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Combination of proteasome inhibitors and autophagy activators in the treatment of cholangiocarcinoma

A proteasome inhibitor and proteasome technology, applied in the field of medicine, can solve the problems of not being widely used, single drug indication, poor targeting of treatment, etc., and achieve the effect of easy clinical use and promotion

Active Publication Date: 2018-08-28
SECOND MILITARY MEDICAL UNIV OF THE PEOPLES LIBERATION ARMY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

They are all aimed at the most basic life process of cells, and the targeting of the treatment is poor; the indications of the drugs that have been marketed are relatively single, and they cannot be widely used at present

Method used

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  • Combination of proteasome inhibitors and autophagy activators in the treatment of cholangiocarcinoma
  • Combination of proteasome inhibitors and autophagy activators in the treatment of cholangiocarcinoma
  • Combination of proteasome inhibitors and autophagy activators in the treatment of cholangiocarcinoma

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0054] Example 1: Detecting the expression level of PTEN in the paraffin-embedded carcinoma and adjacent normal liver tissues of patients with intrahepatic cholangiocarcinoma after surgical resection by immunohistochemical method.

[0055] Paraffin sections of tumor tissues from 127 patients with cholangiocarcinoma were selected (the liver cancer tissue sections were all from the Eastern Hepatobiliary Surgery Hospital, and were diagnosed as hepatocellular carcinoma by 2 pathologists), and the expression of PTEN protein in liver cancer tissues was detected by immunohistochemical method PTEN immunohistochemical detection was used to analyze the prognosis of patients with intrahepatic cholangiocarcinoma.

[0056] For antigen retrieval for 2 minutes, the primary antibody was incubated with monoclonal rabbit-derived PTEN antibody 1:75 at 4°C overnight, and the normal rabbit-derived IgG antibody 1:75 was used as a negative control; biotin-labeled secondary antibody was incubated at 3...

Embodiment 2

[0058] Example 2: PTEN overexpression adenovirus causes death of deleted cholangiocarcinoma cell line

[0059] Introduce four cholangiocarcinoma cell lines HCCC-9810, RBE, QBC939, and FRH-201 into 6 wells respectively. After the cells grow to 80% confluency, use 150ul of IP lysate (Beyond, P0013) to collect Cell protein, after ultrasonic treatment, centrifuge at 12000 rpm for 15 minutes, add SDS high temperature denaturation after quantification, go through SDS-PAGE electrophoresis, transfer membrane and block with 5% BSA, incubate with primary antibody overnight at 4°C, then incubate with secondary antibody, and use Odyssey Scan detection.

[0060] figure 2 A shows that the expression of PTEN in HCCC-9810 is negative; PTEN in RBE, QBC939, and FRH-201 is positive.

[0061] To further study the effect of PTEN on cholangiocarcinoma cells, we introduced HCCC-9810 and RBE into 96-well plates with 4000 cells per well. After adherence, each type of cell was added with PTEN adeno...

Embodiment 3

[0064] Example 3: Gene chip analysis of signaling pathway changes in hepatic duct carcinoma cell lines after PTEN overexpression

[0065] Introduce cholangiocarcinoma cells HCCC-9810 and RBE in a 10cm cell culture dish, add PTEN and control GFP adenovirus respectively after reaching 50% fusion, change the medium after 6h, then continue to culture for 30h, discard the medium, and replace with normal saline Gently rinse once, add 1ml Trizol, extract cell RNA for gene chip analysis of expression profiles. The chip used is affymetrix2.0 human gene expression profile chip, and the data analysis was completed by Shanghai Qiming Information Technology Co., Ltd. Use the multiple method to screen the control group and the experimental group of the two cells for pairwise differences (horizontal and vertical), to obtain the differential mRNA, and analyze the significant signaling pathways of the obtained differential mRNA according to the 2014 commercial version of the KEGG database, fin...

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Abstract

The invention relates to the technical field of medicines, and concretely relates to an application of combination of a proteasome inhibitor and a cell autophagy activator in bile duct cancer treatment. In recent years, phosphatase and tensin homologue PTEN and a signal channel thereof get more and more attention in tumor prevention and treatment researches. The growth of PTEN deleted bile duct cancer cells and primary generation xenograft tumors is effectively inhibited through a PTEN targeted bile duct cancer customized treatment scheme and combined use of the proteasome inhibitor and the cell autophagy / lysosome activator. The bile duct cancer customized treatment scheme is provided through using a micro-molecular inhibitor and medicines based on PTEN detection, so clinic use and application are easy.

Description

Technical field: [0001] The invention relates to the field of medical technology, in particular to a method for detecting PTEN expression in cholangiocarcinoma, the construction and packaging of PTEN overexpression non-proliferating adenoviral vector, and the combination of proteasome inhibitors and autophagy / lysosome activators in Application in the treatment of PTEN-deficient cholangiocarcinoma. Background technique: [0002] Cholangiocarcinoma (carcinoma of bile duct, referred to as CC) refers to the malignant tumor originating from the extrahepatic bile duct, including the bile duct from the hilar area to the lower end of the common bile duct. It is a type of primary liver cancer, accounting for about 10% of primary liver cancer %; Clinically, it is characterized by long incubation period, high degree of malignancy, resistance to radiotherapy and chemotherapy, and poor prognosis; epidemiology shows that the incidence of cholangiocarcinoma has continued to rise in recent ...

Claims

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Application Information

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IPC IPC(8): C12Q1/6886A61K48/00A61K45/06A61P35/00
CPCA61K45/06A61K48/005C12Q1/6886C12Q2600/118C12Q2600/158
Inventor 王红阳董立巍谈冶雄蒋添翼
Owner SECOND MILITARY MEDICAL UNIV OF THE PEOPLES LIBERATION ARMY
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