Background Lateral retroperitoneal laparoscopic adrenalectomy (LRLA) is widely performed for the resection of adrenal disorders, but when larger and more malignant lesions are involved, the difficulty of LRLA increases. We aimed to develop and evaluate a predictive model for the surgical difficulty of LRLA. Methods A retrospective, observational, single-center study was performed involving all consecutive cases of unilateral RLA for adrenal disease from 2012.01 to 2021.12. Cases were randomly divided into training and validation cohorts (split ratio =7:3), then the least absolute shrinkage and selection operator (LASSO) regression was applied to reduce data dimension and select predictors. Multivariate logistic regression followed to develop the prediction nomogram for the surgical difficulty of LRLA. Finally, receiver operating characteristic (ROC) curve, calibration curve plot and decision curve analysis (DCA) were used to evaluate the nomogram’s discrimination, calibration, and clinical usefulness, respectively. Results A total of 621 cases were enrolled with a median age of 53 years and a median tumor diameter of 1.7 cm. After LASSO regression analysis, surgeon’s experience, tumor diameter, resection procedure, histological type, patient’s sex and body mass index (BMI) were identified to establish the nomogram. The model displayed good discrimination with area under the curve (AUC) in both the training cohort (0.754, 95% CI: 0.701–0.806) and validation cohort (0.742, 95% CI: 0.646–0.838). Additionally, excellent calibration curves were revealed for surgical difficulty evaluation in both the training cohort (P=0.999) and validation cohort (P=0.444). DCA results indicated the prediction model was clinically useful. Conclusions Our novel and effective predictive model can be used to assess the individual surgical difficulty of LRLA. By stratifying patients at risk of having a difficult LRLA for adrenal disease, the model could contribute to improvements in perioperative strategy and therapy.
目的:比较机器人辅助腹腔镜肾部分切除术(RAPN)与传统腹腔镜肾部分切除术(LPN)对于囊性肾脏肿瘤术后五连胜达成情况.方法:回顾性分析2017年1月至2021年12月在两个中心诊治的囊性肾肿瘤的患者资料,比较行RAPN手术与LPN手术患者一般临床资料、手术资料及术后资料.结果:74例囊性肾脏肿瘤患者中,27例行LPN手术,47例行RAPN手术.两组患者一般临床资料、平均手术时间[(120±50)min vs.(140±45)min,P=0.195)]、热缺血时间[(19.5±1.3)min vs.(19.0±1.8)min,P=0.835]及出血量[(30±20)ml vs.(50±30)ml,P=0.427)]均无显著差异.患者术后1年eGFR与术前相比,行RAPN手术患者保留率显著优于行LPN手术患者(86.6%vs.79.7%,P=0.031),且五连胜达成比例更高(57.4%vs.33.3%,P=0.002).两组患者术后下地时间、术后进食时间、引流管以及导尿管拔除时间均无显著差异.多因素分析结果表明热缺血时间和行机器人手术或传统腹腔镜手术是影响术后eGFR保留(OR=1.095,95%CI:1.001-1.198;P=0.047;OR=0.055,95%CI:0.009-0.332;P=0.002)和五连胜达成(OR=1.106,95%CI:1.009-1.212;P=0.038;OR=0.112,95%CI:0.023-0.559;P=0.006)的独立危险因素.结论:囊性肾肿瘤行RAPN手术相较于LPN手术患者术后一年eGFR保留及五连胜达成率更高.
Objective:To explore the risk factors of prolonged operation time and higher intraoperative blood loss of retroperitoneal laparoscopic radical nephrectomy (LRN).Methods:The data of patients who underwent retroperitoneal LRN from August 2010 to December 2021 were analyzed retrospectively. Demographic and hospital admission data were collected from these patients with complete medical records. Furthermore, univariate and multivariate logistic analysis were performed to determine the risk factor related to prolonged operation time and increased blood lose following LRN. Receiver operating characteristic (ROC) curve was used to assess the value of risk factors for predicting prolonged operation time and high intraoperative blood loss.Results:A total of 22 patients (24.4%) had prolonged operation time, and 14 patients (15.6%) had high intraoperative blood loss. The risk factor associated with prolonged operation time in a multivariate analysis was surgical experience (OR=0.13, P<0.001). The area under the ROC curve was 0.759 (95% confidence interval: 0.638-0.880) in the multivariate logistic regression model for predict prolonged operation time. Those associated with high intraoperative blood loss were surgical experience (OR=0.25, P=0.032) and tumor T stage (OR=3.18, P=0.007). The area under the ROC curve was 0.769 (95% confidence interval: 0.627-0.910) in the multivariate logistic regression model for predict high intraoperative blood loss.Conclusions:Surgical experience and tumor T stage were associated with the risk of prolonged operation time and high intraoperative blood loss.
