• Title/Summary/Keyword: role-efficacy

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Mechanistic insights into differential requirement of receptor dimerization for oncogenic activation of mutant EGFR and its clinical perspective

  • Cho, Jeonghee
    • BMB Reports
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    • v.53 no.3
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    • pp.133-141
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    • 2020
  • The epidermal growth factor receptor (EGFR), a member of the ErbB family (EGFR, ErbB2, ErbB3 and ErbB4), plays a crucial role in regulating various cellular responses such as proliferation, differentiation, and survival. As a result, aberrant activation of EGFR, mostly mediated through different classes of genomic alterations occurring within EGFR, is closely associated with the pathogenesis of numerous human cancers including lung adenocarcinoma, glioblastoma, and colorectal cancer. Thus, specific suppression of oncogenic activity of mutant EGFR with its targeted drugs has been routinely used in the clinic as a very effective anti-cancer strategy in treating a subset of tumors driven by such oncogenic EGFR mutants. However, the clinical efficacy of EGFR-targeted therapy does not last long due to several resistance mechanisms that emerge in the patients following the drug treatment. Thus, there is an urgent need for the development of novel therapeutic tactics specifically targeting mutant EGFR with the focus on the unique biological features of various mutant EGFR. Regarding this point, our review specifically emphasizes the recent findings about distinct requirements of receptor dimerization and autophosphorylation, which are critical steps for enzymatic activation of EGFR and signaling cascades, respectively, among wildtype and mutant EGFR and further discuss their clinical significance. In addition, the molecular mechanisms regulating EGFR dimerization and enzymatic activity by a key negative feedback inhibitor Mig6 as well as the clinical use for developing potential novel drugs targeting it are described in this review.

Application of an Efficient Method for Isolation of Mitochondria from Biological Samples

  • Jun, Jin Hyun;Kim, Jihyun;Kim, Kyung Tae;Sung, Ho Joong
    • Biomedical Science Letters
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    • v.20 no.3
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    • pp.180-184
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    • 2014
  • Mitochondria play a crucial role in many essential biological events by way of the electron transport chains and intermembrane proteins that they contain. Abnormalities in the mitochondria are strongly correlated with the development of diseases such as atherosclerosis, cancer, and diabetes. However, the study of mitochondria has been referred to as 'labor-intensive' because of the difficulty in isolating the organelles from their various sources, which can include cultured cells and tissues. Multiple companies provide mitochondria isolation kits, and it is possible for investigators to use different kits and apply different protocols depending on the source of the mitochondria. Therefore, we focused on producing an isolation buffer that could be applied to both cultured cells and tissues, and optimized an isolation protocol that could be used with both. Specifically, we adjusted the buffer condition that can be applied to human cervical cancer cells, fibroblasts, and tissues such as mouse liver and spleen. We also optimized the protocol to improve the efficacy and efficiency of the steps involved in the isolation of mitochondria. These methodological improvements may contribute to advanced research by allowing investigators to overcome the difficulties involved in isolation of mitochondria from biological samples.

Usefulness of Speech Therapy for Patients with Submucous Cleft Palate Treated with Furlow Palatoplasty (점막하 구개열 치료에 있어 Furlow 구개성형술 전후 언어 치료의 유용성)

  • Baek, Rongmin;Park, Mikyong;Heo, Chanyeong
    • Archives of Plastic Surgery
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    • v.32 no.3
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    • pp.375-380
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    • 2005
  • Furlow palatoplasty has been favored by many plastic surgeons as the primary treatment for the velopharyngeal insufficiency associated with submucous cleft palate. The purpose of this article is to introduce an efficacy of Furlow palatoplasty and speech therapy performed on patients who were diagnosed belatedly as having submucous cleft palates. From 2002 to 2004, four submucous cleft palate patients over 5 years of age with velopharyngeal insufficiency received Furlow palatoplasty. The patients were evaluated through the preoperative perceptual speech assessment, nasometry, and videonasopharyngoscopy. Postoperatively, two patients achieved competent velopharyngeal function in running speech. One of the remaining two could achieve competent velopharyngeal function with visual biofeedback speech therapy and the other could not use her new velopharyngeal function in running speech because of her age. Speech therapy can correct the articulation errors and thus improve the velopharyngeal function to a certain extent by eliminating some compensatory articulations that might have an adverse influence on velopharyngeal function. This study shows that Furlow palatoplasty can successfully correct the velopharyngeal insufficiency in submucous cleft palate patients and speech therapy has a role in reinforcing surgical result. But age is still a restrictive factor even though surgery was well done.

