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.

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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

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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.
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