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了解药物在患者靶向疾病微环境中的摄取和结合:转化医学的新工具。

Understanding drug uptake and binding within targeted disease micro-environments in patients: a new tool for translational medicine.

机构信息

Clinical Protein Science & Imaging, Biomedical Center, Dept, of Measurement Technology and Industrial Electrical Engineering, Lund University, BMC C13, SE-221 84, Lund, Sweden.

出版信息

Clin Transl Med. 2012 May 31;1(1):8. doi: 10.1186/2001-1326-1-8.

DOI:10.1186/2001-1326-1-8
PMID:23369501
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3560985/
Abstract

BACKGROUND

For many common global diseases, such as cancer, diabetes, neurodegenerative and cardiovascular diseases there is an unmet need for diagnosing early indications of disease that could enable medical intervention and early treatment. The treatment of these diseases will require detailed knowledge of targeted pathways involved in disease pathogenesis but also the mode of drug actions at the biological location on these targets. Translational medicine is a new area of research where expert from different disciplines involved in basic science and clinical disciplines meet and join forces. Mode-of-drug-action mechanisms elucidation is key in the characterization of drugs that can relate to both efficacy and safety.

METHODS

Matrix assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) was used providing evidence into the fate (destinations and distributions) of administered drugs within tumor regions of lung compartments.

RESULTS

We hereby present a pulmonary study in which we have isolated lung tissue after inhaled drug administration and then localized the drug within airway wall compartments. The histology also provides evidence of drug binding to smooth muscle cell microenvironments. We also identified lung tissue regions with tumor cell invasion in these COPD patients.

CONCLUSIONS

The ultimate goal is to identify bridging comprehension that forms a knowledge base that can be used by society to develop a better treatment and medicine for patients. Our results demonstrated that robust imaging data could be generated confirming drug localization in pulmonary regions of COPD patients with tumor pathology.

TRIAL REGISTRATION

Tallinn Medical Research Ethical Committee decision #1724, 18.06.2009.

摘要

背景

对于许多常见的全球性疾病,如癌症、糖尿病、神经退行性疾病和心血管疾病,人们迫切需要诊断出疾病的早期迹象,以便进行医学干预和早期治疗。这些疾病的治疗需要详细了解参与疾病发病机制的靶向途径,还需要了解药物在这些靶点的生物位置上的作用模式。转化医学是一个新的研究领域,涉及基础科学和临床学科的专家汇聚一堂,共同努力。药物作用模式机制的阐明是描述与疗效和安全性相关的药物的关键。

方法

基质辅助激光解吸/电离质谱成像(MALDI-MSI)用于提供证据,证明药物在肺部区域肿瘤内的命运(去向和分布)。

结果

我们在此介绍一项肺部研究,我们在吸入药物给药后分离了肺组织,然后定位了气道壁隔室中的药物。组织学还提供了药物与平滑肌细胞微环境结合的证据。我们还在这些 COPD 患者的肿瘤细胞侵袭的肺组织区域中鉴定了药物。

结论

最终目标是确定形成知识库的桥梁理解,该知识库可被社会用于为患者开发更好的治疗方法和药物。我们的结果表明,可以生成强大的成像数据,以确认 COPD 患者肺部区域肿瘤病理学中的药物定位。

试验注册

塔林医学研究伦理委员会决定 #1724,2009 年 6 月 18 日。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a46b/3560985/5d748d84b20b/2001-1326-1-8-6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a46b/3560985/767320267735/2001-1326-1-8-1.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a46b/3560985/767320267735/2001-1326-1-8-1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a46b/3560985/abd58b960609/2001-1326-1-8-2.jpg
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