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T Iwaguchi

Publications and source records attributed to T Iwaguchi.

At least 19 recordsLinked to original sources
PubMed1995

In vitro and in vivo antitumor activity of the interferon inducer bropirimine.

In vivo and in vitro antitumor effects of an interferon (IFN)-alpha inducer, bropirimine (2-amino-5-bromo-6-phenyl-4(3H)-pyrimidinone), were examined in the murine tumor system. The antitumor effects were studied in Meth A cells, which were the most sensitive to bropirimine in the murine cell lines tested. The direct inhibitory activity of the drug was not reduced when Meth A cells were incubated with bropirimine and anti-IFNs, indicating that the inhibition is not due to autocrine IFN induction from tumor cells. The drug partially inhibited the uptake of [3H]thymidine, [3H]uridine and [3H]leucine. Cell cycle analysis with flow cytometry showed that the drug decreased G0/G1 phase and increased G2/M phase Meth A cells. The drug administered i.p. exhibited a remarkable antitumor effect against Meth A cells which were implanted i.p. These results suggested that the drug induced the in vivo antitumor effect by its direct antitumor activity.

Animals↗
PubMed1994

Effects of CD4+ and CD8+ T cells in tumor-bearing mice on antibody production.

The function of T cell subsets in tumor-bearing mice was examined using an in vitro culture system of anti-(sheep red blood cell) antibody production, which is known to be dependent on T cells. The helper function of T cells of fibrosarcoma-MethA-bearing mice in antibody production decreased with the tumor stage of the mice. T cells were separated into CD4+ and CD8+ cells for further analysis of T cell subsets by the panning method using monoclonal antibodies. The helper function of CD4+ T cells in antibody production began to decrease significantly in tumor-bearing mice 1 week after the tumor transplantation. On the other hand, the suppressive function of CD8+ T cells was retained and had not decreased in the mice even 3 weeks after the transplantation. The same changes in function of CD4+ and CD8+ T cells were also observed in Meth1-bearing mice. These results suggested that this tumor-associated immunosuppression in antibody production is attributable to the decrease in helper activity of CD4+ T cells and the maintenance of the suppressive activity of CD8+ T cells.

Animals↗
PubMed1993

[Angiogenesis and its regulation].

Angiogenesis (formation of new blood vessels) is essential in embryonal development, female reproduction and wound repair. Under these physiological conditions, angiogenesis is highly regulated by the endogenous angiogenic factor and its inhibitor. However, angiogenic diseases such as rheumatoid arthritis, diabetic retinopathy, solid tumor, hemangioma and psoriasis are driven by persistent unregulated angiogenesis. The angiogenic process consists of such multi-steps as degradation of basement membrane, cell migration and proliferation, and tube formation following activation of vascular endothelial cells by stimulators appearing at the pathological site. Thus, for modulating the pathological conditions, it is most important to elucidate the angiogenic mechanism at the molecular level. It is not sufficiently clear yet as compared with the blood coagulation and hematopoietic systems. On the other hand, there have been advances in the study of new anticancer metastatic agents as a target of activated endothelial cells and they have been found to have promising substances. In this study, the angiogenic factor, its inhibitor, and then the anticancer effect of the angiogenic inhibitor, have been investigated from the standpoint of cancer therapy.

Angiogenesis Inducing Agents↗
PubMed1992

Cell electrophoretic characterization of abnormally expanded lymphocytes in autoimmune lprcg, lpr, gld and Yaa mice, and of thymocyte subsets.

