MicroRNA-34b/c rs4938723 T>C多态性与中国汉族人群肾细胞癌易感性的相关性

目的研究中国汉族人群microRNA-34b/c启动子区TC(rs4938723)多态性与肾细胞癌易感性之间的关系。方法采用病例对照研究模式,通过TaqMan探针PCR法检测年龄和性别匹配的710例中国汉族人群肾细胞癌患者和760例正常人群的microRNA-34b/c启动子区TC(rs4938723)基因型,探讨该位点基因多态性与肾细胞癌易感性之间的关系。结果与TT/TC基因型携带者相比,CC型(OR=1.53,95%CI=1.06~2.21,CC基因型比TT基因型;OR=1.48,95%CI=1.05~2.10,CC基因型比TT/TC基因型)携带者发生肾细胞癌的危险性明显升高。分层分析显示携带CC基因型的老年患者(OR=1.80,95%CI=1.08~3.01)、男性患者(OR=1.64,95%CI=1.08~2.51)、吸烟患者(OR=2.07,95%CI=1.16~3.69)及饮酒患者(OR=1.94,95%CI=1.01~3.73)发生肾细胞癌的危险性明显升高。结论 microRNA-34b/c启动子区TC(rs4938723)基因多态性与我国汉族人群肾细胞癌易感性有关,CC型携带者发生肾细胞癌的危险性要明显高于TT/TC型携带者。     

表皮生长因子5'非编码区rs4444903单核苷酸多态性与儿童肾母细胞瘤易感性及预后因素的研究

目的 研究表皮生长因子(epidermal growth factor,EGF)5'非编码区rs4444903单核苷酸多态性(SNP)与儿童肾母细胞瘤易感性及病理分期的关系.方法 采用病例对照研究,收集临床病理确诊的儿童肾母细胞瘤外周血96例,及正常同龄儿童外周血200例,应用聚合酶链反应-连接酶特异检测技术(PCR-LDR)分析两组儿童外周血DNA中EGF rs444490位点的多态性,比较不同基因型与前列腺癌易感性及病理分期的关系.结果 Logistic回归分析显示,儿童携带EGF rs4444903 GG和GG+ GA基因型能增加罹患肾母细胞瘤的风险(OR =2.45,95％CI=1.12～4.87,OR=1.25,95％ CI=1.08～ 2.34,P＜0.05),与患儿病理分期呈正相关(Ⅲ-Ⅴ期vs Ⅰ-Ⅱ期:OR =2.28,95％ CI=1.30 ～4.48,P＜0.01),并且GG/GA携带者其EGF血清表达亦增高(P＜0.05).结论 EGFrs444490位点多态性与肾母细胞瘤易感性及其预后相关,携带GG/GA基因型的肾母细胞瘤患儿预后较差.     

pre-miR-146a基因rs2910164位点单核苷酸多态性与胆管癌的关系

目的：探讨pre-miR-146a基因表达及其rs2910164位点多态性与胆管癌的关系。 方法：分别用基因直接测序与定量PCR方法检测70例胆管癌患者的胆管癌组织（胆管癌组）及 39例胆管非肿瘤性疾病患者的胆管组织（对照组）中pre-miR-146a基因rs2910164位点单核苷酸多态性与pre-miR-146a表达,分析不同基因型与pre-miR-146a表达量、胆管癌临床病理及其预后的关系。 结果：胆管癌组的pre-miR-146a基因型分布与对照组有明显差异,前者表现为GG和GC基因型比例明显高于CC基因型,且G等位基因频率明显高于C等位基因（均P<0.05）;对照组GG和GC基因型人群的pre-miR-146a表达量较CC基因型低,但差异无统计学意义（P>0.05）,胆管癌组织pre-miR-146a表达量明显低于对照组胆管组织（P<0.05）;Logistic多元回归分析显示GG和GC基因型可能是胆管癌的危险因素（P=0.052）,分层分析显示GG和GC基因型与胆管癌患者的临床分期和淋巴结转移有关（均P<0.05）;生存分析显示GG和GC基因型胆管癌患者的生存率低于CC基因型胆管癌患者,但差异无统计学意义（P=0.178）。 结论：pre-miR-146a基因rs2910164位点G等位基因频率升高可能是导致pre-miR-146a基因表达降低以及胆管癌发生发展的危险因素。

