Biomedical subjects

M Ishihara

Publications and source records attributed to M Ishihara.

424 records · Page 24Linked to original sources

PubMedDate not supplied

Interferon gamma increases the antitumor activity of mitomycin C against human colon cancer cells in vitro and in vivo.

A combined antitumor activity of mitomycin C (MMC) and interferon gamma-1a (IFN-gamma) was evaluated to be synergistic by the 3-(4, 5-dimethylthiazol-2yl)-2,5-diphenyl-2H tetrazolium bromide assay and human tumor xenografts/severe combined immunodeficient (SCID) mouse system using colon cancer cell lines. The experimental metastasis of WiDr cells in SCID mouse was inhibited by MMC and IFN-gamma with their synergism. Intracellular uptake of MMC in WiDr cells in vitro was significantly increased by IFN-gamma, suggesting the mode of synergism of these agents. This model may also partly explain the antitumor activity of combined MMC, 5-fluorouracil and interleukin-2 treatment on hepatic metastasis of colon cancer.

Animals↗

PubMedDate not supplied

Combined antitumour activity of mitomycin C, 5-fluorouracil and interleukin-2 against human colon cancer cells.

Combined treatment of interleukin-2 (IL-2), 5-fluorouracil (5-FU) and mitomycin C (MMC) is reported to be effective against hepatic metastasis of colon carcinoma. To clarify this modality, we investigated lymphokine activated killer (LAK) activity of human peripheral lymphocytes on colon cancer cell lines by 51Cr release assay. LAK activity against Colo 205 cells by untreated lymphocytes was 12%, which increased to 25% upon the addition of 5-FU, but remained unchanged upon the addition of MMC. The combined antitumour activity of MMC or 5-FU with or without LAK-supernatant was evaluated by MTT assay; antitumour activity of MMC was increased by the addition of LAK-supernatant. The concentration of interferon-gamma (IFN-gamma) and tumour necrosis factor-alpha (TNF-alpha) was increased in LAK-supernatant, and the antitumour activity of combined IFN-gamma and MMC was synergistic. The mechanism of this therapy seemed to be associated with both increased LAK activity by 5-FU and increased antitumour activity of MMC with IFN-gamma.

Antineoplastic Combined Chemotherapy Protocols↗

PubMedDate not supplied

Loss of interhemispheric connectivity in patients with lacunar infarction reflected by diffusion-weighted MR imaging and single-photon emission CT.

BACKGROUND AND PURPOSE: Although decreased neuronal connectivity in white matter has been reported to be a key mechanism of vascular dementia, assessment of white matter changes by diffusion-weighted MR imaging in relation to measures of associative function has not been previously addressed. We evaluated the loss of interhemispheric neuronal connectivity in vascular dementia by measuring diffusional anisotropy of the corpus callosum and determining its relationship to the regional cortical activity as reflected by cortical perfusion. METHODS: Nine patients with multiple lacunar infarction and six healthy volunteers (25-35 years old) were examined. We developed a method to determine the active cortical volume (ACV) by masking iodine-123 iodoamphetamine SPECT scans to eliminate the effect of brain atrophy. The anisotropic rate (AR) was calculated as a ratio of two perpendicular diffusion coefficients in diffusion-weighted MR imaging. RESULTS: Compared with the ACVs of the healthy volunteers, there were significant decreases in the ACVs in the frontal associative areas in the patients, and these were significantly correlated with cognitive scores. The frontal ACVs showed good correlations with the AR of the anterior corpus callosum among all participants; however, only insignificant trends toward correlation were observed between these two parameters within the patient group. CONCLUSION: A possible relationship between diffusional anisotropy of the anterior corpus callosum and frontal associative function was suggested; however, an estimation of the decrease in neuronal connectivity in patients with multiple lacunar infarction in terms of the deterioration in diffusional anisotropy requires further documentation.

Aged↗

PubMedDate not supplied

Interaction between sodium ascorbate and polyphenols.

