荧光腹腔镜肝切除术与常规腹腔镜肝切除术治疗HCC患者效果分析

目的探讨肝细胞癌(hepatocellular carcinoma,HCC)治疗中选择荧光腹腔镜肝切除术(laparoscopic hepatectomy,LH)与常规腹腔镜肝切除术(LH)的安全有效性。方法根据随机数表法对150例、2020年1月~2022年12月期间收治的HCC患者展开分组,对比观察组(荧光LH,75例)与(常规LH,75例)的临床疗效及安全性。结果观察组患者的手术情况及预后效果更佳(P<0.05)。术后,观察组的免疫球蛋白(IgA、IgG、IgM)水平(2.58±0.68)g/L、(9.68±1.63)g/L、(1.97±0.54)g/L均高于对照组(t=11.600,15.313,9.738;P<0.05)。术后,观察组的丙氨酸、天门冬氨酸氨基转移酶(ALT、AST)水平(32.48±5.18)U/L、(35.18±4.96)U/L均低于对照组(t=6.268,4.574;P<0.05)。观察组的并发症发生率2.67%低于对照组16.00%,差异显著(x^(2)=7.878,P<0.05)。结论在HCC肿瘤切除治疗中应用荧光LH对肿瘤切缘安全具有保障作用,可改善患者免疫功能,降低ALT、AST水平及术后并发症风险、复发率,手术及预后效果更佳。

Serum soluble ST2 is a promising prognostic biomarker in HBV-related acute-on-chronic liver failure

BACKGROUND： The IL-33/ST2 axis is involved in the pathogenesis of many diseases such as autoimmune diseases, cancer,and heart failure. However, studies of the IL-33/ST2 pathway in HBV-related acute-on-chronic liver failure（HBV-ACLF） are lacking. The present study aimed to determine the prognostic role of serum IL-33/soluble ST2（s ST2） in HBV-ACLF.METHODS： Serum levels of IL-33 and sS T2 in healthy controls（HC, n=18）, chronic hepatitis B（CHB, n=27） and HBV-ACLF（n=51） patients at the 1st and 4th week after enrollment were detected using ELISA, and clinical data were collected. The follow-up of HBV-ACLF patients lasted for 6 months at least.RESULTS： There was no significant difference of serum IL-33 level among HC, CHB and HBV-ACLF patients at week 1.However, serum s ST2 level differed significantly among the three groups： highest in the HBV-ACLF group, moderate in the CHB group and lowest in the HC group. There was a reverse correlation between serum s ST2 level and the survival of HBV-ACLF patients. The level of serum s ST2 in HBV-ACLF survivors was significantly declined from week 1 to week 4 following the treatment, whereas that in HBV-ACLF nonsurvivors remained at a high level during the same period. Furthermore, serum sS T2 level was significantly correlated with laboratory parameters and the most updated prognostic scores（CLIF-C OF score, CLIF-C ACLF score and ACLF grades）. Thereceiver operating characteristics curves demonstrated that serum sS T2 level was a good diagnostic marker for predicting the 6-month mortality in HBV-ACLF patients, comparable to the most updated prognostic scores. Serum sS T2 cut-off points for predicting prognosis in HBV-ACLF patients were 76 ng/mL at week 1 or 53 ng/mL at week 4, respectively. HBV-ACLF patients with serum sS T2 level above the cut-off point often had a worse prognosis than those below the cut-off point.CONCLUSION： Serum s ST2 may act as a promising biomarker to assess severity and predict prognosis of patients with HBV-ACLF and help for the early identification and optimal treatment of HBV-ACLF patients at high risk of mortality.

