Netrin-1:the new tumor markers in renal clear cell carcinoma

Objective:To explore the expression of Netrin-1 protein in human renal clear cell carcinoma(RCCC) and the relationships between Netrin-1.pathology and prognosis.Methods:72 cases of RCCC admitted in our hospital from 2008 June to 2009 June and their adjacent tissues were selected for study.They included 30 cases in stage Ⅰ-Ⅱ.42 cases in stage Ⅲ-Ⅳ;9 cases in grade Ⅰ.9 cases in grade Ⅱ.40 cases in grade Ⅲ and 14 cases in grade Ⅳ.All cases were followed up for more than 5 years.Survival analysis lines were made by Kaplan—Meier method and the difference between groups was tested by the Log-rank test.The expression of Netrin-1 protein was detected by immunohistochemistry staining and its clinical significance was analyzed.Results:Renal clear cell carcinoma:51 cases in high expression of Netrin-1and 21 cases in low expression,normal tissues:12 cases in high expression of Netrin-1and 60 cases in low expression,the difference between the two groups is significant(x^2=42.921,P<0.01).The difference of the expression of Netrin-lin Fuhrman grade and AJCC clinical stage is significant(x^2=8.000.x^2=6.203:P<0.05).The 5-year survival rate in low protein expression group and in high protein expression group was 79% (17/21) and 62% (32/51).The survival curve had different trend,with no significant difference between groups(x^2=1.360.P=0.245).Conclusions:Netrin-1 protein plays an important role in the development of RCCC.It might be a new specific tumor marker of RCCC.and might become a new target in treatment of RCCC.

Aberrant DNA methyltransferase 1 expression in clear cell renal cell carcinoma development and progression

Objective： To better understand the contribution of dysregulated DNA methyltransferase 1 （DNMT1） expression to the progression and biology of clear cell renal cell carcinoma （ccRCC）. Methods： We examined the differences in the expression of DNMT1 in 89 ecRCC and 22 normal tissue samples by immunohistochemistry. In addition, changes in cell viability, apoptosis, colony formation and invading ability of ccRCC cell lines （786-0 and Caki-1） were assessed after transfection with DNMT1 siRNA. Results： We found DNMT1 protein was significantly higher expressed in ccRCC than that of in no-tumor tissues （56.2% and 27.3%, respectively, P=0.018）. The expression of DNMT1 was strongly associated with ccRCC tumor size, tumor pathology stage, histological grading, lymph node metastasis, vascular invasion, recurrence and prognosis. Moreover, knockdown of DNMT1 expression significantly inhibited ccRCC cell viability, induced apoptosis, decreased colony formation and invading ability. Conclusions： Expression of DNMTI protein is increased in ccRCC tissues, and DNMT1 expression is associated with poor prognosis of patients. Experiments in vitro further showed DNMT1 played an essential role in proliferation and invasion of renal cancer cells. Moreover, targeting this enzyme could be a promising strategy for treating ccRCC, as evidenced by inhibited cell viability, increased apoptosis, decreased colony formation and invading ability.

Association of hypoxia-inducible factor-1α (HIF1α) 1772C/T genepolymorphism with susceptibility to renal cell carcinoma/prostatecancer

In this study,we used a meta-analysis method to evaluate the relationship between hypoxia-inducible factor-1α(HIF1α)1772C/T gene polymorphism(rs 11549465)and renal cell carcinoma(RCC)/prostate cancer risk.We searched for relevant studies(before March 1,2019)on Cochrane Library,Embase,and PubMed.Studies meeting the inclusion criteria were recruited into this meta-analysis.The outcome of dichotomous data was showed in the way of odds ratios(OR),and 95%confidence intervals(CI)were also counted.In this investigation,there was no association between HIF1α1772C/T gene polymorphism and susceptibility to RCC in Caucasians,Asians as well as overall populations.In addition,HIF1α1772C/T gene polymorphism was not found to be relevant to the survival in RCC.Interestingly,the T allele was relevant to prostate cancer risk in all populations,but not in Caucasians and Asians.However,the TT genotype and the CC genotype were not related to prostate cancer susceptibility in Asian,Caucasian,and all populations.In conclusion,the T allele of the HIF1α1772C/T gene polymorphism was related to prostate cancer risk in the overall populations.

