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Biomedical subjects

K Enomoto

Publications and source records attributed to K Enomoto.

At least 253 records · Page 14Linked to original sources
PubMed1987

Induction of a novel Ca2+-dependent protease in preneoplastic and neoplastic liver tissues during rat liver carcinogenesis.

The activity of a novel Ca2+-dependent protease in preneoplastic and neoplastic tissues of male Fisher 344 rat liver was examined during experimental liver carcinogenesis. This protease activity is significantly high in hyperplastic nodules and hepatocellular carcinomas which were induced by the method of Solt and Farber. Taken together with our previous report on the promoter-specific induction of this protease, the results suggest the possible importance of this protease in the promotion stage of liver carcinogenesis.

Animals↗
PubMed1987

Studies of the effects of FK506 on renal allografting in the beagle dog.

The immunosuppressive activities of a newly discovered macrolide extracted from Streptomyces tsukubaensis, FK506, were examined using 38 renal allografts in the beagle dog. The median survival time was 15.5 days in dogs without treatment, 61 days with a dose of 0.08 mg/kg/day and 176 days with a dose of 0.16 mg/kg/day of intramuscularly administered FK506. Prolongation of survival was statistically significant when compared with controls (P = 0.02, 0.0044, respectively). None of 6 recipient dogs receiving the agent at a dose of 0.16 mg/kg/day encountered rejection during the treatment course. Three of them survived over 200 days. Oral administration of FK506 at a dose of 0.32 mg/kg/day did not prolong the median survival time (20.5 days) compared with the placebo treated control (16.5 days), but oral treatment with 1.0 mg/kg/day resulted in all of the recipient dogs surviving over 130 days. Histological studies of 7 kidney graft biopsy specimens of the dogs surviving over 3 months revealed no cell infiltration or only some degree of reversible interstitial cell infiltration, but vascular and glomerular changes were not observed in any of the specimens. Irregularity of nuclear shape and cytoplasmic vacuolation of the pars recta of the proximal tubules were observed in one dog each. Liver biopsy specimens showed no consistent evidence of hepatocellular damage. Three dogs died of intussusception 2-3 weeks posttransplant. The dogs treated intramuscularly with 0.32 mg/kg/day suffered from anorexia. Two dogs receiving oral treatment at a dose of 1.0 mg/kg developed papilloma of the skin around day 60, but the tumors disappeared by day 120. We conclude that FK506 is a powerful immunosuppressant in the dog with tolerable side effects.

Administration, Oral↗
PubMed1987

Induction of a novel Ca2+-dependent serine protease in rat liver treated with various promoters of liver carcinogenesis.

The induction of a novel Ca2+-dependent protease in rat liver treated with various liver promoters, as well as its increase in preneoplastic lesions during liver carcinogenesis, was demonstrated. Six groups of male Fischer 344 rats (150 g body weight) were fed separately diets containing one of the following promoters: 0.05% phenobarbital (PB), 0.05% dichlorodiphenyltrichloroethane (DDT), 0.25% ethyl-alpha-chlorophenoxyisobutyrate (CPIB), 0.5% butylated hydroxytoluene (BHT), 10 ppm 17-alpha-ethynylestradiol (EE), and 0.05% of the non-promoter diphenylhydantoin (DH). After feeding the indicated diets for 1 week, rats were killed and protease activity in the microsomal fraction of liver tissue was determined using N-benzoyl-L-tyrosine ethyl ester as substrate. The activity of protease increased 3- to 5-fold after treatment with the promoters and compared with normal liver; the non-promoter (DH) induced a slight increase in activity. Hyperplastic nodules were induced according to the method of Solt and Farber. The activity of protease was significantly high in these preneoplastic lesions compared with the surrounding liver tissue. Biochemical characterization of this protease revealed the following properties: high Ca2+ dependency, different molecular weight and optimum pH from previously reported proteases, and preferential distribution in the SER fraction. These results suggest that a novel type of protease is induced specifically in the liver by promoters of liver carcinogenesis. The possible importance of this protease in the carcinogenic process is discussed.

