• Biomolecules & Therapeutics
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• v.29 no.2
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• pp.166-174
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• 2021

Multiple myeloma is a malignant cancer of plasma cells. Despite recent progress with immunomodulatory drugs and proteasome inhibitors, it remains an incurable disease that requires other strategies to overcome its recurrence and non-response. Based on the high expression levels of programmed death-ligand 1 (PD-L1) in human multiple myeloma isolated from bone marrow and the murine myeloma cell lines, NS-1 and MOPC-315, we propose PD-L1 molecule as a target of anti-multiple myeloma therapy. We developed a novel anti-PD-L1 antibody containing a murine immunoglobulin G subclass 2a (IgG2a) fragment crystallizable (Fc) domain that can induce antibody-dependent cellular cytotoxicity. The newly developed anti-PD-L1 antibody showed significant antitumor effects against multiple myeloma in mice subcutaneously, intraperitoneally, or intravenously inoculated with NS-1 and MOPC-315 cells. The anti-PD-L1 effects on multiple myeloma may be related to a decrease in the immunosuppressive myeloid-derived suppressor cells (MDSCs), but there were no changes in the splenic MDSCs after combined treatment with lenalidomide and the anti-PD-L1 antibody. Interestingly, the newly developed anti-PD-L1 antibody can induce antibody-dependent cellular cytotoxicity in the myeloma cells, which differs from the existing anti-PD-L1 antibodies. Collectively, we have developed a new anti-PD-L1 antibody that binds to mouse and human PD-L1 and demonstrated the antitumor effects of the antibody in several syngeneic murine myeloma models. Thus, PD-L1 is a promising target to treat multiple myeloma, and the novel anti-PD-L1 antibody may be an effective anti-myeloma drug via antibody-dependent cellular cytotoxicity effects.

• IMMUNE NETWORK
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• v.1 no.1
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• pp.14-25
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• 2001

Background: Bone marrow stromal cells (BMSCs) express many cell surface molecules, which regulate the proliferation and differentiation of immune cells within the bone marrow. Methods: To identify cell surface molecules, which can regulate cell proliferation through cell interaction, monoclonal antibodies (MoAbs) against BMSCs were produced. Among them, 1H8 MoAb, which recognized distinctly an 80 kDa protein, abolished myeloma cell proliferation that was induced by co-culturing with BMSCs. Results: IL-6 gene expression was increased when myeloma or stromal cells were treated with 1H8 MoAb. In addition, the expression of IL-6 receptor and CD40 was up-regulated by 1H8 treatment, suggesting that the molecule recognized by 1H8 MoAb is involved in cell proliferation by modulating the expression of cell growth-related genes. Myeloma cells contain high levels of reactive oxygen species (ROS), which are related to gene expression and tumorigenesis. Treatment with 1H8 decreased the intracellular ROS level and increased PAG antioxidant gene concomitantly. Finally, 1H8 induced the tyrosine phosphorylation of several proteins in U266. Conclusion: Taken together, 1H8 MoAb recognized the cell surface molecule and triggered the intracellular signals, which led to modulate gene expression and cell proliferation.

• The Korean Journal of Cytopathology
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• v.3 no.2
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• pp.90-93
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• 1992

A case of multiple myeloma with massive pleural effusion is reported. A 53 year-old previous known multiple myeloma patient vistited our hospital complaining of cough with sputum. Radiologic study revealed multiple osteolytic bony lesions and left side pleural effusion. The effusion were bloody exudates containing numerous atypical plasma cells. The tumor cells showed pleomorphism, eccentric nuclei, prominent nucleoli, perinuclear halo, multincleation, and chromatin patterns of occasional cart-wheel appearance. The cytological examination of pleural fluid established the malignant nature of the effusion with multiple myeloma.

• The Journal of the Korean life insurance medical association
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• v.29 no.2
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• pp.33-35
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• 2010

Multiple myeloma is characterized by the neoplastic proliferation of a single clone of plasma cells producing a monoclonal immunoglobulin and it is frequently associated with primary amyloidosis. I experienced a medical claims review case of plasma cell dyscrasia with primary amyloidosis. This medical consulting work to insurance claims will be helpful for another similar claims administration.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.16
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• pp.7103-7110
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• 2015

