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Query: UMLS:C0020437 (hypercalcemia)
 10,293 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hypercalcemia is one of well-recognized paraneoplastic syndromes and occurs occasionally in patients with oral cancers. Because bone is the richest source of calcium in the body, it has been proposed that humoral bone resorbing factors which are released by tumors are responsible for the pathogenesis of hypercalcemia. In the present study, partial purification and identification of bone resorbing humoral factors were carried out employing VX2 squamous cell carcinoma which has been known to induce hypercalcemia in rabbits. In addition, extra- and intra-cellular mechanisms which are operating to confer autonomous growth on VX2 cancer cells were also studied. VX2 carcinoma induced marked hypercalcemia not only in rabbits but also in nude mice in parallel with tumor enlargement. Administration of indomethacin (INDO), a prostaglandin (PG) synthesis inhibitor, before onset of the hypercalcemia prevented an elevation of serum calcium levels and growth of the tumor. INDO, however, failed to decrease serum calcium levels and tumor growth when administered after development of the hypercalcemia and tumor enlargement. These results indicate that not only PGs but other humoral factors are involved in the pathogenesis of the hypercalcemia seen in VX2 cancer-bearing animals. VX2 cancer cells in culture retained their cancerous phenotypic properties, synthesized PGE2, PGF2 alpha and 6-keto PGF1 alpha and secreted highly levels of PGE2, a powerful bone resorber, into the culture medium in a time- and cell density-dependent manner. The culture supernatants also contained a trypsin- and heat-sensitive bone risorbing factor (BRF) with a molecular weight of approximately 20kD. BRF was presumed to be similar to parathyroid hormone related protein (PTHrP) from its biological and biochemical behaviors. Both PGE2 and PTHrP promoted VX2 cell growth, thus suggesting that these two substances are autocrine growth factors for VX2 cells. Calcium stimulated VX2 cell growth and secretion of PGE2 and BRF (PTHrP) in a concentration-dependent fashion. Stimulation of VX2 cell proliferation by PGE2 and PTHrP was closely correlated with a transient elevation of intracellular free calcium ion ([Ca2+]i). [Ca2+]i elevated transiently in response to PGE2 and PTHrP was shown to be supplied by influx of extracellular free calcium ion ([Ca2+]e) through calcium channel present in plasma membrane. Involvement of protein kinase C in autocrine growth stimulation of VX2 cells by PGE2 and PTHrP was unclear. These results demonstrate that PGE2 and PTHrP secreted by VX2 cancer cells not only induce hypercalcemia but promote VX2 cell growth as autocrine growth factors.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:[Mechanism of hypercalcemia associated with malignancy: interactions between induction of hypercalcemia and autonomous growth in VX2 cancer cells]. 263 47

Three examples of malignant neoplasms primary to the oral cavity and associated with paraneoplastic syndromes are presented. The first case is a squamous cell carcinoma of the maxilla associated with leukocytosis. The second case is a mandibular squamous cell carcinoma associated with hypercalcemia in the absence of bony metastases. The third case is a squamous cancer of the tongue that metastasized to the lumbar vertebrae and right second rib and was associated with both hypercalcemia and leukocytosis. There was no evidence of acute infection or leukemia that could be expected to account for leukocytosis. Hypercalcemia in the second case was defined as humoral hypercalcemia of malignancy by biochemical and clinical evaluations. To our knowledge, this is the first definitive report of a carcinoma primary to the oral cavity associated with humoral hypercalcemia of malignancy. In each case, the severity of hypercalcemia, leukocytosis, or both very closely correlated with tumor growth. Surgical excision of the tumors or regression of tumor mass due to aggressive anticancer drug administration resulted in decreases in leukocyte number, serum calcium level, or both. In contrast, recurrence or regrowth of tumors induced further development of hypercalcemia, leukocytosis, or both. It is therefore likely that humoral factors released by these oral carcinomas are responsible for the hypercalcemia, leukocytosis, or both.
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PMID:Three cases of oral squamous cancer associated with leukocytosis, hypercalcemia, or both. 281 15

