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.

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.

Oncolytic virus-based hepatocellular carcinoma treatment:Current status,intravenous delivery strategies,and emerging combination therapeutic solutions

Current treatments for advanced hepatocellular carcinoma(HCC)have limited success in improving patients’quality of life and prolonging life expectancy.The clinical need for more efficient and safe therapies has contributed to the exploration of emerging strategies.Recently,there has been increased interest in oncolytic viruses(OVs)as a therapeutic modality for HCC.OVs undergo selective replication in cancerous tissues and kill tumor cells.Strikingly,pexastimogene devacirepvec(Pexa-Vec)was granted an orphan drug status in HCC by the U.S.Food and Drug Administration(FDA)in 2013.Meanwhile,dozens of OVs are being tested in HCC-directed clinical and preclinical trials.In this review,the pathogenesis and current therapies of HCC are outlined.Next,we summarize multiple OVs as single therapeutic agents for the treatment of HCC,which have demonstrated certain efficacy and lowtoxicity.Emerging carrier cell-,bioengineered cell mimetic-or nonbiological vehicle-mediated OV intravenous delivery systems in HCC therapy are described.In addition,we highlight the combination treatments between oncolytic virotherapy and other modalities.Finally,the clinical challenges and prospects of OV-based biotherapy are discussed,with the aim of continuing to develop a fascinating approach in HCC patients.

Gut Microbiota Modulation:A Viable Strategy to Address Medical Needs in Hepatocellular Carcinoma and Liver Transplantation

Hepatocellular carcinoma(HCC)is the most common malignancy of the liver,posing a significant threat to public health.Although liver transplantation(LT)is an effective treatment for HCC,ischemia–reperfusion(I/R)injury,transplant rejection,and complications after LT can greatly reduce its effectiveness.In recent years,transplant oncology has come into being,a comprehensive discipline formed by the intersection and integration of surgery,oncology,immunology,and other related disciplines.Gut microbiota,an emerging field of research,also plays a crucial role.Through the microbiome–gut–liver axis,the gut microbiota has an impact on the onset and progression of HCC as well as LT.This review summarizes the mechanisms by which the gut microbiota affects HCC and its bidirectional interactions with chronic liver disease that can develop into HCC as well as the diagnostic and prognostic value of the gut microbiota in HCC.In addition,gut microbiota alterations after LT were reviewed,and the relationship between the gut microbiota and liver I/R injury,the efficacy of immunosuppressive drugs used,and complications after LT were discussed.In the era of LT oncology,the role of the gut microbiota in HCC and LT should be emphasized,which can provide new insights into the management of HCC and LT via gut microbiota modulation.

Xiaoaiping injection affects the invasionand metastasis of hepatocellular carcinomaby controlling AFP expression

Objective Xiaoaiping (XAP) is a traditional Chinese medicine that is a commonly used as an anticancerdrug in clinical practice owing to its high efficiency and low toxicity. Specifically, XAP can effectively inhibitthe growth of hepatocellular carcinoma (HCC). Alpha-fetoprotein (AFP) is a key HCC diagnostic marker andis closely related to certain malignant cytological behaviors of HCC. However, whether AFP expression andXAP treatment are related to the invasion and metastasis of HCC remains unclear. In the present study, weaimed to evaluate the effects and underlying mechanism of XAP on the invasion and metastasis of HCC..Methods Using a cell scratch assay, Transwell technology, and western blotting we detected the differentinvasion and metastatic abilities of Hep3B cells in XAP treatment and blank control groups. This allowedcomparison of the invasion and metastatic abilities of Hep3B cells with differing levels of AFP expression.AFP mRNA sequencing technology was used to analyze the mechanism of tumor invasion and metastasisassociated with AFP and XAP treatment.Results Cell invasion and metastasis abilities in the XAP group were significantly lower than those in thecontrol group (P < 0.05). Additionally, compared to the control group, the expression of AFP significantlydecreased after XAP treatment (P < 0.05). The ability of Hep3B cells to invade and metastasize waspromoted when AFP expression was up-regulated, whereas it was inhibited when AFP was silenced. XAPinjection and AFP regulate the invasion and metastatic ability of HCC by affecting matrix metalloproteinases(MMPs).Conclusion XAP injection inhibits the invasion and metastatic ability of HCC by influencing the expressionof AFP;additionally, this inhibition of AFP is achieved by affecting MMPs.

