Study of fibrosis in pancreatic ductal adenocarcinoma (PDAC) and application of adipose-derived stromal/stem cells for PDAC treatment
| Project/Area Number |
23K15035
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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 53010:Gastroenterology-related
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| Research Institution | Kanazawa University |
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Principal Investigator |
Ho ThuyBichTuyen 金沢大学, 医薬保健学総合研究科, 博士研究員 (80971085)
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| Project Period (FY) |
2023-04-01 – 2027-03-31
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| Project Status |
Granted (Fiscal Year 2023)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2026: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2025: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2024: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2023: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
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| Keywords | PDAC / fibrosis / immune response / ADSCs / combination therapy |
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| Outline of Research at the Start |
We will first explore how fibrosis affects the PDAC progression in the murine PDAC models, then we will investigate the anti-fibrotic capabilities of ADSCs and the consequential therapeutic effect in PDAC. The successful achievement of this purpose will provide a profound insight on the PDAC fibrosis and ADSCs potential application to cancer treatment.
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| Outline of Annual Research Achievements |
We examined the fibrosis in a mouse model of pancreatic cancer (PDAC mouse model) and the effect of treatments on these fibrotic tumors. PDAC mouse model was established by inoculating C57 BL/6J mice with PAN02 cell line (NCI, Frederick), and analyzed the fibrosis as well as the immune status of the host using immunohistochemistry (IHC). Tumor tissue of PDAC mouse model characterized by increased fibrotic component, confirmed by AZAN, Anti-Collagen I and Anti-Collagen IV staining. Regarding the immune response in tumor microenvironment, we observed the infiltration of immune-mediating cells including CD8a+, CD4+, and CD11b+ cells and myeloid-lineage inflammatory cells including F4/80+, Ly-6C+, Ly-6G+, CD86+, CD206+ cells in tumor tissue of these mice.
Next, we explored the effect of treatments on fibrosis and host immune system. We confirmed administration of Gemcitabine, a first-line anticancer drug, and immunotherapy reduced the fibrosis in these tumors. In addition, we observed a substantial increase in the infiltration of CD11b+, F4/80+, CD8a+, CD4+ cells into tumors of treated mice.
The current experiments provide a preclinical study suited to evaluate the efficacy of drugs targeting the tumor stroma.
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| Current Status of Research Progress |
Current Status of Research Progress
2: Research has progressed on the whole more than it was originally planned.
Reason
Basic research examines the fibrosis in microenvironment of pancreatic cancer. Preliminary studies have been conducted, a mouse model with fibrotic tumor has been established, and the procedure has been established in other past studies, so we believe that the overall project is progressing rather smoothly.
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| Strategy for Future Research Activity |
Plans for FY2024 will include the further analysis of immune responses in host system and the possible impact of fibrosis on treatment in PDAC mouse models.
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Report
(1 results)
Research Products
(8 results)
