Mutation profile and its correlation with clinicopathology in Chinese hepatocellular carcinoma patients

BackgroundHepatocellular carcinoma (HCC) is one of the most common causes of cancer worldwide. Although many studies have focused on oncogene characteristics, the genomic landscape of Chinese HCC patients has not been fully clarified.MethodsA total of 165 HCC patients, including 146 males and 19 females, were enrolled. The median age was 55 years (range, 27–78 years). Corresponding clinical and pathological information was collected for further analysis. A total of 168 tumor tissues from these patients were selected for next-generation sequencing (NGS)-based 450 panel gene sequencing. Genomic alterations including single nucleotide variations (SNV), short and long insertions and deletions (InDels), copy number variations, and gene rearrangements were analyzed. Tumor mutational burden (TMB) was measured by an algorithm developed in-house. The top quartile of HCC was classified as TMB high.ResultsA total of 1,004 genomic alterations were detected from 258 genes in 168 HCC tissues. TMB values were identified in 160 HCC specimens, with a median TMB of 5.4 Muts/Mb (range, 0–28.4 Muts/Mb) and a 75% TMB of 7.7 Muts/Mb. The most commonly mutated genes were TP53, TERT, CTNNB1, AXIN1, RB1, TSC2, CCND1, ARID1A, and FGF19. SNV was the most common mutation type and C:G>T:A and guanine transformation were the most common SNVs. Compared to wild-type patients, the proportion of Edmondson grade III–IV and microvascular invasion was significantly higher in TP53 mutated patients (P<0.05). The proportion of tumors invading the hepatic capsule was significantly higher in TERT mutated patients (P<0.05). The proportion of Edmondson grade I-II, alpha fetoprotein (AFP) <25 µmg/L, and those without a history of hepatitis B was significantly higher in CTNNB1 mutated patients (P<0.05). CTNNB1 mutations were associated with TMB high in HCC patients (P<0.05). Based on correlation analysis, the mutation of TP53 was independently correlated with microvascular invasion (P=0.002, OR =3.096) and Edmondson grade III–IV (P=0.008, OR =2.613). The mutation of TERT was independently correlated with tumor invasion of the liver capsule (P=0.001, OR =3.030), and the mutation of CTNNB1 was independently correlated with AFP (<25 µmg/L) (P=0.009, OR =3.414).ConclusionsThe most frequently mutated genes of HCC patients in China were TP53, TERT, and CTNNB1, which mainly lead to the occurrence and development of HCC by regulating the P53 pathway, Wnt pathway, and telomere repair pathway. There were more patients with microvascular invasion and Edmondson III–IV grade in TP53 mutated patients and more patients with hepatic capsule invasion in TERT mutated patients, while in CTNNB1 mutated patients, there were more patients with Edmondson I–II grade, AFP <25 µmg/L, and a non-hepatitis B background. Also, the TMB values were significantly higher in CTNNB1 mutated patients than in wild type patients.     

肺癌侵犯膈肌6例外科治疗体会

对6例侵犯膈肌的非小细胞肺癌进行回顾性分析,其中肺叶切除4例,双肺叶切除1例,左全肺切除1例,6例均伴受侵膈肌切除+膈肌修复术,术后辅助化疗。结果表明,6例切除标本病理证实均为肺鳞状细胞癌侵犯膈肌,术前均未疑诊。2例N_0病人术后14、31个月健在,1例N_1病人术后25个月死亡。3例N_2病人分别于术后9、10、18个月死亡。因此,正确评价纵隔状态以采取不同的治疗组合是改善预后的关键。     

Mepyramine对肝脏疾病肝微粒体膜流动性的影响

目的:探讨Mepyramine对肝脏疾病肝微粒体膜流动性的影响.方法:以1,6-diphenyl-1,3,5-hexatriene(DPH)作为荧光探剂,应用荧光偏振技术研究大鼠急性肝炎、大鼠肝硬化肝微粒体膜流动性(LMMF)的变化,并在体外实验观察mepyramine(MPR)对LMMF的影响.结果:①LMMF在大鼠发生急性肝炎时升高,与对照组相比有显著性差异(P＜0.o1),而大鼠发生肝硬化时降低,与对照组相比有显著性差异(P＜0.05).②10-4mol/L MPR可使正常大鼠、大鼠肝硬化及人体肝癌组织LMMF升高(P分别小于0.01,0.01,0.05).结论:肝病时LMMF出现异常;MPR可以升高LMMF,其机制可能与阻断抗组胺药敏感性细胞色素P450(HP-450)有关.     

Triple approach for diagnosis and grading of meningiomas: Histology,morphometry of Ki-67/feulgen stainings,and cytogenetics