The interaction between sodium ascorbate and polyphenols was investigated by two different parameters: radical intensity and cytotoxicity induction. ESR spectroscopy shows that sodium ascorbate, lignins (alkali-lignin, lignin sulfonate, pine cone-derived lignin) and tannins (gallic acid, epigallocatechin gallate (EGCg), tannic acid) all produced radicals with different intensities under alkaline conditions. All lignin samples significantly enhanced the radical intensity and cytotoxic activity of sodium ascorbate, whereas all tannin samples slightly reduced the radical intensity of sodium ascorbate. Sodium ascorbate efficiently scavenged the radical and cytotoxic activity of gallic acid, as expected by the ionization potential and heat of reaction by the PM3 semiempirical method. EGCg and tannic acid slightly reduced the cytotoxic activity of sodium ascorbate. The present study demonstrates that lignins and tannins modify the radical intensity and cytotoxic activity of sodium ascorbate in different manners, and suggests the applicability of ESR spectroscopy for the screening of drug to drug interaction.

Ascorbic Acid↗

PubMedDate not supplied

Radical modulating activity and cytotoxic activity of synthesized eugenol-related compounds.

The ability of nine synthetic eugenol-related compounds to scavenge O2- (generated by the hypoxanthine-xanthine oxidase reaction) was compared with their radical generation and cytotoxic activity. ESR spectroscopy showed that eugenol (4-allyl-2-methoxyphenol), 2-allyl-4-methoxyphenol, 2-allyl-4-t-butylphenol and 2,4-dimethoxyphenol efficiently scavenged O2- and produced radicals under alkaline conditions. 2-allyl-4-t-butylphenol showed the highest cytotoxic activity and DNA-synthesis inhibitory activity, possibly due to the hydrophobic radical reactivity. 2-allyl-4-methoxyphenol and 2,4-dimethoxyphenol showed higher antioxidant activity than 3-t-butyl-4-hydroxyanisol (BHA), but all these compounds showed comparable cytotoxic activity with each other. These findings suggest a possible link between the cytotoxic activity and radical generation/scavenging activity in eugenol-related compounds.

Antineoplastic Agents↗

PubMedDate not supplied

Effect of cobalt ion on radical intensity and cytotoxic activity of antioxidants.

The effect of CoCl2 on the cytotoxic activity of various antioxidants against human oral tumor cell lines (HSC-2, HSG) and normal human gingival fibroblasts (HGF) was investigated. Noncytotoxic concentrations of CoCl2 significantly reduced the cytotoxic activity of sodium ascorbate, gallic acid, epigallocatechin gallate (EGCG), curcumin and dopamine, but not that of sodium 5,6-benzylidene-L-ascorbate (SBA) and benzaldehyde. Among these compounds, benzaldehyde showed the most prominent tumor-specific cytotoxic action. ESR spectroscopy showed that these antioxidants produced radicals under alkaline condition and that their radical intensity was transiently enhanced and finally disappeared by addition of CoCl2. Antioxidants which are sensitive to CoCl2 generally had higher cytotoxic activity and oxidation potential (measured by NO monitor) and addition of CoCl2 significantly reduced their oxidation potential. The present study suggests that cobalt ion stimulates the oxidation of antioxidants to their inactive products.

Antioxidants↗

PubMedDate not supplied

Cytotoxic activity of polyprenylalcohols and vitamin K2 derivatives.

Cytotoxic activity of 9 polyprenylalcohols and 6 vitamin K2 derivatives (MK-1 to MK-6) with various lengths of prenyl units was investigated. Among these compounds, geranylgeraniol with 4 prenyl units, and MK-2 with 2 prenyl units, showed the highest cytotoxic activity against human oral tumor cell lines (HSC-2, HSG), without induction of internucleosomal DNA fragmentation. Higher molecular weight compounds showed selective cytotoxicity against tumor cell lines than normal human gingival fibroblasts HGF. ESR spectroscopy showed that all polyprenylalcohols did not produce radical, nor scavenged O2- generated by hypoxanthine and xanthine oxidase reaction, and only slightly enhanced the radical intensity of sodium ascorbate. Vitamin K2 derivatives scavenged O2- more efficiently, but did not produce radical (except MK-3) and only slightly modified the ascorbate radical intensity. Cytotoxic activity of these compounds might be affected by the molecular weight, hydrophobicity, van der Waals area and stabilization of hydration of the molecule.

