Vascular endothelial growth factor before and after locoregional treatment and its relation to treatment response in hepatocelluar carcinoma patients

Objective:To evaluate vascular endothelial growth factor(VEGF)levels in hepatocellular carcinoma patients before and after transcatheter arterial chemoembolization(TACE)and percutaneous ethanol injection(PEI)and its relation to treatment response.Methods:A total of 40 patients with unrespectable hepatocelluar carcinoma were assessed clinically.Twenty patients were suitable to be treated by TACE,while other 20patients were treated with PEI.Serum VEGF levels were measured before and 1 month after each procedure by ELISA.Response was assessed after 1 month according to Union Internationale Contre le Cancer evaluation criteria based on change in tumor size as measured by ultrasound.Results:There was no significant difference between TACE and PEI groups with regard to age,sex,tumor size,response to local therapy,or VEGF and alpha-fetoprotein before and after therapy.VEGF levels after TACE were significantly higher than before TACE[(298.1±123.6)pg/m L vs.(205.8±307.3)pg/m L;P=0.001].Also,VEGF levels were significantly higher after PEI than before PEI[(333.8±365.6)pg/m L vs.(245.3±301.8)pg/m L;P=0.000].Non-responders of both groups had significantly high VEGF levels than responder's,both before[(985.0±113.2)pg/m L vs.(117.1±75.3)pg/m L;P<0.001]and after therapy[(1 330.6±495.7)pg/m L vs.(171.0±94.7)pg/m L;P=0.000)].Conclusions:Both TACE and PEI were associated with an increase in serum VEGF in hepatocelluar carcinoma patients.Higher levels of VEGF before and after therapy were found in non-responders,suggesting that VEGF is a useful marker in predicting treatment response.

Effects of kanglaite capsules combined with transcatheter arterial chemoembolization （TACE） on patients with mid or late-stage primary hepatocellular carcinoma （HCC）

Objective： To observe the clinical effects of kanglaite （KLT） capsules combined with transcatheter arterial chemoembolization （TACE） in treating patients with mid or late-stage primary hepatocellular carcinoma （HCC）. Methods： Sixty-five cases were randomly divided into 2 groups, 32 patients in combination group received the treatment of KLT capsules ＋ TACE and 33 patients in control group were treated with TACE alone. The objective response rate （RR）, serum alpha fetoprotein （AFP）, peripheral blood T lymphocyte subgroups （T-LS）, quality of life （QOL）, time to progression （TTP） and adverse reaction were observed and compared between 2 groups. Results： The objective response rate and serum alpha fetoprotein levels had no significant difference between the two groups （P 〉 0.05）. Combination group was superior to control group in quality of life （QOL）, time to progression （TTP）, peripheral blood T lymphocyte subgroups （CD3＋, CD4＋, CD4＋／CD8 ratio） and liver adverse reactions, with significant differences （P 〈 0.05）. Conclusion： KLT capsules combined with TACE is an effective method to treat primary hepatocellular carcinoma （HCC） patients who have lost the opportunity of surgical therapy.

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.

Degradation of FAK-targeting by proteolytic targeting chimera technology to inhibit the metastasis of hepatocellular carcinoma

Liver cancer is a prevalent malignant cancer,ranking third in terms of mortality rate.Metastasis and recurrence primarily contribute to the high mortality rate of liver cancer.Hepatocellular carcinoma(HCC)has low expression of focal adhesion kinase(FAK),which increases the risk of metastasis and recurrence.Nevertheless,the efficacy of FAK phosphorylation inhibitors is currently limited.Thus,investigating the mechanisms by which FAK affects HCC metastasis to develop targeted therapies for FAK may present a novel strategy to inhibit HCC metastasis.This study examined the correlation between FAK expression and the prognosis of HCC.Additionally,we explored the impact of FAK degradation on HCC metastasis through wound healing experiments,transwell invasion experiments,and a xenograft tumor model.The expression of proteins related to epithelial-mesenchymal transition(EMT)was measured to elucidate the underlying mechanisms.The results showed that FAK PROTAC can degrade FAK,inhibit the migration and invasion of HCC cells in vitro,and notably decrease the lung metastasis of HCC in vivo.Increased expression of E-cadherin and decreased expression of vimentin indicated that EMT was inhibited.Consequently,degradation of FAK through FAK PROTAC effectively suppressed liver cancer metastasis,holding significant clinical implications for treating liver cancer and developing innovative anti-neoplastic drugs.

