Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0026764 (multiple myeloma)
 36,148 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cancer-associated hypercalcemia is due to the: (a) elaboration of systemically-acting humoral factors by neoplasms which alter calcium metabolism in bone, kidney, and intestine; or (b) stimulation of bone resorption at sites of tumor metastasis to bone. It is likely that both mechanisms occur in the same patient with certain neoplasms. There are many humoral factors that can be produced by tumors, secreted into the circulation, and have distant effects which induce hypercalcemia. The stimulation of increased osteoclastic bone resorption is a principal feature of humoral hypercalcemia of malignancy, but the kidney also plays an important role. In addition, intestinal absorption of calcium may be a factor in the pathogenesis of hypercalcemia in certain neoplasms. Parathyroid hormone-related protein plays a dominant role in the pathogenesis of HHM. PTHrP alone is able to induce nearly all of the clinical signs of HHM in experimental animals, but other humoral factors, such as cytokines, can interact with PTHrP to contribute to the development of hypercalcemia. Neoplasms which metastasize widely to bone and induce local osteoclastic bone resorption, such as multiple myeloma, also are capable of inducing hypercalcemia. Based upon existing data it is not clear what percentage of neoplasms which metastasize to bone and stimulate local bone resorption also are capable of stimulating hypercalcemia by systemic factors. Future research is needed to delineate the systemic and local factors associated with CAH; to define interactions of humoral factors in the pathogenesis of hypercalcemia; and to investigate the regulation of transcription, translation, modification, and secretion of hypercalcemia-inducing factors in normal and neoplastic tissues.
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PMID:Mechanisms of cancer-induced hypercalcemia. 146 Aug 60

Hypercalcemia occurs for various reasons in patients with malignant diseases. Most of these patients show a relative increase in bone resorption over bone formation. Increased renal tubular calcium reabsorption is also important for maintaining hypercalcemia in the majority of patients. Calcium absorption from the gut is usually decreased. In a few patients, fixed impairment of glomerular filtration contributes to hypercalcemia. Because the pathophysiology of hypercalcemia is heterogeneous, it may be considered as three separate syndromes: the humoral hypercalcemia of malignancy caused by systemic mediators; the hypercalcemia associated with localized osteolytic disease; and the hypercalcemia associated with myeloma and related hematologic malignancies. Increased bone resorption is a key feature in each of these syndromes. In malignant disease, bone resorption is enhanced because osteoclast activity is increased by the production of humoral mediators. These mediators are often produced by the tumor cells but are also produced by normal host cells that have been activated by the presence of the tumor. some of these mediators of hypercalcemia are systemic factors, but some act only locally. They include parathyroid hormone-related protein, transforming growth factor alpha, lymphotoxin, tumor necrosis factor, interleukin-1 alpha and 1,25-dihydroxyvitamin D.
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PMID:Incidence and pathophysiology of hypercalcemia. 210 29

During the past decade, specific mediators of bone destruction in hypercalcemia of malignancy have been identified and characterized. These humoral factors include parathyroid hormone-related protein, transforming growth factor alpha, and cytokines such as interleukin-1 and tumor necrosis factor. In metastatic hypercalcemia associated with breast cancer, prostaglandin secretion by tumor cells may be one of the important factors. Among the osteoclast activating factors associated with hypercalcemia in patients with myeloma, lymphotoxin plays a central but probably not exclusive role. Alterations of renal function in hematologic hypercalcemia may potentiate bone destruction that usually occurs in the presence of impaired rates of glomerular filtration. Further research is required to determine the relative contributions of bone and kidney to the pathogenesis of hypercalcemia of malignancy.
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PMID:Pathophysiology of cancer-associated hypercalcemia. 218 48

The mechanisms of paraneoplastic hypercalcemic syndromes are heterogeneous. Neoplastic hypercalcemia without bone metastatic disease is caused by parathyroid hormone related protein, whose action is comparable to parathyroid hormone. Growth transforming factors, platelet derived growth factor, tumor necrosis factors and interleukin 1 are also involved in humoral hypercalcemia of malignancy. In addition to these substances, hypercalcemia in bone metastatic disease may be related to PGE. Tumor necrosis factors and interleukin 1 play a major role in multiple myeloma as well as in Adult T cell Leukemia/Lymphoma where overproduction of vit D3 by lymphomatous cells can also be significant.
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PMID:[Hypercalcemia and neoplasms: recent advances in pathogenesis]. 229 Oct 7

Hypercalcemia of malignancy is caused by different mechanisms in different types of tumors. In most solid tumors, increased bone resorption and decreased urine calcium excretion are responsible. However, in myeloma, increased bone resorption and decreased glomerular filtration are the cause. In most solid tumors, factors working in conjunction cause the hypercalcemic syndrome. In addition to PTHrP, these include transforming growth factor alpha, interleukin-1, tumor necrosis factor, and lymphotoxin.
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PMID:Hypercalcemic factors other than parathyroid hormone-related protein. 267 74

