Published on June 13, 2012 at 7:40 AM In life, we sort soiled laundry from clean; ripe fruit from rotten. Two Johns Hopkins engineers say they have found an easy way to use gravity or simple forces to similarly sort microscopic particles and bits of biological matter -- including circulating tumor cells. In the May 25 online issue of Physical Review Letters, German Drazer, an assistant professor of chemical and biomolecular engineering, and his doctoral student, Jorge A. Bernate, reported that they have developed a lab-on-chip platform, also known as a microfluidic device, that can sort particles, cells or other tiny matter by physical means such as gravity. By moving a liquid over a series of micron-scale high diagonal ramps -- similar to speed bumps on a road -- the device causes microscopic material to separate into discrete categories, based on weight, size or other factors, the team reported. The process described in the journal article could be used to produce a medical diagnostic tool, the Whiting School of Engineering researchers say. "The ultimate goal is to develop a simple device that can be used in routine checkups by health care providers," said doctoral student Bernate, who is lead author on the paper. "It could be used to detect the handful of circulating tumor cells that have managed to survive among billions of normal blood cells. This could save millions of lives." Ideally, these cancer cells in the bloodstream could be detected and targeted for treatment before they've had a chance to metastasize, or spread cancer elsewhere. Detection at early stages of cancer is critical for successful treatment. How does this sorting process occur? Bernate explained that inside the microfluidic device, particles and cells suspended in liquid flow along a "highway" that has speed-bump-like obstacles positioned diagonally, instead of perpendicular to the path. The speed bumps differ in height, depending on the application. "As different particles are driven over these diagonal speed bumps, heavier ones have a harder time getting over than the lighter ones," the doctoral student said. When the particles cannot get over the ramp, they begin to change course and travel diagonally along the length of the obstacle. As the process continues, particles end up fanning out in different directions. "After the particles cross this section of the 'highway,'" Bernate said, "they end up in different 'lanes' and can take different 'exits,' which allows for their continuous separation."
Wednesday, June 13, 2012
儿童用药研发难制约临床应用
