• Title/Summary/Keyword: Phosphatidylinositol 3-Kinase

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Immunohistochemical Study of Phosphatase and Tensin Homolog Deleted on Chromosome Ten in Gefitinib Treated Nonsmall Cell Lung Cancer Patients (폐암 조직에서의 PTEN 발현 정도와 Gefitinib의 반응율과의 관계)

  • Lee, Sung Yong;Lee, Ju Han;Jung, Jin Yong;Lee, Kyoung Ju;Lee, Seung Hyeun;Kim, Se Joong;Lee, Eun Joo;Hur, Gyu Young;Jung, Ki Hwan;Jung, Hye Cheol;Lee, Sang Yeub;Kim, Je Hyeong;Shin, Chol;Shim, Jae Jeong;In, Kwang Ho;Kang, Kyung Ho;Yoo, Se Hwa
    • Tuberculosis and Respiratory Diseases
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    • v.58 no.5
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    • pp.473-479
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    • 2005
  • Background : Gefitinib targets the epidermal growth factor receptor r(EGFR), and Gefitinib has antitumor activity in patient with non-small cell lung cancer (NSCLC). However, only 10 to 20 percent of patients show a clinical response to this drug, and the molecular mechanisms underlying patient sensitivity to gefitinib are unknown. PTEN (Phosphatase and tensin homolog deleted on chromosome Ten) plays a role for the modulation of the phosphatidylinositol 3-kinase pathway (PI3K), which is involved in cell proliferation and survival, so that it can inhibit cell cycle progression and induce G1 arrest. Therefore, we analyzed the relationship between PTEN expression and gefitinib's responsiveness in patients having advanced non small cell lung cancer that had progressed after previous chemotherapy. Methods : The expression of PTEN was studied by immunohistochemistry in paraffin-embedded tumor blocks that were obtained from 22 patients who had been treated with gefitinib from JAN, 2001 to AUG. 2004. For the evaluation of the relationships between the PTEN expression, the clinical stage and the basal characteristics, those cases that showed the respective antigen expression in >50% of the tumor cells were considered positive. Results : The positive rate of PTEN staining was 55% of the total of 22 patients. There was a significant relationship between the increased expression of PTEN and the response group (p=0.039). However, there was no significant relationship between the expression of PTEN and other clinicopathologic characteristics. Conclusion: The expression of PTEN in patients with advanced non small cell lung cancer that has progressed after previous chemotherapy may play a role in gefitinib's responsiveness.

Analysis of Potential Active Ingredients and Treatment Mechanism of Ponciri Fructus Immaturus for Dermatitis Accompanied by Pruritus Using Network Pharmacology (네트워크 약리학을 이용한 소양증을 동반한 피부 염증에 대한 지실(枳實)의 잠재적 치료기전 탐색)

  • Seo, GwangYeel;Kim, Jundong;Kim, Byunghyun;Kim, Kyu-Seok;Nam, Hae-jeong;Kim, Yoon-Bum
    • The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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    • v.35 no.4
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    • pp.75-94
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    • 2022
  • Objectives : To identify the active ingredient of Poncirus Trifoliata Immaturus and to explore the mechanism expected to potentially act on dermatitis accompanied by pruritus. Methods : We conducted the network pharmacological analysis. We selected effective ingredients among the active compounds of Poinciri Fructus Immaturus. We found the target protein of the selected active ingredient, disease(dermatitis accompanied by pruritus) and fexofenadine. Then we established the network between the proteins which Poinciri Fructus Immaturus and fexofenadine intersected with disease respectively, and the coregene was also extracted. After that, the active pathways in the human body involving the groups and coregenes were searched. Results : Total of 7 active ingredients were selected, and 202 target proteins were collected. There were 756 proteins related to inflammatory skin disease accompanied by pruritus, and 75 proteins were related to fexofenadine. 42 proteins crossed by Poinciri Fructus Immaturus with a disease, and 31 proteins crossed by fexofenadine with a disease. 12 proteins were found as a coregene from the proteins that cross Poinciri Fructus Immaturus and disease. Coregenes are involved in 'Nitric-oxide synthase regulator activity', 'Epidermal growth factor receptor signaling pathway'. 2 groups that extracted are invloved in 'Fc receptor signaling pathway', 'Central carbon metabolism in cancer', 'Phosphatidylinositol 3-kinase complex, class IB', and 'omega-hydroxylase P450 pathway'. Conclusion : It is expected that Poinciri Fructus Immaturus will be able to show direct or indirect anti-pruritus and anti-inflammatory effects on skin inflammation accompanied by pruritus in the future. And it is also expected to have a synergy effect with fexofenadine on skin disease.

Tenebrio molitor (Mealworm) Extract Improves Insulin Sensitivity and Alleviates Hyperglycemia in C57BL/Ksj-db/db Mice (C57BL/Ksj-db/db 제 2형 당뇨모델을 이용한 갈색거저리 유충(밀웜) 추출물의 인슐린 감수성 및 혈당개선효과)

  • Kim, Seon Young;Park, Jae Eun;Han, Ji Sook
    • Journal of Life Science
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    • v.29 no.5
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    • pp.570-579
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    • 2019
  • Diabetes is one of the serious chronic metabolic diseases caused by Westernized eating habits, and the goal of diabetes treatment is to keep blood glucose at a normal level and prevent diabetic complications. This study was designed to investigate the anti-diabetic effects of a mealworm (Tenebrio molitor larva) extract (MWE) on hyperglycemia in an animal model with type 2 diabetes. Diabetic C57BL/Ksj-db/db mice were divided into three groups: diabetic control, rosiglitazone, and MWE. The mice supplemented with MWE showed significantly lower blood levels of glucose and glycosylated hemoglobin when compared with the diabetic control mice. The homeostatic index of insulin resistance was significantly lower in mice supplemented with MWE than in diabetic control mice. MWE supplementation significantly stimulated the phosphorylation of insulin receptor substrate-1 and Akt, and activation of phosphatidylinositol 3-kinase in insulin signaling pathway of skeletal muscles. Eventually, MWE increased the expression of the plasma membrane glucose transporter 4 (GLUT4) via PI3K/Akt activation. These findings demonstrate that the increase in plasma membrane GLUT4 expression by MWE promoted the uptake of blood glucose into cells and relieved hyperglycemia in skeletal muscles of diabetic C57BL/Ksj-db/db mice. Therefore, mealworms are expected to prove useful for the prevention and treatment of diabetes, and further studies are needed to improve type 2 diabetes in the future.