Tohru Nakayama

Anticancer effects of a chinese Herbal medicine, Juzen-taiho-to, in combination with or without 5-fluorouracil derivative on DNA-synthesizing enzymes in 1,2-dimethylhydrazine induced colonic cancer in rats

Juzen-taiho-to (JTT; [Shi-quan-da-bu-tang], a Japanese modified Chinese herbal prescription) in combination with an anticancer drug UFT (5-fluorouracil derivative) prevented the body weight loss and the induction of the colonic cancer in rats treated with a chemical carcinogen 1,2-dimethylhydrazine (DMH), and suppressed markedly the activity of thymidylate synthetase (TS) involved in the de novo pathway of pyrimidine synthesis in colonic cancer induced by DMH.

Splenomegaly induced by recombinant human granulocyte-colony stimulating factor in rats

Spontaneous ruptures of the spleen have been observed in donors and patients with malignancy during mobilization of peripheral blood stem cells. Thus, we investigated the morphological and histological alteration of the spleen, and mRNA expression levels and activities of the DNA-synthesizing enzymes thymidylate synthase (TS) and thymidine kinase (TK) in the splenic cells, of rats treated with recombinant human granulocyte-colony stimulating factor (rhG-CSF). Daily injections of rhG-CSF for 5 or 7 days slightly enhanced the splenic weight. Single or 3-day treatment with rhG-CSF markedly enhanced the number of granulocytes in peripheral blood. Expression levels of TS and TK mRNA in the splenic cells were significantly increased 6 hours after rhG-CSF treatment. Early expression of TS and TK mRNA in the splenic cells may indicate a reseeding of hematopoietic cells from the bone marrow. Daily injections with rhG-CSF enhanced the TS and TK activities in the splenic cells. As continuous elevations of DNA-synthesizing enzyme activity and spleno-megaly are suggestive of a possible splenic rupture, the monitoring of peripheral granulocytes and splenic size is necessary during the rhG-CSF treatment.

EARLY PROGRESSION FROM DIMETHYL SULFOXIDE-INDUCED G0/G1 ARREST IN L1210 CELLS

Recently, dimethyl sulfoxide (DMSO) has been used as a convenient cryoprotectant for stem cells in stem cell transplantation using allogenic peripheral blood or umbilical cord blood. As the stem cells have a multipotency, clarification of the extent of cell proliferation after transplantation is difficult. In the present study, DMSO gradually induced G0/G1 arrest in mouse leukemia L1210 cells with good cell viability. After removal of DMSO, the cells proliferated appropriately, resulting in expression of the DNA‐synthesizing enzymes thymidylate synthase and thymidine kinase within 6h, and the cells entering into S phase within 12h. The sequence was followed by the marked activation of both enzymes within 24h and the increase of bromodeoxyuridine (BrdU) immunoreactive (S phase) cells with rapid cell proliferation within 36h. In conclusion, mouse leukemia L1210 cells, which were treated with 1.5% DMSO for 96h, tolerated the treatment and reversed the cell cycle arrest within 36h.

Pharmacotherapeutic Effects of Toki-shakuyaku-san on Leukorrhagia in Young Women

Toki-shakuyaku-san is a traditional Chinese herbal prescriptions that is composed of 6 herbal plants, i.e., peony root, atractylodes lancea rhizome, alisma rhizome, hoelen, cnidium rhizome and Japanese angelica root. Administration with Toki-shakuyaku-san normalized irregular menstrual cycle, healed cervical pseudo-erosion and reduced leukorrhagia in young women who had insufficient luteal function.

Suppression by kampo medicine, sho-saiko-to, on papillomas induced by 7,12-dimethylbenz(a)anthracene in mice.

Sho-saiko-to (SST) is a Japanese modified, traditional Chinese herbal medicine (Kampo medicine) consisting of seven medical plants. We examined the effects of SST on formation and growth of squamous cell papillomas induced by 7,12-dimethylbenz(a)anthracene application in mouse skin. Chronic oral administration of SST reduced the incidence and growth of papillomas with the reduction of activities of succinate-dehydrogenase and thymidylate synthetase, which were evaluated as the cell viability and DNA synthesis via the de novo pathway, respectively.

EFFECTS OF RECOMBINANT HUMAN ERYTHROPOIETIN ON DNA SYNTHESIS IN RAT HEMATOPOIETIC ORGANS

In an attempt to define the effects of recombinant human erythropoietin (rEPO) on DNA synthesis in hematopoietic organs, we investigated DNA-synthesizing enzyme activities, i.e., thymidylate synthetase and thymidine kinase activities, and bromodeoxyuridine-immunohistochemistry during the recovery phase of hematopoietic cells in bone marrow and spleen after the hypoplastic period induced by cyclophosphamide (Cy) treatment in rats. Treatment with rEPO increased enzyme activities and cell number of erythroid series in bone marrow cells; it also increased organ weight and S-phase cells in the spleen, followed by an augmentation of the number of erythrocytes and a rise in the hemoglobin and hematocrit levels in peripheral blood with or without Cy treatment.

1???(2???Tetrahydrofuryl)???5???fluorouracil in combination with uracil suppresses mammary carcinogenesis and growth of tumors induced with 7,12???dimethylbenz[a]anthracene in rats

The effects of 1-(2-tetrahydrofuryl)–5–fluorouracll in combination with uracil (UFT) on mammary carcinogenesis and growth of tumors induced with 7,12-dlmethylbenz– [a]anthracene (DMBA) were Investigated In rats. Daily oral administration of UFT reduced the Incidence and number of mammary tumors compared with those of the DMBA control group, resulting in lower activities in DNA synthesizing enzymes, thymidylate synthetase and thymldine klnase, and a reduction of bromodeoxyuridlne– Immunoreactlve (S–phase) cells in mammary tumors of UFT–treated rats.