2020 Fiscal Year Research-status Report
Development of a lymphatic drug delivery system to treat very early metastatic lymph nodes
| Project/Area Number |
20K20161
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| Research Institution | Tohoku University |
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Principal Investigator |
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| Project Period (FY) |
2020-04-01 – 2022-03-31
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| Keywords | がん / リンパ節 / 転移 / 薬物送達法 / リンパ行性 |
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| Outline of Annual Research Achievements |
ISSUE A. perfusion defects in LNs were observed with each imaging modality, and the LNs were subjected to pathological analyses to determine whether they were cN0 or N1. The present finding was that in the early stage of metastasis, tumor cells replace microvascular areas to form a perfusion defect that is not pathologically necrotic tissue. During perfusion defect formation, replacement of parenchyma with tumor supplied by only a few microvessels occurs, intranodal pressure increased, pO2 remained constant and tumor neovascularization was not induced. Perfusion defects, which are formed by the replacement of LN parenchyma with tumor cells, have also been observed with intranodal lymphangiography in non-enlarged LNs. The characteristics of perfusion defect formation in LNs may explain why metastatic LNs show an inadequate response to hematologic systemic chemotherapy using small-molecule and macromolecular anticancer agents.
Issue B. From this study, we found that optimal osmotic pressure range of LDDS solution for the treatment of metastatic LNs is 695 - 2,780 kPa, and for viscosity less than 40 mPas. Up to this viscosity value, the macroscopic flow dynamics of the drug did not significantly differ.
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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
We are doing normally for our research and analysis. But due to COVID-19 pandemic, last year, for sometime we stopped experiment for some researchers. Trying to catch up time.
For issue A and B, need to clarify few things and they will be finish.
For issue C, under investigation.
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| Strategy for Future Research Activity |
[Issue C] Clarify the parameters (factors) of the LDDS administration and antitumor effects on clinical N0 lymph nodes
We assumed that cN0LN can be treated and/or prevented using LDSS by receiving chemotherapeutic agents directly into SLN and deliver them into its downstream LN. Also, chemotherapeutic agent dosage and rate of administration are considerable parameters too. Our research members found that amount of the delivered fluorescent solution from SiLN to PALN is depends on the administration velocity and duration (J Biophotonics. 2018 Aug;11(8):e201700401). In this study, we determined administration parameters for the better delivery from SiLN to PALN along with optimized ranges of osmotic pressure and viscosity for the cN0LN described in Issue A and B. Tumor growth and volume changes of LN, therapeutic effect, pharmacokinetics, and side effects were evaluated according to Issue A and B.
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| Causes of Carryover |
The unused amount generated by the efficient promotion of research in the current fiscal year will be used in next fiscal year (FY). This amount, together with the amount requested for FY2021, will be used to carry out research in FY2021.
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