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)

A 12-year-old female, neutered German shepherd dog developed progressive hindlimb followed by forelimb ataxia leading to tetraplegia. Neurological examination suggested lower motor dysfunction. Biochemical evaluation revealed a monoclonal hypergammaglobulinaemia, hypoalbuminaemia and hypercalcaemia. Multiple lytic lesions were identified radiographically in numerous bones. A bone marrow aspirate confirmed the diagnosis of multiple myeloma, with large numbers of plasma cells seen in clusters. An electromyogram revealed positive sharp waves and fibrillation potentials in the skeletal muscles of the limbs, suggesting a polyneuropathy. The dog was treated with chemotherapy using melphalan and prednisolone. Both the hypergammaglobulinaemia and the polyneuropathy resolved and the dog had normal motor function four weeks after commencing treatment. Polyneuropathy may occur as a paraneoplastic syndrome secondary to myeloma, and in this case was reversible following treatment of the underlying disease.
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PMID:Multiple myeloma with associated polyneuropathy in a German shepherd dog. 963 62

Expression of parathyroid hormone-related protein (PTHrP) in breast carcinoma is a frequent cause of the paraneoplastic syndrome of hypercalcemia. In response to treatment with estrogen or tamoxifen, some breast cancer patients also develop a transient hypercalcemia. Therefore, the effect of 17beta-estradiol (E2), tamoxifen, or its more potent metabolite, 4-hydroxytamoxifen (OH-tamoxifen), on PTHrP expression in an estrogen receptor (ER)-positive breast carcinoma cell line (MCF-7) was evaluated. E2 increased PTHrP mRNA levels in MCF-7 cells and stimulated PTHrP(1-86) release in a dose-dependent fashion (10(-10)-10(-6) M). Tamoxifen and OH-tamoxifen also stimulated PTHrP release in a concentration-dependent fashion that paralleled their relative ER binding affinities (10(-6) or 10(-8)-10(-6) M, respectively). Combined treatment with the partial estrogen agonist, OH-tamoxifen, and E2 decreased E2-stimulated PTHrP secretion in MCF-7 cells to the levels seen with OH-tamoxifen treatment alone. These results suggest that transient estrogen- or tamoxifen-induced hypercalcemia in patients with breast carcinoma may be a PTHrP-mediated effect that is a marker of ER positivity.
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PMID:Regulation of parathyroid hormone-related protein expression in MCF-7 breast carcinoma cells by estrogen and antiestrogens. 979 Sep 98

Hypercalcemia is a common paraneoplastic syndrome due to the secretion by tumors of parathyroid hormone-related protein (PTHrP) and/or other osteolytic factors. In the present study, we have measured plasma PTHrP using two immunoradiometric assays for PTHrP, assay N (Nichols) and assay I (INCSTAR), recognizing the 1-86 domain of PTHrP, for the evaluation of malignancy-associated hypercalcemia. The study included 25 tumor patients with hypercalcemia (HCa) [corrected serum calcium (SCa) > or = 2.70 mmol/L], 20 normocalcemic patients with cancer (NCa), and ten healthy control subjects. Plasma PTHrP was either undetectable or within the respective normal range in the majority of NCa patients and in the control subjects, with both assays. Plasma PTHrP was increased in 13 and 15 of HCa cases with assay N and assay I, respectively. PTHrP was elevated in plasma in 5/6 (assay N) and 3/6 (assay I) HCa patients with squamous tumors. However, plasma PTHrP was high in only 2/9 (assay N) and 1/9 (assay I) HCa cases with hematological tumors. Less than 40% of HCa patients with bone metastases, and >75% of those without bone involvement, had elevated plasma PTHrP with both assays. Detectable plasma PTHrP and SCa were significantly correlated using assay N (p = 0.025) and assay I (p = 0.01), in the HCa group. A highly significant correlation (p <0.001) was found between detectable plasma PTHrP with both assays, and a high agreement between them based on simple kappa statistics (p < 0.001), in the latter group. Our results indicate that each assay may be similarly useful in detecting PTHrP hyperproduction in cancer patients.
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PMID:Comparison of two immunoradiometric assays for parathyroid hormone-related protein in the evaluation of cancer patients with and without hypercalcemia. 985

3 weeks after commencing treatment with estramustine phosphate, typical manifestations of hemolytic-uremic syndrome occurred in a 66-year-old patient with prostate cancer. Urinary tract obstructions were excluded and no renal damage could be identified. An improvement in renal function was achieved by stopping estramustine phosphate and infusing adequate amounts of fluids and electrolytes. Anemia and thrombocytopenia also progressively improved after the discontinuation of chemotherapy. Nausea and vomiting, hepatotoxicity, impotence, reduced libido and hypercalcemia are major side effects of estramustine phosphate, and would be difficult to explain our observations without considering the role played by estramustine phosphate. Our observations suggest that estramustine phosphate might play either a direct role or produce a side effect within the context of latent paraneoplastic syndrome. The improvement in renal function which occurred when treatment stopped might confirm our hypothesis.
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PMID:Hemolytic-uremic syndrome during therapy with estramustine phosphate for advanced prostatic cancer. 994 96

Hypercalcemia is a paraneoplastic syndrome that is associated with squamous cell cancers and which may be of life-threatening proportions. We investigated the incidence and prognostic importance of hypercalcemia in patients with esophageal cancer at the Department of Veterans Affairs Medical Center, Washington, DC, USA. The medical records of 170 patients with esophageal cancer from January 1988 to January 1998 were examined. Of the 170 patients with esophageal cancer, 47 (27.6%) had hypercalcemia during the course of their disease. Five (10.6%) of the 47 hypercalcemic patients were found to have hypercalcemia at the time of diagnosis. Forty-six of the 47 hypercalcemic patients had squamous cell carcinoma and 1 had adenosquamous cell carcinoma. Seven (14.8%) had bony metastasis. The median survival of patients with hypercalcemia and esophageal cancer was 12.4 months and 12.6 months for patients without hypercalcemia. Hypercalcemia is a common complication of squamous cell esophageal carcinoma. The survival of patients with or without this complication is similar; thus, it may not be a poor prognostic factor.
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PMID:Hypercalcemia in patients with esophageal cancer. 1037 79

