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Biomedical subjects

F Suzuki

Publications and source records attributed to F Suzuki.

732 records · Page 41Linked to original sources
PubMedDate not supplied

Release of a mitogenic factor by splenic Lyt 1+ T-cells from mice treated with SSM, an immunomodulator extracted from human type tubercle bacilli.

A production of the soluble factor activity in culture fluids of murine splenic mononuclear cells (SMNC) treated with SSM, an immunopotentiator extracted from Mycobacterium tuberculosis strain Aoyama B, was investigated. The soluble factor activity was determined as a mitogenic activity released from SMNC of mice previously treated with a 500 micrograms/kg dose of SSM (primed SMNC). The mitogenic activity was produced when primed SMNC were challenged in vitro with SSM at a concentration of 5 micrograms/ml. The activity was not produced in culture fluids of primed SMNC treated with anti-Thy 1.2 or anti-Lyt 1.2 monoclonal antibody plus complement followed by a challenge with SSM. However, the production of the activity was not affected by pretreatment of primed SMNC with anti-Lyt 2.2 monoclonal antibody plus complement. Since the non-specific resistance to tumors of mice stimulated with SSM was not demonstrated in mice depleted of Thy 1+ and Lyt 1+ T-cells, and Lyt 1+ T-cells from SSM-treated mice did not show any direct cytotoxic activities against tumor cells in vitro, the soluble factor released from Lyt 1+ T-cells by SSM stimulation may play an important role in developing the non-specific resistance of mice treated with SSM.

Adjuvants, Immunologic↗
PubMedDate not supplied

Interferon induction by SMANCS: a polymer-conjugated derivative of neocarzinostatin.

Poly (styrene-co-maleic acid)-conjugated neocarzinostatin, SMANCS, induced antiviral activities in the circulation of mice. The maximum titer of the activity (240 U/ml) was observed 20 h after administration an 8 mg/kg iv dose of SMANCS. Various experiments showed that this antiviral substance induced by SMANCS was an interferon (IFN). Sixty percent of the IFN response stimulated by SMANCS was impaired in mice pretreated with anti-IFN gamma antiserum. This suggests that the serum IFN induced by the agent contained about 60% of IFN gamma. When Thy 1+ or Lyt 2+ T-cells were depleted from mice by administration of anti-Thy 1.2 or anti-Lyt 2.2 monoclonal antibody (mAb), this IFN response was eliminated. However, when natural killer cells were depleted from mice by treatment with antiasialo GM1 antiserum, no alteration in the IFN response was observed. The SMANCS-stimulated IFN response was also abrogated in mice treated with macrophage blockers (carrageenan and trypan blue), whereas administration of anti-Lyt 1.2 mAb had no effect on the IFN response. These results suggest that macrophage and T-cells w Lyt 1-2+ phenotype may have an important role in the IFN response stimulated by SMANCS.

Animals↗
PubMedDate not supplied

Biological activities and antitumor mechanism of an immunopotentiating organogermanium compound, Ge-132 (review).

The biological activities and antitumor mechanism of an immunopotentiator, Ge-132, is reviewed herein. Ge-132 exhibited antitumor activity against certain syngeneic and allogeneic experimental tumors. It was shown that T-cells and macrophages were involved when tumor-bearing mice were protected by the compound. This protective effect could be transferred to tumor-bearing mice, not treated with the compound, by a macrophage fraction and serum specimens obtained from Ge-132-treated mice. Interferon gamma (IFN gamma) was detected in the circulation of Ge-132-treated mice and when sera obtained from Ge-132-treated mice were treated with anti-IFN gamma antiserum in vitro, the antitumor activity was abolished. On the other hand, in mice treated with anti-IFN gamma antiserum, Ge-132 did not induce serum IFN and failed to protect against death due to ascites tumor progression. The in vivo administration of monoclonal anti-Thy 1.2 antibody prevented the expression of the antitumor activity of Ge-132. However, serum specimens obtained from Ge-132-treated mice effectively inhibited the tumor growth of T-cell-depleted mice bearing ascites tumors. Since it has been reported that T-lymphocytes produce IFN gamma, this suggested that Ge-132 may first stimulate T-cells to produce IFN gamma in the expression of the observed antitumor efficacy. In addition, sera obtained from Ge-132-treated mice did not show any antitumor activity in mice depleted of macrophage functions. Additionally, passive transfer of macrophages from mice treated with these serum specimens to tumor-bearing mice also resulted in the inhibition of tumor growth. Pretreatment of these serum specimens with anti-IFN gamma antiserum effectively prevented the generation of cytotoxic macrophages. Also, tumor-bearing mice treated exogenously with this antiserum did not differ significantly in survival as compared to controls, despite the administration of Ge-132. Furthermore, the antitumor activity of Ge-132 was detected in NK cell-depleted mice. Therefore, the antitumor mechanism of Ge-132 in the murine ascites tumor system may be expressed as follows: (a) Ge-132 stimulates T-cells to induce IFN gamma when mice are treated orally with the compound, (b) IFN gamma activates macrophages to become cytotoxic, and (c) the cytotoxic macrophages eliminate tumor cells.

