CN106148475A - Wild type IDH2 gene is as target application in preparing Treatment for Non-small Cell Lung medicine - Google Patents
Wild type IDH2 gene is as target application in preparing Treatment for Non-small Cell Lung medicine Download PDFInfo
- Publication number
- CN106148475A CN106148475A CN201610511906.9A CN201610511906A CN106148475A CN 106148475 A CN106148475 A CN 106148475A CN 201610511906 A CN201610511906 A CN 201610511906A CN 106148475 A CN106148475 A CN 106148475A
- Authority
- CN
- China
- Prior art keywords
- cell
- idh2
- wild type
- lung
- process lan
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Withdrawn
Links
Classifications
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/5005—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells
- G01N33/5008—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics
- G01N33/5011—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics for testing antineoplastic activity
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
Abstract
The present invention relates to wild type IDH2 gene as target application in preparing Treatment for Non-small Cell Lung medicine.IDH2 is up-regulated in cancerous lung tissue, and wild type IDH2 promotes proliferation of lung cancer cells and the growth of lung carcinoma cell transplanted tumor in nude mice, suppresses cell death.Strike subtract wild type IDH2 can effectively suppress cell proliferation and lung carcinoma cell transplanted tumor in nude mice growth, increase cell death.IDH2 process LAN reduces intracellular alpha Ketoglutarate content, uses the mode adding alpha Ketoglutarate can suppress the propagation of non-small cell lung cancer cell, and IDH2 process LAN too increases the content of intracellular 2 hydroxyl 1,3-propanedicarboxylic acids, may suppression cell death.The present invention is that the treatment of clinical pulmonary carcinoma provides target gene IDH2, and the research for related drugs target spot provides theoretical foundation.
Description
Technical field
The invention belongs to biomedical sector, be specifically related to wild type IDH2 gene and preparing non-small cell lung as target
Application in cancer medicine.
Background technology
Along with development and the change of spectrum of disease of economic society, the sickness rate of the tumors such as China's pulmonary carcinoma substantially rises.According to
China's tumor registration annual report (2012), China's whole nation tumor registration area Incidence is primary is pulmonary carcinoma.Its morbidity
Rate is 53.57/10 ten thousand, is 25.34/10 ten thousand after population mark, and five year survival rate only has 10%-15%.Pulmonary carcinoma is divided into minicell
Pulmonary carcinoma and nonsmall-cell lung cancer.In China, the pulmonary carcinoma of about 80% is diagnosed as nonsmall-cell lung cancer.
Isocitrate dehydrogenase 2 (isocitrate dehydrogenase 2, IDH2) is to participate in cellular metabolic pathways
The enzyme of tricarboxylic acid cycle, is positioned at chromosome 15q26.1, and Subcellular Localization is in mitochondrial matrix.Its physiological function is forward catalysis
Isocitrate oxidation produces α-ketoglutaric acid, and reduction NADP+ produces NADPH simultaneously.Its backward reaction catalysis α-ketoglutaric acid is produced
Raw 1-Hydroxy-1,2,3-propanetricarboxylic acid., and consume NADPH generation NADP+.
Recently, WHO second phase and three phase gliomas in find more than 70% IDH1/2 sudden change, IDH1R132 and
IDH2R140/172 mutational site is also found in other tumor, such as acute myeloblastic leukemia, thyroid carcinoma, cartilage meat
Tumor, intrahepatic cholangiocellular carcinoma, carcinoma of prostate, B-lineage Acute Lymphocyte Leukemia, pheochromocytoma, colorectal cancer and melanoma
Etc. tumor.Obtain new function after IDH1/2 sudden change, i.e. catalysis a-ketoglutaric acid produces carcinogenic metabolites 2 hydroxyl 1,3-propanedicarboxylic acid
(2-HG).On the one hand IDH1/2 sudden change consumes a-ketoglutaric acid, on the other hand produces 2 hydroxyl 1,3-propanedicarboxylic acids, finally suppresses with a-ketone
1,3-propanedicarboxylic acid is the activity of a series of de-dioxygenase of substrate reactions, thus strengthens cellular metabolism, and suppression cell collagen albumen is formed
Break up with cell.At present, saltant type IDH2 targeted drug has been enter into I phase clinical trial, and IDH2 is administered orally selective depressant
AG-221 studies discovery in the extension I phase, 63 disease amelioration (40%) in 158 late period patients with hematological tumors, the patient of 76%
Curative effect is continued above 6 months, and some patients was more than 15 months.
