Enhancement of T cell proliferative response against autologous cancer cells of a metasatic renal cell carcinoma patient after unexplained regression

The unexplained regression of a metastasis of renal cell carcinoma (RCC) is rare phenomenon. While an immune mechanism has been proposed for spontaneous or unexplained regression of RCC, only limited data are available regarding immunological response. We report a case of a 62-year-old man with RCC whose paravertebral pleural tumor regressed after the withdrawal of interferon-alpha. In the present case, we demonstrate the enhancement of T cell proliferative response against autologous RCC cells secondary to the unexplained regression using the mixed-lymphocyte tumor culture. To our knowledge, the enhancement of an antitumor immunity secondary to an unexplained regression of RCC has not previously been reported.     

结石肾并肾癌的诊断和治疗

目的 探讨结石肾合并肾癌的诊断与治疗策略.方法 回顾分析9例结石肾合并肾癌患者的病例资料及诊治经过.结果 9例患者中2例术前检查已发现结石肾合并肾占位病变行根治性肾切除;另7例中4例因结石手术术中发现可疑病灶行快速冰冻切片病检证实为肾细胞癌而行根治性肾切除,3例因结石肾积水合并感染形成脓肾行患肾切除,术后病理证实为肾癌...     

Cyst-associated renal cell carcinoma: Clinicopathologic characteristics and evaluation of prognosis in 27 cases

BACKGROUND: No consistent clinicopathologic characteristics of cyst-associated renal cell carcinoma (CRCC) have previously been determined. METHODS: In total, 768 patients with renal cell carcinoma (RCC) underwent radical or partial nephrectomy. Renal cell carcinoma was classified as CRCC in 27 of these patients (3.5%, subdivided into RCC originating in a cyst and cystic RCC), clear-cell RCC in 662 patients (86.2%), chromophobe cell renal carcinoma in 36 patients (4.7%) and papillary RCC in 43 patients (5.6%) according to the criteria of the World Health Organization. RESULTS: The pathologic stage and nuclear grade were usually lower in those with CRCC (low stage/low grade; 89%/96%) or chromophobe cell renal carcinoma (low stage/low grade; 89%/80%) than in those with clear-cell RCC (low stage/low grade; 59%/65%) or papillary RCC (low stage/low grade; 53%/69%). Of the 27 CRCC patients, only 19 (70%) could be diagnosed through preoperative imaging studies. Patients with CRCC showed a favorable prognosis (survival rate: 95% at 1 year, 89.7% at 3 years and 84.4% thereafter) and, especially among the patients with RCC originating in a cyst, no cancer-related death was observed. Comparing the survival among four types of RCC, a favorable outcome was observed in cases of CRCC or chromophobe cell renal carcinoma compared with clear-cell RCC or papillary RCC (clear vs chromophobe: P = 0.002; chromophobe vs papillary: P = 0.019; clear vs cyst-associated: P = 0.001; papillary vs cyst-associated: P = 0.00079). CONCLUSIONS: In cases of CRCC, the disease was usually detected at lower stages and grades and therefore the prognosis was better than in cases of other types of RCC. Preoperative diagnosis of this disease was very difficult, especially in cases of RCC originating in a cyst.     

肾嫌色细胞癌的超声造影表现

Objective To discuss the imaging characteristics of chromophobic cell renal carcinoma (CCRC) and study the features on the contrast-enhanced ultrasound (CEUS). Methods The CEUS features of CCRC in 28 cases identified by pathology were reviewed. The blood supply and enhancement characteristic were observed and analyzed on time intensity curve parameters. Results The 28 cases of CCRC showed poor blood supply in contrast with the renal cortex. The CCRC presented with heterogeneity enhancement, part of the tumor took on a high wash-in and wash-out, and enhanced less intense than the surrounding renal cortex. The actinomorphous strong echo of the tumors might be revealed with CEUS in 15 cases (54%). The time intensity curve analysis demonstrated that the CCRCs' difference of peak intensity and area under the curve were lower than the renal cortex (P＜0.05), but arrival time, time-to-peak and slope of ascending curve were higher than the renal medulla (P＜0.05). Conclusion The actinomorphous enhancement and poor blood supply in the tumor of CEUS could provide diagnostic evidence for CRCC.     

