LACTIC DEHYDROGENASE IN HUMAN NEOPLASTIC TISSUES.

Summary A definite and consistent shift in the pattern of molecular forms of lactic dehydrogenase (LDH) has been found in a large series of malignant human neoplasms as compared with benign tumors and normal controls. This has been associated in most cases with an absolute increase in the muscle-type LDH (migrating negatively on electrophoresis). No correlation was found between the degree of these changes and the histologic grading of the tumors. Suggestive but not conclusive evidence was found for an increase in total LDH activity in malignant tumors. In contrast, metastatic nodules were shown to have lower enzyme activity levels and different LDH compositions when compared with their associated primary tumors. The benign tumors were essentially indistinguishable from their normal tissue of origin. The significance of these findings in relation to the known characteristic increase of glycolytic activity in malignant neoplasms is discussed. Consideration is also given to the possible implications of these results for carcinogenesis and cancer chemotherapy.

[1]  H. Bierman,et al.  Correlation of serum lactic dehydrogenase activity with the clinical status of patients with cancer, lymphomas, and the leukemias. , 1957, Cancer research.

[2]  A. Meister Lactic dehydrogenase activity of certain tumors and normal tissues. , 1950, Journal of the National Cancer Institute.

[3]  B. Hill,et al.  Elevation of a serum component in neoplastic disease. , 1954, Cancer research.

[4]  K. Bensch,et al.  The effect of nitrogen on the enzymatic pattern of strain L cells. , 1961, Cancer research.

[5]  J. Greenstein Some biochemical characteristics of morphologically separable cancers. , 1956, Cancer research.

[6]  S. Colowick,et al.  The role of glycolysis in the growth of tumor cells. I. Effects of oxamic acid on the metabolism of Ehrlich ascites tumor cells in vitro. , 1961, The Journal of biological chemistry.

[7]  N. Kaplan,et al.  Developmental Changes of Mammalian Lactic Dehydrogenases , 1963 .

[8]  L. White Serum enzymes. II. Glycolytic enzymes in patients with cancer and other diseases. , 1958, Journal of the National Cancer Institute.

[9]  O. Warburg On the origin of cancer cells. , 1956, Science.

[10]  C. Huggins,et al.  Steroid influences on respiration, glycolysis, and levels of pyridine nucleotide-linked dehydrogenases of experimental mammary cancers. , 1960, Cancer research.

[11]  C. Brindley,et al.  Serum lactic dehydrogenase and glutamic-oxaloacetic transminase correlations with measurements of tumor masses during therapy. , 1963, Cancer research.

[12]  K. Jacobson,et al.  Studies on plasma lactic dehydrogenase in mice with myeloid leukemia. II. On the site of production of the enzyme. , 1963, Cancer Research.

[13]  F. Wróblewski,et al.  Lactic dehydrogenase activity of serum in mice with transplantable leukemia. , 1956, Science.

[14]  K. Jacobson,et al.  Studies on plasma lactic dehydrogenase in mice with myeloid leukemia. I. Relation of enzyme level to course of disease. , 1963, Cancer research.

[15]  J. Philip,et al.  COMPARATIVE STUDIES OF THE ISOZYMES OF LACTIC DEHYDROGENASE IN RABBIT AND MAN , 1962, The Journal of experimental medicine.

[16]  K. M. Hsieh,et al.  Serum lactic dehydrogenase activity after excision of transplanted tumors. , 1959, Cancer research.

[17]  S. Weinhouse Oxidative metabolism of neoplastic tissues. , 1955, Advances in cancer research.

[18]  G. E. Boxer,et al.  Low levels of soluble DPN-linked alpha-glycerophosphate dehydrogenase in tumors. , 1960, Cancer research.

[19]  G. Pfleiderer,et al.  ISOENZYMES IN THE HUMAN EPIDERMIS , 1961, Annals of the New York Academy of Sciences.

