Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A 57-year-old female was admitted to our hospital with general lassitude, loss of appetite, nausea, upper abdominal pain, thirst, polydipsia and polyuria. On admission, she had an asymmetrical pear-shaped tumor in the right supraclavicular region and severe hypercalcemia. Plasma C-PTH was elevated to 22.72ng/ml. Plasma calcitonin was also elevated to 336 pg/ml. She died of respiratory and cardiac failure of two weeks after admission without any positive response to the treatment, including hemodialysis. Pathohistologically, the tumor was a parathyroid adenoma. The concentrations of C-PTH, intact PTH and calcitonin in the tumor tissue were markedly high: 4.56 micrograms/g wet, 13.9 ng/g wet and 50.7 ng/g wet, respectively. Immunohistologically, the tumor cells and the fibrous stroma were stained strongly positive to rabbit anti-human calcitonin antibody and rabbit anti-human N-PTH antibody by indirect immunoperoxidase staining. Calcitonin-producing tumors, except for medullary thyroid carcinoma are rarely reported. To our knowledge, this is the first report of such a calcitonin-producing parathyroid adenoma associated with primary hyperparathyroidism.
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PMID:A case of calcitonin-producing parathyroid adenoma with primary hyperparathyroidism. 258 94

A review of 208 cases of surgically treated squamous cell carcinoma of the esophagus revealed 16 (7.7%) with hypercalcemia. There was no evidence of bone metastases in 13 (6.3%) of the patients with hypercalcemia. Pathogenesis of this hypercalcemia without bone metastases was suggested to be multifactorial. Anastomotic leakage and malnutrition because of fasting were the most possible causes of mild hypercalcemia, and moderate to severe hypercalcemia was thought to be due to subclinical and clinical recurrence of the tumor, probably with PTH-like hormonal activity. Overall survival rates in the groups with and without hypercalcemia were 18.2 and 61.7% at the 12th postoperative month and 9.1 and 37.8% at the 24th month, respectively. Thus hypercalcemia is a significant prognostic factor linked to an unfavorable clinical course even in patients with no evidence of bone metastases.
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PMID:Hypercalcemia related to the poor prognosis of patients with squamous cell carcinoma of the esophagus. 259 66

We have previously reported that the J774A.1 macrophage-like tumor cell line produces two potent monokines which stimulate the growth of osteoblasts and chondrocytes. These growth factors, which have an affinity for heparin-agarose, have been termed HEP I (a 30 Kd PDGF-like molecule) and HEP II (an approximately 20 Kd molecule), respectively, based on their elution profile. Unlike HEP I, HEP II does not stimulate the growth of fibroblasts. Extensive biological and chromatographic studies disclosed that HEP II appears to be a unique bone cell mitogen unlike any known growth factor, including the FGFs, IL-1s, and TNFs, EGF, IGF-I and -II, TGF-beta, beta 2 microglobulin, G-CSF, CSF-1 and GM-CSF. To characterize more fully the effects of the macrophage-derived monokines on osteoblast growth and function, clones were derived from calvaria explant cultures. Two clones, SDFRC-2.05 and SDFRC-3, were developed and found to exhibit osteoblastic characteristics, including high levels of alkaline phosphatase, synthesis of type I but not type III collagen, and an increased intracellular cAMP production in response to PTH. The SDFRC-3 cells exhibited a polygonal morphology like that of the explant-derived cells while SDFRC-2.05 cells exhibited a more fibroblastic morphology. When tested on the explant cultures and clones, HEP I and HEP II were found to stimulate DNA synthesis and increase protein per culture, but decreased alkaline phosphatase activity. Clone SDFRC-3 was found to be more responsive to HEP II than clone SDFRC-2.05. Both monokines were found to be more potent mitogens for bone cells than TGF-beta. HEP II, but not HEP I or TGF-beta, induced a transformation of bone cells from a polygonal to a fibroblastic morphology, suggesting the induction of migration prior to proliferation. Thus, macrophages may be responsible not only for bone repair but also for ensuring the linkage of bone formation to resorption during physiological remodeling.
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PMID:Monokines produced by macrophages stimulate the growth of osteoblasts. 263 Jan 69

We report a case of hypercalcemia in a 20-year-old woman with an ovarian seminoma. She had neither evidence of bone metastasis nor hyperparathyroidism. Hypercalcemia was well controlled by corticotherapy and chemotherapy, and remained normal after remission was obtained. Different patterns in paraneoplastic hypercalcemia are detailed, with emphasis on PTH-related proteins and vitamin-D metabolites. Eleven cases of neoplasm with hypercalcemia and elevated calcitriol level are reported in the literature. One of them is a seminoma. These elevated levels could be related either to a PTH-like protein, either to 1 alpha-hydroxylase activity in some tumoral cells. Three other cases of seminoma associated with hypercalcemia without dosage of vitamin-D metabolites are reported. Dosage of calcitriol might be performed in paraneoplastic hypercalcemia of seminoma.
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PMID:[Paraneoplastic hypercalcemia and ovarian seminoma. Review of the literature and etiological discussion apropos of a case]. 266 77

