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K Kuwa

Publications and source records attributed to K Kuwa.

At least 37 records · Page 2Linked to original sources
PubMed1990

Thymidine kinase and alpha-fetoprotein as biochemical markers of hepatocarcinogenesis induced by 3'-methyl-4-dimethylaminoazobenzene treatment in rats.

It is known that a high incidence of hepatocellular carcinoma in rat liver can be induced by such azo dye carcinogens as 3'-methyl-4-dimethylaminoazobenzene (3'-MeDAB). Thymidine kinase (TK) catalyzes the formation of deoxythymidine monophosphate (dTMP) by the phosphorylation of thymidine via the salvage pathway. In the present study, we investigated serum alpha-fetoprotein (AFP) and TK levels, and tissue TK and its isozyme activities in the liver of rats treated with 3'-MeDAB. Serum TK activities rose abruptly directly after the onset of 3'-MeDAB treatment, peaking after 1 week and then gradually decreasing. At 3 weeks, though serum TK was decreasing, serum AFP and tissue TK began to increase, and oval cells appeared in the liver. At 5 weeks, though serum TK reached a nadir, serum AFP and tissue TK formed transient peaks, and oval cells occupied a major part of the hepatic lobules with hyperplastic nodules. Thereafter, serum TK continued to increase, and serum AFP and tissue TK, after transiently decreasing, re-increased; at 20 weeks, each value was at high level, and mixed type hepatocarcinoma was observed. The liver TK isozymes were separated into three types by DEAE-cellulose column chromatography. A 3'-MeDAB diet induced a remarkable increase in activity of cytosolic and fetal type isozyme in non-tumorous regions of livers at 5 weeks and tumorous regions at 20 weeks. These results indicate that early biochemical changes in 3'-MeDAB-induced hepatocarcinoma in rats may serve as a useful model and provide a valuable insight in hepatocarcinogensis.

Animals↗
PubMed1989

[Effects of neo-adjuvant chemotherapy with UFT (a combination of tegafur and uracil) on DNA-synthesizing enzyme activities in human colorectal carcinomas].

Thymidylate synthetase (TS) and thymidine kinase (TK) are known to catalyse the methylation of dUMP for the de novo synthesis of dTMP and the phosphorylation of thymidine for the salvage synthesis of dTMP in the pyrimidine pathway, respectively. High TS and TK activities have been observed in rapidly proliferating tissues such as foetal tissue, regenerating liver and carcinomas. TS and TK activities were measured in histologically normal colon mucosa and colorectal carcinomas with or without neo-adjuvant chemotherapy of an antitumor drug UFT (a combination of tegafur and uracil) in humans. In colorectal carcinomas, 5-FU and uracil levels were increased to 2.6- and 3.2-fold, respectively, those in normal colon mucosa by neo-adjuvant chemotherapy of UFT. In colorectal carcinomas, TS and TK activities were both increased to approximately 2- and 3-fold, respectively, those in normal colon mucosa without UFT treatment. In normal colon mucosa and colorectal carcinomas with neo-adjuvant chemotherapy of UFT, TS activities were reduced to approximately 50% and 40%, respectively, those without UFT treatment. These results indicate that neo-adjuvant chemotherapy with UFT may prevent dissemination of cancer cells during operation, and local recurrence and distant metastasis after operation, inhibiting DNA synthesis via the de novo pathway of pyrimidine synthesis in carcinomas.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1987

Relative activities of thymidylate synthetase and thymidine kinase in 1,2-dimethylhydrazine-induced colon carcinomas in rats.

Thymidylate synthetase (TS) and thymidine kinase (TK) are known to catalyse the methylation of dUMP for the de novo synthesis of dTMP and the phosphorylation of thymidine for the salvage synthesis of dTMP in the pyrimidine pathway, respectively. High TS and TK activities and the existence of TK isozymes have been observed in rapidly proliferating tissues. TS and TK activities in 1,2-dimethylhydrazine (DMH)-induced colon carcinomas in rats increased significantly to 331 and 207% of the activities in normal colon, respectively, and were well correlated inversely (y = -0.93x + 5.24), with a correlation coefficient of -0.787. The colonic TK isozymes were separated into two types by DEAE-cellulose column chromatography. The TK isozyme eluted from the column by the elution buffer alone without NaCl was markedly higher (23.6-fold) in activity in DMH-induced colon carcinoma than in normal control colon and was not affected by deoxycytidine triphosphate. This isozyme, whose mol. wt is 100,000 by h.p.l.c., is thought to be closely involved in rapid DNA replication. These results indicate that early biochemical changes in DMH-induced colon carcinoma in rats may serve as a useful model and provide valuable insight into the mechanisms involved in colonic carcinogenesis.

