Enzyme pathology of the liver in patients with and without nonhepatic cancer

Abstract

Preliminary studies of 13 enzymes subserving various metabolic pathways were undertaken in tumor-free liver biopsy samples from cancer patients and control subjects. The observations indicate that as a result of nonhepatic neoplasms, with (7 cases) or without (6 cases) hepatic involvement, the biochemical composition of the liver becomes partially undifferentiated. Quantification of appropriate enzymes in histologically normal liver samples could thus distinguish clearly between cancer hosts and controls. The best discriminators include two hepatic enzymes whose concentrations were decreased to less than 30% of normal (soluble glutamate dehydrogenase and the cold stable pyrroline-5-carhoxylate reductase) and three for which it was elevated two to four-fold (hexokinase, peptidyl proline hydroxylase and thymidine kinase) in response to distant neoplasms. The same alterations in hepatic enzyme pattern were not seen in any cancer-free patients with or without morphologic liver damage. Cancer 45:2383-2388, 1980. TUDIES OF THE NATURE of morbidity in cancer S patients suggest that the degree of cachexia bears no simple relationship to the type, size, and anatomic site of neoplasms, or to caloric intake.2 Explanations for the host syndrome are thus sought in the systemic effects of neoplasms, in the alteration they cause in remote tissues via chemical mediators released into the circulatory system.2 Indications that the liver is a sensitive host tissue came from the many biochemical investigations on experimental animals carrying extra-hepatic neoplasms. Studies in this laboratory of some two dozen enzymes showed, for example, that the biochemical composition of the uninvolved, histo-logically normal host liver tends to change in the direction of that of immature liver.g Signs of partial hepatic dedifferentiation were detectable a few days after the

Abnormal liver metabolism in cancer patients detected by31P MR spectroscopy

“…[21][22][23][24][25][26][27][28][29][30] However, in the latter types of liver disease, metabolic alterations can be explained by massive losses of normal cells and consequent regenerative responses within the liver, whereas no such visible signs accompany the pathophysiological changes in the cancer-free liver of patients with a distant malignant tumour. 8 The metabolic abnormalities observed here in cancer patients are therefore remarkable, supporting the view of cancer as a systemic rather than a local disease. Prospective studies will be needed in order to assess the etiological role of the observed abnormalities, as well as their prognostic value for subsequent weight loss and survival in human cancer.…”

“…7 Enzyme studies in tumour-free liver biopsies from patients with distant tumours and healthy control subjects revealed marked abnormalities in the liver of cancer hosts, such as 2-4-fold rises in concentrations of hexokinase, peptidyl proline hydroxylase and thymidine kinase, and b70% reductions in soluble glutamate dehydrogenase and cold-stable pyrroline-5-carboxylate reductase. 8 Overall, liver enzymes showed a striking pattern of dedifferentiation resembling enzymic changes observed within malignant tumours. A similar dedifferentiation of liver enzyme patterns was observed in various experimental cancer models, including renal, submaxillary and mammary cancer.…”

Crystal Structure of Human Pyrroline-5-carboxylate Reductase

“…However, overexpression of the mRNA for P5CR was reported by DNA microarray analysis in carcinoma, [12][13][14] and the raised activity of P5CR changes as a marker of pulmonary tumors and adult neoplastic colon. 15,16 The decreased P5CR activity may be associated with retinal degeneration in mice, 17 and could be used to distinguish clearly between patients with and without non-hepatic cancer. 6 The expression of P5CR in LoVo cells can be inhibited by adriamycin.…”

Pro-tumorigenic activity of PYCR1 in gastric cancer through regulating the PI3K/AKT signaling

“…PYCR1 exhibits the capability to protect cells from mitochondrial fragmentation induced by oxidative stress [ 16 ]. Furthermore, investigations have revealed that PYCR1 overexpression and increased activity have been observed in various carcinoma types, encompassing lung, prostate, colon, liver, and breast cancers [ [17] , [18] , [19] , [20] , [21] ]. PI3K/AKT pathway plays an important role in inducing cell malignant transformation, tumor angiogenesis and apoptosis [ 22 ].…”