Apoptotic cell death and Smad4 expression in transitional cell carcinoma of the renal pelvis and ureter

PURPOSE: To investigate the frequency of apoptosis and the expression of Smad4 protein as well as their roles in transitional cell carcinoma (TCC) of the renal pelvis and ureter. METHODS: Apoptosis was detected by using terminal deoxynucleotidyl transferase (TdT)-mediated dUTP-biotin nick end labeling (TUNEL) technique in 34 formalin-fixed and paraffin-embedded specimens of renal pelvic and ureteral TCC. The expression of Smad4 was immunohistochemically studied. RESULTS: The incidence of apoptosis ranged from 1.10 to 3.75% with a median of 2.50% in TCC of the renal pelvis and ureter. The incidence of apoptosis was noted to be closely related to histologic grade but not to pathologic stage of the cancer. The expression of Smad4 was detected in six of 34 cases (17.6%). Regarding subcellular distribution, Smad4 protein was localized both in cytoplasm and nucleus of the cancer cells. In comparing the incidence of apoptosis with the expression of Smad4, no significant associations were seen between them. The expression of Smad4 was not related to the tumor grade nor stage of the cancer. CONCLUSIONS: The present study demonstrated close association of the incidence of apoptosis with the tumor grade of TCC of the renal pelvis and ureter. Significance of Smad4 expression was not noted in the study. It suggests that apoptotic cell death may play an important role in the tumor progression of renal pelvic and ureteral TCC.     

Sensitization of human renal cell carcinoma cell lines to TRAIL-induced apoptosis by anthracyclines

BACKGROUND: Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a new member of the tumor necrosis factor family. The present study investigated whether anthracyclines enhance TRAIL-induced apoptosis and cytotoxicity in renal cell carcinoma (RCC) cells. METHODS: Cytotoxicity was measured using the microtiter assay. Apoptosis was monitored using DNA ladder analysis. Caspase activity was determined using a quantitative colorimetric assay. RESULTS: Treatment of ACHN and Caki-1 human RCC lines with TRAIL, in combination with subtoxic concentrations of epirubicin (EPI) or pirarubicin (THP), enhanced induction of apoptosis and cytotoxicity. Sequential treatment with EPI followed by TRAIL induced significantly more cytotoxicity than the inverse treatment. The combined cytotoxicity of TRAIL and EPI was significantly inhibited by the TRAIL-neutralizing fusion protein DR5:Fc, although EPI did not affect the mRNA expression of DR4, DR5, DcR1 or DcR2. The combination treatment with TRAIL and EPI activated caspase-6 and -3, which were downstream molecules of the death receptor. Furthermore, the combined cytotoxicity of TRAIL and EPI was almost completely inhibited by Z-VAD-FMK, and partly inhibited by Ac-DMQD-CHO. CONCLUSION: These findings indicate that anthracyclines sensitize RCC cells to TRAIL-induced apoptosis and cytotoxicity through activation of caspases, suggesting that TRAIL, in combination with anthracyclines, has a therapeutic potential in the treatment of RCC.     