Autoimmune mice carrying the lprcg/lprcg(lprcg),lpr/lpr(lpr),gld/gld(gld) and Yaa genes exhibit massive lymphoproliferation and a systemic lupus erythematosus-like syndrome. The surface markers of abnormally expanded lymphocytes used were Thy-1+, CD4-CD8- (double negative, DN) and CD45+ for lprcg, lpr, gld and (lprcg X gld) hybrid (F1-lprcg-gld) mice, and Ig+ for Yaa mice. To characterize the cell surface properties and differentiation pathway of lymphocytes in autoimmune mice, the cell electrophoretic mobility (EPM) was determined for the lymph node (LN), spleen and thymus cells. The EPM of lymphocytes derived from swollen LN was of the T cell type in lprcg, lpr, gld and F1-lprcg-gld mice, but of the B cell type in Yaa mice, indicating that the EPM of abnormally proliferated lymphocytes in autoimmune mice reflects their origin, and that the surface properties detected as a net negative charge were the same in abnormal and normal lymphocytes. The electrophoretic behavior of whole thymocytes was also the same in autoimmune and normal mice. The DN, and CD4+CD8- and CD4-CD8+ (single positive, SP) thymocytes from normal mice exhibited high EPM, while CD4+CD8+ (double positive, DP) thymocytes exhibited low EPM. According to the recent concept of intrathymic T cell differentiation (Schwartz, R. H., Cell. 1989, 57, 1073-1081), it is suggested that EPM of thymocytes may change with maturation in the following manner: DN thymocytes with high EPM----DP thymocytes with low EPM----SP thymocytes and autoimmune DN T cells with high EPM.

Animals↗
PubMed1992

Cyclophosphamide-induced suppressor cells in nude mice.

Lymphocytes regenerated after treatment with a high dose of cyclophosphamide (CY) were characterized in nude mice. Ten days after a single injection of 200 mg/kg CY into nude mice, regenerated spleen cells suppressed in vitro primary and second antibody production against sheep red blood cells. The CY-treated spleen cells exhibited normal natural killer (NK) activity, very low B and T cell content, but increases in cell surface charge [electrophoretic mobility (EPM)] and histamine receptors. The suppressor cells could not be removed by treatment with anti-Thy-1 plus complement (C), or treatment with antiasialo GM1 (aGM1) plus C, which abrogated NK activity. It was concluded that CY-treated spleen cells, which exhibited high EPM and histamine receptors, comprise the natural suppressor cells which are Ig-, Thy-1- and aGM-1.

Animals↗
PubMed1991

Angiogenic factor of a rat mammary tumor cell line (RMT-1) (I). Secretion of two distinct angiogenic factors into serum-free conditioned medium by RMT-1 cells.

Serum-free conditioned medium of a rat mammary tumor cell line RMT-1, established from a rat mammary carcinoma induced by 7,12-dimethylbenz[a]anthracene (DMBA), produced the complete angiogenic response in both rabbit cornea and chick embryo chorioallantoic membrane assays. The angiogenic activity in the RMT-1 conditioned medium was separated into two fractions on a column of heparin-Sepharose; one was eluted with 0.1 M NaCl and the other with 0.5 M NaCl, which are referred to hereafter as rAF-1 and rAF-2, respectively. These two angiogenic factors were further purified separately by FPLC on a Superose 12 column. The partially purified rAF-2 had an apparent Mr of 30,000-50,000 and seemed to exhibit mitogenic activity toward Balb/c 3T3 cells, while the partially purified rAF-1, with an apparent Mr of 10,000-30,000 did not have a mitogenic effect on these cells. Both rAF-1 and rAF-2 were resistant to heat and acid treatment, and exhibited trypsin sensitivity, suggesting that they are heat and acid stable peptides. The two angiogenic factors did not stimulate the proliferation of cultured vascular endothelial cells. These results suggest that RMT-1 secretes two distinct angiogenic factors into the medium and that these two secretable angiogenic factors participate cooperatively in the induction of the angiogenic response produced by a DMBA-induced rat mammary tumor in vivo.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1991

Enkephalin-degrading aminopeptidase in the longitudinal muscle layer of guinea pig small intestine: its properties and action on neuropeptides.

