Asia-wide collaborative clinical research on Prostate Cancer

Recent Progress on Nanobio-target Therapy at ICONT and Initiation of An Asia-wide Translational Research .

Hiromi KUMON
Professor and Chairman, Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences

Okayama University is conducting a fully developed national project to form the Innovation Center Okayama for Nanobio-targeted Therapy (ICONT) with resources from both the government and collaborating companies. To date, its research and development accomplishments are superb, especially in the gene therapy field. Okayama University, where promising scientific seeds are being sewn and clinical trials staged, demonstrates leading performances in Japanese gene therapy; its biotech startup company was created to promote drug development.

Furthermore, in this year’s competition for government Special Coordination Funds for Promoting Science and Technology, Okayama University’s proposal of “An Asia-wide translational research on high-risk group detection based on ms-SNP and IL-12 immunogene therapy for prostate cancer” has been adopted to consolidate translational research infrastructure in Asia with the cooperation of top institutes in China, Korea and Singapore.

The current accelerating progress in creating a globally recognizable gene therapy research center at Okayama University is reported, and the prospects of its mutually beneficial relationship with Asia are presented.

Beneficial effects of neoadjuvant hormonal therapy prior to radical prostatectomy in patients with clinically localized prostate cancer.

Yasutomo NASU
Associate Professor, Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences

Interleukin-12 is a potent cytokine which activates an anti-tumor immunity. We initiated IL-12 gene therapy against prostate cancer using adenovirus vector from May 13, 2008 after an official approval of the government. In this project, protocols and technique will be introduced to the collaborating countries. Thorough the promotion of clinical studies we will establish the translational research network in advanced clinical application fields including gene therapy.

We have analyzed genotypes of about 300 SNPs in cancer-related genes on 450 controls and 1,300 patients with a variety of cancers. We found that 48 missense SNPs of 43 genes are associated with incidence of at least one of 8 major cancers in Japan, including lung, head & neck, esophageal, colorectal, gastric, pancreatic, breast and prostate cancers. Associations of 39 of these 48 SNPs with any cancer are novel findings. Of 101 significant single associations, 59 were very significant in 99% confidence interval and in permutation test. We then addressed the overlap of the SNP genotypes at risk in each individual. The net numbers of overlapping SNPs were much higher in cases than in controls for all cancer types. Thus, we demonstrate that about 0.5 to 10% of healthy subjects can be identified as the highest-risk group for each major cancer in Japan. Since Asians share the common genetic background, our strategies can be expanded on whole Asia. Especially, we are focusing into prostate cancer, which is rapidly increasing in most Asian countries and discuss the concrete perspectives for the collaboration.

科学技术振兴调整费支助亚洲的共同研究推进的项目（日本）（A program for promoting Asian collaborative research by Special Coordination Funds for Promoting Science and Technology in Japan）

独立行政法人・科学技术振兴机构　科学技术振兴调整费项目主管
西垣隆

关于日本的科学技术政策，基本方针是由日本首相主席召开综合科学技术会议(Council for Science and Technology Policy:) CSTP)进行讨论，,制定计划，并且需要在内阁会议上通过，以及从预算措施到政策实施必须经过的过程，根据不同的分类在各相关政府机关实施．

科学技术振兴调整的基本方针是：在政府的协调引导下，设立科学技术振兴调整费基金合理用在科学技术振兴．科学技术振兴调整费是由文部科学省,科学技术，学术政策委员会，科学技术学术协调委员会(由调整部门担当)等相关部门使用在科学技术的申报，审查，,资金分配，评价等方面．其中独立行政法人 科学技术振兴机构承担大部分任务．

学技术振兴调整费是用于通过综合科学技术会议讨论，为科学技术振兴发展需要的重要项目提供经费，并需要满足以下的其中之一：各政府部厅的重点项目，目前没有列入个政府部厅优先发展的重点项目，多部门共同合作将产生巨大成就的项目，以及根据项目的要求需要重组的项目等，并且灵活的应用政府的政策诱导，使其产生很好的效果．