1,2-Dimethylhydrazine↗
PubMed1980

Occurrence of persistent elevated levels of serum glutamic oxaloacetic transiminase as a result of enzyme-immunoglobulin complex formation --with a report of two cases--.

Two cases of macro-molecular GOT (glutamic oxaloacetic transaminase) were encountered recently. Both were middle-aged women, showing no abnormality in laboratory test results including those for GPT (glutamic pyruvic transaminase), except that abnormality high values (ca. 200 Karmen unit) were obtained for GOT. Clinical examinations and tests on the liver, heart, skeletal muscle and other organs were negative. By column chromatography, immunoelectrophoresis and other procedures, this macro-molecular GOT was shown to be an anzyme immunoglobulin complex with a molecular weight of about 250,000 formed by the binding of the GOT of the cytoplasmic fraction to Ig-G-Kappa.

Alanine Transaminase↗
PubMedDate not supplied

Effects of a Chinese herbal medicine, keishi-bukuryo-gan, on the gonadal system of rats.

Keishi-bukuryo-gan (TJ-25) is a traditional Chinese herbal remedy containing five components: bark of Cinnamomum cassia, root of Paeonia lactiflora, seed of Prunus persica or P. persiba var. davidiana, carpophores of Poria cocos and root bark of Paeonia suffruticosa. This preparation has been used in the treatment of gynecological disorders such as hypermenorrhea, dysmenorrhea and infertility. In the present study, the effects of TJ-25 on plasma levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH) and estradiol (E2), and on uterine wet weight and thymidine kinase (TK) activity were documented in immature rats. Long-term daily oral administration of TJ-25 (300 mg/kg) for 14 days decreased plasma levels of LH, FSH and E2 by 94%, 67% and 50%, respectively, compared to controls. Uterine wet weight and TK activity were reduced to 65% and 64% that of controls, respectively. Short-term effects of TJ-25 on E2 were also examined. Thirty hours after administration of E2 (1.0 micrograms/kg) alone, uterine wet weight and TK activity were elevated 2.4- and 21-fold, respectively, over controls. However, simultaneous administration of TJ-25 (three consecutive doses, every 12 h) with E2 reduced E2-induced increases in uterine wet weight and TK activity by 29% and 39%, respectively. Treatment with TJ-25 also enhanced LH-RH-induced increases in plasma LH and FSH levels 1.2- and 2.5-fold, respectively, as compared with controls. The results obtained in the present study indicate that TJ-25 may act as a LH-RH antagonist and/or as a weak anti-estrogen.

Administration, Oral↗
PubMedDate not supplied

Correlation between histological differentiation and DNA-synthesizing enzymes in rat colorectal tumors induced with 1, 2-dimethylhydrazine.

Thymidylate synthase and thymidine kinase are key enzymes involved in de novo and salvage pathways for pyrimidine nucleotide synthesis. Colorectal carcinogenesis induced with 1,2-dimethylhydrazine in rats enhanced mRNA expression levels of both enzymes, resulting in the increase of both enzyme activities and bromodeoxyuridine-immunoreactive S-phase cells. Poorly and well differentiated adenocarcinomas of the colorectum showed the relative elevation of activities of thymidylate synthase and thymidine kinase, respectively. These results indicate that the relationship between de novo and salvage pathways for pyrimidine nucleotide synthesis may depend on the histopathological grades of cell differentiation.

Animals↗
PubMedDate not supplied

Effects of 5-fluorouracil derivative UFT on thymidylate synthetase and thymidine kinase in rat colorectal tumors.

