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

Clinical research over the last decade has confirmed the helpful role of bisphosphonates in the management of patients with bone metastases secondary to breast cancer and other malignancies. This role is also expanding in myeloma and in the management of osteoporosis. Current clinical research in oncology is focusing on their potential for the prevention of skeletal complications of malignant disease and the development of bone metastases while basic researchers are developing compounds of higher potency and, perhaps, higher therapeutic efficacy. One of the earliest agents to be investigated, etidronate, is effective in the management of malignant hypercalcemia and, when used orally and intermittently, results in reduced bone loss in osteoporosis. However, it does not appear to reduce pain in patients with malignant disease. Clodronate has been shown to be an effective agent in the management of hypercalcemia and can be used as a single intravenous infection for this purpose. Clodronate is also effective in some patients in reducing bone pain and improving mobility. When used orally, it can, as can pamidronate, reduce the skeletal complications of breast cancer such as hypercalcemia, bone fractures and bone pain. It may have fewer gastrointestinal side effects than oral pamidronate. There is emerging evidence that bisphosphonates may delay or prevent the clinical appearance of bone metastases as well as reduce other skeletal complications. Trials of adjuvant bisphosphonates such as clodronate and pamidronate in operable breast cancer are currently under way in Europe and North America.
 ...
PMID:Role of bisphosphonates in prevention and treatment of bone metastases from breast cancer. 885 26

This review of recent data on the techniques and results of spinal magnetic resonance imaging in plasma cell dyscrasias provides a basis for selecting those patients who are most likely to benefit from this investigation. Sagittal images should be obtained using T1-weighted spin-echo and T2-weighted gradient-echo sequences. Epiduritis is best detected on sagittal or axial images acquired after gadolinium injection using T1-weighted spin-echo or phase-opposed gradient-echo sequences. Among patients with symptomatic multiple myeloma, 80% have abnormal magnetic resonance images of the lower spine due to plasma cell infiltration and this proportion increases with the stage in the Durie and Salmon staging system. Bone marrow signal abnormalities can be focal, diffuse and homogeneous, or diffuse and variegated. Vertebral fractures due to spinal infiltration or osteoporosis are seen in 48% of cases and spinal canal narrowing with impingement of bone tumors or epiduritis on nervous structures in 20%. The response to chemotherapy as evaluated based on conventional criteria is fairly well correlated with changes in magnetic resonance imaging findings. Among asymptomatic multiple myeloma patients with normal roentgenograms, 50% have tumor-related abnormalities on magnetic resonance images of the lower spine, which are associated with an increased likelihood of rapid progression to symptomatic disease. Similarly, one third of patients with an apparently solitary plasmacytoma of bone have evidence of other plasma cell tumors on magnetic resonance images of the lower spine, and this finding is associated with persistence of monoclonal component production after irradiation therapy, which may be of adverse prognostic significance. Patients with monoclonal gammopathies of uncertain significance have no evidence of tumorous lesions on magnetic resonance images of the lower spine.
 ...
PMID:Magnetic resonance imaging of the spine in plasma cell dyscrasias. A review. 901 Sep 72

Interleukin-6 (IL-6) is known to enhance osteoclast recruitment, and thereby bone resorption. Thus, IL-6 has been proposed to mediate hypercalcemia in multiple myeloma and the enhanced osteoclastic activity seen in postmenopausal osteoporosis. We recently reported that the calcium concentration in plasma affects IL-6 secretion from mononuclear blood cells. To investigate the underlying mechanism, we have studied the effect of calcium on IL-6 formation in mononuclear blood cells ex vivo and in vitro. Thirteen healthy volunteers were given 1 g of calcium orally after overnight fasting. Plasma levels of ionized calcium (pCa2+) and serum levels of parathyroid hormone (sPTH) were measured after 2 and 4 h, with all subjects still fasting. After 2 h, pCa2+ was increased and sPTH decreased in all 13 persons. IL-6 secretion ex vivo from mononuclear blood cells drawn 4 h after calcium intake was increased 185% as compared with IL-6 secretion from cells drawn just before calcium intake. In control experiments without calcium intake, there was no alteration in pCa2+ and no effect on IL-6 secretion from mononuclear blood cells. In vitro studies revealed that stimulation of isolated mononuclear blood cells with physiological concentrations of calcium dose-dependently increased IL-6 secretion with an estimated EC50 at 1.2 mM Ca2+. No effect on the IL-6 secretion was seen following treatment of the isolated mononuclear blood cells with PTH or calcitonin. These observations demonstrate that the plasma calcium concentration affects IL-6 secretion from mononuclear blood cells. The in vitro data indicate the involvement of a direct calcium sensing mechanism. These findings might have implications in hypercalcemia and should also be borne in mind when considering the role of cytokines in osteoporosis.
 ...
PMID:Regulation of interleukin-6 secretion from mononuclear blood cells by extracellular calcium. 904 Oct 54