Background: While laparoscopic adrenalectomy (LA) represents a gold standard for treating most adrenal lesions, no effective visual model for the prediction of perioperative complications of retroperitoneal laparoscopic adrenalectomy (RLA) exists.Methods: A retrospectively study was conducted involving all consecutive patients underwent unilateral RLA for adrenal disease from January 2012 to December 2021. The entire cohort was randomly divided into 2 subsets (70% of the data for training, 30% for validation). Subsequently, a Least Absolute Shrinkage Selection Operator (LASSO) regression was performed to select the predictor variables, which were further consolidated via random forest (RF) and Boruta algorithm. Then the nomogram was established using the bivariate logistic regression analysis. Eventually, the receiver operating characteristic (ROC) curve, calibration curve, and decision curve analysis (DCA) were employed to evaluate discrimination, calibration and clinical usefulness of the model, respectively.Results: A total of 610 patients underwent unilateral RLA for adrenal diseases were enrolled. After machine learning analyses, a weighted nomogram was established with 7 factors associated with complications including operative time, lesion laterality, intraoperative blood loss, pheochromocytoma, body mass index (BMI) and 2 preoperative comorbidities (respiratory diseases, cardiovascular diseases (CVD)). The model displayed a fine calibration curve for perioperative complications evaluation in both the training dataset (P=0.847) and validation dataset (P=0.248). ROC with AUC revealed an excellent discrimination in the training dataset (0.817, 95% CI: 0.758-0.875) and validation dataset (0.794, 95% CI: 0.686-0.901). DCA curves showed that using this nomogram provided a more net benefit where threshold probabilities lay in the range of 0.1 to 0.9.Conclusions: An effective nomogram that incorporating 7 predictors was established in this study to identify patients at high risk of perioperative complications for RLA. It would contribute to the improvement of perioperative strategy due to its accuracy and convenience.
目的 探讨经腹膜后入路腹腔镜肾上腺切除术(RLA)手术时间延长的危险因素.方法 回顾性分析2016年1月-2021年12月该院泌尿外科收治的420例因肾上腺病变行RLA手术的患者的临床资料,包括:年龄、性别、体重指数(BMI)、合并症、既往腹部手术史、手术时间、瘤体大小、术后病理类型和肿瘤位置等.以手术时间的第75百分位数(140 min)为分界点,手术时间超过140 min的,定义为手术时间延长.分别应用单因素和多因素Logistic回归模型,分析引起RLA手术时间延长的危险因素,计算受试者操作特征曲线(ROC curve)的曲线下面积(AUC),分析相关因素对RLA手术时间延长的预测价值.结果96例(22.86%)出现手术时间延长.单因素Logistic回归分析结果显示,男性、BMI≥31 kg/m2、术者经验(≤30例)、手术方式(肾上腺全切)、瘤体直径≥3.6 cm、病理类型(肾上腺皮质增生和嗜铬细胞瘤),与RLA手术时间延长有关.多因素Logistic回归分析结果显示,男性、BMI≥31 kg/m2、术者经验(≤30例)、瘤体直径≥3.6 cm和嗜铬细胞瘤,是引起RLA手术时间延长的独立危险因素.以病理类型(嗜铬细胞瘤)、性别(男性)、术者经验(≤30 例)、BMI≥31 kg/m2 和瘤体直径≥3.6 cm为预测因素,AUC为 0.735(95%CI:0.678~0.793).结论 RLA手术时间延长与性别、BMI、病理类型、术者经验和瘤体直径等因素有关,术前对这些危险因素进行识别,有助于更准确地选择手术方案,缩短手术时间.