Expression of caveolin-1 in clear cell renal cell carcinoma and its correlation with microvessel density

Objective:The aim of the study was to investigate the clinicopathologic significance of caveolin-1 expression in clear cell renal cell carcinoma (CCRCC) and its correlation with microvessel density (MVD).Methods:The expression of caveolin-1 was detected by the immunohistochemistry method,while the microvessel density was detected by the immunohistochemistry expression of CD34.Results:In the CCRCCs,the positive rate of caveolin-1 was 67.4%,the over expression of caveolin-1 was not related with sex and age,but related with clinicopathologic parameter,such as tumor sizes,clinical TMN stage,nuclear stage and survival time (P < 0.05).The MVD of positive caveolin-1 cases was significantly higher than that without caveolin-1 expression (P < 0.05).Conclusion:The expression of caveolin-1 is helpful in the prognostic evaluation of CCRCCs and it may be involved in the tumor angiogenesis.

Eosinophilic solid and cystic renal cell carcinoma with aggressive behavior:Two case reports

BACKGROUND Eosinophilic solid and cystic(ESC)renal cell carcinoma(RCC),a unique and emerging subtype of RCC,has an indolent nature;in some rare instances,it may exhibit metastatic potential.Current cases are inadequate to precisely predict the clinical outcome of ESC RCC and determine treatment choices.CASE SUMMARY Herein,we report two patients with ESC RCC.Patient 1 was a young woman with classical pathological characteristics.Patient 2 was a 52-year-old man with multifocal metastases,involving the pulmonary hilar and mediastinal lymph nodes,liver,brain,mesosternum,vertebra,rib,femur,and symphysis pubis.Awareness of ESC RCC,along with its characteristic architecture and immunophenotype,would contribute to making a definitive diagnosis,even on core biopsy samples.CONCLUSION The discovery of ESC RCC molecular signatures may provide new therapeutic strategies in the future.

Network pharmacology and molecular docking analysis reveal insights into the molecular mechanism of Gualou Qumai Wan in clear cell renal cell carcinoma

Background:To initially clarify the potential therapeutic targets and pharmacological mechanism regarding Gualou Qumai Wan(GQW),a kind of traditional Chinese medicine(TCM),in clear cell renal cell carcinoma(ccRCC)by virtue of the network pharmacology analysis and molecular docking analysis.Methods:The screening of bioactive components and targets of GQW was based on the Traditional Chinese Medicine System Pharmacology(TCMSP)and the UniProt platform served for standardizing their targets.Online Mendelian Inheritance in Man(OMIM),PharmGkb,TTD,DrugBank and GeneCards databases were searched to collect the disease targets of ccRCC.Cytoscape assisted in constructing herb-compound-target(H-C-T)networks.The STRING database was searched for constructing the target protein-protein interaction(PPI)networks,while the R programming language served for analyzing GO functional terms and the KEGG pathways related to potential targets.Analyses of core genes related to survival and tumor microenvironment(TME)were conducted respectively based on the GEPIA2 database and TIMER 2.0 database.Human Protein Atlas(HPA)and The Cancer Genome Atlas(TCGA)helped to obtain core genes’protein expression as well as transcriptome expression level.Autodock Vina software validated the molecular docking regarding GQW components and pivotal targets.Results:The constructed H-C-T networks mainly had 33 compounds and 65 targets.A topological analysis of the PPI network identified that ESR1,AKT1,HIF1A,PTGS2,TP53 and VEGFA serve as core targets in the way GQW affects ccRCC.According to the GO and KEGG pathway enrichment analyses,the effects of GQW are mediated by genes related to hypoxia and oxidative stress as well as the Chemical carcinogenesis-receptor activation and PI3K-Akt signaling pathways.AKT1 shows a close relation to the recruitment of various immune cells and can remarkably affect disease prognosis according to reports.Molecular docking and molecular dynamics simulations showed that diosgenin has higher affinity with core targets.Conclusion:The study makes a comprehensive explanation of the biological activity,potential targets,as well as molecular mechanism regarding GQW against ccRCC,which promisingly assists in revealing the action mechanism of TCM formulae in disease treatment and the respective and scientific basis.

