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Medicine for treating acute myelogenous leukemia and application thereof

A technology for acute myeloid and leukemia, applied in the field of biomedicine, can solve the problem that the role of HMA needs to be studied, and achieve the effect of enriching treatment strategies

Inactive Publication Date: 2022-07-08
THE FIRST AFFILIATED HOSPITAL OF JINAN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Studies have confirmed the effectiveness of HMA in the treatment of breast cancer, however, due to the obvious heterogeneity of solid tumors and hematological tumors, the role of HMA in AML remains to be studied

Method used

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  • Medicine for treating acute myelogenous leukemia and application thereof
  • Medicine for treating acute myelogenous leukemia and application thereof
  • Medicine for treating acute myelogenous leukemia and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0052] Proliferation inhibition and apoptosis promotion of NHE1 inhibitor HMA on leukemia cells:

[0053] Will 4x10 6 MV4-11 cells were seeded in a six-well plate, and different concentrations of NHE1 inhibitors were added to make the final concentrations 0, 5 μM, 10 μM, and 20 μM, respectively. Blow evenly, and put them in an incubator for 48 hours. After culturing for 48 hours, the following experiments were performed:

[0054] (1) Intracellular pH detection:

[0055] To develop a standard curve: wash cells twice with PBS, add BCECF-AM probe at a final concentration of 5 μM, and stain for 30 minutes at room temperature in the dark. Wash once with PBS, resuspend with different pH calibration buffers, add 10 μmol Nigericin and Valinomycin, and incubate for 10 minutes to make the intracellular pH reach 4.5, 5.5, 6.5, and 7.5, respectively; use a microplate reader to detect when the excitation light is 490 nm and 440nm, the emission light is the fluorescence intensity of 535nm...

Embodiment 2

[0065] Proliferation-inhibiting and apoptosis-promoting effects of HMA on primary cells of AML patients:

[0066] (1) Isolation and culture of bone marrow mononuclear cells:

[0067] Collect 5mL of fresh bone marrow samples from AML patients into a purple-headed heparin anticoagulant tube, mix the fresh bone marrow samples with an equal volume of PBS (pre-cooled at 4°C) evenly; take a clean 15mL centrifuge tube, add 3mL of human lymphocytes to the tube to separate Aspirate the above diluted bone marrow sample, tilt the centrifuge tube at 45 degrees to avoid shaking, and slowly add the bone marrow sample to the lymphocyte separation solution along the wall of the centrifuge tube, so that there is a clear separation between the separation solution and the bone marrow fluid level. Floor. The centrifuge tube was placed in a centrifuge and centrifuged at 2000 rpm for 20 minutes. Gently take out the centrifuge tube, avoid shaking, take another 15mL sterile centrifuge tube and add ...

Embodiment 3

[0074] The combined application of HMA and venetoclax inhibits the proliferation and promotes apoptosis of leukemia cells:

[0075] Will 4x10 6 MV4-11 cells were seeded in a six-well plate, and were given no drug, 0.1 μM venetoclax, 10 μM HMA and the combination of the two drugs; they were blown evenly and placed in an incubator for 48 hours to conduct the following experiments:

[0076] (1) Cell viability detection:

[0077] MV4-11 cells were plated at 5 x 10 4 Cells / mL were seeded in 96-well plates. Cells with different treatments were set to 3-4 sub-wells, and the volume of each well was 100 μL. Put it into a cell incubator and cultivate for 48 hours; add 10 μl of CCK8 working solution to each well, mix well, and continue to incubate in the dark in the incubator for 3 hours, and then use a microplate reader to detect the absorbance at a wavelength of 450 nm. The result is as Figure 7 shown, Figure 7 It shows that both venetoclax and HMA can significantly inhibit the ...

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Abstract

The invention relates to a medicine for treating acute myelogenous leukemia and application thereof. The medicine for treating acute myelogenous leukemia comprises an NHE1 inhibitor HMA. The invention creatively finds that the NHE1 inhibitor HMA can significantly inhibit the progress of acute myelogenous leukemia, is used as a medicine for treating acute myelogenous leukemia, and enriches the treatment strategy of acute myelogenous leukemia. The invention also relates to a pharmaceutical composition for treating acute myelogenous leukemia, the pharmaceutical composition comprises HMA and a chemotherapeutic drug, and the invention proves that the combination of HMA and the chemotherapeutic drug can enhance the killing effect of the chemotherapeutic drug on AML cells on one hand; on the other hand, the dosage of chemotherapeutic drugs can be reduced, and toxic and side effects of the chemotherapeutic drugs on human bodies are relieved.

Description

technical field [0001] The invention belongs to the technical field of biomedicine, relates to a new drug use of NHE1 inhibitor HMA, and in particular relates to a drug for treating acute myeloid leukemia and its application. Background technique [0002] Acute myeloid leukemia (AML) is a group of highly heterogeneous hematological malignancies caused by the clonal proliferation of immature myeloid blasts. Currently, there are limited treatment options for AML, and induction chemotherapy is still the standard Although some patients respond to induction chemotherapy, refractory disease and relapse are major causes of treatment failure. In addition, elderly patients are less effective, with a median survival of only 5-10 months. Several new drugs for the treatment of AML have been approved by the FDA since 2017, including the BCL2-specific inhibitor Venetoclax (VEN). However, clinically acquired resistance to venetoclax is a problem. Therefore, it is crucial to explore new ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/55A61K45/06A61P35/02A61K31/706A61K31/7068A61K31/496
CPCA61K31/55A61K45/06A61P35/02A61K31/706A61K31/7068A61K31/496A61K2300/00
Inventor 曾辉姜欣雅杜鹃刘芳舒华蕾孙晓凡
Owner THE FIRST AFFILIATED HOSPITAL OF JINAN UNIV
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