• Asian Pacific Journal of Cancer Prevention
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• v.17 no.3
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• pp.1009-1014
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• 2016

It is not clear how gene polymorphisms affecting drugs can contributes totheir efficacy in multiple myeloma (MM). We here aimed to explore associations among gene polymorphisms of tumor necrosis factor alpha (TNFalpha), nitric oxide synthesis 3 (NOS3) and multi-drug resistance 1 (MDR1), clinical parameters, prognosis and survival in MM patients treated with VAD (vincristine-adriamycine-dexamethasone), MP (mephalane-prednisolone), autolougus stem cell transplantation (ASCT), BODEC (bortezomib-dexamethasone-cyclophosphamide) and TD (thalidomide-dexamethasone). We analyzed TNFalpha, NOS 3 and MDR1 in 77 patients with MM and 77 healthy controls. The genotyping was performed with PCR and/or PCR-RFLP. There was no clinically significant difference between MM and control groups when TNFalpha (-238) and (-857) and MDR1 gene polymorphisms were studied. However, the TNFalpha gene polymorphism (-308) GG genotype (p=0.012) and NOS3 (+894) TT genotype (p=0.008) were more common in the MM group compared to healthy controls. NOS3 (VNTR) AA (p=0.007) and NOS3 (+894) GG genotypes (p=0.004) were decreased in the MM group in contrast. In conclusion, the NOS3 (+894) TT and TNFalpha (-308) GG genotypes may have roles in myeloma pathogenesis.

• 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.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.47 no.6
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• pp.471-475
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• 2021

Solitary plasmacytoma (SP) is an uncommon form of plasma cell neoplasm occurring intraosseously or in soft tissue and presents as a single mass of monoclonal plasma cells. SP in the maxillary sinus is rare and can be misdiagnosed as other maxillary sinus tumors. The essential examinations in patients with the initial diagnosis of plasmacytoma are bone marrow biopsy, serum and urine electrophoresis, and kappa/lambda ratio (κ:λ ratio) to rule out multiple myeloma (MM). Herein, a rare case of SP in the maxillary sinus treated by surgery and localized radiation is reported. At the 10-year follow-up examination, local recurrence or disseminated development of MM were not evident.

• Journal of Yeungnam Medical Science
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• v.3 no.1
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• pp.103-110
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• 1986

Cytochrome P-450(CP-450) is one of the three components of the liver microsomal enzyme system which hydroxylates fatty acids, hydrocarbons and a variety of drugs and other foreign compounds. Female Balb/c mice were immunized with purified polychlorinated bipheny(PCB)-induced CP-450 LMII. The spleen cells derived from immunized mice were fused with $SP^2$ myeloma cells using polyethylene glycol(PEG 3500). The hybrid cells were selected by hypoxanthine-aminopterine and thymidine(HAT) medium and the culture fluid were screened by enzyme-linked immunosorbent assay to CP450 LMII. The hybrid cess(${\times}10^7$) were innoculated into intraperitoneal cavity of Balb/c mice for the purpose of production of ascitic fluids. Monoclonal antibody(Mab) was purified from ascitic fluid by DEAE cellulose ion exchange chromatography and $I^{125}$-labeled Mab was also confirmed by autoradiography and SDS-polyacrylamide gel electrophoresis (MW : 55,000 and 110,000).

• Genomics & Informatics
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• v.15 no.3
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• pp.87-97
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• 2017

Multiple myeloma (MM) is a malignant disease caused by an abnormal proliferation of plasma cells, of which the prognostic factors include chromosomal abnormality, ${\beta}$-2 microglobulin, and albumin. Recently, the term chromothripsis has emerged, which is the massive but highly localized chromosomal rearrangement in response to a one-step catastrophic event. Many studies have shown an association of chromothripsis with the prognosis in several cancers; however, few studies have investigated it in MM. Here, we studied the association between chromothripsis-like patterns and treatment resistance or prognosis. First, we analyzed nine MM cell lines (U266, MM.1S, RPMI8226, KMS-11, KMS-12-BM, KMS-12-PE, KMS-28-BM, KMS-28-PE, and NCI-H929) and bone marrow samples of four patients who were diagnosed with MM by next-generation sequencing-based copy number variation analysis. The frequency of the chromothripsis-like pattern was observed in seven cell lines. We analyzed the treatment-induced chromothripsis-like patterns in KMS-12-BM and KMS-12-PE cells. As a result, breakpoints and chromothripsis-like patterns were increased after drug treatment in the relatively resistant KMS-12-BM. We further analyzed the patients' results according to the therapeutic response, which was divided into sensitive and resistant, as suggested by the International Myeloma Working Group. The chromothripsis-like pattern was more frequently observed in the resistant group. In the sensitive group, the frequency of the chromothripsis-like pattern decreased after treatment, whereas the resistant group showed increased chromothripsis-like patterns after the treatment. These results suggest that the chromothripsis-like pattern is associated with treatment response in MM.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.11
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• pp.5409-5413
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• 2012

