Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A premenopausal woman with soft tissue metastases from a carcinoma of the breast developed hypercalcemia with hypophosphatemia, reduced tubular reabsorption of phosphate, elevated urinary cyclic AMP levels and normal serum PTH levels was observed. Hormonal therapy with testosterone followed by tamoxifen induced normalization of her serum calcium concomitant with the disappearance of the pleural effusion and reduction in the size of her lung metastases. The correlation between the efficacy of antitumor treatment on pleural effusion, lung metastases, and normalization of serum calcium, as well as the elevated PTH level in the pleural effusion, suggest that this breast carcinoma secreted a PTH-like substance.
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PMID:Hypercalcemia in carcinoma of the breast without evidence of bone destruction: beneficial effect of hormonal therapy. 729 87

Tumor cells in bone metastases are thought to induce bone resorption primarily by releasing paracrine factors. Parathyroid hormone related protein (PTHrp) has been proposed to mediate osteolytic activity of many tumors. PTHrp is produced by 40% to 60% of breast tumors and is elevated in the serum of up to 50% of patients with breast cancer metastases to bone. Most biologic processes in humans are heterogeneous in nature, so the purpose of this study was to investigate the hypothesis that paracrine factors other than PTHrp could mediate bone resorption by breast tumor cells. Serum-free conditioned medium (CM) was collected from five human breast tumor cell lines and tested for bone resorption-stimulating activity (BRSA) in mouse calvaria organ cultures. CM from all tumor cells studied produced significant bone resorption, comparable to that produced by 10 nM PTH. Small amounts of immunoreactive PTHrp (1.4-12.5 pM) were produced by all breast tumor cell lines. When tested in vitro, equivalent amounts of human PTHrp [1-36] did not produce significant bone resorption. Indomethacin (1 microM) significantly blocked BRSA by CM from all cell lines but did not decrease BRSA by PTHrp. In contrast PTHrp antibody (130 micrograms/ml) completely blocked BRSA by 1 nM PTHrp but did not modify BRSA by CM of breast tumor cells. The results of this study support the hypothesis that breast cancer cells release paracrine factors in vitro that stimulate bone resorption by a mechanism that is partially dependent on prostaglandin synthesis and at least in part different from that of PTHrp.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Parathyroid hormone-related protein: primary osteolytic factor produced by breast tumor cells in vitro? 775 38

1,25-dihydroxyvitamin D (1,25-(OH)2D) stimulates differentiation and controls proliferation in breast cancer cells. The role of endogenous 1,25-(OH)2D and its relation to PTH related protein (PTHrP) during the progression of breast cancer is not known; we therefore investigated these hormones in two studies. In a cross-sectional study of patients with breast cancer at different stages of disease, serum 1,25-(OH)2D levels (mean +/- SE) were highest in early disease (102 +/- 3.7 pmol/L), fell in normocalemic patients with bone metastases (52 +/- 5.3 pmol/L; P < 0.01), and were lowest in hypercalcemic patients (33 +/- 5.6 pmol/L; P < 0.001). PTHrP was detectable in the serum of only one normocalcemic patient with progressive metastases but was present in 11 of the 12 hypercalcemic patients, thus PTHrP did not stimulate 1,25-(OH)2D synthesis. In a 6-month longitudinal study of normocalcemic patients with bone metastases undergoing hormonal therapy, serum 1,25-(OH)2D concentrations fell in patients whose disease progressed (P = 0.0056), but remained constant in those who were stable or responded to treatment. These changes in 1,25-(OH)2D preceded clinical signs of progression and predicted disease response. In the progressive group, five of whom died during the study, 1,25-(OH)2D decreased between the initial and final samples, PTH fell significantly from 24.8 to 13.5 ng/L (P = 0.025), serum calcium rose from 2.27 to 2.39 mmol/L (P = 0.017), and the urinary calcium/creatinine ratio rose from 0.37 to 0.68 (P = 0.046). PTH and 1,25-(OH)2D were significantly correlated in the final samples from this group, Spearman's rank correlation = 0.80, P = 0.022. The results indicate that normocalcemia in these patients is maintained, at the expense of suppressing PTH and 1,25-(OH)2D, in the face of increased calcium released from lytic lesions in bone. Loss of the antiproliferative effects of 1,25-(OH)2D may then permit more rapid secondary growth of the tumor.
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PMID:Serum 1,25-dihydroxyvitamin D may be related inversely to disease activity in breast cancer patients with bone metastases. 932 98

