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| 1 | DNA-PKcs subunits in radiosensitization by hyperthermia on hepatocellular carcinoma hepG_2 cell line显示文摘AIM: To investigate the role of DNA-PKcs subunits inradiosensitization by hyperthermia on hepatocellularcarcinoma HepG2 cell lines.METHODS: Hep G2 cells were exposed to hyperthermiaand irradiation. Hyperthermia was given at 45.5 ℃Cellsurvival was determined by an in vitro clonogenic assay forthe cells treated with or without hyperthermia at varioustime points. DNA DSB rejoining was measured usingasymmetric field inversion gel electrophoresis (AFIGE). TheDNA-PKcs activities were measured using DNA-PKcs enzymeassay system.RESULTS: Hyperthermia can significantly enhanceirradiation-killing cells. Thermal enhancement ratio ascalculated at 10 % survival was 2.02. The difference inradiosensitivity between two treatment modes manifestedas a difference in the α components and the almost sameβ components, which α value was considerably higher inthe cells of combined radiation and hyperthermia ascompared with irradiating cells (1.07 Gy-1 versus 0.44 Gy1). Survival fraction showed 1 logarithm increase after an8-hour interval between heat and irradiation, whereas DNA-PKcs activity did not show any recovery. The cells wereexposed to heat 5 minutes only, DNA-PKcs activity wasinhibited at the nadir, even though the exposure time waslengthened. Whereas the ability of DNA DSB rejoining wasinhibited with the increase of the length of hyperthermictime. The repair kinetics of DNA DSB rejoining aftertreatment with Wortmannin is different from thehyperthermic group due to the striking high slow rejoiningcomponent.CONCLUSION: Determination with the cell extracts andthe peptide phosphorylation assay, DNA-PKcs activity wasinactivated by heat treatment at 45.5 C, and could notrestore. Cell survival is not associated with the DNA-PKcsinactivity after heat. DNA-PKcs is not a unique factor affectingthe DNA DSB repair. This suggests that DNA-PKcs do notplay a crucial role in the enhancement of cellularradiosensitivity by hyperthermia. | Walter J.Curran George Iliakis | 2002 | World Journal of Gastroenterology2002，8，5： | 87 |
| 2 | Immunohistochemical analysis of p53,cyclinD1,RB1,c-fos and N-ras gene expression in hepatocellular carcinoma in Iran显示文摘AIM: To study the effect of some genes especially those involved in cell cycle regulation on hepatocellular carcinoma. METHODS: Paraffin-embedded tissue samples of 25 patients (18 males and 7 females) with hepatocellular carcinoma were collected from 22 pathology centers in Tehran during 2000-2001, and stained using immunohistochemistry method (avidin-biotin-peroxidase) for detection of p53, cyclinD1, RB1, c-fos and N-ras proteins. RESULTS: Six (24%), 5 (20%), 12 (48%) and 2 samples (8%) were positive for p53, cyclinD1, C-fos and N-ras expression, respectively. Twenty-two (88%) samples had alterations in the G1 cell-cycle checkpoint protein expression (RB1 or cyclinD1). P53 positive samples showed a higher (9 times) risk of being positive for RB1 protein than p53 negative samples. Loss of expression of RB1 in association with p53 over-expression was observed in 4 (66.7%) of 6 samples. Loss of expression of RB1 was seen in all cyclinD1 positive, 20 (90.9%) N-ras negative, and 11 (50%) C-fos positive samples, respectively. CyclinD1 positive samples showed a higher (2.85 and 4.75 times) risk of being positive for c-fos and N-ras expression than cyclinD1 negative samples. CONCLUSION: The expression of p53, RB1 and c-fos genes appears to have a key role in the pathogenesis of hepatocellular carcinoma in Iran. Simultaneous overexpression of these genes is significantly associated with their loss of expression during development of hepatocellular carcinoma. | SJ Moghaddam EN Haghighi S Samiee N Shahid AR Keramati S Dadgar MR Zali | 2007 | World Journal of Gastroenterology2007，13，4： | 73 |
