수지상세포의 방사선 저항성에 대한 연구

김은실,김종순,이명호,범희승,민정준,정환정,김성민,허영준,송호천,이제중 대한핵의학회 2003 핵의학 분자영상 Vol.37 No.3

목적 : 림프구와 비교되는 수지상 세포의 방사선 민감성을 보기 위하여 본 연구를 시행하였다. 대상 및 방법 : 말초혈액에서 분리한 T 림프구에 0 Gy, 10 Gy, 30 Gy의 방사선을 조사하고 4시간 후에 유세포 분석기를 이용하여 선량별 세포고사 빈도를 관찰하였다. 또한 조혈모세포에서 미성숙 및 성숙 수지상 세포를 단계적으로 분리 배양하여 각각 0 Gy, 10 Gy, 30 Gy, 100 Gy의 방사선을 조사하고 4시간, 24시간 그리고 48 시간 후에 선량별 세포고사 빈도를 관찰하였다. 사이토스핀(cytospin)슬라이드에 림프구와 미성숙 및 성숙 수지상세포를 3×104개 씩 분주하고 May Grunwald-Giemsa 염색한 후, 광학 현미경 하에서 각각의 세포군 당 100개의 세포에서 세포 면적당 핵의 면적 비를 측정하였다. 결과 : 림프구에서는 방사선조사 선량별로 세포고사 빈도가 유의하게 증가하였으나, 수지상 세포에서는 그 분화정도나 방사선조사 선량에 따른 세포고사의 빈도차이가 없었다. 또한 수지상 세포는 방사선선량과 관계없이 용량에 의존적으로 강력한 T-세포 자극능을 보였다. 림프구의 세포에 대한 핵의 면적 비는 미성숙 및 성숙 수지상세포의 세포에 대한 핵의 면적 비보다 현저히 큰 반면, 두 가지 수지상세포간에 유의한 차이는 없었다. 결론 : 수지상세포는 그 분화도와 상관없이 림프구에 비하여 방사선 저항성을 나타내었고, 이는 세포의 형태적 차이에 따른 표적의 크기와 관련이 있을 것으로 생각되며, 향후 분자 생물학적인 연구의 기초 자료로 활용할 수 있을 것으로 생각된다. Purpose : To evaluate radiation sensitivity of dendritic cells in comparison with lymphocytes. Materials and methods : T lymphocytes captured from peripheral blood were irradiated by 0 Gy, 10 Gy, 30Gy. Apoptosis was measured by flowcytometry for staining of Annexin V 4 hours after irradiation. Immature and mature dendritic cells processed from blood hematopoietic stern cell were irradiated by 0 Gy, 10 Gy, 30 Gy, 100 Gy respectively and apoptosis was measured by flowcytometry with time difference as 4h, 24h and 48h after irradiation. Morphometric analysis by percent nucleus was measured in three cell groups, also. Results : Lymphocytes showed radiation sensitivity by increasing apoptotic fraction according to radiation dose. However, both mature and immature dendritic cells showed consistent fraction of apoptosis in spite of increasing radiation dose. Percent nucleus ratio is significantly higher in lymphocytes than that of mature or immature dendritic cells. Stimulation of T-cell by dendritic cells was not changed after irradiation. Conclusion : Dendritic cells showed radioresistance which was associated with small size of nucleus in comparison with lymphocytes and this result would be used as a basal data of radio-labelling for the cellular trafficking studies in nuclear medicine fields.

