CN103616519A - Application of macrophage inhibition factor 1 in hepatopathy - Google Patents
Application of macrophage inhibition factor 1 in hepatopathy Download PDFInfo
- Publication number
- CN103616519A CN103616519A CN201310612603.2A CN201310612603A CN103616519A CN 103616519 A CN103616519 A CN 103616519A CN 201310612603 A CN201310612603 A CN 201310612603A CN 103616519 A CN103616519 A CN 103616519A
- Authority
- CN
- China
- Prior art keywords
- liver cancer
- inhibition factor
- mic
- hepatopathy
- reagent
- 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.)
- Pending
Links
Images
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
- G01N33/53—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
- G01N33/57488—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 involving compounds identifable in body fluids
-
- 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
- G01N33/57438—Specifically defined cancers of liver, pancreas or kidney
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2333/00—Assays involving biological materials from specific organisms or of a specific nature
- G01N2333/435—Assays involving biological materials from specific organisms or of a specific nature from animals; from humans
- G01N2333/52—Assays involving cytokines
- G01N2333/53—Colony-stimulating factor [CSF]
- G01N2333/535—Granulocyte CSF; Granulocyte-macrophage CSF
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2800/00—Detection or diagnosis of diseases
- G01N2800/08—Hepato-biliairy disorders other than hepatitis
- G01N2800/085—Liver diseases, e.g. portal hypertension, fibrosis, cirrhosis, bilirubin
Abstract
The invention relates to application of a macrophage inhibition factor 1 in hepatopathy and in particular relates to application of the macrophage inhibition factor 1 in preparation of a reagent or a kit for diagnosing and/or monitoring the hepatopathy of a testee. The invention also relates to the reagent or the kit for diagnosing and/or monitoring the hepatopathy of the testee. The reagent or the kit comprises a reagent for detecting the macrophage inhibition factor 1. The macrophage inhibition factor 1 disclosed by the invention can be well complemented with an alpha fetoprotein, so that the detection efficiency of the liver cancer can be greatly improved, and the macrophage inhibition factor 1 has a good application prospect.
Description
Technical field
The present invention relates to diagnosing hepatism monitoring field.Particularly, the present invention relates to the application of macrophage inhibition factor 1 in diagnosing hepatism and monitoring.
Background technology
Hepatopathy is liver cancer serious threat human health especially, and wherein primary carcinoma of liver is to be primary in the liver cell of liver or the malignant tumour of intrahepatic biliary epithelium cell, for mortality ratio is high, one of the malignant tumour of serious harm human health.Onset of liver cancer rate has in the trend ， China Incidence rising year by year and is number four in world wide, and number of the infected accounts for the more than half of the whole world, and the incidence of disease is about 28.7/10 ten thousand.Due to the early stage normal classical symptom that lacks of anatomical features morbidity, be easy to out in the cold and delay treatment, while there is manifest symptom, patient has entered middle and advanced stage, loses best occasion for the treatment.Early diagnosis and operative treatment are the keys that improves hepatocarcinoma patient survival rate.For the people at highest risk of liver cancer, now the most frequently used monitoring means is regularly to detect in blood plasma Level of Alpha Fetoprotein and imaging examination as ultrasonic etc.Yet the susceptibility of alpha-fetoprotein and specificity are all unsatisfactory, susceptibility can reach 60～70%, specificity approximately 90% left and right.Also have and report that the joint inspection of CEA, AFP, CA199 can improve the positive rate of diagnosis (department's order, Tan Guiju, Jilin medical science the 29th the 16th phase of volume of August in 2008).In addition, use as a token of thing of alpha-fetoprotein, the liver cancer case of 30%-40% can not early detection (being AFP negative patient) in addition.Research in AFP negative HCC (58 example) shows, 4 kinds of tumor markers individual event Positive rates are respectively AFU64%, CEA28%, CA19922%, TSGF66% (modern combination of Chinese tradiational and Western medicine magazine, in February, 2011,20 (6), 660-662).Therefore explore and new there is more hypersensitivity, specificity and accuracy and may there is liver cancer tumor markers that early diagnosis is worth for improving China's liver cancer clinical diagnosis level and even improving the significant and necessity of curative effect.