2012年06月13日 儿童是特殊的用药人群，目前缺乏儿童专用药品已经成为全世界范围内的共性问题。我国儿童用药所面临的主要问题包括儿童专用药品研发进展乏力，儿童专用剂型缺乏，药品说明书中缺少儿童用药说明或信息不充分等。其深层次的原因则是儿童临床试验开展困难，国家层面缺乏专门针对儿童用药的管理和激励政策等。本报将针对儿童用药领域存在的种种问题进行系列深入报道，与业内专家和读者一起探讨解决之道，以期尽快为儿童用药安全撑起强大的"保护伞"。据统计，我国患病儿童占总患病人数的20%左右，但是目前市场上流通的数千种药品中，专门用于儿童治疗的仅占2%左右。近期，部分媒体和业内专家在呼吁公众重视儿童用药安全性的同时强调，儿童用药缺乏且研发困难是一个世界范围内的共性问题，其后果直接导致儿童临床用药的高风险，改善这一现状需要业内专家、医疗机构、药品生产和研发企业、药品监管部门和其他相关部门等多方面的共同努力。
研发难是世界共性问题据专家介绍，儿童用药缺乏是一个世界性的问题，即使是在药品研发、生产、监管水平都很高的美国，也有超过75%的药品没有儿童用药信息。2011年，美国食品药品管理局（FDA）批准上市的所有新分子实体中，只有4种药品说明书中有儿童用药信息。据世界卫生组织资料显示，世界范围内，采用专门针对儿童开发的配方的药物数量极少，即使说明书中标示了儿童用法用量等信息的药物，也不一定是适合儿童的最优处方。当没有儿童特定药物时，卫生保健工作者和家长往往会使用少量成人剂型药，或将药片碾碎或把部分胶囊溶解在水中来配制儿童药物。这一做法对家长或照护者有一定难度，儿童服用起来也很困难，并可能导致儿童用药剂量不准确，可能出现不良反应或治疗无效。首都儿科研究所附属儿童医院药剂科主任张钧丽介绍说，药品剂量、规格不适合儿童使用的现象在临床中非常多见。如一些针剂的最低规格是100毫克/支，但儿童可能只用70毫克，剩下的部分只好浪费掉；某些颗粒剂一包需要分2~3次服用，但是其最小包装上没有相应的压线等二次分量的设计，使用起来非常不便；一些治疗窗窄的药品如地高辛片，控制剂量极为重要，但儿童只需使用其1/7或者1/8，难以分量，很容易引起不良反应。首都医科大学附属北京儿童医院药剂科副主任史学介绍说，儿童常见病用药剂型已经包含了口服溶液、干混悬剂、注射剂、软膏剂、喷雾剂、洗剂、栓剂、酊剂等，但与成人用药相比，仍不够丰富，尤其是从口感、口味方面更易被儿童接受的剂型更是少见，造成儿童用药依从性低下。随着疾病发病的日益低龄化，如2型糖尿病、高血压、血脂异常、抑郁症等疾病在儿童中的发病率日趋增高，导致许多本来儿童并不需要使用的成人药亟待用于儿童，更加凸显了儿童用药的缺乏。据报道，2002～2005年间，口服降糖药物的使用在青少年男性中增加了39%，在青少年女性中增加了166%；调脂药物的使用在儿科患者中也增加了15%，其中主要是他汀类药物。但是，这些药物在儿童中应用的经验很有限，治疗的时机也还不明确。早在2004年FDA就首次警示，儿童和青少年使用抗抑郁药物有增加自杀倾向的风险，然而不予以确诊的抑郁症患儿药物治疗又不符合医学伦理，抗抑郁药物在低龄人群中使用的安全性还需要严格的临床试验来验证。专家表示，儿童用药信息缺乏，以及药品中缺少专为儿童设计的配方、剂型、规格，不仅是世界范围内的共性问题，还是一个十分复杂、充满矛盾的问题。
临床研究难开展是主因研发适当的儿童用药，对于实现儿童健康目标至关重要。但是，儿童用药研发困难却是一个世界性的难题，原因在于儿童用药临床研究难以开展。专家们介绍说，儿童不是缩小的成人，儿童处于生长发育阶段，特别是婴幼儿时期肝肾功能、中枢神经系统和内分泌系统的发育尚不健全，药物在其体内呈现的药代动力学和药效学特征与成人相比有较大差别；儿童对许多药物的代谢、排泄和耐受性较差，不良反应发生率比较高。因此，特别针对儿童的药物临床研究就显得尤为重要。但是，儿童用药要想获得临床研究数据非常困难。专家分析认为，由于伦理学要求，儿童参与临床研究必须征得监护人认可，但是监护人存在不希望自己的孩子成为试验品的观念，这使得临床研究参与者的招募非常困难；我国临床研究机构中有条件承担儿童用药临床研究的还相对较少，而且集中在儿童专科医院和部分有儿科的综合性医院里；由于缺乏临床试验受试者保障机制（保险、赔偿机制等），风险较高，使得广大监护人和临床研究机构都不愿参与儿童用药的临床研究；由于儿童用药研发成本较成人药物高许多，但是目前在定价、招标采购、进入基本药物和医保目录等领域都没有相应的优惠政策，企业或其他研发者开展针对儿童的药物临床研究需花费更多的成本，却没有更多的利益预期，因而积极性不高。专家认为，诸多因素的交织，使得儿童用药的临床研究难以开展。
临床面临高安全风险据著名药学专家、首都医科大学金有豫教授介绍，由于缺乏应在临床研究中得到的疗效和安全性数据，很多药物没有针对儿童的剂型，因此在儿科临床应用并未获得许可，也就是说，这些药物应用在儿科属于超说明书用药。首都医科大学附属北京儿童医院药剂科药师刘莹介绍，目前儿科超说明书用药现象非常普遍。儿科临床医生由于缺乏循证依据，只能以成人用量进行折算后的剂量给儿童使用。"从理论上说，这样的用药行为忽视了儿童独特的生理、病理情况及药动学和药效学特点，不但不能保证治疗效果，更可能导致儿童用药不良反应的发生，甚至产生导致儿童伤残和死亡的严重后果。"刘莹坦言，"但是由于治疗需要，在面对患儿确实需要用药的情况下，临床上也会根据临床经验，慎重为儿童用药。"著名儿科专家、首都医科大学胡仪吉教授谈到，临床上由于缺乏儿童用药造成的风险不仅包括药物成分所带来的风险，还包括药物剂型、规格、给药方式等因素造成的风险。如某国外健康治疗项目，给予儿童体积很大的咀嚼片，结果造成有些儿童在参与时因服用该咀嚼片而窒息，由于项目现场没有专业的救护措施，最终致10余名儿童死亡。如果药物设计合理的话，这些死亡是可以避免的。但是在药物研发过程中，研发者经常首先考虑的问题是节约成本和方便使用，而不会重点去考虑儿童用药的特殊性。常见的问题还包括液体、糖浆制剂的容积太大，糖浆剂的稳定性不可靠等。此外，儿童用药由于分装剂量小，成本高，一般的价格比较贵，过高的价格也导致部分监护人代之以成人用药，同样增加了用药风险。
