Publisher: University of Macau Chief Editor: Katrina Cheong Deputy Chief Editor: Ella Cheong Editors: Davis Ip, Debby Seng Translators: Ruby Chen, Anthony Sou Advisors Timothy Simpson, Associate Professor, Department of Communication, Faculty of Social Sciences Tang Keng Pan, Professor Emeritus, Department of Chinese Language and Literature, Faculty of Arts and Humanities Lampo Leong, Distinguished Professor and Director, Centre for Arts and Design, Faculty of Social Sciences Design: Li Lin, Lampo Leong Address: Room G012, Administration Building, University of Macau, N6, Avenida da Universidade, Taipa, Macau, China Contact: Tel: (853) 8822 8833 Fax: (853) 8822 8822 Email: prs.publication@um.edu.mo Printing: Hamah (Macau), Limitada ISSN: 2077‑2491 Published biannually since 2009, UMagazine aims to report great ideas and research breakthroughs from the University of Macau. It also showcases the latest developments and achievements of the university in teaching, research, and service. 出版: 澳門大學 總編輯: 張惠琴 副總編輯: 張愛華 編輯: 葉浩男、盛惠怡 翻譯: 陳靜、蘇恩霆 顧問 社會科學學院傳播系副教授Timothy Simpson 人文學院中國語言文學系榮休教授鄧景濱 社會科學學院藝術設計中心主任／特聘教授梁藍波 美術設計: 林力、梁藍波 地址 中國澳門氹仔大學大馬路澳門大學N6行政樓G012室 聯絡 電話: (853) 8822 8833 傳真: (853) 8822 8822 電郵: prs.publication@um.edu.mo 製版印刷: 澳門豪邁實業有限公司 國際刊號: 2077‑2491 《澳大新語》創於2009年，為澳門大學官方 刊物，每年出版兩期，旨在展示澳門大學的創見和 突破、報導教研和社會服務的最新 發展和成果。 2020年 | 總第22期 Spring/Summer 2020 | Issue 22 《澳大新語》UMagazine
Image provided by Prof Liu Tzu-Ming
Image provided by Prof Deng Chuxia
澳門大學近年在學術研究上騰飛精進， 更形成了包括科技創新和人文社科領域的 「3+3+3+3」研究戰略佈局。在眾多卓越 研究領域中，2013年才從零起步的腫瘤精 準醫療至今已匯聚一群頂尖的專家學者。 他們結合跨學科創新技術，進行深入的癌 症基礎研究，更取得了多項矚目的創新成 果，備受學術界關注和認同。 今期的封面專題聚焦在癌症研究，我們訪 問了17位來自健康科學學院、中華醫藥研 究院、微電子研究院的專家，剖析他們各 自範疇的研究項目如何通過創新技術提升 癌症精準診療的成效。 在人文社科方面，新成立的人文社科高等 研究院致力打造跨越學院疆界的校級研究 平台，並計劃引進高端人文社科人才開展 專題研究。我們訪問了兼任該研究院代院 長的蘇基朗副校長，介紹研究院的發展和 戰略佈局。 新型冠狀病毒肺炎肆虐全球，心理學系副教 授賀佰恩與澳大專家組成一支九人的心理輔 導專業團隊，為隔離人士及工作人員提供心 理輔導。長期關注心理健康問題的賀教授， 在專訪裡娓娓道出他的教研故事。「寶劍鋒 從磨礪出，梅花香自苦寒來。」應用物理及 材料工程研究院的孫國星教授是首位提出用 水泥製造最便宜的納米顆粒、研發出破世界 紀錄先進材料的專家，他以其刻苦求學的勵 志經歷，道出了堅持是研究成功的關鍵。 在「學術研究」專欄中，微電子研究院助理 教授李家明、法學院高級導師翁文挺分別撰 文分享最新研究成果。 In recent years, the academic research of the University of Macau (UM) has progressed in leaps and bounds, with a ‘3+3+3+3’ strategic research structure gradually taking shape. A particularly noteworthy research field at UM is precision medicine for cancer research. The university initiated research in precision medicine in 2013, and today it has developed a team of leading experts in the field. Working together and adopting a multidisciplinary approach, these experts have achieved many impressive results that are widely recognised in academia. This issue’s cover story focuses on cancer research. We interview 17 experts in the Faculty of Health Sciences, Institute of Chinese Medical Sciences, and Institute of Microelectronics. They discuss how their ongoing research projects hold the promise for improving cancer treatment by using the latest technologies in precision medicine. On the front of humanities and social sciences, the newly established Institute of Advanced Studies in Humanities and Social Sciences is committed to creating a university-level research platform that breaks down the boundaries of different disciplines. In this issue, we talk to Vice Rector Billy So, who is also the interim director of the institute, about how the institute plans to recruit high-calibre talent to carry out special research projects, as well as the strategic plan for the institute’s future development. With the novel coronavirus raging across the globe earlier this year, many people, especially frontline workers and those in quarantine, found themselves grappling with a silent problem— mental health issues. Prof Brian Hall in the Department of Psychology rose to the challenge and, along with eight other UM experts, he formed a psychological counselling team to provide counselling to people in need. In this issue, Prof Hall shares his research findings on mental health, a subject of his perennial interest. Prof Sun Guoxing in the Institute of Applied Physics and Materials Engineering was the first in the world to propose using cement to make the world’s cheapest, mass-producible nanoparticles. Interestingly, as a brilliant researcher who has developed a world-record-breaking material, Sun was quite unimpressive in his college years and monopolised the bottom spot in his class. If you want a real-life example that proves persistence is the key to success, you need to look no further than Prof Sun’s story. Other articles not to be missed in this issue include those featured in the ‘Academic Research’ column, which discuss the latest research findings by Lei Ka Meng, an assistant professor in the Institute of Microelectronics, and Iong Man Teng, a senior instructor in the Faculty of Law. 編者的話 EDITOR’S WORDS 張惠琴 Katrina Cheong
