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The Expression And Effect Of Leptin In Gastrointestinal Cancer

Posted on:2014-09-22Degree:DoctorType:Dissertation
Country:ChinaCandidate:Y WangFull Text:PDF
GTID:1314330398955383Subject:Internal Medicine
Abstract/Summary:PDF Full Text Request
Nowadays,the obesity which secreted by fat tissue similar cytokine protein hormones-leptin (of leptin).It enters the hypothalamus and its specific targeted receptor (ob-R)interaction occurs combined regulating feeding signals and fat metabolism, regulation of the body's energy balance. Currently, there are some experimental findings [2-4], leptin and its expression is widely distributed in the body a plurality of locations, multiple systems can participate in the regulation of endocrine,such as:immune, hematopoietic, and digestion, and thus can be considered to be a multifunctional neural immune regulating hormones. In addition, leptin and the leptin receptor can be expressed in a variety of different tumor cells, and can play the inhibition of tumor cell apoptosis and promote the growth of tumor cells.The leptin and its receptor are playing an important role of in tumor metastasis and chemotherapy resistance. However, for the expression of leptin in the gastrointestinal tumorigenesis process and its mechanism is yet to be studied further. This study using immunohistochemical methods to detect the distribution of the leptin receptor expression in colon cancer and gastric cancer tissue, leptin and its receptor protein expression levels calculated by semi-quantitative method to analyze its relationship with clinicopathological parameters;2. using RT-PCR, in situ RT-PCR method leptin mRNA in gastric and colon cancer tissues and cells, leptin receptor isomers ob-Ra, ob-Rb mRNA expression was detected;3. MTT assay, flow cytometry to detect exogenous leptin on gastric adenocarcinoma of human gastric cancer cell line SGC7901and human colon cancer cell line HT-29cell proliferation, apoptosis and cell cycle aimed at clarifying colon leptin expression in gastric carcinoma, sources and effect, so as to further explore the biological effects of leptin play in the process of colon cancer and gastric cancer by blocking the leptin provide theoretical support for the treatment of gastric cancer and colon cancer.Part I The expression of leptin and leptin receptor protein in gastrointestinal tumorsObjective:To investigate leptin and its receptor expression in the human gastrointestinal tract tumors by detected in different clinical stages of leptin and thus determine the initial leptin for stomachthe possible role of intestinal tumors with clinical pathological stage. Methods:collected70cases of colon cancer specimens,40cases of intestinal metaplasia,90cases of atypical hyperplasia (mild, moderate and severe30cases),50cases of intestinal type gastric carcinoma,40cases of diffuse gastric cancer tissues by immunohistochemistry method and organization situ RT-PCR assay leptin and leptin receptor expression site of the tumor tissue in the gastrointestinal tract, and to calculate the rate of positive cells and semi-quantitative analysis to classify. Results:82.9%of intestinal metaplasia,84.3%mild dysplasia,86.5%moderate dysplasia,94.3%severe dysplasia,94.5%of intestinal type gastric cancer,33.4%of diffuse gastric cancer tissue leptin and leptin the double receptor protein expression in intestinal metaplasia, dysplasia and intestinal type gastric carcinoma between light, moderate, and severe atypical hyperplasia tissue between leptin double positive expression rate was no significant difference, however, expression of intestinal type gastric carcinoma double positive rate was significantly higher than diffuse gastric cancer tissues(x2=37.022, P0.001). Leptin in tubular adenocarcinoma, papillary adenocarcinoma, mucinous adenocarcinoma, signet ring cell carcinoma, undifferentiated carcinoma, the positive expression rate were88.7%,87.73%,86.21%,77.27%,74.10%; leptin receptor The positive expression rate of94.52%,87.17%,80.17%,76.67%, and74.20%, respectively. Through the statistical analysis, no significant difference (P>0.05) in the rate of leptin and leptin receptor expression in colon cancer and colon cancer pathology type. Conclusion:The high frequency of intestinal type gastric carcinoma and precancerous lesions of leptin and leptin receptor expression may play an important role in the evolution of intestinal type gastric cancer in an autocrine regulation in the form. Key words Part ? The impact of leptin on proliferation and apoptosis of gastrointestinal cancer cell linesObjective:To study leptin proliferation and apoptosis of gastric cancer cell lines SGC7901and colon cancer cell line HT-29cells. Methods:MTT assay and flow cytometry exogenous leptin on gastric cancer cell line SGC79011and colon cancer cell line HT-29cell growth, apoptosis and cell cycle. Results:1).Application concentration of0,5ng/ml,50ng/ml,100ng/ml,200ng/ml leptin has a growing role to stimulate gastric adenocarcinoma cell line SGC79011colon cancer cell line HT-29;2).5ng/ml,72h50ng/ml,100ng/ml,200ng/ml of exogenous leptin on the growth of gastric cancer cell lines SGC7901and colon cancer cell lines HT-29cells has a significant inhibitory effect, in which the cell lines SGC7901and HT-29200ng/ml exogenous leptin to inhibit the effect are most obvious inhibition rate. Conclusion:In the range of certain concentration and duration of action of endogenous and exogenous leptin has a role to stimulate the growth of gastric cancer cell lines and colon cancer cell lines, and promote tumor cell proliferation and/or inhibition of tumor cell apoptosis is a possible mechanism. Part ? The expression of leptin mRNA in gastrointestinal tumorsObjective:To study the gastric adenocarcinoma and colon cancer tissue leptin mRNA expression whether explicitly the presence of leptin autocrine regulatory capacity and a synthesis of endogenous leptin square gastric adenocarcinoma cells. Methods:By RT-PCR method detected30cases of gastric adenocarcinoma and30cases of colon cancer tissue leptin mRNA expression. Results:The results of30patients with gastric adenocarcinoma and30cases of colon tissue leptin mRNA expression were positive. Conclusion:gastrointestinal cancer cell synthesis and secretion of endogenous leptin, the presence of leptin autocrine regulatory phenomena can be regarded as the gastrointestinal tract endogenous leptin in the tumor tissue of the gastrointestinal tract, ectopic secretion."...
Keywords/Search Tags:leptin, leptin receptor, precancerous lesions, gastrointestinal tumorsleptin, apoptosis, cell cycleleptin, RT-PCR, gastrointestinal tumors
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