Serum levels of macrophage migration inhibitory factor,Interleukin-17 and Interleukin-10 in patients with HBV-related liver disease

Objective To study the potential role of macrophage migration inhibitory factor(MIF),Interleukin-17(IL-17) and Interleukin-10(IL-10) in the development of HBV-related liver disease.Methods 48 patients with chronic hepatitis B(HBeAg negative and positive,24 cases;21cases of HBV-DNA negative and 27 cases of HBV-DNA positive),81 cases of hepatitis B patients with decompensated cirrhosis and 48 cases of primary liver cancer patients were collected as the experimental group,26 healthy people were as control group.Serum MIF,IL-17 and IL-10 were measured.Results MIF and IL-17 significantly increased,IL-10 significantly decreased in experimental group,compared with the control group(P<0.05),there was significant difference.In addition,there was no significant difference(P>0.05) between positive and negative of chronic hepatitis B.MIF,IL-17 and ALT levels were positively correlated(r=0.693,P<0.01;r=0.897,P<0.001),IL-10 and ALT was negatively correlated(r =-0.285,P=0.037).Conclusion These results indicated that MIF,IL-17 and IL-10 may participate in the pathological process of HBV-related liver disease,serum levels of MIF,IL-17 and IL-10 appear to reflect the severity of tissue injury in HBV-related liver disease.

Genetic variants in pseudogene E2F3P1 confer risk for HBV-related hepatocellular carcinoma in a Chinese population

Recent studies showed that pseudogenes can regulate the expression of their coding gene partners by competing for miRNAs. The E2F family plays a crucial role in the control of cell cycle checkpoint. E2F3P1 is a pseudogene of E2F3. Few studies focused on genetic variations on pseudogenes. In this study, we performed a case-control study to assess the association between single nucleotide polymorphisms （SNPs） in E2F3P1 and hepatocellular carcinoma （HCC） risk in 1050 hepatitis B virus （HBV）-positive HCC cases and 1050 chronic HBV carders. Logistic regres- sion analysis was applied to estimate odds ratios （ORs） and 95% confidence intervals （CIs） for the associations between genotypes and HCC risk. We found that the variant CT/TT genotypes of rs1838149 were associated with a significantly decreased risk of HCC （adjusted OR = 0,66, 95% CIs = 0.51-0.86, P = 0.002） compared to those with wildtype CC homozygote. Furthermore, the AA genotype of rs9909601 had an increased HCC risk with an adjusted OR of 1.41 （95% CIs = 1.07-1.86）, and the A allele of rs9909601 was significantly associated with HCC risk com- pared to those with the G allele （adjusted OR = 1.17, 95% CIs = 1.03-1.33, P = 0.017）. These results indicate that genetic variations in the pseudogene E2F3P1 may confer HCC risk.

Is P2/MS score valuable for prediction in HBV-related variceal bleeding?

Objective:To determine the predictive value of P2/MS in patients with chronic HBV-related cirrhosis, and to predict high-risk esophageal varices, and obtain a cut-off value.Methods:A total of 412 patients with HBV-related cirrhosis who were admitted to our hospital between August 2014 and August 2017 were retrospectively evaluated. A diagnosis of cirrhosis was made with standard laboratory, radiological and physical examination findings. According to these evaluations, esophageal varices were classified as small, medium and large. For all obtained data, P2/MS was calculated. Two threshold values (P2/MS<11 and P2/MS>25) were considered in predicting the presence of high-risk EVs during recording. And the optimal cut-off value of the P2/MS index was determined for high-risk esophageal varices in patients with chronic viral hepatitis B.Results:A total of 375 patients who met the inclusion criteria were included in the study. When the P2/MS index was compared with other noninvasive tests, the mean and median P2/MS scores were respectively 54.17 and 33.25. The P2/MS value of the patients without esophageal varices was higher than that of the patients with esophageal varices. When these results were evaluated, the higher the score, the lower the risk of varices. We obtained a positive predictive value of 93.80% [95%CI(80.20-98.70)] when the cut-off value of P2/MS was taken as <11, and obtained a negative predictive value of 94.30% [95%CI(86.20-98.20%)] when the cut-off value of P2/MS was taken as >25.Conclusions:We could predict the patients with high-risk esophageal varices within this group at a extremely good rate. We also compared the results of this test with other non-invasive tests and achieved successful results. We have shown that P2/MS can be used in order to optimally select patients for endoscopic screening and prevent all of the expensive and unnecessary procedures safely.

