Sunitinib malate for the treatment of solid tumours: a review of current clinical data

Receptor tyrosine kinases (RTKs) play important roles in the regulation of cellular growth, and mutated or overexpressed RTKs have been implicated in various human cancers. Sunitinib malate is an oral multitargeted tyrosine kinase inhibitor with antitumour and antiangiogenic activity that recently received approval from the FDA for the treatment of advanced renal cell carcinoma and of gastrointestinal stromal tumours after disease progression on or intolerance to imatinib mesilate therapy. Sunitinib has also demonstrated promising clinical activity in the treatment of other advanced solid tumours. The present review provides an updated summary of emerging clinical experience with this promising new anticancer agent.     

磁共振DWI及DTI在肾透明细胞癌与乏脂性肾血管平滑肌脂肪瘤鉴别中的价值

目的探讨磁共振扩散加权成像(DWI)及扩散张量成像(DTI)在肾透明细胞癌(ccRCC)与乏脂性肾血管平滑肌脂肪瘤(MFAML)鉴别诊断中的价值。方法回顾性搜集行腹部MRI检查、经手术病理证实为ccRCC及MFAML的患者共55例(ccRCC 42例,MFAML 13例)。两组患者均行1.5T(GE 1.5T Signa HDXT,美国)MRI常规T1WI、T2WI扫描、LAVA增强扫描、DWI(b=0,600 s/mm^2)、DTI序列扫描(b=0,600 s/mm^2,在6个方向)。由两位放射科医师采用双盲法进行图像分析和测量。在ADW4.6工作站上应用Functool后处理软件进行后处理,使用DWI序列生成ADC图,使用DTI序列生成ADC图和FA图,分别在相应的ADC图和FA图中的ccRCC及MFAML病灶实质部分放置ROI,测量各ROI的ADC值及FA值,对两次测量结果的平均值进行统计分析。应用组内相关系数(ICC)检验两观察者所测数据一致性。使用独立样本t检验比较DWI的ADC值(ADCDWI)及DTI的ADC值(ADCDTI)在ccRCC与MFAML之间的差异,使用Mann-Whitney U检验比较FA值在ccRCC与MFAML之间的差异。应用ROC曲线分析DWI的ADCDWI值及DTI参数中ADCDTI值、FA值对鉴别ccRCC与MFAML的诊断效能,并且分析ADCDWI、ADCDTI及FA值三者联合诊断对鉴别ccRCC与MFAML的效能。结果两位观察者测量各参数的一致性良好。ccRCC的ADCDWI值显著高于MFAML[(1.93±0.44)×10^-3mm^2/s与(1.40±0.29)×10^-3mm^2/s,P<0.001],ccRCC的ADCDTI值显著高于MFAML[(2.06±0.45)×10^-3mm^2/s与(1.63±0.33)×10^-3mm^2/s,P=0.002],但ccRCC的FA值显著低于MFAML[(0.20±0.07)与(0.31±0.20),P=0.020]。ADCDWI值对鉴别ccRCC与MFAML的曲线下面积为0.845,阈值为1.63×10^-3mm^2/s时,其诊断ccRCC排除MFAML的敏感性和特异性分别为71.4%、84.6%;ADCDTI值对鉴别两者的曲线下面积为0.788,阈值为1.77×10^-3mm^2/s时,其诊断ccRCC排除MFAML的敏感性和特异性分别为76.2%、76.9%;FA值对鉴别两者的曲线下面积为0.722,阈值为0.27时,其诊断ccRCC排除MFAML的敏感性和特异性分别为88.1%、53.8%。应用ADCDTI与FA联合诊断鉴别ccRCC和MFAML的效能具有较高的诊断效能,ROC曲线下面积达到0.811,并且诊断特异性达到92.3%。结论磁共振DWI及DTI均能有效鉴别ccRCC与MFAML。其中,ADCDWI对鉴别两者有更高的诊断效能及诊断特异性。应用DWI及DTI的参数进行联合诊断更能提高对两者的诊断效能及敏感性。     

SMARCC1 expression is positively correlated with pathological grade and good prognosis in renal cell carcinoma