Macrophage inhibition factor 1 (MIC1), is also referred to as growth and differentiation factor 15 (GDF15), is an important member in TGF-beta superfamily.The biological processes such as MIC1 wide participation Apoptosis, metastasis.Ripe MIC-1 albumen in normal human serum is low-level stably express, can one crosses property significantly raise under pathological state as its expression of tumour, acute injury and inflammation.Although the concrete biological function of MIC1 is not yet illustrated, large quantity research prompting MIC1 relates to the generation of inflammation, apoptosis and tumour.But up to now, the function of MIC1 in liver cancer is still not clear, also have no in the world the diagnosis of MIC-1 and liver cancer and the correlative study for the treatment of monitoring.
Summary of the invention
Result of study of the present invention shows, macrophage inhibition factor 1 (MIC-1) can be as the mark of hepatopathy especially liver cancer for diagnosing hepatism and/or monitoring.Research of the present invention also finds that MIC-1 combines the detector efficiency that can significantly improve liver cancer with AFP.Therefore, MIC-1 is independent or combine the hepatopathy can be used in diagnosis and/or monitoring experimenter with AFP, comprises reagent or kit for the preparation of hepatopathy in diagnosis and/or monitoring experimenter.
Therefore, one aspect of the present invention relates to the purposes of macrophage inhibition factor 1 hepatopathy in diagnosis and/or monitoring experimenter.
In one embodiment of the invention, described hepatopathy comprises liver cancer, liver benign tumour and chronic hepatitis, preferably liver cancer.Analyzing and testing of the present invention found that, MIC-1 and AFP have good complementarity, and in the middle of AFP negative patient, astonishing discovery presents MIC-1 seropositivity up to 73% patient.Therefore in one embodiment of the invention, described hepatopathy is Examination For The Diagnosis of Afp Negative Hepatoma.
In another scheme of the present invention, macrophage inhibition factor 1 of the present invention can further be combined use with other hepatic disease marker that is different from macrophage inhibition factor 1, thereby be conducive to improve specificity, such hepatic disease marker can be any hepatic disease marker known in the art (TSG, IAP, GGT, IAP, PHC, CEA, CA199).This area has lot of documents to disclose such mark.In one embodiment, other hepatic disease marker that is different from macrophage inhibition factor 1 can be known liver cancer marker as alpha-fetoprotein, known liver benign tumour mark or known chronic hepatitis mark.In one embodiment of the invention, for example tumour as Hepatocarcinoma screening in, in view of MIC-1 and AFP have good complementarity, macrophage inhibition factor 1 of the present invention is further combined use with alpha-fetoprotein, thereby improves the detector efficiency that can significantly improve liver cancer.
Research of the present invention shows aspect the early stage aobvious diagnosis of liver cancer, be significantly higher than AFP with MIC-1 of the present invention.Therefore, in one embodiment of the invention, MIC-1 of the present invention is for early diagnosis I phase liver cancer or II phase liver cancer.
In one embodiment of the invention, reagent of the present invention or kit can be used for that tissue in situ detects and/or the expression (for example mRNA level) of monitoring macrophage inhibition factor 1, or for detection of and/or the serum levels of monitoring macrophage inhibition factor 1.
In one embodiment of the invention, the critical value of the serum levels of described macrophage inhibition factor 1 is made as 600pg/ml, thereby can improve sensitivity, is advantageously used in the diagnosis of the examination of liver cancer, particularly I or II phase liver cancer.
In one embodiment of the invention, the critical value of the serum levels of described macrophage inhibition factor 1 is made as 1000pg/ml, thereby improves diagnosis and/or monitoring specificity.
The opposing party of the present invention aspect relates to reagent or the kit of hepatopathy in diagnosis and/or monitoring experimenter, comprising above-described reagent or kit.In the present invention, find that MIC-1 can be used for after the detection or monitoring of hepatopathy, such reagent and/or kit can easily be prepared by this area routine techniques.For example described reagent and/or kit can comprise the antibody that detects MIC-1 and/or AFP, preferred monoclonal antibody, or the primer of expressing for detection of MIC-1 and/or AFP and/or probe etc.Described reagent or kit can also comprise the conventional damping fluid that carries out PCR reaction, polymerase, dNTPs potpourri etc.Kit of the present invention can also comprise operation instructions etc.
Accompanying drawing explanation
Fig. 1. in tumor tissues, the expression of MIC-1 is significantly higher than the other normal structure of cancer and cirrhotic tissue.
Fig. 2. SABC shows this expression and the distribution of MIC-1 in tumor tissues.
Fig. 3. the western blot of the other MIC-1 level of tumor tissues and cancer analyzes.
Fig. 4. the ROC curve of tumor markers MIC-1 diagnosing liver cancer.
