Biomedical subjects

T Mitamura

Publications and source records attributed to T Mitamura.

85 records · Page 5Linked to original sources

PubMedDate not supplied

Effects of lentinan on colorectal carcinogenesis in mice with ulcerative colitis.

Lentinan; i.e., polysaccharides extracted from a kind of black mushroom shiitake, has been clinically applied as an antitumor and antimetastatic drug, and has been reported to prevent both chemical and viral carcinogenesis. It is known that lentinan affects the tumorous vascular system resulting in the induction of hemorrhagic necrosis which is dependent on T-cells in the tumor. Repeated mucosal necrosis-regeneration sequence in chronic ulcerative colitis induced with 3% dextran sulfate sodium led to colorectal carcinogenesis in azoxymethane-pretreated mice. In the present study, the additive treatment with lentinan in the azoxymethane-dextran sulfate sodium treated mice enhanced the colorectal high-grade dysplasia, though not significantly, and the splenic weight. This may show the proliferation of pathogenic splenic T cells resulting in a change for the worse of ulcerative colitis, anemia induced with hemorrhage and colorectal carcinogenesis; i.e., high-grade dysplasia of the mucosa and/or invasive adenocarcinomas of the colorectum. The present results may recommend chemoimmunotherapy while using lentinan, but not immunotherapy using lentinan alone, is indicated for the management of cancer patients.

Animals↗

PubMedDate not supplied

Does macrophage-colony stimulating factor stimulate rat haematopoietic cells?

It is known that colony stimulating factors (CSFs) stimulate the myeloid cells of bone marrow and splenic cells in rodents. The effects of macrophage (M)-CSF on the activities of thymidylate synthase and thymidine kinase, involved in de novo and salvage pathways for pyrimidine nucleotide synthesis, respectively, in haematopoietic cells of bone marrow and spleen were investigated in rats. A single M-CSF injection did not elevate the mRNA expression levels of the enzymes in bone marrow cells 6 h after treatment, but it enhanced the splenic thymidylate synthase mRNA expression. M-CSF stimulated the splenic thymidylate synthase activity without an increase of the peripheral granulocytes. The effect of M-CSF on granulocytes is considered to be weak compared with that of granulocyte (G)-CSF, because of the indirect secretion of endogenous G-CSF from the cells with M-CSF receptors stimulated by exogenous M-CSF. Since M-CSF was able temporarily to lead progenitor cells from long G1-phase into S-phase, M-CSF might accelerate the anticancer effects when used together with anticancer agents.

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 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

Preventive effects of sulphasalazine on colorectal carcinogenesis in mice with ulcerative colitis.

Sulphasalazine has been used in the treatment of ulcerative colitis and is known to be a prodrug and split into sulphapyridine and 5-aminosalicylic acid by bacteria in the colon. An increased incidence of colorectal carcinoma is known to occur in patients with ulcerative colitis, which displays a recurrence-remission cycle on colorectal mucosa, i.e., the ulceration and regeneration periods of the colorectal mucosa. Repeated mucosal necrosis-regeneration sequence in chronic ulcerative colitis induced with 3% dextran sulfate sodium led to colorectal carcinogenesis in azoxymethane-pretreated mice. Additive treatment with sulphasalazine normalized the enlarged organs, i.e. liver, spleen and kidney and anemia and leucocytosis induced with 3% dextran sulfate sodium resulted in the reduction of tumorous regions with high-grade dysplasia.

Animals↗

PubMedDate not supplied

Effects of lycopene on spontaneous mammary tumour development in SHN virgin mice.

Effects of the chronic ingestion of lycopene, a carotenoid from tomato, on the development of spontaneous mammary tumours were examined in a high mammary tumour strain of SHN virgin mice. Beginning at 40 days of age, the control and the experimental groups were allowed free access to an AIN-76TM diet and a diet supplemented further with lycopene at the concentration of 5.0 x 10(-5)%, respectively. The treatment significantly suppressed the mammary tumour development, which suppression was associated with the decrease in the mammary gland activity of thymidylate synthetase, and serum levels of free fatty acid and prolactin. Body weight was little affected and no deleterious side-effects of lycopene were detected. All results show that lycopene could be promising as a chemopreventive agent for mammary and other types of tumours.

Animals↗

PubMedDate not supplied

Effects of 5-fluorouracil derivatives on papillomas induced by application of 7,12-dimethylbenz(a)anthracene in mice.

We examined the effects of an application of 5-fluorouracil (5-FU) ointment and a chronic oral administration of 1-(2-tetrahydrofuryl)-5-FU plus uracil (UFT) on 7,12-dimethyl-benz(a)-anthracene-induced squamous cell papillomas in mice. Although application of 5-FU ointment reduced the growth of papillomas slightly, chronic oral administration of UFT could prevent tumorigenesis and suppress the growth of papillomas, resulting in the reduction of the tumorous viability and DNA synthesis.

