Summary of Study ST001467

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 PR000999. The data can be accessed directly via it's Project DOI: 10.21228/M8K10H This work is supported by NIH grant, U2C- DK119886.

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Study IDST001467
Study TitleMetabolites changes related to glucose-mediated energy production in chemotheraphy-induced cachexia
Study SummaryTargeted metabolomics platforms included amino acids and metabolites related to glucose-mediated energy production. The targeted metabolome changed with chemotheraphy-induced cachexia, and the changes were reversed with potential treatment of the cachexia. .rdb files were included as raw data files where detailed information regarding MRM transitions and internal standards can be found. Several amino acids (Gly, Pro, Gln, Taurine) were analyzed after dilution because their peak intensities were too high. Thus their analysis was performed separately from other amino acids, and their rdb files were saved in separate rdb files.
Institute
Asan Medical Center; University of Ulsan
Last NameYoo
First NameHyun Ju
Address88, Olympic-ro, 43-gil, Songpa-gu, Seoul 05505, South Korea
Emailyoohyunju@amc.seoul.kr
Phone82-02-3010-4029
Submit Date2020-08-18
Raw Data AvailableYes
Analysis Type DetailLC-MS
Release Date2020-09-21
Release Version1
Hyun Ju Yoo Hyun Ju Yoo
https://dx.doi.org/10.21228/M8K10H
ftp://www.metabolomicsworkbench.org/Studies/ application/zip

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Project:

Project ID:PR000999
Project DOI:doi: 10.21228/M8K10H
Project Title:Treatment of chemotherapy-induced cachexia with BST204: a multimodal validation study
Project Summary:A multimodal approach was performed to investigate the effects of BST204 on the alleviation of chemotherapy-induced cachexia. The targeted metabolome changed with chemotheraphy-induced cachexia and the changes were reversed with potential treatment of the cachexia.
Institute:Asan Medical Center; University of Ulsan
Last Name:Yoo
First Name:Hyun Ju
Address:88, Olympic-ro, 43-gil, Songpa-gu, Seoul 05505, South Korea
Email:yoohyunju@amc.seoul.kr
Phone:82-02-3010-4029

Subject:

Subject ID:SU001541
Subject Type:Mammal
Subject Species:Mus musculus
Taxonomy ID:10090

Factors:

Subject type: Mammal; Subject species: Mus musculus (Factor headings shown in green)

