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1.
目的:探讨以树突状细胞(dendritic cells,DC)联合细胞因子介导杀伤细胞(cytokine induced killer,CIK)为基础的免疫途径治疗恶性实体肿瘤的临床疗效.方法:将60例临床确诊的肾透明细胞癌患者随机分为两组:治疗组给予手术联合细胞免疫治疗,对照组给予手术及细胞因子治疗.采集肿瘤患者的外周血单核细胞,体外诱导培养成熟DC及CIK细胞,最后再回输给患者.观察疗效和治疗前后细胞免疫指标变化(CD3+、CD4+、CD8+、CD4+/CD8+、NK细胞)、外周血象、肝肾功能变化(白细胞、转氨酶、尿素氮、肌酐)及不良反应.结果:治疗组有效率43.33%,对照组有效率26.67%,治疗组与对照组相比,差异有统计学意义(P<0.05).治疗组CD3+、CD4+、CD4+/CD8+免疫学指标治疗前后比较,差异有统计学意义(P值分别为0.010,0.026,0.021),治疗组细胞免疫学指标(CD3+、CD4+、CD4+/CD8+)在治疗前后变化与对照组相比,结果差异有统计学意义(P值分别为0.001,0.023,0.012).两组患者外周血象及肝肾功能检测无异常,免疫治疗过程中未出现明显的毒副作用.结论:以DC、CIK细胞为基础的细胞免疫治疗可以明显改善肾癌术后患者临床疗效,提高外周血淋巴细胞亚群及NK细胞水平,临床应用无明显不良反应,是肾癌术后重要的辅助治疗手段.  相似文献   

2.
目的 观察树突状细胞(dendritic cells,DC)和细胞因子诱导的杀伤细胞(cytokine-induced killer cells,CIK)联合白介素-2(interleukin-2,IL-2)治疗肾癌的疗效.方法 回顾性分析2005年7月至2011年6月间60例肾癌术后患者,分离外周血单核细胞,体外诱导生成DC细胞;T淋巴细胞体外诱导生成CIK细胞.患者在切除原发病灶后,接受DC+CIK细胞免疫治疗,并给予IL-2静滴21 d.免疫学反应和临床疗效分别通过淋巴细胞亚群分析、影像学检查进行评估.结果 治疗后患者外周血细胞毒T细胞、NK细胞、NKT细胞百分比较治疗前增高,差异有统计学意义.42例Ⅰ~Ⅲ期行根治性肾切除术患者,2例失访,1例复发,余未见复发、转移,随访时间7~67个月,中位随访时间16个月;18例Ⅳ期行姑息性肾切除患者中1例失访,随访的17例中1例CR,3例PR,8例SD,5例PD,随访时间6~66个月,中位随访时间15个月,无显著不良反应出现.结论 DC+CIK联合IL-2治疗能够增强肾癌术后患者的免疫功能,降低根治性切除术后肿瘤的复发率,并且对于转移性肾癌的治疗也显现一定的疗效,耐受性良好.  相似文献   

