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)

The presence of parathyroid hormone-related protein (PTHrP) in the apocrine adenocarcinoma tumor line (CAC-8) derived from a hypercalcemic dog was demonstrated by western and northern blot analyses. Western blots of CAC-8 tumor extracts revealed a major protein with a molecular weight of approximately 18,000 daltons that cross-reacted with antiserum to human PTHrP. Northern blots demonstrated multiple-sized messenger RNA transcripts in CAC-8 that hybridized to a full-length cDNA probe to human PTHrP. Adenocarcinomas derived from apocrine glands of the anal sac also were stained immunohistochemically for antigens that cross-react with antiserum to human PTHrP. The tumor line (CAC-8) maintained in nude mice stained positively for PTHrP in 13 of 24 tumors. Three of ten apocrine adenocarcinomas from dogs with hypercalcemia stained for PTHrP, whereas zero of ten tumors were positive from normocalcemic dogs. Normal canine epidermal keratinocytes and areas of squamous metaplasia in a perianal gland carcinoma also were positive for PTHrP. These data demonstrated that canine tissues contained a homologue to human PTHrP that likely is important in the pathogenesis of humoral hypercalcemia of malignancy.
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PMID:Identification of parathyroid hormone-related protein in canine apocrine adenocarcinoma of the anal sac. 234 42

A cDNA complementary to the parathyroid hormone related protein (PTHrP), the humoral hypercalcemia factor in malignancy, was recently isolated and sequenced. PTHrP expression in human carcinomas was examined (determined) by Northern blot hybridization, Southern blot hybridization and radioimmunoassay (RIA). Expression of PTHrP mRNA was detected in three out of four lung squamous cell carcinomas, two out of ten breast carcinomas and the one adenosquamous carcinoma of the maxilla. No clinical hypercalcemia was found in these PTHrP mRNA positive carcinomas. No expression of PTHrP was detected in normal human or rat tissues. In Southern blot hybridization, no amplification of PTHrP gene was found in PTHrP positive cases. An insertion in one allele of promotor region of the gene was identified in one PTHrP positive lung squamous cell carcinoma. The serum level of PTHrP was examined using human PTHrP (1-34) RIA in lung carcinomas. We found no correlation between the level of PTHrP and clinical hypercalcemia or the histopathological diagnosis. We discuss some problems of the PTHrP assay as a novel tumor marker for malignancies. A new RIA assay study using recombinant human PTHrP expressed in Escherichia coli is also reported.
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PMID:[A parathyroid hormone related protein (PTHrP) implicated in hypercalcemia associated with malignancy: research of the PTHrP for novel hormonal tumor marker]. 234 64

Parathyroid carcinoma is a rare endocrine tumor infrequently seen in the mediastinum. This report describes a patient who underwent en bloc resection of a primary mediastinal parathyroid carcinoma. The tumor originated from the thymus and extended from the aortic arch to the thyroid; local invasion suggested malignancy. En bloc resection of this carcinoma with all surrounding tissue provided local control of the tumor and relief of symptomatic hypercalcemia.
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PMID:Extended en bloc resection of a primary mediastinal parathyroid carcinoma. 236 17

Two patients with metastatic small cell carcinoma of the ovary managed by the Clinical Gynecologic Oncology Service at Roswell Park Memorial Institute are presented. Despite intensive multimodal therapy after extensive cytoreductive surgery, both patients expired from this rare tumor within 6 months of diagnosis. Neither tumor was associated with hypercalcemia, previously reported in the only existing review of the tumor in the world literature. Because of the highly aggressive nature of this cancer, effective combination chemotherapy must be found if the natural history of this tumor is to be altered.
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PMID:Small cell carcinoma of the ovary: a rapidly lethal tumor occurring in the young. 241 62