물리학 선량법을 이용한 갑상선암의 개인별 최대안전용량 I-131 치료법 개발과 유용성 평가

김정철,윤정한,범희승,제갈영종,송호천,민정준,정환정,김성민,허영준,이명호,박영규,정준기 대한핵의학회 2003 핵의학 분자영상 Vol.37 No.2

목적 : 분화갑상선암 환자에 대한 방사성옥소(I-131) 치료는 재발율과 사망률을 감소시키는 효과적인 치료법이지만, 치료용량을 증가시킴으로써 치료율을 향상시킬 수 있는지에 대해서는 아직 논란이 있다. 본 연구에서는 최대허용선량 치료법의 효용성을 검증하고자 하였다. 대상 및 방법 : 임상적 병기가 제3, 4병기이고, 6개월 이후에 I-131 전신스캔(이하 IWBS)과 혈중 thyroglobulin (이하 Tg), anti-thyroglobulin antibody (이하 ATA), 초음파검사 (이하 US) 및 F-18 FDG PET 등을 통해 치료여부를 확인할 수 있었던 58명(남:여=9:49, 평균연령 50±11세)의 유두상갑상선암 환자를 대상으로 하였다. 이중 11명은 제4병기, 47명은 제3병기였으며, 43명(남:여=4:39), 평균연령 50±11세)은 7.4 GBq 이하의 고식적인 저용량치료법으로 치료하였고, 9.25 GBq 이상의 고용량 치료를 받은 환자는 15명(남:여=5:10, 평균연령 50±12세)으로 고용량군에서 남자가 더 많았으나 연령의 차이는 없었다. 고용량군 환자 모두에서 추적용량의 방사성옥소(평균 77±3 MBq)를 경구 투여한 후 혈중 방사능소실곡선을 통해 최대허용선량(maximum permissible dose, 이하 MPD)을 계산하였으며, 7명에서는 말초혈액림프구의 중기염색체분석법에 의해 생물학적으로 MPD를 계산하였다. 14명에서는 치료용량의 방사성옥소를 투여한 후 혈중 방사능소실곡선을 통해 MPD를 계사하였다. 완전치유(complete response, 이하 CR)는 IWBS에서 병소가 없어지고, 혈중 Tg치가 1 ng/mL 이하로 감소한 경우로 정의하였으며, 부분치유(partial response, 이하 PR)는 IWBS에서 병소가 없어졌더라도 혈중 Tg, ATA치가 높거나, US 또는 PET 검사에서 병소가 남아있는 경우로 정의하였다. 치료후 IWBS에서 병소가 오히려 증가하거나 변함없는 경우는 없었다. 방사성옥소 치료에 의한 부작용은 입원기간 중 타액선이 현저하게 붓고 통증이 있거나, 구토를 심하게 하는 경우, 그리고 퇴원후 1개월째 백혈구수가 20% 이상 감소한 경우로 정의하였다. 결과 : 양 군간에 연속적인 수치변화를 비교하는 경우는 paired t-test를 이용하였으며, 대상군간 치료효과와 부작용의 비교는 chi-square test를 이용하였다. p값 0.05 미만을 통계적으로 유의한 차이로 인정하였다. 고용량군 환자 모두에서 추적용량과 치료용량의 방사성옥소 투여 후 혈액의 피폭선량은 각각 0.012±0.3 Gy, 1.66±25 Gy였으며, 방사성옥소 투여 후 혈액에 전달되는 피폭선량은 추적용량보다 치료용량에서 더 많았고 (1.21: 166 rad, p<0.001), 방사성옥소 1 mCi당 혈액에 전달되는 피폭선량은 차이가 없었다(0.58±0.1 vs. 0.56±0.1 rad/37 MBq, p=0.34). 추적용량 방사성옥소 투여 후 구한 MPD는 평균 13.3±1.9 GBq (9.7 ~ 16 GBq) 이였고, 치료용량 방사성옥소 투여 후 구한 MPD는 평균 13.8±2.1 GBq (10.4 ~ 16.3 GBq)로 유의한 차이가 없었으며 (p=0.20), 두 수치간에는 유의한 상관 관계가 있었다(r=0.8, p<0.0001). 7명의 환자에서 말초혈액림프구 중기염색체 분석법으로 MPD를 측정하였는데 혈액의 피폭선량은 1.78±0.03 G였으며, 같은 환자에서 혈중 방사능소실곡선으로부터 구한 피폭선량은 1.54±0.03 G로 유의하게 낮았으나 (p=0.01), 두 측정치 간에는 유의한 상관관계(r=0.86, p=0.01)가 있었다. 저용량 치료군 43명 중 22명(51.2%)에서 완전치유를 보였고 21명(48.8%)에서는 부분치유를 보인 반면 고용량 치료군 15명 중 12명(80%)에서 완전치유를 보였고 3명(20%)에서만 부분치유를 보여 고용량 치료군에서 유의하게 높은 완전치유를 얻을 수 있었다(p=0.05). 한편 부작용 발생빈도는 저용량 치료군 43명 중 13(30.2%), 고용량 치료군 15명 중 6명(40%)로 양군간에 유의한 차이가 없었다(p=0.46). 임상적인 병기, 연령 및 성별에 따라서는 치유의 차이가 없었다(p>0.05). 결론 : 혈중소실곡선으로부터 MPD를 결정하고 이를 토대로 환자 개개인별로 적절한 선량을 선택하여 치료하는 방법은 부작용을 최소화하면서도 치료효과를 높일 수 있는 매우 유용한 치료법이며, 고위험군 분화갑상선 암 환자에게 가장 적절한 치료법이라고 사료되었다. Purpose: Radioiodine (1-131) therapy is an effective modality to reduce both recurrence and mortality rates in differentiated thyroid cancer. Whether higher doses shows higher therapeutic responses was still debatable. The purpose of this study was to validate curve-fitting (CF) method measuring maximum permissible dose (MPD) by a biological dosimetry using metaphase analysis of peripheral blood lymphocytes. Materials and Methods: Therapeutic effects of MPD was evaluated in 58 patients (49 females and 9 males, mean age 50±11 years) of papillary thyroid cancer. Among them 43 patients were treated with ≤7.4 GBq, while 15 patients with ≥9.25 GBq. The former was defined as low-dose group, and the latter high-dose group. Therapeutic response was defined as complete response when complete disappearance of lesions on follow-up 1-131 scan and undetectable serum thyroglobulin levels were found. Statistical comparison between groups were done using chi-square test. P value less than 0.05 was regarded as statistically significant. Results: MPD measured by CF method using tracer and therapeutic doses were 13.3±1.9 and 13.8±2.1 GBq, respectively (p=0.20). They showed a significant correlation (r=0.8, p<0.0001). Exposed doses to blood measured by CF and biological methods were 1.54±0.03 and 1.78±0.03 Gy (p=0.01). They also showed a significant correlation (r=0.86, p=0.01). High-does group showed a significantly higher rate of complete response (12/15, 80%) as compared to the low-dose group (22/43, 51.2%) (p=0.05). While occurrence of side effects was not different between two groups (40% vs. 30.2%, p=0.46). Conclusion: Measurement of MPD using CF method is reliable, and the high-dose 1-131 therapy using MPD gains significantly higher therapeutic effects as compared with low-dose therapy.

