生长抑素与肾癌的关系及肿瘤坏死因子的影响

为探索肾癌生物治疗的新途径，将肾癌细胞接种于裸鼠背部皮下，荷瘤裸鼠随机分为３个ＴＮＦ组及２个对照组。给药后第３天取血０５～０８ｍｌ，及移植瘤、瘤旁及正常组织各１ｇ，放射免疫法测定组织标本中生长抑素（ＳＳ）浓度。结果：肿瘤组织、对照组肿瘤旁、正常组织中ＳＳ浓度（ｐｇ／ｍｌ）依次为０．６７３、０９００、０５１４；ＴＮＦ组分别为０．７９１、０８７０、１０４３。结论：肾癌生长（对照组）时瘤旁组织中ＳＳ浓度最高，而肿瘤及正常组织中较低，提示瘤旁组织具有抑制肿瘤生长的作用。应用ＴＮＦ后ＳＳ含量以正常组织中最高，瘤旁及肿瘤组织较低。表明ＴＮＦ不但对肿瘤有直接杀伤作用，而且能促进机体增强抑制肿瘤生长、扩散作用。     

热疗对荷VX2瘤动物细胞因子影响的实验研究

目的探讨热疗对荷VX2瘤动物细胞因子的影响。方法选健康雄性大白兔40只,随机分为热疗组20只、对照组20只。移植VX2瘤株11d后,对实验组动物进行热疗照射,监测白介素-2(IL-2)、肿瘤坏死因子(TNF)、胰岛素样生长因子(IGF)的变化。结果实验动物生存期较对照组延长15d左右。移植前IL-2、TNF、IGF为(134±6)ng/ml、(4·5±0·9)ng/ml、(96±28)ng/ml;治疗后1周为(81±7)ng/ml、(7·6±1·8)ng/ml、(678±183)ng/ml;3周为(61·8±2·0)ng/ml、(15·1±3·0)ng/ml、(991±108)ng/ml;4周为(54·8±2·6)ng/ml、(17·2±2·1)ng/ml、(1136±89)ng/ml。结论热疗对于表浅肿瘤的治疗是有效的辅助疗法;热疗后肿瘤细胞变性坏死的分解产物被机体吸收后作为一种抗原,刺激机体的免疫系统产生细胞因子,起到抗肿瘤免疫功能。     

细胞因子对精子发生及其功能的影响

细胞因子是细胞与细胞间相互沟通的信号分子,细胞因子之间彼此诱生,相互协同或拮抗作用介导并维持细胞间的协调关系。男性精浆中白细胞介素(IL)-2、IL-6、肿瘤坏死因子(TNF)-α等细胞因子对男性生殖有一定的影响。     

胆碱能递质对LPS刺激外周血释放细胞因子的影响

目的观察拟胆碱药物对LPS刺激正常人全血细胞释放TNFα,IL-6和IL-10的影响,评价胆碱能递质在全血中抗炎的综合效应.方法在LPS刺激的全血中分别加入不同浓度的乙酰胆碱和氯化氨甲酰胆碱孵育5h;用ELISA方法测定培养细胞上清液中TNFα,IL-6和IL-10的浓度.结果乙酰胆碱和氯化氨甲酰胆碱对LPS刺激外周血释放TNF和IL-6均有抑制作用,并呈现一定的剂量依赖关系,但氯化氨甲酰胆碱的抑制作用强于乙酰胆碱.IL-10也呈现类似的规律.结论胆碱能递质不仅抑制LPS刺激的外周血释放炎症性细胞因子,在一定程度上也影响抗炎因子的释放,提示其具有免疫调节作用.     

Th1/Th2类细胞因子在胰腺癌组织中的表达模式及临床意义

自Th1和Th2的概念提出以来，人们对其在机体免疫应签中的作用进行了大量的体内外实验研究，但未见有胰腺癌组织中T1/Th2偏移的研究报道。我们以IFN-γ和IL-2代表Th1类细胞因子，IL-4和IL-10代表Th2类细胞因子，以免疫组织化学方法检测胰腺癌组织中Th1/Th2类细胞因子的表达，观察Th1/Th2类细胞因子在胰腺癌中的表达特征，探讨胰腺癌的发病的机制。     

