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Raman micro-spectroscopy monitors acquired resistance to targeted cancer therapy at the cellular level.

ABSTRACT: Monitoring the drug efficacy or resistance in vitro is usually carried out by measuring the response of single few proteins. However, observation of single proteins instead of an integral cell response may lead to results that are not consistent with patient's response to a drug. We present a Raman spectroscopic method that detects the integral cell response to drugs such as tyrosine kinase inhibitors (TKIs). Non-small cell lung cancer (NSCLC) patients with EGFR mutations develop acquired resistance to first (erlotinib)- and third (osimertinib)-generation TKIs. Large erlotinib-induced differences were detected by Raman micro-spectroscopy in NSCLC cells without T790M EGFR mutation but not in cells with this mutation. Additionally, Raman difference spectra detected the response of NSCLC cells with T790M EGFR mutation to second- (neratinib) and third-generation (osimertinib) TKIs, and the resistance of cells with T790M/C797S EGFR mutation to osimertinib. Thus, the in vitro Raman results indicated that NSCLC cells with T790M and T790M/C797S EGFR mutations are resistant to erlotinib- and osimertinib, respectively, consistent with the observed responses of patients. This study shows the potential of Raman micro-spectroscopy to monitor drug resistance and opens a new door to in vitro companion diagnostics for screening personalized therapies.

SUBMITTER: Hammoud MK

PROVIDER: S-EPMC6189084 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature

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Raman micro-spectroscopy monitors acquired resistance to targeted cancer therapy at the cellular level.

Hammoud Mohamad K MK Yosef Hesham K HK Lechtonen Tatjana T Aljakouch Karim K Schuler Martin M Alsaidi Wissam W Daho Ibrahim I Maghnouj Abdelouahid A Hahn Stephan S El-Mashtoly Samir F SF Gerwert Klaus K

Scientific reports 20181015 1

Monitoring the drug efficacy or resistance in vitro is usually carried out by measuring the response of single few proteins. However, observation of single proteins instead of an integral cell response may lead to results that are not consistent with patient's response to a drug. We present a Raman spectroscopic method that detects the integral cell response to drugs such as tyrosine kinase inhibitors (TKIs). Non-small cell lung cancer (NSCLC) patients with EGFR mutations develop acquired resist ...[more]

PMID: 30323297

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Project description:BackgroundBiochemical cervical change during labor is not well understood, in part, because of a dearth of technologies capable of safely probing the pregnant cervix in vivo. The need for such a technology is 2-fold: (1) to gain a mechanistic understanding of the cervical ripening and dilation process and (2) to provide an objective method for evaluating the cervical state to guide clinical decision-making. Raman spectroscopy demonstrates the potential to meet this need, as it is a noninvasive optical technique that can sensitively detect alterations in tissue components, such as extracellular matrix proteins, lipids, nucleic acids, and blood, which have been previously established to change during the cervical remodeling process.ObjectiveWe sought to demonstrate that Raman spectroscopy can longitudinally monitor biochemical changes in the laboring cervix to identify spectral markers of impending parturition.Study designOverall, 30 pregnant participants undergoing either spontaneous or induced labor were recruited. The Raman spectra were acquired in vivo at 4-hour intervals throughout labor until rupture of membranes using a Raman system with a fiber-optic probe. Linear mixed-effects models were used to determine significant (P<.05) changes in peak intensities or peak ratios as a function of time to delivery in the study population. A nonnegative least-squares biochemical model was used to extract the changing contributions of specific molecule classes over time.ResultsWe detected multiple biochemical changes during labor, including (1) significant decreases in Raman spectral features associated with collagen and other extracellular matrix proteins (P=.0054) attributed to collagen dispersion, (2) an increase in spectral features associated with blood (P=.0372), and (3) an increase in features indicative of lipid-based molecules (P=.0273). The nonnegative least-squares model revealed a decrease in collagen contribution with time to delivery, an increase in blood contribution, and a change in lipid contribution.ConclusionOur findings have demonstrated that in vivo Raman spectroscopy is sensitive to multiple biochemical remodeling changes in the cervix during labor. Furthermore, in vivo Raman spectroscopy may be a valuable noninvasive tool for objectively evaluating the cervix to potentially guide clinical management of labor.

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Raman micro-spectroscopy monitors acquired resistance to targeted cancer therapy at the cellular level.

Publications

Raman micro-spectroscopy monitors acquired resistance to targeted cancer therapy at the cellular level.

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