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Involvement of miR-214 and miR-375 in Malignant Features of Non-Small-Cell Lung Cancer by Down-Regulating CADM1

Journal of Cancer Therapy 2012年第4期3卷 379-387页

作者： Megumi Ishimura mika sakurai-yageta Tomoko Maruyama Tomoko Ando Masashi Fukayama Akiteru Goto Yoshinori Murakami Department of Pathology Graduate School of Medicine The University of Tokyo Tokyo Japan Division of Molecular Pathology The University of Tokyo Tokyo Japan Laboratory of Pathology Institute of Medical Science The University of Tokyo Tokyo Japan

A tumor suppressor gene, CADM1, encoding an immunoglobulin superfamily cell adhesion molecule, is inactivated in various cancers, including non-small-cell lung cancer (NSCLC). Although promoter methylation is one of the mechanisms to suppress CADM1 expression, about half of tumors lacking CADM1 expression do not show methylation of the gene promoter. We herein investigated the possible involvement of microRNA (miRNA) in the down-regulation of CADM1. Using computational algorithms, miR-214 and miR-375 were identified as candidate miRNAs targeting CADM1. A luciferase reporter assay demonstrated that miR-214 and miR-375 repressed the promoter activity through 3’-UTR of CADM1. Quantitative RT-PCR analysis demonstrated that miR-214 and miR-375 was highly expressed in 21 (62%) and 17 cases (50%) of 34 primary NSCLCs. Notably, increased expression of miR-214 was preferentially observed in tumors with advanced pathological stages and in those lacking CADM1 expression but were not associated with the promoter methylation, suggesting that miR-214-mediated silencing would be another mechanism to suppress CADM1 expression. On the other hand, introduction of miR-214 or miR-375 into NSCLC cells decreased CADM1 protein expression. Furthermore, overexpression of miR-214 enhanced anchorage-independent growth of NSCLC cells, A549, whereas transfection of miRNA inhibitor, miR-214 or miR-375, significantly suppressed the in vitro wound healing activity of HCC827 cells. These findings suggest that overexpression of miR-214 and miR-375 could participate in the malignant features of NSCLC through down-regulating CADM1 and would provide a potential target for the treatment of a subset of NSCLC.

关键词： CADM1 miR-214 miR-375 Non-Small-Cell Lung Cancer

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Promoter Methylation of the CADM1 and 4.1BGenes Occurs Independently of the EGFRor the KRAS2 Mutation in Non-Small Cell Lung Cancer

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Journal of Cancer Therapy 2015年第3期6卷 273-285页

作者： Hiroyuki Kogai Shinji Kikuchi Takashi Obana Yumi Tsuboi Tomoko Maruyama mika sakurai-yageta Hisao Asamura Yae Kanai Yoshinori Murakami Division of Molecular Pathology Institute of Medical Science The University of Tokyo Tokyo Japan Division of Thoracic Surgery National Cancer Research Center Hospital Tokyo Japan Division of Pathology National Cancer Research Center Research Institute Tokyo Japan

Objective: Targeting mutated EGFR by EGFR-tyrosine kinase inhibitors (EGFR-TKI) is a potent approach to a subset of non-small cell lung cancer (NSCLC). However, the response to EGFR-TKI varies in individual cases even among tumors carrying the same?EGFR?mutation, suggesting the involvement of modifying factors. To characterize possible modifiers, we examined mutation state of the?EGFR?and the?KRAS?genes in Japanese NSCLC and compared them with the methylation state of lung tumor suppressors, the?CADM1 and?4.1B,?whose products have potentials to modify the functions of EGFR or KRAS. Materials and methods: A total of 103 Japanese NSCLC and 11 NSCLC cell lines were examined. Genomic DNA of exons 18–21 of the?EGFR?and exons 1 and 2 of the?KRAS?were amplified by polymerase chain reaction (PCR), followed by single-strand conformation polymorphism analysis and direct sequencing. Methylation status of gene promoters in NSCLC cells were examined by methylation-specific PCR. Results: Mutations of the?EGFR?and?KRAS?were detected mutually exclusively in 27 and 11 out of 103 NSCLC cases, respectively.?EGFR?mutations were observed exclusively in adenocarcinoma (27 of 69, 41%) and preferentially in tumors from female and non-smokers (p < 0.00001). Eight (30%) and 12 (44%) of 27 tumors carrying mutated?EGFR?and 4 (36%) and 8 (73%) of 11 tumors carrying mutated?KRAS?showed methylation of the?CADM1 and 4.1B, respectively.?EGFR-mutated tumors with methylation of either?CADM1 or 4.1B?showed more malignant features than those with unmethylated?CADM1 and 4.1B?(p < 0.05). Conclusion: Methylation state of the?CADM1 and?4.1B?are independent of the mutation status of the?EGFR?or?KRAS?but play roles in the malignant progression of NSCLC. Integration of epigenetic information would be useful for identifying possible modifiers to predict the response or recurrence of lung adenocarcinoma to the EGFR-TKI therapy.