HMGB1 regulates autophagy through increasing transcriptional activities of JNK and ERK in human myeloid Leukemia cells

( Ming Yi Zhao ),( Ming Hua Yang ),( Liang Chun Yang ),( Yan Yu ),( Min Xie ),( Shan Zhu ),( Rui Kang ),( Dao Lin Tang ),( Zhi Gang Jiang ),( Wu Zhou Yuan ),( Xiu Shan Wu ),( Li Zhi Cao ) 생화학분자생물학회(구 한국생화학분자생물학회) 2011 BMB Reports Vol.44 No.9

HMGB1 is associated with human cancers and is an activator of autophagy which mediates chemotherapy resistance. We here show that the mRNA levels of HMGB1 are high in leukemia cells and it is involved in the progression of childhood chronic myeloid leukemia (CML). HMGB1 decreases the sensitivity of human myeloid leukemia cells K562 to anti-cancer drug induced death through up-regulating the autophagy pathway, which is confirmed by the observation with an increase in fusion of autophagosomes and autophagolysosomes. When overexpressing HMGB1, both mRNA levels of Beclin-1, VSP34 and UVRAG which are key genes involved in mammalian autophagy and protein levels of p-Bcl-2 and LC3-II are increased. Luciferase assays document that over-expression of HMGB1 increases the transcriptional activity of JNK and ERK, which may be silenced by siRNA. The results suggest that HMGB1 regulates JNK and ERK required for autophagy, which provides a potential drug target for therapeutic interventions in childhood CML. [BMB reports 2011; 44(9): 601-606]

