Establishment and characterization of cell lines from three human thyroid carcinomas: Responses to all-trans-retinoic acid and mutations in the BRAF gene

Koh, C.S.,Ku, J.L.,Park, S.Y.,Kim, K.H.,Choi, J.S.,Kim, I.J.,Park, J.H.,Oh, S.K.,Chung, J.K.,Lee, J.H.,Kim, W.H.,Kim, C.W.,Cho, B.Y.,Park, J.G. North-Holland 2007 Molecular and cellular endocrinology Vol.264 No.1

We report the characteristics of three cell lines (designated, SNU-80, SNU-373 and SNU-790), which were established from two papillary carcinomas and one anaplastic carcinoma obtained from three Korean thyroid carcinoma patients. All cell lines grow as adherent cells. Electron microscopy characteristically showed cytoplasmic invaginations of nuclei and intranuclear cytoplasmic inclusions. SNU-80 and SNU-790 cells showed a positive reaction to anti-cytokeratin antibody, and SNU-790 cells positivity for CK-19. All lines were free of mycoplasma or bacteria and were proven unique by DNA fingerprinting analysis. The p15 and p16 genes are deleted in the SNU-790 line. Mutations of the p53 gene were found in two lines (SNU-80 and SNU-373), but no mutations in the RET or MEN1 genes were observed. Mutations of the BRAF gene were found in the SNU-80 (G468R) and the SNU-790 (V599E) cell lines, but no mutations in the K-ras gene were present. SNU-80 and SNU-790 cells showed a positive reaction to anti-cytokeratin antibody, and no evidence of the production of thyroglobulin or calcitonin was observed. The cell lines were unable to trap radioactive iodine but did not contain TSH receptor. In addition, we investigated the mRNA expression levels of Tg, TSHR, TTF-1, PAX-8, NIS, IL-6, and LIF, and of the α, β and γ retinoic acid receptors in these cell lines. IL-6 was down-regulated in all three cell lines by all-trans-retinoic acid treatment. RAR-α was expressed but RAR-β was not expressed in the three cell lines, and RAR-γ was not expressed in SNU-790. Interestingly, RAR-β (SNU-80 and SNU-373) and RAR-γ (SNU-790) was up-regulated by all-trans-retinoic acid treatment. We believe that these well-characterized thyroid carcinoma cell lines may be useful tools for investigations on the biological characteristics of thyroid carcinoma, particularly for investigations related to gene alterations, especially of the BRAF gene. These cell lines may also be useful for redifferentiation therapy studies on thyroid carcinoma using all-trans-retinoic acid.

Production and Developmental Pattern of Embryogenic Callus in Oenanthe javanica (BL.) DC

Koh, G. C 한국식물조직배양학회 1995 식물생명공학회지 Vol.22 No.5

Anatomical Observation of Somatic Embryogenesis in Oenanthe javanica (BL.) DC

Koh, G. C 한국식물조직배양학회 1995 식물생명공학회지 Vol.22 No.6

Translatome analysis of CHO cells to identify key growth genes

Courtes, F.C.,Lin, J.,Lim, H.L.,Ng, S.W.,Wong, N.S.C.,Koh, G.,Vardy, L.,Yap, M.G.S.,Loo, B.,Lee, D.Y. Elsevier Science Publishers 2013 Journal of biotechnology Vol.167 No.3

