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Drug intervention target for tumor-related secondary lymphedema and application thereof

A technology related to lymphedema and tumors, applied in the field of biomedicine, can solve problems that affect the quality of life of patients, heavy physical and psychological burdens, and achieve the effect of alleviating adipose tissue fibrosis

Pending Publication Date: 2021-04-23
PEKING UNION MEDICAL COLLEGE HOSPITAL CHINESE ACAD OF MEDICAL SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Lymphedema often brings heavy physical and psychological burdens to cancer patients, seriously affecting the quality of life of patients
However, there is still a lack of effective drug therapy to intervene and prevent it

Method used

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  • Drug intervention target for tumor-related secondary lymphedema and application thereof
  • Drug intervention target for tumor-related secondary lymphedema and application thereof
  • Drug intervention target for tumor-related secondary lymphedema and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0023] This example proves that the expression of CLEC3B gene is up-regulated in ADSCs of patients with lymphedema.

[0024] 1. Isolation and culture of ADSCs

[0025] All samples in this study came from the Department of Plastic and Aesthetic Surgery of Peking Union Medical College Hospital. All operating procedures of this study have been approved by the Ethics Review Committee of Peking Union Medical College Hospital, and all subjects have signed informed consent. In the present invention, a total of 11 patients with unilateral leg lymphedema occurred in stage III after gynecological tumor surgery were enrolled. Put the fresh adipose tissue separated from the affected and healthy thighs of patients with lymphedema into 50ml sterile centrifuge tubes, about 10ml in each tube; add 10ml of HBSS solution to each tube to wash the adipose tissue for 2-3 times, and then Add 20ml of 0.15% collagenase I + 4% penicillin / streptomycin double antibody solution to each tube and digest a...

Embodiment 2

[0033] This example demonstrates that knocking down CLEC3B gene by siRNA in ADSC cells of patients with lymphedema can down-regulate the expression of fibrosis-related genes and TGF-β signaling pathway-related genes.

[0034] 1. Transfection experiment

[0035]ADSCs were cultured in 6-well plates with low-sugar DMEM+10% FBS, and adhered overnight in an incubator. CLEC3B siRNA (ON-TARGETplus Human CLEC3B siRNA Smartpool) / Negative control (ON-TARGETplus non-targeting pool) 10ul, serum-free low-sugar DMEM 190ul, transfection reagent (DharmaFECT 4siRNATransfection Reagent) 5ul, serum-free low-sugar DMEM 195ul, at room temperature Mix well for 5 minutes. Finally, mix the serum-free low-sugar DMEM dilution of CLEC3B siRNA and Negative control with the serum-free low-sugar DMEM dilution of the transfection reagent, incubate at room temperature for 20 minutes, a total of 400ul system, and then mix with 1.6ml low-sugar DMEM+10%FBS Mix and prepare a 2ml transfection system to culture ...

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Abstract

The invention discloses a drug intervention target for tumor-related secondary lymphedema. The target is a CLEC3B gene and an encoding protein thereof. The expression of the gene provided by the invention in adipose-derived stem cells derived from tumor-related secondary lymphedema patients is significantly up-regulated. The siRNA-mediated CLEC3B gene knock-down can significantly down-regulate fibrosis and TGF-beta signal pathway related gene expression, so that lymphedema adipose tissue fibrosis can be effectively relieved. On this basis, drugs including siRNA designed for the target can be used for treating and relieving lymphedema. The invention provides the new drug target for the treatment of lymphedema.

Description

technical field [0001] The invention belongs to the field of biomedicine, and specifically relates to a drug intervention target for tumor-associated secondary lymphedema and its application in alleviating pathological fibrosis of adipose tissue. Background technique [0002] Lymphedema generally refers to the pathological phenomenon in which interstitial fluid accumulates in tissues caused by obstruction or dysfunction of lymphatic return in certain parts of the body. Secondary lymphedema is the most common form and occurs after dissection of tumor lymph nodes, so-called tumor-associated secondary lymphedema. It has been reported that up to 20% of breast cancer patients develop secondary lymphedema after treatment. Lymphedema generally manifests as progressive swelling of subcutaneous adipose tissue of limbs, chronic inflammatory response of adipose tissue, pathological fibrosis of adipose tissue and excessive fat deposition and other pathological processes. Lymphedema of...

Claims

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Application Information

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IPC IPC(8): A61K45/00A61K31/7088A61P7/10A61P43/00
CPCA61K45/00A61K31/7088A61P7/10A61P43/00
Inventor 刘宣雨袁梦向琴琴陈文李竹君陈洁黄久佐俞楠泽周洲龙笑
Owner PEKING UNION MEDICAL COLLEGE HOSPITAL CHINESE ACAD OF MEDICAL SCI
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