A membrane-bound enkephalin-degrading aminopeptidase was purified from the longitudinal muscle layer of the guinea pig small intestine by four steps of column chromatography using L-tyrosine beta-naphthylamide. The molecular weight of the enzyme was estimated to be 105,000 by gel filtration. The maximum activity was observed between pH 6.5 and 7.0. The Km value for leucine-enkephalin was 137 microM. The aminopeptidase activity toward aminoacyl beta-naphthylamide substrates was restricted to basic, neutral, and aromatic aminoacyl derivatives. No action was detected on acidic amino acid and proline derivatives. The enzyme was potently inhibited by the aminopeptidase inhibitors actinonin, amastatin, and bestatin, and bioactive peptides such as angiotensin III, substance P, and Met-Lys-bradykinin. The enzyme activity was also inhibited by the antibody against the purified serum enkephalin-degrading aminopeptidase of guinea pig at concentrations similar to those at which activity was observed toward serum enkephalin-degrading aminopeptidase and renal aminopeptidase M. The enzyme rapidly hydrolyzed Leu-enkephalin and Met-enkephalin with the sequential removal of the N-terminal amino acid residues. The enzyme also hydrolyzed two enkephalin derivatives, angiotensin III and neurokinin A. However, neurotensin, substance P, and bradykinin were not cleaved. These properties indicated that the membrane-bound enkephalin-degrading aminopeptidase in the longitudinal muscle layer of the small intestine is similar to the serum enkephalin-degrading aminopeptidase and resembles aminopeptidase M. It is therefore suggested to play an important role in the metabolism of some bioactive peptides including enkephalin in peripheral nervous systems in vivo.

Aminopeptidases↗
PubMed1991

Antitumor effect of 22-oxa-1 alpha,25-dihydroxyvitamin D3, a potent angiogenesis inhibitor, on rat mammary tumors induced by 7,12-dimethylbenz[a]anthracene.

The effect of 22-oxa-1 alpha,25-dihydroxyvitamin D3 (22-oxa-1,25(OH)2D3) on the growth of autochthonous rat mammary tumors induced by 7,12-dimethylbenz[a]anthracene (DMBA) was examined on the basis of our previous finding that this synthetic vitamin D3 analog has a potent angiogenesis inhibitory effect. Two doses of 22-oxa-1,25(OH)2D3, 0.1 and 1 microgram/kg of body weight, due to the limited amount of the compound available, were used. The daily administration of 22-oxa-1,25(OH)2D3 at the dose of 1 microgram/kg/day resulted in significant inhibition of the growth of these mammary tumors at 1, 2 and 3 weeks after the administration of this agent, although the agent caused little or no regression of the tumors. After daily administration for 3 weeks, a significant antitumor effect was also observed in the group treated with 0.1 microgram/kg/day. Treatment with 22-oxa-1,25(OH)2D3 did not affect the serum calcium levels in the treated rats. The lower dose of 22-oxa-1,25(OH)2D3 neither affected weight gain nor caused a decrease in body weight, while the higher dose, although having some effect on weight gain, did not induce a decrease in body weight. There were no significant differences in the weights of adrenals, uteri and ovaries between the treated groups and controls. These results suggest that 22-oxa-1,25(OH)2D3 has a significant growth inhibitory effect on DMBA-induced autochthonous mammary tumors in rats, without producing severe side effects, including hypercalcemic activity.(ABSTRACT TRUNCATED AT 250 WORDS)

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1990

A novel angiogenic inhibitor derived from Japanese shark cartilage (I). Extraction and estimation of inhibitory activities toward tumor and embryonic angiogenesis.

Guanidine extraction and crude fractionation of Japanese shark cartilage by ultrafiltration on a molecular weight basis were conducted and the antiangiogenic activities were assayed as to the inhibitions of tumor and embryonic angiogenesis. Significant inhibition of angiogenesis was found, and there was a linear relationship between the results of the two assays. The inhibitory activities were concentrated in the fraction in the molecular weight range of 103 to 104, and were resistant to heat treatment.

Animals↗
PubMed1990

Inhibition of angiogenesis by vitamin D3 analogues.

The effects of vitamin D3 and two analogues on embryonic angiogenesis were studied in 4.5-day-old chick embryo chorioallantoic membranes. The active metabolite of vitamin D3, 1 alpha,25-dihydroxyvitamin D3, and a synthetic vitamin D3 analogue, 22-oxa-1 alpha,25-dihydroxyvitamin D3, inhibited angiogenesis in a dose-dependent manner, the inhibition occurring in the picomolar range. In contrast, vitamin D3 was not effective. The results suggest that these two vitamin D3 analogues might be promising anti-angiogenic agents for controlling the angiogenesis which occurs in several pathological conditions, including tumor development.

