WO2007074966A1 - Mac-2bp as a marker for the diagnosis of gastric cancer - Google Patents
Mac-2bp as a marker for the diagnosis of gastric cancer Download PDFInfo
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- WO2007074966A1 WO2007074966A1 PCT/KR2006/003802 KR2006003802W WO2007074966A1 WO 2007074966 A1 WO2007074966 A1 WO 2007074966A1 KR 2006003802 W KR2006003802 W KR 2006003802W WO 2007074966 A1 WO2007074966 A1 WO 2007074966A1
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- 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
- G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
- G01N33/574—Immunoassay; Biospecific binding assay; Materials therefor for cancer
- G01N33/57407—Specifically defined cancers
- G01N33/57446—Specifically defined cancers of stomach or intestine
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- 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
- G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
- G01N33/574—Immunoassay; Biospecific binding assay; Materials therefor for cancer
- G01N33/57484—Immunoassay; Biospecific binding assay; Materials therefor for cancer involving compounds serving as markers for tumor, cancer, neoplasia, e.g. cellular determinants, receptors, heat shock/stress proteins, A-protein, oligosaccharides, metabolites
Definitions
- the present invention relates to a diagnostic marker for gastric cancer. More particularly, the present invention relates to a diagnostic kit for gastric cancer, comprising an agent capable of detecting Mac-2BP (Mac-2 binding protein) , which is identified as a gastric cancer marker. Also, the present invention is concerned with a method for detecting the gastric cancer marker using the kit.
- a diagnostic marker for gastric cancer More particularly, the present invention relates to a diagnostic kit for gastric cancer, comprising an agent capable of detecting Mac-2BP (Mac-2 binding protein) , which is identified as a gastric cancer marker.
- Mac-2BP Mac-2 binding protein
- cancer marker antigens Human tumors express and secrete various specific molecules called cancer marker antigens.
- antigens include AFP, gamma, beta, beta, beta, beta, beta, beta, beta, beta, beta, beta, beta, beta, beta, beta, beta, beta, beta, beta, beta, beta, beta, beta, beta, beta, beta, beta, beta, beta, beta, beta, beta, beta, beta, beta, beta, beta, beta, beta, beta-2, beta-2, beta-2, beta-2, beta-2, beta-2, beta-2, beta-2, beta-2, beta-2, beta-2, beta-2, beta-2, beta, beta, beta, beta, beta, beta, beta, beta, beta, beta, beta, beta, beta, beta, beta, beta, beta, beta, beta, beta, beta, beta, beta, beta, beta, beta, beta, beta, beta, beta, beta, beta, beta, beta, beta, beta, beta, beta, beta, beta, beta, beta, beta, beta
- Gastric cancer is one of the cancers showing the highest morbidity and mortality rates in the world, and is a main cause of death in various countries including Korea, Japan, China, Russia, Hong Kong, and countries in central Europe, Central and South America and Scandinavia. Markers or therapeutic agents which are highly useful in the diagnosis and treatment of gastric cancer, however, have not yet been developed.
- Mac-2BP Mac-2 binding protein
- FIG. IA shows the expression of a Mac-2BP transcript at higher levels in metastatic secondary cancer tissues than in primary cancer tissues with the solid tumor marker Legumain serving as a control, as assayed by Northern blotting.
- FIG. IB shows the specific expression of Mac-2BP protein in gastric cancer cell lines as assayed by flow cytometry in which each cell line is fixed with formaldehyde and stained with a monoclonal antibody against Mac-2BP;
- FIG. 2A shows the expression levels of Mac-2BP protein in gastric cell lines as assayed by Mac-2BP ELISA using the cell lysates of the cell lines.
