• Title/Summary/Keyword: Resistance Mechanism

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Glucose Transporters and Insulin Action : Some Insights into Diabetes Management

  • Jung, Chan-Y.;Lee, Wan
    • Archives of Pharmacal Research
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    • v.22 no.4
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    • pp.329-334
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    • 1999
  • Insulin stimulates glucose uptake in muscle and adipose cells primarily by recruiting GLUT4 from an intracellular storage pool to the plasma membrane. Dysfunction of this process known as insulin resistance causes hyperglycemia, a hallmark of diabetes and obesity. Thus the understanding of the mechanisms underlying this process at the molecular level may give an insight into the prevention and treatment of these health problems. GLUT4 in rat adipocytes, for example, constantly recycles between the cells surface and an intracellular pool by endocytosis and exocytosis, each of which is regulated by an insulin-sensitive and GLUT4-selective sorting mechanism. Our working hypothesis has been that this sorting mechanism includes a specific interaction of a cytosolic protein with the GLUT4 cytoplasmic domain. Indeed, a synthetic peptide of the C-terminal cytoplasmic domain of GLUT4 induces an insulin-like GLUT4 recruitment when introduced in rat adipocytes. Relevance of these observations to a novel euglycemic drug design is discussed.

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Flavonoids: An Emerging Lead in the P-glycoprotein Inhibition

  • Gadhe, Changdev G.;Cho, Seung Joo
    • Journal of Integrative Natural Science
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    • v.5 no.2
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    • pp.72-78
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    • 2012
  • Multidrug resistance is a major obstacle in cancer chemotherapy. Cancer cells efflux chemotherapeutic drug out of cell by means of transporter and reduce the active concentration of it inside cell. Such transporters are member of the ATP binding cassettes (ABC) protein. It includes P-gp, multiple resistant protein (MRP), and breast cancer resistant protein (BCRP). These proteins are widely distributed in the human cells such as kidney, lung, endothelial cells of blood brain barrier etc. However, there are number of drugs developed for it, but most of them are getting transported by it. So, still there is necessity of a good modulator, which could effectively combat the transport of chemotherapeutic agents. Natural products origin modulators were found to be effective against transporter such as flavonoids, which belongs to third generation modulators. They have advantage over synthetic inhibitor in the sense that they have simple structure and abundant in nature. This review focuses on the P-gp structure its architecture, efflux mechanism, herbal inhibitors and their mechanism of action.

A Case of Mucus Plug Impaction resulted in Bronchial Obstruction (광범위 기관지 폐쇄를 유발한 점액전 1례)

  • 고중화;전영명;김휘준
    • Korean Journal of Bronchoesophagology
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    • v.3 no.2
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    • pp.313-317
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    • 1997
  • Airway mucus provides the protective functions such as lubrication, barrier, disposal of trapped materials, and humidification. In the normal state, the mucus do not interfere with Bas transport and the other vital functions of lung. In diseases such as asthma, bronchitis, and cystic fibrosis, the mucus hypersecretion was physiologically developed in the response of multiple neurohumoral mechanism system. And regardless of the mechanism, many clinical sequelae result from mucus hypersecretion: atelectasis, infection, increased airway resistance, increased work of breathing, increased cough with its resultant complication. And the condensation of mucus tv mucus hypersecretion can make the mucus plug by which bronchial obstruction is developed. We have experienced a 7 Pear-old male patient with recurrent pneumonic symtom, which the bronchial obstruction was developed by the impacted mucus plug on the bronchoscopic finding. We report this case with the review of literature.