The sequence of wild type IDH2 is disclosed, the numbered NG_023302.1 of genebank.Research shows wild type IDH2 also
In tumor cell proliferation and death, there is critical function.Melanoma cell transplanted tumor shape in IDH2 knock out mice body
Becoming substantially to be suppressed, tumor-blood-vessel growth mark significantly reduces.IDH2 backward reaction can be at hypoxia condition by paddy ammonia
Amide metabolism produces citric acid through a-ketoglutaric acid, thus promotes glioma and increase cell viability.Breast carcinoma
Cell Myc gene drives reverse IDH1/2 reaction to produce 2 hydroxyl 1,3-propanedicarboxylic acids, inhibited apoptosis.Wild type and saltant type at present
IDH2 research in pulmonary carcinoma not yet has document to report.
Summary of the invention
The present inventor's research shows that IDH2 messenger RNA high expressed in cancerous lung tissue, prompting IDH2 are probably lung
The therapeutic targets of cancer.Inventor is at non-small cell lung cancer cell H460 and A549 process LAN and strikes and subtracts IDH2, uses MTS, cell
Counting and flow cytometry means detection IDH2 are for biological behaviours such as non-small cell lung cancer cell growth, propagation and death
Impact.Immunoprophylaxis deficient mice further, observes the effect that transplanted tumor in nude mice is grown by IDH2.Find that IDH2 can promote lung
Cancer cell multiplication and the growth of lung carcinoma cell transplanted tumor in nude mice, suppress cell death.Strike and subtract IDH2 and can effectively suppress cell proliferation
Grow with lung carcinoma cell transplanted tumor in nude mice, increase cell death.IDH2 process LAN reduces intracellular α-ketoglutaric acid (α-KG) and contains
Amount, uses the mode adding α-ketoglutaric acid can suppress the propagation of non-small cell lung cancer cell, and IDH2 process LAN too increases
The content of intracellular 2-hydroxyl 1,3-propanedicarboxylic acid, may suppression cell death.That is, the present invention wild type IDH2 is proposed can be as non-little
The potential therapeutic targets of cell lung cancer.Wild type IDH2 gene can as target be used for preparing Treatment for Non-small Cell Lung medicine,
For preparing the medicine of suppression cell proliferation of NSCLC, for preparing the medicine that induction non-small cell lung cancer cell is dead
Thing.
IDH2 is up-regulated in cancerous lung tissue, and wild type IDH2 promotes proliferation of lung cancer cells and lung carcinoma cell nude mice model
Tumor grows, and suppresses cell death.Strike and subtract wild type IDH2 and can effectively suppress cell proliferation and lung carcinoma cell transplanted tumor in nude mice raw
Long, increase cell death.IDH2 process LAN reduces intracellular α-ketoglutaric acid content, and the mode using interpolation α-ketoglutaric acid can
To suppress the propagation of non-small cell lung cancer cell, IDH2 process LAN too increases the content of intracellular 2-hydroxyl 1,3-propanedicarboxylic acid, can
Cell death can be suppressed.The present invention is that the treatment of clinical pulmonary carcinoma provides target gene IDH2, for the research of related drugs target spot
Provide theoretical foundation.
