• Biomolecules & Therapeutics
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• v.30 no.5
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• pp.435-446
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• 2022

The present study evaluated the anti-cancer activity of histone deacetylase (HDAC)-inhibiting CKD-581 in multiple myeloma (MM) and its pharmacological mechanisms. CKD-581 potently inhibited a broad spectrum of HDAC isozymes. It concentration-dependently inhibited proliferation of hematologic cancer cells including MM (MM.1S and RPMI8226) and T cell lymphoma (HH and MJ). It increased the expression of the dishevelled binding antagonist of β-catenin 3 (DACT3) in T cell lymphoma and MM cells, and decreased the expression of c-Myc and β-catenin in MM cells. Additionally, it enhanced phosphorylated p53, p21, cleaved caspase-3 and the subG1 population, and reversely, downregulated cyclin D1, CDK4 and the anti-apoptotic BCL-2 family. Finally, administration of CKD-581 exerted a significant anti-cancer activity in MM.1S-implanted xenografts. Overall, CKD-581 shows anticancer activity via inhibition of the Wnt/β-catenin signaling pathway in hematologic malignancies. This finding is evidence of the therapeutic potential and rationale of CKD-581 for treatment of MM.

• 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 Korean Neurosurgical Society
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• v.51 no.3
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• pp.127-134
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• 2012

Objective: To analyze the prognostic factors thought to be related with survival time after a spinal metastasis operation. Methods: We retrospectively analyzed 217 patients who underwent spinal metastasis operations in our hospital from 2001 to 2009. Hematological malignancies, such as multiple myeloma and lymphoma, were excluded. The factors thought to be related with postoperative survival time were gender, age (below 55, above 56), primary tumor growth rate (slow, moderate, rapid group), spinal location (cervical, thoracic, and lumbo-sacral spine), the timing of radiation therapy (preoperative, postoperative, no radiation), operation type (decompressive laminectomy with or without posterior fixation, corpectomy with anterior fusion, corpectomy with posterior fixation), preoperative systemic condition (below 5 points, above 6 points classified by Tomita scoring), pre- and postoperative ambulatory function (ambulatory, non-ambulatory), number of spinal metastases (single, multiple), time to spinal metastasis from the primary cancer diagnosis (below 21 months, above 22 months), and postoperative complication. Results: The study cohort mean age at the time of surgery was 55.5 years. The median survival time after spinal operation and spinal metastasis diagnosis were 6.0 and 9.0 months. In univariate analysis, factors such as gender, primary tumor growth rate, preoperative systemic condition, and preoperative and postoperative ambulatory status were shown to be related to postoperative survival. In multivariate analysis, statistically significant factors were preoperative systemic condition (p=0.048) and postoperative ambulatory status (p<0.001). The other factors had no statistical significance. Conclusion: The factors predictive for postoperative survival time should be considered in the surgery of spinal metastasis patients.

• BMB Reports
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• v.31 no.1
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• pp.58-63
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• 1998

In this study, a mouse monoclonal antibody (mAb) against gp41(584-618), the immunodominant epitope protein, was generated. For this purpose, BALB/c mice were immunized with double branched multiple antigenic peptides derived from the HIV-1 gp41(584-618) sequence, and antibody-secreting hybridoma were produced by fusion of mice splenocytes with SP2/0 myeloma cells. One clone producing an antigen specific mAb, termed KI-41(isotype IgG1) was identified, whose specific reactivity against gp41(584-618) could be confirmed by ELISA and Western blot analysis. Epitope mapping revealed the recognition site of the mAb KI-41 to be located around the sequence RILAVERYLKDQQLLG, which comprises the N-terminal region within the immunized gp41(584-618) peptied. Since this mAb recognizes this specific epitope within the HIV-1 gp41 without any cross-reactivity to other immunodominant regions in the HIV-2 gp35, KI-41 will provide some alternative possibilities in further applications such as the development of indirect or competitive ELISA for specific antibody detection in HIV-1 infection or for other basic researches regarding the role and function of HIV-1 gp41.

• 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.

• The Journal of Internal Korean Medicine
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• v.29 no.4
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• pp.1061-1074
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• 2008

Objectives : Recently, the number of cancer patients who use complementary and alternative medicine (CAM), including oriental medicine, are increasing. Also, evidence for efficacy and safety of cancer CAM is reported continuously. This study was designed to evaluate the quality of the published papers for clinical studies about oriental medical cancer treatment in Korea. Methods : We searched for clinical research papers on the websites of the Korean oriental medical society and subsidiary academies, Korean traditional knowledge portal. Koreanstudies information service system (KISS), etc. We used the reference words 'cancer', 'malignant tumor', 'leukemia', 'lymphoma', 'multiple myeloma', 'melanoma', etc, We then chose studies that had been presented between 1991 and 2008 and analyzed them by publication year, design, cancer type, intervention, subject and journal. Results : There were 86 clinical research papers that were published between 1991 and 2008. The number of clinical studies has increased in a time-dependent manner. Case reports and case series studies account for 78% of total clinical research. Studies of lung cancer account for 17%. Studies of cancer-related symptoms of cancer patients account for 38%. Studies of Hang-Am-Dan account for 33%. Studies published in the journal of the Korean Society of Oriental Internal Medicine account for 35%. Conclusion : The clinical research papers about oriental medicine are increasing over time, but most of the studies are retrospective case reports or case series. Well-designed and prospective clinical trials would be recommended to provide more reliable evidence.

