HBV感染所致免疫失衡与肝细胞癌的研究进展

乙型肝炎病毒（hepatitis B virus,HBV）感染是肝细胞癌（hepatocellular carcinoma,HCC）发生的主要危险因素,但HBV是非细胞毒性病毒,本身不会引起肝细胞损伤。HBV感染时的肝脏损伤主要由机体的抗HBV免疫应答引起,因此免疫应答相关的病理机制对HBV相关性HCC的发生至关重要,HBV驱动HCC的机制也成为目前研究的热点之一。大量研究显示,慢性HBV持续感染可导致先天性和适应性免疫反应功能障碍。本文就HBV感染导致的HCC特异性先天性免疫和适应性免疫反应研究进展作一综述。     

丙型肝炎病毒与原发性肝细胞癌

自美国加州Ｃｈｉｒｏｎ公司成功地从受感染的黑猩猩血液中克隆出了丙型肝炎病毒（ＨＣＶ）ｃＤＮＡ,为丙型肝炎的研究奠定了基础,亦为肝细胞癌（ＨＣＣ）病因研究开辟了一个新领域。本文就丙型肝炎病毒（ＨＣＶ）与ＨＣＣ间的关系作一综述。１ＨＣＶ与ＨＣＣ关系的流行...     

原发性肝细胞癌组织Shh和Ptch-1与Gli-2表达及生物学意义的研究

目的:探讨原发性肝细胞癌(HCC)Sonic hedgehog信号通路信号肽Shh、膜受体Ptch-1和核转录因子Gli-2的表达及其生物学意义.方法:将44例HCC组织及其相应的癌旁肝组织制成含88个微组织的组织芯片,采用免疫组织化学方法分别检测了Shh、Ptch-1和Gli-2在两种组织中的表达情况.结果:在HCC组织中,Shh与Ptch-1阳性率(63.6%和45.5%)均显著高于癌旁肝组织(36.4%和25.0%),P均<0.05.Gli-2在HCC中表达阳性率(68.2%)显著高于癌旁肝组织(38.6%),P<0.01;且与HCC的组织学分级以及侵袭性相关,P均<0.05;与肿瘤大小和HBV感染无关.结论:增强的Gli-2活性导致细胞异常增殖,其所引起的Shh信号通路的过度激活可能促进HCC的发生和发展.     

肝移植治疗原发性肝细胞癌的进展

肝移植已经成为治疗肝癌的重要手段.选择合适的病人是一个重要的问题,国际通行的是米兰标准,我国一般公认的适应证主要包括:合并有肝硬变失代偿、不能接受肝切除治疗的小肝癌患者和肿瘤多发且波及左右两叶、肝功能严重损害、行切除术后肿瘤容易复发或出现肝功能衰竭者.血管侵犯,细胞分化程度等因素可以影响治疗的预后.围手术期辅助治疗(经皮肝动脉化学栓塞、经皮无水酒精瘤内注射、射频消融,氩氦刀治疗)对于提高肝移植的疗效有一定的意义.     

原发性肝细胞癌病灶形态学的CT研究

我们对２３２例原发性肝细胞癌病灶的术前ＣＴ表现进行分析。以病灶的形态、轮廓光整度、边缘整齐度作为指标，将肝癌病灶术前ＣＴ表现分为３种类型：类圆膨胀生长型（Ⅰ型）、不规则膨胀生长型（Ⅱ型）、不规则浸润型（Ⅲ型）。对不同ＣＴ分型与手术病理结果对照观察发现：从Ⅰ型～Ⅲ型，肿瘤的肝内播散率分别为１８．６％、３７．７％、４７．８％，肝外淋巴结转移率分别为０、７．８％、２３．２％，门静脉瘤栓形成率分别为２．３     