3.
目的 探讨树突细胞(DC)与细胞因子诱导的杀伤细胞(CIK)共培养后产生的DC-CIK细胞对原发性肝恶性淋巴瘤生长和术后复发转移的抑制作用.方法 制备健康人和原发性肝淋巴瘤患者来源的DC和CIK细胞,共培养后获得DC-CIK细胞.取上述原发性肝淋巴瘤患者的恶性淋巴瘤组织,采用外科原位移植技术建立人原发性肝恶性淋巴瘤裸鼠原位移植模型HLBL-0102.另外,在此模型基础上,通过根治性切除术,建立术后肝淋巴瘤肝内复发转移裸鼠模型HLBL-0701.将以上2种模型裸鼠按照以下干预措施分为7组,分别给予CHOP方案化疗、健康人CIK细胞输注、健康人DC-CIK细胞输注、肝淋巴瘤自体CIK细胞输注、肝淋巴瘤自体DC-CIK细胞输注、肝淋巴瘤自体DC-CIK输注联合CHOP方案化疗,以及生理盐水对照.CHOP方案和生理盐水为0.3ml/(kg·d),CIK或DC-CIK细胞均以6×107/(kg·d)[约0.3ml(kg·d)]输注.连续干预21d,末次用药后72h,经心脏采血,测定乳酸脱氢酶(LDH)浓度.取死亡裸鼠,测量肿瘤体积,计算抑瘤率和肝内复发转移率.分析DC-CIK细胞治疗与化疗的协同作用.结果 在HLBL-0102模型中进行的实验表明,与对照比较,化疗,健康人CIK、DC-CIK细胞,肝淋巴瘤自体CIK、DC-CIK细胞,以及肝淋巴瘤自体DC-CIK细胞+化疗干预后的抑瘤率分别为52.1%、40.2%、54.3%、41.7%、60.6%和84.3%,而在HLBL-0701模型中,上述干预措施对肝内肿瘤复发转移的抑制率分别为75.0%、75.0%、50.0%、62.5%、37.5%和25.0%;干预后裸鼠平均生存时间分别为70.32±6.54d、68.25±5.37d、77.00±6.37d、75.25±5.80d、79.50±8.07d、84.75±8.26d,显著长于对照组(35.00±4.17d,P<0.01).在HLBL-0102模型中,瘤体积与LDH浓度呈显著正相关(r=0.9898,P<0.05),协同分析证实肝淋巴瘤自体DC-CIK细胞与化疗具有相加作用(q=1.038).结论 共培养DC-CIK细胞输注能抑制裸鼠原发性肝淋巴瘤生长和肝淋巴瘤根治切除术后的复发转移.肝淋巴瘤患者来源的自体DC-CIK细胞疗效优于健康人来源的细胞,DC-CIK联合化疗的抑瘤效果更佳.  相似文献   

4.
目的 评价自体树突细胞(DC)联合细胞因子诱导的杀伤细胞(CIK)治疗转移性肾癌的临床疗效、免疫功能变化及随访结果.方法 采集27例转移性肾癌患者的外周血单个核细胞(PBMC),经实验室体外培养诱导产生DC和CIK细胞,经无菌检测、流式细胞术表型鉴定及细胞计数后回输给患者.于第7、9、11、13天皮下注射DC,第11、13天静脉回输CIK,每疗程间隔3个月,直至疾病进展,观察临床疗效及免疫功能的变化.结果 27例转移性肾癌患者经DC-CIK治疗后的客观反应率为37%,疾病控制率为85%,2年总生存率为81.5%.与治疗前比较,治疗后患者外周血CD3+CD4+CD8-、CD3+CD4-CD8+、CD3+CD19-、CD3-CD19+、CD3-CD16+CD56+、CD3+CD 16+CD56+、CD3+HLA-DR、CD3+HLA-DR+、CD3+CD28+CD8+细胞亚群及Th2细胞无显著变化(P>0.05),Th1细胞有升高趋势(P<0.05),多次治疗后CD3+CD4+CD25+T细胞(即调节性T细胞,Treg细胞)有降低的趋势(P<0.05).治疗过程中27例患者均未出现明显不良反应.结论 DC-CIK细胞免疫治疗为转移性肾癌患者提供了一种新的安全有效的治疗方法,可改善转移性肾癌患者的免疫抑制状态,提高患者的抗肿瘤免疫反应,无明显不良反应.  相似文献   

5.
近年来,生物学方法应用于临床治疗恶性肿瘤逐渐显现出较好的疗效。树突状细胞(dendriticcell,DC)是体内免疫系统最强大的抗原递呈细胞,在抗原摄取、加工和提呈中起关键作用;抗原刺激后的DC在体内既可以诱发免疫记忆,还可增强机体的非特异性免疫应答。细胞因子诱导杀伤细胞(cytokine—inducedkiller,CIK)是一种杀瘤活性高、广谱的非主要组织相容性复合体(majorhisto-compatibilitycomplex,MHC)限制性免疫效应细胞。两者的联合能有效地抑制和杀死肿瘤细胞,  相似文献   

6.
目的 研究细胞因子激活的杀伤细胞对肿瘤患者的免疫治疗效果.方法 选择3例恶性实体瘤患者术后行细胞因子激活的杀伤细胞治疗,观察细胞因子激活的杀伤细胞体外的生长和增殖情况,同时观察患者细胞因子激活的杀伤细胞回输后的反应.结果 细胞因子激活的杀伤细胞体外增殖良好,培养14 d可以扩增100倍左右,各种检测结果符合临床应用要求,回输后患者精神体力有明显提高.结论 初步观察显示自体细胞因子激活的杀伤细胞体外增殖良好,回输治疗对患者安全有效.  相似文献   

