• Biomolecules & Therapeutics
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• 제29권2호
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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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• 제1권1호
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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.

• 대한세포병리학회지
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• 제3권2호
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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.

• 보험의학회지
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• 제29권2호
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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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• 제16권16호
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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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• 제34권3호
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• pp.231-234
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• 1991

동물세포에 미치는 웅담의 영향을 조사하기 위해서 원숭이 kidney cell 유래의 COS-7 cell과 hybridoma cell(murine myeloma cell과 rat의 spleen cell을 융합)을 가지고 이들 세포의 생육과 단백질 발현기작에 미치는 영향을 조사했다. COS-7 cell과 hybridoma cell을 웅담이 첨가된 10% FCS DMEM complete medium에서 78시간 배양한 결과 COS-7 cell에는 거의 영향을 미치지 않았으나 myeloma cell과 spleen cell과의 융합세포는 48시간내에 거의 모든 세포가 사멸됐다. 또한 cDNA를 COS-7 cell에 transfection에서 발현되는 단백질양을 조사한바 웅담이 첨가된 배지에서의 단백질 생산량이 첨가되지 않은 배지에서 보다 $30{\sim}40%$ 감소되었다.

• Journal of Chest Surgery
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• 제7권1호
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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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• 제30권12호
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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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• 제45권2호
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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.

• 대한임상검사과학회지
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• 제50권2호
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• pp.197-204
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• 2018

다발성 골수종(MM)은 혈액 종양의 주요 사망 원인이다. 최근에 다발성 골수종 진단에 microRNA를 이용한 실험이 보고되고 있다. 이에 우리는 다발성 골수종 진단 마커로 miR-221을 이용 할 수 있는지 확인하고자 하였다. 본 연구는 다른 혈액학적 질환이 없는 다발성 골수종 환자 20명을 대상으로 하였다. MicroRNA 추출은 다발성 골수종 환자의 파라핀 포매 조직을 이용하였다. 우리는 다발성 골수종의 microRNA 표적 유전자로 miR-15a, miR-16, miR-21, miR-181a 그리고 miR-221을 선택하였다. 유의성 검정은 fold change 값을 기준으로 1.5이상 또는 -1.5 미만의 결과를 유의성이 있는 경우로 하였다. Fold change 값은 인간 유전자 SNORD43에 의해 표준화된 데이터를 기준으로 하였다. Fold change 값이 1.5 이상은 "overexpression", -1.5 미만의 값은 "underexpression"으로 정의되었다. miR-221의 65.0% (13/20)에서 "overexpression"으로 유의성이 있음을 확인하였고, 다발성 골수종 환자에서 형질세포가 30% 이상인 그룹과 이하의 그룹은 유의성을 보이지 않았다. MiR-221은 서구인과 같은 결과를 얻었으며, 다발성 골수종 환자에서 miR-221이 다발성 골수종 환자 진단에 매우 중요한 지표가 될 수 있을 것으로 생각된다. 결론적으로 miR-221은 한국인의 다발성 골수종 진단 또는 예후 지표로 활용할 수 있음을 확인하였다.