement of ODC activity may thus be considered as one method of estimating the risk of carcinogenesis.
BACKGROUND/AIM: There are various indices of liver regeneration, but no clinically useful index that reflects the current status of liver regeneration. We assayed human erythrocyte polyamine levels after partial hepatectomy to define the relationship between erythrocyte polyamine levels and liver regeneration. MATERIALS AND METHODS: Levels of human erythrocyte polyamines (putrescine, spermidine, and spermine) were assayed by high-pressure liquid chromatography in 91 patients after partial hepatectomy and in 13 patients after surgery other than partial hepatectomy (controls). Of the patients after partial hepatectomy, 37 underwent hepatectomy of 20% or more of the liver (group A), 27 underwent segmentectomy or subsegmentectomy of the liver amounting to less than 20% of the liver (group B), and 27 underwent an operation smaller in scale than sub-segmentectomy (group C). RESULTS: The greater the proportion of the liver resected, the greater was the percent increase. In groups A, B, and C, erythrocyte levels of spermidine and spermine increased after surgery compared with the base line, and were significantly higher at 7 or 14 days, decreasing later. The differences in spermidine among the three groups were significant. CONCLUSIONS: After partial hepatectomy, the erythrocyte polyamine levels, especially the level of spermidine, were related to the proportion of liver resected. They seemed to reflect the degree of liver regeneration.
Ras proteins must be isoprenylated at a conserved cysteine residue near the carboxyl terminus (Cys-186 in mammalian Ras p21 proteins) in order to extend their biological activity. Previous studies have indicate an intermediate in the mevalonate pathway, most likely farnesyl pyrophosphate, is the donor of this isoprenyl group, and that using inhibitors of the mevalonate pathway could block the transforming properties of ras oncogene. Unfortunately, mevalonate is a precursor of various end products essential to mammalian cells, such as dolichols, ubiquinones, heme A, and cholesterol. In this study, we partially purified farnesyl protein transferase (FPTase) capable of catalyzing the farnesylation of unprocessed Ras p21 proteins in vitro from porcine kidney epithelial-like LLC-PK 1 cells, human lung adenocarcinoma A549 cells and human pancreatic cancer MIA PaCa-2 cells. This FPTase activity requires a divalent cation, such as Mg2+ or Zn2+ ions, sulfhydryl protecting agent, DTT, as well as certain pH which is linear with time and with enzyme concentration, and is present in many mammalian normal cell and tumor cell lines. Sequentially, we observed the effects of the monoterpene compound, d-limonene; curcumin derivatives, CD-I and CD-II; polyphenol compound, gallotannin; Salvia miltiorrhiza derivative, SMD; and retinoid acid derivative, RAD on FPTase activity. We found that curcumin derivatives and gallotannin had a strong inhibition on FPTase besides d-limonene, while gallotannin was the strongest among synthetic and natural compounds tested. Salivia miltiorrhiza and retinoid acid derivatives had no influence on FPTase activity. Our results suggest that compounds containing polyphenol hydroxyl may be a new source of FPTase inhibitors. The experiment also showed that availability of an in vitro farnesyl protein transferase assay could be useful in screening for potential inhibitors of ras oncogene function that will not interfere with other aspects of the mevalonate pathway.
Hepatocyte growth factor (HGF) induced apoptosis and decreased the DNA synthesis in Hep G2 cells. In the HGF group interleukin-1 converting enzyme, ornithine decarboxylase (ODC) activity and intracellular polyamine concentrations were increased compared to those of the control group. Administration of the ODC inhibitor decreased polyamine concentration, and inhibited apoptotic changes in the cells. These changes were reversed by exogenous addition of polyamine. These findings suggest that one of the mechanisms by which HGF exerts its antiproliferative effect is induction of apoptosis and that increase in intracellular polyamine concentration may be one of the triggers of cell death.