新生物信息技术暗示抗菌素可能有助于治疗进展期肾癌

新生物信息技术暗示抗菌素可能有助于治疗进展期肾癌
Novel bioinformatics approach suggests antimicrobial drug mayhelp in treating advanced kidney cancer
Developing and testing a new anti-cancer drug can cost billionsof dollars and take many years of research. Finding an effective anti-cancermedication from the pool of drugs already approved for the treatment of othermedical conditions could cut a considerable amount of time and money from theprocess.
新生物信息技术提示抗微生物药物可能有助于治疗进展期肾癌。
开发和测试一个新的抗癌药物可耗资数十亿美元，且研究费时多年。而从已被批准用于治疗其他疾患的药物库中发现一个有效的抗癌药则可节省相当大量时间和金钱。
Now, using a novel bioinformatics approach, a team led byinvestigators at Beth Israel Deaconess Medical Center (BIDMC) has found thatthe approved antimicrobial drug pentamidine may help in the treatment ofpatients with advanced kidney cancer. Described online in the journal MolecularCancer Therapeutics, the discovery reveals how linking cancer gene expressionpatterns with drug activity might help advance cancer care.
现在，Beth Israel Dea coness医学中心(BIDMC)研究人员领导的一个团队应用一种新的生物信息技术已发现，已被批准的抗微生物药物戊烷脒（pentamidine）或许可有助于治疗进展期肾癌病人。按在期刊Molecular Cancer Therapeutics在线描述的，该发现揭示癌基因表达模式是如何与药物活性相关联，或许有助于推进进展期肾癌的处理。
"The strategy of repurposing drugs that are currentlybeing used for other indications is of significant interest to the medicalcommunity as well as the pharmaceutical and biotech industries," sayssenior author Towia Libermann, PhD, Director of the Genomics,Proteomics,Bioinformatics and Systems Biology Center at and Associate Professor ofMedicine at Harvard Medical School. "Our results demonstrate thatbioinformatics approaches involving the analysis and matching of cancer anddrug gene signatures can indeed help us identify new candidate cancertherapeutics."
BIDMC基因组学、蛋白质组学、生物信息和系统生物学中心主任兼哈佛大学医学院医学副教授，资深作者Towia Libermann 博士说：“医学界以及制药企业、生物技术工业界对将目前用于其他指证的药物改变其用途的策略很关注。我们的结果证实，有关癌症与药物基因“签名”（signatures）分析、配对的生物信息技术确可帮助我们鉴定新的候选癌症治疗方法。”
Renal cell cancer consists of multiple subtypes that are likelycaused by different genetic mutations. Over the years, Libermann has beenworking to identify new disease markers and therapeutic targets through geneexpression signatures of renal cell cancer that distinguish these differentcancer subtypes from each other, as well as from healthy individuals. In thisnew paper, he and his colleagues were looking for drugs that might be effectiveagainst clear cell renal cancer, the most common and highly malignant subtypeof kidney cancer. Although patients with early stage disease can often besuccessfully treated through surgery, up to 30 percent of patients with renalcell cancer present with advanced stages of disease at the time of theirdiagnosis.
肾细胞癌由多个亚型组成，各亚型似由不同的基因突变引起。多年来Libermann一直在研究通过肾细胞癌基因表达“签名”鉴定出新的疾病标志物和治疗靶点，肾细胞癌各亚型即藉“签名”相互区别以及与健康个体区别。在这篇新论文中，他和他的同事在寻找对透明细胞癌（肾癌最常见的亚型和高度恶性的亚型）有效的药物。虽然早期肾癌常可成功手术治疗，但高达30%的肾细胞癌病人在诊断时已是进展期。
To pursue this search, they made use of the Connectivity Map(C-MAP) database, a collection of gene expression data from human cancer cellstreated with hundreds of small molecule drugs.