Development of Drugs and Technology for Radiation Theragnosis

  • Jeong, Hwan-Jeong;Lee, Byung Chul;Ahn, Byeong-Cheol;Kang, Keon Wook
    • Nuclear Engineering and Technology
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    • v.48 no.3
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    • pp.597-607
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    • 2016
  • Personalized medicine is tailored medical treatment that targets the individual characteristics of each patient. Theragnosis, combining diagnosis and therapy, plays an important role in selecting appropriate patients. Noninvasive in vivo imaging can trace small molecules, antibodies, peptides, nanoparticles, and cells in the body. Recently, imaging methods have been able to reveal molecular events in cells and tissues. Molecular imaging is useful not only for clinical studies but also for developing new drugs and new treatment modalities. Preclinical and early clinical molecular imaging shows biodistribution, pharmacokinetics, mechanisms of action, and efficacy. When therapeutic materials are labeled using radioisotopes, nuclear imaging with positron emission tomography or gamma camera can be used to treat diseases and monitor therapy simultaneously. Such nuclear medicine technology is defined as radiation theragnosis. We review the current development of drugs and technology for radiation theragnosis using peptides, albumin, nanoparticles, and cells.

In Vitro Antilisterial Potential of a Marine Isolate of Aspergillus sp. Collected from the South Coast of Korea

  • Bajpai, Vivek K.;Kang, Sun-Chul
    • Korean Journal of Environmental Agriculture
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    • v.28 no.1
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    • pp.75-81
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    • 2009
  • This study was carried out to assess the antilisterial potential of ethyl acetate (EtOAc) extract of a marine isolate of Aspergillus sp. The in vitro antilisterial efficacy of ethyl acetate extract was examined using disc diffusion, minimum inhibitory concentration (MIC) determination, cell viable count and scanning electron microscopic (SEM) methods against the employed strains of Listeria monocytogenus. The ethyl acetate extract ($300{\mu}g\;disc^{-1}$) exhibited a promising antilisterial effect as diameters of inhibition zones against L. monocytogenes ATCC 19111, 19116, 19118, 19166 and 15313, which were found in the range of 11-17 mm along with their MIC values ranging from 125 to $1000{\mu}g\;ml^{-1}$ respectively. Also the EtOAc extract had strong detrimental effect on the viable count of the tested L. monocytogens ATCC 19166. Furthermore, scanning electron microscopic (SEM) study demonstrated potential detrimental effect of ethyl acetate extract on the morphology of L. monocytogenes ATCC 19116 at the used MIC concentration. These findings strongly support the role of ethyl acetate extract of a marine isolate of Aspergillus sp. as an antiliterial potential.

Dysregulation of NRF2 in Cancer: from Molecular Mechanisms to Therapeutic Opportunities

  • Jung, Byung-Jin;Yoo, Hwan-Sic;Shin, Sooyoung;Park, Young-Joon;Jeon, Sang-Min
    • Biomolecules & Therapeutics
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    • v.26 no.1
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    • pp.57-68
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    • 2018
  • Nuclear factor E2-related factor 2 (NRF2) plays an important role in redox metabolism and antioxidant defense. Under normal conditions, NRF2 proteins are maintained at very low levels because of their ubiquitination and proteasomal degradation via binding to the kelch-like ECH associated protein 1 (KEAP1)-E3 ubiquitin ligase complex. However, oxidative and/or electrophilic stresses disrupt the KEAP1-NRF2 interaction, which leads to the accumulation and transactivation of NRF2. During recent decades, a growing body of evidence suggests that NRF2 is frequently activated in many types of cancer by multiple mechanisms, including the genetic mutations in the KEAP1-NRF2 pathway. This suggested that NRF2 inhibition is a promising strategy for cancer therapy. Recently, several NRF2 inhibitors have been reported with anti-tumor efficacy. Here, we review the mechanisms whereby NRF2 is dysregulated in cancer and its contribution to the tumor development and radiochemoresistance. In addition, among the NRF2 inhibitors reported so far, we summarize and discuss repurposed NRF2 inhibitors with their potential mechanisms and provide new insights to develop selective NRF2 inhibitors.

Effects of the supportive nursing care on the chronic arthritis patients : outcomes of the treatment for 8-week followup. (만성 관절염환자의 지지간호 효과)

  • Kim Myung-Ja;Jo Kae-Wha;Kang Sung-Sil;Song Hyo-Jeong
    • Journal of Korean Academy of Fundamentals of Nursing
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    • v.6 no.3
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    • pp.559-569
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    • 1999
  • The purpose of this study is to identify the effects of the supportive nursing care for arthritis patients enrolled in a rheumatoid clinic. To achieve this purpose, this study adopted a quasi-experimental, pre- and post-test research design, categorized subjects into experimental and control groups. Outpatient clinic nurse alloted the subjects by experimental and control groups and nurse researcher meets the experimental subject with in-depth, direct personal interview and advices via telephone for 8 weeks. During this pre and after the treatment period, the level of pain, uncertainty, self-efficacy, family support, and perception for health were measured. Analyses for the measured results for pre- and post-test showed that the supportive program conducted during this study decreased the level of uncertainty and increased the perception of family support in experimental group. So, the supportive healing interpersonal communication service proved to be effective and this result justifies the argument that the role of the nursing professionals at out-patient clinic should be extended for the more qualified care for the patient.

