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Biomedical subjects

M Miyazaki

Publications and source records attributed to M Miyazaki.

At least 829 records · Page 46Linked to original sources
PubMed1985

Biodegradable mitomycin C microspheres given intra-arterially for inoperable hepatic cancer. With particular reference to a comparison with continuous infusion of mitomycin C and 5-fluorouracil.

Thirty-two patients with inoperable hepatic cancer underwent intra-arterial hepatic infusion using mitomycin C (MMC) and 5-fluorouracil (5-FU) or intra-arterial hepatic chemoembolization using heated albumin microspheres containing MMC with an average diameter 45 +/- 8 micron. Nineteen of the 32 patients received the MMC microsphere treatment and another 13 received the conventional infusion treatment, lasting for 3.4 months. The administered doses of MMC microspheres were 11.7 +/- 11.1 mg as MMC in the 12 with metastatic cancer and 6.9 +/- 2.1 mg as MMC in the 7 with hepatocellular cancer (HCC). On the contrary, the 13 patients who underwent conventional infusion had average doses of MMC 34.5 +/- 17.3 mg and of 5-FU 13.4 +/- 7.7 g, over 3.4 months. An objective tumor response was obtained in 13/19 (68.4%) under MMC microsphere chemoembolization, compared to 6/13 (46.2%) under the conventional infusion. The average level of CEA in the 12 with metastatic cancer, who underwent MMC microsphere therapy, dropped from 57.7 ng/ml to 16.5 ng/ml, while that in the 10 patients on conventional infusion dropped from 24.0 ng/ml to 17.4 ng/ml; that of alpha-fetoprotein dropped in all 7 with HCC on MMC microsphere chemoembolization, compared to a fall in 1/3 on conventional infusion. With the MMC microsphere treatment, 5 patients from colorectal cancer lived for 15.6 +/- 7.6 months, 2 are alive with a long life expectancy; and 7 patients from gastric or pancreatic cancer lived for only 9.3 +/- 3.3 months. In case of conventional infusion, 6 patients from colorectal cancer survived for 8.6 +/- 3.2 months; and 4 patients from gastric or gallbladder cancer survived for 6.0 +/- 1.0 months. The MMC microsphere treatment is superior at P = 0.059 in survival duration to the conventional infusion treatment. However, much the same survival occurred in 7 on MMC microsphere chemoembolization and 3 on continuous infusion.

Adult↗
PubMed1985

Antitumor effects of two polyamine antimetabolites combined with mitomycin C on human stomach cancer cells xenotransplanted into nude mice.

The antitumor effects of alpha-difluoromethylornithine (DFMO), methylglyoxal-bis-guanylhydrazone (MGBG) and mitomycin C (MMC), administered separately or in various combinations, on human stomach cancer cells xenotransplanted into BALB/c nude mice were studied using the protocol of Battelle's Columbus Laboratories (Ovejera et al., 1978). DFMO (1,000 mg/kg in 2 divided doses) and MGBG (50 mg/kg) were given intraperitoneally (i.p.) for 7 consecutive days from the time when the tumor weighed about 100 mg. MMC (2 mg/kg) was given i.p. every other day from the same time. Animals treated with either DFMO or MGBG alone displayed tumor growth comparable to that seen in untreated controls. In mice treated with DFMO plus MGBG with or without MMC, or in mice treated only with MMC, tumor growth was significantly lower than in untreated mice. In the group which received only combined DFMO/MGBG there was a rapid regrowth of the tumor after termination of therapy. Tumor putrescine levels decreased within 4 days following the administration of DFMO; however, spermidine levels did not decline with either DFMO or MGBG treatment even after 7 days. When combined DFMO/MGBG was given, there was a significant decline in spermidine levels 7 days after the initiation of treatment. In contrast, when MMC alone was administered, putrescine and spermidine levels in the tumor did not differ from those in control mice. Spermine decreased markedly in tumor with the combined administration of DFMO/MGBG as well as with combined DFMO/MGBG/MMC, but decreased only slightly when MMC alone or MMC plus either DFMO or MGBG was administered. By the 7th treatment day, DNA biosynthesis in the tumor had dropped markedly in all groups except those receiving DFMO or MGBG alone.

Adenocarcinoma, Papillary↗
PubMed1985

Isolation of gram quantities of isoleucyl-tRNA synthetase from an overproducing strain of Escherichia coli and its use for purification of cognate tRNA.

The ileS gene coding for isoleucyl-tRNA synthetase was cloned on a runaway-replication plasmid. From the cells harboring the plasmid, gram quantities of the synthetase were isolated using two column procedures. The synthetase was used for the purification of cognate tRNA. Isoleucine tRNAGAU of greater than 90% purity was easily isolated by taking advantage of a specific complex formation of the synthetase with cognate tRNA.