为从事这一研究，他们使用了Connectivity Map数据库(C-MAP)，C-MAP是由数以百计小分子药物处理过的人癌细胞的基因表达数据汇聚集合所得。
"C-MAP uses pattern-matching algorithms to enableinvestigators to make connections between drugs, genes and diseases throughcommon, but inverse, changes in gene expression," says Libermann. "Itprovided us with an exciting opportunity to use our renal cell cancer genesignatures and a new bioinformatics strategy to match kidney cancer geneexpression profiles from individual patients with gene expression changesinducted by various commonly used drugs."
Libermann说：“C-MAP应用模式-配对算法使研究人员可通过常见、但逆向的（inverse）基因表达改变建立药物、基因和疾病间的连接。这给我们提供了令人激动的机会来使用我们的肾细胞癌基因签名和新的生物信息技术策略，从各病人被各种常用过的药物诱发的基因表达改变来配对肾细胞癌基因表达谱。”
After identifying drugs that may reverse the gene expression changes associated with renal cell cancer,the investigators used assays to measure the effect of the selected drugs oncells. This led to the identification of a small number of FDA-approved drugsthat induced cell death in multiple kidney cancer cell lines. The investigators then testedthree of these drugs in an animal model of renal cell cancer and demonstratedthat the antimicrobial agent pentamidine (primarily used for the treatment of pneumonia)reduced tumor growth and enhanced survival. Gene expression experiments using microarrays alsoidentified the genes in renal cell cancer that were counteracted bypentamidine.
在鉴定了可能逆转肾细胞癌相关的基因表达改变的药物后，该组研究人员使用各种试验测量选定的药物对细胞的效应。由此鉴定出少量原已被FDA批准的药物可诱发多个肾癌细胞系的细胞死亡。尔后该组研究人员在一种肾细胞癌动物模型测试了这些药物中的三种，证实了主要用于治疗肺炎的抗微生物药戊烷脒（pentamidine）可减缓肿瘤生长、增加动物存活。微阵列基因表达实验也在肾细胞癌鉴定出被戊烷脒“消解”（counteract）的基因。
"One of the main challenges in treating cancer is theidentification of the right drug for the right individual," explains firstauthor Luiz Fernando Zerbini, PhD, of the International Center for GeneticEngineering and Biotechnology in Cape Town, South Africa, adding that thisbioinformatics approach could be a particularly valuable lower-cost model indeveloping countries.
第一作者、南非开普敦基因工程和生物技术国际中心的Luiz Fernando Zerbini博士解释说：“癌症治疗中的主要挑战之一是为合适的个人确定合适的药（the identification of the right drug for the right individual）”，在发展中国家这一生物信息技术可能会是特别有价值的低费用模型。
The authors say their next step will be to evaluate the potential ofpentamidine in combination with the current standard-of-care therapies to treatkidney cancer. "Since the drugs we are evaluating are alreadyFDA-approved, successful studies in preclinical animal models may enable us torapidly move these drugs into clinical trials," adds Libermann.
作者们说，他们下一步是要评估戊烷脒与现有的标准治疗联用来治疗肾癌的潜能。Libermann补充道：“既然我们正在评估的药物均已被FDA批准过，成功的临床前动物模型或许可使我们能迅速让这些药物进入临床试验”。

总有希望！是个好消息。。。

你想试这个吗？副作用大吗？

戊烷脒，仅用于对锑剂有耐药性或不能用锑剂的黑热病（利什曼原虫病）和卡氏肺孢子虫病（首选药为复方磺胺甲恶唑）。也可用于治疗早期非洲锥虫病，但对晚期伴中枢神经系统感染的锥虫病患者的疗效差。

副作用，1.肌内注射后局部可发生硬结和疼痛，偶见形成脓肿。静脉注射易引起低血压及其他严重的即刻反应。 2.偶引起肝肾功能损害（均为可逆性）、低血糖或高血糖、焦虑、头晕、头痛、嗜睡等。 3.妊娠和哺乳期妇女、血液病、心脏病、糖尿病或低血糖、肝肾功能不全、低血压患者应慎用或禁用。 4.在用药期间宜作血糖、肝肾功能、血常规、心电图、血压等监测。 5.该药可使原有肺结核病灶恶化。 6.静脉注射易引起低血压以及其他严重即刻反应，某些系统由于组织胺释放所致。

只能作为信息了解，没有进一步数据支持，不敢尝试的