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The Effect Of 5' -Dfur Oral Administered Pre-Operation For Gastrointestinal Malignant Tumor

Posted on:2003-07-31Degree:DoctorType:Dissertation
Country:ChinaCandidate:W J WangFull Text:PDF
GTID:1104360092455176Subject:Surgery
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Malignant tumor exists in organism continuously as a systemic disease. Therefore, a rational treatment should not be interrupted. To develop the mode of pre-operation chemotherapy-operation-post-operation chemotherapy accord with the purpose. However the mode of operation-post-operation chemotherapy is often employed in clinic now. There is lack of knowledge about pre-operation chemotheray.Objective To investigate the changes of apoptosis; proliferaton, invasion and metastasis; drug resistance and cancer cachexia following 5 ' -DFUR oral administered pre-operation in patients with gastrointestinal malignant tumor, explore the suitable time of pre-operation chemotherapy, and develop the mode of pre-operation chemotherapy-operation-post-operation chemotherapy.Methods Immunohistochemistry(IH), immunoelectron microscopy, western blot and reverse transcription polymerase chain reaction(RT-PCR), etc. were utilized to observe the level changes of calpain, bax, bcl-2; PCNA, micro vessel density(MVD) and nitric oxide(NO; P-glycoprotein(P-gp) and tumor necrosis factor-a(TNF-a) in tumor tissues in different time of pre-operation chemotherapy, three days(27 cases), one week(22), two weeks(15), and two months(9).Results 1. There were structural changes associating with cell functions in three days after 5' -DFUR oral administered pre-operation chemotherapy. There appeared to be irrecoverable,lethal changes in tumor cells one week after 5' -DFUR administered. And the changes could be found more often in two weeks.5But outlines of tumor cells were normal under light microscope, and there were more fibroconnective tissues in interstitial substance of tumor in two months group.2. The levels of mRNA expression and protein production of pyrimidine nucleoside phosphorylase(PyNPase), and bcl-2 reduced significant in three days after chemotherapy, and most significant in two weeks. But there were no differences between the groups after two weeks or two months chemotherapy. On the contrary, the contents of calpain, and mRNA expression and protein production of bax had reverse tendency. The correlation coefficients between the level of PyNPase mRNA and protein, bcl-2 mRNA and protein, bax mRNA and protein were r=0.92, p<0.0001; r=0.87, p<0.0001;and r=0.89; p<0.0001 respectively. In addition, the correlation coefficients between calpain and bax mRNA and protein, calpain and bcl-2 mRNA and protein were r=0.87, p<0.0001 ; r=0.84, /X0.0001; and r=-0.79, p<0.0001 ; r=-0.85,p<0.0001 respectively. And the correlation coefficient between the result of immunoelectron microscopy and western blot was r=0.86; /?<0.0001.3. The content of PCNA decreased significant in three days after chemoherapy, and most significant in two weeks. Yet there were no differences for the results in two weeks or two months. The level of MVD lowered down three days after chemotherapy, still more the level changed significant after two months. The alteration occurred significant only in one week after chemotherapy for NO, and it continued in two months. The correlation coefficient between the level of PyNPase labeling( PyNPase LI) and MVD was r=0.88, p<0.0001. 4. The levels of mRNA and protein expression of P-gp in tumor tissues increased significant with time of chemotherapy prolonging. The correlation coefficient between the level of P-gp mRNA and protein was r=0.73,/K0.0001.The tendency was opposite between P-gp and PyNPase. 5. The content of mRNA and protein expression of TNF-a decreased significant in three days after chemotherapy, and most significant in two weeks. The differences had not occured between two months group and two weeks group. The correlation coefficient between the level of TNF-a mRNA and protein was r=0.82, p<0.0001Conclusions61. There was a definite efficacy for 5' -DFUR oral administered pre-operation to gastrointestinal malignant tumor.2. 5' -DFUR oral administered pre-operation could induce cell apoptosis of gastrointestinal malignant tumor. This was associated with not only bax, b...
Keywords/Search Tags:pre-operation chemotherapy, gastrointestinal malignant tumor, apoptosis, PCNA, P-gp, TNF-α
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