We report the first investigation of translational efficiency on a global scale, also known as translatome, of a Chinese hamster ovary (CHO) DG44 cell line producing monoclonal antibodies (mAb). The translatome data was generated via combined use of high resolution and streamlined polysome profiling technology and proprietary Nimblegen microarrays probing for more than 13K annotated CHO-specific genes. The distribution of ribosome loading during the exponential growth phase revealed the translational activity corresponding to the maximal growth rate, thus allowing us to identify stably and highly translated genes encoding heterogeneous nuclear ribonucleoproteins (Hnrnpc and Hnrnpa2b1), protein regulator of cytokinesis 1 (Prc1), glucose-6-phosphate dehydrogenase (G6pdh), UTP6 small subunit processome (Utp6) and RuvB-like protein 1 (Ruvbl1) as potential key players for cellular growth. Moreover, correlation analysis between transcriptome and translatome data sets showed that transcript level and translation efficiency were uncoupled for 95% of investigated genes, suggesting the implication of translational control mechanisms such as the mTOR pathway. Thus, the current translatome analysis platform offers new insights into gene expression in CHO cell cultures by bridging the gap between transcriptome and proteome data, which will enable researchers of the bioprocessing field to prioritize in high-potential candidate genes and to devise optimal strategies for cell engineering toward improving culture performance.

패혈증 환자에서 유전자 재조합 인 성장 호르몬 투여가 질소 균형에 미치는 효과

고정민(J . M . Koh),박중열(J . Y . Park),채희복,김진엽(J . Y . Kim),김철희(C . H . Kim),최철수(C . S . Choi),김양수(Y . S . Kim),임채만(C . M . Lim),고윤석(Y . S . Koh),이기업(K . U . Lee),김기수(G . S . Kim) 대한내과학회 1997 대한내과학회지 Vol.53 No.1

N/A Background: Increased catabolism in patients with severe sepsis results in loss of body protein, which is associated with loss of skeletal muscle, impaired immune function and delayed wound healing. However, conventional nutritional support has been unsuccessful in inducing a positive nitrogen balance in septic patient. Recently, growth hormone (GH) has been reported to improve the nitrogen balance in patients with burns and multiple trauma. Methods: As a prospective, randomized, placebo-controlled trial, we studied the effects of 8 day treatment of recombinant human GH(rhGH) on nitrogen balance in patients with sepsis. Twenty four patients with sepsis admitted to medical intensive care unit from July, 1993 to June, 1995 were divided into GH-group(n=13) and control group(n=11). RhGH (EutropinR, Lucky) 0.4IU/kg or same volume of saline was administered once daily as subcutaneous injection for 8 days. Results: Twenty one patients((H group; 12, control group; 9) completed the study. Nitrogen balance was negative on day O, but became positive on day 2 and remained positive throughout the study period in the GH group. Mean nitrogen production rate [nitrogen excretion rate(g/day+△BUN(mmol/L/day)×0.019×body weight(kg)) was significantly lower in GH group than that in control group(12.8±3.9g/day vs. 16.8±4.1g/day p<0.05). Conclusion: GH treatment improved nitrogen balance in patients with severe sepsis and this improvement was associated with a decrease in nitrogen production rate. These results suggest that GH administration may be beneficial in nutritional sup- port for patients with severe sepsis.

Effect of annealing of graphene layer on electrical transport and degradation of Au/graphene/n-type silicon Schottky diodes

Kim, D.J.,Kim, G.S.,Park, N.W.,Lee, W.Y.,Sim, Y.,Kim, K.S.,Seong, M.J.,Koh, J.H.,Hong, C.H.,Lee, S.K. Elsevier Sequoia 2014 JOURNAL OF ALLOYS AND COMPOUNDS Vol.612 No.-

