11 segment human digestive tract tumoure blood vessel speicfic conjugated cyclopeptide GX series

A digestive tract tumor specific technology, applied in the field of biomedicine, can solve the problems of loss of tissue specificity of endothelial cells, no combination of natural molecules, limited curative effect, etc.

Active Publication Date: 2005-02-16
FOURTH MILITARY MEDICAL UNIVERSITY
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Problems solved by technology

However, although tumor vascular suppression therapy has obvious advantages, it also has some disadvantages: ① Tumor blood vessels are not well targeted, it is difficult to completely cure the tumor, and there is a potential risk of inhibiting normal endothelial cells
②Low expression efficiency and limited curative effect
③Most of the angiogenesis inhibitory molecules currently entering clinical trials have low expression efficiency in vivo, and cannot maintain therapeutic concentrations locally in tumor blood vessels
[0005] At present, most of the screening methods use in vitro screening, but for tumor vascular endothelial cells, direct isolation and in vitro culture of human tumor vascular endothelial cells, one is the difficulty of separation technology operation, and the other is that long-term in vitro culture makes endothelial cells lose their vitality in vivo. The living environment of endothelial cells loses tissue specificity
Some in vivo experiments mostly use human tumor cell lines or nude mouse models of transplanted tissue tumors, and some use tra

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  • 11 segment human digestive tract tumoure blood vessel speicfic conjugated cyclopeptide GX series
  • 11 segment human digestive tract tumoure blood vessel speicfic conjugated cyclopeptide GX series
  • 11 segment human digestive tract tumoure blood vessel speicfic conjugated cyclopeptide GX series

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Embodiment Construction

[0035] The present invention will be further described in detail below in conjunction with the accompanying drawings.

[0036] Molecular surface markers of tumor vascular endothelial cells are the basis of tumor vascular therapy. For this reason, the applicant selected phage random peptide library screening technology in vivo, and successfully obtained a group of specific combinations of human gastric poorly differentiated adenocarcinoma and human esophageal squamous cell carcinoma blood vessels. Cyclic 7-peptide GX series, and use plaque formation experiments, immunohistochemistry to detect the specific homing of GX series, and the binding activity of GX series in vivo competition inhibition experiments in tumor-bearing mice, etc., this series of GX peptides have relatively High ability to bind gastrointestinal tumor vascular endothelial cells.

[0037] 1. Technical solution and its route

[0038] 1.1 Establishment of human tumor tissue subrenal capsule xenograft model:

[...

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Abstract

The invention discloses 11 sections special associative cyclic peptide GX of tumor veins of human alimentary canal. The invention makes use of the human transferred tumor model under the random phage cricoid 7-peptide and immunosuppression mouse nephridial envelope and screens the cricoid 7 peptide GX1-GX11 which can combine with the high specificity of human oesophagus cancer and human adenocarcinoma of stomach with poor differentiation. The competitive inhibition experiments among the plaque titration of the transplanted tumors' tissue, transplanting the tumors' tissue and the tissues of human cancer of stomach and esophageal carcinoma, GX1 compound peptide and GX1 present phage all show the specificity of the association of the 7-peptide with the tumor tissue of human alimentary canal. After sequencing, we can affirm the uniqueness of the protein sequence. These polypeptide sequences have great potential in the targeting treatment of tumor veins and the development of the symbol reagent of the specific molecule of the tumor veins.

Description

technical field [0001] The invention belongs to the technical field of biomedicine, and relates to in vivo screening of blood vessel-specific binding peptides, in particular to the GX series of 11-segment human digestive tract tumor blood vessel-specific binding cyclic peptides. Background technique [0002] Although gastric cancer has gradually decreased in recent years, it still ranks third among the top ten causes of cancer death in China. The traditional treatment methods are still surgery, chemotherapy and radiotherapy. In 1971, Professor Folkman proposed the theory that tumor growth and metastasis depend on blood vessels, and blocking tumor angiogenesis became a method to inhibit tumor growth. Compared with traditional methods, tumor vascular inhibition therapy has the following advantages: ① drug resistance is not easy to develop; ② drugs are easy to reach the target site; ③ inhibit tumor metastasis; ④ no genotoxicity; ⑤ strong effect, etc. F...

Claims

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Application Information

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IPC IPC(8): C07K14/435
Inventor 吴开春郅敏董蕾郝志明乔泰东丁杰樊代明
Owner FOURTH MILITARY MEDICAL UNIVERSITY
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