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)

PTHrP has had an unidentified role in medicine since 1930, when Albright described a patient with renal cortical cell carcinoma with hypercalcemia. Since then hypercalcemia has been recognized as the most common paraneoplastic syndrome. At that time the concept of "ectopic PTH syndrome" was introduced, and remained in literature until the true etiology was finally described. In the early 1970's Roof and Benson presented evidence that PTH in humoral hypercalcemia differed from "authentic" PTH. This marked the starting point for researchers to try identifying the molecule that mimicked PTH action and structure. This molecule, named parathyroid-related peptide, has been associated to hypercalcemia seen with solid tumors, such as squamous cell carcinoma of the lung and renal cortical cell carcinoma. PTHrP has been demonstrated to have similar actions to PTH but to differ in decreasing osteoblastic activity while increasing osteoclastic activity. The more fascinating finding was the presence of the PTHrP genes throughout the body, mostly the lactating breast as well as the heart, lungs and skin among others. Despite its identification, finding its physiological roles on normal tissue still remains to be clarified.
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PMID:An update on the discovery, pathophysiological actions, clinical manifestations and possible physiology of parathyroid related peptide. 916 Mar 98

Excessive production of a parathyroid hormone-related protein (PTHrP) by tumours commonly results in the syndrome of humoral hypercalcaemia of malignancy. We have investigated whether epigenetic changes play a role in over-expression of the PTHrP gene, using cultures lung cells as a model system. Study of the methylation status of CpG dinucleotides in the 5' region of the gene showed that in normal cells the CpG island was completely unmethylated. In the lung squamous cell carcinoma cell line, BEN, two-thirds of the CpG island was substantially methylated. RT-PCR analysis showed that this heavy methylation did not prevent expression of any of the three PTHrP gene promoters. This is a surprising finding, since methylation is usually associated with inhibition of gene activity. Methylation of the 5' non-coding region of the PTHrP gene may not play a role in the regulation of adjacent promoters. Alternatively, maintenance of a demethylated state in the 170 bp at the 3' end of the CpG island may be fundamental for the use of PTHrP promoters.
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PMID:CpG island methylation and promoter usage in the parathyroid hormone-related protein gene of cultured lung cells. 922 54

This paper describes humoral hypercalcemia of malignancy (HHM) associated with squamous cell carcinoma (SCC) of the breast and its association with assayed levels of parathyroid hormone related protein (PTHrP). A 57-year-old woman presented with locally advanced SCC of the breast. The diagnosis was supported by serum analysis and histological and immunohistochemical findings. She was initially treated with chemotherapy to reduce the tumor bulk but developed symptomatic hypercalcemia after on course. The hypercalcemia was effectively treated with intravenous amino hydroxy propildene diphosphonate. Subsequently the tumor progressed despite multimodality therapy and was associated with recurrent hypercalcemia. The patient died nine months after presentation.
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PMID:Association of hypercalcemia, PTHrP expression and disease progression in a woman with primary squamous cell carcinoma of the breast. 927 Oct 26

Hypercalcemia is the most common metabolic disorder associated with malignancies. Squamous cell carcinoma of the penis is a tumor for which this abnormality has rarely been described. This report presents a case of hypercalcemia seen in a patient with advanced penile cancer. A chemotherapy regimen of intravenous cisplatin and fluorouracil caused regression of the primary tumor and normalization of the serum calcium. A literature review supported an association between squamous cell carcinoma of the penis and hypercalcemia.
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PMID:Hypercalcemia and carcinoma of the penis. 932 48

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

We report a case of symptomatic hypercalcemia in a patient with muscle-invasive, resectable squamous cell carcinoma of the bladder. Serum parathyroid hormone was consistent with secretion of parathyroid hormone-related protein. After radical cystoprostatectomy, calcium levels returned to normal. Patients with squamous cell carcinoma and an abnormal serum calcium level may have localized disease and should not be denied definitive local therapy.
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PMID:Localized squamous cell carcinoma of the bladder causing hypercalcemia and inhibition of PTH secretion. 951 Mar 60

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

Humoral hypercalcemia of malignancy is a cancer-related hypercalcemia caused by production of humoral factors by malignant cells in patients without bone metastases. Squamous cell carcinomas are the tumors most frequently associated with humoral hypercalcemia of malignancy, and parathyroid hormone-related protein is the main humoral factor implicated. In spite of the fact that normal keratinocytes produce parathyroid hormone-related protein, it is highly unusual for patients with squamous cell carcinomas of the skin to present with humoral hypercalcemia of malignancy. We present a well-documented case of cutaneous squamous cell carcinoma complicated by hypercalcemia in a patient with high levels of plasma parathyroid hormone-related protein and immunohistochemical evidence of high parathyroid hormone-related protein production by the tumoral cells.
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PMID:Immunohistochemical detection of parathyroid hormone-related protein in a cutaneous squamous cell carcinoma causing humoral hypercalcemia of malignancy. 1042 Feb 32

The cardiac effects of hypercalcaemia are usually manifest as a shortening of the QT-interval. Hypercalcaemia is infrequently associated with a clinically manifest arrhythmia. However, concomitant therapy with digoxin or underlying cardiac disease can potentiate the arrhythmogenic effects of hypercalcaemia, leading to a symptomatic rhythm disorder. We describe a symptomatic arrhythmia, which developed in a patient with hypercalcaemia secondary to squamous cell carcinoma of the bronchus. The patient was on digoxin therapy at the time. The arrhythmia did not recur after discontinuation of digoxin therapy and correction of the hypercalcaemia. Because of its effect on cardiac conduction, hypercalcaemia should be considered in the evaluation of any patient with an unexplained bradyarrhythmia. Conversely, patients with hypercalcaemia should discontinue digoxin therapy and be evaluated for the presence of rhythm disorders while receiving appropriate treatment for hypercalcaemia.
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PMID:Digoxin, hypercalcaemia, and cardiac conduction. 1061 93


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