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
Email	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:

Treatment:

Treatment ID:	TR003098
Treatment Summary:	Then, tumor-bearing mice were randomized into the following groups: untreated xenografts (positive controls) and three treatment groups, DOX, 5-FU, and a combination of DOX and 5-FU. The mice in the DOX group were administered 1mg/kg of DOX once weekly , and the mice in the 5-FU group received 50 mg/kg of 5-FU daily for five consecutive days both treatments administered via an intraperitoneal (i.p.) route [32]. The mice in the combination therapy group received DOX & 5-FU as separate injections, and the treatment duration was two weeks. An overview of the experiment flow. The body weight of the mice was measured at the start of the study and twice weekly from the beginning of the treatments. Tumor growth and progression were monitored by palpation and measurement of tumor size periodically using a digital vernier caliper. The tumor volume in cm3 was determined using the formula (volume = π/6 × length × width2) [33]. All mice were anesthetized and euthanized via cardiac puncture at the end of the treatment period. Tumors were excised and weighed, and their sizes were measured. Also, blood serum was collected from each mouse. Both tumor and serum samples were stored at -80°C for further analysis.

Treatment ID:

TR003098

Treatment Summary:

Then, tumor-bearing mice were randomized into the following groups: untreated xenografts (positive controls) and three treatment groups, DOX, 5-FU, and a combination of DOX and 5-FU. The mice in the DOX group were administered 1mg/kg of DOX once weekly , and the mice in the 5-FU group received 50 mg/kg of 5-FU daily for five consecutive days both treatments administered via an intraperitoneal (i.p.) route [32]. The mice in the combination therapy group received DOX & 5-FU as separate injections, and the treatment duration was two weeks. An overview of the experiment flow. The body weight of the mice was measured at the start of the study and twice weekly from the beginning of the treatments. Tumor growth and progression were monitored by palpation and measurement of tumor size periodically using a digital vernier caliper. The tumor volume in cm3 was determined using the formula (volume = π/6 × length × width2) [33]. All mice were anesthetized and euthanized via cardiac puncture at the end of the treatment period. Tumors were excised and weighed, and their sizes were measured. Also, blood serum was collected from each mouse. Both tumor and serum samples were stored at -80°C for further analysis.