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Biomedical subjects

M Satoh

Publications and source records attributed to M Satoh.

1,235 records · Page 69Linked to original sources

Clinical studies of immunohistochemical staining of DNA-dependent protein kinase in oropharyngeal and hypopharyngeal carcinomas.

PURPOSE: DNA-dependent protein kinase (DNA-PK), a serine/threonine kinase composed of p470 catalytic subunit (DNA-PKcs) and p85/p70 heterodimer (Ku antigen), is considered a critical enzyme in the repair of the DNA double-strand breaks (DSB) that are the major lethal lesions induced by ionizing radiation. We investigated the expression of DNA-PK subunits in human tumors. MATERIALS AND METHODS: We examined immunohistochemically the biopsy specimens of 44 patients with oropharyngeal carcinoma and 32 patients with hypopharyngeal carcinoma who had been treated with radiotherapy. RESULTS: Immunopositivity to Ku85 and DNA-PKcs was found in all patients. The staining of Ku85 and DNA-PKcs was nuclear, with none of the normal epithelial cells or malignant cells exhibiting cytoplasmic or membrane immunoreactivity. Normal epithelial cells were all stained intensely. In tumors, intense nuclear staining of DNA-PKcs was seen in 75 of 76 tumors, while that of Ku85 was seen in all 76 patients. The radiation responses of a primary tumor that was stained weakly with DNA-PKcs were excellent. CONCLUSION: Our results suggest the possibility of predicting the intrinsic radiosensitivity of human tumors in clinics able to perform immunohistochemical analysis of DNA-PK.

Aged↗

Time courses of PIVKA-II and AFP levels after hepatic artery embolization and hepatic artery infusion against hepatocellular carcinoma: relation between the time course and tumor necrosis.

We examined 35 untreated patients with unresectable hepatocellular carcinoma who exhibited positivity for both plasma PIVKA-II and serum AFP, and studied the weekly course of these markers from the pre-TAE or -HAI period to the third week of treatment. We correlated changes in these markers with the tumor necrosis rate and the time course on X-ray CT images. One week after TAE, the tumor necrosis rate and the time course of PIVKA-II showed a significant correlation (r = 0.7), while the correlation was between the time course of AFP and the tumor necrosis rate was insignificant (r = 0.2). At two and three weeks after TAE, both the time course of AFP and PIVKA-II showed significant correlations with the tumor necrosis rate. In 16 patients with tumor necrosis rates of not less than 90%, the mean of the actual half-life (AHL) of PIVKA-II was 3.2 days, the shortest was 1.83 days, and 75% of all AHLs clustered from two days to four days, while the mean and shortest AHLs of AFP were six days and 2.98 days, respectively, exhibiting a broader distribution. On the other hand, in three out of the nine cases of hepatocellular carcinoma complicated with portal tumor thrombi, PIVKA-II increased after HAI in spite of a reduction in tumor size. It was suggested that the PIVKA-II level requires careful interpretation in cases of portal vein obstruction after intensive hepatic arterial infusion of anticancer agents.

Aged↗

Tissue-specific induction of metallothionein by bismuth as a promising protocol for chemotherapy with repeated administration of cis-diamminedichloroplatinum (II) against bladder tumor.

The effects of bismuth nitrate pretreatment on the toxicity and antitumor activity of repeatedly administered cis-diamminedichloroplatinum (Cisplatin; CDDP) were examined using nude mice inoculated with human bladder tumor tissues. Lethal and renal toxicities exerted by the repeated administration of CDDP were effectively prevented by pretreatment with bismuth (Bi) without affecting its antitumor activity against transplanted human bladder tumor as in the case of single dose of the drug reported previously. The renal Bi level was gradually increased with the frequency of Bi administration, and metallothionein (MT) induced by Bi in the kidneys maintained its substantially high level during the treatment. It was confirmed that MT was not induced in the tumors even by the 5 cycles of repeated Bi administration. This specific protection shown by the Bi preadministration against the toxicity of repeatedly injected CDDP can be explained by the fact that Bi markedly induces MT in the kidney, a major target organ of CDDP toxicity, but not in the tumor tissues inoculated in the nude mice, probably because Bi is efficiently taken up by the kidney but hardly incorporated into the tumor tissues as reported previously. These data obtained by repeated doses of CDDP as described above strongly suggest a promising protocol for chemotherapy using CDDP with Bi compounds, a tissue specific MT inducer, against advanced bladder tumor in human.