- FIG. 2B shows the levels of Mac-2BP secreted from gastric cell lines SNU-484, -620, and -638, which are different in intracellular expression level, as assayed by ELISA using concentrates of cell culture media;
- FIG. 3 shows the overexpression of Mac-2BP at higher levels in gastric cancer tissues (3B and 3D) than in normal tissues (3A and 3C) as assayed by the immunohistochemistry using a monoclonal antibody to Mac-2BP; and
- FIG. 4 shows the levels of Mac-2BP secreted to the extracellular environment as assayed by ELISA using sera taken from gastric cancer patients and normal persons .
- the present invention pertains to a diagnostic kit for gastric cancer, comprising an agent with which the level of mRNA or protein of a Mac-2BP gene can be determined.
- the present invention pertains to a method for detecting a gastric cancer marker, comprising the contact of a biological sample with an agent which determines the level of mRNA or protein of a Mac-2BP gene.
- marker means a material that is capable of identifying cancer cells among normal cells, and may be a nucleotide marker for Mac-2BP genes or a polypeptide marker for Mac-2BP proteins. The expression of these makers is increased in gastric cancer cells as compared with the normal cells .
- diagnosis means the identification of the existence or features of gastric cancer and, particularly, is associated with the metastasis of gastric cancer, including both whether or not metastasis has occurred and the possibility of metastasis.
- Mac-2BP (NCBI number; L13210) is known to be overexpressed in lung cancer, breast cancer, colorectal cancer and ovarian cancer.
- the level of Mac- 2BP in plasma or other human fluids is recognized as a critical reference indicating the metastasis of cancer cells and the survival rate of patients with lung cancer or breast cancer (Iacobelli S et al . , Br. J. Cancer, 1994, 69, 171-76; Antonio M et al., Cancer Res, 2002, 62, 2535-39).
- no publications prior to the present invention disclose the relationship of a Mac-2BP gene with the occurrence of gastric cancer.
- Mac-2BP as a gastric cancer marker
- a Mac-2BP transcript was found to be expressed specifically in the SNU strain, a gastric cancer cell originating in Korean patients.
- the primary cancer tissue cells SNU-I and -484 have very low expression levels of the Mac-2BP transcript
- the secondary cancer tissue strains SNU-l ⁇ , -216, -620 and -638 were distinctively increased in level (FIG. IA) .
- AZ521 is a gastric cancer cell strain taken from a Japanese patient, and is used as a control.
- HS677st is a gastric cancer cell strain taken from a Korean patient, and is used as a negative control.
- HLF HLF
- Mac-2BP Human lung fibroblast
- HLF normal cell
- AZ521 gastric cancer
- Legumain a gene known to be overexpressed in solid cancer cells and to be involved in cancer metastasis, was used as a standard marker (Cheng L et al., Cancer Res. 2003, 63, 2957-2964).
- a Mac-2BP protein was also examined for specific expression in the gastric cancer cell strains.
- Mac-2BP proteins were stained using a monoclonal antibody.
- the results of an immunohistochemical staining assay using a monoclonal antibody were similar to those of Northern blotting analysis, demonstrating that Mac-2BP is expressed specifically in SNU-620 and SNU-638, both capable of metastasizing (FIG. IB) .
- lysates of gastric cancer cell strains were subjected to ELISA in order to quantitatively analyze the expression level of Mac-2BP.
- Mac-2BP protein was found to be produced at a level of up to 0.4 ⁇ g/mg in SNU-620 and -638 each, but was not produced in SNU-484, which has almost no Mac-2BP transcripts therein.
- the expression level of the gastric cancer marker gene Mac-2BP in a biological sample can be determined by quantitatively analyzing the mRNA or protein thereof. Various well-known techniques may be used to isolate mRNA and protein from a biological sample and to determine the amounts thereof.
- biological sample means a material which allows the analysis of the gastric marker gene Mac-2BP for the level of mRNA or protein thereof, examples of which include tissue, cells, urine, blood, plasma, sera, etc., but are not limited thereto.
- analysis for mRNA level it is meant that the quantity of mRNA in a biological sample is measured to examine the existence and extent of expression of mRNA of the gastric cancer marker gene Mac-2BP, thereby detecting the gastric cancer marker gene.
