Regulation of cancer cell death by a novel compound, C604, in a c-Myc-overexpressing cellular environment

Jo, M.J.,Paek, A.R.,Choi, J.S.,Ok, C.Y.,Jeong, K.C.,Lim, J.H.,Kim, S.H.,You, H.J. North-Holland ; Elsevier Science Ltd 2015 european journal of pharmacology Vol.769 No.-

<P>The proto-oncogene c-Myc has been implicated in a variety of cellular processes, such as proliferation, differentiation and apoptosis. Several c-Myc targets have been studied; however, selective regulation of c-Myc is not easy in cancer cells. Herein, we attempt to identify chemical compounds that induce cell death in c-Myc-overexpressing cells (STF-cMyc and STF-Control) by conducting MTS assays on approximately 4000 chemical compounds. One compound, C604, induced cell death in STF-cMyc cells but not STF-Control cells. Apoptotic proteins, including caspase-3 and poly(ADP-ribose) polymerase (PAPP), were cleaved in C604-treated STF-cMyc cells. In addition, 5W620, HCT116 and NCI-H23 cells, which exhibit higher basal levels of c-Myc, underwent apoptotic cell death in response to C604, suggesting a role for C604 as an inducer of apoptosis in cancer cells with c-Myc amplification. C604 induced cell cycle arrest at the G2/M phase in cells, which was not affected by apoptotic inhibitors. Interestingly, C604 induced accumulation of c-Myc and Cdc25A proteins. In summary, a chemical compound was identified that may induce cell death in cancer cells with c-Myc amplification specifically through an apoptotic pathway. (C) 2015 Elsevier B.V. All rights reserved.</P>

TmSR-C, scavenger receptor class C, plays a pivotal role in antifungal and antibacterial immunity in the coleopteran insect Tenebrio molitor

Kim, S.G.,Jo, Y.H.,Seong, J.H.,Park, K.B.,Noh, M.Y.,Cho, J.H.,Ko, H.J.,Kim, C.E.,Tindwa, H.,Patnaik, B.B.,Bang, I.S.,Lee, Y.S.,Han, Y.S. Pergamon Press ; Elsevier Science Ltd 2017 Insect biochemistry and molecular biology Vol.89 No.-

Scavenger receptors (SRs) constitute a family of membrane-bound receptors that bind to multiple ligands. The SR family of proteins is involved in removing cellular debris, oxidized low-density lipoproteins, and pathogens. Specifically, class C scavenger receptors (SR-C) have also been reported to be involved in phagocytosis of gram-positive and -negative bacteria in Drosophila and viruses in shrimp. However, reports are unavailable regarding the role of SR-C in antifungal immune mechanisms in insects. In this study, a full-length Tenebrio molitor SR-C (TmSR-C) sequence was obtained by 5'- and 3'-Rapid amplification of cDNA ends-polymerase chain reaction (RACE-PCR). The TmSR-C full-length cDNA comprised 1671 bp with 5'- and 3'-untranslated regions of 23- and 107-bp, respectively. TmSR-C encodes a putative protein of 556 amino acid residues that is constitutively expressed in all tissues of late instar larvae and 2-day-old adults, with the highest transcript levels observed in hemocytes of larvae and adults. TmSR-C mRNA showed a 2.5-fold and 3-fold increase at 24 and 6 h after infection with Candida albicans and β-glucan, respectively. Immunoassay with TmSR-C polyclonal antibody showed induction of the putative protein in the cytosols of hemocytes at 3 h after inoculation of C. albicans. RNA interference (RNAi)-based gene silencing and phagocytosis assays were used to understand the role of TmSR-C in antifungal immunity. Silencing of TmSR-C transcripts reduced the survivability of late instar larvae at 2 days post-inoculation of C. albicans, Escherichia coli, or Staphylococcus aureus. Furthermore, in TmSR-C-silenced larvae, there was a decline in the rate of microorganism phagocytosis. Taken together, results of this study suggest that TmSR-C plays a pivotal role in phagocytosing not only fungi but also gram-negative and -positive bacteria in T. molitor.

