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CyclinD1 And Nm23-H1 Gene Expression In Peripheral Non Small Cell Lung Cancer And Those Relationship With The CT Sign And Prognosis And Effects Of CT Perfusion Imaging On Differential Diagnosis Of Lung Benign And Malignancy Nodules

Posted on:2006-10-01Degree:DoctorType:Dissertation
Country:ChinaCandidate:S H MaFull Text:PDF
GTID:1104360155976299Subject:Medical imaging and nuclear medicine
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IntroductionMedical imaging is playing an increasing important role in clinical diagnosis , selection of treatment plan, and prognosis evaluation of therapeutic - effect judgement with improvement of imaging technology. All imaging manifestation have their histopathology foundations.Modern molecular biological research has put in protein and gene level on knowledge of disease, especial lung cancer, and formed new frontier branches of science such as molecular pathology, tumor immunology, i. e. It is possible for the further research of oncogene, anti - oncogene and many cytokines that are related with cell proliferation, differentiation and neovascularization to explain histopathological character of lung cancer so as to explain diversity and complexity of lung cancer imaging.Growing pattern, characteristic shapes, degree of malignancy, relapse, and metastasis of cancer are mainly determined by their molecular biology. Change of tumor shape, decided by the tumor biological behavior, is the basis of CT observations. That is the pathological change which acts as a bridge linking the CT observation to molecular biology, which makes the investigation of internal relationship between CT sign and molecular biology behavior possible.The contrast research of gene and imaging has been becoming focus of attention in early diagnosis realm of lung cancer with prosperous development in resent years. The combination can make it possible for us to comprehend the correlation between biology factors of degree of malignancy and prognosis of lungcancer and the growth pattern and morphology manifestation.There have not been any reports from overseas about the relationship between gene expression of CyclinDl or nm23 - HI and medical imaging in peripheral lung cancer. There has been only one report about the relationship between CyclinDl gene expression and CT sign in China. About the relationship between nm23 -HI gene expression and CT, MR signs in peripheral lung cancer, there has been a report respectively in China.The above mentioned reports detected protein expression using immunohis-tochemical method and studied the relationship between the protein expression and CT, MR signs in lung cancer. The research fixed half quantitation by Western - blot and PCR, and proved each other. Therefore, it made gene and protein detection more accurate and persuasive with higher degree of confidence. It can provide an objective reference basis, evaluate prognosis of non small cell lung cancer lighter, make patients obtain reasonable scientific methods, and elevate survial rate of patients suffering lung cancer.CT has been playing an important role in the diagnosis and differential diagnosis of pulmonary lesions for its high time and density resolution. The previous CT diagnosis of pulmonary nodules mainly depended on the morphological characteristics and simple changes of enhancement value. In recent years, with the further development of scientific research, the study emphasis of pulmonary nodule has been diverted from macroscopic view to microscopic view, i. e. from the morphological differences to the functional changes. CT perfusion imaging can reflect the microscopic state of nodule functionally, provide more information for the diagnosis, differential difference and therapeutic methods of pulmonary nodules , and is becoming the main concern of research.But there has been fewer reports about differential diagnosis of pulmonary nodules by CT perfusion imaging from overseas and China. There have been only two reports in China. The two reports introduced that the peak of time dense curve of inflammatory nodule was lower than peripheral lung cancer, and did not introduce perfusion parameter about specific diagnosis. The experiment made differential diagnosis of pulmonary nodules by drawing the mean time dense curve and specific perfusion parameters, and introduced own view point. How-ever, the experiment also discovered some shortages of CT perfusion technology. It still needs to continue consummation and furter exploration.Purpose1. To investigate the relationship of CyclinDl gene expression to CT sign and prognosis in peripheral non small cell lung cancer.2. To detect the unity of nm23 - HI protein