消炎痛抑制肝细胞肝癌生长转移的研究

Objective To study the effects of indomethacin on proliferation and invasion of hepatocellular carcinoma (HCC) cell line MHCC97L with metastatic potential and the effect of indomethacin on the growth and metastasis of HCC. Methods (1) In vitro; Proliferation, Transwell invasion assay, cell motility assay, vascular endothelial growth factor (VEGF) and matrix metalloproteinase-2 (MMP-2) protein activity were evaluated after cells were treated with 0. 2 mmol/L indomethacin. (2)In vivo: Mice bearing xenografts in the liver were randomly divided into control and indomethacin groups. At the end of sixth week, the mice were killed and tumor volume, inhibitory rate, immunohistochemistry assay (IHA) and metastasis were evaluated. Results (1)In vitro; 0. 2 mmol/L indomethacin could inhibit the proliferation of MHCC97L cells markedly (P ＜0. 01). The average amount of invading cells per field in cell invasion assay and motility assay was 2. 2 ± 1. 3 and 4.4 ± 1. 1 respectively in indomethacin group, significantly less than in control group ( 11. 4 ± 1. 9 and 12. 8 ± 1. 8 respectively, P ＜0. 01). The expression of VEGF and MMP-2 in cells treated with indomethacin was significantly lower than in control group (P ＜0. 01). (2)In vivo; Tumor volume, incidence and number of lung metastases in control and indomethacin groups were (1700 ±422) mm3 and (1170 ± 585) mm3 (P ＜ 0. 05), 75% and 50% ( P ＞ 0.05), 2. 92 ± 2. 07 and 1.33 ±1.56 (P＜0. 05) , respectively. Inhibition rate in indomethacin group was 31.2%. IHA showed that the expression of VEGF, MMP-2, and cyclooxygenase-2 ( COX-2) was down-regulated in indomethacin group (P ＜0.01). Conclusion Indomethacin could inhibit the growth and metastasis of HCC, which was in part mediated by down-regulation of VEGF and MMP-2.     

老年肝癌的诊治进展

恶性肿瘤好发于中老年人。随着社会安定、经济生活改善及医药卫生事业的进步 ,我国人口老龄化的趋势已经日益明显。人口构成的老龄化必然导致癌症发病率的增高。老年人常有多数器官功能减退 ,故老年人的癌症在诊断治疗方面与年轻人亦常有所不同。原发性肝癌 (以下简称肝癌 )是我国常见恶性肿瘤之一 ,在沿海的一些地区、其死亡率仅次肺癌居第二位。在各种恶性肿瘤中 ,肝癌的发病年龄偏轻。 1973年我们曾统计全国 32 82例肝癌。其中位年龄为 4 3 5岁。近年各地临床医师发现老年肝癌病例增多 ,我院收治的一组 3578例中≥ 6 0岁者 6 0 3例 ,占16…     

肝癌的局部治疗

原发性肝癌和转移性肝癌是常见的恶性肿瘤 ,目前外科手术仍是首选的方法之一 ,但原发或转移的肝癌在发现时只有 2 0 %的患者有手术机会[1] 。近年来针对肝癌的综合治疗日益发展 ,其中肝癌的局部治疗越来越显示其在治疗中的重要作用。已广泛应用的肝癌的局部治疗包括经皮无水酒精注射、经皮穿刺乙酸注射、射频治疗、激光间质热疗、微波固化治疗、高强度聚焦超声治疗 ,另外还有术中的局部治疗 ,如冷冻治疗 ,经血管的肿瘤栓塞化疗以及在研究中的高温液体热损伤、沸腾化疗药物瘤内注射治疗等。本文对以下几种局部治疗的现状作一综述。1　无水酒…     

肿瘤免疫检查点抑制剂联合治疗策略及临床应用

目的：免疫检查点抑制剂（immune checkpoint inhibitions，ICIs）的应用显著改善了多种肿瘤的预后，是当前肿瘤治疗中备受重视的手段。以程序性死亡因子-1（programmed death 1，PD-1）、程序性死亡因子配体-1（programmed death ligand 1，PD-L1）和细胞毒性T淋巴细胞相关抗原4（cytotoxic T lymphocyte antigen 4，CTLA-4）单克隆抗体为主的免疫检查点的临床研究结果显示，单一ICIs临床效果有限。不同ICIs的联合治疗、联合化疗及联合抗肿瘤血管生成药物可明显提高疗效，新发现的免疫检查点淋巴细胞激活基因-3（lymphocyte activation gene-3，LAG-3）、T细胞免疫球蛋白黏液素3（T cell immunoglobulin mucin-3，TIM-3）、T细胞免疫球蛋白和ITIM域（T cell immunoglobulin and ITIM domain，TIGIT）等抑制剂的转化和联合应用，对难治性或ICIs耐药患者的疗效值得期待。     

