將聚乙烯亞胺(Polyethylenimine, PEI)修飾到硫酸化軟骨素(Chondroitin sulfate, CS)，形成一個PEI 接枝CS 之共聚物(簡稱CS-PEI)。PEI是目前市售的一個黃金商品，具高轉染效能的非病毒式基因載體，但是PEI 所擁有的高正電荷密度也對細胞造成很高的毒性。本研究利用低分子量的PEI 接枝到天然的多醣體CS之側鏈上，一來解決臨床未來使用高分子量的PEI對細胞造成的毒性問題；二來以螞蟻雄兵之優勢，利用接掛多條低分子量PEI，使其仍然保留對基因的高轉染率。由於CD44常被發現於腫瘤細胞上，而CS可以辨識細胞膜表面的CD44受體，利用CS-PEI做為基因藥物載體，將增加CS-PEI攜帶之任何基因藥物對細胞表面過度表現CD44的腫瘤或腫瘤幹細胞的靶向性，經由CD44介導的胞飲作用，有效地進入細胞內，提高基因藥物在癌細胞的轉染效能。本研究即以這個低毒性、高轉染的CS-PEI來做為調控自噬作用的Beclin siRNA基因遞送載體；並以紫杉醇(Paclitaxel, PTX)抗藥性的腫瘤細胞株做為細胞模型(如肺癌NCI-H23-TXR)，期待藉由抑制細胞的自噬作用，來恢復PTX對腫瘤組織的抑制生長效果。結果發現Beclin siRNA不但抑制Beclin蛋白表現，同時也抑制數個多重抗藥性蛋白的表現，進而促使PTX有效地抑制腫瘤組織的增生。本研究同時也建立一套利用斑馬魚植入腫瘤，快速篩選藥物抑制腫瘤生長的測試平台，未來此平台可延伸至其他腫瘤植入的動物模型。除此，本研究使用的基因載體材料CS-PEI已經獲准台灣專利(I434934)及美國專利(US 8,445,025 B2; US 8,716,399 B2; US 9,050,362 B2)，顯見此材料開發具有相當優越的市場開拓新契機。
本校主要研究者之簡介:
本校醫藥暨應用化學系王麗芳教授領導的團隊，集結醫藥化學、生物醫學、奈米醫學、生醫工程、臨床醫學等跨領域專業人才，從化學合成、基因載體的設計、MDR細胞株的建立、自噬作用基因表現、班馬魚腫瘤植入之建立等等，是一個成功的跨系、院、校的成功例子。研究經費由科技部與高雄醫學大學共同支持。
研究聯繫Email: lfwang@kmu.edu.tw ; cchiu@kmu.edu.tw
期刊出處: Molecular Therapy: Nucleic Acids, 2019, 17(9), 477-490.
期刊線上參閱網址:
https://www.cell.com/action/showPdf?pii=S2162-2531(19)30180-5
Polyethyleneimine (PEI) is one of leading cationic polymer for gene delivery because of its high transfection efficiency. However, PEI induced high cytotoxicity due to the positively charged surface characteristics. Herein, we grafted PEI onto chondroitin sulfate (CS) to yield CS-PEI which not only showed transgene efficiency, but reduced PEI cytotoxicity. CD44 is overexpressed in many solid tumor cells. It has been found that CS has the potential to be internalized into cells via CD44-mediated endocytosis. Thus, using CS-PEI as a gene drug delivery system, actively targeting to CD44-overexpressing cancer cells is an ideal approach to enhance transgene efficiency. Multidrug resistance (MDR) is the major obstacle in limitation of therapeutic efficacy of Paclitaxel (PTX). PTX-resistant non-small-cell lung cancer cell line (NCI-H23-TXR) was established and CS-PEI/Beclin-small interfering RNA (siRNA) was constructed to restore sensitivity of PTX against NCI-H23-TXR. Results revealed that knockdown of Beclin simultaneously inhibited MDR-related proteins, and renewed the sensitivity of PTX against NCI-H23-TXR. In vivo study showed that pre-transfection with CS-PEI/Beclin-siRNA followed by PTX treatment decreased the tumor size in NCI-H23-TXR zebrafish xenografts. (Taiwan Patent No. I434934; United States Patent US 8,445,025 B2; US 8,716,399 B2; US 9,050,362 B2)
Main researcher Intro.
Dr. Li-Fang Wang, a professor of Department of Medicinal and Applied Chemistry at Kaohsiung Medical University.
Author Email: lfwang@kmu.edu.tw ; cchiu@kmu.edu.tw
Paper cited from: Molecular Therapy: Nucleic Acids, 2019, 17(9), 477-490.
