Une connaissance de la strategie biochimique des cellules cancereuses et de la «voie royale» pour la conception de la chimiotherapie anticancereuse dirigee par l'enzymogramme. Dans cet article on souligne l'essence et la substance des progres theoriques et experimentaux vers une connaissance de la strategie biochimique et de la logique de l'expression des genes dans les cellules cancereuses et on identifie un programme enzymatique et metabolique commun dans les diverses tumeurs animales et humaines

https://cancerres.aacrjournals.org/content/canres/43/8/3466.full.pdf

Biochemical Strategy of Cancer Cells and the Design of Chemotherapy: G. H. A. Clowes Memorial Lecture

Enzymes of the pyrimidine base catabolism, dihydrouracil dehydrogenase (EC 1.3.1.2), dihydropyrimidinase (EC 3.5.2.2), and β-ureidopropionase (EC 3.5.1.6) were compared in the cytosolic extract of several normal and neoplastic human tissues. The activity was measured by following the catabolism of [6-14C]-uracil to dihydrouracil, carbamyl-β-alanine, and β-alanine. Substrate inhibition, hysteresis, allosterism, and the lack of dihydropyrimidinase are pointed out as special problems in assaying enzymes of pyrimidine degradation. The activity of dihydrouracil dehydrogenase has been demonstrated in several human extrahepatic tissues and tumors. The enzyme is rate limiting in extrahepatic solid tumors but not in their normal counterparts. Some of these solid tumors contain greater amounts of activity than do their normal equivalents, which encourages the use of inhibitors of this enzyme in conjunction with treatment of these tumors by 5-fluorouracil. Because of the lack of a pattern in dihydrouracil dehydrogenase activity between tumors and normal tissues, the enzyme is not a good marker for tumorigenicity. Dihydropyrimidinase, on the other hand, is highly active in all solid tumors studied but not in their normal counterparts; therefore, we suggest that dihydropyrimidinase can serve as a good marker of tumorigenicity as well as a target for cancer chemotherapy of human solid tumors.

https://cancerres.aacrjournals.org/content/canres/45/11_Part_1/5405.full.pdf

Enzymes of Uracil Catabolism in Normal and Neoplastic Human Tissues

While specific genes are hypermethylated in the genome of cancer cells, overall methylcytosine content is often decreased as a consequence of hypomethylation affecting many repetitive sequences. Hy...

Causes and consequences of DNA hypomethylation in human cancer.

https://www.inf.ed.ac.uk/teaching/courses/csb/CSB_lectures_2006/laszlo_cascante_metabolic_profiling_2002_ddt.pdf

Metabolic profiling of cell growth and death in cancer: applications in drug discovery.

Cellular distribution, metabolism and regulation of the xanthine oxidoreductase enzyme system.

Biochemical strategy of the genome as expressed in regulation of pyrimidine metabolism

Colon tumor: Enzymology of the neoplastic program

Cancer-associated retinopathy syndrome: a case of small cell lung cancer expressing recoverin immunoreactivity.

This paper critically evaluates the advances made with the molecular correlation concept as a conceptual and experimental approach in elucidating the biochemical strategy of the cancer cells. New advances made in gaining an insight into the behavior of pyrimidine metabolism are also used to illustrate the method and current status of the molecular correlation concept. Investigation of the hepatomas of different growth rates and comparison with appropriate control systems such as the normal, differentiating and regenerating liver has led to the discovery that in neoplastic cells there is an ordered pattern of enzymatic and metabolic imbalance. We documented in detail the linking of biochemical discriminants with neoplastic transformation and progression in carbohydrate, pentose phosphate, purine, pyrimidine, ornithine and polyamine metabolism and in membrane cAMP systems. We pointed out the importance of selecting for such investigations the analysis of the activity, concentration and isozyme pattern of opposing key enzymes in antagonistic pathways of synthesis and degradation. We demonstrated that the control of gene expression operates through reciprocal regulation of opposing key enzymes in antagonistic and competing metabolic pathways.

The Molecular Correlation Concept of Neoplasia: Recent Advances and New Challenges

An insight into the ordered pattern of enzymatic and biochemical imbalance of cancer cells was made possible, at least in part, by the molecular correlation concept, the concept of key enzymes, and the use of biological model systems. With these approaches the pattern of gene expression in neopiasia can be studied in terms of the activities of key enzymes and their linking with neoplastic transformation and progression. An ordered pattern of biochemical imbalance was recognized in carbohydrate, pentose phosphate, purine, pyrimidine, DNA, and polyamine metabolism and in other biochemical areas. Current work is directed to clarifying the enzymology and metabolic pattern of thymidine metabolism and CTP biosynthesis since these areas are of particular importance in selective chemotherapy and rescue. The activities of key enzymes in thymidine metabolism have been correlated with the growth rates in a spectrum of hepatomas. Increases in the activities of four key enzymes in CTP biosynthesis appear to be specifi...

Taiichi Shiotani

Papers

Biochemical strategy of the genome as expressed in regulation of pyrimidine metabolism

Colon tumor: Enzymology of the neoplastic program

Cancer-associated retinopathy syndrome: a case of small cell lung cancer expressing recoverin immunoreactivity.

The Molecular Correlation Concept of Neoplasia: Recent Advances and New Challenges

Biochemical strategy of hepatomas.