姜黄素对人肾癌ACHN细胞放疗增敏作用的实验研究

目的研究姜黄素对人肾癌ACHN细胞放射增敏作用并探讨其作用机制。方法不同浓度姜黄素作用于ACHN人肾癌细胞24h后,MTT法检测姜黄素药物毒性;克隆形成实验观察其对放射敏感性的影响;流式细胞术检测姜黄素诱导细胞的凋亡率、细胞周期分布。结果姜黄素对人肾癌ACHN细胞有明显的抑制作用,可引起细胞的凋亡,且存在剂量和时间依赖;较低浓度的姜黄素（5μmol和10μmol）即可降低放射后ACHN细胞的克隆形成率,其放射增敏比分别为1．61及2．36;姜黄素及姜黄素联合辐射组的细胞周期阻滞在辐射敏感时相G2／M期;结论低剂量的姜黄素对人肾癌ACHN细胞有放射增敏作用,其机制可能与其引起细胞的凋亡增加,细胞周期阻滞有关。     

姜黄素抑制肾癌ACHN细胞增殖及促凋亡的实验研究

目的观察姜黄素对人肾癌ACHN细胞株增殖及细胞凋亡的影响,探讨姜黄素诱导ACHN细胞株凋亡的作用机制。方法不同浓度姜黄素作用人肾癌ACHN细胞24 h后,应用MTT比色法检测姜黄素对人肾癌ACHN细胞的增殖抑制率;流式细胞术检测姜黄素诱导细胞的凋亡率;RT-PCR检测姜黄素对ACHN细胞Bcl-2、Bax、NF-κBP65 mRNA表达的影响;Western blot方法检测其对细胞Bcl-2、Bax、NF-κBP65I、κB蛋白表达的影响。结果姜黄素对人肾癌ACHN细胞有明显的抑制作用,可引起细胞凋亡,并且存在剂量和时间依赖;不同浓度姜黄素作用细胞24 h后,Bcl-2、NF-κBP65 mRNA水平下降,Bax mRNA水平升高(P0.05),Bcl-2、NF-κBP65蛋白表达量下降,BaxI、κB蛋白表达量升高(P0.05)。结论姜黄素通过上调IκB,下调NF-κB活性,调控凋亡基因Bcl-2/Bax的表达,抑制人肾癌ACHN细胞的增殖,诱导人肾癌ACHN细胞的凋亡。     

Primary apoptosis as a prognostic index for the classification of metastatic renal cell carcinoma

PURPOSE: We identified novel biological markers of prognosis in primary histopathological specimens from patients with metastatic renal cell carcinoma. MATERIALS AND METHODS: Apoptotic indexes (terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end-labeling), proliferation rates (Ki-67 antigen), p21 (WAF1/cip1) expression and CD95 (APO-1/Fas) expression were determined in paraffin embedded nephrectomy specimens from 73 patients with histologically confirmed, progressive metastatic disease. Kaplan-Meier survival analysis, log rank statistics and 2-proportional Cox regression analysis were done to identify new risk factors in addition to conventional classification criteria, and demonstrate statistical independence. RESULTS: Multivariate analysis indicated that primary tumor apoptosis (p = 0.0116) and the interval from diagnosis to metastatic disease (p = 0.002) had a high predictive impact on overall survival after initial diagnosis. Patients were assigned to 2 risk groups, namely a poor prognosis group with a median survival of 20 months, defined by apoptosis less than 6% in the primary tumor nephrectomy specimen and a time from initial diagnosis to metastatic disease of less than 6 months, and a good prognosis group with a median survival of 56 months, defined as the absence of 1 or 2 risk factors. CONCLUSIONS: Our findings showed that primary tumor apoptosis is a novel independent predictor in patients with metastatic renal cell carcinoma at initial diagnosis. It leads to a new prognostic index in the pretreatment classification of metastatic renal cell carcinoma.     

5t4在肾透明细胞癌中的表达及意义

目的探讨滋养层糖蛋白5t4在肾透明细胞癌中的表达及其意义。方法采用免疫组织化学技术检测72例肾透明细胞癌组织标本、17例癌旁肾组织以及14例非癌因素的肾脏组织标本中5t4的表达,并对5t4在肾透明细胞癌的表达与组织学分级的关系进行分析。结果 5t4在肾细胞癌组织中的阳性率为70.8%,癌旁肾组织中的阳性率为41.2%,两者具有差异性(P0.05)。5t4在肾癌组织学分级中低分级与高分级的表达存在显著差异(P0.01)。结论 5t4可作为判断肾透明细胞癌分化程度的标志物。     