Animals↗

Inhibition of morphine dependence by a lipopolysaccharide from Pantoea agglomerans.

A lipopolysaccharide from Pantoea agglomerans (LPSp) was purified and examined for relief of morphine dependence by observing its inhibition of the jumping of mice on naloxone-precipitate withdrawal. Administration of LPSp either intravenously or intradermally showed marked inhibition of the jumping. Beta-endorphin in mouse serum and brain tissue were recognized to be in synchrony with the time course of the relief. Administration of TNF-alpha gave similar effect, suggesting that LPSp induces a cytokine cascade to produce endogenous TNF followed by ACTH/beta-LPH gene products and beta-endorphin. The effect of LPSp was better than that of LPS from E. coli or Bordetella pertussis, and thus is considered to be applicable for clinical use.

Animals↗

Effects of aprotinin on prostaglandin metabolism and platelet function in open heart surgery.

The effects of the protease inhibitor, aprotinin, on plasma prostaglandin levels and platelet function during and after cardiopulmonary bypass (CPB) were studied in a group of 23 patients which consisted of 11 untreated patients (control group) and 12 aprotinin-treated patients (aprotinin group). Thromboxane B2 (TXB2, a stable metabolite of thromboxane A2) and beta-thromboglobulin levels in the control group increased significantly during CPB compared with preoperative values. These increases were significantly suppressed in the aprotinin group. 6-Keto-PGF1 alpha (stable metabolite of prostacyclin) increased significantly during CPB in both groups, and there was no significant difference between the two groups. In the aprotinin group, the TXB2/6-Keto-PGF1 alpha ratio decreased significantly during CPB compared with the preoperative value, whereas no significant decrease was observed in the control group. Platelet counts decreased significantly during and after CPB in both groups. Platelet aggregability decreased significantly during CPB in the control group, whereas no significant decrease was found in the aprotinin group. In conclusion, aprotinin treatment improved prostaglandin metabolism and preserved platelet function during open heart surgery.

6-Ketoprostaglandin F1 alpha↗

Short-term intrathrombotic injection of ultrahigh-dose urokinase for treatment of iliac and femoropopliteal artery occlusions.

Thirty-two patients with iliac and femoropopliteal artery occlusions were treated with direct intrathrombotic injection of ultrahigh-dose urokinase (10,000 IU/min). Occlusions ranged from 3 to 25 cm (average 13.3 cm) in length and the total urokinase dose from 120,000 to 1,410,000 IU (average 688,000 IU). The procedure was usually followed by balloon angioplasty to dilate the underlying stenoses. The initial recanalization rate was 96.9%, the two week patency rate 81.3%, and the cumulative one-year patency rate 66.3%. Complications associated with this procedure included three episodes of minimal bleeding, two distal embolisms, one local hematoma, and one low-grade fever. All were well controlled by palliative treatment. Results indicate that this procedure can provide rapid recanalization at a higher success rate and with fewer complications than previously reported.

Adult↗

An attempt of hyperthermia with balloon catheter and immunochemotherapeutic agent.

The following studies were performed to develop a new technique of hyperthermia by vascular catheterization for the treatment of malignant neoplasm. A balloon catheter was inserted into the artery of a cancer-affected organ and inflation of the balloon temporarily occluded the artery, after which an anticancer drug solution warmed to 45 degrees C was infused. The purpose of this technique was to enable the solution to arrive at the affected area undiluted by blood. It would then remain in the organ and act on the lesion. When OK-432 was intravenously administered to induce pyrexia of 40 degrees C, followed by the above-mentioned arterial infusion, it was expected that the effects of hyperthermia and chemotherapy would be synergistic. In cases of liver cancer and urinary bladder cancer subjected to the arterial infusion of warmed anticancer drugs, however, the temperature in the hepatic vein increased by only 0.5 degree C while that in urethra near the tumor increased by only 1 degree C. In the future, further improvement needs to be made to obtain effective local heating with this technique.

