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Gevab: a prototype genome variation analysis browsing server
Kim, Woo-Yeon,Kim, Sang-Yoon,Kim, Tae-Hyung,Ahn, Sung-Min,Byun, Ha Na,Kim, Deokhoon,Kim, Dae-Soo,Lee, Yong Seok,Ghang, Ho,Park, Daeui,Kim, Byoung-Chul,Kim, Chulhong,Lee, Sunghoon,Kim, Seong-Jin,Bhak, BioMed Central 2009 BMC bioinformatics Vol.10 No.suppl15
<P><B>Background</B></P><P>The first Korean individual diploid genome sequence data (KOREF) was publicized in December 2008.</P><P><B>Results</B></P><P>A Korean genome variation analysis and browsing server (Gevab) was constructed as a database and web server for the exploration and downloading of Korean personal genome(s). Information in the Gevab includes SNPs, short indels, and structural variation (SV) and comparison analysis between the NCBI human reference and the Korean genome(s). The user can find information on assembled consensus sequences, sequenced short reads, genetic variations, and relationships between genotype and phenotypes.</P><P><B>Conclusion</B></P><P>This server is openly and publicly available online at http://koreagenome.org/en/ or directly http://gevab.org.</P>
Kim, Jeong Eun,Kim, Deokhoon,Hong, Yong Sang,Kim, Kyu-pyo,Yoon, Young Kwang,Lee, Dae Ho,Kim, Sang-We,Chun, Sung-Min,Jang, Se Jin,Kim, Tae Won Neoplasia Press 2018 Translational oncology Vol.11 No.2
<P>Pemetrexed and platinum (PP) combination chemotherapy is the current standard first-line therapy for treatment of malignant mesothelioma (MM). However, a useful predictive biomarker for PP therapy is yet to be found. Here, we performed targeted exome sequencing to profile somatic mutations and copy number variations in 12 MM patients treated with PP therapy. We identified 187 somatic mutations in 12 patients (65 synonymous, 102 missense, 2 nonsense, 5 splice site, and 13 small coding insertions/deletions). We identified somatic mutations in 23 genes including <I>BAP1</I>, <I>TP53</I>, <I>NRAS,</I> and <I>EGFR</I>. Interestingly, rare <I>NRAS</I> p.Q61K and <I>EGFR</I> exon 19 deletions were observed in 2 patients. We also found somatic chromosomal copy number deletions in <I>CDKN2A</I> and <I>CDKN2B</I> genes. Genetic alteration related to response after PP therapy was not found. Somatic mutation profiling in MM patients receiving PP therapy revealed genetic alterations in potential therapeutic targets such as <I>NRAS</I> and <I>EGFR</I>. No alterations in genes with potential predictive role for PP therapy were found.</P>
Chae, Heejung,Kim, Deokhoon,Yoo, Changhoon,Kim, Kyu-pyo,Jeong, Jae Ho,Chang, Heung-Moon,Lee, Sang Soo,Park, Do Hyun,Song, Tae Jun,Hwang, Shin,Kim, Ki-Hun,Song, Gi-Won,Ahn, Chul Soo,Lee, Jae Hoon,Hwang Elsevier 2019 European journal of cancer Vol.120 No.-
<P><B>Abstract</B></P> <P><B>Purpose</B></P> <P>In biliary tract cancer (BTC), standard chemotherapy has limited benefit and no molecular targeted agents have been approved. This study investigated the genetic profile of BTC to identify potential new therapeutic targets and predictive biomarkers.</P> <P><B>Methods</B></P> <P>Targeted exome sequencing was performed for 124 patients with BTC [gallbladder cancer (GBC), 25; intrahepatic cholangiocarcinoma (ICC), 55; extrahepatic cholangiocarcinoma (ECC), 44]. Survival analysis was performed in 112 patients who received palliative chemotherapy for locally unresectable or metastatic disease.</P> <P><B>Results</B></P> <P>Genetic alterations were observed in 104 patients (83.8%); the most commonly mutated genes were <I>TP53</I> (44.4%), <I>KRAS</I> (29.0%), <I>ARID1A</I> (12.1%) and <I>IDH1</I> (9.7%). <I>IDH1/2</I> mutations appeared more frequently in ICC (23.6%, P = 0.0002) than in GBC (4.0%) or ECC (2.3%), while <I>ERBB2</I>/<I>3</I> mutations were found only in GBC (20.0%) and ECC (11.4%). Patients harbouring <I>TP53</I> mutations had shorter overall survival (OS; median 15.2 vs. 37.8 months, <I>P</I> = 0.018), while <I>IDH1</I> mutations showed a tendency for longer progression-free survival (PFS; 10.6 vs. 6.1 months, <I>P</I> = 0.124). Potentially actionable genetic alterations were found in 54.8%, and 7.1% received appropriate molecular targeted therapy in the clinical trial setting. Germline or somatic mutations in DNA damage repair (DDR) genes were found in 63.5% of patients and were significantly associated with longer PFS (6.9 vs. 5.7 months, <I>P</I> = 0.013) and OS (21.0 vs. 13.3 months, <I>P</I> = 0.009) in patients who received first-line platinum-containing chemotherapies (n = 88).