Acyclic Monoterpenes↗

PubMedDate not supplied

Cytotoxic activity of vitamins K1, K2 and K3 against human oral tumor cell lines.

Vitamin K1, K2 and K3 were compared for their cytotoxic activity, radical generation and O2- scavenging activity. Among these compounds, vitamin K3 showed the highest cytotoxic activity against human oral tumor cell lines (HSC-2, HSG), human promyelocytic leukemic cell line (HL-60) and human gingival fibroblast (HGF). Vitamin K3 induced internucleosomal DNA fragmentation in HL-60 cells, but not in HSC-2 or HSG cells. The cytotoxic activity of vitamins K2 and K1 was one and two orders lower, respectively, than K3. Vitamin K2, but not vitamin K3, showed tumor-specific cytotoxic action. ESR spectroscopy showed that only vitamin K3 produced radical(s) under alkaline condition and most potently enhanced the radical intensity of sodium ascorbate and scavenged O2- (generated by hypoxanthine-xanthine oxidase reaction system); vitamin K2 was much less active whereas vitamin K1 was inactive. These data suggest that the cytotoxic activity of vitamin K3 is generated by radical-mediated oxidation mechanism and that this vitamin has two opposing actions (that is, antioxidant and prooxidant), depending on the experimental conditions.

Carcinoma, Squamous Cell↗

PubMedDate not supplied

Dynamic human glycogen and glucose metabolism detection utilizing in vivo 13C NMR.

The dynamic detection studies of glucose-glycogen metabolism of the human liver were performed with normal volunteers. A single tuned surface coil of 20-cm diameter was used for 13C (at 16.04 MHz). Natural glucose 100 g was administered for the natural abundance 13C MR dynamic study and 13C enriched (99%) 1-13C-D-glucose 1 g mixed 75 g glucose was administered to study the 13C enrichment effect. The total scan time of this dynamic study was 1 hr and each single scan time was 20 min. We did not use proton decoupling for the human 13C MR study. Localized (PRIME) proton shimming was performed and the shim value was less than 20 Hz. Glucose and glycogen spectra were clearly visible at 120 to 80 ppm and about 3 hr later both peaks almost disappeared. These data demonstrate that dynamic hepatic glucose-glycogen metabolism should be possible to detect which should allow for the direct diagnosis of hepatic glucose-glycogen metabolic disorders.

Carbon Isotopes↗

PubMedDate not supplied

Induction of apoptosis by cooperative action of vitamins C and E.

Millimolar concentrations of sodium ascorbate (vitamin C) induced apoptotic cell death in human promyelocytic leukemic HL-60 cells. The apoptotic cells displayed a smaller cell volume, disappearance of cell surface microvilli, appearance of cytoplasmic vacuoles, chromatin condensation, nuclear fragmentation and production of apoptotic bodies. The apoptosis-inducing activity of sodium ascorbate was significantly enhanced by noncytotoxic concentrations of CuCl2, but was almost completely eliminated by FeCl3. CuCl2 transiently stimulated the hydrogen peroxide (H2O2) production by sodium ascorbate, whereas FeCl3 slightly reduced the H2O2 production. alpha-Tocopherol (vitamin E) slightly enhanced the radical and H2O2 productions, and apoptosis induction by sodium ascorbate. The effect of alpha-tocopherol seems to be rather specific for ascorbic acid, since alpha-tocopherol did not significantly affect the cytotoxic activity of CuCl2, FeCl3 nor gallic acid. The present study demonstrated the cooperative action of vitamins C and E.

Antioxidants↗