Biomedical subjects

N Miwa

Publications and source records attributed to N Miwa.

99 records · Page 6Linked to original sources

PubMedDate not supplied

Serum levels of macrophage colony-stimulating factor and aortic calcification in hemodialysis patients.

Hemodialysis (HD) patients have accelerated atherosclerosis. Recent reports have shown that aortosclerosis is more frequently observed in HD patients than in healthy subjects. Macrophage colony-stimulating factor (M-CSF) secreted by activated macrophages may be involved in the process of aortosclerosis in HD patients. To understand the mechanism behind the increased incidence of aortosclerosis in HD patients, we examined the relationships between serum M-CSF levels and aortic calcification index (ACI) estimated by CT scan. A significant increase in serum M-CSF concentrations was found in HD patients (3.8 +/- 0.2 ng/ml) as compared with controls (1.5 +/- 0.1 ng/ml). No significant differences were observed between chronic glomerulonephritis and diabetes mellitus groups of patients. We also found no significant differences between the groups using different membranes (triacetate 3.8 +/- 0.2 ng/ml vs. polysulfone 3.8 +/- 0.4 ng/ml). There was no correlation between serum M-CSF concentrations and clinical parameters such as age, duration of HD, blood pressure, serum concentrations of nitrogen, creatinine, cholesterol, triglyceride, LDL, Ca x P products, and intact parathyroid hormone. A positive correlation was observed between serum M-CSF levels and ACI in HD patients (r = 0.596, p < 0.01). These results suggest that M-CSF may be involved in the process of aortosclerosis in HD patients.

Aortic Diseases↗

PubMedDate not supplied

Enhanced inhibition of DNA synthesis and release of membrane phospholipids in tumour cells treated with a combination of acylated ascorbate and hyperthermia.

Combined antitumour effects of mono- or diacyl ascorbates and heat treatment were studied in comparison with the parent compound, L-ascorbic acid (AsA). At 37 degrees C, 75 microM 6-O-palmitoyl (6P) and 6-O-stearoyl (6S) ascorbates appreciably inhibited DNA synthesis in Ehrlich ascites tumour cells. Hyperthermia at 42 degrees C for 1 h increased the inhibition. In contrast, AsA or 2,6-O-dipalmitoyl ascorbate (DP), even at concentrations as high as 100 microM, caused no inhibition at 37 degrees C or 42 degrees C. The results suggest that the inhibitory action is not caused by the fatty acid moiety itself; it is more likely to be caused by the balance in the hydrophobicity and hydrophilicity of the monoacylated AsA, a property not found in diacylated or intact AsA. Inhibition of DNA synthesis caused by exposure to 6P during hyperthermia of tumour cells was greater than before or after hyperthermia. 6P or 6S, but not AsA or DP, released phospholipids such as phosphatidylcholine and phosphatidylethanolamine from cells labelled with [14C]oleic acid, as shown by radiocurves taken from thin-layer chromatograms. Damage of the cell membrane seemed to be involved in the inhibition of DNA synthesis caused by monoacylated AsA, which is surface-active.

Acylation↗

PubMedDate not supplied

Cytotoxicity of docosahexaenoic acid and eicosapentaenoic acid in tumor cells and the dependence on binding to serum proteins and incorporation into intracellular lipids.

Docosahexaenoic acid (DHA) inhibited the DNA synthesis in Ehrlich ascites tumor cells more markedly than eicosapentaenoic acid (EPA), which was more inhibitory than oleic-, linoleic-, linolenic-, and arachidonic acids. Their activities augmented according to the increase of number of double bonds in the molecule. To correlate the cytotoxicity with lipid syntheses in the cells, distribution of EPA and DHA incorporated into cellular lipids was assessed. EPA was incorporated into triglycerides (TG) and DHA into phosphatidylcholine (PC). These synthesis into TG and PC etc., which shattered from cytotoxicity, may be involved in tumor-cellular protecting actions against EPA or DHA. EPA and DHA involved in cytotoxicity exhibition are their free acid forms. Thus, as an anticancer reaction, intracellular accumulation in the free acid form of DHA was more marked than that of EPA.

Animals↗

PubMedDate not supplied

Correlation of DNA synthesis-inhibiting activity and the extent of transmembrane permeation into tumor cells by unsaturated or saturated fatty alcohols of graded chain-length upon hyperthermia.

The carcinostatic activity has been studied for fatty acids of diverse species but scarcely for fatty alcohols. Three unsaturated fatty alcohols at 35-50 microM inhibited DNA synthesis and the proliferation of tumor cells by a combination with hyperthermia to greater extents in the order: oleyl (C18:1)-> linoleyl (C18:2)-> alpha-linolenyl (C18:3) alcohol, which is an order inverse to that known for the corresponding fatty acids (4). In contrast, two saturated fatty alcohols, palmityl (C16:0)- and stearyl (C18:0) alcohols, did not inhibit at the same concentrations. At 100 microM, palmityl alcohol inhibited, whereas stearyl alcohol did not. The effective fatty alcohols appreciably permeated the cells. The inhibition of the unsaturated fatty alcohols on DNA synthesis and proliferation was nearly proportional to the amount of their intercellular accumulation at 37 degrees C or 42 degrees C; the most inhibitory, oleyl alcohol, was the most membrane-permeable, whilst inversely the least inhibitory, alpha-linolenyl alcohol, was the least permeable. A proportional correlation was not observed for saturated fatty alcohols; palmityl alcohol underwent an approximate 2-fold more abundant accumulation than other fatty alcohols, but was weakly inhibitory. Thus, oleyl alcohol may exert an antitumor action via appropriately efficient transmembrane permeation and a combination with hyperthermia.