• Journal of Korean Clinical Nursing Research
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• v.20 no.3
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• pp.384-394
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• 2014

Purpose: To improve professional intensive care by analyzing admission causes, causes of death, disease conditions, and treatment processes in patients with hematological malignancies admitted to intensive care units (ICUs) in South Korea. Methods: This was a retrospective study approved by IRB, and conducted on admission with 559 adults, in the hematology ICU of a hospital located in Seoul. The study was carried out from April 2009 to March 2012. Data were analyzed using SAS. Results: Pneumonia was the most frequent cause of ICU admission and death, followed by sepsis. The condition at discharge was death (53.6%), recovery (39.9%), or hopeless (5.1%). Mortality of patients in states of incomplete remission was higher than that of patients with complete remission and of patients with multiple myeloma, severe aplastic anemia, and lymphoma. Conclusion: Results show that pneumonia and sepsis are the most frequent causes of ICU admission and for the death of patients with hematological malignancies. The most frequent status at discharge of patients with hematological malignancies was death (53.6%), with mortality of patients at Incomplete Remission status, of mechanically ventilated patients, and of patients on continuous renal replacement therapy (CRRT) being higher than others.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.36 no.6
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• pp.543-547
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• 2010

Plasmacytoma is a rare malignant neoplasm in the head and neck region and comprises approximately 3% of all plasma cell tumors. This lesion is a unifocal, monoclonal, neoplastic proliferation of plasma cells that usually arises within the bone. Infrequently, it is observed in soft tissue, in which case, the term extramedullary plasmacytoma is used. Approximately 80-90% of extramedullary plasmacytomas involve the mucos-Associated-Lymphoid Tissue of the upper airways with 75% of these involving the nasal and paranasal regions. The plasmacytoma is usually detected in adult males, with an average age at diagnosis of 55 years. The male-to-female ratio is 3:1.Radiographically, the lesion may be seen as a well-defined, unilocularradioluceny with no evidence of a sclerotic border. Some investigators believe that this lesion represents the least aggressive part of the spectrum of plasma cell neoplasms that extend to multiple myeloma.Therefore, plasma cytoma is believed to have clinical importance. We report a case of extramedullary plasmacytoma in the right maxillary sinus of a 59-year-old male with review of the relevant literature.

• 대한예방의학회:학술대회논문집
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• 1994.02a
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• pp.651-657
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• 1994

To assess quantitatively the association between benzene exposure and leukemia, we examined the mortality rate of a cohort with occupational exposure to benzene. Cumulative exposure for each cohort member was estimated from historical air-sampling data and, when no sampling data existed, from interpolation on the basis of existing data. The overall standardized mortality ratio (a measure of relative risk multiplied by 100) for leukemia was 337 (95 percent confidence interval, 154 to 641), and that for multiple myeloma was 409 (95 percent confidence interval, 110 to 1047). With stratification according to levels of cumulative exposure, the standardized mortality ratios for leukemia increased from 109 to 322, 1186, and 6637 with increases in cumulative benzene exposure from less than 40 parts per million-years (ppm-years), to 40 to 199, 200 to 399, and 400 or more. respectively. A cumulative benzene exposure of 400 ppm years is equivalent to a mean annual exposure of 10 ppm over a 40-year working lifetime; 10 ppm is the currently enforceable standard in the United States for occupational exposure to benzene. To examine the shape of the exposure-response relation, we performed a conditional logistic-regression analysis, in which 10 controls were matched to each cohort member with leukemia. From this model, it can be calculated that protection from benzene induced leukemia would increase exponentially with any reduction in the permissible exposure limit.

• Journal of Chest Surgery
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• v.42 no.2
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• pp.268-271
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• 2009

Solitary plasmacytoma of bone is a rare disease that accounts for only about $3{\sim}5%$ of all plasma cell tumors. Especially, no case of solitary plasmacytoma of a rib origin has been described in the Korean literature. A 54 year old Korean man was referred to our hospital for further evaluation of a lung mass that had been detected on a screening chest radiograph. A tumor with a left 6th rib origin was revealed by the computed tomography(CT) and positive emission tomography (PET-CT); therefore, surgical resection was performed. The histopathological findings of the tumor revealed plasmacytoma of a rib origin. The postoperative screening test revealed no evidence of multiple myeloma. Postoperative radiation therapy was not performed, and no new lesion has been noted during the 2 years of follow up.