Paper online website:
https://www.cell.com/action/showPdf?pii=S2162-2531(19)30180-5
量身訂做的教育介入提升兒童癌症存活者之健康行為自我效能
治療和照護的進步雖然提高癌症兒童的存活率，但兒癌存活者仍須面臨癌症和治療相關不利健康的結果。約60%的兒癌存活者至少罹患ㄧ種長期合併症，其中80%存活者的合併症需要接受治療。因此提高兒癌存活者徵狀管理之自我效能和健康促進行為，將有助於提高其自我效能，進而採取健康的生活方式。因此，規劃兒癌存活者的健康促進策略就顯得特別重要。
本研究為隨機重複測量試驗，利用自我效能理論，首創兒童癌症存活者衛教課程，內容包含：建立自我意識(了解疾病和治療的潛在副作用)、預防健康(飲食和運動)和促進健康(自我照顧和重返學校)。全程共設計6次活動，於一周結束，每次進行約45-60分鐘，並於衛教介入後一個月，4個月電訪追蹤，以提升兒癌存活者健康行為自我效能。
結果顯示實驗組在健康行為自我效能和健康促進生活得分隨著時間而顯著增加(all p < 0.05)，且教育介入後4個月的健康行為自我效能得分顯著高於對照組(F= 5.32, p= 0.02, η2= 0.25)，控制組在健康行為自我效能並未隨著時間顯著性改變。研究對象給與介入措施很高的評價(M=9.29)。本研究亦發現運動是癌症兒童存活者最大的障礙，設計簡單可行的運動，並能在住院期間執行，以及增加運動意願和持續的動機，都是未來努力的方向。未來研究可持續評值教育介入的長期效果，以及可能的聯動效益。
透過隨機對照且持續追蹤4個月的實驗性研究設計，研究結果發現量身訂做的教育介入，可以提升兒癌存活者的健康行為自我效能進而促進健康生活型態
本校研究者之簡介:
1. 吳麗敏 高雄醫學大學護理學系教授兼系主任
2. 許心恬 高雄醫學大學護理學系副教授
3. 劉 怡 高雄醫學大學護理學系副教授
4. 蘇秀蘭 高雄醫學大學附設中和紀念醫院專科護理師
研究聯繫Email:painting@kmu.edu.tw
期刊出處:
Li-Min Wu, Chin-Mi Chen, Hsin-Tien Hsu, Fan-Ray Kuo & Hsiu-Lan Su. (2019).
Tailored education enhances healthy behavior self-efficacy in childhood cancer survivors: A ramdomised controlled study with a 4-month follow up.
研究全文下載:
Tailored education enhances healthy behaviour self‐efficacy in childhood cancer survivors: A randomised controlled study with a 4‐month follow‐up
This study was to evaluate the acceptability and effectiveness of a tailored education on healthy behaviors self‐efficacy (HBSE) and health promotion lifestyle (HPL) for childhood cancer survivors. A two‐group, randomized study with repeated measures was conducted in Taiwan. Participants were randomly assigned to receive six 45–60 min individual education and follow‐up telephone counselling sessions (n = 34) or standard of care only (n = 35). Each participant was assessed with HBSE and HPL questionnaires and was evaluated at three time points (at baseline, and then 1 and 4 months after intervention). The attrition rate was 7.2%. HBSE and HPL scores increased across the three time points in the experimental group (all p < 0.05), except for the HBSE exercise subscale (p= 0.85). HBSE scores were significantly higher for the experimental group than for the control group after 4 months of intervention (F = 5.32, p = 0.02, η2 = 0.25). No significant improvements in HBSE were observed over time in the control group. The intervention was acceptable and effective in promoting HBSE in childhood cancer survivors. Further empirical work is needed to reveal the effects of the intervention over a longer period of time and to improve patient engagement in exercise.
A tailored education can improve childhood cancer survivors’ health behavior self-efficacy by conducting the randomized controlled study with a 4‐month follow‐up
Main researcher Intro.
https://pubmed.ncbi.nlm.nih.gov/31020742/
Researcher
1. Li‐Min Wu RN, PhD, Professor, chair, School of Nursing, Kaohsiung Medical
University, and Department of Medical Research, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.
2. Chin‐Mi Chen RN, PhD, Associate Professor, Department of Nursing, Fu Jen Catholic
University, New Taipei City, Taiwan.
3. Hsin‐Tien Hsu RN, PhD, Associate Professor, School of Nursing, Kaohsiung Medical
University, and Department of Medical Research, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.
4. Yi Liu RN, PhD, Associate Professor, School of Nursing, Kaohsiung Medical
University, Kaohsiung, Taiwan.
5. Hsiu‐Lan Su RN, MSN, Nurse Practitioner, School of Nursing, Kaohsiung Medical
University, and Department of Medical Research, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.
Author Email: painting@kmu.edu.tw
Paper cited from:
Li-Min Wu, Chin-Mi Chen, Hsin-Tien Hsu, Fan-Ray Kuo & Hsiu-Lan Su (2019). Tailored education enhances healthy behavior self-efficacy in childhood cancer survivors: A ramdomised controlled study with a 4-month follow up.