</P> <P><B>Conclusions</B></P> <P>A subgroup of patients with BTC may benefit from targeted therapy by the aid of genetic information. In particular, DDR alterations may be a predictive biomarker for response to platinum-containing chemotherapy in patients with BTC.</P> <P><B>Highlights</B></P> <P> <UL> <LI> We examined genetic landscape of biliary tract cancer with targeted sequencing. </LI> <LI> Certain genetic mutations were associated with clinical outcomes. </LI> <LI> More than half of patients harboured at least one potentially actionable alteration. </LI> <LI> DNA damage repair gene alterations were associated with a better response to platinum-based treatment. </LI> </UL> </P>
Depigmenting action of platycodin D depends on the cAMP/Rho‐dependent signalling pathway
Jung, Eunsun,Hwang, Wangtaek,Kim, Seungbeom,Kim, Young‐,Soo,Kim, Yeong‐,Shik,Lee, Jongsung,Park, Deokhoon Blackwell Publishing Ltd 2011 Experimental dermatology Vol.20 No.12
<P><B>Abstract: </B> The overproduction and accumulation of melanin in the skin could lead to a pigmentary disorders, such as melasma, freckle, postinflammatory melanoderma and solar lentigo. Therefore, this study was conducted to investigate the effects of platycodin D (PD) on melanogenesis and its action mechanisms. In this study, we found that PD significantly inhibited melanin synthesis at low concentrations. These effects were further demonstrated by the PD‐induced inhibition of cAMP production, phosphorylation of the cAMP‐response element‐binding protein and expression of microphthalmia‐associated transcription factor and its downstream genes, tyrosinase, tyrosinase‐related proteins‐1 and Dct/tyrosinase‐related proteins‐2, suggesting that PD inhibits melanogenesis through the downregulation of cAMP signalling. Furthermore, PD induced significant morphological changes in melanocytes, namely, the retraction of dendrites. A small GTPase assays revealed that PD stimulated an increase in GTP‐bound Rho content, one of downstream molecules of cAMP, but not in Rac or CDC42 content. Moreover, a Rho inhibitor (C3 exoenzyme) and a Rho kinase inhibitor (Y27632) attenuated the dendrite retraction induced by PD. Taken together, these findings indicate that PD inhibits melanogenesis by inhibiting the cAMP‐protein kinase A pathway and also suppresses melanocyte dendricity through activation of the Rho signal that is mediated by PD‐induced reduction in cAMP production. Therefore, these results suggest that PD exerts its inhibitory effects on melanogenesis and melanocyte dendricity via suppression of cAMP signalling and may be introduced as an inhibitor of hyperpigmentation caused by UV irradiation or pigmented skin disorders.</P>
사과 ‘히로사키’ 캘러스 추출물의 기능성 화장품 소재로서의 특성
고승희(Seunghee Ko),김영수(Young-Soo Kim),이진혁(Jin-Hyuck Lee),김일현(Il-Hyun Kim),김승범(Seungbeom Kim),노경백(Kyungbaeg Roh),신승우(Seungwoo Shin),정은선(Eunsun Jung),박덕훈(Deokhoon Park) 한국생물공학회 2013 KSBB Journal Vol.28 No.4
In order to investigate functional characterization of callus extracts of apple ‘Hirosaki’ for cosmetic materials, biological activities of its extracts including wrinkle improvement, hair growth, and anti-inflammatory effect were investigated. The callus extract showed similar activity with TGF-β used as positive control at 50 μg/mL in the test of collagen synthesis, and increased 40% of proliferation of hair follicle dermal papilla cells. Especially, in case of anti-inflammatory effect, callus extract inhibited about 50% of COX-2 expression which was known as response for intermediating inflammation, and about 70% of eotaxin-1 production which was increased by atopy dermatitis.
