乌司他丁在多发创伤并发休克中的应用

目的研究乌司他丁在多发创伤合并休克治疗中的作用。方法将81例多发创伤合并休克的患者随机分为治疗组41例和对照组40例。对照组采用常规抗休克治疗,治疗组加用乌司他丁10万单位静点,q8h连用5d。观察两组平均在ICU的观察时间、死亡率、多脏器功能衰竭发生率及两组肿癌坏死因子在治疗前、治疗后第2、4、6d的血中的含量。结果两组对比在死亡率、多脏器功能衰竭发生率方面有显著差异;在治疗后第4d血浆肿瘤坏死因子检测结果有显著差异,且第6d差异极显著。结论乌司他丁可以抑制多种蛋白酶及炎症因子,从而起到治疗创伤合并休克,保护多个脏器,防治多脏器功能衰竭的作用。

丙泊酚对肺缺血再灌注损伤大鼠炎性反应机制的影响

目的:探讨丙泊酚对肺缺血再灌注损伤大鼠炎性反应机制的影响。方法:健康雄性SD大鼠30只,随机平均分为3组:假手术对照组开胸游离左肺门但不夹闭;肺缺血再灌注组夹闭左肺门90min后开放,机械通气2h;丙泊酚预处理组经尾静脉注射丙泊酚20mg/kg,20min后夹闭左肺门,余处理同肺缺血再灌注组。采用酶联免疫吸附(ELISA)测定肺泡灌洗液(BALF)中的TNF-α、IL-6含量,采用722型光栅分光光度计测定SOD、MDA含量,计算肺组织湿干质量比(W/D)。结果:与假手术组比较,肺缺血再灌注组BALF中TNF-α、IL-6,含量和肺组织W/D均增高,SOD含量明显下降,MDA含量明显上升,差异均有统计学意义(P<0.01)。给予丙泊酚预处理,与肺缺血再灌注组相比,BALF中TNF-α、IL-6,含量和肺组织W/D均降低,肺组织SOD含量明显升高,MDA含量明显下降,差异有统计学意义(P<0.05)。结论:丙泊酚通过抑制缺血再灌注过程中TNF-α、IL-6等炎性介质的释放,降低脂质过氧化水平,减轻肺水肿,从而对肺缺血再灌注产生保护作用。

Expression Profiles of TRAIL Receptors and Their Clinical Significance in Human Hepatocellular Carcinoma

Objective To investigate the expression profiles and their clinical significance of TRAIL receptors (TRAILR) in human hepatocellular carcinoma (HCC). Methods The expression profiles of TRAILR were determined in 60 samples from hepatocellular carcinoma, 20 from normal liver tissue and two HCC cell lines HepG2, SMMC-7721 by in situ hybridization. Results Both DR4 and DR5 were present in all HCC tissues as well as normal hepatic tissues. In contrast, 54 HCC tissues did not express DcR1 and 25 did not express DcR2. But both DcR were detectable in all of the normal liver tissues. The expression patterns of DR and DcR in HCC samples (higher DR expression level and lower DcR expression level) were quite different from those in normal tissue. DR5, DR4, and DcR2 expressed in both cell lines, while no DcR1 expression was detected. The expression level of DR was correlated with HCC differentiation and stage. The weaker expression was more commonly found in HCC with poor differentiation and late stage, while the stronger expression was more common in HCC with middle to high-differentiation and early stage. No relationship was found between DR and gender, age, negative or positive HBsAg, tumor size, grade or metastasis. Multidrug resistance cell lines expressed lower level DR. Conclusion TRAILR expression was prevalent and discrepancy of receptor types was exited in HCC. Loss of DcR1 may contribute for TRAIL therapy for HCC. Key words TRAILR - apoptosis - hepatocellular carcinoma Supported by the Major Fundation of Ministry of Health, NO. 2001–2003

Augmentation of tumor necrosis factor family-induced apoptosis by E3330 in human hepatocellular carcinoma cell lines via inhibition of NFκB

AIM- To investigate the reduction of cell viability in human hepatocellular carcinoma （HCC） cell lines induced by inhibition of nuclear factor kB （NFkB）. METIIOI）S： HLE, SKHep1, and HepG2 were incubated and E3330 was used to compare the stimulation of some chemotherapeutic drugs with that of TNF family, Fas ligand, TNF（x and TNF-related apoptosis-inducing ligand （TRAIL） at the point of the reduction of cell viability by inhibiting NFkB. RESULTS： E3330 decreased NFKB levels in HLE cells stimulated by TNF and TRAIL. The cytotoxicity of the combination of TRAIL, TNFa, Fas ligand, and E3330 increased synergistically in a dose-dependent manner compared to either E3330 alone in all HCC cell lines by MTT assay. However, the combination of some chemotherapeutic drugs and E3330 did not decrease the cell viability. CONCLUSION： Inhibition of NFd3 sensitizes human HCC cell lines to TNF-mediated apoptosis including TRAIL, and TRAIL-based tumor therapy might be a powerful potential therapeutic tool in the treatment of human HCC.

