Enzymes of glucose metabolism in carcinoma of the cervix and endometrium of the human uterus

Abstract

Summary.-Twelve enzymes related to the direct oxidative and glycolytic pathways of glucose metabolism were assayed in 88 cancers of the cervix and 48 cancers of the endometrium of the human uterus, and the activities compared with those obtained from a group of control tissues. Significant increases for all but one of the enzymes studied (a-glycerolphosphate dehydrogenase) were found in cancer of the cervix, when compared with normal cervix epithelium. Hexokinase, phosphofructokinase, and aldolase appear to be rate-limiting in normal cervix epithelium; however, since the increase in activity of the first two in cancers was least of all the glycolytic enzymes, redundant enzyme synthesis probably occurs in the malignant cell for the enzymes catalysing reversible reactions. There was virtually no correlation between the activity of any enzyme measured in the cancer sample and histological assessments of the degree of malignancy of the tumour, or the clinical stage of the disease. All enzymes except pyruvate kinase had significantly higher activity in normal endometrium than in normal cervix epithelium, presumably reflecting the greater metabolic requirements of the former tissue. Only phosphoglucose isomerase and pyruvate kinase were significantly higher in endometrial cancer than in normal endometrium, and there were few significant differences between cancers of the cervix and of the endometrium, despite the marked differences in their tissues of origin. These results suggest the changes occur during malignant transformation to the activities of both regulatory enzymes and those catalysing reversible reactions, in a manner justifying the conclusion that the general metabolism of tumours is convergent.

Uptake of Tritiated Thymidine, Deoxyglucose and Methionine in Three Lung Cancer Cell Lines: Deoxyglucose Uptake Mirrors Tritiated Thymidine Uptake

“…By contrast, a study in a group of cervical and endometrial cancers on the possible association between glycolytic enzymes and tumour grading did not find any correlation between hexokinase activity and degree of malignancy [6]. In a recent study by our group [7], FDG uptake in primary breast cancer was shown to be associated with tumour grade and p53 status.…”

Effect of radiotherapy upon enzymes of the glycolytic and related pathways in human uterine cancer

“…For every enzyme, the mean value in the post-radiation samples was less than that in the preradiation tissues. All enzymes studied, with the exception of aGPD, were higher in the pre-radiation cancer samples than in normal cervical epithelium (Marshall et al, 1978a). The reduced activities in the post-radiation samples brought the mean values closer to those of normal cervical epithelium, although most were still significantly higher; exceptions were HK and PGM, where the means were not significantly different, and PFK, where the mean activity in the post-radiation samples was actually less than in the normal cervical epithelium (P<0 O1).…”

“…Table I presents the radiation dose to the tissues after the first 137Cs implantation. Table II summarizes the enzyme data from all cancer patients, and normal values from our previous paper (Marshall et al, 1978a). In cancer of the cervix, significant reduction in the specific activiAccepted 28 September 1978 ties of the following enzymes occurred in the post-radiation samples: PFK, Ald, En, and LDH (all P<0001), and PGM, and G6PD (P < 0.05).…”

“…DURING a study of enzymes of glycolysis and related pathways in normal and malignant cervix and endometrium of the human uterus (Marshall et al, 1978a), significant increases in all but one were found in cancer of the cervix, but only 2 were raised in cancer of the endometrium when compared with the normal tissues of origin. Since many of these patients had a second biopsy after a period of intracavitary radiation, an opportunity was taken to study the effects of 137Cs implantation upon the activities of these enzymes in the malignant tissue using the methods previously described (Marshall et al, 1978b).…”

Whole-body 18FDG PET plus pelvic MRI in the pre-treatment assessment of cervical cancers: an alternative to the FIGO clinical staging

“…Also, 18 FDG PET appears particularly appropriate for the detection of distant tumour sites through the entire body [13,14,32,36]. Interestingly, cervical cancers exhibit high rates of GLUT-1 (type-1 glucose transporter) and glycolytic enzymes (type-2 hexokinase, phosphofructokinase and pyruvate kinase), which makes the imaging by means of the glucose analogue theoretically and practically valid for such gynaecological malignancies [37,38,39,40,41]. In addition, metabolic imaging offers the possibility of non-invasive whole-body scanning in a single session, whereas the FIGO staging system recommends a number of radiological and endoscopic studies, iterative explorations that are not only invasive and expensive, but often clinically fruitless [2,3,4,5].…”