Optimizing Production of Two Potential Probiotic Lactobacilli Strains Isolated from Piglet Feces as Feed Additives for Weaned Piglets

Ming-Lun Chiang,Hsi-Chia Chen,Kun-Nan Chen,Yu-Chun Lin,Ya-Ting Lin,Ming-Ju Chen 아세아·태평양축산학회 2015 Animal Bioscience Vol.28 No.8

Two probiotic strains, Lactobacillus johnsonii x-1d-2 and Lactobacillus mucosae x-4w-1, originally isolated from piglet feces, have been demonstrated to possess antimicrobial activities, antibiotic resistances and interleukin-6 induction ability in RAW 267.4 macrophages in our previous study. These characteristics make L. johnsonii x-1d-2 and L. mucosae x-4w-1 good candidates for application in feed probiotics. In this study, soybeal meal, molasses and sodium acetate were selected to optimize the growth medium for cultivation of L. johnsonii x-1d-2 and L. mucosae x-4w-1. These two strains were then freeze-dried and mixed into the basal diet to feed the weaned piglets. The effects of L. johnsonii x-1d-2 and L. mucosae x-4w-1 on the growth performance and fecal microflora of weaned piglets were investigated. The results showed that the bacterial numbers of L. johnsonii x-1d-2 and L. mucosae x-4w-1 reached a maximum of 8.90 and 9.30 log CFU/mL, respectively, when growing in optimal medium consisting of 5.5% (wt/vol) soybean meal, 1.0% (wt/vol) molasses and 1.0% (wt/vol) sodium acetate. The medium cost was 96% lower than the commercial de Man, Rogosa and Sharpe medium. In a further feeding study, the weaned piglets fed basal diet supplemented with freeze-dried probiotic cultures exhibited higher (p<0.05) body weight gain, feed intake, and gain/feed ratio than weaned piglets fed basal diet. Probiotic feeding also increased the numbers of lactobacilli and decreased the numbers of E. coli in the feces of weaned piglets. This study demonstrates that L. johnsonii x-1d-2 and L. mucosae x-4w-1 have high potential to be used as feed additives in the pig industry.

The tyrosine kinase inhibitor nintedanib activates SHP-1 and induces apoptosis in triple-negative breast cancer cells

Chun-Yu Liu,Tzu-Ting Huang,Pei-Yi Chu,Chun-Teng Huang,Chia-Han Lee,Wan-Lun Wang,Ka-Yi Lau,Wen-Chun Tsai,Tzu-I Chao,Jung-Chen Su,Ming-Huang Chen,Chung-Wai Shiau,Ling-Ming Tseng,Kuen-Feng Chen 생화학분자생물학회 2017 Experimental and molecular medicine Vol.49 No.-

Triple-negative breast cancer (TNBC) remains difficult to treat and urgently needs new therapeutic options. Nintedanib, a multikinase inhibitor, has exhibited efficacy in early clinical trials for HER2-negative breast cancer. In this study, we examined a new molecular mechanism of nintedanib in TNBC. The results demonstrated that nintedanib enhanced TNBC cell apoptosis, which was accompanied by a reduction of p-STAT3 and its downstream proteins. STAT3 overexpression suppressed nintedanib-mediated apoptosis and further increased the activity of purified SHP-1 protein. Moreover, treatment with either a specific inhibitor of SHP-1 or SHP-1-targeted siRNA reduced the apoptotic effects of nintedanib, which validates the role of SHP-1 in nintedanib-mediated apoptosis. Furthermore, nintedanib-induced apoptosis was attenuated in TNBC cells expressing SHP-1 mutants with constantly open conformations, suggesting that the autoinhibitory mechanism of SHP-1 attenuated the effects of nintedanib. Importantly, nintedanib significantly inhibited tumor growth via the SHP-1/p-STAT3 pathway. Clinically, SHP-1 levels were downregulated, whereas p-STAT3 was upregulated in tumor tissues, and SHP-1 transcripts were associated with improved disease-free survival in TNBC patients. Our findings revealed that nintedanib induces TNBC apoptosis by acting as a SHP-1 agonist, suggesting that targeting STAT3 by enhancing SHP-1 expression could be a viable therapeutic strategy against TNBC.

