Experimental study both in vitro and in vivotogether with clinical trials showed that LAKcells have antitumor and antimetastatic effects(1-5)and that these effects are closely related tothe number of LAK cells transfe...Experimental study both in vitro and in vivotogether with clinical trials showed that LAKcells have antitumor and antimetastatic effects(1-5)and that these effects are closely related tothe number of LAK cells transferred and the ad-ministration of rIL-2(1,6-8).Usually,autologousPBL’s are used as the source of LAK precursorsin the adoptive immunotherapy of cancer patients.But this not only puts an added burden on thecancer patient,it can cause serious side effectsas well(9).Although TIL’s may provide a solu-tion to this problem(10,11),their isolation fromsolid tumors is complex and consumes many rea-gents.We have reported that the isolation oflymphocytes from malignant ascites or from ma-lignant pleural effusions is not only simple展开更多
Activity of succinic dehydrogenase(SDH)and acid phosphatase(AcPase)of effector-target cells during the process of LAK cells killing HR8348 cells was estimated by enzyme cyto-chemistry technique.SHD positive granules a...Activity of succinic dehydrogenase(SDH)and acid phosphatase(AcPase)of effector-target cells during the process of LAK cells killing HR8348 cells was estimated by enzyme cyto-chemistry technique.SHD positive granules and AePase gray level were assayed with MIAS-300image analyser.The results showed:(1)After cocultivation of effector and target cells for vari-ous times,the activity of AcPase of HR8348 cells was apparently higher than that of the controlgroup,and it increased following prolonged coincubation.SDH activity of target cells increasedmarkedly within 30 and 60 rain cocultivation,but became low after 90 min treatment.(2)Ac-Pase content within LAK cells at 60,90,120,180 and 240 rain cocultivation was significantlyhigher than that of control group(P【0.01).The phenomenon of high AcPase and SDH activitywithin effector-target cells indicates that the function of the two types of cells was in an activestate.At the early stage of effector-target combining,the increase of SDH with HR8348 cellsmay be related to defensive function of the target cells.Higher AcPase activity of target cells in-dicates the activation of lysosomal enzyme which serves as the material basis for autolysis of thecells.展开更多
The human rectal adenocarcinoma cell line(HR8348)was treated withlympholdne activated killer(LAK)cells in vitro and the changes of the microtubulin inboth the effector and target cells were investigated with the aid o...The human rectal adenocarcinoma cell line(HR8348)was treated withlympholdne activated killer(LAK)cells in vitro and the changes of the microtubulin inboth the effector and target cells were investigated with the aid of immunofluorescencemicroscopy.It was revealed that after the attachment of LAK cells to the tumor cells,theeffector-target conjugates formed and distribution of the microtubulin in both the effectorand target cells changed.In the LAK cells,the microtubulin concentrated mainly in thecontact region,forming a crescent-like structure,while in the target cells,themicrotubulin condensed into patches and fused with the crescent-like structure of the LAKcells,Eventually,the target cells degenerated and died.It was suggested that the lysis ofthe target cells may be related to the redistribution of the microtubulin in both theeffector and target cells.展开更多
Human LAK cells were prepared by culturing normal human peripheral blood mononuclear cells (PBMC) with or without rIL-2 and assayed for T cell surface markers as well as anti-tumor activity against PC in vitro and in ...Human LAK cells were prepared by culturing normal human peripheral blood mononuclear cells (PBMC) with or without rIL-2 and assayed for T cell surface markers as well as anti-tumor activity against PC in vitro and in nude mice. Although the percentages of T3, T4, and T8 positive cells in rIL-2-activated cells did not differ significantly from those of control cells in vitro, the former showed stronger cytotoxicity than control cells to PG tumor cells in vitro. In vivo, LAK cells completely inhibited the growth of PG tumor in nude mice, whereas PBMC control cells were to be of no effect. The anti-tumor effect of human LAK cells in nude mice may offer a useful model to study the role of human LAK cells against human tumor in vivo.展开更多
Alloimmunization was combined with lympho-kine activated killer (LAK) cells to assess its effect on mammary carcinoma in rats. The animals were injected with both irradiated allosplenocytes and syngeneic LAK cells. Me...Alloimmunization was combined with lympho-kine activated killer (LAK) cells to assess its effect on mammary carcinoma in rats. The animals were injected with both irradiated allosplenocytes and syngeneic LAK cells. Metastatic lung nodules were markedly reduced using combined therapy when compared with the transfer of LAK cells or alloimmuni-zation alone. IL-2 activity in the serum of alloim-munized rats could be detected. This activity, maintained in vivo for one week, may be responsible for enhancing the antitumor effect of transferred LAK cells.展开更多
