Stimulation of non-specific resistance to tumors in the mouse using a poly(maleic-acid-styrene)-conjugated neocarzinostatin

Fujio Suzuki, Richard B. Pollard, Hiroshi Maeda

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

The development of non-specific resistance to tumors following stimulation with poly(maleic-acid-styrene)-conjugated neocarzinostatin (SMANCS), a polymer-conjugated derivative of neocarzinostatin, was investigated in mice. The growth of syngeneic solid tumors (Meth-A fibrosarcoma and RL ♂ 1 leukemia) inoculated into BALB/c mice was suppressed after one treatment with SMANCS at doses ranging from 0.14 mg/kg to 3.4 mg/kg i.v. 24 h before tumor implantation. Since previously observations concerning SMANCS have shown that it disappeared within 1.5 h after i.v. administration in mice and that it was inactivated quickly in plasma, SMANCS evidently inhibited tumor growth by mediating non-specific resistance. In addition, the non-specific resistance to tumors stimulated by SMANCS could be passively transferred to untreated mice by serum which was shown to contain interferon (IFN) from 12 h to 20 h after SMANCS administration. However, the resistance was not produced by serum prepared from mice at 8 h or 32 h after administration presumably because of the observation that the interferon activity was only demonstrated from 12 h to 28 h after SMANCS stimulation. When the serum specimens were treated with anti-IFN-γ antiserum, the antitumor activity of the sera was abrogated. However, no significant change was detected in the antitumor activity of the specimens following treatment with anti-IFN-α/β antiserum. Treatment of mice with SMANCS and anti-IFN-γ antiserum together resulted in the elimination of the non-specific resistance to tumors. The IFN induced in the sera of mice by SMANCS was shown to be 57% IFN-γ and 41% IFN-α/β. Half of the interferon produced in SMANCS-stimulated mice could be eliminated by treatment with anti-IFN-γ, and treatment of SMANCS-stimulated mice with both anti-IFN-γ and anti-IFN-α/β antisera resulted in a total absence of detectable interferon. These findings suggest that while the administration of SMANCS induces both IFN-γ and IFN-α/β production, in this case, it is only the former which mediates the non-specific resistance to tumors.

Original languageEnglish (US)
Pages (from-to)97-104
Number of pages8
JournalCancer Immunology Immunotherapy
Volume30
Issue number2
DOIs
StatePublished - Mar 1989

Fingerprint

Interferons
Neoplasms
Immune Sera
Serum
poly(maleic acid-styrene)neocarzinostatin
Zinostatin
Fibrosarcoma
Growth
Polymers
Leukemia

ASJC Scopus subject areas

  • Oncology
  • Immunology
  • Cancer Research

Cite this

Stimulation of non-specific resistance to tumors in the mouse using a poly(maleic-acid-styrene)-conjugated neocarzinostatin. / Suzuki, Fujio; Pollard, Richard B.; Maeda, Hiroshi.

In: Cancer Immunology Immunotherapy, Vol. 30, No. 2, 03.1989, p. 97-104.

Research output: Contribution to journalArticle

@article{708392c01f4447909dd78f3bd2dea4dd,
title = "Stimulation of non-specific resistance to tumors in the mouse using a poly(maleic-acid-styrene)-conjugated neocarzinostatin",
abstract = "The development of non-specific resistance to tumors following stimulation with poly(maleic-acid-styrene)-conjugated neocarzinostatin (SMANCS), a polymer-conjugated derivative of neocarzinostatin, was investigated in mice. The growth of syngeneic solid tumors (Meth-A fibrosarcoma and RL ♂ 1 leukemia) inoculated into BALB/c mice was suppressed after one treatment with SMANCS at doses ranging from 0.14 mg/kg to 3.4 mg/kg i.v. 24 h before tumor implantation. Since previously observations concerning SMANCS have shown that it disappeared within 1.5 h after i.v. administration in mice and that it was inactivated quickly in plasma, SMANCS evidently inhibited tumor growth by mediating non-specific resistance. In addition, the non-specific resistance to tumors stimulated by SMANCS could be passively transferred to untreated mice by serum which was shown to contain interferon (IFN) from 12 h to 20 h after SMANCS administration. However, the resistance was not produced by serum prepared from mice at 8 h or 32 h after administration presumably because of the observation that the interferon activity was only demonstrated from 12 h to 28 h after SMANCS stimulation. When the serum specimens were treated with anti-IFN-γ antiserum, the antitumor activity of the sera was abrogated. However, no significant change was detected in the antitumor activity of the specimens following treatment with anti-IFN-α/β antiserum. Treatment of mice with SMANCS and anti-IFN-γ antiserum together resulted in the elimination of the non-specific resistance to tumors. The IFN induced in the sera of mice by SMANCS was shown to be 57{\%} IFN-γ and 41{\%} IFN-α/β. Half of the interferon produced in SMANCS-stimulated mice could be eliminated by treatment with anti-IFN-γ, and treatment of SMANCS-stimulated mice with both anti-IFN-γ and anti-IFN-α/β antisera resulted in a total absence of detectable interferon. These findings suggest that while the administration of SMANCS induces both IFN-γ and IFN-α/β production, in this case, it is only the former which mediates the non-specific resistance to tumors.",
author = "Fujio Suzuki and Pollard, {Richard B.} and Hiroshi Maeda",
year = "1989",
month = "3",
doi = "10.1007/BF01665960",
language = "English (US)",
volume = "30",
pages = "97--104",
journal = "Cancer Immunology and Immunotherapy",
issn = "0340-7004",
publisher = "Springer Science and Business Media Deutschland GmbH",
number = "2",

}

TY - JOUR

T1 - Stimulation of non-specific resistance to tumors in the mouse using a poly(maleic-acid-styrene)-conjugated neocarzinostatin

AU - Suzuki, Fujio

AU - Pollard, Richard B.

