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K-ras Gene Into The Mouse Lung And Clinical Significance Of Malignant Transformation Of The Cell Adhesion Capacity

Posted on:2001-02-25Degree:DoctorType:Dissertation
Country:ChinaCandidate:Q G ZhangFull Text:PDF
GTID:1114360092995885Subject:Surgery
Abstract/Summary:PDF Full Text Request
As we know, the incidence of malignant tumor is rising yearly in the world-wide. With the improvement of therapeutic strategies, the therapy effect, however is not increased obviously. The reason might be malignant infiltration and metastasis can not be controlled and blocked from the basis so far. As a focused point in cancer research, attention has been paid to the infiltration and metastasis of cancer cell, but the problem has not been solved yet.It is a complicated, multi-step continuoas process for the infiltration and metastasis of tumor cell, which can be summarized as: primary tumor-change or disappear of adhension of infercellular between tumor cell and stroma - disturbance of cellular junction, separation of primary focus -invasion of blood or lymphatic vessels by exfolicated cell - formation of metastatic focus during this process, cell differentiation, proliferative signal transduction, adhension and mobility of tumor cells play a decisive role. As a result of a deep investigation of adhensive structure, adhensive decules composing adhension and movement-related molecules, will benefit the study of infiltration and metastasis of tumor cell.Currently well-known adhensive molecules can be classified as: cadhen family, intergradin family, immunoglobulin suprafamily and selectin family. Compared with the other three families, cadherin family plays an important role in intercellular adhension. While actin filament composed of actin, apart from acting as the main structure of cellalar adhension concomitant with cadherin family, also contributes to cell metamorphsis, mobility and intercellular junction. The structure of gap-junction remains unclear, but its function in signal trans duction has already been verified.Concerning The above molecules and gap injuction with the functionin the process of infiltration and metastasis a lot of domestic and overseas sholars have dedicated to the study. Nonetheless, former study usually concentrated on the level of histology and histopathology, which can be easily affected, and a homogenous conclusion has not been drawn yet.Recently The development of cloning technique, genetic engineering and molecular biology make investigators probe the bilogical features of some diseases, which enables the study more direct, more thorough, and lessens the affecting factors.In this study, we used RNA virus-K-ras virus as carrier, introduced K-ras gene into fibrocytes of normal mice (NRL cells), which weve transformed as malignant cell (KNRL cells). Taking KNRL cells as the expermental group and normal fibrocytes as the control group, we investigated the changes of adhensive structure, adhensive protein and distribution of actin-filament when the malignant cells had the ability of invasion and lymphatic metastasis in nude mice after induction of onogene into normal cells. Our study was characterized by: (1)definite cell source; (2) ascertained oncogene; (3) comparatle between the noraml and malignant-trarsforming cells in case of cultivation under the same condition in vitro and exclusion of affecting factors. Consequently, it is especially important explore the biological variance following the induction of a specified, oncogene into normal cells.Objective: To investigate the role of adhensive structure, adhensive molecule and microfilament protein in the process of cancer infiltration and metastasis, to study the effect of caltrium and temperature on cell aggregation and to investigate the methods of diminish the exfoliation and spread of cancer cells during surgical treatment. Methods: Taking K-ras gene transfected fibrocytes of mice (KNRL cells)-malignant-transformiy cells as the study group, and NRL cells as normal control.First, two kinds of cells were cultivated with cell culture technique, then the doubling time and productive ability in soft agar media were measured, observation of intraperitoneal growth mode and pathological examination were performed after injection of KNRL cells into nude mice. By electronic microscope, intercellular ad...
Keywords/Search Tags:Transformation
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