Biochemical studies on human and rat breast tissues.

Smith, JA; King, R. J. B.; Meggitt, B. F.; Allen, Lynsey-Dawn

doi:10.1038/bjc.1966.41

Cited by 27 publications

(21 citation statements)

References 11 publications

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“…Thus, by a combination of these factors, the rise in citrate lyase that was seen in our fibrocystic and tumour-bearing patients was apparently not observed earlier (Hilf et al, 1970;Smith et al, 1966).…”

Section: Resultssupporting

confidence: 59%

“…On the other hand, in normal breast tissue although we sometimes could not even detect citrate lyase activity our values are on the average comparable to those of Hilf (1970a). The activity of NADP-specific isocitrate dehydrogenase in tumours was 3 x that in Hilf's experiments (Table II), whilst the activities of hexokinase, lactate dehydrogenase and malate NADP dehydrogenase were 2-3 5 x higher than those found by Hilf et al (I 970a) and Smith et al (1966).…”

Section: Resultscontrasting

confidence: 43%

“…The homogenizing medium used was slightly hyperosmotic and contained the thiol group protecting agent, dithiothreitol. In the experiments reported by Hilf et al (1970a) and by Smith et al (1966), freezing, thawing and homogenization in hypo-osmotic medium could disrupt the mitochondria and release some mitochondrial enzymes into the supernatant fraction, explaining the relatively higher cytosol activity of isocitrate NADP dehydrogenase which occurs in both intra-and extra-mitochondrial locations.…”

Section: Resultsmentioning

confidence: 92%

“…In view of the fact that these previous experiments were carried out with tissue that had been frozen before the enzyme determinations were made (Hilf et al, 1969(Hilf et al, , 1970a(Hilf et al, , b, 1973Smith et al, 1966;Smith & Abraham, 1970), it was postulated that such procedures could adversely affect this activity, as well as that of other enzymes involved in lipogenesis. Therefore, it was of interest to determine the activities of the "lipogenic enzymes" involved in fatty-acid synthesis from carbohydrate sources in normal, fibrocystic and cancerous breast tissues that had not been previously frozen.…”

mentioning

confidence: 99%

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Lipogenetic and glycolytic enzyme activities in carcinoma and nonmalignant diseases of the human breast

Szutowicz¹,

Kwiatkowski²,

Angielski³

1979

Br J Cancer

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Activities of some enzymes associated with carbohydrate and lipid metabolism were determined in 48 human breast carcinomas and compared with those found in 35 nonmalignant breast tumours and also in 13 normal breast tissues. In fibrocystic disease only the activity of citrate lyase was markedly higher (14-fold) than in normal tissue. The activities of the remaining enzymes did not differ significantly from those in normal tissue. Enzyme activities in breast carcinoma were 4--160 x those determined in normal tissue according to the following sequence : phosphofructokinase less than malate NADP dehydrogenase less than hexokinase less than lactate dehydrogenase less than isocitrate NADP dehydrogenase less than ATP citrate lyase. Activity of citrate lyase, very low in normal breast (0.0017 mumol/min/g of tissue) rose gradually to 0.039, 0.072 and 0.258 mumol/min/g of tissue in localized fibrocystic disease, fibroadenomas and carcinomas respectively. These data support the idea that citrate lyase may play an important role in lipogenesis in hyperplastic human breast tissues.

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Section: Resultssupporting

confidence: 59%

Section: Resultscontrasting

confidence: 43%

Section: Resultsmentioning

confidence: 92%

mentioning

confidence: 99%

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Lipogenetic and glycolytic enzyme activities in carcinoma and nonmalignant diseases of the human breast

Szutowicz¹,

Kwiatkowski²,

Angielski³

1979

Br J Cancer

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“…There is well-documented evidence that oestradiol-17, induces glucose-6-phosphate dehydrogenase (GPDH) in both normal and neoplastic mammary tissue (Hilf et al, 1967;Ringler & Hilf, 1975). Furthermore, GPDH activity is higher in neoplastic tissue (Smith et al, 1966;Knox, 1967;Richards & Hilf, 1972) and neoplastic mammary tissue contains higher oestrogen-receptor concentrations than normal mammary tissue, thus suggesting a correlation between GPDH and oestrogen receptor (Daehnfeldt & Schulein, 1975). An increase in NADPH/NADP+, via raised GPDH levels, could then account for the increase in the rate of oestradiol-17, formation from oestrone in DMBA-induced tumours after oestrogen administration to oophorectomized animals.…”

