CN105572380A - Application of IL-12 to diagnosis and treatment of non-small cell lung cancer (NSCLC) distant metastasis - Google Patents
Application of IL-12 to diagnosis and treatment of non-small cell lung cancer (NSCLC) distant metastasis Download PDFInfo
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Abstract
The invention discloses application of IL-12 to diagnosis and treatment of non-small cell lung cancer (NSCLC) distant metastasis, particularly relates to application of IL-12 to preparation of a reagent kit for prediction or diagnosis of NSCLC distant metastasis. Experiments show that the inflammatory cytokine IL-12 participates in occurrence and development of NSCLC (squamous cell carcinoma) distant metastasis, and IL-12 inhibition has an inhibiting effect on NSCLC invasiveness.
Description
Technical field
The present invention relates to diagnosing tumor and treatment field.Particularly, the present invention relates to the application of IL-12 in Diagnosis and Treat non-small cell lung cancer DISTANT METASTASES IN.
Background technology
Lung cancer is one of modal malignant tumour of many countries in the world, and in China, it is the first that lung cancer occupies the malignant tumour cause of the death.Lung cancer can be divided into non-small cell lung cancer (non-smallcelllungcancer, and small-cell carcinoma of the lung (smallcelllungcancer NSCLC), SCLC) two large classes, wherein non-small cell lung cancer (NSCLC) accounts for 80% ~ 85% of all cases of lung cancer, comprises squama cancer, gland cancer, undifferentiated carcinoma, non-small cell type lung cancer and large cell carcinoma.Squama cancer is the most common in lung cancer, and account for 40% of lung cancer, the male sex then accounts for about 80%.Wherein only have the non-small cell lung cancer of 15-25% to have the chance of operative treatment, even and if accept radical surgery treatment, still have the NSCLC patient of 50% to recur.
But lack the effective diacritics thing to non-small cell lung prognosis in current treatment means, cause the patient of different prognosis still to accept identical treatment, even if operation, still having recurrence may.Therefore, this area in the urgent need to developing a kind of detection method or the label that can distinguish non-small cell lung cancer aggressive height, thus judges in advance to the prognosis of patient, and provides personalized therapy program.
Summary of the invention
The invention discloses the correlativity of IL-12 and non-small cell lung metastasis of cancer.
First aspect present invention, provides IL-12 (IL-12) or it detects the purposes of reagent, for the preparation of the kit of prediction or diagnosing non-small cell lung cancer DISTANT METASTASES IN.
In another preference, described IL-12 derives from mammal, preferably, derives from people, mouse, rat.
In another preference, described non-small cell lung cancer comprises lung squamous cancer, adenocarcinoma of lung, low differentiation lung cancer, maxicell lung cancer; Preferably, be lung squamous cancer.
In another preference, described kit also contains the detection reagent of interleukin-8 (IL-8) and/or il-1 (IL-1).
In another preference, described detection measures tissue sample, blood sample, blood serum sample or humoral sample, and preferably, described tissue sample comprises cancerous tissue and/or cancer beside organism.
In another preference, described detection comprises Bio-plex suspension chip system, enzyme linked immunoassay method (ELISA method) detects or Time-resolved Fluoimmunoassay (TRFIA method) detects.
In another preference, described DISTANT METASTASES IN comprises the transfer of other organs except lung.
In another preference, described DISTANT METASTASES IN comprises brain metastes, Bone tumour, hepatic metastases, pleura metastasis.
In another preference, the detection reagent of described IL-12 is the antibody of IL-12.
In another preference, in described kit, be also used for positive control containing IL-12.
Second aspect present invention, provides that a kind of described kit contains a container for predicting or the kit of diagnosing non-small cell lung cancer DISTANT METASTASES IN, the detection reagent containing IL-12 in described container; And label or instructions.
In another preference, described prediction or judge that non-small cell lung metastasis of cancer refers to judge whether metastases occurs, and/or judge possibility (neurological susceptibility) size that metastases occurs.
In another preference, the object of described prediction or diagnosis is non-small cell cancerous tissue and/or cancer beside organism.