At present, multiple myeloma (MM) remains an incurable disease and cologenic cells may be responsible for disease relapse. It has been proposed that CD20+/CD138- NCI-H929 cells could be hallmarks of MM clonogenic cells. Here, the immunology phenotype of NCI-H929 cells is described. Only a small population of CD20+/CD138- cells (<1%) was found in the NCI-H929 cell line, but CD20+/CD138- cells were not detected. We found that CD20+/CD138+ cells were able to exhibit cologenic capacity by colony formation assay and continuous passage culture. Proteins were analyzed by 1D-SDS-PAGE and TMT based quantitative differential liquid chromatography tandem mass spectrometry (LC-MS/MS). 1,082 non-redundant proteins were identified, 658 of which were differentially expressed with at least a 1.5-fold difference. 205 proteins in CD20+ cells were expressed at higher levels and 453 proteins were at lower levels compared with CD20- cells. Most proteins had catalytic and binding activity and mainly participated in metabolic processes, cell communication and molecular transport. These results proved that there are different biological features and protein expression profile between CD20+ and CD20- cells in the NCI-H929 cell line.

• BMB Reports
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• v.47 no.5
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• pp.274-279
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• 2014

Bortezomib has been known as the most promising anti-cancer drug for multiple myeloma (MM). However, recent studies reported that not all MM patients respond to bortezomib. To overcome such a stumbling-block, studies are needed to clarify the mechanisms of bortezomib resistance. In this study, we established a bortezomib-resistant cell line (U266/velR), and explored its biological characteristics. The U266/velR showed reduced sensitivity to bortezomib, and also showed cross-resistance to the chemically unrelated drug thalidomide. U266/velR cells had a higher proportion of CD138 negative subpopulation, known as stem-like feature, compared to parental U266 cells. U266/velR showed relatively less inhibitory effect of prosurvival NF-${\kappa}B$ signaling by bortezomib. Further analysis of RNA microarray identified genes related to ubiquitination that were differentially regulated in U266/velR. Moreover, the expression level of CD52 in U266 cells was associated with bortezomib response. Our findings provide the basis for developing therapeutic strategies in bortezomib-resistant relapsed and refractory MM patients.

• Maxillofacial Plastic and Reconstructive Surgery
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• v.18 no.1
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• pp.109-114
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• 1996

Plasmacytoma is one of the malignant neoplasm that originate in immunoglobulin-producing plasma cell, and occurrence in gingiva is known to be rare. About 7% of all patients with plasma cell malignancies present with solitary lesions in bone or soft tissues. In 30% to 40% of patients, the disease progresses to mulitiple myeloma on long-term follow-up. the incidence of progression to multiple myeloma is higher in patients with a bone lesion as compared with an extramedullary lesion. Several studies have shown a relatively favorable course for both these groups of patients, but many long-term studies have demonstrated the distinct difference in ultimate prognosis between patients with solitary lesions in bone and those with extramedullary lesions. The primary objective in the past has been to suppress the immune system to permit allotransplantation. But immunosuppressant also increases the incidence of malignant neoplasms in patients after allograft transplantation. We treated a 15-year patient with plasmacytoma on gingiva who had received kindny transplantation & immunosuppressant therapy. We excised this lesion & performed radiotherapy and had a favorable result.

• IMMUNE NETWORK
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• v.12 no.3
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• pp.126-128
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• 2012

We report on a case of severe hepatotoxicity in a 52-year-old male with multiple myeloma (MM) who had received bortezomib therapy. At patient presentation, liver enzymes were normal, but started to markedly increase 3 days after the patient's second dose of bortezomib was administered, when free kappa light chains were noticeably reduced in the serum. After discontinuation of bortezomib, liver enzymes recovered gradually to baseline. Then, the patient was started on a thalidomide-containing regimen, which he was able to tolerate well. The patient achieved complete remission prior to autologous stem cell transplantation (ASCT). The patient underwent ASCT without occurrence of further liver toxicity.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.4
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• pp.1833-1835
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• 2016

Background: Multiple myeloma (MM) is an acquired clonal B-cell malignancy which primarily affects elderly individuals with an annual incidence of approximately 1% of all malignancies. Our aim is to study demographic and clinicopathological features of adult Pakistani MM patients at presentation. Materials and Methods: This single centre retrospective study extended from January 2010 to December 2014. Data were retrieved from the patients' maintained records on predetermined performa. Results: Overall, 61 patients were diagnosed at our institution with MM during the study period. There were 43 males and 18 females. Age ranged between 34 and 81 years with a mean of $56.1{\pm}12.8$ and a median of 57 years. The male to female ratio was ~2:1. Common presenting complaints included fatigue (81.9%), backache (80.3%) and bone pain (67.2%). Physical findings revealed pallor (44.2%) as a presenting clinical feature. The mean hemoglobin value was $8.9{\pm}1.7g/dl$ with a mean MCV of $85.3{\pm}11.0fl$. Severe anemia with hemoglobin <8.5 gm/dl was seen in 40.9%. The mean total leukocyte count was $8.9{\pm}8.2{\times}10^9/l$, the ANC was $5.0{\pm}3.1{\times}10^9/l$ and the mean platelet count was $188.4{\pm}150.6{\times}10^9/l$. Conclusions: MM in Pakistani patients is seen in a relatively young population with male preponderance. The majority of patients present with symptomatic anemia and backache to seek medical attention. However, clinico-pathological features appear comparable to the published literature.