Section: Discussionmentioning

confidence: 99%

Effect of hormone manipulation on oxidation, reduction and sulphurylation of dehydroepiandrosterone and oestrone in DMBA-induced rat mammary tumours

Li¹,

Chandra²,

Pewnim³

et al. 1980

Br J Cancer

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Summary.-Using the DMBA-induced mammary tumour as a model, the effect of hormone manipulation on steroid sulphurylation and on oxidative and reductive metabolism has been investigated. or oestradiol-17p + progesterone, administered to oophorectomized animals, had no effect on adenosine-3'-phosphate-5'-phosphosulphate formation in the tumours. Dehydroepiandrosterone sulphotransferase was also unaffected. A large increase in oestrogen sulphotransferase following administration of oestrogen + progesterone was observed in some but not all tumours, and the overall results were not statistically significant. The major metabolities of dehydroepiandrosterone, by both human and carcinogen-induced rat mammary tumours in vitro, are 7-oxygenated derivatives. Oestrogen administration led to a significantly decreased production of total 7-oxygenated derivatives of dehydroepiandrosterone. Conversion to 5-androstene-3p,17p-diol was unaffected by the hormones. The rate of formation of oestradiol-17p from oestrone was increased 5-fold in growing tumours from animals receiving oestrogen, or oestrogen+proges-terone, compared to regressing tumours in oophorectomized control animals.A HYPOTHESIS has been presented implicating adrenal dehydroepiandrosterone (DHEA) and DHEA sulphate (DHEAS) in the aetiology of human breast cancer (Adams, 1977). The main metabolites of DHEA, produced by in vitro incubation with human mammary tumours, are 7-oxygenated derivatives (7a-hydroxy DH-EA, 7P-hydroxy DHEA and 7-oxo DHEA) and 5-androstene-3g, 17/-diol (Li et al., 1978). The latter can cause translocation of the oestrogen receptor in both the uterus and mammary tumours Nicholson et al., 1978). Although it is difficult to be certain of the exact role played by the 7-hydroxylation system in mammary tissue, it has been suggested ) that it could function as an inactivation step to modify oestrogen receptor translocation by 33-hydroxy-A5-androstenes, which are known to occur in relatively high concentrations in human mammary tumours (Maynard et al., 1977). Thus high levels of DHEAS in the blood could lead to high intracellular levels of DHEA and its metabolites formed in situ in mammary tissue.Pathways of DHEA metabolism similar to those established in human mammary tumours also occur in 7,12-dimethylbenz-(a)anthracene (DMBA)-induced rat mammary tumours (Li et al., 1976). It was thus of interest to use this as a model to study the influence of an altered sexhormone milieu in tumour-bearing rats upon subsequent DHEA metabolism in the tumour. In parallel studies, the influence of an altered hormone milieu on oestrogen metabolism by these tumours has been investigated.One other aspect of DHEA metabolism by human mammary tumours, i.e. formation of the sulphate ester, is of relevance when considered together with the sulphurylation of oestradiol-17/. Measurement of these conversions by the tumour

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Enzyme pathology and the histologic categorization of human lung tumors: The continuum of quantitative biochemical indices of neoplasticity

Greengard

Head

Goldberg

et al. 1982

Cancer

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The purpose of the present enzymic and histologic analysis of pulmonary samples from 39 subjects was to discern a common, meaningful pattern which may underlie the biochemical heterogeneity of lung neoplasms. The distribution among the different tumors of thymidine kinase, uridine kinase, phosphoserine phosphatase, hexokinase and adenylate kinase was found to correlate with each other. By averaging their standardized units (normal lung = 0) an enzymic index of neoplasticity was calculated for each tumor and used (in increasing order) to rank all 39. The index, showing a significant positive correlation with mitotic frequency, encompassed a continuous 100-fold range. Poorly differentiated carcinomas ranked high while neoplasms with better differentiation and prognosis placed in the lower half of the range. The results indicate that enzymes showing coordinated variations over a broad spectrum of tumors could contribute objective criteria to the rating of any individual tumor against a continuous, quantitative scale of neoplasticity.

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Biochemical studies on human and rat breast tissues.

Cited by 27 publications

References 11 publications

Lipogenetic and glycolytic enzyme activities in carcinoma and nonmalignant diseases of the human breast

Lipogenetic and glycolytic enzyme activities in carcinoma and nonmalignant diseases of the human breast

Effect of hormone manipulation on oxidation, reduction and sulphurylation of dehydroepiandrosterone and oestrone in DMBA-induced rat mammary tumours

Enzyme pathology and the histologic categorization of human lung tumors: The continuum of quantitative biochemical indices of neoplasticity

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