体外局部高频热疗联合放疗治疗进展期肝细胞癌患者临床疗效研究

目的 研究体外局部高频热疗辅助放疗治疗进展期肝细胞癌(HCC)患者的临床疗效.方法 采用随机数字表法将66例进展期HCC患者分为对照组33例和观察组33例,分别采取放疗或在放疗的基础上联合体外局部高频热疗治疗,随访12个月.结果 观察组客观缓解率(ORR)为63.6％,显著高于对照组的35.5％(P<0.05);治疗后...     

经皮穿刺注射无水乙醇治疗高强度聚焦超声治疗后残留肝癌的疗效观察

目的探讨经皮穿刺注射无水乙醇治疗高强度聚焦超声(HIFU)后残留肝癌的疗效及其影响因素。方法对HIFU治疗肝癌术后的83例残留病灶进行无水乙醇注射(PEI)治疗。观察治疗前后患者临床症状、肿瘤标记物的变化,并用彩色多普勒血流显像(CDFI)定期随访肿瘤变化。结果79例患者临床症状明显改善。6个月和1、2年生存率分别为95.5%、82.5%、60.5%。CDFI随访,所有患者治疗区病灶回声增强,血供减少或消失,其中77例(92.8%)病灶体积缩小。51例AFP阳性患者中,46例(90.2%)AFP下降。结论HIFU联合无水乙醇能有效破坏肿瘤血供,灭活肿瘤,延长患者的生存期和提高生存质量,是肝癌非手术治疗的一种有效方法。     

肝癌组织热休克蛋白 gp96 异常表达及其临床病理学特征

目的分析热休克蛋白（HSP）gp96在人肝细胞性肝癌（HCC）及非癌组织中的表达,并探讨其与肿瘤发生、发展及预后的关系。方法采用免疫组织化学方法分别检测30例HCC癌灶组织及其自身对照的非癌组织HSPgp96的表达,并以生物素标记的HBVDNA探针检测肝癌组织中HBVDNA,分析HSPgp96表达与HBV复制及其临床病理学特征的关系。结果无论是原发性肝癌还是转移性肝癌,HSPgp96均呈较高表达;HSPgp96在肝癌灶及非癌组织表达阳性率分别为73．3％和46．7％（P〈0．05）。HCC的癌灶组织中HSPgp96阳性表达与肿瘤分化程度及肿瘤大小显著相关（P〈0．05）,而与肿瘤数目无关（P〉0．05）。HBVDNA阳性肝癌组织中HSPgp96表达显著高于HBVDNA阴性组。结论HSPgp96在HCC中过度表达,且与HCC的分化程度和大小有关,可作为肝癌早期诊断及预后判断的标志。     

瘦素在肝脏中的生理功能及其在肝脏疾病中的作用

瘦素是由肥胖基因(obese gene,ob)编码,体内瘦素主要由脂肪组织分泌,通过结合瘦素受体调节中枢及外周组织多种重要生理功能.正常肝组织不表达瘦素,但有瘦素受体的表达,通过与肝细胞瘦素受体结合,参与调节葡萄糖的产生、转运、代谢,脂肪的分解合成及胰岛素信号的调控.近年研究发现,在多种肝脏疾病状态下,血浆及肝组织局部瘦素或瘦素受体的表达发生改变,通过干扰胰岛素信号功能、激活肝星状细胞(hepatic stellate cell,HSC)、介导肝Kupffer细胞的激活,进而诱导多种促炎、促细胞增殖及纤维化的相关基因表达,加剧了炎症细胞的浸润、细胞外基质堆积,在肝脏炎性反应、肝纤维化以及肝细胞癌发生发展中发挥作用.本文对瘦素在肝脏中的作用及其与肝病的关系进行综述.     

Gut-derived lipopolysaccharide promotes alcoholic hepatosteatosis and subsequent hepatocellular carcinoma by stimulating neutrophil extracellular traps through toll-like receptor 4

Background/AimsBinge drinking leads to many disorders, including alcoholic hepatosteatosis, which is characterized by intrahepatic neutrophil infiltration and increases the risk of hepatocellular carcinoma (HCC). Molecular mechanisms may involve the migration of bacterial metabolites from the gut to the liver and the activation of neutrophil extracellular traps (NETs).MethodsSerum samples from both binge drinking and alcohol-avoiding patients were analyzed. Mouse models of chronic plus binge alcohol-induced hepatosteatosis and HCC models were used.ResultsA marker of NETs formation, lipopolysaccharide (LPS), was significantly higher in alcoholic hepatosteatosis and HCC patients and mice than in controls. Intrahepatic inflammation markers and HCC-related cytokines were decreased in mice with reduced NET formation due to neutrophil elastase (NE) deletion, and liver-related symptoms of alcohol were also alleviated in NE knockout mice. Removal of intestinal bacteria with antibiotics led to decreases in markers of NETs formation and inflammatory cytokines upon chronic alcohol consumption, and development of alcoholic hepatosteatosis and HCC was also attenuated. These functions were restored upon supplementation with the bacterial product LPS. When mice lacking toll-like receptor 4 (TLR4) received chronic alcohol feeding, intrahepatic markers of NETs formation decreased, and hepatosteatosis and HCC were alleviated.ConclusionsFormation of NETs following LPS stimulation of TLR4 upon chronic alcohol use leads to increased alcoholic steatosis and subsequent HCC.     

