Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020437 (hypercalcemia)
 10,293 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Thirty-eight normocalcemic patients with bone metastases from breast carcinoma were randomized to receive dichloromethylene diphosphonate (CL2MDP) in addition to their specific antitumor treatment (chemotherapy and/or hormone therapy), at a dose of 300 mg/day/i.v. or placebo for the first 7 dys. The CL2MDP treatment then continued at a dose of 100 mg day/i.m. for 3 weeks and finally at 100 mg i.m. on alternate days for at least another 2 months. In both groups of patients there was a reduction in the intensity of pain (Scott-Huskisson analog), but there was a more frequent reduction in the daily consumption of analgesics in patients treated with CL2MDP (p = 0.02). Unlike the controls, the patients who received CL2MDP presented a significant reduction in urinary calcium (p = 0.003) and in hydroxyproline (p = 0.05) on the 7th day. As regards the clinical evolution, negative events such as the appearance of hypercalcemia, pathological fractures, new bone lesions or a substantial increase in the preexisting ones, were observed in 9 of the 12 evaluable patients treated with placebo and in 3 out of 9 treated with CL2MDP. Thickening of the preexisting osteolytic lesions was reported in 2 patients treated with CL2MDP. Tolerance was excellent: only a few patients complained of pain at the intramuscular drug injection site.
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PMID:Controlled clinical study on the use of dichloromethylene diphosphonate in patients with breast carcinoma metastasizing to the skeleton. 182 15

Bone metastases and hypercalcemia are common in patients with advanced cancer and may present major problems for physicians treating these patients. The recent development of the bisphosphonates has improved therapy for these two conditions. These compounds, pyrophosphate analogs with a P-C-P backbone, which binds tightly to calcified bone matrix, include etidronate, clodronate, and pamidronate. All three are useful for the treatment of hypercalcemia, but pamidronate seems to be the most effective. Currently investigational in the United States, pamidronate is now in active clinical testing. The author discusses the administration, dosage and side effects, and results of current studies.
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PMID:Bisphosphonate treatment of bone metastases and hypercalcemia of malignancy. 183 53

The bisphosphonate clodronate has been widely used in the treatment of hypercalcaemia and osteolytic bone metastases. It can normalize plasma calcium in most hypercalcaemic, rehydrated cancer patients when increased bone resorption is the prevailing disturbance of calcium metabolism. When given intravenously either as a single infusion or as repeated daily administrations, serum calcium levels fall to normal 3-5 days after the onset of therapy. Long-term maintenance treatment must be adjusted individually since relapse appears to depend upon the tumour type, the degree of malignancy and any anticancer therapy. In patients in whom increased tubular calcium reabsorption is the prevailing disturbance of calcium metabolism, the effect of clodronate on plasma calcium is incomplete, despite the normalization of bone resorption. This type of therapeutic response can be reproduced experimentally in bisphosphonate-treated animals receiving a constant infusion of parathyroid hormone-related peptide, a peptide isolated from various tumour types including lung, kidney, breast and neuroendocrine tumour of the pancreas. In patients having a good response to clodronate, the fall in plasma calcium is accompanied by an increase in the calcium-regulating hormones, parathyroid hormone and 1,25-dihydroxyvitamin D3. This homeostatic response probably explains why hypocalcaemia occurs rarely in clodronate-treated patients. No serious side-effects of treatment have been reported. Clodronate appears to be a safe and effective treatment for the hypercalcaemia of malignancy, where increased bone resorption is the major mechanism disturbing the homeostasis of extracellular calcium.
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PMID:Treatment of hypercalcaemia of malignancy with clodronate. 183 97

