Summary of Study ST002255
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
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 | ST002255 |
| Study Title | Functional metabolic molecules were identified as novel therapeutic targets to facilitate gemcitabine treatment against pancreatic cancer (Cells metabolomics with ATP) |
| Study Summary | With 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 |
| 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 |
| jingjing2018@sjtu.edu.cn | |
| Phone | 18818211315 |
| Submit Date | 2022-08-04 |
| Raw Data Available | Yes |
| Raw Data File Type(s) | d |
| Analysis Type Detail | LC-MS |
| Release Date | 2022-08-22 |
| Release Version | 1 |
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: | SU002341 |
| Subject Type: | Cultured cells |
| Subject Species: | Homo sapiens |
| Taxonomy ID: | 9606 |
Factors:
Subject type: Cultured cells; Subject species: Homo sapiens (Factor headings shown in green)
| mb_sample_id | local_sample_id | Treatment |
|---|---|---|
| SA217097 | ASPC-CATP-1 | 25µl DMSO and 40µM ATP for 72h |
| SA217098 | ASPC-CATP-5 | 25µl DMSO and 40µM ATP for 72h |
| SA217099 | ASPC-CATP-4 | 25µl DMSO and 40µM ATP for 72h |
| SA217100 | ASPC-CATP-2 | 25µl DMSO and 40µM ATP for 72h |
| SA217101 | ASPC-CATP-3 | 25µl DMSO and 40µM ATP for 72h |
| SA217102 | ASPC-GATP-5 | 50µM gemcitabine and 40µM ATP for 72h |
| SA217103 | ASPC-GATP-4 | 50µM gemcitabine and 40µM ATP for 72h |
| SA217104 | ASPC-GATP-1-r002 | 50µM gemcitabine and 40µM ATP for 72h |
| SA217105 | ASPC-GATP-2 | 50µM gemcitabine and 40µM ATP for 72h |
| SA217106 | ASPC-GATP-3 | 50µM gemcitabine and 40µM ATP for 72h |
| Showing results 1 to 10 of 10 |
Collection:
| Collection ID: | CO002334 |
| Collection Summary: | After 72 hours of drug treatment, the cells were washed twice with ice PBS and scraped in 80% ice methanol |
| Sample Type: | Tumor cells |
Treatment:
| Treatment ID: | TR002353 |
| Treatment Summary: | Cells were evenly divided into 3 groups of 6 discs each. 24h after cell inoculation, gemcitabine administration group(GATP) was treated with gemcitabine with final concentration of 50μM for 72h and ATP with a final concentration of 40μM, Meanwhile, the control group (CATP) was given the same volume of DMSO with 40μM ATP. One plate of cells was taken from each group for counting, and the rest were collected for metabolite extraction |
Sample Preparation:
| Sampleprep ID: | SP002347 |
| Sampleprep Summary: | The cells were cultured as described above and fixed with 1 ml of 80% ice-cold menthol after being washed twice with ice-cold PBS. The cells were scraped from the plates, and 0.5-mm beads were added to process the cells by grinding and shaking. The supernatants were collected after centrifugation and deproteinized by mixing with 800μL acetonitrile on ice. Then, the supernatants collected and spun down under nitrogen at room temperature. The samples were resuspended in 100 μL of distilled H2O, and 5 μL was used for LC-TQ-MS-based metabolome assay. |
Combined analysis:
| Analysis ID | AN003683 | AN003684 |
|---|---|---|
| Analysis type | MS | MS |
| Chromatography type | Reversed phase | Reversed phase |
| Chromatography system | Agilent 1290 Infinity | Agilent 1290 Infinity |
| Column | Waters Acquity HSS T3 (100 x 2.1mm,1.8um) | Waters Acquity HSS T3 (100 x 2.1mm,1.8um) |
| 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: | CH002731 |
| Instrument Name: | Agilent 1290 Infinity |
| Column Name: | Waters Acquity HSS T3 (100 x 2.1mm,1.8um) |
| Chromatography Type: | Reversed phase |
MS:
| MS ID: | MS003434 |
| Analysis ID: | AN003683 |
| 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: | MS003435 |
| Analysis ID: | AN003684 |
| Instrument Name: | Agilent 6495 QQQ |
| Instrument Type: | Triple quadrupole |
| MS Type: | ESI |
| MS Comments: | Agilent MassHunter Workstation Data Acquisition Agilent MassHunter |
| Ion Mode: | NEGATIVE |