双肾癌诊断和治疗策略

目的探讨双肾癌诊断和治疗策略。方法回顾分析22例双肾癌患者的临床资料。男15例，女7例；年龄32-69岁；同时性12例，异时性10例。3例有家族史。结果22例患者行保留肾单位的手术或肾癌根治术。随访18-91个月，5例肿瘤复发，1例死于尿毒症，1例死于肿瘤转移，10例无瘤生存，3例非癌死亡，2例失访。结论双肾癌多见于遗传性肾癌，保留肾单位手术是治疗双肾癌的首选方法，CT血管造影及三维重建有助于制定手术方案，异时性双肾癌预后较同时性双肾癌差。     

偶发肾癌和症状肾癌临床诊疗特点比较的Meta分析

目的 比较偶发肾癌和症状肾癌的临床诊疗特点,阐述早期检出肾癌的重要意义.方法 检索Medline、PubMed、Cochrane Library、Web of Science、万方数据库、CNKI中文期刊数据库2000年1月1日至2016年12月31日国内外公开发表的所有关于偶发肾癌和症状肾癌临床研究的文献,按照纳入和排除标准对文献进行筛选,对纳入研究的文献进行数据提取和质量评价,采用Review Manager 5.3软件进行Meta分析.结果 共纳入23篇文献,总计肾癌患者10 065例,其中偶发肾癌患者4 251例,症状肾癌患者5 814例.两组患者在肿瘤直径上平均差(MD)为-1.58(95% CI:-2.05~-1.11),在肿瘤病理分级(G1和G2)、保留肾单位手术例数、临床分期(T1和T2)、淋巴结转移、远处器官转移上比值比(OR)分别为3.01(95% CI:2.62~3.45)、3.47(95% CI:2.72~4.44)、3.95(95% CI:3.24~4.81)、0.20(95% CI:0.11~0.35)和0.24(95% CI:0.17~0.35),差异均有明显统计学意义(P<0.000 1);在手术年龄上MD为0.23(95% CI:-1.64~2.09),差异无统计学意义(P=0.81).结论 与症状肾癌相比,偶发肾癌具有肿瘤体积小、肿瘤病理分级低、临床分期早、淋巴结转移及远处器官转移少等特点,因此早期发现肾癌对提高患者生活质量及生存率十分重要.     

Cystic renal cell carcinoma diagnosed by cystofiberscopy

A 64-year-old man suffered from hypertensive syncope and was admitted to Branch Hospital, Faculty of Medicine, The University of Tokyo. On admission he had no symptoms; however, two renal cysts of about 5 cm in diameter were found in his left kidney. Cystofiberscopy with a thin optical fiberscope was performed in addition to puncture and cystography. Cytology revealed class I, but the wall surface of the lower cyst was uneven, fluid-filled, colloid-like and white-gray compared with that seen in the upper cyst. It was diagnosed as renal cell carcinoma (RCC) and left nephrectomy was performed (5 cm in diameter, RCC, papillary tubular, common, clear cell subtype, G2>G1, INF beta, pT2, pMx, pV0, ew(-)).     

Combined small cell carcinoma and sarcomatoid squamous cell carcinoma in the renal pelvis

We report here a case of combined small cell carcinoma and sarcomatoid squamous cell carcinoma in the renal pelvis. A 61-year-old female presented with right flank discomfort, microhematuria and progressive renal dysfunction. Following diagnosis of right renal pelvic carcinoma, radical nephroureterectomy with lymph node dissection was performed through a midline incision. The tumor was pathologically diagnosed to be combined small cell carcinoma and sarcomatoid squamous cell carcinoma in the renal pelvis. The patient had no evidence of recurrence or metastasis, 16 months postoperatively. Small cell carcinoma or sarcomatoid squamous cell carcinoma of the renal pelvis is very rare. We believe this is the first such case to be reported in the world.     

