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)

Alendronate, a bisphosphonate compound, lowers serum calcium in patients with cancer-associated hypercalcemia through its inhibitory effect on bone resorption and as a result symptoms associated with hypercalcemia improve. This study was carried out to investigate the effects of alendronate in patients with hypercalcemia due to bone metastasis of hepatocellular carcinoma (HCC). Two patients were evaluated. Their corrected serum calcium and alpha-fetoprotein (AFP) levels and their computed tomography (CT), bone scintigraphy and magnetic resonance imaging (MRI) findings were evaluated before and during alendronate treatment. After treatment, not only the corrected serum calcium levels but also AFP levels and bone pain decreased; in addition, the regression of the metastatic focus was noted in the MRI analysis. These tumor inhibitory effects of alendronate have not been reported in HCC before; and alendronate might serve to prevent bone metastases in patients with HCC. In conclusion, two patients who developed hypercalcemia associated with bone metastasis after surgery for HCC were treated with alendronate and they experienced alleviation of the pain due to bone metastasis, improvement of their quality of life and a marked decrease in AFP levels with tumor regression.
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PMID:Effects of alendronate on bone metastases and hypercalcemia after surgery for hepatocellular carcinoma. 1109 40

A 57-year-old male patient, recently known with an anal carcinoma with inguinal lymph node involvement, was admitted because of anorexia, nausea, vomiting and constipation. On physical examination the patient was dehydrated, and a systolic murmur, grade III/VI, punctum maximum apex cordis, was heard. Serum calcium was raised (4.50 mmol/l), as was the serum creatinine (328 mumol/l). Both values had been normal 14 days before admission. Serum parathormone was suppressed. A bone scan did not reveal evident lesions in the skeleton. FDG-PET scan showed uptake of the tracer into the bone marrow. A bone biopsy showed metastasis of a squamous cell carcinoma. Shortly after that the patient died. Hypercalcaemia is associated with cancer. Colorectal/anal carcinomas have a low incidence of hypercalcaemia. The prognosis of patients with cancer associated with hypercalcaemia is poor.
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PMID:[Clinical thinking and decision making in practice. A patient with anal cancer and hypercalcemia]. 1110 69

Basic fibroblast growth factor (bFGF) is a potent tumor angiogenesis factor and normal constituent of bone extracellular matrix which does not normally circulate in serum of nonpregnant adult humans. We examined the effects of acute administration of intravenous bisphosphonates on release of bFGF in human serum. Twenty seven men and women (mean age, 64 yr) with cancer-associated hypercalcemia, the majority of whom had osseous metastases, were treated once with an intravenous bisphosphonate. Nearly all twelve patients with elevated baseline serum bFGF ranging from 5-27 pg/mL showed significant decreases in serum bFGF (2-7 days) after iv bisphosphonate treatment. The mathematical product of the patients' initial serum bFGF and intial serum calcium concentration, the 'Ca x bFGF product', was significantly negatively (r = -0.91, P < 0.001) correlated with the acute change in serum bFGF level. No consistent relationship was observed between serum bFGF and serum parathyroid hormone related peptide (PTHrP) levels in the hypercalcemic cancer patients. In a subset of patients with non-hematological malignancies and low baseline serum bFGF, acute changes in serum bFGF were significantly negatively (r = -0.66, P < 0.01) correlated with acute change in serum calcium concentration. These results indicate that release of bFGF in serum of patients with cancer-associated hypercalcemia likely depends predominantly on increased bone resorption. Acute change in low serum levels of bFGF in patients with cancer-associated hypercalcemia treated with intravenous bisphosphonates may be physiologically inversely regulated by acute change in the serum calcium concentration.
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PMID:Effect of intravenous bisphosphonates on release of basic fibroblast growth factor in serum of patients with cancer-associated hypercalcemia. 1200 79