The present study was conducted to investigate the effect of ${\gamma}$-radiation alone or combined with a cytotoxic drug, simvastatin, on viability and cell cycling of a myeloma cell line. P3NS1 myeloma cells were treated with the selected dose of simvastatin ($0.1{\mu}M/l$) 24 hours prior to ${\gamma}$-irradiation (0.25, 0.5 and 1Gy). The cell viability, induction of apoptosis, cell death, cell cycling, generation of ROS, and expression of P53, Bax, Bcl2, caspase3, PARP1 and Fas genes were estimated. The results indicated that simvastatin ($0.1{\mu}M/l$) treatment for 24 hours prior to ${\gamma}$-irradiation increased cell death to 37.5% as compared to 4.81% by radiation (0.5Gy) alone. It was found that simvastatin treatment before irradiation caused arrest of cells in G0/G1 and G2/M phases as assessed using flow cytometry. Interestingly, simvastatin treatment of P3NS1 cells increased the intracellular ROS production and decreased antioxidant enzyme activity with increased P53, Bax and Caspase3 gene expression while that of Bcl2 was decreased. Consequently, our results indicated that pre-treatment with simvastatin increased radio sensitivity of myeloma tumor cells in addition to apoptotic effects through an intrinsic mitochondrial pathway.

• 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.

• Journal of Chest Surgery
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• v.7 no.1
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• pp.67-72
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• 1974

This is a case report of total sternal resection and successful reconstruction of the sternum applying Tantalum plate in multiple myeloma. The patient was a 57 year old male with a tumor located on the middle sternum invading the manubrium and the body of the sternum developing symptoms after a contusion of the anterior sternum. The sternum resected with left and right. from first to sixth costochondral cartilages, and then Tantalum plate was fixed to the all fragments of the ribs with wire sutures. After reconstruction of the sternum applying Tantalum plate, the patient has had good breathing movements of the chest wall and also maintenance of respiratory function was satisfactory. Histopathologically, the tumor was consisted of a tissue of plasma cells, which was identical to multiple myeloma. Postoperative chemotherapy with Endoxan for multiple myeloma was administered. No recurrent symptoms of multiple myeloma could be observed during one year follow up period.

• Journal of Korean Neurosurgical Society
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• v.30 no.12
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• pp.1435-1438
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• 2001

A case of nonsecretory multiple myeloma in a 66 year-old-woman is reported. At first, she complained severe neck pain and radiologic finding showed C2 pathologic fracture. She complained severe low back pain 4 month later and L1 compression fracture was found. The lumbar MRI showed a 1.4cm-sized round enhancing lesion in the body of T12. Bone marrow aspiration biopsy at L1 spine showed a few polymorphous and small nests of mononuclear cell. L1 lamina bone biopsy showed many abnormal plasma cells. Pathologic diagnosis was multiple myeloma. However, plasma electrophoresis and protein immunoelectrophoresis of serum and urine of patient were normal. So, it is a nonecretory multiple myeloma case and the incidence of nonsecretory multiple myeloma is known to about 1% of all multiple myeloma.

• Journal of Oral Medicine and Pain
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• v.45 no.2
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• pp.34-38
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• 2020

Multiple myeloma is malignant neoplasm of plasma cells. Mandible lesions are rarely the first symptoms of multiple myeloma. While sensory dysfunction and pain are the main symptoms of traumatic trigeminal neuropathy, the same oral symptoms can appear in cases of multiple myeloma with developed mandible lesions. In addition, if the radiological osteoporosis or lytic lesion is seen in older patients, further examination is required to find the cause of the symptoms. In this paper, we present a case that was tentatively diagnosed as traumatic trigeminal neuropathy after left third molar extraction, but later confirmed as multiple myeloma.

• Korean Journal of Clinical Laboratory Science
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• v.50 no.2
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• pp.197-204
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• 2018

Multiple myeloma (MM) is the leading cause of death among hematologic neoplasms. Recently, microRNA has been reported to be useful in the diagnosis of multiple myeloma. This study examined whether miR-221 could be used as a diagnostic marker for multiple myeloma. The study was performed on 20 patients with multiple myeloma without any other hematological diseases. MicroRNA extraction was performed using formalin-fixed paraffin-embedded (FFPE) tissues obtained from the bone marrow of patients with multiple myeloma. miR-15a, miR-16, miR-21, miR-181a, and miR-221 were selected as the microRNA target genes for multiple myeloma. The significance of microRNA was based on a fold change of <1.5. To quantify the fold changes, data normalized to the human gene, SNORD43, were used as the values of the patient group. Fold change values greater than 1.5 were defined as "overexpression", whereas values less than -1.5 were defined as "underexpression". Of note, 65.0% (13/20) of samples showed significant "overexpression" in the levels of miR-221 expression and plasma cells with a group of more and less than 30% in MM patients did not show any significance of plasma cell (P<0.05). The results of other studies showing a correlation between the expression of miR-221 and MM in Caucasians were confirmed. These results suggest that miR-221 may be a useful indicator for diagnosing patients with MM. In conclusion, miR-221 is useful in the diagnosis and determining the prognosis of multiple myeloma in Koreans.