Radotinib induces high cytotoxicity in c-KIT positive acute myeloid leukemia cells

Heo, S.K.,Noh, E.K.,Kim, J.Y.,Jo, J.C.,Choi, Y.,Koh, S.,Baek, J.H.,Min, Y.J.,Kim, H. North-Holland 2017 European journal of pharmacology Vol.804 No.-

<P>Previously, we reported that radotinib, a BCR-ABL1 tyrosine kinase inhibitor, induced cytotoxicity in acute myeloid leukemia (AML) cells. However, the effects of radotinib in the subpopulation of c-KIT-positive AML cells were unclear. We observed that low-concentration radotinib had more potent cytotoxicity in c-KIT-positive cells than c-KIT-negative cells from AML patients. To address this issue, cell lines with high c-KIT expression, HEL92.1.7, and moderate c-KIT expression, H209, were selected. HEL92.1.7 cells were grouped into intermediate and high c-HIT expression populations. The cytotoxicity of radotinib against the HEL92.1.7 cell population with intermediate c-HIT expression was not different from that of the population with high c-KIT expression. When H209 cells were grouped into c-KIT expression-negative and c-HIT expression-positive populations, radotinib induced cytotoxicity in the c-KIT-positive population, but not the c-KIT-negative population. Thus, radotinib induces cytotoxicity in c-KIT-positive cells, regardless of the c-KIT expression intensity. Therefore, radotinib induces significant cytotoxicity in c-KIT-positive AML cells, suggesting that radotinib is a potential target agent for the treatment of c-KIT-positive malignancies including AML.</P>

Measurements of surgeons’ exposure to ionizing radiation dose: comparison of conventional and mini C-arm fluoroscopy

Sung, K. H.,Min, E.,Chung, C. Y.,Jo, B. C.,Park, M. S.,Lee, K. SAGE Publications 2016 The journal of hand surgery. journal of the Britis Vol.41 No.3

<P>This study was performed to measure the equivalent scattered radiation dose delivered to susceptible organs while simulating orthopaedic surgery using conventional and mini C-arm fluoroscopy. In addition, shielding effects on the thyroid, thymus, and gonad, and the direct exposure delivered to the patient's hands were also compared. A conventional and mini C-arms were installed in an operating room, and a hand and an operator phantom were used to simulate a patient's hand and a surgeon. Photoluminescence dosimeters were used to measure the equivalent dose by scattered radiation arriving at the thyroid, thymus, and gonad on a whole-body phantom in the position of the surgeon. Equivalent scattered radiation doses were measured in four groups: (1) unshielded conventional C-arm group; (2) unshielded mini C-arm group; (3) lead-shielded conventional C-arm group; and (4) lead-shielded mini C-arm group. Equivalent scattered radiation doses to the unshielded group were significantly lower in the mini C-arm group than those in the conventional C-arm group for all organs. The gonad in the lead-shielded conventional C-arm group showed the highest equivalent dose among operator-susceptible organs, and radiation dose was reduced by approximately 96% compared with that in the unshielded group. Scattered radiation was not detected in any susceptible organ in the lead-shielded mini C-arm group. The direct radiation dose to the hand phantom measured from the mini C-arm was significantly lower than that measured from the conventional C-arm. The results show that the equivalent scattered radiation dose to the surgeon's susceptible organs and the direct radiation dose to a patient's hand can be decreased significantly by using a mini C-arm rather than a conventional C-arm. However, protective lead garments, such as a thyroid shield and apron, should be applied to minimize radiation exposure to susceptible organs, even during use of mini C-arm fluoroscopy.</P>

Frequent frameshift mutations in 2 mononucleotide repeats of RNF43 gene and its regional heterogeneity in gastric and colorectal cancers

Jo, Y.S.,Kim, M.S.,Lee, J.H.,Lee, S.H.,An, C.H.,Yoo, N.J. W. B. Saunders Co ; Centrum Philadelphia 2015 Human pathology Vol.46 No.11