BACKGROUND: Thymidylate synthetase and thymidine kinase are key enzymes involved in de novo and salvage pathways for pyrimidine nucleotide synthesis, respectively. MATERIALS AND METHODS: Weekly injections of 1,2-dimethyl-hydrazine induced high incidence of colorectal adenocarcinomas in rats. RESULTS: An increased activity of thymidylate synthetase was found in the poorly differentiated adenocarcinomas of the chemically induced rat colorectal tumors. Six-week oral administration of 1-(2-tetrahydrofuryl)-5-fluorouracil in combination with uracil (UFT) reduced the total number of colorectal tumors, with the reduction of thymidylate synthetase activity in the poorly-differentiated type, though the mRNA expression of thymidylate synthetase and thymidine kinase differed little between the groups with or without UFT treatment. CONCLUSIONS: These results indicate that the long-term oral administration using UFT suppresses colorectal carcinogenesis and the growth of the poorly-differentiated type tumors.

Animals↗
PubMedDate not supplied

Effects of long-term administration of UFT plus leucovorin on colorectal tumors induced with 1,2-dimethylhydrazine in rats.

Thymidylate synthase and thymidine kinase are key enzymes involved in the de novo and salvage pathways for pyrimidine nucleotide synthesis, respectively. Thymidylate synthase is inhibited by 5-fluorodeoxyuridine monophosphate, forming an inactive ternary complex with intracellular folate. We investigated the effects of 1-(2-tetrahydrofuryl)-5-FU plus uracil (UFT) with or without leucovorin on 1,2-dimethylhydrazine-induced rat colorectal carcinomas. Thirty-week administration of UFT with or without leucovorin markedly suppressed both colorectal carcinogenesis and tumor growth, resulted in the increase of thymidylate synthase inhibition and the decrease of thymidine kinase activity in the tumor cells. These results indicate that the combination of UFT with leucovorin could be useful in the development of pre- and post-operative adjuvant chemotherapy programs.

1,2-Dimethylhydrazine↗
PubMedDate not supplied

Effects of a low dose leucovorin with 5-fluorouracil derivative on colorectal tumors induced with 1,2-dimethylhydrazine in rats.

Thymidylate synthase, which is a key enzyme involved in the de novo pathway for pyrimidine nucleotide synthesis, is inhibited by 5-fluorodeoxyuridine monophosphate, forming an inactive ternary complex with intracellular folate. We investigated the effect of a 5-fluorouracil derivative (UFT) with or without low dose leucovorin on the number of 5-fluorodeoxyuridine monophosphate binding sites, thymidine kinase activity and intracellular folate concentration in 1,2-dimethylhydrazine-induced rat colorectal carcinomas. A 10-day administration of UFT with or without leucovorin enhanced the thymidine kinase activity and the number of 5-fluorodeoxyuridine monophosphate binding sites, with an increase of thymidylate synthase mRNA expression. Thymidylate synthase inhibition was slightly increased as the intracellular folate concentration increased. These results indicate that thymidylate synthase inhibition increases when the intracellular folate is exogenously supplemented and maintained at an adequate concentration.

1,2-Dimethylhydrazine↗
PubMedDate not supplied

Thermal effects on DNA synthesis in bone marrow cells of patients with acute myeloblastic leukemia.

It has been known that thymidylate synthetase (TS) and thymidine kinase (TK) are DNA-synthesizing enzymes via the de novo and salvage pathways, respectively, in pyrimidine metabolism, and an immunological method using a monoclonal antibody to bromodeoxyuridine (BrdU) is useful for the detection of S-phase cells. We investigated the effects of hyperthermia on DNA synthesis in bone marrow cells obtained from patients with acute myeloblastic leukemia. TK isozymes in bone marrow cells of patients with acute myeloblastic leukemia were separated into two types, i.e., fetal type isozyme in cytosolic cell fraction and adult type isozyme in mitochondrial cell fraction. Heating at over 43 degrees C as a hyperthermia markedly suppressed enzyme activity of fetal type TK isozyme and number of S-phase cells labelled with BrdU, but not activities of adult type TK isozyme and TS. These results indicate that hyperthermia may regulate the proliferation of S-phase cells by the suppression of salvage synthesis of DNA.

Bone Marrow↗
PubMedDate not supplied

Inhibition by 1-(2-tetrahydrofuryl)-5-fluorouracil in combination with uracil of hepatocarcinogenesis induced by 3'-methyl-4-dimethylaminoazobenzene in rats.

