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Lee, Na Yeon,Ermakova, Svetlana P.,Choi, Hoo-Kyun,Kusaykin, Michail I.,Shevchenko, Natalya M.,Zvyagintseva, Tatyana N.,Choi, Hong Seok Wiley Subscription Services, Inc., A Wiley Company 2008 Molecular carcinogenesis Vol.47 No.8
<P>Fucoidan, a sulfated polysaccharide extracted from brown seaweeds, has anticoagulant and antithrombotic activities. Unlike heparine, fucoidan is known to exhibit anticarcinogenic activities. However, the underlying molecular mechanisms of the chemopreventive activities of fucoidan are not understood. Here we report that fucoidan from Laminaria cichorioides inhibited the epidermal growth factor (EGF) or 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced neoplastic cell transformation, but had less cytotoxic effects on JB6 mouse epidermal cells. The EGF-induced phosphorylation of extracellular signal-regulated kinases 1/2 and c-Jun N-terminal kinases, and c-Jun was inhibited by fucoidan, resulting from the inhibition of phosphorylation of epidermal growth factor receptor (EGFR). Fucoidan dose-dependently attenuated the c-fos or c-jun transcriptional activity, and thereby inhibited the associated activator protein-1 (AP-1) transactivation activity. In vitro binding assay revealed that fucoidan directly interacted with EGF, suggested that antitumor promoting effect of fucoidan might be due to preventing the binding of EGF to its cell surface receptor (EGFR). These findings are the first to reveal a molecular basis for the anticarcinogenic action of fucoidan and may partially account for the reported chemopreventive effects of brown seaweeds. © 2008 Wiley-Liss, Inc.</P>
Impact of postoperative complications on clinical and economic consequences in pancreatic surgery
Filip ?e?ka,Bohumil Jon,Eva ?ermakova,Zden?k ?ubrt,Alexander Ferko 대한외과학회 2015 Annals of Surgical Treatment and Research Vol.90 No.1
Purpose: Patients who develop complications consume a disproportionately large share of available resources in surgery; therefore the attention of healthcare funders focuses on the economic impact of complications. The main objective of this work was to assess the clinical and economic impact of postoperative complications in pancreatic surgery, and furthermore to assess risk factors for increased costs. Methods: In all, 161 consecutive patients underwent pancreatic resection. The costs of the treatment were determined and analyzed. Results: The overall morbidity rate was 53.4%, and the in-hospital mortality rate was 3.7%. The median of costs for all patients without complication was 3,963 Euro, whereas the median of costs for patients with at least one complication was significantly increased at 10,670 Euro (P < 0.001). In multivariate analysis American Society of Anesthesiologists ≥ 3 (P = 0.006), multivisceral resection (P < 0.001) and any complication (P < 0.001) were independently associated with increased costs. Conclusion: Postoperative complications are associated with an increase in mortality, length of hospital stay, and hospital costs. The treatment costs increase with the severity of the postoperative complications. Those factors that are known to increase the treatment costs in pancreatic resection should be considered when planning patients for surgery.
( Andrey L Rakitin ),( Alexandra Y Ermakova ),( Nikolai V Ravin ) 한국미생물 · 생명공학회 2015 Journal of microbiology and biotechnology Vol.25 No.9
Three endoxylanase-encoding genes from the moderately themophilic chemoorganotrophic bacterium Melioribacter roseus were cloned and expressed in Escherichia coli. Genes xyl2091 (Mros_2091) and xyl2495 (Mros_2495) encode GH10 family hydrolases, whereas xyl2090 (Mros_2090) represents the GH30 family. In addition to catalytic domains, Xyl2090 and Xyl2091 contain carbohydrate-binding modules that could facilitate their binding to xylans and Por sorting domains associated with the sorting of proteins from the periplasm to the outer membrane, where they are covalently attached. Recombinant endoxylanase Xyl2495 exhibited a high specific activity of 1,920 U/mg on birchwood xylan at 40oC. It is active at low temperatures, exhibiting more than 30% of the maximal activity even at 0oC. Endoxylanases Xyl2090 and Xyl2091 have lower specific activities but higher temperature optima at 80oC and 65oC, respectively. Analysis of xylan hydrolysis products revealed that Xyl2090 generates xylo-oligosaccharides longer than xylopentaose. Xylose and xylobiose are the major products of xylan hydrolysis by the recombinant Xyl2091 and Xyl2495. No activity against cellulose was observed for all enzymes. The presence of three xylanases ensures efficient xylan hydrolysis by M. roseus. The highly processive “free” endoxylanase Xyl2495 could hydrolyze xylan under moderate temperatures. Xylan hydrolysis at elevated temperatures could be accomplished by concerted action of two cell-bound xylanases; Xyl2090 that probably degrades xylans to long xylo-oligosaccharides, and Xyl2091 hydrolyzing them to xylose and xylobiose. The new endoxylanases could be useful for saccharification of lignocellulosic biomass in biofuels production, bleaching of paper pulp, and obtaining low molecular weight xylooligosaccharides.