     

巨噬细胞清道夫受体单核苷酸多态性与前列腺癌易感及患者预后的相关性分析

目的探讨分析巨噬细胞清道夫受体(MSR1)单核苷酸多态性与前列腺癌易感及患者治疗预后的相关性。方法选择2017年3月至2019年5月在本院治疗的前列腺癌患者103例设为前列腺癌组,再选取同期在本院健康体检的男性受试者97例设为对照组。检测两组受试者MSRI基因r918位点及rs1904577位点的基因多态性分布情况,并分析前列腺癌化疗相关因素及MSRI基因rs918.rs1904577位点与前列腺癌患者生存预后的关系。结果两组受试者MISRI基因rs918位点基因型GG、AG.AA比较,差异具有统计学意义(P<0.05),携带AG、AA基因型者相对于携带GG基因型者罹患前列腺癌的OR值分别为1.364.7.941;两组受试者MSRI基因rs1904577位点基因型GG,AG.AA比较,差异具有统计学意义(P<0.05),携带AG、AA基因型者相对于携带GG基因型者罹患前列腺癌的OR值分别为1.819.8.228。对可能影响患者化疗疗效的各因素进行单因素及多因素logstie回归分析,其中T分期.CGleason评分以及MSRI基因rs1904577位点基因型进人回归模型(P<0.05),是影响患者化疗疗效的重要因素。MSR1基因rs918位点CG以及AG+AA基因型前列腺癌患者生存情况比较,差异无统计学意义(P>0.05)。MSRI基因rs1904577位点GG基因型前列腺癌患者生存情况显著优于AG+AA基因型患者(P<0.05)。结论MSR1基因ns918位点和rs1904577位点单核苷酸多态性与前列腺癌易感性相关,其中rs1904577位点单核苷酸多态性与患者化疗的疗效及生存预后有关。     

汉族人群白介素17受体C基因单核苷酸多态性与青少年特发性脊柱侧凸的相关性

【摘要】　目的：探讨白介素17受体C（IL-17RC）基因单核苷酸多态性与中国汉族人群青少年特发性脊柱侧凸（adolescent idiopathic scoliosis,AIS）易感性之间的相关性。方法：收集529例AIS女性患者及512例正常同龄女性青少年的静脉血标本,采用聚合酶链反应－限制性片段长度多态性（PCR-RFLP）方法鉴定和统计两组人群IL-17RC基因rs708567和rs279545多态性位点的基因型及等位基因分布频率;比较两组间不同多态性位点各基因型及等位基因分布频率的差异。结果：研究Power值（81%）大于80%,AIS患者组及正常对照组各多态性位点的基因型分布均符合Hardy-Weinberg遗传平衡定律。AIS组rs708567多态性位点GG基因型和G等位基因的分布频率显著高于对照组GG基因型（90.17% vs. 85.55%,P=0.023）和G等位基因（95.1% vs. 92.8%,P=0.028）的分布频率;携带GG基因型青少年中AIS的发病率约为携带AG基因型青少年的1.5倍（OR值=1.55;95% CI:1.45~3.11）。rs279545多态性位点各基因型及等位基因的分布频率在两组间均无统计学差异。结论：中国汉族人群中IL-17RC基因单核苷酸多态性与AIS的发生相关。     