Clinical and Epidemiological Aspects of Hepatocellular Carcinoma at the Internal Medicine Department of Point “G” Teaching Hospital in Mali

Liver cancer is the malignant transformation of liver cells. It develops in 90% of cases of cirrhosis, more rarely on chronic non-cirrhotic liver disease, and exceptionally in a healthy liver. This study aimed to investigate the clinical aspects of Hepatocellular Carcinoma (HCC). It was a retrospective descriptive study covering 10 years, focusing on HCC cases seen in outpatient and inpatient settings at the Internal Medicine Department. We recorded 153 cases out of 7021 patient records, resulting in a hospital frequency of 2.17%. The male-to-female ratio was 3.5. The mean age was 52.37 ± 14.34 years. The most common presenting complaint was pain in 16.3% of cases. A history of jaundice was found in 25.5% of cases. Alcohol consumption was observed in 15.38% of cases. The main physical sign found was hepatomegaly in 76% of cases. HBsAg was positive in 33.3% of cases. Alpha-fetoprotein levels were above 400 IU/ml in 50.81% of cases. Patients classified as CHILD PUGH A represented 39.72% of cases. Abdominal ultrasound revealed portal thrombosis associated with heterogeneous multinodular hepatomegaly in 11% of cases. Cytology confirmed HCC in four out of six patients who underwent the examination. We recorded 63 deaths out of 111 hospitalized patients. Complications included encephalopathy, hematemesis, and ascites in 48 patients. Hepatocellular carcinoma remains a significant public health issue. Its predominance in men and its occurrence in adults with factors such as viral infections and ethylism mean that prevention of this pathology could greatly reduce its incidence.

Treatment of recurrent hepatocellular carcinoma following liver resection,ablation or liver transplantation

Hepatocellular carcinoma(HCC)is the most common primary liver malignancy and causes one third of cancer related deaths world-wide.Approximately one third of patients with HCC are eligible for curative treatments that include hepatic resection,liver transplantation or imaging guided tumor ablation.Recurrence rates after primary therapy depends on tumor biology and pre-treatment tumor burden with early recurrence rates ranging from 30%-80%following surgical resection and ablation.HCC recurs in over ten percent following liver transplantation for HCC.Treatment modalities for tumor recurrence following resection and ablation include repeat liver resection,salvage liver transplantation,locoregional therapies,and systemic chemotherapy/immunotherapy.Locoregional and immune mediated therapies are limited for patients with tumor recurrence following liver transplantation given potential immune related allograft rejection.Given the high HCC recurrence rates after primary tumor treatment,it is imperative for the clinician to review the appropriate treatment strategy for this disease entity.This article will review the current literature regarding HCC recurrence after primary curative therapies and will discuss the relevant future trends in the HCC field.

不同配伍比例的半枝莲-白花蛇舌草药对对肝癌细胞增殖活性的影响

目的:研究不同配伍比例的半枝莲-白花蛇舌草药对(简称半白药对,SB-OD)对肝癌细胞株(MHCC97H细胞和Huh7细胞)增殖活性的抑制作用。方法:运用CCK-8法观察不同配伍比例的半白药对(半白1∶1,半白2∶1,半白1∶2)干预MHCC97H和Huh7细胞24 h,分别计算其IC_(50)值;并应用细胞平板克隆形成实验检测细胞克隆形成能力,分析不同配伍比例的半白药对对MHCC97H和Huh7细胞增殖活性的影响。结果:不同配伍比例的半白药对作用MHCC97H和Huh7细胞后的生存活力明显下降(P<0.01),并呈浓度依赖性,其中半白1∶1组作用于MHCC97H和Huh7细胞的IC_(50)值分别为6.69 mg/mL和7.95 mg/mL;半白2∶1组作用于MHCC97H和Huh7细胞的IC_(50)值分别为2.58 mg/mL和3.43 mg/mL;半白1∶2组作用于MHCC97H和Huh7细胞的IC_(50)值分别为15.04 mg/mL和16.60 mg/mL。不同配伍比例的半白药对干预MHCC97H和Huh7细胞后的克隆形成率明显降低(P<0.01)。结论:不同配伍比例的半白药对均能够抑制肝癌MHCC97H和Huh7细胞的增殖活性,2∶1配伍比例的抑制作用最佳,可作为半白药对抗肿瘤研究的实验基础。

