CN102329374B - Gastric-cancer targeted peptide and application thereof - Google Patents
Gastric-cancer targeted peptide and application thereof Download PDFInfo
- Publication number
- CN102329374B CN102329374B CN 201110264377 CN201110264377A CN102329374B CN 102329374 B CN102329374 B CN 102329374B CN 201110264377 CN201110264377 CN 201110264377 CN 201110264377 A CN201110264377 A CN 201110264377A CN 102329374 B CN102329374 B CN 102329374B
- Authority
- CN
- China
- Prior art keywords
- cancer
- stomach
- phage
- gastric
- polypeptide
- 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.)
- Expired - Fee Related
Links
Images
Landscapes
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
Abstract
The invention discloses a gastric-cancer targeted peptide and an application thereof. The sequence of the peptide is shown in SEQ. ID. NO. 1. The gastric-cancer targeted peptide provided by the invention can be bonded with the tissues of the gastric cancer specifically, both a phage expressing the peptide and a synthetic peptide probe can be specifically bonded with tissues of the gastric cancer; and the bonding force of the phage (expressing the peptide) with the tissues of the gastric cancer is 615 times higher than that of a no-load phage, and the phage expressing the peptide is almost not bonded with a normal gastric mucosa. Under a fibered confocal fluorescence microscopy, in case the gastric-cancer targeted peptide is used in cooperation with the peptide probe, the real-time positioning diagnosis of the gastric cancer can be realized, and a targeted biopsy can be guided.
Description
Technical field
The invention belongs to the molecular imaging technical field of tumour, relate to a kind of stomach cancer target polypeptide and application thereof.
Background technology
Cancer of the stomach is the malignant tumour that originates from gastric epithelial cells, estimates that the whole world has 700,000 people to die from cancer of the stomach every year, occupies second of tumour lethality rate.China's incidence gastric cancer rate reached 37.1/10 ten thousand in the male sex in 2005, and the women is that 17.4/10 ten thousand incidence gastric cancer total numbers of persons reach global more than 42%.The annual New Development patients with gastric cancer of China reaches 400,000 people, and death toll reaches 300,000 people.In the coroner's inquest for the second time of the whole nation of sanitation Ministry tissue, the mortality ratio of China's cancer of the stomach accounts for all because of 23.2% of cancer mortality number, is one of disease of serious harm China people ' s health.
Incidence gastric cancer concealment, nearly half early gastric cancer patient does not have clinical symptom, only part has symptoms such as slight maldigestion, as upper abdomen secret anguish discomfort, slightly glutted, pain, feel sick, belch etc.Although cancer of the stomach is through actively treatment such as operation, radiotherapy, chemotherapy, survival rate of overall 5 years of each phase still only has about 30%, and early gastric cancer (Early gastric cancer, EGC) 5 years survival rates of postoperative surpass 90%, small cancer of the stomach then almost reaches 100%, therefore early discovery, early treatment are key (the Wai K Leung that improves the cancer of the stomach curative effect, Ming-shiang Wu, Yasuo Kakugawa, et al.Screening for gastric cancer in Asia:current evidence and practice.The Lancet Oncology, 2008; 9 (3): 279-287).
But the diagnosis of China's early gastric cancer is very low for various reasons, early gastric cancer operability＜10%, and state-of-the-art Japan of diagnosing gastric cancer in early days, and the early gastric cancer operability accounts for more than 50%.So how to improve diagnosis and the operability of early gastric cancer, thereby key subjects that to improve 5 years survival rates of integral body of Patients with Gastric Cancer be China's cancer of the stomach research.
The diagnosis of cancer of the stomach relates generally to scope, image, pathology, check and specialties such as Digestive System Department, gastrointestinal surgery, and gastroscopy is the method for finally making a definite diagnosis of crowd's examination.Mainly contain the early diagnosis of the factor affecting cancer of the stomach of following two aspects at present:
1, the biological characteristics of development takes place in early gastric cancer
The generation of cancer of the stomach, development are considered to be under the carcinogen effect, a chronic process that builds up that begins from the gastric mucosa inflammation.Comparatively the emergence pattern of the cancer of the stomach of approval is that Correa in 1988 proposes at present: " normal gastric mucosa-superficial gastritis-atrophic gastritis-small intestine type intestinal epithelial metaplasia-slight atypical hyperplasia (Low grade dysplasia; LGD)-the severe atypical hyperplasia (high grade dysplasia, HGD)-cancer of the stomach (visible peristalsis visible intestinal peristalsis) " (Correa P.A human model of gastric carcinogenesis.Cancer Res.1988; 48:3554-60.), this is continuous, a very long pathological process.
