• 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.

• Korean Journal of Environmental Biology
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• v.39 no.4
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• pp.452-462
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• 2021

Pretilachlor (PRE) is a common acetanilide herbicide used worldwide. However, its effects on aquatic organisms, particularly marine photosynthetic life, are not sufficiently known. Herein, we evaluated the toxic effects of PRE by physiological and molecular parameters in the photosynthetic dinoflagellate Prorocentrum minimum. The cell density, pigment content, and photosynthetic parameters (F_v/F_m and PI_ABS) were considerably decreased with increased PRE exposure time and doses. In addition, photosynthesis-related genes, PmpsbA, PmpsaA, and PmatpB, were significantly upregulated when exposed to 1.0 mg L^-1 of PRE for 24 h (p<0.001). In 72 h treatment, the relative gene expression was significantly increased (0.1 and 0.5 mg L^-1; p<0.01). In contrast, PmrbcL was decreased or little changed compared to the controls. Reactive oxygen species (ROS) increased after 24 h exposure (p<0.001). However, the transcriptional fold-changes in glutathione S-transferase (GST) were significantly increased (0.5 and 1.0 mg L^-1; p<0.001) at 72 h. These findings suggested that the PmGST might be involved in PRE detoxification in P. minimum. In addition, PRE may affect the photosystem function in phytoplankton similar to other acetanilides, causing severe damage or cell death.

• IMMUNE NETWORK
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• v.23 no.6
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• pp.45.1-45.22
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• 2023

Interstitial lung disease (ILD) involves persistent inflammation and fibrosis, leading to respiratory failure and even death. Adult tissue-derived mesenchymal stem cells (MSCs) show potential in ILD therapeutics but obtaining an adequate quantity of cells for drug application is difficult. Daewoong Pharmaceutical's MSCs (DW-MSCs) derived from embryonic stem cells sustain a high proliferative capacity following long-term culture and expansion. The aim of this study was to investigate the therapeutic potential of DW-MSCs in experimental mouse models of ILD. DW-MSCs were expanded up to 12 passages for in vivo application in bleomycin-induced pulmonary fibrosis and collagen-induced connective tissue disease-ILD mouse models. We assessed lung inflammation and fibrosis, lung tissue immune cells, fibrosis-related gene/protein expression, apoptosis and mitochondrial function of alveolar epithelial cells, and mitochondrial transfer ability. Intravenous administration of DWMSCs consistently improved lung fibrosis and reduced inflammatory and fibrotic markers expression in both models across various disease stages. The therapeutic effect of DW-MSCs was comparable to that following daily oral administration of nintedanib or pirfenidone. Mechanistically, DW-MSCs exhibited immunomodulatory effects by reducing the number of B cells during the early phase and increasing the ratio of Tregs to Th17 cells during the late phase of bleomycin-induced pulmonary fibrosis. Furthermore, DW-MSCs exhibited anti-apoptotic effects, increased cell viability, and improved mitochondrial respiration in alveolar epithelial cells by transferring their mitochondria to alveolar epithelial cells. Our findings indicate the strong potential of DW-MSCs in the treatment of ILD owing to their high efficacy and immunomodulatory and anti-apoptotic effects.

• Journal of Life Science
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• v.24 no.2
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• pp.191-195
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• 2014

Essential oils extracted or purified from various plants have shown various beneficial effects. Seed parts of Schizandra chinensis Baillon (Schisandrae Semen) have been used as a traditional medicine for thousands of years in parts of Asia, including Korea, China, and Japan. However, the pharmacological mechanisms of essential oils purified from S. fructus (S. chinensis Baillon) remain largely unresolved. The aim of this study was to investigate the safety of Schisandrae Semen essential oil (SSeo) by a single- dose toxicity study in mice. SSeo was orally administered at a dose of 5,000 mg/kg in ICR mice. All animals were sacrificed after 14 days of treatment. After a single administration, mortality, clinical signs, body weight changes, and gross pathological findings were observed for 14 days. We also measured parameters of organ weight, clinical chemistry, and hematology. No toxicological change related to the test substance or mortality was observed after administration of a single oral dose of SSeo. There were no adverse effects on clinical signs, body weight, or organ weight and no gross pathological findings in any treatment group. The clinical chemistry and hematological parameters were within the normal ranges except total bilirubin. Therefore, the approximate lethal dose for oral administration of SSeo in mice was considered to be over 5,000 mg/kg. The results on the single-dose toxicity of SSeo indicate that it is not possible to reach oral dose levels related to death or dose levels with any harmful side effects.