关键词： Non-Small Cell Lung Cancer EGFR Mutation KRAS Mutation CADM1 Methylation 4.1B Methylation

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Mitochondrial Respiration Is Associated with Alloxan-Induced Mitochondrial Permeability Transition

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Journal of Biophysical Chemistry 2016年第4期7卷 87-97页

作者： Koichi sakurai mika Itoh Department of Life Science Hokkaido Pharmaceutical University School of Pharmacy Sapporo Japan

We previously showed that increased mitochondrial inner membrane permeability which is known as mitochondrial permeability transition (MPT) is triggered by adding succinate in the presence of the diabetogenic agent alloxan. Here, our aim was to investigate whether mitochondrial respiration is associated with alloxan-induced MPT. After mitochondria isolated from rat liver were incubated with alloxan at 37°C for 5 min, the addition of succinate immediately triggered the MPT in the presence of rotenone. However, little or no induction occurred at incubation temperatures below 25°C. Malate/glutamate also triggered MPT by alloxan in the absence of rotenone. In mitochondrial suspensions containing alloxan, succinate accelerated oxygen consumption that was completely inhibited by cyanide. These results suggest that mitochondrial respiration is associated with the alloxan-induced MPT. Alloxan radical production was investigated using ESR spectroscopy. Mitochondria incubated with succinate and alloxan elicited low signal intensity (radical formation) that increased significantly in the presence of cyanide. When the incubation of alloxan with mitochondria after the addition of succinate, a little intensity of the signal was observed, but it was remarkably increased after the addition of cyanide. Ubiquinone analogues inhibited the MPT induction. These results suggest that the initiation of MPT is associated with alloxan redox cycling via an electron transfer process at a quinone-binding site in respiratory mitochondria.

关键词： Mitochondria Permeability Respiration Alloxan Redox Cycle Radical

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Synthesis of malachite@clay nanocomposite for rapid scavenging of cationic and anionic dyes from synthetic wastewater

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Journal of Environmental Sciences 2017年第1期29卷 97-110页

作者： Varsha Srivastava mika Sillanpää Laboratory of Green Chemistry School of Engineering ScienceLappeenranta University of TechnologySammonkatu 12FI 50130MikkeliFinland

Synthesis of malachite@clay nanocomposite was successfully carried out for the removal of cationic（Methylene Blue,MB） and anionic dyes（Congo Red,CR） from synthetic *** was characterized by TEM,SEM,FT-IR,EDS analysis and zeta *** analysis indicated that the particle diameter of nanocomposite was in the range of 14 to23 *** important parameters *** time,concentration of dyes,nanocomposite dosage,temperature and solution pH were optimized to achieve maximum adsorption *** the case of MB,removal decreased from 99.82%to 93.67%while for CR,removal decreased from 88.55%to 75.69%on increasing dye concentration from 100 to 450 mg/*** study confirmed the higher removal of CR in acidic range while MB removal was higher in alkaline *** study revealed the applicability of pseudo-second-order model for the adsorption of both *** values of AG0 for both systems suggested the feasibility of dye removal and support for spontaneous adsorption of CR and MB on *** showed 277.77 and 238.09 mg/g Langmuir adsorption capacity for MB and CR *** of dyes from the dye loaded nanocomposite was easily carried out with *** results indicate that the prepared malachite@clay nanocomposite is an efficient adsorbent with high adsorption capacity for the aforementioned dyes.