Synergistic effect of bromocriptine and tumor necrosis factor-a on reversing hepatoceiiuiar carcinoma multidrug resistance in nude mouse MDRl model of liver neoplasm

AIM： To investigate the effect of bromocripUne （BCT） and tumor necrosis factor-α ClNF-α） on hepatocellular carcinoma （HCC） multidrug resistance （MDR） in nude mouse HDR model of liver neoplasm. METHODS： Human hepatocarcinoma cell line HepG2t drug resistant hepatocarcinoma cell line HepG2/adriamycin （ADM） and hepatocarcinoma cell line transfected with TNF-α gene HepG2JADM/TNF were injected into the liver of nude mice via orthotopic implantation and MDR model of liver neoplasm in vivo was established （HepG2t ADM, TNF, BCT groups）. Among these groups, BCT group and TNF group were treated with BCT through gastric canal. Each group was divided into control group and chemotherapy group. Size and weight of the tumor were measured. Furthermore, tumor his^logical character and growth of the nude mice were observed and their chemosensitivity was tested. MDR-associated genes and proteins （MRP, LRP） of implanted tumors were detected by immunohistochemistry, reverse transcriptase polymerase chain reaction, and apoptosis rate of hepatocarcinoma cells was detected by TUNEL assay. RESULTS： The nude mouse model of each cell line was inoculated successfully. The tumor growth rate and weight were significantly different among groups. After chemotherapy, abdominal cavity tumor growth inhibition rate was higher in BCT group （67%） compared to ADM and TNF groups, and similar to HepG2group （54%）. MDRI and LRPmRNA could be detected in all groups, but TNF-α was detected only in TNF and BCT groups. Furthermore, MDR1 and LRP protein expression of tumors in TNF and BCT groups was low similar to HepG2 group. The apoptosis rate of hepatocarcinoma cells was much higher in BCT group than in other groups with TUNEL assay. CONCLUSION： BCT and TNF-a can reverse HCC MDR in nude mouse MDR1 model of liver neoplasm. 2005 The WJG Press and Elsevier Inc. All rights reserved

TRAF4 mediates activation of TGF-β signaling and is a biomarker for oncogenesis in breast cancer

The tumor-promoting arm of transforming growth factor beta(TGF-β)receptor signaling contributes to advanced cancer progression and is considered a master regulator of breast cancer metastasis.In mammals,there are six distinct members in the tumor-necrosis factor receptor(TNFR)-associated factor(TRAF)family(TRAF1–TRAF6),with the function of TRAF4 not being extensively studied in the past decade.Although numerous studies have suggested that there is elevated TRAF4 expression in human cancer,it is still unknown in which oncogenic pathway TRAF4 is mainly implicated.This review highlights TGF-β-induced SMAD-dependent signaling and non-SMAD signaling as the major pathways regulated by TRAF4 involved in breast cancer metastasis.

Regulation of Acupuncture on Interferon-γand Tumor Necrosis Factor of Lung Cancer-Operative Cases

Objective： To investigate tumor necrosis factor （TNF） of lung the regulation of acupuncture on γ-interteron （LNF-γ） and cancer-operative cases. Methods： to determine the INF-γ and TNF contents in the blood serum of lung cancer patients by double antibody sandwich immunoenzymatic method （ELISA）; to measure the INF-γ and TNF contents of 30 lung cancer patients in the acupuncture anesthesia group and 30 lung cancer patients in general anesthesia group before the operation and at the 8th days, the 12th day after the operation respectively and make comparison between the two groups. Results. The pre-operation INF-γ contents of the two groups showed no significant difference （P〉 0.05）; the post operation INF-γ contents of the two groups showed significant difference at 8th day and 12th day after the operation （P〈 0.05）; the acupuncture anesthesia group was superior to the general anesthesia group; the self-comparison of the anesthesia group showed significant difference at the 12th day and 8th day after the operation （P〈 0.05）; the pre-operation TNF contents of the two groups showed no significant difference （P〉 0.05） and the post-operation TNF contents of the two groups showed significant difference at the 8th day and 12th day after the operation （P〈 0.05）. Conclusion：Acupuncture can increase the serum INF-γ and TNF contents of lung cancer patients and therefore regulate the immunity of the patients.