A potential impact of A Disintegrin and Metalloproteinase Domain-Like Protein Decysin-1(ADAMDEC1)on clear cell renal cell carcinoma propagation

Clear cell renal cell carcinoma(KIRC)is the most common and aggressivemalignancy subtype of renal neoplasm that arises from proximal convoluted tubules.It is characterized by poor clinical outcomes and high mortality of patients due to the lack of specific biomarkers for varying stages of the disease and no effective treatment.Proteases are associated with the development of several malignant tumors in humans by their ability to degrade extracellular matrices,facilitating metastasis.Herein,differentially expressed genes in KIRC cases compared to healthy kidneys were screened out from the Gene Expression Profiling Interactive Analysis(GEPIA)database.This data was applied to determine the most elevated protease in KIRC and as a result,A Disintegrin and Metalloproteinase Domain-Like Protein Decysin-1(ADAMDEC1)was selected.This expression pattern was exclusive for KIRC and not observed for papillary and chromophobe renal cell carcinomas,in which ADAMDEC1 was at the same level in tumors and non-cancer specimens.Furthermore,the ADAMDEC1 significant increase was detected in the fourteen other human malignancies compared to healthy samples,which suggested its strong involvement in cancer development.Next,GEPIA and Pathology Atlas correlated ADAMDEC1 high expression with more advanced tumor grade and shorter survival of KIRC patients.Xena Functional Genomics Explorer presented that ADAMDEC1 could be hypermethylated in some tumor cases and one somatic mutation in the gene sequence was detected.Finally,a Search Tool for the Retrieval of Interacting Genes/Proteins;STRING base was utilized to predict the interactions of ADAMDEC1 with other molecules and construct the signaling network.In summary,ADAMDEC1 showed the tremendous potential to be the predictive marker for the KIRC and its development.Therefore,this review with data analysis can be a good base for further in vitro and in vivo research that experimentally can confirm the ADAMDEC1 as prognostic biomarkers and therapeutic target of KIRC.

BRMS1 performs an anti-tumor effect on renal cell carcinoma via inhibition of PI3K/AKT/mTOR signaling pathway

Objective:To explore the anti-tumor of breast cancer metastasis suppressor 1(BRMS1)on renal cell carcinoma.Methods:BRSM1 stabilized overexpressed and knockdown cell models were constructed to detect the effect of BRMS1 overexpression and knockdown on viability rate of 769-P cells.Activation of PI3K/AKT-mTOR-NFκB signaling pathway,expression of cellular apoptosis-related proteins,DNA damage repair-related proteins and angiogenesis-related proteins were detected using Western blotting analysis.Results:The viability rate of 769-P cells were significantly decreased in BRMS1 overexpression cells while significantly increased in BRMS1 knockdown cells(P<0.05).The activity of PI3K/AKT-mTOR-NFκB signaling pathway was significantly inhibited with BRMS1 overexpression(P<0.05),and expression of BAX was significantly increased with significantly decreased expression of Bcl-2(P<0.05).Besides,BRMS1 overexpression could significantly decrease the expression of DNA damage repair-related proteins and angiogenesis and cell-matrix degradation related proteins(P<0.05).Conclusion:BRMS1 induces apoptosis of renal cell carcinoma and performs an anti-tumor effect via inhibition of PI3K/AKT-mTOR-NFκB signaling pathway,expression of DNA damage repair-related proteins and angiogenesis-related proteins.

Expression of DLK1 protein and its correlation with renal cell carcinoma pathological characteristics

Objective To identify the expression of DLK1 protein in different types of renal cell carcinomas and its correlations with pathological characteristics and metastasis. Methods Immunohistochemistry analysis was performed to evaluate the expression of DLK1 protein in

