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)

Serum samples drawn at diagnosis from 174 myeloma patients were analyzed for the presence of the heparan [corrected] sulfate proteoglycan, syndecan-1. Syndecan-1 was elevated in 79% of patients (median, 643 units/mL) compared with 40 healthy controls (median, 128 units/mL), P <.0001. Serum syndecan-1 correlated with the following: serum creatinine, secretion of urine M-component over the course of 24 hours, soluble interleukin-6 (IL-6) receptor, C-terminal telopeptide of type I collagen, beta(2)-microglobulin, percentage of plasma cells in the bone marrow, disease stage, and serum M-component concentration. In order to evaluate syndecan-1 as a prognostic marker in multiple myeloma, it was entered into a multivariate Cox regression model. Data from 138 patients were available for this analysis. As a continuous variable, syndecan-1 was an independent prognostic parameter in addition to serum beta(2)-microglobulin and World Health Organization performance status. When syndecan-1 was dichotomized by the best cutoff (66th percentile, 1170 units/mL), the survival difference between the groups was highly significant: "high" syndecan-1 group had a median survival of 20 months, and the "low" syndecan-1 group had a median of 44 months (P <.0001). We conclude that syndecan-1 is a new independent prognostic parameter in multiple myeloma, and its role in prognostic classification systems should be further investigated. (Blood. 2000;95:388-392)
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PMID:Serum syndecan-1: a new independent prognostic marker in multiple myeloma. 1062 39

Bone involvement is a central feature of multiple myeloma (MM). We investigated whether serum markers of osteoblastic and osteoclastic activity correlate with the presence of bone disease and survival in 313 MM patients enrolled in a phase III trial (E9486). Five markers were measured, including osteocalcin (OC), carboxy-terminal propeptide of type I collagen (PICP), bone alkaline phosphatase (BAP), carboxy-terminal telopeptide of type I collagen (ICTP) and tartrate-resistant acid phosphatase (TRAP). We analysed the relationship between serum levels of these markers and the presence of bone manifestations, and survival. Serum levels of ICTP and BAP correlated significantly with bone pain, lesions and fractures. Serum level of ICTP was also higher in stage II-III compared with stage I disease. The serum level of ICTP was significantly associated with shortened survival in the univariate analysis. The median survival times were 4.1 and 3.5 years for low and high ICTP respectively (P = 0.02). There was a strong relationship between ICTP and beta-2-micrgolobulin (B2M). ICTP stands out as a significant marker of bone disease. Incorporation of these markers into clinical trials assessing the use of bisphosphonates in MM is needed to determine whether they might serve as indicators of effectiveness of these agents.
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PMID:Prognostic value of serum markers of bone metabolism in untreated multiple myeloma patients. 1084 78

Bisphosphonates are potent inhibitors of osteoclastic activity and reduce the disease-related skeletal complications when they are used in combination with chemotherapy in patients with multiple myeloma (MM). Pamidronate also inhibits apoptosis of primary osteoblastic cells and probably induces apoptosis on human MM cells and osteoclasts. It has been reported that interferon-alpha (IFN-alpha) decreases bone resorption and that low doses of IFN-alpha result in a significant increase in serum osteocalcin (OSC). The aim of this study was to determine the effects of pamidronate treatment on biochemical markers of bone resorption [cross-linked N-telopeptides of type I collagen (NTx)], bone formation [bone alkaline phosphatase (BAP) and OSC], disease activity [beta2-microglobulin, CRP, paraprotein], and interleukin-6 (IL-6) in patients with MM in plateau phase under IFN-alpha maintenance. The above parameters were evaluated in 28 patients (13 M, 15 F, median age 70 years) during maintenance treatment, before the addition of pamidronate and after 1, 3, 6, 9, 12, and 14 months of the combined therapy. The addition of pamidronate to maintenance treatment resulted in a significant reduction of NTx, IL-6, beta2-microglobulin, CRP from the 3rd month and paraprotein from the 6th month of treatment, whereas BAP and OSC were significantly increased from the 6th month. These changes continued during the 14-month follow-up of the combined treatment. Multivariate analysis showed a significant negative correlation between changes of BAP and OSC and the patients' age. The greater increase of the bone formation markers was observed in younger patients. These results suggest that, in addition to the inhibition of osteoclastic activity, pamidronate in combination with IFN-alpha was shown to induce bone formation in patients with MM in the plateau phase.
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PMID:Pamidronate increases markers of bone formation in patients with multiple myeloma in plateau phase under interferon-alpha treatment. 1168 35

