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)

Humoral hypercalcemia of malignancy (HHM) is mediated primarily by skeletal and renal responses to tumor-derived PTHrP. PTHrP mobilizes calcium from bone by inducing the expression of receptor activator for nuclear factor-kappaB ligand (RANKL), a protein that is essential for osteoclast formation, activation, and survival. RANKL does not influence renal calcium reabsorption, so RANKL inhibition is a rational approach to selectively block, and thereby reveal, the relative contribution of bone calcium to HHM. We used the RANKL inhibitor osteoprotegerin (OPG) to evaluate the role of osteoclast-mediated hypercalcemia in two murine models of HHM. Hypercalcemia was induced either by sc inoculation of syngeneic colon (C-26) adenocarcinoma cells or by sc injection of high-dose recombinant PTHrP (0.5 mg/kg, s.c., twice per day). In both models, OPG (0.2-5 mg/kg) caused rapid reversal of established hypercalcemia, and the speed and duration of hypercalcemia suppression were significantly greater with OPG (5 mg/kg) than with high-dose bisphosphonates (pamidronate or zoledronic acid, 5 mg/kg). OPG also caused greater reductions in osteoclast surface and biochemical markers of bone resorption compared with either bisphosphonate. In both models, hypercalcemia gradually returned despite clear evidence of ongoing suppression of bone resorption by OPG. These data demonstrate that osteoclasts and RANKL are important mediators of HHM, particularly in the early stages of the condition. Aggressive antiresorptive therapy with a RANKL inhibitor therefore might be a rational approach to controlling HHM.
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PMID:The inhibition of RANKL causes greater suppression of bone resorption and hypercalcemia compared with bisphosphonates in two models of humoral hypercalcemia of malignancy. 1600 71

Humoral hypercalcemia can arise from a variety of malignancies, but its association with primary colorectal carcinoma is rare, with only 20 such cases documented in the English-language literature to date. We report an additional case to clarify the clinicopathologic features of colorectal carcinoma with humoral hypercalcemia. A 54-year-old woman was admitted with symptomatic hypercalcemia of 14.2 mg/dl and multiple hepatic metastases, 2 years after resection of sigmoid colon cancer. The hypercalcemia was caused by the circulating parathyroid hormone-related peptide (PTHrP) produced by poorly differentiated adenocarcinoma in the liver. The PTHrP level on admission was 13.5 pmol/l. Despite systemic chemotherapy, the patient died of disease progression 3 weeks after the humoral hypercalcemia was diagnosed. A review of the 21 reported cases, including ours, suggests that colorectal carcinoma associated with humoral hypercalcemia is characterized by a poorly differentiated tumor with or without squamous or neuroendocrine features, distant metastases, and a dismal prognosis.
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PMID:Humoral hypercalcemia complicating adenocarcinoma of the sigmoid colon: report of a case. 1603 53

The objective of this study was to present some clinical and radiological manifestations of PNS in relation to bronchogenic carcinoma (BC) and to evaluate the usefulness of imaging findings in the diagnosis of asymptomatic BC. In the study group of 204 patients (146 male and 58 female) with proven bronchogenic carcinoma, PNS was present in 18 (8.62%) patients. The patients with PNS were divided into two groups. The first one consisted of 13 (72.2%) patients with symptoms related to primary tumours while the second one consisted of 5 (27.7%) patients with symptoms, at initial appearance, indicative of disorders of other organs and systems. The predominant disorder was Lambert-Eaton Syndrome, associated with small-cell carcinoma. Endocrine manifestations included: inappropriate antidiuretic hormone production syndrome (small-cell carcinoma), a gonadotropin effect with gynaecomastia and testicular atrophy (planocellular carcinoma, small-cell carcinoma), a case of Cushing Syndrome (small-cell carcinoma), and hypercalcaemia, due to the production of the parathyroid hormone-related peptide, which was associated with planocellular carcinoma. A rare case of bilateral exophthalmos was found as PNS at adenocarcinoma. Digital clubbing and hypertrophic osteoarthropathy (HO) were associated with planocellular and adenocarcinoma, while clubbing was much more common than HO, especially among women. The differences between the two groups were related to the time of PNS appearance. In the first group, PNS occurred late on in the illness, while in the second group, PNS preceded the diagnosis of BC. Alternatively, the disappearance of a clinical or a radiological manifestation of PNS after surgery or chemotherapy may be an indicator of an improvement in health or PNS may be the first sign of illness recurrence. Radiological manifestations of PNS in asymptomatic patients may serve as a useful screen for identifying primary BC. In symptomatic patients, it may be an indicator of a higher likelihood of metastatic disease.
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PMID:[Clinical and radiological manifestations of paraneoplastic syndrome of bronchogenic carcinoma]. 1639 81