Basic fibroblast growth factor (bFGF) is a potent tumor angiogenesis factor which lacks an amino-terminal signal sequence and does not normally circulate in serum from normal subjects. Naturally-occurring autoantibodies which mimicked basic fibroblast growth factor were described in serum from patients with multiple endocrine neoplasia type 1 prolactinoma or sporadic growth-hormone-secreting adenoma associated with increased bFGF. Since bFGF was increased in serum from a variety of cancers, we used endothelial cell proliferation assay(s) to test for bioactivity in the IgG fraction of serum from 56 patients with cancer-associated hypercalcemia, and normal or control subjects. We now report increased IgG-like endothelial cell activity in serum from a hyper prolactinemic subset (4/19 breast cancer; 1/14 renal cancer; 0/23 lung cancer) of cancer-associated hypercalcemic subjects. Highest activity was found in serum from three breast cancer patients who suffered spinal cord compression/metastases. The activity had properties of antiidiotype bFGF antibodies including reaction with anti-human IgG antibodies, and complete neutralization by rabbit antibodies to intact bFGF. The activity in endothelial cells persisted after storage at 0-4 C for 5 yrs; and [prepared by SDS-PAGE and immunoblotting with anti-human IgG] had apparent mol wt corresponding to the heavy chains of IgG. Serum IgG-like activity from 5 of 5 breast cancer patients and 2 of 2 prostate cancer subjects tested [prepared by anti-bFGF antibody, protein-A immunoaffinity, and hydroxyapatite (HA) chromatography] yielded peak HA-adsorbed activity that eluted with 0.4 M sodium phosphate, and was neutralized 70% by antibodies to intact bFGF. Cancer sera mean peak specific activity (12.0 ng-eq bFGF/ug protein) (n = 7) significantly exceeded (P < 0.001) normal sera mean peak specific activity (0.46 ng-eq bFGF/ug protein) (n = 6) in the 0.4 M sodium phosphate eluate fraction from hydroxyapatite columns. These results imply that long-lasting, bioactive FGF-like autoantibodies may arise spontaneously (and contribute to pathophysiology) in subsets of cancer patients with osseous metastases.
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PMID:Increased fibroblast growth factor-like autoantibodies in serum from a subset of patients with cancer-associated hypercalcemia. 1238 79

This manuscript reviews the theories behind the propensity of prostate cancer to cause bone metastases and skeletal implications of the prostate cancer biology and treatment modalities. The escape of tumor cells from the primary tumor in the prostate to secondary tumor sites in the axial skeleton probably occurs before the primary tumor is detected. Several theories offer explanations for the observed proclivity of prostate tumors to selectively colonize the axial skeleton. The interaction between the tumor cells and cells that populate bone marrow, in particular osteoblasts and osteoclasts, is important for creating a 'fertile' environment where tumor cells can establish and grow. Prostate cancer cells are capable of producing growth factors that can affect both osteoblasts, resulting in osteoblastic bone formation, and osteoclasts, resulting in excessive bone resorption. In addition to the capability to progress from testosterone-dependent to testosterone-independent phenotype, the hallmark of metastatic prostate cancer is osteosclerosis similar to one induced experimentally in nude rats using CWR22 human prostate cancer cell line. Metastatic bone disease caused by excessive bone formation and bone resorption is the major cause of morbidity in patients with prostate cancer. The most common symptoms include pain, pathological fractures, spinal cord compression, cranial nerve palsies, bone marrow suppression and hypercalcemia. The introduction of prostate-specific antigen in clinical practice created a shift to where more prostate cancer patients with early disease receive androgen ablation treatment, which in return causes more bone loss and cancer-associated osteoporosis. Introduction of third generation bisphosphonates to treat skeletal consequences of malignancy further stressed the important interaction between the bone marrow stroma and cancer cells. Nevertheless, animal models and human prostate tumor cell lines that mimic all aspects of skeletal conditions in prostate cancer patients including osteoblastic bone response are needed to develop and screen for novel therapeutic and diagnostic modalities.
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PMID:Skeletal implications of prostate cancer. 1575 51

Nude rats bearing the LC-6-JCK human lung cancer xenograft displayed cancer-associated wasting syndrome in addition to humoral hypercalcemia of malignancy. In these rats, not only PTHrP but also several other human proinflammatory cytokines, such as IL-6, leukemia-inducing factor, IL-8, IL-5 and IL-11, were secreted to the bloodstream. Proinflammatory cytokines induce acute-phase reactions, as evidenced by a decrease of serum albumin and an increase in alpha1-acid glycoprotein. Tumor resection abolished the production of proinflammatory cytokines and improved acute-phase reactions, whereas anti-PTHrP antibody affected neither proinflammatory cytokine production nor acute-phase reactions. Nevertheless, tumor resection and administration of anti-PTHrP antibody similarly and markedly attenuated not only hypercalcemia but also loss of fat, muscle and body weight. Body weight gain by anti-PTHrP antibody was associated with increased food consumption; increased body weight from anti-PTHrP antibody was observed when animals were freely fed but not when they were given the same feeding as those that received only vehicle. Furthermore, nude rats bearing LC-6-JCK showed reduced locomotor activity, less eating and drinking and low blood phosphorus; and anti-PTHrP antibody restored them. Although alendronate, a bisphosphonate drug, decreased blood calcium, it affected neither locomotor activity nor serum phosphorus level. These results indicate that PTHrP represses physical activity and energy metabolism independently of hypercalcemia and proinflammatory cytokine actions and that deregulation of such physiologic activities and functions by PTHrP is at least in part involved in PTHrP-induced wasting syndrome.
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PMID:Parathyroid hormone-related protein (PTHrP) as a causative factor of cancer-associated wasting: possible involvement of PTHrP in the repression of locomotor activity in rats bearing human tumor xenografts. 1580 Sep 41

