Application of rack1 as a target in the preparation of anti-shh subtype medulloblastoma drugs

A medulloblastoma and drug technology, applied in the field of tumor drug targeting research, can solve problems such as drug resistance

Active Publication Date: 2021-11-30
ACADEMY OF MILITARY MEDICAL SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] SHH subtype medulloblastoma is a major subtype of medulloblastoma, accounting for about 30% of all medulloblastoma molecular subtypes. There are many reasons for the formation of SHH subtype medulloblastoma, and any cause of SHH signaling The abnormal and continuous activation of the pathway can lead to the occurrence of SHH subtype medulloblastoma. Finding and discovering new and specific medulloblastoma-related genes and targeting them is the focus of the research and development of medulloblastoma treatment. At present, some therapeutic targets for medulloblastoma have been found, but drug resistance has appeared in many existing therapeutic targets, therefore, the emergence of new therapeutic targets is urgently needed

Method used

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  • Application of rack1 as a target in the preparation of anti-shh subtype medulloblastoma drugs
  • Application of rack1 as a target in the preparation of anti-shh subtype medulloblastoma drugs
  • Application of rack1 as a target in the preparation of anti-shh subtype medulloblastoma drugs

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0061] Example 1 Establishment of SHH Subtype Medulloblastoma Animal Model

[0062] 1. Experimental materials

[0063] Atoh1-cre mice were purchased from "The Jackson Laboratory" (No. 011104); SmoM2 mice were purchased from "The Jackson Laboratory" (No. 005130); Rack1 loxP / loxP The mice were provided by Mr. Zhang Jiyan, Institute of Military Cognitive and Brain Science, Academy of Military Medical Sciences. The second exon 172bp of the mouse Rack1 gene was marked by loxP; NeuN was purchased from Milipore, the article number is MAB377; DAPI (H-1200; VECTASHIELD); goat anti-mouse IgG (H+L) AlexaFlour 568 was purchased from Biotium; 4% paraformaldehyde was purchased from Solebol.

[0064] 2. Experimental method

[0065] Combine Atoh1-cre genotype mice with SmoM2 + / + The mice were crossed, and the Cre / loxp strategy was used to specifically express the activated SmoM2 receptor in the cerebellar granule neurons of At oh1-cre mice, thereby inducing the excessive activation of the ...

Embodiment 2

[0068] Example 2 Establishment of a tumor mouse model for gene therapy of Rack1 gene knockout

[0069] experimental method:

[0070] (1) Establish a Rack1 knockout tumor mouse model: first use Atoh1-cre; SmoM2 + / - and Atoh1-cre; Rack1 F / F Mouse hybrid generation to obtain heterozygous mice: Atoh1-cre; Rack1 F / W , and then heterozygous mice with SmoM2 + / - ;Rack1 F / F The mice were crossed and the genotype was Atoh1-cre; SmoM2 + / - ;Rack F / F gene therapy mice.

[0071] (2) Take four genotype mice of P30 respectively: SmoM2 + / - ;Rack1 F / F , Atoh1-cre; Rack1 F / F , Atoh1-cre; SmoM2 + / - , Atoh1-cre; SmoM2 + / - ;Rack F / F . The mice of four genotypes were anesthetized with 1% pentobarbital, and then perfused with normal saline and 4% paraformaldehyde respectively. The whole brain was peeled off, soaked in 4% paraformaldehyde and fixed.

[0072] (3) After being fixed in 4% paraformaldehyde for 24 hours, they were dehydrated in 15% and 30% sucrose solution (prepared in PBS) f...

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Abstract

The invention discloses the application of Rack1 as a target in the preparation of anti-SHH subtype medulloblastoma drugs. In the present invention, a mouse model of SHH subtype medulloblastoma was firstly constructed, and then the Rack1 gene was simultaneously knocked out in the granule neurons of the constructed mouse model. survival time of mice, suggesting that the Rack1 gene plays a key role in the regulation of SHH subtype medulloblastoma in mice. The present invention discovers for the first time that the Rack1 gene can be used as a novel target of an anti-medulloblastoma drug, and has potential application value in immunotherapy of medulloblastoma.

Description

technical field [0001] The invention belongs to the technical field of tumor drug targeting research. Specifically, the invention relates to the application of a Rack1 gene as a target in the preparation of anti-SHH subtype medulloblastoma drugs. Background technique [0002] Medulloblastoma (MB) is the most common malignant tumor of the nervous system in children, and it is a primitive neuroectodermal tumor that mainly occurs in the cerebellum. Medulloblastoma mostly occurs in the posterior cranial fossa, with hidden growth and lack of characteristic early symptoms. The common initial symptoms are headache, vomiting, and unsteady gait, followed by diplopia, ataxia, vision loss, forced head position, enlarged head, coughing, and subarachnoid hemorrhage and cerebellar crisis in severe cases. elephant. At present, the disease accounts for 25% of all intracranial tumors in children, and the prevalence rate among children under 15 years old is 0.5 / 100,000, and the age of onset...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C12Q1/6886G01N33/574A61K45/00A61P35/00
CPCA61K45/00A61P35/00C12Q1/6886C12Q2600/136C12Q2600/158G01N33/57407G01N33/57484G01N2500/04
Inventor 吴海涛刘凤姣邵靖媛
Owner ACADEMY OF MILITARY MEDICAL SCI
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