The Rice H500 tumor is a transplantable nonmetastasizing testicular tumor of Fischer rats associated with hypercalcemia and increased urine cyclic adenosine monophosphate (AMP) excretion, features similar to those of the clinical syndrome of humoral hypercalcemia of malignancy. Tumor cells can be maintained in tissue culture; one million cells grown in culture reinoculated in Fischer rats reproduce the syndrome of tumor growth and lethal hypercalcemia. Infusion of concentrated, serum-free cell culture supernatant into parathyroidectomized rats produced an increase in urine cyclic AMP similar to that produced by an infusion of bovine parathyroid hormone. Light and electron microscopic appearance of the H500 tumor in vivo and in vitro is similar to previous descriptions of a hypercalcemia-associated rat testicular tumor believed to be of Leydig cell origin. Ultrastructural characteristics of microvilli, intracellular glandlike lumina, and cell-cell attachments, however, suggest an epithelial origin. Absence of smooth endoplasmic reticulum typical of steroid-secreting Leydig cells suggest these cells are not actively involved in steroid synthesis and secretion. The ultrastructure of this tumor is sufficiently different from that of normal Leydig cells that the cell of origin is unclear. Nonetheless, this tumor provides a useful model of hormonally mediated tumor-associated hypercalcemia.
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PMID:Morphologic and functional studies of a rat hypercalcemia-associated testicular tumor maintained in cell culture. 300 12

Recent reports have suggested that the sensitivity to chemotherapy of endocrine-dependent breast cancer may be enhanced by transient exposure to hormonal stimulation. To test this concept, 39 postmenopausal women with proven metastatic breast carcinoma and measurable disease were entered into this prospective, double-blind trial; 35 are currently evaluable. All patients were continuously treated with aminoglutethimide and hydrocortisone to lower estrogen production, plus cyclic chemotherapy. Patients in the "stimulation" arm received in addition, Estrace 2 mg b.i.d. sublingually for 3 days before and on the day of chemotherapy. Estrace administration appeared to accelerate tumor growth as demonstrated by increased bone pain, hypercalcemia, and growth of skin lesions. Response rates, response duration, and survival were similar in the stimulation and control groups.
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PMID:A randomized trial of aminoglutethimide +/- estrogen before chemotherapy in advanced breast cancer. 354 14

The effect of a hypercalcemia-producing Leydig cell tumor on vascular reactivity in Fischer rats was studied. Seven to eight days after tumor implantation, there was no difference between tumor (T) and control (C) animals in serum calcium, serum phosphate, plasma catecholamine levels, mean arterial pressure (MAP), or blood pressure responses to norepinephrine (NE) infusion. At day 12-13 of tumor growth, the serum calcium in the tumor-bearing rats was significantly higher (12.2 +/- 0.8 vs. 9.7 +/- 0.3 mg%, P less than .01) and their serum phosphate significantly lower (4.5 +/- 0.3 vs. 5.7 +/- 0.4 mg%, P less than .01) than controls. Plasma epinephrine (E) (497 +/- 154 vs. 62 +/- 13 pg/ml, P less than .05), and norepinephrine (NE) (686 +/- 85 vs. 329 +/- 75 pg/ml, P less than .01) were markedly elevated in the tumor rats. MAP and the blood pressure responses to graded NE infusions were significantly lower in tumor animals at Day 12-13, whereas there was no change in sensitivity to angiotensin II (AII) infusions. In vitro contractile responses of tail artery segments to transmural nerve stimulation (TNS) in animals with tumors were lower than in controls but there were no differences in sensitivity to exogenous NE in vitro. These results suggest that the tumor stimulates production of a circulating factor which desensitizes NE receptors and that this tumor also decreases neurovascular function by an undefined mechanism.
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PMID:Decreased vascular reactivity to norepinephrine in Fischer rats with neoplasia-induced hypercalcemia. 356 Nov 57

Based on our in vivo observation that growth of VX2 carcinoma transplanted in rabbits paralleled development of hypercalcemia, we studied the regulation of VX2 tumor growth using a clonal cell line isolated from VX2 tumor (VX2-L). VX2-L cell growth was dependent on prostaglandins released by the cultured cells into the medium, since indomethacin suppressed VX2-L growth, and prostaglandins A2, E1, E2, F1 alpha, and F2 alpha stimulated VX2-L proliferation. In contrast, prostaglandins D2 and I2 inhibited VX2-L proliferation. In contrast to previous reports, increases in extracellular calcium concentration promoted VX2-L growth not only directly but indirectly through augmentation of prostaglandin E synthesis. Antagonists of the intracellular calcium binding protein calmodulin inhibited cell replication. Increases in extracellular calcium also stimulated production of a nonprostaglandin macromolecular bone-resorbing factor. This factor may account for the hypercalcemia which we were unable to block by indomethacin. These results suggest a close relationship between VX2-L growth, prostaglandin production, and hypercalcemia. It is proposed that calcium blockers and anticalmodulin drugs might be powerful anticancer and/or antihypercalcemic agents for malignant cells such as VX2-L.
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PMID:Control of VX2 carcinoma cell growth in culture by calcium, calmodulin, and prostaglandins. 391 74