We have investigated the effect of annealing of graphene sheets on the electrical properties of Au/graphene/n-type silicon Schottky diode. Large scale graphene sheets were grown by chemical vapor deposition and then annealed at 300, 400, and 500<SUP>o</SUP>C; one sheet was left un-annealed as the control. The diodes were fabricated by transferring the graphene sheets directly onto n-type Si substrates and the current-voltage (I-V) and capacitance-voltage (C-V) characteristics were evaluated. The average values of the Schottky barrier height (SBH) and ideality factor (η) for the as-fabricated Au/graphene/n-type silicon Schottky diode from I-V measurements were determined to be ~0.8+/-0.01eV and ~1.79+/-0.05, respectively, whereas the SBH from C-V measurements was ~0.89+/-0.01eV. The electrical transport characteristics measured at room temperature indicated that annealing of graphene sheet prior to the transfer of the graphene onto the n-Si substrates significantly reduces the electric degradation of the Schottky diodes, even though no distinct differences in other electric properties, including ideality factors and SBHs, before or after annealing of the graphene sheets were observed. Thus, by simply annealing the graphene sheets at 500<SUP>o</SUP>C, we found that the Au/graphene/n-type silicon Schottky diode showed an approximately 3.3-fold lower series resistance as compared with the un-annealed Schottky diode under air exposure of up to 7days. These annealed diodes showed significantly reduced electrical degradation by removing the potentially trapped H<SUB>2</SUB>O and/or O<SUB>2</SUB> at the interface between the graphene layer and the n-Si substrate.

자발성 뇌실질내출혈 환자의 치료에서 개두술과 정위수술의 비교

문희태,황금철,고영초,박효일 인제대학교 1999 仁濟醫學 Vol.20 No.1S

자발성 뇌 실질내출혈 환자에 있어서 개두술군과 정위수술군을 비교하여 적절한 적응증과 치료 결과를 알기 위해서 연구를 시작하였다. 수술적 치료를 받은 86예를 대상으로 그중 개두술 42예, 정위수술 44예를 대상으로 다음과 같은 결과를 얻었다. 혈종의 위치는 개두술군에서 기저핵부(47.6%), 시상부(42.9%), 뇌피질하부(9.5%) 순이었으며 정위수술군에서는 기저핵부(79.5%), 시상부(20.5%)로 개두술군에서 시상부의 비율이 정위수술군에 비하여 높았다. 혈종의 양은 개두술군은 50cc이상이 88.1%이고 정위수술군은 30∼50cc가 59.1%, 50cc이상이 31.8%였다. 혈종의 양이 많을수록 예후는 불량하였으며 이는 통계학적 유의성을 보였다(P<0.05). 초기 의식 상태는 개두술군은 주로 Grade 3,4로 90.5%였고, 정위수술군은 Grade 2,3이 86.4%였다. 초기 의식상태가 좋으면 예후도 비교적 나은 편이었으며 이는 통계학적 의의를 지닌다(P<0.05). 퇴원시의 GOS 비교에서 개두술군에서는 Vegetative가 33.3%, Dead가 23.8%였고, 정위수술군에서는 Moderately disabled가 45.6%였고 Severely disabled가 25.0%였다. 이상에서 Herniation sign을 보이는 경우는 즉시 Open craniotomy를 하는 것이 좋겠고, 혈종의 양이 30∼50cc이고, Neruological grade 2,3인 경우 24시간이내 Stereotactic evacuation하는 것이 좋겠다. The purpose of this study is to evaluate appropriate indication & result of treatment. between the conventional craniotomy and stereotactic evacuation in the treatment of SICH. Authors operated 86 cases of ICH: 42 cases were operated with conventional craniotomy, and 44 cases were operated with stereotactic evacuation. Aauthor analyzed the result of two therapeutic modalities. Frequent anatomical locations were basal ganglia in 47.6%, thalamus in 42.9% and subcortex of 9.5% in craniotomy group, basal ganglia in 79.5% and thalamus in 20.5% stereotactic group. The Proportion of thalamus in craniotomy group is larder than that in stereotactic grouts. Volume of hematoma was more than 50ml in 88.1% of craniotomy group. Volume of hematoma was 30∼50ml in 59.1% and more than 50ml in 31.896 of stereotactic groups. The prognosis was unfavorable in patients with larger volume. The statistical difference was significant (P<0.05). Neurological grade on admission was grade 3 or 4 in 90.5% of craniotomy group, grade 2 or 3 in 86.496 of stereotactic groups. The prognosis was favorable in those with good neurological grade on admission. The statistical difference was significant(P<0.05). Glasgow outcome scale on discharge among patients who underwent craniotomy were Vegetative in 33.3%, and Dead in 23.8%. Those among patients who underwent stereotactic evacuation were Moderately disabled in 47.7%, severely disabled in 25.0%. Immediate craniotomy is recommended in patient with life - threatening brain herniation. Stereotactic evacuation is recommended within 24 hours of onset in patients with 30∼50ml of hematoma, and neurological grade 2 or 3 on admission.

