【作者】 邢华；

【导师】 王巍；

【作者基本信息】 吉林大学 ， 外科学， 2006， 博士

【摘要】 血清肿瘤标志物检测用于肿瘤的早期诊断已成为肿瘤防治的重点和热点,但采用蛋白芯片技术检测乳管液肿瘤标志物还未见有报道。我们重点以乳管冲洗液为检测标本,对乳腺癌、积乳症、乳管扩张症、乳管内乳头状瘤(病)进行检测,研究乳管液肿瘤标志物对早期乳腺癌诊断的意义。发现:(1)采用乳管液检测肿瘤标志物是可行的,尤其在乳管镜应用于临床以来,使乳管液的采集更有针对性。(2)乳管液肿瘤标志物表达的灵敏度高于血清。(3)蛋白芯片法检测肿瘤标志物可提高诊断的灵敏度。(4)蛋白芯片法检测乳管液肿瘤标志物对乳腺癌的早期诊断有一定意义。(5)积乳症、乳管内乳头状瘤(病)与乳腺癌具有内在相关性。(6)蛋白芯片法可选择肿瘤标志物组合。(7)对无症状高危人群的筛查引起多肿瘤蛋白芯片的某些指标增高时,有必要监控随访。更多还原

【Abstract】 As the most frequently morbility of malignancy diseases,breasr cancer Severitily infected the health of women. Recently,it’s inception rate ascensus obviously in the wordwide range.The incidence rate of our nation is lower, but still obviouslyrised recently years. To the existing treatment level, the utilitytreatment of tumour determined by early discovery in the fairlymagnum extent. For this reason, it is necessary to do deepresearch to all kinds of breast diseases, so can we detect theearly breast cancer or the breast diseases intimately related withbreast cancer promptly. At present, the clinical examinations tothe breast cancer have such following kinds: near infrared rayscan, nipple conduit visualization, nipple ductoscopy, prickercytological examination, breast gland puncture biopsy, surgicalintervention biopsy ,frozen section biopsy and etc. But thesedetections are not for the commitment of tumour or be traumaticocclusion, localed themselves. Tumor markers always bedeemed as the metabolism level of tumour constitution orcellomolecular, reside in blood, body fluid, corpuscle, orconstitution in the patients, may be examined by the means ofbiochemistry, immunology, or molecular biology. That willshow the physiologic and pathologic status in the definite timeand diseases’ effluence and development progress of the cytes.It had been developed and used hundred years, and foundeddozens of tumor markers. Since the era of 60s-70s of twentycentury, alpha fetoprotein (AFP)and carcinoembryonic antigen(CEA)had been found and used in clinic, tumor markers’examinations had been the relative test facility of tumour,contributed to the diagnosis and curative effect observation oftumour. But at present, there is none tumor marker is effectiveto breast cancer. Maijor single indicatrixes are enzyme-linkedimmunoassay, radio-immunity, and immunoluminescence, theseindicatrixes single exponential exam, it also have many demeritssuch as need to use huge dosage blood serum, high cost topatients, low sensibility and etc, especially low detection toearlier period tumour. To improve the accurate of diacrisis tothe tumour, people always compact the coherent markers to theassociation marker system clinically, at equal pace, do thedetection to certain tumour, to improve the accuratissime ofdiagnostic of tumour by making use of multivariate analysProtein chip system for multi-tumor markers detection(c-12) isbased on the principle of immunology and biotic signal integration.This method can detect the minimal tumor marker proteins in theliving bodies through microarray technique, such as AFP、CEA、CA125、CA153、NSE、CA199、CA242、PSA、f-PSA、β-HCG、Ferritin、HGH .By this means ,traditional analytic methods can becompleted in both small space and short time. At the same time , thissystem can transform the biotic signals to light and electrical signalsby the sensitive tracer technique, meanwhile this system can alsointake and analyze these signals by utilizing related detectiveequipment and computer software. C-12 combines themicroelectronics, micromachine, chemical physics technique andcomputer technique, the course of its analysis is continuous,integrated and miniature, it also has the characteristic of high speed,high-flux, high sensitivity, which is consider as the effective tool inthe field of research on life science. At present his method is beingapplied for detecting tumor markers in the blood serum, thenanalyzing the result by quantities. It is a better detection method toinspect the level of CEA、CA15-3、CA125、CA199、CA242、SFtogether for the patients of breast carcinoma, especially for theearlier period ones.Almost all the breast carcinoma derive from epithelial cells ofmammary gland duct, its secretory juice either detain in the ducts orsecrete outer the ducts. Recent years, the clinical application ofbreast duct endoscope, we can directly observe the breast duct cavityand the change of breast duct wall, and collect the breast duct juicein the abnormal breast duct. Nipple discharge or rinse solution fromabnormal breast duct directly derive from pathological changesmammary gland, in the earlier period of tumor before the tumortissue invading the basement membrane, the concentration of tumormarkers in the blood scarcely changed, but the concentration of thatin the nipple discharge or rinse solution from abnormal breast duct isin a very high level. Previous reports showed that the content ofepithelial cells in the rinse solution of mammary gland duct is 100times compared with that in the nipple discharge. We can obtainlarge quantities of epithelial cells and foam cells derived from tissue.Therefore , it has a pivotal estimation value to take juice from ductsas detected specimen. From above all , it will be more sensitive todetect the tumor markers in the breast duct juice than that in theblood serum for intraductal pathological changes and intraductalcarcinoma in the earlier period by applying protein chip technique.更多还原