Accompanying drawing explanation
Fig. 1 is that embodiment 1 experimental result picture: Fig. 1 shows IDH2 messenger RNA table in cancerous lung tissue with cancer beside organism
Reach；
Fig. 2,3,4,5 are embodiment 2 experimental result picture:
Fig. 2 a shows the comparison result of H460 and A549 cell IDH2 hot spot mutation sequence and ncbi database；
Fig. 2 b shows the western testing result of IDH2 overexpressing cell IDH2 protein content, and Fig. 2 c shows IDH2
Strike the western testing result subtracting cell IDH2 protein content；
Fig. 3 a shows the testing result of IDH2 overexpressing cell proliferation activity；Fig. 3 b shows that IDH2 strikes and subtracts cell proliferation
The testing result of activity；
Fig. 4 a shows the testing result of IDH2 overexpressing cell proliferation number；Fig. 4 b shows that IDH2 strikes and subtracts cell proliferation
The testing result of number；Fig. 4 c shows IDH2 overexpressing cell α-ketoglutaric acid content；Fig. 4 d shows that IDH2 strikes and subtracts cell
α-ketoglutaric acid content；As Fig. 4 e shows the cell training of lung carcinoma cell H460-IDH2 and A549-IDH2 at process LAN IDH2
α-ketoglutaric acid is added, it is suppressed that the propagation of cell during Yanging；
Fig. 5 a shows the testing result of IDH2 overexpressing cell death rate；Fig. 5 b shows that IDH2 strikes and subtracts cell death
The testing result of ratio；Fig. 5 c shows the 2-HG content of the lung carcinoma cell of IDH2 process LAN；
Fig. 6 is embodiment 3 experimental result picture:
After Fig. 6 a shows IDH2 process LAN, the change of lung carcinoma cell transplanted tumor in nude mice volume；Fig. 6 b shows IDH2 mistake
After expression, the change of lung carcinoma cell nude mice model tumor weight；
After Fig. 6 c shows that IDH2 strikes and subtracts, the change of lung carcinoma cell transplanted tumor in nude mice volume；Fig. 6 d shows that IDH2 strikes and subtracts
After, the change of lung carcinoma cell nude mice model tumor weight.
Detailed description of the invention
Embodiment 1.IDH2 messenger RNA is expressed to be increased in cancerous lung tissue
Current multiple data base comprises massive tumor clinical sample data, as american cancer " Lunar Probe Project " is announced in the recent period
The initial data of 1.2 ten thousand cancer patients, for researcher analysis.Poor in the expression of cancerous lung tissue Yu cancer beside organism for analyzing IDH2
Different, applicant transfers IDH2 cancerous lung tissue and the messenger RNA expression of cancer beside organism in clinical sample data base, is analyzed system
Meter.
Experimental technique:
Data are expressed by IDH2 in inquiry oncomine data base.Use t-test Functional Analysis to express data, draw
IDH2 differential expression data, and carry out statistical analysis.
Experimental result:
IDH2 is the equal high expressed of relative cancer beside organism, the lowest expression in cancerous lung tissue in the multiple chip data of data base
Sample.Experimental group that wherein number of samples is most is as it is shown in figure 1, IDH2 high expressed in cancerous lung tissue, and has statistics
Difference (P=2.8E-13).
Embodiment 2.IDH2 promotes cell proliferation of NSCLC, suppresses cell death.
This part, with non-small cell lung cancer cell H460 and A549 as blast cell, constructs in the way of slow virus importing
H460 and A549 process LAN and strike the cell model subtracting wild type IDH2.Detection IDH2 process LAN and strike and subtract rear nonsmall-cell lung cancer
Cell proliferation and dead change.
1.H460 and A549 process LAN and striking subtracts the cell model of wild type IDH2 and builds
First the IDH2 hot spot mutation region of H460 and A549 cell is checked order by we, confirms IDH2 in cell model
For wild type.For research IDH2 cell proliferation and dead effect, the mode using slow virus to import construct H460 and
A549 process LAN and strike the cell model subtracting wild type IDH2.