Transplantation of a murine mammary carcinoma (CE maca) into mice induces marked granulocytosis and hypercalcemia secondary to excessive bone resorption. Such responses are not induced by another murine mammary carcinoma Bc66. In order to understand the mechanisms of these unique phenomena, we analyzed mRNA of tumor cells for expression of murine granulopoietic growth factors and studied interactions of tumor-derived factors using antiserum to a growth factor in vitro and in vivo. The Northern blot analysis of CE tumor clones revealed the expression of granulocyte colony stimulating factor (G-CSF) and macrophage colony stimulating factor (M-CSF), but no other CSF genes, while the Bc66 clone expressed only M-CSF. The G-CSF and M-CSF gene expression in CE tumor clones was accompanied by secretion of these proteins in culture. The granulocyte stimulating activity of CE tumor-derived G-CSF or recombinant human G-CSF was markedly enhanced by purified M-CSF in vitro. Significant but variable neutrophilia was observed in mice inoculated with CE tumor clones. Anti-M-CSF treatment of CE tumor-bearing mice significantly reduced neutrophilia, but did not affect hypercalcemia. These studies document that G-CSF and M-CSF are produced constitutively from the CE maca, and G-CSF is likely responsible for granulocytosis induced by this tumor. G-CSF and M-CSF function synergistically in granulocyte stimulation in vitro and this synergism may also play a role in marked granulocytosis of tumor-bearing animals, providing further evidence of the effect of CSFs in vivo.
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PMID:Mechanisms of tumor-induced neutrophilia: constitutive production of colony-stimulating factors and their synergistic actions. 247 93

Small cell carcinoma of the ovary is a rare, poorly understood aggressive tumor of young women, associated with paraendocrine hypercalcemia in two-thirds of the cases. Immunohistochemical staining of 15 small cell carcinomas, one-third of which were associated with hypercalcemia, 15 adult granulosa cell tumors, 15 juvenile granulosa cell tumors, and 5 Sertoli cell tumors, was performed with the use of antibodies against cytokeratins (AE-1/AE-3, CAM 5.2, 902), epithelial tumor-associated antigens (B72.3, epithelial membrane antigen [EMA]), vimentin, S-100, neuron-specific enolase (NSE), lysozyme, parathyroid hormone, and chromogranin-A in an attempt to define histogenetically this tumor type. One-third of the small cell carcinomas were positive for EMA, whereas all of them were negative for B72.3 and S-100. In contrast, one-third of the granulosa cell tumors were positive for S-100 and all of them were negative for EMA and B72.3. One of five Sertoli cell tumors were positive for EMA and two were positive for B72.3, but all were negative for S-100. Differences existed in the frequency, intensity, and/or pattern of staining for cytokeratin, vimentin, lysozyme, and NSE among the various tumor types. A single small cell carcinoma from a patient with hypercalcemia stained focally for parathyroid hormone, whereas all 30 granulosa cell tumors and 4 of 5 Sertoli cell tumors were nonreactive. Chromogranin-A staining was noted in four of five small cell carcinomas, none of ten granulosa cell tumors, and two of five Sertoli cell tumors. These immunohistochemical findings, as well as previous light and electron microscopic data, do not clearly indicate any specific cell as the cell of origin of the ovarian small cell carcinoma.
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PMID:Ovarian small cell carcinoma. Histogenetic considerations based on immunohistochemical and other findings. 247 44

Malignancy-related hypocalcaemia has received less attention in the literature than the opposite perturbation, hypercalcaemia. Only, scarce and contradictory data exist about hypocalcaemia associated with bone metastases (BMH). We have reviewed the clinical records of 155 patients with bone metastases of solid tumours, 122 of which were followed during the whole course of the disease until death. The frequency of hypocalcaemia ranged from 5 to 13%, depending on the formula used to correct calcium values for protein concentration. BMH was almost exclusively limited to patients with osteoblastic metastases. The frequency of BMH among patients with prostate carcinoma was 13-27%, depending on the formula used. Only two of 60 patients with lytic bone lesions presented hypocalcaemia, and in both cases it was rather mild. The development of hypocalcaemia did not seem to imply a worse prognosis, at least in patients with carcinoma of the prostate. Thus, the prevalence of BMH appears to be higher than is usually considered. Adequate attention should be given to this disorder because of the potentially deleterious effects on several organ systems.
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PMID:The clinical spectrum of hypocalcaemia associated with bone metastases. 248 31