The ability of human recombinant interleukin-6 (IL-6) to regulate the induction and cytotoxic function of lymphokine activated killer (LAK) cells from human fetal spleen was studied. The results showed that IL-6 alone...The ability of human recombinant interleukin-6 (IL-6) to regulate the induction and cytotoxic function of lymphokine activated killer (LAK) cells from human fetal spleen was studied. The results showed that IL-6 alone was unably to Induce fetal splenic mononuclear cells (FSMC) to develop functional LAK cells, nor was it able to affect the number of IL-2-induced LAK cells and to alter the lytic activity of LAK cells against tumor cells in effector phase. However, when IL-6 was used in combination with IL-2 during the induction phase , the resulting LAK cells displayed considerably greater lytic, activity than that with IL-2 alone (P<0. 01), and this effect was IL-6 dose-dependent. The possible machanism of the synergistic effect of IL-2 and IL-6 in LAK cell Induction from human fetal spleen is discussed.展开更多
By using DNA electrophoresis and propidium iodide(PI) staining flow cytometry(FACS) analysis, we studied the mechanisms of lymphokine-activated killer(LAK) cell-mediated cytotoxicity. In the presence of pokeweed mitog...By using DNA electrophoresis and propidium iodide(PI) staining flow cytometry(FACS) analysis, we studied the mechanisms of lymphokine-activated killer(LAK) cell-mediated cytotoxicity. In the presence of pokeweed mitogen(PWM), human LAK cells induced DNA fragmentation of two leukemic cell lines(U937 cells and Raji cells) and two solid tumor cell lines(SW1116 cells and Hep-2 cells), a hallmark of apoptosis. The reactions were carried out at the effector/target ratio of 1:1 in 4h co-culture. Pretreatment with RNA and protein synthesis inhibitors(actinomycin D and cyclo hexamide) did not prevent the target cells from apoptosis.As the TNF-resistant tumor cell lines such as SW1116 cells and Raji cells were also triggered to apoptosis, other factors than TNF may play the role. DNA-PI staining FACS analysis also suggested that a part of LAK cells underwent apoptosis to some extent during incubation with target cells. The results provide a new way to investigate the mechanisms of the cytotoxicity of LAK cells, and a new possibility to enhance the efficiency of adoptive tumor therapy with LAK cells.展开更多
The in vitro induction of LAK cell activity was studied in cancer and AIDS patients. F3, an immuno regulatory component of Astragalus membranaceus was shown capable of potentiating LAK cell activity induced by rIL-2. ...The in vitro induction of LAK cell activity was studied in cancer and AIDS patients. F3, an immuno regulatory component of Astragalus membranaceus was shown capable of potentiating LAK cell activity induced by rIL-2. The LAK cells killing activity against Hs294T melanoma cell line induced by 50 U/ml rIL-2 in the Presence of F3 (55 μg/ml) reached 64%, which was comparablc to that (60%) induced by 500 U/ml of rIL-2alone. With F3 and rIL-2, the effcctor to target ratio could be reduced to one-half in order to obtain an equivalent level of cytotoxicity induced by rIL-2 alone.In some patients whose Peripheral blood Iymphocytes were relatively inert of rIL-2, F3 could make them responsive to rIL-2 induction. These results imply that F3 may be useful to potentiate LAk cell activity, reduce the dosage of rIL-2 and thus minimize the later's toxic side effects when used in vivo.展开更多
文摘Experimental study both in vitro and in vivotogether with clinical trials showed that LAKcells have antitumor and antimetastatic effects(1-5)and that these effects are closely related tothe number of LAK cells transferred and the ad-ministration of rIL-2(1,6-8).Usually,autologousPBL’s are used as the source of LAK precursorsin the adoptive immunotherapy of cancer patients.But this not only puts an added burden on thecancer patient,it can cause serious side effectsas well(9).Although TIL’s may provide a solu-tion to this problem(10,11),their isolation fromsolid tumors is complex and consumes many rea-gents.We have reported that the isolation oflymphocytes from malignant ascites or from ma-lignant pleural effusions is not only simple
文摘Activity of succinic dehydrogenase(SDH)and acid phosphatase(AcPase)of effector-target cells during the process of LAK cells killing HR8348 cells was estimated by enzyme cyto-chemistry technique.SHD positive granules and AePase gray level were assayed with MIAS-300image analyser.The results showed:(1)After cocultivation of effector and target cells for vari-ous times,the activity of AcPase of HR8348 cells was apparently higher than that of the controlgroup,and it increased following prolonged coincubation.SDH activity of target cells increasedmarkedly within 30 and 60 rain cocultivation,but became low after 90 min treatment.(2)Ac-Pase content within LAK cells at 60,90,120,180 and 240 rain cocultivation was significantlyhigher than that of control group(P【0.01).The phenomenon of high AcPase and SDH activitywithin effector-target cells indicates that the function of the two types of cells was in an activestate.At the early stage of effector-target combining,the increase of SDH with HR8348 cellsmay be related to defensive function of the target cells.Higher AcPase activity of target cells in-dicates the activation of lysosomal enzyme which serves as the material basis for autolysis of thecells.