| 3 | Detection of HBV, PCNA and GST-π in hepatocellular carcinoma and chronic liver diseases显示文摘AIM: To investigate the change of HBV DNA, PCNA and GST-π in chronic liver disease and hepatocellular carcinoma (HCC).METHODS: Hepatitis B surface antigen (HBsAg), proliferating cell nuclear antigen (PCNA) and glutathione S-transferases (GST-π) were detected by immunohistochemical staining and HBV DNA was detected by in situ hybridization (ISH) in formalin-fixed and paraffin-embedded sections with a total of 111 specimens of chronic hepatitis, liver cirrhosis,paratumorous tissue, HCC and normal liver tissue.RESULTS: The positive rates of HBsAg and HBVDNA were 62.5 %(15/24) and 75.0 %(12/16) in chronic hepatitis,64.0 %(16/25) and 83.3 %(15/18) in liver cirrhosis, 72.7 %(16/22) and 85.7 %(12/14) in the paratumorous tissu and 45.0 %(14/31) and 64.3 %(9/14) in HCC. The positive HBVDNA granules in chronic hepatitis, liver cirrhosis and the paratumorous tissue were more intense than that in HCC.The positive rates of PCNA and GST-π were 34.8 %(8/23)and 25.0 %(4/16) in chronic hepatitis, 73.7 %(14/19) and 17.6 %(3/17) in liver cirrhosis, 86.7 %(13/15) and 53.3 % (8/15) in the paratumorous tissue, 100 %(15/15) and 60.0 %(9/15) in HCC, respectively, and the positive rate of GST-πin the paratumorous tissue was significantly higher than that in the liver cirrhosis without tumor (P<0.05), but same as that in HCC(P>0.05).CONCLUSION: The HBV infection may increase expression of PCNA and GST-π. The paratumor cirrhosis may be a sequential lesion of precancerous cirrhosis around HCC. | Li-JuanShen, Hua-XianZhang Zong-JiZhang Jin-YunLi Ming-QinChen Wei-BoYang RunHuang | 2003 | World Journal of Gastroenterology2003，9，3： | 31 |
| 4 | Expression of p53 and C-myc genes and its clinical relevance in the hepatocellular carcinomatous and pericarcinomatous tissues显示文摘AIM: To investigate the possible roles of p53 and C-mycgenes in the primary hepatocellular carcinogenesis and therelationship between the liver hyperplastic nodule(LHN) andhepatocellular carcinoma(HCC).METHODS: The expression of p53 and C-myc genes wasdetected immunohist-ochemically in 73 and 60 cases of HCCand pericarcinomatous tissues, respectively .RESULTS: The positive expression of p53 in HCC wassignificantly higher than that in pericarcinomatous tissues(P<0.05). In pericarcinomatous tissues, the p53 expressionwas observed only in LHN, but not in liver cirrhosis (LC) andnormal liver tissues. The positive expression rate of C-mycin HCC or LHN was significantly higher than that in LC ornormal liver tissues (P<0.05 and P<0.01), however, nosignificant difference was found between HCC and LHN(P>0.05). The positive expression rate of p53 and C-myc inHCC was correlated with the histological differentiation, thatin the poorly differentiated was significantly higher than thatin well differentiated samples (P<0.05).CONCLUSION: The overexpression of p53 and C-myc genesmight play a role in the carcinogenesis of HCC; And LHNseems a preneoplastic lesion related to hepatocarcinogenesis;No evidence supports that LC contribute directly to thehepatocarcinogenesis. | Zhao-Shan Niu Bo-Kian Li Department of Pathology,Medical College of Qingdao University,Qingdao 266021,Shandong Province,China Mei Wang Department of Foreign languages,Qingdao institute of Architecture and Engineering,Qingdao 266033,Shandong Province,China | 2002 | World Journal of Gastroenterology2002，8，5： | 30 |
