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Application of ERBB4 in gastric cancer treatment aspect

A technology for ERBB4 and gastric cancer, which is applied in the field of biomedicine, can solve negative problems and achieve the effect of significantly increasing sensitivity and inhibiting tumor growth

Active Publication Date: 2018-12-21
SUN YAT SEN UNIV CANCER CENT
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Although the study was well designed with appropriate endpoints, inclusion criteria, chemotherapy backbone, and toxicity management protocol, the results of this trial should still be considered negative

Method used

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  • Application of ERBB4 in gastric cancer treatment aspect
  • Application of ERBB4 in gastric cancer treatment aspect
  • Application of ERBB4 in gastric cancer treatment aspect

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0033] Example 1 Effect of ERBB4 mutation on the growth of gastric cancer cells

[0034] 1. Experimental materials

[0035] (1) Cancer cells: human gastric cancer cells AGS, MKN74, MKN45.

[0036] 2. Experimental grouping

[0037] (1) Control group: fluorescent blank control (RFP), that is, it does not affect the expression of ERBB4 in cancer cells.

[0038] (2) Wild-type experimental group: WT, that is, the expression of ERBB4 overexpression, without mutation.

[0039] (3) Mutant experimental group: R50C, R393W, S774G, L798R, and ERBB4 overexpression and mutation.

[0040] 3. Effect of ERBB4 mutation on cell growth and tumorigenesis

[0041] (1) Pave gastric cancer cells in a six-well plate, and after they adhere to the wall, transfect ERBB4-RFP, WT, R50C, R393W, S774G, L798R adenovirus, observe the transfection efficiency with 72h fluorescence, and observe its effect on gastric cancer cells growth effect.

[0042] The specific method of cell growth curve determination ...

Embodiment 2

[0052] Example 2 The effect of ERBB4 overexpression and the sensitivity of mutant gastric cancer cells to small molecule inhibitors (lapatinib, pyrotinib)

[0053] 1. Experimental materials

[0054] (1) Drugs:

[0055] 1) Lapatinib (lapatinib): purchased from Selleck, catalog number S2111.

[0056] The chemical structural formula of lapatinib is as follows:

[0057]

[0058] 2) Pyrotinib (pyrrotinib maleate): provided by Jiangsu Hengrui Company.

[0059] The chemical structural formula of Pyrotinib is as follows:

[0060]

[0061] (2) Cancer cells: Same as Example 1.

[0062] (3) Commercially available MTS kit.

[0063] 2. The activity of AGS cells after treatment with lapatinib and pyrotinib was detected by MTT method

[0064] (1) Pave the gastric cancer AGS cells in a 96-well plate, and after they adhere to the wall, add the medium containing 0 μM, 8 μM, 10 μM, 12 μM, 15 μM, 20 μM, 25 μM laptinib to treat the cells, and the concentration distribution of pyrotinib i...

Embodiment 3

[0071] Example 3 Small molecule inhibitors (lapatinib, pyrotinib) significantly increase the tumor inhibition rate of ERBB4 overexpression and mutation in vivo

[0072] 1. Experimental materials

[0073] (1) Drugs: According to Selleck drug recommendations, both lapatinib and pyrotinib were prepared with 2% DMSO+30% PEG300+5% Tween 80+ddH2O.

[0074] (2) Gastric cancer cells: human gastric cancer cells MKN74 and MKN45.

[0075] 2. Through in vivo experiments in nude mice, observe the tumor suppressive effect of small molecule inhibitors (lapatinib, pyrotinib) on ERBB4 overexpression and mutation

[0076] (1) Use MKN74 and MKN45 to construct ERBB4 control, overexpression (WT), and mutation (R393W, L798R) cells in vitro. After reaching a certain number, inoculate them subcutaneously in mice until the tumor grows to about 100mm 3 Start grouping lapatinib and pyrotinib.

[0077] The specific method is as follows:

[0078] 1) Evenly spread MKN74 and MKN45 in the logarithmic gro...

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Abstract

The invention discloses an application of ERBB4 in gastric cancer treatment aspect, and specifically relates to the application of the ERBB4 as the marker for guiding the gastric cancer patient personalized medication and as therapeutic target aspect, and the application of small molecule inhibitor for preparing the medicine for ERBB4 over-expressed and / or ERBB4 mutant gastric cancer treatment. The research shows that the sensitivity on the small molecule inhibitor by the ERBB4 over-expressed gastric cancer cell is increased, the small molecule inhibitor can produce obvious inhibition effect the ERBB4 over-expressed gastric cancer cell, thereby achieving the therapeutic effect of obviously inhibiting the tumor growth; and meanwhile, the ERBB4 over-expressed and mutant gastric cell sensitivity is increased more obviously, thereby playing the obvious effect for inhibiting the tumor growth. The personalized precise medicine of the gastric cancer patient can be guided, the ERBB4 mutant andover-expressed gastric cancer is treated in a targeted way by using the small molecule inhibitor, thereby providing further accuracy for the gastric cancer treatment.

Description

technical field [0001] The invention belongs to the technical field of biomedicine. More specifically, it relates to the application of ERBB4 in the treatment of gastric cancer, especially in guiding personalized medicine for gastric cancer patients and as a therapeutic target. Background technique [0002] Gastric cancer is a common gastrointestinal tumor in the world, ranking first among all kinds of malignant tumors in my country, and one of the main causes of death worldwide, and there are great difficulties in clinical treatment. [0003] The family of receptor tyrosine kinases (RTKs) mainly includes: epidermal growth factor receptor (EGFR), HER2, HER3, HER4. Lapatinib is a small molecule tyrosine kinase inhibitor (TKI) that targets HER2 and EGFR and has been approved by the FDA in combination with capecitabine for the treatment of HER2-positive metastatic disease refractory to trastuzumab. breast cancer. Since lapatinib showed single-agent activity in the HER2-posit...

Claims

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Application Information

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IPC IPC(8): G01N33/68G01N33/574A61K45/00A61P35/00
CPCA61K45/00A61P35/00G01N33/57446G01N33/6872G01N2333/475
Inventor 徐瑞华曾昭蕾陆佳欢
Owner SUN YAT SEN UNIV CANCER CENT
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