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Research Article| Volume 1, ISSUE 2, P175-181, August 1978

A defect in thromboxane a2 synthesis may be a factor predisposing to cancer

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      Abstract

      A failure of thromboxane (TX) A2 synthesis may be a factor in cancer. Such a loss could explain the susceptibility to mutation, the excess prostaglandin production, the glycolytic mode of metabolism and the deranged calcium pumping characteristic of cancers. Ionising radiation and phorbols both have actions similar to inhibitors of TXA2 synthesis whereas colchicine and oxygen have actions consistent with stimulation of TXA2 synthesis. The concept accounts logically for hitherto unexplained features of cancer and suggests new strategies for the prevention and treatment of cancer.
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      References

        • Karim S.M.M.
        • Rao B.
        Prostaglandins and tumours.
        in: Karim S.M.M. Prostaglandins: Physiological, Pharmacological and Pathological Aspects. MTP, Lancaster1976: 303
        • Jaffe B.M.
        Prostaglandins and cancer: an update.
        Prostaglandins. 1974; 6: 453
        • Easty G.C.
        • Easty D.M.
        Prostaglandins and cancer.
        Cancer Treat. Rev. 1976; 3: 217
        • Beerthuis R.K.
        • Nugteren D.H.
        • Pabon H.J.J.
        • van Dorp D.A.
        Biologically active prostaglandins from some new odd-numbered essential fatty acids.
        Rec. Trav. Chim. 1978; 87: 461
        • Mead J.F.
        • Fulco A.J.
        The Unsaturated and Polyunsaturated Fatty Acids in Health and Disease.
        CC Thomas, Springfield1976
        • Horrobin O.F.
        • Karmali R.A.
        • Manku M.S.
        • Ally A.I.
        • Karmazyn M.
        • Morgan R.O.
        Systemic lupus erythematosus: a disease of thromboxane A2 synthesis and action.
        IRCS J Med Sci. 1977; 5: 547
        • Nijkamp F.P.
        • Moncada S.
        • White H.L.
        • Vane J.R.
        Diversion of prostaglandin endoperoxide metabolism by selective inhibition of thromboxane A2 biosynthesis in lung, spleen or platelets.
        Eur J Pharmacol. 1977; 44: 179
        • Horrobin D.F.
        • Manku M.S.
        • Karmali R.A.
        • Oka M.
        • Ally A.I.
        • Morgan R.O.
        • Karmazyn M.
        • Cunnane S.C.
        Thromboxane A2: a key regulator of prostaglandin biosynthesis and of interactions between prostaglandins, calcium and cyclic nucleotides.
        Med Hypotheses. 1978; 4: 178
        • Warburg O.
        The Metabolism of Tumours.
        1930 (London)
        • Smith A.E.
        • Kenyon D.H.
        A unifying concept of carcinogenesis and its therapeutic implications.
        Oncology. 1973; 27: 459-479
        • Papaconstantinou I.
        • Colowick S.P.
        The role of glycolysis in the growth of tumour cells.
        J Biol Chem. 1961; 236: 278
        • Gold J.
        Cancer cachexia and gluconeogenesis.
        NY Acad Sci. 1974; 230: 103
        • Moncada S.
        • Bunting S.
        • Mullane K.
        • Thorogood P.
        • Vane J.R.
        • Raz A.
        • Needleman P.
        Imidazole: a selective inhibitor of thromboxane A2 synthetase.
        Prostaglandins. 1977; 13: 611
        • Parvin R.
        • Kalant N.
        Stimulation of glycolysis by imidazole.
        Life Sci. 1973; 13: 1347
        • Rossi E.C.
        The effect of imidazole upon platelets incubated in vitro.
        Thromb Diath Haemorrh. 1968; 19: 53-63
        • Loewenstein W.R.
        Some reflections on growth and differentiation.
        Perspect Biol Med. 1968; 11: 260
        • Burton A.C.
        Cellular communication, contact inhibition, cell clocks and cancer.
        Perspect Biol Med. 1968; 11: 260
        • Horrobin D.F.
        • Morgan R.O.
        • Karmali R.A.
        • Ally A.I.
        • Manku M.S.
        • Karmaqn M.
        • Cunnane S.C.
        Thymic changes in muscular dystrophy and evidence for an abnormality related to prostaglandin synthesis or action.
        Ann NY Acad Sci. 1978; (in press)
        • Horrobin D.F.
        • Manku M.S.
        • Ally A.I.
        • Morgan R.O.
        • Karmali R.A.
        Quinacrine as a prostaglandin antagonist.