- Analysis methods for mRNA level may be exemplified by RT-PCR, competitive RT-PCR, real-time RT-PCR, RPA (RNase protection assay) , Northern blotting, and DNA chip, but are not limited thereto. Using these methods, the expression level of mRNA can be compared between a normal control and a subject under consideration. Also, these methods are useful to examine whether there is an increase in the level of transcription from the marker gene Mac-2BP to mRNA, which is the basis on which diagnosis of gastric cancer can be conducted.
- a kit for analyzing mRNA levels through RT-PCR comprises respective pairs of primers specific for gastric marker Mac-2BP genes.
- Each of the primers having a nucleotide sequence specific for a stretch of a marker gene, ranges in length from approximately 7 to 50 bp, and preferably from approximately 10 to 30 bp.
- the kit may comprise primers specific for a stretch of the nucleotide sequence of a control gene.
- the RT-PCR kit may comprises a test tube or a suitable container, a reaction buffer (pH and magnesium concentration variable) , dNTPs, Taq-polymerase and reverse transcriptase, DNAse, RNAse-free DEPC-water, and sterile water.
- the term "primer” means a short nucleotide sequence which can form base pairs with a complimentary template, and has a free 3' hydroxyl group which serves as a starting point for the DNA replication of the template.
- a primer is required because most enzymes
- Primers e.g., DNA polymerases or reverse transcriptases
- DNA polymerases or reverse transcriptases that catalyze the replication of DNA can only add to an existing strand of nucleotides under conditions of an appropriate buffer, temperature, various reagents, and four different nucleoside triphosphates .
- Primers may be incorporated with additional features without changing their fundamental function of serving as a starting point for DNA synthesis.
- Primers may be chemically synthesized using a phosphoramidite solid support method or some other well- known method. These nucleotide sequences may also be modified through well-known methods .
- analysis for protein level it is meant that the quantity of the protein encoded by the gastric cancer marker gene Mac-2BP is determined, preferably using an antibody specific therefor so as to examine the existence and extent of expression of the protein.
- the term "antibody” means a protein molecule which is produced in response to an antigen as part of an immune response.
- the antibody indicates protein molecules coupling specifically to the gastric cancer marker protein Mac-2BP, including polyclonal antibodies, monoclonal antibodies, and recombinant antibodies.
- Various methods may be used to analyze protein levels using antibodies, examples of which include, but are not limited to, Western blotting, ELISA (enzyme linked immunosorbent assay, RIA
- radioimmunoassay radioimmunoassay
- ouchterlony immunodiffusion rocket Immunoelectrophoresis, immunohistochemical staining, immunoprecipitation assay, complement fixation assay), FACS, and protein chip.
- the quantity of an antigen- antibody complex is compared between a normal control and a subject under consideration. Also, these methods are useful to examine whether there is a significant increase in the expression level from the marker gene Mac-2BP to the protein, which is the basis on which a diagnosis of gastric cancer can be made .
- antigen-antibody complex means a complex which is formed by the binding of an Mac- 2BP protein and an antibody specific therefor.
- the antigen- antibody complex can be quantitatively determined using the signal intensity of a detection label.
- detection label selected from among enzymes, fluorescents, ligands, luminescents, microparticles, redox molecules, and radioisotopes.
- detection labels may be employed in the quantitative analysis of antigen-antibody complex.
- Examples of the enzyme available as a detection label for the analysis include ⁇ -glucuronidase, ⁇ -D-glucosidase, ⁇ -D- galactosidase, urease, peroxidase, alkaline phosphatase, acetylcholine esterase, glucose oxidase, hexokinase and GDPase, RNase, glucose oxidase and luciferase, phosphofructokinase, phosphoenolpyruvate carboxylase, aspartate aminotransferase, phosphoenolpyruvate decarboxylase, and ⁇ -lactamase, but are not limited thereto.