• Journal of Chest Surgery
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• v.32 no.6
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• pp.567-572
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• 1999

Background: Surgical correction of the full spectrum of esophageal atresia with tracheoesophageal fistula has improved over the years, but the mortality and morbidity assoiated with repair of these anomalies still remains high. Material and Method: We retrospectively analyzes 27 surgically treated patients with esophageal atresia and tracheoesophageal fistula at Dong-A University Hospital between January 1992 and March 1997. Result: There were 21 male and 6 female patients. Mean birth weight was 2.62$\pm$.385 kg(2.0~3.4 kg). Twenty- four(88.9%) had esophageal atresia with distal tracheoesophageal fistula, and 3(11.1%) had pure esophageal atresia. Four(14.8%) infants were allocated to Waterston risk group A, 18(66.7%) to group B, and 5(18.5%) to group C. In eighteen(66.7%) infants with associated anomalies, cardiovascular anomalies were the most common. Three had a gap length of 3.5 cm or greater(ultra-long gap) between esophageal segments, 7 had 2.0 to 3.5 cm(long gap), 8 had 1.0 to 2.0 cm(medium gap), and 9 had 1 cm or less(short gap) gap length. Among 27 neonates, 3 cases underwent staged operation, late colon interposition was done in 2, and all other 24 cases underwent primary esophageal anastomosis. Oerative mortality was 2/27(7.4%). Causes of death included acute renal failure(n=1), empyema from anastomotic leak(n=1), necrotizing enterocolitis(n=1), sepsis(n=1), insulin-dependent diabetus mellitus(n=1 . There were 4 anastomosis- related complications including stricture in 3, leakage in 1. Mortality was related to the gap length(p<.05). Conclusion: Although the complication rate associated with surgical repair of these anomalies is high, this does not always implicate the operative mortality. The overall survival can be improved by effective treatment for combined anomalies and intensive postoperatve care.

• Clinical and Experimental Pediatrics
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• v.52 no.1
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• pp.93-98
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• 2009

Purpose : The purpose of this study was to evaluate the clinical characteristics and outcomes of patients with neuroblastoma aged less than 1 year. Methods : From January 1997 to December 2007, 41 patients aged less than 1 year were diagnosed with neuroblastoma. Patients were divided into 3 risk groups according to the stage of the disease and N-myc amplification. Low-risk patients underwent surgery with (stage 2) or without (stage 1) short-term chemotherapy. Intermediate-risk patients underwent chemotherapy and surgery with or without local radiation therapy. High-risk patients underwent chemotherapy, surgery, radiation therapy, and high-dose chemotherapy/autologous stem cell rescue (HDCT/ASCR). Results : While tumor relapse occurred in only 1 patient, 7 patients died of treatment-related toxicities. Causes of treatment- related death included infection during conventional chemotherapy in 5 patients and acute myocarditis during HDCT/ASCR in 2 patients. The overall 5-year survival (${\pm}$ standard error) and 5-year event-free survival (EFS) rates after diagnosis for all 41 patients were $82.8{\pm}5.9%$ and $80.0{\pm}$6.3%$, respectively, with a median follow-up of 58 (9-137) months. The 5-year EFS rates for low-risk, intermediate-risk, and high-risk patients were 100%, $68.4{\pm}10.8%$, and $66.7{\pm}19.3%$, respectively. Conclusion : Increased efforts to reduce infection-associated toxicity deaths during conventional chemotherapy are needed to further improve the survival of patients with neuroblastoma aged less than 1 year.