In another preference, in described label or instructions, indicate following content:
When detecting the IL-12 expression C1 in sample compared with IL-12 expression C0 in check sample, C1 >=1.3C0, preferably C1 >=1.5C0, more preferably, C1 >=2.0C0, then show that this detection sample is have the non-small cell lung cancer probability of DISTANT METASTASES IN large, or DISTANT METASTASES IN may be there is in this non-small cell lung cancer sample of surface.
Third aspect present invention, provides a kind of purposes of IL-12 inhibitor, for the preparation of the pharmaceutical composition suppressing non-small cell lung cancer DISTANT METASTASES IN and/or suppress non-small cell lung cancer cell invasion and attack or move.
In another preference, described IL-12 inhibitor comprises IL-12 specific antibody, the activity inhibitor of IL-12 and receptor antagonist.
In another preference, described pharmaceutical composition contains IL-12 inhibitor, and pharmaceutically acceptable carrier.
In another preference, described pharmaceutical composition is also containing optional chemotherapeutics.
In another preference, in described pharmaceutical composition, the amount of application of IL-12 is 0.01-10mg/kg, preferably, is 0.1-5mg/kg.
Fourth aspect present invention, be supplied to a kind of prediction of nondiagnostic or judge whether non-small cell lung cancer cell strain is high method of attacking sexual cell strain, comprise step: the expression of IL-12 in the non-small cell lung cancer cell strain described in mensuration, when the expression of IL-12 is significantly higher than the expression of IL-12 in normal lung cell, then illustrate that described non-small cell lung cancer cell strain is for the strain of high invasion and attack sexual cell.
Fifth aspect present invention, provides a kind of suppression non-small cell lung cancer cell invasion and attack of external non-therapeutic or the method for migration, comprises step:
Under IL-12 inhibitor existent condition, cultivate non-small cell lung cancer cell, thus suppress non-small cell lung cancerous invasion or migration.
Sixth aspect present invention, provides a kind of method of screening IL-12 inhibitor, comprises step:
A () adds candidate compound in non-small cell carcinoma tumor cell culture system, as test group, do not add candidate compound, as a control group in identical cell culture system;
B the invasion and attack of cell and migration in () observation test group, wherein, in the invasion and attack of cell in test group and extent of migration M1 are significantly lower than control group, the invasion and attack of cell and extent of migration M0, then show that described candidate compound is Il-12 inhibitor.
Seventh aspect present invention, provides a kind of method preparing non-small cell lung cancer DISTANT METASTASES IN animal model, comprises step: use IL-12 to non-small cell lung cancer tumor animal, thus produces non-small cell lung cancer DISTANT METASTASES IN animal model.
Eighth aspect present invention, provides a kind of method for the treatment of Metastatic Nsclc, uses IL-12 inhibitor to the object needed, thus treatment Metastatic Nsclc.
Should be understood that within the scope of the present invention, above-mentioned each technical characteristic of the present invention and can combining mutually between specifically described each technical characteristic in below (eg embodiment), thus form new or preferred technical scheme.As space is limited, tiredly no longer one by one to state at this.
Embodiment
The present inventor is through extensive and deep research, by the screening of large sample, be surprised to find that first, inflammatory cytokine IL-12 take part in generation and the development of non-small cell lung cancer (squama cancer) DISTANT METASTASES IN, namely IL-12 has the effect promoting transfer, invasion and attack in non-small cell lung cancer, therefore when detect in Non-Small Cell Lung Carcinoma (or serum) there is expression too high IL-12 time, can think that this tumor tissues has (or patient suffers from) high invasive non-small cell lung cancer.In addition, the present inventor also finds, is reduced the expression of IL-12 by the inhibitor of IL-12, can weaken the aggressive of non-small cell lung cancer, reduce the transfer ability of cancer cell.On this basis, the present invention is completed.
Term
As used herein, term " invasion and attack ", " transfer ", " migration " all refer to the DISTANT METASTASES IN ability of non-small cell lung cancer cell, such as, in transwell Matrigel, and the invasive ability of tumour cell finding or confirm; Or in vivo, idiopathic non-small cell lung cancer is in the growth of its hetero-organization except lung, organ and propagation.Term " strain of high invasion and attack sexual cell " refers to the cell line that DISTANT METASTASES IN or migration easily occur.