IL-7的诱导表达增强靶向GPC3 CAR-T细胞的增殖及体外抗肿瘤活性

目的:探讨IL-7的诱导表达对靶向磷脂酰肌醇蛋白聚糖3(GPC3)嵌合抗原受体基因修饰T淋巴细胞(CAR-T细胞)的增殖和体外抗肿瘤活性的影响。方法:通过无缝克隆将GPC3 CAR序列片段插入GV400载体的Bam HⅠ/Eco RⅠ位置,构建第二代CAR慢病毒载体GPC3-BBZ及GPC3-BBZ-NFAT-IL-7,以293T细胞包装相应的慢病毒载体后,感染人T细胞制备CAR-T细胞。实验分为未转导T细胞(NT)组、GPC3-BBZ CAR-T细胞组、GPC3-BBZ-NFAT-IL-7 CAR-T细胞组。采用流式细胞术检测各组CAR-T细胞中CAR的表达水平,qPCR法检测经GPC3蛋白激活的CAR-T细胞中IL-7 m RNA的表达水平,细胞计数法检测CAR-T细胞在GPC3抗原刺激下的增殖能力,ELISA检测CAR-T细胞在受到肿瘤细胞刺激后IL-7、IFN-γ和TNF-α的分泌水平。应用实时细胞分析(RTCA)技术检测CAR-T细胞对人肝癌Huh-7细胞的杀伤作用。结果:成功构建慢病毒载体GPC3-BBZ和GPC3-BBZ-NFAT-IL-7,制备出靶向GPC3的CAR-T细胞。经GPC3抗原激活后,GPC3-BBZ-NFAT-IL-7 CAR-T细胞可有效表达IL-7 mRNA(P<0.01),其表现出更强的增殖能力(P<0.05)。与GPC3-BBZ CAR-T细胞相比,GPC3-BBZ-NFAT-IL-7 CAR-T细胞与GPC3阳性靶细胞Huh-7细胞共培养后,分泌更高水平的IL-7、IFN-γ和TNF-α(P<0.01或P<0.001)。RTCA结果显示,GPC3-BBZ-NFAT-IL-7 CAR-T细胞对GPC3阳性Huh-7细胞的杀伤活性显著高于GPC3-BBZ CAR-T细胞(P<0.05)。结论:成功制备可诱导表达IL-7的靶向GPC3的CAR-T细胞,IL-7的诱导表达增强靶向GPC3 CAR-T细胞的免疫活性,在体外展现出较强的肿瘤细胞杀伤能力。

华蟾素片联合肝动脉化疗栓塞术治疗原发性肝细胞癌的临床疗效及其影响因素分析

目的:评价华蟾素片联合肝动脉化疗栓塞术(TACE)治疗原发性肝细胞癌(HCC)效果及其影响因素。方法:按照纳入和排除标准收集108例HCC病人的临床资料,随机分为试验组和对照组。试验组采用华蟾素片联合TACE治疗,对照组采用单纯TACE治疗。以无进展生存期(PFS)和总生存期(OS)作为评价指标,采用COX回归分析评价两组生存预后及其影响因素。结果:试验组OS 13.5个月,对照组OS 9.2个月;试验组PFS 6.8个月,对照组PFS 5.3个月,组间比较,差异均有统计学意义(P均<0.05)。多因素COX回归分析显示,Child⁃Pugh分级和肝硬化是HCC病人PFS预后独立的危险因素;Child⁃Pugh分级是HCC病人OS预后独立的危险因素;ALBI是HCC病人OS预后的保护因素。结论:华蟾素片联合TACE治疗HCC有效延缓肝癌进展,延长病人PFS和OS,其中Child⁃Pugh分级、肝硬化和ALBI是影响HCC病人预后的重要因素。