• Journal of Haehwa Medicine
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• v.8 no.2
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• pp.211-243
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• 2000

This study was performed to investigate the cause, symptom, treatment, medicine of Wei symptom through the literature of oriental and western medicine. The results obtained were as follows: 1. Wei symptom is the symptom that reveals muscle relaxation without contraction and muscle relaxation occures in the lower limb or upper limb, in severe case, leads to death. 2. Since the pathology and etiology of Wei symptom was first described as "pe-yeol-yeop-cho"(肺熱葉焦) in Hung Ti Nei Ching(黃帝內經), for generations most doctors had have accepted it. but after Dan Ge(丹溪), it had been classified into seven causes, damp-heat(濕熱), phlegm-damp(濕痰), deficiency of qi(氣虛), deficiency of blood(血虛), deficiency of yin(陰處), stagnant blood(死血), stagnant food(食積). Chang Gyeng Ag(張景岳) added the cause of deficiency of source qi(元氣). 3. The concept of "To treat Yangming, most of all"(獨治陽明) was emphasized in the treatment of Wei symptom and contains nourishment of middle warmer energy(補益中氣), clearance of yangming-damp-heat(淸化陽明濕熱). 4. Since Nei-ching era(內經時代), Wei and Bi symptom(痺症) is differenciated according to the existence of pain. After Ming era(明代) appeared theory of co-existence of Wei symptom and pain or numbness but they were accepted as a sign of Wei symptom caused by the pathological factor phelgm(痰), damp(濕), stagnancy(瘀). 5. In the western medical point of view, Wei symptom is like paraplegia, or tetraplegia. and according to the causative disease, it is accompanied by dysesthesia, paresthsia, pain. thus it is more recommended to use hwal-hyel-hwa-ae(活血化瘀) method considering damp-heat(濕熱), qi deficiency of spleen and stornach(脾胃氣虛) as pathological basis than to simply differenciate Wei and Bi symptom according to the existence of pain. 6. The cause of Gullian-Barre syndrome(GBS) is consist of two factors, internal and external. Internal factors include asthenia of spleen and stomach, and of liver and kidney. External factors include summur-damp(暑濕), damp-heat(濕熱), cold-damp(寒濕) and on the basis of "classification and treatment according to the symptom of Zang-Fu"(臟腑辨證論治), the cause of GBS is classified into injury of body fluid by lung heat(肺熱傷津), infiltration of damp-heat(濕熱浸淫), asthenia of spleen and kidney(脾腎兩虛), asthenia of spleen and stomach(脾胃虛弱), asthenia of liver and kidney (肝腎兩虛). 7. The cause of GBS is divided by according to the disease developing stage: Early stage include dryness-heat(燥熱), damp(濕邪), phlegm(痰濁), stagnant blood(瘀血), and major treatment is reducing of excess(瀉實). Late stage include deficiency of essence(精虛), deficiency with excess(虛中挾實), and essencial deficiency of liver and kidney(肝腎精不足) is major point of treatment. 8. Following is the herbal medicine of GBS according to the stage. In case of summur-damp(暑濕), chung-seu-iki-tang(淸暑益氣湯) is used which helps cooling and drainage of summer-damp(淸利暑濕), reinforcement of qi and passage of collateral channels(補氣通絡). In case of damp-heat, used kun-bo-hwan(健步丸), In case of cool-damp(寒濕), used 'Mahwang-buja-sesin-tang with sam-chul-tang'(麻黃附子細辛湯合蓼朮湯). In case of asthenia of spleen and kidney, used 'Sam-lyeng-baik-chul san'(蔘笭白朮散), In case of asthenia of liver and kidney, used 'Hojam-hwan'(虎潛丸). 9. Following is the herbal medicine of GBS according to the "classification and treatment according to the symptom of Zang-Fu"(臟腑辨證論治). In the case of injury of body fluid by lung heat(肺熱傷津), 'Chung-jo-gu-pae-tang'(淸燥救肺湯) is used. In case of 'infiltration of damp-heat'(濕熱浸淫), us-ed 'Yi-myo-hwan'(二妙丸), In case of 'infiltration of cool-damp'(寒濕浸淫), us-ed 'Yui-lyung-tang', In case of asthenia of spleen, used 'Sam-lyung-bak-chul-san'. In case of yin-deficiency of liver and kidney(肝腎陰虛), used 'Ji-bak-ji-hwang-hwan'(知柏地黃丸), or 'Ho-jam-hwan'(虎潛丸). 10. Cervical spondylosis with myelopathy is occuered by compression or ischemia of spinal cord. 11. The cause of cervical spondylosis with myelopathy consist of 'flow disturbance of the channel points of tai-yang'(太陽經兪不利), 'stagnancy of cool-damp'(寒濕凝聚), 'congestion of phlegm-damp stagnant substances'(痰濕膠阻), 'impairment of liver and kidney'(肝腎虛損). 12. In treatment of cervical spondylosis with myelopathy, are used 'Ge-ji-ga-gal-geun-tang-gagam'(桂枝加葛根湯加減), 'So-hwal-lack-dan-hap-do-hong-eum-gagam(小活絡丹合桃紅飮加減), 'Sin-tong-chuck-ue-tang-gagam(身痛逐瘀湯加減), 'Do-dam-tang-hap-sa-mul-tang-gagam'(導痰湯合四物湯加減), 'Ik-sin-yang-hyel-guen-bo-tang'(益腎養血健步湯加減), 'Nok-gakyo-hwan-gagam'(鹿角膠丸加減). 13. The cause of muscle dystropy is related with 'the impairement of vital qi'(元氣損傷), and 'impairement of five Zang organ'(五臟敗傷). Symptoms and signs are classified into asthenia of spleen and stomach, deficiency with excess, 'deficiency of liver and kidney'(肝腎不足) infiltration of damp-heat, 'deficiency of qi and blood'(氣血兩虛), 'yang deficiency of spleen and kidney'(脾腎陽虛). 14. 'Bo-jung-ik-gi-tang'(補中益氣湯), 'Gum-gang-hwan'(金剛丸), 'Yi-gong-san-hap-sam-myo-hwan'(異功散合三妙丸), 'Ja-hyel-yang-gun-tang'(滋血養筋湯), 'Ho-jam-hwan'(虎潛丸) are used for muscle dystropy. 15. The causes of myasthenia gravis are classified into 'insufficiency of middle warmer energy'(中氣不足), 'deficiency of qi and yin of spleen and kidney'(脾腎兩處), 'asthenia of qi of spleen'(脾氣虛弱), 'deficiency of qi and blood'(氣血兩虛), 'yang deficiency of spleen and kidney'(脾腎陽虛). 16. 'Bo-jung-ik-gi-tang-gagam'(補中益氣湯加減), 'Sa-gun-ja-tang-hap-gi-guk-yang-hyel-tang'(四君子湯合杞菊地黃湯), 'Sa-gun-ja-tang-hap-u-gyi-eum-gagam'(四君子湯合右歸飮加減), 'Pal-jin-tang'(八珍湯), 'U-gyi-eum'(右歸飮) are used for myasthenia gravis.

