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肿瘤生物学国家重点实验室

肿瘤生物学国家重点实验室

  肿瘤生物学国家重点实验室是在第四军医大学全军消化病研究所、全军医学重点实验室、分子生物学全军医学重点实验室、国家863计划西安细胞工程中心和第四军医大学肿瘤研究所基础上建立起来的。实验室于2005年4月通过科技部建设计划论证进入立项建设期,2006年初实验室在建设期内通过当年的全国医学重点实验室评估,2006年5月通过科技部验收,成为同批立项建设实验室中首个正式挂牌运行的国家重点实验室。现任学术委员会主任为中国工程院院士程书钧教授、副主任为中国工程院院士郝希山教授,实验室主任为中国工程院院士樊代明教授。

  恶性肿瘤仍然是严重威胁国民健康的重要疾病。认识肿瘤生物学的特点和规律,特别是阐明肿瘤发生发展过程中的各种分子事件及其调控机制,进而找出理想的诊断技术,设计有效的治疗方法,是目前肿瘤生物学研究的主要内容。肿瘤生物学国家重点实验室以人体最常见的消化系肿瘤特别是胃癌和肝癌为主要研究对象,确定了如下研究方向:(1)肿瘤细胞生物学行为相关分子群的发现及其网络调控。(2)肿瘤分子预警系统和早期诊断技术的建立及推广。(3)肿瘤生物治疗新策略新方法的探索及其应用。依据研究方向和相应的科学问题,实验室设置了12个研究单元:肿瘤多药耐药研究单元、肿瘤细胞增殖和转移研究单元、肿瘤细胞分化研究单元、细胞凋亡研究单元、肿瘤血管生成与血管抑制治疗研究单元、胃癌分子预警研究单元、肿瘤基因治疗研究单元、肿瘤疫苗研究单元、抗体工程/ 亲和蛋白组学研究单元、生物芯片研究单元、肿瘤靶向治疗单元、生物信息学研究单元。

  实验室自建成运行以来,科研工作取得了一系列重要成果:(1)系统研究了影响胃癌多阶段进程的重要分子及作用机制,发现了调控胃癌凋亡、增殖、耐药等表型的5个分子群,从中找出了胃癌进程中的关键节点,并以此提出“根除Hp、应用NSAIDs、监测MG7Ag、逆转MDR”的“三级四步”序贯预防策略,获国家科技进步一等奖。(2)获得自主知识产权的肝癌单抗HAb18,用131I标记HAb18 F(ab')2片段抗体,研制成功肝癌放射免疫靶向药物“碘[131I]美妥昔单抗注射液”(商品名:利卡汀),证实了该药对肝癌的治疗和抗复发、转移的作用,获得国家生物制品I类新药证书及生产文号。(3)研制成高效、低免疫原性的分泌型靶向促凋亡蛋白分子,证实其可特异性杀伤HER2阳性肿瘤细胞,并已完成临床前研究。(4)研制了肝癌靶向性SEA/CD80共表达免疫基因治疗剂和基于超抗原的基因工程纳米疫苗,完成了临床前研究并已进入中试生产。(5)发明了组合式生物芯片,研制成胃癌早期诊断芯片并已经进入临床研究。(6)系统研究并阐明了NDRG2和Notch信号通路对肿瘤细胞和肿瘤血管生成的调控作用。

  上述重要的研究进展和成果先后荣获国家科技进步一等奖和二等奖各1项、中国药学科学技术一等奖1项、省部级科技奖励数十项,获得生物制品类国家Ⅰ类新药证书1项、检测试剂类国家Ⅰ类新药证书1项,获得国家发明专利近百项,在Nature Clinical Practice Oncology、Lancet和Hepatology等SCI收录杂志发表论文200余篇,取得了良好的经济效益和社会效益。

