• Journal of Yeungnam Medical Science
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• v.39 no.4
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• pp.300-308
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• 2022

Background: This study investigated the prognostic impact of spine magnetic resonance imaging (MRI) in patients newly diagnosed with multiple myeloma (MM). Methods: We retrospectively evaluated 214 patients who were newly diagnosed with MM between March 2015 and December 2019. The patients were classified into five different infiltration patterns based on spine MRI as follows: (1) normal appearance, (2) focal, (3) diffuse, (4) combined focal and diffuse infiltration, and (5) "salt-and-pepper." Results: Forty patients (18.7%) showed a normal appearance, whereas focal, diffuse, combined focal and diffuse infiltration, and "salt-and-pepper" patterns were identified in 68 (31.8%), 40 (18.7%), 52 (24.3%), and 14 patients (6.5%), respectively. The patients with normal and "salt-and-pepper" patterns were younger than patients with other patterns (median age, 61.6 vs. 66.8 years; p=0.001). Moreover, 63% and 59.3% of patients with normal and "salt-and-pepper" patterns were scored International Staging System (ISS) stage I and revised ISS (R-ISS) stage I, respectively, whereas only 12.5% of patients with other patterns were scored ISS stage I and R-ISS stage I. Patients with normal and "salt-and-pepper" patterns had a better prognosis than those with other patterns, whereas relapse and death rates were significantly higher in patients with focal, diffuse, and combined MRI patterns. Conclusion: Characteristic MRI findings have a significant prognostic value for long-term survival in patients newly diagnosed with MM. In particular, focal, diffuse, and combined focal and diffuse infiltration patterns are unfavorable prognostic factors.

• Journal of Chest Surgery
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• v.13 no.4
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• pp.507-511
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• 1980

Most cases of plasma-cell granuloma occur in adult skeleton system. They usually present as a single lesion, but multiple lesions are not uncommon. Roentgenographically, the lesions are lytic, sclerotic or mixed, but in the majority there is some degree of sclerosis. No specific etiologic agent is known, but it is postulated that the reaction may be associated with a variety of organisms of low-grade virulence. Certain organisms have long been known to produce predominantly plasmacytic infiltrate, notably spirochetes, mycobacteria and some exotic viruses. It is most important, however, that this entity, plasma-cell granuloma, be distinguished from multiple myeloma so those potentially life-threatening chemotherapeutic agents are not prescribed. Histologically, aggregates of chronic inflammatory cells are intermingled with the meets of plasma cells, and note the markedly thickened bone trabeculae in surrounding bone. We experienced a case of plasma-cell granuloma of right 7th. rib, occurring in 32 year old male and reported it with review of literatures.

• Annals of Clinical Neurophysiology
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• v.17 no.1
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• pp.24-27
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• 2015

Amyloidosis is a systemic disorder associated with clonal plasma cell dyscrasia. Nephrotic syndrome, congestive heart failure, autonomic and peripheral neuropathy is often associated features in amyloidosis. Early diagnosis is most important because of different prognosis by stage. The diagnosis can be delayed since symptoms of amyloidosis may vary or nonspecific. We describe a patient of myeloma-associated amyloidosis, who showed orthostatic intolerance as the first symptom of the disease.

• Molecules and Cells
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• v.38 no.6
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• pp.482-495
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• 2015

Sphingolipids such as ceramide, sphingosine-1-phosphate and sphingomyelin have been emerging as bioactive lipids since ceramide was reported to play a role in human leukemia HL-60 cell differentiation and death. Recently, it is well-known that ceramide acts as an inducer of cell death, that sphingomyelin works as a regulator for microdomain function of the cell membrane, and that sphingosine-1-phosphate plays a role in cell survival/proliferation. The lipids are metabolized by the specific enzymes, and each metabolite could be again returned to the original form by the reverse action of the different enzyme or after a long journey of many metabolizing/synthesizing pathways. In addition, the metabolites may serve as reciprocal biomodulators like the rheostat between ceramide and sphingosine-1-phosphate. Therefore, the change of lipid amount in the cells, the subcellular localization and the downstream signal in a specific subcellular organelle should be clarified to understand the pathobiological significance of sphingolipids when extracellular stimulation induces a diverse of cell functions such as cell death, proliferation and migration. In this review, we focus on how sphingolipids and their metabolizing enzymes cooperatively exert their function in proliferation, migration, autophagy and death of hematopoetic cells, and discuss the way developing a novel therapeutic device through the regulation of sphingolipids for effectively inhibiting cell proliferation and inducing cell death in hematological malignancies such as leukemia, malignant lymphoma and multiple myeloma.