血液滤过治疗对重症急性胰腺炎患者血浆炎性细胞因子水平的影响

目的比较单次短时血液滤过 (血滤 )与间断短时血滤对重症急性胰腺炎 (SAP)患者血浆细胞因子失衡的影响。方法对符合血滤指征的 5 8例SAP患者行单次短时血滤 (SS组 )治疗 17例、间断短时血滤 (IS组 )治疗 2 1例 ,2 0例未行血滤治疗者作为对照 (N组 )。观察各时点肿瘤坏死因子α(TNF α)、白细胞介素 (IL) 6、IL 8和IL 10的血浆水平 ,以APACHEⅡ评分、液体平衡状况衡量病情变化。结果两血滤组APACHEⅡ评分在入组第 1天即显著下降 ,第 4天起显著低于N组 ,且IS组较SS组更低 ,P值均 <0 0 5。N组、SS组和IS组分别有 1、1、0例中转手术和 3、2、0例死亡 ,液体负平衡出现时间分别为入组 (5 9± 1 8)d、(3 5± 2 1)d和 (2 7± 1 4 )d。入组第 4天和第 10天 ,血滤组与N组比较促炎症因子水平显著下降 ,IL 10与促炎症因子的比值显著增高 ,IS组的TNF α和IL 6水平更低 ,P值均 <0 0 5。结论　血滤尤其是间断短时血滤可以有效纠正SAP患者血浆炎症细胞因子失衡 ,改善患者预后。     

氯胺酮对前炎性细胞因子的影响

在机体对创伤和应激的免疫防御反应中 ,细胞因子 (ｃｙ ｔｏｋｉｎｅｓ,ＣＫ)起着至关重要的作用。细胞因子是传递细胞间信息的小分子蛋白质或多肽 ,主要由激活的白细胞产生 ,也可由成纤维细胞和内皮细胞产生[1] 。细胞因子种类繁多 ,细胞因子之间相互影响、相互作用 ,构成了错综复杂的细胞因子网络 (ｃｙｔｏｋｉｎｅｎｅｔｗｏｒｋ)。目前认识到 ,在细胞因子网络中 ,促炎症细胞因子和抗炎症细胞因子的平衡 ,是机体产生合适免疫应答的关键。前炎性细胞因子 (ｐｒｏｉｎｆｌａｍｍａｔｏｒｙｃｙｔｏｋｉｎｅ)属于促炎症细胞因子类 ,主要包…     

高容量血液滤过对外周血细胞因子的影响

目的研究高容量血液滤过(HVHF)对外周血肿瘤坏死因子(TNF-α)、白细胞介素-1β(IL-1β)、白细胞介素6(IL-6)的清除作用。方法18例重症急性肾功能衰竭(ARF)患者,随机选择10例行HVHF,另8例为对照组,行血液透析(HD)。酶联免疫法检测治疗前和治疗1h、2h、4h、6h和8h时血、超滤液及透析液中TNF-α、IL-1β、IL-6的浓度(单位均为ng/L)。结果(1)HVHF组9/10例、HD组6/8例患者肾功能恢复正常;(2)HVHF组治疗前血TNF-α1784±437、IL-1β960±173、IL-61320±325分别与治疗后4h1267±401、519±127、761±259比较,差异有显著性意义,P＜0.01;超滤液中未能检测出TNF-α,但可持续检测到IL-1β、IL-6;(3)HD组治疗过程中TNF-α、IL-1β、IL-6血中浓度无明显变化,透出液中未检测出上述细胞因子。结论HVHF可通过对流作用清除大量的细胞因子;AN69滤器对细胞因子有吸附作用。     

癌症患者血浆细胞因子水平的变化

应用同位素掺入法及酶联法检测癌症患者血浆白细胞介素１、２、６（ＩＬ１、２、６）活性、肿瘤坏死因子（ＴＮＦ）含量。结果表明：癌症患者血浆ＩＬ１、ＩＬ２、ＩＬ６活性均显著低于对照组，而ＴＮＦ含量却显著高于对照组。提示细胞因子水平的异常可能在肿瘤发生过程中起重要作用。     

肾移植受者体内细胞因子及其受体的水平及意义

检测了７２例肾移植患者血中可溶性白细胞介素２受体（ＳＩＬ－２Ｒ）、肿瘤坏死因子（ＴＮＦ）及白细胞介素６（ＩＬ－６）的水平。结果发现，正常健康对照组ＳＩＬ－２Ｒ为１２５±５４ｋＵ／Ｌ，术后肾功能平稳组为２５６±９３ｋＵ／Ｌ，环孢素Ａ中毒组为３３８±７３ｋＵ／Ｌ，而ＴＮＦ在这几组中均测不出，ＩＬ－６均小于５ｋＵ／Ｌ。肾移植术后ＳＩＬ－２Ｒ迅速下降，与血肌酐有明显的一致性，ＩＬ－６水平升高，第２天达高峰（１８．２５±２．３６ｋＵ／Ｌ），以后逐渐下降，１０天后降至５ｋＵ／Ｌ。发生急性排斥反应组ＳＩＬ－２Ｒ为１０７７±４４８ｋＵ／Ｌ，升高较血肌酐提早２．２天，敏感性达９４．４％，特异性达９１．７％；ＩＬ－６为５９．９±３５．２７ｋＵ／Ｌ，并较临床症状出现平均提早１．２天；ＴＮＦ为３３．６７±１３．７μｇ／Ｌ，检出率为６７％。感染组的ＳＩＬ－２Ｒ、ＩＬ－６、ＴＮＦ分别为１６２０±３９７ｋＵ／Ｌ、７９．７５±６１ｋＵ／Ｌ及１２７．５±８３．８μｇ／Ｌ。结果表明，ＳＩＬ－２Ｒ、ＴＮＦ、ＩＬ－６可作为监测肾移植排斥反应的指标。     