| 5 | p53 gene therapy in combination with transcatheter arterial chemoembolization for HCC:One-year follow-up显示文摘AIM:To evaluate the efficacy and safety of combination therapy with recombinant adenovirus p53 injection (rAdp53) and transcatheter hepatic arterial chemoembolization (TACE) for advanced hepatocellular carcinoma (HCC).METHODS:A total of 82 patients with advanced HCC treated only with TACE served as control group.Another 68 patients with HCC treated with TACE in combination with recombinant adenovirus-p53 injection served as p53 treatment group.Patients were followed up for 12 mo.Safety and therapeutic effects were evaluated according to the improvement in clinical symptoms,leukocyte count,Karnofsky and RECIST criteria.Survival rate was calculated with Kaplan-Meier method.RESULTS:The total effective rate was 58.3% for p53 treatment group,and 26.5% for control group (P < 0.05).The incidence of gastrointestinal symptoms was lower in p53 treatment group than in control group (P < 0.05).The 3-,6-and 12-mo survival rates were significantly higher for p53 treatment group than for control group (P < 0.01).The combination treatment was well tolerated with such adverse events as fever (51.5%,P=0.006) and pain of muscles and joints (13.2%,P=0.003),which were significantly higher than the chemotherapy.Except for these minor adverse effects,no severe vector-related complications were identified.With respect to the efficacy,patients in p53 treatment group had less gastrointerestinal symptoms (P=0.062),better improvement in tumor-related pain (P=0.003),less downgrade of leukocyte counts (P=0.003) and more upgrade of Karnofsky performance score (P=0.029) than those in control group.The total effective rate (CR + PR) for p53 treatment group and control group was 58.3% and 26.5%,respectively,with distributions of different effect in two groups (P=0.042).The survival rates were 89.71%,76.13%,and 43.30% for p53 treatment group,and 68.15%,36.98%,and 24.02% for control group,respectively,3,6 and 12 mo after treatment,suggesting that the survival rates are significantly higher for p53 treatment group than for control group (P=0.0002).CONCLUSION:The rAd-p53 gene therapy in combination with TACE is a safe and effective treatment modality for advanced HCC. | Yong-Song Guan Yuan Liu Qing He Xiao Li Lin Yang Ying Hu Zi La | 2011 | World Journal of Gastroenterology2011，17，16： | 21 |
| 6 | Codon 249 mutation in exon 7 of p53 gene in plasma DNA:maybe a new early diagnostic marker of hepatocellular carcinoma in Qidong risk area,China显示文摘AIM: One of the characteristics of hepatocellular carcinoma (HCC) in Qidong area is the selective mutation resulting in a serine substitution at codon 249 of the p53 gene (1,20),and it has been identified as a 'hotspot' mutation in heptocellular carcinomas occurring in populations exposed to aflatoxin and with high prevalence of hepatitis B virus carriers (2, 3, 9, 10, 16, 24). We evaluated in this paper whether this 'hotspot' mutation