Embodiment
For the effect in MIC1 in assessment hepatocellular carcinoma, we first studied 80 assembly to liver cancer tissue and corresponding patient treatment before MIC1 in serum sample express.By the mRNA of 80 groups of liver cancer tissues and contiguous pairing tissue is analyzed, we find that in 70% (56/80) hepatocellular carcinoma, MIC1 exists high expressed, showing higher than the other hepatic tissue (P<0.001) of cancer and without cancer cirrhotic tissue (P<0.001) (Fig. 1), in Showed by immune group result liver cancer tissue, MIC1 dispersivity is distributed in (Fig. 2) in hepatocellular tenuigenin.4 parts of representational patient tissue sample extraction total proteins are carried out to Westernblot analysis (Fig. 3), and result further confirms in liver cancer tissue that the expression of MIC1 is significantly higher than cancer beside organism and without cancer cirrhotic tissue; Results suggest MIC-1 may have vital role in the developing of liver cancer.In addition, research finds that the MIC-1 expression in tumor tissues becomes marked positive correlation (r=0.551 with blood serum sample, P<0.001), in tissue, MIC1 expresses positive patients serum MIC1 median (N=56) and is significantly higher than negative group (N=24) (P<0.001).In research prompting serum there is significant correlation in the remarkable rising of MIC-1 level and the expression of crossing of liver cancer tissue MIC-1, MIC-1 serum in serum is detected, the expression that can react MIC-1 in specimens changes, and MIC-1 can play a significant role as liver cancer tumor markers in the diagnosis of liver cancer and treatment monitoring.
For exploring the using value of MIC1 in hepatopathy, we detect respectively 440 liver cancer, 30 liver benign tumours, 30 chronic hepatitiss and 500 Normal group serum MIC-1 concentration, and result malignant tumors group MIC-1 concentration is significantly higher than benign tumour (P<0.001), chronic inflammation (P<0.001) and Normal group (P<0.001); Chronic hepatitis group MIC-1 level is significantly higher than benign tumour (P<0.001) and Normal group (P<0.001); Benign tumour group MIC-1 level is significantly higher than Normal group (P<0.001), the results are shown in Table 1.
Table 1: the MIC-1 serum-concentration comparison in liver cancer, hepatic benign lesions, chronic inflammation and Normal group
A: each group compares gained P value with Normal group; B: malignant tumors group, chronic hepatitis group and benign tumour group be gained P value relatively; C: malignant tumors group and chronic hepatitis group be gained P value relatively
Detect the above-mentioned level of respectively organizing serum MIC-1 and AFP, and draw ROC curve with MIC-1 and the AFP concentration of malignant tumors group and Normal group, the area under curve of MIC-1 diagnosing liver cancer is 0.911, is significantly higher than AFP (P<0.001) (Fig. 4).We have considered the MIC-1 level of ROC curve and normal population, and according to 2 times of standard deviations of normal person MIC-1 mean value ±, the critical value of establishing MIC-1 is 1000pg/ml.The specificity of MIC-1 and AFP diagnosing liver cancer is 97%, MIC-1 susceptibility and is better than AFP (77.0%vs61.4%), the results are shown in Table 2.
Table 2:MIC-1 and AFP be not to the diagnostic value of liver cancer (containing benign disease group)
For exploring the distinguishing ability of MIC-1 to benign and malignant diseases, this research, to benign tumour group, chronic hepatitis group and normal control are combined as to non-malignant group, is drawn ROC curve with MIC-1 and the AFP concentration of malignant tumors group and non-malignant tumors group; The specificity of MIC-1 diagnosing liver cancer drops to 89.8% from 97%, by case is analyzed, in 30 routine chronic hepatitis cases, there are respectively 21 routine MIC-1,4 routine AFP levels higher than critical value, in 30 routine benign tumours, there are respectively 6 routine MIC-1,7 routine AFP to exceed critical value, presentation of results MIC-1 is inferior to AFP in difference diagnosing chronic hepatitis, but suitable with AFP in discriminating benign tumour.
Compare with AFP, MIC-1 is demonstrating good using value aspect the early stage aobvious diagnosis of liver cancer, and the sensitivity of MIC-1 diagnosis I phase and II phase liver cancer is 77.9% (53/68), is significantly higher than 51.5% (P<0.01) of AFP.If the examination for liver cancer, can consider to reduce specificity and improve sensitivity, while being 600pg/mL according to ROC curve setting critical value, sensitivity in this research can be increased to 91.2%, and specificity is down to 80.6%, the diagnostic sensitivity of corresponding I-II phase liver cancer can be increased to 89.7% (61/68) (table 3).