Plasmacytoma is a malignant tumour composed of plasma cells. Most commonly this takes the form of a plasma cell infiltration of bone marrow-multiple myeloma. This may be seen radiologically as either discrete lytic lesions or diffuse osteoporosis. Plasma cells are seen on bone marrow biopsy, and monoclonal immunoglobulins may occur in plasma and/or urine. Less frequently, plasma cell tumours may present as a solitary myeloma of bone, which often progresses to multiple myeloma, or as a plasma cell leukemia. Primary plasma cell tumours in an extramedullary site are relatively rare. Such soft tissue plasmacytomas usually occur in the nasopharynx or conjectiva, and are seldom located in the lower gastrointestinal tract. We report a case of primary plasmacytoma associated with a diverticular stricture in the sigmoid colon, an occurrence not previously documented, and review the current literature.
 ...
PMID:Plasmacytoma of the sigmoid colon associated with a diverticular stricture: case report and review of the literature. 904 47

Cytokine messenger RNA expression was studied using the reverse transcription/polymerase chain reaction in 23 patients with multiple myeloma (MM), 16 with monoclonal gammopathy of undetermined significance (MGUS), 12 with post menopausal osteoporosis, (OP) and 12 normal controls. Messenger RNAs for IL-1 alpha, IL-1 beta, TNF-alpha, TNF-beta, IL-6 and M-CSF were sought in view of their reported pathogenic role in myeloma. Transcripts for IL-1 beta, TNF-alpha, TNF-beta and M-CSF were found frequently in all four groups of patients. The only significant difference in cytokine expression between the groups was for IL-6 which was expressed in 17% of controls compared with 87% of patients with MM (p < 0.001), 62% of patients with MGUS (p < 0.02) and 67% of patients with osteoporosis (p < 0.02). Further analysis of IL-6 expression by quantitative PCR showed significantly higher IL-6 mRNA levels in MM compared with MGUS (p < 0.006). There was no correlation however between expression of individual cytokines and clinical features of myeloma such as osteolytic bone disease or hypercalcaemia. We conclude that expression of IL-6 mRNA is significantly enhanced in multiple myeloma when compared with MGUS. However, since MGUS and osteoporosis were also associated with a high prevalence of IL-6 expression when compared with controls it is probable that factors other than IL-6 are responsible for the local osteolytic lesions which characterise MM, but which are not seen in MGUS or osteoporosis.
 ...
PMID:Cytokine expression in multiple myeloma and monoclonal gammopathy: analysis by reverse transcription/polymerase chain reaction and quantitative PCR. 904 67

Gaucher's disease is characterized by hepatosplenomegaly, bone-marrow infiltration, osteonecrosis and bone thinning, associated with the presence of pathological macrophages that contain undegraded glycosphingolipids. To investigate the possible role of cytokines in the systemic and local manifestations of established Gaucher's disease, interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6), tumour necrosis factor-alpha (TNF alpha) and interleukin-10 (IL-10) were measured in freshly-separated serum. Samples from eight male and 14 female patients with type 1 Gaucher's disease were compared with sera from 22 healthy age- and sex-matched controls. Concentrations of IL-6 and IL-10 were significantly elevated in sera from patients with Gaucher's disease (11.9 +/- 1.8 (SEM) pg/ml and 5.4 +/- 0.5 (SEM) pg/ml, respectively) compared with those of controls (4.1 +/- 0.9 (SEM) and 0.8 +/- 0.3 (SEM) pg/ml, p < 0.0001). No significant differences in concentrations of TNF alpha or IL-1 beta were identified. IL-6 has been implicated in the development of localized osteolysis in multiple myeloma and in the development of post-menopausal osteoporosis. High concentrations of IL-6 in the serum of patients with Gaucher's disease may thus reflect the development of the bone lesions commonly associated with this disorder. Since IL-6 and IL-10 are important regulators of lymphocyte growth and differentiation, and IL-6 concentrations were significantly raised in patients with oligo- or polyclonal increases in serum immunoglobulins, enhanced release of these cytokines from pathological macrophages provides a pathological link between Gaucher's disease and associated lympho-proliferative disorders.
 ...
PMID:Pro-inflammatory cytokines and the pathogenesis of Gaucher's disease: increased release of interleukin-6 and interleukin-10. 909 85

