A SNP marker associated with myelosuppressive toxicity of platinum-based chemotherapy drugs and its application

A chemotherapeutic drug, myelosuppression technology, applied in the fields of genetic engineering and oncology

Active Publication Date: 2016-11-30
NANJING MEDICAL UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0006] However, there is no report on the application of SNPs in the diagnosis of myelosuppressive toxicity of platinum-based chemotherapy drugs. If SNPs that are susceptible to myelosuppressive toxicity of platinum-based chemotherapy drugs can be screened out as biomarkers, and corresponding diagnostic kits can be developed, it will be beneficial to our country. The status quo of the diagnosis of myelosuppressive toxicity of platinum-based chemotherapy drugs will be a powerful impetus, and it will also open up a new way for its drug prevention and control

Method used

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  • A SNP marker associated with myelosuppressive toxicity of platinum-based chemotherapy drugs and its application
  • A SNP marker associated with myelosuppressive toxicity of platinum-based chemotherapy drugs and its application
  • A SNP marker associated with myelosuppressive toxicity of platinum-based chemotherapy drugs and its application

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0072] Example 1: collection of samples and arrangement of sample data

[0073] The inventor collected a large number of blood samples from primary NSCLC patients from April 2005 to January 2011 from the Affiliated Cancer Hospital of Nanjing Medical University and the First Affiliated Hospital of Nanjing Medical University. A total of 328 genome-wide microarray scan samples meeting the following criteria were selected:

[0074] (1) New-onset NSCLC patients admitted to the hospital for the first time and confirmed by histopathology or cytology, whose diagnosis is confirmed by at least two pathologists according to the standards issued by the World Health Organization;

[0075] (2) All indicators of blood routine examination before the first chemotherapy were normal;

[0076] (3) Receive 2 to 6 cycles of platinum-based chemotherapy; exclude NSCLC patients who received radiotherapy before or during chemotherapy;

[0077] (4) There is detailed information on the evaluation of my...

Embodiment 2

[0079] Example 2: Genome-wide scanning of SNPs in peripheral blood DNA

[0080] Affymetrix6.0 chip detection was performed on the peripheral blood DNA of the 328 eligible NSCLC patients receiving platinum-based chemotherapy to obtain relevant results. The specific steps are:

[0081] 1. Add hemolysis reagent (i.e., lysate, 40 parts) to the peripheral blood stored in a 2ml cryopreservation tube. The volume of the solution was adjusted to 2000ml, the same below), and it was completely transferred after inverting and mixing.

[0082] 2. Removal of red blood cells: Fill the 5ml centrifuge tube to 4ml with hemolysis reagent, mix by inverting, centrifuge at 4000rpm for 10 minutes, and discard the supernatant. Add 4ml of hemolysis reagent to the precipitate, invert and wash again, centrifuge at 4000rpm for 10 minutes, and discard the supernatant.

[0083] 3. Extract DNA: Add 1ml of extract solution to the precipitate (each 300ml contains 122.5ml0.2M sodium chloride, 14.4ml0.5M eth...

Embodiment 3

[0093] Example 3: Sequenom MassARRAY Genotyping of SNPs

[0094] The above-mentioned genome-wide scanning found that the SNPs related to the myelosuppressive toxicity of platinum-based chemotherapy drugs were detected on the SequenomMassARRAY genotyping platform, and the specific steps were as follows:

[0095] 1. Add the hemolysis reagent to the peripheral blood stored in the 2ml cryopreservation tube, mix it upside down and transfer it completely.

[0096] 2. Removal of red blood cells: Fill the 5ml centrifuge tube to 4ml with hemolysis reagent, mix by inverting, centrifuge at 4000rpm for 10 minutes, and discard the supernatant. Add 4ml of hemolysis reagent to the precipitate, invert and wash again, centrifuge at 4000rpm for 10 minutes, and discard the supernatant.

[0097] 3. Extract DNA: Add 1ml of extract solution to the precipitate (each 300ml contains 122.5ml0.2M sodium chloride, 14.4ml0.5M ethylenediaminetetraacetic acid, 15ml10% sodium dodecyl sulfate, 148.1ml double...

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Abstract

The invention belongs to the field of genetic engineering and oncology, and discloses a SNP marker related to myelosuppressive toxicity of platinum chemotherapy drugs and application thereof. 该标志物为rs12883763、rs13014982、rs6750741、rs11892526、rs430253、rs7610842、rs12639117、rs623393、rs2051802、rs11968978、rs9390164、rs1485282、rs1904023、rs11026144、rs830379、rs712476、rs8006004、rs6497934、rs6502373、rs9909179和rs2830451的组合。 The marker can be used to prepare a diagnostic kit for myelosuppressive toxicity of platinum chemotherapy drugs.

Description

technical field [0001] The invention belongs to the fields of genetic engineering and oncology, and relates to a SNP marker related to myelosuppressive toxicity of platinum chemotherapy drugs and an application thereof. Background technique [0002] Since the 1960s, platinum-based anticancer drugs represented by cisplatin have been widely used in the treatment of malignant tumors such as non-small cell lung cancer (NSCLC), and have become an indispensable drug in NSCLC chemotherapy. Platinum drugs are quickly distributed throughout the body after entering the human body, which can not only inhibit tumor growth and spread, but also kill distantly metastatic tumors, and have therapeutic effects on primary tumors, metastatic foci, and subclinical metastatic foci. However, due to the poor selectivity of platinum-based chemotherapeutic drugs to cells, while killing tumor cells, they also have a great destructive effect on normal cells, often causing some toxic and side effects. ...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C12Q1/68C12N15/11
Inventor 沈洪兵胡志斌靳光付马红霞江玥潘芸
Owner NANJING MEDICAL UNIV
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