KAI-1、Ki-67和HER-2/neu表达在T_(1-3)N_0M_0肾癌术后转移中的意义

背景与目的:随着我国经济水平的提高和国民自我保健意识的增强,体检成为发现肾癌的重要手段,因此早期肾癌的比例上升,但是国内尚缺乏大样本T_(1-3)N_0M_0肾癌术后转移发生率的调查,而且术后转移机制目前尚不明确,有关KAI-1、Ki-67标记指数、HER-2/neu与肾癌迟发性转移关系的研究更少。因此本研究拟探讨KAI1、Ki-67和HER-2/neu表达与T_(1-3)N_0M_0肾癌术后迟发性转移的相关性和临床意义。方法:随访1991—2000年经手术治疗T_(1-3)N_0M_0肾癌患者。以术后转移病例为转移组,未转移者为对照组。应用EnVision二步法以HER-2/neu和Ki-67多克隆抗体、用PowerVision二步法以KAI-1单克隆抗体分别对两组肾癌标本行免疫组织化学染色。采用卡方检验对比两组KAI-1、Ki-67和HER-2/neu表达差异。结果:T_(1-3)N_0M_0肾癌241例术后发现迟发性转移24例(转移组),未转移194例(对照组),失访23例。218例肿瘤KAI-1、HER-2/neu和Ki-67表达率分别是82.6%、27.5%和83.5%。转移组KAI-1表达率(20.8%)和过表达率(4.2%)显著低于对照组的90.2%、73.7%(均P<0.001)。转移组HER-2/neu表达(62.5%)和过表达率(20.8%)均高于对照组的23.2%、0(均P<0.05、0.001)。转移组Ki-67过表达率(54.2%)显著高于对照组的3.6%(P<0.001)。结论:KAI-1、Ki-67和HER-2/neu均与T_(1-3)N_0M_0肾癌术后转移的发生存在相关性。三者均有助于评估肾癌预后。应对KAI-1表达缺失、HER-2/neu和Ki-67过表达的T_(1-3)N_0M_0期肾癌手术后进行密切随访。

手术标本YAP1、POU2F2、Cath-D表达与局限性肾癌术后复发的相关性及预测意义

目的研究手术标本Yes相关蛋白1(YAP1)、POU2家族同源框2(POU2F2)和组织蛋白酶D(Cath-D)表达与局限性肾癌术后复发的相关性及预测意义。方法回顾性分析2019年1月至2022年3月新乡医学院第一附属医院收治的282例局限性肾癌手术患者的临床资料,根据术后2年随访期内(2例失访)复发情况分为复发组42例和未复发组238例。比较两组患者的基线资料以及手术标本YAP1、POU2F2、Cath-D表达水平,采用多因素Logistic回归分析局限性肾癌术后复发的影响因素,采用受试者工作特征(ROC)曲线分析手术标本YAP1、POU2F2和Cath-D表达单一及联合预测局限性肾癌术后复发价值,采用Pearson相关分析法分析手术标本YAP1、POU2F2和Cath-D表达与复发时间的相关性。结果复发组患者的2017AJCCTNM分期T2期、Fuhrman分级Ⅳ级患者占比分别为80.95%、40.48%,明显高于未复发组患者的62.31%、21.85%,差异均有统计学意义(P<0.05);复发组患者的YAP1阳性率、POU2F2 mRNA和Cath-D阳性率分别为78.57%、1.70±0.36和83.33%,明显高于未复发组患者的47.90%、1.48±0.41、50.00%,差异均有统计学意义(P<0.05);校正前多因素Logistic回归分析结果显示,2017AJCCTNM分期T2期、Fuhrman分级>Ⅱ级、YAP1阳性、POU2F2mRNA、Cath-D阳性均与局限性肾癌术后复发相关(P<0.05),校正后YAP1阳性、POU2F2 mRNA和Cath-D阳性仍是局限性肾癌术后复发的独立相关危险因素(P<0.05);ROC分析结果显示,三者联合预测局限性肾癌术后复发的AUC为0.915,敏感度为80.95%,特异度为89.00%,明显高于各指标单独预测(P<0.05);Pearson相关性分析结果显示,手术标本YAP1、POU2F2、Cath-D表达与复发时间呈负相关(r=-0.802、-0.769、-0.834,P<0.05)。结论局限性肾癌患者手术标本YAP1、POU2F2和Cath-D表达水平与术后复发密切相关,其联合预测局限性肾癌术后复发具有良好参考价值。