A patient with post-operative recurrent parathyroid adenoma was treated with percutaneous injection of absolute ethanol under ultrasonographic guidance. Serum calcium and PTH level were both successfully normalized, while recurrent nerve palsy was encountered as side effect. Six months later, she was suffered from hyperparathyroidism again, because of local tumor recurrence. Her recurrent nerve palsy was cured at that time. This technic could be a simple and non-invasive alternative for the conventional surgical procedure, but the indication for larger adenomas like this case should be carefully considered.
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PMID:[Percutaneous ethanol injection of parathyroid adenoma under US guidance]. 266 89

When available, state of the art noninvasive localization studies should be utilized routinely in previously unexplored patients for localizing parathyroid pathology, even when exceptional surgical experience exists. These studies can both minimize the 3 to 20% incidence of missed pathology and promote an approach of limited neck exploration with consequent lowering of morbidity, complications, and costs. Choice of imaging modalities for localizing these small masses is largely dependent on the level of state of the art of available equipment, the interest and experience of the performing physicians, and the attention to technical detail for each of the modalities at an individual institution. In choosing a single test, CT, and most recently cine CT with three-dimensional modeling, is favored because of higher probability of providing the kinds of information most useful to the surgeon. This includes precise anatomic localization and identification of locations likely to be missed by the surgeon (such as mediastinum, deep neck) and the capability for predicting multiple gland disease, for detecting smaller lesions, and for lower incidence of false-positive results. Ultrasound is attractive because of the low cost and noninvasiveness, and it is particularly sensitive in the thyroid region and upper neck. In difficult cases, CT, cine CT, and ultrasound may be augmented by needle aspiration of fluid for PTH assay. Thallium-technetium scanning and MRI are useful alternatives. In the previously explored patient and in patients with difficult diagnostic problems (such as ectopic adenoma, parathyroid carcinoma), the use of multiple noninvasive studies is strongly recommended, preferably CT (particularly, cine CT with three-dimensional imaging) and isotope scanning or MRI. The concurrence of two or more of these studies has a relatively high predictive value (82 to 88%) for localization. However, highly selective venous catheterization and selective magnification arteriography remain the most accurate modalities in these patients (91 to 95% sensitivity with few false-positive results) and may be combined with interventional radiologic techniques for tumor ablation in selected patients without compromising subsequent surgical alternatives. Stereotactic ablation techniques are in development.
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PMID:Parathyroid localization, three-dimensional modeling, and percutaneous ablation techniques. 267 67

Primary hyperparathyroidism is a common disorder and one that can usually (approximately 95%) be successfully treated by parathyroidectomy. PTH assays have become quite accurate for confirming the diagnosis. In patients with malignancy-associated hypercalcemia, parathyroid-like protein levels are usually increased, and radioimmunoassays being developed to quantitate serum levels of this protein will make the diagnosis easier. Treatment for a parathyroid adenoma is removal of the tumor and identification of the normal parathyroid glands. Treatment for primary or secondary hyperplasia is usually subtotal parathyroidectomy. Recurrent hyperparathyroidism is uncommon, except in patients with familial hyperparathyroidism, MEN-1 parathyroid carcinoma, or renal failure and secondary hyperparathyroidism. Persistent hyperparathyroidism is more common and is usually due to surgeon inexperience, but it is also caused by ectopically situated parathyroid glands, multiple abnormal parathyroid glands, or supranumerary parathyroid glands. Preoperative localization studies using ultrasound, thallium-technetium scanning, MRI, or CT scanning are reliable in patients with solitary parathyroid adenomas, but often fail to detect all of the abnormal parathyroid tissue in patients with multiple abnormal parathyroid glands. Intraoperative use of urinary cyclic AMP assays and rapid PTH assays have recently been used experimentally during parathyroid explorations to determine whether all hyperfunctioning parathyroid tissue has been removed, but these methods are not yet reliable or fast enough to be generally accepted. Most patients with primary hyperparathyroidism who are successfully treated by parathyroidectomy experience psychological, clinical, and metabolic benefits.
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PMID:Primary hyperparathyroidism. A surgical perspective. 267 68

