研究內容簡介

基底細胞癌(basal cell carcinoma)

基底細胞癌是最常見的皮膚癌，大約佔所有皮膚惡性腫瘤的80%以上，好發於頭臉、頸和手部。這種癌症生長緩慢而通常不會轉移到其他部位，但是若沒有處置，會局部破壞及侵犯組織，例如骨頭及神經。在基因層次方面的研究，基底細胞癌其主要成因為sonic hedgehog (shh)訊息傳遞路徑過度活化所導致的癌症。在動物模式的實驗中，以小鼠的研究為例，Oro等人(1997)將被keratin啟動子所驅動的shh基因利用基因轉殖的技術，讓shh基因專一性地在表皮組織過度表現，結果這些基因轉殖小鼠，呈現出多趾(polydactyly)、脊柱裂開(spina bifida)與一些典型的基底細胞癌的症狀，成功地重建基底細胞癌的動物模式。而這種品系的小鼠，在出生前即死亡，並不適合用來當成篩選抗癌藥物的工具。因此，我們建立了基底細胞癌的基因轉殖斑馬魚品系，以便用來開發抗腫瘤新藥。

斑馬魚當成藥物篩選平台之優點

斑馬魚(zebrafish, Danio rerio)是一種小型觀賞魚，成魚體長約3公分，好養又便宜，體積小，一般的家用一尺水族箱大約可養20隻左右，可大大地降低養殖成本。這類小型魚種擁有卵的數量多(每週可產100-300顆卵)，卵徑大而且透明，沒有產卵期的限制，體外授精，整個胚胎發育及器官形成的過程都可以直接在顯微鏡下觀察，基因轉殖操作簡單、成熟期又只有2-3個月等優點。因此，斑馬魚已成為研究癌症、心血管疾病、器官發育、脊椎動物胚胎發育、神經發育、細胞凋亡的重要模式，在藥物毒性的篩檢也扮演重要角色。斑馬魚在抗癌藥物的篩選上最大的好處是生長週期短，可以很快速、很有效率的評估療效，並且飼養成本只有小白鼠的百分之一至千分之一，非常適合藥物的篩選。

專利

卵黃油脫色脫味之製備方法(中華民國專利，發明第I741469號，已領證，美國專利領證中)

近五年著作目錄

(1) Zhang HW, Tsai ZR, Kok VC*, Peng HC, Chen YH, Tsai JJP, Hsu, CY (2022) Long-term ambient hydrocarbon exposure and incidence of urinary bladder cancer. Scientific Reports 12: 20799.

(2) Pan HC^#, Chen YH^#, Fang WC, Wu VC, Sun CY* (2022) Essential roles of the histone demethylase KDM4C in renal development and acute kidney injury. International Journal of Molecular Sciences 23: 9318.

(3) Lu PH, Liao TH, Chen YH, Hsu YL, Kuo CY, Chan CC, Wang LK, Chern CY*, Tsai FM* (2022) Coumarin derivatives inhibit ADP-induced platelet activation and aggregation. Molecules27: 4054.

(4) Liu CF, Ou Yang Y, Huang CY, Jao SW, Kuo YK, Chen HC, Cheng SC, Wang NK, Chuang LH, Chen YH*, Chen WY* (2022) Zebrafish (Danio rerio) is an economical and efficient animal model for screening potential anti-cataract compounds. Translational Vision Science & Technology 11: 21.

(5) Kuo YK, Chen YT, Chen HM, Wu PC, Sun CC, Yeung L, Lin KK, Chen HC, Chuang LH, Lai CC, Chen YH, Liu CF* (2022) Efficacy of myopia control and distribution of corneal epithelial thickness in children treated with orthokeratology assessed using optical coherence tomography. Journal of Personalized Medicine 12: 278.

(6) Tang PWH, Wu PH, Lin YT, Chiu CH, Cheng TL, Guan WH, Lin HYH, Lee KT, Chen YH, Liu W* (2022) Zebrafish model-based assessment of Indoxyl sulfate-induced oxidative stress and its impact on renal and cardiac development. Antioxidants 11: 400.

(7) Sun CY, Chang SC, Wang HP, Lee YJ, Pan KH, Lin CL, Hsieh YT, Ta YC, Chen YH, Chang MF* (2021) LMBD1 protein participates in cell mitosis by regulating microtubule assembly. Biochemical Journal 478: 2321-2337.

(8) Tsai JN, Ding YJ, Lo KC, Lu PH, Chang CF, Wen CC, Wang BC*,Yang LL*, Chen YH* (2021) Protective role of Bu-Zhong-Yi-Qi decoction on aristolochic acid-intoxicated zebrafish. Tropical Journal of Pharmaceutical Research 20: 605-611.

(9) Hsieh KH, Hsu CY, Hung IJ, Yeh CL, Chen YH, Cheng CC*(2021) Positively charged liposomes consisting of the KTTKS pentapeptide conjugated with rhodamine increase rhodamine toxicity in E. coli and zebrafish embryo. Journal of the Chinese Chemical Society 68: 34-38.

(10) Lu PL, Lee HY, Liou YL, Tung SF, Kuo KL, Chen YH* (2020) Nephroprotective role of Zhibai Dihuang Wan in aristolochic acid intoxicated zebrafish. BioMed Research International Article ID 5204384.

(11) Wang YH*, Chen YH, Shen WH (2020) Amikacin suppresses human breast cancer cell MDA-MB-231 migration and invasion. Toxics 8: 108.

(12) Sun CY, Chou CY, Hsieh YT, Lo KC, Liou YL, Chen YH* (2020) Klotho exerts an emerging role in cytokinesis. Genes 11: 1048.

(13) Chen YH*, Chen YJ, Chou CY, Wen CC, Cheng CC* (2019) UV-protective activities of pineapple leaf extract in zebrafish embryos. Research on Chemical Intermediates 45: 65-75.

(14) Chen YH, Tai HY, Fu E, Don TM* (2019) Guided bone regeneration activity of different calcium phosphate/chitosan hybrid membrane. International Journal of Biological Macromolecules 126: 159-169.

(15) Hsieh CS, Tsai CT, Chen YH, Chang SN, Hwang JJ, Chuang EY*, Wu IH* (2018) Global expression profiling identifies a novel hyaluronan synthases 2 gene in the pathogenesis of lower extremity varicose veins. Journal of Clinical Medicine 7: 537.

(16) Tsai JN, Sun CY, Ding YJ, Wang YH, Lo KC, Weng CC, Lin JW, Chang CF, Hsu LS, Chen HM, Fong TH*, Chen YH* (2018) Embryonic exposure to 4-methylimidazole leads to zebrafish myofibril misalignment. Environmental Toxicology 33: 1321-1328.

(17) Sun CY*, Wu MS, Lee CC, Chen SH, Lo KC, Chen YH* (2018) A novel SNP in the 5’ regulatory region of organic anion transporter 1 is associated with chronic kidney disease. Scientific Reports 8: 8085.

(18) Chu HF, Chen CC, Moses DC, Chen YH, Lin CH, Tsai YC, Chou CY (2018) Porcine epidemic diarrhea virus papain-like protease 2 can be noncompetitively inhibited by 6-thioguanine. Antiviral Research 158: 199-205.

(19) Lin MH, Moses DC, Cheng SC, Chen YH, SunCY*, Chou CY* (2018) Disulfiram can inhibit MERS and SARS coronavirus papain-like proteases via different modes.Antiviral Research 150: 155-163.

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