INTS10对HCC细胞周期、凋亡、生长和迁移能力的影响

为了探究整合因子复合物亚基10(integrator complex subunits 10,INTS10)对人肝细胞癌(hepatocellular carcinoma,HCC)细胞周期、凋亡、生长和迁移能力的影响及其潜在的分子作用机制,利用慢病毒感染法获得稳定过表达或敲低INTS10的HCC细胞系,采用qRT-PCR和Western blotting检测INTS10 mRNA和蛋白表达水平,接着采用CCK-8法、克隆形成和BrdU实验检测细胞生长情况,采用Transwell小室实验检测细胞迁移能力,采用流式分析术检测细胞的周期和凋亡.结果显示:过表达INTS10可显著抑制HCC细胞的凋亡、生长和迁移能力,促进G1期细胞数量的增加,而敲低INTS10则呈现相反的表型.通过通路富集分析发现,周期相关通路被显著富集,过表达INTS10后,CDC25A和CDK4的mRNA和蛋白质水平显著减少,而CDKN1A的水平显著增加,敲低INTS10则呈现相反趋势.综上,本研究初步揭示了INTS10在HCC细胞中可能通过影响G1/S期相关蛋白质的表达而发挥抑癌基因的功能,为下一步更为深入的功能和机制研究提供了基础.

苦丁冬青苷D对人HCC-1806乳腺癌细胞增殖、凋亡、自噬的影响及机制研究

目的探讨苦丁冬青苷D(KD-D)对人HCC-1806乳腺癌细胞增殖、凋亡、自噬的影响及机制。方法将人HCC-1806乳腺癌细胞作为研究对象,给予不同浓度KD-D处理后,采用CCK-8法检测细胞存活率;EdU法检测细胞增殖能力;结晶紫染色法检测细胞克隆形成能力;流式细胞术(Annexin V-FITC/PI法)检测细胞凋亡;JC-1染色法检测细胞线粒体膜电位;免疫荧光法检测细胞Cleaved Caspase-3、LC3、P62蛋白表达;Western Blot法检测细胞Cleaved Caspase-3、Pan-AKT、Phosp-AKT、LC3Ⅱ蛋白表达;自噬双标mRFP-EGFP-LC3腺病毒感染实验检测细胞自噬流。结果与对照组比较,12.5、25、50、100、200、400μmol·L^(-1)KD-D处理HCC-1806细胞24、48 h后,随着给药浓度增大和处理时间延长,细胞活性显著降低(P<0.001),细胞内吸光度值显著降低(P<0.001),细胞增殖受到抑制;60、80μmol·L^(-1)KD-D组的细胞克隆形成计数显著减少(P<0.001);50、100、150μmol·L^(-1)KD-D组细胞的早期及晚期凋亡比例均显著升高(P<0.05,P<0.001);40、60、80μmol·L^(-1)KD-D组的红色荧光比例显著下降(P<0.001),绿色荧光比例显著升高(P<0.01,P<0.001),HCC-1806细胞线粒体膜电位下降;60、80、100μmol·L^(-1)KD-D组细胞的Cleaved Caspase-3蛋白表达均显著上调(P<0.001),60μmol·L^(-1)KD-D组细胞的Pan-AKT、Phosp-AKT蛋白表达均显著上调(P<0.001);60μmol·L^(-1)KD-D组细胞的LC3蛋白荧光小点数量显著增加(P<0.001),P62蛋白平均荧光强度显著降低(P<0.001),LC3Ⅱ蛋白表达显著上调(P<0.001),自噬小体及自噬溶酶体数量显著增加(P<0.01,P<0.001),自噬流激活。与60μmol·L^(-1)KD-D组比较,KD-D+AKT抑制剂(Afuresertib)组细胞的Cleaved Caspase-3、Pan-AKT蛋白表达显著下调(P<0.01,P<0.001),Phosp-AKT蛋白表达显著上调(P<0.001)。结论KD-D能抑制人乳腺癌HCC-1806细胞增殖,并诱导其发生凋亡和自噬,KD-D诱导HCC-1806细胞凋亡可能与激活AKT信号影响Cleaved Caspase-3表达有关。