Japan discovers, the patient who has a gastric mucosa severe atypical hyperplasia in the observation period in 4 to 48 months 60-85% be diagnosed as cancer of the stomach, the perspective study of the large case in Europe shows, in the follow-up period in 10 years, among the precancerous lesion patients such as atrophic gastritis, intestinal epithelial metaplasia, LGD and HGD, there is 0.8%, 1.8%, 3.9% and 32.7% patient that cancer of the stomach takes place respectively.This conclusion is that more than 20,000 patients are reached 10 years following up a case by regular visits to, and each patient carries out just drawing on the basis of 3-5 gastroscope, biopsy.As seen, must follow up a case by regular visits to examination repeatedly the high risk population according to present method, just might accomplish the early diagnosis of cancer of the stomach.In addition, in the medical institutions, surpassed 70% in the cancer of the stomach that detects and be EGC under Japan's " association is examined in the early gastric cancer inspection " since 2004, so high early gastric cancer recall rate then has benefited from asymptomatic crowd is carried out gastric cancer screening.
But gastroscope examination expense height, cycle are grown and take a large amount of medical resources, are subjected to the restriction of factors such as patient dependence, scope doctor level simultaneously.Even the whole world in developed country, also can't be carried out the long-term gastroscope examination of disease before the cancer at cancer of the stomach except Japan.China is populous, and patient's radix of potential precancerous lesion is big, and the scope doctor who lacks in training and be always or usually as specified carries out on a large scale, prospective study difficulty repeatedly is bigger.In vast rural area even have a lot of patients to suffer from chronic gastropathy all not accept gastroscopy for many years, just begin active treatment up to the severe complication that cancer of the stomach occurs.So, set up tally with the national condition economic, practical, efficiently based on the gastric cancer screening scheme of gastroscopic biopsy, and the early gastric cancer examination of making great efforts to carry out asymptomatic crowd is the task of top priority.
2, present gastroscope diagnosis and treatment technology defectiveness
At present, gastroscopy is still the most direct, accurate, the reliable diagnostic method of cancer of the stomach, but there is following shortcoming in the conventional pathological diagnostic mode of gastroscope+biopsy: 1. the early gastric cancer diagnosis is low, loss, misdiagnosis rate height.At first, the precancerous lesion of cancer of the stomach often relates to the stomach mucous membrane extensive region, conventional endoscopic biopsy is taked segmentation, multidraw method at random, and the possibility of the focal cancerous issue of omission is very big, the particularly then easier appearance of scope doctor " looking cancer loses " that lacks of experience; Secondly, need a large amount of case accumulation, training at microscopically for the judgement of atypism hyperplasia and early gastric cancer, between different pathologist or same pathologist repeatedly diagnose same group of gastroscopic biopsy sample, all exist certain difference; 2. " physics " of endoscopic technic progress not and the oncomolecularbiology progress further merge.Have multiple new endoscopy method to be used for clinical in recent years as: magnifying endoscope, dyeing scope, EUS, fluorescence scope, near infrared ray video image dendoscope, narrow spectral imaging technology, the micro-scope of confocal laser etc.But owing to lack the oncomolecularbiology marker of high specific and susceptibility, endoscope operator can only be according to experience, upward the suspicious lesions of stomach mucous membrane is judged from morphology (comprising both macro and micro), can not diagnose from Associated Genes in Gastric Carcinoma or molecular level, inreal real-time, the in-situ diagnostics that realizes tumour, this just might lose the diagnosis of subclinical phase of tumour and the opportunity for the treatment of.In addition, these methods mostly lack the ebm evidence in Clinical Application all soon, and the working specification of extensively not approved and Case definition can be complied with, so mostly be applied to clinical study usefulness, are difficult to popularize.3. also there is bottleneck in the development of stomach mucous membrane ablation technique under the scope.What the raising of Japan's early gastric cancer curative ratio also had benefited from mucosa resection operation under its scope extensively carries out (Endoscopic Mucosal Resection, EMR), cooperate dyeing scope and this operation of narrow spectral imaging technology can excise diameter 3cm safely with interior gastric mucosal lesion.Owing to can obtain more tissue than conventional biopsy, EMR not only can improve the diagnosis rate of early gastric cancer, can also optionally treat small gastric carcinoma and small cancer of the stomach.But surpass the precancerous lesion of 5cm for diameter, use this technology after complication hemorrhage and gastric perforation obviously occurred frequently, use limited.If can in the EMR art, locate in real time, confirm the canceration kitchen range, carry out optionally pathology mucosa resection, the scope of dwindling mucosa resection then helps extensively carrying out of this technology.
