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Mechnism Reasch On The Formation And Malignant Trasfomation Of Colorectal Polyps

Posted on:2013-02-20Degree:DoctorType:Dissertation
Country:ChinaCandidate:L XiangFull Text:PDF
GTID:1114330374478447Subject:Children outside of science
Abstract/Summary:
Objective: To clarify the mechanism of the formation and malignanttransformation of colorectal polyps by testing the expression of somemolecular markers in the different pathological types of colorectal polypsand establishing a BMP colorectal polyps mice model with the new RNAinterference (RNAi) technology, which was targeted to postimplantationstaged mouse embryos by using tail vein injection. Methods:1) detecte theexpression of MBP2,TLR4, TLR3, COX2in children's colorectal juvenilepolyps, children's colorectal hamartoma polyps, adult colorectalinflammatory polyps, colorectal adenomas, colorectal adenocarcinoma byusing immunohistochemical methods.2) deliver siRNA targeted to BMP4to postimplantation staged mouse embryos using tail vein injection.Pregnant mice were completely random delivered three groups:Ringer'sliquid blank control group (blank group), pSES negative control group(negative group), pSES-SiBMP4group (experimental group). Results:一,outcomes of histochemistry and immunohistochemistry tests:1. BMP2was present in uniform diffuse cell plasma particles, the expression of BMP2 in children's juvenile polyps (OD68.65±18.15), children's hamartomapolyps (OD34.8±18), adult inflammatory polyps (OD42.9±10.24),colorectal adenomas (OD50.3±10.2) was higher than that in colorectalcancer (OD19.1±5.3), the expression of BMP2in colorectal cancer wassignificantly decline (p <0.05).2. TLR4expression:1) The express betweenchildren's juvenile polyps (OD4.05±1.36) and children's hamartoma polypswas significant difference (p <0.05); The express between children'sjuvenile polyps and colorectal adenocarcinoma polyp was significantdifference (p <0.05).2) There was a significant difference betweenchildren's hamartoma polyps (OD29.5±11) and colorectal adenomas (p <0.05);3) There was a significant difference between colorectal adenomas(OD16.2±6.5) and colorectal adenocarcinoma (OD47.6±11.5)(p <0.05).3. The expressions of TLR3in children's juvenile polyps (OD270+90.42),children's hamartoma polyps (OD191.3±47), colorectal adenomas (OD147.1±58), colorectal adenomas (OD94.9±39.8) have been graduallydecline, the decline trend in colorectal adenocarcinoma significantlydifference (p <0.05).4. The expression of COX2is mainly diffuse inglandular epithelium cells of the cytoplasm and cell membrane, theexpression in children's juvenile polyps (OD60.7±20.7), children'shamartoma polyps (OD69.1±31.5), colorectal adenomas (OD53.8±16.4),colorectal cancer (OD60.5±20.4) was higher than that in colorectal polyps(OD12.65±4.21), but compared each other no significant difference (p> 0.05).二,the characteristics of BMP polyps mice model:1. Using RT-PCR,western blot method to detect the generation mice, the expressions of BMP4are significantly lower than normal control group;6. Generation mice of oneweek have not been seen the exact polypoid organization in the colon, thereare visible plypoid organization in the colon of eight weeks and ten weeks ofgeneration mice. the polypoid organization in the colon was polyp testedby hematoxylin-eosin staining.Conclusion:1)In the evolution process ofcolorectal polyps from colorectal polyps, colorectal adenomas, to colorectaladenocarcinoma, there are significant difference molecular markers: thelack of BMP may lead to the formation and malignant transformation ofcolorectal polyps by affecting the proliferation and differentiong ofglandular epithelium; the lower expression of TLR3may indicate thetendency of malignant transformationof colorectal polyps; TLR4may bethe important molecular marker in the gradual transformation ofcolorectal polyps.2) we successfully established the colon polyps micemodel by delivering siRNA targeted to BMP4to postimplantation stagedmouseembryos using tail vein injection. Objective: To find the meaningful molecular markers for theformation and malignant transformation of colorectal polyps by testingthe expression of some molecular markers in the colorectal polyps,colorectal adenomas and colorectal adenocarcinoma. Methods: detectethe expression of MBP2,TLR4, TLR3, COX2in children's colorectaljuvenile polyps, children's