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研究提升順鉑藥物在腫瘤治療之療效

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國立成功大學「邁向頂尖大學計畫」

  延攬優秀人才工作報告表

NCKU’s “Aim for the Top University Project” Work Report Form for Distinguished Scholars

□續聘continuation of employment 離職resignation

100 年 7 月 13 日更新 受聘者姓名

Name of the Employee 郭天恩

男 □女 Male Female 聘 期 Period of Employment From 105 年(y) 12 月(m) 01 日(d) to 105 年(y) 12 月(m) 28 日(d) 研究或教學或科技研發與 管理計畫名稱 The project title of research,

teaching, technology development and management

研究提升順鉑藥物在腫瘤治療 之療效 計畫主持人 (申請單位主管) Project Investigator (Head of Department/Center) 陳海雯 補助延聘編號

Grant Number HUA105-21T-7-185

一、 研究、教學、科技研發與管理工作全程經過概述。(由受聘人填寫)

Please summarize the entire research, teaching, or science and technology R&D and management work process (To be

completed by the employee)

It was a great honor for me to be appointed as a Visiting Professor in the Department of Radiology, National Cheng Kung University (NCKU). My appointment started on December 1, 2016 and concluded on December 28, 2016. During this time, I have performed/accomplished the following tasks.

Research:

My laboratory has a long-term collaboration in research with Professor Helen H. W. Chen, MD, PhD, in the Department of Radiology, NCKU. Over the past several years, we have jointly published 10 peer-reviewed articles in international journals. We have successfully competed and got funding by grants from the Mistry of Science and Technology, Taiwan, entitled “Improving the treatment efficacies of cisplatin in cancer chemoradiation therapy”

(MOST-105-2314-B-006-046-My3 to Dr. Helen Chen) and from National Cancer institute, USA, entitled “Mechanism of Resistance to Arginine Deiminase Therapy in Advance Melanoma” (R01-CA152197 to Dr. Macus Kuo) and “Improving the Efficacy of Cisplatin-Based Cancer Chemotherapy” (1RO1 CA149260 to MK).

Based on this highly successful collaborative research, my main task at NCKU during this visit was to push forward our collaboration to another level. We have formulated short-term and

long-term research plans. We have assigned these planned works for Dr. Chen’s laboratory at

NCKU and for my laboratory at MD Anderson Cancer Center, Houston, USA. We believe this shared work will facilitate the progress and completion of the projects.

For the short-term research projects, we have been focusing on improving platinum-based chemoradiottherapy using nano-particule technology. The following two main projects will be carried out.

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Project 1: This project aims at investigating the efficacy of FePt nanoparticules (FePt NPs) in

overcoming resistance to antitumor agents, including resistance to cisplatin, multi-drugs (doxorubicin and vincristine) and receptor-tyrosine kinase inhibitor (epidermal growth factor inhibitors). We will also investigate whether X-radiation in combination with FePt NPs would enhance cell killing abilities by overcoming these various drug resistance.

Project 2: This project aims at investigating mechanisms of enhanced cell killing of FePt NPs in

combination therapy with irradiation. Several studies will be performed. These, include: (a) we plan to further investigate whether the high-affinity copper transporter 1 (hCtr1), which is also a major transporter of cisplatin, is involved in the transport of FePt NPs; (b) we will investigate whether FePt NPs-mediated cell killing follows DNA damages, as does cisplatin, using gamma-H2AX staining, which is an established marker for detecting DNA damage; (c) our preliminary results showed that hCtr1 also enhances FePt NPs transport, we plan to investigate mechanism of hCtr1-mediated FePt NPs transport using site-directed mutagenesis approach of mutant hCtr1 molecule; (d) we plan to investigate whether FePt NPs-induced cell death is mediated by autophagic, apoptotic, or necrotic mechanisms; and (e) we plan to investigate the possible synergistic cell killing effect in combination of FePt NPs and radiation and elucidating the underlying mechanism of the synergism.

For the long-term project: We plan to initiate a new project using nanoparticle technology to delivery antioxidant glutathione (GSH) to chelate intracellular copper level, resulting in reduced the bioavailable intracellular copper. Reduced copper levels will promote upregulation of hCtr1 and increase cisplatin transport to enhance cellular uptake of platinum-based antitumor and to elicit the therapeutic effect. This project will include the collaboration of three laboratories, i.e., Professor Dar-Bin Shieh (Institute of Basic Medical Science, NCKU) who will prepare GSH-NP, Professor Helen Chen and my laboratory in Houston. We will perform the biochemical and pharmacological characterizations of GSH-NP. We plan to generate preliminary results for submitting a grant application for the next run of MOST application.

Perspectives: As stated, the planned works have been ongoing simultaneously in Dr. Chen’s and

Dr. Kuo’s laboratories. The research addresses the current bottle-neck problems in cancer research. The experimental approaches use methodologies which have been established in our laboratories. We anticipate that results will be forthcoming and publications in peer-reviewed journals will be anticipated. In the meantime, we have a joint manuscript in preparation which will be submitted for publication (Chen HHW and Kuo MT, “Improving Radiation Therapy in Cancer Treatment: Promise and Challenge.”)