Experimental technique:
H460 and A549 cell is after RNA extracts and reverse transcription prepares cDNA, and PCR expands IDH2 hot spot region sequence
Row, send Hua Da gene to check order, finally compare with wild type IDH2 sequence in ncbi database.
Process LAN, strike the blast cell recovery subtracting cell, after cultivation, by after the cell infected is inoculated in culture dish, treat thin
Pei Ji is abandoned when intracellular growth is to the degrees of fusion of 80%-90%.Slow virus solution presses addition culture dish after 1:3 mixes with fresh culture
In, the polybrene being simultaneously introduced final concentration of 1ug/ml promotes that virus infects.Peptic cell after 24 hours, adds final concentration
Puromycine for 1ug/ml screens cell, arranges matched group.After about 72 hours, cellular control unit mortality, experimental group
The cell of middle residual is that virus infects successful cell.Whether cell model is determined by Western detection IDH2 protein expression
Successfully construct.
Experimental result: as shown in Figure 2 a, IDH2 hot spot mutation sequence and wild type in data base in H460 Yu A549 cell
462 bases 100% of sequence are identical, it was demonstrated that H460 Yu A549 cell IDH2 is wild type.As shown in Figure 2 b, process LAN wild type
IDH2 cell H460-IDH2 with A549-IDH2 increases relative to its compared with control cells H460-EV and A549-EV, the protein content of IDH2
Add.As shown in Figure 2 c, IDH2 wild type strikes that to subtract cell H460-sh1, H460-sh2 right relative to it with A549-sh1, A549-sh2
The protein content of photo cell H460-shcon and A549-shcon, IDH2 reduces.Prove IDH2 process LAN and strike and subtract cell construction
Success.
2.IDH2 promotes cell proliferation of NSCLC activity
MTS is tetrazolium salts (MTT) colorimetric test modification method, the method being commonly used for detecting cell-proliferation activity.Live thin
Succinate dehydrogenase in born of the same parents' mitochondrion can make ectogenic MTS be reduced to the bluish violet first crystal of solubility-
Formazan, and inactive cell is without this function, measures its absorption value at 490nm wavelength by microplate reader, can indirectly reflect
Cell-proliferation activity, the method is widely used to large-scale screening anti-tumor medicine.
Experimental technique:
Using the lung carcinoma cell model built, collect logarithmic (log) phase cell, adjust concentration of cell suspension, every hole adds 100 μ
L cell suspension (arranges the multiple hole of more than 3), makes cell to be measured adjust density 1000-10000 hole, is placed in 5%CO2,37 DEG C of cultivations
Cultivating 72 hours in case, various kinds sample wells adds MTS solution 20 μ l, hatches 1.5 hours in biochemical cultivation case.At microplate reader 490nm ripple
Strong point measures the light absorption value in each hole and draws growth relationship curve.
Experimental result:
As shown in Figure 3 a, lung carcinoma cell H460-IDH2 and the A549-IDH2 proliferation activity relative comparison of process LAN IDH2 are thin
Born of the same parents H460-EV and A549-EV increases.As shown in Figure 3 b, strike and subtract lung carcinoma cell H460-sh1, H460-sh2 and A549-of IDH2
Sh1, A549-sh2 reduce relative to its compared with control cells H460-shcon and A549-shcon proliferation activity.
3.IDH2 increases cell proliferation of NSCLC number
When cell injury or death, trypan blue can penetrate the cell membrane of degeneration, is combined with the DNA disintegrated so that it is coloring.And
It is intracellular that living cells can stop dyestuff to enter.Therefore dead cell and living cells can be differentiated.Strictly speaking, Trypan Blue detects
It is the integrity of cell membrane, it is generally recognized that cell membrane lost integrity, i.e. it is believed that cell is the most dead.