CONTENTS 目錄 2020年 | 總第22期 Spring/Summer 2020 | Issue 22 封面專題 COVER STORY 06 澳大腫瘤精準醫療取得突破性進展 UM Achieves Breakthroughs in Tumour Precision Medicine 10 抑制乳腺癌轉移和復發的新機制 A New Mechanism for Inhibiting Breast Cancer Metastasis and Recurrence 14 用細胞自噬抑制劑治療乳腺癌 Treating Breast Cancer with Autophagy Inhibitors 16 通過大規模人群基因突變檢測預防癌症 Preventing Cancer Through Large-scale Populational Genetic Testing 18 以青蒿素及其衍生物治療眼科腫瘤 Artemisinin and Its Derivatives in the Treatment of Eye Cancer 20 治療前列腺癌的新機制 A New Mechanism for Prostate Cancer Treatment 22 以激素替代療法與化療法相結合治療卵巢癌 Combining Hormone Replacement Therapy with Chemotherapy for Ovarian Cancer Treatment 24 遺傳學理論在結腸直腸癌治療中的應用 Applying Genetic Theory in Colorectal Cancer Treatment 26 新型抗體降低肺癌抗藥性 A New Antibody for Reducing Drug Resistance in Lung Cancer 28 新型多功能藥物助力腫瘤光動力療法 A Novel Multifunctional Drug for Tumour Photodynamic Therapy 30 以多光子活體顯微術探究黑色素瘤血管新生動態 Investigating the Dynamics of Melanoma Angiogenesis with Multiphoton in vivo Microscopy
32 納米技術抑制卵巢癌轉移 Nanotechnology for Regulating Ovarian Cancer Metastasis 34 納米粒子運載藥物高溫摧毀癌細胞 Nanoparticles Carry Drugs and Turn the Heat on Cancer Cells 36 結合中藥天然化合物提升癌症免疫治療效果 Chinese Herbal Products Could Help Immune System Fights Tumours 38 中藥誘導癌細胞程序性壞死 Inducing Necroptosis of Cancer Cells with Chinese Medicine 40 數位微流控技術助篩選腫瘤藥物 Digital Microfluidics for Cancer Drug Screening 專題探討 TOPIC INSIGHT 42 高研院打造人文社科研究平台 IAS Creates a Research Platform for Humanities and Social Sciences 人物專訪 EXCLUSIVE INTERVIEW 46 賀佰恩：關注疫情下全球心理健康問題 Brian Hall Addresses Global Mental Health Challenges amid the Pandemic 50 首位提出用水泥製造納米材料——孫國星 Sun Guoxing: The First to Propose the Use of Cement for Nanomaterials 學術研究 ACADEMIC RESEARCH 56 跨越電子學與核磁共振的矽芯片 Silicon Chips Bridging Electronics and NMR 62 在澳門違反知情同意的刑事責任 Criminal Liability for Violation of Informed Consent in Macao
COVER STORY•封面專題 2020 UMAGAZINE 22•澳大新語 6 The University of Macau (UM) is making rapid progress in scientific research. A few years ago, UM began to vigorously promote interdisciplinary research through a strategy that can be summarised as ‘highlighting characteristics’, ‘capitalising on advantages’, ‘building peaks’, and ‘strengthening cooperation’. The result is a ‘3+3+3+3’ strategic research structure. In the Essential Sciences Indicators (ESI), UM is now ranked among the top 1 per cent in eight subjects, namely Engineering, Chemistry, Computer Science, Pharmacology & Toxicology, Materials Science, Clinical Medicine, Psychiatry/Psychology, and Social Sciences, General. Among the many research fields where UM excels, precision medicine for cancer treatment is an important one. In the cover story of this issue, we interview 17 experts to learn about their breakthroughs in cancer research. 澳門大學在科研發展上突飛猛進，近年更透過突出特色、發揮優勢、構建高峰和 加強合作的策略，大力推動跨學科研究，形成了含括科技創新和人文社科領域的 「3+3+3+3」研究戰略佈局。目前有八大學科領域：工程學、化學、計算機科學、藥 理學與毒理學、材料科學、臨床醫學、精神病學/心理學、社會科學總論進入基本科 學指標資料庫（ESI）前1%之列。在眾多突出的研究領域中，腫瘤精準醫療是其中一 個重要板塊。本期封面專題專訪了17位專家，分享他們在癌症研究上的突破性進展。 澳大腫瘤精準醫療取得突破性進展 UM Achieves Breakthroughs in Tumour Precision Medicine 文/張愛華‧圖/編輯部 English Translation / Ruby Chen ‧ Photo / Editorial Board
封面專題•COVER STORY 澳大新語•2020 UMAGAZINE 22 7 Interdisciplinary Approach to Cancer Research Cancer is one of the leading causes of death worldwide. In a quest to develop cures for cancer, UM founded the Faculty of Health Sciences (FHS) in 2013. FHS focuses on cancer research and the development of health products, in order to support the local community. FHS cooperates with other UM faculties and institutes, including the Faculty of Science and Technology (FST), the Institute of Chinese Medical Sciences (ICMS), the Institute of Applied Physics and Materials Engineering (IAPME), and the Institute of Microelectronics (IME), in order to carry out interdisciplinary research on cancers commonly found in Macao. Scholars use state‑of‑the‑art technologies, such as microfluidic technology and nanotechnology, to enhance the effectiveness of cancer diagnosis and treatment. To improve the quality of cancer research, UM focuses on tackling key issues in two areas: biomedical mechanisms and biomedical materials. FHS has identified eight research areas, one of them being precision cancer medicine. FHS Dean Prof Deng Chuxia, who is also the director of the Cancer Centre, leads his team to establish a frozen tissue bank and a live cell bank for the most common cancers found in Macao. FHS researchers also study tumour growth, metastasis, recurrence, and drug resistance mechanisms, in order to develop early cancer diagnosis methods, identify cancer driver genes, and screen for high‑efficiency drugs that can kill cancer cells. They also conduct research on carcinogenic