mb_sample_id local_sample_id Group Treatment Sample Source
SA1243285FU_2mbatch1 5FU muscle
SA1243295FU_1m_1batch1 5FU muscle
SA1243305FU_1mbatch1 5FU muscle
SA1243315FU_3mbatch1 5FU muscle
SA1243325FU_3m_2batch1 5FU muscle
SA1243335FU_2m_1batch1 5FU muscle
SA1243345FU_1m_2batch1 5FU muscle
SA1243355FU_3m_1batch1 5FU muscle
SA1243365FU_2m_2batch1 5FU muscle
SA1243375FU_3pbatch1 5FU plasma
SA1243385FU_1p_2batch1 5FU plasma
SA1243395FU_2pbatch1 5FU plasma
SA1243405FU_3p_2batch1 5FU plasma
SA1243415FU_2p_2batch1 5FU plasma
SA1243425FU_1pbatch1 5FU plasma
SA124343BST100_2m_2batch1 BST204 muscle
SA124344BST200_3m_2batch1 BST204 muscle
SA124345BST200_1m_2batch1 BST204 muscle
SA124346BST100_3m_2batch1 BST204 muscle
SA124347BST100_1m_2batch1 BST204 muscle
SA124348BST100_2mbatch1 BST204 muscle
SA124349BST200_1mbatch1 BST204 muscle
SA124350BST100_3mbatch1 BST204 muscle
SA124351BST200_1m_1batch1 BST204 muscle
SA124352BST200_2m_1batch1 BST204 muscle
SA124353BST200_3m_1batch1 BST204 muscle
SA124354BST200_2mbatch1 BST204 muscle
SA124355BST100_3m_1batch1 BST204 muscle
SA124356BST200_2m_2batch1 BST204 muscle
SA124357BST100_1m_1batch1 BST204 muscle
SA124358BST100_2m_1batch1 BST204 muscle
SA124359BST100_1mbatch1 BST204 muscle
SA124360BST100_1p_2batch1 BST204 plasma
SA124361BST200_1pbatch1 BST204 plasma
SA124362BST100_1pbatch1 BST204 plasma
SA124363BST100_2pbatch1 BST204 plasma
SA124364BST200_2p_2batch1 BST204 plasma
SA124365BST200_1p_2batch1 BST204 plasma
SA124366BST100_2p_2batch1 BST204 plasma
SA124367BST100_3p_2batch1 BST204 plasma
SA124368BST200_3p_2batch1 BST204 plasma
SA124369BST200_2pbatch1 BST204 plasma
SA124370BST200_3pbatch1 BST204 plasma
SA124371TB_2m_2batch1 Control muscle
SA124372TB_1m_2batch1 Control muscle
SA124373NTB_1m_2batch1 Control muscle
SA124374TB_3m_2batch1 Control muscle
SA124375NTB_2m_2batch1 Control muscle
SA124376TB_3mbatch1 Control muscle
SA124377NTB_2mbatch1 Control muscle
SA124378NTB_1m_1batch1 Control muscle
SA124379NTB_1mbatch1 Control muscle
SA124380TB_1m_1batch1 Control muscle
SA124381TB_3m_1batch1 Control muscle
SA124382TB_2m_1batch1 Control muscle
SA124383TB_1mbatch1 Control muscle
SA124384NTB_2m_1batch1 Control muscle
SA124385TB_2mbatch1 Control muscle
SA124386TB_3pbatch1 Control plasma
SA124387TB_3p_2batch1 Control plasma
SA124388TB_2pbatch1 Control plasma
SA124389NTB_1pbatch1 Control plasma
SA124390NTB_2pbatch1 Control plasma
SA124391TB_1pbatch1 Control plasma
SA124392TB_1p_2batch1 Control plasma
SA124393TB_2p_2batch1 Control plasma
SA124394NTB_2p_2batch1 Control plasma
SA124395NTB_1p_2batch1 Control plasma
SA1243965FU_5mbatch2 5FU muscle
SA1243975FU_4mbatch2 5FU muscle
SA1243985FU_6mbatch2 5FU muscle
SA1243995FU_6m_1batch2 5FU muscle
SA1244005FU_4m_2batch2 5FU muscle
SA1244015FU_6m_2batch2 5FU muscle
SA1244025FU_4m_1batch2 5FU muscle
SA1244035FU_5m_1batch2 5FU muscle
SA1244045FU_5m_2batch2 5FU muscle
SA1244055FU_4p_2batch2 5FU plasma
SA1244065FU_4pbatch2 5FU plasma
SA1244075FU_6p_2batch2 5FU plasma
SA1244085FU_6pbatch2 5FU plasma
SA1244095FU_5p_2batch2 5FU plasma
SA1244105FU_5pbatch2 5FU plasma
SA124411BST200_6mbatch2 BST204 muscle
SA124412BST200_4m_2batch2 BST204 muscle
SA124413BST200_6m_2batch2 BST204 muscle
SA124414BST200_5mbatch2 BST204 muscle
SA124415BST100_6mbatch2 BST204 muscle
SA124416BST200_3mbatch2 BST204 muscle
SA124417BST200_4mbatch2 BST204 muscle
SA124418BST100_4mbatch2 BST204 muscle
SA124419BST100_4m_1batch2 BST204 muscle
SA124420BST100_6m_2batch2 BST204 muscle
SA124421BST200_4m_1batch2 BST204 muscle
SA124422BST200_5m_1batch2 BST204 muscle
SA124423BST200_6m_1batch2 BST204 muscle
SA124424BST100_5mbatch2 BST204 muscle
SA124425BST100_5m_2batch2 BST204 muscle
SA124426BST100_5m_1batch2 BST204 muscle
SA124427BST100_6m_1batch2 BST204 muscle
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Collection:

Collection ID:CO001536
Collection Summary:Mice were randomized into five groups (n = 10 each): untreated, non-tumor-bearing mice (NTB group); untreated, tumor-bearing mice (TB group); tumor-bearing mice receiving 5-FU (5-FU group); tumor-bearing mice receiving 5-FU and 100-mg/kg BST204 (BST204100 group); and tumor-bearing mice receiving 5-FU and 200-mg/kg BST204 (BST204200 group). CT26 murine colon carcinoma cells (1 × 106) (Korean Cell Line Bank, Seoul, Korea) resuspended in 100 μL of phosphate-buffered saline were subcutaneously implanted in the right flank of 8-week-old BALB/c mice (Orient Bio, Seongnam, Korea). When tumor volumes reached 100–200 mm3 (approximately 10 days after tumor cell injection), day 0 was assigned and drug administration started for 5-FU and BST204 groups. BST204 (batch number 31037/H1) was obtained from Green Cross Wellbeing (Seongnam, South Korea), and 5-FU was purchased from Sigma-Aldrich (St. Louis, MO, USA). 5-FU (50 mg/kg) was injected intraperitoneally in 3-day cycles (1st cycle: days 0–2; 2nd cycle: days 6–8), in doses that did not exceed the clinically acceptable. BST204 (100 or 200 mg/kg) was orally administered in 5-day cycles (1st cycle: days 0–4; 2nd cycle: days 6–10). The BST204 doses were determined according to its effects on chemotherapy-related fatigue and toxicity. The endpoint of our study was determined according to IACUC guidelines, which recommend euthanasia with a maximum tumor volume of 1,500 mm3 and a BW loss of 20%. Therefore, our study period was limited to day 11. At this point, the change in tumor volumes was up to 810%, and significant cachexia was observed.
Sample Type:Blood (plasma)
Collection Location:muscle
Storage Conditions:-20℃