Animals↗
PubMed1987

[Phase II study of peplomycin in breast cancer. A cooperative study. Clinical Study Group of Peplomycin for Breast Cancer in Japan].

A phase II study of peplomycin, an analogue of bleomycin, was carried out in 42 patients with advanced or recurrent breast cancer by a cooperative group consisting of 15 institutes throughout Japan, and the following results were obtained. Among the 42 patients, 38 were evaluable, in whom the overall response rate was 7.9% (3/38). For the various histologic types, the response rate was 33.3% (2/6) for papillotubular carcinoma and 9.1% (1/11) for medullary tubular carcinoma. The response rate was 33.3% (2/6) in patients without prior treatment and 3.1% (1/32) in those with prior treatment. Side effects of nausea, anorexia, malaise, alopecia and pyrexia occurred frequently, and a decrease in WBC and an increase in GOT were observed temporally. Pulmonary toxicity was observed in 7 patients.

Adult↗
PubMed1987

[A case of Ewing's sarcoma treated successfully by combination chemotherapy consisting of high-dose methotrexate, aclacinomycin-A and vindesine].

A 22-year-old man was admitted to Kyushu University Hospital because of high fever, and pain in the right foot and back. An X-ray examination revealed an osteolytic lesion on the 5th metatarsal bone of the right foot. Paraplegia and disturbance of bladder function occurred and compression of the spinal cord between T3 and L5 was found by myelography. An extradural tumor was removed by emergent laminectomy, and a histological examination of the tumor showed aggregations of small round cells, which suggested Ewing's sarcoma. Although T-9 protocol was started with initial effect, the tumor recurred during the therapy. The patient was then treated with HD-MTX, ACR and VDS, which induced a clinical improvement for 4 months without maintenance therapy. This result showed that HD-MTX, ACR and VDS warrant further consideration for the treatment of refractory Ewing's sarcoma.

Aclarubicin↗
PubMed1986

Synthesis of water-soluble, branched polysaccharides having D-mannopyranose, D-arabinofuranose, or oligo-D-arabinofuranose side-chains and their antitumor activity.

Branched polysaccharides having D-mannopyranose, D-arabinofuranose, or oligo-D-arabinofuranose side-chains were synthesized by the reaction of 3,4,6-tri-O-acetyl-(1,2-O-ethylorthoacetyl)-beta-D-mannopyranose, 3,5-di-O-benzoyl-(1,2-O-ethylorthobenzoyl)-beta-D-arabinofuranose, or 3-O-benzoyl-(1,2,5-O-orthobenzoyl)-beta-D-arabinofuranose with cellulose acetate or curdlan acetate, followed by desterification. The structure and antitumor activity of the water-soluble portion of the polysaccharides thus obtained were investigated. Polysaccharides synthesized from (1----3)-beta-D-glucan as the main chain with oligo-D-arabinofuranose side-chains exhibited high antitumor activity.

Animals↗
PubMed1986

Effects of memantine on the frog neuromuscular junction.

The effects of memantine, an adamantane derivative, on neuromuscular transmission in the frog sartorius muscle preparation were studied by measuring the endplate current (EPC) by the voltage clamp method. Memantine (0.5-50 microM) reduced the peak amplitude and shortened the duration of the EPC, and the membrane voltage-peak EPC relationship became non-linear. Since it decreased the quantal height of the EPC without affecting the mean quantal content, the effects were considered to be mainly postsynaptic. Noise analysis revealed that memantine decreased the mean lifetime of the ACh-activated channel. In addition, lineweaver-Burk analysis of the response to ionophoretically applied carbamylcholine showed that memantine acted essentially as a linear mixed-type inhibitor. Thus memantine seems to block neuromuscular transmission by reacting with the ACh receptor-ion channel complex in both the open and closed states.

Acetylcholine↗
PubMed1986

Involvement of the Ca2+-dependent K+ channel activity in the hyperpolarizing response induced by epidermal growth factor in mammary epithelial cells.