IL-1 receptor-associated kinase 1 participates in the modulation of the NLRP3 inflammasome by tumor-associated macrophages in hepatocellular carcinoma

BackgroundHepatocellular carcinomas (HCCs) occur frequently in the digestive system and are associated with high mortality. This current study examined the regulatory relationship between interleukin (IL)-1 receptor-associated kinase 1 (IRAK1), NLR family pyrin domain-containing 3 (NLRP3) inflammasomes, and tumor-associated macrophages (TAMs) in the growth and metastasis of HCC.MethodsThe expression of IRAK1 and NLRP3 was assessed in tissues and cells via quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot analysis. Immunohistology was performed to detect the macrophage markers CD68, CD163, and CD168 in tumor tissues. Small interfering (si)RNA targeting IRAK1 (si-IRAK1) was designed to silence IRAK1 expression. Following si-IRAK1 transfection and/or co-culture with TAMs, HCC cell viability, proliferation, migration, and invasion, as well as the expression of NLRP3 and pro-inflammatory cytokines IL-1 β, IL-18, and monocyte chemotactic protein 1 (MCP-1) were assessed.ResultsHCC tissues showed elevated expression of IRAK1 and NLRP3, as well as increased expression of the macrophage markers CD68, CD163, and CD168, compared to adjacent healthy tissues. Silencing of IRAK1 expression in HepG2 and Huh7 cells resulted in suppression of cell proliferation, migration, and invasion, and also reduced expression of NLRP3 and the pro-inflammatory cytokines IL-1β, IL-18, and MCP-1. Moreover, TAMs promoted HepG2 and Huh7 cell proliferation, migration, and invasion, and elevated the expression of NLRP3, IL-1β, IL-18, and MCP-1. Furthermore, IRAK1 silencing reversed the effects of TAMs on HepG2 and Huh7 cells.ConclusionsThe expression of IRAK1 was associated with HCC growth and metastasis, as well as NLRP3 inflammasome activation. The ability of TAMs to promote HCC growth and metastasis may be activated by NLRP3 inflammasomes and regulated by IRAK1.     

Comparison of the safety and prognosis of sequential regorafenib after sorafenib and lenvatinib treatment failure in patients with unresectable hepatocellular carcinoma: a retrospective cohort study

BackgroundThere is lack of studies on sequential regorafenib after sorafenib and lenvatinib treatment failure in patients with unresectable hepatocellular carcinoma (HCC). This study was to explore the safety and prognosis of sequential regorafenib after sorafenib and lenvatinib failure in HCC patients.MethodsThis study was a retrospective, real-world study that included 50 HCC patients who received sequential regrafinib after sorafenib and lenvatinib failure. The safety and prognosis of two groups were compared.ResultsThe incidence of all grade and III/IV adverse events were 68% and 24%. According to Response Evaluation Criteria in Solid Tumours (RECIST) 1.1 and modified (m) RECIST standards, the objective response rates (ORRs) after receiving regorafenib were 14.0% and 22.0%, respectively. The disease control rates (DCRs) were 62.0% and 60.0%, respectively. Based on different first-line targeted drugs, 50 patients were divided into sorafenib (n=22) and lenvatinib group (n=28). There was no differences between two groups except age and bilirubin. And there was no differences in other treatments before or after regorafenib. The baseline between two groups was basically same and had good comparability. There was no difference in incidence of all grade and III/IV adverse events, ORR and DCR between two groups (P>0.05). On long-term prognosis, total overall survival (TOS) in sorafenib and lenvatinib group were 23.0 (95% CI: 15.1–30.9) vs. 29.7 (95% CI: 21.4–38.1) months. The difference was statistically significant (P=0.041). Besides, regorafenib overall survival (ROS) in sorafenib and lenvatinib group were 11.7 (95% CI: 7.1–16.3) vs. 15.9 (95% CI: 8.3–23.5) months. The difference was statistically significant ( P=0.045). The regorafenib progression-free survival (RPFS) was 5.6 (95% CI: 1.9–9.2) vs. 8.0 (95% CI: 5.1–10.9) months in sorafenib and lenvatinib group, respectively, and difference was not statistically significant (P=0.380).ConclusionsRegorafenib is an effective drug for second-line treatment of HCC, with fewer severe adverse events, ORR and DCR was 14–22% and 62–60%, respectively. Both TOS and ROS in lenvatinib group were better than those in sorafenib group. For HCC patients whose first-line targeted drug is lenvatinib, it is safe and effective to accept regorafenib after disease progresses.     

基于网络药理学和生物信息学探讨小柴胡汤治疗肝细胞癌的作用机制

目的 采用TCGA数据挖掘和网络药理学方法分析小柴胡汤治疗肝细胞癌(HCC)的药效物质基础及药理机制.方法 通过TCGA数据库挖掘HCC差异表达基因、通过TCMID、TCMSP数据库和文献检索得到小柴胡汤的活性成分及其作用靶点;绘制韦恩图获得小柴胡汤-HCC共有靶点.通过Cytoscape软件构建疾病-药物-有效成分-...     

三氧化二砷治疗中晚期原发性肝癌的近期疗效

目的观察三氧化二砷治疗中晚期原发性肝癌的近期疗效及不良反应。方法对33例采用单药三氧化二砷10 mg/d加入生理盐水静脉滴注连续14 d为1个周期,间歇2周,至少使用2个周期。结果全组4例PR,22例NC,7例PD,客观有效率12%。临床受益率:78.8%;疼痛缓解率为82.7%,81.8%患者生存质量提高;该治疗方案不良反应主要表现为Ⅰ^Ⅱ度胃肠道反应和血液学毒性,轻度的肝功能损害。结论三氧化二砷治疗中晚期原发性肝癌有较好疗效,不良反应较小,是肝癌治疗用药的较佳选择,值得临床推广。