LAK细胞治疗对肝癌患者免疫功能影响的研究

目的:研究LAK细胞治疗前后免疫功能的改变。方法:应用人胚胎脾脏及胸腺制备同种异体LAK细胞治疗晚期肝癌30例。在治疗前及治疗10d后检测末梢T细胞亚群、mIL—2R表达(间接免疫荧光法).NK细胞活性(~(125)I—UdR释放法)及血清sIL-2R水平(ELISA法)。结果:治疗后患者末梢血CD_4/CD_8比值增加(1.11± 0.24→1.31±0.25,P<0.01)NK细胞活性提高(36.4％→24.3％→47.6％±25.1％,P<0.01)、mIL-2R表达阳性率增高(33.3％±7.2％→±39.5％±8.4％,P<0.05)、而血清中sIL-2R含量降低[280.8±96.5→248.4±89.4(×10~3U/L)P<0.05]。结论:LAK细胞治疗可增强肝癌患者的免疫功能。     

IL—2和LAK细胞的临床联用

近年,白细胞介素-2(IL-2)和淋巴因子活化的杀伤细胞(LAK细胞)联用治疗肿瘤已初见疗效,但因应用时间短,仍需观察和探索,加之价格昂贵,其应用受到了限制。因此,目前大多数医生对其缺乏认识。为此,本文作一简要介绍。     

实体瘤IL─2／LAK细胞治疗研究进展

实体瘤ＩＬ＿２／ＬＡＫ细胞治疗研究进展王小众福建医学院附属协和医院消化内科福建省福州市３５０００１主题词肿瘤／治疗杀伤细胞，淋巴因子激活免疫疗法，过继Ｓｕｂｊｅｃｔｈｅａｄｉｎｇｓｎｅｏｐｌａｓｍｓ／ｔｈｅｒａｐｙｋｉｌｅｒｃｅｌｓ，ｌｙｍｐｈｏ...     

自体与异体LAK细胞治疗慢性肝炎130例

目的对ＬＡＫ细胞治疗慢性肝炎作客观估价．方法治疗与对照组均口服维生素，肌注肝炎灵．治疗Ａ组加回输自体ＬＡＫ细胞，每周２次，６周为１个疗程；Ｂ组每周输注异体ＬＡＫ细胞悬液１次，５次为１疗程．结果ＬＡＫ细胞治疗慢性肝炎能使部分患者ＨＢｅＡｇ及ＨＢＶＤＮＡ阴转．治疗结束时ＨＢｅＡｇ阴转率Ａ组为４７５％，Ｂ组为５８０％；而对照组Ｃ为１５０％（Ｐ＜００５）．ＨＢＶＤＮＡ阴转率Ａ组为４５０％，Ｂ组为６６０％，而对照组Ｃ为１１８％，（Ｐ＜００５％）．结论ＬＡＫ细胞治疗对ＨＢＶ复制有明显抑制作用．异体ＬＡＫ组的ＨＢｅＡｇ及ＨＢＶＤＮＡ阴转率高于自体ＬＡＫ组．     

重组IL2联合LAK和TIL细胞治疗癌性胸腔积液

采用自体淋巴因子激活的杀伤细胞(LAK)和重组白细胞介素2_rIL_2静脉滴注,同时将胸液中的肿瘤浸润淋巴细胞(TIL)体外培养、扩增后联同_rIL_2注入胸腔治疗肺癌癌性胸腔积液30例。结果显示完全缓解(CR)16例(53％),部分缓解(PR)12例(40％),无效(NC)2例(7％)。治疗后多数患者闷喘减轻,精神好转,食欲增加,体力增强,外周血白细胞增加,PR、NC病例胸液中淋巴细胞增多,癌胚抗原(CEA)下降。除12例(40％)出现一过性发热,4例(13％)出现荨麻疹,未作处理好转。表明本疗法治疗肺癌癌性胸腔积液是有效的,能提高患者的生存时间及生活质量。     