Non-small cell lung cancer
Lung cancer can be divided into non-small cell lung cancer (non-smallcelllungcancer from pathological, and small-cell carcinoma of the lung (smallcelllungcancer NSCLC), SCLC) two large classes, wherein non-small cell lung cancer (NSCLC) accounts for 80% ~ 85% of all cases of lung cancer, comprises squama cancer, gland cancer, undifferentiated carcinoma (poor differentiated carcinoma), non-small cell type lung cancer and large cell carcinoma.Wherein, the pathology that undifferentiated carcinoma (poor differentiated carcinoma) refers to determines that the type cell cancer is original lung carcinoma cell; But not Small Cell Lung Cancer With Selective refer to pathology cannot be classified as squama cancer, gland cancer, large cell carcinoma or undifferentiated carcinoma any one, and do not belong to the non-small cell lung cancer of small-cell carcinoma of the lung yet.
IL-12
IL-12 (IL-12) is the cell factor with extensive biologic activity, produces primarily of B cell and macrophage; IL-12 mainly acts on T cell and NK cell, stimulates activated form T cell propagation, and the cytotoxic activity of induced NK cell also promotes the cell factor such as its secretion of gamma-IFN, TNF-α, GM-CSF; Strengthen the lethal effect to tumour cell.
It has been generally acknowledged that, IL-12 contributes to, to the lethal effect of tumour cell, it is reported, in cancer of the stomach, colorectal cancer, cervical carcinoma, the expression of IL-12 all has reduction in various degree.But, the present inventor is found by pathology screening sample and experimental verification, IL-12 is the performance in high expressed in non-small cell lung cancer (especially squama cancer), and closely related with the invasion and attack degree of cancer, namely to show the ability of DISTANT METASTASES IN stronger for the non-small cell lung cancer of high expressed IL-12.
In addition, the present inventor also proves by experiment, and after the expression reducing IL-12, the invasive ability of non-small cell lung cancer is also decreased significantly.This has not only pointed out in the generation and transfer of non-small cell lung cancer, and inflammatory reaction and inflammatory factor IL-12 play an important role, especially can using IL-12 as treatment non-small cell lung cancer, the especially therapy target of Metastatic Nsclc.
Detection method and kit
The present invention relates to quantitative and detection and localization people IL-12 protein level or mRNA level in-site diagnostic testing process.These tests are known in the art.The people IL-12 protein level detected in test, may be used for diagnosing non-small cell lung cancer transfer or migration.
A kind of method that whether there is IL-12 albumen in sample that detects utilizes the specific antibody of IL-12 albumen to detect, and it comprises: contacted with IL-12 protein specific antibody by sample; Observe and whether form antibody complex, define antibody complex and just represent in sample to there is IL-12 albumen.
IL-12 albumen or its polynucleotide can be used for the Diagnosis and Treat of IL-12 protein related diseases.Part or all of polynucleotide of the present invention can be used as probe and is fixed in microarray or DNA chip, for analyzing Differential expression analysis and the gene diagnosis of gene in tissue.The antibody of anti-IL-12 can be fixed on protein-chip, for detecting the IL-12 albumen in sample.
Present invention also offers a kind of kit detecting non-small cell lung cancer, it contains the primer pair of specific amplification IL-12 and/or IL-12 specific antibody and label or instructions.
Wherein, described label or instructions indicate following content: as the mrna expression amount of the p-actin of IL-12 phase of detected object and the ratio >2 of the mrna expression amount of the p-actin of IL-12 phase of cancer beside organism, then point out the probability of this detected object metastases higher than general population.
A kind of typical kit of the present invention can be used for detecting Non-small cell lung carcinoma tissue sample or blood sample.
Inhibitor
Utilize albumen of the present invention, by various conventional screening assays, can filter out, with IL-12 albumen, interactional material occur, especially inhibitor etc.
The inhibitor (comprising antibody and other inhibitor) of IL-12 of the present invention, when carrying out using (administration) on treating, can suppress expression and/or the activity of IL-12 albumen, and then suppresses transfer or the migration of non-small cell lung cancer.Usually, but these materials are formulated in nontoxic, inertia with in pharmaceutically acceptable aqueous carrier medium, wherein pH is about 5-8 usually, and preferably pH is about 6-8, although pH value can with being formulated the character of material and illness to be treated and changing to some extent.The pharmaceutical composition prepared can carry out administration by conventional route, comprising (but being not limited to): in knurl, in intramuscular, peritonaeum, intravenous, subcutaneous, intracutaneous or topical.
