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 69-year-old man visited in the department of ophthalmology of this university, complained with exophthalmos. He was pointed out hypercalcemia and transferred to the department of endocrinology. The chest X-ray and thoracic CT showed a large mass in lower lobe of the left lung. Cytological diagnosis of this tumor was squamous cell carcinoma. In clinical examination, serum CA was 12.2 mg/dl in spite of normal level of PTH, calcitonin, 1 alpha, -25 (OH) 2D3 and uric cAMP. On the other hand, PTHrP-intact in serum was 9.8 pmol/l. His thyroid gland had no abnormality in palpation or roentogenological examination. The thyroid functions, thyroglobulin, thyrotropin receptor antibody, thyroid test and microsome test were all in normal limit. From these results, he was diagnosed of lung cancer with humoral hypercalcemia of malignancy and euthyroid "isolated" Graves' ophthalmopathy. Left lower lobectomy with mediastinal lymph node dissection (R 2 a) was done and p-stage was IIIA. After operation, serum Ca decreased in normal level and the exophthalmos was also improved gradually. He was in well until 10 months after operation, and died with multiple lung metastases and hypercalcemia. Exophthalmos was also recurred in his terminal stage. Similar case could not find in literature and some discussion of the literatures was mentioned.
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PMID:[A case of squamous cell carcinoma of the lung associated with exophthalmos and hypercalcemia]. 949 73

A 41-year old woman with lung cancer was admitted to our hospital with constipation, lumbago and paraplegia. Her serum calcium level was 13.9 mg/dl. She expired on the 33rd hospital day despite vigorous fluid and supportive therapy. An autopsy was performed 1 hour later. The cause of death was rupture of the sigmoid colon and panperitonitis. To evaluate the etiology underlying the symptomatic hypercalcemia in the autopsied lung, we measured serum and tumor tissue concentrations of PTH-related protein (PTHrP) by radioimmunoassay using a specific antibody against human PTHrP (1-34), and performed immunohistochemical staining by the peroxidase-anti-peroxidase method with the same PTHrP antiserum. Northern blot analysis was also performed to detect messenger RNA in cancer tissue. All of these tests were positive for PTHrP. To the best of our knowledge, this is the first reported autopsied case demonstrated to be a PTHrP-producing large cell lung cancer by molecular biological methods.
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PMID:[A case of PTH related protein-producing large cell carcinoma of the lung]. 961 51

Hypercalcemia and elevation of a serum PTH level (9800 pg/mL (normal: 160-520) were found in a 72-yr-old woman who had a lung cancer. She underwent pulmonary lobectomy for a suspected PTH-producing lung cancer. However, hypercalcemia and elevation of the serum PTH level were persistent postoperatively. Subsequent examination, using parathyroid scintiscanning, revealed a hot spot in the right lower part of the thyroid gland, suggesting hypercalcemia caused by a parathyroid tumor. She underwent bilateral exploration of the neck; however, four apparently normal parathyroid glands were seen. Therefore, hemithyroidectomy was performed for the possibility of an intrathyroidal parathyroid adenoma. Serum calcium and PTH levels declined after this operation. A nodular lesion was found in the cut sections of the resected specimen, which was consistent with the result of the scintiscanning. Histological examinations revealed a papillary adenocarcinoma of the thyroid gland, and the PTH-immunoreactivity in the tumor cells was confirmed. These findings strongly suggest that PTH could be produced ectopically by the papillary adenocarcinoma of the thyroid gland.
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PMID:Hypercalcemia caused by ectopic production of parathyroid hormone in a patient with papillary adenocarcinoma of the thyroid gland. 970 27

A 65-year-old man was facing to tracheal stenosis due to proximally developed lung cancer with hypercalcemia mediated by production of PTHrP from the cancer cells. We treated the stenosis use of Dumon stent and hypercalcemia with drugs such as biphosphonate and so on. The treatment was effectively keep the patient under better performance status for about 3.5 months.
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PMID:[A case of treatment with Dumon stent for tracheal stenosis due to lung cancer with hypercalcemia]. 974 28