Animals↗
PubMed1990

Lymphocyte electrophoresis as an indicator of modulation of concanavalin A-induced suppressor T-cells in vivo by anti-cancer drugs.

We have previously reported that concanavalin A (Con A)-induced suppressor T-cells in vivo are located in the lower electrophoretic mobility (EPM) zone as judged by the ratio of low mobility T-cells to high mobility T-cells (LMT/HMT ratio) in terms of lymphocyte electrophoresis, and that the administration of 5-fluorouracil (5-FU) eliminates their suppressor activity as assayed by Con A-induced lymphocyte blastogenesis in vitro. The current study was undertaken to clarify the relation between changes in EPM and suppressor activity of Con A-induced suppressor T-cells by the administration of antitumor drugs such as cyclophosphamide (CY) and 5-FU when assayed by production of anti-sheep red blood cell antibody in vitro. The pretreatment with 5-FU, but not CY, abrogated the suppressor activity of Con A-induced T-cells followed by restoration of the LMT/HMT ratio of Con A-induced T-cells to that of normal T-cells. These finding suggest that lymphocyte electrophoresis can be applied to an assay for screening immunomodulating agents in Con A-induced suppressor T-cells.

Animals↗
PubMed1990

Immunological properties of type IV collagen from mouse kidney.

Some immunological properties of mouse kidney type IV collagen (MKIVC) were investigated. In enzyme-linked immunosorbent assay (ELISA), rabbit anti-MKIVC antiserum reacted strongly with MKIVC but not at all with type I collagen or laminin of mouse origin. Thus, the purified MKIVC preparation was not contaminated with detectable amounts of other constituents of the extracellular matrix and the basement membrane including interstitial collagens, as suggested previously (T. Oikawa et al., Chem. Pharm. Bull., 34, 789 (1986)). In ELISA inhibition assay, human kidney type IV collagen (HKIVC) only partially inhibited the binding of MKIVC to anti-MKIVC antiserum. Similarly, HKIVC showed a far weaker binding capacity to the antiserum compared to MKIVC in ELISA direct binding assay. After the anti-MKIVC antiserum was absorbed with acetone powder of human kidney, the resulting antiserum still possessed a considerable binding activity to MKIVC but did not react with HKIVC. In accord with these findings, anti-MKIVC antiserum immunostained both mouse and human renal basement membranes, while it stained the former but not the latter after being absorbed with human kidney. Taken together, these results suggest that MKIVC possesses at least two antigenic determinants; one but not the other cross-reacts with human kidney basement membrane collagen.

Animals↗
PubMed1990

Inhibition of angiogenesis by bleomycin and its copper complex.

The effects of bleomycin (BLM) and its copper complex on embryonic angiogenesis were studied in the chorioallantoic membranes of 4.5-day-old chick embryos. Copper-free BLM inhibited embryonic angiogenesis in a dose-dependent manner, with activity detectable at 1 ng/egg and maximal at 1000 ng/egg. Also, treatment with copper-BLM complex dose-dependently caused inhibition of embryonic angiogenesis in a lower dose range. Since tumor growth is believed to depend on angiogenesis, the present results may indicate that the antiangiogenic activity of BLM is, at least in part, implicated in the antitumor activity of the drug.

Animals↗
PubMed1990

[Diagnosis of cancer using lymphocyte electrophoresis (3): Electrophoretic mobility, interleukin 1 and prostaglandin E2 productions of monocytes in peripheral blood of cancer patients].

