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Cancer Biology and Therapeutics pp 3–21Cite as

Biochemical Strategy of Cancer Cells and the Targeting of Chemotherapy with Tiazofurin, Acivicin, and Dipyridamole

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Abstract

It is 25 years since I introduced the ideas of the molecular correlation concept as a theoretical and experimental method for discovering the pattern of biochemical imbalance and its link with neoplastic transformation and progression (1). This approach was tested through application of the concept of key enzymes in a particularly meaningful model system, the rat hepatomas of different growth rates. The testing of the molecular correlation concept proved that the biochemical strategy of the genome in neoplasia can be identified by elucidating the pattern of gene expression as revealed in the activity, amount, and isozymic program of the key enzymes. It was shown that the activities of the key enzymes and metabolic pathways and the concentrations of strategic nucleotides and amino acids are stringently linked with neoplastic transformation and progression. Parameters that are not stringently linked yield no pattern. The conclusion was drawn that what is important about cancer is ordered; what is not, is the random element and the diversity. This field was recently reviewed (2,3).

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References

  1. G. Weber, Behavior of Liver Enzymes During Hepatocarcinogenesis, Adv. Cancer Res. 6: 403 (1961).

    Article  PubMed  CAS  Google Scholar 

  2. G. Weber, Enzymology of Cancer Cells, Parts 1 and 2, N. Eng. J. Med. 296: 486 (1977).

    Article  CAS  Google Scholar 

  3. G. Weber, Biochemical Strategy of Cancer Cells and the Design of Chemotherapy: G. H. A. Clowes Memorial Lecture, Cancer Res. 43: 3466 (1983).

    PubMed  CAS  Google Scholar 

  4. K. Snell, Enzymes of Serine Metabolism in Normal, Developing and Neoplastic Rat Tissues, Adv. Enz. Reg. 22: 325 (1984).

    Article  CAS  Google Scholar 

  5. K. Snell and G. Weber, Enzymic Imbalance in Serine Metabolism in Rat Hepatomas, Biochem. J. 233: 617 (1986).

    PubMed  CAS  Google Scholar 

  6. M.-H. T. Lai and G. Weber, Increased Concentration of Thymidine Kinase in Rat Hepatomas, Biochem. Biophys. Res. Comm. 111: 280 (1983).

    Article  PubMed  CAS  Google Scholar 

  7. M. A. Reardon and G. Weber, Increased Carbamoyl-phosphate Synthetase II Concentration in Rat Hepatomas: Immunological Evidence, Cancer Res. 45: 4412 (1985).

    PubMed  CAS  Google Scholar 

  8. T. Ikegami, Y. Natsumeda, and G. Weber, Decreased Concentration of Xanthine Dehydrogenase (EC 1.1.1.204), submitted for publication (1986).

    Google Scholar 

  9. N. Prajda, Biochemical Phenotype in Human and Animal Liver Tumors, Proc. 13th International Cancer Congress, Part D, Research and Treatment, A. R. Liss, Inc., New York (1983).

    Google Scholar 

  10. J. E. Denton, M. S. Lui, T. Aoki, J. Sebolt, E. Takeda, J. N. Eble, J. L. Glover, and G. Weber, Enzymology of Pyrimidine and Carbohydrate Metabolism in Human Colon Carcinomas, Cancer Res. 42: 1176 (1982).

    PubMed  CAS  Google Scholar 

  11. Y. Natsumeda, M. S. Lui, J. Emrani, M. A. Faderan, M. A. Reardon, J. N. Eble, J. L. Glover, and G. Weber, Purine Enzymology of Human Colon Carcinomas, Cancer Res. 45: 2556 (1985).

    PubMed  CAS  Google Scholar 

  12. M. S. Lui, M. A. Faderan, J. J. Liepnieks, Y. Natsumeda, E. Olah, H. N. Jayaram, and G. Weber, Modulation of IMP Dehydrogenase Activity and Guanylate Metabolism by Tiazofurin (2–13-D-ribofuranosylthiazole-4carboxamide), J. Biol. Chem. 259: 5078 (1984).

    PubMed  CAS  Google Scholar 

  13. G. Weber, Y. Natsumeda, M. S. Lui, M. A. Faderan, J. J. Liepnieks, and W. L. Elliott, Control of Enzymic Programs and Nucleotide Pattern in Cancer Cells by Acivicin and Tiazofurin, Adv. Enz. Reg. 22: 69 (1984).

