EP1354202A1 - Procede de detection de maladies pancreatiques et gastro-intestinales - Google Patents

Procede de detection de maladies pancreatiques et gastro-intestinales

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Publication number
EP1354202A1
EP1354202A1 EP01273296A EP01273296A EP1354202A1 EP 1354202 A1 EP1354202 A1 EP 1354202A1 EP 01273296 A EP01273296 A EP 01273296A EP 01273296 A EP01273296 A EP 01273296A EP 1354202 A1 EP1354202 A1 EP 1354202A1
Authority
EP
European Patent Office
Prior art keywords
slpi
stool
serum
antibodies
elastase
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Withdrawn
Application number
EP01273296A
Other languages
German (de)
English (en)
Inventor
Manfred Nilius
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Vivotec Biomedical Technologies GmbH
Original Assignee
Vivotec Biomedical Technologies GmbH
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by Vivotec Biomedical Technologies GmbH filed Critical Vivotec Biomedical Technologies GmbH
Publication of EP1354202A1 publication Critical patent/EP1354202A1/fr
Withdrawn legal-status Critical Current

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
    • G01N33/53—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
    • 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
    • G01N33/573—Immunoassay; Biospecific binding assay; Materials therefor for enzymes or isoenzymes
    • 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
    • G01N33/68—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
    • G01N33/6893—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids related to diseases not provided for elsewhere
    • 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
    • G01N2333/81—Protease inhibitors
    • G01N2333/8107—Endopeptidase (E.C. 3.4.21-99) inhibitors
    • G01N2333/811—Serine protease (E.C. 3.4.21) inhibitors
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2800/00—Detection or diagnosis of diseases
    • G01N2800/06—Gastro-intestinal diseases
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2800/00—Detection or diagnosis of diseases
    • G01N2800/06—Gastro-intestinal diseases
    • G01N2800/065—Bowel diseases, e.g. Crohn, ulcerative colitis, IBS
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2800/00—Detection or diagnosis of diseases
    • G01N2800/06—Gastro-intestinal diseases
    • G01N2800/067—Pancreatitis or colitis

