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

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

Hypercalcemia is one of the most serious metabolic disorders associated with cancer. The incidence and clinical circumstances associated with hypercalcemia vary in different types of cancer. Hypercalcemia is the most frequent metabolic complication of breast cancer and is usually related to widespread osteolytic metastases; however, local and systemic humoral factors mediating bone resorption have been described. In some patients with breast cancer, hypercalcemia results from treatment with estrogens, antiestrogens, androgens, or progestins. Coexisting primary hyperparathyroidism rarely confounds the diagnosis. In patients with lung cancer, the incidence of hypercalcemia varies with histology and is often unrelated to bone metastases. Hypercalcemia may occur either late or early in the disease but is seldom a presenting symptom. In patients with cancers of the head and neck region, hypercalcemia is most often associated with advanced recurrent and terminal disease, presumably humorally mediated. In renal cell carcinoma, hypercalcemia is also an adverse prognostic indicator, commonly mediated by humoral factors. On the other hand, almost all patients with multiple myeloma have extensive osteolytic bone destruction and hypercalcemia is frequently a presenting symptom. Hypercalcemia is uncommon in most lymphomas; however, it is usually a prominent feature of adult T-cell lymphomas and also occurs in some large cell, diffuse B-cell lymphomas. Awareness of the setting in which hypercalcemia of malignancy occurs will lead to its prompt diagnosis and institution of appropriate therapy.
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PMID:Overview of cancer-related hypercalcemia: epidemiology and etiology. 218 51

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

We have studied the administration of both oral and intravenous dichloromethylene diphosphonate (Cl2MDP) in patients with hypercalcemia and/or hypercalciuria due to increased bone resorption in the setting of multiple myeloma (N = 16) or chronic lymphocytic leukemia (N = 1). The effectiveness of 1600 mg of oral Cl2MDP twice daily was studied in 14 subjects with refractory multiple myeloma, active osteolytic disease and either persistent hypercalciuria (urinary Ca greater than 200 mg per g creatine on a low Ca intake) or hypercalcemia (serum Ca greater than 11.0 mg/dl), in a double-blind, placebo-controlled, 16 week-long trial. Of the 12 patients who received Cl2MDP (2 died in the placebo phase), 11 had marked reductions in urinary calcium (P less than 0.001), which fell into the normal range in 9. Urinary hydroxyproline decreased significantly in 8. Eight of the 11 responders also appeared to have decreases in bone pain associated with Cl2MDP therapy. Similar results were found when this protocol was used in a study of 10 women with breast cancer metastatic to bone. In addition, intravenous Cl2MDP was studied in 12 patients with hypercalcemia of malignancy, of whom 2 had multiple myeloma and 1 had chronic lymphocytic leukemia (CLL) associated with extensive osteolytic bone destruction. We gave 2.5 mg/kg on the first treatment day and 5 mg/kg daily thereafter for up to six more days. Serum calcium fell to normal after a mean of four days in the three patients with hematologic malignancies as well as in eight of the nine with solid tumors. Both urinary Ca and OHP also declined significantly.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Dichloromethylene diphosphonate action in hematologic and other malignancies. 296 56

Increased bone resorption (BR) and increased renal tubular reabsorption of calcium (TRCa) may both be involved in the pathogenesis of hypercalcemia of malignancy (HM). We have evaluated the relative importance of these two mechanisms in 33 patients with HM after extracellular volume expansion and after single infusion of clodronate (C12MDP: 500 mg iv over 8 h). The fasting urine Ca/creatinine ratio was taken as an index of BR (BRI). An index of TRCa was calculated (TRCaI) from a nomogram based on the relationship between urine Ca excretion per unit of glomerular filtration rate and plasma Ca (PCa). Mean (+/- SEM) PCa fell from 3.29 +/- 0.07 to 2.69 +/- 0.05 mmol/l three days after C12MDP (n = 33, p less than 0.001), a response similar to that obtained with repeated daily iv injections of 500 to 1000 mg C12MDP. The pathogenesis of hypercalcemia varied according to the type of neoplasm. BRI was the highest in multiple myeloma and breast tumors. TRCaI was markedly increased in squamous-cells lung, bladder, kidney and liver carcinomas, reaching levels observed in primary hyperparathyroidism. TRCaI was normal in most cases of multiple myeloma. Breast tumors appeared to be heterogeneous with respect to TRCaI. The fall in PCa in response to a single infusion of C12MDP was usually most marked in cancer patients with elevated BRI and normal TRCaI. It was very modest in patients with high TRCaI and slightly elevated BRI. In conclusion, this study confirms that stimulation of bone resorption is not the only mechanism of the maintenance of hypercalcemia of malignancy.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Bone and renal components in hypercalcemia of malignancy and responses to a single infusion of clodronate. 297 82

