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)

An immunoperoxidase method has been developed to detect parathyroid hormone-related protein (PTHrP) in histological specimens of tumors and of normal skin. A rabbit polyclonal antiserum against PTHrP-(1-16) was used that did not cross-react with PTH-(1-34) either under radioimmunoassay conditions or at the high antiserum concentrations used in neutralizing biologic activity. PTHrP antigen was detected in the keratinocyte layer of normal skin and in 100% of 34 samples of squamous cell cancers but in only one of six breast cancers, and none of 15 other adenocarcinomata. It was also detected in four of four samples of renal cortical carcinoma and two of two of melanoma, both of which can be associated with hypercalcemia, and three of three small cell carcinomata of the lung. Immunologic detection of PTHrP could be useful in the diagnosis of tumors of squamous cell origin, particularly in the cytological differentiation of lung cancers, where it may be of value in distinguishing between squamous cell and small cell carcinoma on the one hand and poorly differentiated adenocarcinoma on the other.
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PMID:Parathyroid hormone-related protein: immunohistochemical localization in cancers and in normal skin. 272 30

In a population of 621 patients with morphologically proven bronchogenic carcinoma the rate of hypercalcaemia in particular morphologic types of bronchogenic carcinoma was ascertained during the establishment of diagnosis. Regardless of type, there were 10.3% of hypercalcaemic patients in the whole population. Hypercalcaemia was found most frequently in epidermoid carcinoma (10.98%), followed by adenocarcinoma (10.51%), small cell carcinoma (10.11%) and undifferentiated carcinoma (9.72%). In the group of 19 large cell carcinomas the hypercalcaemia was not established. Except large cell carcinoma, the differences among the groups were not statistically significant.
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PMID:[Hypercalcemia in bronchogenic carcinoma]. 274 69

A case of prostatic carcinoma with the cellular patterns of an adenocarcinoma and carcinoid tumor is reported. The tumor contained ultrastructural dense core neuroendocrine granules, and immunoperoxidase staining revealed prostatic acid phosphatase, prostatic-specific antigen, chromogranin, neuron-specific enolase, serotonin, adrenocorticotrophic hormone (ACTH), somatostatin, parathormone, calcitonin, bombesin, and glucagon but no insulin. The patient had exhibited hypercalcemia that may have been related to hormone production by the tumor. The literature on the endocrine aspect of the prostate and its tumor is reviewed.
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PMID:Prostatic carcinoma with endocrine features. A report of a neoplasm containing multiple immunoreactive hormonal substances. 289 Dec 93

The clinical and pathologic features of 29 cases of ovarian clear cell adenocarcinoma (OCCA) were studied to evaluate outcome and potential predictors of survival. Patients' ages ranged from 30 to 89 years (median, 54 years). The study group, using the FIGO classification, consisted of 10 Stage I, 5 Stage II, 7 Stage III, 5 Stage IV, and 2 unstaged patients. Previous or concurrent endometriosis was noted in 45% of patients. Three patients (10.3%) had hypercalcemia. Only stage and the presence of macroscopic residual disease had a statistically significant association with survival. Stage I and II patients experienced a survival similar to a group of 305 patients with adenocarcinomas of non-clear cell type in our ovarian cancer registry with the exception of the very poor survival among Stage IC OCCA patients. Patients with Stage III and IV OCCA had a worse survival than non-OCCA registry patients of similar stage. Few objective responses to adjuvant chemotherapy could be demonstrated in these high-stage OCCA patients. Further study of postoperative adjuvant therapies is warranted.
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PMID:Ovarian clear cell adenocarcinoma. 292 Sep 55