TROVE2 regulated invasion and migration of hepatocellular carcinoma cells via heparanase

Background:The role of TROVE domain family member 2(TROVE2)has been well-demonstrated in autoimmune diseases;however,its involvement in liver cancer remains unclear.Therefore,this study aimed to explore the biological function and clinical significance of TROVE2 in hepatocellular carcinoma(HCC).Methods:The expression level of TROVE2 was analyzed in HCC and paired adjacent tissue samples using real-time reverse transcription-quantitative polymerase chain reaction.The impact of TROVE2 on migration and invasion in HCC cells was analyzed through Transwell assays and Western blotting.High-throughput transcriptome sequencing and bioinformatics analyses were performed to identify downstream target genes.Back-complementation experiments were employed to verify the influence of downstream proteins on TROVE2-induced invasion and migration of HCC cells.Results:TROVE2 exhibited significant overexpression in liver cancer tissue,correlating with shorter overall survival.Overexpression of TROVE2 facilitated the invasion,metastasis,and epithelial-mesenchymal transition(EMT)process of HCC cells,whereas TROVE2 knockdown restrained migration,invasion,and EMT in these cells.Transcriptome sequencing and bioinformatics analysis identified heparanase(HPSE)as a downstreamtarget protein of TROVE2.Subsequent back-complementation experiments provided evidence that HPSE overexpression promoted TROVE2-mediated prometastasis effects.Moreover,the study revealed that TROVE2 was capable of regulating the EMT pathway through GSK-3βphosphorylation.Conclusions:TROVE2 facilitated the invasion,migration,and EMT process ofHCC cells through phosphorylation of the HPSE/GSK-3βaxis,indicating its significance as an important protein in tumor progression.

Advances in Research of Post Embolism Syndrome after Transarterial Chemoembolization(TACE)for Hepatocellular Carcinoma

This article reviews the concept and clinical manifestations of post embolism syndrome after transarterial chemoembolization(TACE),and the prevention or timely intervention of post embolism syndrome in advance is expected to reduce its incidence and degree in clinical treatment,and to improve the quality of treatment of Hepatocellular Carcinoma Carcinoma(HCC).

Hemoperitonium: Atypical Presentation Caused by Spontaneous Rupture of Hepatocellular Carcinoma in an Undiagnosed Patient

Introduction: Acute hemoperitoneum due to the spontaneous rupture of hepatocellular carcinoma (HCC) is a rare case of non-traumatic intra-abdomen bleeding that requires a high index of suspicion to approach, especially if no known history of HCC. It can mislead the physicians when the patient presents in an atypical way. Case Presentation: In this case report, we describe a fortuitous rupture of hepatocellular carcinoma in a 58-year-old male who was not previously diagnosed as having HCC and who came with atypical symptoms and signs of hemoperitoneum. He was then treated by trans-arterial embolectomy. Discussion: Diagnosis of hemoperitoneum in a case with bradycardia and hypotension is uncommon, as it goes more towards cardiogenic shock than hypovolemic shock, especially in a patient who is previously not symptomatic and has no risk factor for hepatocellular carcinoma. Conclusion: physicians should be alert to the possibility of encountering a hemorrhagic shock, although no trauma injury in any hypotensive patient with no clear reason for his condition.

Research Progress of circRNAs during Epithelial- Mesenchymal Transition of Hepatocellular Carcinoma

Hepatocellular carcinoma is prone to invasion and metastasis.It often receives a low diagnosis rate in the early stage but has an extremely high mortality rate.Epithelial-mesenchymal transformation(EMT)is a key factor in promoting tumor cell invasion and metastasis.Circular RNA(circRNA)is involved in regulating EMT in hepatocarcinoma cells through multiple pathways,thereby affecting the occurrence and progression of hepatocellular carcinoma.This article mainly reviews the research progress of circRNA related to EMT core transcription factors,circRNA that promotes EMT in liver cancer,and circRNA that inhibits EMT in liver cancer.