肝移植术后受体他克莫司个体化用药与供体细胞色素P4503A亚家族多肽5和白细胞介素-18基因多态性的关系

目的 探讨肝移植供体细胞色素P4503A亚家族多肽5(CYP3A5)和白细胞介素-18(IL-18)基因多态性与受体术后他克莫司血药浓度/给药剂量的关系.方法 应用测序技术检测84例肝移植患者供体CYP3A5 rs776746和IL-18rs5744247位点单核苷酸多态性,分析基因多态性与他克莫司代谢表型(全血谷浓度/剂量比值,C/D,ng· ml-·mg-·kg-)的相关性.结果 肝移植术后,供体IL-18 rs5744247 GG+ GC基因型患者他克莫司C/D值[(163.1±100.8)ng·ml-1.mg-1·kg-1]明显高于CC基因型患者[116.7±78.2)ng.ml-1·mg-1·kg-1,P＜0.01].移植表达CYP3A5蛋白(*1基因型)供体的患者中,不同供体IL-18基因型患者C/D值(ng.ml-1·mg-1·kg-1) (GG+ GC:133.4±65.3;CC:88.3±39.9)差异有统计学意义(P＜0.05).结论 联合检测供体CYP3A5rs776746和IL-18 rs5744247基因型有助于指导他克莫司个体化用药.     

含缬酪肽蛋白基因单核苷酸多态性在肝细胞癌中的研究

目的:探讨含缬酪肽蛋白(valosin containing protein,VCP)基因不同位点单核苷酸多态性(single nucleotide polymorphism,SNP)与肝细胞癌(hepatocellular carcinoma,HCC)的关系。方法:采用病例组与对照组研究,收集122例HCC(HCC组)和120例非HCC(对照组)外周血标本,对VCP基因的4个标签SNPs采用直接测序法进行基因测定分型。采用卡方检验比较基因型及等位基因在HCC组与对照组之间分布的差异,采用非条件Logistic回归分析多态基因型与HCC的关系。结果:rs546982位点等位基因及基因型在HCC组与对照组中的分布具有显著性差异(P<0.05)。携带rs546982位点AA基因型者比GG基因型者发生HCC风险低,而携带AA基因型的HCC病人比携带GG基因型的HCC病人发生脉管癌栓及淋巴结转移的风险高。位点rs2074549、rs607671、rs10972300的基因型在HCC组和对照组之间差异无统计学意义。结论:VCP基因多态性与HCC存在关联,rs546982位点AA基因型可降低HCC发生率,但可增加HCC病人的淋巴结转移及脉管癌栓的风险。     

COX-2基因–765G>C位点多态性与结直肠癌易感性的meta分析

目的采用meta分析的方法定量评价环氧化酶-2(COX-2)基因–765GC位点多态性与结直肠癌易感性的关系。方法计算机检索Pub Med、Embase、The Cochrane Library、CNKI、CBM、VIP和万方数据库,搜集有关COX-2基因–765GC位点多态性与结直肠癌发病风险相关性的病例对照研究,检索时限均从建库至2016年5月。由两位评价员独立筛选文献并提取资料,采用Stata 12.0软件进行meta分析。结果共纳入13个病例对照研究,包括4 998例结直肠癌患者和7 750位健康对照者。总体人群的meta分析结果显示:COX-2基因–765GC位点多态性与结直肠癌易感性无关[GG vs.GC:OR=0.98,95%CI(0.89,1.07),P=0.590;GC vs.CC:OR=0.85,95%CI(0.65,1.11),P=0.236;GG vs.CC:OR=0.86,95%CI(0.66,1.12),P=0.275;GG+GC vs.CC:OR=0.87,95%CI(0.67,1.13),P=0.288);GG vs.GC+CC:OR=0.97,95%CI(0.89,1.05),P=0.425]。亚组分析结果显示,COX-2基因–765GC位点多态性的GG vs.GC和GG vs.GC+CC模型与亚洲人种结直肠癌的易感性可能有关[GG vs.GC:OR=0.70,95%CI(0.58,0.86),P=0.001;GG vs.GC+CC:OR=0.71,95%CI(0.58,0.87),P=0.001],而其他模型与结直肠癌的易感性无关[GC vs.CC:OR=1.74,95%CI(0.61,5.00),P=0.301;GG vs.CC:OR=1.18,95%CI(0.40,3.45),P=0.762;GG+GC vs.CC:OR=1.50,95%CI(0.53,4.23),P=0.440];COX-2基因–765GC位点多态性与高加索人种结直肠癌的易感性无关[GG vs.GC:OR=1.05,95%CI(0.95,1.16),P=0.321;GC vs.CC:OR=0.80,95%CI(0.61,1.01),P=0.129;GG vs.CC:OR=0.85,95%CI(0.64,1.11),P=0.228;GG+GC vs.CC:OR=0.83,95%CI(0.64,1.09),P=0.198;GG vs.GC+CC:OR=1.03,95%CI(0.94,1.13),P=0.526]。结论当前证据显示,COX-2基因–765GC位点多态性可能与亚洲人种结直肠癌易感性有关,而与高加索人种结直肠癌易感性无关。     