IL—2／LAK细胞联合应用治疗原发性肝癌

用IL-2/LAK细胞联合治疗81例原发性肝癌,分别采用经静脉输注、肌肉注射及肿瘤局部用药。治疗后作CT、B超检查,观察肿瘤占位、淋巴细胞亚群、肝功能及临床症状、体征改变等。结果表明,局部用药组总有效率显著高于其他各组(P<0.01)。T细胞亚群检测表明,各治疗组治疗后的细胞免疫水平均显著提高。     

经埋植式给药装置肝动脉门静脉输注自体LAK细胞及化疗药物治疗中晚期肝癌

目的探讨肝动脉门静脉输注自体ＬＡＫ细胞在肝癌肝脏灌注化疗中的临床价值。方法病理证实的原发性肝癌患者９２例，１４例肝动脉门静脉输注自体ＬＡＫ细胞及化疗药物，７８例肝动脉门静脉输注化疗药物作为对照。结果自体ＬＡＫ细胞加化疗组ＣＲ６例，ＰＲ６例，有效率８５．７％；对照组ＣＲ１７例，ＰＲ２８例，有效率５７．７％；两组间疗效有显著性差异（Ｐ＜０．０５）。结论肝动脉门静脉输注自体ＬＡＫ细胞可以提高肝癌肝脏灌注化疗的效果，经埋植式给药装置肝动脉门静脉输注自体ＬＡＫ细胞及化疗药物治疗中晚期肝癌的研究具有实际临床意义。     

肝癌患者外周血LAK细胞活性测定及其影响因素的研究

近年来通过白细胞介素2(IL-2)诱导产生的淋巴因子活化性杀伤细胞(Lym-phokine-activated killer cell,LAK)在继承性免疫治疗肿瘤动物模型和人体肿瘤中已显出一定的疗效,但至今尚未见到有关研究肝癌患者LAK细胞活性变化的     

回生口服液对晚期非小细胞肺癌患者Fib、PLT水平的影响

目的观察回生口服液对晚期非小细胞肺癌患者血浆纤维蛋白原（Fib）和血小板（PLT）水平的影响。方法将56例晚期非小细胞肺癌患者随机分为观察组30例和对照组26例,观察组在对症止痛、支持等处理基础上口服回生口服液治疗,对照组仅予对症止痛、支持治疗。采用Sysmex CA-7000血凝分析仪分别检测治疗前后两组血浆Fib和PLT水平的变化。结果观察组治疗前后Fib、PLT水平无统计学差异,P〉0.05;观察组治疗后Fib、PLT水平明显低于对照组,P〈0.05。对照组治疗后Fib、PLT水平均较治疗前明显升高,P〈0.05。结论回生口服液改善患者血液高凝状态、降低肿瘤细胞粘附及运动能力、抑制肿瘤血管生成的作用,其机制可能为抑制Fib、PLT水平。     

All trans retinoic acid enhances human LAK activity

Abstract: All trans retinoic acid has various effects on normal and malignant cells. Lymphokine-activated killer (LAK) activity can be derived from T lymphocytes and natural killer cells. This study shows that all trans retinoic acid significantly enhances this activity by increasing production of tumour necrosis factor and gamma interferon, which results in enhanced expression of the p55 part of the interleukin 2 receptor. This effect is dependent on the concentration of all trans retinoic acid and the length of time of culture.     

Effects of lymphokine-activated killer cells and interleukin-2 on the ascites formation and the survival time of nude mice bearing human ovarian cancer cells

Summary The effect of intraperitoneal instillations of interleukin-2 (IL-2) and/or lympokine-activated killer (LAK) cells on the ascites formation and the survival time was examined using nude mice as a model, with malignant ascites produced by intraperitoneal inoculation of human ovarian cancer cells derived from ascites of a patient with serous cystadenocarcinoma of the ovary. Twenty-eight days after tumor inoculation, all nude mice in the untreated group and in the group treated with spleen cells alone formed ascites. Two of ten nude mice treated with IL-2 alone after tumor inoculation survived without forming ascites during the experimental period. On the other hand, all nude mice treated with LAK cells alone had formed ascites 14 days after tumor inoculation. When LAK cells and IL-2 were combined, five of ten mice survived without forming ascites during the experimental period. The survival time of the group treated with IL-2 alone was significantly prolonged compared to the groups that received medium alone, spleen cells alone and LAK cells alone. When administration of LAK cells was followed by IL-2, the survival time was further prolonged.Supported in part by a grant from the Special Scientific Research Program of the Defense Agency in Japan Offprini requests to: Y. Kikuchi     

IL2- and IL4-dependent proliferation of T-cell clones derived early after allogeneic bone marrow transplantation: studies of patients with chronic myelogenous leukaemia.

