Spleen tyrosine kinase as a therapeutic target for intrahepatic cholangiocarcinoma

A technology for inner bile duct and cell carcinoma, applied in the field of biomedicine, can solve the problems of unknown, limited curative effect, and ineffective treatment of the pathogenesis of patients, and achieve the effect of inhibiting proliferation

Active Publication Date: 2021-05-07
TCM INTEGRATED HOSPITAL OF SOUTHERN MEDICAL UNIV
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  • Abstract
  • Description
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Problems solved by technology

However, simple surgery cannot effectively treat most patients (the pathogenesis is unknown, lack of early diagnostic markers, and the chance of surgery has been lost when it is discovered), and the postoperative survival rate is low (5-year survival rate is 8% to 47%). High rate (postoperative intrahepatic recurrence rate of 46% to 68%); non-surgical patients lack effective treatment means, local treatment may benefit a single lesion <3cm, and residual or local recurrence after surgery (overall curative effect Worrying); for unresectable or metastatic advanced cholangiocarcinoma, the chemotherapy regimen of gemcitabine combined with platinum antineoplastic drugs can prolong the survival of patients with cholangiocarcinoma, but it is limited by drug toxicity and drug resistance; radiotherapy alone The curative effect is very limited, and it is often used as an adjuvant therapy. There is no evidence that intraoperative radiotherapy and intraductal brachytherapy are better than standard chemotherapy, combined chemotherapy and radiotherapy for advanced cholangiocarcinoma
So far, there is no standard targeted drug for cholangiocarcinoma, and it is only in the stage of exploration and clinical trials, and there is no conclusion of definite curative effect

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  • Spleen tyrosine kinase as a therapeutic target for intrahepatic cholangiocarcinoma
  • Spleen tyrosine kinase as a therapeutic target for intrahepatic cholangiocarcinoma
  • Spleen tyrosine kinase as a therapeutic target for intrahepatic cholangiocarcinoma

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Embodiment Construction

[0032] Application of SYK gene or SYK protein as therapeutic target for intrahepatic cholangiocarcinoma.

[0033] Application of SYK antagonist in preparation of medicine for treating intrahepatic cholangiocarcinoma.

[0034] Further, the SYK antagonist is selected from GS-9973, Fostamatinib, R406, and PRT062607.

[0035] Application of SYK expression inhibitor in preparation of medicine for treating intrahepatic cholangiocarcinoma.

[0036] Further, the SYK expression inhibitor is selected from SYK-siRNA, SYK-targeting miRNA or antisense nucleotides and other nucleic acids that down-regulate the expression of SYK.

[0037]Further, intrahepatic cholangiocarcinoma is intrahepatic cholangiocarcinoma in which the expression of SYK is significantly higher than that of normal intrahepatic cholangiocarcinoma. The change in the expression level of SYK can be determined by methods commonly used in the art, such as evaluating the change in expression level by comparing immunohistoche...

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Abstract

The present invention discloses the application of spleen tyrosine kinase as a target for the treatment of intrahepatic cholangiocarcinoma. The inventor found through experiments that the expression of SYK in intrahepatic cholangiocarcinoma increases; both in vitro cell and in vivo animal experiments found that, The SYK antagonist GS‑9973 can effectively inhibit the proliferation of intrahepatic cholangiocarcinoma, and the inhibitory effect is close to that of the first-line chemotherapy drug gemcitabine.

Description

technical field [0001] The invention belongs to the field of biomedicine, and in particular relates to the application of spleen tyrosine kinase as a therapeutic target for intrahepatic cholangiocarcinoma. Background technique [0002] Spleen tyrosine kinase (Spleen tyrosine kinase, SYK) gene was first cloned from pig spleen cDNA in 1991, encoding a non-receptor protein tyrosine kinase. The human SYK gene is located in the q22 region of chromosome 9. The SYK protein contains 635 amino acids. It is a kind of specific protein kinase that can catalyze the phosphorylation of tyrosine residues in substrate proteins, including receptor tyrosine kinases, cytoplasmic Type tyrosine kinases and nuclear tyrosine kinases. Tyrosine protein kinases can regulate signal transduction within and between cells, play an important role in cell differentiation, proliferation and spread, and are closely related to the occurrence and development of tumors. It plays an important role in autoimmune...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K45/00A61K31/675A61K31/506A61K31/538A61K31/5377A61K31/7105A61P35/00
CPCA61K31/506A61K31/5377A61K31/538A61K31/675A61K31/7105A61K45/00A61P35/00
Inventor 洪健袁辉林泽龙
Owner TCM INTEGRATED HOSPITAL OF SOUTHERN MEDICAL UNIV
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