Stimulation of Non-specific Resistance to Tumors in the Mouse Using a Poly(maleic-acid-styrene)-conjugated Neocarzinostatin

Overview

Journal Cancer Immunol Immunother

Specialties Allergy & Immunology
Oncology
Pharmacology

Date 1989 Jan 1

PMID 2480846

Citations 1

Authors

F Suzuki

R B Pollard

H Maeda

Affiliations

Soon will be listed here.

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 male 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-gamma 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-alpha/beta antiserum. Treatment of mice with SMANCS and anti-IFN-gamma 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-gamma and 41% IFN-alpha/beta. Half of the interferon produced in SMANCS-stimulated mice could be eliminated by treatment with anti-IFN-gamma, and treatment of SMANCS-stimulated mice with both anti-IFN-gamma and anti-IFN-alpha/beta antisera resulted in a total absence of detectable interferon. These findings suggest that while the administration of SMANCS induces both IFN-gamma and IFN-alpha/beta production, in this case, it is only the former which mediates the non-specific resistance to tumors.

Citing Articles

The antiviral effect of keishi-ni-eppi-ichi-to, a traditional Chinese herbal medicine, on influenza A2(H2N2) virus infection in mice.

Ball M, Utsunomiya T, Ikemoto K, Kobayashi M, Pollard R, Suzuki F Experientia. 1994; 50(8):774-9.

PMID: 7520870 DOI: 10.1007/BF01919381.

References

Oda T, Morinaga T, Maeda H . Stimulation of macrophage by polyanions and its conjugated proteins and effect on cell membrane. Proc Soc Exp Biol Med. 1986; 181(1):9-17. DOI: 10.3181/00379727-181-42218. View

Maeda H, Takeshita J, Kanamaru R . A lipophilic derivative of neocarzinostatin. A polymer conjugation of an antitumor protein antibiotic. Int J Pept Protein Res. 1979; 14(2):81-7. DOI: 10.1111/j.1399-3011.1979.tb01730.x. View

Crane Jr J, Glasgow L, Kern E, Youngner J . Inhibition of murine osteogenic sarcomas by treatment with type I or type II interferon. J Natl Cancer Inst. 1978; 61(3):871-4. View

Suzuki F, Pollard R . Alterations of interferon production in a mouse model of thermal injury. J Immunol. 1982; 129(5):1806-10. View

Iwai K, Maeda H, Konno T . Use of oily contrast medium for selective drug targeting to tumor: enhanced therapeutic effect and X-ray image. Cancer Res. 1984; 44(5):2115-21. View

Maeda H . Neocarzinostatin in cancer chemotherapy (review). Anticancer Res. 1981; 1(3):175-86. View

Napier M, Holmquist B, Strydom D, Goldberg I . Neocarzinostatin: spectral characterization and separation of a non-protein chromophore. Biochem Biophys Res Commun. 1979; 89(2):635-42. DOI: 10.1016/0006-291x(79)90677-6. View

Merigan T, De Clercq E, Bausek G . Nonviral interferon inducers. J Gen Physiol. 2009; 56(1):57-75. PMC: 2225883. DOI: 10.1085/jgp.56.1.57. View

Suzuki F, Brutkiewicz R, Pollard R . Importance of T-cells and macrophages in the antitumor activity of carboxyethylgermanium sesquioxide (Ge-132). Anticancer Res. 1985; 5(5):479-83. View

10.

De Clercq E, Merigan T . Induction of interferon by nonviral agents. Arch Intern Med. 1970; 126(1):94-108. DOI: 10.1001/archinte.126.1.94. View

11.

Suzuki F, Brutkiewicz R, Pollard R . Ability of sera from mice treated with Ge-132, an organic germanium compound, to inhibit experimental murine ascites tumours. Br J Cancer. 1985; 52(5):757-63. PMC: 1977232. DOI: 10.1038/bjc.1985.254. View

12.

Merigan T . Induction of circulating interferon by synthetic anionic polymers of known composition. Nature. 1967; 214(5086):416-7. DOI: 10.1038/214416a0. View

13.

Suzuki F, Brutkiewicz R, Pollard R . Lack of correlation between antitumour response and serum interferon levels in mice treated with SSM, an immunotherapeutic anticancer agent. Br J Cancer. 1986; 53(4):567-70. PMC: 2001438. DOI: 10.1038/bjc.1986.89. View

14.

Konno T, Maeda H, Iwai K, Maki S, Tashiro S, Uchida M . Selective targeting of anti-cancer drug and simultaneous image enhancement in solid tumors by arterially administered lipid contrast medium. Cancer. 1984; 54(11):2367-74. DOI: 10.1002/1097-0142(19841201)54:11<2367::aid-cncr2820541111>3.0.co;2-f. View

15.

Suzuki F, Munakata T, Maeda H . Interferon induction by SMANCS: a polymer-conjugated derivative of neocarzinostatin. Anticancer Res. 1988; 8(1):97-103. View

16.

DE SOMER P, De Clercq E, Billiau A, Schonne E, CLAESEN M . Antiviral activity of polyacrylic and polymethacrylic acids. II. Mode of action in vivo. J Virol. 1968; 2(9):886-93. PMC: 375708. DOI: 10.1128/JVI.2.9.886-893.1968. View

17.

Aso H, Suzuki F, Yamaguchi T, Hayashi Y, Ebina T, Ishida N . Induction of interferon and activation of NK cells and macrophages in mice by oral administration of Ge-132, an organic germanium compound. Microbiol Immunol. 1985; 29(1):65-74. DOI: 10.1111/j.1348-0421.1985.tb00803.x. View

18.

Takeshita J, Maeda H, Kanamaru R . In vitro mode of action, pharmacokinetics, and organ specificity of poly (maleic acid-styrene)-conjugated neocarzinostatin, SMANCS. Gan. 1982; 73(2):278-84. View

19.

Konno T, Maeda H, Iwai K, Tashiro S, Maki S, Morinaga T . Effect of arterial administration of high-molecular-weight anticancer agent SMANCS with lipid lymphographic agent on hepatoma: a preliminary report. Eur J Cancer Clin Oncol. 1983; 19(8):1053-65. DOI: 10.1016/0277-5379(83)90028-7. View

20.

Osborne L, Georgiades J, Johnson H . Large-scale production and partial purification of mouse immune interferon. Infect Immun. 1979; 23(1):80-6. PMC: 550692. DOI: 10.1128/iai.23.1.80-86.1979. View