Inhibitor used in the present invention comprises: the antibody of IL-12 or the activity inhibitor of L-12.Typically, the technical scheme of the target spot of the medicine that IL-12 gene is moved as preparation prevention or the metastasis of cancer for the treatment of non-small cell lung, such as. obtaining can polypeptide, the monoclonal antibody of specific inhibition of IL-6-12 expression and/or activity, thus reality suppresses the object of non-small cell lung cancer cell transfer or migration.
Present invention also offers a kind of pharmaceutical composition, it contains the IL-12 inhibitor of the present invention of safe and effective amount and pharmaceutically acceptable carrier or excipient.This kind of carrier comprises (but being not limited to): salt solution, damping fluid, glucose, water, glycerine, ethanol and combination thereof.Pharmaceutical preparation should match with administering mode.Pharmaceutical composition of the present invention can be made into injection form, such as, be prepared by conventional method by physiological saline or the aqueous solution containing glucose and other assistant agents.The pharmaceutical composition of such as Tablet and Capsula and so on, is prepared by conventional method.Pharmaceutical composition such as injection, solution, Tablet and Capsula should aseptically manufacture.The dosage of active component is treatment effective dose, such as every day about 1 microgram-10 mg/kg body weight.
Antibody
The present invention also comprises and has specific polyclonal antibody and monoclonal antibody to people IL-12 albumen, especially monoclonal antibody.Here, " specificity " refers to that antibody capable is incorporated into people IL-12, preferably, refers to that those can be combined with people IL-12 but nonrecognition and be incorporated into the antibody of other non related antigen molecule.Antibody of the present invention can be prepared by the various technology that those skilled in that art are known.Equally, the cell of expressing people's IL-12 factor or its antigen also can be used for causing immunity to animal and producing antibody.
The present invention not only comprises complete monoclonal or polyclonal antibody, but also comprises and have immunocompetent antibody fragment, as Fab' or (Fab) 2 fragment; Heavy chain of antibody; Light chain of antibody; Genetically engineered Single Chain Fv Molecule A; Or chimeric antibody.
Antibody of the present invention comprises the antibody that can suppress IL-12 function, also can be the antibody not affecting people IL-12 function.Each antibody-like can by causing immunity to the fragment of people IL-12 gene outcome or functional domain and produce, and people IL-12 gene outcome and fragment thereof can produce with recombination method or synthesize with Peptide synthesizer.With the antibody that the IL-12 gene outcome of non-modified form is combined, the gene outcome produced in prokaryotic (as E.coli) can be utilized to carry out immune animal and obtain.Antibody with posttranslational modification form is combined as glycosylation or phosphorylation IL-12 albumen or polypeptide, can utilize the gene outcome produced in eukaryotic is as yeast or insect cell carry out immune animal and obtain.
IL-12 antibody used in the present invention can be anti-human IL-12 protein antibodies.Anti-human IL-12 protein antibodies of the present invention can be used in immunohistochemistry technology, detects the people IL-12 factor in biopsy specimen.
Pharmaceutical composition and administering mode
The invention provides containing active component (a) IL-12 inhibitor; (b) pharmaceutically acceptable carrier; And the pharmaceutical composition of optional (c) chemotherapeutics.
In pharmaceutical composition of the present invention, the content of IL-12 inhibitor IL-12 inhibitor is not particularly limited, and is generally 0.01-95wt%, is preferably 0.1-90wt%.
Pharmaceutical composition of the present invention can be single preparations of ephedrine, also can be compound preparation.
