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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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

A decrease in renal tubular reabsorption of inorganic phosphate (Pi) can be observed in hypercalcemia of malignancy. In the present study we investigated the effect of serum-free conditioned medium (CM) from cells, derived from a lung carcinoma (BEN) of a hypercalcemic patient, and of PTH on cyclic AMP (cAMP) production and sodium-dependent Pi transport (NaPiT) in epithelia of two renal cell lines. In opossum kidney cells (OK), PTH is known to enhance cAMP production and inhibit NaPiT; in contrast, in LLC-PK1 cells, PTH has no effect on NaPiT since this kidney cell line is devoid of PTH receptors. In OK cells, BEN CM induced a three- to fourfold increase of cAMP production, which was blunted by the PTH inhibitors bPTH(3-34) and bPTH(7-34). NaPiT, as assessed by measuring the initial rate of Pi uptake, was inhibited in a dose-dependent manner by BEN CM, with an effect maximal between 1h30 and 6 hr of incubation (40 +/- 4% and 47 +/- 4%, respectively), corresponding to the effect produced by 1-3 nM bPTH(1-34). The Na-dependent transport of a glucose analog was affected neither by BEN CM nor by PTH. In LLC-PK1 cells, neither BEN CM nor PTH altered cAMP production nor NaPiT after 1h30 of incubation. At 6 hr, BEN CM caused a slight decrease in NaPiT. In conclusion, these results constitute the first evidence of a direct and selective inhibition by tumor-derived factor(s) of NaPiT in cultured renal epithelia. Most of the renal NaPiT inhibitory activity produced by the lung tumor required the presence of a PTH receptor-adenylate cyclase system.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Factor derived from human lung carcinoma associated with hypercalcemia mimics the effects of parathyroid hormone on phosphate transport in cultured renal epithelia. 321 17

A 45-year-old female manifested lower abdominal fullness and symptoms of hypercalcemia with nausea, vomiting, and thirst. Physical examination showed a right ovarian mass and laboratory data demonstrated hypercalcemia (14.6 mg/dl). The radiographic findings confirmed a right ovarian tumor without any evidence of bone metastasis. Tests revealed that her PTH, nephrogenic urinary cyclic AMP, and 1-25 (OH)2 Vitamin D were not high but that her prostaglandin E2 (PGE2) was elevated. After correction of her calcium elevation with infusion and prednisolone, right oophorectomy with tumor excision was performed. A histological examination of the tumor revealed a mucinous cysto-adenocarcinoma. The postoperative course has been uneventful, with normal calcium and PGE2 values. This case illustrates that hypercalcemia associated with an ovarian carcinoma (Malignancy-associated hypercalcemia) can be mediated by the patient's PGE2 in part.
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PMID:[A case of hypercalcemia with ovarian carcinoma]. 323 Jun 42

To determine the pathogenesis of humoral hypercalcemia associated with esophageal carcinoma in a 65-yr-old patient, clonal cell lines (EC-GI) were established from the tumor. The EC-GI cells produced bone-resorbing activity which eluted from a Sephadex G-75 column in a broad peak, with an apparent mol wt of 10,000-50,000. In addition to PTH-like factor(s), the EC-GI cells produced a factor with thymocyte proliferation-stimulating activity which had an apparent mol wt of 15,000-20,000. This interleukin-1 (IL-1)-like factor(s) with acidic pI (4.8 and 5.2) exactly coeluted with the bone-resorbing activity upon DEAE-Sepharose ion exchange chromatography. Both bone-resorbing and thymocyte proliferation-stimulating activities were completely inhibited by anti-IL-1 alpha antiserum, but not by anti-IL-1 beta antiserum. Northern blot hybridization studies revealed that EC-GI cells produced exclusively mRNA for IL-1 alpha. Furthermore, fractions containing IL-1-like activity and PTH-like activity synergistically stimulated bone resorption in vitro, and transplantation of EC-GI cells into nude mice caused hypercalcemia in vivo. These findings suggest that IL-1 alpha and PTH-like factor produced by this squamous cell carcinoma synergistically stimulate bone resorption and are related to humoral hypercalcemia in tumor-bearing nude mice and in the patient.
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PMID:Production of interleukin-1 alpha and a parathyroid hormone-like factor by a squamous cell carcinoma of the esophagus (EC-GI) derived from a patient with hypercalcemia. 326 32