原发性肝癌肝动脉化疗栓塞合并LAK/IL-2灌注治疗的临床Ⅲ期观察

评价肝动脉化疗栓塞合并ＬＡＫ／ＩＬ┐２灌注治疗原发性肝癌的初步疗效。方法不能切除的肝癌患者经肝动脉化疗栓塞后灌注自体ＬＡＫ细胞及ＩＬ┐２，并与单独行肝动脉化疗栓塞的不能切除肝癌患者比较其肿瘤大小，生活质量的变化及毒副反应。结果经肝动脉化疗栓塞合并ＬＡＫ／ＩＬ┐２灌注治疗的２２例肝癌有效率（ＣＲ＋ＰＲ）为１３．６％，包括１例完全缓解和２例部分缓解，而单独化疗栓塞对照组１７例中仅１例显示部分缓解（有效率５．９％）。化疗栓塞＋ＬＡＫ／ＩＬ┐２治疗组与单独化疗栓塞对照组中ＭＲ、ＳＤ、ＰＤ分别为５、１２、１例和１、１１、４例。治疗组中大多数病人生活质量改善或稳定，而对照组中生活质量则无提高。两组病人的毒副反应均较轻而短暂。结论经肝动脉化疗栓塞合并ＬＡＫ／ＩＬ┐２灌注治疗原发性肝癌疗效较优于单独肝动脉化疗栓塞治疗，原发性肝癌更有效的综合治疗方案有待进一步探索     

nm23-H1对肝癌细胞株SMMC7721转移特性的抑制

[目的]研究转移抑制基因nm23-H1与肝癌细胞转移行为的关系.[方法]体外构建真核细胞表达重组体DNA pcDNA 3.1(-)-nm23-H1;采用Lipofectamine介导将目的基因nm23-H1体外转染肝癌细胞株SMMC7721,通过软琼脂克隆实验、内皮细胞异质粘附实验和Boyden小室侵袭实验对转染细胞的生物学活性进行检测.[结果]粘附实验中,实验组肿瘤细胞株与内皮细胞粘附计数为(50～60)/mm2,少于对照组的(200～300)/mm2,实验组细胞株粘附性降低,t检验P＜0.05;软琼脂克隆实验对照组形成多个细胞克隆(47%～62%),而实验组无克隆形成,克隆能力明显降低;Boyden小室侵袭实验中,每视野穿透Matrigel膜的细胞数分别为1.34～3.26和27.46～32.94,实验组细胞株侵袭能力明显低于对照组细胞株,t检验P＜0.01.[结论]nm23-H1能够降低肿瘤细胞株SMMC7721在体外的转移潜能.     

射频及手术切除在小肝癌治疗中价值的探讨

目的 :评价射频及手术切除在小肝癌治疗中的价值。方法 :分别对我院肝内科及肝外科随机选取的 2 0 0 3年采用射频和手术切除治疗小肝癌的病例各 10 0例 ,对两组在住院费用、住院天数、肝功能恢复时间、术后 1年复发率及并发症等方面进行比较。结果 :射频治疗组患者术后肝功能恢复时间为 9.0 9± 4 .5 9d ,少于手术组 10 .5 5± 3.0 9d(P <0 .0 1) ;射频治疗组患者术后并发症 (发热 ,黄疸 )比手术组患者明显少 (P <0 .0 0 1) ,且持续时间短 ;对于直径 3.0cm以下的肿瘤 ,射频治疗组患者术后 1年的肿瘤复发率等同于手术组 (p >0 .0 5 ) ,而直径在 3.0～ 5 .0cm的肿瘤 ,射频治疗组患者术后 1年的肿瘤复发率明显高于手术组 (P <0 .0 1) ;射频治疗组患者平均住院费用是 2 35 0 4 .2 8± 4 936 .6 2元 ,手术组为 2 2 6 6 3.6 6± 394 9.6 1元。两组基本相当 (p >0 .0 5 ) ;射频治疗组患者平均住院天数为 14 .4 9± 7.6 1d ,少于手术组 17.5 8± 4 .87d(P <0 .0 1)。结论射频治疗是一种创伤小、恢复快、安全性高的治疗方法 ,其对于 3cm以下的肿瘤的疗效等同于手术切除。且其治疗费用与手术切除相当。严格掌握射频治疗的指征是降低术后复发的关键。     

肝癌的化学药物治疗

尽管外科手术切除是肝癌治疗的首要选择，但由于多数肝癌在诊断时已发生肝内或远处转移，或由于合并有严重的肝硬化，实际能接受手术切除的病例不超过20％，因而有相当部分的肝癌病人需要接受化学药物治疗。     

绿脓杆菌制剂对人肝癌MHCC97L细胞增殖和侵袭能力的影响

Objective To investigate the effects of Pseudomonas aeruginosa vaccine (PA) on proliferation and invasiveness of the hepatocellular carcinoma cell line MHCC97L with metastatic potential. Methods Proliferation, growth curve, plate efficiency, flow cytometry, transwell invasion assay, cell motility assay, scarification test, vascular endothelial growth factor (VEGF) and matrix metalloproteinase-2 (MMP2) protein activity were evaluated after cells were treated with PA at various concentrations. Results PA can inhibit the proliferation and plate efficiency of MHCC97L cell markedly in a dose-dependent manner. The IC50 of cells treated with PA for 48 h and 72 h was 3.1 ×108/ml and 1.9 × 108/ml, respectively. The doubling time increased and plate efficiency decreased gradually when cells treated with 0.5 × 108/ml, 1 × 108/ml and 2 × 108/ml PA (P＜0.01). PA could induce cell cycle arrest at the G1 phase in a dose-dependent manner by flow cytometric analysis. The average amount of invading cell per field in cell invasion assay and motility assay were 4. 8 ± 1.3 and 8. 8±2.2 when cells treated with 1× 108/ml PA, which was significantly lower than that of control group (8. 6±2. 1 and 15. 6±1.2 ) (P＜0.01) Scarification test showed that the metastatic ability of cells treated with 1 × 108/ml PA significantly lower than that in the control group. Comparison between cells treated with 1 × 108/ml PA and control group, no remarkable difference was found regarding expression of VEGF and MMP2 in supernatant of cell culture. Conclusion PA can inhibit proliferation and plate efficiency of HCC cell line MHCC97L, which is in part mediated by the cell cycle arrest at the G1 phase. PA could inhibit invasiveness of HCC cell line MHCC97L, which is unrelated to the VEGF and MMP2 protein activity.