mechanisms and preventive treatment for mutant genes of breast cancer, nasopharyngeal cancer, colorectal cancer, liver cancer, and lung cancer. For its part, ICMS carries out innovative research on how traditional Chinese medicine induces necroptosis of cancer cells, and how the natural compounds of traditional Chinese medicine help the immune system fight tumours. In terms of biomedical materials, IME has developed a new digital microfluidic system to assist medical personnel to cultivate single cells and select cancer drugs. IAPME has established a world-class nano-bio-optics research platform, through which it promotes collaboration with the university’s oncology research team, and accelerates the progress of research projects on carbon-point cancer diagnosis and treatment. 跨學科攻關癌症研究 癌症是全球人口死亡主因之一。為攻克 癌症這頑疾，澳大在2013年成立健康科 學學院，重點開展癌症研究和醫療保健 產業研發，以填補澳門在這些領域的空 白。澳大在腫瘤精準醫療領域由零開始 研究工作，結合健康科學學院、科技學 院、中華醫藥研究院、應用物理及材料 工程研究院以及微電子研究院之間的跨 學科研究優勢，融合尖端技術，針對常 見癌症，進行深入的癌症基礎研究，包 括利用先進的微流控技術和納米技術， 提升癌症診療成效。 為提升癌症研究水平，澳大分別從生物 醫學機理和生物醫學材料兩大方向攻 關。健康科學學院訂立八大研究板塊， 其中之一是致力癌症精準醫療研究。其 轄下的癌症中心由鄧初夏院長兼任主 任，帶領團隊致力建立澳門主要腫瘤冷 凍組織庫及活細胞庫，研究腫瘤生長、 轉移、復發及耐藥機制，開發早期診斷 癌症方法，鑒定癌症驅動基因，以及篩 選可殺死癌細胞的高效藥物等；並繼續 針對乳腺癌、鼻咽癌、大腸癌、肝癌和 肺癌等的突變基因，進行更多致癌機理 及預防治療的研究。與此同時，中華醫 藥研究院開拓中藥如何誘導癌細胞程序 性壞死，以及中藥天然化合物助力免疫 系統抵抗腫瘤等創新研究。 在生物醫學材料領域則發揮跨學科研究 的優勢，例如微電子研究院研發了一款 嶄新的數位微流控系統，協助醫療人員 培養單細胞和選擇腫瘤藥物；應用物理
COVER STORY•封面專題 2020 UMAGAZINE 22•澳大新語 8 及材料工程研究院搭建國際先進的納米 生物光學研究平台，促進與大學腫瘤研 究團隊的深入合作，加速碳點癌症診療 項目的研究進程等。 頂尖癌症研究團隊 癌症是目前澳門的10大死因之首，隨著 人口逐漸老化，這一趨勢還將繼續，因 此在澳門加強癌症研究是當務之急。目 前，澳大匯聚研究不同癌症範疇的頂尖 專家，包括鄧初夏教授、沈漢明教授、 王山鳴教授、鄭文華教授、張仲榮教 授、狄利俊教授、沈仲燮教授、郭珩輝 教授、袁振教授、劉子銘教授、陳新教 授、陳修平教授、李子安教授、代雲路 教授等。 澳大的癌症研究團隊以腫瘤精準醫療為 主攻方向，在抑制乳腺癌轉移和復發的 新機制、用細胞自噬抑制劑治療乳癌、 通過大規模人群基因突變檢測預防癌 症、以青蒿素及其衍生物治療眼科腫 瘤、治療前列腺癌的新機制、以激素替 代療法與化療法相結合治療卵巢癌、遺 傳學理論在結腸直腸癌治療中的應用、 新型抗體降低肺癌抗藥性、新型多功能 藥物助力腫瘤光動力療法、以多光子活 體顯微術探究黑色素瘤血管新生動態、 納米技術抑制卵巢癌轉移、納米粒子運 載藥物高溫摧毀癌細胞、結合中藥天然 化合物提升癌症免疫治療效果、中藥誘 導癌細胞程序性壞死，以及數位微流控 技術助篩選腫瘤藥物等範疇深入研究， 取得多項突破性發展。 建設跨學科研究平台 澳大正在向國家教育部申請建立一個腫 瘤精準醫學領域的前沿研究中心，通過 健康科學學院、科技學院、中華醫藥研 究院及應用物理及材料工程研究院之間 的合作，專注精準腫瘤學跨學科研究。 中心旨在成為澳門以至粵港澳大灣區癌 症免疫學和精準腫瘤學研究的國際領先 中心，以滿足未來十年因人均壽命延長 而衍生對癌症研究和相關人員不斷增長 的需求。 A Top-notch Cancer Research Team Cancer is currently one of the ten leading causes of death in Macao, and this trend is expected to continue with the ageing of the population in the city. For this reason, it is imperative to strengthen cancer research in Macao. UM boasts leading experts specialising in different aspects of cancer research. They include Prof Deng Chuxia, Prof Shen Hanming, Prof Wang San Ming, Prof Zheng Wenhua, Prof Edwin Cheung Chong Wing, Prof Di Lijun, Prof Shim Joong Sup, Prof Henry Kwok Hang Fai, Prof Yuan Zhen, Prof Liu Tzu‑Ming, Prof Chen Xin, Prof Chen Xiuping, Prof Leo Lee Tsz On, and Prof Dai Yunlu. UM’s cancer research team has already achieved multiple breakthroughs in the following areas: inhibiting breast cancer metastasis and recurrence, treating breast cancer with autophagy inhibitors, preventing cancer through large-scale populational genetic testing, treating ophthalmic tumours with artemisinin and its derivatives, discovering a new mechanism for prostate cancer treatment, combining hormone replacement therapy with chemotherapy for ovarian cancer treatment, applying genetic theory in colorectal cancer treatment, reducing drug resistance in lung cancer by developing new inhibitory antibodies, developing a novel multifunctional drug for tumour photodynamic therapy, improving precision medicine for cancer treatment by using the multiphoton microscopy system to observe the microenvironment of tumours, inhibiting ovarian cancer metastasis with nanotechnology, destroying cancer cells at high temperatures by using nanoparticles as drug carriers, enhancing the effectiveness of cancer immunotherapy with natural compounds of traditional Chinese medicine, inducing necroptosis of cancer cells with Chinese medicine, and creating a digital microfluidics system for cancer drug screening. Establishing an Interdisciplinary Research Platform UM is currently applying to the Ministry of Education to establish a cutting-edge research centre in the field of precision medicine for cancer treatment. FHS, FST, ICMS, and IAPME collaborate with one another to carry out interdisciplinary research in this field. The aim is to create an internationally leading centre for cancer immunology and precision medicine for cancer treatment in Macao and the Guangdong-Hong