影像组学在经导管动脉化疗栓塞术治疗原发性HCC中的研究进展

原发性肝细胞癌(HCC)是常见的肝脏富血供恶性肿瘤,由于早期缺乏特异性的症状及体征,绝大多数患者就诊时已经错过手术根治的机会,对于不可切除的原发性HCC,经导管动脉化疗栓塞术是首选的治疗手段。影像组学是一种可以高通量、深层次地挖掘并利用医学图像中的信息,从而反映肿瘤的异质性等细胞生物学特征的技术,在原发性HCC的诊断、鉴别诊断、治疗反应及生存预后等方面展现出独特的优势。本文主要就影像组学在经导管动脉化疗栓塞术对原发性HCC的疗效预测、复发预测及生存预测等方面的应用进展进行阐述,并对其存在的问题及未来研究的方向进行探讨和展望。

Drug-Based Reversal of Drug Resistance in Hepatocellular Carcinoma (HCC) Using TPGS

Hepatocellular carcinoma (HCC) is a cancer with high incidence and mortality rates worldwide. In the various treatment methods for HCC, the lack of cancer cell specificity and the development of multidrug resistance (MDR) are two major obstacles in the treatment of HCC. P-glycoprotein (P-gp) is an ATP-dependent drug efflux pump that can reduce the accumulation of drugs in cells and make cancer cells acquire drug resistance. D-α-tocopheryl polyethylene glycol succinate (Vitamin E TPGS or TPGS) can inhibit the activity of ATP-dependent P-gp and serves as an effective excipient for overcoming tumor multidrug resistance (MDR). TPGS has been approved by the FDA as a safe adjuvant and is widely used in drug delivery systems. The biological and physicochemical properties of TPGS provide multiple advantages for its application in drug delivery, such as high biocompatibility, enhanced drug solubility, improved drug permeation, and selective antitumor activity. In recent years, more and more studies have found that using TPGS-modified nanomaterials to load chemotherapy drugs to treat tumors can effectively reverse the drug resistance of tumors, including HCC. This review summarizes and discusses the role of TPGS in reversing tumor drug resistance and the therapeutic effects of TPGS-based drugs on drug-resistant HCC.

Microstructure and properties of LZQT600-3 HCCDIBs for plunger pump cylinder

It is important to improve the comprehensive performance of the ductile iron bars(DIBs)for the cylinder block of the extra high pressure hydraulic plunger pump and accelerate the industrial application.In this work,the LZQT600-3 DIBs with the diameter of 145 mm were prepared by the horizontal continuous casting(HCC)process,that is,LZQT600-3 HCCDIBs.The microstructure and room temperature tensile properties of different sections[left-edge(surface layer),left-1/2R(left half of the radius),and the center of the HCCDIBs]were studied.The results show that the spheroidization of LZQT600-3 HCCDIBs matrix from the left-edge,left-1/2R to the center is at nodulizing grade II and above.As the cooling rate gradually decreases from surface to the center of the HCCIBs,the number of spheroidized graphite is gradually reduced,the size is gradually increased,the shape factor is decreased,and the pearlite content and lamellate spacing are increased.Along the horizontal direction of the section,the hardness of the material is distributed symmetrically around the center of the HCCDIBs.In the vertical direction,the hardness distribution in the center of the HCCDIBs is asymmetrical due to the gravity during the solidification process.Therefore,the microstructure in the lower part of the section solidifies relatively quickly.The left-edge has the best tensile mechanical properties,and the ultimate tensile strength,yield tensile strength and elongation are 597.3 MPa,418.5 MPa and 9.6%,respectively.The tensile fracture belongs to the ductile-brittle hybrid fracture.The comprehensive performances of LZQT600-3 HCCDIBs meet the actual application requirements of ultra-high pressure hydraulic plunger pump cylinder.

