肝细胞损伤时鸟嘌呤酶的释放与动态改变

（目的）探讨鸟嘌呤酶（ＧＵＡ）在肝细胞损伤过程中的动态改变及其临床价值。（方法）以２－ＦＡＡ喂饲ＳＤ大鼠,观察大鼠肝细胞同伤到癌变过程中血清及肝组织中的ＧＵＡ的活性变化。（结果）在鼠肝细胞发生变性至肝组织全数为时,各实验组务清及肝组织中ＧＵＡ与正常对照组相比,ＧＵＡ第二周开始升高,以后酶活性持续升高,但肝癌鼠ＧＵＡ的动力学常数（Ｋｍ值）与正常鼠的ＧＵＡ相比,未见异常改变,（结论）胞浆酶ＧＵＡ为肝细     

肝细胞癌边缘部的CT征象与病理改变的关系

目的：探讨肝细胞癌的大小与边缘部ＣＴ征象及有关病理基础的关系。方法：收集４５例经手术、病理证实的肝细胞癌,观察其大小与边缘部的ＣＴ表现及有关的病理改变。结果：肝细胞癌的大小与其ＣＴ边缘部的形态改变及瘤旁小门静脉癌栓的发生率无关,病理上瘤旁周围肝组织内癌细胞的浸润程度与肝细胞癌边缘部的形态有关,而与它的大小无关。结论：肝细胞癌本身的膨胀性或浸润性生长方式,是测定肿瘤边缘部形态的主要因素;在分析肝细胞     

肝细胞癌变过程中端粒酶的表达及动态改变

［目的］探讨端粒酶在肝癌发生过程中的表达与动态改变。［方法］SD大鼠以2－FAA喂饲制备肝癌模型,观察肝细胞癌变过程中瑞粒醇和总RNA的表达与改变;并收集人肝癌组织,匀浆后以PCR-ELISA法定量分析了癌和远癌组织中端粒酶活性。［结果］鼠肝癌模型证实：在肝细胞癌变过程中,随组织学改变端粒酶表达逐步增加,并与总RNA浓度是正相关（r＝0．59,P＜0．01）;人肝癌组和远癌组间的端粒酶表达水平,若以△A／mgP表示其差别无显著性（P＞0．05）;但以△A／RNA计算结果,则肝癌组酶活性明显高于远癌组（P＜0．05）。［结论］分析肝癌组织中端粒酶活性有助于监测肝细胞癌变和肝癌的早期诊断。     

乙醇诱导小鼠急性肝细胞损伤模型中NF-κB的表达

目的：研究核因子NF-κB在乙醇诱导小鼠急性肝细胞损伤中的表达及意义。方法：40只小鼠随机分成对照组和3个乙醇(250、500、1000mmol/kg)染毒组,每组10只。一次性灌胃染毒,16h后检测小鼠血清中天冬氨酸转氨酶(AST)、丙氨酸转氨酶(ALT)的活力;染毒24h后采用HE及油红O染色进行病理学观察;采用免疫组织化学法观察小鼠肝细胞中NF-κB蛋白的表达。结果：3个乙醇染毒组小鼠血清中的转氨酶AST和ALT活力均高于对照组 (P均<0.05);HE染色发现小鼠肝组织中出现肝细胞内空泡变性。油红O染色显示损伤的肝细胞内出现大量脂滴。免疫组织化学检测发现500和1000mmol/kg乙醇染毒组小鼠肝细胞胞质及胞核内NF-κB蛋白表达的积分光密度明显高于对照组(P<0.05)。结论：成功复制了急性小鼠酒精性肝损伤的模型,NF-κB升高是小鼠急性酒精性肝细胞损伤的一个重要分子事件。     

肝脏动态增强CT与MRI检查对肝细胞癌的诊断效能比较

目的 比较肝脏动态增强CT与MRI检查对肝细胞癌(HCC)的诊断效能.方法 选取102例肝脏病变患者,均接受增强CT、MRI检查,以病理学检查结果为金标准,比较肝脏动态增强CT与MRI对HCC的诊断效能.结果 102例肝脏病变患者病理学检查结果显示,HCC患者68例,共178个结节.动态增强CT检查诊断HCC阳性65例,阴性37例;MRI检查诊断HCC阳性69例,阴性33例.Kappa一致性分析结果显示,增强CT诊断HCC与金标准诊断结果具有中等一致性(Kappa=0.555),MRI诊断与金标准结果具有很强一致性(Kappa=0.844).受试者工作特征(ROC)曲线结果显示,MRI检查诊断HCC的效能优于增强CT检查(P﹤0.05).结论 与增强CT检查相比,肝脏MRI检查诊断HCC的结果与病理检查结果的一致性强,诊断效能更优,可用于早期HCC的诊断.     