The study aimed to investigate the anti-tumor effects and underlying mechanisms of Enzalutamide (ENZ) and Arsenic trioxide (ATO) co-treatment on castration-resistant prostate cancer (CRPC). The effects on C4-2B cells were initially evaluated by colony formation assay, FACS analysis, and DNA fragmentation detection. Bioinformatics methods including mRNA-sequencing and gene enrichment analysis were used to screen the underlying target genes and pathways related to their actions. Western blot was employed to assess the expression levels of protein-related angiogenesis, apoptosis, DNA repair, and the screened genes. Finally, the effects were further verified in subcutaneous tumor models and tissue sections from the xenografts. It was found that not only could ENZ combination with ATO significantly inhibit cell proliferation and angiogenesis, but also induce cell arrest and apoptosis in C4-2B cells. In addition, interruption of the DNA damage repair-related pathways also occurred as a result of their combined effects. Western blot analysis further suggested that proteins involved in these pathways, especially P-ATR and P-CHEK1 were significantly reduced. In addition, their combination also inhibited the tumor growth of xenografts. Altogether, ENZ combination with ATO synergistically improved the therapeutic effects and suppressed CRPC progression through regulation of the ATR-CHEK1-CDC25C pathway.
目的 利用生物信息分析的方法筛选恩杂鲁胺(ENZ)耐药细胞株的潜在耐药基因.方法 从GEO数据库中下载ENZ耐药的前列腺癌(PCa)细胞株的数据集(GSE104935),利用生物信息分析的方法筛选差异表达基因,进行GO/KEGG富集分析,构建蛋白质互作(PPI)网络筛选潜在耐药的中枢(Hub)基因.结果 C4-2B耐药株与LNCaP耐药株共表达的上调基因为106个,下调基因为88个.GO/K EGG富集分析表明共表达基因在前列腺上皮组织生发、转录翻译的调节、泛素化蛋白的降解、化学致癌相关受体激活、癌症的表达失调及前列腺癌相关的生物过程及通路中富集.PPI网络分析得到在共表达的194个基因中起核心作用的前10Hub基因(上调:ACPP、AR和LEF1,下调:KLK2、TMPRSS2、ZBTB16、FOXO1、NKX3-1、PMEPA1和SLC45A3).生存分析表明Hub基因中AR、FOXO1、NKX3-1和SLC45A3与PCa患者生存预后密切相关.结论 AR、FOXO1、NKX3-1和SLC45A3四个Hub基因,尤其是FOXO1和NKX3-1与去势抵抗型前列腺癌(CRPC)的恶性进展密切相关,可能成为改善ENZ疗效、延长CRPC患者生存时间的潜在治疗靶点.
Objective:To investigate the experience, safety and feasibility of robot assisted simple prostatectomy for large volume benign prostatic hyperplasia (BPH).Methods:The clinical data of 21 patients who underwent robot assisted simple prostatectomy in our hospital from Jan. 2017 to Jan. 2021 were retrospectively analyzed, and the surgical procedures, intraoperative and postoperative problems were summarized.Results:All cases were operated successfully without conversion to open surgery. The average operation time was (135.7±23.2) min. The average blood loss was (168.4±21.5) ml without blood transfusion in all cases. Bladder irrigation time was within 24 h after operation. The average suprapubic catheter time was 2 days. The average drain time was 3 days, and the mean catheter time was (12.5±2.4) days. Post-void residual, international prostate symptom score (IPSS) and maximum urine flow were improved significantly 3 months after operation (P<0.01).Conclusions:Transperitoneal robot assisted simple prostatectomy is a safe and effective minimally invasive method for large volume benign prostatic hyperplasia, which may become an alternative treatment.