文摘The human rectal adenocarcinoma cell line(HR8348)was treated withlympholdne activated killer(LAK)cells in vitro and the changes of the microtubulin inboth the effector and target cells were investigated with the aid of immunofluorescencemicroscopy.It was revealed that after the attachment of LAK cells to the tumor cells,theeffector-target conjugates formed and distribution of the microtubulin in both the effectorand target cells changed.In the LAK cells,the microtubulin concentrated mainly in thecontact region,forming a crescent-like structure,while in the target cells,themicrotubulin condensed into patches and fused with the crescent-like structure of the LAKcells,Eventually,the target cells degenerated and died.It was suggested that the lysis ofthe target cells may be related to the redistribution of the microtubulin in both theeffector and target cells.
文摘Human LAK cells were prepared by culturing normal human peripheral blood mononuclear cells (PBMC) with or without rIL-2 and assayed for T cell surface markers as well as anti-tumor activity against PC in vitro and in nude mice. Although the percentages of T3, T4, and T8 positive cells in rIL-2-activated cells did not differ significantly from those of control cells in vitro, the former showed stronger cytotoxicity than control cells to PG tumor cells in vitro. In vivo, LAK cells completely inhibited the growth of PG tumor in nude mice, whereas PBMC control cells were to be of no effect. The anti-tumor effect of human LAK cells in nude mice may offer a useful model to study the role of human LAK cells against human tumor in vivo.
文摘Alloimmunization was combined with lympho-kine activated killer (LAK) cells to assess its effect on mammary carcinoma in rats. The animals were injected with both irradiated allosplenocytes and syngeneic LAK cells. Metastatic lung nodules were markedly reduced using combined therapy when compared with the transfer of LAK cells or alloimmuni-zation alone. IL-2 activity in the serum of alloim-munized rats could be detected. This activity, maintained in vivo for one week, may be responsible for enhancing the antitumor effect of transferred LAK cells.
文摘The ability of human recombinant interleukin-6 (IL-6) to regulate the induction and cytotoxic function of lymphokine activated killer (LAK) cells from human fetal spleen was studied. The results showed that IL-6 alone was unably to Induce fetal splenic mononuclear cells (FSMC) to develop functional LAK cells, nor was it able to affect the number of IL-2-induced LAK cells and to alter the lytic activity of LAK cells against tumor cells in effector phase. However, when IL-6 was used in combination with IL-2 during the induction phase , the resulting LAK cells displayed considerably greater lytic, activity than that with IL-2 alone (P<0. 01), and this effect was IL-6 dose-dependent. The possible machanism of the synergistic effect of IL-2 and IL-6 in LAK cell Induction from human fetal spleen is discussed.
文摘By using DNA electrophoresis and propidium iodide(PI) staining flow cytometry(FACS) analysis, we studied the mechanisms of lymphokine-activated killer(LAK) cell-mediated cytotoxicity. In the presence of pokeweed mitogen(PWM), human LAK cells induced DNA fragmentation of two leukemic cell lines(U937 cells and Raji cells) and two solid tumor cell lines(SW1116 cells and Hep-2 cells), a hallmark of apoptosis. The reactions were carried out at the effector/target ratio of 1:1 in 4h co-culture. Pretreatment with RNA and protein synthesis inhibitors(actinomycin D and cyclo hexamide) did not prevent the target cells from apoptosis.As the TNF-resistant tumor cell lines such as SW1116 cells and Raji cells were also triggered to apoptosis, other factors than TNF may play the role. DNA-PI staining FACS analysis also suggested that a part of LAK cells underwent apoptosis to some extent during incubation with target cells. The results provide a new way to investigate the mechanisms of the cytotoxicity of LAK cells, and a new possibility to enhance the efficiency of adoptive tumor therapy with LAK cells.
文摘The in vitro induction of LAK cell activity was studied in cancer and AIDS patients. F3, an immuno regulatory component of Astragalus membranaceus was shown capable of potentiating LAK cell activity induced by rIL-2. The LAK cells killing activity against Hs294T melanoma cell line induced by 50 U/ml rIL-2 in the Presence of F3 (55 μg/ml) reached 64%, which was comparablc to that (60%) induced by 500 U/ml of rIL-2alone. With F3 and rIL-2, the effcctor to target ratio could be reduced to one-half in order to obtain an equivalent level of cytotoxicity induced by rIL-2 alone.In some patients whose Peripheral blood Iymphocytes were relatively inert of rIL-2, F3 could make them responsive to rIL-2 induction. These results imply that F3 may be useful to potentiate LAk cell activity, reduce the dosage of rIL-2 and thus minimize the later's toxic side effects when used in vivo.