干细胞药物从毒性测试到新药的开发

发布时间：2012/6/4 11:47:00 来源：药品资讯网信息中心 在很多人想象中,干细胞几乎能治愈太阳底下的所有疾病。人们的注意力几乎都放在了它们神话般的再生医学功能上,热切期望着它们尽快从天落地。而与此同时,干细胞却在药物开发领域不声不响地站稳了脚跟。作为研究工具,干细胞技术在行业里变得越来越多元化。"在该领域,目前的发展态势很像DNA重组技术早期。上世纪70年代中期,人们并没有意识到DNA重组会有现在这么广泛的用途,而且人们也低估了其用于治疗手段的困难程度。"威斯康辛州麦迪逊莫格里奇研究院再生生物学研究所主任詹姆斯·汤姆森说,"而现在,干细胞也处在相似位置。尽管直接用于治疗最终可能带来丰硕成果,但作为一种研究工具,人们也低估了它的使用范围。"

从毒性测试到新药开发大约两年前,一些药物公司开始尝试性地涉入干细胞领域。现在,制药行业越来越多地用干细胞来测试药物毒性,以发现潜在的新疗法。比如CellularDynamics公司出售人类心肌细胞,生产脑细胞和血管上皮细胞,还将推出一系列人类肝脏细胞。心肌细胞来自诱导多能干细胞(iPS细胞)。汤姆森说,"基本上所有的大型制药公司"都买过一些。此外还有总部在英国的医疗技术公司通用电气医疗集团(GEHealthcare)。3年前,英国干细胞生物学家斯蒂芬·明格辞去学术工作,带领通用电气医疗集团进入干细胞领域。他们出售人类心脏细胞已经一年有余,这些细胞来自胚胎干细胞,他们很快也会卖肝脏细胞。最关键的问题是,在许多药物问题的案例中,只有那些药得到了美国食品和药物管理局(FDA)等机构的许可并进入市场后才能发现其中的问题。明格说:"这些药只是通过了各种动物实验,然后通过了制药工业的I期、Ⅱ期、Ⅲ期临床阶段,获得了FDA许可。""在这方面,许多动物模型并不得力。小鼠实验虽然效率很高,但在临床实验后期却不能在人类身上重复。因此多年前人们就开始使用试管模型,以此来代表人类疾病,这是一个巨大的进步。"位于加利福尼亚旧金山的生物制药公司iPierian战略与合作开发高级主管亚当·罗森塔尔说。明格及其研究小组曾对心脏细胞进行盲评实验,以检验这些细胞对各种不知名的药物化合物的反应,看它们是否具有毒性。明格说,当药物被打开时,他们发现细胞对那些已知有毒的化合物立刻起了反应。使用干细胞测试能带来明显的健康利益,可以在药物上市之前消除其危险的副作用,同时也能避免继续投入开发成本,节约了数百万资金。除了测试药物毒性,干细胞还是一种开发新药的重要工具。CellularDynamics和通用电气医疗集团两家公司销售的干细胞,都有这方面的功用。iPierian公司并不向其他药物公司出售其产品,而是用于内部开发。他们正在研究治疗老年痴呆症等神经退行性疾病的药物。该公司不久前曾宣布,他们正在开发一种瞄准tau蛋白的单克隆抗体,这种蛋白在老年痴呆症中起重要作用,此外还有其他与神经退行性疾病有关的蛋白质。公司表示,这些决策都是建立在干细胞研究的成果之上的。

未来之路影响深远这一新生领域也有着许多未知数。iPierian共同创始人、哈佛干细胞研究院转化医学部主任李·鲁宾说,比如能够将干细胞用于研究某种特殊类型的疾病还存在很多争议,尤其悄切┓且糯缘幕蛲矸⑿偷奈陕?以及与多组织间相互作用有关的疾病等。目前,鲁宾在用干细胞作为一种脊椎肌肉萎缩疾病的模型,这是一类早发型遗传紊乱。他指出,将干细胞用于药物开发,有望成为发现特效药物的更好途径,但只有真正经过证明的技术,才称得上是更好的方法体系。"目前,人类胚胎干细胞和诱导多能干细胞所做的,只是提供一种途径,让人们能利用人体最基本的物质材料进行基础研究。"汤姆森指出,干细胞还可能有更广阔的用途,不止于药物开发研究。有了这些细胞,我们能从更多细节层面理解人体。究竟要怎样使用它们,还不能定论,但其必将对人类医学产生深远影响。