could be detected in cellfree DNA circulating in plasma of patients with hepatocellular carcinoma and cirrhosis in Qidong, China, and tried to illustrate the significance of the detection of this molecular biomarker.METHODS: We collected blood samples from 25hepatocellular carcinoma patients, 20 cirrhotic patients and 30 healthy controls in Qidong area. DNA was extracted and purified from 200 μl of plasma from each sample. The 249ser p53 mutation was detected by restriction digestion analysis and direct sequencing of exon-7 PCR products.RESULTS: We found in exon 7 of p53 gene G→T transversion at the third base of codon 249 resulting 249Arg→249ser mutation in 10/25 (40%) hepatocellular carcinoma cases,4/20 (20%) cirrhotics, and 2/30 (7 %) healthy controls.The adjusted odds ratio for having the mutation was 22.1(95 % CI, 3.2~91.7) for HCC cases compared to controls.CONCLUSION: These data show that the 249ser p53mutation in plasma is strongly associated with hepatocellular carcinoma in Qidong patients. We found this mutation was also detected, although it was at a much lower frequency,in plasma DNA of Qidong cirrhotics and healthy controls;We consider that these findings, together with the usual method of HCC diagnosis, will give more information in early diagnosis of HCC, and 249ser p53 mutation should be developed to a new early diagnostic marker for HCC. | Xing-HuaHuang Lu-HongSun Dong-DongLu YanSun Li-JieMa Xi-RanZhang JianHuang LongYu | 2003 | World Journal of Gastroenterology2003，9，4： | 18 |
| 7 | Effect of arsenic trioxide on rat hepatocarcinoma and its renal cytotoxicity显示文摘AIM: To study the effect of arsenic trioxide (As2O3) on rat experimental hepatocarcinoma and its renal cytotoxicity.METHODS: The hepatocarcinoma model was established by diethaylnitrosamine perfusion in stomach of 120 Wistar rats, and the treatment began at the end of 20 weeks.Before the treatment, the rat models were randomly divided into 5 groups. In the treatment groups, three doses of As2O3 were injected into rat abdominal cavity, the total time of drug administration was 4 weeks. Cisplatin control or the blank group was injected into abdominal cavity with equal amount of cisplatin or saline at the same time,respectively. On the 7th, 14th and 28th day after the treatment, the hepatocarcinoma nodules were obtained and the morphologic changes of hepatocarcinoma cells were observed under light and electron microscopes;Immunohistochemistry (S-P methods) was employed to detect the expression of bcl-2, bax and PCNA in hepatocarcinoma tissues; flow cytometry (TUNEL assay)was used to detect the apoptosis of liver cancer cells and the change of cytokinetics. On the 28th day, the kidneys were obtained and their histologic changes were observed under light microscope, and immunohistochemistry (SP stain) was also employed to detect the expression of bcl-2and PCNA. Cisplatin and saline solution were used as the control.RESULTS: As2O3 could induce the apoptosis of rat liver cancer cells and exhibited typical morphologic changes.The incidence of apoptosis of hapatocarcinoma cells was elevated (P=0.001). The elevation was the most higher in the group of middle-dose of As2O3 (1 mg.kg-1), significantly higher than that of the other arsenic groups and the controls (P=0.001). Large dose of As2O3 (5 mg.kg-1) was able to arise the incidence of apoptosis, but also produced a large amount of necrosis and inflammatory reaction. Middle dose