Research Paper available online on website
三陰性乳癌新進展-奈米級白蛋白載體新藥
有「乳癌殺手」之稱之三陰性乳癌好發於40歲前，且其來自於名為BRCA-1基因所發生之變異疾病，也是讓女星安潔莉娜裘莉發現自己具有BRCA基因變異後，選擇切除乳房作為預防癌症發生之主因，近年來透過癌細胞基因解密讓乳癌分類更加明朗化，乳癌基因表現大致分為三類:雌激素受體(ER)、黃體素受體(PR)、人類上皮生長受體第二對(HER-2)，如癌細胞三種基因表現皆為陰性則歸類為「三陰性乳癌」，目前是臨床上治癒率最低、復發率最高之乳癌類型，導致選用標靶藥物存在諸多限制，病患仍使用化學治療為主。
近日，高雄醫學大學方逸萍副教授及其研究生林欣哲之論文刊登於國際知名藥劑領域期刊，研究中指出「抗癌藥SN-38 白蛋白奈米載體」是針對三陰性乳癌新劑型藥物，SN-38為有強大抗癌活性之喜樹鹼衍生物，但因難溶於水且副作用大等特性限制了其於臨床上之應用；為此，方老師研究團隊藉由研發白蛋白奈米載體結合SN-38之技術克服其於臨床使用限制。白蛋白為人體內生性蛋白所構成，是血漿中最豐富蛋白質、能維持血漿滲透壓、運送血液營養物等，除了是人體中不可或缺之蛋白質外，也容易被代謝且不易致敏，利用白蛋白結構中之親水性及親脂性特質，可有效將SN-38包裹在奈米粒子之間。方老師研究團隊所合成之「抗癌藥SN-38 白蛋白奈米載體」經細胞實驗證實：可有效抑制三陰性乳癌細胞株生長，且白蛋白奈米粒子可增加SN-38進入癌細胞之有效劑量，且SN-38從奈米粒子釋出後更可標靶精準毒殺癌細胞。
乳癌有逐漸年輕化之趨勢，多數年輕患者在發現乳癌當下，家庭與事業皆處於黃金時期，一旦確診三陰性乳癌除了生理上不適，心裡也會帶來諸多壓力，期待新劑型開發能順利進行，未來上市後作為治療三陰性乳癌之新選擇。 
本篇為高雄醫學大學2019年月傑出論文11月份得獎文章，代表作者為藥學系方逸萍副教授。
本校主要研究者之簡介
研究聯繫Email:
ypfang@kmu.edu.tw
期刊出處:
Pharmaceutics 2019, 11, 569
期刊線上參閱網址:
The Progress in Triple Negative Breast Cancer Research Continues: the albumin nano drug carrier
Triple negative breast cancer (TNBC), related to BRCA1 mutation, is an aggressive breast cancer common in female younger than age 40. Potentially being in the TNBC population, the actress Angelina Jolie made the difficult decision to undergo a preventative mastectomy due to the alarming nature of TNBC. Lacking estrogen receptor (ER), progesterone receptor (PR) and HER2 receptor, TNBC has limited options on targeted medications, which results in low survival rate and high recurrence among the breast cancer subtypes.
Recently, Professor Yi-Ping Fang with graduate student Hsin-Che Lin in Kaohsiung Medical University published a research on “anticancer agent SN-38 entrapped albumin nanoparticles to TNBC.” SN-38 is a camptothecin derivative with very potent anticancer effect. The clinical application of SN-38, however, is limited by its low solubility and serious adverse effects. For this reason, Professor Fang’s team proposed a solution to combine SN-38 with albumin carrier, considering albumin is not only one of the most abundant protein in human and maintains osmotic pressure, delivers substances in blood circulation, but also can be easily metabolized and further eliminated. By utilizing the natural amphiphilic property of albumin, Professor Fang’s team developed a procedure to formulate SN-38 in albumin nanoparticles which further showed promising targeting effect by accumulation these albumin nanoparticles in TNBC cell line to suppress TNBC cell line growth.
Upon the trend of younger breast cancer diagnosed such as TNBC in this case, majority of breast cancer patients are at their pinnacle of life and career, and this disease only brings serious distress physically and mentally. Through this research, the contribution to the solution to the unmet TNBC clinical need may be expected, with the ultimate goal in mind, to improve TNBC patients’ quality of life.
This article-“High Potency of SN-38-Loaded Bovine Serum Albumin Nanoparticles Against Triple- Negative Breast Cancer” , written by Rept. Author Associate Professor Yi-Ping Fang from School of Pharmacy, is award for Kaohsiung Medical University 2019 Monthly Excellent Paper Award in Nov.
Main researcher Intro.
Author Email: ypfang@kmu.edu.tw
Paper cited from: Pharmaceutics 2019, 11, 569
Paper online website: https://pubmed.ncbi.nlm.nih.gov/31683822/
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