胰岛素降解酶基因单核苷酸多态性与前列腺癌的关系研究

目的研究胰岛素降解酶(IDE)基因单核苷酸多态性与前列腺癌之间的关系。方法运用TaqMan探针SNP分析法测定192例胰腺癌患者和258例正常对照IDE基因rs4646953和rs2251101两个位点基因型,并分析IDE基因多态性与前列腺癌的关系。结果病例组IDE基因rs4646953位点TT、CT以及CC3种基因型等位基因频率分别为85.4%、14.1%和0.5%;对照组3种基因型等位基因频率分别为88.4%、10.1%和1.6%。病例组rs2251101位点TT、CT以及CC3种基因型频率分别为81.8%、16.7%和1.6%;对照组3种基因型等位基因频率分别为73.6%、23.3%和3.1%。病例组IDE基因rs4646953位点的基因型分布与正常对照组比较未见统计学差异(P=0.348),rs2251101位点病例组CT和CC基因型低于正常对照组(P=0.039)。结论 IDE基因rs2251101位点变异与前列腺癌相关。     

eNOS基因单核苷酸多态性与习惯性流产患者的相关性研究

目的探讨内皮型一氧化氮合酶(eNOS)基因21个单核苷酸多态性位点(SNP)与习惯性流产(RSA)的相关性。方法选择eNOS基因21个位点,通过基质辅助激光解吸电离飞行时间质谱技术对227例RSA患者和232例健康对照进行了基因分型及数据统计分析。结果 RSA组及对照组eNOS基因8个位点基因频率分布符合H-W平衡。3个Block处于强连锁不平衡(D’0.9)。RSA组rs11771443位点CC基因型[χ2=5.107,P=0.004,OR(95%CI)=1.710(1.071,2.731)]及C等位基因频率[χ2=7.076,P=0.008,OR(95%CI)=0.682(0.514,0.905)]显著高于对照组;RSA组rs1799983位点GG基因型[χ2=10.587,P=0.001,OR(95%CI)=0.487(0.314,0.754)]及G等位基因频率(χ2=6.250,P=0.012,OR(95%CI)=0.615(0.420,0.902)]显著高于对照组;对照组中T-T-G单倍型频率显著高于RSA组(P=0.015)。结论eNOS基因rs11771443(Promoter)和rs1799983(Exon 7)位点多态性可能与RSA有关,携带有rs11771443多态性位点C等位基因与rs1799983多态性位点G等位基因的个体可能更容易患RSA;携带有T-T-G单倍型可能是RSA的保护因素。     

Renal cell carcinoma with non-islet cell tumor hypoglycemia

We report a case of an elderly gentleman with renal cell carcinoma presenting with the rare entity of non-islet cell tumor hypoglycemia (NICTH). Non-islet cell tumor hypoglycemia syndrome is caused by the tumor producing insulin-like growth factor II, causing hypoglycemia. The syndrome is most commonly associated with very large fibromas or fibrosarcomas.     

体细胞核移植的研究进展——核移植供体细胞与受体细胞的选择

根据近年来国外的研究进展,对核移植研究中的有关内容,如供体核的获得、受体卵母细胞与去核、核卵重组进行了综述,望能对核移植研究有所帮助。     

Synchronous ipsilateral conventional renal cell and transitional cell carcinoma

Simultaneous occurrence of renal cell carcinoma (RCC) and transitional cell carcinoma (TCC) in the same kidney is unusual. We report a 61-year-old man with ipsilateral synchronous renal adenocarcinoma and renal pelvic TCC. He was referred to our department for gross hematuria and right flank pain. CT and MRI studies revealed a 57 × 50 mm irregular and infiltrative upper right kidney mass with necrotic components. A right radical nephrectomy was done. Pathological diagnosis was a high grade tumor originating from just beneath the intact urothelium of renal pelvis and infiltrating through the parenchyma showing solid and occasional tubular growth patterns. A second tumor in close proximity to the first was reported as well differentiated RCC. This is a rare case of combined renal malignancies.     