The S/F ratio of slow electrophoretic mobility cells (less than 0.95 micron/sec/V/cm) to fast mobility cells (greater than or equal to 0.95) increased significantly in the peripheral blood mononuclear cells of cancer patients. Since one of slow mobility cells was mainly composed of monocytes, the relationship between the mobility and the functions of monocytes in the peripheral blood of patients with cancer was examined. The cancer patients (total 27) consisted of 12 patients with rectum, 7 with colon, 3 with stomach, one with ovary and 4 with recurrent cancers and of 3 with stage 1, 11 with stage 2, 3 with stage 3 and 6 with stage 4 + 5. We determined the releases of interleukin 1 (IL-1) and prostaglandin E2 (PGE2) from monocytes, which were stimulated with lipopolysaccharide, as an index for the function of monocytes. The mobility of monocytes and productions of IL-1 and PGE2 from monocytes decreased with the stage of cancer patients, indicating a decreased function of monocytes in the patients. These findings suggest that S/F ratio of the peripheral blood mononuclear cells and mobility, IL-1 and PGE2 productions of monocytes are a good index for the judgement of treatment efficacy of cancer.

Colorectal Neoplasms↗
PubMed1989

A highly potent antiangiogenic activity of retinoids.

Four retinoids, i.e. retinol (vitamin A), retinoic acid, retinyl acetate and synthetic chalcone carboxylic acid (Ch 55), were examined for their effects on embryonic angiogenesis using 4.5-day chorioallantoic membranes of chick embryo. The effects of these retinoids were compared with that of antibiotic herbimycin A, which was the most powerful inhibitor of the angiogenesis reported previously. The four retinoids strongly inhibited embryonic angiogenesis; the order of inhibitory activity was Ch 55 greater than retinoic acid greater than herbimycin A greater than retinyl acetate based on the dose required for the half-maximal inhibitory effect. The present results suggest that retinoids are effective inhibitors of angiogenesis, and can be applied for the management of certain diseases accompanied by aberrant angiogenesis, particularly that which occurs during progressive growth of solid tumors.

Animals↗
PubMed1989

Medroxyprogesterone acetate, an anti-cancer and anti-angiogenic steroid, inhibits the plasminogen activator in bovine endothelial cells.

Medroxyprogesterone acetate (MPA) is an anti-cancer drug for mammary carcinomas and an angiostatic steroid. The effects of MPA on the growth and plasminogen activator (PA) activity of bovine endothelial cells were investigated to elucidate the inhibitory mechanism observed in angiogenesis. MPA did not suppress the growth of capillary endothelial cells, even at high concentrations. On the other hand, in bovine endothelial cells of 3 types (adrenal cortical capillary, aortic and pulmonary artery endothelial cells), MPA inhibited extracellular and cell-associated activity of PA, which might be a protease involved in the neovascular response. MPA also greatly inhibited the high level of PA induced by basic fibroblast growth factor (FGF). The same result was obtained when PA production was induced by 4 beta-phorbol-12-myristate-13-acetate (PMA) in endothelial cells. These findings suggest that one of the points of inhibitory action of MPA in the process of angiogenesis may be the suppression of PA activity, and that inhibition of this protease might be useful for reduction of tumorigenic or excessive angiogenesis in vivo.

Animals↗
PubMed1989

Analysis of electrophoretic mobility histograms of mouse splenocytes and thymocytes during tumor growth and after combined chemotherapy and immunotherapy.

Changes in electrophoretic mobility histograms of splenocytes and thymocytes were studied in plasmacytoma X5563-bearing mice as an indicator of response to treatment with mitomycin C (MMC) alone or combined with the immunomodulator Krestin (PSK). Tumor growth was inhibited by 80-90% in the MMC-treated and was further inhibited in the MMC and PSK-treated group. Electrophoretic mobility histograms of splenocytes were used to determine the fraction of cells having intermediate mobility between high mobility (T cells) and low mobility (B cells). This fraction of intermediate-mobility cells increased in tumor-bearing mice, but a normal electrophoretic mobility pattern was obtained following successful antitumor treatment. In the electrophoretic mobility histogram of thymocytes, on the other hand, the low-mobility cells (cortical thymocytes) decreased in number during tumor growth and were further reduced in the MMC-treated group. This reduction was less in the MMC and PSK-treated group. These results suggest that combined therapy with MMC and PSK prevents damage of the host defence mechanism and allows more efficient antitumor treatment. Analysis of electrophoretic mobility histograms of splenocytes and thymocytes using a fully automated cell electrophoretic instrument makes possible the rapid evaluation of the immunological effects of drug therapy of tumor-bearing mice.

Animals↗