19 research outputs found
(A) study on international cooperation to control drug trafficking in the Asia-Pacific
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Όλ¬Έ (μμ¬)-- μμΈλνκ΅ λνμ : κ΅μ νκ³Ό(κ΅μ νλ ₯μ 곡), 2011.8. λ°±μ§ν.Maste
HIF-1Ξ± μμ‘΄μ μ μ μ΄ λ° μ±μ₯ μ΄μ§ μΈμλ‘μ μ§λ°©μ° μν μ κ΄ν μ°κ΅¬
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Όλ¬Έ(λ°μ¬) -- μμΈλνκ΅λνμ : μκ³Όλν μκ³Όνκ³Ό, 2021.8. μ μμ.Although obesity is a newly considered risk factor for cancer, the mechanisms by which adipocyte-derived metabolites accelerate cancer malignancy have yet to be elucidated. To identify the mechanism of fatty acids (FA) in promoting the proliferation and metastasis of cancer, I focused on the Hypoxia-inducible factor-1 alpha (HIF-1Ξ±) in various types of cancer. In hepatocellular carcinoma (HCC) cells, the treatment of FA enhances HIF-1Ξ± activity, and this triggers cell growth via fatty acid binding protein 5 (FABP5). Mechanistically, FABP5 upregulates HIF-1Ξ± activity by enhancing HIF-1Ξ± de novo synthesis while disrupting FIH/HIF-1Ξ± interaction at the same time. It is found that the FA/FABP5/HIF-1Ξ± axis shifts lipid metabolism towards lipid storage, thereby enhancing cell growth. Next, to verify further where FA comes from, I established an oxygen permeable polydimethylsiloxane (PDMS)-based three-dimensional (3D) culture system to allow direct attachment between human adipocyte derived stem cells (ADSCs) and cancer cells. Co-culture of cancer cells with ADSCs resulted in a dispersion phenomenon, and the dispersed spheroid was well matched with the enhanced metastatic potential of cancer cells. Lipid profiling suggested that lipids are the driving force for cancer metastasis via HIF-1Ξ± upregulation. The lipid/HIF-1Ξ± axis promoted tumor metastasis in a colon cancer xenograft mouse model. This study provides new mechanistic insights into the effects of ADSC-released fatty acids on cancer cells as cancer-promoting metabolites, and presents an in vitro model of a biomimetic tumor microenvironment (TME).μμ μμ΄ λΉλ§μ΄ μλ‘μ΄ μνμΈμλ‘ λλλκ³ μμ§λ§, μ§λ°©μΈν¬λ‘λΆν° μ΄λ ν μ§μ§ λμ¬μ²΄κ° λΆλΉλμ΄ μμ μ