目的 分析输尿管软镜钬激光碎石术及其细节护理在上尿路结石合并心衰患者的临床应用效果,为该术式的临床推广提供实验依据.方法 选取2019年1月至2021年1月北京安贞医院泌尿外科行输尿管软镜激光碎石术的上尿路结石合并心衰患者共82例,并按照围手术期采用细节护理(实验组)和常规护理(对照组)分成两组,每组41例.分析患者的不良反应发生率、手术治疗满意度、患者手术前后的焦虑自评量表(self-rating anxiety scale,SAS)和抑郁自评量表(self-rating depression scale,SDS)评分,以及疼痛评分和生活能力Barthel量表评分,同时比较两种护理模式的差异.结果 行输尿管软镜钬激光碎石术82例手术患者中发生不良反应共13例,占比15.9%,其中实验组不良反应发生率低于对照组(P<0.05).对手术满意有75例,为91.5%,实验组手术满意度高于对照组(P<0.05).手术后,患者的疼痛和日常生活能力评分都好于术前,且实验组疼痛评分低于对照组(P<0.05),日常生活能力评分高于对照组(P<0.05).患者术后的SAS量表和SDS量表评分低于术前(P<0.05),且实验组SAS量表和SDS量表评分低于对照组(P<0.05).结论 针对上尿路结石合并心衰患者,输尿管软镜钬激光碎石术具有较好的临床应用前景,且细节护理可有效提高临床疗效.
Objective:To analyze the side effects and complications in prostate cancer patients treated with brachytherapy.Methods:A total of 120 prostate cancer patients with average age of (73±5) years were recruited. All the patients were diagnosed as prostate cancer and accepted prostate brachytherapy from 2011 to 2019 under the guidance of transrectal ultrasound. The adverse reactions of urinary tract and their complications after prostate cancer 125I seed implantation were analyzed retrospectively.Results:A total of 120 patients with prostate cancer were collected and the clinical average Gleason score was (8.4±1.1). The IPSS scores of the patients were (13.1±3.6), (21.6±4.6), (19.2±4.4), (15.9±3.9), (13.9±3.1) and (13.5±2.7) before operation, 1 month after operation, 3 months after operation, half a year after operation, 1 year after operation and 2 years after operation, respectively. The incidence of grade I and grade II complications was 14.2% and 5.8% respectively within 1 month after operation, and 5.0% and 2.5% respectively within 3 months after operation. There were no grade III or IV complications.Conclusions:Prostate brachytherapy is a minimally invasive treatment for prostate cancer. Although the implantation of particles has a certain impact on the urination of patients, but the degree is relatively light, with a certain degree of self-limiting. Intraoperative accurate localization and making accurate implantation plan are factors to the prevention of serious complications.
Background Recently, there are growing evidence indicated that pyroptosis play a critical role in the incidence of many diseases. Here, we aimed to identify the specific function and prognosis predictive of pyroptosis-related genes (PRGs) in bladder cancer (BLCA) patients. Methods The gene expression and corresponding clinical data of BLCA patients were obtained from The Cancer Genome Atlas (TCGA), and the expression level of PRGs was identified between normal and tumor tissues. Furthermore, univariate Cox regression was conducted to filter the PRGs related to overall survival, and LASSO Cox regression was subsequently conducted to establish the PRGs risk model. Besides, the correlation of risk score with patients’ clinical features, tumor mutational burden (TMB) as well as tumor microenvironment (TME) was also investigated. Results A total of 6 PRGs was used to establish the risk prognostic model. According the median value of risk score, the patients were classified into low- and high-risk subgroup. Kaplan-Meier survival analysis revealed that the BLCA patients in low-risk group exhibited a better survival prognosis compared with high-risk group. More important, after adjusting for age, gender, tumor grade, and clinical stage, the risk score resulted as an independent factor affecting the clinical prognosis of BLCA patients. In addition, the PRGs risk signature was also correlated with immune cell infiltration, TMB and TME. Conclusions The present study offered a novel PRGs risk model to access the clinical prognosis of BLCA and provided new insight for future study to improve overall survival and responses to cancer therapy targeting pyroptosis.