• Journal of Chest Surgery
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• v.42 no.3
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• pp.299-304
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• 2009

Background: Although the results of the surgical management for complete atrioventricular septal defect (c-AVSD) have improved, the optimal surgical strategy is still controversial. The aims of this study are to evaluate the outcome of c-AVSD repair and to define the risk factors related to reoperation. Material and Method: We retrospectively reviewed the medical records of 35 patients (8 males and 27 females) who underwent the total correction of c-AVSD from August 1996 to March 2008. The median age at repair was 5.2 months (range: 3 days$\sim$82 months). Sixteen patients (45.7%) were associated with Down syndrome. Prior palliative operations were performed in 4 patients. The one-patch techniques were performed in 3 patients, and the two-patch techniques were done in 32 patients. Result: There was 1 early death (2.9%). The median follow-up period was 68 months (range: $2\sim134$ months) for 34 survivors. There was no late death. Reoperations were performed in 5 patients (14.3%) for severe left atrioventricular valvular regurgitation (AVVR). Nine patients (25.7%) showed left an AVVR of more than grade III. Associated major cardiac anomalies and the use of Gore-Tex patch for ventricular septal closure were the risk factors for postoperative left atrioventricular valve failure and reoperation. Conclusion: In this study, we found that surgical repair of c-AVSD was safe and effective. However, the high reoperation rate after repair remains a problem to be solved.

