• Title/Summary/Keyword: Myeloma protein

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Antigen Excess in Free Light Chain Assay U sing the Hitachi 7600 P-module Automatic Chemistry Analyzer (Hitachi 7600 p-모듈을 이용한 유리형경쇄 정량검사의 항원과잉역 반응)

  • Cha, Kyong-Ho;Kim, Sung-Hee;Song, Chang-Un;Sim, Yang-Bo;Chae, Hyo-Jin
    • Korean Journal of Clinical Laboratory Science
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    • v.41 no.4
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    • pp.173-179
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    • 2009
  • The analysis of serum free light chains (sFLCs) can improve the diagnosis and monitoring of multiple myeloma and other plasma cell dyscrasias. As with other immunoassays, sFLCstests are subject to potential antigen excess and heterophilic antibody interference. We describe 9 cases of sFLCs antigen excess in patients with multiple myeloma using the FreeliteTM Human Kappa and Lambda Free Kits (The Binding Site ltd., Birmingham, UK) and the Hitachi7600 P module turbidimetric system. A total of 1,247 consecutive samples from 250 patients with multiple myeloma were assayed for sFLCs from April to September, 2009. The samples were assayed using an initial dilution of 1 :5and subsequent dilutions of 1 :50 and 1: 100. The same samples were analyzed for the presence of monoclonal gammopathies using serum protein electrophoresis (SPE) and immunofixation electrophoresis (IFE). There were 9 samples (0.72%) of antigen excess with 3 cases of kappa (0.24%) and 6 cases of lambda (0.48%). These cases represents an example of antigen excess or "hook effect" using the serum free light chain assays and mandates high level of attention to falsely low sFLC levels due to antigen excess, especially when it is disaccordant to other assay results or clinical manifestations.

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Scutellaria Extract Decreases the Proportion of Side Population Cells in a Myeloma Cell Line by Down-regulating the Expression of ABCG2 Protein

  • Lin, Mei-Gui;Liu, Li-Ping;Li, Chen-Yin;Zhang, Meng;Chen, Yuling;Qin, Jian;Gu, Yue-Yu;Li, Zhi;Wu, Xin-Lin;Mo, Sui-Lin
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.12
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    • pp.7179-7186
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    • 2013
  • Background and Aims: Scutellaria is one of the most popular traditional Chinese herbal remedies against various human diseases, including cancer. In this study, we examined the active effects of Scutellaria extract and its main flavonoid constituents on the proportion of side population cells within human multiple myeloma cell line RPMI8226 in vitro and explored the potential molecular mechanisms involved. Materials and Methods: The contents of flavonoids in ethanolic extract of Scutellaria baicalensis Georgi were determined using high performance liquid chromatography. The antiproliferative effect of the ethanolic extract on RPMI-8226 was determined by CCK assay. Apoptosis was measured by annexin combining with propidium iodide in a flow cytometer. Cell cycle analysis was performed by propidium iodide staining in combination with flow cytometry analysis. Hoechst 33342 exclusion assay was used for the identification of side population within RPMI8226 cells. The expression of ABCG2 protein was assessed by Western blotting assay. Results: The content of major flavonoids constitutents of Scutellaria extract was baicalin (10.2%), wogonoside (2.50%), baicalein (2.29%), and wogonin (0.99%), respectively. The crude Scutellaria extract did not show significant anti-proliferative effect, apoptosis induction and cell cycle arrest in RPMI-8226 within the concentrations of $1-75{\mu}g/mL$. However, the ethanolic extract, baicalein, wogonin and baicalin reduced the side population cells in RPMI-8226, and data showed that baicalein and wogonin had stronger inhibitory effects. Correspondingly, they also exhibited significant effects on decreasing the expression level of ABCG2 protein in RPMI-8226 in vitro. Conclusions: Our results for the first time demonstrated a novel mechanism of action for Scutellaria extract and its main active flavonoids, namely targeting SP cells by modulating the expression of ABCG2 protein. This study provides an insight for new therapeutic strategies targeting cancer stem cells of multiple myeloma.