Paraneoplastic syndromes including leukocytosis, thrombocytosis and hypercalcemia are occasionally seen in patients suffering from progressive malignant disorders. Recent studies have revealed the production of several humoral factors by tumor cells and normal splenic cells of tumor-bearing patients to be the major cause of these reactions. Granulocyte-macrophage colony-stimulating factor (GM-CSF), granulocyte-colony stimulating factor (G-CSF), parathyroid hormone-related peptide, interleukin (IL)-1, IL-6, and tumor necrosis factor (TNF) have been implicated. We describe a 58-year-old Japanese man with squamous cell carcinoma (SCC) on the left sole, which developed in a deep linear scar after a train crash. He developed pulmonary and lymph node metastases, then leukocytosis (57,110/mm3 with 95% neutrophilia), thrombocytosis (86.3 x 10(4)/mm3), and hypercalcemia (7.0 mEq/1), and finally cachexia, followed by death. Serum G-CSF, IL-1 alpha, IL-1 beta, and TNF-beta were determined; revealing G-CSF and IL-1 beta levels were above the upper limits of their normal ranges at 39.2 pg/ml and 4.63 pg/ml, respectively. It is probable that these humoral factors were partially responsible for the paraneoplastic syndromes induced by the cutaneous SCC with metastasis in the present case.
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PMID:Paraneoplastic syndromes of leukocytosis, thrombocytosis, and hypercalcemia associated with squamous cell carcinoma. 1040 79

Paraneoplastic syndromes are rarely described in animal models. It may be useful to have a suitable experimental model to study the mechanisms by which they are produced. In this study, we describe a murine lung adenocarcinoma, P07, which presents hypercalcemia, leukocytosis and cachexia. We determined the presence of PTHrP in plasma as well as GM-CSF produced by P07 cells. TNF-alpha, which is responsible for cachexia, could neither be detected in serum nor in P07 cell supernatants. We conclude that this model, which shows paraneoplastic syndromes similar to those of lung tumor patients, should be useful to study the pathways and significance of these signs.
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PMID:Mechanisms of paraneoplastic syndromes in mice bearing a spontaneous lung adenocarcinoma. 1056 76

Two patients with malignancy-associated hypercalcemia from bone metastases of breast cancer, accompanied by consciousness disturbance, were treated by a combination therapy of pamidronate and salmon calcitonin. The cause of the hypercalcemia in both cases was thought to be expanded bone metastases, which induced a local osteolytic hypercalcemia (LOH). In the end, this regimen could not control the growth of the metastatic tumor, but it produced a more rapid and prolonged decrease in serum calcium level than a single agent, and resulted in lessened consciousness disturbance without adverse effects. Hypercalcemia is a life-threatening paraneoplastic syndrome which requires urgent medical treatment, since malignant hypercalcemia progresses very rapidly and induces several severe complications. In conclusion, this combination therapy was extremely effective for consciousness disturbance accompanying hypercalcemia due to widespread bone metastases of cancer.
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PMID:[Two cases of malignancy-associated hypercalcemia from bone metastases of breast cancer successfully treated with combination therapy using pamidronate and calcitonin]. 1083 49

A 66-year-old man was admitted to our hospital complaining of non-productive cough and low-grade fever. Chest X-ray examination revealed a mass shadow in the right hilum. Transbronchial lung biopsy of the tumor mass yielded a diagnosis of adenocarcinoma. Despite repeated chemotherapy using CDDP and VDS, metastasis to the right adrenal gland and right femur occurred, and was accompanied by hypercalcemia and hypophosphatemia. Serological study revealed elevated levels of PTH-rP and G-CSF. Six months after adenocarcinoma was diagnosed, multiple skin metastases of the cancer were observed. Immunohistochemical staining for PTH-rP and G-CSF indicated that production of cytokines had caused a paraneoplastic syndrome including hypercalcemia and leukocytosis. It appeared that the elevation of G-CSF was induced by IL-6 produced from PTH-rP in cancer tissue. Documentation of similar cases is required.
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PMID:[A case of adenocarcinoma complicated with massive leukocytosis and hypercalcemia]. 1101 67

Hypercalcemia is a common paraneoplastic syndrome. Tumors induce hypercalcemia by a local mechanism associated with the tumor's production of various cytokines increasing bone osteolysis. In addition, many tumors release humoral factors, mainly parathyroid hormone (PTH)-related protein (PTHrP), which stimulates bone resorption and/or tubular calcium reabsorption leading to hypercalcemia. Interaction of PTHrP with other tumor-elaborated cytokines might explain some nonPTH-like features associated with the hypercalcemia of malignancy syndrome. Using assays recognizing various PTHrP epitopes, the majority of hypercalcemic cancer patients have higher immunoreactive PTHrP levels in either plasma or urine than normal subjects. Present data support the concept that PTHrP might also be a factor which promotes tumor growth and also the development of osteolytic metastasis. A variety of therapeutic approaches are available to lower serum calcium in hypercalcemic cancer patients. The pathophysiological mechanisms of hypercalcemia appear to be a determinant of the efficacy of different antihypercalcemic treatments.
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PMID:Hypercalcemia of malignancy--new insights into an old syndrome. 1121 25


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