Lytic bone lesions, pathological fractures, hypercalcaemia and osteoporosis are common features in patients with multiple myeloma. Adjunctive therapeutic modalities in addition to antimyeloma therapy have been sought to ameliorate these clinical consequences of bone disease. Bisphosphonates appear to be useful in this respect. In addition to correcting hypercalcaemia, they reduce the amount of new bone lesions and pathological fractures in myeloma patients. Bisphosphonates also relieve bone pain. In placebo-controlled studies clodronate (1600-2400 mg/d orally) and pamidronate (90 mg intravenously once every month) have produced clinically significant effects in myeloma patients. Bisphosphonates are a useful adjunct therapy in patients with multiple myeloma.
 ...
PMID:Bisphosphonate therapy in multiple myeloma. 914 66

Interleukin-6 (IL-6) is a multifunctional cytokine that plays a central role in host defense due to its wide range of immune and hematopoietic activities and its potent ability to induce the acute phase response. Overexpression of IL-6 has been implicated in the pathology of a number of diseases including multiple myeloma, rheumatoid arthritis, Castleman's disease, psoriasis, and post-menopausal osteoporosis. Hence, selective antagonists of IL-6 action may offer therapeutic benefits. IL-6 is a member of the family of cytokines that includes interleukin-11, leukemia inhibitory factor, oncostatin M, cardiotrophin-1, and ciliary neurotrophic factor. Like the other members of this family, IL-6 induces growth or differentiation via a receptor-system that involves a specific receptor and the use of a shared signaling subunit, gp130. Identification of the regions of IL-6 that are involved in the interactions with the IL-6 receptor, and gp130 is an important first step in the rational manipulation of the effects of this cytokine for therapeutic benefit. In this review, we focus on the sites on IL-6 which interact with its low-affinity specific receptor, the IL-6 receptor, and the high-affinity converter gp130. A tentative model for the IL-6 hexameric receptor ligand complex is presented and discussed with respect to the mechanism of action of the other members of the IL-6 family of cytokines.
 ...
PMID:Interleukin-6: structure-function relationships. 914 66

Cytokines are polypeptides that bind to membrane receptors and may act in an endocrine, paracrine or autocrine way. Several cytokines and growth factors may be produced by bone cells, stored in the matrix or act on them. Osteoclasts derive from the bone marrow stem cell and, as monocytes, belong to the family of tissue macrophages. Their specific function is bone resorption. Interleukin 1, 6 and 11, transforming growth factor and tumor necrosis factor stimulate osteoclast mediated bone resorption. Interleukin 1 is the most potent bone resorption agent and seems to be identical to osteoclast activation factor, identified in multiple myeloma. The role of interleukin 1, 6, 11 and tumor necrosis factors in postmenopausal osteoporosis triggered by the fall in estrogen levels, has not been well defined yet. Cytokines that increase bone formation are insulin like growth factors I and II, transforming growth factor, platelet derived growth factor and bone morphogenic proteins. Probably, tumor necrosis factor and interferon-gamma have a depressor effect on bone formation. Cytokines and growth factors, liberated from bone cells or from the matrix during osteoclastic work, could be the signals responsible for coupling bone formation and resorption.
 ...
PMID:[Cytokines, growth factors, and metabolic bone disease]. 921 95

IL-6 has many novel activities both within the adaptive immune system and without. It has therapeutic potential in acute inflammation, such as toxic or septic shock, and it is a potential target for cachexia, multiple myeloma, and osteoporosis. Further work on these aspects of IL-6 biology should yield new insight into the possibility of IL-6 both as a therapeutic agent and as a target for antagonists.
 ...
PMID:IL-6: insights into novel biological activities. 932 64


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>