MR和CT动态扫描对小肝癌强化特征的比较研究

目的 前瞻性比较研究小肝癌（SHCC）在动态MR和螺旋CT多期扫描中的强化特征,探讨MR优于螺旋CT的原因。方法 53例SHCC患者,均行螺旋CT和MR动态增强扫描。螺旋CT全肝平扫后分别行动脉期、门脉期和延迟期的增强扫描。MR和SE序列和FMPSPGR序列动态增强多期扫描。结果 53例患者共发现病灶76个,MR和CT动脉期扫描分别有69个病灶和49个病 灶有明显强化。SHCC在MR和CT动脉期－门脉期－延迟期扫描中的典型表现为高－低－低信号（密度）和高－等－低信号（密度）;不典型的表现为高－高－高信号（密度）、高－等－等信号（密度）和低－低－低信号（密度）。结论 动态MR和螺旋CT多期扫描均可显示SHCC的强化特征。MR动脉期扫描更能充分反映SHCC富血供的特点;在定性诊断方面,结合SE序列上的一些信号特征,MR更优于螺旋CT。     

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.     

乙型肝炎病毒感染与肝细胞癌发生的关系

目的：探讨乙型肝炎病毒（HBV）的可能致癌机理，方法：采用免疫组化和原位分子杂交方法，对慢性乙型肝炎，肝硬化，癌旁肝硬化，肝细胞癌和正常肝组织中的乙型肝炎表面抗原（HBsAg)，核心抗原（HBcAg),HBV,DNA和甲胎蛋白（AFP）水平进行检测。结果：HBsAg,HBcAg和HBV DNA的阳性率在慢性乙型肝炎组中分别为61．9％（13／21），42．9％（9／21），75．0％（12／16），在肝硬化组中分别为64．0％（16／25），36．0（9／25），83．3％（15／18），在癌旁肝硬化组中分别为72．7％（16／22），61．1％（11／18），85．7％（12／14），在肝细胞癌组中分别为45．2％（14／31），50．0％（14／28），64．3％（9／14），慢性乙型肝炎，肝硬化和癌旁肝硬化组中HBV DNA阳性信号较肝细胞癌多而,AFP主在癌旁肝硬化（33．3％，9／27）和肝细胞癌（43．6％，17／39）组中表达，而在慢性肝炎和肝硬化组中不表达，癌旁肝硬化与不伴肝癌的肝硬化有非常显著性差异（P＜0．01），结论：大多数肝细胞癌的发生与HBV感染所致的慢性乙型肝炎和肝硬化密切相关，癌旁肝硬化可能是癌前肝硬化在癌周的残留。     

Hepatocyte Growth Factor Enhancement of Preneoplastic Hepatic Foci Development in Rats Treated with Diethylnitrosamine and N-Ethyl-N-hydroxyethylnitrosamine

Effects of hepatocyte growth factor were investigated in a two-stage rat liver carcinogenesis protocol. Male F344 rats were first treated with diethylnitrosamine (200 mg/kg, i.p.) and then, starting two weeks later, with N-ethyl-N-hydroxyethylnitrosamine (EHEN) for 6 weeks at a dose of 0.01% in drinking water. Hepatocyte growth factor, which was injected i.v. at a dose of 200 μg/kg body weight one (at week 3) or two times (at weeks 3 and 4) during EHEN administration, significantly increased the development of preneoplastic glutathione S-transferase placental form-positive foci. Although the observed effects of hepatocyte growth factor were weaker than that of the two-thirds partial hepatectomy (PH) performed at week 3, the present results suggest that the enhancing effects of PH performed during the promotion stage may be largely mediated through induction of hepatocyte growth factor.     