Non-myeloablative allogeneic stem cell transplantation for metastatic renal cell carcinoma

Between 1999 and 2004, 11 patients with metastatic renal cell carcinoma (RCC) underwent non-myeloablative stem cell transplantation (NST) with conditioning using fludarabine-based regimens in two institutions of Korea. Among 11 patients, only one patient showed partial response (response rate: 9%), three showed stable disease, and six progressive disease. Three patients developed acute graft-versus-host disease (GVHD), and among them, one developed grade III acute GVHD which caused early death at day 60 after transplantation, and this patient showed partial response at day 30. Six patients developed chronic GVHD, three limited, and three extensive GVHD, respectively. Survival after one yr was 18% in transplanted patients. Median overall survival for entire cohort was 4.3 months. Eight patients died from progressive disease and three (27%) from treatment-related mortality. Only one patient survived 51.2 months after NST with slowly progressive disease. This patient received donor lymphocyte infusion three times after NST and achieved complete donor chimerism. NST does not lead to durable response and prolonged overall survival in the majority of patients with RCC in our series.     

Human rhabdosphincter cell culture: a model for videomicroscopy of cell contractions

BACKGROUND: Physiology of the human rhabdosphincter and its innervation are still a subject to controversy. A better understanding of rhabdosphincter function and anatomy might help to solve important urological problems like urinary incontinence. It was the aim of the present study to develop a human sphincter cell culture model for investigation of contraction mechanisms in vitro. METHODS AND RESULTS Cells were isolated from human rhabdosphincter tissue obtained from prostatectomy and cystoprostatectomy specimens. Cultured cells expressed typical features of striated muscle cells. By means of videomicroscopy with a time lapse videosystem cell contractions could be documented. Under control conditions without any contractile stimulant 8% of the cells were seen to contract. Cholinergic stimulation with 10 mM of acetylcholine induced a significant increase in contraction rate to 49%. CONCLUSIONS: These results demonstrate that cholinergic stimulation triggers contraction of cultured human rhabdosphincter cells. This model might help to understand external urethral sphincter physiology and to establish new therapies for the treatment of sphincter dysfunctions. Prostate 47:189-193, 2001.     

Roscovitine对增生期肝癌细胞周期的影响

目的 探讨细胞周期蛋白依赖激酶抑制剂Roscovitine对增生期肝癌细胞SMMC-7721细胞周期的影响.方法 采用体外培养的肝癌细胞SMMC-7721,经过Roscovitine作用后,对SMMC-7721细胞的形态、生长情况、细胞周期时相的分布、凋亡以及CDK2、Caspase-3、bcl-2 mRNA的表达情况进行观察.结果 MTT提示:Roscovitine对SMMC-7721细胞的增生有抑制作用,作用效果呈时间、剂量依赖性,并促进细胞的凋亡;流式细胞仪发现G0期、G1期的比例增加,细胞出现凋亡;R-T PCR显示CDK2 mRNA表达水平降低,凋亡相关基因bel-2表达降低,Caspase-3 mRNA水平表达升高.结论 Roscovitine可以抑制增生期肝癌细胞的生长、增生,阻滞细胞周期于G0/G1期,诱导细胞的凋亡,凋亡机制与bcl-2、Caspase-3的表达改变有关.     