循环肿瘤细胞检测在转移性肾细胞癌中的应用

目的:探讨循环肿瘤细胞(circulating tumor cells,CTC)检测在转移性肾细胞癌临床诊断中的应用价值。方法:2013年3月~2015年5月收治的肾癌患者52例,所有患者在治疗前取外周静脉血标本7.5ml,用细胞搜索系统(cell search system,CSS)对患者外周血进行CTC定量检测,其中男41例,女11例。结果:CTC检测总体阳性率为48.1%(25/52),存在淋巴结转移及远处转移的患者,其CTC阳性率明显高于无淋巴转移及远处转移的患者,中晚期患者(Ⅲ期+Ⅳ期)其阳性率明显高于早期患者(Ⅰ期+Ⅱ期)。结论:CTC检测结果和传统上用来评价肾癌患者的预后的指标其结果一致,CTC的检测可以用来评估肾癌患者的预后,为肾癌患者术后是否应早期进行干预提供依据。     

NNMT在肾透明细胞癌的表达及对肾癌细胞侵袭能力的影响

目的:研究NNMT在肾透明细胞癌中的表达情况及对肾癌细胞侵袭能力的影响。方法:采用RT-PCR和Western blot方法检测正常肾小管上皮细胞株HKC、肾癌细胞株786-O及30例肾透明细胞癌组织、相应癌旁组织中NNMT的mRNA和蛋白的表达水平,并分析NNMT的mRNA水平与临床病理参数的关系。化学合成针对NNMT特异的siRNA序列,应用脂质体Lipofectamine 2000将其转染进786-O细胞中,利用RT-PCR和Western blot法检测NNMT在786-O细胞中的表达水平,用Transwell小室法检测肾癌细胞786-O侵袭能力的变化。结果:NNMT在肾癌细胞786-O中的mRNA和蛋白表达水平显著高于正常肾小管上皮细胞株HKC(P<0.001);肾透明细胞癌组织和对应的癌旁组织中NNMT的mRNA相对表达量分别为(1.582±0.2145)、(0.1269±0.04279),两组比较P<0.001。NNMT的mRNA水平与肿瘤大小、临床分期有关(P<0.05);Tran-swell法检测结果显示降低NNMT的表达后786-O细胞的侵袭能力明显下降。结论:NNMT在肾透明细胞癌组织和细胞中表达升高,可能在肾癌发生、发展过程中发挥重要作用。     

肾肿瘤剜除术治疗肾细胞癌、肾血管平滑肌脂肪瘤

目的探讨肾肿瘤剜除术治疗肾细胞癌及肾血管平滑肌脂肪瘤的疗效。方法回顾分析15例在我院进行肾肿瘤剜除术的肾细胞癌及肾血管平滑肌脂肪瘤患者的临床及病理资料。结果全部肾肿瘤均成功剜除,平均热缺血时间为15min,术中肿瘤剜除面平均出血25ml,术后无继发出血,无急性肾小管坏死、慢性肾功能不全及尿瘘等并发症发生。术后平均随访时间为2．5年,均未见肿瘤复发或转移。依据2003AJCC肾癌分期方法,所有肾癌患者均为Tla期,组织学形态为透明细胞癌。病理分级按Fuhrman标准为G1。结论肾肿瘤剜除术对有假性包膜的Tla肾细胞癌和肾血管平滑肌脂肪瘤是有效和安全的,术后并发症少,可以最大程度地保留肾脏功能。     

Enhancement of Siglec-8 expression predicts adverse prognosis in patients with clear cell renal cell carcinoma

Purpose

Sialic acid-binding immunoglobulin-like lectins (siglecs) family has important functions in tumor progression. The purpose of our study is to figure out the correlation between the expression level of Siglec-8 and prognosis of patients with clear cell renal cell carcinoma (ccRCC), and then to predict the overall survival (OS) via a novel nomogram.