Bone metastases secondary to myeloma, are characterized by severe bone pain, pathological fractures, hypercalcaemia and hypercalciuria. Histological and biochemical investigations have shown a wide spectrum of abnormalities in bone turnover in patients with multiple myeloma. The increased osteoclast activity caused by various osteoclast activating factors secreted by myeloma cells, is responsible for the diffuse localized osteolytic lesions. These lesions are responsible for the symptoms and respond poorly to standard chemotherapy, justifying the use of a bone-sparing agent. Clodronate is a potent inhibitor of osteoclast activity and does not impair bone mineralization. Several studies have shown that clodronate can normalize serum calcium in hypercalcaemic patients with metastatic bone disease, and a similar response is seen in multiple myeloma. In a long-term (18 months) placebo-controlled study we have shown that clodronate, given orally at a daily dose of 1.6g, can decrease both the incidence of pathological fractures and the activity of osteoclasts, as judged by measurements in iliac crest biopsy. These results, along with those from two other studies, are promising and suggest that clodronate may inhibit the progression of osteolytic lesions in multiple myeloma.
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PMID:The use of clodronate in multiple myeloma. 183 98

The case of hypercalcemia secondary to metastasis to a benign parathyroid adenoma is reported. The patient had documented lung adenocarcinoma with multiple bone metastases and a mass in the lower anterior neck for at least 5 months before hypercalcemia and hypophosphatemia resistant to treatment developed. Autopsy revealed widespread metastatic disease including metastatic tumor invading a benign parathyroid adenoma. The analysis of four cases of metastatic cancer spread to a benign parathyroid adenoma reported previously revealed that two of them also had hypercalcemia during a late stage of the disease. There are data that the incidence of metastases to parathyroid gland might be as high as 11.9%, and the incidence of parathyroid adenomas in patients with cancer is significantly higher than in controls. The metastases to benign parathyroid adenomas might be another mechanism of hypercalcemia of malignancy.
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PMID:A case of adenocarcinoma of the lung associated with a neck mass and hypercalcemia. 191 81

To elucidate the actual incidence of hypercalcemia in patients with esophageal carcinoma, 382 consecutive cases admitted to the National Cancer Center Hospital (Tokyo, Japan) from 1983 to 1988 were investigated. Hypercalcemia was detected in 5 patients of 376 (1.3%) at the time of primary detection of cancer, and in 45 patients of 120 (38%) patients with recurrent or unresectable cancer who were monitored within 2 months of death. These observations demonstrated that this electrolyte imbalance is a frequent paraneoplastic syndrome observed in patients with advanced esophageal carcinoma. With regard to the etiology, bone metastases were detected in 13 of 49 patients with hypercalcemia; the remaining 36 patients were assumed to be induced by the production of hypercalcemic substance(s) by tumor tissues. Parathyroid hormone-related protein (PTHrP) is a newly discovered factor which increases serum calcium in vivo. The detection of PTHrP mRNA in tumor tissues as well as the production of PTHrP-like immunoreactivity by tumor tissues were closely associated with the development of hypercalcemia, suggesting that PTHrP is the major cause of hypercalcemia in patients with esophageal carcinoma.
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PMID:Hypercalcemia in patients with esophageal carcinoma. The pathophysiologic role of parathyroid hormone-related protein. 193 13

A RIA for PTH-related protein (PTHrP) is described, using a polyclonal goat antiserum against synthetic PTHrP-(1-40) and recombinant PTHrP-(1-84) as standard. The detection limit is 2 pmol/L, and intra- and interassay coefficients of variation are 4.8% and 13.6%, respectively. This assay does not detect PTH even at concentrations of up to 2000 pmol/L. Cross-reactivity studies using various synthetic PTHrP peptides localize the antibody-binding epitope between residues 20 and 29. Hypercalcemic patients with a range of solid tumors and no evidence of bone metastases on radionuclide scanning (n = 27) all had detectable PTHrP levels (range, 2.8-51.2 pmol/L). Of 17 patients with solid tumors (other than breast) and bone metastases, 11 (64%) also had detectable PTHrP levels (range, 4.9-47.5 pmol/L). Twenty samples from breast cancer patients with hypercalcemia, 19 with evidence of bone metastases, and 1 with a negative bone scan were assayed, and detectable PTHrP levels were found in 13 (65%; range, 3.8-61.6 pmol/L). Patients with squamous cell carcinomata and normal serum calcium levels (n = 11) had no detectable PTHrP or levels close to the detection limit of the assay (range, less than 2 to 3.7 pmol/L). Plasma levels in normal volunteers were below the detection limit of the assay in all but 1 of 38 normal subjects. Patients with chronic renal failure on hemodialysis (n = 18) and patients with primary hyperparathyroidism (n = 14) all had undetectable PTHrP in this assay. This assay allows positive identification of patients with PTHrP-mediated hypercalcemia and, therefore, should be useful in the clinical investigation of the hypercalcemic patient. Furthermore, it has allowed detection of circulating PTHrP in hypercalcemic breast cancer patients with bone metastases, indicating a significant role for PTHrP in this disease.
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PMID:Parathyroid hormone-related protein: elevated levels in both humoral hypercalcemia of malignancy and hypercalcemia complicating metastatic breast cancer. 195 13