RNA干扰受体相互作用蛋白激酶1基因表达对肾透明细胞癌生物活性的影响

目的探讨受体相互作用蛋白激酶1(RIPK1)对肾透明细胞癌(ccRCC)生物功能的影响及机制。方法通过RNA干扰技术降低RIPK1在ccRCC中的表达后,光镜观察细胞形态变化,CCK-8法检测细胞增殖变化情况,Transwell细胞迁移实验检测细胞迁移能力的变化,流式细胞仪检测细胞发生凋亡、坏死水平,Western blot法检测cleaved caspase-3、混合谱系蛋白激酶样结构域(MLKL)和RIPK3表达变化。结果小干扰RNA(siRNA)干扰48 h后,RIPK1-siRNA组细胞增殖吸光度值(0.563±0.042)低于NC-siRNA组(0.944±0.039;t=11.550,P=0.003);siRNA干扰72 h后,RIPK1-siRNA组吸光度值(0.408±0.019)低于NC-siRNA组(1.717±0.108;t=20.620,P<0.001)。与NC-siRNA组(72.000±12.120)比较,RIPK1-siRNA组(31.660±10.020)ccRCC细胞的迁移数量明显减少(t=4.442,P=0.011)。与NC-siRNA组(0.360±0.090、0.510±0.060、0.880±0.070)比较,RIPK1-siRNA组ccRCC细胞内cleaved caspase3、MLKL、RIPK3表达明显增加(0.780±0.070、1.490±0.100、1.680±0.130;t=6.380,P=0.003;t=8.656,P=0.001;t=14.150,P=0.001)。结论RIPK1是ccRCC内调控细胞增殖、死亡及迁移能力的重要基因,抑制RIPK1能够促进ccRCC发生凋亡及坏死性凋亡。

LncRNA UCA-1对肾细胞癌OS-RC-2细胞增殖、凋亡的影响及机制

目的研究尿路上皮癌相关基因1(UCA-1)对肾细胞癌OS-RC-2细胞恶性生物学进程的影响。方法通过实时荧光定量PCR方法分析肾细胞癌组织与癌旁组织中UCA-1的表达;将肾细胞癌OS-RC-2细胞随机设置为3个实验组:siRNA NC组、siRNA UCA-1组与LY294002组。采用MTT实验方法分析OS-RC-2细胞的增殖速度;采用Transwell实验方法分析OS-RC-2细胞的侵袭数量;采用流式细胞术检测OS-RC-2细胞的凋亡情况;采用蛋白免疫印迹方法分析PI3K/AKT通路相关蛋白的表达。结果与肾细胞癌旁的组织比较,肾细胞癌组织的UCA-1表达上调。与siRNA NC组比较,siRNA UCA-1组以及LY294002组的OS-RC-2细胞增殖能力下降(P<0.05);OS-RC-2细胞侵袭数量下降(P<0.05);OS-RC-2细胞凋亡率增加(P<0.05);OS-RC-2细胞PI3K、AKT蛋白表达下调(P<0.05)。结论UCA-1在肾细胞癌细胞中表达增加,抑制UCA-1表达后,OS-RC-2细胞的增殖速度与侵袭数量降低,凋亡率增加,该机制与UCA-1调节PI3K/AKT信号通路相关。

梅奥粘连概率评分对T_(1)期肾癌患者外科治疗的指导效果研究

目的探讨肾周脂肪梅奥粘连概率(MAP)评分对T1期肾癌患者外科治疗的指导效果。方法回顾性分析2014年1月-2018年12月该院收治的200例T1期肾癌患者的临床资料,依据肿瘤切除术式进行分组。其中,A组行经腹腔开腹部分肾切除术(OPN)(n=49)、B组行腹腔镜部分肾切除术(LPN)(n=67)、C组行开放性肾癌根治术(ORN)(n=33)、D组行腹腔镜根治性肾切除术(LRN)(n=51)。按照MAP评分标准将各组进行亚分组:MAP低度组(0~1分)、MAP中度组(2~3分)和MAP高度组(4~5分)。分析MAP评分系统与肾切除术式的关系,并评估围术期不同术式组MAP评分与手术时间、术中出血量、术后并发症的相关性。结果A组和C组患者中,MAP低度组、中度组、重度组的手术时间、术中出血量比较,差异无统计学意义(P>0.05);MAP低度组的术后并发症发生率低于中度组和高度组,中度组低于高度组,差异有统计学意义(P<0.05);B组和D组患者中,MAP低度组手术时间短于中度组和重度组、术中出血量少于中度组和重度组、术后并发症发生率低于中度组和重度组,且中度组低于重度组,差异有统计学意义(P<0.05)。B组和D组影像学MAP评分与手术时间、术中出血量、术后并发症呈正相关(P<0.05)。结论MAP评分可有效指导T1期肾癌切除术式的选择,MAP评分低度和中度患者可选择腹腔镜手术,MAP评分高度患者可选择开放性手术,且MAP评分可用于评估LPN及LRN的围手术期相关临床指标。