• Korean Journal of Microbiology
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• v.34 no.1_2
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• pp.31-36
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• 1998

A broad spectrum of antibiotic action was studied with Centipedin purified from centipede Scolopendra subspinipes multilans L. Koch aganist gram-positive, gram-negative bacteria and fungi. The minimal inhibitory concentrations(MICs) were determined in liquid medium. The significant antibiotic activity was obtained aganist gram-negative Klebsiella pneumoniae ATCC 8308 responsible for causing infection at lung and intestine. The MIC value against Klebsiella pneumoniae ATCC 8308 was $2{\mu}g/ml$, and this Centipedin was active against Proteus vulgaris NRRL B-123. In addition, it has been shown that Centipedin blocks procaryotic RNA transcription and a little of DNA replication system in vitro. Centipedin did not exhibit any significant cytotoxicity against animal cells such as human blood leukemia (HL-60) and mouse B lymphocyte myeloma cell.

• BMB Reports
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• v.47 no.7
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• pp.399-404
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• 2014

B7-H4 is a member of B7 family of co-inhibitory molecules and B7-H4 protein is found to be overexpressed in many human cancers and which is usually associated with poor survival. In this study, we developed a therapeutic vaccine made from a fusion protein composed of a tetanus toxoid (TT) T-helper cell epitope and human B7-H4IgV domain (TT-rhB7-H4IgV). We investigated the anti-tumor effect of the TT-rhB7-H4IgV vaccine in BALB/c mice and SP2/0 myeloma growth was significantly suppressed in mice. The TT-rhB7-H4IgV vaccine induced high-titer specific antibodies in mice. Further, the antibodies induced by TT-rhB7-H4IgV vaccine were capable of depleting SP2/0 cells through complement-dependent cytotoxicity (CDC) in vitro. On the other hand, the poor cellular immune response was irrelevant to the therapeutic efficacy. These results indicate that the recombinant TT-rhB7-H4IgV vaccine might be a useful candidate of immunotherapy for the treatment of some tumors associated with abnormal expression of B7-H4.

• Molecules and Cells
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• v.39 no.12
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• pp.898-908
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• 2016

Despite recent groundbreaking advances in multiple myeloma (MM) treatment, most MM patients ultimately experience relapse, and the relapse biology is not entirely understood. To define altered gene expression in MM relapse, gene expression profiles were examined and compared among 16 MM patients grouped by 12 months progression-free survival (PFS) after autologous stem cell transplantation. To maximize the difference between prognostic groups, patients at each end of the PFS spectrum (the four with the shortest PFS and four with the longest PFS) were chosen for additional analyses. We discovered that integrin-${\alpha}8$ (ITGA8) is highly expressed in MM patients with early relapse. The integrin family is well known to be involved in MM progression; however, the role of integrin-${\alpha}8$ is largely unknown. We functionally overexpressed integrin-${\alpha}8$ in MM cell lines, and surprisingly, stemness features including $HIF1{\alpha}$, VEGF, OCT4, and Nanog, as well as epithelial mesenchymal transition (EMT)-related phenotypes, including N-cadherin, Slug, Snail and CXCR4, were induced. These, consequently, enhanced migration and invasion abilities, which are crucial to MM pathogenesis. Moreover, the gain of integrin-${\alpha}8$ expression mediated drug resistance against melphalan and bortezomib, which are the main therapeutic agents in MM. The cBioPortal genomic database revealed that ITGA8 have significant tendency to co-occur with PDGFRA and PDGFRB and their mRNA expression were up-regulated in ITGA8 overexpressed MM cells. In summary, integrin-${\alpha}8$, which was up-regulated in MM of early relapse, mediates EMT-like phenotype, enhancing migration and invasion; therefore, it could serve as a potential marker of MM relapse and be a new therapeutic target.