Alterations in bone architecture and mineral metabolism are common complications of malignancy. Cancers such as breast, prostate, and lung can affect the skeleton either indirectly through the elaboration of factors that act to disrupt normal calcium homeostasis at the level of the kidney and bone; or directly via secondary spread of tumor to bone. Although the pathophysiology of these skeletal complications is diverse, it is clear that the osteoclast and osteoblast are not just bystanders but are active participants in the development and progression of hypercalcemia and bone metastasis. Our understanding of the molecular mechanisms of metastasis leading to tumor cell escape, homing, adhesion, and secondary growth in a hospitable environment are evolving. Treatment modalities aimed at not only reducing tumor burden but altering the skeletal response to tumor have shown benefit. Newer generation bisphosphonates are quite effective in controlling hypercalcemia of malignancy and have been shown to delay progression of skeletal metastases. Clearly, cancer-associated bone morbidity remains a major public health problem. To improve therapy and prevention it is important to understand the pathophysiology of the effects of cancer on bone. This review will detail scientific advances regarding this area.
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PMID:Mechanisms and treatment for bone metastases. 1616 96

The osteonecrosis of the jaws (ONJ) has been reported occasionally in cancer patients treated with radiotherapy and chemotherapy. However, bisphosphonate (BP)-associated ONJ in patients with cancer such as multiple myeloma, breast cancer and prostate cancer mainly administered with intravenous BPs has been first reported in 2003. Since then, many cases over 2,500 are accumulating worldwide. Since BPs are often used for osteoporosis, cancer-associated hypercalcemia and osteolytic bone metastasis, it is speculated that ONJ cases will increase in Japan where a small number of them were reported until now. Most of ONJ in cancer patients receiving BP administration occur after dental treatments such as tooth extraction, periodontal surgery and dental implants, and do not respond to conventional treatment modalities such as debridement, antibiotic therapy and hyperbaric oxygen therapy. No effective therapy for ONJ is established yet and empirical conservative therapy is recommended in the guidelines for prevention, diagnosis, and treatment of ONJ. Therefore, dentists and oral and maxillofacial surgeons need to recognize ONJ as a serious side effect of BPs and to make informed consent to the patients and a close consultation with medical oncologists for administration of BPs.
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PMID:[Bisphosphonates and osteonecrosis of the jaws]. 1727 82

We describe the use of pamidronate to control marked hypercalcemia in an extremely premature infant with neonatal hyperparathyroidism that resulted from an inactivating mutation (R220W) of the calcium-sensing receptor. Despite improvement in bone mineralization and subsequent parathyroidectomy with normalization of the serum calcium level, the combination of chronic lung disease, osteomalacia, and poor thoracic cage growth ultimately proved fatal. Pamidronate therapy seems to be safe in the short-term and effective in helping control hypercalcemia even in the very premature infant, allowing for planned surgical intervention when it becomes feasible.
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PMID:Neonatal hyperparathyroidism and pamidronate therapy in an extremely premature infant. 1797 27

Bisphosphonates (BPs) are often used for the treatment of several diseases such as osteoporosis, cancer-associated hypercalcemia, and osteolytic bone metastasis. Recently, there have been reports of osteonecrosis of the jaw (ONJ) in cancer patients whose treatment regimens include BPs. In this case report, we describe complications and treatment of ONJ in a breast cancer patient with bone metastases who received long-term treatment with BPs. A 70-year-old woman underwent modified radical mastectomy on her left breast cancer and received oral 5-fluorouracil derivatives for 2 years in another hospital. Eleven years after the surgery, she came to our hospital complaining of spinalgia and was diagnosed with recurrent breast cancer with multiple metastases to the stomach, liver, multiple lymph nodes, and spine. After surgery for spine metastases, she was given a combination therapy of trastuzumab (initial bolus: 170 mg/body, followed by two or more cycles of 85 mg/body) every week, docetaxel (100 mg/body) every 3 weeks, and BPs (90 mg/body) every 4 weeks. About 1 year and 4 months later, she complained of pain in her right maxilla; biopsy revealed ONJ. Medical oncologists need to recognize ONJ as a serious side effect of BP treatment; dentists and oral and maxillofacial surgeons need to thoroughly consult patients regarding the administration of BPs and have them make an informed consent.
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PMID:A case of osteonecrosis of the jaw in a breast cancer patient with bone metastases receiving long-term treatment with bisphosphonates. 1868 23


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