Purification, Characterization, and Cloning of Fibrinolytic Metalloprotease from Pleurotus ostreatus Mycelia

( Ming Hua Shen ),( Jae Sung Kim ),( Kumar Sapkota ),( Se Eun Park ),( Bong Suk Choi ),( Seung Kim ),( Hyun Hwa Lee ),( Chun Sung Kim ),( Hong Sung Chun ),( Cheon In Ryoo ),( Sung Jun Kim ) 한국미생물생명공학회 2007 Journal of microbiology and biotechnology Vol.17 No.8

Tazarotene-Induced Gene 1 Interacts with DNAJC8 and Regulates Glycolysis in Cervical Cancer Cells

Chun-Hua Wang,Rong-Yaun Shyu,Chang-Chieh Wu,Mao-Liang Chen,Ming-Cheng Lee,Yi-Yin Lin,Lu-Kai Wang,Shun-Yuan Jiang,Fu-Ming Tsai 한국분자세포생물학회 2018 Molecules and cells Vol.41 No.6

The tazarotene-induced gene 1 (TIG1) protein is a retinoid-inducible growth regulator and is considered a tumor suppressor. Here, we show that DnaJ heat shock protein family member C8 (DNAJC8) is a TIG1 target that regulates glycolysis. Ectopic DNAJC8 expression induced the translocation of pyruvate kinase M2 (PKM2) into the nucleus, subsequently inducing glucose transporter 1 (GLUT1) expression to promote glucose uptake. Silencing either DNAJC8 or PKM2 alleviated the upregulation of GLUT1 expression and glucose uptake induced by ectopic DNAJC8 expression. TIG1 interacted with DNAJC8 in the cytosol, and this interaction completely blocked DNAJC8-mediated PKM2 translocation and inhibited glucose uptake. Furthermore, increased glycose uptake was observed in cells in which TIG1 was silenced. In conclusion, TIG1 acts as a pivotal repressor of DNAJC8 to enhance glucose uptake by partially regulating PKM2 translocation.

Chilling Tolerance of Cucumber during Germination is Related to Expression of Lysine Decarboxylase Gene

Ming-hui Lu,Xiao-ming Li,Jin-feng Chen,Long-zheng Chen,Chun-tao Qian 한국원예학회 2006 한국원예학회 기타간행물 Vol.- No.-

Power and Resistance in The Remains of the Day

Ming, Chun-Yan 신영어영문학회 2021 신영어영문학 Vol.80 No.-

This paper examines the theme of power and resistance in Ishiguro’s novel The Remains of the Day by applying Marxian class theory to analyse how individuals like Stevens, the novel’s protagonist who is a butler, are manipulated and exploited in a class society and how social institutions like the Hayes Society help to mentally dominate the working class. Under the constant power in the class system, most individuals have been deprived of the ability to think, judge and act, just like Stevens who turns himself into a working machine and falls victim to self-alienation. On the other hand, characters who resist the power and keep their judgment and morality have also been presented in the novel, with the representative being Miss Kenton, through the depiction of whom the author of the novel shows his faith in the inner power of human beings.

Predisposing Factors of Pressure Sore in Patients with Spinal Surgery

Ming Chi Sung,Chun Jung Peng,Ming Feng Kang 한국간호과학회 2009 한국간호과학회 학술대회 Vol.2009 No.10