Treatment of malignancy-associated hypercalcemia with intravenous aminohydroxypropylidene diphosphonate.

Body, Jean‐Jacques; Borkowski, Abraham; Cleeren, Anny; Bijvoet, O. L. M.

doi:10.1200/jco.1986.4.8.1177

Cited by 71 publications

(24 citation statements)

References 16 publications

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“…Although immunohistochemical and molecular analyses clearly demonstrate that the majority of breast cancer cells express PTHrP in primary tumours and metastatic sites and, in particular, in bone metastasis (Southby et al, 1990;Powell et al, 1991;Bundred et al, 1992;Vargus et al, 1992;Bouizar et al, 1993;Kohno et al, 1994a,b), only a little experimental data have been published so far concerning PTHrP secretion from established breast cancer cell lines (Tabuenca et al, 1995;Birch et al, 1995 (Martin, 1988;Mundy, 1990). Recently, newly developed agents, such as bisphosphonate, which decrease the osteolytic activity of osteoclasts, have been used clinically for malignancy-associated hypercalcaemia caused by multiple osteolytic metastases or a high blood level of PTHrP secreted by malignancies (Body et al, 1986(Body et al, , 1989Dumon et al, 1991). However, it has been suggested that those agents are less effective against PTHrPinduced hypercalcaemia than against that caused by multiple bone metastases (Body et al, 1993;Walls et al, 1994 …”

Section: Microcalcifications In the Transplanted Tumoursmentioning

confidence: 99%

A new human breast cancer cell line, KPL-3C, secretes parathyroid hormone-related protein and produces tumours associated with microcalcifications in nude mice

Kurebayashi

Kurosumi²,

Sonoo³

1996

Br J Cancer

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Summary Parathyroid hormone-related protein (PTHrP) is the main cause of humoral hypercalcaemia of malignancy (HHM). We recently established a new human breast cancer cell line, designated KPL-3C, from the malignant effusion of a breast cancer patient with HHM. Morphological, cytogenetic and immunohistochemical analyses indicated that the cell line is derived from human breast cancer. The KPL-3C cells stably secrete immunoreactive PTHrP measured by a two-site immunoradiometric assay, possess both oestrogen and progesterone receptors and are tumorigenic in female nude mice. The addition of phorbol-12-myristate-13-acetate to the medium significantly increased PTHrP secretion from the cells. In contrast, hydrocortisone, medroxyprogesterone acetate and 22-oxacalcitriol decreased PTHrP secretion in a dose-dependent manner. Unexpectedly, a number of microcalcifications were observed in the transplanted tumours. Radiographical examination indicated that the microcalcifications in the tumours are very similar to those commonly observed in human breast cancer. These findings suggest that this KPL-3C cell line may be useful for studying the regulatory mechanisms of PTHrP secretion and the mechanisms that lead to the deposition of microcalcifications in breast cancer.Keywords: breast cancer; hypercalcaemia; cell line; parathyroid hormone-related protein; microcalcification Parathyroid hormone-related protein (PTHrP) is a recently discovered protein sharing strong homology with parathyroid hormone in the N-terminal amino acid sequence as well as biological activity (Suva et al., 1987;Mangin et al., 1988). This protein was originally isolated from human malignant tumours associated with humoral hypercalcaemia. A number of clinical studies indicate that PTHrP is the main cause of HHM (Burtis et al., 1990;Grill et al., 1991;Ratcliffe et al., 1992). In other words, tumour-derived PTHrP acts as a circulating hormone like parathyroid hormone and induces hypercalcaemia. Recently, a series of studies has indicated that PTHrP is commonly expressed in breast cancer and that a higher expression of PTHrP may induce bone metastasis (Southby et al., 1990;Powell et al., 1991;Bundred et al., 1992;Vargus et al., 1992;Bouizar et al., 1993;Kohno et al., 1994a;Kohno et al., 1994b). It is conceivable that the PTHrP secreted by breast cancer cells, which exist in bone marrow, may act as a paracrine effector on osteoclasts, resulting in osteolytic involvement. These findings suggest that the PTHrP secreted by malignant tumours may act as a hormone or paracrine effector in different pathological situations.Microcalcifications are commonly observed in breast cancer tissues (Snyder and Rosen, 1971 al., 1993).We recently established a new human breast cancer cell line, designated KPL-3C, which is derived from the malignant effusion of a breast cancer patient with HHM. Preliminary characterisation of this cell line and the inhibitory effect of steroid hormones on PTHrP secretion are described in the present paper. Materials and methodsThe clinical co...