国际癌症研究称2030世界癌症病例增长将达75%

 发布时间：2012/6/4 11:49:00 来源：药品资讯网信息中心据澳大利亚《每日电讯报》6月1日报道，总部位于法国里昂的国际癌症研究机构(IARC)近日称，受人口增加和生活方式因素影响，到2030年，全球癌症病例可能增加75%。国际癌症研究机构的弗雷迪·布雷(Freddie Bray)说，2008年有1270万人患癌，到2030年将有2220万人患癌，其中90%发生在最贫困国家。布雷称，许多国家因感染导致的癌症病例在减少，但与西方饮食习惯有关的癌症病例却在增加。2008年，富裕国家癌症病例中有一半是乳腺癌、肺癌、肠癌以及前列腺癌。而在中等收入国家，食道癌、肝癌以及胃癌相对更常见。但在这两类国家中，宫颈癌与胃癌病例都在减少。在贫困国家中，宫颈癌病例更多，远超乳腺癌和肝癌患癌病例。研究称："通过早期预防、接种疫苗、早期诊断以及有效治疗，当可减少癌症病例。"

Excessive endurance training can be too much of a good thing, research suggests

June 4, 2012 in Health  Micah True, legendary ultra-marathoner, died suddenly while on a routine 12-mile training run March 27, 2012. The mythic Caballo Blanco in the best-selling book, Born to Run, True would run as far as 100 miles in a day. On autopsy his heart was enlarged and scarred; he died of a lethal arrhythmia (irregularity of the heart rhythm). Although speculative, the pathologic changes in the heart of this 58 year-old veteran extreme endurance athlete may have been manifestations of "Phidippides cardiomyopathy," a condition caused by chronic excessive endurance exercise.  Regular exercise is highly effective for the prevention and treatment of many common chronic diseases, and improves cardiovascular health and longevity. However, recent research suggests that chronic training for, and competing in, extreme endurance exercise such as marathons, iron man distance triathlons, and very long distance bicycle races may cause structural changes to the heart and large arteries, leading to myocardial injury. A study in the June issue of Mayo Clinic Proceedings reviews the literature and outlines in detail for the first time the mechanisms, pathophysiology, and clinical manifestations of cardiovascular injury from excessive endurance exercise."Physical exercise, though not a drug, possesses many traits of a powerful pharmacologic agent. A routine of daily physical activity can be highly effective for prevention and treatment of many diseases, including coronary heart disease, hypertension, heart failure, and obesity," says lead author James H. O'Keefe, MD, of Saint Luke's Hospital of Kansas City, MO. "However, as with any pharmacologic agent, a safe upper dose limit potentially exists, beyond which the adverse effects of physical exercise, such as musculoskeletal trauma and cardiovascular stress, may outweigh its benefits."Dr. O'Keefe and his colleagues present emerging data suggesting that extreme endurance training can cause transient structural cardiovascular changes and elevations of cardiac biomarkers, all of which return to normal within one week. For some individuals, over months and years of repetitive injury, this process can lead to the development of patchy myocardial fibrosis, particularly in the atria, interventricular septum, and right ventricle, and an increased susceptibility to atrial and ventricular arrhythmias. In one study, approximately 12% of apparently healthy marathon runners showed evidence for patchy myocardial scarring, and the coronary heart disease event rate during a two-year follow up was significantly higher in marathon runners than in controls.Although it has been recognized that elite-level athletes commonly develop abnormal electrocardiograms and atrial and ventricular entropy, these adaptations traditionally have not been thought to predispose to serious arrhythmias or sudden cardiac death. However, it now appears that the cardiac remodeling induced by excessive exercise can lead to rhythm abnormalities. Endurance sports such as ultramarathon running or professional cycling have been associated with as much as a 5-fold increase in the prevalence of atrial fibrillation.Chronic excessive sustained exercise may also be associated with coronary artery calcification, diastolic dysfunction, and large-artery wall stiffening.Lifelong vigorous exercisers generally have low mortality and disability rates and excellent functional capacity, Dr. O'Keefe notes. He suggests that further investigation is needed to identify who is at risk for adverse cardiovascular remodeling, and to formulate physical fitness regimens for conferring optimal cardiovascular health and longevity.In a video interview accompanying the article, Dr. O'Keefe stresses that the report does not detract from the importance of physical exercise. "Physically active people are much healthier than their sedentary counterparts. Exercise is one of the most important things you need to do on a daily basis," he explains. "But what this paper points out is that a lot of people do not understand that the lion's share of health benefits accrue at a relatively modest level. Extreme exercise is not really conducive to great cardiovascular health. Beyond 30-60 minutes per day, you reach a point of diminishing returns."More information: "Potential Adverse Cardiovascular Effects From Excessive Endurance Exercise," by James H. O'Keefe, MD, Harshal R. Patil, MD, Carl J. Lavie, MD, Anthony Magalski, MD, Robert A. Vogel, MD, and Peter A. McCullough, MD, MPH. Mayo Clinic Proceedings, Volume 87, Issue 6 (June 2012), DOI: 10.1016/j.mayocp.2012.04.005Journal reference:Mayo Clinic Proceedings