The molecular imaging of tumour (Molecular Imaging) technology, be to seek tumour cell or the specific small molecules probe of mesenchyma stroma of tumors (as the substrate of the Fab fragment of antibody, polypeptide, enzyme and part etc.), connect to form the tumour-specific probe with isotropic substance, fluorescein, paramagnetism mixture and acoustics contrast medium, video picture means such as applied optics, ultrasonic, nuclear medicine and mr are diagnosed tumour, this new technology makes subclinical phase diagnosis and the treatment of tumour become possibility at the molecular level diagnosing tumour.The development of the burnt scope of fluorescence scope, magnifying endoscope, micro-scope and copolymerization is for the molecular imaging diagnosis of digestive tract tumor provides opportunity.The micro-scope of confocal laser (confocal laserendomicroscopy wherein, CLE) be the endoscope system that comes out newly developed in recent years, be on the top of traditional visual scope the confocal laser microscope to be installed, reach the cross section image that subcutaneous height amplifies at the Endoscopic digestive tube epithelium that obtains simultaneously, the image that this amplification is 1000 times can clear identification weave construction, cell and subcellular structure, can accomplish real-time high-resolution histodiagnosis, be known as the result that can reach optical biopsy pathology.But CLE apparatus expensive, the application time is short, still belong to the tumor morphology diagnosis, and image color is single, the Case definition that shortage is extensively approved, all carry out on a small scale as clinical study both at home and abroad, as probe, then its clinical value can improve greatly as if energy combined utilization oncomolecularbiology marker.
Utilize fluorescently-labeled tumor tissues specific polypeptide diagnosing tumour, the method for diagnosing than monoclonal antibody commonly used at present has following advantage: 1. screen polypeptide and need not to pre-determine tumour specific antigen, the latter is the maximum difficult point of tumor diagnosis and treatment research; 2. polypeptide molecular weight is little, and immunogenicity is low, no obvious toxic and side effects, and tissue penetration is strong, can be in patient's vivo applications; 3. with respect to Antibody Preparation, the synthetic expense of polypeptide is low, is easy to large-scale production and application.
Summary of the invention
The problem that the present invention solves is to provide a kind of stomach cancer target polypeptide and application thereof, utilizes cancer of the stomach specific polypeptide probe can targeting to identify the characteristic of early stage cancerous issue, and the combined with fluorescent endoscope can improve the diagnosis rate of early gastric cancer under the gastroscope.
The present invention is achieved through the following technical solutions:
A kind of stomach cancer target polypeptide, the sequence of described polypeptide is shown in SEQ.ID.NO.1.
Also be connected with fluorescence molecule at described polypeptide.
Described stomach cancer target polypeptide is applied to the preparation of cancer of the stomach early diagnosis reagent.
Described polypeptide connects after the fluorescence molecule indication as targeting.
Described polypeptide is expressed in phage, the phage of polypeptide is arranged as detection probes with surface expression.
Compared with prior art, the present invention has following beneficial technical effects:
Stomach cancer target polypeptide provided by the invention can be combined with the cancer of the stomach specificity, no matter is to express the phage of this polypeptide or synthetic polypeptide probe, can both be specific in conjunction with stomach organization; Express the phage of this polypeptide and the bonding force of stomach organization and be higher than about 615 times of unloaded phage, and be combined with normal stomach mucous membrane hardly.Unite real-time, the level diagnosis that this polypeptide probe of use can be realized cancer of the stomach at the fluorescence co-focusing microscopically, and can instruct the targeting biopsy.