• Tuberculosis and Respiratory Diseases
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• v.65 no.6
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• pp.476-486
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• 2008

Background: TRAIL (TNF-related apoptosis inducing ligand) is a newly identified member of the TNF gene family which appears to have tumor-selective cytotoxicity due to the distinct decoy receptor system. TRAIL has direct access to caspase machinery and induces apoptosis regardless of p53 phenotype. Therefore, TRAIL has a therapeutic potential in lung cancer which frequently harbors p53 mutation in more than 50% of cases. However, it was shown that TRAIL also could activates $NF-{\kappa}B$ in some cell lines which might inhibit TRAIL-induced apoptosis. This study was designed to investigate whether TRAIL can activate $NF-{\kappa}B$ in lung cancer cell lines relatively resistant to TRAIL-induced apoptosis and inhibition of $NF-{\kappa}B$ activation using proteasome inhibitor MG132 which blocks $I{\kappa}B{\alpha}$ degradation can sensitize lung cancer cells to TRAIL-induced apoptosis. Methods: A549 (wt p53) and NCI-H1299 (null p53) lung cancer cells were used and cell viability test was done by MTT assay. Apoptosis was confirmed with Annexin V assay followed by FACS analysis. To study $NF-{\kappa}B$-dependent transcriptional activation, a luciferase reporter gene assay was used after making A549 and NCI-H1299 cells stably transfected with IgG ${\kappa}-NF-{\kappa}B$ luciferase construct. To investigate DNA binding of $NF-{\kappa}B$ activated by TRAIL, electromobility shift assay was used and supershift assay was done using anti-p65 antibody. Western blot was done for the study of $I{\kappa}B{\alpha}$ degradation. Results: A549 and NCI-H1299 cells were relatively resistant to TRAIL-induced apoptosis showing only 20~30% cell death even at the concentration 100 ng/ml, but MG132 ($3{\mu}M$) pre-treatment 1 hour prior to TRAIL addition greatly increased cell death more than 80%. Luciferase assay showed TRAIL-induced $NF-{\kappa}B$ transcriptional activity in both cell lines. Electromobility shift assay demonstrated DNA binding complex of $NF-{\kappa}B$ activated by TRAIL and supershift with p65 antibody. $I{\kappa}B{\alpha}$ degradation was proven by western blot. MG132 completely blocked both TRAIL-induced $NF-{\kappa}B$ dependent luciferase activity and DNA binding of $NF-{\kappa}B$. Conclusion: This results suggest that inhibition of $NF-{\kappa}B$ can be a potentially useful strategy to enhance TRAIL-induced tumor cell killing in lung cancer.

• Journal of Chest Surgery
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• v.29 no.12
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• pp.1360-1365
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• 1996

From September 1992 to May 1996, 38 patients ranging in age from 23 to 78, were operated for aortic dissection at Asan medical center There were 21 men and 17 women. The underlying aortic pathology were acute aortic dissection in 23, chronic aortic dissection in 15. Eight patients had Martian syndrome. In 34 cases of DeBakey type I, II patients, femoral artery and vein and/or right atrial auricle were used as cannulation site. With deep hypothermic c rculatory arrest (esophageal temperature 12 $\pm$ 2.5$^{\circ}C$) and retrograde cerebral perfusion of cold oxygenated blood through SVC, we replaced the ascending aorta and the part of arch if necessary. The mean duration of the total circulatory arrest time was 25 $\pm$ 1.7 mintstuts. In 4 cases of DeBakey type III patients, we replaced descending thoracic aorta or thoracoabdomlnal aorta without shunt or bypass under normothermia with an average 30: 1.5 minutesaortic cross clamp time. One death(2.6%) occurred on the twenty-second postoperative day owing to asphyxia related to ulcer bleeding. Postoperative complications were myocardial infarction with transient left peroneal palsy in 1 case, transient lower extremity weakness in 1 case and prolonged ventilatory support in 1 case. Two patients required reoperation due to retrograde extended dissection and aortic insufuciency. There was no late death with an average 25 months follow-up period.