A case of ovarian clear cell carcinoma associated with hypercalcemia is reported. A 67-year-old woman developed the lung metastasis 8 months after primary surgery. The patient manifested symptoms of humoral hypercalcemia of malignancy (HHM) during the last 3 months of her clinical course. Serum and urinary C-terminus parathyroid hormone-related protein (PTHrP) levels were remarkably high. No increase in interleukin (IL) 1beta, tumor necrosis factor (TNF) alpha, vitamin D3 metabolites or intact PTH was detected. Pamidronate disodium treatment was transiently suppressed her serum calcium level. The patient died despite seven courses of chemotherapy. Autopsy showed multiorgan metastases and accelerated osteoclastic bone resorption; skeletal metastasis was not detected. Immunohistochemical analysis clearly showed the localization of PTHrP at both the primary and metastatic sites. The transcripts of PTHrP at pulmonary metastatic sites were revealed by in situ hybridization and the reverse transcription polymerase chain reaction (RT-PCR) method. PTHrP was the causative factor for HHM in this case. It is therefore suggested that hypercalcemia may have occurred after PTHrP production had overcome the homeostatic level during the terminal stage, although PTHrP production continued irrespective of the patient's serum calcium level.
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PMID:In situ detection of parathyroid hormone-related protein in ovarian clear cell carcinoma. 904 5

An unusual case of multiple brown tumors due to parathyroid carcinoma is reported. The patient presented with lower leg pain. Plain radiographs demonstrated multiple lytic lesions of the lower legs and a Tc-99m MDP bone scan depicted multiple areas of increased uptake suggesting skeletal metastases. Tc-99m sestamibi tumor scintigraphy showed multiple sites of tumor uptake in bones and a large area of increased uptake with a cystic component in the right lower pole of the thyroid gland. An open biopsy from the right tibial lesion revealed a brown tumor. A large parathyroid carcinoma with a necrotic cyst was removed. After parathyroidectomy and right thyroid lobectomy, the patient became free of bone pain and serum PTH levels normalized. A 9-month follow-up Tc-99m MDP bone scan demonstrated less intense uptake in the pelvis, tibia, and fibulae. Nine-month follow-up tumor imaging with Tc-99m MIBI revealed disappearance of the preoperative uptake of multiple brown tumor.
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PMID:Multiple brown tumors in parathyroid carcinoma mimicking metastatic bone disease. 934 25

We report the case of a 46-year-old male patient who, after disease-free intervals of five, four and one and a half years following resection of an 'atypical' parathyroid adenoma in 1982, relapsed with clinical and laboratory recurrence of primary hyperparathyroidism (PHP). Noninvasive, traditional and modern imaging methods localized small distinct metastatic foci in both lungs without evidence of primary thyroid, neck or mediastinal tumor. Three successive bilateral lung nodule excisions resulted in a long PHP remission, while a three month treatment with normal saline infusions, diuretics, calcitonine and pamidronate infusions, following the last recurrence, resulted in moderate improvement of hypercalcemia and hypercalciuria with no effect on both PTH secretion or on the size of new metastatic lung foci. Recurrent mPCa with or without secretion of biologically active PTH is optimally treatable with successive surgical resections of the metastases and intermittent medical treatment to achieve PTH secreting tumor mass reduction and a beneficial metabolic effect.
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PMID:Metastatic parathyroid carcinoma (mPCa): natural history and treatment of a case. 950 19

With the variety of radiopharmaceutical agents and refined imaging techniques, thyroid and parathyroid imaging provides much valuable clinical information. The use of imaging is most important in the follow-up of differentiated (DTC) and medullary thyroid cancer (MTC). Patients with DTC are followed with serum thyroidglobulin and 131I whole body scintigraphy when the serum thyroglobulin level is elevated. When the 131I scintigram is negative, 201Tl scintigraphy may best identify the site of recurrent DTC. Alternative radioisotopes, ultrasound, CT, and FDG PET are also useful in localizing the site of DTC metastases. MTC recurrences and metastases are more difficult to image. Selective venous catheterization is the most sensitive and specific method for detecting areas of recurrent MTC. High-resolution ultrasound, CT, MR imaging, and scintigraphy are all capable of, and useful in, detecting macroscopic foci of metastatic tumor. Somatostatin receptor scintigraphy and 99mTc DMSA have been the most frequently used nuclear imaging agents in patients with recurrent MTC. Imaging for hyperparathyroidism remains controversial. Sestambi has become the preferred isotope for parathyroid scintigraphy; whereas high-resolution ultrasound is also frequently used. Preoperative imaging is being used as a method to allow a unilateral neck exploration, more recently, in conjunction with intraoperative 1-84 PTH assay and with intraoperative use of the gamma probe. Most often, parathyroid imaging is performed before reoperation for persistent hyperparathyroidism.
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PMID:The use of imaging studies in the diagnosis and management of thyroid cancer and hyperparathyroidism. 982 66