Resveratrol directly targets COX-2 to inhibit carcinogenesis
Zykova, Tatyana A.,Zhu, Feng,Zhai, Xiuhong,Ma, Wei-Ya,Ermakova, Svetlana P.,Lee, Ki Won,Bode, Ann M.,Dong, Zigang Wiley Subscription Services, Inc., A Wiley Company 2008 Molecular carcinogenesis Vol.47 No.10
<P>Targeted molecular cancer therapies can potentially deliver treatment directly to a specific protein or gene to optimize efficacy and reduce adverse side effects often associated with traditional chemotherapy. Key oncoprotein and oncogene targets are rapidly being identified based on their expression, pathogenesis and clinical outcome. One such protein target is cyclooxygenase-2 (COX-2), which is highly expressed in various cancers. Research findings suggest that resveratrol (RSVL; 3,5,4′-trihydroxy-trans-stilbene) demonstrates nonselective COX-2 inhibition. We report herein that RSVL directly binds with COX-2 and this binding is absolutely required for RSVL's inhibition of the ability of human colon adenocarcinoma HT-29 cells to form colonies in soft agar. Binding of COX-2 with RSVL was compared with two RSVL analogues, 3,3′,4′,5′,5-pentahydroxy-trans-stilbene (RSVL-2) or 3,4′,5-trimethoxy-trans-stilbene (RSVL-3). The results indicated that COX-2 binds with RSVL-2 more strongly than with RSVL, but does not bind with RSVL-3. RSVL or RSVL-2, but not RSVL-3, inhibited COX-2-mediated PGE<SUB>2</SUB> production in vitro and ex vivo. HT-29 human colon adenocarcinoma cells express high levels of COX-2 and either RSVL or RSVL-2, but not RSVL-3, suppressed anchorage independent growth of these cells in soft agar. RSVL or RSVL-2 (not RSVL-3) suppressed growth of COX-2<SUP>+/+</SUP> cells by 60% or 80%, respectively. Notably, cells deficient in COX-2 were unresponsive to RSVL or RSVL-2. These data suggest that the anticancer effects of RSVL or RSLV-2 might be mediated directly through COX-2. © 2008 Wiley-Liss, Inc.</P>
Mi Jeong Ku(구미정),Ji Won Jung(정지원),Myeong Sook Lee(이명숙),Byung Kyu Cho(조병규),Soon Rye Lee(이순례),Hye-Sook Lee(이혜숙),Olesya S. Vischuk,Tatyana N. Zvyagintseva,Svetlana P. Ermakova,Yong Hwan Lee(이용환) 한국생명과학회 2010 생명과학회지 Vol.20 No.11
Fucoidan은 갈조류의 세포벽에 존재하는 황산화 다당류이다. 본 연구에서는 자외선 B를 인체각질형성세포에 조사하여 matrix metalloproteinase-1 (MMP-1)을 발현 시킨 후 Fucus evanescens fucoidan이 MMP-1 promoter, mRNA, 단백 발현과 mitogen-activated protein kinases (MAPKs)의 인산화에 미치는 영향을 확인하고자 하였다. 자외선 B에 의해 생성된 MMP-1의 promoter activity와 mRNA, 단백 발현은 fucoidan 10 μg/ml와 100 ㎍/ml를 투여하였을 때 fucoidan을 투여하지 않고 자외선만 조사한 군에 비하여 유의하게 억제되었다. 그리고 F. evanescens fucoidan은 extracellular signal regulated kinase (ERK)의 활성은 현저히 억제시켰으나 c-JUN N-terminal kinase (JNK)와 p38의 활성에 미치는 영향은 약하였다. 따라서 이 연구결과들은 F. evanescens fucoidan이 피부 광노화의 예방과 치료에 도움이 될 가능성을 확인할 수 있었다. Fucoidans are sulfated fucosylated polymers from the cell wall of brown algae. We assessed the effects of Fucus evanescens fucoidan on ultraviolet-B (UVB)-induced expression of matrix metalloproteinase-1 (MMP-1) protein, mRNA, and promoter, and the phosphorylation of mitogen-activated protein kinases in vitro using an immortalized human keratinocyte cell line. Pretreatment with 10 and 100 ㎍/ml fucoidan significantly inhibited UVB-induced MMP-1 protein, mRNA and promoter activity, compared to UVB irradiation alone. Extracellular signal regulated kinase activation was markedly inhibited by treatment with fucoidan, though c-JUN N-terminal kinase activity and p38 activation were only marginally affected by fucoidan. F. evanescens fucoidan may be a potential therapeutic agent for the prevention and treatment of skin photoaging.