- the fluorescents may be exemplified by, but are not limited to, fluorescein, isothiocyanate, rhodamine, phycoerytherin, phycocyanin, allophycocyanin, o- phthaldehyde, and fluorescamine.
- a biotin derivative may be used as the ligand, but this is non-limiting.
- Luminescents useful as the detection label include acridinium ester, luciferin, and luciferase, but are not limited thereto.
- Illustrative, non-limiting examples of the microparticles include colloidal gold and colored latex.
- the detection label in the form of redox molecules may be ferrocene, ruthenium complexes, viologen, quinone, Ti ions, Cs ions, diimide, 1, 4-benzoquinone, hydroquinone, K 4 W (CN) a, [Os(bpy) 3 ] 2+ , [RU(bpy) 3 ] 2+ or [MO(CN) 8 ] 4" , but is not limited thereto.
- Useful as radioisotopes are 3 H, 14 C, 32 P, 35 S, 36 Cl, 51 Cr, 57 Co, 58 Co, 59 Fe, 90 Y, 125 I, 131 I and 186 Re, but these are not intended to limit the present invention.
- ELISA enzyme-linked immunosorbent assay
- the protein level is determined using the sandwich ELISA, in which an antibody attached to a solid support is reacted with a sample to form an antigen- antibody complex and the complex is then associated with a labeled antibody recognizing the antigen, followed by enzyme-mediated color development, or in which a labeled secondary antibody is coupled with an antibody recognizing the antigen of an antigen-antibody complex and is subsequently subjected to enzyme-mediated color development.
- the level of a complex in which the gastric cancer cell marker protein Mac-2BP is coupled with an antibody can be used to diagnose gastric cancer.
- proteins are separated from a sample and hybridized with a protein chip to form an antigen-antibody complex, which is then read to examine the presence or expression level of the protein of interest, thereby diagnosing the occurrence of gastric cancer.
- Another preferred analysis method is a Western blotting technique, which takes advantage of one or more antibodies against the gastric cancer marker Mac-2BP.
- proteins are isolated from a sample, separated according to size by electrophoresis, transferred onto a nitrocellulose membrane, and reacted with an antibody against the gastric cancer marker Mac-2BP.
- the antigen-antibody complex is quantitatively analyzed using a labeled antibody so as to diagnose gastric cancer.
- the detection method according to the present invention comprises comparing the expression level of the marker gene between a control affected with no gastric cancer and a cell of interest.
- the expression level of mRNA or protein may be represented in an absolute quantity of the marker protein (e.g., ⁇ g/ml) or in a relative unit (e.g., relative intensity of signal).
- the present invention provides a diagnostic kit for gastric cancer, comprising an antibody binding specifically to a Mac-2BP protein.
- the present invention provides a method for detecting a gastric cancer marker, comprising bringing an antibody against a Mac-2BP protein into contact with a biological sample.
- Mac-2BP has been identified as a gastric cancer marker, as described above, antibodies thereto can be readily produced using well-known techniques.
- Polyclonal antibodies can be prepared using a method well known to those skilled in the art, for example, by injecting the gastric cancer marker protein Mac-2BP into animals and taking the sera from the animals.
- any mammalian animal such as goats, rabbits, sheep, monkeys, horses, pigs, cows, dogs, etc., may be used.
- monoclonal antibodies may be conducted using a well-known method, such as a hybridoma method (K ⁇ hler and Milstein (1976) European Journal of Immunology 6:511-519), or a phage antibody library technique (Clackson et al, Nature, 352:624-628, 1991; Marks et al, J. MoI. Biol., 222:58, 1-597, 1991).
- a hybridoma method takes advantage of the cells from an immunologically suitable host animal, such as a mouse injected with the antigenic, gastric marker protein Mac-2BP, and a cancer or myeloma cell line.
- an immunologically suitable host animal such as a mouse injected with the antigenic, gastric marker protein Mac-2BP, and a cancer or myeloma cell line.