Apoptosis-Induced Gene Profiles of a Myeloma Cell P3-X63-Ag8.653

  • Bahng, Hye-Seung;Chung, Yong-Hoon
    • IMMUNE NETWORK
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    • v.6 no.3
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    • pp.128-137
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    • 2006
  • Background: Apoptosis is a physiologic phenomenon involved in development, elimination of damaged cells, and maintenance of cell homeostasis. Deregulation of apoptosis may cause diseases, such as cancers, immune diseases, and neurodegenerative disorders. The mouse myeloma cell P3-X63-Ag8.653 (v653) is an HGPRT deficient $(HGPRT^-)$ mutant strain. High dependency on de novo transcription and translation of aminopterin induced apoptosis of this cell seems to be an ideal experimental system for searching apoptosis-induced genes. Methods & Results: For searching apoptosis-related genes we carried out GE-array (dot blot), Affymetrix GeneChip analysis, Northern analysis and differential display-PCR techniques. The chip data were analyzed with three different programs. 66 genes were selected through Affymetrix GeneChip analyses. All genes selected were classified into 8 groups according to their known functions. They were Genes of 1) Cell growth/maintenance/death/enzyme, 2) Cell cycle, 3) Chaperone, 4) Cancer/disease-related genes, 5) Mitochondria, 6) Membrane protein/signal transduction, 7) Nuclear protein/nucleic acid binding/transcription binding and 8) Translation factor. Among these groups number of genes were the largest in the genes of cell growth/maintenance/death/enzyme. Expression signals of most of all groups were peaked at 3 hour of apoptosis except genes of Nuclear protein/nucleic acid binding/transcription factor which showed maximum signal at 1 hour. Conclusion: This study showed induction of wide range of proapoptotic factors which accelerate cell death at various stage of cell death. In addition apoptosis studied in this research can be classified as a type 2 which involves cytochrome c and caspase 9 especially in early stages of death. But It also has progressed to type 1 in late stage of the death process.

Recombinant Protein Expression and Purification of the Human HMTase MMSET/NSD2

  • Morishita, Masayo;Mevius, Damiaan;Shen, Yunpeng;Di Luccio, Eric
    • Current Research on Agriculture and Life Sciences
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    • v.31 no.3
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    • pp.157-164
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    • 2013
  • Chromatin remodelers that include histone methyl transferases (HMTases) are becoming a focal point in cancer drug development. The NSD family of three HMTases, NSD1, NSD2/MMSET/WHSC1, and NSD3/WHSC1L are bona fide oncogenes found aberrantly expressed in several cancers, suggesting their potential role for novel therapeutic strategies. Several histone modifiers including HMTase have clear roles in human carcinogenesis but the extent of their functions and regulations are not well understood, especially in pathological conditions. The extents of the NSDs biological roles in normal and pathological conditions remain unclear. In particular, the substrate specificity of the NSDs remains unsettled and discrepant data has been reported. NSD2/MMSET is a focal point for therapeutic interventions against multiple myeloma and especially for t(4;14) myeloma, which is associated with a significantly worse prognosis than other biological subgroups. Multiple myeloma is the second most common hematological malignancy in the United States, after non-Hodgkin lymphoma. Herein, as a first step before entering a pipeline for protein x-ray crystallography, we cloned, recombinantly expressed and purified the catalytic SET domain of NSD2. Next, we demonstrated the catalytic activities, in vitro, of the recombinantly expressed NSD2-SET on H3K36 and H4K20, its biological targets at the chromatin.

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[ $^{18}F-FDG$ ] PET/CT in POEMS Syndrome (POEMS syndrome에서의 $^{18}F-FDG$ PET/CT 소견)

  • An, Young-Sil;Yoon, Joon-Kee;Hong, Seon-Pyo;Joh, Chul-Woo;Yoon, Seok-Nam
    • Nuclear Medicine and Molecular Imaging
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    • v.41 no.1
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    • pp.66-67
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    • 2007
  • POEMS syndrome is a rare disorder, also known as Crow-Fukase, PEP or Takatsuki syndrome. The acronym, POEMS, represents polyneuropathy, organomegaly, endocrinopathy, M protein and skin change. However, there are associated features not included in the acronym such as sclerotic bone lesions, Castleman disease, papilledema, thromobocytosis, peripheral edema, ascites, effusion, polycythemia, fatigue and clubbing. In most cases, osseous lesions in POEMS syndrome present as an isolated sclerotic deposit and that reveal as osteosclerotic myeloma. Several cases of $^{18}F-FDG$ PET in multiple myeloma involvements were reported, but there was no previous literature that reported FDG PET findings in POEMS syndrome. We describe here a 66-year-old patient with POEMS syndrome who underwent $^{18}F-FDG$ PET/CT image.

Significance of Oligoclonal Bands after Stem Cell Transplantation in Multiple Myeloma Cases

  • Liu, Ai-Jun;Zong, Hong;Yang, Guang-Zhong;Zhai, Yu-Hua;Li, Li-Hong
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.4
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    • pp.1483-1486
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    • 2012
  • Objective: To determine the characteristics of oligoclonal bands that are frequently detected by serum protein electrophoresis (SPEP) and immunofixation electrophoresis (IFE) after stem cell transplantation. Methods: We retrospectively analyzed 56 patients with multiple myeloma (MM) undergoing transplantation, and standard immunofixation electrophoresis was used to identify and quantify paraproteins. Results: The median follow-up was 35 months (range, 10-76months) and 21 patients relapsed. Twelve (25.0%) demonstrated oligoclonal bands after a median time 1.4 months (range, 1-3months), with a median duration of 5.8 months (range, 1-15months). The majority patients with oligoclonal bands had normal quantities of immunoglobulins and the one year event free survival (EFS) was 92%, even higher than for patients without OBs (P=0.002). Conclusion: Oligoclonal bands frequent develop post-transplantation in MM cases. In the vast majority of patients, they may not represent relapsed disease, and more likely represent a transient phenomenon representing recovery of impaired immunoglobulin production.