μ±νλ₯Ό μ΄λνλκ°μ λν μμΈν κΈ°μ μ μμ§ λ°νμ§μ§ μμλ€. λ³Έ λ
Όλ¬Έμμλ μμ μ±μ₯ λ° μ μ΄ κΈ°μ μμμ μ§λ°©μ° μν μ κ·λͺ
νκΈ° μν΄, μ μ°μ μ μ μ λμΈμ (HIF-1Ξ±)μ νκ²μΌλ‘νλ μ°κ΅¬λ₯Ό μ§ννμλ€. κ°μμΈν¬μ£Όμ μ§λ°©μ° μ²λ¦¬ μ, HIF-1Ξ±κ° νμ±νλκ³ μΈν¬ μ±μ₯μ΄ μ΄μ§λμλλ°, μ΄ κ³Όμ μ μμ΄ μ§λ°©μ° κ²°ν© λ¨λ°±μ§μΈ FABP5κ° λ§€κ°νλ κ²μ νμΈνμλ€. 맀컀λμ¦μ μΌλ‘, FABP5λ HIF-1Ξ±μ μ μν©μ±μ μ΄μ§μν€λ λμμ FIH/HIF-1Ξ± κ²°ν©μ λ°©ν΄νμ¬ κΆκ·Ήμ μΌλ‘ HIF-1Ξ±μ μ μ¬νμ±μ μ¦κ°μν΄μ κ·λͺ
νμλ€. μ§λ°©μ°/FABP5/HIF-1Ξ±λ‘ μ΄μ΄μ§λ μ νΈκ²½λ‘λ κ°μμΈν¬μ μ§μ§λμ¬λ₯Ό μ§μ§μΆμ λ°©ν₯μΌλ‘ λ³νμμΌ κ°μμΈν¬μ μ±μ₯μ μ λνλ κ²μΌλ‘ νμΈλμλ€. λ€μμΌλ‘, μ§λ°©μ°μ΄ μ΄λλ‘λΆν° μ λλλμ§ κ·λͺ
νκ³ μ, λ³Έ μ°κ΅¬μμλ μ°μ ν¬κ³Όλκ° λμ polydimethylsiloxane (PDMS)λ₯Ό κΈ°λ°μΌλ‘νλ 3μ°¨μ 곡배μ μμ€ν
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νμ¬, μ§λ°© μ λ μ€κΈ°μΈν¬μ μμΈν¬λ₯Ό μ§μ 곡배μμμΌ μ’
μ λ―ΈμΈνκ²½μ ꡬμΆνλ€. μ§λ°© μ λ μ€κΈ°μΈν¬μ 곡배μ λ μμΈν¬λ 3μ°¨μ λ°°μ μ μ’
μμ κ°μ₯μ리μμ λΆμ°λλ νμμ 보μλλ°, μ΄ λΆμ° νμμ μ¦κ°λ μμΈν¬ μ΄λλ₯κ³Ό μΌμΉν¨μ λ°νλ€. μ§μ§ λΆμλ²μ ν΅ν΄ μμΈν¬μ 곡배μ λ μ§λ°©μ λ μ€κΈ°μΈν¬μμ μ§λ°©μ° λΆλΉκ° μ¦κ°λ¨μ νμΈνμκ³ , μ΄ μ§λ°©μ°λ€μ μμΈν¬ λ΄μ HIF-1Ξ± λ°ν μ¦κ°λ₯Ό μ λνμ¬ μ’
ν©μ μΌλ‘ μ μ μ΄λ₯Ό μ΄μ§μν¨λ€λ κ²μ κ·λͺ
νμλ€. μμΈν¬μμμ μ§λ°©μ°/HIF-1Ξ± μ νΈκ²½λ‘λ κ²°μ₯ μ’
μ μ΄μ λ§μ°μ€ λͺ¨λΈμ μ μ μ΄λ₯Ό μ¦κ°μν¨ κ² λν νμΈνμλ€. κ²°λ‘ μ μΌλ‘ λ³Έ μ°κ΅¬λ, μ’
μ λ―ΈμΈνκ²½ λ΄μ μ§λ°©μΈν¬ μ λ μ§λ°©μ°μ΄ μμΈν¬λ₯Ό μ
μ±ν μν€λ κΈ°μ μ μ μνκ³ μ체 μ μ¬ μ’
μ λ―ΈμΈνκ²½μ μ€νμ λͺ¨λΈλ‘μμ νμ© κ°λ₯μ±μ μμ¬νλ€.Introduction 1
Material and Methods 5
Results 24
Discussion 73
References 80
Abstract in Korean 91λ°
ν°λΉμ΄λΌλ²λ μΆν λμμ± λ§λ ¨μ μν λ―Όκ΄ μ λ¬Έκ° ν©λ ν λ‘ ν(μ΄μμ§,μμ§μ)
O μ£Ό μ : ν°λΉμ΄λΌλ²λ μΆν λμμ±
λ§λ ¨μ μν λ―Όκ΄ μ λ¬Έκ° ν©λ ν λ‘ ν
O λ΄ μ©
- λ°ν1)κΈκ° μ€,νλ₯μ λ¬Όνκ²½ νν© λ° λ³ν νΉμ±_μ΄μμ§
- λ°ν2)ν°λΉμ΄λΌλ²λ μ μννΉμ± λ° λ¬Όνκ²½μ λ―ΈμΉλ μν₯_μμ§μ
O ν λ‘ μ
- μ’μ₯ : νμ¬μ λμ λνκ΅ ν λͺ©κ³΅νκ³Ό κ΅μ
- ν λ‘ μ : μ΄μ¬μ€ μΆ©μ²λ¨λ μμ§κ΄λ¦¬κ³Ό κ³Όμ₯/μΈμΉκ²½ 보건νκ²½μ°κ΅¬ λΆμ₯/κΉμ’
μ μ€λ§μ΄λ΄μ€ κΈ°μ/μ¬κΈΈμ± μΆ©λ¨νκ²½μ΄λμ°ν© λν- λ°ν1)κΈκ° μ€,νλ₯μ λ¬Όνκ²½ νν© λ° λ³ν νΉμ±_μ΄μμ§
- λ°ν2)ν°λΉμ΄λΌλ²λ μ μννΉμ± λ° λ¬Όνκ²½μ λ―ΈμΉλ μν₯_μμ§