- These two kinds of cells are fused with well known method using such as a polyethylene glycol, and the antibody-producing cells thus formed are cultured according to a standard tissue culture method.
- the positive clones are further subcloned using limited dilution technique to ensure monoclonality.
- the hybridoma cells which can produce antibodies specific for the gastric cancer marker protein Mac-2BP are cultured in vitro or in vivo on a large scale using a typical technique .
- the monoclonal antibodies produced by the hybridoma cells are preferably purified to a high level using a method well known in the art.
- Mac-2BP is constructed in vitro by cloning genes coding for the antibodies and expressing them in the form of fusion proteins on phage surfaces, followed by the separation of monoclonal antibodies binding to the Mac-2BP protein from the library.
- various methods may be used, including gel electrophoresis, dialysis, salting out, ion exchange chromatography, and affinity chromatography.
- the antibody included in the kit of the present invention may be an intact form consisting of two full- length light chains and two full-length heavy chains or a functional antigen fragment.
- a functional antigen fragment means a fragment having an antigenic binding function, exemplified by Fab, F(ab'), F(ab')2 and Fv.
- the kit comprising an antibody binding specifically to the Mac-2BP protein in accordance with the present invention, is preferably a diagnostic ELISA kit. It may- comprise an antibody specific for a control protein, a reagent for detecting an antigen-antibody complex, for example, a labeled secondary antibody, a chromophore, an enzyme (e.g., antibody-conjugated) and a substrate thereof, or other materials binding to the antibody.
- a diagnostic ELISA kit may- comprise an antibody specific for a control protein, a reagent for detecting an antigen-antibody complex, for example, a labeled secondary antibody, a chromophore, an enzyme (e.g., antibody-conjugated) and a substrate thereof, or other materials binding to the antibody.
- SW13/pcDNA and SW13/hTERT were cultured in DMEM (Invitrogen Corporation) .
- a pcDNA3/hTERT full length plasmid obtained from the lab of Professor Han-Woong Lee, Ph. D at Sungkyunkwan University, was used as an hTERT cDNA expression vector.
- SW13 cells were transformed with the expression vector.
- 5 mg of the expression vector was diluted in a serum-free medium to form a final volume of 500 ml.
- 30 ml of Lipofectamine (GIBCO, Grand Island, NY) was added to 475 ml of a serum-free medium and incubated for 15 min at room temperature.
- the DNA-added medium was mixed with the Lipofectamine-added medium, followed by incubation at room temperature for 30 min.
- the cells were washed twice with a serum-free medium.
- To the DNA-Lipofectamine complex was added to 5 ml of a medium to form a total volume of 6 ml after which the diluted complex was overlaid on the washed cells.
- the cells were incubated at 37 0 C for 6 hrs in a 5% CO 2 incubator before the medium was replaced with a normal growth medium. 24 hrs following the start of transfection, the transformed cells were screened against G418 for two weeks in a medium containing 0.8 mg/ml of G418 (Sigma, St Louis, MO).
- the G418-resistant cells were seeded into 96-well plates at a density of 0.5-1 cell per well to select monoclones. Finally selected was a SW13/hTERT #31 clone, which exhibited the highest expression rate of hTERT.
- RNA pellet thus formed was dried and dissolved in DEPC-treated water. The RNA was analyzed for concentration and purity using a UV spectrophotometer.
- RNA was separated on 2% agarose gel by electrophoresis to identify 18S and 28S bands, and transferred onto a nylon membrane.
- Hybridization with radiolabeled Mac-2BP probes (NCBI number; L13210, 683bp- 1275bp) and Legumain probes (NCBI number; NM_005606, 525bp- 1325bp) was conducted. Exposure to X-ray films for 2 days enabled visualization of the expression of Mac-2BP and Legumain genes in each cell. The results are shown in FIGS. IA.
- Flow cytometry was conducted to examine the intracellular expression level of Mac-2BP.