of As2O3 dramatically increased the cell number in G2/M phase (P=0.0001), and apoptosis happened apparently.The expression of bcl-2 and bax was related to the dose of As2O3. With the up-regulation of apoptotic incidence, the ratio of bcl-2/bak decreased. But the incidence of apoptosis was not the highest status and the ratio of bcl-2/bax was at the lowest when the highest-dose of As2O3 was used.There was significant difference among the PCNA indexes (PCNA L1) of the five groups. Of them, three arsenic groups all showed decrease of different degrees, and this downregulation was most obvious in group A. There was significant difference among the three groups (P=0.016).Under the light microscope, the rat kidney in the cisplatin group exhibited tubular epithelium swelling and degeneration, protein casts in collecting tubules; While all arsenic groups didn't show the significant changes (P=0.013).In the arsenic groups, the expression of bcl-2 in the renal tubular epithelium was increased (P=0.005), no obvious changes happened to PCNA L1. But in the group of cisplatin,the PCNA L1 increased significantly (P=0.001).CONCLUSION: AS2O3 can induce apoptosis of rat hepatocellular carcinoma cells. And there is optimum dose;too high dose will induce the cytotoxic effect, while certain dose of As2O3 is able to block the cell cycle at G2/M phase.As2O3 had the most remarkable influence on G2/M cells,and it can also induce apoptosis to cells at other phases.As2O3 can restrain the proliferation of rat hepatocellular carcinoma cells, in a dose-time dependent manner.Compared with cisplatin, As2O3 didn't show obvious renal toxicity, which was related to the increasing expression of bcl-2 in renal tubular epithelium, the inhibition of apoptosis and the anti-oxidation effects. | Shao-Shan Wang Ti Zhang Xi-Lu Wang Li Hong Department of Surgery of Dagang Hospital 300270,Tianjin,China Qing-Hui Qi Department of Chinese and Western Integral Surgery of Master Hospital of Tianjin Medical University 300052,Tianjin,China | 2003 | World Journal of Gastroenterology2003，9，5： | 17 |
| 8 | COX-2在胰腺癌组织中的表达及其与p53的相关性研究显示文摘目的:探讨环氧化酶-2(COX-2)和p53在胰腺癌组织中的表达与生物学行为之间的关系并探讨二者的相关性及可能机制.方法:用免疫组织化学Envision法对51例胰腺导管癌和11例癌旁非肿瘤胰腺组织的COX-2和p53的表达进行检测.结果:51例胰腺导管癌中COX-2和p53蛋白的表达率分别为74.5%和60.8%;二者在11例癌旁非肿瘤胰腺组织中均未发现阳性表达.COX-2的表达与临床分期和淋巴结转移有关(P=0.022,0.036),而与组织学分级关系不大(P=0.152);p53的表达与淋巴结转移有关(P=0.035),而与组织学分级、临床分期关系不大(P=0.131,0.078);COX-2的表达与p53的表达密切相关(r=0.452,P=0.001).二者的表达与患者的性别、年龄、肿瘤的大小、部位均无关.结论:COX-2和p53的协同作用可能在胰腺癌的发生发展过程中起重要作用,可能为胰腺癌的治疗提供了新的靶点. | 刘江伟 李开宗 窦科峰 | 2003 | 世界华人消化杂志2003，11，2： | 14 |
| 9 | 中药复方胃肠安血清诱导肝癌SMMC-7721细胞分化显示文摘目的:观察中药复方胃肠安诱导肝癌细胞分化的作用.方法:以SMMC-7721人肝癌细胞为研究对象,维甲酸为对照,采用药物血清添加法,通过 MTT法和 Alamar Blue法观察胃肠安对肝癌细胞增生的抑制作用;放射免疫法观察对肝癌细胞分泌甲胎蛋白和白蛋白的影响;Western blot观察对肝癌细胞P53、P16以及P21蛋白表达的影响.结果:MTT法显示胃肠安与维甲酸对SMMC-7721人肝癌细胞增生均有抑制作用,胃肠安在48 h达到最大,而维甲酸对细胞增生的抑制作用在48 h后逐渐下降,较胃肠安组明显降低.Alamar Blue法结果显示,16 h后,胃肠安组细胞还原的 Alamar Blue值较对照组明显减少,并在32 h后较维甲酸组显著下降,提示与维甲酸相比,胃肠安作用起效慢但持续时间长;胃肠安组分泌的甲胎蛋白较对照组显著减少(11.4 ±1.4μg/L vs 17.2 ± 1.1μg/L,P=0.036),而白蛋白显著增多(0.40 ± 0.02mg/L vs 0.29 ± 0.01mg/L,P=0.043);胃肠安组突变型P53蛋白的表达较对照组明显减少,而P16蛋白和P21蛋白的表达较对照组增多.结论:胃肠安方剂具有抑制SMMC-7721人肝癌细胞增生、诱导细胞分化的作用,其机制可能在于减少突变型P53蛋白表达和增加P16,P21蛋白表达。 | 赵海磊 刘成 赵爱光 | 2003 | 世界华人消化杂志2003，11，9： | 13 |
| 10 | 人工智能时代的病理组学显示文摘在人工智能时代,计算机辅助的病理诊断为病理学提供了新的发展空间,病理学的研究不再局限于医师人工分析病理切片。在人工智能的辅助下,计算机不但可以实现定量化病理诊断,还可完成疾病预后等病理学的相关研究。该文通过总结近10年来人工智能在病理学中的研究成果,提出病理组学的概念。病理组学的研究内容包括基于人工智能将病理图像转化为高保真度、高通量的可挖掘的数据,并用于定量化病理诊断和疾病预后,最后自动生成病理诊断报告。在人工智能技术的支撑下,病理组学的研究正向着更加自动化更加精准的方向发展,这也有益于充分利用现有医疗资源、节省研究成本、推动医疗发展。 | 闫雯 李楠楠 张益肇 来茂德 许燕 | 2018 | 临床与实验病理学杂志2018，34，6： | 7 |