RNF43, an E3 ligase, inhibits Wnt signaling by removing Wnt receptors and behaves as a candidate tumor suppressor. Recent studies identified that RNF43 gene was frequently mutated in gastric (GC), colorectal (CRC), and endometrial cancers with high microsatellite instability (MSI-H). The aim of this study is to explore whether RNF43 gene is mutated in GC and CRC in Korean patients and whether the mutations show regional intratumoral heterogeneity (ITH). We analyzed 2 exonic repeats (C6 and G7) of RNF43 in 78 GCs and 130 CRCs by single-strand conformation polymorphism and DNA sequencing analyses. Also, we analyzed regional ITH of RNF43 mutation in 16 CRCs. We found RNF43 frameshift mutation in MSI-H (50/118), the incidence of which was significantly higher than that in microsatellite stable/low microsatellite instability (1/90). GCs showed a significantly higher incidence of the mutation than CRCs (66.7% of GC and 32.9% of CRC with MSI-H). Also, we found that all of the 7 CRCs with the mutations harbored mutational ITH. By immunohistochemistry, we observed that loss of RNF43 expression was significantly more common in those with RNF43 frameshift mutation than those with wild-type RNF43. Our data indicate that RNF43 gene harbored not only exceedingly high mutations but also mutational ITH, which together might play a role in tumorigenesis of GC and CRC. We suggest that regional analysis is required for a more comprehensive evaluation of the mutation status in these tumors.

Molecular characterization and homologous overexpression of [FeFe]-hydrogenase in Clostridium tyrobutyricum JM1

Jo, J.H.,Jeon, C.O.,Lee, S.Y.,Lee, D.S.,Park, J.M. Pergamon Press ; Elsevier Science Ltd 2010 International journal of hydrogen energy Vol.35 No.3

The H<SUB>2</SUB>-evoving [FeFe]-hydrogenase in Clostridium tyrobutyricum JM1 was isolated to elucidate molecular characterization and modular structure of the hydrogenase. Then, homologous overexpression of the hydrogenase gene was for the first time performed to enhance hydrogen production. The hydA open reading frame (ORF) was 1734-bp, encodes 577 amino acids with a predicted molecular mass of 63,970 Da, and presents 80% and 75% identity at the amino acid level with the [FeFe]-hydrogenase genes of Clostridium kluyveri DSM 555 and Clostridium acetobutylicum ATCC 824, respectively. One histidine residue and 19 cysteine residues, known to fasten one [2Fe-2S] cluster, three [4Fe-4S] clusters and one H-cluster, were conserved in hydA of C. tyrobutyricum. A 2327-bp DNA region containing the ORF and the putative promoter region was amplified and subcloned into a pJIR418 shuttle vector. The gene transfer of the recombinant plasmid into C. tyrobutyricum JM1 was performed by a modified electrotransformation method. Homologous overexpression of the [FeFe]-hydrogenase gene resulted in a 1.7-fold and 1.5-fold increase in hydrogenase activity and hydrogen yield concomitant with the shift of metabolic pathway.

플랜지가 있는 제품에서 부분패드의 영향에 관한 연구

고관영,허주환,문정효,장재석,김동윤,정민섭,김주찬,박기용,이강연,조명우,이권진,조영호,이효걸,김주호,이경희 울산과학대학 2000 연구논문집 Vol.27 No.1

본 논문에서는 기존의 Motion-JPEG 기반 감시시스템에서 낮은 동영상 압축성능 문제를 해결하기 위한 새로운 동영상 압축기법을 제안하였다. 제안된 방법에서는 현재 프레임의 JPEG 데이터 중 변화된 압축 데이터만이 실시간으로 추출하고 저장된다. 제안된 방법에 의해 저장된 데이터는 기존의 JPEG과는 다른 고유의 포맷을 가지기 때문에, 동영상 데이터는 더욱 안전하게 유지될 수 있다. 실험을 통해, 제안된 동영상 압축기법의 압축률이 기존의 Motion-JPEG 기반 감시시스템에 비해 3배정도 높다는 것을 확인할 수 있었다.

공정육묘 온실의 표준모델 및 자동화 시스템 개발과 활용기술연구 2 : 제2장 공정육묘를 위한 온실 표준화 연구 Chapter2 Research on the Greenhouse Standardization for the Plug Production Systems

박중춘,민영봉,정병룡,설인준,이영만,윤용철,강호종,김태규,김광용,장사문,정한택,오태한,김평태,김진일,손영걸,박봉식,김시론,이형정,오상석,김명승,조정호,하종규,임동희,이은주,변정희,이정한,최우진,강환규 경상대학교 시설원예연구소 1997 施設園藝硏究 Vol.4 No.-