[20]  H. Blumenthal,et al.  Serum Lactic Dehydrogenase Levels in Various Disease States.∗ , 1956, Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine.

[21]  S. Weinhouse Discussion of Doctor Greenstein's paper. , 1956, Cancer research.

[22]  F. Wróblewski,et al.  Lactic Dehydrogenase Activity in Blood.∗ , 1955, Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine.

[23]  G. Beaudreau,et al.  Glucose and lactate utilization by myeloblasts and erythroblasts of avian viral leukemias. , 1959, Journal of the National Cancer Institute.

[24]  S. Weinhouse,et al.  Metabolism of neoplastic tissue. II. A survey of enzymes of the citric acid cycle in transplanted tumors. , 1952, Cancer research.

[25]  M. Mori,et al.  Histochemical evaluation of enzymatic activities in human squamous-cell cancer. , 1963, Cancer research.

[26]  R. T. Jordan,et al.  Serum lactic dehydrogenase activity in mice with transplantable leukemia. , 1957, Cancer research.

[27]  N. Kaplan,et al.  Nature and Development of Lactic Dehydrogenases: The two major types of this enzyme form molecular hybrids which change in makeup during development. , 1962, Science.

[28]  H. Schoch,et al.  Some observations on the lactate dehydrogenase of human neoplastic tissue. , 1962, Biochimica et biophysica acta.

[29]  C. Manso,et al.  Glutathione reductase and lactic dehydrogenase activities of tissues of rodents with transplanted tumors. , 1958, Cancer research.

[30]  E. Vesell SIGNIFICANCE OF THE HETEROGENEITY OF LACTIC DEHYDROGENASE ACTIVITY IN HUMAN TISSUES * , 1961, Annals of the New York Academy of Sciences.

[31]  L. White Serum enzymes. III. The significance of abnormalities of glycolytic enzymes in the serum of cancer patients. , 1958, Journal of the National Cancer Institute.

[32]  H. Aebi,et al.  A study of lactic dehydrogenase isoenzyme pattern of human tissues by adsorption-elution on Sephadex-DEAE. , 1963, Clinica chimica acta; international journal of clinical chemistry.

[33]  O. Warburg [Origin of cancer cells]. , 1956, Oncologia.

[34]  B. Sacktor,et al.  Alpha-glycerophosphate and lactic dehydrogenases of hematopoietic cells from leukemic mice. , 1960, Cancer research.

[35]  C. Crispens Serum lactic dehdrogenase levels in mice during the development of autochthonous and chemically induced tumors. , 1963, Journal of the National Cancer Institute.

[36]  G. E. Boxer,et al.  Pathways of intracellular hydrogen transport. , 1961, Science.

[37]  Macbeth Ra,et al.  Oxygen consumption and anaerobic glycolysis of human malignant and normal tissue. , 1962 .

[38]  H. Goldblatt,et al.  INDUCED MALIGNANCY IN CELLS FROM RAT MYOCARDIUM SUBJECTED TO INTERMITTENT ANAEROBIOSIS DURING LONG PROPAGATION IN VITRO , 1953, The Journal of experimental medicine.

[39]  N. Kaplan,et al.  ALTERATIONS OF TISSUE LACTATE DEHYDROGENASE IN HUMAN NEOPLASMS. , 1963, Biochimica et biophysica acta.

[40]  B. Moore,et al.  Chromatographic patterns of protein and enzymes in extracts of rhabdomyosarcoma and muscle in mice. , 1960, Cancer research.

[41]  J. Hill Serum lactic dehydrogenase in cancer patients. , 1957, Journal of the National Cancer Institute.

[42]  F. Wróblewski,et al.  LACTIC DEHYDROGENASE ISOZYMES AND THEIR DISTRIBUTION IN NORMAL TISSUES AND PLASMA AND IN DISEASE STATES * , 1961, Annals of the New York Academy of Sciences.