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)

Breast and prostate carcinomas are the tumors most commonly associated with skeletal metastases, and the skeleton is the most common site of metastatic disease and of first distant relapse in breast cancer. Bone metastases are the source of considerable morbidity, including pain and functional disability, fractures, hypercalcemia, and epidural compression. The classical radionuclide bone scan remains the most effective tool for the screening of metastatic bone disease, but X-rays are more specific and remain the essential tool for the diagnosis and characterization of bone metastases. Computed tomography is much more useful to diagnose early metastatic involvement of bone, particularly of the spine. Patients with exclusive skeletal metastatic involvement are still frequently excluded from classical therapeutic trials because of the difficulties in the assessment of response. Recalcification of osteolytic lesions is indeed required when defining an objective response, but this criterion is insensitive and not quantitative. Moreover, the development of new osteoblastic lesions is often of difficult interpretation. A concomitant bone scan will help, but the absence of quantification of the changes and the "flare" phenomenon limit the usefulness of the technique. Pain and quality of life constitute simple, but frequently neglected, parameters of response to therapy. The clinical utility of tumor markers and of biochemical markers of bone turnover should also be more fully investigated. Neoplastic osteolysis is essentially mediated by the osteoclasts, which seem to be activated, maybe indirectly through the osteoblasts, by some tumor products. Various substances of tumoral origin have been proposed as mediators for this osteoclast activation, such as transforming growth factors, prostaglandins, and, more recently, products of the immune cells or parathyroid hormone-related peptide.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Metastatic bone disease: clinical and therapeutic aspects. 158 Nov 21

Seventy-five female patients suffering from advanced breast cancer were treated with toilet mastectomy, radiotherapy and oophorectomy (if premenopausal) or tamoxifen therapy (if postmenopausal) as well as chemotherapy with cyclophosphamide, methotrexate, 5-fluorouracil and prednisone. The most common side-effects of combined chemohormonal therapy were gastro-intestinal (nausea, vomiting, rarely diarrhoea) in 43 patients (57.3%), followed by alopecia in 23 patients (30.6%), myelosuppression in 12 patients (16%), extravasation and thrombophlebitis in 7 patients (9.3%), and mucositis and oral erythema in 3 patients (4%). Side-effects of tamoxifen therapy such as vaginal discharge, bleeding, hot flushes were encountered in 10 patients (13.3%). Hypercalcaemia, tumour flare and hepatic, renal, cardiac, pulmonary and neurological toxicities were not encountered. Improvement of 10-30% in Karnofsky performance status was noted in responders while 20-30% deterioration was observed in non-responders. Combination therapy was mostly well tolerated, side-effects were few and toxicities were temporary and reversible.
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PMID:Toxicity and side-effects of combination chemohormonal therapy of advanced breast cancer. 158 18

The presence of parathyroid hormone related protein (PTHRP) in human breast cancers has been assessed by immunohistochemistry using a polyclonal antiserum specific for the mid-region sequence 37-67 in an immunoperoxidase technique. The primary tumours from 155 normocalcaemic, consecutive women with early breast cancer who had been followed up for a minimum of 5 years were assessed. Dewaxed paraffin sections of formalin fixed tissue was used throughout. Positive PTHRP staining was detected in 56% of the cancers and was unrelated to standard prognostic factors, recurrence or survival. However, PTHRP positivity was related to the development of bone metastases (P less than or equal to 0.03) and hypercalcaemic episodes. PTHRP is implicated as the humoral factor responsible for hypercalcaemia associated with breast cancer and tumour positivity may be a useful predictor of which women will develop bone metastases.
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PMID:Parathyroid hormone related protein and skeletal morbidity in breast cancer. 159 Oct 95

Complications of breast cancer involving the skeleton include hypercalcaemia, bone pain and fracture. These complications arise because of progressive osteolysis which is in turn dependent on the activation of osteoclasts by tumour and host tissues. Clodronate is a powerful inhibitor of osteoclastic bone resorption which led us to evaluate its potential in metastatic breast cancer. When given intravenously it lowers serum calcium in the majority of hypercalcaemic patients. A convenient regimen is 600 mg iv as a single dose infused over several hours. We have additionally shown in a double-blind cross-over study that this regimen also has a significant effect on bone pain. This had led us to assess the longer term effects of clodronate by mouth in a prospective double-blind study of patients with established skeletal metastases. These studies are not yet complete but the agent appears to prevent hypercalcaemia and trends are emerging which indicate that the incidence of bone pain and fractures may also decrease.
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PMID:Treatment of skeletal disease in breast cancer with clodronate. 172 12

Osteolytic bone metastases secondary to breast cancer are extremely common, occurring in more than 50% of breast cancer patients. The resulting increased bone resorption leads to significant symptomatic morbidity caused by bone pain, hypercalcaemia and pathological fracture. Clodronate, an anti-osteolytic agent, inhibits osteoclastic bone resorption and has considerable therapeutic value. Recent studies have shown that clodronate is effective in the treatment of malignancy hypercalcaemia, relief of bone pain and decreases the risk of pathological fracture. The use of clodronate in the future, other than as a palliative therapy, may focus upon the prevention of osteolytic bone metastases at the time of primary diagnosis or later in the disease progression in those patients at risk, for example, those with non-osseous relapse. Since patients with bone metastases secondary to breast cancer often have an increased duration of survival, any agent that would decrease the symptomatic morbidity would have a significant impact upon quality of life, even more so if the actual development of osteolytic bone metastases was delayed or prevented.
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PMID:Clodronate: the potential for the future. 172 14