外周血CD3^(+)CD4^(-)CD8^(+)T细胞与T_(1)期高级别尿路上皮癌预后的关系

目的研究外周血CD3^(+)CD4^(-)CD8^(+)T细胞数量与T_(1)期高级别尿路上皮癌术后预后的相关性。方法回顾性分析2012年1月至2016年12月在上海市第一人民医院诊治为T_(1)期高级别尿路上皮癌的患者168例,以外周血细胞数量为320个/μl分界将患者分为CD3^(+)CD4^(-)CD8^(+)正常组(87例)和数量低组(81例)。采用Kaplan-Meier法制作生存曲线,Cox回归模型分析外周血CD3^(+)CD4^(-)CD8^(+)T细胞数量与T_(1)期尿路上皮癌的无复发生存和无进展生存(PFS)的关系。结果CD3^(+)CD4^(-)CD8^(+)正常组和CD3^(+)CD4^(-)CD8^(+)数量低组的PFS均值分别为54.97个月vs 49.07个月,外周血CD3^(+)CD4^(-)CD8^(+)T细胞数量低和更短的PFS相关(P=0.017,HR=2.31,95%CI=1.163~4.570)。结论外周血CD3^(+)CD4^(-)CD8^(+)T细胞数量低是T_(1)期尿路上皮癌进展的独立危险因素。

Combination drug regimens for metastatic clear cell renal cell carcinoma

Renal cell carcinomas(RCC)make up about 90%of kidney cancers,of which 80%are of the clear cell subtype.About 20%of patients are already metastatic at the time of diagnosis.Initial treatment is often cytoreductive nephrectomy,but systemic therapy is required for advanced RCC.Single agent targeted therapies are moderately toxic and only somewhat effective,leading to development of immunotherapies and combination therapies.This review identifies limitations of monotherapies for metastatic renal cell carcinoma,discusses recent advances in combination therapies,and highlights therapeutic options under development.The goal behind combining various modalities of systemic therapy is to potentiate a synergistic antitumor effect.However,combining targeted therapies may cause increased toxicity.The initial attempts to create therapeutic combinations based on inhibition of the vascular endothelial growth factor or mammalian target of rapamycin pathways were largely unsuccessful in achieving a profile of increased synergy without increased toxicity.To date,five combination therapies have been approved by the U.S.Food and Drug Administration,with the most recently approved therapies being a combination of checkpoint inhibition plus targeted therapy.Several other combination therapies are under development,including some in the phase 3 stage.The new wave of combination therapies for metastatic RCC has the potential to increase response rates and improve survival outcomes while maintaining tolerable side effect profiles.

Renal cell carcinoma:An update for the practicing urologist

Systemic therapy for metastatic renal cell carcinoma(mRCC)has evolved drastically,with agents targeting vascular endothelial growth factor(VEGF)and the mammalian target of rapamycin(mTOR)now representing a standard of care.The present paper is to review the current status of relevant clinical trials that were either recently completed or ongoing.(1)Though observation remains a standard of care following resection of localized disease,multiple trials are underway to assess VEGF-and mTOR-directed therapies in this setting.(2)While the preponderance of retrospective data favors cytoreductive nephrectomy in the context of targeted agents,prospective data to support this approach is still forthcoming.(3)The first-line management of mRCC may change substantially with multiple studies exploring vaccines,immune checkpoint inhibitors,and novel targeted agents currently underway.In general,prospective studies that will report within the next several years will be critical in defining the role of adjuvant therapy and cytoreductive nephrectomy.Over the same span of time,the current treatment paradigm for first-line therapy may evolve.

