Summary of Study ST002976
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.
See: https://www.metabolomicsworkbench.org/about/howtocite.php
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.
| Study ID | ST002976 |
| Study Title | Metabolomics Insights into Doxorubicin and 5-Fluorouracil Combination Therapy in Triple-Negative Breast Cancer: A Xenograft Model Study (Part 2) |
| Study Type | LC/MS/MS |
| Study Summary | Background: 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. This part of study involves comprehensive metabolomic profiling of the tumor tissue samples specifically and tumor growth assessment provide valuable insights into these treatments' efficacy and potential synergistic effects in TNBC. |
| Institute | Sharjah Institute for Medical Research |
| Last Name | Facility |
| First Name | Core |
| Address | M32, SIMR, College of Pharmacy, Health Sciences, University of Sharjah, Sharjah, UAE, Sharjah, 000, United Arab Emirates |
| tims-tof@sharjah.ac.ae | |
| Phone | +971 6 5057656 |
| Submit Date | 2023-11-08 |
| Raw Data Available | Yes |
| Raw Data File Type(s) | d |
| Analysis Type Detail | LC-MS |
| Release Date | 2024-05-08 |
| Release Version | 1 |
Select appropriate tab below to view additional metadata details:
Combined analysis:
| Analysis ID | AN004886 |
|---|---|
| Analysis type | MS |
| Chromatography type | Reversed phase |
| Chromatography system | Bruker Elute |
| Column | Hamilton Intensity Solo 2 C18 (100 x 2.1mm, 1.8um) |
| MS Type | ESI |
| MS instrument type | QTOF |
| MS instrument name | Bruker timsTOF |
| Ion Mode | POSITIVE |
| Units | AU |
MS:
| MS ID: | MS004630 |
| Analysis ID: | AN004886 |
| Instrument Name: | Bruker timsTOF |
| Instrument Type: | QTOF |
| MS Type: | ESI |
| MS Comments: | The ESI source conditions were set with a capillary voltage of 4500 V, drying gas flow rate of 10.0 l/min at 220°C, nebulizer pressure of 2.2 bar, and the End Plate offset at 500 V. Sodium formate (10 mM) was injected at the beginning of each sample run and used as a calibrant for internal calibration during data processing. The MS acquisition process consisted of two phases. First, an auto MS scan lasting from 0 to 0.3 minutes was utilized for calibrating sodium formate. The second phase encompassed auto MS/MS scanning with CID acquisition, including fragmentation, which extended from 0.3 to 30 minutes. Both acquisition phases were conducted in positive mode at a rate of 12 Hz. The automatic mass scan range within each run spanned from 50 to 1300 m/z, with a precursor ion width of ±0.5, a cycle time of 0.5 seconds, and a threshold of 400 counts. Active exclusion was initiated after three spectra and lifted after 0.2 minutes. For MS2 acquisition, a data-dependent acquisition (DDA) approach was employed, with collision energy settings varying between 100% and 250% and being set at 20 eV. TRX-2101/RT-28-calibrants from Nova Medical Testing Inc. for the Bruker T-ReX LC-QTOF were injected before sample analysis to assess the column's performance, reversed-phase liquid chromatography (RPLC) separation, multipoint retention time calibration, and the mass spectrometer. Additionally, TRX-3112-R/MS Certified Human serum solution for Bruker T-ReX LC-QTOF (provided by Nova Medical Testing Inc.) was prepared from pooled human blood and administered before sample analysis to validate the performance of the LC-MS instruments. The analysis followed a randomized sequence order, commencing with five injections of solvent A (0.1% formic acid in deionized water) to facilitate apparatus equilibration. Subsequently, five injections of the pooled QC sample were carried out. Furthermore, one QC injection was conducted every (9-10 samples) to assess the consistency of the analysis. |
| Ion Mode: | POSITIVE |