소성준,Song Lee,Yeonmi Lee,Jongsuk Han,Soonsuk Kang,Jiwan Choi,Bitnara Kim,Deokhoon Kim,유현주,In-Kyong Shim,Ju-Yun Oh,Yu-Na Lee,Song Cheol Kim,Eunju Kang 생화학분자생물학회 2022 BMB Reports Vol.55 No.9
Diabetes mellitus (DM) is a serious disease in which blood sugarlevels rise abnormally because of failed insulin production ordecreased insulin sensitivity. Although many studies are beingconducted for the treatment or early diagnosis of DM, it is notfully understood how mitochondrial genome (mtDNA) abnormalitiesappear in patients with DM. Here, we induced iPSCs fromfibroblasts, PBMCs, or pancreatic cells of three patients with type2 DM (T2D) and three patients with non-diabetes counterpart. The mtDNA mutations were detected randomly without anytendency among tissues or patients. In T2D patients, 62% (21/34)of iPSC clones harbored multiple mtDNA mutations, of which37% were homoplasmy at the 100% mutation level comparedto only 8% in non-diabetes. We next selected iPSC clones thatwere a wild type or carried mutations and differentiated into pancreaticcells. Oxygen consumption rates were significantly lowerin cells carrying mutant mtDNA. Additionally, the mutant cellsexhibited decreased production of insulin and reduced secretionof insulin in response to glucose. Overall, the results suggest thatscreening mtDNA mutations in iPSCs from patients with T2Dis an essential step before pancreatic cell differentiation for diseasemodeling or autologous cell therapy.
Chun, Sung-Min,Sung, Chang Ohk,Jeon, Hyejoon,Kim, Tae-Im,Lee, Ji-Young,Park, Hwan,Kim, Yujin,Kim, Deokhoon,Jang, Se Jin Elsevier 2018 The Journal of molecular diagnostics Vol.20 No.6
<P>Next-generation sequencing (NGS) testing of formalin-fixed, paraffin-embedded (FFPE) tissues is widely used in clinical diagnosis. However, the failure of high-quality DNA library construction, a critical step for NGS, often limits NGS application for FFPE tissues, particularly for old FFPE tissues. The aim was to develop a high-quality DNA library construction method optimized for NGS of FFPE specimens. DNA library construction was developed for FFPE specimens by using S1 nuclease and compared with the Covaris method—the widely accepted DNA library construction protocol. The Covaris method includes a DNA shearing step with sonication to generate shortened DNA fragments. DNA shearing was found to be unnecessary, and S1 nuclease treatment only during genomic DNA extraction significantly improved the success rate of library construction from FFPE tissues. Moreover, poor-quality FFPE tissues that failed the Covaris method were rescued with the S1 method. Higher complexity was observed in DNA libraries constructed by the S1 method. Among 223 FFPE specimens, DNA libraries were successfully constructed for 134 cases with the Covaris method (60.0% success rate), whereas the success rate was 86.5% (193 of 223) with the S1 method (<I>P</I> = 5.255e<SUP>−10</SUP>). Furthermore, we were able to rescue 59 samples, including 25 primary lung cancers, from the 89 failed Covaris method cases. In conclusion, the S1 method is optimal for NGS testing of poor-quality FFPE specimens.</P>
임지희 ( Ji Hee Lim ),정광선 ( Kwang Seon Jung ),이종성 ( Jongsung Lee ),정은선 ( Eunsun Jung ),김대경 ( Dae Kyung Kim ),김영수 ( Youngsoo Kim ),김영우 ( Yong-woo Kim ),박덕훈 ( Deokhoon Park ) 대한화장품학회 2008 대한화장품학회지 Vol.34 No.3
본 연구에서는 제주도 해안에 자생하는 45종의 해양식물 추출물에 대한 항균 활성을 조사하였다. 해양식물 추출물은 80 % 메탄올에서 유효 성분을 추출하여 시료화 하였고 항균활성을 검증하였다. 그 결과, 45종의 해조류 중에서 넓패, 패, 구멍갈파래 등을 포함한 6종의 해양식물이 미생물 생육을 억제하는 결과를 보였다. 항균활성을 갖는 해양식물 중 패, 감태 2종은 항산화 효능도 동시에 가지고 있음을 확인하였다. 이러한 결과를 통해, 본 실험에서 확보된 추출물이 항균 물질로 사용될 수 있는 가능성을 확인하였다. In this study, we investigated the antimicrobial and antifungal activity from the wild seaweeds of Jeju island. The active ingredients of the seaweeds were prepared by 80 % methanol extraction. Antimicrobial and antifungal activity of seaweed extracts was examined. We found that 6 plant extracts among 45 plants, namely, Codium contractum, Undaria pinnatifida, Ishige sinicola, Ishige okamurai, Ishige okamurai, Ecklonia cava, Hizikia fusiformis, Ulva fasciata, Ulva pertusa, Sargassum siliquastrum, Ecklonia kurome, Gracilaria textorii, significantly inhibited growth of harmful microorganisms. Additionally, according to DPPH assay, 2 plant extracts were found to have antioxidant activities. Taken together, these results suggest the possibility that 11 plant extracts can be utilized as an antimicrobial agent.