Recent advances in the techniques of preoperative parathyroid localization include ultrasonography, computed tomography, thallium-technetium subtraction scanning, magnetic resonance imaging, digital subtraction angiography with selective venous catheterization for PTH measurement, and ultrasound or CT-guided needle aspiration biopsy for cytological examination or PTH assay. These techniques are helpful for patients with hyperparathyroidism undergoing the initial operation, and essential for patients with persistent or recurrent hyperparathyroidism undergoing reoperation. Noninvasive procedures should be performed first, and the combination of any two positive studies localizes the tumor with near certainty. Invasive procedures have a higher risk of complications and are recommended only in selected patients before reoperation.
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PMID:Parathyroid localization. Clinical review. 330 54

Regional chromosome homologies were found in a comparison of human 11p with Chinese hamster 3p. By use of probes that recognize six genes of human 11p (INS, CAT, HBBC, CALC, PTH, and HRAS), the corresponding genes were localized by in situ hybridization on Chinese hamster chromosome 3. INS and CAT were located close to the centromere on 3p, whereas HBBC, CALC, and PTH were at 3q3-4 and HRAS at 3q4. Extensive prior data from chromosome studies of tumorigenic and tumor-derived Chinese hamster cells have suggested the presence of a tumor-suppressor gene on 3p. Two tumor-suppressor genes have been described on human 11p, one linked to CAT and one to INS. The present study raises the possibility that the Chinese hamster suppressor may be closely linked to INS or CAT.
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PMID:Genetic analysis of tumorigenesis: a conserved region in the human and Chinese hamster genomes contains genetically identified tumor-suppressor genes. 332 Oct 67

Hypophosphatemia and hyperphosphaturia characteristically occur in patients with humoral hypercalcemia of malignancy (HHM). To determine if a tumor product causes these abnormalities in phosphate metabolism, rather than, for example, hypercalcemia, we investigated the effect of partially-purified adenylate cyclase-stimulating activity (ACSA) from human and animal HHM-associated tumors on sodium-dependent phosphate transport (Na PiT) in a PTH-responsive renal epithelial cell line. Thirty minute exposure to 7 X 10(-10) MbPTH (1-34) equivalents of ACSA from the human and animal tumors, reduced NaPiT by 20% and 14%, respectively. We also recently isolated an adenylate cyclase-stimulating protein (hACSP) from two human tumors associated with HHM and identified a cDNA clone for this protein which encodes a 141 amino-acid peptide. Based on the deduced amino-acid sequence, we synthesized tyr36 (1-36) hACSP. This synthetic peptide induced a 22% decrease in the initial rate of NaPiT by the epithelial monolayer. Its inhibitory activity was roughly equipotent to that of bPTH (1-34). We conclude that the ACSP derived from HHM-associated tumors decreases phosphate transport in renal epithelial cells. This peptide appears to play a key role in mediating the changes in phosphate metabolism in this syndrome.
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PMID:Synthetic and partially-purified adenylate cyclase-stimulating proteins from tumors associated with humoral hypercalcemia of malignancy inhibit phosphate transport in a PTH-responsive renal cell line. 333 17