Teaching:

Although I did not offer formal course to students at NCKU, I have maintained extensive contacts with students, postdoctoral fellows, junior clinician scientists and residents. My activities

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including reading manuscripts and making suggestions for postdoctoral fellows, providing guidance of grant writing to young physician scientist who is applying for funding from MOST, attending journal reading meetings in the Department of Radiation Oncology, and laboratory meetings of Dr. Helen Chen, Wu-Chou Su’s group (Department of Internal Medicine, NCKU) and Dr. Ying-Jan Wang (Department of Health, College of Medicine, NCKU). I also gave a lecture entitled, “My 40 Years Research Life in Cancer Research” in the Department of Radiation Oncology to young physician scientists.

Science and technology R&D:

I also have a long-term collaboration with Professor Cheng-Yang Chou, MD (Department of Obstetrics and Gynecology, College of Medicine, NCKU) in research and technology

development in improving cancer chemotherapy of ovarian and peritoneal cancer. Professor Chou and his team has completed phase 1 clinical trial using trientine plus liposomal doxorubicin and carboplatin at NCKU Hospital. The results revealed that this technology shows improvement of the treatment efficacy of ovarian and peritoneal cancer. Our collaboration has resulted in a patent application which has been filed by National Cheng Kung University in Taiwan and in USA. The title of this application is “METHOD OF TREATING OVARIAN, TUBAL AND

PERITONEAL CANCER”. I am a co-inventor of the patent applications. During this visit, we have discussed plan to move into phase 2 clinical trial and the approaches of commercialization of this technology.

The GSH-NP technology as mentioned above uses the same principle as the trientine/liposomal doxorubicin/carboplatin. Should the GSH-NP technology shows intellectual value, we will move into clinical trial and apply for potent protection.

In summary: My short visit has made productive working relationships with faculty and

physician scientists at NCKU. We believe that these collaborative effects between MD Anderson Cancer Center and NCKU will continue to be productive in research and science and technology development in the future.

Finally, once again, I would like to express my sincere gratitude for inviting me to visit the National Cheng Kung University.

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二、研究或教學或科技研發與管理成效評估(由計畫主持人或單位主管填寫)

Please evaluate the performance of research, teaching or science and technology R&D and management Work: (To be completed

by Project Investigator or Head of Department/Center)

(1)是否達到延攬預期目標?

Has the expected goal of recruitment been achieved? Yes.

是。

(2)研究或教學或科技研發與管理的方法、專業知識及進度如何?

What are the methods, professional knowledge, and progress of the research, teaching, or R&D and management work?

郭天恩教授在美國一流的學術機構從事癌症研究已超過四十年,聲譽卓著且專業知識非常豐 富,具備卓越的研究與教學能力。

(3)受延攬人之研究或教學或科技研發與管理成果對該計畫(或貴單位)助益如何?

How have the research, teaching, or R&D and management results of the employed person given benefit to the project (or your unit)?

郭天恩教授指導本部的研究計畫,並合作科技部專題研究計畫,研究如何提升順鉑藥物在腫 瘤化學及放射治療之療效,並結合奈米科技以提升癌症治療的效益,對本科部助益良多。

(4)受延攬人於補助期間對貴單位或國內相關學術科技領域助益如何?

How has the employed person, during his or her term of employment, benefited your unit or the relevant domestic academic field?

郭天恩教授也定期參與校內數位老師的實驗室會議,指導多位年輕的博士後研究人員、主治 醫師與住院醫師,參與實驗結果之討論、提供解決之方案、啟發其研究的構想與興趣、幫助 訓練醫師科學家與學術研究之人才培育,有助於提升本校在癌症相關的學術與科技領域之研 究。

(5)具體工作績效或研究或教學或科技研發與管理成果:

Please describe the specific work performance, or the results of research, teaching, or R&D and management work:

1) 參與科技部專題研究計畫:MOST-105-2314-B-006-046-My3 2) 指導 放射腫瘤部 106 年 科技部新進人員專題研究計畫之申請

3) 論文撰寫:Chen HH and Kuo MT: “Improving Radiation Therapy in Cancer Treatment: Promise and Challenge”

4) 放射腫瘤部學術演講:“My 40 Years Research Life in Cancer Research” 5) 指導與修改數篇欲發表於國際期刊之論文

6) 與本校相關研究領域之實驗室建立長期的合作關係

(6)是否續聘受聘人? Will you continue hiring the employed person?

□續聘Yes 不續聘No:郭天恩教授聘任屆滿後將返回美國,故不接受續聘。

※ 此報告表篇幅以三~四頁為原則。This report form should be limited to 3-4 pages in principle.

※ 此表格可上延攬優秀人才成果報告繳交說明網頁下載。

This report form can be downloaded in http://scholar.lib.ncku.edu.tw/explain/

參考文獻

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