EXPRESSION AND SIGNIFICANCE OF TUMOR INFILTRATING DENDRITIC CELLS IN RENAL CELL CARCINOMA

Objective: To study the expression of dendritic cells in human renal cell carcinoma and explore the cause, so to reveal the mechanism of escaping immune surveillance in RCC. Methods: The expressions of CD83+DCS, CD1a+DCS,VEGF and TGF-β1 in tumoral, peritumoral and normal kidney tissues of RCC in 30 cases were detected by immunohistochemistry using streptavidin/peroxidese(SP) Results: CD83+DCS were mainly located in the peritumoral areas; whereas CD1a+DCS、were mainly retained within the cancer nests. The number of CD83+DCS was inversely correlated with the clinical stage(P<0.05); but there were no significant correlations between the number of CD1a+DCS、and the clinical stage(P>0.05). The expressions of CD83+DCS and CD1a+DCS have significant difference between the tumoral, peritumoral and normal kidney tissues(P<0.001). The expression of VEGF and TGF-β1 were significantly lower in samples with highly infiltrating CD83+DCS(P<0.05); Whereas CD1a+DCS were not (P>0.05). Conclusion: DC has the tendency to gathering in tumor, but because of the immunosuppressive cytokins, for example VEGF and TGF-β1, inhibits the maturation of DC, there are less mature TIDCS(CD83+TIDCS) in the tumoral tissues, they are mainly located in the peritumoral areas. This may contribute to the mechanism of escaping immune surveillance in RCC.

3D LAVA-FLEX和2D T_(1)WI-IDEAL序列在鼻咽癌MRI增强扫描中的应用对比

目的:通过对比鼻咽癌患者3D LAVA-FLEX和2D T1WI-IDEAL MRI增强扫描序列的图像质量、对病灶的显示能力以及序列的诊断价值,评估3D LAVA-FLEX序列在分期扫描中的应用价值。方法:2020年7—11月连续对30例就诊于我院的鼻咽癌初诊患者进行磁共振检查。鼻咽颈部平扫后,注射0.2mmol/kg的钆喷酸葡胺,进行2D T_(1)WI-IDEAL序列和3D LAVA-FLEX序列增强扫描。比较两个增强序列的总体图像质量等主客观指标。结果:2D T_(1)WI-IDEAL与3D LAVA-FLEX总体图像质量评分没有统计学差异(P=0.366),LAVA-FLEX(3.1分)的伪影少于T_(1)WI-IDEAL(2.57分)(P<0.001),LAVA-FLEX(3分)的肿瘤显示效果优于T_(1)WI-IDEAL(2分)(P<0.001),LAVA-FLEX肌肉脂肪对比度、原发灶脂肪对比度及转移淋巴结脂肪对比度(0.69、0.83、0.81)均优于T_(1)WI-IDEAL(0.42、0.62、0.58)(P<0.001),两序列的信噪比(SNR)肿瘤及SNR肌肉差异均没有统计学意义(P=0.926,P=0.141),但是对于两个序列脂肪抑制均匀度的评价,主观和客观评价都表明T_(1)WI-IDEAL优于LAVA-FLEX(P<0.001)。结论:3D LAVA-FLEX序列可以作为鼻咽癌分期磁共振扫描的首选增强序列。

Immunotherapy:A new standard in the treatment of metastatic clear cell renal cell carcinoma

Renal cell cancer(RCC)represents 2%-3% of all adulthood cancers and is the most common malignant neoplasm of the kidney(90%).In the mid-nineties of the last century,the standard of treatment for patients with metastatic RCC was cytokines.Sunititib and pazopanib were registered in 2007 and 2009,respectively,and have since been the standard first-line treatment for metastatic clear cell RCC(mccRCC).Renal cell cancer is a highly immunogenic tumor with tumor infiltrating cells,including CD8+T lymphocytes,dendritic cells,natural killer cells(NK)and macrophages.This observation led to the design of new clinical trials in which patients were treated with immunotherapy.With the growing evidence that proangiogenic factors can have immunomodulatory effects on the host’s immune system,the idea of combining angiogenic drugs with immunotherapy has emerged,and new clinical trials have been designed.In the last few years,several therapeutic options have been approved[immunotherapy and immunotherapy/tyrosine kinase inhibitors(TKI)]for the first-line treatment of mccRCC.Nivolumab/ipilimumab is approved for the treatment of patients with intermediate and poor prognoses.Several checkpoint inhibitors(pembrolizumab,nivolumab,avelumab)in combination with TKI(axitinib,lenvatinib,cabozantinib)are approved for the treatment of patients regardless of their International mRCC Database Consortium prognostic group and PD-L1 expression.There is no specific and ideal biomarker that could help in selecting the ideal patient for the appropriate first-line treatment.