In an attempt to explore T-cell functions shortly after allogeneic bone marrow transplantation more fully, IL2- and IL4-dependent proliferation was assessed on CD4+ TCR alpha beta+ T-cell clones derived 4-6 weeks after transplantation. Both allogeneic pooled peripheral blood mononuclear cells and Epstein-Barr virus-transformed B-cell lines (BCL) could function as accessory cells (AC) for PHA activation of T-cell clones. Although minimal clonal proliferation was seen when the T-cell activation signal was BCL+PHA+IL4, a majority of the clones could undergo IL4-dependent proliferation after previous activation with AC+PHA+IL2. For certain clones, IL4 also showed an additive effect with IL2. Thus, IL4 was a growth factor for a majority of the investigated posttransplant T-cell clones, and in vivo modulation of IL4-dependent T-cell functions may thus become a future therapeutic possibility to enhance graft-versus-leukaemia effects in bone marrow transplant recipients.     

低氧对人外周血单个核细胞迁移活性的影响及其临床意义

目的探讨低氧对机体外周血单个核细胞（PBMC）迁移的影响及其临床意义。方法分离外周血单个核细胞,采用Transwell小室实验检测常氧和低氧条件下PBMC迁移能力的变化,流式细胞术（FCM）检测常氧和低氧条件下T、B淋巴细胞,NK细胞及单核细胞迁移的变化。结果低氧环境下PBMC的迁移率降低31％。对其细胞亚群的分析结果显示,NK细胞的迁移率降低31．7％,单核细胞的迁移率降低63．1％,T、B淋巴细胞的迁移率无显著变化。结论低氧能显著影响单核细胞及NK细胞的迁移功能;检测低氧条件下PBMC的迁移能力,可为以免疫细胞迁移功能为靶点的炎症等疾病提供新的治疗对策。     

Effect of TNF gene-transfected LAK cells on the ascitic liver carcinoma-bearing mice

AIM To investigate the therapeutic effect of TNF gene transfected LAK cells on ascitic liver carcinoma-bearing mice.METHODS TNF gene was transfected into murine LAK cells by retrovirus. Low dose TNF gene-transfectcdLAK cells and IL-2 were i.p. injected into murine model. Cytotoxicity of gene transfected LAK cells wasstudied in vitro growth and the survival time of murine model was observed.RESULTS TNF gene-transfected LAK cells secreted higher level of TNF than that of normal LAK cells orcontrol gene-transfected LAK ceils. The in vitro growth ability and cytotoxicity of TNF gene-transfectedLAK cells were markedly inhibited by anti-TNF monoclonal antibodies. Significant therapeutic effect onascitic liver carcinoma-bearing mice was achieved.CONCLUSION TNF gene-transfected LAK cells have therapeutic effect on ascitic liver carcinoma-bearingmice.     

The effect of iron, iron-binding proteins and iron-overload on human natural killer cell activity

The in vitro natural killer (NK) activity of peripheral blood lymphocytes (PBL) was assessed in 13 patients with genetic haemochromatosis (HC) and 27 normal subjects, using a ⁵¹Cr-release cytotoxicity assay against the target K-562 leukaemic cell line. Mean NK function did not differ between these two groups. This conclusion differs from the reported deficit in NK activity in other diseases in which increased iron stores may occur, including alcoholic cirrhosis and β-thalassaemia major. The effect of ferric citrate (0.1–1.0 mmol/1), normal human liver ferritin (100–10 000 μg/1) and transferrin (2 g/1) on NK activity was also assessed for both groups. In neither group was NK activity affected by any of these additives. These results suggest that peripheral blood NK function is not compromised in haemochromatosis, and that the diminished NK activity which has previously been reported in some patients with thalassaemia or alcoholic cirrhosis is due to factors other than to a direct effect of increased iron stores.