IDH2 mutain reduces the content of intracellular α-ketoglutaric acid, for determining that wild type IDH2 consumes α-one penta 2
Acid, thus promote cell survival and propagation.We use the α-ketoglutaric acid reagent box for detecting content of biovision company
(K677-100), to wild type IDH2 process LAN and strike and subtract intracellular α-ketoglutaric acid content and detect.And use external source to add
Add and can enter the octylatcd α-ketoglutaric acid of α-ketoglutaric acid analog that cell utilizes, verify α-ketoglutaric acid cell proliferation
Effect.
Experimental technique:
0.1% trypan blue solution is prepared with Hanks liquid；Disappear with 0.5% trypsin and 0.2%EDTA 1:1 mixed liquor
Change the attached cell cultivated；Adding appropriate cell culture medium liquid and terminate digestion, Hanks liquid makes cell suspension after rinsing 3 times；
Cell to be dyed is diluted to desired concn (method and concentration range are identical with cell counting)；Every 0.1ml cell suspension about adds
Freshly prepared dye liquor one droplet, contaminates 3 5min under room temperature；The cell material dyeed, takes a cell suspension and puts hemocytometer
Number plate, puts high power Microscopic observation and counts after adding coverslip；Dead cell light blue and expands, matt.Living cells is not
Colour and keep normal morphology, glossy.
The wild type IDH2 process LAN that builds and strike and subtract H460 and A549 model cell and be inoculated in 6 orifice plates, added after 12 hours
Add the octylatcd α-ketoglutaric acid of 1mM (cayman), use the detection cell number change of blood counting chamber different time points, and carry out
Statistical analysis.
Experimental result:
As shown in fig. 4 a, the cell number phase of lung carcinoma cell H460-IDH2 and A549-IDH2 of process LAN wild type IDH2
Compared with control cells H460-EV and A549-EV are increased.As shown in Figure 4 b, strike and subtract lung carcinoma cell H460-sh1, H460-sh2 of IDH2
Reduce relative to its compared with control cells H460-shcon and A549-shcon cell number with A549-sh1, A549-sh2.
As illustrated in fig. 4 c, the intracellular α-ketoglutaric acid of lung carcinoma cell H460-IDH2 and A549-IDH2 of process LAN IDH2
Content relative comparison cell H460-EV and A549-EV increase, as shown in figure 4d, strike subtract IDH2 lung carcinoma cell H460-sh1,
H460-sh2 with A549-sh1, A549-sh2 are relative to its compared with control cells H460-shcon and A549-shcon intracellular α-one penta 2
Acid content reduces.
As shown in fig 4e, in the cell cultivation process of lung carcinoma cell H460-IDH2 and A549-IDH2 of process LAN IDH2
Add α-ketoglutaric acid, it is suppressed that the propagation of cell.
4. wild type IDH2 suppression non-small cell lung cancer cell is dead
Propidium iodide (Propidium Iodide, PI) is a kind of nucleic acid dye, and it can not pass through complete cell membrane, but
The cell of apoptosis middle and advanced stage and dead cell can make nuclei dyeing through cell membrane due to the increase of permeability of cell membrane, PI
Red.Can be by the death rate of the ratio-dependent cell of Flow cytometry PI positive cell.
2-hydroxyl 1,3-propanedicarboxylic acid is the product of saltant type IDH2, and in breast carcinoma, IDH2 backward reaction can produce 2-HG and press down
Apoptosis processed.2-HG content in wild type IDH2 process LAN H460 and A549 model cell is detected by we.
Experimental technique:
After without the collected by trypsinisation of EDTA, it is centrifuged 5～10 minutes in room temperature 2000rpm, collects cell；Use pre-cooling
Once, 2000rpm is centrifuged 5～10 minutes to 1 × PBS (4 DEG C) re-suspended cell, washed cell；Add the 1 × Binding of 300 μ L
Buffer suspension cell；Upper machine adds the PI dyeing of 5 μ L for first 5 minutes and carries out flow cytometer detection.
2-HG content detection uses the test kit (K213-100) of biovision company to detect, and operation is according to explanation
Book step is carried out.