封面專題•COVER STORY 澳大新語•2020 UMAGAZINE 22 9 Kong‑Macao Greater Bay Area, to meet the growing demand for cancer research and researchers in the next decade that will accompany the increase in life expectancy. Earlier this year, UM established a joint cancer research centre with the Institute of Cancer and Basic Medicine, Chinese Academy of Sciences, in order to make full use of the strengths of both institutions in personnel, medical resources, and innovative research, and to support the pursuit of healthy living in Macao, the Greater Bay Area, and the rest of China. The centre tackles key scientific and technological issues in the prevention and treatment of cancers as well as in the development of cancer drugs. Scholars conduct innovative clinical research and aspire to create a world-renowned oncology research and training centre. 為充分發揮澳大和中國科學院在科技人 才、醫療資源以及創新研究方面的合作 優勢，提高澳門、大灣區乃至全國人民 追求健康生活的願景，澳大今年已與中 國科學院腫瘤與基礎醫學研究所成立聯 合癌症研究中心，發揮澳大先進水準的 研究力量，強強聯合，共同打造澳門和 大灣區癌症免疫學和精準腫瘤學研究的 國際領先中心，針對腫瘤防治和診療及 抗癌藥物研發的關鍵科學和技術問題， 開展創新型的基礎和臨床研究，致力將 中心建設成為國際知名的腫瘤科學研究 與人才培養基地。 掃二維碼 觀看癌症研究系列視頻 Scan the QR code for a video on UM's cancer reserach The ‘3+3+3+3’ Research Structure The four ‘3’s in the ‘3+3+3+3’ research structure refer to the university's three state key laboratories (for Chinese medical sciences, analogue and mixed signal very large scale integrated circuits, and internet of things for smart cities, respectively), three key research directions (precision medicine for cancer treatment, advanced materials, and regional oceanography), three interdisciplinary research fields (cognitive and brain science, artificial intelligence and robotics, and data science), and three research platforms for the humanities and social science (Institute of Advanced Studies in Humanities and Social Sciences, Centre for Macau Studies, and Asia Pacific Academy of Economics and Management). UM focuses on the world ’s cutting edge academic issues and encourages interdisciplinary collaboration, and promotes the integration of modern technology in research in the humanities and social sciences. 「3+3+3+3」研究戰略佈局 「3+3+3+3」包括三間國家重點實驗室（中藥質量研究、模擬與混合信號超大規模集成電路、智 慧城市物聯網）、三個重點發展方向（精準醫療、先進材料、區域海洋）、三個跨學科交叉領域 （認知與腦科學、人工智能與機器人、數據科學）、三個人文社科研究平台（人文社科高等研究 院、澳門研究中心、亞太經濟與管理研究所）。重點研究世界尖端學術問題、鼓勵跨學科合作， 打破學科壁壘，尤其是人文社會科學和現代科技的結合。
COVER STORY•封面專題 2020 UMAGAZINE 22•澳大新語 10 左圖是BRCA1野生型組，右圖是BRCA1缺失組。 Left: The wild-type copy of the BRCA1 gene Right: The defective-type copy of the BRCA1 gene According to GLOBOCAN, in 2018, there were about 18.1 million new cancer cases and 9.6 million cancer deaths worldwide, of which 2.1 million were female breast cancer cases causing 630,000 deaths. Indeed, breast cancer has become the leading cause of cancer death in women. Prof Deng Chuxia, dean of the Faculty of Health Sciences (FHS) and director of its Cancer Centre, and Dr Chen Qiang, a senior instructor in FHS, have uncovered a new mechanism for inhibiting breast cancer metastasis and recurrence, bringing new hope for patients. 全球癌症資料庫（GLOBOCAN）顯示，全球在2018年約有1,810萬癌症 新發病例和960萬癌症死亡病例，當中女性乳腺癌佔210萬例，63萬人死 亡，是威脅女性健康的「頭號殺手」。健康科學學院院長、癌症中心主 任鄧初夏教授和高級導師陳強博士發現了抑制乳腺癌轉移和復發的新機 制，為患者帶來新曙光。 抑制乳腺癌轉移和復發的新機制 A New Mechanism for Inhibiting Breast Cancer Metastasis and Recurrence 文/余偉業‧圖/編輯部，部分由受訪者提供 English Translation / Ruby Chen ‧ Photo / Editorial Board, with some provided by the interviewees
封面專題•COVER STORY 澳大新語•2020 UMAGAZINE 22 11 Studying the Mechanisms of Cancer Prof Deng’s research team studies the molecular mechanisms of breast cancer development, drug resistance, and metastasis. The team’s latest study found that the susceptibility gene BRCA1 can inhibit post-surgery breast cancer metastasis and recurrence by promoting mitochondrial autophagy and reducing the activity of inflammatory bodies. The study was published as a cover article in the internationally renowned SCI-indexed journal Advanced Science, and opens up new directions for the treatment of triple-negative breast cancer (TNBC). The study was jointly conducted by Prof Deng Chuxia, Prof Xu Xiaoling, and Dr Chen Qiang. As one of the foremost Chinese-American scientists in the field of life sciences, Prof Deng has studied the pathogenesis and treatment of breast cancer for more than two decades and has published over 380 papers on the subject. According to him, the incidence rate of breast cancer is very high worldwide, posing a serious threat to women’s health. ‘Cancer research at UM covers a variety of cancers, and our laboratory focuses on the most common types of cancer in women,’ he explains. ‘We focus on the BRCA1 gene, whose mutations increase the risk for breast cancer. We have made some good progress in studying the carcinogenic mechanism of TNBC.’ Treatment of TNBC According to clinicopathological classification, about 10 to 20 per cent of breast cancer cases are TNBCs. TNBC is cancer that tests negative for estrogen receptor (ER), progesterone receptor (PR), and epithelial growth factor (HER2). If it is ER- and PR-positive breast cancer, hormone therapy is possible; if it is HER2-induced breast cancer, anti-HER2 target therapy can be used. However, there are currently no effective targeted drugs for TNBC. According to Prof Deng, TNBC is the most difficult‑to‑cure type of breast cancer. It not only has an earlier onset than other types of breast cancer, but also has a high degree of malignancy. Cancer cells can easily metastasise to lymph nodes and spread quickly, so the mortality rate is high. He says, ‘Even after chemotherapy and mastectomy, the risk of TNBC recurrence within the first five years is still higher than other types of breast cancer, because surgery often 研究癌症機理 鄧教授的研究團隊深入研究乳腺癌的 發生發展、耐藥和轉移的分子機制， 他們最新的發現，乳腺癌易感基因1 （BRCA1）可以通過促進線粒體自噬 和降低炎症小體的活性，抑制手術後乳 腺癌的復發及轉移，成果獲著名SCI期 刊《Advanced Science》作為封面文 章刊登，為治療三陰性乳腺癌（Triple negative breast cancer，簡稱TNBC） 開拓新方向。研究由鄧初夏教授、徐曉 玲副教授、陳強博士（第一作者）等共 同完成。 作為生命科學領域頂級美籍華人科學 家，鄧教授過去20多年來研究乳腺癌的 發病機制和治療方法，發表論文380多 篇。他表示，乳腺癌在總體癌症的發病 率非常高，威脅全球女性健康。「澳大 癌症研究領域較廣，涉及多種癌症，而 我們實驗室盯住在女性當中發病最高的 來做研究，聚焦突變時提高患乳腺癌風 險的抑癌基因BRCA1，並在研究『三 陰性乳腺癌』致癌機理上取得成果。」 治療三陰性乳腺癌 按臨床病理分型，在所有乳腺癌個案 中，約有10%至20%屬於三陰性乳腺 癌。「三陰性」指癌細胞對雌激素受 體（ER）、孕酮受體（PR）、上皮生 長素因子（HER2）都呈陰性。我們可 以採用荷爾蒙治療ER和PR陽性的乳腺 癌，以及使用抗HER2的標靶治療來應 對HER2誘發的乳腺癌，但是三陰性乳 腺癌目前尚無有效的靶向藥物。 鄧教授表示，三陰性乳腺癌一直被視 為最棘手、最難根治的乳癌，不僅比 一般乳腺癌早發病、惡性程度較高， 癌細胞也較容易轉移淋巴結，同時很 快擴散，因此死亡率較高。「即使經 過化療和乳房切除手術，三陰性乳腺 癌首五年內復發風險仍較高，因為手 術往往會刺激整個機體的免疫，釋放 一些促進生長的因素令癌細胞復發和 轉移，當務之急是為三陰性乳腺癌治 療找到新的有效標靶。」
COVER STORY•封面專題 2020 UMAGAZINE 22•澳大新語 12 導致遺傳型乳腺癌的元兇 BRCA1基因具有重要的抑癌作用，能 抑制惡性腫瘤，突變時卻容易提高患乳 腺癌的風險。鄧教授表示，BRCA1也 是導致遺傳型乳腺癌的元兇，並且多數 為三陰性乳腺癌。他們在小鼠模型中證 實，BRCA1在線粒體自噬、線粒體動力 學方面具重要調控作用，可以通過促進 線粒體自噬清除有損傷的線粒體，以及 降低炎症小體活性，抑制手術後乳腺癌 的復發及轉移。 今次研究發現，BRCA1在細胞核和細胞 質中發揮不同作用，能令線粒體維持正 常自我修復的功能（如分裂、融合及自 噬），對細胞健康至關重要。不過，當 BRCA1發生突變或變異時，就會影響乳 腺細胞中線粒體的正常運作。 陳強博士解釋指，這時候乳腺細胞出問 題，是因為裏面線粒體的自噬功能會漸 漸緩慢，令原本需要清除的受損線粒體 大量積累，同時增加了活性氧，激發 炎症小體的活性。他說：「這個過程會 誘發腫瘤相關巨噬細胞的募集，抑制 CD8+T細胞的活性，從而令腫瘤的免 疫微環境發生改變，促進腫瘤發生和 轉移。因此，採用炎症小體抑制劑如 Glibenclamide（格列本脲）等，可以 有效緩解因為BRCA1突變而誘發的乳腺 癌的復發和轉移，這為治療三陰性乳腺 癌開拓了新方向。」 stimulates the body’s own immune system, causing it to release growth-promoting factors that lead to cancer recurrence and metastasis. Therefore, it is imperative to find new effective targets for the treatment of TNBC.’ The Main Cause of Hereditary Breast Cancer The BRCA1 gene plays an important role in suppressing cancer. It can suppress malignant tumours, but when mutated, it can easily increase the risk of breast cancer. Prof Deng explains that BRCA1 is also the main cause of hereditary breast cancer, most of which are TNBC. Prof Deng’s team has also found through experiments on mice that BRCA1 plays an important role in regulating mitochondrial autophagy and mitochondrial dynamics, which can eliminate mitochondrial damage by promoting mitochondrial autophagy and reducing the activity of inflammatory bodies, thereby inhibiting post-surgery recurrence and metastasis of breast cancer. Prof Deng’s latest study has found that BRCA1 plays different roles in the nucleus and cytoplasm, which can help mitochondria maintain normal self-repair functions (such as division, fusion, and autophagy), which are essential for cell health. But when BRCA1 mutates, it will affect the normal function of mitochondria in breast cells. Dr Chen explains that it is when the BRCA1 gene mutates that the problem occurs. The autophagy function of the mitochondria gradually slows down, which causes damaged mitochondria to accumulate instead of being removed. It also increases reactive oxygen species, which stimulates the activity of inflammatory bodies. ‘This process will induce the recruitment of tumour-associated macrophages and inhibit the activity of CD8+ T Cells, thereby changing the immune microenvironment of the tumour and promoting tumorigenesis and metastasis,’ Dr Chen explains. ‘Therefore, the use of inflammatory body inhibitors such as Glibenclamide can effectively relieve the recurrence and metastasis of breast cancer induced by BRCA1 mutation, which opens up a new direction for the treatment of TNBC.’ 研究成果獲國際著名SCI期刊《Advanced Science》作為 封面文章刊登（本期UMagazine的封面也採用了此圖） The study was published as a cover article in the internationally renowned SCI-indexed journal Advanced Science (Image also on the cover of this UMagazine)
