| Project/Area Number |
19K16761
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 50010:Tumor biology-related
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| Research Institution | Tokyo Medical University |
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Principal Investigator |
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| Project Period (FY) |
2019-04-01 – 2020-03-31
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| Project Status |
Discontinued (Fiscal Year 2019)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2020: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2019: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
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| Keywords | single-cell / drug resistance / breast cnacer / single cell / transcriptome / single-cell sequencing / metastasis / breast cancer |
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| Outline of Research at the Start |
In this study, we will use single-cell techniques with the objective to identify cells with metastatic ability within breast cancer primary tumors. First, using scRNA-seq we will characterize the metastatic nodes, to later, search for similar cells within the paired primary tumor. Moreover, we will analyze the possible presence of CTC in blood and their relation with the primary and metastatic tumors. Knowing the genes responsible for CSC phenotype and their role, will be the first step to develop a novel targeted-therapy to eventually increase the surveillance of cancer patients.
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| Outline of Annual Research Achievements |
During the obtainment of Young Scientist JSPS KAKENHI Grant we mainly focused on two topics.
The first one was in continuation to our previous studies on RNA single-cell qPCR, in which we found that the transcription factor Lef1 regulated a conjunct of genes responsible for drug resistance, paper published in the journal Cancer research. During this period of one year, we studied the application of the small molecule Quercetin to inhibit Lef1 and restore the sensitivity to docetaxel of Luminal A subtype of drug resistant breast cancer cells. These studies were presented in November in an International Conference, in New York, USA and will be presented this October, in the 79th Japanese Cancer Association. Moreover, the paper in which Quercetin properties were analyzed is summarized has been published this June in the journal Molecules.
In relation with single-cell analysis procedures and protocols, a protocol-paper was published in the journal Bioprotcol.
Finally, we started the main project regarding RNA single-cell sequencing. We stablished the protocol for single-cell dissociation and sequencing with patient-derived tumor samples on the 10X Genomics system. Overall, we started the collection of those samples and initiated with single-cell analysis and sequencing. This project was planned to be carried for 2-3 years. However, after one year of the acceptance of KANKENHI grant, the main researcher was granted with JSPS fellowship, which unable the reception of other grants including this one. We will continuous this project under the concession of JSPS fellowship.
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