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

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

The tumor-promoting phorbol ester 12-O-tetradecanoyl-phorbol-13-acetate (TPA) increases 25-hydroxyvitamin D3 (25OHD3)-24-hydroxylase and decreases 25OHD3-1-hydroxylase activity in cultured kidney cells, effects similar to those exerted by 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] and opposite those of PTH, forskolin, and cAMP. In this paper it is shown that the effects of TPA and 1,25-(OH)2D3 are additive, suggesting that they operate through distinct mechanisms. TPA did not alter cAMP metabolism by cultured chick kidney cells, not did it alter their response, in terms of 25OHD3 metabolism, to cAMP, suggesting that these two regulators of 25OHD3 metabolism also operate through distinct pathways. Another presumed activator of protein kinase-C 1,oleoyl-2-acetyl-glycerol, was tested and found to have the same effect as TPA in decreasing 1-hydroxylase activity, but it does not increase 24-hydroxylase activity. In addition, 1-oleoyl-2-acetyl-glycerol increases intracellular cAMP levels to approximately 25% of those attained by stimulation with PTH. None of the treatments resulted in altered [3H]PDBu binding by the cells. The results, taken together, suggest that 25OHD3-1-hydroxylase and the 25OHD3-24-hydroxylase are subject to multifactorial regulation and can be regulated independently of one another.
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PMID:Interactions between intracellular signals involved in the regulation of 25-hydroxyvitamin D3 metabolism. 253 73

A canine adenocarcinoma model (CAC-8) of humoral hypercalcemia of malignancy was evaluated for transforming growth factors (TGF)-alpha and -beta, PTH-like activity [adenylate cyclase-stimulating activity (ACSA)], and in vitro bone-resorbing activity. Biological activities present in CAC-8 were separated by reverse phase or cation exchange HPLC. TGF alpha in tumor extract was separated from TGF beta and ACSA by reverse phase HPLC. TGF alpha eluted between 26-30% acetonitrile and was identified by RIA. After the initial reverse phase separation, TGF beta and ACSA in tumor extract coeluted between 36-38% acetonitrile. Sequential cation exchange followed by reverse phase HPLC separated TGF beta from ACSA. Evaluation of fractions containing ACSA using an in vitro bone-resorbing assay demonstrated copurification of ACSA and bone-resorbing activity. The PTH receptor antagonist [Nle8,18,Tyr34]bovine PTH-(3-34)-amide, but not [Nle8,18,Tyr34]bovine PTH-(7-34)-amide, completely inhibited ACSA in column eluates. Conditioned cell culture medium from CAC-8 primary cultures contained predominantly latent TGF beta that could be activated by acidification. These findings indicate that the CAC-8 model of cancer-associated hypercalcemia produces a PTH-like factor, TGF alpha, and TGF beta that were separable by reverse phase or cation exchange HPLC. This feature should be useful to investigate the role of TGFs and PTH-like proteins in the pathogenesis of humoral hypercalcemia of malignancy.
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PMID:Separation of parathyroid hormone-like activity from transforming growth factor-alpha and -beta in the canine adenocarcinoma (CAC-8) model of humoral hypercalcemia of malignancy. 253 81

Severe hypercalcemia (serum calcium, 4.37-4.84 nmol/L) was found in a 70-yr-old man who had a small cell carcinoma of the lung with multiple metastases. The plasma immunoreactive PTH concentration was markedly elevated, as measured in three different PTH assays [N-terminal PTH, 4,650 ng/L (normal, 230-630); midregion PTH, 13,850 ng/L (normal, 180-560); C-terminal PTH, 9,900 ng/L (normal, less than 1,300)], but at autopsy the parathyroid glands were histologically normal. The PTH concentration of a liver metastasis was 503.5 ng/g wet wt (normal liver, less than 4.2-5.9), and the PTH in the tumor extract eluted at nearly the same position as synthetic human PTH-(1-84) on gel filtration chromatography. Northern blot analysis revealed PTH mRNA in the tumor as a single band of 0.9 kilobase. These results indicate that the ectopic PTH production by the lung cancer was the cause of hypercalcemia in this patient.
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PMID:Ectopic production of parathyroid hormone by small cell lung cancer in a patient with hypercalcemia. 254 Nov 61

Recent work indicates that PTH can stimulate osteoblastic cells to secrete neutral collagenase, an enzyme thought to be linked to bone matrix turnover. Since recent studies suggest that the calcium/protein kinase-C (PKC) message system is involved in signal transduction stimulated by PTH, we examined the role of these putative second messengers of PTH in the regulation of collagenase production by the osteoblastic tumor cell line UMR 106-01. Immunohistochemical staining of cells exposed to PTH (10(-7) M) revealed that about 20% of the entire population was positive for collagenase, compared to less than 3% staining positively in control untreated cells. Incubation with the cAMP analog 8-bromo-cAMP (8BrcAMP) increased the number of collagenase-staining cells in a dose-dependent manner (ED0.5 = 2.5 x 10(-4) M), but to a lower level than PTH, with the maximal effect producing about 15% positive cells. The calcium ionophore ionomycin (10(-7) M) was ineffective, whereas phorbol 12-myristate 13-acetate (PMA), a PKC activator, increased collagenase-specific staining to about 5%, but only at high concentrations (10(-5) M). Incubation of UMR 106-01 cells with ionomycin and PMA did not change the effect of the latter. When the three agents were used in combination, an additive effect was observed, which fully reproduced that of PTH. Similarly, the amount of collagenase released into the medium by cells stimulated with maximal concentrations of 8BrcAMP (10(-3) M) was only 80% of that induced by maximal doses of PTH (10(-7) M). PMA (10(-5) M) was slightly stimulatory, and ionomycin was ineffective alone, but they were synergistic with submaximal doses of 8BrcAMP (10(-4) M). In agreement with the immunohistochemical results, the full hormonal effect was reproduced when the three second messenger analogs were used in combination. In conclusion, signal transduction from PTH receptor to collagenase production is mediated mainly by cAMP; the Ca2+/PKC system appears to have a contributory role necessary for the full expression of hormonal response. These results support the hypothesis of a dual pathway of target cell activation by PTH.
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PMID:Second messenger signaling in the regulation of collagenase production by osteogenic sarcoma cells. 254 4

