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Fluosol-DA/carbogen with lonidamine or pentoxifylline as modulators of alkylating agents in the FSaIIC fibrosarcoma

  • Original Articles
  • Fluosol-DA/Carbogen, Lonidamine, Pentoxifylline, FSallC Fibrosarcoma
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Summary

In an effort to increase the efficacy of several antineoplastic alkylating agents (CDDP,l-PAM, CTX, or BCNU), we examined the effect of the modulator Fluosol-DA/carbogen in combination with a second modulator, either lonidamine or pentoxifylline, on the survival of FSaIIC tumor cells and of bone marrow CFU-GM from tumor-bearing C3H mice. Fluosol-DA/carbogen increased the tumor-cell killing activity of each alkylating agent by about 10 times. In contrast, lonidamine alone did not significantly increase the cytocidal activity of any of the alkylating agents tested. However, in combination with Fluosol-DA/carbogen, the use of lonidamine produced about a 100-fold increase in the tumor cell kill achieved with CDDP as compared with CDDP alone. No increase in tumor cell kill over that produced with the single modulator Fluosol-DA/carbogen was seen following the addition of lonidamine to the combination treatment withl-PAM, CTX, or BCNU. Unfortunately, although neither lonidamine nor Fluosol-DA/carbogen alone significantly increased alkylator toxicity to bone marrow CFU-GM, the combination of modulators increased the toxicity of each alkylating agent to bone marrow by about 10 times. Pentoxifylline caused an increase in alkylator activity against the FSaIIC fibrosarcoma only when used with BCNU; this effect was further augmented by the addition of Fluosol-DA/carbogen. The combination of modulators pentoxifylline plus Fluosol-DA/carbogen was more effective than Fluosol-DA/carbogen alone only when the former was used with BCNU, whereas only minimal increases in tumor-cell killing activity were obtained with this modulator combination and CDDP,l-PAM, or CTX. Pentoxifylline increased the bone marrow CFU-GM toxicity ofl-PAM by about 10 times. The bone marrow CFU-GM toxicity was further increased by Fluosol-DA/carbogen, as was the toxicity of each of the other alkylating agents. Lonidamine plus Fluosol-DA/carbogen may be useful in increasing the therapeutic efficacy of CDDP, and the combination of pentoxifylline plus Fluosol-DA/carbogen might improve the antitumor activity of BCNU.

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Abbreviations

CDDP:

cis-diamminedichloroplatinum(II)

l-PAM:

l-phenylalanine mustard, melphalan

thioTEPA:

N,N′,N″-triethylenethio-phosphoramide

CTX:

cyclophosphamide

BCNU:

N,N′-bis(2-chloroethyl)-N-nitrosourea

CFU-GM:

granulocyte-macrophage colony-forming unit

αMEM:

alpha minimal essential medium

PBS:

phosphatebuffered saline

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Authors and Affiliations

  1. Dana-Farber Cancer Institute, 44 Binney Street, 02 155, Boston, MA, USA

    Beverly A. Teicher, Terence S. Herman, Juichi Tanaka, Bruce Dezube, Arthur Pardee & Emil Frei III

  2. Joint Center for Radiation Therapy, 44 Binney Street, 02 115, Boston, MA, USA

    Beverly A. Teicher & Terence S. Herman

Authors
  1. Beverly A. Teicher
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  2. Terence S. Herman
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  3. Juichi Tanaka
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  4. Bruce Dezube
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  5. Arthur Pardee
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  6. Emil Frei III
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Additional information

This work was supported by National Cancer Institute grant IPO1-CA38493, by a grant from DeSanctis Consultants, Montreal, Canada, and by a grant from the Mathers Foundation

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Teicher, B.A., Herman, T.S., Tanaka, J. et al. Fluosol-DA/carbogen with lonidamine or pentoxifylline as modulators of alkylating agents in the FSaIIC fibrosarcoma. Cancer Chemother. Pharmacol. 28, 45–50 (1991). https://doi.org/10.1007/BF00684955

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  • DOI: https://doi.org/10.1007/BF00684955

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