Today the indication for palliative embolization of inoperable renal carcinoma is more restricted than several years ago. Reviewing 31 own palliative occlusions of the renal artery in 29 patients over a period of 5 1/2 years two main reasons for this attitude are presented: 1. Because of collateral or parasitic vascular supply of kidney tumors the occlusion of the renal arteries only results in a retarded tumor growth rate and does not seem to prolong patient survival. 2. the "postembolization syndrome" after tumor occlusion has a relatively high complication rate and lethality (20% serious side effects, 3% deaths directly related to embolization). Therefore embolization of inoperable renal carcinomas is justified only in patients whose remaining lifetime can be alleviated by this measure. Certain indications are: massive hematuria, severe local pain due to the tumor and life endangering endocrine tumor activity, e.g. hypercalcemia. Uncertain indications such as recurring but not perilous hematuria causing progressive anemia and refusal of tumor surgery should be carefully balanced against the hazards of embolization.
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PMID:[Limitations and hazards of palliative renal tumor embolization]. 618 73

This paper reviews work on the role of prostaglandins in cancer. A substantial body of evidence demonstrates elevated amounts of E series of prostaglandins in human and experimental tumors. Blockade of prostaglandin synthesis in vitro or in vivo results in inhibition of tumor growth. Involvement of prostaglandins is implicated in the actions of tumor promoters like phorbol and polycyclic aromatic hydrocarbon carcinogens. Symptoms like hypercalcemia, osteolysis and tumor metastasis are discussed where disordered synthesis and/or action of prostaglandins and related substances might have a role in the altered metabolism associated with neoplasia.
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PMID:Review: prostaglandins and cancer. 625 Jan 76

This study was designed to elucidate the effect of ethane-1-hydroxy-1,1-diphosphonate (EHDP) in experimental rodent tumors. EHDP had no antitumor activity against the L1210 leukemia implanted i.p. and against sarcoma 180, Lewis lung carcinoma (3LL) and Walker 256/B carcinoma injected i.p., s.c. or i.m. respectively. EHDP did not interfere with the antitumor activity of commonly used conventional chemotherapeutic agents (adriamycin, cyclophosphamide, 5-fluorouracil, bis-chloroethylnitrosourea) in the L1210 and 3LL models. EHDP reduced proportionally to the dose the hypercalcemia and hypercalciuria due to the Walker 256/B carcinoma growth. In an effort to evaluate whether EHDP-treated osseous tissues were more refractory to tumor growth, cells from sarcoma 180 and 3LL carcinoma were implanted intratibially (i.t.). Growth of 3LL cells was not consistently affected by EHDP, whereas a modest, but significant, growth inhibition was consistently observed with sarcoma 180 injected i.t. Growth of sarcoma 180 implanted i.p. or s.c. was not reduced by this drug, thus suggesting that inhibition of i.t. sarcoma 180 was in fact related to alterations of osseous tissues by EHDP. Inoculation of Walker 256/B carcinoma intra-aortically resulted in osteolytic bone lesions in the hind limbs. EHDP inhibited the formation of bone metastasis under these conditions.
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PMID:Effects of disodium etidronate in murine tumor models. 642 94

In an attempt to gain insight into the relationship between bone marrow and bone tissue, studies of bone metabolism and quantitative analysis of bone structure were carried out in mice following a transplantation of a granulocytosis-inducing mammary carcinoma. With the progression of the tumor growth and development of granulocytosis, there was a sharp increase in plasma calcium and urine calcium, both reaching over 200% of control values. Hypercalcemia was associated with a significant increase in urinary hydroxyproline (P less than 0.005), an increase in marrow medullary area (P less than 0.05), and an increase in number of endosteal osteoclasts (P less than 0.005), together indicating that the cause of hypercalcemia was an increase in bone resorption. In parallel with hypercalcemia and hypercalcuria, there was an increase in urinary cyclic AMP excretion. The removal of the tumor normalized both blood neutrophil counts and plasma calcium levels, suggesting that a humoral agent from the tumor tissue, rather than tumor metastasis to bones, may be responsible for the phenomena. These studies documented the association of excessive bone resorption in this animal model of tumor-induced neutrophilia; the model may prove useful for studies of tumor-associated hypercalcemia as well as studies of marrow and bone interactions.
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PMID:Hypercalcemia, excessive bone resorption, and neutrophilia in mice bearing a mammary carcinoma. 684 52


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