It is known that a high incidence of hepatocellular carcinoma in rat liver can be induced by 3'-methyl-4-dimethylaminoazobenzene (3'-MeDAB). The administration of 3'-MeDAB in combination with 1-(2-tetrahydrofuryl)-5-fluorouracil and uracil (UFT) delayed the appearance of oval cells and the formation of hyperplastic nodules, which were observed in the liver from 3 and 5 weeks, respectively, after the onset of 3'-MeDAB feeding, and also delayed the transient increase of serum alpha-fetoprotein level, which transiently peaked at 5 weeks, and completely suppressed the transient increase of tissue thymidylate synthetase activity, but not thymidine kinase, which were induced by 3'-MeDAB at 5 weeks, and finally reduced markedly the incidence of hepatocarcinomas. These results indicate that the suppression of de novo synthesis in pyrimidine metabolism prevents hepatocarcinogenesis.

Animals↗
PubMedDate not supplied

Synergistic effect of oral UFT in combination with cisplatin on DNA synthesis in rat hepatocarcinomas.

We investigated the synergistic efficacy of CDDP and UFT, an oral anticancer derivative of 5-fluorouracil, on DNA synthesis of 3'-MeDAB-induced hepatocarcinomas in rats. Chronic treatment with CDDP slightly reduced tissue activities of thymidylate synthetase and thymidine kinase in the hepatocarcinomas, and, moreover, simultaneous administration of a low dose of UFT with CDDP markedly suppressed both enzyme activities, i.e., UFT and CDDP showed a potent synergism on DNA synthesis in hepatocarcinomas.

Administration, Oral↗
PubMedDate not supplied

Effects of danazol on thrombopoiesis in rats.

A synthetic analog of ethinyltestosterone, Danazol, has been used clinically for the treatment of immune thrombocytopenia. We investigated the effects of Danazol on thrombopoiesis in normal rats. Though 4-week treatment by Danazol slightly enhanced the DNA synthesizing enzyme activities and the number of S-phase cells in bone marrow and spleen, the number of megakaryocytes and thrombocytes were not increased in bone marrow and peripheral blood, respectively. These findings suggest that Danazol treatment will not induce thrombosis with thrombocytosis in normal human beings and animals.

Animals↗
PubMedDate not supplied

Effects of luteinizing hormone-releasing hormone analogue on DNA synthesis in rat prostate and uterus.

Buserelin, a potent LH-RH agonist, has been used for the treatment of hormonal disorders such as precocious puberty, endometriosis, cystic mastitis and prostatic carcinoma. Prolonged treatment with buserelin has been known to induce a refractory phase of pituitary desensitization. In the present study, we found that two-week treatment with buserelin strongly suppressed the activities of thymidylate synthetase and thymidine kinase, and markedly reduced the appearance of BrdU-immunoreactive (S-phase) cells in both prostate glands and uteri in male and female adult rats, respectively.

Animals↗
PubMedDate not supplied

Effects of estrone with or without medroxyprogesterone acetate on the femur in aged rats.

In an attempt to define the efficacy of hormone replacement therapy in postmenopausal osteoporosis, we investigated the effects of estrone with or without medroxyprogesterone acetate on the bone mineral density of the femur of aged rats, of which plasma levels of luteinizing hormone (LH), follicle stimulating hormone (FSH) and estradiol were markedly reduced in comparison with those of younger rats. Although additional sex hormones had little effect on the plasma levels of gonadotropins, chronic administration of estrone significantly enhanced the bone mineral density of femur in aged animals.

Aging↗
PubMedDate not supplied

Effects of a new clerodane diterpenoid isolated from propolis on chemically induced skin tumors in mice.

Propolis is a resinous material gathered by honey bees from the buds and bark of certain trees and plants, and used inside their hives. Characteristic components of propolis are many kinds of flavonoid aglycones. The methanol extract of a Brazilian propolis was fractionated by HPLC, and a tumoricidal substance was isolated and characterized as a new clerodane diterpenoid (PMS-1) with a molecular formula of C20H32O3 (MW: 320). We investigated the effects of PMS-1 on skin tumorigenesis and the development of skin tumors induced by 7,12-dimethylbenz(a)anthracene application on mouse back skin. It was tentatively concluded that PMS-1 reduced the incidence of skin tumors by inhibition of DNA synthesis in a de novo pathway, and suppressed the growth of the tumors by decreasing DNA synthesis in a salvage pathway.

9,10-Dimethyl-1,2-benzanthracene↗