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Phosphoinositide-3kinase In Colorectal Carcinoma

Posted on:2006-01-31Degree:MasterType:Thesis
Country:ChinaCandidate:J F GuFull Text:PDF
GTID:2144360152981709Subject:Surgery
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Objective: Colorectal carcinoma is one of nine cancer frequent in our country, its malignancy is higher, including colon cancer and rectal cancer. For the past few years, because of changing of people's mode of life, especially changing of dietary pattern, its incidence was rising year by year. With the improvement of its early diagnosis and its methods of treatment for the past few years, its levels of combined therapy have been raised. But its five year survival rate is still low. Traditionary viewpoints though that the oncogene activation and the anti-oncogene inactivation results in the tumours.The researches recently year find that many productions of oncogene and anti-oncogene are the member of cell signal transduction pathway,such as cell growing,cell proliferation and cell differentiation,so the new opinions consider that the activity abnormal of cell signal transduction pathway results in cell proliferate abnormally and resulted in cell canceration. Phosphoinositide-3kinase(PI-3K) is one of lipides second messenger. its was found eleven yeas ago and participate in intra -cellular signal conduction. PI-3K can make the third hydroxy of monophosphoinositide phosphorylation to from ptdinsp(PI3P). PI-3K mainly phosphorylates ptdins4(PI4P) and ptdins4,5p2(PIP2) and to from ptdins3,4,5ps(PIP3). These lipids induce a marked effect as the second messenger. Under circumstances common, intra-cellular hardly contained the above lipids. Once cell is stimulated, these lipidsis is induced and emerge quikly. PI-3K is an important molecule of intra-cellular.PI-3K participates in many events of biology,such as transportation, cystoskeleton remodeling, cell survival and tumorigenesis apoptosis.We found the member of PI-3K cascade signal pathway has abnormal change in many people's tumours, such as genetic structure, protein expression and kinase activity. Classics PI-3K pathway includs PI-3K ,PKB and p70s6k. PI-3K is consists of two activity subunit, p110 (catalytic subunit)and p85(regulation subunit). Under the stimulation of various kinds growth factors and hormonal, such as fibroblact growth factor(FGF), insulin-like growth factor(IGF) ,transformi-ng growth factor (TGF), two subunits can interact with each other and induce PI-3K activation. PI-3K has the affect of signal transmissi-on between cell membrane and cytoplasma as the important member of the PI-3K cascade signal pathway. Now we found PI-3K had the change of protein expression and activation in patients with breast cancer,ovarian cancer and colon cancer.Using the flow cytomtechnique observed protein expression of PI-3K and cell proliferation in colorectal carcinoma tissues, investigate the relationship between PI-3K and colorectal carcinoma. Methods:1 Specimens: 15 cases of colorectal carcinoma specimens and paired normal tissues were collected frompatients operated in the Surgery Department of the Fourth Hospital of Hebei Medical University during September 2003 to December 2003. All specimens were verified by pathology. The distance from carcinoma to normal tissue was at least 10 centimeters. All specimens were collected within half an hour after the operation and stored at –70℃. 2 Flow cytometry detected the protein expression of PI-3K and the cell proliferation index: We prepared the extracts from the normal and the tumor tissues. The cellular supernatant was inturn( 1×105/ml) ,added polyclonal antibody of anti-PI-3K( 1:200 dilution ), incubated 30 minutes at room temperature, washed one time using 10 ml PBS ,throw away supernatant, added FITC-IgG 100, incubated 30 minutes at room temperature , centrifugated 10 ml PBS , filtered from 500 screen opening copper screen. At last, two quantity cell was detected the expression of PI-3K by the flow cytometry and the cell proliferation index after stain by EB, respectively. Results:The expression rate of PI-3K was 80% in fifteen normal, but the expression rate of PI-3K was 100% in fifteen tumor tissues. The PI-3K expression level in fifteen tumor tissues was obviously higher than that of normal tissues. The cel...
Keywords/Search Tags:human, colorectal carcinoma, Phosphoinositide-3kinase, cell proliferation
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