    Article  CAS  Google Scholar 

  14. H. N. Jayaram, Biochemical Mechanisms of Resistance to Tiazofurin, Adv. Enz. Reg. 24: 67 (1985).

    Article  CAS  Google Scholar 

  15. G. Weber, Y. Natsumeda, and K. Pillwein, Targets and Markers of Selective Action of Tiazofurin, Adv. Enz. Reg. 24: 45 (1985).

    Article  CAS  Google Scholar 

  16. Y.-S. Zhen, M. S. Lui, and G. Weber, Effects of Acivicin and Dipyridamole on Hepatoma 3924A Cells, Cancer Res. 43: 1616 (1983).

    PubMed  CAS  Google Scholar 

  17. R. C. Jackson, G. Weber, and H. P. Morris, IMP Dehydrogenase, an Enzyme Linked with Proliferation and Malignancy, Nature 256: 331 (1975).

    Article  PubMed  CAS  Google Scholar 

  18. G. Weber, Enzymes of Purine Metabolism in Cancer, Clin. Biochem. 16: 57 (1983).

    Article  PubMed  CAS  Google Scholar 

  19. T. J. Boritzki, R. C. Jackson, H. P. Morris, and G. Weber, Guanosine5’-phosphate Synthase and Guanosine-5’-phosphate Kinase in Rat Hepatomas and Kidney Tumors, Biochim. Biophys. Acta 658: 102 (1981).

    Article  PubMed  CAS  Google Scholar 

  20. R. C. Jackon, M. S. Lui, T. J. Boritzki, H. P. Morris, and G. Weber, Purine and Pyrimidine Nucleotide Patterns of Normal, Differentiating and Regenerating Liver and Hepatomas in Rats, Cancer Res. 40: 1286 (1980).

    Google Scholar 

  21. Y. Natsumeda, N. Prajda, J. P. Donohue, J. L. Glover, and G. Weber, Enzymic Capacities of Purine De Novo and Salvage Pathways for Nucleotide Synthesis in Normal and Neoplastic Tissues, Cancer Res. 44: 2475 (1984).

    PubMed  CAS  Google Scholar 

  22. E. Takeda and G. Weber, Role of Ribonucleotide Reductase in Expression of the Neoplastic Program, Life Sci. 28: 1007 (1981).

    Article  PubMed  CAS  Google Scholar 

  23. G. Weber, N. Prajda, and R. C. Jackson, Key Enzymes of IMP Metabolism: Transformation-and Proliferation-linked Alterations in Gene Expression, Adv. Enz. Reg. 14: 3 (1976).

    Article  CAS  Google Scholar 

  24. R. K. Robins, G. R. Revankar, P. A. McKernan, B. K. Murray, J. J. Kirsi, and J. A. North, The Importance of IMP Dehydrogenase Inhibition in the Broad Spectrum Antiviral Activity of Ribavirin and Selenazofurin, Adv. Enz. Reg. 24: 29 (1985).

    Article  CAS  Google Scholar 

  25. G. Gebeyehu, V. E. Marquez, A. C. Van Cott, D. A. Cooney, J. A. Kelley, H. N. Jayaram, G. S. Ahluwalia, R. L. Dion, Y. A. Wilson, and D. G. Johns, Ribavirin, Tiazofurin, and Selenazofurin; Mononucleotides and Nicotinamide Adenine Dinucleotide Analogs, Synthesis, Structure and Interactions with IMP Dehydrogenase, J. Med. Chem. 28: 99 (1985).

    Article  PubMed  CAS  Google Scholar 

  26. D. A. Cooney, H. N. Jayaram, R. I. Glazer, J. A. Kelley, V. E. Marquez, G. Gebeyehu, A. C. Van Cott, L. A. Zwelling, and D. G. Johns, Studies on the Mechanism of Action of Tiazofurin Metabolism to an Analog of NAD with Potent IMP Dehydrogenase-inhibitory Activity, Adv. Enz. Reg. 21: 271 (1983).

    Article  CAS  Google Scholar 

  27. J. J. Liepnieks, M. A. Faderan, M. S. Lui, and G. Weber, Tiazofurin-induced Selective Depression of NAD Content in Hepatoma 3924A, Biochem. Biophys. Res. Comm. 122: 345 (1984).