Definitions

  • the present invention relates to methods for the detection of pancreatic and gastrointestinal diseases, in particular methods for the detection of pancreatic carcinomas, chronic pancreatitis, gastric lesions and inflammatory bowel diseases.
  • Pancreatic diseases such as pancreatic carcinoma or chronic pancreatitis, as well as gastrointestinal diseases, for example gastric lesions or inflammatory bowel diseases, pose serious threats to the human and animal body.
  • gastrointestinal diseases for example gastric lesions or inflammatory bowel diseases
  • invasive methods endoscopy, colonoscopy, ERCP, etc.
  • imaging methods sonography, x-ray, computer tomography, etc.
  • some laboratory methods have become established as routine methods that can provide information about the insufficiency of certain internal organs such as the pancreas.
  • breath tests have recently been carried out (for example 13 C-urea breath test, H 2 -glucose breath test, 13 C-triglyceride breath test, etc. ), but their implementation has so far only been possible at a few centers, since correspondingly expensive equipment (e.g. mass spectrometer) must be available, and the costs thereof, for example due to expensive 13 C marking, can no longer be reduced.
  • correspondingly expensive equipment e.g. mass spectrometer
  • test for pancreatic elastase it can be stated that the test is a useful method for diagnosing severe exocrine pancreatic insufficiency, but it proves relatively poorly to mild to moderate functional restrictions.
  • K-Ras mutations can be detected at a pre-malignant stage, i.e. at a stage in which a carcinoma is "developing", while the tumor suppressor genes pl ⁇ and p53 are inactivated when the carcinoma is present
  • Carcinoma development have the disadvantage, however, that they also occur in the preliminary stages of tumor development, so-called “pre-malignant” conditions and in patients with chronic pancreatitis without tumor can be detected, which in turn limits their predictive power.
  • a combination of different tumor markers or other specific markers for pancreatic carcinoma should therefore be aimed for.
  • CA 19-9 a tumor marker used as a progression parameter, which is determined in patient serum as a progression marker and recurrence indicator.
  • CCA carboxypeptidase A
  • PCPA procarbypypasease A
  • PCPA is increased in the serum of pancreatic tumor patients.
  • carboxypeptidase A is only secreted to a small extent by the healthy pancreas (approx. 5% of the enzyme secretion). It is therefore to be expected that a pathological change in the pancreas (pancreatitis, pancreatic carcinoma) leads to the enzyme falling below the detection limit and / or to an increase in the “immature” proenzyme (PCPA).
  • Another advantage is that carboxypeptidase A survives the bowel passage undamaged and can be quantified in the stool.
  • Crohn's disease and ulcerative colitis are chronic inflammatory bowel diseases (IBD) of unclear etiology. logic for which there are currently no satisfactory diagnostic or therapeutic options available.
  • IBD chronic inflammatory bowel diseases
  • the methods currently used to diagnose Crohn's disease or ulcerative colitis include determining inflammation parameters and microbiological and serological examinations of body fluids and stool. In addition, there are sonographic and endoscopic examination procedures in some cases.
  • US Pat. No. 5,455,160 describes methods for diagnosing oncological diseases of the gastrointestinal tract and Crohn's disease and ulcerative colitis.
  • the document discloses the use of antibodies that are directed against calprotectin, in particular the power of • an enzyme immunoassays for the quantification of calprotectin in faeces of patients with an increased amount of calprotectin gives an indication of one of the aforementioned diseases.
  • DE 41 07 765 AI describes a method for obtaining a highly specific pancreatic elastase 1 antibody which reacts both with body fluids and with stool. An antibody obtained according to this procedure is suitable for the diagnosis of chronic and acute pancreatitis in the stool.
  • SLPI Secretory Leukocyte Proteinase Inhibitor
  • Si-Tahar Gastroenterology 118 (2000), 1061-1071
  • SLPI SLPI
  • WO 99/17800 describes the use of SLPI in powdered form as a pharmaceutical agent.
  • the powdered dosage form specifically described there serves the use of SLPI in the context of inhalation therapy.
  • US Pat. No. 5,633,227 shows the use of SLPI for the treatment of asthma or allergic rhinitis.
  • ⁇ logical sandwich assays for SLPI or SLPI go from JP 07103977 immunological elastase complexes indicate where SLPI fragments are detected with the amino acid residues 1 to 54 and 55 to the 107th It is described that diseases of the respiratory tract can be detected using the system described.
  • JP 03279862 also discloses antibody-based test methods for SLPI.