封面專題•COVER STORY 澳大新語•2020 UMAGAZINE 22 13 鄧初夏教授2014年起出任健康科學學院院長。在1995至2014年於美國國立衛生研究院任終身研究員和遺傳研究 室主任。長期深入研究乳腺癌的發生發展、耐藥和轉移的分子機制，已發表SCI期刊論文380餘篇。 陳強博士是健康科學學院高級導師，主要研究癌症發展及代謝疾病等。他從廈門大學細胞生物學專業哲學博士學位 畢業，曾在美國國立衛生研究院進行博士後培訓。 Prof Deng Chuxia assumed office as the dean of FHS in 2014. Between 1995 and 2014, he served as a tenured researcher at the United States National Institutes of Health (NIH) and the director of its genetics research laboratory. Prof Deng has been long involved in the studies of the molecular mechanisms for breast cancer occurrence and development, drug resistance, and metastasis. He has published over 380 research papers in SCI-indexed journals. Dr Chen Qiang is a senior instructor in FHS. His main research interests are cancer development and metabolic disorders. He obtained his PhD degree in cell biology from Xiamen University and received post-doctoral training at the NIH. 精準對症治病 所有癌症都有機會轉移和復發，情況因 人而異。鄧教授補充指出，有些人在手 術前或癌症初期腫瘤就發生轉移，有些 人則是在手術後促進了細胞激素、生長 因子和炎症因子的表達，刺激腫瘤的生 長，令癌症復發。鄧教授強調，只有以 癌症病患為軸心，透過檢測和分析癌症 基因的特徵，發掘其致癌機理，才能精 確對症下藥，這就是愈趨普及的精準醫 療，也是澳大生物醫學一直努力的研究 方向。 未來五年，鄧教授將帶領研究癌症的團 隊，構建澳門及周邊地區幾種高發腫瘤 的生物庫，並繼續針對乳腺癌、鼻咽 癌、大腸癌、肝癌和肺癌等的突變基 因，進行更多致癌機理及預防治療的研 究。與此同時，他們以精準醫療方法， 研究癌症驅動基因的作用機理，以及開 展癌症個性化治療。他說：「澳大的研 究經驗不僅可以服務澳門，也可推廣到 整個粵港澳大灣區，貢獻人類健康。」 Precision Medicine for Cancer Treatment All cancers can metastasise and recur, and the situation often varies from person to person. Prof Deng says that some people have metastasised tumours before surgery or during the early stage of cancer, while others experience cancer recurrence after surgery because the surgery promoted the expression of cytokines, growth factors, and inflammatory factors, which stimulated the growth of tumours and caused cancer to recur. For this reason, Prof Deng stresses that only by identifying the characteristics of cancer genes and the carcinogenic mechanism can researchers develop tailor-made treatment for the individual patient. This is known as ‘precision medicine’, one of the key research areas at UM. In the next five years, Prof Deng plans to lead his research team to build a biobank of several high-risk cancers in Macao and neighbouring regions. The team will focus on cancer-causing mutant genes for breast cancer, nasopharyngeal cancer, colorectal cancer, liver cancer, and lung cancer, in order to identify the carcinogenic mechanism and develop preventive therapies. At the same time, they will apply precision medicine to identify the mechanism of action of cancer driver genes, and to develop personalised cancer treatment. He says, ‘UM’s research experience not only can serve Macao, but can also be extended to the Greater Bay Area to make a contribution to the health of more people.’
COVER STORY•封面專題 2020 UMAGAZINE 22•澳大新語 14 癌細胞在飢餓情況下激活自噬 Cancer cells undergoing autophagy induced by starvation Caveolin-1 (CAV1) is an important tumour suppressor in breast cancer. Its deficiency and mutation can affect the autophagy and lysosome, thus making breast cancer cells more susceptible to autophagy/lysosome inhibitors. Faculty of Health Sciences Professor Shen Hanming suggests that CAV1’s deficiency and mutation can be used as a biomarker in the selection of breast cancer patients for using autophagy/lysosome inhibitors in cancer therapy. Caveolin-1（CAV1）是一種乳腺癌抑制基因，人體缺少了它或它發生突變時，就 會影響癌細胞的自噬作用和溶酶體功能，增加患上乳腺癌的風險。健康科學學院 教授沈漢明發現，可以用CAV1的缺失或突變作為生物指標，指導在臨床上是否適 合用自噬抑制劑作為治療乳腺癌的手段。 用細胞自噬抑制劑治療乳腺癌 Treating Breast Cancer with Autophagy Inhibitors 文/盛惠怡‧圖/編輯部，部分由受訪者提供 Chinese & English Text / Debby Seng ‧ Photo / Editorial Board with some provided by the interviewee
封面專題•COVER STORY 澳大新語•2020 UMAGAZINE 22 15 Autophagy is an essential mechanism that keeps our cells in proper balance. It does so by transporting dysfunctional components to the lysosome for digestion. Researchers have learned that autophagy plays an important role in physiological processes and has close links to illnesses such as cancer and neurodegenerative diseases. In the early years of autophagy research, some researchers suggested that autophagy could lead to autophagic cell death, but Prof Shen has proved that autophagy can, in principle, resist starvation and other stress conditions and promote cell survival. When it comes to cancer, autophagy is widely believed to be a double-edged sword. According to Prof Shen, efficient autophagy can help prevent cancer, but it can also promote the survival of already-existing cancer cells and the development of tumours. ‘By recycling nutrients such as amino acids in cells, autophagy can help cancer cells function properly and survive under various stress conditions,’ Prof Shen says. 細胞自噬（Autophagy）是生物進化過 程中完整保留的一個重要機制，即細胞 通過溶酶體來清除細胞內的損害物質從 而讓細胞恢復正常的一個過程。目前已 知細胞自噬具有十分重要的生理功能， 而且和癌症、神經退行性疾病等許多疾 病密切相關。在細胞自噬研究的早期， 人們認為細胞自噬會導致細胞自噬性死 亡，而沈教授的研究證明，細胞自噬原 則上是抵抗飢餓及應急狀態的一個重要 的促進細胞生存的機制。 沈教授表示，細胞自噬對癌症是一把雙 刃劍：在癌症發生前，增加機體的自噬 水平可以起到預防作用；但在已有的腫 瘤細胞内，自噬可以促進癌細胞的生存 和腫瘤的發生發展。他說：「細胞在飢 餓及應急情況下會激活自噬，通過重新 利用細胞内的營養元素，例如氨基酸， 維持細胞的功能，促進細胞生存。」 沈漢明教授曾在新加坡國立大學楊潞齡醫學院從事細胞自噬、氧化損傷、細胞信號傳導等方面的研究20多 年，至今在《Autophagy》、《Cell Res》、《Cancer Res》、《Mol Cell》、《Nature Protocol》 等SCI期刊發表論文200餘篇，被引用次數超過25,000次。目前在澳大展開關於細胞自噬及溶酶體、線粒 體自噬、腫瘤靶向治療等方向的研究。 Before joining UM, Prof Shen Hanming studied autophagy, oxidative damage, and cell signalling for over two decades in the Yong Loo Lin School of Medicine at the National University of Singapore. He has published more than 200 research papers in SCI-indexed journals, such as Autophagy, Cell Res, Cancer Res, Mol Cell and Nature Protocol, with a citation frequency of over 25,000. At UM, he continues to study autophagy and lysosome in cancer cell biology, mitophagy, as well as metabolism and cancer targeted therapy. 癌細胞進行線粒體自噬 Cancer cells undergoing mitophagy 沈漢明教授發現可以用CAV1的缺失或突變作為生物指標， 指導在臨床上是否適合用自噬抑制劑作為治療乳腺癌的手段。 Prof Shen Hanming suggests that CAV1’s deficiency and mutation can be used as a biomarker in the selection of breast cancer patients for using autophagy/lysosome inhibitors in cancer therapy