Immunohistochemical Localization of Hepatocyte Growth Factor Protein in Pancreas Islet A-Cells of Man and Rats

Hepatocyte growth factor (HGF), a potent mitogen for adult rat hepatocytes in primary culture, has previously been shown to be primarily expressed in the nonparenchymal cells of the liver. Using polyclonal antisera against human and rat HGFs we studied the tissue distribution of HGF immunohistochemically and found the most intense staining in the pancreas islet cells in both man (autopsy cases) and the rat. Differential localization of 4 pancreas islet hormones, glucagon, insulin, somatostatin and pancreatic polypeptide, revealed HGF to be preferentially expressed within the glucagon-positive cells. The results indicate that HGF is primarily produced or stored in A-cells and may act as a growth factor in a paracrine and an endocrine fashion, like various other hormones.     

DNA Damage Response and Repair Pathway Alteration and Its Association With Tumor Mutation Burden and Platinum-Based Chemotherapy in SCLC

IntroductionImpairment in DNA damage response and repair (DDR) pathway is known as a predictive biomarker of platinum sensitivity. Recently, DDR alteration is re-emphasized as a predictive biomarker of immune checkpoint inhibitor due to its positive correlation to tumor mutation burden (TMB).MethodsTarget gene sequencing (381 genes) was conducted from 100 extensive disease (ED) and 66 limited disease (LD) patients with SCLC. Detected mutations were classified as double-strand breaks (DSB) (n = 82): homologous recombination (n = 54), non-homologous end joining (n = 19), and Fanconi anemia (n = 32); or single-strand breaks (SSB) (n = 31): mismatch repair (n = 19), base excision repair (n = 7), and nucleotide excision repair (n = 6).ResultsCompared to patients with an intact DDR pathway (n = 70), a higher TMB was observed in patients with homologous recombination (p < 0.001), non-homologous end joining (p = 0.002), mismatch repair (p < 0.001), DSB (p < 0.001), and SSB (p < 0.001). Survival analyses based on TMB level showed no predictive or prognostic values in ED patients. In LD patients, prolonged progression-free survival (hazard ratio [HR] = 0.497, p = 0.015), and overall survival (HR = 0.383, p = 0.010) to concurrent chemoradiotherapy were observed in those with TMB above median. Individual DDR pathway alteration showed no survival benefit in ED patients receiving platinum-based chemotherapy. In LD patients, those with mutations in the Fanconi anemia gene set had shorter progression-free survival (HR = 2.048, p = 0.036) to initial treatment.ConclusionsDDR pathway alterations, both DSB and SSB, in SCLC have a positive correlation with high TMB. However, it has shown limited value in prediction of platinum efficacy.     

血清肝细胞生长因子水平与胃癌关系的研究

目的 探讨胃癌患者血清肝细胞生长因子(hepatocyte growth factor,HGF)水平变化的临床意义.方法 采用酶联免疫吸附实验法检测60例胃癌患者血清HGF水平,其中40例行胃癌根治术,12例因有远处转移而未手术,8例为胃癌术后复发,同时选取15例良性胃病患者以及12例门诊健康体检者作为对照,分别检测其血清HGF的水平,并进行比较分析.结果 胃癌组血清HGF水平高于良性胃病组和正常对照组(P＜0.05);胃癌术后复发组血清HGF水平明显高于良性胃病组和正常对照组(P＜0.01);40例胃癌术前组血清HGF水平明显高于胃癌术后组(P＜0.01);胃癌复发组血清HGF水平明显高于胃癌手术组和非手术组(P＜0.01).结论 HGF在胃癌的发生发展过程中可能起重要作用,血清HGF水平的检测可成为胃癌病情程度监测和预后判断的客观指标.     

HGF和其受体c-met在NSCLC组织中的表达及其与VEGF的关系

目的检测肝细胞生长因子（HGF）及其受体（c-met）和血管生长因子（VEGF）在非小细胞肺癌（NSCLC）中的表达，分析其与NSCLC临床病理参数的关系及HGF和VEGF相关关系。方法应用免疫组织化学方法SABC法对68例NSCLC组织中的HGF、c-met和VEGF进行检测。结果68例NSCLC组织中HGF、c-met和VEGF表达率分别为45．6％（31／68）、51．5％（35／68）和41．8％（28／68）。HGF的表达与组织类型、分化程度无关（P〉0．05）。c-met的表达与组织类型、分化程度相关（P〈0．01，P〈0．005）。VEGF的表达与组织类型无关（P〉0．05）而与分化程度相关（P〈0．05）。HGF的表达与c-met的表达呈明显正相关（P=0．000，γ=0．471），HGF的表达与VEGF的表达亦呈明显正相关（P=0．000，7=0．662）。结论HGF、c-met及VEGF的增强表达与NSCLC发展演进和肿瘤血管生成有密切关系。     