人参皂苷Rb1通过KEAP1/PGAM5/AIFM1通路促进肝细胞癌HepG2细胞发生氧死亡

目的:探讨人参皂苷Rb1(Gn-Rb1)对肝细胞癌(HCC)HepG2细胞氧死亡的影响及其可能的分子机制。方法:采用生物信息学方法分析氧死亡的关键基因PGAM5表达对HCC患者生存期的影响。选取辽宁省肿瘤医院收治的8例HCC患者的HCC组织与癌旁组织,通过WB法及qPCR检测氧死亡相关基因蛋白与mRNA的表达情况。将HepG2细胞随机分为对照组与Gn-Rb1组(予以200μmol/L Gn-Rb1干预),采用细胞克隆形成实验、划痕愈合实验分别检测Gn-Rb1对HepG2细胞的集落形成能力、迁移能力的影响,ELISA检测对细胞ROS生成水平的影响,微板法检测对细胞LDH释放水平的影响;WB法、qPCR法检测Gn-Rb1对HepG2氧死亡关键基因蛋白质与mRNA水平表达的影响。结果:生物信息学分析发现,PGAM5高表达肝癌患者总生存时间较低表达患者更长(P<0.05)。在临床HCC组织与癌旁组织样本中发现,相较于癌旁组织,在蛋白质与mRNA水平上,肿瘤组织KEAP1与PGAM5表达显著降低,NRF2表达显著升高(均P<0.01),p-AIFM1蛋白水平显著升高(P<0.05)。对HepG2细胞予以200μmol/L Gn-Rb1干预后,相较于对照组,Gn-Rb1组HepG2细胞的迁移能力与集落形成能力显著降低(均P<0.01),而LDH水平显著升高(P<0.05);相比于对照组,在mRNA和蛋白质水平上,Gn-Rb1组细胞中KEAP1、PGAM5表达均显著升高而NRF2表达均显著降低(均P<0.05),p-AIFM1蛋白表达显著降低(P<0.01)。结论:HCC组织中氧死亡被抑制,而Gn-Rb1能够通过调控KEAP1/PGAM5/AIFM1通路促进HepG2细胞氧死亡的发生,抑制细胞增殖和迁移能力。

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。

Importance of Percutaneous Radiofrequency Ablation for Recurrent Hepatocellular Carcinoma

Objective: To study the importance of percutaneous radiofrequency ablation (PRFA) guided by ultrasound for inoperable recurrent hepatocellular carcinoma.Methods: Forty-seven patients with inoperable recurrent hepatocellular carcinoma underwent percutaneous radiofrequency ablation (PRFA) under ultrasond between October 1999 and July 2001. Twenty-four patients had single recurrent tumor and 23 patients had multiple lesions. Twelve patients had single lesion with less than 3.5 cm in diameter. All patients were followed up to examine the value of AFP, MRI or CT after PRFA. Kaplan-Meier estimation was used to analyze the survival rate.Results: The 1-, 2- and 3-year survival rate in single lesion group was 65.2%, 37.5% and 37.5% respectively. The survival rate of 1 and 2 years was 41.7% and 19.5% in the multiple lesions group. The 1-, 2-and 3-year survival rate in single lesion groups with less than 3.5 cm in diameter was 83.3%, 51.4% and 51.4% respectively.Conclusion: PRFA is one of the important comprehensive methods for recurrent hepatocellular carcinoma. According to the size, number and recurrent time, PRFA can be performed separately or combined with transcatheter arterial chemoembolization for inoperable recurrent hepatocellular carcinoma. This method can control the recurrence and increase the survival rate effectively. Key words recurrence - hepatocellular cacinoma - radiofrequency ablation

基于机器学习方法构建线粒体氧化应激相关肝细胞癌预后风险模型

肝癌是常见的恶性肿瘤之一,晚期肝癌的预后极差。鉴于线粒体氧化应激在肝癌发生发展中的重要作用,选用线粒体氧化应激相关基因构建肝细胞癌(hepatocellular carcinoma,HCC)预后风险模型。首先,结合单因素Cox回归分析与支持向量机、随机森林分析、LASSO回归分析3种机器学习方法筛选预后关键基因,并基于多因素Cox回归分析构建模型;其次,在数据库中对模型的预后价值进行验证;再次,利用基因富集分析探讨高低风险组间预后差异的可能机制,并比较两组间的免疫微环境及治疗反应;最后,使用实时荧光定量逆转录PCR(reverse transcription quantitative real-time PCR;RT-qPCR)验证关键基因在HCC组织中的表达。结果共筛选出PDE2A、TREM2、BMP6、NQO1、CPS1、EPO、MAPT、G6PD、SFN、HMOX1十个基因。与低风险组比较,高风险组HCC患者预后较差(P<0.0001)。富集分析表明,过氧化物酶体增殖物激活受体(peroxisome proliferator-activated receptor,PPAR)信号通路等在高低风险组间存在显著差异。肿瘤免疫分析表明,肿瘤免疫浸润、免疫检查点相关基因、免疫治疗反应等在高低风险组间也存在显著差异。RT-qPCR的验证结果表明,相比正常肝组织,HCC组织中CPS1、PDE2A、BMP6的表达显著降低(P<0.05),而G6PD、SFN的表达显著升高(P<0.05)。总之,本研究建立的线粒体氧化应激相关HCC预后风险模型具有良好的预测效能及准确度,可用于HCC的精准治疗,有较高的临床应用价值。

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。