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Application of Wnt2 to preparation of medicament for inhibiting esophageal cancer

A technology of esophageal cancer and drugs, applied in the field of biomedicine, can solve the problems of no reporting effect and achieve the effect of inhibiting tumor growth

Inactive Publication Date: 2012-03-21
SUN YAT SEN UNIV CANCER CENT
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the role of Wnt2 secreted by tumor fibroblasts in the tumor development of esophageal cancer has not been reported so far.

Method used

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  • Application of Wnt2 to preparation of medicament for inhibiting esophageal cancer
  • Application of Wnt2 to preparation of medicament for inhibiting esophageal cancer
  • Application of Wnt2 to preparation of medicament for inhibiting esophageal cancer

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0020] Example 1: Quantitative PCR (qPCR) was used to compare the expression level of Wnt2 between 10 cases of esophageal cancer tumor fibroblasts and adjacent normal fibroblasts

[0021] The sources of cell lines and primary esophageal cancer specimens used in this example are as follows: Two Chinese esophageal cancer cell lines (EC18 and EC109) were generously provided by Professor TsaoGS (Department of Anatomy, University of Hong Kong). Five Japanese esophageal carcinoma cell lines (KYSE30, KYSE140, KYSE180, KYSE410, KYSE510) were obtained from DSMZ (Braunschweig, Germany), German Resource Center for Biomaterials. Chinese hamster ovary cells (CHO-K1) were purchased from TypeCultureCollection, USA (Manassas, VA). Primary esophageal cancer tissues and their corresponding paracancerous esophageal tissues were collected immediately after surgical resection at Sun Yat-Sen University Cancer Center. A total of 51 formalin-fixed and paraffin-embedded esophageal carcinoma tissues w...

Embodiment 2

[0026] Example 2: Immunohistochemical method to detect the distribution of Wnt2 positive cells in primary esophageal cancer

[0027] In order to further study the distribution of Wnt2(+) cells in esophageal cancer, immunohistochemistry was used to detect Wnt2 expressing cells in 51 cases of primary esophageal cancer specimens. The immunohistochemistry protocol was as follows: Immunohistochemistry was performed using the standard streptavidin-biotin-peroxidase method. Briefly, paraffin-embedded esophageal cancer tissue specimens were deparaffinized, blocked with 10% normal rabbit serum for 10 minutes, and incubated overnight at 4°C with rabbit anti-human Wnt2 polyclonal antibody (MBL, diluted 1:150). The slides were incubated with biotin-labeled goat anti-rabbit immunoglobulin at a concentration of 1:100 at 37°C for 30 minutes. The staining status of cytoplasmically secreted Wnt2 was assessed by three independent investigators who had no prior knowledge of the patients' clinic...

Embodiment 3

[0030] Example 3: Correlation between the prognosis of patients with esophageal cancer and the positive expression of Wnt2

[0031] In this example, a correlation study between the clinicopathological features and the positive expression of Wnt2 was carried out in 51 cases of esophageal cancer patients. The results showed that Wnt2(+) in patients with esophageal cancer was significantly correlated with TNM stage (P=0.001, Fisher's exact test) and lymph node metastasis (P=0.001, Fisher's exact test); see Table 1 for details, and Table 1 shows 51 cases of esophageal cancer specimens Correlation analysis data between positive Wnt2 expression and clinicopathological features. Further analysis, using the Log-rank test, found that compared with patients with negative Wnt2 expression, the survival time of esophageal cancer patients with positive Wnt2 expression was shortened. (The median survival time is 51 months; P image 3 , image 3 It is an analysis chart of the survival time o...

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PUM

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Abstract

The invention provides application of Wnt2 to preparation of a medicament for inhibiting the esophageal cancer, and provides a medicament for inhibiting the development of the esophageal cancer. The medicament comprises a component for inhibiting the action of a Wnt2 gene or / and a Wnt2 protein. The component comprises one or more a polypeptide substance capable of enclosing the Wnt2 gene, an antibody / ligand capable of enclosing the Wnt2, a lethal medicament or a nucleic acid substance carried by an antibody / ligand capable of inhibiting or killing the Wnt2 and a small interfering ribonucleic acid (siRNA) or a miRNA (micro Ribonucleic Acid) or a shRNA (short hairpin Ribonucleic Acid) capable of interfering / blocking the Wnt2 gene. The invention has the advantage: the application of the Wnt2 gene to the preparation of a medicament for inhibiting the esophageal cancer is provided, a WNT signal conduction path in a WNT2 activated tumor cell is blocked under the silencing action or the neutralizing action of an antibody, so that the effect of inhibiting the growth of tumors is achieved.

Description

technical field [0001] The invention relates to the field of biomedicine, in particular to the application of Wnt2 in the preparation of drugs for inhibiting esophageal cancer. Background technique [0002] Numerous evidences have revealed that the tumor microenvironment, composed of non-cancerous cells and their stroma, plays an important role in the development and progression of cancer. Our previous studies have elucidated that many genes are downregulated in esophageal cancer fibroblasts compared with their adjacent paracancerous fibroblasts. About 43% (126 / 292) of the downregulated genes were related to cell proliferation, extracellular matrix remodeling and immune response. Apparently, several members of the Wnt pathway, including WNT2, WNT5A, LEF1, and WISP1, were upregulated in tumor fibroblasts, implying that Wnt signaling may be involved in tumor-stroma interactions in esophageal cancer. [0003] Wnt2 protein is a secretory ligand protein (about 40KDa in size), w...

Claims

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Application Information

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IPC IPC(8): A61K45/00A61K38/17A61K48/00A61K31/7105A61P35/00
Inventor 关新元付利李焱张春玉
Owner SUN YAT SEN UNIV CANCER CENT
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