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Arsenic trioxide antineoplastic new use and anti-tumor preparation

An arsenic trioxide and tumor technology, which can be used in anti-tumor drugs, medical preparations containing active ingredients, preparations for in vivo experiments, etc., and can solve problems such as increasing the process of tumor malignancy.

Active Publication Date: 2016-03-30
SHANGHAI INST OF BIOLOGICAL SCI CHINESE ACAD OF SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

Although p53 protein can inhibit the occurrence of tumors, p53 gene mutations can be found in about 50% of tumor patients. Mutant p53 can promote tumor metastasis, inhibit the effect of chemotherapy drugs, and increase the malignant process of tumors

Method used

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  • Arsenic trioxide antineoplastic new use and anti-tumor preparation
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  • Arsenic trioxide antineoplastic new use and anti-tumor preparation

Examples

Experimental program
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Effect test

Embodiment 1

[0210] Example 1. Dynamic expression profile analysis of arsenic trioxide acting on breast cancer MDA-MB-231 cell line

[0211] Through the expression profile chip, the inventors studied the regulatory mode of arsenic trioxide at the transcriptome level in MDA-MB-231. According to the change trend of gene expression, select Variation in Top5000 genes for CPP-SOM display analysis ( figure 1 A). And by clustering the modulated genes, these genes are divided into 27 Clusters ( figure 1 B). It can be seen from the figure that the gene expression in MDA-MB-231 is in a very dynamic change process after the treatment of arsenic trioxide. Some genes were activated early in the arsenic trioxide treatment, but these genes were decreased in the later time; and the genes that were repressed in the early stage were activated later. And at the end of treatment, ie 36 hours of treatment, most of the changed genes were based on a low expression state. These data suggest that MDA-MB-231 c...

Embodiment 2

[0214] Example 2. Arsenic trioxide inhibits TGFβ and TNFα signaling pathways

[0215] Through the DAVID analysis software, the inventors also conducted cluster analysis of signaling pathway pathways on target genes of arsenic trioxide, hoping to find signaling pathways related to lung metastasis of breast cancer. First, similar to GO’s cell function clustering, pathways related to cell cycle and DNA replication can be enriched. In addition, p53 signaling pathway (p53 signaling pathway), TGF β signaling pathway (TGF β signaling pathway) and NOD-like cell receptor signaling pathway (NOD-like receptor signaling) were significantly enriched ( figure 2 A).

[0216] Transforming growth factor β (TGFβ) is a multifunctional cytokine, its role includes inhibiting tumor cell growth and promoting tumor metastasis. The role of TGFβ is closely related to the stage of tumorigenesis, the type of tumor, and the microenvironment of the tumor. Studies have found that intratumoral cytokine T...

Embodiment 3

[0222] Example 3. Arsenic trioxide reprograms the Signature of breast cancer lung metastasis

[0223]Tumor metastasis is a series of complex interactions between tumor cells, host cells and tumor microenvironment, a continuous process of mutual influence, multiple genes, and multiple pathways participate in the entire process of invasion and metastasis. Therefore, multi-level and multi-gene must be involved in the study of tumor metastasis. And how to study multiple genes involved in metastasis at the same time? The inventors believe that arsenic trioxide may have a significant impact on the signature of lung metastasis of breast cancer.

[0224] In order to confirm the effect of arsenic trioxide on the Signature gene of lung metastasis, the inventors used LM2-4175 cells derived from MDA-MB-231 cells with specific lung metastasis. In breast cancer lung metastasis-related signature genes, genes related to TGFβ signaling pathway, such as ANGPTL4, EREG, MMP2, ID1, LTBP1; genes ...

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Abstract

The present invention relates to a new arsenic trioxide anti-tumor use and an anti-tumor preparation. A new arsenic trioxide anti-tumor mechanism is disclosed for the first time, and a drug or a drug box with an antineoplastic use, and a new arsenic trioxide or arsenic-trioxide-related preparation use are provided on the basis of the new arsenic trioxide anti-tumor mechanism.

Description

technical field [0001] The invention belongs to the field of biopharmaceuticals; more specifically, the invention relates to a new anti-tumor application of arsenic trioxide and an anti-tumor preparation. Background technique [0002] Centuries ago, arsenic (mainly composed of arsenic trioxide) was used to treat psoriasis, rheumatism, leukemia, syphilis, and hemorrhoids. Harbin Medical University first reported that intravenous infusion of arsenic trioxide in the treatment of relapsed acute promyelocytic leukemia (APL) achieved a high rate of complete remission. Subsequently, the Shanghai Blood Institute discovered the mechanism of arsenic trioxide-induced apoptosis and differentiation of APL cells. In recent years, the research on arsenic trioxide and tumors has developed rapidly. Although some results have shown that arsenic trioxide also has certain therapeutic effects in other types of leukemia and even solid tumors, they have not reached the therapeutic efficiency of a...

Claims

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Application Information

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IPC IPC(8): A61K45/00A61K48/00A61K49/00A61P35/00A61P35/04A61K33/36A61K31/167A61K31/436
Inventor 张济杜艳芝王海伟
Owner SHANGHAI INST OF BIOLOGICAL SCI CHINESE ACAD OF SCI
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