  实验室拥有一批在国内相关领域杰出的学术带头人,58名固定人员中85%拥有博士学位,有32人分别从美、英、日等国学成归来,其中中国工程院院士2 名,长江学者奖励计划特聘教授5名,国家杰出青年科学基金获得者5人,国家“973”计划项目首席科学家2名,在国际学术组织中担任常委以上职务者2名。实验室3个课题组先后被评为国家自然科学基金委和教育部创新群体(团队),樊代明院士课题组是国家自然科学基金委首批创新研究群体,杨安钢教授课题组和陈志南院士课题组分别于2005年和2009年被批准为教育部创新团队。

  

  2006年对外开放以来,实验室审批了三批开放课题,吸引了国内外优秀人才来室工作。与美国、英国、加拿大、瑞士、瑞典和香港地区多家大学和研究单位建立了稳定的合作与交流关系。承办或主办了8次全球性学术大会、2次双边性学术大会、21次全国性学术大会。有22人次在国际性学术大会上担任主席、共同主席或分会场主席。实验室主任樊代明院士是亚太地区消化病学会常务理事,担任该学会国际事务委员会主席,并将作为亚太地区消化病大会主席暨世界胃肠病大会主席在我国举办2013年亚太地区消化病大会暨世界胃肠病大会。

  在依托单位第四军医大学和主管部门解放军总后勤部卫生部的有力支持下,肿瘤生物学国家重点实验室(第四军医大学)将努力把实验室建成一个出高水平成果的肿瘤生物学研究基地、一个培养高素质科研人员的人才摇篮、一个进行广泛国内外学术合作的交流中心,为国家的经济建设、社会发展做出更大的贡献。

State Key Laboratory of Cancer Biology (Fourth Military Medical University)

  The State Key Laboratory of Cancer Biology (CBSKL) is mainly comprised of the PLA Key Laboratory of Gastroenterology and PLA Key Laboratory of Molecular Biology, Cell Engineering Base of National 863 Project as well as Cancer Institute of the Fourth Military Medical University. The application for State Key Laboratory of Cancer Biology was initiated in June 2004, and Laboratory was temporarily approved to enter construction stage after investigation and demonstration by Ministry of Science and Technology of China in April 2005. After one year period of construction inspected and reviewed by experts, the laboratory was finally approved in 2006 by Ministry of Science and Technology of China and formally named as The State Key Laboratory of Cancer Biology which became the first one to commence operation among the same batch of constructing laboratories. Prof. Shujun Cheng and Xishan Hao are the present director and associate director of academic committee of CBSKL respectively. Prof Daiming Fan is the director of CBSKL. All of them are academicians of Chinese Academy of Engineering.

  Malignant tumour is still a serious threat to human health. The major tasks of current cancer biology research are to identify the characteristics and patterns of cancer biology , especially molecular events and underlying regulatory mechanisms accounting for tumour formation and development,and to design ideal diagnostic techniques as well as effective treatments. CBSKL mainly focuses on two of the most common tumours of the gastrointestinal tract in human beings, i.e. gastric carcinoma and hepatic cellular carcinoma. We applied ourselves to the following research scopes: (1) The identification and underlying network regulation of tumour associated molecules. (2) Establishment of molecular alerting system and early diagnosis tools of tumours. (3) The exploration and application of novel strategy in tumour bio-therapy. According to distinct research fields and corresponding scientific issues, Laboratory sets up 12 research units as follows: tumour multi-drug resistance, tumour proliferation and metastasis, tumour differentiation, tumour cell apoptosis, tumour angiogenesis and anti-angiogenesis therapy, molecular warning of tumour, tumour gene therapy, tumour vaccine, anti-tumour antibody engineering and affinity proteomics, biochips, tumour targeting therapy, bioinformatics.