国家局积极推动儿童药研发面对儿童用药领域存在的问题，我国已经采取了一系列积极行动，以改善儿童用药的可及性、安全性和有效性。国家食品药品监管局基于自身职能，长期以来一直格外关注儿童用药的有关情况，并在药品研发、审评审批、注册批准等职责范围内对其给予最大力度的支持与推动。国家局药品注册司司长张伟指出，从药品的品种看，目前我国批准注册的药品基本可以满足治疗儿童常见病的需要。世界卫生组织2010年发布的《儿童标准处方集》提供了267个用于0~12岁儿童的用药信息，经对比该处方集列出的药品，绝大多数品种在我国均已批准上市。同时，为保证儿童用药安全，国家局严格儿童用药的审评审批，积极开展儿童用药不良反应监测，启动了针对药品说明书儿童用药信息的修改等工作。国家药品不良反应监测中心相关负责人介绍说，2011年，在全部不良反应中，14岁以下儿童的不良反应构成比为11.5%，在严重不良反应中为10.3%。这一数据多年来保持相对稳定，表明我国儿童用药安全性基本稳定；同时，在我国针对各类药品发布的药品不良反应信息通报中，均包含针对儿童用药者提出的警示和建议。在谈到儿童用药的注册审评工作时，张伟介绍说，从儿童疾病的发展情况看，随着经济的发展和社会生活的变化，人类疾病谱也发生了相应变化，原来成人发生的疾病，在儿童人群中的发病率也有所上升，如糖尿病、高血压等。但由于没有相应的试验数据，用于成人的药物还不能确定合适的剂量供各年龄段的儿童使用。还有一些先天性疾病或者仅在儿童阶段发生的特殊疾病，如新生儿肺透明膜病、先天性代谢酶缺乏等，由于发病率低，研发困难，目前还没有有效的治疗药品，需要通过药物创新，开展儿童临床试验获得科学可靠的使用数据。在对申报儿童用药的资料进行审评时，除了安全、稳定、质量可控的传统标准外，药品注册司及药品审评中心还针对儿童用药的特殊性，对其剂型、规格、口味依从性、给药装置、辅料等方面进行了审评，确认其是否适合儿童并对儿童安全。为了满足对儿童用药的研发需要，提高儿科临床研究的质量和数量至关重要。我国陆续批准设立了一批有能力承担儿童临床研究的临床试验机构，它们已经具有承接全年龄段、全亚分科药物临床研究项目的能力。张伟还介绍说，国家局药品注册司还格外重视针对儿童用药的政策研究工作，并将其作为2012年药品注册司的重点工作。目前，该司已召集了国内药品科研、生产、使用、审评审批以及法律方面的专家，共同参与该政策研究课题，预计年内结题。
Combination therapy for triple-negative breast cancer disappointing
June 13, 2012 in Cancer Lisa A. Carey, MD (Medical Xpress) -- A recent clinical trial testing a combination therapy for basal-like (also known as triple-negative) breast cancer demonstrates that a combination of two drugs with promising preclinical results is not as effective as researchers had hoped. "This trial tested a drug that inhibits the Epidermal growth factor receptor (EGFR) in combination with a standard therapy for Stage IV triple-negative breast cancer," said Lisa A. Carey, MD, who led the study. Carey is the Preyer Professor of Breast Cancer Research and medical director of the UNC Breast Center. She also serves as Associate Director for Clinical Research at UNC Lineberger Comprehensive Cancer Center. "While we were disappointed that the combination of cetuximab plus carboplatin produced responses in fewer than 20 percent of the patients, the study provides important data about how cancers can resist EGFR inhibition and provides direction for future research," she added. The results were published in the Journal of Clinical Oncology. The randomized phase II trial enrolled 102 patients with Stage IV triple-negative breast cancer. Some patients received the combination therapy from the beginning of the trial and others received it only if their disease continued to progress. The investigators chose EGFR inhibition triple negative breast cancer is that in laboratory studies, this kind of breast cancer is dependent on EGFR for growth. Phase II trials are the first step in evaluating both the safety and efficacy of new drugs or new drug combinations. In clinical trials for patients with cancer, new treatments are tested in addition to or in combination with the standard of care. But sometimes just watching the tumors isn't enough. "Because we were able to do laboratory studies