    Article  PubMed  CAS  Google Scholar 

  28. G. Weber, M. S. Lui, J. Sebolt, and M. A. Faderan, Molecular Targets of Anti-glutamine Therapy with Acivicin in Cancer Cells, in: “Glutamine Metabolism in Mammalian Tissues, ” D. Häussinger and H. Sies, eds., Springer Verlag, Heidelberg (1984).

    Google Scholar 

  29. J. S. Sebolt and G. Weber, Negative Correlation of L-glutamine Concentration with Proliferation Rate in Rat Hepatomass, Life Sci. 34: 301 (1984).

    Article  PubMed  CAS  Google Scholar 

  30. N. Prajda, Enzyme Targets of Antiglutamine Agents in Cancer Chemotherapy, Adv. Enz. Reg. 24: 207 (1985).

    Article  CAS  Google Scholar 

  31. R. H. Earhart and G. L. Neil, Acivicin in 1985, Adv. Enzyme Reg. 24: 179 (1985).

    Article  CAS  Google Scholar 

  32. T. Aoki, J. Sebolt, and G. Weber, In Vivo Inactivation by Acivicin of Carbamoyl-phosphate Synthetase II in Rat Hepatoma, Biochem. Pharm. 31:927 (1982).

    Article  PubMed  CAS  Google Scholar 

  33. T. Aoki, H. P. Morris, and G. Weber, Regulatory Properties and Behavior of Activity of Carbamoyl Phosphate Synthetase II (glutamine-hydrolyzing) in Normal and Proliferating Tissues, J. Biol. Chem. 257: 432 (1982).

    PubMed  CAS  Google Scholar 

  34. M. S. Lui, H. Kizaki, and G. Weber, Biochemical Pharmacology of Acivicin in Rat Hepatoma Cells, Biochem. Pharm. 31: 3469 (1982).

    Article  PubMed  CAS  Google Scholar 

  35. J. S. Sebolt, T. Aoki, J. N. Eble, J. L. Glover, and G. Weber, Inactivation by Acivicin of Carbamoyl-phosphate Synthetase II of Human Colon Carcinoma, Biochem. Pharm. 34: 97 (1985).

    Article  PubMed  CAS  Google Scholar 

  36. W. I. Elliott and G. Weber, In Vivo Inactivation of Formylglycinamidine Ribonucleotide Synthetase in Rat Hepatoma, Biochem. Pharm. 34:243 (1985).

    Article  PubMed  CAS  Google Scholar 

  37. G. Weber, J. E. Denton, M. S. Lui, T. Aoki, J. Sebolt, N. Prajda, Y.-S. Zhen, M. E. Burt, M. A. Faderan, and M. A. Reardon, Multi-enzymetargeted Chemotherapy by Acivicin and Actinomycin, Adv. Enz. Reg. 20: 75 (1982).

    Article  CAS  Google Scholar 

  38. J. E. Denton, M. S. Lui, T. Aoki, J. Sebolt, and G. Weber, Rapid In Vivo Inactivation by Acivicin of CTP Synthetase, Carbamoyl-phosphate Synthetase II, and Amidophosphoribosyltransferase in Hepatoma, Life Sci. 30: 1073 (1982).

    Article  PubMed  CAS  Google Scholar 

  39. G. Weber, M. S. Lui, Y. Natsumeda, and M. A. Faderan, Salvage Capacity of Hepatoma 3924A and Action of Dipyridamole, Adv. Enz. Reg.. 21: 53 (1982).

    Article  Google Scholar 

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Authors and Affiliations

  1. Laboratory for Experimental Oncology, Indiana University School of Medicine, Indianapolis, Indiana, USA

    George Weber

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  1. George Weber
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  1. University of South Florida, Tampa, Florida, USA

    Joseph G. Cory  & Andor Szentivanyi  & 

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Weber, G. (1987). Biochemical Strategy of Cancer Cells and the Targeting of Chemotherapy with Tiazofurin, Acivicin, and Dipyridamole. In: Cory, J.G., Szentivanyi, A. (eds) Cancer Biology and Therapeutics. Springer, Boston, MA. https://doi.org/10.1007/978-1-4757-9564-6_1

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  • DOI: https://doi.org/10.1007/978-1-4757-9564-6_1

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4757-9566-0

  • Online ISBN: 978-1-4757-9564-6

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