  With the development of Laboratory, the research work has made significant progress and achievements as follows: (1) We systematically studied the novel molecules and underlying mechanisms involved in the development of tumour multi-step progression and identified 5 groups of molecules associated with tumour apoptosis, proliferation, drug resistance etc, and tried to find the key molecules related to gastric cancer progression, on the basis of which we put forward “III levels & IV steps” serial aleting strategy, including ” Helicobacter Pylori eradication, Non-steroidal anti-inflammatory drug application, MG7Ag monitoring, MDR reversal”, which enabled us to win the Class I prize of National Science and Technology Progress Award. (2) We have developed anti-HAb18G engineering antibodies against liver cancer. Licartin (Iodine [131I] conjugated HAb18) is a new drug and we have 100% of intellectual property right. We have verified the function of this drug on therapy against the recurrence and migration of liver cancer and acquired the class I national new medicine certificates of Biological Products and a production catalogued number. (3) We have successfully got a targeted pro-apoptotic secretory protein with high-efficiency and low-immunogenicity, and verified its specific function against HER2-positive tumour cells and have accomplished the preclinical study. (4) We have developed liver cancer -targeted immunological gene therapy reagent in which SEA/CD80 were co-expressed as well as a gene engineering nano-vaccine based on super-antigen. The preclinical study of these two products above has been accomplished and entered pilot scale production. (5) We have invented composite biochips and developed the diagnostic biochip for gastric cancer, which has also entered the clinical trial. (6) We have systematically studied and clarified the regulatory effects of NDRG2 and Notch signal pathway on tumorigenesis and tumour angiogenesis.

  With these significant research achievements and advancements, we have won the Class I and Class II prizes of National Science and Technology Progress Awards, one Technology Award of Chinese Pharmaceutical Association and dozens of provincial science and technology awards. We have acquired two class I national new medicine certificates of Biological Products and one class I national new medicine certificate of test reagent. We have got nearly one hundred items of invention patents. As the first or corresponding author we have more than two hundreds international publications that mainly presented on well recognized journals such as Nature Clinical Practice Oncology, Lancet, Hepatology etc which have achieved sound economical and social effects.

  The staff of Laboratory is consisted of a group of academic leading scientists with outstanding contributions in domestic associated research fields. Currently, 85% of the stable people have Ph.D degree and 35 of them have experience of oversea training in U.S.A, England or Japan etc. Two are Academicians of Chinese Academy of Engineering and four have been entitled Professorship of Chang jiang Scholars Program. Five have been granted national distinguished youth funds. Two became the chief expert of the State Key Basic Research Grant of China (“973” program) and one is the subject expert of High-Tech R&D Program Grant (“863” program). Two professors serve as standing committee in international academic organizations. The research group under the leadership of Prof. Daiming Fan was the first Innovative Research Group of National Natural Science Foundation of China. The two research groups of Prof. Angang Yang and Zhinan Chen were approved as Innovative Group of Ministry of Education in 2005 and 2009 respectively.

  Since CBSKL was open to the outside in 2006, three batches of Opening Projects have been approved. Laboratory has attracted many domestic and foreign scholars to do research here. Laboratory has established stable academic collaborations and exchanges with a number of famous universities or institutes in countries such as the USA, England, Canada and Switzerland. Laboratory has hosted and undertaken 8 international, 2 bilateral and 21 national academic conferences. 22 persons have been invited as chairmans and co-chairmans in the main venue or chairmans in the branch venue. The director of Laboratory,Prof. Daiming Fan,is the council member of Asia-Pacific Association of Gastroenterology and Chairman of Internal Affair Committee, and elected as congress President of Asia-Pacific Digestive Week and World Congress of Gastroenterology in 2013.

  With the powerful support of the Fourth Military Medical University and PLA General Logistics Department and Ministry of Health, CBSKL strives to construct the laboratory and make it become a cancer biology research base yielding high-level achievements, a cradle in which high quality researchers are cultivated, an exchange centre to make comprehensive research collaborations both at home and abroad. And we are trying to make every effort to make great contributions to the economic construction and social development of our country.