Objective:To explore the risk factors associated with postoperative complications and prolonged length of stay (LOS) following retroperitoneal laparoscopic radical nephrectomy (LRN).Methods:A retrospective data gathering from 103 patients in Beijing Anzhen hospital who underwent retroperitoneal LRN from Aug. 2010 to Aug. 2021 was conducted. The demographic and clinical data of the patients, including age, gender, Body Mass Index (BMI), comorbidities, American Society of Anesthesiologists (ASA) score, previous abdominal surgery, tumor size, T stage, intraoperative blood loss, intraoperative blood transfusions, postoperative complications and postoperative length of stay, were retrospectively collected. We examined the overall postoperative complications, which were categorized using the Dindo-Clavien classification system. A prolonged LOS was quantified in terms of postoperative hospital stay >10 days, which was defined as LOS >75th percentile of the dataset. Furthermore, univariate and multivariate logistic analysis were performed to identify the risk factor related to postoperative Clavien-Dindo complications and prolonged LOS.Results:Overall, 103 participants participated in the study. A total of 16 cases (15.5%) suffered postoperative complications of Clavien-Dindo classification grade of 2 or more, and 17 cases (16.5%) had prolonged LOS. The risk factors associated with an increased prevalence of postoperative complications in a multivariate analysis were: operation time ≥240 minutes (OR: 5.17, P=0.024) and intraoperative blood loss >300 ml (OR: 22.89, P=0.001). Those associated with an increased prevalence of prolonged LOS was intraoperative blood transfusion (OR: 9.94, P=0.023).Conclusions:Postoperative complications and prolonged LOS following LRN were related to intraoperative blood loss, operative time, and intraoperative blood transfusion.
目的 总结心脏移植患者手术后行输尿管硬镜和软镜手术的围手术期处理经验.方法 回顾性分析2008年1月-2021年1月首都医科大学附属北京安贞医院10例心脏移植患者术后行输尿管结石治疗的临床资料.结果 10例患者均顺利完成手术,未出现严重并发症,术后随访1个月,结石消失,其他均未见异常,移植心脏功能良好.结论 通过多学科协作和充分的围手术期准备,心脏移植术后输尿管结石患者行输尿管镜治疗是安全和可行的.
目的 探讨囊性肾细胞癌的临床特征和腹腔镜肾部分切除术治疗囊性肾癌的可行性和安全性.方法 回顾性分析2010年1月-2021年1月首都医科大学附属北京安贞医院泌尿外科收治的15例囊性肾细胞癌患者的临床资料.所有患者术前均行计算机断层扫描(CT)和增强扫描,并在全身麻醉下行腹腔镜肾部分切除术,术后行病理学检查.定期随访肾功能和CT.结果 术前影像学检查提示15例患者存在囊性肾癌,均行腹腔镜肾部分切除术,手术顺利无并发症发生,术后病理检查均为肾透明细胞癌.随访时间15~36个月,平均(26.8±7.5)个月.术后患者肾功能均正常,未见复发和转移.结论 囊性肾细胞癌患者影像学表现相对特殊.根据肿瘤具体情况,选择腹腔镜下肾部分切除术是安全可行的.
以免疫检查点抑制剂(ICI)为代表的新型免疫治疗在中晚期及转移性肾癌的治疗中取得了突破性进展,为肾癌患者带来了明显的生存获益。但并非所有的肾癌患者都能获益于ICI的治疗,仍有部分患者对ICI有着原发性或者获得性耐药。耐药机制与T细胞活化信号的缺失、抗原加工和提呈作用受损、其他替代免疫检查点的上调以及肿瘤免疫微环境等因素有关。本文就肾癌新型免疫治疗及其耐药机制的研究进展作一综述,为临床解决肾癌免疫治疗耐药的难题提供参考思路。
Among many factors of causing castration-resistant prostate cancer (CRPC) progression, a growing number of evidences have shown androgen receptors play a critical role. Therefore, blocking androgen receptor remains a therapeutic goal of CRPC. However, resistance to androgen receptor inhibitors, for example, enzalutamide, limits therapeutic efficacy for many patients. In this study, to develop an enzalutamide-resistant cell model for molecular mechanism investigation of enzalutamide-resistance, we continuously treated C4-2B cells with multiplied concentrations of enzalutamide. The IC50 of resistant cells was identified as 14.7705 µM, and the resistance index was calculated as 12.4. In addition, we verified the resistance of resistant cells through experiments in vivo and found the genes in androgen receptor signaling pathway (androgen receptor, Jagged1, Notch1) and those in androgen receptor alternative signaling pathways behaved the opposite. For some of the former, their mRNA and protein expression reduced markedly while for the latter, for example, CXCR7, AKT, STAT3, FOXP3, they rose dramatically in the expression level of protein and mRNA. More importantly, the tumor volume, tumor wet weight, PSA and VEGF secretion level, positive staining rate of Ki67 nuclei in resistant strain heterogeneous tumor treated with enzalutamide were significantly higher than those of maternal cell heterogeneous tumor treated with enzalutamide, whereas no obvious difference was detected between resistant strain heterogeneous tumor treated with enzalutamide and those of the resistant strain treated with reference drug. Finally, we identified 654 differentially expression genes and 2 compounds (atracurium besilate, methotrexates) associated with the amelioration of enzalutamide-resistance. Overall, we successfully established an enzalutamide-resistance cell model and screened out some resistance genes and candidate small molecule drugs.
