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

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 det...

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Main Authors: György Marko‐Varga, Ákos Végvári, Melinda Rezeli, Kaiu Prikk, Peeter Ross, Magnus Dahlbäck, Goutham Edula, Ruth Sepper, Thomas E Fehniger
Format: Article
Language:English
Published: Wiley 2012-12-01
Series:Clinical and Translational Medicine
Subjects:
Online Access:https://doi.org/10.1186/2001-1326-1-8
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author György Marko‐Varga
Ákos Végvári
Melinda Rezeli
Kaiu Prikk
Peeter Ross
Magnus Dahlbäck
Goutham Edula
Ruth Sepper
Thomas E Fehniger
author_facet György Marko‐Varga
Ákos Végvári
Melinda Rezeli
Kaiu Prikk
Peeter Ross
Magnus Dahlbäck
Goutham Edula
Ruth Sepper
Thomas E Fehniger
author_sort György Marko‐Varga
collection DOAJ
description 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
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spelling doaj.art-c8b302973ae64062b1c4d42d104646032022-12-22T00:04:48ZengWileyClinical and Translational Medicine2001-13262012-12-0111n/an/a10.1186/2001-1326-1-8Understanding drug uptake and binding within targeted disease micro‐environments in patients: a new tool for translational medicineGyörgy Marko‐Varga0Ákos Végvári1Melinda Rezeli2Kaiu Prikk3Peeter Ross4Magnus Dahlbäck5Goutham Edula6Ruth Sepper7Thomas E Fehniger8Clinical Protein Science & ImagingBiomedical CenterDept. of Measurement Technology and Industrial Electrical EngineeringLund UniversityBMC C13SE‐221 84LundSwedenClinical Protein Science & ImagingBiomedical CenterDept. of Measurement Technology and Industrial Electrical EngineeringLund UniversityBMC C13SE‐221 84LundSwedenClinical Protein Science & ImagingBiomedical CenterDept. of Measurement Technology and Industrial Electrical EngineeringLund UniversityBMC C13SE‐221 84LundSwedenInstitute of Clinical MedicineTallinn University of TechnologyAkadeemia tee 1512618TallinnEstoniaInstitute of Clinical MedicineTallinn University of TechnologyAkadeemia tee 1512618TallinnEstoniaAstraZeneca R&D LundLundSwedenAstraZeneca R&D LundLundSwedenInstitute of Clinical MedicineTallinn University of TechnologyAkadeemia tee 1512618TallinnEstoniaClinical Protein Science & ImagingBiomedical CenterDept. of Measurement Technology and Industrial Electrical EngineeringLund UniversityBMC C13SE‐221 84LundSwedenAbstract 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, 18.06.2009https://doi.org/10.1186/2001-1326-1-8Clinical drug administrationIpratropium bromideBronchial tissueMALDI‐MS ImagingMALDI LTQ Orbitrap XL
spellingShingle György Marko‐Varga
Ákos Végvári
Melinda Rezeli
Kaiu Prikk
Peeter Ross
Magnus Dahlbäck
Goutham Edula
Ruth Sepper
Thomas E Fehniger
Understanding drug uptake and binding within targeted disease micro‐environments in patients: a new tool for translational medicine
Clinical and Translational Medicine
Clinical drug administration
Ipratropium bromide
Bronchial tissue
MALDI‐MS Imaging
MALDI LTQ Orbitrap XL
title Understanding drug uptake and binding within targeted disease micro‐environments in patients: a new tool for translational medicine
title_full Understanding drug uptake and binding within targeted disease micro‐environments in patients: a new tool for translational medicine
title_fullStr Understanding drug uptake and binding within targeted disease micro‐environments in patients: a new tool for translational medicine
title_full_unstemmed Understanding drug uptake and binding within targeted disease micro‐environments in patients: a new tool for translational medicine
title_short Understanding drug uptake and binding within targeted disease micro‐environments in patients: a new tool for translational medicine
title_sort understanding drug uptake and binding within targeted disease micro environments in patients a new tool for translational medicine
topic Clinical drug administration
Ipratropium bromide
Bronchial tissue
MALDI‐MS Imaging
MALDI LTQ Orbitrap XL
url https://doi.org/10.1186/2001-1326-1-8
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