  • SLPI is known to have inhibitory activity against chymotrypsin type proteases (such as pancreatic elastase) and trypsin type proteases.
  • the first-mentioned activity is known to be assigned to the C-terminal area and the second-mentioned activity to the N-internal area of SLPI.
  • No. 5,851,983 describes truncated and fusion proteins produced on the basis of these findings, as well as pharmaceutical applications of the same.
  • WO 96/08275 discloses further fragments of SLPI and their use for inhibiting tryptases.
  • the technical problem underlying the present invention is therefore to provide simple, gentle, inexpensive and quick detection methods for pancreatic and gastrointestinal diseases, in particular pancreatic carcinoma, chronic pancreatitis, gastric lesions and inflammatory bowel diseases.
  • the invention solves this problem by providing a method for detecting a disease of a human or animal body, selected from the group consisting of pancreatic carcinoma, chronic pancreatitis, gastric lesion and inflammatory bowel disease, whereby serum or stool of the human or animal body is obtained and SLPI (Secretory Leukocyte Protease Inhibitor), fragments or complexes thereof by contacting them.
  • immunological agents is detected, especially where the concentration ration on SLPI, fragments or complexes thereof is determined in serum or stool.
  • patients suffering from chronic pancreatitis or pancreatic carcinoma can be diagnosed by having SLPI in their stool, in particular in an increased concentration compared to healthy people.
  • the stool of healthy human or animal bodies has very little or no SLPI.
  • not only chronic pancreatitis or pancreatic carcinoma can be determined in the stool of patients by means of the present invention, but also the degree of disease can be quantified by means of an SLPI concentration determination. It was shown that the SLPI concentrations in the stool correlate with the concentrations of elastase-1 present there.
  • the invention is surprising, inter alia, because it could be shown that SLPI is not immediately degraded in the intestinal tract in every case. Rather, SLPI can be demonstrated in stool in patients with chronic pancreatitis and pancreatic carcinoma.
  • the invention thus relates in particular to methods for the immunological detection of pancreatic diseases by detection of SLPI in the stool of human or animal bodies.
  • the present method for the immunological detection of pancreatic and gastrointestinal diseases can also be used for the diagnosis of gastric lesions, an increased SLPI concentration in the serum being detected compared to normal, healthy control subjects.
  • the invention therefore also relates in particular to methods for the immunological detection of gastrointestinal diseases by detection of SLPI in the serum of human or animal bodies.
  • the term “immunological agents” in particular understood the use of antibodies for the detection of antigens, in particular SLPI, SLPI-containing complexes, for example protein-protein complexes of homo- or heteromeric composition or SLPI fragments.
  • SLPI is also understood below to mean its complexes, for example with other proteins, such as an SLPI-elastase-1 complex, or fragments of SLPI, for example C- or N-internal fragments.
  • Such fragments can have, for example, amino acid residues 1 to 54 (N-terminal fragment) or 55 to 107 (C-terminal fragment).
  • the term antibody is understood to mean both monoclonal and polyclonal antibodies and fragments thereof, as long as they specifically recognize SLPI, SLPI-containing complexes, for example SLPI-Elastase-1 complexes, or SLPI fragments and tie. In preferred embodiments bind 'the antibodies or fragments thereof no other antigens.
  • the antibodies or fragments can be modified, for example with others Molecules or parts thereof are conjugated, associated or covalently or non-covalently bound, for example with colored labels, radioactive labels, enzymes which trigger measurable reactions, such as phosphatases, peroxidases, enzyme substrates, fluorescent substances, chemiluminescent substances, cytotoxic agents, spacers , Carriers or the like.
  • the labeled, conjugated or unmodified antibodies can be in soluble or immobilized form, for example on carrier matrices or beads.
  • the enzyme-labeled antibodies can be used in a second enzyme amplification system.
  • the use of immunological agents means contacting a sample, that is to say serum or stool, in particular homogenized stool, with an immunological agent, comprising at least one antibody which specifically recognizes the antigen, that is to say SLPI ,
  • the invention therefore also relates to the use of antibodies against SLPI for the qualitative and / or quantitative determination of SLPI in the stool or serum of a human or animal body. According to the invention, it is thus possible, using the antibody against SLPI, to specifically detect gastrointestinal diseases in serum and pancreatic carcinoma or chronic pancreatitis in the stool.