The diagnosis of parathyroid hormone-related protein (PTHrP)-secreting metastatic uterine endometrioid cancer was made in a 32-year-old Japanese woman with humoral hypercalcemia of malignancy. The primary endometrial cancer had been removed, and the tumor was diagnosed as Grade 1 endometrioid adenocarcinoma with shallow myometrial invasion. Salvage chemotherapy (paclitaxel and calboplatin) was started from 5 months after surgery when recurrent tumors were detected in the peritoneum and liver. Despite the salvage chemotherapy, the tumor progressed and hypercalcemia became evident with elevated PTHrP whereas no bone metastasis was identified. To the best of our knowledge, this is the first reported case of hypercalcemia due to PTHrP secretion in uterine endometrioid adenocarcinoma.
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PMID:Parathyroid hormone-related protein-secreting uterine endometrioid adenocarcinoma. 1641 86

Mice bearing LP07 lung adenocarcinoma present some characteristics similar to those shown in patients with several malignant diseases. LP07 tumor bearers develop paraneoplastic syndromes such as cachexia, leukocytosis, and hypercalcemia, partly due to a systemic inflammatory response. We analyzed some of the mechanisms involved in the effectiveness of the association of the appetite-stimulant medroxiprogesterone acetate (MPA) and the nonselective cyclooxigenase (COX) inhibitor indomethacin (INDO) in LP07 tumor bearing mice. INDO and INDO plus MPA treatments significantly inhibited tumor growth, which was not inhibited by MPA. The number of lung metastatic nodules was decreased with all treatments, being most effective INDO alone and INDO plus MPA. A significant decrease of plasmatic levels of the matrix metalloproteinases MMP-9 and MMP-2 correlated with these results. Paraneoplastic syndromes, leukocytosis, and cachexia were abolished by all treatments. We determined effects of the treatments on circulating cytokines shown to regulate cachexia and inflammation. Both treatments alone, and INDO plus MPA, reduced circulating IL-6 throughout tumor evolution. A pronounced increase in serum IL-1ss levels was detected in untreated tumor bearers. These levels decreased and were closer to normal serum values when LP07 mice were treated with INDO plus MPA. The combination of a nonsteroidal antiinflammatory drug as INDO and MPA showed to be effective in inhibiting tumor and metastatic growth and diminishing paraneoplastic symptoms and SIR. A variety of specific molecules are implicated as playing a role in cancer-induced cachexia and hematological alterations.
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PMID:Inhibition of tumor progression and paraneoplastic syndrome development in a murine lung adenocarcinoma by medroxyprogesterone acetate and indomethacin. 1653 80

This report describes an uncommon clinical case of cystic parathyroid adenocarcinoma. A 17-year-old male Persian cat was presented for evaluation of a ventral cervical mass. The cat was inappetent and showed weight loss, polydipsia and vomiting. Serum biochemistry and urinalysis revealed moderate hypercalcaemia, a mild increase of creatinine, isosthenuria and proteinuria. Sodium dodecyl sulphate-agarose gel electrophoresis showed a mixed tubular proteinuric pattern, in accordance with histological examination that revealed interstitial nephritis and glomerulonephritis. Diagnosis of parathyroid carcinoma was based on histopathological findings.
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PMID:Parathyroid adenocarcinoma in a nephropathic Persian cat. 1665 Oct 17