Human myeloma cells have been supposed to produce osteoclast activating factors (OAF) that stimulate osteoclasts. The OAF from myeloma cell lines and freshly isolated myeloma cells has been attributed to TNF beta and IL-1 beta, respectively, although production of these cytokines is still controversial. Because of the bone resorption and latent renal dysfunction, hypercalcemia appears to develop readily in myeloma patients. The level of the cytokine production by myeloma cells appears to be relatively low; however, it may be sufficient to activate osteoclasts, because myeloma cells are present close to them. Recently, PTH-rP has been suggested to be involved in the bone resorption. In addition to conventional treatment of hypercalcemia, bisphosphonate may be a usefull tool to inhibit bone resorption.
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PMID:[Hypercalcemia in multiple myeloma]. 769 10

Malignant tumors are often complicated by hypercalcemia (malignancy associated hypercalcemia: MAHC) which causes various clinical symptoms. Hypercalcemia may occasionally lead to death. Unfortunately, many physicians caring for patients with malignant diseases are not aware of this danger. Hypercalcemia is seen in about 15% of patients with solid tumors. This condition is more frequent in some malignant proliferative hematological diseases. In patients with multiple myeloma, the incidence of hypercalcemia is about 20%. The rate of complication by hypercalcemia is as high as 80% in patients with adult T cell leukemia. The symptoms of hypercalcemia include anorexia, easy fatigability, nausea, and vomiting. These symptoms are often mistaken for adverse effects of anticancer drugs or as signs of aggravation of malignant disease. If abnormal thirst and polydipsia are noted in patients with malignant disease, a diagnosis of MAHC should always be considered because these two symptoms are highly characteristic of hypercalcemia. Caution should be exercised when CNS symptoms such as unstable emotions or somnolence are noted. These symptoms in patients with MAHC may lead to death, if untreated. The corrected serum calcium level should always be monitored in patients with malignant disease, so that a possible diagnosis of MAHC may not be overlooked when these symptoms appear. MAHC is caused by the bone resorption stimulating factor (BRSF), which is produced and secreted by the tumor cells. BRSF may act systemically to cause increased bone resorption, resulting in hypercalcemia. MAHC occurring in this manner is called the 'humoral hypercalcemia of malignancy (HHM)'. BRSF produced by multiple myeloma or bone metastasis enhances bone resorption through local osteolysis.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Hypercalcemia in malignancy]. 796 19

Hypercalcaemia is common in some lymphoproliferative disorders such as myeloma or T-cell leukaemia-lymphoma, but is rarely described in B cell chronic lymphocytic leukaemia (BCLL). We report the case of a patient with BCLL, hypercalcaemia and osteolytic bone lesions. Parathyroid hormone-related protein (PTHrP) mRNA was identified by Northern blot analysis of liver, spleen and lymph node tumour samples. Serum levels of tumour necrosis factor alpha (TNF alpha) were increased.
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PMID:Hypercalcaemia in B cell chronic lymphocytic leukaemia. 773 84

In malignancy-associated hypercalcemia (MAH) elevated plasma calcium levels are believed to inhibit parathyroid secretion independently of the underlying tumor. This predicts that correction of hypercalcemia should disinhibit circulating parathyroid hormone (PTH) levels, irrespective of the underlying disease. We have tested this hypothesis in subjects with multiple myeloma (MM) and squamous cell carcinoma (SCC) treated with pamidronate. In the MM group, PTH levels returned to normal as hypercalcemia was corrected. In contrast, PTH levels remained low in the SCC group despite a similar fall in plasma calcium. Calcitriol levels were significantly higher and magnesium levels slightly lower in the SCC group than those in the MM group. We conclude that the parathyroid response to the correction of hypercalcemia is blunted in subjects with SCC but not MM. In addition to hypercalcemia, other factors, perhaps related to tumor secretion of PTH-related protein, may therefore contribute to suppressing PTH secretion in MAH due to SCC.
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PMID:Blunted parathyroid response to correction of hypercalcemia in subjects with squamous cell carcinoma. 811 24

We examined whether or not parathyroid hormone-related protein (PTH-rP) is produced in cultured human myeloma cells. PTH-rP protein was detected in the cell extract of one (U266) of 6 myeloma cell lines examined by radioimmunoassay. Also we demonstrated the expression of PTH-rP mRNA in all of the 6 lines. These findings indicate that PTH-rP may be one of the factors responsible for the bone destruction or hypercalcemia in multiple myeloma.
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PMID:Production of parathyroid hormone-related protein by cultured human myeloma cells. 825 14


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