  • the methods according to the invention using immunological agents can preferably be carried out as sandwich ELISA, indirect or competitive ELISA, with HTP (high through put) methods being particularly preferred.
  • the at least two different monoclonal antibodies which are preferably directed against different epitopes, but alternatively also the same epitopes, from SLPI.
  • the at least two antibodies can, for example, be soluble and / or supported in a homogeneous or heterogeneous system.
  • the immunological agents as a system of three different antibodies, one of the antibodies being in the heterogeneous phase and the other two antibodies being soluble.
  • One of the two soluble antibodies is labeled, while the other is unlabeled.
  • the soluble antibody is directed against the unlabeled antibody.
  • Processes carried out according to the invention using immunological agents therefore require, in a particularly preferred embodiment, the incubation of the serum or, preferably homogenized and, if appropriate, diluted stool with at least two different antibodies which are specific for SLPI.
  • one of the two antibodies bound to a solid phase this being done in the usual way.
  • the further anti Body is advantageously in soluble form and in a preferred embodiment bears a marking. If further antibodies are used according to the invention, in a preferred embodiment only one of these bears a label.
  • one embodiment provides that either an antibody that is non-specifically bindable with SLPI or particularly preferably an antibody that is specifically bindable with SLPI is bound to a solid phase.
  • This antibody bound to the solid phase is then incubated with the serum or the stool and, optionally after a washing step, a second antibody which is specifically bindable with SLPI, is in a soluble form and bears a label. If the antibody bound to the solid phase is an antibody that is nonspecifically bindable with SLPI, not only SLPI but also other antigens bind to the solid phase.
  • the second antibody which however binds specifically with SLPI, now specifically reacts only with SLPI or the complex of SLPI and the first antibody, so that only SLPI molecules specifically carry a labeled antibody and can thus be quantified after separation of the solid from the liquid phase ,
  • SLPI-specific first antibody to a support, for example, in a sandwich ELISA
  • a second labeled antibody against SLPI is then added, which specifically reacts with SLPI or the complex of SLPI and the first antibody.
  • the amount of SLPI can be determined by means of the labeling of the second antibody using a calibration solution.
  • the invention also provides that a microtiter plate is coated with a first antibody, which binds specifically or nonspecifically to SLPI, that the serum or the stool is subsequently brought into contact with the coated microtiter plate and, after washing off unbound constituents, a labeled, for example biotin-labeled, second antibody against SLPI is added to the microtiter plate, the microtiter plate being incubated under conditions that the second antibody can bind to SLPI.
  • the solid phase is then separated from the liquid phase and either the labeling is detected directly or, if an enzyme-labeled second antibody is used, a substrate is added and the conversion of the substrate is determined quantitatively.
  • the second antibody labeled with biotin in next incubation with a conjugate of peroxidase (POD) and streptavidin.
  • POD peroxidase
  • streptavidin a conjugate of peroxidase
  • the peroxidase is able to oxidize the substrate ABTS (2,2'-azino-bis- (3-ethylbenzothiazoline-6-sulfonic acid) di-ammonium salt). Oxidized ABTS can then be determined photometrically.
  • the first antibody is bound to a carrier matrix, for example a fleece, tissue or membrane structure, in such a way that it does not represent the bottom of the depression of an ELISA immunoplate, as is usually the case, but is instead integrated directly into the matrix
  • a carrier matrix for example a fleece, tissue or membrane structure
  • Preferred matrixes are hollow fiber membranes or microporous flat membranes, which in an advantageous embodiment of the invention can also be provided with ion exchange groups.
  • Polyclonal antibodies can be produced by immunizing animals with isolated and fully purified SLPI or fragments thereof
  • Antisera with polyclonal antibodies are obtained in a manner known per se. monoclonal
  • Antibodies are produced by methods known per se.
  • the antibodies against SLPI used according to the invention can be commercially available antibodies.
  • the gastric lesions detectable according to the invention can represent symptoms of gastritis or an ulcer.