Antidepressant helps relieve pain from chemotherapy, study finds

 June 4, 2012 in Cancer  The antidepressant drug duloxetine, known commercially as Cymbalta, helped relieve painful tingling feelings caused by chemotherapy in 59 percent of patients, a new study finds. This is the first clinical trial to find an effective treatment for this pain.  Chemotherapy-induced peripheral neuropathy is a common side effect of certain chemotherapy drugs. The tingling feeling -- usually felt in the toes, feet, fingers and hands -- can be uncomfortable for many patients, but for about 30 percent of patients, it's a painful sensation. Previous studies have found no reliable way to treat this type of pain.In the current study, which will be presented Tuesday at the American Society of Clinical Oncology Annual Meeting, researchers looked at 231 patients who reported painful neuropathy after receiving the chemotherapy drugs oxaliplatin or paclitaxel. Patients were randomly assigned to receive duloxetine or a placebo for five weeks. They were asked to report on their pain levels weekly throughout the study.The researchers found that 59 percent of patients who received duloxetine reported reduced pain, while only 39 percent of those taking placebo did."These drugs don't work in everyone. The good news is it worked in the majority of patients. We need to figure out who are the responders. If we can predict who they are, we can target the treatment to the people it's going to work for," said lead study author Ellen M. Lavoie Smith, Ph.D., APRN, AOCN, assistant professor at the University of Michigan School of Nursing and a researcher at the U-M Comprehensive Cancer Center.Duloxetine has previously been shown to help relieve painful diabetic neuropathy. This type of antidepressant is believed to work on pain by increasing neurotransmitters that interrupt pain signals to the brain.In this study, participants received a half dose of duloxetine – 30 milligrams a day - the first week before ramping up to a full dose of 60 mg daily for four more weeks. Few severe side effects were reported with this approach. The most common side effect was fatigue.Treating painful peripheral neuropathy is critical because the condition can lead doctors to limit the patient's chemotherapy dose if the pain becomes too severe."In addition to improving symptoms and quality of life, treating peripheral neuropathy pain potentially improves quantity of life if it helps patients avoid decreasing their chemotherapy medications," Smith says.Often, Smith adds, patients avoid telling their doctors about pain because they do not want their chemotherapy dose decreased."Patients make this trade-off sometimes: They don't want to give up the chemotherapy and decide they'd rather have this pain. That's a terrible trade off to make," Smith says.The researchers' next steps are to determine which patients are most likely to benefit from duloxetine.More information: Reference: "CRA9013: CALGB 170601: A phase III double blind trial of duloxetine to treat painful chemotherapy-induced peripheral neuropathy (CIPN)," Smith et al. American Society of Clinical Oncology Annual Meeting, June 1-5, 2012Provided byUniversity of Michigan Health System

南京江宁高新园: 一校一企一产业 !!

江宁高新园：创业创新活力迸发的国家大学科教创新园区 2012-06-01 新华日报(南京)方山脚下，秦淮之滨，一座国家级高新技术产业开发区崛起腾飞南京江宁高新园。江宁高新园的前身是江宁科学园，经过18年的发展，园区已经形成了高新技术产业区、江宁大学城、方山风景区联动发展的三大功能区域，确立了生命科学、高端装备制造和现代服务业为主导的现代产业发展格局。江宁区副区长、江宁高新园党工委书记周育刚介绍说，江宁科学园更名为江宁高新园，是区委、区政府发展高新技术产业、支撑江宁新一轮跨越发展、科学发展的战略布局，江宁要把高新园打造成为南京创新型经济发展的重要载体平台，成为与全国高新区同台竞争又一个重要引擎。目前，江宁高新园围绕“二次创业”，积极践行“三争一创”，全面落实创新驱动战略，壮大新兴产业支撑，优化环境服务配套，大力弘扬“诚实、创新、包容”的园区精神，全力打造长三角一流的大学科教创新园区，国际领先、国内一流的生命科学城，最具活力和竞争力的国家级高新区，建成创业创新活力迸发的国家级大学科技创新园区，奋力争当全区乃至全市“第二个率先”的先行军。