Multiple myeloma (MM) is a monoclonal B-cell neoplasm characterized by autonomous proliferation of immunoglobulin-secreting plasma cells that are capable of synthesizing amyloidogenic light chains resulting in AL amyloidosis. Clinically occult AL amyloid deposition may occur in up to 31% of patients with MM. The prognosis of combined amyloidosis and MM is improving with new therapeutic options. Thus it is imperative that patients with MM be screened for amyloidosis. Sixty-six consecutive skin biopsies from patients with MM and the diagnosis of graft vs. host disease (GVHD) were stained with Congo red and assessed for the presence of amyloid deposition. Twelve cases that had amyloid deposition in other tissue and had a cutaneous biopsy were also stained with Congo red and assessed for the presence of amyloid deposition. None of the 66 biopsies of GVHD, and none of the 12 cases that had documented amyloid deposition in other tissue showed evidence of amyloid deposition in the cutaneous biopsies. In the absence of specific cutaneous manifestations of amyloidosis, it is unlikely that amyloidogenic light chain deposition in the skin would be found. Type I collagen may appear similar to amyloid, both by light microscopy and fluorescence, after staining with Congo red. Thus care must be taken not to confuse type I collagen autofluorescence with positivity for amyloid when assessing skin biopsies stained with Congo red.
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PMID:AL amyloidosis is not present as an incidental finding in cutaneous biopsies of patients with multiple myeloma. 1207 17

Urinary cross-linked N-telopeptide of type I collagen (NTx) has been reported to be a sensitive and specific marker of bone resorption in multiple myeloma (MM). In this study, we measured the levels of NTx in 30 newly diagnosed MM patients and 25 controls. We examined its association with the overall score of skeletal involvement measured by Tc-99m-MIBI scintigraphy and other biochemical markers of bone disease (tumour necrosis factor a (TNF-a), serum calcium and creatinine). We further studied the correlation of NTx with the stage of disease (according to Durie-Salmon criteria) and bone marrow infiltration by plasma cells. High levels of NTx, bone marrow infiltration, TNF-alpha, calcium and creatinine were noted at advanced stages of disease (p < 0.05). NTx and TNF-a were found at significantly higher concentrations in patients with a high overall score (3 and 4) in Tc-99m-sestaMIBI in comparison to a low score (0, 1 and 2; p < 0.05). Positive correlations were found between NTx and TNF-a, as well as between bone infiltration and TNF-a or calcium. In conclusion, NTx is a useful marker for the monitoring of bone resorption in MM and correlates with imaging findings on Tc-99m-sestaMIBI and other biochemical markers of disease activity.
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PMID:Urinary N-telopeptide levels in multiple myeloma patients, correlation with Tc-99m-sestaMIBI scintigraphy and other biochemical markers of disease activity. 1260 19

Bone disease is a common feature of multiple myeloma (MM). The goal of this study was to assess the prognostic significance of urinary markers of bone metabolism in MM. Urinary levels of total pyridinoline (T-Pyd), deoxypyridinoline (T-Dpd), crosslinked N-telopeptide (Ntx), C-telopeptide (Ctx) of type I collagen and immunologic free deoxypyridinoline (f-Dpd) were assessed in 82 consecutive, previously untreated MM patients (aged 65-75 years) diagnosed between June 1995 and December 1998. A correlation between disease stage according to the Durie-Salmon classification and T-Pyd (p=0.034) and T-Dpd (p=0.007) was observed, while T-Pyd (p=0.015) and to a lesser extent f-Dpd (p=0.081) were correlated to bone involvement measured by plain X-ray. None were correlated to M-component or magnetic resonance imaging (MRI). In univariate analysis high T-Pyd (p=0.007), T-Dpd (p=0.027), f-Dpd (p<0.001), and Ctx (p=0.011) were associated with shorter overall survival, whereas only f-Dpd (p=0.0025) was associated with a shorter disease-free survival. In multivariate analysis, C-reactive protein and f-Dpd were independent prognostic factors for overall survival. This retrospective analysis defined new independent prognostic indicators of survival in patients with newly diagnosed myeloma. Indeed, urinary markers of bone resorption can easily be measured at diagnosis and have independent prognostic significance to refine the prognosis of MM patients.
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PMID:Prognostic value of urinary pyridinium crosslinks and their derivatives in multiple myeloma. 1533 98

Among the four members of the syndecan family there exists a high level of divergence in the ectodomain core protein sequence. This has led to speculation that these core proteins bear important functional domains. However, there is little information regarding these functions, and thus far, the biological activity of syndecans has been attributed largely to their heparan sulfate chains. We have previously demonstrated that cell surface syndecan-1 inhibits invasion of tumor cells into three-dimensional gels composed of type I collagen. Inhibition of invasion is dependent on the syndecan heparan sulfate chains, but a role for the syndecan-1 ectodomain core protein was also indicated. To more closely examine this possibility and to map the regions of the ectodomain essential for syndecan-1-mediated inhibition of invasion, a panel of syndecan-1 mutational constructs was generated, and each construct was transfected individually into myeloma tumor cells. The anti-invasive effect of syndecan-1 is dramatically reduced by deletion of an ectodomain region close to the plasma membrane. Further mutational analysis identified a stretch of 5 hydrophobic amino acids, AVAAV (amino acids 222-226), critical for syndecan-1-mediated inhibition of cell invasion. This invasion regulatory domain is 26 amino acids from the start of the transmembrane domain. Importantly, this domain is functionally specific because its mutation does not affect syndecan-1-mediated cell binding to collagen, syndecan-1-mediated cell spreading, or targeting of syndecan-1 to specific cell surface domains. This invasion regulatory domain may play an important role in inhibiting tumor cell invasion, thus explaining the observed loss of syndecan-1 in some highly invasive cancers.
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PMID:Identification of an invasion regulatory domain within the core protein of syndecan-1. 1556 54