Calcemic alterations in prostate cancer are extremely rare. Hypercalcemia may be seen in cases of multiple osseous dissemination, and even in the absence of this in response to humoral mechanisms. The existence of hypercalcemia may indicate tumoural recurrence, and may at times be a datum prior to the diagnosis of the tumour. In cases of disseminated prostate adenocarcinoma hormones treatment may secure the normalization of blood calcium. We present a case of prostate carcinoma diagnosed in a 76-year-old patient, as a result of the presentation of a hypercalcemic metabolic syndrome, which was corrected after treatment by means of complete androgenic blocking.
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PMID:[Hypercalcemia: a finding indicative of a prostatic adenocarcinoma]. 253 67

To elucidate the mechanism of humoral hypercalcemia elicited by human esophageal carcinoma cells (EC-GI), which constitutively produced interleukin-1 alpha (IL-1 alpha) and PTH-like factor, the effects of IL-1 alpha and PTH-related protein (PTH-rP) on bone resorption in vitro and on serum calcium concentrations in vivo were investigated. Nude mice transplanted with EC-GI cells invariably developed hypercalcemia, although their urinary cAMP excretion remained within the normal range. IL-1 alpha or PTH-rP-(1-34) stimulated 45Ca release from prelabeled fetal mouse forearm bones in a concentration-dependent manner, and when combined, IL-1 alpha and PTH-rP-(1-34) synergistically stimulated bone resorption in vitro. Injection of PTH-rP-(1-34) into mice three times a day for 2 days increased the serum calcium concentration in a dose-dependent manner. Continuous infusion of IL-1 alpha occasionally increased the serum calcium concentration. Simultaneous administration of IL-1 alpha at rates of 1-2.7 micrograms/day and PTH-rP-(1-34) at doses of 15-30 micrograms/day synergistically increased the serum calcium concentration in vivo. These findings suggest that PTH-rP and IL-1 alpha produced by the tumor cells were synergistically responsible for the humoral hypercalcemia observed in both the original patient and the tumor-bearing nude mice, and that at least two bone-resorbing factors [PTH-rP and another nonadenylate cyclase-stimulating bone-resorbing factor(s)] are active in patients with malignancy-associated hypercalcemia, in whom nephrogenous cAMP excretion is neither increased nor decreased.
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PMID:Parathyroid hormone-related protein and interleukin-1 alpha synergistically stimulate bone resorption in vitro and increase the serum calcium concentration in mice in vivo. 253 70

Six cases of primary hyperparathyroidism due to hyperfunctioning intrathyroidal parathyroid glands are reported. In five cases, hyperparathyroidism was due to an intrathyroidal parathyroid adenoma; in the sixth case, hyperparathyroidism resulted from an intrathyroidal parathyroid carcinoma. All five patients with adenoma were female with ages ranging from 40 to 70 yr. The patient with carcinoma was a 55-yr-old male. In all five patients with intrathyroidal parathyroid adenoma, thyroidectomy was performed when an abnormal parathyroid gland could not be located in the neck during surgery for hyperparathyroidism. The patient with intrathyroidal parathyroid carcinoma presented with hypercalcemia and a palpable right thyroid mass. The differential diagnosis of intrathyroidal parathyroid adenoma includes thyroid follicular adenoma. In some cases, the possibility of medullary carcinoma of thyroid might also be considered. Immunocytochemical staining for parathormone (PTH), thyroglobulin, and calcitonin is valuable in establishing the correct diagnosis.
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PMID:The intrathyroidal hyperfunctioning parathyroid gland. 258 70


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