Table 3:MIC-1 and AFP are in the different susceptibility in liver cancer by stages
Tumor markers combine the susceptibility that diagnosis can significantly improve diagnosis, this experiment has been chosen MIC-1 and has been combined diagnosis with liver cancer detection mark AFP, result shows that MIC-1 combines diagnosis and can obtain good susceptibility with AFP, especially in early days in liver cancer, the diagnostic sensitivity of MIC-1+AFP can reach 85.7%.Analyzing and testing found that, MIC-1 and AFP have good complementarity, and in the middle of AFP negative patient, 73% (124/170) patient presents MIC-1 seropositivity (table 4).
Table 4: the distribution of results of MIC-1 level in the horizontal patient of different AFP
Thereby MIC-1 is especially suitable for detecting and/or monitoring AFP negative HCC patient, combines the detector efficiency that MIC-1 and AFP can significantly improve liver cancer simultaneously.MIC-1+AFP has good complementarity in liver cancer serum detects, and has a good application prospect.
Claims (10)
1. the reagent of macrophage inhibition factor 1 hepatopathy in preparation diagnosis and/or monitoring experimenter or the purposes in kit.
2. purposes claimed in claim 1, wherein said hepatopathy comprises liver cancer, liver benign tumour and chronic hepatitis, preferably liver cancer, more preferably Examination For The Diagnosis of Afp Negative Hepatoma.
3. the purposes described in claim 1 or 2, wherein said macrophage inhibition factor 1 is further combined use with other hepatic disease marker that is different from macrophage inhibition factor 1, described other hepatic disease marker can be liver cancer marker as alpha-fetoprotein, liver benign tumour mark or chronic hepatitis mark.
4. purposes claimed in claim 3, wherein said other hepatic disease marker is alpha-fetoprotein, described hepatopathy is liver cancer.
5. the purposes described in claim 1-4 any one, wherein said liver cancer is I phase liver cancer or II phase liver cancer.
6. the purposes described in any one in claim 1-5, wherein said reagent or kit for detection of and/or monitoring hepatic tissue in the expression of macrophage inhibition factor 1.
7. the purposes described in any one in claim 1-6, wherein said reagent or kit for detection of and/or the serum levels of monitoring macrophage inhibition factor 1.
8. purposes claimed in claim 7, the critical value of the serum levels of wherein said macrophage inhibition factor 1 is made as 600pg/ml.
9. purposes claimed in claim 7, the critical value of the serum levels of wherein said macrophage inhibition factor 1 is made as 1000pg/ml.
10. diagnose and/or monitor reagent or the kit of hepatopathy in experimenter, wherein said reagent or kit comprise reagent or the kit defining in any one in claim 1-9.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201310612603.2A CN103616519A (en) | 2013-11-28 | 2013-11-28 | Application of macrophage inhibition factor 1 in hepatopathy |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201310612603.2A CN103616519A (en) | 2013-11-28 | 2013-11-28 | Application of macrophage inhibition factor 1 in hepatopathy |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN103616519A true CN103616519A (en) | 2014-03-05 |
Family
ID=50167225
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201310612603.2A Pending CN103616519A (en) | 2013-11-28 | 2013-11-28 | Application of macrophage inhibition factor 1 in hepatopathy |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN103616519A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109709331A (en) * | 2019-01-29 | 2019-05-03 | 广州瑞博奥生物科技有限公司 | Purposes of the GDF15 in the kit that preparation is used for quantitative detection liver cancer marker |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2003093794A2 (en) * | 2002-05-01 | 2003-11-13 | Irm Llc | Methods for discovering tumor biomarkers and diagnosing tumors |
| US20070128636A1 (en) * | 2005-12-05 | 2007-06-07 | Baker Joffre B | Predictors Of Patient Response To Treatment With EGFR Inhibitors |
| CN102321173A (en) * | 2011-08-12 | 2012-01-18 | 中国医学科学院肿瘤研究所 | Humanized macrophage inhibitory factor 1 monoclonal antibody and application thereof |
| CN103025890A (en) * | 2010-04-06 | 2013-04-03 | 卡里斯生命科学卢森堡控股 | Circulating biomarkers for disease |
-
2013
