AIM To evaluate the treatment effects of recombinant human interleukin-12(rh IL-12) on radiotherapy complications, such as severe myelosuppression or pancytopenia, the decline or imbalance of immune function, etc.METH...AIM To evaluate the treatment effects of recombinant human interleukin-12(rh IL-12) on radiotherapy complications, such as severe myelosuppression or pancytopenia, the decline or imbalance of immune function, etc.METHODS The patients received high-dose and short-course precise radiotherapy, such as Cyber knife and image-guided radiotherapy(IGRT), which can cause myelosuppression or pancytopenia and immune function decline within a short time. One-hundred subjects were enrolled in the study, and 50 were randomized to a treatment group which used rh IL-12 and 50 were randomized to a control group which used symptomatic and supportive therapy after radiotherapy. The 50 subjects in the treatment group were further divided into five subgroups and intervenedwith rh IL-12 at a dose of 50, 100, 150, 200 or 250 ng/kg respectively. The dose-effect relationship was observed. RESULTS Rh IL-12 significantly attenuated the decrease of peripheral blood cells in the treatment group, and immune function was improved after treatment. Due to the different radiation doses, there was a fluctuation within 12 h after treatment but mostly showing an increasing trend. As to the clinical manifestations, 2 patients in the 250 ng/kg subgroup showed low fever after administration, 1 patient in the 200 ng/kg subgroup and 2 patients in the 250 ng/kg subgroup showed mild impairment of liver function during the observation period.CONCLUSION Rh IL-12 has effective therapeutic and protective effects on complications following radiotherapy, such as the decline of blood cells, myelosuppression and the decline or imbalance of immune function, which indicated good prospects for development and application.展开更多
Objective： To evaluate the efficacy and safety of recombinant human interleukin-11 （rhIL-11） for the chemotherapy-induced thrombocytopenia in patients with gastrointestinal cancer. Methods： It was an opened and no...Objective： To evaluate the efficacy and safety of recombinant human interleukin-11 （rhIL-11） for the chemotherapy-induced thrombocytopenia in patients with gastrointestinal cancer. Methods： It was an opened and non-randomized controlled clinical study. When the platelet counts was under 75 × 10^9/L after chemotherapy, rhlL-11 was administered 25 μg/（kg·d） as a daily SC injection last for 7-14 days, or discontinued when platelet counts 〉 100 × 10^9/L. Results： Seventysix patients were enrolled into this study. The treatment group and the control group had thirty-eight cases, respectively. The mean recovery time to PLT ≥ 100 × 10^9/L was 8.1 days in treatment group, while in control group was 12.2 days （P 〈 0.01）. Moreover, the mean recovery time from PLT 〈_ 50 × 10^9/L to 〉 100 × 10^9/L was 8.9 days in treatment group, while in control group was 12.9 days （P 〈 0.05）. There was a statistical difference between the two groups. Major side effects included edema, fever, articular muscle soreness, but they were all mild and well tolerable. Conclusion： rhIL-11 can be safely and effectively used for the treatment of chemotherapy-induced thrombocytopenia in patients with gastrointestinal cancer.展开更多
Intraperitoneal injection of recombinant human interleukin-2（rhIL-2）inhibits neuronal apoptosis in the chronic ocular hypertension retinal ganglion cell layer.Intravitreous injection was performed on retinal ganglio...Intraperitoneal injection of recombinant human interleukin-2（rhIL-2）inhibits neuronal apoptosis in the chronic ocular hypertension retinal ganglion cell layer.Intravitreous injection was performed on retinal ganglion cells in a Wistar rat model of chronically elevated intraocular pressure to observe the effects of LY294002 and AG490 on retinal ganglion cell survival,macrophage activation,and PI3K/Akt and JAK/STAT activation.The number of retinal ganglion cells in the rhIL-2 treatment group was much greater than in the normal control and phosphate-buffered saline groups.Western blot analysis revealed low Akt and STAT3 protein expression in the retina after 3-hour intravitreous injections of