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

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Abstract

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 γ (IFNγ) was detected in the circulation of Ge-132-treated mice and when sera obtained from Ge-132-treated mice were treated with anti-IFNγ antiserum in vitro, the antitumor activity was abolished. On the other hand, in mice treated with anti-IFNγ 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 efectively inhibited the tumor growth of T-cell-depleted mice bearing ascites tumors. Since it has been reported that T-lymphocytes produce IFNγ, this suggested that Ge-132 may first stimulate T-cells to produce IFNγ 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-INFγ 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 IFNγ when mice are treated orally with the compound, (b) IFNγ activates macrophages to become cytotoxic, and (c) the cytotoxic macrophages eliminate tumor cells.

Original languageEnglish (US)
Pages (from-to)189-204
Number of pages16
JournalIn Vivo
Volume1
Issue number4
StatePublished - 1987
Externally publishedYes

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Bioactivity
Tumors
Macrophages
Bearings (structural)
Interferons
T-cells
Neoplasms
Immune Sera
Serum
T-Lymphocytes
Ascites
proxigermanium
Immunologic Adjuvants
Growth
Natural Killer Cells
Cells

ASJC Scopus subject areas

  • Medicine(all)

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Biological activities and antitumor mechanism of an immunopotentiating organogermanium compound, Ge-132. (Review). / Brutkiewicz, Randy; Suzuki, F.

In: In Vivo, Vol. 1, No. 4, 1987, p. 189-204.

Research output: Contribution to journalArticle

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abstract = "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 γ (IFNγ) was detected in the circulation of Ge-132-treated mice and when sera obtained from Ge-132-treated mice were treated with anti-IFNγ antiserum in vitro, the antitumor activity was abolished. On the other hand, in mice treated with anti-IFNγ 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 efectively inhibited the tumor growth of T-cell-depleted mice bearing ascites tumors. Since it has been reported that T-lymphocytes produce IFNγ, this suggested that Ge-132 may first stimulate T-cells to produce IFNγ 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-INFγ 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 IFNγ when mice are treated orally with the compound, (b) IFNγ activates macrophages to become cytotoxic, and (c) the cytotoxic macrophages eliminate tumor cells.",
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N2 - 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 γ (IFNγ) was detected in the circulation of Ge-132-treated mice and when sera obtained from Ge-132-treated mice were treated with anti-IFNγ antiserum in vitro, the antitumor activity was abolished. On the other hand, in mice treated with anti-IFNγ 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 efectively inhibited the tumor growth of T-cell-depleted mice bearing ascites tumors. Since it has been reported that T-lymphocytes produce IFNγ, this suggested that Ge-132 may first stimulate T-cells to produce IFNγ 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-INFγ 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 IFNγ when mice are treated orally with the compound, (b) IFNγ activates macrophages to become cytotoxic, and (c) the cytotoxic macrophages eliminate tumor cells.

AB - 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 γ (IFNγ) was detected in the circulation of Ge-132-treated mice and when sera obtained from Ge-132-treated mice were treated with anti-IFNγ antiserum in vitro, the antitumor activity was abolished. On the other hand, in mice treated with anti-IFNγ 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 efectively inhibited the tumor growth of T-cell-depleted mice bearing ascites tumors. Since it has been reported that T-lymphocytes produce IFNγ, this suggested that Ge-132 may first stimulate T-cells to produce IFNγ 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-INFγ 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 IFNγ when mice are treated orally with the compound, (b) IFNγ activates macrophages to become cytotoxic, and (c) the cytotoxic macrophages eliminate tumor cells.

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