- 2013-11-28 CN CN201310612603.2A patent/CN103616519A/en active Pending
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2003093794A2 (en) * | 2002-05-01 | 2003-11-13 | Irm Llc | Methods for discovering tumor biomarkers and diagnosing tumors |
| US20070128636A1 (en) * | 2005-12-05 | 2007-06-07 | Baker Joffre B | Predictors Of Patient Response To Treatment With EGFR Inhibitors |
| CN103025890A (en) * | 2010-04-06 | 2013-04-03 | 卡里斯生命科学卢森堡控股 | Circulating biomarkers for disease |
| CN102321173A (en) * | 2011-08-12 | 2012-01-18 | 中国医学科学院肿瘤研究所 | Humanized macrophage inhibitory factor 1 monoclonal antibody and application thereof |
Non-Patent Citations (1)
| Title |
|---|
| TERESA A. ZIMMERS ET AL: "Growth Differentiation Factor-15: Induction in Liver Injury Through p53 and Tumor Necrosis Factor-Independent Mechanisms1", 《JOURNAL OF SURGICAL RESEARCH》 * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109709331A (en) * | 2019-01-29 | 2019-05-03 | 广州瑞博奥生物科技有限公司 | Purposes of the GDF15 in the kit that preparation is used for quantitative detection liver cancer marker |
| CN109709331B (en) * | 2019-01-29 | 2022-02-25 | 瑞博奥(广州)生物科技股份有限公司 | Application of GDF15 in preparation of kit for quantitatively detecting liver cancer marker |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Aktas et al. | Could red cell distribution width be a marker of thyroid cancer | |
| Dumlu et al. | Intraductal papillary mucinous neoplasm of the pancreas: current perspectives | |
| Li et al. | Clinical significance of serum tumour M2-PK and CA19-9 detection in the diagnosis of cholangiocarcinoma | |
| Brussino et al. | Inflammatory cytokines and VEGF measured in exhaled breath condensate are correlated with tumor mass in non-small cell lung cancer | |
| Thomas | Risk factors, biomarker and imaging techniques used for pancreatic cancer screening | |
| Yilmaz et al. | Identification of a support vector machine-based biomarker panel with high sensitivity and specificity for nonalcoholic steatohepatitis | |
| Estakhri et al. | Serum levels of CA15-3, AFP, CA19-9 and CEA tumor markers in cancer care and treatment of patients with impaired renal function on hemodialysis | |
| Halim et al. | Significance of growth differentiation factor 15 in chronic HCV patients | |
| CN108254557B (en) | The system for determining the related primary carcinoma of liver prognosis of HBV with PD-1 in the T cell of the CD8 positive and TIGIT | |
| CN103616519A (en) | Application of macrophage inhibition factor 1 in hepatopathy | |
| Al‑Kholy et al. | Pre-treatment serum inflammatory cytokines as survival predictors of patients with nasopharyngeal carcinoma receiving chemoradiotherapy | |
| CN108893534A (en) | General cancer diagnosis marker | |
| CN105461605B (en) | A kind of compound for cancer detection | |
| Kaplama et al. | Evaluation of the predictive role of neutrophil/lymphocyte ratio in the diagnosis of lymphoma in patients with asymptomatic and ısolated cervical lymphadenopathy | |
| Mathias et al. | LIQUID BIOPSY-A COMPLEMENTARY APPROACH TO TISSUE BIOPSY | |
| Oumbiche et al. | Découverte d’une arachnoïdocèle révélée par une asthénie inexpliquée | |
| Zhang et al. | Ischemic colitis caused by polycythemia vera: A case report and literature review | |
| Sahni et al. | 14. Hepatocellular adenoma (HCA)—A case presentation | |
| Zakirzhanovna et al. | The current State of the incidence of gastric cancer in the Andijan region | |
| Zhang et al. | 804P Molecular typing and TMB correlation analysis of endometrial cancer based on targeted NGS | |
| Vemparala et al. | A REVIEW ON APPLICATION OF METABOLOMICS, LIQUID BIOPSY AND FOUNDATION ONE CDx IN CANCER | |
| Hegab et al. | Prognostic significance of serum Growth differentiating factor15 (GDF) in adult acute myeloid leukemia patients | |
| Mehta et al. | Prevalence of EML4-ALK fusion gene in adenocarcinoma lung patients by using immunohistochemistry: A pilot study from cancer centre in Northern India | |
| Jung et al. | EP1123 Apoptotic effect of herbal product, Gyejibokryunghwan on uterine sarcoma cells | |
| Gürbüz et al. | An Unusual Cause of Serum CA-72-4 Elevation: Colchicine |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| WD01 | Invention patent application deemed withdrawn after publication |
Application publication date: 20140305 |
|
| WD01 | Invention patent application deemed withdrawn after publication |