In compound preparation, except containing except IL-12 inhibitor, also can comprise other antitumoral compounds, such as chemotherapeutics.Representational chemotherapeutics comprises (but being not limited to): alkylating agent, antimetabolite, folacin, pyrimidine analogue, purine analogue and related inhibitors, vinca alkaloids, epipodopyvllotoxins, microbiotic, L-asparagus fern phthalein amine enzyme, topoisomerase enzyme inhibitor, interferon, platinum coordination complex, the urea that archen replaces, methyl hydrazine derivatives, adrenal cortex inhibitor, adrenocorticotro, progestational hormone, estrogen, antiestrogenic, androgen, antiandrogen and promoting sexual gland hormone-releasing hormone analog.Preferred chemotherapeutics comprises: 5 one fluorouracils (5-FU), formyl tetrahydrofolic acid, Irinotecan, oxaliplatin, capecitabine, taxol and Duo Xi taxol.
Formulation and the preparation method of pharmaceutical composition of the present invention are not particularly limited, and the conventional general method for making in available this area makes the various formulations such as tablet, capsule, granule, sustained release agent, injection.Preferred formulation is oral formulations (as tablet) and injection.
In the present invention, IL-12 inhibitor or can be used for the transfer of prevention and therapy non-small cell lung cancer cell, invasion and attack or migration containing the pharmaceutical preparation of IL-12 inhibitor.
In the present invention, administering mode is not particularly limited, can by oral, intravenous, intramuscular, abdominal cavity or the administration such as subcutaneous.
Invention formulation can be taken or be administered once or twice or repeatedly every day, or with sustained release fashion administration.Preferably take medicine once every day, adhere to because be convenient to patient like this, thus significantly improve the compliance that patient takes medicine.
When taking, the accumulated dose of general application every day of thumping majority case is everyone 1mg ~ 200g, is preferably 10mg ~ 100g.
Beneficial effect of the present invention
The present invention finds that IL-12 plays important effect in the transfer of non-small cell lung cancer (especially squama cancer), the probability of the non-small cell lung carcinogenesis transfer of IL-12 high expressed is higher, and the expression reducing IL-12 then contributes to the transfer reducing non-small cell carcinoma.Therefore IL-12 not only as prediction or can judge the molecular marked compound whether non-small cell lung cancer shifts, can also as treatment non-small cell carcinoma or its molecular target shifted.
Below in conjunction with specific embodiment, set forth the present invention further.Should be understood that these embodiments are only not used in for illustration of the present invention to limit the scope of the invention.The experimental technique of unreceipted actual conditions in the following example, usual conveniently condition, the people such as such as Sambrook, molecular cloning: laboratory manual (NewYork:ColdSpringHarborLaboratoryPress, 1989) condition described in, or according to the condition that manufacturer advises.Unless otherwise indicated, otherwise number percent and number are percentage by weight and parts by weight.
Universal method
1. protein extraction:
(1) tissue shear is cut into tiny fragment.
(2) get Western and the IP cell pyrolysis liquid of appropriate amount, in several minutes before use, add PMSF and cocktail, make final concentration be 1mM.
(3) ratio adding 100-200 pl of lysis liquid according to every 20 milligrams of tissues adds lysate.
(4) homogenizer homogenate (15000 turns/min), until fully cracking.
(5), after abundant cracking, the centrifugal 3-5 minute of 10000-14000g, gets supernatant, can carry out follow-up Bio-plex suspension chip system cytokine assay.
2.Bio-plex suspension chip system measures cell factor.
1) material:
Bio-plexProtmHumanCytokineGrpIPanel27-Plex,
Cat.#50-0KCAF0Y is purchased from Bio-Rad company.
2) method:
1. with wetting 96 orifice plates of 100uLBio-PlexAssayBuffer, then suck all buffer with vacuum plate-absorbing machine;
2. every hole adds 50uL magnetic bead, and vacuum sucks buffer; Wash 2 times with 100uLBio-Plexwashbuffer, vacuum sucks buffer respectively;
3. flick sample and standard pipe 3-5 time, every hole adds 50uL, covers with aluminium is thin, first 1100 turns of room temperature shaker 30 seconds, then shakes 30min with 300 turns;
4. then remove aluminium gently thin, avoid spilling, vacuum pumps buffer, then 100uLBio-Plexwashbuffer washes 3 times, and vacuum sucks buffer respectively;
5. detect antibody and add the mixing of front whirlpool, every hole adds 25uL, covers aluminium thin, first 1100 turns of room temperature shaker 30 seconds, then shakes 30min with 300 turns;
6. then remove aluminium gently thin, avoid spilling, vacuum pumps buffer, then washes 3 times with 100uLBio-Plexwashbuffer, and vacuum sucks buffer respectively;
7.Streptavidin-PE fluorchrome adds the mixing of front whirlpool, and every hole adds 50uL, covers with aluminium is thin, first 1100 turns of room temperature shaker 30 seconds, then shakes 10min with 300 turns;
8. then remove aluminium gently thin, avoid spilling, vacuum pumps buffer, then 100uLBio-Plexwashbuffer washes 3 times, and vacuum sucks buffer respectively;
With the resuspended microballon of 125uLBio-Plexassaybuffer, cover with sealing bag, 1100 turns of room temperature shaker 30 seconds, just can put into instrument and carry out reading dish and detect.
