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OBJECTIVE: To compare the efficacy of different interventions on chemotherapy induced thrombocytopenia (CIT) in solid tumors. METHODS: Patients, registered at Fudan University Shanghai Cancer Center, who developed CIT (defined as platelet count 0.05). Recovery time were similar between interventions, most group had a median recovery time of 6 or 7 d. In grade III CIT, the recovery time of combination group is shorter than the other intervention groups (5.5 d in combination group vs 7 d in rhTPO group and rhIL-11 group), but there was no significant difference (P = 0.609, 0.605). In grade Ⅱ CIT, the recurrence rate was significantly higher in rhTPO group and rhIL-11 group than untreated group (35%, 38% vs 0%, P = 0.008, P = 0.006). In grade III CIT, the recurrence rate of rhTPO group was significantly higher than that of rhIL-11 group (55% vs 21%, P = 0.017). CONCLUSION: The result of the current study suggests that thrombopoietic agents are not recommended for patients with -Ⅱ CIT. For III - CIT, no significant differences are found in the efficacy between different interventions, thus rhIL-11 is recommended in consideration of cost.
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Objective To observe the effects of recombinant human interleukin 11(rhIL-11) on proliferation, migration and invasion of A549 cells, and the mechanism thereof. Methods Final concentrations of 0, 10, 20, 50 and 100μg/L rhIL-11 were added into pulmonary adenocarcinoma A549 cells. The cell proliferation was detected by MTT. The wound-healing, transwell migration assay were used to validate the capability of the migration and invasion of A549 cells. Matrix metallopro-teinases (MMP)-2 and MMP-9 protein expressions were revealed by Western blot assay. Results The proliferation of A549 cells was not significantly changed by rhIL-11. The cell capability to migrate and invade was significantly increased 24 h af-ter treatment with rhIL-11 (P<0.05). The expression levels of MMP-2 and MMP-9 were significantly un-regulated, and which were increased with the increased concentrations of rhIL-11 (P<0.05). Conclusion rhIL-11 can promote the migra-tion and invasion of A549 cells, and the up-regulation of MMP-2 and MMP-9 expression might be one of the mechanisms.
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Objective:To evaluate the efficacy and pharmacoeconomics of rhIL-11(Ⅰ) and rhTPO in the treatment of thrombocy-topenia caused by gemcitabine chemotherapy in lung cancer patients. Methods:A retrospective analysis was used. Totally 58 hospital-ized lung cancer patients who suffered thrombocytopenia caused by gemcitabine chemotherapy and treated with rhIL-11(Ⅰ) or rhTPO from June 2011 to June 2014 were involved in the study, and the efficacy and pharmacoeconomics of rhIL-11(Ⅰ) and rhTPO were e-valuated and compared. Results:The lowest platelet value after the chemotherapy in rhIL-11(Ⅰ) group was higher than that in rhTPO group (P0. 05). The results of cost-minimization anal-ysis showed that the average cost of rhIL-11(Ⅰ) group was lower than that of rhTPO group(P<0. 01), furthermore, the average cost of the patients with GP, GC or the other gemcitabine chemotherapy regimens in rhIL-11 (Ⅰ) group was lower than that in rhTPO group. Conclusion:The effect of rhIL-11 (Ⅰ) in the treatment of thrombocytopenia caused by gemcitabine based-chemotherapy in lung cancer patients is not inferior to that of rhTPO, and shows certain advantages in economic cost.
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Objective To study the efficacy of recombinant human thrombopoietin (rhTPO)for the treat-ment of chemotherapy -induced thrombocytopenia with leukemia.And to explore its security.Methods 80 thrombo-cytopenia of acute leukemia after chemotherapy were selected.All patients were randomly divided into the research group and the control group according to the single and double of order registration number in clinic,40 cases in each group.The control group was treated with recombinant human interleukin -11 (rhIL -11),the research group was applied rhTPO treatment.The platelet (PLT)level of two groups,and other indicators of change were detected,and adverse reactions were observed.Results PLT resuming maximum value of the research group was (217.4 ±52.7) ×109 /L,which was significantly higher than the control group,the difference was statistically significant (t =15.63, P <0.05).The time of PLT recovery to 100 ×109 /L of the research group after chemotherapy was (15.6 ±3.6)d, which was significantly lower than the control group,the difference was statistically significant (t =10.72,P <0.05). The adverse reactions incidence of the research group was 12.5%,lower than 35.0% of the control group,the differ-ence was statistically significant (χ2 =9.87,P <0.05).Conclusion The treatment effect of RhTPO for thrombocy-topenia of the acute leukemia after chemotherapy is better than that of rhIL -11,can significantly improve the throm-bocytopenia,and has less adverse reaction and higher security.It is worthy of clinical popularization and application.