| 11 | Biological characteristics of HCC by ultrasound-guided aspiration biopsy and its clinical application显示文摘AIM: To probe the pathological biological characteristics of hepatocellular carcinoma (HCC) by the ultrasound-guided aspiration biopsy and assess the clinical application value of this method.METHODS: The biopsy and DNA analysis by flow cytometry (FCM) were taken in 46 cases with HCC nodules, including 26 cases and 20 cases with nodules ≤3 cm and >3 cm in diameters respectively, and 12 cases with intrahepatic benign hyperplastic nodules. They were taken in 22 cases of 46cases with HCC before and after the therapy. Fine-needles and automatic histological incised biopsy needles were used.The fresh biopsy tissue was produced into the single cell suspension, which was sent for DNA detection and ratio analysis of cell period. The ratio of each DNA period of cell proliferation of each group was calculated and compared with each other. The DNA aneuploid (AN) and apoptosis cell peak were observed and their percentages were calculated.RESULTS: The ratios of S and G2/M periods of DNA, which reflect cell hyperproliferation, in the group with HCC tumors >3 cm in diameter were markedly higher than those of the group with HCC nodules ≤3 cm in diameter and the group with the benign hyperplastic nodules (P<0.01 except A:B of S period, P<0.05). The ratios of the middle group were also apparently higher than those of the latter group (P<0.01).The ratio of DNA AN of 46 cases with HCC nodules was 34.8 % (16/46). None of the cases with the intrahepatic hyperplastic nodules appeared AN. The DNA AN appeared more apparently with the growth of the tumors. The AN ratio of the group with tumors >3 cm in diameter was 55 %(11/20), markedly higher than that of the group with tumors ≤3 cm in diameter which was 19.2 % (5/26) (P<0.01). The FCM DNA analysis of 22 specimens of hepatic carcinoma tissue before therapy showed that the aneuploid peaks appeared in 5 cases (22.7 %). The ratio of G1 period rose after therapy while the S period and G2/M ratios fell (P<0.01).The aneuploid peak disappeared in the 5 cases after the therapy, while the apoptosis peaks in 12 cases (54.5 %)appeared.CONCLUSION: Addition to supply the information of the pathological morphology of the tumor, the ultrasound-guided fine-needle aspiration tissue could be sent for FCM DNA analysis to comprehend its pathological biological characteristics. This can not only provide the clinic the reliable information about the occurrence, development,diagnosis, curative effect and prognosis of tumors but also supply biological information for clinic to choose therapeutic schemes. | Li-Wu Lin Xue-Ying Lin Yi-Mi He Shang-Da Gao Xiao-Dong Lin Fujian Provincial Ultrasonic Medicine Institute,Ultrasound Department,Union Hospital of Fujian Medical University,Fuzhou 350001,Fujian Province,China | 2003 | World Journal of Gastroenterology2003，9，5： | 7 |