Embodiment 1 non-small cell lung cancer case is collected
Have collected 22 routine non-small cell lung cancer cases from east hospital, which includes squama cancer, gland cancer, poor differentiated carcinoma (the comprise non-small cell type cancer) type of pathological examination through confirming.
In addition, 22 transfer pathological data of being undertaken being separated by Lymph Node Metastasis and DISTANT METASTASES IN are additionally provided.
The mensuration of cell factor in embodiment 2 non-small cell lung cancer
2.1 adopt universal method, and measure the expression of the IL-12 in these cases, found that, in non-small cell lung cancer, the expression of IL-12 is significantly higher than cancer beside organism (T/N ratio is much larger than 1.5, P < 0.05).
In addition, unexpectedly yes, the T/N ratio (mean value) of squama cancer is 2.4, is significantly higher than the T/N ratio 1.9 of gland cancer.This shows, compared with gland cancer, IL-12 different expression in the squama cancer of non-small cell lung cancer is more remarkable.
More unexpectedly, by the analysis of data, T/N ratio keeps relatively low level in the case without lymph or DISTANT METASTASES IN, and in the case having DISTANT METASTASES IN, T/N ratio is significantly higher than cancer beside organism.The T/N ratio divided by metastasis degree the results are shown in Table 1:
Table 1
| DISTANT METASTASES IN degree | Mean value item: T/N |
| M0 | 0.85 |
| M1 | 2.12 |
| M2 | 2.35 |
The mensuration of IL-8 and IL-1b in 2.2 non-small cell carcinomas
Adopt same procedure, also measure the expression of IL-1b and IL-8, result shows, IL-1b and IL-8 also has the high expressed of highly significant in non-small cell lung cancer.Wherein, the T/N mean value of IL-8 is the T/N mean value of 5.1, IL-1b is 8.2.
The checking of embodiment 3 enlarged sample amount
Adopt same procedure, according to above preliminary result, enlarged sample amount, to each 60 examples, measures respectively and occurs in DISTANT METASTASES IN and the non-small cell lung cancer that do not shift, the expression of IL-12.
Result shows, in the non-small cell lung cancer that DISTANT METASTASES IN occurs, the expression (T/N mean value about 2.2) of IL-12 is significantly higher than the non-small cell lung cancer (T/N mean value about 0.8) do not shifted.
Embodiment 4 process LAN IL-12 is on the invasive impact of non-small cell cancerous cell line
First by human leukemia monocytic series THP-1, after phorbol exters stimulates, differentiation becomes macrophage, detects the expression of cell factor IL-1b, Il-8 and IL-12; Then by Lines in six orifice plate cells with macrophage Dual culture, observe its biology morphology change; Application Transwell attacks the change that cell detects non-small cell lung cancer cell invasive ability in co-culture system.
Found that, IL-12 can make the aggressive of Lines significantly increase.
Embodiment 5 suppresses IL-12 on the invasive impact of Lines
First by human leukemia monocytic series THP-1, after phorbol exters stimulates, differentiation becomes macrophage, detects the expression of cell factor IL-1, Il-8 and IL-12; Then by Lines in six orifice plate cells with macrophage Dual culture, add the antibody of IL-1, Il-8 and IL-12 simultaneously, observe its biology morphology change; Application Transwell attacks the change that cell detects non-small cell lung cancer cell invasive ability in co-culture system.
Found that, suppress IL-12 that Lines aggressive can be made to be inhibited.