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Section: Microcalcifications In the Transplanted Tumoursmentioning

confidence: 99%

A new human breast cancer cell line, KPL-3C, secretes parathyroid hormone-related protein and produces tumours associated with microcalcifications in nude mice

Kurebayashi

Kurosumi²,

Sonoo³

1996

Br J Cancer

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“…After this incubation, OBL were fixed (95% isopropanol/5% H20 for 1 hour on ice) and the cAMP-containing alcoholic extract was evaporated. Dry cAMP was resuspended in 0.05 M sodium acetate (pH 5.2) and measured by an in house radioimmunoassay using antiserum G-829 given by Dr H. Heath [13,14]. All measurements were done in triplicate at appropriate dilutions and all samples from one experiment were run in the same assay.…”

Section: Camp Measurementmentioning

confidence: 99%

Effects of secretory products of breast cancer cells on osteoblast-like cells

Lacroix

Siwek

Body

1996

Breast Cancer Res Tr

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The pathogenesis of breast cancer-induced osteolysis remains largely unknown. To evaluate the potential role of osteoblasts as target cells during this process, we incubated SaOS-2 human osteoblast-like cells (OBL) with culture media conditioned by proliferative (PM, 'Proliferation Media') or confluent (CfM, 'Confluence Media') MCF-7 human breast cancer cells. CfM decreased the growth of OBL by 26% (P < 0.01) while PM was without significant effect on this parameter. In contrast, both PM and CfM obtained from MCF-7 cultures increased the cyclic AMP (cAMP) response of OBL to the osteolytic agents PTH (10(-8) M) and PTH-related peptide (PTHrP, 10(-8) M) by a factor of about 3 (P < 0.001), and to prostaglandin E(2) (PGE(2),10(-6) M) by a factor of about 2 (P < 0.01). No significant modulation of OBL growth or sensitivity to PTH, PTHrP, or PGE2 was induced by media obtained from HBL-100 non-malignant immortalized breast epithelial cell cultures. 17betaestradiol (E(2), 10(-8) M) and the antiestrogen tamoxifen (Tam, 10(-7) M) added for 48 h to MCF-7 cultures before collecting conditioned media attenuated and potentiated, respectively, the PM- but not the CfM-induced increase in the response of OBL to PTH or PTHrP Along the same line, the addition to MCF-7 conditioned media of a polyclonal anti-transforming growth factor-beta (TGF-beta) antibody attenuated by about 25% (P < 0.01) the PM-induced increase in OBL response to PTH and PTHrP while abrogating the modulatory effects of E(2) and Tam on that response. Together, our results indicate that MCF-7 breast cancer cells secrete factors which inhibit the growth of OBL and increase their sensitivity to various osteolytic agents. TGF-beta was only partly responsible for these effects, and accounts for their modulation by E(2) and Tam. The identification of other osteoblast-modulatory factor(s) should contribute to a better understanding and treatment of breast cancer-induced osteolysis.

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“…It has been successfully used in the treatment of a wide variety of hypercalcaemic disorders including cancer-associated hypercalcaemia (Body et al, 1986;Cantwell & Harris, 1987;Coleman & Rubens, 1987;Davis & Heath, 1989;Harinck et al, 1987b;Ralston et al, 1989;Sleeboom et al, 1983), thyrotoxicosis (Tan et al, 1988), immobilisation (McIntyre et al, 1989), sarcoidosis (Gibbs & Peacock, 1986), hypercalcaemia following renal transplantation (Leunissen et al, 1986) and primary hyperparathyroidism (Evans, 1987;van Breukelen et al, 1982). In common with the other bisphosphonates, the onset of action is relatively slow, and 1-2 days may elapse before serum calcium values start to fall after intravenous administration (Ralston et al, 1988;Sleeboom et al, 1983;Yates et al, 1987).…”

Section: Pamidronatementioning

confidence: 99%

Medical management of hypercalcaemia.

Ralston¹

1992

Brit J Clinical Pharma

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1. Hypercalcaemia is a common disorder, which frequently requires specific treatment either to control symptoms, or to prevent the development of irreversible organ damage or death. Although the best and most effective way of controlling hypercalcaemia in the long‐term is to treat the underlying cause, medical antihypercalcaemic therapy is often required in clinical practice, either as a holding measure, or because the primary disease cannot itself be treated. 2. The mainstays of medical antihypercalcaemic therapy are firstly, to promote calcium excretion by the kidney by restoring extracellular volume with intravenous saline and secondly, to administer pharmacological agents which inhibit bone resorption. Measures which seek to reduce intestinal calcium absorption are seldom effective. 3. Intravenous bisphosphonates are the treatment of first choice for the initial management of hypercalcaemia, followed by continued oral, or repeated intravenous bisphosphonates to prevent relapse. These drugs have a relatively slow onset of action (1‐3 days) but have potent and sustained inhibitory effects on bone resorption, resulting in a long duration of action (12‐ 30 days). 4. Of the other agents available, calcitonin has an important place in the management of severe hypercalcaemia where a rapid effect is desirable; calcitonin is best used in conjunction with a bisphosphonate however, because of its short duration of action. Intravenous phosphate also has a place in the emergency management of severe hypercalcaemia, but is probably best reserved for patients in whom other less toxic therapies have failed. Corticosteroids are generally ineffective except in certain specific instances and are best avoided in the routine treatment of undiagnosed hypercalcaemia.

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Treatment of malignancy-associated hypercalcemia with intravenous aminohydroxypropylidene diphosphonate.

Cited by 71 publications

References 16 publications

A new human breast cancer cell line, KPL-3C, secretes parathyroid hormone-related protein and produces tumours associated with microcalcifications in nude mice

A new human breast cancer cell line, KPL-3C, secretes parathyroid hormone-related protein and produces tumours associated with microcalcifications in nude mice

Effects of secretory products of breast cancer cells on osteoblast-like cells

Medical management of hypercalcaemia.

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