Milk-alkali syndrome can be caused by ingesting large amounts of calcium carbonate. Coincident with the promotion of calcium carbonate as treatment for both dyspepsia and osteoporosis, milk-alkali syndrome is now a common cause of hypercalcemia severe enough to require admission to the hospital. The syndrome accounted for less than 2% of such admissions before 1990, but from 1990 through 1993, it was the cause of hypercalcemia for over 12% of these patients. Only primary hyperparathyroidism and hypercalcemia of malignancy (excluding multiple myeloma) are more common. The diagnosis of milk-alkali syndrome is made almost entirely based on the patient's history; careful attention to dietary practices and over-the-counter drug use is required, as numerous over-the-counter medications contain calcium carbonate. Modern assays for PTH demonstrate the expected suppression of PTH by hypercalcemia. Nonetheless, measurement of PTH must be performed in a timely manner as treatment with intravenous saline may result in hypocalcemia and elevated PTH soon after admission. Given the pathophysiology of milk-alkali syndrome compared to other causes of hypercalcemia, hypocalcemia with rebound hyperparathyroidism is probably unique to milk-alkali syndrome.
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PMID:Milk-alkali syndrome associated with calcium carbonate consumption. Report of 7 patients with parathyroid hormone levels and an estimate of prevalence among patients hospitalized with hypercalcemia. 789 47

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

A radioimmunoassay for circulating levels of the pyridinoline cross-linked carboxy-terminal telopeptide of type 1 collagen (1CTP) was developed and can be available as a kit on a commercial base. Using the kits, we evaluated basically and clinically the assay. The assayed values were reproducible and the assay can detect as low as 0.5 ng/ml of 1CTP. In healthy volunteers, circulating level was high under age 24 and over age 46. In patients with bone metastasis, serum levels elevated even in its early stage and correlated well with clinical status. In other bone diseases, such as primary hyperparathyroidism, hyperthyroidism, post-gastrectomy, hypercalcemia of malignancy and myeloma, serum levels elevated according to their clinical conditions. In patients with chronic renal failure, serum levels were high, suggesting decrease of renal clearance of 1CTP. The circulating 1CTP levels seemed to reflect well clinical bone destructive status. A high correlation between serum 1CTP level and urinary pyridinoline (r = 0.884) was shown, whereas essentially no correlation was observed between bone formation markers such as osteocalcin and alkaline phosphatase. Thus, the measurement of circulating 1CTP seems to be a simple and sensitive method to monitor bone destruction.
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PMID:[Radioimmunoassay for the pyridinoline cross-linked carboxy-terminal telopeptide of type 1 collagen (1CTP)--some basic aspects of the RIA kit and clinical evaluation in various bone diseases]. 827 4

Bisphosphonates are a new theraeutic option in the treatment of bone diseases. They inhibit osteoclastic bone resorption and are established in the treatment of osteoporosis, Paget's disease of bone and especially in tumor bone disease. The effects of pamidronate, clodronate and ibandronate in the treatment of hypercalcemia of malignancy and osteolytic bone disease have been extensively studied. These drugs represent the treatment of choice in hypercalcemia of malignancy. The regular application of bisphosphonates reduces skeletal-related events like pathologic fracture, bone pain or hypercalcemia of malignancy, especially in breast cancer and multiple myeloma. Of great interest are the ongoing studies concerning prophylactic application of bisphosphonates in tumors bearing a high risk for bone metastases, especially since the first results suggest a significant reduction in the development of bone metastases in breast cancer patients.
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PMID:[Biphosphonate therapy in the management of skeletal metastases]. 961 82


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