- the gastric cancer cell lines were cultured and harvested. These cells were washed once with FACS staining buffer (0.05% BSA, 0.02% sodium azide, in PBS), dissolved in a 2% paraformaldehyde solution, fixed on ice for 15 min, and washed again once with FACS staining buffer. The washed cell pellet was dissolved in a permeabilization buffer (0.1% saponin and 0.05% sodium azide in PBS) and incubated on ice for 15 min. Following washing with FACS staining buffer, the cells were incubated with a Mac-2BP monoclonal antibody (Alexis) for 30 min.
- FACS staining buffer 0.05% BSA, 0.02% sodium azide, in PBS
- a permeabilization buffer (0.1% saponin and 0.05% sodium azide in PBS
- Each cell line was harvested and completely lysed in a lysis buffer (0.01% Nonidet P-40, 10 mM Tris, pH 7.6, 50 mM KCl, 5 mM MgCl 2 , 2 mM dithiothreitol, 20% glycerol + protease inhibitor cocktail) (Sigma) for 40 min. Water- insoluble proteins were removed by centrifugation at 12,000 rpm at 20 min before quantitative protein analysis. The same amount of protein was used in Mac-2BP ELISA. For this, an s90k/Mac-2BP ELISA kit (Bender Med System) was used.
- a lysis buffer 0.01% Nonidet P-40, 10 mM Tris, pH 7.6, 50 mM KCl, 5 mM MgCl 2 , 2 mM dithiothreitol, 20% glycerol + protease inhibitor cocktail
- the protein mixture was incubated overnight with Mac-2BP monoclonal antibody-coated strips at 4 0 C to attach the Mac- 2BP thereto, followed by washing four times with a washing buffer. Then, the strips were incubated with an HRP- conjugated secondary antibody at 37 0 C for 1 hr, washed four times with a washing buffer, and incubated in 100 ml of a substrate solution for 5 min to develop color before reaction termination with a stop buffer. The well plates were introduced into an ELISA reader, and the absorbance was read at 540 nm and analyzed using a SoftMax program.
- culture media for the gastric cancer cell lines and SW13 cell line were collected. After being cultured in 15 cm-culture dishes, each cell line was washed with, and then incubated in, a serum-free medium. After 24 hours of incubation, the cell cultures were centrifuged twice at 2,000 rpm for 10 min to collect media free of cells. The media were concentrated using Amicon (cutoff MW 50,000Da, Millipore) . The concentrates were placed in active dialysis bags and dialyzed three or more times against Ix PBS at 4 0 C at intervals of 4 hrs. The concentrations of proteins were determined using a BioRad protein assay kit before use in ELISA.
- Immunohistochemical staining was conducted in order to examine the expression level of Mac-2BP in gastric cancer tissues.
- Paraffin sections in which gastric cancer tissues taken from gastric cancer patients were embedded were deparaffinized with xylene and hydrated using graded alcohol washes. The hydrated sections were placed in 10 mM citric acid buffer (pH 6.0) after which microwaves were radiated three times to the hydrated sections for 5 min. Endogenous peroxidase was blocked by treatment with 3% hydrogen peroxide in methanol for 6 min. Thereafter, the sections were treated for 30 min with a working solution of a Vector kit (Cat No. PK6102) so as to prevent non-specific protein binding.
- a Vector kit Cat No. PK6102
- EXAMPLE 8 Relationship between Distribution of Plasma Mac- 2BP and Clinicopathologic Factors
- the level of Mac-2BP in patient's plasma was not influenced by age or sex.
- the Mac-2BP gene is overexpressed specifically in gastric cancer cells and secreted into the extracellular environment of cells.
- the gene of interest is expressed at distinctively high levels in the gastrointestinal tissues of cancer cell tissues having metastatic capacity. Therefore, gastric cancer, particularly metastasizing or metastatic gastric cancer can be diagnosed by detecting the level of mRNA or protein of the Mac-2BP gene.