关键词： Adsorption Bentonite Dyes Kinetic study Methylene blue Congo red

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On the Function of Wall Sculpturing in Xylem Conduits

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Journal of Bionic Engineering 2009年第4期6卷 324-329页

作者： mika M.Kohonen se Helland Department of Physical Sciences University of HullCottingham RoadHU6 7RX UK

The water-conducting network of capillaries in vascular plants has evolved over hundreds of millions of years in order to be able to cope with bubble clogging,a problem which also affects modern microfluidic *** of anatomical studies have revealed that plants growing in habitats in which the formation of bubbles,or emboli,is likely to be a frequent occurrence often have various forms of geometrical sculpturing on the internal surfaces of the xylem *** possible function of such wall sculpturing has long been the subject of *** have investigated the hypothesis that wall sculpturing is a functional adaptation designed to increase the wettability of the walls of xylem conduits,an effect which could be described as the inverse of the well-known *** results show that wall sculpturing does enhance ***,theoretical calculations reveal that the geometric parameters of various types of wall sculpturing are such that the resulting surfaces are sufficiently rough to enhance wettability,but not significantly *** results provide an appealing answer to the long-standing debate on the function of wall sculpturing in xylem conduits,and may provide biomimetic clues for new approaches to the removal of bubbles in microfluidic channels.

关键词： xylem wettability capillary wall sculpturing bubble emboli microfluidic

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Personal Information Self-Management:A Survey of Technologies Supporting Administrative Services

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Journal of Computer Science & Technology 2021年第3期36卷 664-692页

作者： Paul Marillonnet Maryline Laurent mikaël Ates Entr'ouvert Paris 75014France SAMOVAR Télécom SudParisInstitut Polytechnique de ParisEvry 91000France

This paper presents a survey of technologies for personal data self-management interfacing with administrative and territorial public service *** classifies a selection of scientific technologies into four categories of solutions:Personal Data Store(PDS),Identity Manager(IdM),Anonymous Certificate System and Access Control Delegation *** category,along with its technological approach,is analyzed thanks to 18 identified functional criteria that encompass architectural and communication aspects,as well as user data lifecycle *** originality of the survey is ***,as far as we know,there is no such thorough survey covering such a panel of a dozen of existing ***,it is the first survey addressing Personally Identifiable Information(PII)management for both administrative and private service ***,this paper achieves a functional comparison of solutions of very different technical *** outcome of this paper is the clear identification of functional gaps of each *** a result,this paper establishes the research directions to follow in order to fill these functional gaps.

关键词： personal information management privacy enforcement user-centric solution technological survey

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Recent Advances in Catalytic Carbonylation Reactions in Alternative Reaction Media

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Chinese Journal of Chemistry 2024年第4期42卷 406-429页

作者： Csaba Árvai László T.mika Department of Chemical and Environmental Process Engineering Faculty of Chemical Technology and BiotechnologyBudapest University of Technology and EconomicsMűegyetem rkp.3H-1111 BudapestHungary

Since the discovery of the hydroformylation(oxo-synthesis or Roelen reaction)and the Reppe-reaction,the transition metal-catalyzed carbonylation reactions,providing versatile,facile,and even atom-economic methods for the selective incorporation of C=O functionality to various skeletons,have gained tremendous importance in synthetic organic chemistry from laboratories to industrial *** carbonylation of carbon-carbon multiple bonds,aromatic halides,triflates,etc.,in the presence of various nucleophiles has led the way to produce aldehydes,carboxylic acids,esters,amides,etc.,in the fine chemical ***,these protocols usually proceed in conventional,fossil-based,and usually toxic reaction ***,several attempts have been directed to developing efficient carbonylation methods in alternative,less harmful,non-fossil-based and even in renewable reaction *** this review,we overview the recent applications of alternative solvents such as water,biomass-based alcohols,γ-valerolactone(GVL),2-methyltetrahydrofuran(2-MeTHF),ionic liquids(ILs),deep eutectic solvents(DES),alkyl levulinates,limonene,α-pinene,and dimethyl carbonate as well as fluorous media to improve efficiency,safety and environmentally benign nature of carbonylation protocols.

关键词： Carbonylation Catalysis Solvents Green chemistry Carbon monoxide Transition metals Homogeneous catalysis Palladium

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Gadolinium doped tin dioxide nanoparticles: an efficient visible light active photocatalyst

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Journal of Rare Earths 2015年第12期33卷 1275-1283页

作者： Abdullah M Al-Hamdi mika Sillanp?? Joydeep Dutta Laboratory of Green Chemistry Lappeenranta University of Technology Chair in Nanotechnology Water Research Center Sultan Qaboos University Functional Materials Division School of Information and Communication Technology KTH Royal Institute of Technology