expression by immunohisto-chemical, Western - blot and PCR methods in peripheral non small cell lung cancer and prove each other. By which it can increase degree of confidence a-bout the relationship of CyclinDl protein expression to clinical biological characters and CT signs of non small cell lung cancer, provide an objective reference basis, evaluate prognosis of non small cell lung cancer lighter, make patients obtain reasonable scientific methods, and elevate survival rate of patients suffering lung cancer.3. To investigate effects of multi - slice CT perfusion imaging on the diagnosis and differential diagnosis of peripheral lung cancer and lung benign nodules.Materials and Methods1. CyclinDl protein expression in peripheral non small cell lung cancer and its relationship with the CT sign and prognosis were analyzed retrospectively by means of SP immunohistochemical technique and spiral CT scanning in ninety -two patients of peripheral non small cell lung cancer proved by pathology.2. CyclinDl gene expression in peripheral non small cell lung cancer and its relationship with CT sign and prognosis were analyzed retrospectively by means of SP immunohistochemistry, Western - blot, PCR technique (three Jcinds of different means and levels) and multi - slice CT scanning in thirty -one patients of peripheral non small cell lung cancer proved by pathology.3. To investigate effects of multi - slice CT perfusion imaging on the diagnosis and differential diagnosis of peripheral lung cancer, inflammatory noduleand tuberculoma in eighteen patients of peripheral pulmonary nodulesResults1. In the groups of the histological type, differentiation, tumor TNM stage, age and sex, the positive rate of CyclinDl protein expression showed no significant difference, p >0.05. In the groups of deep lobulation, spiculate protuberance , short thin spinule sign and mediastina lymph node metastasis, the positive rate of CyclinDl protein expression showed significant difference, p <0. 05. The level of CyclinDl protein expression was obviously higher in those with any a-bove mentioned signs. A significant difference between positive rate of CyclinDl protein expression was found. In the groups of tumor size, cavity and pleural indentation , the positive rate of CyclinDl protein expression did not show significant difference, p >0.05.2. Nineteen patients were lost to follow - up or died from other diseases in the 92 cases of non small cell lung cancer. Cumulative survival rate and median survival period were estimated by life - span table for the CyclinDl positive and negative expression. The median survival period of the negative group was 35. 88 months. The median survival period of the positive group was 23. 69 months. Cumulative survival rates and median survival period were both higher in negative group than those in positive group. The statistic showed by comparison with Log - rank was 4. 76, and p value was 0. 0291 < 0. 05. The highly significant difference found between the survival periods of the tow groups indicated that CyclinDl was a negative prognostic factor.3. The results of cox regression model multiple factor analysis showed that CyclinDl expression, spiculate protuberance, short thin spinule sign, deep lobulation and mediastina lymph node metastasis revealed statistic significance, p < 0.05. The coefficient value of CyclinDl expression, spiculate protuberance, short thin spinule sign, deep lobulation and mediastina lymph node metastasis were positive, indicating that they were independent hazardous prognostic factors. CyclinDl expression, spiculate protuberance, short thin spinule sign, deep lobulation and mediastina lymph node metastasis had bigger OR value, which in-dicated that they were closely related to the prognosis of lung cancer.4. The examination method of immunohistochemistry displayed that a significant difference of nm 23 - HI protein expression was found among differentiation and tumor TNM stage, p <0.05. In the group of age, sex and histological type, the positive rate of nm23 - HI protein expression showed no significant difference, p >0. 05. In the group of deep lobulation, spiculate protuberance, short thin spinule sign and mediastina lymph node metastasis, the positive rate of nm 23 - HI protein expression showed significant difference, p <0.05.5. The examination method of Western - blot displayed that a significant - difference of nm23 - HI protein expression was found between differentiation, p<0.05. In the group of age, sex, tumor TNM stage and histological type, the positive rate of nm23 - HI protein expression showed no significant difference, p >0.05.6. The examination method of PCR displayed that a significant difference of nm23 - HlmRNA expression was found between differentiation, p <0. 