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Use of cis-platinum in treatment on high-level granulocyte-like myeloid derived suppressor cell (G-MDSC) bladder cancer

A high-level technology for bladder cancer, applied in the field of medicine, can solve the problem of strong side effects of cisplatin, and achieve the effect of enhancing the inhibitory effect and promoting the tumor killing function.

Inactive Publication Date: 2017-07-14
SHANGHAI FIRST PEOPLES HOSPITAL
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the side effects of cisplatin are relatively strong, mainly manifested in: 1) gastrointestinal reactions such as nausea and vomiting

Method used

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  • Use of cis-platinum in treatment on high-level granulocyte-like myeloid derived suppressor cell (G-MDSC) bladder cancer
  • Use of cis-platinum in treatment on high-level granulocyte-like myeloid derived suppressor cell (G-MDSC) bladder cancer
  • Use of cis-platinum in treatment on high-level granulocyte-like myeloid derived suppressor cell (G-MDSC) bladder cancer

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0068] Example 1 Analysis of the level of immunosuppressive cells derived from myeloid bone marrow in bladder cancer tissue

[0069] 1) Increased G-MDSC level in bladder cancer focus tissue

[0070] Firstly, relevant test data were collected, and it was found that CD8+ T cells in the peripheral blood of patients with bladder cancer increased compared with healthy people (such as figure 1 Shown in A); then the immune cells in the bladder cancer focus tissue and paracancerous bladder tissue were obtained by primary isolation, and CD3+CD8+ T cells in the cancer focus tissue were detected by flow cytometry (both flow cytometry antibodies were from Biolegend Company) Significantly less than the adjacent bladder tissue (such as figure 1 B), and CD11b+CD33+CD15+CD14-G-MDSC significantly increased compared with adjacent bladder tissue (such as figure 1 C, shown in 1D). The proportion of G-MDSC in bladder cancer focus tissue was significantly negatively correlated with CD8+ T cells ...

Embodiment 2

[0071] Example 2 In vitro experiments confirm the function of cisplatin in killing bladder cancer cells and G-MDCS

[0072] 1) Cisplatin inhibits proliferation and promotes apoptosis of bladder cancer cell T24

[0073] Cisplatin is a platinum-containing chemical (such as figure 2 shown in A). Concentration gradient 0, 0.1, 1, 10 μ M cisplatin treated T24 cells for 24 hours, the Cell Counting Kit-8 kit was used to detect the number of cells and compared with the control group. T24 cells were treated with 10 μM cisplatin for 0, 12, 24, 48, and 72 hours, and the number of viable cells was detected with the Cell Counting Kit-8 kit (T24 cells were from Shanghai South Model Animal Center, and the Cell Counting Kit-8 kit was from Yeasen Company) . It is found that within a certain range, the increase of cisplatin concentration and the prolongation of treatment time can effectively inhibit the proliferation of bladder cancer cells T24 (such as figure 2 B, shown in 2C). Hochest ...

Embodiment 3

[0076] Example 3 In vitro experiments confirm that cisplatin can indirectly enhance the immune function of CD8+ T cells by killing G-MDSC

[0077] First, we treated CD8+ T cells isolated from peripheral blood with 10 μM cisplatin (CD8+ T cell separation magnetic beads were purchased from Miltenyi). After 48 hours, we used flow cytometry to analyze the proportion of CD8+ T cells. After CD8+ T cells did not change significantly (such as Figure 4 shown in A). CD33+ cells were isolated from PMN by magnetic bead sorting. Cytokines IL-6 and GM-CSF were added to train for 7 days, and then 10 μM cisplatin was added to treat for 48 hours. G-MDSC: CD8+ T cells were 1:100, 1: 10. After 1:1 co-culture for 48 hours, the proliferation of CFSE-labeled CD8+ T cells was analyzed by flow cytometry (CFSE reagents were from Biolegend). The inhibitory effect on cells is the strongest, and at the same time, cisplatin can indirectly promote the proliferation of CD8+ T cells by reducing G-MDSC (su...

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Abstract

The invention relates to the technical field of medicine and relates to a use of cis-platinum and particularly relates to a use of cis-platinum in high-level granulocyte-like myeloid derived suppressor cell (G-MDSC) bladder cancer treatment and a treatment method. In-vitro experiment and in-vivo animal experiment results show that the amount of G-MDSC in a bladder cancer focus is significantly increased than that of G-MDSC in a paracancerous control group and the amount of CD8+T in a bladder cancer focus is reduced than that of CD8+T in the control group so that an immunosuppressive microenvironment is induced and formed and the establishment and growth of bladder cancer are promoted. The cis-platinum chemotherapy can significantly inhibit the progress of bladder cancer caused by abnormal increasing of G-MDSC and can be further used for high level G-MDSC bladder cancer treatment.

Description

technical field [0001] The invention belongs to the technical field of medicine and relates to the use of cisplatin, in particular to the application of cisplatin in the treatment of high-level myeloid bone marrow-derived immunosuppressive cell bladder cancer. In vitro and in vivo animal experiments have shown that cisplatin can effectively reduce the myeloid-myeloid-derived suppressor cells (G-MDSC) in bladder cancer tissues, thereby enhancing the tumor-killing activity of CD8+ effector T cells. Quantity and activity, killing bladder cancer cells. Cisplatin can significantly weaken the immunosuppressive effect in bladder cancer foci, obviously inhibit the growth of bladder cancer cells, promote the apoptosis of bladder cancer cells, and can be further used in the treatment of bladder cancer. Background technique [0002] Bladder cancer is one of the common tumors that seriously endanger human health, and its incidence is increasing year by year. Currently, bladder cancer ...

Claims

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Application Information

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IPC IPC(8): A61K33/24A61K39/395A61P35/00C12Q1/02
CPCA61K39/39558G01N33/5047A61K33/24G01N2800/7028A61K2300/00
Inventor 刘志宏伍科贺银燕李明清周文洁王仁杰
Owner SHANGHAI FIRST PEOPLES HOSPITAL
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