国内某油田集输管道HCC内涂层质量分析

本文根据SY/T 4076-2016《钢质管道液体涂料风送挤涂内涂层技术规范》要求,通过现场取样,对在役内涂层进行了性能检验,分析了在役内涂层质量不合格原因,并提出了合理化建议。

姜黄素纳米粒(NanoCurc^(TM))联合索拉非尼对肝细胞癌(HCC)的协同抑制作用

目的探讨姜黄素纳米粒(NanoCurcTM,NC)单药或联合索拉非尼对人肝细胞癌(hepatocellular carcinoma,HCC)的作用。方法采用体外细胞增殖检测试剂盒(CCK-8)、体外划痕试验和Transwell侵袭试验法检测NC和/或索拉非尼对肝癌细胞株MHCCLM3增殖、迁移、侵袭能力的影响;应用流式细胞术分析其对细胞凋亡的作用。建立裸鼠MHCCLM3原位移植模型并观察NC和/或索拉非尼对肿瘤大小和肺转移率的影响。应用RTPCR、ELISA、Western blot法检测基质金属蛋白酶-9(matrix metalloproteinase-9,MMP-9)、基质金属蛋白酶抑制剂-1(tissue inhibitor of metalloproteinase-1,TIMP-1)、细胞外信号调节激酶1/2(ERK1/2)mRNA或相应蛋白表达变化;并测定ERK1/2的磷酸化变化。结果 NC与索拉非尼联合应用可显著抑制HCC体外增殖和侵袭能力(P<0.01),抑制体内肿瘤生长和肺转移(P<0.01)。单独应用NC和索拉非尼时肺转移率分别为50.0%和66.7%,两者联合用药时则显著降低至16.7%。两药联合应用可协同抑制ERK磷酸化,从而下调MMP-9的表达。结论 NC联合索拉非尼可通过协同诱导细胞凋亡、抑制MMP-9的表达而抑制肝癌生长和转移。

JA1体外诱导HCC细胞凋亡的实验研究

采用噻唑蓝(MTT)还原法,测定了梯度浓度的某植物种子粗提物JA1对人肝癌细胞株HCC增殖作用的影响;同时采用流式细胞术、DNA凝胶电泳和透射电子显微镜技术,在体外观察了JA1对HCC细胞凋亡的诱导作用。结果显示,JA1可显著抑制肝癌细胞HCC的增殖,而且这种抑制有浓度依赖性和时间依赖性;流式细胞仪分析表明,经JA1作用后的肝癌细胞HCC检测标本中有明显的DNA低含量颗粒(“亚G1期”峰);凝胶电泳呈现出典型的DNA梯形条带;电镜下出现细胞凋亡典型的形态学改变。

HBV、HCV、HBV和HCV重叠感染与HCC发生关系的研究

目的:探讨HBV、HCV、HBV和HCV重叠感染及复制与广西HCC发生的关系。方法:在肝癌高发区和低发区分别选择符合全国诊断标准的HCC病人78例作为病例A组(肝癌高发区组)、B组(肝癌低发区组),并分别选择相同乡镇、生活习惯、生活水平、年龄士5岁、同性别的原籍健康人群2组分别78人作为对照组C组(肝癌高发区正常人组)和D组(肝癌低发区正常人组),应用PCR法检测研究对象血清中的HBVDNA、HCVRNA,并对阳性率进行比较。结果:HBVDNA、HCVRNA、HBVDNA+HCVRNA阳性率分别为:A组6 9.2%(5 4/7 8)、2 0.5%(1 6/7 8)、1 6.7%(1 3/7 8);B组5 2.6%(4 1/7 8)、6.4%(5/78)、5.1%(4/78);C组18.0%(14/78)、7.7%(6/78)、3.8%(3/78);D组10.3%(8/78)、2.6%(2/78)、1.3%(1/78);其中A组与C组,A组与B组组间的阳性率比较差异均有统计学意义(均P<0.05),B组与D组中HBVDNA阳性率比较差异也有统计学意义(均P<0.01)。结论:HBV、HCV、HBV和HCV的重叠感染及复制与广西肝癌高发区的肝癌发生有密切关系,其中HBV的感染及复制在肝癌的发生中最为重要,高发区中HCV、HBV和HCV的重叠感染的致癌作用也是不容忽视的。