The mechanisms of hypercalcaemia were assessed in 20 hypercalcaemic patients with breast cancer. Abnormalities suggestive of a PTH-related peptide (PTHrP) mechanism were observed in up to 60% of cases; urinary cyclic adenosine monophosphate (UcAMP) was elevated in nine patients (45%), renal tubular reabsorption of calcium (RTRCa) was elevated in nine (45%) and the renal tubular threshold for phosphate reabsorption (TmPO4) depressed in 12 (60%). While TmPO4 was lower in patients with high UcAMP, there was no consistent relationship between RTRCa and UcAMP or UcAMP and the extent of bone metastases. In a control group of nine normocalcaemic breast cancer patients, bone resorption as assessed by urinary calcium/creatinine ratio was slightly increased but UcAMP, RTRCa and TmPO4 were generally normal. These observations indicate that a PTHrP-mediated mechanism of hypercalcaemia may be operative in up to 60% of patients with breast cancer, irrespective of the presence or extent of bone metastases.
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PMID:Breast cancer-associated hypercalcaemia: a reassessment of renal calcium and phosphate handling. 196 70

In a consecutive series of 771 patients with pathologically verified squamous cell carcinoma of the head and neck, 28 patients (3.6%) had hypercalcemia (greater than 11.0 mg/dl) during the course of their disease. The buccal mucosa (16/205, 7.8%) and tongue (8/148, 5.4%) were the most frequent primary sites. Most of the patients were stage IV patients with recurrence and advanced disease. The prognosis was poor with a median survival of only 6 weeks. The possible etiology of their hypercalcemia included humoral factors, bone metastases and independent primary lung cancer. The treatment of hypercalcemia was evaluated in 22 patients. Success was noted in all patients initially receiving chemotherapy (10 cases) or radiotherapy (3 cases) with or without saline hydration plus furosemide diuretics. However, the response rate in patients (9 cases) initially receiving hydration plus furosemide diuretics alone was 22% (2/9), with 4 of 7 failure cases later responding to chemotherapy. It is suggested that hypercalcemia be treated with chemotherapy or radiotherapy quickly, along with hydration plus diuretics. Also, the serum calcium level must be checked in patients with advanced buccal or tongue cancer.
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PMID:Hypercalcemia in squamous cell carcinoma of the head and neck. 197 96

Hypercalcemia is the most frequent paraneoplastic syndrome observed in cancer patients. This morbidity can be divided into two categories: one is hypercalcemia induced by severe bone metastases; the other the elaboration of hypercalcemic factors by solid tumors, termed humoral hypercalcemia of malignancy (HHM). With regard to humoral factors responsible for HHM, a protein with parathyroid hormone (PTH)-like activity, designated PTH-related protein (PTHrP), was isolated from a cancer cell line established from a hypercalcemic patient's lung cancer tissue, and the structure of PTHrP mRNA was identified. Since the biological activity of PTHrP explained most of the clinical and laboratory findings of HHM patients and recent clinical studies indicated the very close relationship between the development of HHM and the production of PTHrP by tumor, PTHrP is now regarded to be the primary candidate for the actual factor responsible for HHM.
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PMID:[Malignancy-associated hypercalcemia]. 200 37


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