BackgroundRenal cell carcinoma (RCC), which is derived from the renal tubular epithelium, is now the most common urological cancer. Of the four RCC subtypes, clear cell RCC (ccRCC) is the most common subtype and accounts for 75–80% of all RCC cases. SMARCC1, also known as BAF155, together with SMARCA4, SMARCA2, and SMARCB1, comprises the SWI/SNF protein family. It has been reported that the expression of SMARCC1 was correlated with some human cancers including prostate cancer, colon cancer, and pancreatic cancer. However, the mechanisms and regulatory roles of SMARCC1 in ccRCC are not well defined.MethodsOur current study primarily investigated the expression of SMARCC1 and its clinical importance in two common histological types of ccRCC using microarrays (HKidE180Su02, MecDNA-HKidE030CS01).ResultsThe results showed that the expression of SMARCC1 in ccRCC tissues was significantly decreased compared with that in corresponding para-tumor tissue (4.370±2.036 vs. 6.167±1.162, P=0.001). SMARCC1 expression was positively correlated with pathological grade (r=0.224, P=0.011). Moreover, ccRCC patients with high SMARCC1 expression had a better prognosis than those with low SMARCC1 expression (40.0% vs. 95.2%, P=0.000) in the following sub-groups: pathological grade (III and IV), male sex (73.5% vs. 95.3%, P=0.004), and tumor size >5 cm (62.5% vs. 89.5%, P=0.044).ConclusionsA further study is necessary to explain the mechanism of the occurrence and progression of ccRCC.     

Unilateral autosomal dominant polycystic kidney disease with co-existent renal cell carcinoma: A rare entity

Bilateral ADPKD is a well-known entity, but there are only a few reports on unilateral ADPKD in adults, most of which had associated contralateral agenesis. Further rare is the development of RCC in unilateral ADPKD. We present an exceedingly rare case of true unilateral ADPKD with normal contralateral kidney and an associated renal cell carcinoma in the same kidney.     

Differential expression of the sirtuin family in renal cell carcinoma: Aspects of carcinogenesis and prognostic significance

Objectives

Sirtuins (1–7) are evolutionarily conserved NAD-dependent deacetylases that play an important role in carcinogenesis. However, their role in renal cell carcinoma (RCC) remains unclear. The objective of the present study was to examine the role of SIRTs in RCC carcinogenesis and prognosis.

Kinesin Motor Protein KIFC1 Is a Target Protein of miR-338-3p and Is Associated With Poor Prognosis and Progression of Renal Cell Carcinoma

KIFC1 (kinesin family member C1) plays a critical role in clustering of extra centrosomes in various cancer cells and thus could be considered as a promising therapeutic target. However, whether KIFC1 is involved in the procession of renal cell carcinoma (RCC) still remains unclear. In this study, we found that KIFC1 was upregulated in RCC tissues and is responsible for RCC tumorigenesis (p<0.001). The high expression of KIFC1 correlates with aggressive clinicopathologic parameters. Kaplan–Meier analysis suggested that KIFC1 was associated with poor survival prognosis in RCC. Silencing KIFC1 dramatically resulted in inhibition of proliferation, delayed the cell cycle at G₂/M phase, and suppressed cell invasion and migration in vitro. The antiproliferative effect of KIFC1 silencing was also observed in xenografted tumors in vivo. miR-338-3p could directly bind to the 3 -untranslated region (3 -UTR) of KIFC1, and ectopic miR-338-3p expression mimicked the inhibitory functions of KIFC1 silencing on RCC cells through inactivation of the PI3K/AKT signaling pathway. Therefore, these results revealed that KIFC1 may be a novel biomarker and an effective therapeutic target for the treatment of RCC.     

Heparanase、COX-2在肾癌中的表达和肿瘤血管生成的关系

目的:探讨Heparanase、COX-2在肾癌中表达的相关性及与肿瘤血管生成的关系及意义。方法:采用免疫组化PV6000法检测54例肾癌和20例正常肾脏组织中Hpa、COX-2蛋白的表达,以CD34单克隆抗体进行微血管内皮染色,计算微血管密度,分析Hpa、COX-2在肾癌中表达的相关性以及与临床病理特征及微血管密度的关系。结果:Hpa、COX-2在肾癌中的表达均较正常肾脏组织明显增高(P<0.05)。Hpa的表达与肾癌的临床分期、肿瘤大小、远处转移有关(P<0.05),而与患者年龄、性别、肿瘤的分化程度无相关性(P>0.05)。COX-2的表达与肾癌的临床分期、远处转移及分化程度有关(P<0.05),与患者年龄、性别、肿瘤大小无关(P>0.05)。肾癌组织中MVD显著高于正常肾脏组织(P<0.05),高MVD组中Hpa、COX-2表达的阳性率高于低MVD组(P<0.05),Hpa、COX-2阳性表达组中MVD值亦高于阴性表达组(P<0.05)。Hpa、COX-2的表达具有相关性(P<0.05)。结论:Hpa、COX-2可能通过促肿瘤血管生成参与肾癌的恶性生物学行为,并有可能成为判断肾癌预后的指标和靶向治疗的靶点。     

Predictors of Long-Term Response With Pazopanib in Patients With Advanced Renal-Cell Carcinoma

Background

Pazopanib is among the current standards of care for first-line treatment of patients with unresectable advanced renal-cell carcinoma (aRCC) or metastatic renal-cell carcinoma. This real-world study aimed to characterize those with long-term response to pazopanib in the treatment of aRCC in a community oncology setting, and to identify predictors of long-term response.