Effects of cytokines on growth in vitro of primary human renal cell carcinoma

Summary In clinical trials different haematopoietic active cytokines such as granulocyte-macrophage colony-stimulating factor (GM-CSF) and granulocyte colony-stimulating factor (G-CSF) have been proven to alleviate myelosuppressive side effects of intensive chemotherapy in different non-urological malignancies. On the other hand, these cytokines can directly stimulate the proliferation of cells originating from some non-urological tumours. To clarify the impact of these cytokines on the proliferative behaviour of human renal cell carcinoma (RCC), 29 previously untreated RCC tumours were prepared for culturing in vitro using the cell cluster technique. The success rate for growth in vitro was 82.8% (24/29). The malignant renal cells were treated with different cytokines (GM-CSF, G-CSF and interleukin-3) in different dosages. Cell number and proliferation rates detected by immunostaining were used for treatment evaluation. A dosage-dependent stimulation of cell growth could not be observed compared to untreated cells. From the data presented in this study, proliferative stimulation of RCC by administering colony-stimulating factors in clinical trials cannot be assumed.     

化疗药物对荷人胆管癌裸小鼠移植瘤的药效试验

目的：观察化疗药物对荷人胆管癌裸小鼠移植瘤的治疗效果。方法：采用人中分化胆管癌裸小鼠移植瘤模型。将45只荷人胆管癌裸小鼠分为各治疗组和对照组,裸小鼠治疗组每组5只,对照组10只。分组当天称鼠重,由尾静脉用药1次。给药剂量：丝裂霉素(MMC)4mg／kg,阿霉素(ADM)10mg／kg,长春新碱(VCR)0．20mg／kg,泰素(TAXOL)20mg/kg,顺铂(DDP)10mg／kg,环磷酰胺（CTX)120mg／kg,5-氟脲嘧啶(5-Fu)120mg/kg,NS为0．2mL／只。第21天处死裸小鼠,称鼠重,计算体重变化。治疗期间每周测肿瘤瘤径2次,计算相对肿瘤增殖率T／C(％)。结果：MMC,ADM,VCR,TAXOL,DDP和CTX组第21天相对肿瘤增殖率分别为：1％,23％,39％,47％,51％和86％,裸小鼠体重增加分别为：21％,0％,11％,1％,14％和8％。5-Fu组80％裸小鼠死亡,有药物毒性反应。结论：MMC,ADM,VCR,TAXOL,DDP对荷人中分化胆管癌裸小鼠的移植瘤有明显的抗癌作用,CTX无效。     

Local bone resorption induced by serially transplantable human renal cell carcinoma in nude mice

The high incidence of metastatic bone disease in urological cancer makes it necessary for clinicians to look for a valid experimental model to investigate the basic interactions between cancer cells and bone in order to improve the treatment. A new model of bone resorption was defined, namely the subcutaneous injection of tumor cell suspensions of serially transplanted renal cell carcinoma in nude mice after disruption of the periosteum of the calvaria. The tumor induced osteolysis associated with osteoclast proliferation with reactive bone formation. The X-p film from nude mice calvaria showed the same multiple osteolytic punched-out lesions as those of the patient's skull.     

Effect of various anti-cancer drugs on human renal cell carcinoma serially transplanted into nude mice