In patient carries out fluorescence, in the burnt splanchnoscopy of gastroscope or copolymerization, spray combination polypeptide probe in patient's gastric mucosa surface, under the guide of probe, realize the biopsy of targeting stomach mucous membrane.Overcome the deficiency of present conventional endoscope optical, can in gastroscopy, realize early stage, the real-time and level diagnosis of cancer of the stomach.
Present gastric cancer screening scheme is carried out under the ordinary optical endoscope, for the bigger stomach mucous membrane suspicious lesions of area, can only take at random the method for (blindly) multiple punch biopsy, and the possibility of failing to pinpoint a disease in diagnosis the preclinical phase canceration like this is very big.Though the burnt endoscope of copolymerization can be in the microstructure of anthroposcopy to mucous membrane, the micro-endoscopic assistance costliness of common confocal fluorescent, the application time is short, still belong to the tumor morphology diagnosis, and color is single, lacks the Case definition of extensively being approved; If energy combined utilization polypeptide provided by the invention is as probe, then its clinical value can improve greatly.
Description of drawings
Fig. 1 is the detected result figure in conjunction with activity of a plurality of phage clones and stomach cancer cell BGC823;
The immunohistochemical staining of a plurality of tissues of the positive phage clone of Fig. 2 is figure as a result;
Fig. 3 is the AAD polypeptide immunofluorescence dyeing of being combined with stomach organization figure as a result;
The bonding force comparison diagram of the positive clone of Fig. 4 phage AAD-phage, unloaded phage WT-phage and stomach cancer cell BGE823 and stomach normal cell GEC-1;
Fig. 5 is the detected result figure that the phage of express polypeptide AAD is combined with the specificity of stomach organization;
Fig. 6 is the detected result figure of the competition binding ability of AAD-phage and the stomach organization of AAD-peptide;
Fig. 7 is for uniting targeting indication and the partial enlarged drawing that uses AAD polypeptide probe under the fluorescence endoscope.
Embodiment
The invention provides the stomach cancer target polypeptide, this polypeptide is to carry out the elutriation of cancer of the stomach flesh tissue by phage random dodecapeptide storehouse to obtain.With the negative target tissue of subduing of people's normal gastric mucosa, the target tissue of the positive screening of people's stomach organization of excision, method according to the elutriation of phage random peptide library, hatch altogether with phage, flush away debond or the more weak phage of combination, the phage of being combined with the target cell specificity under the wash-out again.With the phage that elutes infection host bacterium again, breeding amplification, purifying are taken turns through 3 and to be subdued elutriation, and after increasing elutriation pressure gradually, enrichment phenomenon occurs.Thereby obtain can with the polypeptide of gastric carcinoma cells and stomach organization specific combination.The present invention is described in further detail below in conjunction with concrete screening process with to the specific target of cancer of the stomach, and the explanation of the invention is not limited.
1, the naughty sieve of the phage of people's stomach organization combination
The concrete phage random peptide library M13 (purchasing the company in NEB) that adopts screens, and its phage content is about 3.0 * 10
10Pfu; The host cell of phage adopts intestinal bacteria ER2738.
The target tissue that adopts is: get the stomach organization and the normal gastric mucosa that downcut in the art, excise necrotic tissue rapidly, separate the cancer of the stomach mucous epithelium, and with after LRS (compound sodium lactate) flushing, be cut into the minced tissue of diameter＜0.1cm, go in the clean centrifuge tube, 0.01M after the PBS flushing five times, place BSA envelope group damping fluid to seal.
The naughty sieve step of the phage of adopting is (carrying out the screening of three-wheel gradient intensity altogether):
Add 3ml 20%DMEM in the normal gastric mucosa and include 10 μ L phage peptide libraries (＞1.0 * 10
8), after 30min is hatched in 37 ℃ of water-bath concussions, draw supernatant and be transferred to clean tube; Stomach organization is added prepared supernatant liquor, and 1h is hatched in 37 ℃ of water-bath concussions, abandons supernatant liquor behind the taking-up water-bath product; After the PBST washing, with non-specific damping fluid 0.2M Glycine-HCl (pH2.2), 1mg/ml BSA gentleness shakes＞and 10min to be to carry out wash-out, uses 150 μ l1M Tris-HCl (pH9.1) the above-mentioned elutriant that neutralizes after elutriant is collected again, and obtain phage and eluriate liquid;
Choose 1 μ l and carry out titer determination, remaining phage is eluriated 4 ℃ of storages of liquid spend the night, and infected intestinal bacteria ER2738 at second day and increase, carry out the naughty sieve of next round then.