• The Journal of the Korean Society for Microbiology
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• v.21 no.3
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• pp.399-406
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• 1986

This study was performed to establish human plasmacytoma cell line as the partner cells for producing human hybridoma. Bone marrow cells from a multiple myeloma patient from Seoul National University Hospital, Korea were cultured and established as the cell line, named as HMC-BM4. HMC-BM4 cells were cultivated in RPMI 1640 media containing 8-azaguanine(8-AG; gradually increasing concentration from $1\;{\mu}g/ml$ to $20\;{\mu}g/ml$). 8-AG resistant cells were collected and cloned by limiting dilution. Each clone was divided and tested to die in hypoxanthine, aminopterine and thymidine (HAT) selection media. Finally one clone was selected and named as HMC-AR, which was sensitive to HAT selection media. HMC-AR cells showed typical morphology of plamacytoma in Wright staining. No cell formed the rosette with sheep erythrocytes. Surface membrane $\mu$ heavy chain was detected in 20% of HMC-AR cells and cytoplasmic $\mu$ heavy chain in 90% of them by direct immunofluorescent staining. Ia-like antigen was found in 90% of HMC-AR cells by indirect immunofluorescent staining using anti-Ia-like antigen monoclonal antibody, 1BD9-2. And about $1.0\;{\mu}g/ml$ of human $\mu$ heavy chain was detected in the 3-day culture supernatant of HMC-AR cells. 88% of cells contained 46 chromosomes. Mycoplasma was not detected in HMC-AR cells by Hoechst 33258 staining. This cell line would be used for making hybridomas secreting human monoclonal antibody.

• Biomolecules & Therapeutics
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• v.32 no.1
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• pp.65-76
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• 2024

Bortezomib (BTZ) is a proteasome inhibitor used to treat multiple myeloma (MM). However, the induction of peripheral neuropathy is one of the major concerns in using BTZ to treat MM. In the current study, we have explored the effects of BTZ (0.01-5 nM) on rat neural stem cells (NSCs). BTZ (5 nM) induced cell death; however, the percentage of neurons was increased in the presence of mitogens. BTZ reduced the B-cell lymphoma 2 (Bcl-2)/Bcl-2 associated X protein ratio in proliferating NSCs and differentiated cells. Inhibition of βIII-tubulin (TUBB3) degradation was observed, but not inhibition of glial fibrillary acidic protein degradation, and a potential PEST sequence was solely found in TUBB3. In the presence of growth factors, BTZ increased cAMP response element-binding protein (CREB) phosphorylation, brain-derived neurotrophic factor (Bdnf) transcription, BDNF expression, and Tubb3 transcription in NSCs. However, in the neuroblastoma cell line, SH-SY5Y, BTZ (1-20 nM) only increased cell death without increasing CREB phosphorylation, Bdnf transcription, or TUBB3 induction. These results suggest that although BTZ induces cell death, it activates neurogenic signals and induces neurogenesis in NSCs.

• Journal of Microbiology
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• v.35 no.2
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• pp.87-91
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• 1997

Monoclonal antibodies were prepared in order to an assay method for Vibrio vulnificus. Sixteen mouse ybridoma cell lines were established by immunization of whole cell antigen to BALB/c mice, fusion with SP2/O myeloma cells, and cloning. Most of them secreted IgM.lambda. antibodies. A sandwich enzyme-linked immunosorbent assay was developed with rabbit anti-V. vulnificus polyclonal antibodies as capture antibody, an IgM monoclonal antibody as detector antibody, and goat anti-mouse IgM-alkaline phosphatase conjugate as developer antibody. The range of detection was 10$\^$4/ to 10 V. vulnificus cells per microplate well. When four related Vibrio species were tested for cross-reactions, V. parahaemolyticus showed 3.5% reactively and V. carchariae, V. fluvialis, and V. furnisii showed negligibal (<1%) cross-reactivity.