Treatment:

Treatment ID:TR001556
Treatment Summary:Mice were randomized into five groups (n = 10 each): untreated, non-tumor-bearing mice (NTB group); untreated, tumor-bearing mice (TB group); tumor-bearing mice receiving 5-FU (5-FU group); tumor-bearing mice receiving 5-FU and 100-mg/kg BST204 (BST204100 group); and tumor-bearing mice receiving 5-FU and 200-mg/kg BST204 (BST204200 group). CT26 murine colon carcinoma cells (1 × 106) (Korean Cell Line Bank, Seoul, Korea) resuspended in 100 μL of phosphate-buffered saline were subcutaneously implanted in the right flank of 8-week-old BALB/c mice (Orient Bio, Seongnam, Korea). When tumor volumes reached 100–200 mm3 (approximately 10 days after tumor cell injection), day 0 was assigned and drug administration started for 5-FU and BST204 groups. BST204 (batch number 31037/H1) was obtained from Green Cross Wellbeing (Seongnam, South Korea), and 5-FU was purchased from Sigma-Aldrich (St. Louis, MO, USA). 5-FU (50 mg/kg) was injected intraperitoneally in 3-day cycles (1st cycle: days 0–2; 2nd cycle: days 6–8), in doses that did not exceed the clinically acceptable. BST204 (100 or 200 mg/kg) was orally administered in 5-day cycles (1st cycle: days 0–4; 2nd cycle: days 6–10). The BST204 doses were determined according to its effects on chemotherapy-related fatigue and toxicity. The endpoint of our study was determined according to IACUC guidelines, which recommend euthanasia with a maximum tumor volume of 1,500 mm3 and a BW loss of 20%. Therefore, our study period was limited to day 11. At this point, the change in tumor volumes was up to 810%, and significant cachexia was observed.
Treatment:5-FU was injected intraperitoneally in 3-day cycles. BST204 was orally administerd in 5-day cycles.
Treatment Compound:5-FU, BST204
Treatment Dose:5-FU (50 mg/kg), BST204 (100 or 200 mg/kg)
Animal Endp Euthanasia:study period was limited by day 11

Sample Preparation:

Sampleprep ID:SP001549
Sampleprep Summary:Metabolites related to glucose-mediated energy metabolism were extracted using LLE. Amino acids and bioamines were also extracted using LLE and underwent chemical derivatization with phenylisothiocyante.
Processing Storage Conditions:4℃
Extraction Method:Liquid Liquid Extraction (LLE)

Combined analysis:

Analysis ID AN002443
Analysis type MS
Chromatography type Reversed phase
Chromatography system Agilent 1290
Column Zorbax Eclipse XDB-C18 (100 x 2mm)
MS Type ESI
MS instrument type Triple quadrupole
MS instrument name ABI Sciex 5500 QTrap
Ion Mode POSITIVE
Units area ratio

Chromatography:

Chromatography ID:CH001788
Chromatography Summary:Metabolites related to glucose-mediated metabolites were analyzed with LC-MS/MS (MRM)
Instrument Name:Agilent 1290
Column Name:Synergi fusion RP (50 x 2mm)
Column Temperature:23
Flow Gradient:0% B for 5 min, 0% to 90% B for 2 min, hold at 90% B for 8 min, 90% to 0% B for 1 min, and then hold at 0% B for 9 min
Flow Rate:70 μL/min except for minutes 7 to 15, when it was 140 µL/min
Internal Standard:13C5-glutamine
Sample Injection:3 uL
Solvent A:100% water; 5 mM ammonium acetate
Solvent B:100% acetonitrile; 5 mM ammonium acetate
Chromatography Type:Reversed phase
  
Chromatography ID:CH001789
Chromatography Summary:Amino acids and bioamines were analyzed with LC-MS/MS (MRM)
Instrument Name:Agilent 1290
Column Name:Zorbax Eclipse XDB-C18 (100 x 2mm)
Column Temperature:50
Flow Gradient:0% B for 0.5 min, 0% to 95% B for 5 min, hold at 95% B for 1 min, 95% to 0% B for 0.5 min, then hold at 0% B for 2.5 min
Flow Rate:500 μL/min
Internal Standard:13C5-glutamine, serotonine-d4, dopamine-d4, tryptophan-d5, serine-d3, and lysine-d8
Sample Injection:3 uL
Solvent A:100% water; 0.2% formic acid
Solvent B:100% acetonitrile; 0.2% formic acid
Chromatography Type:Reversed phase

MS:

MS ID:MS002267
Analysis ID:AN002443
Instrument Name:ABI Sciex 5500 QTrap
Instrument Type:Triple quadrupole
MS Type:ESI
MS Comments:Amino acids and bioamines MRM mode Analyst 1.52
Ion Mode:POSITIVE
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