Adjuvants, Immunologic↗
PubMedDate not supplied

Cooperation of lymphokine(s) and macrophages in expression of antitumor activity of carboxyethylgermanium sesquioxide (Ge-132).

The administration of IFN containing sera (Ge-sera) obtained from Ge-132-treated mice (Ge-mice) or the passive transfer of macrophages (M phi) to mice bearing ascites tumors resulted in the inhibition of tumor growth. The cooperative role of Ge-sera and Ge-M phi in the display of Ge-132-antitumor activity was studied. When mice were pretreated with antimouse IFN gamma antiserum, no IFN-inducing and antitumor activities of the compound were detected. Cytotoxic activities were detected on peritoneal M phi of mice treated with Ge-sera, and passive transfer of these M phi to tumor-bearing mice resulted in the inhibition of tumor growth. When tumor-bearing mice were pretreated with substances toxic to M phi, there was no antitumor activity of Ge-sera observed. However, there was antitumor activity of Ge-sera in mice depleted of T-cells, even though the antitumor effects of the compound itself were not demonstrable in T-cell depleted mice. Therefore, a part of the antitumor activity of Ge-132 may appear to be expressed as follows: (1) Ge-132 stimulated T-cells to produce circulating lymphokine(s) which were inactivated by anti-IFN gamma treatment; (2) activated M phi were generated from resting M phi by such lymphokine(s); (3) the transplanted tumors were inhibited by these M phi.

Animals↗
PubMedDate not supplied

Importance of T-cells and macrophages in the antitumor activity of carboxyethylgermanium sesquioxide (Ge-132).

The purpose of this study was to investigate the effective mechanisms of Ge-132, an organogermanium compound with immunomodulatory activity, on experimental murine ascites tumors. The antitumor effects of Ge-132 were observed when mice inoculated with Ehrlich carcinoma (allogeneic) or RL male 1 leukemia (syngeneic) cells were treated orally. However, Ge-132 had no activity on EL-4 lymphoma (syngeneic) or Meth A fibrosarcoma (syngeneic). The antitumor activity of Ge-132 was not observed when tumor-bearing mice were treated with trypan blue, carrageenan, or monoclonal anti-Thy 1.2 antibody. However, when natural killer (NK) cells were eliminated from mice bearing RL male 1 or Ehrlich ascites tumors by treatment with anti-asialo GM1 antiserum, the antitumor activity of the compound was unchanged. This suggests that Ge-132 was effective against certain ascites tumors regardless of whether the tumor was syngeneic or allogeneic. Furthermore, its effect might be expressed through host defense mechanisms, including macrophages and/or T-cells.

Animals↗
PubMedDate not supplied

Antitumor mechanisms of Z-100, an immunomodulatory arabinomannan extracted from Mycobacterium tuberculosis: the importance of lymphocytes infiltrated into tumor sites.

The mechanisms of increased host resistance to tumors following treatment with Z-100, an arabinomannan extracted from Mycobacterium tuberculosis, were investigated in mice bearing syngeneic solid tumors. When BALB/c mice bearing Meth-A solid tumors were treated intralesionally (i.l.) with a 10 mg/kg dose of Z-100, 74% of tumor growth was inhibited in the test group as compared with control mice treated with saline. However, no significant tumor inhibitory activity was observed when these mice were treated with various doses of Z-100 i.p. or i.v. In addition, tumor growth in X-irradiated mice (450 R, whole-body irradiation) and in mice treated with antilymphocyte serum was not suppressed even though Z-100 was administered into the tumor. The number of lymphocytes isolated from Z-100-treated tumor tissues increased 3.2-fold (14 days after the tumor inoculation), whereas no change in the number of tumor-infiltrating lymphocytes was demonstrated in mice treated with Z-100 i.p. or i.v. as compared to controls. When BALB/c mice were inoculated s.c. with a mixture of Meth-A tumor cells (1 x 10(6) cells) and lymphocytes (2 x 10(5) cells) derived from Z-100-treated tumor tissues in a Winn's neutralization test, decreased growth of solid tumors was demonstrated as compared with that of control mice inoculated with tumor cells alone. However, no such inhibition of tumor growth was observed in mice inoculated with a mixture of the tumor cells and lymphocytes obtained from tumor tissues of control mice at the same effector to target cell ratio.(ABSTRACT TRUNCATED AT 250 WORDS)

Adjuvants, Immunologic↗
PubMedDate not supplied

Prolongation of concomitant antitumor immunity in mice treated with Z-100, an arabinomannan extracted from Mycobacterium tuberculosis.