【科创篇】有载体有政策有公寓，科技特区成创业乐园江苏（江宁）大学科教创新园由南京市江宁区与江苏省教育厅、科技厅合作共建，包括南京紫金（方山）科技创业特别社区、生命科学城、秦淮源国际化品质生活社区、毕业企业创业园四个功能区，包含国际一流的孵化器、加速器、中试用房，以及总部研发中心、人才公寓等功能设施，建立健全公共技术、投融资、信息交流、中介服务和政府服务“五大平台”，构筑集特有功能、特殊政策、特色运作于一体的创业创新“小环境”。紫金（方山）科技创业特别社区：已全面开工建设各类创业载体50万平方米，启动人才公寓、生命科学产业中心（博览馆）、创业大道等配套设施建设，确保年内建成生命科学城活力智岛一期项目和生命科学产业中心。今年，将引进1-2家知名投资基金、2-3家科技小额贷款公司，目前已成立邦信科技贷款公司，注册资本3亿元。“十二五”期间，高新园将建成230万平方米孵化加速载体，全面构建江苏省医药动物实验基地、江苏省基因药物技术中心等专业技术支撑平台，孵化毕业200家企业，培育创新型企业100家，建成创业创新活力迸发的国家级大学科技创新区。
【人才篇】一年集聚5名“千人计划”人才，园区成引才“强磁场”过去的一年里，园区引进国家“千人计划”5人、省“双创”计划6人、市区人才计划近30人。目前，高新园已有近50位高端人才获得了中央千人、省双创、南京市321等人才引进计划资助。去年一季度，园区企业省建筑科学研究院缪昌文博士当选为中国工程院院士，今年一季度引进和培育国家“千人计划”2人，东南大学生命科学研究院院长谢维教授等6位高层次人才落户园区。在园区集聚的高端人才中，有以施一公教授、张丹博士、谢良志博士为首的生命科学领域的领军人物；有以章方良博士、赵子建博士、戴一凡博士等为代表的海归创业团队；有以郭宏新董事长、张杭董事长、陈依军董事长为代表的高校教授创业企业家。2012年，高新园将确保入选国家、省市人才引进计划64名。“十二五”期间内，园区将引进领军创业人才、科技创业家、国家“千人计划”专家分别占全区总量的1/4,力争1/3。
【大学篇】大学城和园区展开“齿合式合作”，大学科技园遍地开花拥有15所高校、25万师生的江宁大学城已经成为江宁高新园的最大优势。园区推动高校重点实验室、研究生部、公共技术平台等创新资源迁入大学城。现在，正以每年不少于3家的速度引入省级以上重点实验室。园区瞄准产业链高端环节，加强与高校的齿合式合作：与高校实现“一校一企一产业”合作，组建一个运作公司、建设一个产业基地、培育一个新兴产业，走出一条园校利益一体、互惠双赢的政产学研合作之路。目前，园区与中国药科大学、南京医科大学、南京工程学院、江苏经贸学院、金陵科技学院合作的五个大学科技园加速推进。加快建立“孵化服务+创业投资+创业导师”的创业孵化体系，为高校师生创业提供从基础服务到投融资、市场拓展的全方位解决方案。“180”大学生创业广场，已经入驻100多家学生创办企业。大学城还将与10所高校展开合作，建成1-2个国家级科技企业孵化器，筹备成立大学城就业创业培训服务中心。
【产业篇】高端高质高新，大批优质项目产业集聚园区高新园一手抓主导产业，做强做优，一手抓新兴产业，培育引导，两手硬、两不误， “主”“新”并举，加速转型升级。生命科学产业：集聚了金斯瑞生物科技、奥赛康研发中心、康缘生物医药科技园、先声药业抗体药物研究所及中试基地、美国异种器官移植医疗中心等一批领军项目以及合源医药创新团队、美国斯坦福大学终身教授王义斌等多个创新创业人才项目。致力打造国际领先、国内一流的生命科学城。高端装备产业：瞄准智能装备领域，南高齿入驻了蒂森克虏伯、舍弗勒、瑞拓、吉地亚、帕艾斯等一批重大项目，建成全国有影响的高端装备制造业基地。现代服务产业：以方山横岭旅游小镇、方山当代文化创意产业园、天景山动漫基地、杨柳湖文化创意园等为平台，发展总部经济、文化创意、动漫网游、软件及服务外包、金融信息等现代服务业，增强城市核心功能和竞争力。未来五年，园区将建成博士后工作站、院士工作站20家以上，培育一批百亿、十亿级以上的企业，累计上市公司突破20家。
【城建篇】高端配套加紧完善，建设幸福乐居新城示范区瞄准国际国内一流园区，以一流的基础设施和精品工程，迅速提升城市形态和整体形象，全面增强高新园对外吸引力。 南京医科大学明德医院、高星级酒店、潭桥小学、龙湖湾小学、加洲城小学等配套重点项目加速推进，园区在生活、医疗、教育等方面的配套将更加完善。方山作为高新园的后花园，成功申报为国家3A级旅游景区。方山当代创意产业园、方山风景区、秦淮湿地公园规划与资源进一步整合，方山横岭将被建设成旅游小镇，以方山当代创意产业园为核心的创意产业集群已经初步形成。建成区域实施“退二进三”，打造现代经济总部区、商务区等功能，争取趋势科技、硕文软件和中国电信呼叫中心等重大项目的落户建设。同时，园区内的拆迁工作和复建房正在稳步推进。高新园统筹城乡发展，建设和谐园区同步取得了新的进展。本版撰稿 孔永祥