9,10-Dimethyl-1,2-benzanthracene↗

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↗

PubMedDate not supplied

Comparison of the spontaneous behaviour of four strains of female mice with different physiological properties.

The behaviour of four strains of virgin and lactating mice with different physiological characteristics (SHN, SLN, GR/A and C3H/He) were compared. In virgin, the motor activity, determined by Supermex, was high in all strains shortly after the start of the test, especially in GR/A. In this strain, the high activity continued longer and was also observed before the dark phase. In both the entire 48 hours and the last 24 hours of measurement, GR/A showed higher activity than the other strains during the light phase, but not during the dark phase. These data suggest that GR/A is more sensitive and thus has lower adaptability to a new environment than the other strains and that the biological clock of this strain differs from the others. The frequency and the period in or out of the nest as estimated by a video monitor were smaller and longer, respectively, in SLN than in the other strains. However, no relationship was found between the pattern of behaviour at lactation and the pup growth as an index of lactational performance.

Animals↗

PubMedDate not supplied

Additional effects of medroxyprogesterone acetate on mammary tumors in oophorectomized, estrogenized, DMBA-treated rats.

Although hormone replacement therapy not only relieves vasomotor symptoms but also reduces cardiovascular disease and osteoporosis, long-term estrogen therapy increases the risk of endometrial and/or mammary cancer. We investigated the effects of conjugated estrogens with or without medroxyprogesterone acetate in oophorectomized, 7,12-dimethylbenz(a)anthracene-treated rats. Chemically induced mammary carcinogenesis was completely suppressed by the simultaneous oophorectomy, but conjugated estrogens replacement with or without medroxyprogesterone acetate markedly stimulated mammary carcinogenesis in the ovariectomized rats. The chronic administration of conjugated estrogens and medroxyprogesterone acetate markedly reduced the activities of thymidylate synthetase and thymidine kinase and bromodeoxyuridine-immunoreactive (S-phase) cells in mammary tumors. These results indicate that the treatment using conjugated estrogens with or without medroxyprogesterone acetate may promote the mammary carcinogenesis in postmenopausal women but the chronic administration of medroxyprogesterone acetate may alter the development of established mammary cancer.

9,10-Dimethyl-1,2-benzanthracene↗

PubMedDate not supplied

Effects of tamoxifen on mammary tumors and bone in 7,12-dimethylbenz-(a)anthracene-treated rats.

We investigated the effects of tamoxifen on the growth of 7,12-dimethylbenz(a)anthracene induced rat mammary tumors, the activity of thymidylate synthetase and thymidine kinase (key enzymes involved in de novo and salvage pathways for pyrimidine nucleotide synthesis), and also their gene expression. The effects on immunohistochemistry using bromodeoxyuridine in the tumors and bone mineral density of the femur in rats were also studied. Chronic administration of tamoxifen markedly reduced the expression of thymidylate synthetase mRNA, followed by a reduction in enzyme activity and S-phase cells in the mammary tumors, and significantly enhanced the bone mineral density. Tamoxifen not only attenuated bone loss in aging but also enhanced bone volume in mammary tumor-bearing rats in which tumor growth was suppressed via both the de novo and salvage pathways for pyrimidine nucleotide synthesis.

9,10-Dimethyl-1,2-benzanthracene↗

PubMedDate not supplied

Conservative management for perimenopausal women with uterine leiomyomas using Chinese herbal medicines and synthetic analogs of gonadotropin-releasing hormone.

The effects of a long-term intranasal administration of each of the gonadotropin-releasing hormone analogs, buserelin and nafarelin on uterine leiomyomas after conservative treatment using Chinese herbal medicines, Keishi-bukuryo-gan and Shakuyaku-kanzo-to were investigated in 30 perimenopausal women with leiomyomas. Hypermenorrhea and/or dysmenorrhea as a chief complaint was moderately improved by the treatment using Chinese herbal medicines in more than 60% of the patients with less than fist-sized leiomyomas, but not the over fist-sized. Afterwards, continuous treatment using analogs produced a long-term reduction in leiomyomas (less than 60%) along with decreases in the serum levels of luteinizing hormone, follicle-stimulating hormone, estradiol, and the tumor marker CA-125, and adverse effects including slight boneloss. Long-term treatment using Chinese herbal medicines and gonadotropin-releasing hormone analogs for the management of uterine leiomyomas could be beneficial for patients a few years before menopause, though possible side effects of this treatment should be monitored.

Adult↗