Using two xenografts of human renal cell carcinomas serially transplanted in nude mice (AM-RC-1 and AM-RC-6), both of which maintained the basic histologic features of the original tumor and showed a constant growth rate, the effects of various anticancer agents against 2 target tumors were evaluated. MitomycinC (MMC), adriamycin (ADM), cisplatinum diaminodichloride (CDDP), 5-fluorouracil (5FU), 5-fluro-2'-deoxy-beta-uridine (FUDR) and human lymphoblastoid interferon (HLBI) against AM-RC-1, and MMC, ADM, CDDP, vinblastin (VBL) and etoposide (VP-16) against AM-RC-6. Drugs other than HLBI were administered 3 times in total every three to five days by intraperitoneal injection according to Battelle Columbus Laboratories Protocol and HLBI was injected daily for 10 days intraperitoneally. Anti-cancer effects were evaluated based on tumor growth curve and changes of histologic findings. In terms of tumor growth only MMC (in a dose of 3 mg/kg) revealed a statistically significant inhibitory effect against both AM-RC-1 and AM-RC-6 (respectively P less than 0.001 and P less than 0.05). Concerning AM-RC-1, a significant difference (P less than 0.01) was recognized in the ADM group (5 mg/kg) at the time of the second administration, but evaluation could not ultimately be done owing to appearance of acute toxity after the last dose. The most remarkable histologic changes by light microscopy were recognized in the MMC group (in a dose of 3 mg/kg) against AM-RC-1. They were degenerative findings such as intracellular and nuclear vacuolation, karyorrhexis, karyolysis, karyopyknosis and marginal hyperchromatosis, which corresponded to grade IIa of the classification of the National Cancer Center. The other drugs administered to AM-RC-1 exhibited only grade O to grade I changes. On the other hand, in AM-RC-6, histologic changes were mild (less than grade II) for all the drugs. Electron microscopic features were as follows. AM-RC-1: Marked increase of vacuole of organella was observed and lumens were filled with a large quantity of debris in MMC group (3 mg/kg). In the ADM group (5 mg/kg) there was debris in lumens, although almost no changes of organella were seen. CDDP groups (both 5.6 mg/kg and 2.8 mg/kg) showed autophagic vacuole in the cytoplasm and increased collagen fibers in the stroma but little changes of organella. AM-RC-6: Mild intracellular vacuolation was recognized in the MMC group (3 mg/kg). Watery degeneration and microfibrils were found in the cytoplasm in both ADM (5 mg/kg) and CDDP (5.6 mg/kg, 2.8 mg/kg) groups.     

重组人生长激素对裸鼠人胃癌移植瘤细胞周期的影响

目的：研究重组人生长激素（recombinant human growth hormone．rhGH）对裸鼠人胃癌移植瘤细胞周期的影响。方法：将24只实验裸鼠随机分为对照组、顺铂（DDP）组、rhGH组和DDP＋rhGH组，每组6只，将体外培养的人胃癌细胞MKN45接种于裸鼠右臀部皮下，裸鼠胃癌移植瘤模型成功建立后开始连续给药6d，给药结束后处死裸鼠。取出移植瘤，用流式细胞仪检测细胞周期，并分析细胞周期、细胞增殖指数（PI）及DNA抑制率。结果：给药结束后DDP＋rhGH组和DDP组S期细胞明显减少，而rhGH组和对照组比较增多（P〈0．05）；G0-G1期、G2-M期的细胞增殖指数（PI）和DNA抑制率各组间比较差异均无统计学意义（P〉0．05）。rhGH组细胞凋亡率增加而对照组、DDP组和DDP＋rhGH组减少（P〈0．05）。结论：未发现rhGH对裸鼠人胃癌移植瘤细胞有明显促进分裂增殖作用。     

Tumor cachexia and hypercalcemia in nude rats and mice bearing human renal carcinomas

Human hypercalcemia-inducing renal tumors have been established as xenografts in nude mice and nude rats. Animals bearing these tumors became cachexic and hypercalcemic and these changes could be reversed by excision of xenograft tumors. Metabolic studies carried out in nude rats suggested that the hypercalcemia-inducing factor was effecting renal excretion of calcium but was probably not parathyroid hormone. Although the hypercalcemia-inducing property of the tumor was stable throughout serial transplantation of tumor from animal to animal, it was lost after passage through cells in culture.     

ACHN人肾癌裸鼠移植瘤模型的生物学特性及放射治疗观察

目的观察ACHN人肾癌裸鼠皮下移植瘤模型的生物学特性及其对放射线的敏感性。方法分别利用瘤细胞悬液接种法、瘤块包埋法获得ACHN人肾癌裸鼠移植瘤模型，观察移植瘤的生长情况、成瘤率、肝肺转移率及病理形态。ACHN皮下荷瘤鼠14只，随机分为空白对照组和放疗组，6MV X直线加速器对放疗组移植瘤局部单次照射12Gy，观察裸鼠的耐受性及肿瘤生长抑制情况；透射电镜观察瘤细胞超微结构变化。结果瘤块包埋法成瘤稳定，成瘤率92．5%，肝转移率43％，未见肺转移。裸鼠对12Gy射线局部照射耐受良好，放疗组移植瘤与空白对照组比较生长明显受抑制（P〈0．01）；放疗组瘤细胞凋亡现象明显。结论ACHN人肾癌裸鼠移植瘤模型可作为肾癌放疗实验研究的有效工具。