- Plasma was found to have a Mac-2BP level of 11 ⁇ g/ml on average over 36 patients with gastric cancer, which is definitely higher than the average value for 9 normal persons, 4.6 ⁇ g/ml.
- Antibodies binding specifically to Mac-2BP are useful in the diagnosis of gastric cancer.
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US12/087,224 US20090130694A1 (en) | 2005-12-28 | 2006-09-25 | MAC-2BP as a Marker for the Diagnosis of Gastric Cancer |
EP06798885A EP1966607A4 (en) | 2005-12-28 | 2006-09-25 | Mac-2bp as a marker for the diagnosis of gastric cancer |
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KR1020050132076A KR100721507B1 (en) | 2005-12-28 | 2005-12-28 | Mac-2bp as a marker for the diagnosis of gastric cancer |
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US (1) | US20090130694A1 (en) |
EP (1) | EP1966607A4 (en) |
KR (1) | KR100721507B1 (en) |
CN (1) | CN101389962A (en) |
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Cited By (1)
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ITRM20090081A1 (en) * | 2009-02-25 | 2010-08-26 | Stefano Iacobelli | USE OF 90K PROTEIN INHIBITORS FOR THE PREPARATION OF A MEDICATION FOR THE CURE OR PREVENTION OF TUMORS. |
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CA2791671A1 (en) * | 2010-03-03 | 2011-09-09 | Toray Industries, Inc. | Marker for detecting gastric cancer and method for detecting gastric cancer |
RU2013131236A (en) | 2010-12-09 | 2015-01-20 | Торэй Индастриз, Инк. | IMMUNO ANALYSIS OF PROTEIN COFILIN 1 |
CN102680688B (en) * | 2012-05-14 | 2014-07-02 | 上海交通大学 | Diagnostic kit and application of BFAR (bifunctional apoptosis regulator) in preparation of gastric cancer early diagnostic reagent |
CN102680706B (en) * | 2012-05-14 | 2014-07-02 | 上海交通大学 | Application of protein CTSF (Cathepsin F) in preparation of reagent for diagnosing gastric cancer and diagnostic reagent kit |
CN112345757B (en) * | 2020-11-13 | 2021-10-22 | 吉林大学 | Application of SCTAG in preparation of kit for diagnosing gastric cancer |
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- 2006-09-25 RU RU2008130888/15A patent/RU2008130888A/en not_active Application Discontinuation
- 2006-09-25 CN CNA2006800534604A patent/CN101389962A/en active Pending
- 2006-09-25 US US12/087,224 patent/US20090130694A1/en not_active Abandoned
- 2006-09-25 EP EP06798885A patent/EP1966607A4/en not_active Withdrawn
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KR20030059852A (en) * | 2001-12-29 | 2003-07-12 | 한국생명공학연구원 | A method for the diagnosis of cancers by measuring the changes of glycosylation of proteins related to tumorigenesis and metastasis and kit for diagnosis of cancers using the same |
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---|---|---|---|---|
ITRM20090081A1 (en) * | 2009-02-25 | 2010-08-26 | Stefano Iacobelli | USE OF 90K PROTEIN INHIBITORS FOR THE PREPARATION OF A MEDICATION FOR THE CURE OR PREVENTION OF TUMORS. |
WO2010097825A1 (en) * | 2009-02-25 | 2010-09-02 | Stefano Iacobelli | Use of anti-90k monoclonal antibodies for the prevention and treatment of tumors and metastases thereof |
US8679495B2 (en) | 2009-02-25 | 2014-03-25 | Mediapharma S.R.L. | Use of anti-90K monoclonal antibodies for the prevention and treatment of tumors and metastases thereof |
Also Published As
Publication number | Publication date |
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CN101389962A (en) | 2009-03-18 |
KR100721507B1 (en) | 2007-05-23 |
RU2008130888A (en) | 2010-02-10 |
EP1966607A1 (en) | 2008-09-10 |
US20090130694A1 (en) | 2009-05-21 |
EP1966607A4 (en) | 2009-01-21 |
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