Epidermal growth factor (EGF) induces a hyperpolarizing response of 5-20 mV amplitude in mouse mammary epithelial cells in culture. The amplitude of the hyperpolarizing response was reduced by more than 60% within several minutes after addition of blockers of voltage and/or Ca2+-dependent K+ channels such as tetraethylammonium (7 mM) or quinine (0.29 mM). Both nifedipine (0.15 mM), a blocker of the Ca2+ channel, and ruthenium red (2 mM), an inhibitor of the Ca2+-binding site, also reduced the amplitude of the hyperpolarizing response by more than 60%. The Ca2+ ionophore, A23187 (3.8 microM), induced a large hyperpolarization, which was 25-40 mV and lasted about 3 min. These data suggest that activity of the Ca2+-dependent K+ channel was involved in the EGF-induced hyperpolarizing response of the mammary epithelial cells.

Animals↗
PubMed1986

Inhibition of catalytic unit of adenylate cyclase and activation of GTPase of Ni protein by beta gamma-subunits of GTP-binding proteins.

A protein factor which inhibited adenylate cyclase was purified to apparent homogeneity from rat brain and identified as the beta gamma-subunits of the GTP-binding regulatory proteins of adenylate cyclase. (i) The beta gamma-subunits (protein factor) inhibited the partially purified catalytic unit of adenylate cyclase in the presence of an activator, forskolin or the stimulative regulatory protein (Ns), to 60 and 40% of the control, respectively; inhibition of the catalytic unit in the presence of forskolin required no guanine nucleotides. (ii) The subunits enhanced the GTPase activity of the purified alpha-subunit of the inhibitory regulatory protein (Ni alpha) 3.8-fold. (iii) The subunits stimulated ADP-ribosylation of Ni alpha catalyzed by islet-activating protein (pertussis toxin). ADP-ribosylation had no effect on the GTPase activity of Ni alpha in the presence of the beta gamma-subunits. The results suggest that direct inhibition of the catalytic unit by the beta gamma-subunits liberated from Ni is essential for the receptor-mediated inhibition of adenylate cyclase.

Adenosine Diphosphate Ribose↗
PubMed1986

Induction of distinct types of spontaneous electrical activities in mammary epithelial cells by epidermal growth factor and insulin.

Electrophysiological measurements of the membrane potentials of mouse mammary epithelial cells in primary culture revealed the presence of spontaneous-oscillating-hyperpolarizing potentials in cells incubated with epidermal growth factor. The hyperpolarizing potentials were 5-20 mV in amplitude and about 10 sec in duration. The peak height of the response was reduced by hyperpolarization, and the input membrane resistance decreased during the response. The response was probably due to activation of K+ channels. The latency period for the epidermal growth factor induction of the hyperpolarizing potential was approximately 3 hr. In contrast, insulin induced spontaneous-depolarizing potentials that were about 5 mV in amplitude and 1 sec in duration. The depolarizing potentials were attributed to activity of ion channels, since the peak height was dependent on the membrane potential and the depolarizing potential was accompanied by a decrease of input membrane resistance. The time lag for the induction of the depolarizing potential was 6-12 hr. Other hormones involved in mammary cell differentiation, such as cortisol and prolactin, neither induced the depolarizing potentials nor changed the induction of depolarizing potential by insulin. In addition, other growth factors, such as nerve growth factor and fibroblast growth factor, elicited no electrical activity.

Animals↗
PubMed1986

Experimental combined hormone therapy on human breast carcinomas serially transplanted into nude mice.