Parathyroid carcinoma is a rare cause of primary hyperparathyroidism (1-2%). In this paper a case of parathyroid cancer of the right inferior parathyroid gland cyst (5 cm in diameter) localised mostly retrosternally is presented in a patient suffering from severe hypercalcaemia (Ca--3.7 mmol/l, Ca(++)--1.8 mmol/l), severe bone pains and weakness, huge osteoporosis with following L5 compression fracture and recurrent nephrolithiasis. PTH blood level before surgical treatment was 1243 pg/ml (Norm: 10-60 pg/ml). In the preoperative ultrasonography of the neck, a lesion was found, but it was considered to be a cyst in the inferior pole of the right thyroid lobe. In a fine-needle biopsy from the lesion-colloid mass without any cells was found. In a 99mTc-MIBI scintigraphy of the neck a suspicion of focus lesion in the right superior parathyroid gland was made, which was not confirmed intra-operatively. Parathyroid carcinoma was diagnosed intraoperatively in histological examination. 'En block' resection of the retrosternal parathyroid tumor and right thyroid lobe was performed from the jugular incision. Any enlarged jugular lymph nodes were not found. In a postoperative period a transient hypocalcaemia was present, which disappeared after pharmacological treatment. During 32 months of follow-up neither no features of local recurrence nor distant metastases were found. Calcium level in blood was normal, PTH 216.0 pg/ml, severity of bone pains and weakness lessened, osteoporosis in a course of pharmacological treatment--with no further progress.
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PMID:[Retrosternal parathyroid gland cystic neoplasm as a cause of primary hyperparathyroidism]. 1069 86

Humoral hypercalcemia of malignancy (HHM) occurs when secretion of parathyroid hormone-related peptide (PTHrP) by cancer cells causes hypercalcemia in the absence of skeletal metastases. High extracellular calcium (Ca(2+)(o)) increases secretion of PTH-like bioactivity by rat H-500 leydig cells, a transplantable model of HHM, an action potentially mediated by the Ca(2+)(o)-sensing receptor (CaR). In this study we investigated whether H-500 cells express the CaR and, if so, whether CaR agonists modulate PTHrP secretion. Northern blot analysis and RT-PCR revealed bona fide CaR transcript(s), and immunocytochemistry and Western analysis with a specific anti-CaR antiserum demonstrated CaR protein expression in H-500 cells. Furthermore, high Ca(2+)(o) and neomycin stimulated PTHrP secretion dose-dependently with maximal 2.7- and 3.3-fold increases at 5 mM Ca(2+)(o) and 300 microM neomycin, respectively. Thus in HHM caused by H-500 cells, the CaR could participate in a vicious cycle whereby PTHrP-induced increases in Ca(2+)(o) further stimulate PTHrP release and exacerbate hypercalcemia.
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PMID:Extracellular calcium-sensing receptor (CaR) expression and its potential role in parathyroid hormone-related peptide (PTHrP) secretion in the H-500 rat Leydig cell model of humoral hypercalcemia of malignancy. 1070 70

The paper presents current diagnostic and therapeutic approach in parathyroid cancer. The suspicion of parathyroid cancer should be taken into account in patients with primary hyperparathyroidism symptoms (and elevated total and ionised calcium blood level and PTH blood level), present palpable cervical mass and enlarged cervical lymph nodes. Further diagnosis should be based on ultrasound of the neck (including power-Doppler ultrasound), subtraction 99mTc-MIBI and 123J scintigraphy, ultrasound-guided fine needle aspiration, and CT or MRI if necessary to assess the stage of the process. The elective surgical procedure should be primary 'en block' excision of the tumour with the unilateral thyroid lobe and the following loco-regional adjuvant radiotherapy. Patients who underwent surgical treatment due to parathyroid cancer require long-term follow-up as the risk of local recurrence or distant metastases (mostly into lungs or bones) remains high even many years after initial operation. Patients with dissemination usually suffer from severe hypercalcemia leading to death if untreated correctly. Thus, so crucial is effective treatment of hypercalcemia (diuresis, biphosphonates, calcitonine, oktreotide).
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PMID:[Parathyroid neoplasm--diagnostic challenge and therapeutic difficulty]. 1090 88


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