AU - Maeda, Hiroshi

PY - 1989/3

Y1 - 1989/3

N2 - The development of non-specific resistance to tumors following stimulation with poly(maleic-acid-styrene)-conjugated neocarzinostatin (SMANCS), a polymer-conjugated derivative of neocarzinostatin, was investigated in mice. The growth of syngeneic solid tumors (Meth-A fibrosarcoma and RL ♂ 1 leukemia) inoculated into BALB/c mice was suppressed after one treatment with SMANCS at doses ranging from 0.14 mg/kg to 3.4 mg/kg i.v. 24 h before tumor implantation. Since previously observations concerning SMANCS have shown that it disappeared within 1.5 h after i.v. administration in mice and that it was inactivated quickly in plasma, SMANCS evidently inhibited tumor growth by mediating non-specific resistance. In addition, the non-specific resistance to tumors stimulated by SMANCS could be passively transferred to untreated mice by serum which was shown to contain interferon (IFN) from 12 h to 20 h after SMANCS administration. However, the resistance was not produced by serum prepared from mice at 8 h or 32 h after administration presumably because of the observation that the interferon activity was only demonstrated from 12 h to 28 h after SMANCS stimulation. When the serum specimens were treated with anti-IFN-γ antiserum, the antitumor activity of the sera was abrogated. However, no significant change was detected in the antitumor activity of the specimens following treatment with anti-IFN-α/β antiserum. Treatment of mice with SMANCS and anti-IFN-γ antiserum together resulted in the elimination of the non-specific resistance to tumors. The IFN induced in the sera of mice by SMANCS was shown to be 57% IFN-γ and 41% IFN-α/β. Half of the interferon produced in SMANCS-stimulated mice could be eliminated by treatment with anti-IFN-γ, and treatment of SMANCS-stimulated mice with both anti-IFN-γ and anti-IFN-α/β antisera resulted in a total absence of detectable interferon. These findings suggest that while the administration of SMANCS induces both IFN-γ and IFN-α/β production, in this case, it is only the former which mediates the non-specific resistance to tumors.

AB - The development of non-specific resistance to tumors following stimulation with poly(maleic-acid-styrene)-conjugated neocarzinostatin (SMANCS), a polymer-conjugated derivative of neocarzinostatin, was investigated in mice. The growth of syngeneic solid tumors (Meth-A fibrosarcoma and RL ♂ 1 leukemia) inoculated into BALB/c mice was suppressed after one treatment with SMANCS at doses ranging from 0.14 mg/kg to 3.4 mg/kg i.v. 24 h before tumor implantation. Since previously observations concerning SMANCS have shown that it disappeared within 1.5 h after i.v. administration in mice and that it was inactivated quickly in plasma, SMANCS evidently inhibited tumor growth by mediating non-specific resistance. In addition, the non-specific resistance to tumors stimulated by SMANCS could be passively transferred to untreated mice by serum which was shown to contain interferon (IFN) from 12 h to 20 h after SMANCS administration. However, the resistance was not produced by serum prepared from mice at 8 h or 32 h after administration presumably because of the observation that the interferon activity was only demonstrated from 12 h to 28 h after SMANCS stimulation. When the serum specimens were treated with anti-IFN-γ antiserum, the antitumor activity of the sera was abrogated. However, no significant change was detected in the antitumor activity of the specimens following treatment with anti-IFN-α/β antiserum. Treatment of mice with SMANCS and anti-IFN-γ antiserum together resulted in the elimination of the non-specific resistance to tumors. The IFN induced in the sera of mice by SMANCS was shown to be 57% IFN-γ and 41% IFN-α/β. Half of the interferon produced in SMANCS-stimulated mice could be eliminated by treatment with anti-IFN-γ, and treatment of SMANCS-stimulated mice with both anti-IFN-γ and anti-IFN-α/β antisera resulted in a total absence of detectable interferon. These findings suggest that while the administration of SMANCS induces both IFN-γ and IFN-α/β production, in this case, it is only the former which mediates the non-specific resistance to tumors.

UR - http://www.scopus.com/inward/record.url?scp=0024393389&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0024393389&partnerID=8YFLogxK

U2 - 10.1007/BF01665960

DO - 10.1007/BF01665960

M3 - Article

C2 - 2480846

AN - SCOPUS:0024393389

VL - 30

SP - 97

EP - 104

JO - Cancer Immunology and Immunotherapy

JF - Cancer Immunology and Immunotherapy

SN - 0340-7004

IS - 2

ER -