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Objectivc To observe the therapeutic effects of combined cytokines on hematopoietic injuries induced by 4.5 Gy60 Co γ-rays irradiation in beagles,and to provide experimental evidences for the clinical treatment of extremely severe myeloid acute radiation sickness(ARS).Methods 16 beagles were given 4.5 Gy60 Co γ-rays total body irradiation,and then randomly assigned into irradiation control group,supportive care group and cytokines group.In addition to supportive care,recombinant human granulocyte colony-stimulating factor (rhG-CSF),recombinant human interleukin-11(rhIL-11)and recombinant human interleukin-2(rhIL-2)were administered subcutaneouly to dogs in cytokines group.Peripheral blood hemogram was examined once every two days.Bone marrow and peripheral blood were collected to proceed colony cultivation 4 d pre-irradiation and 1 and 45 d post-irradiation.Conventional histopathological sections of sternum were prepared to observe the histomorphology changes. Results After irradiation,the population of all kinds of cells in peripheral blood declined sharply.WBC nadir Was elevated(1.04×109/L,but 0.28×109/L and 0.68×109/L for the irradiation control group and the supportive care group separately),the duration of thrombocytopenia was shortened (24 days,but 33 days for the supportive care groug) and red blood cell counts were maintained in the range of normal values after cytokincs treatment in combination.The colony forming efficiency of haemopoietic stem cells(HSCs)in bone marrow and peripheral blood decreased obviously 1 d post irradiation,but recovered to the level of that before irradiation 45 d post irradiation after supportive care and cytokines treatment.Hematopoietic cells disappeared in bone marrow of animals in irradiation control group,but hematopoietic functions were recovered after cytokines were administrated.Conclusions RhG-CSF.rhIL-11 and rhIL-2 used in combination could elevate WBC nadir,accelerate the recovery of leukocytes,platelets and red blood cells and promote the proliferation,differentiation and maturity of HSPCs left in the body after 4.5 Gy γ-rays total body irradiation,eventually restore the hematopoietic function.Hence,combination of rhG-CSF,rhIL-11 and rhIL-2 could serve as better therapeutic strategy to treat extremely severe myeloid ARS.
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Objective To explore the therapeutic effect of recombinant human interleukin(rhIL-11) and curcumin on jejunal damage in mice after neutron irradiation.Methods 140 male BALB/c mice were randomly divided into 4 groups:20 mice in healthy control group,60 mice in mere irradiation group,30 mice in IL-11 treatment group and 30 mice in curcumin treatment group.The mere irradiation group mice were wholly exposed to 3 Gy neutron irradiation.The treatment groups mice were intraperitoneally enterocoelia once a day for 5 d after irradiation.The mortality of the mice were observed.The mice in the control and mere irradiation groups were killed 6 h,1,3,and 6 d post-irradiation,respectively,and the mice of the 2 treatment groups were killed 3 and 6 d post-irradiation,respectively and the samples of jujunum were colleted.HE staining,argyrophilic of nucleaolar organizer regions staining,Feulgen staining,and image analysis were used to observe the pathology and levels of argyrophilic proteins and DNA.Results The mice in the mere irradiation group all died at 5 d post-irradiation,while 2 mice in the IL-11 treatment group and 3 in the curcumin group survived.Large area necrosis and exfoliation were found in the intestinal epithelial mucosa of the mere irradiated group mice since 6 h to 3 d after irradiation.Crypt cell regeneration was seen occasionally found 3 days later and much more 5 days later.Crypt cell regeneration was obviously found in the intestinal epithelial mucosa and lots of new villi were observed 5 d after irradiation in both treatment groups,however,the amounts of crypt cells and new villi of the curcumin treatment group were less than those of the IL-11 treatment group.The contents of AgNOR and DNA in the intestinal epithelial cells 5 days after irradiation of the 2 treatment groups were all significantly higher than those of the mere irradiation group (F = 0.015-0.035,all P ＜ 0.05) but without significant differences between them.Conclusions Jejunal damage in mice could be induced after 3 Gy neutron irradiation.rhIL-11 and curcumin might reduce the damage and promote the regeneration and repair of the intestinal epithelium.