Experimental combined hormone therapy with tamoxifen, aminoglutethimide and medroxyprogesterone acetate was investigated using three hormone-dependent human breast carcinomas serially transplanted into nude mice. The antitumor effect of combined tamoxifen and aminoglutethimide was better than that of either tamoxifen or aminoglutethimide alone. Since aminoglutethimide significantly reduced the level of estrogen and the uterine weight in normal female mice, the antitumor effect of combined tamoxifen and aminoglutethimide was assumed to be a result of the low estrogen level produced by aminoglutethimide, favoring the competition of tamoxifen with estrogen receptors. There was no additive antitumor effect of the combination of tamoxifen and medroxyprogesterone acetate, although serum medroxyprogesterone acetate levels in nude mice were almost equivalent to those of humans. These results indicate that combination hormone therapy, especially with and aminoglutethimide, might be a promising method for clinical application.

Adult↗
PubMed1986

[Phase II study of epirubicin on breast cancer: a cooperative group study].

A phase II multicenter clinical study of epirubicin, a new anthracycline anticancer agent, was carried out in 46 patients with advanced breast cancer. The treatment schedule consisted of either 60 mg/m2 every three weeks or 40 to 50 mg/m2 on day 1 and day 8 every four weeks. Objective responses were observed in 23.7% of 38 evaluable patients (1 CR and 8 PR). Response rates according to previous chemotherapy were 50.0% (4/8) in previously non-treated patients and 36.4% (4/11) in patients previously treated with non-anthracyclines. The major adverse effect was bone-marrow suppression; leukopenia was observed in 82.1% of patients, anemia in 53.8% and thrombocytopenia in 20.0%. Other toxicities frequently observed were anorexia (55.0%), nausea-vomiting (55.0%) and alopecia (66.7%), but these seemed to be milder than those produced by doxorubicin.

Adult↗
PubMed1986

Induction of a novel Ca2+-dependent chymotrypsin-like serine protease by tumor promoters in rat livers.

Induction of a microsomal Ca2+-dependent serine protease by hepatic tumor promoters was studied. Male F344 rats were fed a diet containing one of the following promoting agents: phenobarbital (CAS: 50-06-6), dichlorophenyltrichloroethane (CAS: 50-29-3), butylated hydroxytoluene, ethyl-alpha-chlorophenoxyisobutyrate (CAS: 128-95-0), or 17-alpha-ethynylestradiol (CAS: 57-63-6) or a nonpromoting agent, diphenylhydantoin (CAS: 57-41-0), for 1 week. By treatment with promoters, the protease activity in the microsomal fraction was increased to threefold to fivefold that of control, whereas only a slight increase of activity was found after diphenylhydantoin treatment. The Ca2+-dependent protease activity was determined with the use of N-benzoyl-L-tyrosine ethyl ester as the substrate in a medium containing 50 mM CaCl2 for its maximal activity. This protease was preferentially localized in the smooth microsomal membrane and strongly inhibited by diisopropyl phosphorofluoridate (CAS: 55-91-4), and the optimum pH of the activity was 7.8. It appears that the Ca2+-dependent serine protease measured by using a chymotrypsin substrate is a novel protease, and induction of its activity by hepatic tumor-promoting agents is a common and specific phenomenon.

Animals↗
PubMed1986

[A randomized controlled study of (2'' R)-4'-O-tetrahydropyranyladriamycin and adriamycin in combination with cyclophosphamide and 5-fluorouracil in the treatment of advanced and recurrent breast cancer].

A comparative study of two combination chemotherapy regimens including (2'' R)-4'-O-Tetrahydropyranyladriamycin (THP) or Adriamycin (ADR) was performed to evaluate its efficacy and safety in advanced and recurrent breast cancer. In this study 64 patients were evaluated, and the response rate was 35.1% (13 of 37 patients) in group A (combination chemotherapy of THP, 5-Fluorouracil and cyclophosphamide), and 29.6% (8 of 27 patients) in group B (ADR, 5-Fluorouracil and cyclophosphamide). There was no statistically significant difference between the response rates of the two groups. As for safety, that of group A was significantly superior to group B for alopecia while that of group A tended to be lower than group B for anorexia. From the above results, THP in combination with cyclophosphamide and 5-Fluorouracil is comparable to ADR in efficacy and can be regarded as having better safety than ADR for the treatment of breast cancer.

Anorexia↗