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The Role of Massive Shaking Irrigation and Abdominal Drainage After Laparoscopic Appendectomy for Panperitonitis Secondary to Perforated Appendicitis in Children (소아의 범발성 복막염을 동반한 천공성 충수염에서 복강경하 충수절제술 후 대량 흔들기 세척법 및 배액술의 역할)

  • Kim, Woo-Yeon;Chung, Jae-Hee
    • Advances in pediatric surgery
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    • v.17 no.1
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    • pp.51-57
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    • 2011
  • Use of laparoscopic appendectomy (LA) for perforated appendicitis (PA) in children remains controversial because of the development of postoperative intra-abdominal abscess formation. We developed the irrigation method for the prevention of abscess formation after LA performed for PA in children with severe panperitonitis. We called it 'the shaking irrigation'. The object of this study was to analyze the efficacy of this irrigation method. All cases of PA with severe panperitonitis in children that underwent LA with massive shaking irrigation and drainage between June 2003 and December 2007 were studied retrospectively. We included only PA with panperitonitis and large amounts of purulent ascites throughout the abdomen as well as an inflamed small bowel with ileus. Thirty-four children were involved in this study. The mean patient age was eight years. The mean amount of irrigation fluid was 8.2 L (range: 4-15 L), The mean operative time was 89.5 min. The mean length of the hospital stay was 5.1 days. There were no postoperative intra-abdominal abscesses. There was no conversion to open surgery. In conclusion, Use of LA in PA with severe panperitonitis in children is safe and effective. Massive shaking irrigation and abdominal drainage appears to prevent intra-abdominal abscesses after LA for PA with panperitonitis.

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Efficacy of Curcumin in the Modulation of Anxiety Provoked by Sulfite, a Food Preservative, in Rats

  • Noorafshan, Ali;Vafabin, Masoud;Karbalay-Doust, Saied;Asadi-Golshan, Reza
    • Preventive Nutrition and Food Science
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    • v.22 no.2
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    • pp.144-148
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    • 2017
  • Sulfites are used as food preservatives and excessive sulfite might disturb the body systems including the brain. Curcumin shows protective effects on the nervous system toxicity. The present study aimed to evaluate the protective role of curcumin in sulfite-induced anxiety in rats. Male rats were divided into five groups. The rats in groups I to V received distilled water (vehicle of sulfite, 1 mL/d), olive oil (vehicle of curcumin, 1 mL/d), curcumin (100 mg/kg/d), sulfite (25 mg/kg/d), and sulfite+curcumin, respectively, by daily gastric gavage for 8 weeks. At the end of 8 weeks the rats were tested in the elevated plus-maze for anxiety. The results showed that concomitant treatment of curcumin during sulfite consumption prevented the reduction of the time spent in the open arm and entrance to the open arm (the indexes of anxiety). Besides, an increase was found in motor activity of the rats in the sulfite+curcumin group compared to the sulfite-treated animals. Exposure of sulfite in rats can induce anxiety, and curcumin can act as an anti-anxiety agent.

Role of Curcuma longa, a traditional ayurvedic medicinal plant, in diabetes

  • Ponnusamy, Sudha;Zinjarde, Smita;Bhargava, Shobha;Kumara, Ameeta Ravi
    • CELLMED
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    • v.2 no.4
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    • pp.31.1-31.7
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    • 2012
  • Curcuma longa belongs to the family Zingiberaceae and can be found in the tropical and subtropical regions of the world. It is widely used in Asiatic countries, especially India and South East Asia where it is cultivated commercially as a condiment. Its rhizomes exhibit anti-inflammatory, anti-human immunodeficiency virus, anti-bacterial, antioxidant effects, nematocidal activities, antiproliferative and antiangiogenic activities and are of pharmaceutical importance. Another relevant medicinal property exhibited by it is antidiabetic property which is reviewed here. Studies on the efficacy of crude C.longa extracts against type 2 diabetes in murine models reveal that it demonstrates a hypoglycemic effect by lowering the blood glucose levels under in vivo conditions. Clinical studies have revealed the safety of curucmin (major principle component exhibiting pharmaceutical properties from C.longa) on humans but with very low bioavailability. In view of its effective hypoglycemic effect and its low bioavailability, further studies are needed for the characterization of the bioactive principles and formulating the development of C.longa extracts as a novel anti-diabetic therapeutic agent.