Font Size: a A A

Joint Cytokines Of Dendritic Cells Induced Killer Cells On The Growth Of Hepatic Malignant Lymphoma And Postoperative Recurrence And Metastasis Suppression

Posted on:2012-07-26Degree:MasterType:Thesis
Country:ChinaCandidate:S TuoFull Text:PDF
GTID:2204330338450892Subject:Chinese medical science
Abstract/Summary:PDF Full Text Request
Purpose : Toexpore the inhibitory effect of DC-CIKC cells yielded by co-cutivation of dendritic cells(DC) and homologous cytokine induced killer cells(CIKC)on the growth and postoperative recurrence and metastasis of primary liver lymphoma.Material and method:The peripheral blood mononuclear cells(pbmcs) from healthy donors and a patient with primary liver lymphoma were isolated and separately cultured ex vivo to prepare DC and CIKC cells. The prepared DC and CIKC cells were then co-cultured for 14 days in the proportion of 1:5 to yield DC-CIKC cells The resected liver tumor specimens from the patient mentioned above were implanted into the liver of nude mice by surgical orthotopic implantation to establish the orthotopic nude mouse model of human primary liverlymphoma ,namde HLBL-0102. on the basis of HLBL-0102 model, recurrent and metastatic nude mouse model of primary liver lymphoma,designated HLBL-0701,was reprouced by radical resection of primary tumor of HLBL-0102 model. The HLBL-0701 models were randomly and avragely assigned into seven groups (8 each):CHOP chemotherapy regimen group, healthy donor CIKC group ,health donor DC-CIKC group, patient CIKCC group, patient DC-CIKC group, patient DC-CIKC plus CHOP chemotherapy group ,and control group. Animals in control group the animals were given physiological saline of 0.3ml/(kg.d), in chemotherapy group, the anmals were given CHOP regimen( cyclophosphamide 100mg, adriamycin 40mg, oncovin 2mg, dexamethasone 5mg)of 0.3ml/(kg.d),and in anmals of CIKC and DC-CIKC groups were administered with effector cells in the dosage of 6×107/(kg.d). All the treatent lasted for 21 days. Cancer-baering nude mice were sacrificed 72 hours after last treament. Blood samples were collected from heart for lactate dehydrogenase (LDH) detection. The tumors were removed to measure the weight, and the longest and shortest diameters of tumors.The volume of tumors and inhibitory rate of tumor weight wre calculated, respectively. Both light and electron microscopy were employed to observe the pathological changes in transplanted tumors post-treatment, and to determine the recurrence and metastasis rates.Recurrent and metastatic rate and life prolongation rate after the end of treatment in HLBL-0701 model were documented. The synergitie effect of the 2 regimens, DC-CIKC cells and chemotherapy, was evaluated thereafter.Results:1.The results as found in the HLBL-0102models showed that the tumor inhibition rates were 52.1%,40.2%,54.3%,41.7%,60.6%,84.3% . after being treated with CHOP regimen chemotherapy, haelthy donor CIKC, healthy donor DC-CIKC ,patient's CIKC, patient's CIKC,and patient's CIKC plus CHOP chemotherapy, while saline treatment (control)showed no inhibition on proliferation of tumors.2.In HLBL-0701 models, those treatments mentioned above showed that inhibitive effects on local recurrence and metastasis in the liver were of 75.0%,75.0%,50.0%,62.5%, 37.5% and 25.0%.and the nude mice survived for 70.32±6.54d,68.25±5.37d,77.00±6.37d,75.25±5.80d,79.50±8.07d and 84.75±8.26d after the respective treatment, and were significantly longer than the mice treated with saline (control), with the survival period of 35.00±4.17d (P<0.01).Conclusion:1.DC-CIKC exerts an inhibitory effect on xenograft growth of primary liver lymphoma and local recurrence and mestastasis after radical excision.2.The DC-CIKC derived from patients with primary liver lymphoma shows a better therapeutic than those derived from healthy donors, and an especially better inhibitory effect on tumor is expected when combined with chemotherapy.
Keywords/Search Tags:primary liver lymphoma, disease model, dendritic cells, killer cells, cytokine-activated, immunotherapy
PDF Full Text Request
Related items