Antineoplastic Combined Chemotherapy Protocols↗

Age-related alteration of alpha(1)-adrenoceptor mechanisms and Ca2+ inhibitory effects of isradipine.

The effects of age on alpha1-adrenoceptor and Ca2+ channel-mediated contractile mechanisms in the thoracic aorta, isolated from rats of 3, 6, 10, 18 and 40 weeks old, were studied. The potency (pD(2) value) of norepinephrine increased with age from 3 to 10 weeks, but decreased thereafter from 10 to 40 weeks. The change in pD(2) value of norepinephrine was proportional to the logarithm of the maximum number of binding sites (B(max)), obtained in the [(3)H]prazosin binding study. The inhibitory effect of a potent Ca(2)+ channel blocker, israpidine, on the norepinephrine-induced contraction decreased with age from 3 to 10 weeks, but increased in rats aged 10 to 40 weeks. An inverse relationship between the change in isradipine inhibition, the maximum reduction of isradipine on norepinephrine-induced contraction and the logarithm of B(max) was found. The inhibitory effect of a nonselective Ca2+ channel blocker, SKF96365, on the norepinephrine-induced contraction did not change with age. The amplitude of the Ca2+-induced sustained contraction, after pretreatment with isradipine (10(-7) M) in the presence of norepinephrine (10(-6) M), increased with age from 3 to 10 weeks, but decreased thereafter in rats aged 10 to 40 weeks. There was no significant difference in the slope of the regression lines between the cytosolic Ca(2)+ level ([Ca2+]i) and the tension in the presence of norepinephrine at different ages. These results suggest that the changes in alpha(1)-adrenoceptor mechanisms and the reduction by isradipine with age are due to changes in the alpha1-adrenoceptor density and the population of Ca2+ channels, but not to changes in the affinity of drugs to the alpha1-adrenoceptor or Ca2+ sensitivity of contractile elements of aortic smooth muscles.

Adrenergic alpha-Agonists↗

Early bonding of resin cements to dentin--effect of bonding environment.

The aim of this study was to evaluate early tensile bond strengths of three commercial resin cements (a dual-cured and two chemically cured) to bovine dentin. Bonding was performed in two environmental conditions, namely room environment (23 degrees C/50% RH) and oral environment (30 degrees C/80% RH). Tensile bond strengths were recorded at 10 minutes, 1 hour, and 1 day after the bonding procedure was completed and were analyzed using one-way ANOVA, Fisher's PLSD test, and Student's t-test. The results showed that bond strengths were statistically greater for all materials (P < 0.05) over time, except for Bistite Resin Cement between 10 minutes and 1 hour (P > 0.05). Variation between the bonding environments was observed only for Bistite Resin Cement at both 10 minutes and 1 hour, and Panavia 21 at 10 minutes. It was concluded that bond strengths were initially weak for the chemically cured materials, and all materials showed significantly greater bond strengths over the first 24 hours, but bonding environment had little influence.

Analysis of Variance↗

Amino acid utilization during cell growth and apoptosis induction.

The amino acid utilization between human promyelocytic leukemia (HL-60), human oral squamous carcinoma (HSC-2, HSC-4, NA), human salivary gland tumor (HSG) and rat neuron cells (PC-12) were compared, using amino acid analyzer. All these cells consumed four essential amino acids (valine, methionine, isoleucine, leucine), glutamine and arginine, whereas they produced glycine, alanine and ammonia, without significantly affecting threonine, tyrosine, phenylalanine, histidine or lysine concentration. Serine and glutamine utilization varied considerably from cell to cell. HL-60 cells consumed serine and arginine at much higher rates than other cells. Serine depletion accumulated the G1 arrested cells, and produced increasing numbers of the apoptotic cells. Supplementation of serine significantly extended the period of logarithmic cell growth. During apoptosis induction of HL-60 cells by dopamine, sodium ascorbate or sodium 5,6-benzylidene-L-ascorbate, the oxidation of methionine to methionine sulfoxide was enhanced, but the consumption of serine, glutamine and arginine was reduced. In the presence of HL-60 cells, the methionine oxidation was significantly inhibited, suggesting the antioxidant action of the cells. These present study suggests the importance of re-evaluation of culture condition for each cell lines.

Amino Acids↗