利用基因表达谱筛选肝细胞癌中炎性微环境形成相关新基因的研究

目的:利用基因表达谱芯片筛选肝细胞癌(HCC)中的差异表达基因,并分析神经降压素(NTS)表达与HCC中炎性微环境形成的相互关系.方法:收集10例原发性HCC癌与癌旁组织,提取RNA进行Affymetrix全基因组表达谱芯片检测,同时整合GEO数据库中同芯片平台的亚洲人原发性HCC的mRNA表达谱数据30例,利用R2.9.0软件获得差异基因列表,应用MemCore(R)2.5,Pathway Studio(R)6.0和Ingenuity(R)1.0软件进行信号通路分析.最后,结合HE染色比较不同NTS表达水平的HCC标本中炎症反应强度.结果:所有RNA样品无降解,各芯片数据的信号强度分布均一.SMA聚类和信号通路分析结果显示40例HCC标本中存在一组独特亚群,呈现神经降压素(NTS)高表达,并伴有胞外间质重构、细胞粘附、白细胞移动、血管新生等生物学过程显著增强.HE染色证实NTS高表达标本中炎细胞浸润、纤维增生和血管生成明显高于NTS低表达的标本.结论:NTS高表达可能促进HCC中炎性环境的形成.     

信号调节蛋白α1在肝细胞癌中的作用

目的 研究信号调节蛋白SIRPα_1与肝细胞癌的发生与侵袭之间的关系,探索可能的分子作用机制。 方法 提取正常细胞系Hs680,肝癌细胞系HepG2、H4-H7、Chang liver和SK-Hepl的总RNA,通过Northen杂交观察和确定SIRPα_1的表达。利用Northen杂交和免疫组化技术比较了42例病人肝癌组织和癌旁组织及6例正常肝组织SIRPα_1 mRNA和蛋白表达。体外对转染SIRPα_1的HuH7肝癌细胞系进行HGF和SIRPα_1相关性研究。 结果 SIRPα_1在Hs680、HepG2和H4-H7高表达,而在Chang liver和SK-Hepl中低表达。Northern杂交和免疫组化发现肝细胞癌组织中的SIRPα表达低于癌旁组织和正常肝组织。体外实验发现HGF刺激后SIRPα_1的磷酸化水平升高,而且野生型SIRPα_1的表达对HGF体外刺激的肝癌细胞增殖有促进作用。 结论 SIRPα_1和肝细胞癌的发生和转移相关,HGF刺激引起SIRPα_1磷酸化,影响下游信号转导可能是其作用相关机制之一。     

含奥沙利铂化疗方案治疗晚期原发性肝细胞癌的研究进展

索拉非尼是目前唯一被多国批准的治疗晚期原发性肝细胞癌（HCC）的分子靶向药物,但其对生存期改善有限,最终出现病情进展。近几年,含奥沙利铂的化疗方案显示出良好的临床疗效,且患者耐受性可,为晚期 HCC 患者提供了新的治疗选择。     

Immune checkpoint inhibitors in hepatocellular carcinoma: A review of current clinical trials

Hepatocellular carcinoma (HCC) is the most common primary liver cancer with a poor prognosis due to advanced disease presentation or recurrence despite curative-intent resection. Since the approval of sorafenib in 2007, few systemic therapies offered a significant improvement in treatment outcomes. Over the last 3 years, however, rapid advancements in the field of immunotherapy have led to approval of checkpoint inhibitors in 2020 for use in advanced HCC. Since then, a few other clinical trials have shown promising results in the adjuvant and neoadjuvant setting. The objective of this review is to summarize data from existing clinical trials evaluating the use of systemic immune checkpoint inhibitors in HCC and to follow the natural evolution of this development across the metastatic, adjuvant, and neoadjuvant landscapes.     