HTPAP单体型与基因表达及肝细胞癌(HCC)预后的关系

目的拟通过分析不同HTPAP单体型与基因表达及肝细胞癌(hepatocellular carcinoma,HCC)预后的关系,探讨HTPAP单体型对HCC术后复发及预后的影响。方法随机选取377例HCC样本,提取其中以AGCTAC、GCGGGT、AGCTGC和GCGGAT等4种主要HTPAP单体型组成的HCC RNA。绝对定量PCR检测HTPAP基因表达水平,免疫组化染色、RT-PCR和Western blot检测HTPAP蛋白表达水平,分析单体型与基因表达的关系。随机选取665例HCC样本并提取DNA,焦磷酸测序方法对6个单核苷酸多态性(singlenucleotide polymorphisms,SNPs)进行检测。单体型构建后,分析HTPAP单体型与HCC预后的关系。结果 377例HCC中有327例由上述4种主要单体型构成。基因表达分析提示,HCC中HTPAP在GCGGGT纯合子组和AGCTAC/GCGGGT杂合子组的表达低于AGCTAC/GCGGAT杂合子组、AGCTAC/AGCTGC杂合子组及AGCTAC纯合子组,但差异无统计学意义(P=0.062)。免疫组化染色发现GCGGGT纯/杂合子组HCC较其他单体型HCC的HTPAP表达显著降低(P=0.035)。Kaplan-Meier分析提示,GCGGGT纯/杂合子组HCC较其他单体型HCC术后易复发且预后差(P<0.001)。Cox风险比例模型发现GCGGGT单体型是HCC术后复发及预后差的独立相关因子。结论 HCC的不同HTPAP单体型在mRNA水平的表达差异无统计学意义,但在蛋白水平存在显著差异。GCGGGT单体型可作为HCC术后复发和预后差的预测指标。

广西肝癌高发区TTV感染与HCC关系的病例-对照研究

目的 :探讨我区肝癌高发区中 TTV的感染在原发性肝癌 (HCC)发病中的作用。方法 :在高发区中选择原发性肝癌4 9例 ,并按病例 -对照的配对原则 ,选择同乡镇 ,同职业 ,同性别 ,年龄± 5岁的正常人作为对照 ,采用套式 - PCR方法对两组血清进行 TTVDNA检测。结果 :病例组 TTVDNA的阳性率为 2 6 .5 % (13/ 4 9) ,对照组的阳性率为 2 8.6 % (14 / 4 9) ,两组 TTVDNA的阳性率无明显差异 (P >0 .1) ;OR=0 .83(95 %可信区间为 0 .2 5～ 2 .8)。结论 :广西肝癌高发区中 TTV的感染率虽然很高 ,但

TTV与HBV、HCV的重叠感染与HCC家庭聚集性的关系研究

目的：探讨广西肝癌高发区输血传播病毒（TTV）与乙型肝炎病毒（HBV）、丙型肝炎病毒（HCV）的重叠感染在原发性肝细胞癌（HCC）家庭聚集性中的作用。方法：分别采用巢式PCR和RT-PCR技术对研究对象外周血清中TTVDNA、HBVDNA和HCVRNA进行检测，应用x^2检验进行统计学分析。结果：HCC高发家庭成员组及无癌家庭成员组中TTVDNA、HBVDNA、HCVRNA阳性率分别为35．4％（46／130）、29．2％（38／130）、10．0％（13／130）和24．6％（32／130）、10．8％（14／130）、3．8％（5／130），两组间TTVDNA、HBVDNA、HCVRNA阳性率差异有统计学意义（X^2=4．12、P=0．04、RR=1．81、95％CI=1．018～3．219；X^2=14．97、P=0．0001、RR=3．765、95％CI=1．88～7．54；X^2=3．91、P=0．048、RR=2．84、95％CI=0．972～8．29）。两组TTV与HBV、HCV重叠感染率分别为7．7％（10／130）、3．8％（5／130）和1．5％（2／130）、1．5％（2／130），TTVDNA＋HBVDNA感染率在两组间差异有统计学意义（X^2=5．5914、P=0．0180、RR=5．33、95％CI=1．15～24．84）；而TTVDNA＋HCVRNA阳性率在两组间差异无统计学意义（X^2=1．3213、P=0．2504、RR=2．56、95％CI=0．49～13．44）。结论：TTV、HBV、HCV感染以及TTV和HBV的重叠感染与广西HCC家庭聚集性存在一定的相关关系，但TTV和HBV重叠感染在致肝癌上无明显协同作用。