The effect of a low calcium diet, mithramycin, or dichlorodimethylene bisphosphonate were evaluated in nude mice with humoral hypercalcemia of malignancy associated with the transplanted canine adenocarcinoma (CAC-8). Low calcium (0.01%) diet significantly reduced serum calcium levels in hypercalcemic nude mice and reduced urine calcium excretion to control levels. Mithramycin (8 mg/kg) decreased serum calcium concentration and urine calcium excretion to the range of control non-tumor-bearing nude mice at day 5 after a single injection, but there was no change in the number of tartrate-resistant acid phosphatase-positive osteoclasts in lumbar vertebrae. Osteoclasts from CAC 8-bearing nude mice after mithramycin administration were decreased in size, had small ruffled borders, and increased relative size of clear zones. Dichlorodimethylene bisphosphonate (Cl2MDP) (45 mg/kg) partially reduced serum calcium concentration of hypercalcemic tumor-bearing nude mice, decreased urine calcium excretion to control levels, and markedly reduced the numbers of tartrate-resistant acid phosphatase-positive osteoclasts in lumbar vertebrae. Osteoclasts from Cl2MDP-treated nude mice were smaller and had a reduced frequency of ruffled borders than saline-treated hypercalcemic nude mice. In vitro bone resorption induced by CAC-8 extract was significantly reduced by Cl2MDP and mithramycin. The results of these investigations suggest that the hypercalcemia and hypercalciuria associated with HHM in nude mice with CAC-8 are the combined result of altered calcium homeostasis in the bone, kidney, and intestine. Chemotherapeutic agents that specifically affect only bone or feeding a low calcium diet alone may not completely ameliorate the hypercalcemia of HHM.
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PMID:The effect of low calcium diet, mithramycin, and dichlorodimethylene bisphosphonate on humoral hypercalcemia of malignancy in nude mice transplanted with the canine adenocarcinoma tumor line (CAC-8). 297 5

A serially transplantable tumor line, designated CAC-8, has been developed in nude mice from a spontaneously occurring adenocarcinoma of the anal sac from a hypercalcemic dog. Nude mice with transplanted CAC-8 developed hypercalcemia (mean 16.3 +/- 0.6 mg/dl) and moderate hypophosphatemia without bone metastasis. Urinary excretion of calcium and hydroxyproline were increased 6- and 2.3-fold, respectively. Urinary excretion of cAMP was moderately increased but phosphorus excretion was not significantly altered. Serum 1,25-dihydroxycholecalciferol was increased significantly in tumor-bearing nude mice in proportion to the magnitude of tumor-induced hypercalcemia. Histomorphometric evaluation of lumbar vertebrae from nude mice with CAC-8 revealed decreased total and cortical bone volume, a 3.3-fold increase in bone resorption rate and a 2.5-fold increase in bone formation rate at the tissue level. The transplanted CAC-8 has maintained the histologic pattern of the original carcinoma up to the present sixth passage. Ultrastructural evaluation of transplanted tumor cells revealed 150-250-nm secretory-like granules. The granules did not stain by using an ultrastructural cytochemical (uranaffin) stain specific for neuroendocrine secretory granules. Ultrastructurally, the parathyroid glands of nude mice with CAC-8 appeared inactive with large intracytoplasmic whorl of agranular membranes. These data suggest the transplanted carcinoma secreted a humoral factor which resulted in hypercalcemia. The tumor line (CAC-8) propagated in nude mice represents an animal model of humoral hypercalcemia of malignancy that shares many features with the syndrome described in human patients. Unique features of this transplanted carcinoma associated with hypercalcemia include increased serum dihydroxycholecalciferol, increased rate of bone formation as well as bone resorption, an absence of bone metastases, and evidence of parathyroid gland suppression.
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PMID:Humoral hypercalcemia of malignancy in nude mouse model of a canine adenocarcinoma derived from apocrine glands of the anal sac. Biochemical, histomorphometric, and ultrastructural studies. 301 99

In a 47-year-old woman with a pancreatic mass associated with hypercalcemia and mental confusion, medical measures failed to restore her serum calcium level to normal. To do so, radical resection of a locally invasive vascular neoplasm arising from the body and tail of the pancreas was necessary. The neoplasm was a pancreatic islet-cell tumour. Serum parathormone assays demonstrated abnormally high secretion of a parathormone-like substance. Ectopic secretion of such substances from islet-cell tumours should be considered in association with refractory metabolic disturbances. In view of the often indolent clinical course of islet-cell tumours and the potential for life-threatening hormonal effects, biopsy confirmation of adenocarcinoma should be obtained before resorting to palliative surgical management of pancreatic neoplasms.
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PMID:Pancreatic islet-cell neoplasia, with secretion of a parathormone-like substance and hypercalcemia. 303 May 25

