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The Expression Of Livin, Smac And Mcm3in Nasal Polyps And Correlation With The Clinical Stages And Recurrence Rate

Posted on:2013-01-21Degree:DoctorType:Dissertation
Country:ChinaCandidate:H L ZhangFull Text:PDF
GTID:1114330374480691Subject:Clinical Medicine
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Background and Objective:Nasal Polyps (NP) is a common proliferative disease of Rhinology, its pathogenesis is complex, has not really been clarified. Since the widespread of functional endoscopic sinus surgery technology, the recurrence rate is significantly reduced. But part of the nasal polyps, such as nasal polyposis, the recurrence rate after surgery is always high. Some patients have to take low-dose hormone oral preparations for a long time after undergoing multiple surgeries and long-term use of topical corticosteroid hormone nasal spray, and even doing like this, some polyps will still relapse again, has greatly increased the suffering, ideas and economic burden of patients.Individual prognosis of such patients with nasal polyps, is now almost entirely dependent on the clinical experience of Rhinology physician subjective judgments, there is no widely accepted objective indicators of clinical reference value. In recent years, studies on apoptosis in the pathogenesis of nasal polyp is gradually increasing. some fruitful works Have been made. Especially in glandular proliferation/suppressing proliferation or promoting apoptosis/suppression of apoptotic factors in dynamic equilibrium, the polyp epithelium, polyps, eosinophils. These results in preliminarily that the nasal polyp epithelial cell proliferation; apoptotic genes/antiapoptotic gene imbalance, apoptosis inhibition is an important factor in nasal polyps, the eosinophil count increased.Livin is a new member of inhibitors of apoptosis proteins, IAPs. Livin also have the BIR and RING zinc finger domains, ralative to Caspases inhibition mediated apoptosis. It was not expressed in most normal adult tissues, high expression in the tumors and the proliferation of diseased cells. The Caspases protein plays an important position in apoptosis. Necessarily through Caspase cascade reaction, follow the activation and induction of apoptosis. Livin can be of interaction with multiple members of the inhibition of apoptosis protein, for example, Livin can inhibit its function by the combination of caspase-9precursor protein.Smac/DIABLO is a pro-apoptosis-related protein, with a239-amino acid residues, usually located in the mitochondrial membrane gap. When apoptotic signals stimulate Smac/DIABLO and Smac release into the cytoplasm along with cytochrome c, the mature Smac after leaving the mitochondria, the domain BIR3surface groove binding of XIAP, of Livin and other IAPs family members, is for the combination with caspase9, through Smac's competitive removal of IAPs inhibition of apoptosis, then further activated Caspase cascade reactions that ultimately induce apoptosis.Mcm3, minichromosome maintenance protein3, as an MCMS family, closely related organisms during DNA replication. MCMs family includes seven members. Minichromosome is formed by the yeast nucleosome packaging structure, the structural basis of yeast replication.Compared with the classic proliferation marker Ki-67, although both are located in the proliferating cells. Only Mcm3expressed in the growth of a considerable number of quiescent cells positive contrasted to Ki-67's negative expression. Mcm3, considered as a cell proliferation marker, is more meaningful than the Ki-67.There is rare report of Livin, Smac and Mcm3expression in NP research. Combined detection and analysis, and make the correlation analysis with NP clinical classification stage and postoperative recurrence rate, and to be worked as meaningful referrence indexes for the otolaryngologist, and to make more appropriate individualized surgical treatment and follow-up program.Objective of This research is to explore the apoptosis mechanism of nasal polyps' pathogenesis via detecting the expressions of two related factors of Apoptosis:Livin and Smac, and Mcm3, a kind of index protein which is sensitive to multiplication of human cells, in human nasal polyps (NP). Furthermore, by investigating the relationships with NP's different clinical stages and recurrence rate, to find a reliable, molecular level's approach by which ENT doctor can prejudge the possibility of postoperative recurrence, and may be applied as a referrence index for ENT doctors to make the plan of follow up and treatment.Methods:Choosing randomly80cases from the preserved blocks of nasal polyps patients who were followed at least12months after FESS operation.12cases of normal uncinate process mucosa were served as contrast. With polyclonal anti-human Livin, monoclonal anti-human Smac and monoclonal anti-human Mcm3, immunohistochemistry SP method was used to examine the expression of Livin,Smac and Mcm3in every case. Beige or puce granules appearing in NP cells were regarded as positive signal. Every case was observed randomly for ten eyeshots (microscope X400). The results were judged by semi-quantificational integral standard. All the data were disposed by statistics.Results:Of the80NP cases, Livin positive were54, positive rate was66.7%(54/80),cytoplasm coloration, the main location was in gland epithelium cells. Of the contrast, Livin positive was none. Mcm3positive were46, positive rate was56.7%(46/80), caryon coloration, the