青年原发性肝癌临床特点分析

目的探讨青年原发性肝癌的临床特点.方法分析86例青年肝癌患者(年龄＜40岁)的临床特点,包括临床症状体征、肝癌家族史、饮酒史、HBV感染率、HCV感染率、ALT异常、AFP阳性、AFU阳性、合并肝硬化、门静脉癌栓以及肝癌类型,并与同期122例老年肝癌患者(年龄＞60岁)进行比较.结果青年肝癌患者占原发性肝癌患者的13.6%,在以下方面比例高于老年组,且有显著性或极其显著性差异:发热(36.0%)、HBV感染(86.0%)、ALT异常(74.4%)、AFP阳性(76.7%)、AFU阳性(81.4%)、门静脉癌栓(29.1%)和弥漫性肝癌(33.7%).结论青年肝癌恶性程度高,对HHBV感染ALT反复异常的青年人要定期进行B超和AFP检查,以便早期发现、早期治疗原发性肝癌.     

Fractionated stereotactic radiotherapy in patients with primary hepatocellular carcinoma

OBJECTIVE: The purpose of our study was to evaluate the feasibility and treatment outcomes of fractionated stereotactic radiotherapy (SRT) for primary hepatocellular carcinoma (HCC). METHODS: We enrolled 20 patients who had been histologically diagnosed as HCC patients and treated by fractionated SRT. Tumor size was 2-6.5 cm (average: 3.8 cm). We prescribed 50 Gy in 5 or 10 fractions at the 85-90% isodose line of the planning target volume for 2 weeks. The follow-up period was 3-55 months (median: 23 months). RESULTS: The overall response rate was 80%, with 4 patients showing complete response (20%), 14 patients showing partial response (60%) and 4 patients showing stable disease (20%). The 1-year and 2-year survival rates were 70.0 and 43.1%, respectively (median: 20 months). The 1-year and 2-year disease-free survival rates were 65.0 and 32.5%, respectively (median: 19 months). The fractionated SRT was well tolerated, because grade 3 or grade 4 toxicity was not observed. CONCLUSION: These results suggest that fractionated SRT is a relatively safe and effective method for treating small primary HCC. Thus, fractionated SRT may be suggested as a local treatment of choice for small HCC when the patients are inoperable or when the patients refuse operation.     

大分割三维适形放疗治疗不能手术原发性肝癌

背景与目的：在原发性肝癌患者中，大部分失去手术机会，三维适形放疗（3-DCRT）因为具有物理剂量分布优势而被越来越多应用于本类病例治疗。本研究着眼于评价大分割3-DCRT治疗不能手术原发性肝癌的疗效和毒副作用。方法：对52例原发性肝癌行3-DCRT，≥90％等剂量面包括计划肿瘤区域（PTV），单次剂量3．54～6．31Gy，照射次数7～15次。采用SPSS10．0统计软件，生存率以Kaplan—Meier法计算，近期疗效和放射反应评价采用x^2检验，相关因素对预后的影响采用Cox回归。结果：1、2年生存率分别为64．1％和12．6％，中位生存期13个月。近期有效率（CR＋PR）55．8％，肿块小于6cm及大于6cm者有效率分别为91．7％和45．0％（P=0．007）。肝脏急性不良反应Ⅰ级5例，1例发生严重放射性肝损伤，Ⅰ／Ⅱ级上消化道反应分别为23例（44．2％）和15例（28．8％）。肿块较大和合并门静脉痛栓（PVTT）为影响生存率的危险冈素（P值分别为0．042和0．001）。结论：3-DCRT治疗不能手术原发性肝癌在可接受的毒副作用前提下可获得一定的疗效，肿块较大和合并门静脉癌栓为影响生存率的危险因素。     

肝切除治疗原发性肝癌自发性破裂

目的 探讨肝切除治疗原发性肝癌自发性破裂(简称肝癌破裂)的作用。方法 分析我院1973年以来采用肝切除术治疗肝癌破裂12例的临床资料。结果 本组男10例，女2例。平均年龄42(22—65)岁。11例为急症肝切除术，1例为2期肝切除，包括肝左外叶切除6例，左内叶切除1例，左半肝切除1例，右肝部分切除2例，肿瘤局部切除2例。本组中Child-Paugh肝功能分级A组的11例中无死亡；B组者1例术后死于肝衰，手术死亡率为8．3％。术后生存的1例均获随访，平均生存时间为16．5个月，1，3，5年生存率分别为72．7，18．2％，9．1％。其中1例已无瘤生存25年9个月。结论 肝切除是治疗肝癌破裂的最好方法，当有可能时应争取施行。肝切除治疗肝癌破裂可能使患者获行长时间生存。     

