Marker KIFC1 for predicting drug resistance and recurrence of tumors and inhibitor thereof and use of marker KIFC1 and inhibitor thereof

A marker and inhibitor technology, which can be used in anti-tumor drugs, drug combinations, biochemical equipment and methods, etc., and can solve problems such as genomic instability

Active Publication Date: 2021-02-05
SHANGHAI FIRST PEOPLES HOSPITAL
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Cells with redundant centrosomes maintain cell survival through the mechanism of centrosome clustering, but the surviving cells are often accompanied by genome instability

Method used

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  • Marker KIFC1 for predicting drug resistance and recurrence of tumors and inhibitor thereof and use of marker KIFC1 and inhibitor thereof
  • Marker KIFC1 for predicting drug resistance and recurrence of tumors and inhibitor thereof and use of marker KIFC1 and inhibitor thereof
  • Marker KIFC1 for predicting drug resistance and recurrence of tumors and inhibitor thereof and use of marker KIFC1 and inhibitor thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0067] Example 1 In breast cancer and colon cancer tumor tissues, the amount of KIFC1 protein was significantly positively correlated with tumor recurrence rate.

[0068] Human breast cancer tissue chips were purchased from Shanghai Xinchao Biotechnology Co., Ltd. (HBreD140Su04). Colon cancer tumor tissue chips were purchased from Shanghai Zhuohao Pharmaceutical Technology Co., Ltd. (COC1601). Clinical data can be downloaded from the relevant company websites. The amount of KIFC1 protein was divided into three groups according to the degree of staining (low, 0–4 points; medium, 5–8 points; high, 9–12 points) [14]. To ensure statistical authenticity, these data were performed in a double-blind manner Scoring and counting.

[0069] Among them, the tumor tissue was collected and processed uniformly by the company, and the relevant experimental process, parameter conditions, and measurement process were consistent with standard immunohistochemical experiments [15]. Among them, ...

Embodiment 2

[0072] Example 2 Screening of KIFC1-specific sites and antibody preparation thereof.

[0073] The experiment was performed in MDA-MB-231 breast cancer tumor cells. Experiments such as Western blot, Flag IP and mass spectrometry are all routine molecular biology and cell biology experiments. Relevant chemotherapy drugs were purchased from MedChemExpress (Monmouth Junction, NJ, USA). Antibodies used included KIFC1 (HPA055997, Sigma-Aldrich), anti-γH2AX (ab26350; Abcam), Flag (F3165; Sigma-Aldrich) and β-actin (A5316; Sigma-Aldrich), which were commercially available For existing antibodies, the specific information can be clearly identified according to the relevant number. These antibodies were the experimental material used in the discovery process of the present invention.

[0074] Experimental results: In this example, it was found that DNA damage-based radiotherapy and chemotherapy would lead to an increase in the amount of KIFC1 protein ( figure 2 A), and related inhib...

Embodiment 3

[0075] Example 3 ATM / ATR inhibitor VE-822 inhibits excess centrosome aggregation through KIFC1.

[0076] Related immunofluorescence experiments were carried out in breast cancer MDA-MB-231 cells. Antibodies used included γ-tubulin (T5326; Sigma-Aldrich), Centrin (C7736; Sigma-Aldrich), and α-tubulin (T5199; Sigma-Aldrich).

[0077] On the basis of the MDA-MB-231 cells of KIFC1 gene silencing, the present invention first established the wild type (WT), the simulated S26 dephosphorylation state (S26A) and the simulated S26 phosphorylation state (S26D) cell lines of KIFC1 ( image 3 A). DNA damage resulted in significantly increased centrosome clustering and significantly reduced multipolarmitosis.

[0078] Experimental results: In the KIFC1-S26A cell line, the ratio of excess centrosome aggregation / multipolarization was significantly reduced. In the KIFC1-S26D cell line, the ratio of excess centrosome aggregation / multipolarization was significantly increased. In the KIFC1-S2...

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Abstract

The present invention belongs to the field of tumor treatment and drug resistance detection, discloses a marker KIFC1 for predicting drug resistance and / or a recurrence rate and / or lifetime and / or treatment of tumors, and further discloses a molecular target for predicting the drug resistance and / or the recurrence rate and / or the lifetime and / or the treatment of tumors by phosphorylation of 26th serine of the KIFC1. The present invention also discloses a KIFC1 specific antibody and the antibody can be used as a detection index for predicting drug resistance and / or a recurrence rate and / or lifetime of tumors. The present invention also discloses a KIFC1 phosphorylation inhibitor. The inhibitor can be used for inhibiting an expression amount of a KIFC1 protein, inhibiting KIFC1 phosphorylation and functions thereof, inhibiting centrosome agglutination induced by the KIFC1 as a key factor, and can be used as an antitumor drug and a drug for reducing drug resistance and / or recurrence of tumors. The present invention aims to formulate corresponding strategies to reduce drug resistance and recurrence probability of tumors in a chemoradiotherapy process and reduce a survival rate of tumorcells. The marker KIFC1 and the inhibitor thereof have a wide application prospect in the field of treatment of tumors.

Description

technical field [0001] The invention belongs to the field of tumor treatment and drug resistance detection, and relates to a marker KIFC1 and a phosphorylation inhibitor used for predicting tumor drug resistance, recurrence, and treatment, and specifically relates to a method for reducing tumor drug resistance and recurrence during adjuvant tumor radiotherapy and chemotherapy The method is used as the marker KIFC1 for tumor drug resistance and recurrence detection, and the detection and application of KIFC1-Ser26 phosphorylation. Background technique [0002] In recent years, the incidence of tumors has increased year by year. In terms of clinical treatment, tumor treatment is still difficult. At present, radiotherapy and chemotherapy are still the main and indispensable means of tumor treatment. In tumor treatment, one of the most commonly used methods is DNA damage radiotherapy and chemotherapy, including: X-ray and etoposide, etoposide, cisplatin, oxaliplatin, mitomycin...

Claims

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Application Information

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IPC IPC(8): C12Q1/6886G01N33/574G01N15/14C07K16/18A61P35/00A61K45/00A61K31/497
CPCC12Q1/6886G01N33/57415G01N33/57419G01N33/57484G01N15/14C07K16/18A61K45/00A61K31/497A61P35/00G01N2800/52G01N2800/54C12Q2600/118C12Q2600/158C12Q2600/136
Inventor 王传贵范广建孙莲慧张胜萍
Owner SHANGHAI FIRST PEOPLES HOSPITAL
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