1. 1） 利用先进的科学技术创造，改造优秀成果的改革
2. 2） 对于未来发展前景的领域/部门进行长远的计划
3. 3） 推进科学技术活动的国际化

其中3)作为推进科学技术国际化的项目，从2008年起实施的亚洲科学技术交流的推进项目。不仅在亚洲，今年同时增加非洲国家,这个项目：通过整和亚洲，非洲各国的先进科学技术，加强各国间科学技术交流合作，同时支助日本的相关研究机构与各国优秀的研究机构互相交流，合作，建立国际间共同合作研究（平等互利，互惠关系）．

每年有许多的单位参加此项目的竞争，因此现在的入选率逐年下降。今年，作为冈山大学的代表，公文裕己教授的提案：联合中国，韩国，新加坡的相关研究机关进行国际共同临床研究“亚洲人的癌体质和基因治疗的共同临床实验研究项目(An Asia-wide Translational Research on High-risk Group Detection Based on Ms-SNP & IL-12 Immunogene Therapy for Prostate Cancer.)”被成功采纳，作为科学技术振兴调整费支助的一个项目．此资助项目为期3年．

个项目以前列腺癌的基因治疗为基础，进行先进医疗技术的开发，从而建立以临床医生主导的临床试验研究的合作网络．参与本项目合作的单位有：北京大学(那彦群教授，中国泌尿器学会理事长)，北京肿瘤医院(李鳴教授),浙江大学(謝立平教授)等的中国研究机关，进行关于前列腺癌的基因治疗的临床研究以及基因治疗效果的评价，并且在冈山大学现有的癌症遗传研究成果以及基因治疗成果的基础上，进行进一步深入的共同合作研究，希望此共同研究能取得更大的成果．

Current Status of Prostate Cancer in China

Ming LI
Director, Professor, Peking University School of Oncology, Beijing Cancer Hospital & Institute

Prostate cancer incidence has been rapidly increased in China. Data from most of the cities and area in China in year 1988-2002 showed a sharp increase trend of incidence of prostate cancer. In year 1988-1992 PC incidence in China was 1.96/10,000, in year 1993-1997 was 3.09/10,000, and in year 1998-2002 was 4.36/10,000. Data from several single institutes since 2002 up to now showed also remarkable increased trend.

More recently, studies demonstrated that there was about 1/4 prostate cancer with PSA less than 4ng/ml. Some of the urologists in the USA and European countries suggest to lower the PSA value to 2.5ng/ml, so that to increase diagnostic rate and to find more earlier stage prostate cancer. Is this lower PSA cutoff point applicable to Chinese men? Data showed that the prostate cancer detection rates in the tPSA ranges of ＜4ng/ml, 4-10ng/ml were 3.1%, 11.6% respectively. To lower PSA cutoff point to ＜4ng/ml may not be applicable to Chinese men except positive DRE.

Since PSA was introduced In China in early 1990s, more and more early stage prostate cancer patients have been diagnosed. There are currently about 20-30% localized prostate cancer patients who received radical prostatectomy, which compared to ＜10 % patients who received radical prostatectomy in 1980s. Even though more and more early stage PC was detected, there are still more than half late stage PC patients at diagnosis. The major reason is that it’s still impossible to do PSA screening for the population in China. We do PSA test only for the patients who are older than 50 years and see doctors for LUTS or other urinary symptoms.

Treatment selections for PC are extremely various in different parts of China. More accurate pre-treatment staging and grading were done and more curable techniques were selected in big cities, while more operative castration was used in the rural area. In 2006 Chinese Urological Association (CUA) organized specialists from all over the China to make guideline for prostate cancer and published the “China guideline for prostate cancer” in 2007. The aim of the guideline is to improve the diagnosis and treatment for PC and to unify the opinion of urologists in all over of China.