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The Crack Resistance and the Dielectric Breakdown properties of Epoxy Composities due to the Multi Stresses Variation (다중 응력 변화에 따른 에폭시 복합체의 내크랙성 및 절연 파괴 특성)

  • 송봉철;김상걸;안준호;김충혁;이준웅
    • Proceedings of the Korean Institute of Electrical and Electronic Material Engineers Conference
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    • 2000.07a
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    • pp.136-139
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    • 2000
  • Epoxy materials are used as insulation material for electric power cables. In the case of a flow of excess current due to the temperature difference which occurs between the heat of the conductor and the atmosphere, heat degrades connection point of the cables. Also, the mechanical stress, which occurs due to the thermal expansion coefficient of cable connection electrode system and epoxy insulation materials along with the gap between thermal conduction based on the extra high voltage of transmitted voltage, increases possibility of cracks to occur. The relationship between mechanical stress and electrical breakdown mechanism is verified for the epoxy materials such as high toughness epoxy materials, which comes to be used contemporarily, and for the breakdown mechanism of epoxy materials on the multi-stresses (mechanical and electrical) due to the variation of the temperature.

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Corrosion Properties of Carbon-Coated Metallic Bipolar Plate for PEMFC (고분자 전해질 연료전지 금속 분리판 적용을 위한 탄소 박막의 증착과 내식성 평가)

  • Jang, Dong-Su;Lee, Jung-Joong
    • Journal of the Korean institute of surface engineering
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    • v.48 no.3
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    • pp.87-92
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    • 2015
  • Carbon thin films were deposited on STS 316L sheets by inductively coupled plasma enhanced magnetron sputtering with or without substrate bias voltage. Typical Raman spectrum for amorphous diamond-like carbon (DLC) was obtained, and the interfacial contact resistance (ICR) was measured to show its conductive nature. The electrochemical impedance spectroscopy (EIS) was used to investigate the corrosion mechanism of the carbon coating under the polymer electrolyte membrane fuel cell (PEMFC) condition. According to the pore-corrosion mechanism, the electrolyte penetrates the carbon coating through the pores and reacts with the substrate. As the substrate corrosion proceeds, the pore enlargement occurs and the surface area of the substrate exposed to the electrolyte. Applicability of the carbon coating for the PEMFC bipolar plate was evaluated by potentiodynamic polarization experiments. Finally, an adhesion problem was briefly considered.

Friction and Wear Behaviors of Conventional Composite Resins (재래형 콤포짓트 레진의 마찰 . 마멸거동)

  • 임정일;서세광;김교한;김석삼
    • Tribology and Lubricants
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    • v.16 no.3
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    • pp.166-172
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    • 2000
  • The friction and wear characteristics of dental composite resins such as Charisma, Elitefil, TPH and Veridonfil were investigated. Furthermore, The surface characteristics examination, the analysis of contents of filler, Victors hardness and fracture toughness measurement of composite resins were preformed. The wear test applied ball to move reciprocationally on flat wear tester at room temperature. Microstructure of surfaces and worn surfaces were observed by SEM. Experimental results indicate that the friction coefficient of TPH was quite low, and the wear resistance of TPH was better than that of Charisma, Elitefil or Veridonfil at the same condition. The main wear mechanism was found to be plastic flow and abrasive wear by failure of filler's bond to the matrix.

A study on the shunt effect in resistance spot welding (저항점 용접에 있어서 Shunt영향에 대한 연구)

  • Boo, Kwang-Seok;Cho, Hyeong-Seok
    • Journal of the Korean Society for Precision Engineering
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    • v.3 no.2
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    • pp.39-54
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    • 1986
  • One of the important factors in practical welding situations is shunt effect which deteriorates weld quality due to a shunt current which flows in the exis- ting spot. Previously, this effect has not been analytically investigated, since the mechanism of shunt effect shows very complicated phenomena in the thermal and electrical behavior. In this paper this effect is extensively studied through theoretical and experimental analysis. The theoretical results obtained from a numerical analysis of the modelling of shunt effect are compared with experimental ones. Both results show good agreement and represent well the mechanism of shunt effect.

