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 novel cDNA encoding a secreted form of osteoclast differentiation factor/tumor necrosis factor-related activation-induced cytokine (sODF/TRANCE, GenBank Accession No. AB037599) was sequenced from 5' RACE cDNA clones of squamous cell carcinoma cell lines, SCC-4 and T3M-1 Cl.2, of which parental malignant tissues had caused severe humoral hypercalcemia. The sODF/TRANCE cDNA was composed of unknown 5' end sequence followed by the 100% identical sequence of the ODF/TRANCE extracellular domain-coding region. The longest open reading frame (ORF) of the novel cDNA completely matched the 3' end of the ORF of the ODF/TRANCE cDNA encoding C-terminal amino acid residues (74-318) in the extracellular region. The corresponding protein that reacted with the antibody specific for the extracellular domain of ODF/TRANCE was detected in the culture media conditioned by the cancer cells. Furthermore, human promyeloblastic leukemia cells, HL60, differentiated into osteoclast-like cells (OCLs) when cultured in the media conditioned by SCC-4 and T3M-1 Cl. 2 cells. The differentiation of HL60 cells into OCLs was inhibited by the anti-ODF/TRANCE antibody. These results strongly suggest that sODF/TRANCE plays an important role in enhanced bone-resorption in humoral hypercalcemia of malignancy.
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PMID:Cancer cells responsible for humoral hypercalcemia express mRNA encoding a secreted form of ODF/TRANCE that induces osteoclast formation. 1070 88

A retrospective study was conducted to characterize the diseases, clinical findings, and clinicopathologic and ultrasonographic findings associated with hypercalcemia (serum calcium concentration >11 mg/dL) in 71 cats presented to North Carolina State University Veterinary Teaching Hospital. The 3 most common diagnoses were neoplasia (n = 21), renal failure (n = 18), and urolithiasis (n = 11). Primary hyperparathyroidism was diagnosed in 4 cats. Lymphoma and squamous cell carcinoma were the most frequently diagnosed tumors. Calcium oxalate uroliths were diagnosed in 8 of 11 cats with urolithiasis. Cats with neoplasia had a higher serum calcium concentration (13.5 +/- 2.5 mg/dL) than cats with renal failure or urolithiasis and renal failure (11.5 +/- 0.4 mg/dL; P < .03). Serum phosphorus concentration was higher in cats with renal failure than in cats with neoplasia (P < .004). Despite the fact that the majority of cats with uroliths were azotemic, their serum urea nitrogen and creatinine concentrations and urine specific gravity differed from that of cats with renal failure. Additional studies are warranted to determine the underlying disease mechanism in the cats we identified with hypercalcemia and urolithiasis. We also identified a small number of cats with diseases that are not commonly reported with hypercalcemia. Further studies are needed to determine whether an association exists between these diseases and hypercalcemia, as well as to characterize the underlying pathophysiologic mechanism for each disease process.
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PMID:Hypercalcemia in cats: a retrospective study of 71 cases (1991-1997). 1077 91

Parathyroid hormone-related protein (PTHrP) is now well established as the major, if not the sole mediator of the humoral hypercalcaemia of malignancy. This is the phenomenon of elevated blood calcium in the absence of bony metastases in patients with certain solid tumours, most commonly squamous cell carcinoma (SCC) of the lung, but also occurring in SCC at other sites including skin, and other cancers including melanoma. Although discovered because of its hormonal action in cancer, there is at present no indication that PTHrP acts as a circulating hormone in normal animals or in humans after birth, with the possible exception of the period during lactation. Along with its significant effects on calcium metabolism in cancer patients, PTHrP is widely expressed in mammalian tissue, and evidence to date indicates that the major physiological role of PTHrP is as a paracrine factor affecting growth and development of cells in several tissues.
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PMID:Parathyroid hormone-related protein and skin cancer. 1099 65