examining the effect of the drug on the patients' tumors both before and after therapy, we gained important insight about the genetic patterns of the EGFR pathway in these tumors and their response to therapy," Carey said. "Triple-negative breast cancer remains difficult to treat but with each clinical trial we learn more about how these tumors work that allows us to develop smarter approaches to treatment," she added. Multiple research projects – including several studies conducted at the University of North Carolina at Chapel Hill – have used DNA microarray analysis to identify biologically different breast cancer subtypes, including luminal A, luminal B, basal-like and HER2-enriched. Simple tests are being developed to help doctors identify these subtypes and to treat their patients in a more biologically-based way. In the UNC Gillings School of Global Public Health-based Carolina Breast Cancer Study, researchers found that the basal-like, or triple negative breast cancer, affects African American women far more than white women. It is likely that this plays a role in racial differences in breast cancer survival. More information: Other members of the research team included Anastasia Ivanova, PhD, Wing-Keung Chio, MS, Madlyn Ferraro, RN, Emily Burrows, MPH, Katherine A. Hoadley, PhD, and Charles M. Perou, PhD, from the University of North Carolina at Chapel Hill; P. Kelly Marcom, MD, from Duke University; Hope S. Rugo, MD, from the University of California at San Francisco; Erica L. Mayer, MD, and Eric P. Winer, MD, from the Dana-Farber Cancer Institute; Francisco J. Esteva, MD; from the University of Texas MD Anderson Cancer Center; Mothaffar F. Rimawi, MD, from Baylor University College of Medicine; Cynthia X. Ma, MD, from Washington University in St. Louis; Minetta C. Liu, MD, from Georgetown University; Anna Maria Storniolo, MD, from Indiana University; Andrew Forero-Torres, MD, from the University of Alabama, Birmingham; Antonio C. Wolff, MD, from Johns Hopkins, University; Timothy J. Hobday, MD from the Mayo Clinic; and Philip S. Bernard, PhD, from the University of Utah. The project was funded by the UNC Breast Cancer Specialized Program of Research Excellence, funded by the National Cancer Institute and by an additional grant from the National Institutes of Health. Other funders include Bristol-Myers Squibb and Avon Partners-for-Progress. The Translational Breast Cancer Research Consortium, which collaborated on the study, is supported by the Breast Cancer Research Foundation, the Avon Foundation, and Susan G. Komen for the Cure. Journal reference: Journal of Clinical Oncology
Mutant gut bacteria reverse colon cancer in lab models !!!!