Prediction of HLA-A*0201-Restricted Antigenic Epitopes Targeting Multiple Myeloma (다발성 골수종 적용을 위한 HLA-A*0201 제한 항원성 펩타이드 예측)

  • Kang, Yoon Joong
    • Journal of Convergence for Information Technology
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    • v.10 no.6
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    • pp.209-216
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    • 2020
  • Protein antigens and their epitopes are targets for epitope based vaccines. There are many prediction servers which can be used for identification of binding peptides to MHC molecules. However, choosing of appropriate prediction servers is difficult. This study compared data obtained from prediction servers and evaluate them in scope of binding affinity to MHC-I molecules. Here we predicted HLA-A2-restricted cytotoxic T lymphocyte epitopes from survivin as a potential target for multiple myeloma. We suggest a procedure for prediction of antigenic peptides which could bind to MHC-I molecule. The results of this study will assist researchers in selection and prediction of noble antigenic peptides.

Effect of bear's gall on mammalian cell growth (웅담이 mammalian세포의 생육에 미치는 영향)

  • Joo, Hyun-Kyu;Kim, Youn-Uck;Park, Dong-Ki
    • Applied Biological Chemistry
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    • v.34 no.3
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    • pp.231-234
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    • 1991
  • In the present investigation we have studied the effect of bear's gall on mammalian cells and demonstrated that COS-7 cells, which were derived Monkey kidney cells, had shown almost same extent of growth with 78 hrs in 10% FCS Dulbecco's Modified Eagle's medium with bear's gall and without bear's gall. But the hybridoma cells which were fused murine myeloma cells and the rat spleen cells for monoclonal antibody production died almost within 48 hrs. To investigate the effect of biosynthetic mechanism, cDNA were transfected to COS-7 cells, and it was shown that cDNA-transfected COS-7 cell had produced 30-40% less the amount of recombinant protein than the medium without bear's gall.

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KSP inhibitor SB743921 induces death of multiple myeloma cells via inhibition of the NF-κB signaling pathway

  • Song, In-Sung;Jeong, Yu Jeong;Nyamaa, Bayalagmaa;Jeong, Seung Hun;Kim, Hyoung Kyu;Kim, Nari;Ko, Kyung Soo;Rhee, Byoung Doo;Han, Jin
    • BMB Reports
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    • v.48 no.10
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    • pp.571-576
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    • 2015
  • SB743921 is a potent inhibitor of the spindle protein kinesin and is being investigated in ongoing clinical trials for the treatment of myeloma. However, little is known about the molecular events underlying the induction of cell death in multiple myeloma (MM) by SB743921, alone or in combination treatment. Here, we report that SB743921 induces mitochondria-mediated cell death via inhibition of the $NF-{\kappa}B$ signaling pathway, but does not cause cell cycle arrest in KMS20 MM cells. SB743921-mediated inhibition of the $NF-{\kappa}B$ pathway results in reduced expression of SOD2 and Mcl-1, leading to mitochondrial dysfunction. We also found that combination treatment with SB743921 and bortezomib induces death in bortezomib-resistant KMS20 cells. Altogether, these data suggest that treatment with SB743921 alone or in combination with bortezomib offers excellent translational potential and promises to be a novel MM therapy.

Multiple Myeloma Combined with Stomach Cancer - A case report - (위암이 동반된 다발성 골수종 1례)

  • Yang, Chang-Heon;Hyun, Myung-Soo;Lee, Hyun-Woo
    • Journal of Yeungnam Medical Science
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    • v.6 no.1
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    • pp.197-204
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    • 1989
  • A case of multiple myeloma combined with stomach cancer and related literatures were reviewed. A 67 year-old male patient entered the hospital with dysphagia and weight loss for 3 months. Peripheral blood examination revealed anemia with rouleaux formation. Total protein of the serum was 9.9g/$d{\ell}$ with hyperglobulinemia(albumin 2.7g/$d{\ell}$, globulin 7.2g/$d{\ell}$, A/G ratio 0.375). On the electrophoresis and immunoelectrophoresis of the serum, the abnormal protein with the pattern of monoclonal gammopathy(IgG-K type) was shown. There were multiple variable sized osteolytic lesions on skull X-ray and abnormal hot uptakes of ribs on bone scan and result of rib biopsy was plasmacytoma. Gastrofiberscopy was performed to search for the cause of upper gastrointestinal bleeding, revealed stomach cancer, and the result of the gastric mucosal biopsy proved to be well-differentiated adenocarcinoma.

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