A human osteosarcoma cell line was established from a biopsy specimen from a 13-year-old girl. The osteosarcoma tissue was maintained in athymic nude mice (Balb C nu/nu) by serial transplantation for three years. The tumor was excised from a host mouse and digested with collagenase. The isolated cells were cultured by 98 passages in 14 months, and clones of osteosarcoma cells were obtained by limiting dilution. A clone named human osteosarcoma cell 6 (H-OS-6) that showed the osteoblastic phenotypes of productions of bone morphogenetic protein (BMP) and alkaline phosphatase and a response to human parathyroid hormone (h-PTH 1-34) was selected. The morphology of its chromosomes indicated its human origin. This human osteosarcoma cell line is unique in producing BMP under in vitro conditions.
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PMID:Establishment of a cell line producing bone morphogenetic protein from a human osteosarcoma. 254 99

A clonal cell line, BFO-6, was established in culture from a Dunn osteosarcoma cell line (BFO) and characterized on the basis of bone-inducing activity, alkaline phosphatase activity, PTH sensitive cAMP production and tumorigenicity. Lyophilized pellets of devitalized cells, when implanted into the back muscles of allogenic host mice, consistently elicited heterotopic bone formation at 3 weeks postimplantation. BFO-6 cells were found to be rich in alkaline phosphatase activity and showed a significant response to h-PTH stimulation. The doubling time in the logarithmic phase was 17.2 h and the cells revealed an acrocentric karyotype. Subcutaneous transplantation of cells (1 x 10(7) cells) into a C3H mouse resulted in the production of a tumor with histological features of osteosarcoma. This tumor also retained bone-inducing activity and high alkaline phosphatase activity.
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PMID:Establishment of an osteoinductive murine osteosarcoma clonal cell line showing osteoblastic phenotypic traits. 255 82

We retrospectively studied data of 24 patients with surgically proven hyperparathyroidism to determine whether biochemical function correlated with the calculated volume of parathyroid adenoma. Carboxyl-terminal parathyroid hormone (C-PTH), amino-terminal parathyroid hormone (N-PTH), nephrogenous cyclic AMP (N-CAMP), and other markers of calcium metabolism were measured with standard techniques. Tumors were divided into small (less than 1.0 cm3) or large (greater than or equal to 1.0 cm3) sizes. N-PTH and C-PTH measurements were increased in 10% and 30% of patients with small tumors and in 71 and 78% of patients with large tumors. Serum calcium, N-CAMP, C-PTH and N-PTH tended to be greater with large tumors, but only C-PTH was significant. We concluded that the size of parathyroid adenoma influenced biochemical measurements of its activity and that the measurements of PTH in patients with small tumors are not as sensitive as those in patients with large tumors.
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PMID:Relationship of parathyroid adenoma volume and biochemical function. 256 Apr 56

The DNAs from two independent pancreatic cancers (tumors 1 and 2) in a patient with multiple endocrine neoplasia type 1 were analyzed. No amplification or gross rearrangement of 19 protooncogenes was observed. However, Southern blot analysis using polymorphic DNA probes revealed loss of heterozygosity at loci on chromosome 11p in both tumors. In tumor 1, an extensive region including the HRAS1, PTH, CALCA, and D11S151 loci was deleted, while in tumor 2 loss of heterozygosity was limited at the HRAS1 and D11S151 loci. Because loss of heterozygosity at other chromosomal loci in the two tumors was quite rare, loss of genes on 11p might be nonrandom. It is noteworthy that the same allele at the HRAS1 locus and also the same allele at the D11S151 locus were lost in the two independent tumors. These results suggest that loss of genes at the HRAS1 and/or D11S151 loci plays an important role unmasking the remaining sequences probably having a recessive mutation.
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PMID:Loss of the same alleles of HRAS1 and D11S151 in two independent pancreatic cancers from a patient with multiple endocrine neoplasia type 1. 256 62

Traditional cytogenetic approaches have been unsuccessful in the study of parathyroid adenomas. We now describe one parathyroid adenoma in which a molecular cytogenetic approach revealed clonal loss of one chromosome 11. Restriction fragment length polymorphism analysis of the patient's normal leukocyte DNA demonstrated heterozygosity at four loci (PTH, INT2, APOA1, and ETS1) that span the length of chromosome 11. However, the adenoma DNA showed clonal deletion of one allele, i.e. loss of heterozygosity, at each locus. Use of five nonpolymorphic probes from chromosome 11 was consistent with 50% loss of total chromosome 11 DNA in the adenoma. No tumor-specific loss of heterozygosity was observed when restriction fragment length polymorphisms from five other autosomes (no. 1, 5, 6, 7, and 12) were analyzed, and an X-chromosome probe also showed no tumor DNA loss. We have demonstrated tumor-specific chromosome loss in a parathyroid adenoma; such a lesion has been described only rarely in benign tumors. Our finding adds to the evidence for monoclonality in parathyroid adenomatosis, indicates that only one PTH gene copy is sufficient for hyperparathyroid tumor function, and raises the possibility that a tumor-suppressor gene important in the development of nonfamilial parathyroid neoplasia is located on chromosome 11.
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PMID:Clonal loss of one chromosome 11 in a parathyroid adenoma. 256 72


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