Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020437 (hypercalcemia)
 10,293 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

POEMS syndrome is an acronym defined by Bardwick (Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal component and Skin changes). Other various clinical and biological features are reported: edema, cachexia, microangiopathic glomerulopathy, most rarely pulmonary hypertension, cutaneous necrosis. Thrombocytosis or polycythemia may be a prominent feature. POEMS syndrome is sometimes associated with lymphoproliferative disorder. Castelman-like disease is frequently observed as pathologic findings on lymph nodes. Distinction between POEMS syndrome and osteosclerotic myeloma is delicate. The rate of the monoclonal protein is modest-always less than 30 g/L-and is almost of the lambda light chain class. In contrast to multiple myeloma this syndrome is rarely associated with hypercalcemia, skeletal fracture, renal involvement and increasing of M component during evolution. Bone marrow plasmocytosis is usually less than 15% and the kinetic phenotype and genetic characteristics of the plasma cell remain those found in monoclonal gammopathy of undetermined significance. The pathophysiology of this syndrome remains largely unknown but overproduction of pro-inflammatory cytokines are reported, especially TNF alpha, IL-6 and IL-1 beta. Some clinical manifestations seem to be cytokine related. Polyneuropathy and cachexia are the main cause of death. A part corticosteroid and cure of solitary bone lesion, treatment is disappointing and survival is 60% at five years.
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PMID:[POEMS syndrome]. 925 73

Cachexia consists of a constellation of metabolic changes that occur in cancer patients, including the reduction of muscle and fat tissue, asthenia, anorexia, hypoglycemia and hypercalcemia. These syndromes complicate therapeutic intervention and decrease the quality of life of the patient. This review discusses the involvement of cytokines in cancer cachexia and describes the contribution of IL-6 and other cytokines to the wasting of C-26-bearing mice. The neutralization of IL-6 by antibody, or IL-6 receptor antagonism by suramin, significantly reduce the severity of key parameters of cachexia. The participation of several other factors (PGE2, IL-1, IL-10 and TNF-alpha) in the cellular communication between the C-26 tumor cell and tumor-infiltrating macrophages is also described.
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PMID:Inhibition of experimental cancer cachexia by anti-cytokine and anti-cytokine-receptor therapy. 938 67

Hypercalcaemia is a rare feature of acute lymphoblastic leukaemia (ALL) in adults, particularly of the T cell type. We report on a 24-year-old patient with T-ALL, who presented with symptoms of hypercalcaemia (vomitus, acute renal failure), bone pain, extensive osteolytic lesions and normal white cell count without circulating blasts. An increased serum tumor necrosis factor (TNF-alpha) concentration of 35 pg/ml was found; it remained elevated at 52 pg/ml four weeks later, after having achieved haematological remission. Serum concentrations of IL-1beta, IL-6 and IL-2 were within the control range. The pathophysiology of hypercalcaemia in malignancy and possible mediators of bone resorption, in particular TNF-alpha, are discussed.
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PMID:Severe hypercalcaemia and extensive osteolytic lesions in an adult patient with T cell acute lymphoblastic leukaemia. 964 32

Circulating parathyroid hormone-related protein (PTHrP) is the primary humoral factor in dogs with spontaneous humoral hypercalcemia of malignancy (HHM) and adenocarcinomas derived from apocrine glands of the anal sac. A canine apocrine adenocarcinoma model of HHM in nude mice (CAC-8) was developed and characterized. After 32 passages in vivo, a spontaneous variant of the tumor (CAC-8 Lo Ca) that has altered cellular morphology and that fails to induce HHM in tumor-bearing nude mice has been discovered. The hypercalcemic and nonhypercalcemic tumor lines were compared by tumor weight, effect on body weight, serum calcium concentration, plasma PTHrP concentration, histopathology, expression of PTHrP protein by radioimmunoassay and immunohistochemistry, and expression of PTHrP mRNA by in situ hybridization and northern blot analysis. Messenger RNA expression for other factors and cytokines known to alter PTHrP secretion or bone resorption in vivo, including tumor necrosis factor alpha (TNF alpha), interleukin (IL)-1, IL-6, and transforming growth factor beta (TGF beta), were also measured in the adenocarcinomas. There was no significant difference in weight of individual tumors. Nude mice bearing the CAC-8 (Lo Ca) tumor maintained normal body weight as compared with non-tumor-bearing control mice. In contrast, mice with the CAC-8 (Hi Ca) tumor had markedly decreased body weights. The CAC-8 (Hi Ca) tumor-bearing mice had severe hypercalcemia (mean = 13.4 mg/dl) and increased plasma concentrations of PTHrP (30.4 pM), whereas the CAC-8 (Lo Ca) tumor-bearing mice had a mean serum calcium concentration of 10.1 mg/dl and mildly increased PTHrP concentrations (5.7 pM) as compared with control mice (9.0 mg/dl and 1.0 pM, respectively). The original tumor (CAC-8 [Hi Ca]) is a well-differentiated adenocarcinoma, whereas the variant tumor (CAC-8 [Lo Ca]) is a solid carcinoma with both polygonal and spindle-shaped cells. The CAC-8 (Lo Ca) tumor had decreased PTHrP mRNA expression and protein synthesis. Messenger RNA expression of TGF beta, TNF alpha, IL-1, and IL-6 was similar in both tumors and was consistent with the central role of PTHrP in the induction of hypercalcemia in this animal model.
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PMID:Dependence of humoral hypercalcemia of malignancy on parathyroid hormone-related protein expression in the canine anal sac apocrine gland adenocarcinoma (CAC-8) nude mouse model. 975 39