rhIL-2.However,protein expression was increased at 12 hours,but decreased again at 24 hours,with very low expression at 96 hours.LY294002 and AG490,which are inhibitors of the PI3K/Akt and JAK/STAT3 signal pathways,prevented upregulation of Akt and STAT3 protein expression in the retina,respectively.Intravitreous injection of rhIL-2 exhibited neuroprotective effects by decreasing retinal ganglion cell layer damage in a rat model of chronic glaucoma.These results suggest that intravitreal injection of rhIL-2 could induce the PI3K/Akt and JAK/STAT3 signaling pathways to protect retinal ganglion cells in chronically elevated intraocular pressure models.展开更多
Background: Despite the recent development of new therapies, multiple myeloma(MM) remains an incurable disease. Thus, new, efective treatments are urgently needed, particularly for relapsed or refractory MM(RRMM). In ...Background: Despite the recent development of new therapies, multiple myeloma(MM) remains an incurable disease. Thus, new, efective treatments are urgently needed, particularly for relapsed or refractory MM(RRMM). In an earlier phase I study, a novel form of recombinant human Apo2L/tumor necrosis factor-related apoptosis-inducing ligand(TRAIL) that is currently in clinical development for the treatment of hematologic malignancies, i.e., circularly permuted TRAIL(CPT), was well tolerated at a dose of 2.5 mg/kg per day and showed promising preliminary activity in patients with RRMM. This phase II, open-label, multicenter study further investigated the eicacy and safety of 2.5-mg/kg per day CPT as single-agent therapy for patients with RRMM.Methods: Patients with RRMM were treated once daily with CPT(2.5 mg/kg, intravenously) for 14 consecutive days for each 21-day cycle. Clinical response and toxicity were assessed after each treatment cycle.Results: Twenty-seven patients received CPT. Using the European Group for Blood and Marrow Transplantation criteria, we calculated the overall response rate of 33.3% with 1 near-complete response(n CR) and 8 partial responses(PRs). The clinical beneit rate(48.1%) included 1 nCR, 8 PRs, and 4 minimal responses. The most common treatmentrelated adverse events(TRAEs) were fever, aspartate aminotransferase elevation, alanine aminotransferase elevation, leucopenia, rash, neutropenia, and thrombocytopenia. We graded toxicity using the Common Toxicity Criteria for Adverse Events, version 3.0, and determined that 37.0% of patients had at least 1 grade 3–4 TRAE.Conclusions: CPT as a single agent can elicit a response in patients with RRMM and is well tolerated. Further clinical investigation is warranted.展开更多
目的探讨重组人Ⅱ型肿瘤坏死因子受体-抗体融合蛋白(recombinant human tumor necrosis factor-α receptorⅡ:IgG Fc fusion protein for injection,rhTNFR:Fc)联合甲氨蝶呤(methotrexate,MTX)短期治疗银屑病关节炎(psoriaticarthritis...目的探讨重组人Ⅱ型肿瘤坏死因子受体-抗体融合蛋白(recombinant human tumor necrosis factor-α receptorⅡ:IgG Fc fusion protein for injection,rhTNFR:Fc)联合甲氨蝶呤(methotrexate,MTX)短期治疗银屑病关节炎(psoriaticarthritis,PsA)的疗效与安全性。方法对入院前传统治疗方案(非甾体类消炎药联合甲氨蝶呤或其他免疫抑制剂)治疗3个月以上疗效欠佳的15例患者,入院后给予重组人Ⅱ型肿瘤坏死因子受体-抗体融合蛋白(益赛普,etanercept)25mg,2次/周,皮下注射,同时给予甲氨蝶呤7.5～15mg,1次/周,12周后停用重组人Ⅱ型肿瘤坏死因子受体-抗体融合蛋白,观察患者治疗前后的临床症状、炎性实验室指标的改善情况及药物安全性。结果15例患者关节压痛数、关节肿胀数、银屑病面积和严重度指数(psoriasis area and severity index,PASI)均明显降低,同时血沉及C反应蛋白亦明显下降,且与治疗前相比差异具有统计学意义。1例患者出现注射部位皮肤片状红肿及瘙痒,未予特殊处理后消失,其余患者均未出现明显不良反应。结论重组人Ⅱ型肿瘤坏死因子受体-抗体融合蛋白联合甲氨蝶呤短期治疗银屑病关节炎有效、安全、可行。展开更多
目的:探究重组人Ⅱ型肿瘤坏死因子(TNF)受体-抗体融合蛋白联合风湿骨痛片对类风湿性关节炎(RA)患者的疗效。方法:将90例RA患者随机分为观察组和对照组,每组各45例。对照组给予注射重组人Ⅱ型TNF受体-抗体融合蛋白;观察组注射重组人Ⅱ型...目的:探究重组人Ⅱ型肿瘤坏死因子(TNF)受体-抗体融合蛋白联合风湿骨痛片对类风湿性关节炎(RA)患者的疗效。方法:将90例RA患者随机分为观察组和对照组,每组各45例。对照组给予注射重组人Ⅱ型TNF受体-抗体融合蛋白;观察组注射重组人Ⅱ型TNF受体-抗体融合蛋白联合口服风湿骨痛片。比较两组患者的血清炎症因子、炎性指标、临床疗效、美国健康评估问卷(HAQ)、RA28处关节疾病活动度评分(DAS28)。结果:治疗后,两组患者的IL-6、TNF-α水平比治疗前低,IL-10比治疗前高( P <0.05),观察组的IL-6、TNF-α水平低于对照组,IL-10水平高于对照组( P <0.05);两组患者的类风湿因子(RF)、红细胞沉降率(ESR)、C反应蛋白(CRP)炎性指标均较治疗前更低( P<0.05),且观察组低于对照组(P <0.05);观察组患者临床疗效总有效率为93.33%,高于对照组的73.33%( P <0.05);两组患者HAQ 评分、DAS28及症状积分较治疗前更低( P <0.05),且观察组患者HAQ 评分、DAS28 评分及症状积分低于对照组( P <0.05)。结论:对RA患者采用注射重组人Ⅱ型TNF受体-抗体融合蛋白联合口服风湿骨痛片治疗,提高了临床治疗效果和患者生活质量,减轻了患者的痛苦。展开更多