The incidence and prognosis of patients with bone metastasis in primary advanced lung cancer were studied retrospectively. Between Jan. 1980 and Dec. 1985, 289 cases entered various kinds of chemotherapy protocol studies. Patients with bone metastasis of non-small cell lung cancer (NSC) comprised 44% (86/192), and those with small cell lung cancer (SC) comprised 43% (42/97). Histologically, 48% of adenocarcinoma, 50% of large cell carcinoma and 31% of squamous cell carcinoma showed bone metastasis. 8 percent of NSC bone meta (+) cases had an initial symptom of bone metastasis. Bone scan and bone X-ray were complementary and useful for diagnosis of bone metastasis, and sequential examinations tended to reduce the incidence of false-positive cases. Vertebral column, rib, pelvis and femur were the most common sites. Over 70% of the bone metastasis were in multiple skeletal systems, and 90% showed multiple-site involvement for both NSC and SC. Radiation therapy effectively reduced severe pain but paralysis was hard to control. In very few cases surgical treatment was indicated because of multiple bone metastasis, and systemic dissemination. Bone scan in 12% of SC patients showed apparent improvement with systemic chemotherapy. Among the M1 group of adenocarcinoma, median survival was 9 months in bone (+) cases, 11 months in bone (-) cases, 2 year survival was 8%, and 24%, and 3-year survival 2% and 22%, respectively. Among the bone(+) group and bone(-) group in ED cases of SC, median survival was 10 months vs. 11 months, and 2-year survival rates were both 13%. 22 percent (8/36) of squamous cell carcinomas without bone metastasis showed hypercalcemia (5.5 mEq/l). In patients with advanced lung cancer the major goal of treatment is recovery of the performance status of the patient and the relief of pain. In the case of SC, intensive systemic chemotherapy should be conducted as an adjuvant to local therapy.
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PMID:[Recent status of the diagnosis and treatment of bone metastasis in patients with advanced lung cancer]. 303 14

The three biologic activities most commonly associated with tumors that produce Humoral Hypercalcemia of Malignancy (HHM) include; 1) adenylate cyclase stimulating activity (PTH-like activity), 2) in vitro bone resorbing activity, and 3) transforming growth factor activity. The canine adenocarcinoma (CAC-8) model of HHM contains all three activities and the first two are inhibited by a PTH receptor antagonist. These data in light of the recent purification of PTH-related peptides from human tumors suggest that CAC-8 produces a PTH-related protein that is important in the pathogenesis of hypercalcemia. The CAC-8 tumor is a well characterized example of HHM and offers several advantages for further investigations on the pathogenesis of HHM: 1) transplantable tumor line from a spontaneous neoplasm in the dog, 2) tumor extracts contain the three biologic activities associated with HHM, 3) slow progressive growth rate in nude mice permits investigations on treatment of HHM, 4) increased bone resorption and formation in nude mice mimics the effects of PTH on bone, and 5) the only model of HHM that has been demonstrated to contain bone resorbing activity that can be inhibited by a PTH receptor antagonist.
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PMID:Pathogenesis of humoral hypercalcemia of malignancy. 306 80

Canine apocrine cell adenocarcinoma of the anal sac (APO-AS) is a spontaneously occurring tumor that causes humorally mediated hypercalcemia in 90% of cases. To further define the nature of the responsible mediator in APO-AS, we examined tumor extracts from five APO-AS and four control tumors for adenylate cyclase-stimulating activity (ACSA). All extracts from APO-AS contained potent ACSA, whereas the four control tumors did not. The ACSA extracted from one tumor demonstrated a dose response curve parallel to that of synthetic bovinePTH-(1-34) and was 80% inhibited by Nle8,18,Tyr34 bPTH-(3-34)amide at a concentration of 10(-5) M. Extracts from three APO-AS and three control tumors were also examined for in vitro bone-resorbing activity (BRA). All APO-AS contained significant BRA, stimulating resorption 1.47 to 2.13-fold over basal, whereas none of the control tumors stimulated resorption. Purification of one extract using C18 reverse-phase high pressure liquid chromatography (RP-HPLC) resulted in a single sharp peak of ACSA which was 400-fold purified compared with the initial extract. This pool also contained significant bone-resorbing activity, whereas none of the adjacent pools did. Purification of a second extract using sequential CN and C18 RP-HPLC followed by size exclusion HPLC resulted in material that was at least 10,000-fold purified, and showed co-purification of ACSA and B TGF-like activity.
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PMID:Adenylate cyclase-stimulating, bone-resorbing and B TGF-like activities in canine apocrine cell adenocarcinoma of the anal sac. 314 25


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