7.
赵花  刘征丽  许霞 《武警医学》2017,28(4):358-360
 目的 观察鳞癌、腺癌、腺鳞癌3种类型宫颈癌根治术后使用细胞因子诱导的杀伤细胞(cytokine induced killer,CIK)治疗前后外周血中免疫指标的变化,为临床使用CIK治疗宫颈癌效果评估提供依据。方法 收集我院2014-01至2016-05肿瘤科和妇产科行宫颈癌根治术后患者98例(其中鳞癌56例,腺癌25例,腺鳞癌17例)CIK治疗前1 d和治疗1个周期后的外周血各5 ml,收集的外周血按CIK细胞治疗流程进行血清分离,分离后的血清用流式细胞计数仪对血清中CD3+、CD4+、CD8+、CD4/CD8、NK细胞的比例进行检测分析。结果 (1)98例宫颈癌根治术后使用CIK细胞治疗前后外周血中免疫指标的对比显示CD3+、NK细胞的比例均升高,CD4+、CD4/CD8比例仅在鳞癌和腺癌中升高,CD8+治疗前后变化不明显。(2)以CD3+和NK细胞为例可以看出使用CIK细胞治疗后腺癌免疫指标较鳞癌、腺鳞癌有显著提升(P<0.05),鳞癌治疗前后,CD3+:(60.71±5.84)/(67.27±3.04),NK细胞:(8.92±3.64)/(12.93±6.25);腺癌治疗前后,CD3+:(59.91±2.49)/(68.32±8.24),NK细胞:(9.04±5.31)/(17.87±6.46);腺鳞癌治疗前后,CD3+:(59.01±5.90)/(65.23±7.07),NK细胞:(8.59±3.97)/(15.07±2.71)。结论 CIK 细胞治疗可以显著提升宫颈癌根治术后患者的免疫功能,对延长生存期,提高生存质量具有重要意义。  相似文献   

8.
目的采用旋转式生物反应器(rotating wall-vessel bioreactor,RWV)与传统的T-Flask培养瓶培养人外周血细胞因子诱导的杀伤(cytokine-induced killer,CIK)细胞,比较CIK细胞的增殖能力、细胞因子分泌情况、细胞杀伤力。方法提取健康志愿者的外周血,分离出外周单个核细胞(peripheral blood mononuclear cell,PBMC),体外诱导成CIK细胞,分别接种到T-Flask培养瓶及RWV中培养。采用台酚蓝染色法检测细胞活率并绘制其生长曲线;ELISA法检测各组CIK细胞的IL-2,IFN-γ,TNF-α分泌情况;乳酸脱氢酶测定法检测CIK细胞对靶细胞的杀伤力。结果与传统的T-Flask培养瓶培养CIK细胞比较,RWV培养CIK细胞增殖数量明显多且生长力旺盛;使用RWV培养CIK细胞能使其分泌更多的IL-2,IFN-γ,TNF-α细胞因子;RWV组培养的CIK细胞对肿瘤细胞的杀伤力更强。结论RWV培养CIK细胞更能提高其增殖能力、细胞因子分泌能力及肿瘤杀伤活力,同时可解决传统细胞培养数量少、稳定性差、易污染、工作量大及周期长等问题,有效地降低临床治疗成本。  相似文献   