  • the inflammatory diseases detectable according to the invention can be attributed, for example, to a Helicobacter pylori infection. or symptoms of Crohn's disease or ulcerative colitis.
  • the elastase 1 concentration is also detected at the same time.
  • Human pancreatic elastase-1 survives the passage through the intestine undamaged and can be quantified in the stool as a protein.
  • the concentration of elastase 1 in the stool reflects the exocrine pancreatic function. Values greater than 200 ⁇ g elastase / per gram of stool indicate normal exocrine pancreatic function and values less than 200 ⁇ g elastase / per gram of stool indicate exocrine prancreatic insufficiency.
  • elastase-1 is released into the serum in the acute inflammatory phase, so that quantification of the elastase in the serum allows the diagnosis or the exclusion of this disease.
  • a high concentration of elastase-1 in the serum therefore indicates pancreatitis.
  • FIG. 1 a histogram of SLPI concentration in the stool
  • FIG. 2 shows a histogram for the elastase 1 concentration in the stool
  • 3 and 4 each show a histogram of the SLPI concentration in the serum.
  • the extraction is carried out by vigorously mixing the stool sample suspension several times at room temperature with a test tube shaker.
  • the chairs must be well homogenized to ensure full extraction. After at least five minutes of extraction, the mixture is finally mixed again. After the particles have settled, the stool sample extracts are diluted as follows.
  • sample extracts were diluted for the measurement of SLPI in a dilution of 1: 100 and for the comparative measurement of Elastase-1 with a dilution of 1: 500.
  • the - SLPI concentrations in the stool were determined using an SLPI ELISA (Quantikine ® , Cat. No. DP 100, 6/99) from R&D Systems (R&D Systems GmbH, Wiesbaden, Germany).
  • This ELISA uses a 96-well polystyrene microtiter plate coated with mouse monoclonal anti-human SLPI antibody. After pipetting the extract into the wells, SLPI becomes monoclonal through the immobilized. Antibody bound. After washing away unbound substances, an enzyme-linked polyclonal antibody, which is specific for human SLPI, is added to the wells (polyclonal antibody against human SLPI, linked to horseradish peroxidase). After washing off unbound antibody-enzyme reagents, a substrate solution is added to the wells and the color development is measured as a measure of bound SLPI. '
  • pankreatitischer elastase-1 The concentration of pankreatitischer elastase-1 was measured by an elastase-1-ELISAs Company ScheBo-Tech ® (Giessen, Germany, cat. No. 07, April 2000 EP 0547059 Bl) is determined.
  • FIG. 1 shows the SLPI concentrations in the stool of the patient (SLPI in picogram per gram of stool), ' plotted for the patient group without chronic pancreatitis, the patient group with pancreatic carcinoma and the patient group with chronic pancreatitis. It clearly shows that the control group members have no or only have very little SLPI in the stool, while the two patient groups with chronic pancreatitis and pancreatic carcinoma have significantly increased SLPI concentrations in the stool.
  • FIG. 2 shows the concentration measurements of elastase-1 carried out on the same patient groups.
  • the healthy control group has an elastase content well above 200 ⁇ g / g stool, while the two patient groups with chronic pancreatitis and pancreatic carcinoma have significantly reduced elastase 1 concentrations in the stool.
  • the serum samples were diluted to measure SLPI at a dilution of 1: 100.
  • the SLPI concentrations in the serum were determined by means of SLPI ELISAs (Quantikine®, Cat. No. DP 100, 6/99) from R&D Systems (R&D Systems GmbH, Wiesbaden, Germany). The ELISA was carried out as described in Example 1.
  • FIG. 3 shows the SLPI concentration in ng / ml in the control group and the patients.
  • the patient group showed significantly higher SLPI serum concentrations than the control group.
  • 17 ml of blood were obtained from 17 patients with normal gastric findings (controls), 16 patients with chronic gastritis and 18 patients with ulcer disease, and serum was obtained by centrifuging at 3000 rpm, RT, 10 min.
  • the serum samples were diluted to measure SLPI in a dilution of 1: 100.
  • SLPI concentrations in the serum were determined by means of SLPI ELISAs (Quantkine®, Cat. No. DP 100, 6/99) from R&D Systems (R&D Systems GmbH, Wiesbaden, Germany).
  • the ELISA was carried out as described in Example 1.
  • Figure 4 shows the SLPI concentration in ng / ml in the serum of patients with normal gastric finding Patients with chronic gastritis and patients with ulcers. The figure clearly shows that the healthy control group has a significantly lower SLPI concentration in the serum than both the patient group with chronic gastritis and those with ulcer disease.
  • SLPI serum concentrations are also suitable as markers for gastrointestinal lesions.