Photocatalytic degradation of phenol with sol-gel prepared rare earth doped tin dioxide （SnO2） nanoparticles was reported. Gadolinium doped tin dioxide （SnO2：Gd） nanoparticles were found to absorb higher visible light compared to lanthanum, neodymium and cerium doped materials that were studied in detail. Photocatalytic degradation of phenol under artificial white light and sunlight in the presence of SnO2：Gd nanoparticles was studied with high performance liquid chromatography （HPLC）, capillary electrophoresis （CE）, total organic carbon （TOC） measurements and the determination of chemical oxygen demand （COD）. Clear correlations be- tween the results obtained from these multiple measurements were found, and a kinetic pathway for the degradation process was pro- posed. Within 150 min of solar irradiation, the TOC of a 10 ppm phenol solution in water was reduced by 95%-99%, thus demon- strating that SnO2：Gd nanoparticles are efficient visible light photocatalysts.

关键词： rare earth dopants solar irradiation phenol photo-degradation tin dioxide nanoparticles organic by-products

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Synthesis and application of biocompatible nontoxic nanoparticles for reclamation of Ce^3＋ from synthetic wastewater： Toxicity assessment, kinetic, isotherm and thermodynamic study

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Journal of Rare Earths 2018年第9期36卷 994-1006页

作者： Varsha Srivastava Sidra Iftekhar ZhaoWang Indu Babu mika Sillanpaa Laboratory of Green Chemistry School of Engineering Science Lappeenranta University of Technology Sammonkatu 12 FI-50130 Mikkeli Finland Department of Civil and Environmental Engineering Florida International University Miami EL 33174 USA

The aim of present study is to synthesize forsterite nanoparticles（FRST） for the reclamation of cerium ions（Ce3＋） from synthetic *** aim to synthesize FRST nanoparticles is due to its biocompatible and nontoxic *** formation of nanoparticles with average diameter of 58 nm was confirmed by TEM *** images of bare FRST nanoparticles show a heterogeneous surface with porous *** surface area of FRST nanoparticles is calculated to be 33.69 m2/*** significant uptake of Ce3＋ ions can be obtained for all the selected concentrations（25-150 mg/L） within 2 h of adsorbent—adsorbate *** pH study shows that by increasing pH from acidic to alkaline range,higher removal can be *** study demonstrates the endothermic nature of Ce3＋*** value of sticking probability suggests very high sticking probability of Ce3＋ ion for FRST ***3＋ uptake is favored by higher temperature and with the increase in temperature from298 to 328 K,Langmuir adsorption capacity increases from 36.45 to 42.99 m2/*** of FRST nanoparticles was also investigated for other light and heavy rare earth elements in single solute and multisolute systems,FRST nanoparticles show the significant removal of divalent metallic pollutants as *** assessment of chemical toxicity of treated wastewater was carried out with the bioluminescent photobacterium（Vibrio fischeri） and decreased toxicity was observed in treated water *** outcome of present study suggests that the FRST nanoparticles can be efficiently utilized for the removal of Ce3＋ ions and a wide range of other pollutant species as well.

关键词： Forsterite Rare earth elements Isotherm model Cerium Metallic pollutants

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Involvement of mitochondrial swelling in cytochrome c release from mitochondria treated with calcium and Alloxan

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Journal of Biophysical Chemistry 2011年第1期2卷 10-18页

作者： Takuya Ichimura mika Ito Kiyoshi Takahashi Kyohei Oyama Koichi sakurai 不详

An early event in the induction of apoptosis is cytochrome c (Cyt c) release from mitochondria. We investigated the involvement of mitochonrial permeability transition (MPT) and mitochondrial swelling in Cyt c release from mitochondria treated with alloxan and/or calcium (Ca2+). When mitochondria were treated with a high concentration of Ca2+. alone or Ca2+. with alloxan (alloxan-Ca2+), the MPT was accompanied by mitochondrial swelling and the release of Cyt c. Cyclosporin A prevented the induction of MPT but only slightly decreased the release of Cyt c. High molecular weight polyethylene glycol almost completely inhibited MPT-dependent osmotic mitochondrial swelling and Cyt c release. However, MPT-independent mitochondrial swelling and Cyt c release induced by exogenous K+. were inhibited by the high molecular weight polyethylene glycol. Ruthenium red strongly decreased the amount of Cyt c released. These results suggest that mitochondrial swelling but not MPT is necessary for Cyt c release induced by Ca2+ alone or alloxan and Ca2+.

关键词： Mitochondrial Swelling Cytochrome C Release Calcium Alloxan Mitochondrial Permeability Transition

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