Application of reagent targeting biomarker in preparation of medicine for relieving/treating liver cancer

A biomarker and a technology for the treatment of liver cancer, applied in the field of biomedicine, can solve problems such as changes in subcellular ceramide levels, impaired autophagy flux, and a five-year survival rate of less than 10%

Active Publication Date: 2021-08-03
INST OF CHINESE MATERIA MEDICA CHINA ACAD OF CHINESE MEDICAL SCI +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

However, due to the characteristics of easy metastasis and recurrence, the recurrence rate of HCC patients after surgical resection is as high as 50-70%, and the five-year survival rate is less than 10%. The long-term prognosis of patients is still not ideal, which indicates that more effective treatment is still needed Strategies to improve clinical outcomes of HCC patients
Both hyperactivation and inactivation of GBA alter subcellular ceramide levels, resulting in impairment of autophagic flux

Method used

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  • Application of reagent targeting biomarker in preparation of medicine for relieving/treating liver cancer
  • Application of reagent targeting biomarker in preparation of medicine for relieving/treating liver cancer
  • Application of reagent targeting biomarker in preparation of medicine for relieving/treating liver cancer

Examples

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Embodiment 1

[0060] This example is used to illustrate that GBA can be used as a new target for the treatment of liver cancer.

[0061] Case source and sample size: This disclosure collected 99 HCC tissue samples and 18 paracancerous liver tissue samples from 100 liver cancer patients. The samples were from the Fifth Medical Center of the PLA General Hospital and met the inclusion criteria. Among them, three pairs of liver cancer and paracancerous liver tissues were used for microarray detection, and other tissues were used for experimental verification of GBA expression and its relationship with various clinicopathological features.

[0062] Inclusion criteria: (1) Histologically confirmed HCC; (2) Surgical resection; (3) Complete clinical data available; (4) No preoperative chemotherapy or radiotherapy; (5) No history of other malignant tumors. Tissue samples were collected immediately after surgery and stored in liquid nitrogen.

[0063] The disclosure collects RNA sequencing (RNA-Seq)...

Embodiment 2

[0075] This example is used to illustrate that siRNA knockdown technology can inhibit the overexpression of GBA, thereby inducing impaired autophagic degradation of hepatocytes, and further reversely prove that GBA can be used as a target for liver cancer treatment by using LT1291.

[0076] Human HCC cell lines (HepG2 and MHCC-97H) were purchased from the American Type Culture Collection (ATCC, Rock-ville, MD, USA). These cell lines were kept in modified Eagle medium (DMEM, HyClone, Logan, UT, USA) and then added with 10% fetal bovine serum and 1% penicillin G and streptomycin, and incubated at 37°C in humid air. (with 5% CO 2 )save.

[0077] Then three small interfering RNA (siRNA) constructs specific for GBA were inserted into the hRNU6-MCS-CMV-Puro vector (LncBio Co., shRNA-304, Shanghai, China). The three siRNA targeting sequences are si-GBA-313, si-GBA-1255 and si-GBA-1620, wherein si-GBA-313 includes SEQ ID NO.1 and SEQ ID NO.2; si-GBA-1255 Including SEQ ID NO.3 and S...

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Abstract

The invention relates to an application of a reagent targeting a biomarker in preparation of a medicine for relieving/treating liver cancer, wherein the biomarker is GBA. The reagent targeting the biomarker inhibits the overexpression of GBA, the overexpression of GBA is closely related to the malignant development and poor prognosis of liver cancer, and the mechanism can be that the overexpression of GBA induces autophagy of liver cancer cells and promotes the proliferative activity of the liver cancer cells, thereby promoting the malignant development of liver cancer. The reagent targeting the biomarker prevents degradation of autophagosome in the liver cancer cells by inhibiting abnormal high expression of GBA, so that the downstream of autophagy flow is blocked, and the anti-liver cancer drug effect of the reagent is exerted.

Description

technical field [0001] The present disclosure relates to the technical field of biomedicine, and in particular, relates to the application of GBA as a biomarker for hepatocellular carcinoma. Background technique [0002] Hepatocellular Carcinoma (HCC) is the main type of primary liver cancer, and its incidence is on the rise worldwide. As one of the most common malignant cancers in the world, HCC has a high mortality rate. With the development of medical level, the diagnosis and treatment of liver cancer have been greatly improved, such as surgical resection, local ablation, liver transplantation and molecular targeted drug therapy (such as sorafenib) have been approved as treatment options for the treatment of HCC , the prognosis of patients has improved compared with the past. However, due to the characteristics of easy transfer and recurrence, the recurrence rate of HCC patients after surgical resection is as high as 50-70%, and the five-year survival rate is less than 1...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K45/00A61K31/7088A61K31/713A61P1/16A61P35/00
CPCA61K45/00A61K31/7088A61K31/713A61P1/16A61P35/00
Inventor 张彦琼林娜陈文佳郭晓东余灵祥韩敏
Owner INST OF CHINESE MATERIA MEDICA CHINA ACAD OF CHINESE MEDICAL SCI
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