Purpose To identify the differences in oncological outcomes for patients with different pT3a renal tumor invasion patterns and pathological features. Methods The protocol of this study was registered on PROSPERO (CRD42021234475). Relevant studies were identified by searching the PubMed, Cochrane library, Embase, and Web of Science databases. Cancer-specific survival (CSS) was selected as the endpoint. Pooled hazard ratio (HR) and 95% confidence interval (CI) extracted from multivariate Cox models were evaluated to identify the hazard association. Results A total of 22 studies, which enrolled 12384 patients were included for quantitative synthesis. Sinus fat invasion (SFI) + perinephric fat invasion (PFI) was associated with inferior CSS compared to SFI only (p = 0.02). Comparable CSS was observed between SFI and PFI (p = 0.57). SFI +/- PFI showed inferior CSS compared to PFI only (p = 0.0002). The presence of pelvicalyceal system invasion significantly increased the risk of cancer-specific mortality (p = 0.0005). Renal vein invasion (RVI) indicated poor oncological outcomes in terms of CSS (p = 0.002). The concomitant RVI and fat invasion (FI) significantly increased the risk of deterioration of CSS compared to RVI or FI (p < 0.0001). Multiple invasion patterns translated into a significantly decreased CSS (p < 0.0001). Aggressive tumor behavior, including lymph node involvement (p = 0.006), distant metastases (p < 0.00001), sarcomatoid differentiation (p < 0.0001), necrosis (p < 0.0001), Fuhrman grade III or IV (p < 0.0001), positive margin (p < 0.0001), and tumor size >7cm (p < 0.0001) were the predictors of inferior CSS. The lymphovascular invasion (p = 0.67) was indolent in terms of CSS. Conclusion This study confirmed the heterogenicity of pT3a renal tumors. Multiple invasion patterns could translate into a significantly decreased CSS, and SFI should not be merged in the SFI + PFI group. The presence of PSI or RVI could significantly increase the risk of cancer-specific mortality. Lymph node involvement, distant metastases, sarcomatoid differentiation, necrosis, high Fuhrman grade, positive margin, and size >7cm were the predictors of inferior CSS. A precise-risk grade of CSS for different invasion patterns including comprehensive combinations may be useful for the further refinements of the TNM system. Systematic Review Registration The current study was registered on PROSPERO, and the registration numbers is CRD42021234475.