05. In the group of age, sex, tumor TNM stage and histological type, the positive rate of nm23 -HI mRNA expression showed no significant difference, p >0.05.7. The examination method of Western - blot and PCR displayed that in the group of deep lobulation, spiculate protuberance, spine sign and mediastina lymph node metastasis, nm23 - HI protein and mRNA expression showed significant difference, p < 0. 05. However, in the group of tumor size, cavity and pleural indentation, nm23 - HI protein and mRNA expression showed no significant difference, p>0.05.8. Three examination methods of immunohistochemistry, Western - blot and PCR displayed a basic concordance of the relationship of nm23 - HI gene expression to clinical biological characters. But immunohistochemical method displayed relationship between nm23 - HI gene expression and tumor TNM stage. Western - blot and PCR methods displayed no relationship between nm23 -HI gene expression and tumor TNM stage. Three examination methods displayed a complete concordance of the relationship of nm23 - HI gene expression to CT signs.9. The time dense curves of peripheral lung cancer and inflammatory nodulewere manifested as obvious upward trend with the rapid infusion of contrast medium. The peak of inflammatory nodule is the highest, peripheral lung cancer is next, tuberculoma are lowest. Inflammatory nodule and peripheral lung cancer became flat after peak, and formed plateau. The two time dense curves were similar. But the time dense curve of inflammatory nodule decreased more early than that of peripheral lung cancer. The time dense curve of peripheral lung cancer and inflammatory nodule was obviously different from tuberculoma. The curve of tuberculoma was manifested as flat trend with the infusion of contrast medium and no obvious increase of nodular CT value.10. The PS of peripheral lung cancer was obviously higher than those of inflammatory nodule and tuberculoma, p < 0. 05, with statistic significance in comparing between groups, while BF, BV and MTT without statistic significance, p >0.05.11. There was a obviously positive correlation between BF and BV, PS, p <0. 01, correlation coefficient is 0. 615, 0. 651 respectively. There was notcorrelation between BF and MTT, p >0.05. No correlation is found among BV\ MTI\PS, p>0.05.12. After the CT perfusion images of parameters were pseudocolor processed, CT perfusion parameter images displayed extent of disease was bigger than common CT, parenchymatous tissue of tumor was more truly and reliably displayed.Conclusion1. The expression of CyclinDl protein may play an important role in the occurrence , progress and CT sign of lung cancer. Detection of the protein and observation of the CT sign can be considered as a marker of clinical diagnosis and prognostic evaluation.2. The expression of nm23 - HI protein and mRNA may play an important role in the occurrence, progress and CT sign of lung cancer. Detection of the gene and observation of the CT sign can be considered as a marker of clinical diagnosis and prognostic evaluation.agnosis and prognostic evaluation.3. To detect the unity of nm23 - HI protein and mRNA expression by im-munohistochemistry, Western - blot and PCR methods in peripheral non small cell lung cancer and prove each other. Therefore, it can increase degree of confidence about the relationship of nm23 - HI gene and protein expression to clinical biological characters and CT signs of peripheral non small cell lung cancer, provide an objective reference basis.4. CT perfusion imaging can provide quantitative information about blood perfusion of pulmonary tumor. It can be used to identify pulmonary tumor of different blood supply. It may provide function information to diagnosis of pulmonary tumor.5. In CT perfusion image parameters, PS is more important. The relatively correct diagnosis and differential diagnosis of peripheral lung cancer and inflammatory nodule could also be made by PS, combining with time dense curve, disease history and morphological manifestations.6. The relatively correct diagnosis and differential diagnosis between tuber-culoma and peripheral lung cancer, inflammatory nodule could be made by time dense curve and PS. The time dense curve may have significance to differential diagnosis of pulmonary tumor, and is worthy of further research.7. CT perfusion parameter images displayed the pulmonary blood perfusion more directly and clearly, extent of disease bigger than common CT, and paren-chymatous tissue in tumor more truly and reliably.
Keywords/Search Tags:Lung neoplasm, CyclinD1, nm23 - H1, Computed, X -ray tomography, pulmonary nodule, perfusion
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