The all documents mentioned in the present invention are quoted as a reference all in this application, are just quoted separately as a reference as each section of document.In addition should be understood that those skilled in the art can make various changes or modifications the present invention, and these equivalent form of values fall within the application's appended claims limited range equally after having read above-mentioned instruction content of the present invention.
Claims (10)
1. IL-12 (IL-12) or its detect the purposes of reagent, it is characterized in that, for the preparation of the kit of prediction or diagnosing non-small cell lung cancer DISTANT METASTASES IN.
2. purposes as claimed in claim 1, it is characterized in that, described non-small cell lung cancer comprises lung squamous cancer, adenocarcinoma of lung, low differentiation lung cancer, maxicell lung cancer; Preferably, be lung squamous cancer.
3. purposes as claimed in claim 1, is characterized in that, described kit also contains the detection reagent of interleukin-8 (IL-8) and/or il-1 (IL-1).
4. purposes as claimed in claim 1, it is characterized in that, described DISTANT METASTASES IN comprises the transfer of other organs except lung.
5. purposes as claimed in claim 1, it is characterized in that, the detection reagent of described IL-12 is the antibody of IL-12.
6. for predicting or the kit of diagnosing non-small cell lung cancer DISTANT METASTASES IN, it is characterized in that, described kit contains a container, the detection reagent containing IL-12 in described container; And label or instructions.
7. kit as claimed in claim 5, is characterized in that, indicates following content in described label or instructions:
When detecting the IL-12 expression C1 in sample compared with IL-12 expression C0 in check sample, C1 >=1.3C0, preferably C1 >=1.5C0, more preferably, C1 >=2.0C0, then show that this detection sample is have the non-small cell lung cancer probability of DISTANT METASTASES IN large, or DISTANT METASTASES IN may be there is in this non-small cell lung cancer sample of surface.
8. a purposes for IL-12 inhibitor, is characterized in that, for the preparation of the pharmaceutical composition suppressing non-small cell lung cancer DISTANT METASTASES IN and/or suppress non-small cell lung cancer cell invasion and attack or move.
9. a nondiagnostic prediction or judge that whether non-small cell lung cancer cell strain is the method for high invasion and attack sexual cell strain, it is characterized in that, comprise step: the expression of IL-12 in the non-small cell lung cancer cell strain described in mensuration, when the expression of IL-12 is significantly higher than the expression of IL-12 in normal lung cell, then illustrate that described non-small cell lung cancer cell strain is for the strain of high invasion and attack sexual cell.
10. the suppression non-small cell lung cancer cell invasion and attack of external non-therapeutic or a method for migration, is characterized in that, comprise step:
Under IL-12 inhibitor existent condition, cultivate non-small cell lung cancer cell, thus suppress non-small cell lung cancerous invasion or migration.
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| Application Number | Priority Date | Filing Date | Title |
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| CN201410624289.4A CN105572380A (en) | 2014-11-06 | 2014-11-06 | Application of IL-12 to diagnosis and treatment of non-small cell lung cancer (NSCLC) distant metastasis |
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| CN201410624289.4A CN105572380A (en) | 2014-11-06 | 2014-11-06 | Application of IL-12 to diagnosis and treatment of non-small cell lung cancer (NSCLC) distant metastasis |
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Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101120087A (en) * | 2004-12-21 | 2008-02-06 | 森托科尔公司 | Anti-il-12 antibodies, epitopes, compositions, methods and uses |
| WO2011085163A2 (en) * | 2010-01-08 | 2011-07-14 | The Regents Of The University Of California | Protein markers for lung cancer detection and methods of using thereof |
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2014
- 2014-11-06 CN CN201410624289.4A patent/CN105572380A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101120087A (en) * | 2004-12-21 | 2008-02-06 | 森托科尔公司 | Anti-il-12 antibodies, epitopes, compositions, methods and uses |
| WO2011085163A2 (en) * | 2010-01-08 | 2011-07-14 | The Regents Of The University Of California | Protein markers for lung cancer detection and methods of using thereof |
Non-Patent Citations (1)
| Title |
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| 陈嫯: "非小细胞肺癌患者血清IL-12、IL-10测定的临床意义", 《万方数据库》 * |
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Application publication date: 20160511 |