Summary With regard to meningioma grading and the recently introduced atypical meningioma, we evaluated 160 cases retrospectively by conventional histology and image analysis. For that, the cell nuclei were stained with a Ki-67 (MIB1)/Feulgen-method on paraffin sections, thus enabling the assessment of both the Ki-67 proliferation index and nuclear morphometric features, such as tumour cell arrangement, nuclear pleomorphism, and cellularity.It could be demonstrated that the Ki-67 proliferation index is the most important criterion for distinguishing anaplastic meningiomas (WHO grade III) (mean Ki-67 index: 11%) from those of common type (WHO grade I) (mean Ki-67 index: 0.7%). The parameter for the relative volume weighted mean nuclear volume is another valuable morphometric feature. The atypical meningioma (WHO grade II) which should represent an intermediate category between common type and anaplastic meningiomas is characterized by a mean Ki-67 proliferation index of 2.1%. Common type meningiomas which comprise almost 50% of the cases of this series have a relapse rate of 9%. Atypical and anaplastic meningiomas recurred in 29% and 50%, respectively. Since the term atypical meningioma is confusing in the context of tumour grading, the term intermediate type meningioma is proposed.Furthermore, the results of cytogenetic analyses of 142 cases of this series were evaluated and compared with the meningioma grades. Thereby, 25 cases disclosed, independent of the typical loss of one chromosome 22, cytogenetic features assumed to be progression-associated, e.g., the gain or loss of different chromosomes and the deletion of the short arm of one chromosome 1 (hyperdiploidy, increased hypodiploidy, Ip-), when correlated to the histological and morphometric findings or the high relapse rate.For meningioma diagnosis and grading, a practical guideline is proposed based upon histology, morphometry (Ki-67), and cytogenetics.     

The yeast two-hybrid system reveals no interaction between p73α and SV40 large T-antigen

Summary.  SV40 and/ or DNA sequences indistinguishable from SV40 have been detected in several types of human tumours. The oncoprotein of Simian virus 40, SV40 large T-antigen (Tag), is known to bind and inactivate tumour suppressor proteins, such as members of the retinoblastoma family and p53, thereby promoting cell transformation. In this study, we used the yeast two-hybrid system to investigate whether the Simian virus 40 (SV40) large T-antigen is able to interact with p73, a noval discovered putative tumour suppressor, that is homologous both structurally and functionally to p53. The yeast two-hybrid system is a genetic method to detect protein-protein-interactions in vivo. Our results suggest that the SV40 large T-antigen is not able to bind p73 in yeast although both proteins are expressed in the transformed yeast strain as was shown by western blot analysis. Received May 20, 1998 Accepted September 28, 1998     

小鼠树突状细胞过继转移抗原作用的实验研究

用绵羊红细胞（SRBC）免疫小鼠,取其脾脏分离树突状细胞（dendriticcellsDCs）将这些带有抗原信息的DCs经尾静脉注射给小鼠．以观察DCs过继转移抗原的作用。结果表明,各试验组小鼠抗体形成细胞（AFC）及血清中SRBC处价明显高于对照组,P＜0．01,再次免疫DC组抗SRBC放价高于初次免疫DC组P＜0．05,提示：DCs具有过继转移抗原的作用。     

胰高血糖素对胆道梗阻大鼠肝脏葡萄糖和酮体合成的作用

目的观察胰高血糖素对胆道梗阻大鼠肝脏葡萄糖和酮体合成作用的影响。方法大鼠胆道结扎４８小时后,用胶原酶灌流后分离肝细胞,加入胰高血糖素温育,用分光光度计按标准酶学方法检测葡萄糖、乙酰乙酸和三羟基丁酸。结果在基础或最大刺激条件下,加胰高血糖素结扎组、假手术组葡萄糖异生均明显大于未加胰高血糖素组（Ｐ＜０．０５）,加胰高血糖素对结扎组和假手术组的酮体异生无促进作用。结论胰高血糖素对胆道梗阻４８小时大鼠肝细胞的糖异生存在有意义的刺激作用,对酮体异生则无刺激作用     

格列齐特致畸作用观察

目的观察国产格列齐特的致畸作用。②方法对受孕后第６天Ｗｉｓｔａｒ大鼠分别以８５,１７０,６８０ｍｇ／ｋｇ体质量的国产格列齐特（容积为５ｍＬ／ｋｇ体质量）灌胃给药,每天１次,连用１０ｄ;同步设立生理盐水组和敌枯双（５ｍｇ／ｋｇ体质量）对照组。于妊娠第２０天剖腹,取出胎鼠,观察并记录各组活胎数、死胎数以及活胎鼠生长发育等情况。③结果格列齐特各剂量组胚胎数损失率、活胎生长、发育等指标与生理盐水组相比,差异均无显著性（χ２＝０．３７５～３．０９８,Ｐ＞０．０５;Ｆ＝０．０３２～０．１７８,Ｐ＞０．０５）。④结论国产格列齐特无致畸作用     

无框架脑立体定向手术

目的：应用国产ＣＲＡＳ－ＢＨ２型机器人系统（ｃｏｍｐｕｔｅｒ ａｎｄ ｒｏｂｏｔ ａｓｓｉｓｔｅｄ ｓｕｒｇｅｒｙ,ｔｙｐｅ ＢＨ２）,临床实施３０例无框回脑立体定向手术。方法：机器人系统由智能机械臂影像引导装置、三维定位软件等模块组成,该系统取代了传统的定向仪框架,通过识别贴附是头部的标志点,建立相庆的三维坐标体系,并可自动标出靶点位置和穿刺轨迹。智能机械臂按照模拟轨迹固定方向,为术者提供准确导     

高龄高危肺癌患者外科治疗（附41例报告）

目的:为了探讨高龄高危肺癌患者的外科治疗经验.方法和结果:作者对1989年6月～1997年5月手术切除的41例高龄高危肺癌患者进行分析,由于强化围术期管理和正确处理并发症,取得了满意的治疗效果,全组无住院死亡.作者强调积极术前准备,创造有利手术条件,选择合理手术方法,加强术后心功能保护及呼吸道管理,特别是环甲膜穿刺注药刺激咳嗽排痰,气管镜检查吸痰、抗菌素药液支气管灌洗及酌情合理使用呼吸机等.结论:上述措施均为扩大手术适应范围安全度过手术难关创造了十分有利的条件.