Summary of Study ST002975

This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench, https://www.metabolomicsworkbench.org, where it has been assigned Project ID PR001852. The data can be accessed directly via it's Project DOI: 10.21228/M8B424 This work is supported by NIH grant, U2C- DK119886.

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This study contains a large results data set and is not available in the mwTab file. It is only available for download via FTP as data file(s) here.

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Study IDST002975
Study TitleMetabolomics Insights into Doxorubicin and 5-Fluorouracil Combination Therapy in Triple-Negative Breast Cancer: A Xenograft Model Study (Part 1)
Study TypeLC/MS/MS
Study SummaryBackground: Breast cancer is one of the most prevalent malignancies and a leading cause of death among women worldwide. Among its subtypes, triple-negative breast cancer (TNBC), which poses significant clinical challenges due to its aggressive behavior and limited treatment options. Aim: This study explored the effects of doxorubicin (DOX) and 5-fluorouracil (5-FU) as monotherapies and in combination on MDA-MB-231 xenograft model. Employing advanced metabolomics analysis, the study was designed to investigate molecular alterations triggered by these treatments. Methods: State-of-the-art metabolomics analysis using Ultra-high-performance liquid chromatography-electrospray ionization quadrupole time-of-flight mass spectrometry (UHPLC-ESI-QTOF-MS) was conducted including comprehensive plasma and tumor tissue sample profiling. Results: The study explored alterations induced by DOX, 5-FU, and their combination treatment. Each treatment group exhibited unique metabolic profiles in plasma and tumor analysis. Univariate and enrichment analyses identified alterations in metabolic pathways, including glycine and serine metabolism, spermidine and spermine biosynthesis, and purine and pyrimidine pathways. The combination of DOX and 5-FU significantly influenced plasma and tumor metabolites. The comprehensive metabolic profiling of both plasma and tumor samples shed light on the intricate changes within the tumor microenvironment and their systemic implications. Conclusion: The study findings offer insights into the metabolic vulnerabilities of TNBC in vivo induced by the studied chemotherapeutics. These findings highlight the involved metabolites and metabolic pathways in the response of MDA-MB-231 cells to DOX, 5-FU, and their combination which advance our understanding of TNBC treatment strategies, offering new possibilities for enhancing therapeutic outcomes.
Institute
Sharjah Institute for Medical Research
Last NameFacility
First NameCore
AddressM32, SIMR, College of Pharmacy, Health Sciences, University of Sharjah, Sharjah, UAE, Sharjah, 000, United Arab Emirates
Emailtims-tof@sharjah.ac.ae
Phone+971 6 5057656
Submit Date2023-11-08
Raw Data AvailableYes
Raw Data File Type(s)d
Analysis Type DetailLC-MS
Release Date2024-05-08
Release Version1
Core Facility Core Facility
https://dx.doi.org/10.21228/M8B424
ftp://www.metabolomicsworkbench.org/Studies/ application/zip

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Combined analysis:

Analysis ID AN004885
Analysis type MS
Chromatography type Reversed phase
Chromatography system Bruker Elute
Column Hamilton Intensity Solo 2 C18 (100 × 2.1mm, 1.8um)
MS Type ESI
MS instrument type QTOF
MS instrument name Bruker timsTOF
Ion Mode POSITIVE
Units AU

Chromatography:

Chromatography ID:CH003686
Chromatography Summary:Mobile phases A (water with 0.1% formic acid) and B (acetonitrile with 0.1% formic acid) were used with the following gradient elusion mode: 0 to 2 min, 1% B; 2 to 17 min, 1–99% B; 17 to 20 min, 99% B; 20 to 20.1 min, 99–1% B; 20.1 to 30 min, 1% B. The flow rate was 0.25 mL/min from 0 to 20 min, 0.35 mL/min from 20 min to 28.3 min, and 0.25 mL/min from 28.3 to 30 min. The sample injection volume was 10 μl, and separation occurred on a Hamilton® Intensity Solo 2 C18 column (2.1 × 100 mm, 1.8 µm) (Bruker Daltonik) at 35°C.
Instrument Name:Bruker Elute
Column Name:Hamilton Intensity Solo 2 C18 (100 × 2.1mm, 1.8um)
Column Temperature:35
Flow Gradient:gradient elusion mode: 0 to 2 min, 1% B; 2 to 17 min, 1–99% B; 17 to 20 min, 99% B; 20 to 20.1 min, 99–1% B; 20.1 to 30 min, 1% B.
Flow Rate:0.25 mL/min from 0 to 20 min, 0.35 mL/min from 20 min to 28.3 min, and 0.25 mL/min from 28.3 to 30 min.
Solvent A:Water (0.1% Formic Acid)
Solvent B:ACN (0.1% Formic Acid)
Chromatography Type:Reversed phase
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