The effect of Z-100, a natural immunomodulator extracted from Mycobacterium tuberculosis strain Aoyama B, on concomitant antitumor immunity (CAI) was investigated in mice immunized with Meth-A tumor cells (primary inoculation) in combination with Corynebacterium parvum. CAI, which was observed in mice 10 days after immunization (I10 mice), disappeared in mice 20 days after immunization (I20 mice). However, no growth of secondary inoculated Meth-A tumors was demonstrated in I20 mice treated with Z-100 (IZ20 mice). CAI was demonstrated in tumor-bearing recipients when splenic mononuclear cells (SMNC) from I10 mice or IZ20 mice were transferred to recipients intralesionally. However, CAI was not detected when recipients received SMNC from I20 mice or a SMNC mixture from I10 and I20 mice. The SMNC mixture from I10 and IZ20 mice inhibited the growth of Meth-A solid tumors in the recipients. The activity of non-specific suppressor cells, which were characterized as CD8+ T cells, was demonstrated in SMNC from I20 mice, while SMNC from I10 and IZ20 mice did not show any suppressor cell activities. In addition, clear inhibition of tumor growth was demonstrated in recipient mice which received a SMNC mixture from I20 mice, previously treated with anti-Lyt-2+ MAb plus complement, and I10 mice. These results suggest that Z-100 might be able to prolong CAI observed in I10 mice through the inhibition of Lyt-2+ T suppressor cells detected in SMNC from I20 mice.

Adjuvants, Immunologic↗
PubMedDate not supplied

Keishi-ka-kei-to, a traditional Chinese herbal medicine, inhibits pulmonary metastasis of B16 melanoma.

Keishi-ka-kei-to, a traditional Chinese herbal medicine composed of a mixture of crude extracts from five medicinal plants (Cinnamomi cortex, Paeoniae radix, Zizyphi fructus, Zingiberis rhizoma and Glycyrrhizae radix), inhibited experimental pulmonary metastasis in mice implanted with B16F10 melanoma cells. When 136 to 145 metastatic colonies were produced in lungs of mice inoculated with 1 x 10(5) cells/mouse of melanoma cells, less than 15 metastatic colonies were demonstrated when these tumor-inoculated mice were treated orally with 80 to 320 mg/kg doses of Keishi-ka-kei-to. The most active component in the mixture was shown to be 6-gingerol, derived from the Zingiberis rhizoma extract. The antimetastatic activity of 6-gingerol was expressed through the host's antitumor immune functions, as the growth of B16F10 melanoma cells was not affected by this substance in vitro. The splenic CD8+ T cells from mice treated with the compound showed inhibitory activities on pulmonary metastasis when these T cells were adoptively transferred to mice bearing B16F10 melanoma cells. These results may suggest that Keishi-ka-kei-to inhibits pulmonary metastasis in mice bearing B16F10 melanoma cells through the stimulation of CD8+ T cells.

Animals↗
PubMedDate not supplied

Shikonin, an ingredient of Lithospermum erythrorhizon, inhibits angiogenesis in vivo and in vitro.

Angiogenesis is critical for tumor growth and inflammation. Shiunko is a Chinese herbal ointment used for the treatment of burns in Japan. Its main ingredient is the root of Lithospermum erythrorhizon, which had been used for treating tumors and inflammation in China since the 5th century. We report here that shikonin, the main chemical ingredient of L. erythrorhizon is a novel inhibitor of angiogenesis. It inhibited tumor necrosis factor-alpha-induced and B16 melanoma-induced angiogenesis in mice and normal developmental angiogenesis in the yolk-sac membranes of chick embryos. Shikonin also inhibited proliferation and migration of endothelial cells in culture and network formation by endothelial cells on Matrigel in vitro. The dose-responsive study suggests that the mechanism of this inhibitory effect on angiogenesis involves the prevention of network formation by endothelial cells via blocking integrin alpha v beta 3 expression.

Animals↗