9.
目的 观察细胞因子诱导杀伤(CIK)细胞在动物体内分布的特点.方法 99Tcm标记CIK细胞采用亚锡还原法.昆明种小白鼠40只,按随机数字表法分为8组,每组5只,进行小鼠体内分布实验,计算每克组织百分注射剂量率(%ID/g).新西兰家兔3只行动态显像,连续观察99Tcm-CIK细胞体内分布图像特点.结果 分离纯化后99Tcm-CIK细胞的放化纯>95%,室温下6 h内保持稳定.小白鼠体内99Tcm-CIK细胞血液清除较快,观察到血液中1和24 h的再分布现象.99Tcm-CIK细胞主要分布于肺、肝、脾和肾,心脏、脑、骨骼和肌肉等其他脏器组织均分布较少.家兔动态显像示99Tcm-CIK细胞早期分布以肺为主,随时间延长肺内放射性逐渐减少,肝放射性逐渐增多,并超过肺部放射性,2 d后仍可见肝放射性浓聚.心脏、脑、骨骼和肌肉等其他脏器组织均未见明显放射性分布.结论 99Tcm-CIK细胞在血循环中滞留时间较短,注射后1 h内主要聚集于肺,随后肺的摄取逐渐减少,其主要浓聚于肝和脾,尤以肝为甚.  相似文献   

10.
直肠癌是常见的恶性肿瘤,常规治疗是手术后结合放疗和化疗。本例患者在手术后放化疗基础上早期接受了细胞因子激活的杀伤细胞输注治疗,不仅减轻了放化疗的不良反应,而且提高了生活质量,随访5年依然状况良好。  相似文献   

11.
目的评价肾癌患者术后化疗联合自体树突状细胞(DC)联合细胞因子诱导的杀伤(CIK)治疗的临床疗效和安全性。方法收集2007年1月至2010年7月在辽宁省肿瘤医院45例肾癌化疗联合DC-CIK治疗的患者(化疗联合DC-CIK治疗组)及同期对照30例单纯化疗的肾癌患者(单纯化疗组),比较两组患者临床疗效、不良反应以及生存差异,并对外周血淋巴细胞亚群和细胞因子水平进行检测,比较组间差异。结果化疗联合DC-CIK治疗组实体瘤近期缓解情况显著优于化疗组;与治疗前比较,化疗与DC-CIK细胞免疫联合治疗的患者外周血淋巴细胞亚群中CD3~+CD4~+CD8~+、CD3~+CD16~+CD56~+T细胞计数增加(P<0.05);化疗联合CIK治疗组患者的总生存时间(OS)为64个月,明显高于单纯化疗组的45个月(P<0.05)。治疗过程中患者均未出现发热和寒颤等相关不良反应。结论自体DC-CIK细胞回输在联合化疗的基础上治疗晚期肾癌更有生存优势,而且安全性及耐受性良好。  相似文献   

12.
肾细胞癌(RCC)是泌尿生殖系统中侵袭性最高的恶性肿瘤之一,预后不佳,尤其是发生RCC转移的患者。传统观点一般认为肾细胞癌对放疗不敏感。立体定向体部放射治疗(SBRT)与常规放疗相比,具有高精准度、较高照射剂量、对周围组织损伤小等特点。近年来,SBRT在原发性及转移性RCC治疗中均展现了确切的疗效。SBRT联合靶向治疗以及免疫治疗等联合方案可以提高原发和晚期转移RCC患者的肿瘤局部控制率,且不良反应较小。本文就SBRT 联合靶向治疗以及免疫治疗的策略和进展等方面进行综述。  相似文献   

13.
目的分析肾透明细胞癌的CT影像特点。方法回顾性分析经病理证实的肾透明细胞癌16例,从病灶数目、大小、形态、强化方式及与邻近结构关系等方面总结其CT影像特点。结果本组16例均为单发病灶,多位于肾皮质,形态多为圆形或类圆形,多凸出肾轮廓之外,平均4.7cm(2.2~10cm不等),伴或不伴邻近结构受累;增强扫描大多数(12例)动脉期明显不均质强化,静脉期及分泌期强化程度降低,低于周围肾实质,即典型的"快进快出"式强化,1例动脉期中等度强化,2例仅轻度强化,1例肿瘤内形成动静脉瘘。本组病例其中1例为囊性肾透明细胞癌,内可见多发点状及条状钙化,增强后呈中等强化,囊内容物不强化。结论 CT扫描是肾透明细胞癌的重要检查手段,其较特征性的动脉期强化方式是与其它类型肾癌相鉴别的重要参考依据。  相似文献   