Through 3 take turns screening after, every titre of taking turns the phage that The selection result all obtains by wash-out is evaluated, concrete The selection result is as shown in table 1:
Table 1 phage is washed in a pan sieve selectivity enrichment condition
| The first round | Second takes turns | Third round | |
| The PBST washing times | 5(tween0.5％) | 8(tween1.0％) | 10(tween2.0％) |
| Phage add-on (PFU) | 3.0×10 10 | 2.0×10 9 | 3.1×10 10 |
| Phage yield (PFU) | 5.0×10 2 | 2.5×10 3 | 1.9×10 5 |
| The rate of recovery (%) | 1.67×10 -6 | 1.25×10 -4 | 0.61×10 -2 |
| The enrichment multiple | 1 | 74.8 | 3652.7 |
* the rate of recovery (%)=(phage yield * 100)/(phage add-on)
* enrichment multiple: the rate of recovery of the first round is decided to be 1, the rate of recovery of later several rounds respectively with the ratio of the first round rate of recovery.Take turns and compare with the 1st as can be seen, the 3rd screening of taking turns, phage titre and the rate of recovery that target tissue reclaims all increase highly significant, and the phage of being combined with people's stomach organization has obtained specific enrichment.
2, the evaluation of positive colony
1) ELISA detects and identifies positive colony
, titre that three-wheel screens from passing through is 10
5Polyclone phage culture dish on select 50 mono-clonals, choose after the amplification wherein 10 mono-clonals be used for be full cell ELISA test determination its with stomach cancer cell BGC823 (with the stomach normal cell in contrast, to inoculate the density of elisa plate be 5 * 10 for stomach cancer cell and stomach normal cell in conjunction with active
5, primary antibodie be rabbit anti--M13 antibody, two anti-ly are goat anti-rabbit antibody).With stomach cancer cell BGC823 in conjunction with active detected result as shown in Figure 1, that can see the 2nd, 4, No. 10 phage polypeptide clone can have higher avidity with stomach cancer cell BGC823.
2) immunohistochemical methods is identified
Carry out next step screening with No. 4 phage polypeptide that has high-affinity with stomach cancer cell BGC823 in the middle of the 2nd, 4, No. 10 phage polypeptide clone, extract its single stranded DNA, and carry out sequencing and amino acid analysis, obtaining its aminoacid sequence is AADNAKTKSFPV (shown in SEQ.ID.NO.1); Synthetic this polypeptide, and carry out and being connected of fluorescein, obtain the polypeptide that fluorescence connects, be called for short Biotin-AAD and Fitc-AAD.
Carry out immunohistochemical staining with the polypeptide that is synthesized and detect (paraffin section), identify itself and the binding ability of normal gastric epithelial tissue, cancer of the stomach and other cancerous tissues, qualification result as shown in Figure 2:
The result shows that Biotin-AAD all has specificity to be combined with various cancer of the stomach (visible peristalsis visible intestinal peristalsis A and diffuse type B), and not with normal gastric mucosa (C), breast cancer tissue (D) and colon cancer tissue (E) combination, prove that this polypeptide has higher avidity and specificity to cancer of the stomach.In addition, Biotin-AAD also with gastric precancerous lesion, as atypical hyperplasia (F) and intestinal epithelial metaplasia (G) a small amount of combination is arranged.Rondom polypeptide (H) and the negative contrast of PBS (I).
3) identified by immunofluorescence
Utilize synthetic polypeptide Fitc-AAD to carry out identified by immunofluorescence (paraffin section), with unloaded phage in contrast, identify the combination that it is combined with normal gastric mucosa, stomach organization, detected result is shown in Fig. 3 (* 200):
Wherein the A group is unloaded phage contrast, the B group detects for normal gastric mucosa, the C group detects for stomach organization, FITC-AAD is at illuminated back green-emitting fluorescence, unloaded phage does not see obvious fluorescence as can be seen, FITC-AAD and healthy tissues are only sent faint fluorescence, and the target spot that FITC-AAD is combined with stomach organization mainly is positioned at the epithelioglandular karyon of body of gland and endochylema, this illustrate this polypeptide really can with people's stomach organization body of gland specific combination.