COVER STORY•封面專題 2020 UMAGAZINE 22•澳大新語 16 Prof Wang San Ming’s research team in the Faculty of Health Sciences recently completed a three-year study on cancer prevention in Chinese population. This study determined the frequency of mutation-carrying and the number of carriers of BRCA1/BRCA2 gene mutations in the Chinese population, and laid a solid foundation for cancer prevention through large-scale populational genetic testing. The related paper, titled ‘Prevalence of BRCA1/BRCA2 Pathogenic Mutation in Chinese Han Population’, has been published in the Journal of Medical Genetics, a sub-journal of the British Medical Journal. 健康科學學院王山鳴教授的研究團隊，最近完成了一項歷時三年的中國人群癌症 預防研究。該研究確定了中國人群中BRCA1/BRCA2基因突變的攜帶頻率和攜帶 者數量，為在中國人群中運用大規模人群基因突變檢測進行癌症預防打下堅實基 礎。有關這項研究的論文題為《中國漢族人群BRCA1/BRCA2致病性突變的攜帶 率》在《英國醫學雜誌》子刊《醫學遺傳學雜誌》發表。 通過大規模人群基因突變檢測預防癌症 Preventing Cancer Through Large-scale Populational Genetic Testing 文/張愛華‧圖/編輯部，部分由受訪者提供 English Translation / Ruby Chen ‧ Photo / Editorial Board with some provided by the interviewee 王山鳴教授與研究生把血液樣本放進DNA自動提取儀 Prof Wang San Ming and his student put blood samples into the automatic DNA extraction instrument
封面專題•COVER STORY 澳大新語•2020 UMAGAZINE 22 17 研究中使用的 樣本來自中國內地 不同省份，不同顏 色漸變代表每個省 的參與者比率。 Samples used in the study originated from different provinces of mainland China. The colour gradients represent the rates of participants from each province. 乳腺癌跟遺傳基因突變有著密切關係， 其中攜帶BRCA1和BRCA2基因突變的人 群發病風險極高。王教授和上海交通大 學、中國科學院以及內地健康企業等組 成的團隊合作，對中國人群進行BRCA1/ BRCA2基因檢測，他說：「我們運用第 二代基因測序，在澳門大學高性能計算集 群超級電腦展開生物信息學大數據分析， 並通過實驗方法驗證，篩查了來自全國 各省份11,386個體。研究發現，中國人 群中平均每256人中就有一位帶有遺傳性 BRCA1/BRCA2致病性突變，共有510萬 突變攜帶者。」 基於是次發現，王教授建議所有18歲以 上人士一生做一次BRCA1/BRCA2基因檢 測，「突變攜帶者有以下四種癌症預防手 段，一是定期身體檢查；二是藥物預防； 三是預防性手術；四是採用試管嬰兒的辦 法阻斷下一代攜帶家族性的遺傳突變。」 王教授表示，BRCA1和BRCA2基因突變 檢測成本低而防癌效果確切。他計劃通 過澳大在粵港澳大灣區的首個產學研示範 基地——珠海澳大科技研究院，與業界合 作推廣大規模人群基因檢測，「BRCA1 和BRCA2基因突變檢測具有極大應用價 值，希望通過市場化的推廣，為廣大市民 提供相關檢測服務。」 Breast cancer is closely related to inherited genetic mutations, and people with mutations in BRCA1 and BRCA2 genes are at high risk for cancer. By working with a team formed by cancer experts at Shanghai Jiaotong University, Chinese Academy of Sciences, and health examination companies in mainland China, Prof Wang tested the BRCA1/BRCA2 genes of people in various Chinese provinces. He says, ‘In our study, we used second-generation gene sequencing to collect BRCA sequences, and bioinformatics tools to analyse big sequence data with the help of the high-performance computing cluster at the University of Macau (UM), and obtained experimental validation of the results. We screened 11,386 individuals from nearly all provinces in China. The study has found that an average of one in every 256 people in China carries a hereditary BRCA1/BRCA2 pathogenic mutation, and there are a total of 5.1 million mutation carriers in China.’ Based on the findings of the study, Prof Wang recommends that those over the age of 18 should have a BRCA1/BRCA2 gene testing during their lifetime. He explains that for mutation carriers, there are four ways to prevent cancer: regular physical examination, preventive drugs, preventive surgery, and in vitro fertilisation to prevent the transmission of hereditary genetic mutation to the next generation. According to Prof Wang, the detection of BRCA1 and BRCA2 gene mutations is a low-cost yet highly effective way to prevent cancer. Next, he plans to promote large-scale populational genetic testing by working with the Zhuhai UM Science and Technology Research Institute, which is UM’s first institute in the Guangdong‑Hong Kong‑Macao Greater Bay Area for industry-university-research collaboration. He says, ‘BRCA1 and BRCA2 gene mutation detection has great practical value, and I hope to promote the testing services to the general public.’ 王山鳴教授的研究重點為運用醫學遺傳學、基因組學和生物信息學的方法理解遺傳因素在癌症發生上的作用，以 及發展在群體水平預防遺傳突變所致癌症的策略。 Prof Wang San Ming focuses on medical genetics, genomics, and bioinformatics approaches to understand the roles of genetic mutations in the development of cancer, so that his team can develop strategies to prevent cancer caused by genetic mutations.