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。

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。

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。

Caspase12和Caspase3在内质网应激介导的HCC细胞凋亡中的作用

目的探讨Caspase12与Caspase3的表达变化在内质网应激(ERS)介导的肝细胞肝癌(HCC)发生细胞凋亡过程中的作用。方法选取25例临床病理分级为Ⅰ-Ⅱ级(高分化)的HCC组织作为HCCⅠ-Ⅱ级组、25例Ⅲ-Ⅳ级(低分化)HCC组织作为HCCⅢ-Ⅳ级组,分别各取25例癌旁组织作为癌旁对照组;采用原位未端标记法(TUNEL)法检测各组肝组织的细胞凋亡情况,免疫组织化学法、Western Blot检测各组肝组织中Caspase12、Caspase3及GRP78蛋白表达,Real-time PCR检测各组肝组织中Caspase 12、Caspase 3及GRP 78 mRNA表达水平。结果与相应癌旁对照组比较,TUNEL法检测结果表明,HCCⅠ-Ⅱ级、Ⅲ-Ⅳ级组细胞的凋亡数目升高(P<0.05);免疫组织化学法、Western Blot及Real-time PCR检测显示HCCⅠ-Ⅱ级及HCCⅢ-Ⅳ级组中Caspase3与GRP78蛋白及mRNA表达增加(P<0.05);Caspase12蛋白及mRNA表达在各组间比较,差异无统计学意义(P>0.05)。结论ERS参与了HCC发展过程中的细胞凋亡,且是通过介导Caspase12以外的信号通路激活Caspase3执行的细胞凋亡。

5F-Na注射液对人肝癌MHCC97L细胞毒性及凋亡的影响

目的探讨5F-Na对低转移型人肝癌MHCC97L细胞的抗癌效应。方法不同浓度5F-Na注射液(20、40、80μg·m L^(-1))处理MHCC97L细胞,MTT法检测细胞生长抑制率;Annexin V-EGFP染色及半胱氨酸蛋白酶-3活性检测细胞凋亡;流式细胞术检测细胞周期。结果 5F-Na注射液对MHCC97L细胞增殖抑制作用呈明显的时间、剂量依赖关系;不同浓度5F-Na注射液作用细胞24 h后,细胞凋亡比例较对照组明显升高(P<0.05);并可使细胞阻滞于G_2期。结论 5F-Na注射液抑制MHCC97L增殖与阻滞细胞于G_2期,促进凋亡有关。

HCC患者多肽生长因子及肿瘤标志物测定的临床意义

目的:分析血清多肽生长因子水平与肝硬化、肝癌的关系,初步探讨其发病机制。方法:采用放射免疫分析(RIA)测定32例肝癌(HCC)、34例肝硬化(LC)患者及30名正常对照组人员的血清TGF-α、TGF-β1、AFP及AFU水平四项指标。结果:HCC患者组血清TGF-α、TGF-β1、AFP及AFU水平均显著高于LC组及正常对照组(P均<0.05),LC组则AFP及AFU水平均显著高于正常对照组(P<0.05),但TGF-α、TGF-β1水平与正常对照组比较无显著性差异(P>0.05)。结论:HCC患者血清多肽生长因子TGF-α、TGF-β1、AFP及α-L、岩藻糖苷酶(AFU)水平发生了明显的变化,提示四项指标水平的升高及过度表达与肝癌的恶性增殖生长、病情的进展关系密切。

大鼠肝癌促进模型的HCC-X mRNA表达谱差异分析

目的:了解肝癌相关基因HCC-X与正常肝组织及癌旁组织的差异。方法:建立大鼠肝癌的动物模型,将化学致癌后的肝组织、肝癌旁组织进行HCC-X mRNA水平分析。结果:HCC-X在肝癌组织中为低表达或不表达,与正常组织比较有显著性差异(P<0.01),提示可能是肝癌的致病基因。结论:HCC-X对大鼠肝癌细胞有明显抑制作用。

非酒精性脂肪肝肝细胞肝癌（HCC）的MR诊断

目的观察非酒精性脂肪肝肝细胞肝癌（HCC）的MR诊断表现及检出率。方法对2009年10月至2010年5月在我院确诊为非酒精性脂肪肝肝细胞肝癌的67例患者进行MR检测。结果MR结果显示，67例患者均出现长T1、长T2信号，且对其进行MRI测定后发现其动脉期出现明显强化，而门脉期和平衡期的强化程度则明显下降。部分患者显示出强化的环形肿瘤包膜。MR对于HCC的诊断率为100％。结论非酒精性脂肪肝肝细胞肝癌（HCC）的MR诊断检出率高。