Amino Acyl-tRNA Synthetases↗
PubMed1985

Effects of intra-arterially infused biodegradable microspheres containing mitomycin C.

We prepared biodegradable microspheres containing about 5% mitomycin C (MMC) and of 45 +/- 8 microns in diameter. These preparations were infused into the rat hepatic artery as a preclinical model of intra-arterial infusion treatment for patients with inoperable hepatic tumor. The leaked MMC levels in the hepatic vein decreased below the assay limitation 2 hours after conventional MMC injection, whereas in the case of MMC microsphere the leaked drug levels were maintained at almost the same concentration for over 2 hours after infusion. The entrapped period of MMC microspheres within the hepatic artery was at least 2 weeks, and the necrobiotic foci due to antitumor effects of the condensed MMC released from the microspheres were observed in the area fed by these entrapped arterioles. This phenomenon was never observed in the case of conventional MMC and placebo microspheres. Intra-arterial infusion of MMC microspheres may be a promising clinical treatment for patients with malignant hepatic tumor.

Animals↗
PubMed1985

Effect of phenobarbital on adult rat liver cells treated with 3'-methyl-4-dimethylaminoazobenzene in primary culture.

The effect of phenobarbital (PB) on liver cells treated with 3'-methyl-4-dimethylaminoazobenzene (3'-Me-DAB) was studied using primary cultures of normal adult rat liver cells. Following a 1-day attachment period, primary liver cell cultures were treated with 0.24 mM 3'-Me-DAB for 6 days, and then treated with or without PB at 0.75, 1.5 and 3 mM for 19 days. Similarly, control cultures were treated with 0.5% dimethylsulfoxide (DMSO), a solvent for 3'-Me-DAB, for 6 days, and then treated with or without PB in the same way. Each treatment was done on 8 cultures. Chromosome analysis and cytochemical assay for gamma-glutamyltranspeptidase (GGT) activity were carried out on the carcinogen-treated and control cultures between 1 and 2 months after initiation of primary culture. Chromosomal abnormalities were detected in 23 of 32 carcinogen-treated cultures and also in 2 of 28 control cultures tested. However, GGT positive cells were detected only in the carcinogen-treated cultures at a frequency of 22/32. Of the 23 carcinogen-treated cultures with chromosomal abnormalities, 18 contained GGT positive cells. These results show a good correlation between chromosomal abnormality and acquisition of GGT activity at culture dish level. Furthermore, in the carcinogen-treated cultures, PB treatment caused a dose-dependent increase in the number of GGT positive cultures and in the percentage of GGT positive cells in each culture, and also caused a dose-dependent increase in the number of cultures with chromosomal abnormalities.

Animals↗
PubMed1985

Characterization of blasticidin S-resistant mutants of Saccharomyces cerevisiae.

Blasticidin S-resistant mutants of S. cerevisiae were isolated and characterized. Resistant mutations were found to fall into two complementation groups. A single recessive nuclear gene was responsible for each group, donated as bls1 and bls2, respectively. A gene bls1 was linked to an ilv3 gene located on the right arm of chromosome X. The resistant phenotypes from both genes were not associated with ribosomes known to be target sites of Blasticidin S, when analyzed by poly(U)-directed polyphenylalanine synthesis. The resistant mechanisms of the mutations are discussed in this paper.

Antifungal Agents↗
PubMed1985

Long-term survivors of colorectal cancer with unresectable hepatic metastases.

Five patients with colorectal cancer and unresectable synchronous liver metastases have survived for over five years at this writing. Four of the five had multiple metastases over both lobes, as diagnosed preoperatively, and the other had multiple metastases in the right lobe not evident preoperatively. The primary foci were excised completely in four patients. For one patient with multiple metastases limited to the right lobe, the postoperative cancer chemotherapy prescribed was intravenous mitomycin C (MMC; 12 mg) and oral ftorafur (a derivative of 5-FU) for a total dose of 291 gm over 63 weeks. The remaining four patients underwent postoperative intra-arterial infusion therapy with the average total dose of 20.5 mg of MMC plus 5600 mg of 5-FU; subsequently, they received protracted chemotherapy with oral ftorafur of 354 gm as an average, with little or no side effects. In these four patients, duration of intra-arterial treatment was an average of 3.2 weeks, and the subsequent oral treatment continued for an average of 85 weeks. Recent hepatic echography and CEA determinations show these patients to be free from intrahepatic metastasis.

Administration, Oral↗
PubMed1985

Long-term survival of functional hepatocytes from adult rat in the presence of phenobarbital in primary culture.