文摘AIM To evaluate the treatment effects of recombinant human interleukin-12(rh IL-12) on radiotherapy complications, such as severe myelosuppression or pancytopenia, the decline or imbalance of immune function, etc.METHODS The patients received high-dose and short-course precise radiotherapy, such as Cyber knife and image-guided radiotherapy(IGRT), which can cause myelosuppression or pancytopenia and immune function decline within a short time. One-hundred subjects were enrolled in the study, and 50 were randomized to a treatment group which used rh IL-12 and 50 were randomized to a control group which used symptomatic and supportive therapy after radiotherapy. The 50 subjects in the treatment group were further divided into five subgroups and intervenedwith rh IL-12 at a dose of 50, 100, 150, 200 or 250 ng/kg respectively. The dose-effect relationship was observed. RESULTS Rh IL-12 significantly attenuated the decrease of peripheral blood cells in the treatment group, and immune function was improved after treatment. Due to the different radiation doses, there was a fluctuation within 12 h after treatment but mostly showing an increasing trend. As to the clinical manifestations, 2 patients in the 250 ng/kg subgroup showed low fever after administration, 1 patient in the 200 ng/kg subgroup and 2 patients in the 250 ng/kg subgroup showed mild impairment of liver function during the observation period.CONCLUSION Rh IL-12 has effective therapeutic and protective effects on complications following radiotherapy, such as the decline of blood cells, myelosuppression and the decline or imbalance of immune function, which indicated good prospects for development and application.
文摘Objective： To evaluate the efficacy and safety of recombinant human interleukin-11 （rhIL-11） for the chemotherapy-induced thrombocytopenia in patients with gastrointestinal cancer. Methods： It was an opened and non-randomized controlled clinical study. When the platelet counts was under 75 × 10^9/L after chemotherapy, rhlL-11 was administered 25 μg/（kg·d） as a daily SC injection last for 7-14 days, or discontinued when platelet counts 〉 100 × 10^9/L. Results： Seventysix patients were enrolled into this study. The treatment group and the control group had thirty-eight cases, respectively. The mean recovery time to PLT ≥ 100 × 10^9/L was 8.1 days in treatment group, while in control group was 12.2 days （P 〈 0.01）. Moreover, the mean recovery time from PLT 〈_ 50 × 10^9/L to 〉 100 × 10^9/L was 8.9 days in treatment group, while in control group was 12.9 days （P 〈 0.05）. There was a statistical difference between the two groups. Major side effects included edema, fever, articular muscle soreness, but they were all mild and well tolerable. Conclusion： rhIL-11 can be safely and effectively used for the treatment of chemotherapy-induced thrombocytopenia in patients with gastrointestinal cancer.
基金the New Century Excellent Talents Project Grant by the Ministry of Education of China,No.NCET-06-0677the Natural Science Foundation of Hu-nan Province,No.05JJ30051
文摘Intraperitoneal injection of recombinant human interleukin-2（rhIL-2）inhibits neuronal apoptosis in the chronic ocular hypertension retinal ganglion cell layer.Intravitreous injection was performed on retinal ganglion cells in a Wistar rat model of chronically elevated intraocular pressure to observe the effects of LY294002 and AG490 on retinal ganglion cell survival,macrophage activation,and PI3K/Akt and JAK/STAT activation.The number of retinal ganglion cells in the rhIL-2 treatment group was much greater than in the normal control and phosphate-buffered saline groups.Western blot analysis revealed low Akt and STAT3 protein expression in the retina after 3-hour intravitreous injections of rhIL-2.However,protein expression was increased at 12 hours,but decreased again at 24 hours,with very low expression at 96 hours.LY294002 and AG490,which are inhibitors of the PI3K/Akt and JAK/STAT3 signal pathways,prevented upregulation of Akt and STAT3 protein expression in the retina,respectively.Intravitreous injection of rhIL-2 exhibited neuroprotective effects by decreasing retinal ganglion cell layer damage in a rat model of chronic glaucoma.These results suggest that intravitreal injection of rhIL-2 could induce the PI3K/Akt and JAK/STAT3 signaling pathways to protect retinal ganglion cells in chronically elevated intraocular pressure models.