14.
Purpose The aim of this retrospective study was to evaluate the clinical value of percutaneous radiofrequency ablation (RFA) for the treatment of renal cell carcinoma (RCC). Materials and Methods In a recent 3 years seven RCCs in six patients were treated by percutaneous RFA. RCC had been diagnosed based on the typical findings by computed tomography and/or magnetic resonance imaging. A cool-tip RF system (Vallylab) was mainly used with a RF2000 generator. The maximum tumor size ranged from 8 to 40 mm in diameter. The follow-up period was 14–36 months after initial RFA treatment. Results Complete disappearance of contrast enhancement during the early arterial phase was noted immediately after each session of percutaneous RFA. Two RCCs ≥ 3 cm in diameter showed tumor recurrence and required re-RFA during the follow-up period. In one patient, retroperitoneal hematoma was observed as a noteworthy complication. Conclusion Despite our limited number of patients, we believe that percutaneous RFA is clinically feasible and can be an alternative treatment of choice for RCC.  相似文献   

15.
The transfusion of allogenic, in vitro expanded natural killer cells (NKC) is a novel therapy option in oncology. To date, however, the biodistribution and kinetics of allogenic NKC have not been investigated. Therefore, in this study three patients with renal cell carcinoma received 3–7×108 NKC labelled with indium-111 oxine with a tenfold excess of unlabelled cells during NKC therapy. Whole-body scintigrams were obtained (0.5–144 h) in the anterior and posterior views. Scintigrams were analysed using a region of interest technique, and single-photon emission tomography (SPET) studies of the abdomen were performed. Results were compared to those obtained with polymerase chain reaction (PCR) of the peripheral blood (determination of foreign DNA, nested PCR, limit of detection 0.01%). Shortly after transfusion of NKC, more than 50% of the activity was accumulated in the lungs. We observed redistribution effects from lungs to liver, spleen and bone marrow. No significant loss of activity could be detected. In two of four large metastases, tracer accumulation could be proven by SPET. As confirmed by scintigrams and PCR, the fraction of circulating transfused cells was low at all times. Long-term activity retention might be caused either by survival of the allogenic cells, as confirmed by PCR (up to 3 days p.i.), or by phagocytosis of labelled cellular fragments. However, PCR data and uptake in metastases indicated long survival of a portion of allogenic NKC. Such long survival and low retention of the cells in the lung are requirements for an effective immunotherapeutic approach.  相似文献   

