Parathyroid Hormone‐related Protein in Hypercalcaemia of Malignancy

Martın, Thomas; Suva, Larry J.

doi:10.1111/j.1365-2265.1989.tb01288.x

Cited by 87 publications

(45 citation statements)

References 72 publications

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“…The response in patients with breast carcinoma and haematological tumours was significantly British Journal of Cancer (1997) 75 (2) better than in those with other tumours. These effects are likely to relate to the underlying mechanisms of hypercalcaemia, which would be expected to be predominantly local osteolytic in the group with haematological tumours (Ralston, 1991), mixed in those with breast tumours (Percival et al, 1985;Isales et al, 1987;Gallacher et al, 1990;Grill et al, 1991) and predominantly humoral in the other solid tumour types (Ralston, 1991;Martin and Suva, 1989). These findings concur with the experience of several previous investigators who have found that patients with humoral hypercalcaemia are more resistant to the effects of bisphosphonates Gurney et al, 1989), probably because of PTHrP-mediated increases in renal tubular reabsorption of calcium, which is unaffected by inhibitors of osteoclastic bone resorption Bonjour et al, 1988;Thiebaud et al, 1990).…”

Section: Discussionmentioning

confidence: 99%

“…The pathophysiology of hypercalcaemia differs depending on the tumour type, but two broad categories are recognized (Mundy and Martin, 1982). In humorally mediated hypercalcaemia, the elevation in blood calcium is most often caused by release of parathyroid hormone-related protein (PTHrP), which causes a generalized increase in osteoclastic bone resorption and increased reabsorption of calcium by the renal tubule (Yates et al, 1988;Ralston, 1987;Martin and Suva, 1989). Alternatively, hypercalcaemia may arise as the result of tumour metastases in bone, which stimulate osteoclastic bone resorption on a multifocal basis, with release of calcium at a rate in excess of that which can be excreted by the kidney.…”

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confidence: 99%

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Dose-response study of ibandronate in the treatment of cancer-associated hypercalcaemia

Ralston

Thiébaud²,

Herrmann³

et al. 1997

Br J Cancer

131

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Summary Hypercalcaemia is an important cause of morbidity in malignant disease. We studied the efficacy and safety of intravenous ibandronate (a new, potent bisphosphonate) in a multicentre study of 147 patients with severe cancer-associated hypercalcaemia which had been resistant to treatment with rehydration alone. Of 131 randomized patients who were eligible for evaluation, 45 were allocated to receive 2 mg ibandronate, 44 patients to receive 4 mg and 42 patients to receive 6 mg. Serum calcium values fell progressively in each group from day 2, reaching a nadir at day 5, and in some patients normocalcaemia was maintained for up to 36 days after treatment. The 2-mg dose was significantly less effective than the 4-mg or 6-mg dose in correcting hypercalcaemia, as the number of patients who achieved serum calcium values below 2.7 mm after treatment was 50% in the 2-mg group compared with 75.6% in the 4-mg group and 77.4% in the 6-mg group (P < 0.05; 2 mg vs others). In a logistic regression analysis, three factors were found to predict response; ibandronate dose (higher doses were more effective), severity of presenting hypercalcaemia (severe hypercalcaemia was associated with less complete response) and tumour type (patients with breast carcinoma and haematological tumours responded better than those with other tumours). Ibandronate was generally well tolerated and no serious drug-related adverse events were observed. We conclude that ibandronate is a safe, well tolerated and effective treatment for cancer-associated hypercalcaemia, which should prove a useful addition to the current range of therapies available to treat this condition.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Dose-response study of ibandronate in the treatment of cancer-associated hypercalcaemia