Comparison of the Effects of Intravenously Bolus-administered Endothelin-1 and Infused Angiotensin II on the Subcutaneous Tumor Blood Flow in Anesthetized Rats

To evaluate the effects of endothelin-1 (ET-1) on tumor blood flow, the authors measured the mean arterial blood pressure (MABP) of enflurane-anesthetized male Donryu rats and the tissue blood flow of subcutaneously implanted tumor (Yoshida rat ascites hepatoma LY-80) by using a hydrogen clearance method. The tumor blood flow was evaluated in terms of the ratio to the maximum blood flow, which was defined as the largest flow in the same position during successive measurements. After bolus intravenous administration of ET-1 (1.0 nmol/kg), MABP reached approximately 140 mmHg (at 5 30 min), diminishing gradually to the baseline level over 2 h. The tumor blood flow increased from 36.7 ± 20.6 to 59.5 ± 30.2% (n = 32, P <0.001, at 2 min), returning to the baseline level at 10 min. On the other hand, at 2 min after the beginning of continuous intravenous infusion of [Asp¹, Ile⁵]-angiotensin II (AII; the dose was determined by a blood pressure control system for keeping MABP at approximately 150 mmHg, consequently 0.26 μg/kg/min on the average), the tumor blood flow increased from 42.3 ±21.6 to 76.4±22.6% (n = 32, P < 0.001), which was significantly larger than the flow after ET-1. The results indicate that hypertension induced by systemic ET-1 injection is less effective than hypertension induced by continuous systemic AII infusion in increasing tumor blood flow; AII is probably a suitable agent as a safe and effective enhancer of tumor blood flow. Moreover, ET-1 appears to constrict arterial vessels in the microcirculation time-dependently, while AII constricts probably only normal peripheral arterioles.     

Molecular Analysis of a Multistep Lung Cancer Model Induced by Chronic Inflammation Reveals Epigenetic Regulation of p16 and Activation of the DNA Damage Response Pathway

The molecular hallmarks of inflammation-mediated lung carcinogenesis have not been fully clarified, mainly due to the scarcity of appropriate animal models. We have used a silica-induced multistep lung carcinogenesis model driven by chronic inflammation to study the evolution of molecular markers and genetic alterations. We analyzed markers of DNA damage response (DDR), proliferative stress, and telomeric stress: γ-H2AX, p16, p53, and TERT. Lung cancer-related epigenetic and genetic alterations, including promoter hypermethylation status of p16(CDKN2A), APC, CDH13, Rassf1, and Nore1A, as well as mutations of Tp53, epidermal growth factor receptor, K-ras, N-ras, and c-H-ras, have been also studied. Our results showed DDR pathway activation in preneoplastic lesions, in association with inducible nitric oxide synthase and p53 induction. p16 was also induced in early tumorigenic progression and was inactivated in bronchiolar dysplasias and tumors. Remarkably, lack of mutations of Ras and epidermal growth factor receptor, and a very low frequency of Tp53 mutations suggest that they are not required for tumorigenesis in this model. In contrast, epigenetic alterations in p16(CDKN2A), CDH13, and APC, but not in Rassf1 and Nore1A, were clearly observed. These data suggest the existence of a specific molecular signature of inflammation-driven lung carcinogenesis that shares some, but not all, of the molecular landmarks of chemically induced lung cancer.     

大鼠放射性心脏损伤模型建立及其早期检测指标

目的:探索SD大鼠心脏15Gy分3次照射所致放射性心脏损伤模型的建立及其早期检测指标变化,并分析联合重组人血管内皮抑制素(Endostar)的影响。方法:75只SD成年雄性大鼠随机分为空白对照组(C组)、Endostar组(E组)、25Gy照射组(MHD 25组)、15Gy照射组(MHD 15组...