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (AREA)
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  • Urology & Nephrology (AREA)
  • Molecular Biology (AREA)
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  • Chemical & Material Sciences (AREA)
  • Hematology (AREA)
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  • Biotechnology (AREA)
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  • Physics & Mathematics (AREA)
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  • Biochemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Microbiology (AREA)
  • Pathology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Hospice & Palliative Care (AREA)
  • Oncology (AREA)
  • Peptides Or Proteins (AREA)
  • Investigating Or Analysing Biological Materials (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

Abstract

La présente invention concerne un procédé permettant de détecter des maladies gastriques et pancréatiques au moyen d'anticorps dans du sérum et des selles.
EP01273296A 2001-01-17 2001-12-11 Procede de detection de maladies pancreatiques et gastro-intestinales Withdrawn EP1354202A1 (fr)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
DE10101792 2001-01-17
DE10101792A DE10101792B4 (de) 2001-01-17 2001-01-17 Verfahren zum Nachweis von Pankreaskarzinom oder chronischer Pankreatitis und Verwendung von Antikörpern
PCT/EP2001/014511 WO2002057785A1 (fr) 2001-01-17 2001-12-11 Procede de detection de maladies pancreatiques et gastro-intestinales

Publications (1)

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EP1354202A1 true EP1354202A1 (fr) 2003-10-22

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US (1) US20040219540A1 (fr)
EP (1) EP1354202A1 (fr)
JP (1) JP2004524522A (fr)
DE (1) DE10101792B4 (fr)
WO (1) WO2002057785A1 (fr)

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Publication number Priority date Publication date Assignee Title
US20060063190A1 (en) * 2004-09-22 2006-03-23 Tripath Imaging, Inc Methods and compositions for evaluating breast cancer prognosis
EP2947459B1 (fr) * 2014-05-21 2017-07-12 Bühlmann Laboratories AG Procédé de détermination d'une protéine
WO2022091793A1 (fr) * 2020-10-27 2022-05-05 国立大学法人富山大学 Développement d'un biomarqueur du cancer du pancréas à l'aide d'une protéine dérivée de selles
CN113777309A (zh) * 2021-09-07 2021-12-10 复旦大学附属肿瘤医院 自身抗体在制备胰腺导管腺癌诊断试剂盒中的应用
WO2023100910A1 (fr) * 2021-11-30 2023-06-08 株式会社Ｌｓｉメディエンス Procédé de mesure d'élastase 1 dans des matières fécales
JP7355140B2 (ja) * 2022-02-28 2023-10-03 住友ベークライト株式会社 セリンプロテアーゼの検出用または測定用試薬

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US5851983A (en) * 1987-12-28 1998-12-22 Teijin Limited Elastase inhibitory polypeptide and process for production thereof by recombinant gene technology
DE4107765A1 (de) * 1990-07-28 1992-01-30 Schebo Tech Medizinisch Biolog Pankreas-elastase-1-spezifischer antikoerper, ein verfahren zu seiner gewinnung und ein testkit der solche antikoerper enthaelt
JP3517238B2 (ja) * 1992-09-09 2004-04-12 アムジェン インコーポレイテッド レトロウイルス感染の阻害
US5633227A (en) * 1994-09-12 1997-05-27 Miles, Inc. Secretory leukocyte protease inhibitor as an inhibitor of tryptase
US20010006939A1 (en) * 1997-10-03 2001-07-05 Ralph W. Niven Secretory leukocyte protease inhibitor dry powder pharmaceutical compositions
MXPA01012717A (es) * 1999-06-10 2002-07-02 Digital Gene Tech Inc Expresion genica modulada en inflamacion gastrointestinal.

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Title
See references of WO02057785A1 *

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DE10101792A1 (de) 2002-07-25
WO2002057785A1 (fr) 2002-07-25
US20040219540A1 (en) 2004-11-04
JP2004524522A (ja) 2004-08-12
DE10101792B4 (de) 2004-03-18

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