Previously we have established a clonal squamous cell carcinoma cell line OKa-C-1 derived from lung cancer of a patient with marked leukocytosis and hypercalcemia. OKa-C-1 cells simultaneously produce granulocyte colony-stimulating factor (G-CSF) and parathyroid hormone-related protein (PTHrP) at the single cell level and cause paraneoplastic syndromes in nude mice bearing the tumor. It is known that the production of G-CSF and PTHrP is individually regulated by inflammatory cytokines in various malignant cells. To investigate the common factors in the regulation of G-CSF and PTHrP production in OKa-C-1 cells, we examined the effects of some inflammatory agents [lipopolysaccharide (LPS), phorbol-12-myristate-13-acetate (PMA), tumor necrosis factor-alpha (TNF-alpha), interleukin-1 (IL-1) beta and IL-6] on G-CSF and PTHrP production, by means of enzyme-linked immunosorbent assay (ELISA), immunoradiometric assay (IRMA) and quantitative reverse transcription-polymerase chain reaction (RT-PCR). TNF-alpha or IL-1beta induced both G-CSF and PTHrP production in the conditioned medium. TNF-alpha synergized with IL-1beta to significantly increase G-CSF production. In addition, TNF-alpha and IL-1beta strongly induced G-CSF mRNA with peaks at 2 and 6 h respectively. Although PTHrP production was also strongly induced by TNF-a PTHrP mRNA expression was more strongly induced by PMA than by TNF-alpha. Thus, TNF-alpha and IL-1beta could be common factors that individually and synergistically regulate G-CSF and PTHrP production in OKa-C-1 cells. Moreover, G-CSF and PTHrP production could be not only transcriptionally, but also posttranscriptionally regulated by other factors.
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PMID:Regulation of granulocyte colony-stimulating factor and parathyroid hormone-related protein production in lung carcinoma cell line OKa-C-1. 1101 Nov 19

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

Lung cancer is commonly associated with multiorgan metastasis, and bone is a frequent metastatic site for lung cancer. Nevertheless, no bone metastasis model of lung cancer with multiorgan dissemination is available, which could provide opportunity to study the molecular pathogenesis. We examined the abilities of eight human lung cancer cell lines injected intravenously into natural killer (NK) cell-depleted SCID mice to generate metastatic nodules in bone and multiple organs, and explored the correlation of the parathyroid hormone-related protein (PTHrP) with the bone metastasis. Although all the small-cell carcinoma cell lines (SBC-5, SBC-3, SBC-3/ADM, H69, H69/VP) formed metastatic nodules in multiple organs (liver, kidney, and lymph nodes), only SBC-5 cells reproducibly developed bone metastases. Squamous cell carcinoma (RERF-LC-AI) cells metastasized mainly into the liver and kidneys, whereas adenocarcinoma (PC-14, A549) mainly produced colonies in the lungs. As assessed by X-ray photography, the osteolytic bone metastases produced by SBC-5 cells were detected as early as on day 28, and all recipient mice developed bone metastasis by day 35. The expression of PTHrP in eight cell lines was directly correlated with the formation of bone metastasis. No correlation was observed between the formation of bone metastasis and the expression of other metastasis-related cytokines (IL-1, IL-6, IL-8, IL-10, IL-11, TNF-alpha, VEGF, M-CSF). Consistent with the formation of bone metastasis by SBC-5 cells, the levels of PTHrP and calcium in the mouse serum were increased in a time-dependent manner, suggesting that PTHrP produced by human lung cancer may play a crucial role in the formation of bone metastasis and hypercalcemia. These findings indicate that a bone metastasis model of SBC-5 cells may be useful for clarifying the molecular aspects of the metastatic processes in different organ microenvironments and the development of therapeutic modalities for lung cancer patients with bone metastases.
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PMID:Bone metastasis model with multiorgan dissemination of human small-cell lung cancer (SBC-5) cells in natural killer cell-depleted SCID mice. 1141 46

A case history is reported here in which leukocytosis, thrombocytosis and hypercalcemia associated with rapidly relapsing squamous cell carcinoma (SCC) of the renal pelvis were observed. In a 58-year-old man, SCC of the renal pelvis was documented during nephrolithotomy, and right nephrectomy was performed. Local relapse of the tumor occurred rapidly in 2 months' time and hypercalcemia, leukocytosis and thrombocytosis worsened in accordance with tumor volume. Cranial computerized tomography (CT), thorax CT and bone scintigraphy were negative for metastasis. The serum parathyroid hormone level was 28 pg/ml (normal 9- 55 pg/ml). To disclose leukocytosis and thrombocytosis, peripheral smear and bone marrow aspiration were performed and no pathologic finding regarding any hematologic disorder was found; the samples were also BCR-ABL negative and Philadelphia chromosome negative. Production of several factors by tumor cells may be responsible for this paraneoplastic syndrome. The association of SCC of the renal pelvis with this triple paraneoplastic syndrome is an extremely rare occurrence.
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PMID:Rapidly relapsing squamous cell carcinoma of the renal pelvis associated with paraneoplastic syndromes of leukocytosis, thrombocytosis and hypercalcemia. 1149 Feb 18