Radotinib inhibits acute myeloid leukemia cell proliferation via induction of mitochondrial-dependent apoptosis and CDK inhibitors

Heo, S.K.,Noh, E.K.,Gwon, G.D.,Kim, J.Y.,Jo, J.C.,Choi, Y.,Koh, S.,Baek, J.H.,Min, Y.J.,Kim, H. North-Holland ; Elsevier Science Ltd 2016 european journal of pharmacology Vol.789 No.-

<P>Radotinib is a BCR-ABL1 tyrosine kinase inhibitor approved for the second-line treatment of chronic myeloid leukemia. However, effects of radotinib on acute myeloid leukemia (AML) are unclear. In the present study, we observed that radotinib exerted cytotoxic effects on AML cells. Of the various AML cell lines examined (NB4, HL60, HEL 92.1.7, and THP-1), Kasumi-1 was the most sensitive to radotinib. Results of microarray analysis showed that 417 and 595 genes associated with apoptosis and cell cycle regulation, respectively, were differently expressed (i.e., showed > 2-fold difference in expression). Radotinib-induced apoptosis involved the mitochondrial pathway. Moreover, radotinib increased the apoptosis of and induced caspase-3 activity in both Kasumi-1 cells and bone marrow cells (BMCs) obtained from patients with AML. Radotinib also increased cleaved caspase-3, caspase-7, and caspase-9 levels and decreased the number of proliferating Kasumi-1 cells and BMCs from patients with AML. In addition, radotinib induced G(0)/G(1) phase arrest by inducing CDKIs p21 and p27 and by inhibiting CDK2, CDK4, and CDK6. These results indicate that radotinib induces caspase-dependent apoptosis and G(0)/G(1) phase arrest in AML cells by regulating CDKI-CDIC-cyclin cascade. Moreover, these results indicate that radotinib inhibits AML cell proliferation by inducing mitochondria-dependent apoptosis and CDKIs p21 and p27. To our knowledge, this is the first study to show that radotinib can be potentially used for the anti-leukemic therapy of patients with AML. (C) 2016 Elsevier B.V. All rights reserved.</P>

미역부산물의 첨가가 홀스타인 비유우의 비유성적과 내분비생리에 미치는 영향

이홍구,홍중산,이철호,허성웅,김훈,김명국,이현준,최낙진,고태송,최윤재,Lee, H.G.,Hong, Z.S.,Li, Z.H.,Xu, C.X.,Jin, X.,Jin, M.G.,Lee, H.J.,Choi, N.J.,Koh, T.S.,Choi, Yun-Jaie 한국축산학회 2005 한국축산학회지 Vol.47 No.4