| 12 | Maxizyme-mediated specific inhibition on mutant-type p53 in vitro显示文摘AIM: To evaluate the specific inhibition of maxizyme directing against mutant-type p53 gene (mtp53) at codon 249 in exon 7 (AGG→AGT)in vitro.METHODS: Two different monomers of anti-mtp53maxizyme (maxizyme right MzR, maxizyme left MzL) and control mutant maxizyme (G5→A5) were designed by computer and cloned into vector pBSKU6 (pBSKU6MzR,pBSKU6MzL). After being sequenced, the restrictive endonuclease site in pBSKU6MzR was changed by PCR and then U6MzR was inserted into pBSKU6MzL, the recombinant vector was named pU6Mz and pU6asMz (mutant maxizyme).Mtp53 and wild-type p53 (wtp53) gene fragments were cloned into pGEN-T vector under the T7 promoter control.The 32p-labeled mtp53 transcript was the target mRNA. Cold maxizyme transcripts were incubated with 32p-labeled target RNA in vitro and radioautographed after denaturing polyacrylamide gel electrophoresis.RESULTS: In cell-free systems, pU6Mz showed a specific cleavage activity against target mRNA at 37 ℃ and 25 mM MgCL2. The cleavage efficiency of pU6Mz was 42 %, while pU6asMz had no inhibitory effect. Wtp53 was not cleaved by pU6Mz either.CONCLUSION: pU6Mz had a specific catalytic activity against mtp53 in cell-free system. These lay a good fundation for studying the effects of anti-mtp53 maxizyme in HCC cell lines. The results suggest that maxizyme may be a promising alternative approach for treating hepatocellular carcinoma containing mtp53. | Xin-JuanKong Yu-HuSong Ju-ShengLin Huan-JunHuang Nan-XiaWang Nan-ZhiLiu BinLi You-XinJin | 2003 | World Journal of Gastroenterology2003，9，7： | 6 |
| 13 | 经动脉灌注rAd-p53联合TAE治疗中晚期肝癌的疗效观察显示文摘目的 探讨经动脉灌注重组人p53腺病毒注射液联合碘化油栓塞治疗中晚期肝癌的安全性及有效性。方法 回顾性分析2012年5月至2015年6月采用经肿瘤供血动脉灌注重组人p53腺病毒注射液联合碘化油栓塞治疗的31例中晚期原发性肝癌患者的临床资料。所有入组患者均为无法行外科手术治疗的中晚期肝癌患者。患者介入术程顺利,术后采用改良实体瘤评价标准(mRECIST)评价临床疗效。采用SPSS 18.0软件进行统计分析。结果 31例患者共进行76次(平均每例2.4次)介入治疗。随访3-36个月,术后3、6、12个月完全缓解率(CR)均为0,部分缓解率分别为58.1%、38.7%、29%,总有效率分别为58.1%、38.7%、29%;6个月、1年及2年的总生存率分别为77.4%、58.1%、19.3%;6个月、1年及2年的无进展生存率分别为38.7%、25.8%、12.9%。全组患者均未见急性肝衰竭、肝脓肿、肺栓塞等严重并发症,术后87.1%患者出现发热。结论 采用经动脉灌注重组人p53腺病毒注射液联合TAE治疗中晚期肝癌具有良好的安全性和有效性,为中晚期肝癌提供了一种新的治疗选择。 | 刘丽 卲天朋 杨涛 曹建民 卢光明 许健 | 2016 | 介入放射学杂志2016，25，3： | 6 |
| 14 | Hepatocellular Tumors:Immunohistochemical Analyses for Classification and Prognostication显示文摘Following the classification of hepatocellular nodules by the International Working Party in 1995 and further elaboration by the International Consensus Group for Hepatocellular Neoplasia in 2009,entities under the spectrum of hepatocellular nodules have been better characterized.Research work hence has been done to answer questions such as distinguishing high-grade dysplastic nodules from early hepatocellular carcinoma (HCC),delineating the tumor cell origin of HCC,identifying its prognostic markers,and subtyping hepatocellular adenomas.As a result,a copious amount of data at immunohistochemical and molecular levels has emerged.A panel of immunohistochemical markers including glypican-3,heat shock protein 70 and glutamine synthetase has been found to be of use in the diagnosis of small,well differentiated hepatocellular tumors and particularly of HCC.The use of liver fatty acid binding protein (L-FABP),β-catenin,glutamine synthetase,serum amyloid protein and C-reactive protein is found to be helpful in the subtyping of hepatocellular adenomas.The role of tissue biomarkers for prognostication in HCC and the use of biomarkers in subclassifying HCC based on tumor cell origin are also discussed. | Regina Cheuk-Lam Lo Irene Oi-Lin Ng | 2011 | Chinese Journal of Cancer Research2011，23，4： | 5 |
| 15 | 肝细胞癌预后生物标识物的研究进展显示文摘肝细胞癌(HCC)是世界上最常见的恶性肿瘤之一,位居全球恶性肿瘤发病率男性第5位,女性第8位,每年新发病56.4万例。高发的地理区域包括东亚、中非和西非的一些国家。在美国等发达国家其发病率也在增长。 | 郭婧 李强 | 2007 | 中华实验外科杂志2007，24，7： | 3 |