A number of factors have been proposed as potential mediators of the syndrome of humoral hypercalcemia of malignancy (HHM), but to date no firm cause-and-effect relationship has been established. We attempted to establish such a relationship by determining whether the presence or absence of adenylate cyclase-stimulating activity (ACSA) in the media of cultured tumor cells predicted the occurrence of the syndrome of HHM when these cell lines were grown in nude mice in vivo. Conditioned media from 35 human renal carcinoma cell lines were surveyed for ACSA in the PTH-sensitive rat osteosarcoma 17/2.8 cell assay. 12 lines were positive (mean, 13.7-fold stimulation, range, 3.0 to 44.0), and 23 lines were negative (mean, 1.2-fold stimulation, range, 0.9 to 1.5). We were successful in establishing five of the positive and six of the negative lines in three to five nude mice per line. Mice implanted with the positive lines uniformly became hypercalcemic (mean serum calcium, 15.8 mg/dl), whereas mice implanted with the negative lines uniformly remained normocalcemic (mean serum calcium, 9.5 mg/dl), in spite of comparable mean tumor size. Acid-urea tumor extracts from each of four hypercalcemic animals contained potent in vitro ACSA (mean, 15.9-fold stimulation), while 5/5 extracts from normocalcemic animals did not (mean, 1.4-fold stimulation). Our study demonstrates that in this model system in vitro ACSA is a reliable predictive marker for HHM in vivo. Whether the protein responsible for this activity is also the mediator of the bone resorption seen in HHM remains to be demonstrated.
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PMID:In vitro adenylate cyclase-stimulating activity predicts the occurrence of humoral hypercalcemia of malignancy in nude mice. 334 41

A synthetic peptide corresponding to the first 34 amino acids of the parathyroid hormone-related protein (PTH-rP) produced by a human tumor associated with hypercalcemia was examined for skeletal and renal effects on calcium metabolism in vivo and in vitro. These effects were compared with those of human parathyroid hormone (1-34), hPTH (1-34). Equal doses of PTH-rP(1-34) and hPTH(1-34) produced equivalent stimulation of adenylate cyclase in vitro in bone cells and kidney cells and tubules. Subcutaneous injection of PTH-rP(1-34) in mice caused a significant dose-related increase in blood ionized calcium similar to that seen with hPTH(1-34) at equivalent doses. Repeated injections of equal doses of both peptides caused sustained hypercalcemia which was significantly greater in PTH-rP(1-34)-treated mice, although each induced comparable increases in histomorphometric indices of osteoclastic bone resorption. PTH-rP(1-34) and hPTH(1-34) also caused similar increases in bone resorption when incubated with fetal rat long bones in organ culture. Infusion of either peptide into thyroparathyroidectomized rats suppressed urinary calcium excretion and increased urinary excretion of cyclic AMP. PTH-rP appears to have similar effects to those of PTH on the skeleton, the kidney, and overall calcium homeostasis.
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PMID:Effects of a synthetic peptide of a parathyroid hormone-related protein on calcium homeostasis, renal tubular calcium reabsorption, and bone metabolism in vivo and in vitro in rodents. 334 49

Three bioassays are widely employed for the measurement of PTH-like adenylate cyclase-stimulating factors (ACSFs) derived from tumors associated with humoral hypercalcemia of malignancy. These include renal cortical adenylate cyclase (RAC) assays, rat osteosarcoma (ROS) adenylate cyclase assays, and fetal bone resorption (FBR) assays. A previous study has suggested that the potency of one human tumor-derived ACSF, expressed in PTH equivalents, was 30-fold higher in the ROS assay than in the RAC assay, but no study has directly compared all three bioassays using a single PTH standard and a single ACSF preparation. We compared one partially purified ACSF preparation to a single lot of bPTH 1-34 in all three bioassays. The results indicate that the relative potency of this ACSF as compared to the PTH standard varied with the assay employed, with the ROS assay yielding a specific activity estimate 47.5-fold higher than the RAC, and the FBR 6.7-fold higher than the RAC but 7.1-fold lower than the ROS. These findings support the possibility that distinct subpopulations of PTH receptors exist on different PTH target tissues. Further, they underscore the importance of bioassay choice when estimating the specific activity of tumor-derived ACSF preparations.
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PMID:The relative potency of a human tumor-derived PTH-like adenylate cyclase-stimulating preparation in three bioassays. 345 55


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