16.
目的 探讨MR动态增强扫描对肾癌亚型的鉴别诊断价值.方法 搜集77例经病理证实的肾癌患者资料,其中透明细胞癌(CCRCC)55例,乳头状癌(PRCC)14例,嫌色细胞癌(CRCC)8例,回顾性分析各亚型肿瘤患者MR平扫及动态增强扫描表现并与病理对照,根据肿瘤及肾皮质增强前后的皮质期、实质期及延迟期信号变化,分别进行百分比测量、肿瘤-肾皮质增强指数计算,并采用单因素方差分析和LSD法进行比较.结果 CRCC多数信号均匀(7/8);CCRCC及PRCC多数信号不均(分别为51/55和13/14)、常见坏死(36/55和7/14),PRCC最常见出血(9/14)及囊变(9/14).动态增强各期CCRCC强化程度最高,强化模式呈"快进快退",CRCC轻至中度强化,PRCC强化最轻,两者均呈渐进性延迟强化.CCRCC、PRCC及CRCC皮质期信号变化分别为(296.15±60.27)%、(79.70±18.84)%和(119.56±40.76)%,实质期分别为(236.33±58.31)%、(122.81±27.35)%和(163.06±33.91)%,延迟期分别为(216.83±46.72)%、(117.55±20.63)%和(179.72±32.89)%;三者皮质期的肿瘤-皮质增强指数分别为1.26±0.34、0.33±0.12及0.54±0.10,实质期分别为0.92±0.23、0.41±0.23及0.62±0.15,延迟期分别为0.76±0.14、0.35±0.11及0.69±0.12,各亚型增强各期的信号变化(F值分别为940.931、124.515、38.194,P值均<0.01)、肿瘤-皮质增强指数(F值分别为798.625、78.308、73.699,P值均<0.01)差异均有统计学意义.3种亚型的MRI表现与病理学所见基本相符.结论 CCRCC、PRCC及CRCC的MRI动态增强有一定特征性的表现,与其病理特点密切相关,在肾癌亚型的鉴别诊断上有着较高的临床应用价值.
Abstract:
Objective To investigate the differential diagnostic features of subtypes of renal cell carcinoma(RCC) using dynamic contrast-enhanced MRI(DCE-MRI).Methods The MRI appearances of 77 RCCs, including 55 clear cell RCCs(CCRCC),14 papillary RCCs(PRCC) and 8 chromophobe RCCs(CRCC), were retrospectively analyzed and compared with findings of pathology. DCE-MRI was conducted in each case after intravenous administration of contrast agent. Region of interest measurements (cortical, nephrographic and delayed Phases) of signals within tumor and uninvolved renal cortex were used to calculate percentage signal intensity change and tumor-to-cortex enhancement index, and the data was analyzed by AVONA and t test. Results On unenhanced and enhanced MRI, most CRCCs showed homogeneous signal(7/8). CCRCC and PRCC often show inhomogenous signal with necrosis(36/55, 7/14). Hemorrhage and cystic degeneration were often found in PRCC (9/14). On the cortical, nephrographic and delayed phase images, CCRCCs showed greater signal intensity change[(296.15±60.27)%, (236.33±58.31)% and (216.83±46.72)%,respectively than PRCCs (79.70±18.84)%, (122.81±27.35)% and (117.55±20.63)%, respectively], and CRCCs showed intermediate change [(119.56±40.76)%, (163.06±33.91)% and (179.72±32.89)%, respectively].A phenomenon of quick staining and quick fainting was observed in CCRCCs. Both of CRCCs and PRCCs showed delayed enhancement. The tumor-to-cortex enhancement index at the cortical, nephrographic and delayed phases was highest for CCRCCs (1.26±0.34, 0.92±0.23 and 0.76±0.14, respectively), lowest for PRCCs (0.33±0.12, 0.41±0.23 and 0.35±0.11, respectively), and intermediate for CRCCs (0.54±0.10, 0.62±0.15 and 0.69±0.12, respectively,P<0.01). The degree of enhancement was significantly different among the 3 subtypes at the every contrast enhanced phase (F=940.931, 124.515 and 38.194, P<0.01), so was the tumor-to-cortex enhancement index(F=798.625,78.308 and 73.699, P<0.01). There was a good consistency between MR appearances of the 3 RCC subtypes and pathological characteristics. Conclusion DCE-MRI could distinctly show imaging features of CCRCC, PRCC and CRCC, which were related to their pathological characteristics, and these features were helpful in predicting a specific subtype of RCC.  相似文献   

17.

Objective

Although renal sinus fat invasion has prognostic significance in patients with renal cell carcinomas (RCCs), there are no previous studies about the value of multidetector computed tomography (MDCT) about this issue in the current literature.

Materials and methods

A total of 863 consecutive patients (renal sinus fat invasion in 110 patients (12.7%)) from single institutions with surgically-confirmed renal cell carcinoma who underwent MDCT between 2010 and 2012 were included in this study. The area under the curves (AUCs) of the receiver operating characteristic (ROC) analysis was used to compare diagnostic performance. Reference standard was pathologic examination. Weighted κ statistics were used to measure the level of interobserver agreement. Multivariate logistic regression model was used to find the predictors for renal sinus fat invasion. Image analysis was first performed with axial-only CT images. A second analysis was then performed with both axial and coronal CT images. A qualitative analysis was then conducted by two reviewers who reached consensus regarding tumor size, decreased perfusion, tumor margin, vessel displacement, and lymph node metastasis. The reference standard was pathologic evaluation.

Results

The AUCs of the ROC analysis were 0.881 and 0.922 for axial-only images and 0.889 and 0.902 for combined images in both readers. The AUC of tumor size was 0.884, a similar value to that of the reviewers. In multivariate analysis, tumor size, a linear-nodular or nodular type of fat infiltration, and an irregular tumor margin were independent predicting factors for perinephric fat invasion.

Conclusion

MDCT shows relatively high diagnostic performance in detecting perinephric fat invasion of RCC but suffers from a relatively low PPV related to low prevalence of renal sinus fat invasion. Applying tumor size alone we could get similar diagnostic performance to those of radiologists. Tumor size, fat infiltration with a nodular appearance, and an irregular tumor margin were predictors for perinephric invasion.  相似文献   

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