Severe hypercalcemia is a potentially life-threatening complication of several diseases. Most commonly it is caused by cancers that enhance bone resorption. Impaired renal calcium excretion resulting from a combination of volume contraction and calcium-induced renal injury (nephrocalcinosis) plays a critical role in the genesis and aggravation of hypercalcemia. Treatment of hypercalcemia is based on treating the underlying disease, restoring extracellular volume, correcting electrolyte deficiencies (potassium and magnesium), and reducing bone resorption. Several measures are available to reduce bone resorption, of which the most efficacious are the bisphosphonates and plicamycin (mithramycin). One of these agents in combination with volume expansion can reduce serum calcium concentrations to near normal in most patients within 3 to 6 days. Because of the delayed hypocalcemic action of these agents, they should be administered early. Calcitonin has a more modest hypocalcemic action than the bisphosphonates or plicamycin but has a more rapid effect. Combining calcitonin with plicamycin or a bisphosphonate can enhance the rate of decline of the serum calcium level. Bone resorption also can be reduced by getting patients out of bed to stand or walk. Glucocorticoids may be effective in patients with hypercalcemia associated with high levels of vitamin D, such as sarcoidosis, some lymphomas, or vitamin D intoxication. Patients with mild to moderate hypercalcemia may be asymptomatic. Therapy in these patients should be directed at the primary disease as well as at preventing complications that could raise the level of serum calcium. Efforts should be made to prevent volume contraction and prolonged bed rest. Sedatives and narcotic analgesics, by reducing activity and oral intake, can raise serum calcium levels. In the future it may be possible to predict which patients with cancer are likely to develop accelerated local tumor-mediated or humorally mediated osteolysis. For example, high circulating levels of PTH-like peptides in patients with lung cancer might suggest a greater risk of developing hypercalcemia. These patients could be monitored more closely by periodically measuring urinary calcium. Another prophylactic approach would be to treat patients at risk of developing hypercalcemia with drugs, such as the bisphosphonates, that inhibit bone resorption.
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PMID:Treatment of hypercalcemia. 267 75

PTH-like peptide (PLP) is produced by a number of tumors commonly associated with the development of hypercalcemia. Analysis of the expression of the PLP gene has demonstrated that a variety of non-neoplastic endocrine and nonendocrine tissues contain PLP mRNA transcripts. Using a combination of Northern blot analysis, immunohistochemistry, and RIAs, we have demonstrated that the PLP gene is expressed in normal human and rat fetal and adult islets of Langerhans. PLP gene expression was not confined to cells containing a single pancreatic islet hormone, but was found in cells of all four major endocrine subtypes. PLP mRNA transcripts were also detected in RNA prepared from isolated rat islets, and small amounts of PLP immunoreactivity were secreted by cultured rat islets. Fifteen human pancreatic endocrine tumors not associated with hypercalcemia were analyzed and PLP-immunopositive tumor cells were found in 13. These observations demonstrate that the PLP gene is expressed in the normal and neoplastic islets of Langerhans, and suggests a possible role for this peptide in the growth or function of the endocrine pancreas.
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PMID:The parathyroid hormone-like peptide gene is expressed in the normal and neoplastic human endocrine pancreas. 269 79

The mechanisms of hypercalcemia were assessed in 15 patients with humoral hypercalcemia of malignancy (HHM) who had tumors at various stages of progression. In patients with early tumors, bone biopsies were generally normal and the hypercalcemia was due to an elevation in renal tubular resorption of calcium. Conversely, osteoclastic resorption was markedly increased in patients with advanced tumors, particularly those in whom the biopsies were obtained postmortem. Osteoclast surface (Oc.S) correlated positively with the stage of tumor progression (r = 0.80, p less than 0.002), degree of immobility (r = 0.87, p less than 0.002), and level of urinary cyclic AMP excretion (r = 0.60, p less than 0.02). When compared with a group of ambulant patients with primary hyperparathyroidism (HPT), osteoblast surface (Ob.S%) in HHM was depressed (median and range): 1.2% (0-11.6%) versus 5.3% (1.1-32.0%) (p less than 0.001). However, a relatively low Ob.S (4%) and raised Oc.S (43.5%) were also seen in an immobilized patient with severe HPT. These data suggest that the PTH-related peptides currently invoked in the pathogenesis of HHM may initially cause hypercalcemia by enhancing renal tubular calcium resorption. The increase in osteoclastic activity and depression of osteoblastic activity that subsequently occurs is probably due to the combined effects of immobilization and higher circulating levels of PTHrP on the skeleton. However, the release of other bone-resorbing factors by the tumor, which have a depressant effect on osteoblastic activity, remains possible.
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PMID:Contrasting mechanisms of hypercalcemia in patients with early and advanced humoral hypercalcemia of malignancy. 271 73


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