Osteolytic Sterol in Human Breast Cancer

Gordan, Gilbert S.; Cantino, Theodore J.; Erhardt, Linda; Hansen, James; Lubich, Warren P.

doi:10.1126/science.151.3715.1226

Cited by 112 publications

(14 citation statements)

References 5 publications

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“…Destruction of bone by osteolytic métastasés is the usual explanation for the hyper calcemia of breast cancer. G o rd a n et al [9] have demonstrated osteolytic sterols in tumor extracts and plasma of the patients with osseous métastasés, and these sterols have shown to be derivatives of sitosterol and sigmasterol [10]. It is of interest that hypocalcemia has been reported in a small number of cases with osteoblastic métastasés [15].…”

Section: Discussionmentioning

confidence: 99%

Hypercalcemia Complicating Breast Cancer

Belnoue-Davis¹,

Wiseley²,

Ramírez³

et al. 1973

Oncology

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The incidence of significant hypercalcemia in 305 women with disseminated breast cancer was 7.2%. 13 patients developed hypercalcemia spontaneously and eight patients developed hypercalcemia shortly after initiation of additive hormone therapy. One patient developed fatal hypercalcemia shortly after adrenalectomy. All patients had bone metastases documented by X-rays or bone scans. Treatment with volume expansion, diuretics, and steroids was successful in 11 of 19 trials and Mithramycin therapy in very low dosage was successful in 4 of 5 trials. 7 of the 22 hypercalcemia patients expired and four of these deaths were directly as a result of hypercalcemia.

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Section: Discussionmentioning

confidence: 99%

Hypercalcemia Complicating Breast Cancer

Belnoue-Davis¹,

Wiseley²,

Ramírez³

et al. 1973

Oncology

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“…In period 11 (83 days) the patient was given a formula diet containing 40% of calories as corn oil in which 9-sitosterol-22,23-5H had been incorporated during its manufacture; each day the patient ingested 620 mg of 13-sitosterol of specific activity 74,245 dpm/mg. On the 2nd day of this regimen radioactivity was detected in the plasma; it rose to reach a constant level of approximately 1000 dpm/ml plasma in about 2 wk (Fig.…”

Section: Calculationsmentioning

confidence: 99%

Metabolism of β-sitosterol in man

Salen¹,

Ahrens²,

Grundy³

1970

J. Clin. Invest.

473

230

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A B S T R A C T The metabolism of P-sitosterol was compared to that of cholesterol in 12 patients. Sterol balance methods were supplemented by radiosterol studies, with the following results. (a) Plasma concentrations of P-sitosterol ranged from 0.30 to 1.02 mg/100 ml plasma in patients on intakes of 6-sitosterol typical of the American diet. Plasma levels were raised little when intakes were increased greatly, and on fixed intakes they were constant from week to week. On diets devoid of plant sterols, the plasma and feces rapidly became free of p-sitosterol. (b) The percentage of esterified P-sitosterol in the plasma was the same as for cholesterol. However, the rate of esterification of P-sitosterol was slower than that for cholesterol. (c) Specific activitytime curves after simultaneous pulse labeling with #-sitosterol-3H and cholesterol-"C conformed to twopool models. The two exponential half-lives of f-sitosterol were much shorter than for cholesterol, and pool sizes were much smaller. Values of turnover for ,8-sitosterol obtained by the sterol balance method agreed closely with those derived by use of the two-pool model. There was no endogenous synthesis of P-sitosterol in the patients studied; hence, daily turnover of P-sitosterol equaled its daily absorption. Absorption of P-sitosterol was 5% (or less) of daily intake, while cholesterol absorption ranged from 45 to 54% of intake. (d) About 20% of the absorbed f-sitosterol was converted to cholic and chenodeoxycholic acids. The remainder was excreted in bile as free sterol; this excretion was more rapid than that of cholesterol. (e) The employment of i3-sitosterol as an internal standard to correct for losses of cholesterol in sterol balance studies is further validated by the results presented here.

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“…Some tumours, those of the breast in particular, are capable of produc ing sterols which cause osteolysis, thus promoting hypercalcaemia. Gordan et al [5] have demonstrated the activity of these sterols on bones of rats which had previously been parathyroidectomized. True anti-tumour activity of mithramycin may result in an inhibition of these sterols, and thus prevent osteolysis.…”

Section: Discussionmentioning

confidence: 99%

Renal Function and Alterations in Plasma Electrolyte Levels in Normocalcaemic and Hypercalcaemic Patients with Malignant Diseases, Given an Intravenous Infusion of Mithramycin

Fillastre¹,

Maitrot²,

Canonne³

et al. 1974

Chemotherapy

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17 patients suffering from visceral malignant disease were divided into two groups, one of 8 patients with hypercalcaemia secondary to neoplastic osteolysis, the other of 9 patients in whom this was not present. The patients underwent an intravenous infusion of 25 μg/kg mithramycin at a constant rate over 3 h. A study was made of changes in phosphorus and calcium metabolism and of renal function. (1) In 8 hypercalcaemic subjects, serum calcium fell from 133.6 ± 14 to 120.0 ± 18.4 mg/l (p < 0.01). There was a fall in calciuria and in the UV_Ca/UV_inulin ratio. Serum phosphorus and serum magnesium showed no change. Serum potassium showed a significant reduction (p < 0.01) during this study. Renal function, as shown by creatinine, inulin and PAH clearances, was not reduced. (2) In 9 normocalcaemic subjects, the fall in serum calcium was less pronounced, from 92.4 ± 2.4 to 86.6 ± 2.9 mg/l. There was an increase in phosphaturia during the last hour of the test. There was also a fall in serum potassium. Renal function remained normal. The action of mithramycin is discussed. It appears to prevent bony resorption and to act on osteoclasts. Its effects appears to be limited by a secondary secretion of parathormone. The effect of mithramycin on calcaemia varies in degree from individual to individual, is transient, and is often insufficient to restore serum calcium levels to normal.

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Osteolytic Sterol in Human Breast Cancer

Cited by 112 publications

References 5 publications

Hypercalcemia Complicating Breast Cancer

Hypercalcemia Complicating Breast Cancer

Metabolism of β-sitosterol in man

Renal Function and Alterations in Plasma Electrolyte Levels in Normocalcaemic and Hypercalcaemic Patients with Malignant Diseases, Given an Intravenous Infusion of Mithramycin

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