背景与目的 去势抵抗性前列腺癌阶段的恩杂鲁胺耐药问题是临床上亟待解决的难题.本研究旨在建立一种可用于体外研究的人前列腺癌(prostate cancer,PCa)恩杂鲁胺(enzalutamide Enza)耐药细胞模型并筛选相关耐药基因.方法 采用MTT法检测雄激素非依赖的人PCa细胞株C4-2B的IC50值,确定Enza的初始处理浓度.然后,成倍增加Enza的初始浓度作用于C4-2B细胞,诱导建立PCa的Enza耐药细胞株(命名为C4-2B-ENZ).应用酶联免疫吸附测定(enzyme linked immunosorbent assay,ELISA)、MTT法评估C4-2B-ENZ细胞株的耐药情况.采用聚合酶链式反应(polymerase chain reaction,PCR)及蛋白质免疫印迹检测耐药细胞株mRNA和蛋白质的表达情况.在此基础上,通过裸鼠体内成瘤实验,ELISA法检测人前列腺特异性抗原(prostate specific antigen,PSA)和人血管内皮生长因子(vascular endothelial growth factor,VEGF)水平,免疫组化检测Ki67水平,进一步验证C4-2B-ENZ细胞的耐药性.最后,应用高通量芯片技术进一步筛选C4-2B与C4-2B-ENZ细胞差异表达的基因.结果 C4-2B细胞的IC50值为1.2μmol/L,C4-2B-ENZ细胞的IC50为14.77μmol/L,其耐药指数为12.4,属于中度耐药.蛋白质免疫印迹和PCR结果显示,与C4-2B细胞相比,C4-2B-ENZ细胞中Enza耐药基因CXCR7、AKT、STAT3、FOXP3的mRNA及蛋白质高表达,而AR、Jagged1、Notch1低表达.与C4-2B细胞异质瘤相比,耐药细胞C4-2B-ENZ异质瘤Enza处理后,瘤体生长曲线(P=0.0296)、瘤体质量(P<0.0001)、VEGF水平(P=0.0003)、PSA水平(P<0.0001)、Ki67胞核染色阳性率(P=0.0007)均显著升高.芯片筛选结果显示,与C4-2B细胞相比,C4-2B-ENZ细胞中有653个基因表达显著差异,其中211个基因表达上调,443个基因表达下调.结论 本研究建立了Enza耐药细胞模型并筛选出一些潜在的Enza耐药基因,为研究去势抵抗型前列腺癌耐药机制及药物靶点提供了研究线索.
目的 对比近距离照射联合雄激素阻断与根治术联合雄激素阻断治疗对中/低危前列腺癌患者生存预后影响的差异.方法 回顾性分析首都医科大学附属北京安贞医院2015年1月至2019年1月期间接受近距离照射联合雄激素阻断治疗(BT+ADT组,68例)或前列腺癌根治术联合雄激素阻断治疗(RP+ADT组,85例)的153例中/低危前列腺癌患者的临床资料,比较两组患者的生存预后及前列腺特异性抗原(PSA)动力学差异.结果 BT+ADT组与RP+ADT组PSA动力学资料差异无统计学意义(P>0.05).随访过程中死亡7例,其中RP+ADT组4例(4/85),BT+ADT组3例(3/68),两组患者无病生存率及总体生存率差异均无统计学意义(P>0.05).结论 中/低危前列腺癌患者中,根治术联合雄激素阻断与近距离照射联合雄激素阻断治疗治疗效果相当.
Prostate cancer (PCa) is one of the most common malignancies for males, but very little is known about its pathogenesis. This study aimed to identify novel biomarkers associated with PCa prognosis and elucidate the underlying molecular mechanism. First, The Cancer Genome Atlas (TCGA) RNA-sequencing data were utilized to identify differentially expressed genes (DEGs) between tumor and normal samples. The DEGs were then applied to construct a co-expression and mined using structure network analysis. The magenta module that was highly related to the Gleason score (r = 0.46, p = 3e–26) and tumor stage (r = 0.38, p = 2e–17) was screened. Subsequently, all genes of the magenta module underwent function annotation. From the key module, CCNA2, CKAP2L, NCAPG, and NUSAP1 were chosen as the four candidate genes. Finally, internal (TCGA) and external data sets (GSE32571, GSE70770, and GSE141551) were combined to validate and predict the value of real hub genes. The results show that the above genes are up-regulated in PCa samples, and higher expression levels show significant association with higher Gleason scores and tumor T stage. Moreover, receiver operating characteristic curve and survival analysis validate the excellent value of hub genes in PCa progression and prognosis. In addition, the protein levels of these four genes also remain higher in tumor tissues when compared with normal tissues. Gene set enrichment analysis and gene set variation analysis for a single gene reveal the close relation with cell proliferation. Meanwhile, 11 small molecular drugs that have the potential to treat PCa were also screened. In conclusion, our research identified four potential prognostic genes and several candidate molecular drugs for treating PCa.