In the presence of phenobarbital (PB) at 3 mM, hepatocytes isolated from adult rats by a collagenase-perfusion technique survived well on plastic dishes for at least 49 days after initiation of primary culture. PB at concentrations less than 3 mM was ineffective for the maintenance of hepatocytes, and the maintenance of them was attained only in the continuous presence of 3 mM PB. The hepatocytes surviving in the presence of 3 mM PB were morphologically indistinguishable from the hepatocytes after 1-day attachment period, except for the presence of prominent nucleoli in the former. Although both the albumin secretion and tyrosine aminotransferase (TAT) activities of the cells decreased gradually up to day 7 with time in culture, both were thereafter maintained at relatively high levels at least up to day 35 of primary culture. The addition of 10 microM dexamethasone caused a 3-5-fold induction in TAT activity, and the cells were capable of responding to the hormone in this manner at least up to day 28 of primary culture. Furthermore, the cells also had glucose-6-phosphatase activity, even though the level of this enzyme activity was relatively low as compared with that of TAT activity. Survival of hepatocytes in the presence of 3 mM PB was further enhanced by simultaneous addition of dexamethasone (10 microM) and insulin (10 micrograms/ml). The sensitivity of hepatocytes to 3'-methyl-4-dimethylaminoazobenzene (0.24 mM) was remarkably reduced by treatment with PB at 3 mM. PB treatment decreased efficiently the falling rate of total cytochrome P-450 content, but did not induce P-450PB, which is the specific form of cytochrome P-450 induced by PB, in primary cultured hepatocytes. On the other hand, 3-methylcholanthrene (MC, 10 microM) caused an increase of both contents of total cytochrome P-450 and P-450MC, which is the specific form of cytochrome P-450 induced by MC, in primary cultured hepatocytes. However, MC was ineffective for the maintenance of hepatocytes in primary culture. The possible biological actions of PB on primary cultured hepatocytes are discussed on the basis of the experimental data obtained.

Albumins↗
PubMed1985

Mitomycin C carrying microspheres as a novel method of drug delivery.

Biodegradable albumin microspheres containing about 5% mitomycin C (MMC) were prepared in an average diameter of 45 +/- 8 microns by heat denaturation in oil at 120 degrees C and/or cross-linking with glutaraldehyde. These MMC microspheres released, in vitro, about 20% of the contained MMC for over 3 days, and they were intra-arterially infused into albino rabbits and Wistar rats, as a preclinical model of intra-arterial infusion treatment for patients with inoperable hepatic tumor. We infused these microspheres into the femoral artery of rabbits with a VX-2 tumor implanted into the flank of the hindleg. High levels of MMC were maintained for several hours in the tumor and the entrapped MMC microspheres were detected within arterioles in the VX-2 tumors. The growth of VX-2 tumor was inhibited considerably, compared to findings in the control rabbits given conventional MMC. In the next studies, MMC microspheres were infused into the rat hepatic artery, and the levels of MMC in the hepatic vein blood were maintained at much the same concentration for over 2 hours after the infusion, in marked contrast to rapid decreases in the conventional MMC. Histologic findings revealed that MMC micro-spheres were entrapped within the hepatic arterioles for over 2 weeks and released biologically active MMC into the neighboring tissues for prolonged periods of time.

Albumins↗
PubMed1985

Vasodilator effect of indapamide in dog mesenteric vasculature.

Effects of indapamide, trichlormethiazide and hydralazine on isolated, perfused dog mesenteric vasculature and helical strips of the dog mesenteric artery were compared. It appears that indapamide-induced hypotension is associated with a direct relaxant action on arterial and arteriolar smooth muscle, whereas hydralazine acts exclusively on resistance vessels.

Animals↗
PubMed1985

Transformation of primary cultured and co-cultured adult rat liver cells by 3'-methyl-4-dimethylaminoazobenzene.

Under various conditions of culture and carcinogen treatment, the transformation of liver cells by 3'-methyl-4-dimethylaminoazobenzene (3'-Me-DAB) was studied. Primary liver cell (PLC) cultures from adult male rats and co-cultures with PLCs of ARL-D8 cells of a liver epithelial-like clear cell line from adult female rats were treated with 0.24 mM 3'-Me-DAB for 6 days. Four of 8 carcinogen-treated PLC cultures contained cells with marker chromosomes, and 3 of the 8 cultures contained gamma-glutamyltranspeptidase (GGT)-positive cells. Three of 5 carcinogen-treated co-cultures contained cells with marker chromosomes, and 2 of the 5 co-cultures contained GGT-positive cells. Pure cultures of ARL-D8 cells were treated for 6 or 12 days with 3'-Me-DAB (0.24 mM)-containing-medium perfused through the liver of adult male rats in situ. In the 6-day treatment, none of 5 carcinogen-treated cultures showed chromosomal abnormality or cytochemically exhibited GGT activity. However, in the 12-day treatment, 2 of the 5 carcinogen-treated cultures contained cells with marker chromosomes, and 2 of the 5 cultures contained GGT-positive cells. None of the control cultures exhibited chromosomal abnormality or GGT-positive cells. In summary, transformation markers increased in ARL-D8 cells when they were co-cultured with PLCs.

Animals↗