        Biochem Biophys Res Commun. 1977; 76: 1188
        • Manku M.S.
        • Horrobin D.F.
        Chloroquine, quinine, procaine, quinidine and clomipramine are prostaglandin agonists and antagonists.
        Prostaglandins. 1976; 12: 789
        • Manku M.S.
        • Horrobin D.F.
        Chloroquine, quinine, procaine, quinidine, tricyclic antidepressants and methyl xanthines are prostaglandin agonists and antagonists.
        Lancet. 1976; 2: 1115
        • Karmali R.A.
        • Schiller P.
        • Horrobin D.F.
        Prostaglandins can prevent the binding of chloroquine to calf thymus DNA.
        Prostaglandins. 1976; 12: 463
        • Berenblum I.
        • Shubik P.
        A new quantitative approach to the study of the stages of chemical carcinogenesis in mouse skin.
        Br J Cancer. 1947; 1: 383
        • Greaves M.W.
        • Sondergaard J.
        Pharmacologic agents released in ultra violet inflammation studied by continuous perfusion.
        J Invest Dermatol. 1970; 54: 365
        • Snyder D.S.
        • Eaglestein W.H.
        Topical indomethacin and sunburn.
        Br J Dermatol. 1974; 90: 91-93
        • Manku M.S.
        • Horrobin D.F.
        Ultra violet radiation and 8-methoxypsoralen have actions similar to those of known inhibitors of thromboxane A2 synthesis in rat mesenteric blood vessels.
        Prostaglandins Med. 1978; 1: 87-96
        • Horrobin D.F.
        Prostaglandins: Physiology, Pharmacology and Clinical Significance.
        Churchill Livingstone, Edinburgh1978 (Eden Press, Montreal, in press)
        • Vittorio P.V.
        • Whitfield J.F.
        • Rixon R.H.
        The radioprotective, therapeutic effects of imidazole and erythropoietin on erythropoiesis and survivial and irradiated mice.
        Radiation Res. 1971; 47: 191-198
        • Mennie A.T.
        • Dalley V.M.
        • Dineen L.C.
        • Collier H.O.J.
        Treatment of radiationinduced gastrointestinal distress with acetyl salicylate.
        Lancet. 1975; ii: 942
        • Tai H.H.
        • Yuan B.
        On the inhibitory potency of imidazole and its derivatives on thromboxane synthetase.
        Biochem Biophys Res Comm. 1978; 80: 236-242
        • Weinstein I.B.
        • Wigler M.
        Cell culture studies provide new information on tumour promoters.
        Nature. 1977; 270: 659-660
        • Horrobin D.F.
        • Oka M.
        • Manku M.S.
        Effect of imidazole, histidine and colchicine on vascular reactivity: possible relevance to prostaglandin and thromboxane synthesis.
        Eur J Rheumatol. 1978; (in press)
        • O'Brien T.G.
        • Simsiman R.C.
        • Boutwell R.I.C.
        The effect of colchicine on the induction of ornithine decarboxylase by 12-0#tetradecanoyl phorbol13-acetate.
        Cancer Res. 1976; 36: 3766
        • Stern H.
        On the intranuclear environement.
        Science. 1955; 121: 144-146
        • Gerrard J.M.
        • Townsend D.
        • Stoddard S.
        • Witkop C.J.
        • White J.G.
        The influence of prostaglandin G2 on platelet ultrastructure and platelet secretion.
        Am J Path. 1977; 86: 99
        • Moss H.V.
        Xeroderma pigmentosum: report of 2 cases with metabolic studies.
        Arch Dermatol. 1965; 92: 638
        • Reed W.B.
        • May S.B.
        • Nickel W.R.
        Xeroderma pigmentosum with neurological complications.
        Arch Dermatol. 1965; 91: 224
        • Cleaver J.E.
        Xeroderma pigmentosum: a human disease in which an initial stage of DNA repair is defective.
        in: Proc Natl Acad Sci USA. 63. 1969: 428
        • Harris G.C.
        Malignancy during methotrexate and steroid therapy for psoriasis.
        Arch Dermatol. 1971; 103: 501
        • Sams W.M.
        Phototherapy of psoriasis.
        in: Fitzpatrick T.B. Sunlight and Man. University of Tokyo Press, 1974
        • Weber G.
        Combined 8-methoxypsoralen and black light therapy of psoriasis.
        Br J Dermatol. 1974; 90: 317-323
        • Horrobin O.F.
        • Manku M.S.
        • Karmali R.A.
        • Karmazyn M.
        • Morgan R.O.
        • Ally A.I.
        • Menezes J.
        Human interferon stimulates synthesis of prostaglandinlike material: effect blocked by cortisol.
        IRCS J Med Sci. 1977; 5: 554