Summary of Study ST002121

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 PR001346. The data can be accessed directly via it's Project DOI: 10.21228/M8QX47 This work is supported by NIH grant, U2C- DK119886.

See: https://www.metabolomicsworkbench.org/about/howtocite.php

Perform statistical analysis  |  Show all samples  |  Show named metabolites  |  Download named metabolite data  
Download mwTab file (text)   |  Download mwTab file(JSON)   |  Download data files (Contains raw data)
Study IDST002121
Study TitleFunctional metabolic molecule were identified as novel therapeutic targets to facilitate gemcitabine treatment against pancreatic cancer (Tumor tissues metabolomics)
Study SummaryWith the development of frontier technologies in system biology, traditional omics-drove phenotypic studies are insufficient to decipher the diseases. Therefore, for a thorough understanding of the molecular mechanisms of diseases to investigate novel drug targets, traditional phenotypic studies must be broken through to the functional exploration of molecules. Meanwhile, the intuitive role of small molecule compounds (metabolites) in pathogenesis, precision diagnosis and therapy are gradually recognized compared to macromolecules such as DNA, RNA and proteins. Therefore, we pioneeringly proposed Spatial Temporal Operative Real Metabolomics (STORM) strategy that established a relationship between metabolic phenotypes and functions to accurately character abnormal metabolisms and further identify operative functional molecules as novel therapeutic targets. Here, given the difficulty of pancreatic cancer (PC) treatment and the high resistance of clinical drugs, we were committed to explore new targets and drugs of pancreatic cancer from a small molecular functional perspective via STORM strategy. Fortunately, based on targeted metabolomics, we found that gemcitabine, one of the most effective clinical anti-PC drugs, served as a dual modulator that promote the accumulation of functional metabolic molecules in purine metabolism to activate down-streamed kinases. And the quantitative consequences of related enzymes annotated the unique molecular mechanisms of purine metabolism regulations by gemcitabine. Collectively, we broadened the cognitions of gemcitabine in tumor inhibition, providing potential strategies for treating PC with small molecules modification. Even more importantly, with the integration of multiple frontier technologies, the STORM strategy has proven to be well adapted to the phenotypic era of functional molecules devoted to innovate molecule mechanism annotation and therapeutic discovery.
Institute
Shanghai Center for Systems Biomedicine, Shanghai Jiaotong University
Last NameLu
First NameHaitao
Address800 Dongchuan RD. Minhang District, Shanghai,
Emailhaitao_lu@sjtu.edu.cn
Phone15221478139
Submit Date2022-03-25
Raw Data AvailableYes
Raw Data File Type(s)d
Analysis Type DetailLC-MS
Release Date2022-04-20
Release Version1
Haitao Lu Haitao Lu
https://dx.doi.org/10.21228/M8QX47
ftp://www.metabolomicsworkbench.org/Studies/ application/zip

Select appropriate tab below to view additional metadata details:


Project:

Project ID:PR001346
Project DOI:doi: 10.21228/M8QX47
Project Title:Functional metabolic molecule were identified as novel therapeutic targets to facilitate gemcitabine treatment against pancreatic cancer
Project Type:Targeted MS quantitative analysis
Project Summary:Characteristics of pancreatic cancer metabolomics with gemcitabine treatment
Institute:Shanghai Center for Systems Biomedicine, Shanghai Jiaotong University
Department:Shanghai Center for Systems Biomedicine
Laboratory:Lu Group
Last Name:Lu
First Name:Haitao
Address:800 Dongchuan RD. Minhang District, Shanghai, Shanghai, 200240, China
Email:haitao_lu@sjtu.edu.cn
Phone:15221478139

Subject:

Subject ID:SU002206
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 Treatment
SA204233M-12 times per week with 3 weeks consecutive respectively intraperitoneal injection with 0.2ml normal saline
SA204234M-72 times per week with 3 weeks consecutive respectively intraperitoneal injection with 0.2ml normal saline
SA204235M-62 times per week with 3 weeks consecutive respectively intraperitoneal injection with 0.2ml normal saline
SA204236M-32 times per week with 3 weeks consecutive respectively intraperitoneal injection with 0.2ml normal saline
SA204237M-42 times per week with 3 weeks consecutive respectively intraperitoneal injection with 0.2ml normal saline
SA204238M-52 times per week with 3 weeks consecutive respectively intraperitoneal injection with 0.2ml normal saline
SA204239G-72 times per week with 3 weeks consecutive respectively intraperitoneal injection with 25mg/kg gemcitabine in 0.2ml
SA204240G-62 times per week with 3 weeks consecutive respectively intraperitoneal injection with 25mg/kg gemcitabine in 0.2ml
SA204241G-12 times per week with 3 weeks consecutive respectively intraperitoneal injection with 25mg/kg gemcitabine in 0.2ml
SA204242G-22 times per week with 3 weeks consecutive respectively intraperitoneal injection with 25mg/kg gemcitabine in 0.2ml
SA204243G-42 times per week with 3 weeks consecutive respectively intraperitoneal injection with 25mg/kg gemcitabine in 0.2ml
SA204244G-52 times per week with 3 weeks consecutive respectively intraperitoneal injection with 25mg/kg gemcitabine in 0.2ml
Showing results 1 to 12 of 12

Collection:

Collection ID:CO002199
Collection Summary:Tumor tissues were stripped from euthanized mice for further assays
Sample Type:Subcutaneous tumor tissues of pancreatic cancer

Treatment:

Treatment ID:TR002218
Treatment Summary:All mice are fed at a constant temperature of 20-26℃ with a free choice of standard food and water with 12-hour light/dark cycle.After 2 weeks acclimatized breeding, Aspc-1 cells were injected into right armpit of nude mice when they 8 weeks old. When solid tumors can be stably observed, treating mice with 25mg/kg gemcitabine twice a week by intraperitoneal injection of Gem-treated group, meanwhile, the control group received the same volume of normal saline. Measuring tumor volume every two days. 21 days later, tumors were stripped and weighed, parts of which were embedded in paraffin for immunohistochemistry, and the residues were kept in -80 degree refrigerator.

Sample Preparation:

Sampleprep ID:SP002212
Sampleprep Summary:100-130 mg tissue samples tumor tissues have to be broken by oscillation with 60HZ and 2 minutes in iced 80% methanol solution (mixed with internal standard 0.001mg/ml 4-chloro-DL-phenylalanine). centrifuging at 20,000 g for 10 min at 4 °C, and mixing the supernatants with 800 μL ice-cold acetonitrile. Then the supernatant obtained by centrifugation was filtered through a 0.22 µm organic phase membrane, blown dry in nitrogen, reconstituted in 100 µL of water and transferred to vials for metabolomics assay.

Combined analysis:

Analysis ID AN003472 AN003473
Analysis type MS MS
Chromatography type Reversed phase Reversed phase
Chromatography system Agilent 1290 Infinity Agilent 1290 Infinity
Column Waters Acquity HSS T3 column (100 mm×2.1, 1.8 μm) Waters Acquity HSS T3 column (100 mm×2.1, 1.8 μm)
MS Type ESI ESI
MS instrument type Triple quadrupole Triple quadrupole
MS instrument name Agilent 6495 QQQ Agilent 6495 QQQ
Ion Mode POSITIVE NEGATIVE
Units counts counts

Chromatography:

Chromatography ID:CH002563
Instrument Name:Agilent 1290 Infinity
Column Name:Waters Acquity HSS T3 column (100 mm×2.1, 1.8 μm)
Chromatography Type:Reversed phase

MS:

MS ID:MS003233
Analysis ID:AN003472
Instrument Name:Agilent 6495 QQQ
Instrument Type:Triple quadrupole
MS Type:ESI
MS Comments:Agilent MassHunter Workstation Data Acquisition Agilent MassHunter
Ion Mode:POSITIVE
  
MS ID:MS003234
Analysis ID:AN003473
Instrument Name:Agilent 6495 QQQ
Instrument Type:Triple quadrupole
MS Type:ESI
MS Comments:Agilent MassHunter Workstation Data Acquisition Agilent MassHunter
Ion Mode:NEGATIVE
  logo