Animals↗

PubMedDate not supplied

Abnormal cell morphology and cytotoxic effect are induced by 6-0-palmitol-ascorbate-2-0-phosphate, but not by ascorbic acid or hyperthermia alone.

A new derivative of ascorbic acid (AsA), 6-0-palmitoyl-ascorbate 2-0-phosphate (Asc2P6Pal) was developed to enhance the antitumor activity of AsA. When Ehrlich ascites tumor cells were treated with 50 microM Asc2P6Pal at 37 degrees C or 42 degrees C for 1 h and then cultured for 20 h, most of cells exhibited some morphological abnormalities, including exudation of intracellular granules together with other contents on the cell membrane surface, resulting in cell fragmentation. The abnormal features were further enhanced by a long term culture for 96 h and heat treatment at 42 degrees C. In contrast, no abnormality was detected for untreated cells or cells treated with AsA (free acid) at 37 degrees C or 42 degrees C. Cells cultured for 96 h after the treatment suffered from inhibition of DNA synthesis and proliferation. This inhibition was markedly enhanced by combination with the hyperthermic treatment at 42 degrees C, but not for a short-term culture of 20 h after the treatment. No effects were seen upon similar treatment with AsA. The abnormal cells produced during culture for 20 h after the treatment were evaluated to be viable, because they failed to be stained with trypan blue and retained most of the DNA synthesizing ability of Asc2P6Pal-untreated cells. However, they appeared and died after a continuous 76 h of culture (96 h).

Animals↗

PubMedDate not supplied

Anti-metastatic effect of an autooxidation-resistant and lipophilic ascorbic acid derivative through inhibition of tumor invasion.

The invasion of human fibrosarcoma HT-1080 cells through Matrigel was shown to be inhibited by pretreatment with ascorbic acid (Asc) or its four derivatives, such as Asc-6-O-palmitate (Asc6Plm), Asc-2-O-phosphate (Asc2P), Asc-2-O-phosphate-6-O-palmitate (Asc2P6Plm), and Asc-5,6-benzylidene (Asc5,6Bz) of non-cytotoxic concentrations for 1 or 18 hr. Two lipophilic derivatives such as Asc6Plm and Asc2P6Plm exerted an invasiveness-inhibitory activity more markedly with 1-hr pretreatment, being a more practical index in terms of the plasma half-life, than Asc, Asc5,6Bz or Asc2P being less lipophilic. Considerably less cytotoxicity (a > 3.3-fold higher IC50 for 1-hr pretreatment) of Asc2P6Plm sufficiently compensated a slightly lower invasiveness-inhibitory activity (a < 1.8-fold higher EC50) as compared with Asc6Plm. Pulmonary metastasis of mouse melanoma B16BL6 cells injected into the tail vein was also inhibited by intravenous administration with Asc2P6Plm dose-dependently. Thus Asc2P6Plm, a lipophilicity-hydrophilicity balanced molecule protectively blockd in the autooxidation-prone moiety, is anticipated as a potent anti-metastatic agent via inhibition of tumor invasion.

Animals↗

PubMedDate not supplied

Enhancement of ascorbate cytotoxicity by chelation with ferrous ions through prolonged duration of the action.

Fe(II)-L-ascorbic acid complex (FeAsc) exhibited a greater cytotoxicity [50% inhibitory dose (IC50), 24-32 microM] to human carcinoma A 549 or rat SV40-transformed W3Y cells than ascorbic acid (Asc) (IC50, 460-660 microM); a simple mixture of Fe(II) and Asc, or Fe(II) alone was also less cytotoxic. Malignant cells from a variety of tissues of different species were also susceptible to FeAsc. FeAsc exhibited a longer half-life (66-82 hours) during cell contact than that of Asc (2.5-3.1 hours). Thus chelated Fe(II) but not unbound Fe (II) was responsible for the enhanced cytotoxicity of FeAsc, which was attributed primarily to its prolonged duration of action.

Animals↗

PubMedDate not supplied

DNA synthesis inhibition and transmembrane permeation into tumor cells by various dialkyl phthalates upon hyperthermia.

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.

Animals↗

PubMedDate not supplied

Wool grease-derived alpha-monohydric fatty alcohols are carcinostatic depending on their branched alkyl moiety bulkiness.

Wool fatty alcohols (WF-Alc) separated from esterolysates of sheep cutaneous wax were fractionated by molecular distillation and HPLC, resulting in two homogeneous antitumor compounds identified by GC-MS and 13C-/1H-NMR as a-monohydric branched saturated fatty alcohols, 14-methyl-1-pentadecanol (iso-C16OH) and 14-methyl-1-hexadecanol (anteiso-C17OH). Both the alcohols markedly prolonged the life-span of Ehrlich ascites carcinoma- or S180 fibrosarcoma-implanted mice without acute toxic side-effects, whereas other iso- or n-fatty alcohols (C16-C30) contained in WF-Alc were slightly effective. Thus antitumor activity of WF-Alc depended on the molecular balanced hydrophobicity attributed to both the branched alkyl moiety bulkiness derived from the diverse fatty alcohols contained, and a hydroxyl group.

Animals↗