Font Size: a A A

Fundamental And Clinical Study On Combined Chemotherapy Including Flourouracil Lipid For Malignant Tumor

Posted on:2005-01-22Degree:MasterType:Thesis
Country:ChinaCandidate:Y L LvFull Text:PDF
GTID:2144360152981793Subject:Oncology
Abstract/Summary:PDF Full Text Request
Objective: 5-Fluorouracil (5-Fu) is anticancer drug of antimetabolism and it is one of treatment agent in digestive tract tumor. The clinical apply is limitted by its short demiperiod and the unstable assimilation. Recently, the application of 5-Fu was changed, that is, the new preparation was used to improve the effect of it. The main anticancer component of fluorouracil lipid injection (139-3) is also 5-Fu, which becomes lipid encyst because it is envelopped in lipid double-molecule. The demiperiod is 4-5 hours and the stability is higher than that of solution. According to the literatures the effect of the single drug of 139-3 is higher than that of 5-Fu. Because no report of 139-3 used in combined chemotherapy regimens, the 139-3 was used in which for the first time in our clinical study. 139-3 was compared with 5-Fu to show its superiority in the combined chemotherapy of gastric carcinoma. In order to offered some references in clinical treatment for brain metastatic tumor the combined chemotherapy regimens including the lipid were studied to see if they can go through the blood-braid-barrier or not. In addition, the correlation between inhibition of gastric carcinoma cells and that of lymphocytes were studied in thecombined chemotherapy of 139-3 and we tried to find a proper chemotherapy regimen for the inoperable patients.Method: 1.Experiment of gastric carcinoma cells line: The MGC80-3 cell line of human gastric carcinoma was distributed to the single cell liquid according to the method set up by Mosmann, the OD values were measured for the four combined chemotherapy regimens including 5-Fu or 139-3 which are LFAM ( Leucovorin, 5-Fu or 139-3, Pirarubicin, Mitomycin C )n HDLF ( Hydroxycamptothecin, Cisplatin, Leucovorin, 5-Fu or 139-3 ), LFAP ( Leucovorin, 5-Fu or 139-3, Pirarubin, Cisplatin )% ELF (Etoposide, Leucovorin, 5-Fu or 139-3 ) in the enzyme-labelling-instrument with the wavelength of 570nm. The experiments were repeated three times for every regimens. The experimental groups are 5-Fu group ( 750mg/d ) and at different dosage of 139-3 ( 80mg/d, 160 mg/d, 320 mg/d). The control group was the tumor cells without drug and the blank group was PBS without any cell. After that, the CI values was calculated by the formula (1 -experiment-rcontrol)X 100%. 2. Animal experiment: Divided the 30 T739 mices into three groups: every group was 10 mices (T739 mices weight from 18 to 22 grams, Half in male and half in female). Take the sigle cell liquid of the LA-795 lung adenocarcinoma cell line of mice 0.01ml injected into the head. After one week NS? LFAP(5-Fu)> LFAP(139-3) was given respectively into three groups. Observe the tumor weight. The IR values were calculated by the formula (control group tumor weight- experiment group tumor weight)-^ control group tumor weight X 100%. All of them were proved by the HE staining. 3. Experiment of the solid tumor and lymphocytes of gastric carcinoma: 36 tumor tissues and peripheral blood of gastric carcinoma patients from surgical department of the fourth hospital of hebei medical university were obtained the single cell liquid from the fresh tumor tissues and the lymphocytes from the fresh peripheral blood respectively. The OD values were measured with method of MTT and the CI values calculated by the formula. The inhibition of tumor cells and lymphocytes was compared in the regimens of LFAM and HDLF. 4. Clinical experiment: the 148 patients with gastric carcinoma from surgical department and oncology department of the fourth hospital of hebei medical university, female 34, male 114, age 35-72, median age 46.5 and all of them were proved by pathology and/or cytology. The patients were divided into two groups: 76 patients in 139-3 group and 72 patients in 5-Fu group. They were treated by the HDLF regimen. The effect was estimated after four cycles. The T-cell CD3\ CD4\ CD8+ were measured with FCM method before chemotherapy and after four cycles chemotherapy. According to the standard of WHO 1981, the effects are CR> PR> SD, PD. The toxicities are 0> K IK ffl> IV.Result: 1. Fluorouacil lipid injection of different concentrations in combined chemotherapy regimens replacing routine dosage of fluorouacil solution showed strong sensitivities against gastric carcinoma cells respectively. Theconcentration of 320mg/d showed better sensitivity than solution in the four combined chemotherapy regimens and significant difference was observed (p<0.05). There was no significant difference in LFAP regimen (p>0.05), but fluorouracil lipid showed lower sensitivity than solution in ELF regimen and had significant differece (p<0.05). The concentration of 80mg/d showed no difference from 5-Fu solution in the four regimens(P>0.05). 2. Animal experiment: The inhibition rate of 139-3 group was 58.2%, whereas in 5-Fu group was 38.8%. There was significant difference was observed (p<0.05) and it was proved by HE staining. 3. Experiment of solid tumor of gastric carcinoma: The traditional and classical chemotherapy regimen LFAM of gastric carcinoma was chosen. The inhibition rate of lymphocytes was different from the gastric carcinoma cells, the inhibition rate of lymphocytes of 19 patients is higher than that of gastric carcinoma cells but there were no statistical difference. The relation between two kinds of cells were significant ( P = 0.944, p<0.01). The conventional chemotherapy regimen HDLF of gastric carcinoma was chosen. The inhibition rate of lymphocytes was different from the gastric carcinoma cells, the inhibition rate of lymphocytes of 17 patients was higher than that of gastric carcinoma cells but no statistical difference, the relation between two kinds of cells were significant (P = 0.844, p<0.01). 4. Clinical experiment: There are no cases of CR. The response rate of 139-3 was 60.4%. The response rate of...
Keywords/Search Tags:fluorouacil, lipid, combined chemotherapy, gastric carcinoma, anticancer drug sensitivity, lymphocyte, tumor cell, blood-brain-barrier
PDF Full Text Request
Related items