3, the avidity of specific phage polypeptide in conjunction with stomach organization detects
Under the empty carrier contrast, utilize the ELISA test, detect the avidity comparison of being combined phage polypeptide and stomach cancer cell with the stomach organization specificity screen, detected result is as shown in Figure 4: compare with blank, empty carrier contrast, the phage (AAD-phage) of expressing the AAD polypeptide exceeds far away with the avidity phase of stomach cancer cell BGE823.
Under the empty carrier contrast, utilize the ELISA test, detect the avidity comparison of being combined phage polypeptide and stomach organization, normal gastric mucosa with the stomach organization specificity screen, detected result is as shown in Figure 5: compare with the empty carrier contrast, the phage of express polypeptide AAD and the bonding force of stomach organization are higher than about 615 times of unloaded phage, and be combined with normal stomach mucous membrane hardly, its bonding force is higher than the stomach normal mucosa and organizes about 591 times.
In order to detect the polypeptide that screens and the binding ability of stomach organization, synthetic irrelevant polypeptide in contrast, under the constant background of AAD-phage concentration, gradient increases the concentration of AAD-peptide polypeptide, detect the competition binding ability of AAD-phage and AAD-peptide, detected result is shown in Figure 6, and the AAD-peptide concentration gradient increases and can compete in conjunction with stomach organization with AAD-phage; This shows no matter be to express the phage of this polypeptide or synthetic polypeptide probe, can both be specific in conjunction with stomach organization, have the competition binding ability; The control group polypeptide is not suppressing in conjunction with having obviously AAD-phage then.
Comprehensive above the detection, the positive bacteriophage AAD-phage that screens and expressed polypeptide A AD thereof can high specifics, be incorporated into stomach cancer cell high-affinity, can be as a specific target spot of cancer of the stomach detection.
4, the targeting of stomach cancer target polypeptide indication is applied to the early diagnosis of cancer of the stomach
Specific binding ability in view of the AAD polypeptide, artificial synthetic polypeptide also carries out the fluorescence molecule connection, such as FITC-AAD, perhaps with the phage of expressing this polypeptide as detection probes, the burnt scope combination of fluorescence scope or copolymerization is done the indication of targeting for biopsy, overcomes present gastric cancer screening scheme, for the bigger stomach mucous membrane suspicious lesions of area, can only take at random the defective of (blindly) multiple punch biopsy.
Use AAD polypeptide probe to realize the level diagnosis of gastroesophageal junction early gastric cancer (carcinoma of gastric cardia) and process synoptic diagram and the partial enlarged drawing of targeting biopsy targeting referring to Figure 7 shows that under fluorescence endoscope, to unite, when detecting, select stomach mucous membrane chronic inflammatory diseases, ulcer, atrophic gastritis, carcinoma of gastric cardia patient for checking object, confirm no gastroscopic contraindication, fully inform the superiority-inferiority of this inspection method and the side effect that may bring health.At first carrying out routine selects gastroscopy to confirm position and the scope of precancerous lesion, spray 100 μ M polypeptide probe solutions and contrast fluorescent probe to stomach mucous membrane, the unconjugated probe of normal saline flushing after 5 minutes, observe the gastric mucosal lesion place with fluorescence scope (or the burnt scope of copolymerization) and have or not fluorescence, biopsy is sent the tissue of fluorescence and is done conventional pathological examination.
Claims (5)
1. a stomach cancer target polypeptide is characterized in that, the sequence of described polypeptide is shown in SEQ.ID.NO.1.
2. a stomach cancer target polypeptide is characterized in that, the polypeptide shown in SEQ.ID.NO.1 is connected with fluorescence molecule.
3. claim 1 or 2 described stomach cancer target polypeptide are applied to the preparation of cancer of the stomach early diagnosis reagent.
4. application as claimed in claim 3 is characterized in that, described cancer of the stomach early diagnosis reagent is the indicator of targeting, and polypeptide shown in SEQ.ID.NO.1 connects after the fluorescence molecule indication as targeting.