血清SA、Fuc、APP测定对AFP(-)HCC的诊断价值

本文对31例血清甲胎蛋白(AFP)阳性原发性肝细胞性肝癌(HCC)、33例AFP(—)HCC、35例肝硬化和58例正常献血清唾液酸(SA)、岩藻糖(Fuc)及五种急性期蛋白(APP)[a_1-酸性糖蛋白(a_1-AG)、结合珠蛋白(HP)、a_1-抗胰蛋白酶(a_1-AT)、前白蛋白(PA)和转铁蛋白(TF)]同时进行测定.结果表明AFP(—)肝癌组患者血清SA、Fuc、a_1-AG、HP及a_1-AT均显著高于对照组,其中,Fuc、a_1-AG与HP又比AFP(+)肝癌组为高.因此可将上述五项指标视为AFP(—)肝癌患者血清肿瘤标志物.此外,还发现肝癌患者血清两种结合蛋白的糖类含量高与血清a_1-AG。

TNP-470对MHCC97-H体外血管生成拟态的抑制作用

目的研究血管生成抑制剂TNP-470对人肝癌高转移细胞株MHCC97-H体外形成血管生成拟态的影响。方法TNP-470作用于MHCC97-H细胞,应用MTT试验、体外侵袭实验,检测MHCC97-H细胞增殖活性和侵袭力的变化。建立MHCC97-H细胞人工基底膜基质凝胶体外三维细胞培养模型,观察MHCC97-H细胞能否形成血管生成拟态以及TNP-470对其影响,应用扫描电镜、透射电镜观察细胞结构改变。结果TNP-470对MHCC97-H细胞增殖无显著抑制作用,可抑制其体外侵袭能力,明显抑制MHCC97-H细胞形成血管生成拟态,减少细胞表面的微绒毛和细胞间连接。结论人肝癌高转移细胞株MHCC97-H可形成血管生成拟态,TNP-470能抑制人肝癌细胞株MHCC97-H体外血管生成拟态形成。

肝脏Gd-DTPA快速动态增强MRI的临床应用──较小HCC与FNH的动态增强表现

目的：运用梯度回波（ＧＲＥ）的快速场回波（ＦＦＥ）技术，对２０例肝肿块进行Ｇｄ－ＤＴＰＡ动态增强，旨在探明不同肿块的增强规律，提高肝肿块的诊断和鉴别诊断能力。材料与方法：选取经过其他影像学检查未确诊的２０例肝肿块，作常规自旋回波（ＳＥ）平扫后作Ｇｄ－ＤＴＰＡＦＦＥ序列快速动态增强扫描，分别测量病灶信号强度（ＳＩｌｅｓｉｏｎ），灶周正常肝脏信号强度（ＳＩｌｉｖｓｒ），背景噪声信号强度和标准差（ＳＩｎｏｉｓｅｃ±ｓ），计算不同病变不同时相的肝－病灶对比噪声比（Ｃ／Ｎ），描出不同肿块（本文只评价其中手术病理证实的１３例肿块，包括肝细胞癌１０例，局灶性结节增生３例的时间－病灶Ｃ／Ｎ曲线。结果：ＨＣＣ与ＦＮＨ两者曲线较接近（包括强化峰值和升降坡度），但在增强早期，ＨＣＣ的Ｃ／Ｎ值高于ＦＮＨ，３分钟以后二者强化值均下降，且ＦＮＨ的Ｃ／Ｎ值大于０，ＨＣＣ的Ｃ／Ｎ值小于０，此差异可持续１５～２０分钟。结论：不同的肝肿块，动态增强后的时间－Ｃ／Ｎ曲线不同，对ＨＣＣ及ＦＮＨ而言，增强早期（１分钟以内）及３分钟以后曲线差异较大，最有助于鉴别诊断。动态增强ＭＲ成像可作为肝脏常规ＳＥ序列成像的一种有效的补充方法。