COVER STORY•封面專題 2020 UMAGAZINE 22•澳大新語 18 Prof Zheng Wenhua in the Faculty of Health Sciences has studied artemisinin for many years. He has found that artemisinin and its derivatives play an important role in preventing and treating cancer growth and metastasis. The Chinese scientist Tu Youyou said, ‘Artemisinin is a gift of traditional Chinese medicine to the world.’ Prof Zheng has many years of experience studying the mechanism for using artemisinin to treat disease. He was the first to discover that artemisinin has a neuroprotective effect against cell damage caused by oxidative stress, and may become a therapeutic agent for central nervous system diseases. Following the discovery of the neuroprotective effect of artemisinin, Prof Zheng’s team is now studying the role and the action mechanisms of artemisinin, and its derivatives, in the prevention and treatment of cancer, especially the relatively rare eye cancer. ‘We 健康科學學院教授鄭文華研究青蒿素多 年，發現青蒿素及其衍生物在預防和治 療癌症生長和轉移中起到重要作用。 華人科學家屠呦呦稱「青蒿素是中國傳 統醫藥獻給世界的一份禮物」。鄭教授 在探索青蒿素治病機制上積累了多年經 驗，原創性發現青蒿素能對抗氧化應激 導致的細胞損傷，有保護神經作用，可 能成為中樞神經疾病治療用藥。 在發現青蒿素保護神經作用的研究基 礎上，鄭教授的團隊最近聚焦青蒿素 及其衍生物用於癌症的防治，尤其是 治療罕見眼科腫瘤的作用和機制。 他說：「我們已組建了包括惡性眼科 腫瘤在內的多種腫瘤的細胞和動物模 型，發現青蒿素及其衍生物可以抑制 腫瘤細胞的生長和轉移，並延長動物 The chemical structure of artemisinin (A), artemisinin powder (B) and Artemisia annua (C), from which artemisinin is isolated. 圖A是青蒿素的化學結構；圖 Ｂ是青蒿素粉末；圖Ｃ是黃花 蒿，青蒿素來自於此。 以青蒿素及其衍生物治療眼科腫瘤 Artemisinin and Its Derivatives in the Treatment of Eye Cancer 文/張愛華‧圖/編輯部，部分由受訪者提供 English Translation / Ruby Chen ‧ Photo / Editorial Board with some provided by the interviewee
封面專題•COVER STORY 澳大新語•2020 UMAGAZINE 22 19 鄭文華教授獲中山醫科大學醫學學士學位、加拿大麥基爾大學藥理學博士學位，2006年中山大學「百人計 劃」引進回國。2015年加入澳大，研究青蒿素系列化合物神經保護及抑制腫瘤生長、轉移，調節腫瘤免疫 等作用及其機制，並對其進行結構改造並篩選更有效的抗腫瘤／神經保護藥物。已發表SCI期刊論文100餘 篇，其中一篇獲選為2012年中國最具影響力的國際學術論文。 青蒿素濃縮液有效抑制癌細胞的生長 Artemisinin concentration effectively inhibits the growth of cancer cells 青蒿素濃縮液有效抑制癌細胞的侵襲 Artemisinin concentration effectively inhibits the invasion of cancer cells 的生存時間。青蒿素衍生物還可殺死 一些耐藥腫瘤或延緩腫瘤耐藥性的形 成，也能增強動物的抗腫瘤免疫功能。 鄭教授表示，以往治療葡萄膜惡性眼 科腫瘤的方法是患眼摘除術，但最近 已有研究發現患眼摘除術效果存疑或 幾乎無效，「病人得了腫瘤，在一兩 年以後會發生肝臟轉移而死亡，死亡 率特高。因此我們最近在中藥中找到 一種有效的成份，並發現它可以抑制 腫瘤的生長。」這項新發現目前正處 於申請專利的程序中。 have established cell and animal models for various tumours, including malignant ophthalmic tumours, and we have found that artemisinin and its derivatives can inhibit the growth and metastasis of tumour cells, and extend the survival time of animals,’ says Prof Zheng. He explains that artemisinin derivatives can also kill some drug-resistant tumours, or delay the development of drug resistance. Moreover, artemisinin derivatives have been shown to enhance tumour immunology in animals. Prof Zheng says that in the past, the main treatment for malignant ophthalmic tumours in the uvea was eye removal surgery, but recent studies have found that the effect of eye removal is doubtful at best, and ineffective at worst. ‘The mortality rate of patients with tumours in the uvea is extremely high because the tumours tend to metastasise to the liver after one or two years. We recently found an effective ingredient in Chinese herbal medicine, which can inhibit the growth of tumours,’ says Prof Zheng. The team has already applied for a patent for the discovery. Prof Zheng Wenhua received a bachelor’s degree in medical sciences from Sun Yat‑sen University of Medical Sciences and a doctoral degree in pharmacology from McGill University, in Canada. In 2006, he returned to China through Sun Yat‑sen University’s 100 Talent Programme. He joined UM in 2015, studying the role and action mechanisms of artemisinin compounds in inhibiting tumour growth and metastasis and in enhancing tumour immunology. He restructured and screened the compounds to find more effective anti‑tumour/neuroprotective agents. He has published over 100 papers in SCI-indexed journals, one of which was selected as one of China’s most influential international academic papers in 2012.
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