5. application as claimed in claim 3 is characterized in that, described cancer of the stomach early diagnosis reagent is detection probes, and the polypeptide shown in SEQ.ID.NO.1 is expressed in phage, the phage of polypeptide is arranged as detection probes with surface expression.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 201110264377 CN102329374B (en) | 2011-09-08 | 2011-09-08 | Gastric-cancer targeted peptide and application thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 201110264377 CN102329374B (en) | 2011-09-08 | 2011-09-08 | Gastric-cancer targeted peptide and application thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN102329374A CN102329374A (en) | 2012-01-25 |
| CN102329374B true CN102329374B (en) | 2013-07-10 |
Family
ID=45481359
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN 201110264377 Expired - Fee Related CN102329374B (en) | 2011-09-08 | 2011-09-08 | Gastric-cancer targeted peptide and application thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN102329374B (en) |
Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| 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 |
| CN104327161B (en) * | 2014-09-25 | 2017-02-15 | 西安交通大学 | CD44 targeting polypeptide and application thereof for preparing affinitive probe used for screening early gastric cancer |
| WO2016080633A1 (en) * | 2014-11-18 | 2016-05-26 | 울산대학교 산학협력단 | Peptides for targeting gastric cancer, and medical use thereof |
| KR101693431B1 (en) | 2014-11-18 | 2017-01-06 | 울산대학교 산학협력단 | Targeting Peptides for Gastric Cancer and Medical Use Thereof |
-
2011
- 2011-09-08 CN CN 201110264377 patent/CN102329374B/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| CN102329374A (en) | 2012-01-25 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Dohi et al. | Blue laser imaging-bright improves the real-time detection rate of early gastric cancer: a randomized controlled study | |
| Ikematsu et al. | Detectability of colorectal neoplastic lesions using a novel endoscopic system with blue laser imaging: a multicenter randomized controlled trial | |
| Qumseya et al. | Advanced imaging technologies increase detection of dysplasia and neoplasia in patients with Barrett's esophagus: a meta-analysis and systematic review | |
| Ikematsu et al. | The impact of narrow band imaging for colon polyp detection: a multicenter randomized controlled trial by tandem colonoscopy | |
| Gao et al. | Early esophageal cancer screening in China | |
| Hoffman et al. | Acetic acid compared with i-scan imaging for detecting Barrett’s esophagus: a randomized, comparative trial | |
| Kiesslich et al. | Colonoscopy, tumors, and inflammatory bowel disease-new diagnostic methods | |
| Diao et al. | Diagnostic ability of blue laser imaging combined with magnifying endoscopy for early esophageal cancer | |
| CN102329374B (en) | Gastric-cancer targeted peptide and application thereof | |
| Kobayashi et al. | Endoscopic ultrasonographic findings predict the risk of carcinoma in branch duct intraductal papillary mucinous neoplasms of the pancreas | |
| Shibuya et al. | In vivo microscopic imaging of the bronchial mucosa using an endo-cytoscopy system | |
| US20210378642A1 (en) | Sample obtained from the pancreatic juice and analysis thereof | |
| Yang et al. | A new non-muscle-invasive bladder tumor-homing peptide identified by phage display in vivo | |
| Singh et al. | Development of a swallowable diagnostic capsule to monitor gastrointestinal health | |
| Streba et al. | Utility of confocal laser endomicroscopy in pulmonology and lung cancer | |
| Shimizu et al. | Histologic results of EMR for esophageal lesions diagnosed as high-grade intraepithelial squamous neoplasia by endoscopic biopsy | |
| Choi et al. | Confocal laser endomicroscopy and molecular imaging in Barrett esophagus and stomach | |
| Trovato et al. | Confocal laser endomicroscopy for the detection of mucosal changes in ileal pouch after restorative proctocolectomy | |
| CN104327161A (en) | CD44 targeting polypeptide and application thereof for preparing affinitive probe used for screening early gastric cancer | |
| Tofolean et al. | The Importance of Bronchoscopy in Early Lung Cancer (LC) Diagnosis | |
| Coban et al. | The future of EUS | |
| Kawahara et al. | New digital imaging technology I-Scan for upper GI endoscopy: a pilot study | |
| Lavender et al. | Confocal endomicroscopy and other image-enhanced endoscopy in inflammatory bowel disease | |
| Bertani et al. | New techniques in endoscopy: confocal laser endomicroscopy | |
| Zhu et al. | A case report of giant primary esophageal follicular lymphoma. |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| CF01 | Termination of patent right due to non-payment of annual fee | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20130710 Termination date: 20180908 |