Osteoclastic activity is increased in tumor-associated hypercalcemia, which, thus, constitutes an excellent opportunity to assess new markers of the bone resorption rate. We have measured the fasting urinary excretion of the pyridinium cross-links pyridinoline (Pyr) and deoxypyridinoline (D-Pyr) in 36 hypercalcemic cancer patients (mean +/- SD, 3.2 +/- 0.4 mmol/L for total serum Ca and 1.66 +/- 0.24 mmol/L for Ca2+). Thirty-two of them were reevaluated after treatment with iv bisphosphonates. Urinary Pyr and D-Pyr levels were higher than those in healthy controls (130 +/- 62 vs. 40 +/- 19 nmol/mmol creatinine for Pyr and 20 +/- 15 vs. 6 +/- 3 nmol/mmol creatinine for D-Pyr; P less than 0.001 for both). This represented a mean 3.3-fold increase over the normal mean compared to 5.8- and 3.4-fold increases for fasting urinary Ca and hydroxyproline, respectively. Individual values were elevated in 83% and 75% of the cases for Pyr and D-Pyr compared to 97% and 83% for urinary Ca and hydroxyproline, respectively. The levels of Pyr and D-Pyr tended to be higher in patients with head and neck tumors than in patients with breast cancer. Urinary Pyr and D-Pyr correlated with each other (r = 0.72; P less than 0.001) and were highly correlated with hydroxyproline (r = 0.68 and 0.83, respectively; P less than 0.001 for both), but poorly correlated with urinary Ca (r = 0.21; P = NS and r = 0.42; P = 0.01, respectively), suggesting that these markers reflect different events of bone resorption. Similarly, after bisphosphonate therapy, urinary Pyr and D-Pyr levels fell by 31% and 50%, respectively, compared to 38% for hydroxyproline and 76% for urinary Ca. There was a significant correlation between posttreatment D-Pyr and serum Ca levels (r = 0.43; P less than 0.05). In summary, we found that the urinary excretion of Pyr and D-Pyr was markedly increased in hypercalcemic cancer patients and was adequately lowered by bisphosphonate therapy. The urinary excretion of the pyridinium cross-links, especially D-Pyr, should be helpful to specifically quantitate bone matrix resorption and monitor the inhibition of bone resorption in cancer patients receiving antiosteolytic drugs.
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PMID:Urinary pyridinium cross-links as markers of bone resorption in tumor-associated hypercalcemia. 174 Apr 78

Between November 1985 and October 1989, 1413 patients were admitted to the medical intensive care unit (ICU) of our cancer hospital. Data collected at admission and during the ICU stay were analysed for: 1) medical problems and treatment modalities requiring the admission; 2) types of underlying disease; 3) mortality during intensive care; 4) nursing requirements. Of the 1413 admissions, 1220 were for solid tumors (mainly ovarian cancer, breast cancer and lung cancer) and 144 for hematological malignancies. Overall mortality during the ICU stay was 10%. There was a relative lack of nurses, as shown by the evaluation of the nursing activity with the TISS. 621 admissions were because of a medical emergency such as hypercalcemia or respiratory failure. Overall mortality was 22%. Of 64 patients treated by artificial ventilation, 46 (72%) died during their ICU stay. 732 admissions were made in order for administration and monitoring of special treatment or new therapeutic modalities including phase I drug infusion, intraperitoneal chemotherapy, intensive (megadosage) chemotherapy, lipophilic drug containing liposomes and coadministration of platinum derivatives. Our experience emphasizes the role of ICU facilities in modern oncology for both optimal supportive care in emergency cases and the safe development of new anticancer modalities.
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PMID:Medical cancer patients and intensive care. 177 58

PTHrP, a newly characterized peptide is responsible for humoral hypercalcemia of malignancy in squamous cancers. It is also expressed by a variety of normal tissue and might have growth factor propriety. It is expressed by lactating breast and is frequently present in breast cancer. Although it is responsible for humoral hypercalcemia in an animal model of breast cancer its role in breast cancer hypercalcemia is still putative. The possibility that it might be one of the autocrine growth factors implicated in breast cancer cell proliferation has been suggested.
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PMID:Parathyroid hormone related protein (PTHrP) and breast cancer. 181 3

The intravenous administration of Clodronate, a strong inhibitor of osteoclastic activity provides a safe and very effective treatment of hypercalcemia whether secondary to bone metastasis or due to paraneoplastic syndrome. Its action is fast, exclusively osseous and lasts up to 7 days. The response is incomplete when increased renal absorption is the predominant mechanism of hypercalcemia. The data published by Elomaa et al on osteolytic metastases in breast cancer patients show a significant improvement with regard to pain reduction, prevention of fractures as well as hypercalcemia. The results obtained using a 1-yr oral treatment need further confirmation.
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PMID:[Value of Clodronate in the treatment of bone metastasis]. 183 87

A phase I multicenter evaluation of a novel antiestrogen, toremifene, was undertaken in postmenopausal women with various advanced difficult-to-treat malignancies. One hundred and seven women were treated at one of six dosage levels (10, 20, 40, 60, 200, or 400 mg/d orally) for at least 8 weeks. Weekly evaluations for toxicity were conducted. The most common side effects were nausea (31%), vomiting (12%), and hot flashes (29%). Five patients were removed from the study for possible adverse reactions: three patients experienced hypercalcemia; one experienced tremulousness, fatigue, and inability to think clearly; and one had vaginal bleeding. Twelve patients died while on study, 11 with disease progression and one with a pulmonary embolus. Sex hormone-binding globulin (SHBG) levels increased and there was a modest decline in serum antithrombin III levels. Four of 48 assessable patients had partial responses: three with breast cancer and one with endometrial cancer. Toremifene was generally well tolerated at the doses tested.
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PMID:Phase I study of toremifene in patients with advanced cancer. 183 8


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