Experimental result:
As shown in Figure 5 a, the dead cell ratio of lung carcinoma cell H460-IDH2 with A549-IDH2 of process LAN IDH2 is relative
Compared with control cells H460-EV and A549-EV reduce.As shown in Figure 5 b, strike subtract IDH2 lung carcinoma cell H460-sh1, H460-sh2 and
A549-sh1, A549-sh2 increase relative to its compared with control cells H460-shcon and A549-shcon dead cell ratio.
As shown in Figure 5 c, the 2-HG content relative comparison of lung carcinoma cell H460-IDH2 and A549-IDH2 of process LAN IDH2
Cell H460-EV and A549-EV increases.
Embodiment 3. wild type IDH2 promotes the growth of non-small cell lung cancer cell transplanted tumor in nude mice
Zoopery, due to its more can the physiology of simulating human and pathological conditions, the result that zoopery obtains, also known as facing
Evidence before bed.Nude Mouse Model is the animal model that tumor research is the most frequently used.
Experimental technique:
4 week old immunodeficient mouse Bclb are purchased from the animal department of the Chinese Academy of Sciences of Central South University, and after this room raises one week, process LAN is tested
Every nude mice injection 2x106Individual cell, strike subtract cell become tumor every inject 1x106Individual cell.All experiment nude mices are the most after inoculation
Within 4th day, start to measure nude mice body weight and tumor volume, within every 2-3 days, measure once, put to death after corresponding detection of packets to three times difference
Mice, peels off tumor body, and weighs tumor weight.
Experimental result:
1. wild type IDH2 process LAN increases non-small cell lung cancer cell transplanted tumor body volume and weight
As shown in Figure 6 a, the transplanted tumor in nude mice volume of IDH2 process LAN lung carcinoma cell H460-IDH2 with A549-IDH2 is relative
Compared with control cells H460-EV and A549-EV increase.
As shown in Figure 6 b, the nude mice model tumor weight of IDH2 process LAN lung carcinoma cell H460-IDH2 with A549-IDH2 is relative
Compared with control cells H460-EV and A549-EV increase.
2. wild type IDH2 strikes and subtracts reduction non-small cell lung cancer cell transplanted tumor volume and weight
As fig. 6 c, the lung carcinoma cell H460-shIDH2 subtracting IDH2 is struck relative to its compared with control cells H460-shcon volume
Reduce.
As shown in fig 6d, strike subtract IDH2 lung carcinoma cell H460-shIDH2 relative comparison cell H460-shcon weight fall
Low.
Claims (3)
1. wild type IDH2 gene is as target application in preparing Treatment for Non-small Cell Lung medicine.
2. wild type IDH2 gene as target preparation suppression cell proliferation of NSCLC medicine in application.
3. wild type IDH2 gene is as target application in the dead medicine of preparation induction non-small cell lung cancer cell.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610511906.9A CN106148475A (en) | 2016-07-01 | 2016-07-01 | Wild type IDH2 gene is as target application in preparing Treatment for Non-small Cell Lung medicine |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610511906.9A CN106148475A (en) | 2016-07-01 | 2016-07-01 | Wild type IDH2 gene is as target application in preparing Treatment for Non-small Cell Lung medicine |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN106148475A true CN106148475A (en) | 2016-11-23 |
Family
ID=57349700
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201610511906.9A Withdrawn CN106148475A (en) | 2016-07-01 | 2016-07-01 | Wild type IDH2 gene is as target application in preparing Treatment for Non-small Cell Lung medicine |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN106148475A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111521788A (en) * | 2020-04-26 | 2020-08-11 | 青海省人民医院 | Application of PTPMT1 as lung cancer diagnosis marker and/or therapeutic target |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103163293A (en) * | 2012-06-19 | 2013-06-19 | 中国医学科学院肿瘤医院 | Test kit of auxiliary diagnosis of non-small cell lung cancer patients |