Humoral hypercalcemia of malignancy (HHM) is one of the most common metabolic complications associated with cancer. A retrospective study of hypercalcemia in patients with squamous cell carcinoma of the oral cavity was undertaken. All patients were periodically monitored for their serum level of calcium (Ca). Hypercalcemia was defined as a serum Ca concentration higher than 11 mg/dl of the correction for serum albumin concentration. The serum levels of parathyroid hormone related protein (PTH-rP) were also measured by radioimmunoassay. Hypercalcemia was detected in ten of 246 patients (4.1%). All ten patients were at an advanced stage of oral squamous cell carcinoma (SCC, Stage IVA, IVB or IVC). In these ten patients, the serum level of PTH-rP was significantly elevated, 238 +/- 91 pmol/l (range, 108-380 pmol/L). The patients with HHM who underwent antihypercalcemic therapy showed reduced Ca levels relating to PTH-rP levels; however, the Ca concentration was temporarily improved after anti-hypercalcemic treatment. The median survival time after diagnosis of HHM was only 55.8 +/- 19.9 days (range, 27-86 days). HHM in oral cancer is likely attributable to PTH-rP, and its occurrence appears to be an ominous prognostic sign.
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PMID:Hypercalcemia in patients with oral squamous cell carcinoma. 1164 65

Previously we have shown that dexamethasone (DEX) enhances the antitumor activity and ligand binding of the active form of vitamin D, 1alpha,25-dihydroxyvitamin D(3) (1,25-D(3)), in the murine squamous cell carcinoma model SCC VII/SF. DEX also reduces the hypercalcemia toxicity of 1,25-D(3) treatment. However, the mechanism of the enhanced antitumor activity has not been defined. Here, we demonstrate that both cell cycle arrest and apoptosis were enhanced by DEX, effects that were inhibited by RU486. We also demonstrate that vitamin D receptor (VDR) protein levels were increased by the combination of 1,25-D(3) and DEX above the level observed with 1,25-D(3) treatment alone, whereas protein levels of the heterodimeric partner of VDR, retinoid X receptor, were lower for the combination than for 1,25-D(3) alone. Glucocorticoid receptor protein levels and ligand binding were increased by 1,25-D(3) but not by the combination. Treatment with the combination of 1,25-D(3) and DEX did not result in greater activation of a vitamin D response element-reporter than 1,25-D(3) alone or of a glucocorticoid response element-reporter than DEX alone. Nevertheless, the levels of phospho-Erk1/2 and phospho-Akt, signaling molecules that are modulated in 1,25-D(3)-treated squamous cell carcinoma cells, were reduced by the combination of 1,25-D(3) and DEX more than by either agent alone. These trends were also observed in vivo. Our results suggest the involvement of the Erk and Akt signaling pathways in the antiproliferative effects of the combination of 1,25-D(3) and DEX and that phospho-Erk1/2 and phospho-Akt may be useful markers of response to this combination.
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PMID:Combination of 1alpha,25-dihydroxyvitamin D(3) with dexamethasone enhances cell cycle arrest and apoptosis: role of nuclear receptor cross-talk and Erk/Akt signaling. 1175 17

Squamous cell carcinoma of the head and neck is a rare cause of humoral hypercalcemia of malignancy. This paraneoplastic syndrome is usually one of the presenting symptoms of the disease. We report a case of squamous cell carcinoma of the oral cavity that presumably elaborated parathyroid hormone-related peptide (PTH-rP) and caused hypercalcemia only after radiotherapy and chemotherapy.
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PMID:Hypercalcemia induced by parathyroid hormone-related peptide after treatment of carcinoma. 1184 57


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