文摘Background: Despite the recent development of new therapies, multiple myeloma(MM) remains an incurable disease. Thus, new, efective treatments are urgently needed, particularly for relapsed or refractory MM(RRMM). In an earlier phase I study, a novel form of recombinant human Apo2L/tumor necrosis factor-related apoptosis-inducing ligand(TRAIL) that is currently in clinical development for the treatment of hematologic malignancies, i.e., circularly permuted TRAIL(CPT), was well tolerated at a dose of 2.5 mg/kg per day and showed promising preliminary activity in patients with RRMM. This phase II, open-label, multicenter study further investigated the eicacy and safety of 2.5-mg/kg per day CPT as single-agent therapy for patients with RRMM.Methods: Patients with RRMM were treated once daily with CPT(2.5 mg/kg, intravenously) for 14 consecutive days for each 21-day cycle. Clinical response and toxicity were assessed after each treatment cycle.Results: Twenty-seven patients received CPT. Using the European Group for Blood and Marrow Transplantation criteria, we calculated the overall response rate of 33.3% with 1 near-complete response(n CR) and 8 partial responses(PRs). The clinical beneit rate(48.1%) included 1 nCR, 8 PRs, and 4 minimal responses. The most common treatmentrelated adverse events(TRAEs) were fever, aspartate aminotransferase elevation, alanine aminotransferase elevation, leucopenia, rash, neutropenia, and thrombocytopenia. We graded toxicity using the Common Toxicity Criteria for Adverse Events, version 3.0, and determined that 37.0% of patients had at least 1 grade 3–4 TRAE.Conclusions: CPT as a single agent can elicit a response in patients with RRMM and is well tolerated. Further clinical investigation is warranted.
文摘目的探讨重组人Ⅱ型肿瘤坏死因子受体-抗体融合蛋白(recombinant human tumor necrosis factor-α receptorⅡ:IgG Fc fusion protein for injection,rhTNFR:Fc)联合甲氨蝶呤(methotrexate,MTX)短期治疗银屑病关节炎(psoriaticarthritis,PsA)的疗效与安全性。方法对入院前传统治疗方案(非甾体类消炎药联合甲氨蝶呤或其他免疫抑制剂)治疗3个月以上疗效欠佳的15例患者,入院后给予重组人Ⅱ型肿瘤坏死因子受体-抗体融合蛋白(益赛普,etanercept)25mg,2次/周,皮下注射,同时给予甲氨蝶呤7.5～15mg,1次/周,12周后停用重组人Ⅱ型肿瘤坏死因子受体-抗体融合蛋白,观察患者治疗前后的临床症状、炎性实验室指标的改善情况及药物安全性。结果15例患者关节压痛数、关节肿胀数、银屑病面积和严重度指数(psoriasis area and severity index,PASI)均明显降低,同时血沉及C反应蛋白亦明显下降,且与治疗前相比差异具有统计学意义。1例患者出现注射部位皮肤片状红肿及瘙痒,未予特殊处理后消失,其余患者均未出现明显不良反应。结论重组人Ⅱ型肿瘤坏死因子受体-抗体融合蛋白联合甲氨蝶呤短期治疗银屑病关节炎有效、安全、可行。
文摘目的:探究重组人Ⅱ型肿瘤坏死因子(TNF)受体-抗体融合蛋白联合风湿骨痛片对类风湿性关节炎(RA)患者的疗效。方法:将90例RA患者随机分为观察组和对照组,每组各45例。对照组给予注射重组人Ⅱ型TNF受体-抗体融合蛋白;观察组注射重组人Ⅱ型TNF受体-抗体融合蛋白联合口服风湿骨痛片。比较两组患者的血清炎症因子、炎性指标、临床疗效、美国健康评估问卷(HAQ)、RA28处关节疾病活动度评分(DAS28)。结果:治疗后,两组患者的IL-6、TNF-α水平比治疗前低,IL-10比治疗前高( P <0.05),观察组的IL-6、TNF-α水平低于对照组,IL-10水平高于对照组( P <0.05);两组患者的类风湿因子(RF)、红细胞沉降率(ESR)、C反应蛋白(CRP)炎性指标均较治疗前更低( P<0.05),且观察组低于对照组(P <0.05);观察组患者临床疗效总有效率为93.33%,高于对照组的73.33%( P <0.05);两组患者HAQ 评分、DAS28及症状积分较治疗前更低( P <0.05),且观察组患者HAQ 评分、DAS28 评分及症状积分低于对照组( P <0.05)。结论:对RA患者采用注射重组人Ⅱ型TNF受体-抗体融合蛋白联合口服风湿骨痛片治疗,提高了临床治疗效果和患者生活质量,减轻了患者的痛苦。