Osteolytic bone disease is a frequent complication of multiple myeloma, resulting in skeletal complications that are a significant cause of morbidity and mortality. A characteristic feature of myeloma bone disease is that the lesions rarely heal and bone scans are often negative in myeloma patients who have extensive lytic lesions, offering very little in the follow-up of bone disease. X-rays are also of limited value in monitoring bone destruction during anti-myeloma or anti-resorptive treatment. Biochemical markers of bone turnover, such as N- and C-terminal cross-linking telopeptide of type I collagen (NTX, CTX/ICTP, respectively), and newer ones such as the tartrate resistant acid phosphatase isoform 5b, provide information on bone dynamics that in turn may reflect disease activity in bone. Several studies have shown bone markers to be elevated in myeloma patients and reflect the extent of bone disease, while in some of them bone resorption markers correlate with survival. These markers may also be helpful in identifying those patients likely to respond to bisphosphonate treatment, and monitoring the effectiveness of bisphosphonate therapy in the management of myeloma bone disease. This review attempts to summarize the existing data for the role of markers of bone remodeling in assessing the extent of bone destruction in myeloma and monitoring bone turnover during specific anti-myeloma treatment. We also discuss some novel markers that may be of particular interest in the near future.
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PMID:The role of markers of bone remodeling in multiple myeloma. 1574 61

Technetium-99m methoxyisobutylisonitrile ((99m)Tc-MIBI) has been shown to be useful in identifying several types of tumors, such as breast, brain, thyroid gland, malignant lymphomas and multiple myeloma. In this study, 102 patients with multiple myeloma (MM) and 32 patients with monoclonal gammopathy of undetermined significance (MGUS) had been evaluated for correlation between (99m)Tc-MIBI and biochemical and hematological markers of activity of the disease. Significant statistical correlation was found between summary score (SS) of (99m)Tc-MIBI scintigrams and beta2-microglobulin (p<0.001), monoclonal immunoglobulin level MIG (p<0.001), serum thymidinekinase - sTK (p<0.001), CRP (p<0.05) and cross-linked carboxyterminal telopeptide of type I collagen - ICTP (p<0.05) bone marrow plasmocytosis-BMPc (p<0.001) and hemoglobin Hb (p<0.001). All 32 patients with MGUS had physiological activity of (99m)Tc-MIBI scintigrams. Technetium-99m methoxyisobutylisonitrile is a useful indicator of activity of MM and helps in differentiating between multiple myeloma and monoclonal gammopathy of undetermined significance.
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PMID:Scintigraphy using (99m)Tc-MIBI (sestamibi), a sensitive parameter of activity of multiple myeloma. 1605 46

Malignant plasma cells in multiple myeloma home to the bone marrow (BM), accumulate in different niches and, in late disease, migrate from the BM into blood. These migratory events involve cell trafficking across extracellular matrix (ECM)-rich basement membranes and interstitial tissues. Metalloproteinases (MMP) degrade ECM and facilitate tumour cell invasion. The chemokine CXCL12 is expressed in the BM, and it was previously shown that it triggers myeloma cell migration and activation. In the present work we show that CXCL12 promotes myeloma cell invasion across Matrigel-reconstituted basement membranes and type I collagen gels. MMP-9 activity was required for invasion through Matrigel towards CXCL12, whereas TIMP-1, a MMP-9 inhibitor that we found to be expressed by myeloma and BM stromal cells, impaired the invasion. In addition, we show that the membrane-bound MT1-MMP metalloproteinase is expressed by myeloma cells and contributes to CXCL12-promoted myeloma cell invasion across Matrigel. Increase in MT1-MMP expression, as well as induction of its membrane polarization by CXCL12 in myeloma cells, might represent potential mechanisms contributing to this invasion. CXCL12-promoted invasion across type I collagen involved metalloproteinases different from MT1-MMP. These data indicate that CXCL12 could contribute to myeloma cell trafficking in the BM involving MMP-9 and MT1-MMP activities.
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PMID:Role of metalloproteinases MMP-9 and MT1-MMP in CXCL12-promoted myeloma cell invasion across basement membranes. 1627 22


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