Ralston

Thiébaud²,

Herrmann³

et al. 1997

Br J Cancer

131

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“…However, the way in which this protection might occur remains obscure. Parathyroid hormone-related peptide (PTHrP) is a newly characterized calciotropic factor which was originally isolated from tumors associated with the paraneoplastic syndrome of humoral hypercalcemia of malignancy (Broadus et al, 1988;Martin and Suva, 1989). PTHrP might be the putative calciotropic factor functioning during lactation: it has biological effects very similar to PTH (Horiuchi et al, 1987;Orloff et al, 1989); it is synthetized in lactating mammary tissue (Thiede and Rodan, 1988;Ratcliffe et al, 1992) and increases calcium and phosphorus secretion into milk (Barlet et al, 1992); in rats, serum levels of PTHrP are increased during lactation and this coincides with stimulation of bone resorption (Miller et al, 1991 (Horiuchi et al, 1987).…”

Section: Discussionmentioning

confidence: 99%

Plasma osteocalcin concentrations in cows around parturition. The influence of a regular versus a very short dry period

Davicco¹,

Rémond²,

Jabet³

et al. 1992

Reprod. Nutr. Dev.

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Summary ― Plasma Ca, P, Mg and OC concentrations were compared between 2 groups of Holstein cows around 2nd calving. Thirteen cows were milked until their daily milk production was lower than 2 kg, which occurred 4 d before parturition. The control group (8 cows) was normally dried 8 weeks before the expected time of calving. Apart from the week following the initiation of the dry period where plasma OC concentrations were significantly lower in dried cows than in the control group (which would indicate lower bone remodeling in dried cows), no significant difference concerning Ca, P, Mg and OC concentrations were observed between the 2 groups of cows. This indicates that the only lack of 1 8-week-long dry period probably has no major immediate effect upon Ca and bone metabolism in young dairy cows given a convenient Ca and P daily intake. Nevertheless, the lack of the dried period might protect the cow against parturient hypocalcemia: the decrease in plasma Ca and P concentrations observed 12 h after calving was less intense in non-dried cows

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“…Humoral hypercalcaemia of malignancy (HCM) is mediated by tumour cell secretion of parathyroid hormone-related protein (PTHrP), a polypeptide that shares some N-terminal homology with the systemic calcium-regulating hormone parathyroid hormone (PTH) (Goltzman et al, 1989; Martin and Suva, 1989). PTH and PTHrP bind to the same cell-surface receptor (the type 1 PTH/PTHrP receptor) (Abou-Samra et al, 1992), and PTHrP exerts many effects on target cells in common with PTH, including elevation of intracellular cAMP (Birch et al, 1995) and [Ca2+], (Donahue et al, 1988;Schofl et al, 1991).…”

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confidence: 99%

PTHrP and the PTH/PTHrP receptor are co-expressed in human breast and colon tumours

Carron

Fraser²,

Gallagher³

1997

Br J Cancer

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Summary Using RNA extracted from human tumour samples removed during surgery, we have analysed expression of mRNA for parathyroid hormone-related protein (PTHrP) and for the PTH/PTHrP receptor by RT-PCR in a panel of human breast and colon tumours. All but 1 of 18 breast tumour samples expressed PTHrP, whereas receptor expression was detected in 11 of these. Expression of the PTH/PTHrP receptor was found in three out of four metastatic lesions, including one sample in which no receptor was detected in the primary tumour. PTHrP expression was also detected in five colon tumours, and receptor expression detected in two of these. These results demonstrate that PTHrP and the PTHrP receptor are also co-expressed in breast tumours in vivo and provide further evidence that PTHrP may be an important autocrine/paracrine growth factor in breast cancer.

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Parathyroid Hormone‐related Protein in Hypercalcaemia of Malignancy

Cited by 87 publications

References 72 publications

Dose-response study of ibandronate in the treatment of cancer-associated hypercalcaemia

Dose-response study of ibandronate in the treatment of cancer-associated hypercalcaemia

Plasma osteocalcin concentrations in cows around parturition. The influence of a regular versus a very short dry period

PTHrP and the PTH/PTHrP receptor are co-expressed in human breast and colon tumours

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