Palliative therapy is often a major objective for clinicians while treating advanced cancer. This is particularly true in multiple myeloma (MM), where bone involvement markedly influences the quality of life of patients. Bisphosphonates (BP) are a new class of drugs regulating bone turnover, which exert their activity mainly by inhibiting osteoclast bone resorption. Three BP (etidronate, ETD; clodronate, CDN; pamidronate, PMD) have so far been investigated in the clinical setting for treating bone disease in patients with MM. The results of these trials, including our own experience, are reviewed here. Although all three BP were effective in lowering hypercalcemia of MM patients, PMD, a second generation BP, clearly had the most substantial long term clinical benefits regarding bony complications, pain and quality of life. CDN also showed some activity in reducing the development of new lytic lesions, while no significant beneficial effect was seen in patients using ETD. Interestingly, some studies have reported an improved survival in subsets of MM patients receiving BP and this is in agreement with recent evidence of possible direct anti-neoplastic activities of these drugs mediated through reduction of IL-6 production and stimulation of neoplastic cell apoptosis.
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PMID:The role of bisphosphonates for the treatment of bone disease in multiple myeloma. 992 36

Survival for myeloma has improved from a median of 7 months in the 1950s to about 30 months today. Progress in chemotherapy has contributed a great deal to this improvement, although it may also, in part, reflect the improved treatment of infections, renal failure and hypercalcaemia as well as earlier diagnosis. For over 30 years, the gold standard of treatment has been oral melphalan and prednisolone, producing a clinical response in approximately 60% of patients and a median survival of around 36 months. Relapse is unfortunately inevitable in all but a handful and, for the majority, treatment can only hope to produce significant periods of remission with minimal treatment-related morbidity and mortality. Recently, improved results have been seen with the introduction of aggressive chemotherapy and bone-marrow transplantation. Marrow ablative therapies produce remissions in virtually all patients, with complete remissions in approximately 1/3. The best response is seen in those with a lower tumour burden, which will reduce the development of secondary resistance. Current treatment is moving towards an approach using sequential therapy. This involves induction chemotherapy with VAD or a similar regimen such as VAMP (vincristine, adriamycin and methylprednisolone), proceeding to high-dose therapy, often with some form of stem-cell rescue. This ensures minimal tumour burden prior to high-dose treatment as well as reducing graft infiltration, improving general performance status and allowing recovery of renal function. Relapse remains a problem, although the use of IFN may reduce this by prolonging the plateau phase. High-dose therapy should be given early, before prolonged use of alkylating agents induces stem-cell dysplasia, before significant complications arise from the myeloma, and before drug resistance is significant. Unfortunately, these treatments come at a price, in terms of increased treatment-related toxicity. There also remains uncertainty as to the extra benefits of high-dose treatment with marrow rescue over high-dose chemotherapy alone. We await the current MRC trial with interest. For a very few, there is the tantalising possibility of cure with allografting. For those in complete remission after first-line induction therapy, allogeneic bone-marrow transplantation offers the best hope of survival, but comes at a greatly increased risk of toxicity, and it is uncertain if it is superior to autografting for the majority of patients. It may soon be possible to identify those poor prognosis patients in whom an allogeneic transplant should be offered at an early stage. Candidate biochemical markers include serum beta 2 microglobulin, neopterin, IL-6, plasma cell labelling index, CRP or LDH and prognostic clinical features include IgD myeloma or stage III disease at presentation. Many patients will have primary refractory of relapsing disease in whom survival is short despite all current therapeutic modalities. They should therefore be considered for trials of newer agents, drug combinations and therapeutic interventions such as cytokine manipulation or gene therapy. The lack of effective, curative treatment options for patients with myeloma places great importance on effective palliation. While improving survival duration remains elusive in this condition, all possible efforts must be made to ensure quality of life is maximized.
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PMID:Treatment of myeloma. 1020 67

