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)

The tissue sites of monomeric IgA (mIgA) catabolism were determined in a BALB/c mouse model. Mouse mIgA myeloma proteins were labeled either by direct iodination or by coupling the residualizing label, dilactitol-125I-tyramine (125I-DLT) to the proteins; catabolites from protein labeled with 125I-DLT accumulate at the site of protein degradation, allowing identification of the tissue and cellular sites involved in catabolism of the protein. The circulating half-lives of 125I- and 125I-DLT-mIgA were the same. The distribution of radioactivity in tissues was measured at 1, 3, 24, and 96 h after iv. injection of 125I-DLT-labeled mIgA, dimeric IgA (dIgA), IgG, or mouse serum albumin. The greatest uptake of 125I-DLT-mIgA was attributable to the liver. This organ accounted for more internal catabolism of mIgA than all other tissues combined. In contrast, 125I-DLT-IgG was catabolized equally in skin, muscle, and liver. These data indicate that, in mice, the liver is the major site of mIgA catabolism. To determine the cell types involved, collagenase digestion was used to isolate parenchymal and non-parenchymal cells from perfused liver of animals injected with 125-DLT-mIgA. Most of the radioactivity was associated with the hepatocyte fraction, even though both cell types showed uptake of 125I-DLT-mIgA. Inhibition studies, with asialofetuin and mouse IgA demonstrated that the uptake of mIgA by liver cells was mediated primarily by the asialoglycoprotein receptor.
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PMID:The sites of catabolism of murine monomeric IgA. 245 58

Antibodies to surface IgM and IgD were found to induce increased expression of class II antigens on normal and neoplastic human B cells within 24 h of stimulation. Antigens associated with different class II sub-locus genes (DC, DR and SB) were all found to be increased as determined by monoclonal antibodies (Leu-10 and B 3/4 for DC, D 1/12 for DR and MHM4 for SB-associated antigens). The increased expression of class II antigens was selective as anti-immunoglobulins failed to increase expression of other surface antigens such as B1 and beta 2-microglobulin. The effect of anti-mu and anti-delta could be blocked specifically by corresponding myeloma proteins suggesting that antibodies to surface IgM and IgD, respectively, were responsible for the effect observed. Moreover, antibodies to another surface antigen (B1) failed to induce such changes. Increased class II antigen expression appeared to be dependent on protein synthesis, and early changes in ion fluxes, but could not be elicited by membrane depolarization as reported in murine systems.
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PMID:Antibodies to surface IgM and IgD increase the expression of various class II antigens on human B cells. 387 99

This is a communication on the introduction of the first monoclonal marker at Graz University Medical School. Human peripheral blood mononuclear cells were used for immunisation of BALB/c mice by injecting 4,5 X 10(6) cells s. c. Boosting consisted of i.p. injection of 5 X 10(6) cells 4 times in monthly intervals. Spleen cells were taken 4 days after the last boost, fused with NS-1 myeloma cells, using PEG as fusogenic agent. After growth in HAT selective medium, antibody secreting clones were identified by testing the supernatants. Cultures with activity against lymphocytes were closed on normal BALB/C peritoneal cell feeder layers. One of them secreted IgG 1 with strong activity against all lymphoid cells and was named HLy D 1. Further testing showed activity with band cells, polymorphs, eosinophils, macrophages but not with tissue sections from anaplastic undifferentiated cancers and erythroid leukaemias. Since he was named H Le D 1 and introduced for differentiating rare undifferentiated carcinomas from malignant tumors of the lymphoid system.
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PMID:[Cell hybridization: a monoclonal marker as a diagnostic help in haematology and oncology (author's transl)]. 727 18

A Phase I trial (NCT00109109) of oral vorinostat 200, 250 or 300 mg twice daily for 5 days/week/4-week cycle or 200, 300, or 400 mg twice daily for 14 days/3-week cycle until progressive disease or intolerable toxicity was conducted. Patients with measurable, relapsed/refractory multiple myeloma were eligible. The objectives were to determine maximum tolerated doses (MTDs) and assess activity and safety. Thirteen patients (median age, 63 years; median prior therapies, 3) were enrolled. MTDs were not determined due to early study termination by sponsor decision. One patient (250 mg twice daily 5 days/week) developed dose-limiting toxicity (DLT; grade 3 fatigue). There were no other DLTs and the maximum administered doses were 250 mg twice daily for 5 days/week/4-week cycle and 200 mg twice daily for 14 days/3-week cycle. Drug-related adverse experiences included fatigue, anorexia, dehydration, diarrhea, and nausea and were mostly grade <or=2. Of 10 evaluable patients, 1 had a minimal response and 9 had stable disease, demonstrating modest single-agent activity in relapsed/refractory multiple myeloma.
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PMID:Phase I trial of oral vorinostat (suberoylanilide hydroxamic acid, SAHA) in patients with advanced multiple myeloma. 1829 14

Bortezomib (V) was combined with thalidomide (T) and dexamethasone (D) in a phase I/II trial to determine dose-limiting toxicities (DLT's) and clinical activity of the VTD regimen in 85 patients with advanced and refractory myeloma. The starting dose of V was 1.0 mg/m(2) (days 1, 4, 8, 11, every 21 day) with T added from cycle 2 at 50 mg/day, with 50 mg increments per 10 patient cohorts, to a maximum dose of 200 mg. In the absence of DLT's, the same reiteration of T dose increases was applied with a higher dose of V=1.3 mg/m(2). D was added with cycle 4 in the absence of partial response (PR). Ninety-two percent had prior autotransplants, 74% had prior T and 76% abnormal cytogenetics. MTD was reached at V=1.3 mg/m(2) and T=150 mg. Minor response (MR) was recorded in 79%, and 63% achieved PR including 22% who qualified for near-complete remission. At 4 years, 6% remain event-free and 23% alive. Both OS and EFS were significantly longer in the absence of prior T exposure and when at least MR status was attained. The MMSET/FGFR3 molecular subtype was prognostically favorable, a finding since reported for a VTD-incorporating tandem transplant trial (Total Therapy 3) for untreated patients with myeloma (BJH 2008).
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PMID:VTD combination therapy with bortezomib-thalidomide-dexamethasone is highly effective in advanced and refractory multiple myeloma. 1843 60

We conducted a multicenter, open-label study to investigate the safety, efficacy, and pharmacokinetics of lenalidomide in Japanese patients with relapsed or refractory multiple myeloma The study was composed of the "monotherapy phase", a dose-escalation phase, to determine the tolerability to single agent lenalidomide and the "combination phase" to determine the safety and obtain preliminary data on the efficacy of lenalidomide plus dexamethasone. The primary end points were the tolerability to 25 mg lenalidomide and safety. Nine and six patients were enrolled in the monotherapy phase and the combination phase, respectively. Since 25 mg of monotherapy treatment did not satisfy the DLT criteria, this dose was employed in the combination phase. The major adverse event was myelosuppression. At the planned interim analysis (median study duration, 26.3 weeks), grade 3 or grade 4 neutropenia was observed with high frequency (66.7%). However, all adverse events observed were clinically manageable. In the combination cohort, the overall response rate (> or =PR) was 100%. The pharmacokinetics of lenalidomide showed rapid absorption and elimination after both single and multiple doses. In conclusion, 25 mg of lenalidomide was given safely as a single agent or in combination with dexamethasone in Japanese patients. The good efficacy of the combination therapy was also demonstrated in this study.
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PMID:Lenalidomide plus dexamethasone treatment in Japanese patients with relapsed/refractory multiple myeloma. 2181 73