공정육묘 온실의 표준모델 및 자동화 시스템 개발과 활용기술연구 6 : 제3장 공정육묘의 자동화시스템 개발:제4절~제5절 Chapter3 Development of Automated Plug Production System

박중춘,민영봉,정병룡,설인준,이영만,윤용철,강호종,김태규,김광용,장사문,정한택,오태한,김평태,김진일,손영걸,박봉식,김시론,이형정,오상석,김명승,조정호,하종규,임동희,이은주,변정희,이정한,최우진,강환규 경상대학교 시설원예연구소 1997 施設園藝硏究 Vol.4 No.-

소 Adipocyte Differentiation Related Protein (ADRP) 유전자의 Genomic Organization 및 Promoter Region의 특성 규명

장요순,윤두학,김태헌,정일정,조진기 한국동물자원과학회 2003 한국축산학회지 Vol.45 No.2

ADRP 유전자가 24개월령 한우 등심조직에서 발현량이 급격히 증가하여 30개월령 등심조직에서는 발현량이 다소 감소하는 발현양상 분석결과로부터 이전 연구에서는 ADRP 유전자를 한우 성장단계 특이발현 유전자로 선정하였다. 본 연구에서는 ADRP 유전자의 발현조절 기작을 분석하기 위하여 promoter 영역을 포함하는 ADRP 유전자 전체영역을 cloning 하였으며, 구조를 분석하고 promoter의 특성을 조사하였다. 한우 ADRP cDNA 단편을 probe로 합성하여 Southern blot 분석을 실시한 결과로부터 ADRP 유전자가 한우 genome 상에서 single copy로 존재하고 크기는 대략 12kb에 해당하는 것을 확인하였다. Genomic DNA library screening을 실시하여 promoter 영역을 포함하는 ADRP 전체 유전자에 해당하는 clone을 확보하고 HwADRPg-1으로 명명한 후, 염기서열을 결정하고 분석하였다. 한우 ADRP 유전자, HwADRPg-1은 8개의 exon과 7개의 intron으로 구성되어 있으며 모든 exon-intron 경계는 GT/AG 원칙을 따르고 있었고, coding 영역은 7,633 bp로서 6개의 intron에 의해 7개의 exon으로 나누어져 있었다. HwADRPg-1의 promoter영역에서는 TATAA box는 발견되지 않았으며, -70 위치에 근육 특이적 transcription activator인 Myo G 서열이 존재하였고, -629 위치에는 지방세포의 분화를 유도하는 것으로 알려진 C/EBP (CCAAT/enhancer binding protein) 서열이 존재하였다. HwADRPg-1의 조절영역에 있는 Myo G factor가 근육조직에서 ADRP 유전자가 발현될 수 있도록 하며, 근육의 발달정도를 신호로써 감지하여 근육조직에서 성장단계에 따른 ADRP 유전자의 발현량을 조절할 것으로 추정되고, 다른 종류의 지방세포 특이적인 전사인자 및 지방세포의 분화정도를 신호로 인식하는 전사단계 조절인자를 조사하기 위하여 promoter 영역의 추가분석이 이루어져야 할 것으로 사료된다. To understand the structure and regulation of bovine ADRP (Adipocyte Differentiation Related Protein) gene, we have isolated the genomic clone of bovine ADRP and determined its sequence. A genomic Southern blot analysis confirmed that ADRP gene is present as a single copy in bovine genome and the ADRP gene spans 12 kb. Bovine ADRP genomic clone, HwADRPg-1, had 8 exons and 7 introns, and all splicing sites conformed to the GT/AG rule with the exon-intron boundaries located exactly. Analysis of the upstream 649 bp of the sequence of HwADRPg-1 showed that it does not contain any canonical TATAA boxes; however Sp1 binding sites and CAAT boxes are found. The promoter contained potential binding sites for AP-1, AP-2 and several putative transcription factor binding sites. The 5'-flanking region of HwADRPg-1 contained muscle specific transcription activator Myo G and C/EBP (CCAAT/enhancer binding protein) recognizing site. These results suppose that the Myo G transcription activator regulate the transcription of bovine ADRP gene in muscular tissue and its transcriptional activity was triggered by degree of muscular development. Our results provide the necessary analysis for other flanking sequences are needed in addition to the proximal cis elements of his promoter to confer adipocyte differentiation-dependent or growth-dependent transcriptional control.