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Senotherapeutics and Their Molecular Mechanism for Improving Aging

  • Park, Jooho;Shin, Dong Wook
    • Biomolecules & Therapeutics
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    • v.30 no.6
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    • pp.490-500
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    • 2022
  • Aging is defined as physiological dysfunction of the body and a key risk factor for human diseases. During the aging process, cellular senescence occurs in response to various extrinsic and intrinsic factors such as radiation-induced DNA damage, the activation of oncogenes, and oxidative stress. These senescent cells accumulate in many tissues and exhibit diverse phenotypes, such as resistance to apoptosis, production of senescence-associated secretory phenotype, cellular flattening, and cellular hypertrophy. They also induce abnormal dysfunction of the microenvironment and damage neighboring cells, eventually causing harmful effects in the development of various chronic diseases such as diabetes, cancer, and neurodegenerative diseases. Thus, pharmacological interventions targeting senescent cells, called senotherapeutics, have been extensively studied. These senotherapeutics provide a novel strategy for extending the health span and improving age-related diseases. In this review, we discuss the current progress in understanding the molecular mechanisms of senotherapeutics and provide insights for developing senotherapeutics.

The New Way to Define Key Oncogenic Drivers of Small Cell Lung Cancer

  • Kee-Beom Kim
    • Development and Reproduction
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    • v.27 no.1
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    • pp.1-7
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    • 2023
  • Small-cell lung cancer (SCLC) continues to be the deadliest of all lung cancer types. Its high mortality is largely attributed to the unchangeable development of resistance to standard chemo/radiotherapies, which have remained invariable for the past 30 years, underlining the need for new therapeutic approaches. Recent studies of SCLC genome revealed a large number of somatic alterations and identified remarkable heterogeneity of the frequent mutations except for the loss of both RB and P53 tumor suppressor genes (TSGs). Identifying the somatic alterations scattered throughout the SCLC genome will help to define the underlying mechanism of the disease and pave the way for the discovery of therapeutic vulnerabilities associated with genomic alterations. The new technique made it possible to determine the underlying mechanism for the discovery of therapeutic targets. To these ends, the techniques have been focused on understanding the molecular determinants of SCLC.

HS-1200 Overcomes the Resistance Conferred by Bcl-2 in Human Leukemic U937 Cells

  • Park, Jun-Young;Moon, Jeong-Bon;Kim, In-Ryoung;Kim, Gyoo-Cheon;Park, Bong-Soo;Kwak, Hyun-Ho
    • International Journal of Oral Biology
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    • v.37 no.3
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    • pp.91-102
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    • 2012
  • Bcl-2 protects tumor cells from the apoptotic effects of various anti-neoplastic agents. Increased expression of Bcl-2 has been associated with a poor response to chemotherapy in various malignancies, including leukemia. Hence, bypassing the resistance conferred by anti-apoptotic factors such as Bcl-2 represents an attractive therapeutic strategy against cancer cells, including leukemic cells. This study was undertaken to examine whether the anticancer drug, cisplatin and the synthetic chenodeoxycholic acid (CDCA) derivative, HS-1200 show anti-tumor activity in U937 and U937/Bcl-2 cells. Viability assays revealed that HS-1200 overcomes the resistance conferred by Bcl-2 in human leukemic U937 cells. Various apoptosis assessment assays further demonstrated that HS-1200 overcomes the resistance conferred by Bcl-2 in human leukemic U937 cells by inducing apoptosis. In addition HS-1200, but not cisplatin, overcomes the anti-apoptotic effects of Bcl-2 in Bcl-2 over-expressing human leukemic cells (U937/Bcl-2 cells). Notably, we observed that the HS-1200-induced formation of mature promyelocytic leukemia (PML) nuclear bodies (NBs) correlates with a suppression of the anti-apoptotic effects of Bcl-2 in human leukemic cells over-expressing this protein (U937/Bcl-2 cells). Furthermore, HS-1200 was found to induce the association between PML and SUMO-1, Daxx, Sp100, p53 or CBP in the aggregated PML-NBs of U937/Bcl-2 cells. Thus, PML protein and the formation of mature PML-NBs could be considered as therapeutic targets that may help to bypass the resistance to apoptosis conferred by Bcl-2. Elucidating the exact mechanism by which PML regulates Bcl-2 will require further work.