Paraneoplastic syndromes including leukocytosis, thrombocytosis and hypercalcemia are occasionally seen in patients suffering from progressive malignant disorders. Recent studies have revealed the production of several humoral factors by tumor cells and normal splenic cells of tumor-bearing patients to be the major cause of these reactions. Granulocyte-macrophage colony-stimulating factor (GM-CSF), granulocyte-colony stimulating factor (G-CSF), parathyroid hormone-related peptide, interleukin (IL)-1, IL-6, and tumor necrosis factor (TNF) have been implicated. We describe a 58-year-old Japanese man with squamous cell carcinoma (SCC) on the left sole, which developed in a deep linear scar after a train crash. He developed pulmonary and lymph node metastases, then leukocytosis (57,110/mm3 with 95% neutrophilia), thrombocytosis (86.3 x 10(4)/mm3), and hypercalcemia (7.0 mEq/1), and finally cachexia, followed by death. Serum G-CSF, IL-1 alpha, IL-1 beta, and TNF-beta were determined; revealing G-CSF and IL-1 beta levels were above the upper limits of their normal ranges at 39.2 pg/ml and 4.63 pg/ml, respectively. It is probable that these humoral factors were partially responsible for the paraneoplastic syndromes induced by the cutaneous SCC with metastasis in the present case.
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PMID:Paraneoplastic syndromes of leukocytosis, thrombocytosis, and hypercalcemia associated with squamous cell carcinoma. 1040 79

1,25-Dihydroxycholecalciferol [1,25(OH)2D], besides its role in calcium and phosphorus homeostasis, is also an important immunoregulatory molecule. Plasma levels of this hormone may be normal or elevated in patients with primary hyperparathyroidism. 1,25(OH)2D has been reported to inhibit production of the cytokines interleukin-2 (IL-2) and IL-6. In the present study, we examined the effect of parathyroid adenoma excision on serum IL-2 receptor (IL-2R) levels and the release and production of IL-2R and IL-6 by peripheral blood lymphocytes (each measurement was performed twice). Ten patients (5 females and 5 males aged 45 to 78 years) with primary hyperparathyroidism were enrolled in the study. The diagnosis of primary hyperparathyroidism was based on the presence of asymptomatic hypercalcemia, hypophosphatemia, and elevated serum intact PTH levels. Three weeks after removal of the parathyroid adenoma, there was a significant increase in the serum level of IL-2R, as well as the PHA-stimulated peripheral blood lymphocyte production of IL-6 and release of IL-2R. The results indicate that the removal of a parathyroid adenoma in patients with primary hyperparathyroidism causes a significant increase in IL-2R and IL-6 levels. The mechanism by which hyperparathyroidism may affect these cytokines and how they seem related to the levels of vitamin D is discussed.
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PMID:Effect of parathyroid adenoma excision on interleukin-6 (IL-6) and IL-2 receptor levels. 1069 Sep 43

Previously we have established a clonal squamous cell carcinoma cell line OKa-C-1 derived from lung cancer of a patient with marked leukocytosis and hypercalcemia. OKa-C-1 cells simultaneously produce granulocyte colony-stimulating factor (G-CSF) and parathyroid hormone-related protein (PTHrP) at the single cell level and cause paraneoplastic syndromes in nude mice bearing the tumor. It is known that the production of G-CSF and PTHrP is individually regulated by inflammatory cytokines in various malignant cells. To investigate the common factors in the regulation of G-CSF and PTHrP production in OKa-C-1 cells, we examined the effects of some inflammatory agents [lipopolysaccharide (LPS), phorbol-12-myristate-13-acetate (PMA), tumor necrosis factor-alpha (TNF-alpha), interleukin-1 (IL-1) beta and IL-6] on G-CSF and PTHrP production, by means of enzyme-linked immunosorbent assay (ELISA), immunoradiometric assay (IRMA) and quantitative reverse transcription-polymerase chain reaction (RT-PCR). TNF-alpha or IL-1beta induced both G-CSF and PTHrP production in the conditioned medium. TNF-alpha synergized with IL-1beta to significantly increase G-CSF production. In addition, TNF-alpha and IL-1beta strongly induced G-CSF mRNA with peaks at 2 and 6 h respectively. Although PTHrP production was also strongly induced by TNF-a PTHrP mRNA expression was more strongly induced by PMA than by TNF-alpha. Thus, TNF-alpha and IL-1beta could be common factors that individually and synergistically regulate G-CSF and PTHrP production in OKa-C-1 cells. Moreover, G-CSF and PTHrP production could be not only transcriptionally, but also posttranscriptionally regulated by other factors.
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PMID:Regulation of granulocyte colony-stimulating factor and parathyroid hormone-related protein production in lung carcinoma cell line OKa-C-1. 1101 Nov 19

A 66-year-old man was admitted to our hospital complaining of non-productive cough and low-grade fever. Chest X-ray examination revealed a mass shadow in the right hilum. Transbronchial lung biopsy of the tumor mass yielded a diagnosis of adenocarcinoma. Despite repeated chemotherapy using CDDP and VDS, metastasis to the right adrenal gland and right femur occurred, and was accompanied by hypercalcemia and hypophosphatemia. Serological study revealed elevated levels of PTH-rP and G-CSF. Six months after adenocarcinoma was diagnosed, multiple skin metastases of the cancer were observed. Immunohistochemical staining for PTH-rP and G-CSF indicated that production of cytokines had caused a paraneoplastic syndrome including hypercalcemia and leukocytosis. It appeared that the elevation of G-CSF was induced by IL-6 produced from PTH-rP in cancer tissue. Documentation of similar cases is required.
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PMID:[A case of adenocarcinoma complicated with massive leukocytosis and hypercalcemia]. 1101 67


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