We report the histological and biological behavior characteristics of a lung tumor (P07) that arose spontaneously in a Balb/c mouse. P07 is a moderately to poorly differentiated adenocarcinoma that secretes granulocyte-macrophage colony stimulating factor (GM-CSF) in culture supernatants. This tumor presents some paraneoplastic syndromes, such as leukocytosis, hypercalcemia and cachexia. taken together with the peripheral blood leukocyte (PBL) counts and serum calcium levels during s.c. tumor growth and after surgery, this study suggests that P07 may be a useful experimental model to study the biology of lung cancer and paraneoplastic syndromes.
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PMID:Spontaneous murine lung adenocarcinoma (P07): A new experimental model to study paraneoplastic syndromes of lung cancer. 985 41

A 46-year-old man was diagnosed as Stage IV lung cancer with neck lymph node and bilateral adrenal metastases. He was treated with seven courses of combined chemotherapy (CDDP + etoposide), until he showed extreme hypercalcemia and acute renal failure. The bisphosphonate, pamidronate with elcatonin and prednisolone dramatically lowered his serum calcium level and normalized his renal function. This is a representative case of humoral hypercalcemia of malignancy whose serum calcium could be safely and effectively controlled with pamidronate.
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PMID:[A case of lung cancer with hypercalcemia and renal failure responsive to pamidronate]. 1041 Jan 54

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

Breast cancer is the most common malignancy in women, with a worldwide prevalence of 1.5 million throughout the industrialized countries. Its mortality rate is second only to lung cancer in the USA and Europe. Its high incidence and prevalence makes it a major public health problem. Up to one-third of women with early stage breast cancer will eventually succumb to the disease, and most of these will develop bone metastases during the course of the disease. Approximately 70% of patients with breast cancer have bone metastases, with 27% having lung and liver metastases. Hypercalcemia also is very common in advanced breast cancer, manifesting itself in one-third of patients late in the disease. Breast cancer accounts for approximately 25% of the cases of hypercalcemia in cancer. The major skeletal complications of breast cancer--hypercalcemia and bone metastases--almost certainly share certain mechanisms and these will be discussed.
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PMID:Mechanisms in the skeletal complications of breast cancer. 1117 48

Receptor activator of nuclear factor kappaB (RANK) is a membrane-bound tumor necrosis factor receptor homologue that mediates signals obligatory for osteoclastogenesis as well as osteoclast activation and survival in vivo. The present study was undertaken to evaluate the efficacy of a soluble murine RANK-human immunoglobulin fusion protein (muRANK.Fc) as a bone resorption inhibitor in vitro and in vivo. The in vitro studies demonstrated the ability of muRANK.Fc to inhibit human parathyroid hormone-related protein (PTHrP)-induced resorption in fetal rat long bone cultures. Short-term administration of muRANK.Fc to normal growing mice resulted in a complete disappearance of osteoclasts from metaphyses of long bones associated with a pronounced increase in calcified trabeculae and bone radiodensity. In a model of humoral hypercalcemia of malignancy in which PTHrP secreted by s.c. xenografts of human lung cancer in nude mice induces extensive osteolysis and severe hypercalcemia, daily administration of muRANK.Fc from time of tumor implantation profoundly inhibited osteoclastic bone resorption and prevented hypercalcemia. muRANK.Fc had no effect on tumor production of PTHrP, because there was no significant difference between circulating human PTHrP levels in muRANK.Fc-treated and vehicle-treated tumor-bearing mice. Moreover, even when treatment was initiated after hypercalcemia was established, muRANK.Fc significantly attenuated further increases in blood ionized calcium. These data demonstrate the potent antiresorptive effects of muRANK.Fc in vivo as well as highlight the potential utility of disrupting RANK signaling as a novel therapeutic approach in humoral hypercalcemia of malignancy and possibly multiple myeloma and skeletal metastases associated with osteolysis.
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PMID:Therapeutic efficacy of a soluble receptor activator of nuclear factor kappaB-IgG Fc fusion protein in suppressing bone resorption and hypercalcemia in a model of humoral hypercalcemia of malignancy. 1128 33

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


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