HCV感染及复制与广西HCC家庭聚集性关系研究

应用ＲＴ－ＰＣＲ方法分别对肝癌高发家庭及非癌家庭成员各５５人血清中的ＨＣＶＲＮＡ进行检测。结果表明，肝癌高发家庭成员中ＨＣＶＲＮＡ阳性率为１０．９％（６／５５），而非癌家庭成员阳性率为２１．８％（１２／５５），经统计分析两组阳性率无显著性差异（Ｐ＞０．０５）。同时，两组对象均无ＨＣＶＲＮＡ家庭聚集现象。提示：ＨＣＶ的感染和复制与广西ＨＣＣ家庭聚集性无明显关系，但不能除外两组ＨＣＶ基因亚型的差异。

对携带HCC表位的HBc病毒样颗粒负载的DC疫苗的免疫评价

目的:探讨携带肝细胞癌(HCC)表位的嵌合蛋白颗粒HBc-VLPs负载小鼠BMDCs制备的DC疫苗,免疫小鼠后诱导抗原特异的细胞免疫应答和抗肿瘤效应。方法:制备HLA-A2转基因小鼠来源的BMDCs,将三种带有高表达于HCC的HLA-A2限制的CTL表位的HBc-VLPs、三种抗原表位肽和不含HCC表位野生HBc-VLPs分别负载HLA-A2转基因小鼠BMDCs制备成DC疫苗,阴性对照组用PBS替代。将HLA-A2转基因小鼠分为四组,分别免疫上述DC疫苗并对其免疫效果进行评价:体外检测抗原特异性淋巴细胞内IFN-γ的产生和CTL细胞活性并观察不同方法处理的DCs对肿瘤生长的抑制情况。结果:与其他组相比,HBc-VLPs负载的DCs免疫小鼠后第8天,流式细胞仪即可检测到分泌IFN-γ的CD8+T细胞存在;用LDH法检测到较强的抗原特异性CTL活性;在肿瘤接种后的20天之前均未见到明显的肿瘤块,具有显著抗肿瘤作用。结论:利用携带HCC抗原表位的HBc-VLPs负载DCs后得到可强烈诱导免疫活性和明显抗肿瘤作用的DC疫苗,为DC疫苗的优化和评价提供了实验方法,也为进一步深入研究新型肝细胞癌治疗性疫苗的功能和应用奠定了基础。

血清DKK1水平对肝细胞癌(HCC)患者预后判断的临床价值

目的评估血清Dickkopf-l（DKKl）水平与肝细胞癌（hepatocellular carcinoma，HCC）患者术后复发转移和预后的相关性。方法收集2011至2012年间72例在复旦大学附属中山医院进行HCC根治切除患者的术前血清以及其中43例术后1个月的血清，随访至2013年10月。采用ELISA方法定量检测HCC患者术前以及术后血清DKKl水平，分析DKKl高、低组患者主要临床相关资料差异，并评价其与患者复发、预后的相关性。结果1年内共有21人发生复发，1年复发率为26．92％。高DKKl组1年无瘤生存率显著低于低DKKl组（50.0％vs．77．8％，P=0．011）。复发低危亚组中高DKKl组复发率高于低DKKl组患者，包括单个肿瘤（73．3％佻．14．0％，P=0．037）、无卫星灶（56．3％vs．14．3％，P=0．034）、无血管侵犯（37．5％叫．12．5％，P：0．002）、BCLC0＋A（53．3％w．15．2％，P：0．010）。两组患者的临床病理特征的差异无统计学意义。多因素结果提示高DKKl为术后无瘤生存的独立预后因素（HR为3．753，95％CI为1．495-9．424，P=0．005）。受试者工作特征曲线分析显示术前血清DKKl水平对预测HCC患者术后复发具有较好的特异性（82．35％）。术后DKKl持续维持在高水平的患者具有更高的复发率（50．0（）％）。结论术前血清高水平DKKl预示HCC患者早期复发率高。血清DKKl水平可有效预测HCC切除术后患者的预后，监测DKKl可以帮助临床制定最有效的HCC治疗方案。