colorectal hamartoma polyps, adultcolorectal inflammatory polyps, colorectal adenomas, colorectaladenocarcinoma by using immunohistochemical methods. Results:1.BMP2was present in uniform diffuse cell plasma particles, theexpression of BMP2in children's juvenile polyps (OD68.65±18.15),children's hamartoma polyps (OD34.8±18), adult inflammatorypolyps (OD42.9±10.24), and colorectal adenomas (OD50.3±10.2)was higher than that in colorectal cancer (OD19.1±5.3), the expressionof BMP2in colorectal cancer was significantly decline (p <0.05).2.TLR4expression:1) The express between children's juvenile polyps(OD4.05±1.36) and children's hamartoma polyps was significant difference (p <0.05); The express between children's juvenile polypsand colonic adenoma was no significant difference (p>0.05); Theexpress between children's juvenile polyps and colorectaladenocarcinoma polyp was significant difference (p <0.05).2) Therewas a significant difference between children's hamartoma polyps (OD29.5±11) and colorectal adenomas (p <0.05); there was no significantdifference between children's hamartoma polyps and colorectaladenocarcinoma (p>0.05).3) There was a significant differencebetween colorectal adenomas (OD16.2±6.5) and colorectaladenocarcinoma (OD47.6±11.5)(p <0.05).3. The expressions ofTLR3in children's juvenile polyps (OD270+90.42), children'shamartoma polyps (OD191.3±47), colorectal adenomas (OD147.1±58), colorectal adenomas (OD94.9±39.8) have been gradually decline,the decline trend in colorectal adenocarcinoma significantly difference(p <0.05).4. The expression of COX2is mainly diffuse in glandularepithelium cells of the cytoplasm and cell membrane, the expression inchildren's juvenile polyps (OD60.7±20.7), children's hamartomapolyps (OD69.1±31.5), colorectal adenomas (OD53.8±16.4),colorectal cancer (OD60.5±20.4) was higher than that in colorectalpolyps (OD12.65±4.21), but compared each other no significantdifference (p>0.05). Conclusion: In the evolution process of colorectalpolyps from colorectal polyps, colorectal adenomas, to colorectal adenocarcinoma, there are significant difference molecular markers. Inthe evolution process of colorectal polyps from colorectal polyps,colorectal adenomas, to colorectal adenocarcinoma, there aresignificant difference molecular markers: the lack of BMP may lead tothe formation and malignant transformation of colorectal polyps byaffecting the proliferation and differentiong of glandular epithelium;the lower expression of TLR3may indicate the tendency of malignanttransformationof colorectal polyps; TLR4may be the importantmolecular marker in the gradual transformation of colorectalpolyps.We wish to understand the malignant transformation ofcolorectal polyps by testing the expression of molecular markers. Objective: To establish a BMP colorectal polyp's mice model with thenew RNA interference (RNAi) technology, which was targeted to postimplantation staged mouse embryos by using tail vein injection. and toprove that the BMP is related to the formation of the colorectal polyps. Methods: deliver siRNA targeted to BMP4to post implantation stagedmouse embryos using tail vein injection. Pregnant mice were completelyrandom delivered three groups, Ringer's liquid blank control group (blankgroup), pSES negative control group (negative group), pSES-SiBMP4group(experimental group). Results:1. Using RT-PCR, western blot method todetect the generation mice, the expressions of BMP4are significantly lowerthan normal control group;2. generation mice of one week have not beenseen the exact polypoid organization in the colon, there are visible polypoidorganization in the colon of eight weeks and ten weeks of generation mice.The polypoid organization was polyps by hematoxylin-eosinstaining.Conclusion:1. we successfully established the colon polyps' micemodel by delivering siRNA targeted to BMP4to post implantation stagedmouse embryos using tail vein injection. We also prove that the BMP isrelated to the formation of the colorectal polyps.2. The new RNAinterference (RNAi) technology which was targeted to post implantationstaged mouse embryos using tail vein injection is worth further promote andperfect.
Keywords/Search Tags:colorectal, immunohistochemistry, RNAi crossingplacenta, mouse modelColorectal polyps, BMP2, TLR4, immunohistochemistryRNAi crossing placenta, siBMP4, mice model
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