Correlation analysis of intestinal flora and immune function in patients with primary hepatocellular carcinoma

BackgroundThis study applied metagenomic sequencing technology to analyze the intestinal flora distribution and immune function of patients with primary liver cancer.MethodsStool samples were collected from 10 patients with primary liver cancer (primary liver cancer group) and 10 healthy subjects (healthy control group) who were admitted to The Affiliated Changzhou No. 2 People’s Hospital of Nanjing Medical University from March to June 2021. The general data of the patients were recorded. Metagenomic sequencing was performed, and principal component analysis and diversity analysis were used to analyze the structure of the two groups and compare the differences in species abundance. United States Employment Service (USES) Spearman correlation analysis was applied to examine vice Streptococcus blood, saliva, Streptococcus, Streptococcus mutans, Streptococcus thermophilus, and vice Haemophilus influenzae, WeiRong aureus, existing different WeiRong bacteria, Eosinophilic mucins Ekman bacteria, responding to bacteria, the other branch bacteria abundance and in alanine aminotransferase (ALT), aspartate aminotransferase (AST), valley correlation between levels of amyltranspeptidase (GGT), total protein, total bilirubin and alpha-fetoprotein (AFP).ResultsBeta diversity analysis based on Bray and Jensen-Shannon Divergence (JSD) distance measurement showed that the heterogeneity of fecal flora in the hepatic cell carcinoma (HCC) group was significantly lower than that in the healthy control group (P<0.001. At the species level of bacterial taxonomy, there was a statistically significant difference in the distribution of 137 bacteria in the healthy control and primary liver cancer groups (P<0.05). Correlation analysis showed that Streptococcus salivarius (P=0.020), Streptococcus thermophilus (P=0.002), and Haemophilus parainfluenzae (P=0.023) were significantly positively correlated with the serum ALT level. There were also notable correlations with AST (P=0.049), GGT (P=0.037), and total protein (P=0.010).ConclusionsThe diversity of intestinal flora in patients with primary liver cancer is significantly reduced, species abundance is altered, and there is a marked imbalance of intestinal flora. Therefore, specific bacterial species with different intestinal flora may be used as biomarkers for the early diagnosis of primary liver cancer.     

An apparent danazol-induced primary hepatocellular carcinoma: case report

This paper presents an apparent case of danazol-induced primary hepatocellular carcinoma in a 49-year-old patient, following two years of continuous therapy with this inhibitor of pituitary gonadotrophin. Discontinuation of the drug failed to cause regression of the tumour.     

原发性肝癌蛋白质组学研究进展

继人类基因组研究之后,蛋白质组学成为当前生物医学研究的热点。蛋白质组学的不断发展,使我们可以深入理解基因级研究不能明确的细胞和分子机制,促进了肝癌在分子机制上更全面的研究,为了解原发性肝癌的发病机制、早期诊断和预防及治疗提供重要的理论基础。     

同时发生的肝肉瘤样癌与肝细胞癌一例并文献复习

目的:探讨肝肉瘤样癌患者的临床表现、诊断、治疗方法及预后.方法:结合我院收治的1例同时发生的肝肉瘤样癌与肝细胞癌患者,并复习国内外文献,分析该病的临床特点,实验室检查、影像学及病理学表现,治疗及预后.结果:肝肉瘤样癌临床上较少见,病理学上肿瘤包含上皮样成分及梭形细胞肉瘤样成分,肿瘤生长迅速,恶性程度高,预后差.结论:肝肉瘤样癌与肝细胞癌同时发生的病例临床罕见,病因不明,预后较差.