| 16 | Precision medicine: In need of guidance and surveillance显示文摘Precision medicine,currently a hotspot in mainstream medicine,has been strongly promoted in recent years. With rapid technological development,such as next-generation sequencing,and fierce competition in molecular targeted drug exploitation,precision medicine represents an advance in science and technology; it also fulfills needs in public health care. The clinical translation and application of precision medicine-especially in the prevention and treatment of tumors-is far from satisfactory; however,the aims of precision medicine deserve approval. Thus,this medical approach is currently in its infancy; it has promising prospects,but it needs to overcome numbers of problems and deficiencies. It is expected that in addition to conventional symptoms and signs,precision medicine will define disease in terms of the underlying molecular characteristics and other environmental susceptibility factors. Those expectations should be realized by constructing a novel data network,integrating clinical data from individual patients and personal genomic background with existing research on the molecular makeup of diseases. In addition,multi-omics analysis and multi-discipline collaboration will become crucial elements in precision medicine. Precision medicine deserves strong support,and its development demands directed momentum. We propose three kinds of impetus(research,application and collaboration impetus) for such directed momentum toward promoting precision medicine and accelerating its clinical translation and application. | Jian-Zhen Lin Jun-Yu Long An-Qiang Wang Ying Zheng Hai-Tao Zhao | 2017 | World Journal of Gastroenterology2017，23，28： | 3 |
| 17 | 骨桥蛋白对乙型肝炎病毒相关肝细胞肝癌根治性肝切除术后患者预后的预测价值显示文摘目的探讨骨桥蛋白(OPN)、P53、血管内皮生长因子(VEGF)在乙型肝炎病毒(HBV)相关月.F细胞肝癌(肝癌)组织中的表达情况,以及OPN表达与根治性切除fR0)术后短期复发和预后的关系。方法回顾性研究2003年1月至2008年12月在青岛大学医学院附属医院肝胆外科行RO切除术的237例HBV相关肝癌标本。患者男204例,女33例;年龄15-82岁,中位年龄54岁。患者均签署知情同意书,符合医学伦理学规定。另取肿瘤旁lcm内的癌旁组织81例和肝硬化活组织检查(活检)标本79例作为对照组。应用组织:苍片技术和免疫组织化学PV一6000二步法检测HBV相关肝癌组织中OPN、P53、VEGF表达阳性率。采用Ⅳ。检验比较肝癌组织的OPN表达与患者临床病理学参数、P53、VEGF的关系;采用Kaplan。Meier法和Log—rank检验法进行生存分析,采用Cox比例风险回归模型进行肿瘤短期复发和生存预后的危险因素分析。结果所有肝癌患者均接受随访,随访时间1-102个月,中位随访时间43个月。术后短期复发55例,其中肝内复发占56%(31/55),肝外转移占44%(24/55);非短期复发89例,其中肝内复发占80%(71/89),肝外转移占20%(18/89)。OPN在肝癌组织、癌旁组织和肝硬化组织中的表达阳性率分别为37%(88/237)、17%(14/81)和14%(11/79),肝癌组织与癌旁组织、肝硬化组织的OPN表达阳性率比较差异有统计学意义(矿=12.44,16.53;P〈0.05)。短期复发患者OPN表达阳性率5l%(28/55),非短期复发者35%(31/89),无复发患者OPN表达阳性率31%(29/93),短期复发组OPN表达阳性率明显高于非短期复发组和无复发组(矿=4.181,5.679;P=0.041、0.017)。肝癌组织P53表达阳性率为26%(61/237),VEGF表达阳性率为77.2%(183/237)。OPN阳性组P53、VEGF表达阳性率均明显高于阴性组,差异有统计学意义(矿:6.947,4.14;P〈O.05)。血清甲胎蛋白(AFP)≥400txg/L、有卫星灶、血管有癌栓、组织学中低分化和TNM分期Ⅲ~Ⅳ期者OPN表达阳性率明显升高(均为P〈0.05)。OPN表达阳性组的中位生存期为49.6个月,明显低于阴性组84.0个月;两组生存率比较差异有统计学意义(Y。=5.916,P=O.015)。OPN阳性是HBV相关肝癌患者术后短期复发和生存预后的独立危险因素。结论HBV相关肝癌组织中OPN阳性表达增高,OPN与P53、VEGF的表达有关系;OPN的阳性表达是HBV相关肝癌患者术后短期复发和生存预后的独立危险因素,肝癌组织OPN阳性表达预示短期复发率高,预后不良。 | 王祖森 吴力群 李玉军 姚如勇 伊鑫 耿超 胡维昱 韩冰 | 2013 | 中华肝脏外科手术学电子杂志2013，2，2： | 3 |
| 18 | 裸鼠肝内种植人肝癌组织的肿瘤特征显示文摘目的:观察裸鼠肝内种植人肝癌组织能否再现肿瘤特征, 为在活体内研究肝癌的生物学特性,指导临床个体化治疗提供一种研究方式. 方法:用组织学完整的新鲜人肝癌组织种植于裸鼠肝脏, 观察种植瘤的存活率、生长曲线、组织细胞病理特征、转移情况以及肝癌的其他生物学特征,并与皮下、皮下-肝原位种植瘤模型比较. 结果:来源于1例患者肝癌组织的第一代种植瘤存活率100%,自发性肝内转移75.0%,肺转移37.5%,骨转移37.5%;并保持分泌AFP的特性;流式细胞仪分析DI值为1.63.组织细胞病理、器官转移特征以及其他生物学特性与原肝癌相似. 结论:人肝癌组织裸鼠原位种植瘤的生物学特征与肝癌患者基本相似,基本模拟了人肝癌的自然过程,是目前体内研究人肝癌生物学特征、筛选有针对性敏感化疗药的较理想方法. | 郜永顺 陈孝平 张志伟 张万广 李开艳 吴在德 | 2004 | 世界华人消化杂志2004，12，3： | 3 |
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