-
2016
- 2016-07-01 CN CN201610511906.9A patent/CN106148475A/en not_active Withdrawn
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103163293A (en) * | 2012-06-19 | 2013-06-19 | 中国医学科学院肿瘤医院 | Test kit of auxiliary diagnosis of non-small cell lung cancer patients |
Non-Patent Citations (3)
| Title |
|---|
| HIBA SAEED A. BAGADER等: "《Wild Type Isocitrate Dehydrogenase 1 Over-Expression is Related to Cancer Stem Cells Survival in Lung Adenocarcinoma》", 《CANCER INVESTIGATION》 * |
| JIANGJIANG LI等: "《Wild-type IDH2 promotes the Warburg effect and tumor growth through HIF1α in lung cancer》", 《THERANOSTICS》 * |
| 郭旭: "《肿瘤代谢相关基因单核苷酸多态性与非小细胞肺癌预后相关性研究及其机制》", 《国博士学位论文全文数据库医药卫生科技辑》 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111521788A (en) * | 2020-04-26 | 2020-08-11 | 青海省人民医院 | Application of PTPMT1 as lung cancer diagnosis marker and/or therapeutic target |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN104814984B (en) | Application of the Alphavirus in terms of antineoplastic is prepared | |
| CN108079317A (en) | Orally active receptor activators treat obesity-related disease method and system | |
| CN104792756A (en) | Application of tetra-p-sulfonic group-phenyl porphyrin derivative as fluorescent probe in aspect of detecting zinc ions | |
| Zhao et al. | Spontaneous photon emission: A promising non-invasive diagnostic tool for breast cancer | |
| CN104208723B (en) | MiR-638 application in anti-acute myeloid leukemia | |
| CN106148475A (en) | Wild type IDH2 gene is as target application in preparing Treatment for Non-small Cell Lung medicine | |
| CN105232501B (en) | Pierce the purposes of your ketone of Radix Glycyrrhizae Check | |
| CN114306348A (en) | Application of demethyleulaldehyde and derivatives thereof in preparation of non-small cell lung cancer resistant medicines | |
| CN109576371A (en) | Application of the long-chain non-coding RNA in adenocarcinoma of lung | |
| CN105670998B (en) | A kind of method of calcification cancer cell | |
| CN114032277B (en) | Method for detecting drug sensitivity of tumor organoid based on staining method | |
| CN105063196B (en) | Proteasome inhibitor combines the application in cholangiocarcinoma treatment with cell autophagy activator | |
| CN105613285B (en) | A kind of method of rosmarinic acid contents in quick raising Radix Salviae Miltiorrhizae | |
| CN110423812A (en) | Skiv2l2(MTR4) purposes of the gene in oncotherapy | |
| CN100429316C (en) | Recombination adenovirus and its application | |
| CN102939934A (en) | Entire visual nude mouse model with lung adenocarcinoma H1650 and establishment as well as application thereof | |
| CN108642128A (en) | A kind of external white-skinned face function evaluation method of Ping Yin Rose cell liquid | |
| CN110292629A (en) | Application of the Hexokinase 1 in anti-aging | |
| CN106753337B (en) | A kind of near-infrared and two-photon Double-mode imaging fluorescence probe and its preparation and application | |
| CN108611381A (en) | It is a kind of to be conducive to the liquid fermentation culturing method that Flavonoid substances are enriched in Phellinus | |
| CN109512815A (en) | Application of the Artesunate in induction diffusivity large B cell tumour cell | |
| CN100446761C (en) | Application of scutellaria root extract in preparation of anti esophageal cancer medicine | |
| CN107400659A (en) | A kind of cultural method of NK cells | |
| CN110337991A (en) | A kind of preparation and application of the inhibiting tumour cells agent based on Antrodia camphorata extract | |
| CN109777800A (en) | It is a kind of be capable of specificity inhibit ZBED1 gene siRNA construction method and its application |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| WW01 | Invention patent application withdrawn after publication | ||
| WW01 | Invention patent application withdrawn after publication |
Application publication date: 20161123 |