본 시험은 미역분말의 첨가가 홀스타인 젖소의 유생산과 내분비계에 미치는 영향을 규명하기 위하여 실시하였다. 기초사료에 미역분말을 1일 두당 800g 수준으로 급여하여 대조구와 비교하였다. 사료건물섭취량은 처리에 의한 영향을 받지 않았고 비유말기 산유량은 대조구에 비해 일일 6.25kg 이나 많게 유의하게 증가하였다(p<0.05). 하지만 유성분은 처리구간에 유의한 차이를 나타내지 않았다. 대조구의 체세포수는 유동적이었지만 처리구의 체세포수는 시험 종료 시 $10^5$개/ml로 시험개시에 비해 무려 53.77%의 감소효과를 보여 탁월한 체세포 감소효과를 나타내었다. 미역분말의 첨가가 혈중 면역글로부린의 함량에는 영향을 주지 않은 것으로 나타났다. 비유에 직접적인 영향을 미치는 IGF-1의 혈장농도는 미역처리구에서 유의성 있게 증가하였으며 비유와 직접적인 관련이 있는 또 다른 호르몬인 $T_3$ 와 $T_4$의 농도도 유의적으로 증가하는 양상을 나타내었다. 지질대사산물인 TC, HDL-C와 LDL-C의 농도는 모두 처리구에서 증가하는 양상을 나타냈다. 이와 같이 미역부산물의 사료 중 첨가는 유생산량의 증가를 보였는데 이는 혈중 비유관련 호르몬의 분비에 영향을 준 결과로 확인된 바 젖소사료자원으로서의 응용가치가 클 것으로 사료된다. This study was conducted to investigate effects of the brown seaweed waste(BSW) supplementation on milk production and related endocrine response in serum in Holstein dairy cows. A total of 14 Holstein dairy cows(initial mean live weight 625kg, average lactation days 225, Reproduction 2.4) were randomly allocated into control(basal diet) and treatment groups (4% BSW/basal diet) with 7 replications for 90 days. Dry matter intake was not affected by brown seaweed waste supplementation, but daily milk yield(kg) at the last experiment significantly increased (6.25kg) in treatment group compared with control group(p<0.05) at the last experiment. The plasma insulin-like growth factor(IGF)-1, triiodothyronine($T_3$) and thyroxine($T_4$) levels were significantly increased in treatment group compared with control group(p<0.05), although the concentration of plasma growth hormone(GH) was not significantly different. Milk composition was not significantly different between groups. The somatic cell count(SCC) in milk were significantly reduced in treatment group compared with control group(p<0.05), but antibodies(total IgG, G1, G2) were not significantly different between groups. Therefore we strongly believe that the increased milk yield is related to metabolic hormones as IGF-1, $T_3$ and $T_4$ and the mechanism of reducing SCC in milk must do more study related nonspecific immunsystem in the future.

Cartilage Oligometric Matrix Protein-Angiopoietin-1 Promotes Revascularization Through Increased Survivin Expression in Dermal Endothelial Cells of Skin Grafts in Mice

Byun, S.J.,Choi, K.S.,Park, S.H.,Cho, N.W.,Hyun Yoo, C.,Yun, K.J.,Koh, Y.J.,Koh, G.Y.,So, B.J.,Yoon, K.H. American Association of Pathologists and Bacteriol 2007 The American journal of pathology Vol.171 No.5

The present study examined the effects of cartilage oligometric matrix protein angiopoietin-1 (COMP-Ang1) on the revascularization of mice skin grafts. Full-thickness skin grafts were autotransferred into BALB/c mice. The donor grafts were soaked in COMP-Ang1 protein (50 μg/ml, n = 10) or in bovine serum albumin (BSA) (50 μg/ml, n = 10) dissolved in 1 ml of sterile, phosphate-buffered saline for 5 minutes before transfer. Revascularization of the grafts was monitored using an intravital microscope on postoperative days 3, 4, and 5. Morphological and immunohistochemical analyses were performed to evaluate platelet-endothelial cell adhesion molecule-1 and survivin expression and apoptotic signal in the transplanted grafts. Grafts soaked in COMP-Ang1 (COMP-Ang1 group) showed significantly increased revascularization compared with grafts soaked in BSA (BSA group) on intravital microscopy and platelet-endothelial cell adhesion molecule-1 staining. The COMP-Ang1 group showed a significant increase of survivin expression in the endothelial cells and a reduction of apoptotic signal in comparison to the BSA group. Therefore, we believe that COMP-Ang1 provides the therapeutic benefit of enhancing the survival of vascular endothelial cells during transplantation of skin graft.