Adenosquamous carcinoma of the colon is rare. A paraneoplastic syndrome presenting as hypercalcemia may occasionally occur in association with these tumors. Survival for more advanced stages of disease is lower than for patients with adenocarcinoma at a corresponding stage. We report a patient who presented with a primary adenosquamous carcinoma of the rectosigmoid junction and we review the literature regarding the clinical presentation, management, and prognosis of this tumor.
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PMID:Adenosquamous carcinoma of the colon: a rare tumor. 1691 23

Disseminated carcinimatosis of the bone marrow is accompanied by solid tumors, and gastric cancer accounts for the majority. The prognosis of this condition is poor, however, the pathogenesis for wide-spread bone lesions has yet to be elucidated. In 9 patients with gastric cancer demonstrating disseminated carcinomatosis of the bone marrow, the characteristic clinicopathological features were examined. Immunohistochemistry for receptor activator of NF-kappaB ligand (RANKL) and parathyroid hormone-related protein was also performed on gastric cancer tissue and bone marrow specimens to identify the factors responsible for the occurrence of bone lesions in patients presenting with this condition. The characteristic features of disseminated carcinomatosis of the bone marrow due to gastric cancer include a yonger patient age, an elevation of serum alkaline phosphatase and/or lactate dehydrogenase levels, wide-spread bone metastases with osteolytic bone destruction, a low incidence of hypercalcemia and a histological gastric cancer type of either signet ring cell carcinoma or poorly diffentiated adenocarcinoma. The expression of RANKL, which is one of the master regulators of osteoclastic bone resorption in bone metastasis, was also found in gastric cancer cells obtained from such patients. The RANKL expressed in gastric cancer may therefore play a critical role in the promotion of osteoclast formation, which has been suggested to be involved in the pathogenesis of bone lesions.
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PMID:Characteristic features of disseminated carcinomatosis of the bone marrow due to gastric cancer: the pathogenesis of bone destruction. 1696 87

We encountered a case with cholangiocarcinoma of the cystic duct, which was first manifested by multiple lymph node metastases with clear cell changes resembling clear cell adenocarcinoma (CCC). Because the clear cell changes were not prominent at the primary site, clear cell transformation might have occurred preferentially at the metastatic lesion in this case. Alternatively, tumor cells with clear cell transformation, found at the primary site, might have high metastatic potential. The patient showed thromboembolism and hypercalcemia as paraneoplastic syndromes at the terminal stage as reported in patients with CCC of the ovary. Those complications might be common biological features of CCC.
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PMID:Cholangiocarcinoma at the cystic duct discovered by lymph node metastases with clear cell transformation. 1704 71

Paget's disease of the bone, which is characterized by a focal region of highly exaggerated bone remodeling, is very rare in Asia. Most patients with Paget's disease are asymptomatic; they are normocalcemic and show elevated alkaline phosphatase levels. Hypercalcemia in patients with Paget's disease has rarely been reported. We report one Chinese patient with Paget's disease involving the maxilla bone with an initial presentation of facial cellulitis. Asymptomatic hypercalcemia with a low-normal intact parathyroid hormone level developed 9 years later. After clodronate treatment, the level of alkaline phosphatase normalized, but the hypercalcemia did not respond adequately. After analysis of tumor markers and imaging studies, a clinical diagnosis of pancreatic adenocarcinoma with multiple hepatic and lung metastases with pleural effusion was made. We suggest that malignancy-associated hypercalcemia should be considered as one of the causes of hypercalcemia in patients with Paget's disease.
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PMID:Tumor-associated Hypercalcemia in a patient with Paget's disease. 1836 76


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