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Objective To explore the therapeutic effect of rhIL-11 and rhG-CSF on mouse bone marrow injury induced by neutron irradiation.Methods 130 male BALB/c mice were irradiated by 3.0 Gy neutron and mice peripheral blood cells,bone marrow pathological changes,bone marrow nucleated cell counts,AgNOR content,apoptosis and necrosis rates and Bax protein content were observed by means of blood cells automatic analyzer,HE staining,AgNOR staining,flow cytometry,immunohistochemistry staining and image analysis.Results In the irradiation group and the rhIL-11 group,the mice peripheral blood white blood cells,bone marrow nucleated cell counts and AgNOR content was decreased progressively.The Bax protein was positively or strongly positively expressed in the cytoplasm of the hematopoietic cells and the Bax protein content was increased progressively at 6 h,1 d,3 d after irradiation.In the irradiation group,the rates of apoptosis and necrosis in the mice hematopoietic cells were greatly increased and that of necrosis was significant at 6 h after irradiation.In the rhIL-11 + rhG-CSF group,the counts of bone marrow nucleated cell and AgNOR were increased and the Bax protein content was decreased at 3 d after irradiation,while in the rhIL-11 group,the indexes mentioned above were not obviously different compared with those of the irradiation group.Conclusions The mice bone marrow hematopoietic function is seriously damaged by 3.0 Gy neutron irradiation,rhIL-11 and rhG-CSF could improve the mice hernatopoietic function after neutron irradiation,and combination of them is more effective to stimulate the hematopoitic function than either of them alone.
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Objective To explore the levels and the significance of IL-11 and sgp130 in the treatment of newly-diagnosed acute leukemia(AL)during the treatment of the induced remission,and to evaluate the curate effect of rhIL-11 on AL.Methods The levels of IL-11 and sgp130 in patients with AL were determined by ELISA respectively before treatment and after completing remission(CR).1.5 mg of rhIL-11 was injected subcutaneously,once a day,continuously for 14 days as one course,of treatment time 1～2 courses as total.Results Plasm IL-11 level in AL patients was significantly lower than normal(P
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@#ObjectiveTo explore the molecular mechanism of protective effects of recombinant human interleukin-11( rhIL-11) pretreatment on intestinal ischemia/reperfusion (I/R) injury of rats.MethodsThe I/R model of rat was produced by clampi ng the superior mesenteric artery for 1 hour, animals were divided randomly into the normal control group (A), I/R group (B), normal saline control group? and rhIL-11 pretreatment group (D). In group C and D, animals were administered w ith saline(0.25ml/rat/day)or rhIL-11 (600μg/kg/day) two days before the oper ation. Rats in different groups were sacrificed at 6 hours and 24 hours after re perfusion respectively. Intestinal apoptosis was detected by TUNEL staining, and the expression of bcl-2, caspase 3 and caspase 8 were determined by immunohist ochemistry. Meanwhile pathologic pictures were detected by hematoxylin-eosin (HE) staining.ResultsHE and TUNEL examinations showe d that in group D, the intestinal barrier was damaged obviously slighter than th at in the group B and group C, with decreased apoptosis cells, meanwhile, expres sion levels of caspase 3 and caspase 8 were lower, and bcl-2 was higher than th e group B and group C.Conclusions The protective e ffect of rhIL-11 pretreatment on rat intestinal I/R injury might be caused by t hat the expression of activities of caspase 3 and caspase 8 are inhibited and b cl-2 is activated.
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In order to obtain experimental evidences of therapeutic effect of rhIL 11 for clinical use, we observed the effects of rhIL 11 on colony formation of multilineage human hematopoietic cells in vitro and acceleration of platelet count and bone marrow hematopoietic recovery in 3 0Gy ? ray irradiated rhesus monkeys. The results showed that rhIL 11 significantly increased the nadirs of PLT count and shortened the duration of PLT numbers below 50% of their baseline values. The recovery of PLT in irradiated monkeys was accelerated. Dosage related PLT recovery was not observed. rhIL 11 not only promoted the proliferation and maturation of CFU Mk but also improved the proliferation of CFU GM, CFU e, BFU e and CFU Mix. These data suggest that rhIL 11 may be an effective agent in the treatment of hemopoietic suppression and thrombocytopenia.