main location was in the epidermis cells of polyps. Two of the contrast was positive, positive rate was33.3%(4/12). Smac positive were42, positive rate was52.5%(42/80), cytoplasm coloration, the main location was in the epidermis cells of polyps. All of the contrast were positive, positive rate was91.7%(11/12). The expressive intensity of Livin,Smac between NP and normal mucosa were statistical different (P<0.05). Contrarily, there was no statistical difference in the expressive intensity of Mcm3between NP and normal mucosa (P>0.05). The expressive intensity of Livin and Smac between different clinical classifications of NP showed statistical difference (P<0.05). However, the expressive intensity of Mcm3between different classifications of NP didn't have statistical difference (P>0.05).There was a positive correlation between co-expressive intensity of Livin and Mcm3;and NP classifications differentiated by type and stage (R's=0.453, P<0.05). Being completely contrary, for Smac, it was a negative correlation (R's=-0.429, P<0.05).Furthermore, between the co-expressive intensity of Livin and Mcm3and the relapse rate of postoperative patients, a positive linear correlation was presented (R=0.9569, P<0.05).For Smac, it showed a negative linear correlation (R=-0.9781, P<0.05)Conclusion:Livin plays an important role in the genesis and development of the glands of NP. There is an obvious Smac down regulation in NP epidermis cells. In the pathogenesis of NP, the heightening of cell proliferative potential of NP probably acts as a subordinate role, the principal factor is that normal apoptosis is restrained. There is a positive correlation between the classifications of NP and the depressed extent of apoptosis. Detecting Livin,Smac and Mcm3synchronously can be considered as a reliable reference index by which we can forecast the probability of postoperative recurrence of individual NP patient. Objective:To explore the apoptosis mechanism of nasal polyps' pathogenesis via detecting the expressions of two related factors of Apoptosis:Livin and Smac, and Mcm3, a kind of index protein which is sensitive to multiplication of human cells, in human nasal polyps (NP). Furthermore, by investigating the relationships with NP's different clinical stages and recurrence rate, to find a reliable, molecular level's approach by which ENT doctor can prejudge the possibility of postoperative recurrence, and may be applied as a referrence index for ENT doctors to make the plan of follow up and treatment.Methods:Choosing randomly80cases from the preserved blocks of nasal polyps patients who were followed at least12months after FESS operation.12cases of normal uncinate process mucosa were served as contrast. With polyclonal anti-human Livin, monoclonal anti-human Smac and monoclonal anti-human Mcm3, immunohistochemistry SP method was used to examine the expression of Livin, Smac and Mcm3in every case. Beige or puce granules appearing in NP cells were regarded as positive signal. Every case was observed randomly for five eyeshots (microscope×400). The results were judged by semi-quantificational integral standard. All the data were disposed by statistics. Results:Of the80NP cases, Livin positive were54, positive rate was66.7%(54/80), cytoplasm coloration, the main location was in gland epithelium cells. Of the contrast, Livin positive was none. Mcm3positive were46, positive rate was56.7%(46/80), caryon coloration, the main location was in the epidermis cells of polyps. Two of the contrast was positive, positive rate was16.7%(2/12). Smac positive were42, positive rate was52.5%(42/80),cytoplasm coloration, the main location was in the epidermis cells of polyps. All of the contrast were positive, positive rate was91.7%(11/12). The expressive intensity of Livin,Smac between NP and normal mucosa were statistical different (P<0.05). Contrarily, there was no statistical difference in the expressive intensity of Mcm3between NP and normal mucosa (P>0.05).The expressive intensity of Livin and Smac between different clinical classifications of NP showed statistical difference(P<0.05). However, the expressive intensity of Mcm3between different classifications of NP didn't have statistical difference (P>0.05). There was a positive correlation between co-expressive intensity of Livin and Mcm3;and NP classifications differentiated by type and stage (R's=0.606, P<0.05). Being completely contrary, for Smac, it was a negative correlation (R's=-0.628P<0.05). Furthermore, between the co-expressive intensity of Livin and Mcm3and the relapse rate of postoperative patients, a positive linear correlation was presented (R=0.9588, t=4.7779, P<0.05). For Smac, it showed a negative linear correlation (R=-0.9992, t=33.30, P<0.05)Conclusions:Livin plays an important role in the genesis and development of the glands of NP. There is an obvious Smac down regulation in NP epidermis cells. In the pathogenesis of NP, the heightening of cell proliferative potential of NP probably acts as a subordinate role, the principal factor is that normal apoptosis is restrained. There is a positive correlation between the classifications of NP and the depressed extent of apoptosis. Detecting Livin,Smac and Mcm3synchronously can be considered as a reliable reference index by which we can forecast the probability of postoperative recurrence of individual NP patient.
Keywords/Search Tags:nasal polyps, apoptosis, Livin, Smac, Mcm3nasal polyps, Mcm3
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