索拉非尼联合经肝动脉化疗栓塞术治疗原发性肝细胞癌的疗效和安全性

目的 评估索拉非尼联合经肝动脉化疗栓塞术(TACE)治疗原发性肝癌的疗效和安全性。方法 回顾性分析在中国医科大学附属第一医院介入放射科行索拉非尼系统治疗并联合TACE治疗的10例不可切除肝癌患者的临床资料,按照修订的实体瘤疗效评估标准评价疗效,采用Kaplan-Meier法分析患者生存情况,采用美国国立癌症研究所常见毒性反应分级标准3.0版评价安全性。结果 10例患者中,2例为完全缓解,3例为部分缓解,3例为疾病稳定,2例为疾病进展,中位总生存期为29.5个月。有9例出现不同程度的不良反应,均为3级或以下级别,最常见的不良反应为手足皮肤反应(7/10)和腹泻(6/10)。结论 索拉非尼联合TACE治疗原发性肝癌是一种安全、有效的治疗方法。     

High rate of hematological responses to sorafenib in FLT3‐ITD acute myeloid leukemia relapsed after allogeneic hematopoietic stem cell transplantation

Relapse represents the most significant cause of failure of allogeneic hematopoietic stem cell transplantation (HSCT) for FLT3‐ITD‐positive acute myeloid leukemia (AML), and available therapies are largely unsatisfactory. In this study, we retrospectively collected data on the off‐label use of the tyrosine kinase inhibitor sorafenib, either alone or in association with hypomethylating agents and adoptive immunotherapy, in 13 patients with post‐transplantation FLT3‐ITD‐positive AML relapses. Hematological response was documented in 12 of 13 patients (92%), and five of 13 (38%) achieved complete bone marrow remission. Treatment was overall manageable in the outpatient setting, although all patients experienced significant adverse events, especially severe cytopenias (requiring a donor stem cell boost in five patients) and typical hand‐foot syndrome. None of the patients developed graft‐vs.‐host disease following sorafenib alone, whereas this was frequently observed when this was given in association with donor T‐cell infusions. Six patients are alive and in remission at the last follow‐up, and four could be bridged to a second allogeneic HSCT, configuring a 65 ± 14% overall survival at 100 d from relapse. Taken together, our data suggest that sorafenib might represent a valid treatment option for patients with FLT3‐ITD‐positive post‐transplantation relapses, manageable also in combination with other therapeutic strategies.     

辛伐他汀通过抑制Warburg效应改善索拉非尼耐药的肝癌细胞转移侵袭的作用机制

目的 探索辛伐他汀通过抑制Warburg效应改善索拉非尼耐药的肝癌细胞转移侵袭的作用机制.方法 将索拉非尼耐药的人肝癌细胞株SMMC-7721/S(5 μmol·L-1的索拉非尼耐药)分为对照组、索拉非尼组、辛伐他汀组.索拉非尼组为5 μmol·L-1的索拉非尼干预,辛伐他汀组用10 μmol·L-1和20 μmol·...     

索拉菲尼对原发性肝癌术后患者疗效的系统评价

目的:系统评价索拉菲尼对原发性肝癌切除术后患者的疗效。方法:在Medline、Embase、Cochrane Library、中国知网（CNKI）数据库、万方数据库、中国生物医学数据库（CBM）检索有关索拉菲尼对原发性肝癌患者术后辅助治疗效果,主要观察目标为总生存期,次要观察目标为肿瘤复发率和死亡率。结果:索拉非尼治疗组与对照组比较,总生存率无显着性差异（HR=1.39,95％CI:0.71~2.74,P=0.34）;复发率无显著性差异（RR=0.81,95％CI:0.65~1.01,P=0.06）。随即我们根据文献类型,将研究分为试验性研究和观察性研究两个亚组来分析患者死亡率,发现临床试验组中肝癌术后接受索拉菲尼治疗的患者死亡率虽然降低但无统计学意义（P=0.45）,而在观察研究组中是具有统计学意义的（RR=0.66,95％CI:0.51~0.87,P=0.003）。结论:对于肝癌术后患者索拉菲尼并不能提高患者总生存期,也不能降低肿瘤复发率,但亚组分析中可以降低患者的死亡率。因此索拉非尼是否是原发性肝癌切除后患者有效的辅助治疗手段,目前仍缺乏足够证据。     

Contribution of microCT structural imaging to preclinical evaluation of hepatocellular carcinoma chemotherapeutics on orthotopic graft in ACI rats

Animal experimentation is a prerequisite for preclinical evaluation of treatments such as chemotherapy. It's strictly regulated with the purpose of reducing the number of experimental animal as well as their pain. Small animal imaging should provide a painless longitudinal follow up of tumor progression on a single animal. The aim of the study is to validate small animal imaging by microscanner (μscan) in longitudinal follow up of a hepatocellular carcinoma (HCC) and to demonstrate its interest for in vivo evaluation of tumor response to different therapeutics. An HCC model achieved by orthotopic graft of the MH3924A cell line in ACI rats was followed using a Imtek/Siemens microscanner (μscan) with contrast agents (Fenestra^® LC/VC). The procedures giving the optimal enhancement of the liver as well as a reliable determination of tumor volumes by μscan were validated. Three protocols for therapeutic assessment through μscan longitudinal follow up were performed. Each consisted in three groups testing a chemotherapy (gemcitabine, gemcitabine-oxaliplatine or sorafenib) versus two control groups (placebo and doxorubicine). Comparison was done on tumor volumes, median and actual survivals. There was a significant correlation between tumor volumes measured by μscan and autopsy. Treatment by sorafenib, at the contrary of gemcitabine alone or with oxaliplatine, resulted in a significant reduction in tumor volumes and prolongation of actuarial survival. These results are consistent with available clinical data for these diverse therapeutics. In conclusion, small animal imaging with μscan is a non-invasive, reliable, and reproducible method for preclinical evaluation of antitumor agents.