June 13, 2012 in Cancer (Medical Xpress) -- A mutant form of a meek microbe deals a gutsy blow to colon cancer, University of Florida scientists have discovered. The special bacteria halted abnormal inflammation, reduced precancerous growths and reversed progression of severe cancerous lesions in the large intestines of mice. The findings appear June 11 in the Proceedings of the National Academy of Sciences. "We have demonstrated that our bacterial treatment can take on established colon cancer," said principal investigator Mansour Mohamadzadeh, a professor in the UF College of Veterinary Medicine department of infectious diseases and pathology and a faculty member in the UF College of Medicine division of gastroenterology, hepatology and nutrition in the department of medicine. "This is huge, because people don't come to you 10 years before they have colon cancer saying, 'I may get colon cancer, can you treat me?' They come to you and say, 'I have colon cancer.'" For years researchers have understood that uncontrolled inflammation in the large intestine can result in various diseases, including colon cancer and inflammatory bowel diseases such as ulcerative colitis. The new study focused on understanding how to curb immune system processes in the gut that lead to harmful inflammation. Resulting treatments could work not just for diseases of the digestive tract, but also for other conditions such as diabetes and Sjögrens syndrome in which inflammation plays a major role. Some inflammation in the gut is a good thing, as it serves to keep the body's immune system in tip-top, disease-fighting shape. But under stress, the immune system overreacts with a cascade of inflammation-causing reactions. That can lead to afflictions in which the immune system attacks instead of protects the body. It can even cause colon cancer, which kills more than 50,000 Americans every year and is one of the nation's leading causes of cancer deaths, according to the National Institutes of Health. Mohamadzadeh, a member of the UF Shands Cancer Center and the UF Emerging Pathogens Institute, and colleagues previously demonstrated that a genetically modified form of the beneficial bacterium Lactobacillus acidophilus can bring overactive immune responses back to normal. They have now found that proteins on the surface of the bacteria can act on the immune system to either cause inflammation in the gut or tune it down. The researchers removed an inflammation-causing gene from the bacterium, and the result was a form of the bacteria that was even better at controlling disease-causing inflammation. Moreover, mice with severe cases of polyps and cancerous intestinal lesions that were fed the modified bacteria had significantly reduced numbers of colon polyps compared with untreated mice, and showed no signs of active colon cancer or disease-causing inflammation. "This is a major discovery that defines how 'healthy' microbes function in the gut," said Dr. Eugene B. Chang, the Martin Boyer professor of medicine at the University of Chicago Knapp Center for Biomedical Discovery. Chang was not involved in the UF study. "This has far-reaching implications for the development of therapies derived from microbes that can treat many types of complex immune and digestive disorders." The modified bacteria are easy and cost-effective to produce. Mohamadzadeh anticipates that a treatment for humans could be a pill that can be taken by mouth. Patients could receive the beneficial bacterial treatment in combination with surgery or other therapies. Journal reference: Proceedings of the National Academy of Sciences
美時 現金增資2億元 !
美時製藥(1795) 公告變更本公司董事會決議辦理現金增資發行新股案之資金用途及發行價格 發言時間 101/06/0518:10:41 發言人 洪堯樂 發言人職稱 副總經理 發言人電話 02-27785188 主旨 : 公告變更本公司董事會決議辦理現金增資發行新股案之資金用 途及發行價格 符合條款第11款 事實發生日101/06/05 說明 1.董事會決議日期:101/06/05 2.增資資金來源:辦理現金增資發行普通股。 3.發行股數(如屬盈餘轉增資，則不含配發給員工部份):發行普通股2仟萬股以內。 4.每股面額:新台幣10元。 5.發行總金額:預計發行金額為新台幣2億元。 6.發行價格:本次發行價格以除權交易日前五個營業日，皆不得低於其前一、三、五個 營業日擇一計算之普通股收盤價簡單算術平均數扣除無償配股除權（或減資除權）及 除息後平均股價之七至九成辦理，實際發行價格待董事會決議後另行公告。 7.員工認購股數或配發金額:保留增資發行股數之10%由本公司員工認購。 8.公開銷售股數:增資發行股數之10%對外公開承銷。 9.原股東認購或無償配發比例(請註明暫定每仟股認購或配發股數):增資發行股數之 80%由原股東按認股基準日股東名簿之記載股東持有股份比例認購。 10.畸零股及逾期未認購股份之處理方式:不足一股之畸零股可於認購期間內股東自行 併湊，認購不足或併湊不足一股之畸零股，授權由董事長以發行價格洽特定人認足之。 11.本次發行新股之權利義務:與原已發行股份相同。 12.本次增資資金用途:償還銀行借款、研發新藥。 13.其他應敘明事項:無 以上資料均由各公司依發言當時所屬市場別之規定申報後，由本系統對外公佈，資料如有虛偽不實，均由該公司負責.
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