同侧肾脏同时发生透明细胞型与乳头状肾细胞癌

目的探讨同侧肾脏发病并且相对独立的透明细胞型和肾乳头状细胞癌的临床病理特点及免疫表型,提高对该肿瘤的认识和诊断水平。方法本研究回顾了2例病理诊断为透明细胞型合并肾乳头状细胞癌的临床资料,通过光镜和免疫组织化学染色,针对肾细胞癌相关蛋白标志物[包括 Vimentin、CD10、CK（AE1/AE3）、CK7、CK8/18、PAX2、PAX8、CAⅨ、AMACR]进行了观察和分析。结果2例患者为男性,年龄分别为70、63岁。2例患者的两处独立肿瘤均位于左侧肾脏,镜下观察均可见两处独立肿瘤,肿瘤间隔有正常肾脏组织,分别为乳头状肾细胞癌及透明细胞型肾细胞癌,且免疫组化显示2例患者肿瘤的表型一致。结论单侧肾脏肾透明细胞癌合并肾乳头状细胞癌是一种少见的临床现象,这种现象的存在以及类似的免疫组化表型提示透明细胞型肾细胞癌和乳头状肾细胞癌在发生过程中可能存在着内部的联系。     

肿瘤干细胞的研究进展

肿瘤具有异质性的特征,随着研究的深入,越来越多的证据提示肿瘤组织中也存在少量具有干细胞性质的肿瘤干细胞,于是人们在此基础上提出了肿瘤干细胞学说,肿瘤干细胞已成为当今肿瘤研究领域的热点。目前,已经从白血病、脑肿瘤、乳腺癌、恶性黑色素瘤及前列腺癌等多种恶性肿瘤中初步分离鉴定出肿瘤干细胞。肿瘤干细胞学说的提出,使得靶向性杀伤肿瘤干细胞从而根治肿瘤成为可能。     

Therapeutic dendritic cell vaccination of patients with renal cell carcinoma

OBJECTIVE: Dendritic cell (DC) vaccination against cancer is a new specific immunotherapeutic approach given with either therapeutic or adjuvant intent. We provide a review of DC vaccination as a treatment for metastatic renal cell carcinoma (RCC). METHOD: A total of 197 patients with metastatic RCC were treated with DC vaccination in 14 phase I/II clinical trials. Different vaccine preparations, administration routes, and treatment schedules have been tested in these trials. Clinical response and immune response were analysed. RESULTS: Seventy-three (37%) patients had clinical response with 4 complete responses, 8 partial responses and 61 disease stabilisations, whereas 4 patients had mixed response, but most of these responses have not been transformed into durable clinical effects. Immune responses were observed in a subset of the treated patients but were not always associated with a clinical response. Only mild toxicity was observed in these trials. CONCLUSION: DC vaccination therapy in patients with metastatic RCC is currently experimental but the results are encouraging with achievement of tumour regression and induction of antigen-specific immune response combined with minimal toxicity in a subset of the treated patients. Future emphasis should be placed on therapy in the adjuvant setting because patients with minimal residual disease are more likely to benefit from the treatment. Combination approaches with DC vaccination and immune-enhancing therapies or antiangiogenic therapy should be further investigated to develop new and more efficient treatment strategies for patients with RCC.     

索拉非尼治疗转移性非透明细胞肾癌的疗效观察

目的 初步探讨索拉非尼治疗转移性非透明细胞肾癌的疗效.方法 转移性非透明细胞肾癌21例,中位年龄45(25～76)岁.12例为根治性肾切除术后出现转移,9例就诊时诊断为肾癌伴转移,行减瘤性肾切除术.术后病理证实乳头状癌15例、嫌色细胞癌1例、未分类癌5例.转移部位包括肺、淋巴结、肾上腺、骨、肝和甲状腺.治疗方法:①索拉非尼400 mg,2次/d治疗15例;②索拉非尼400 mg,2次/d加干扰素α 300万U,每周连续5 d皮下注射治疗6例.中位治疗时间8(2～21)个月.随访0～22个月.结果 部分缓解(PR)3例(14.3%),其肿瘤病理亚型分别为乳头状癌、嫌色细胞癌和未分类癌各1例,转移灶分别位于腹膜后加纵隔淋巴结、肺加腹膜后淋巴结和腹膜后加盆腔淋巴结.疾病稳定(SD)13例(61.9%),疾病进展(PD)5例(23.8%),疾病控制率76.2%.截至2009年7月,出现PD 13例,中位无疾病进展时间为7(0～21)个月.结论 索拉非尼治疗转移性肾乳头状癌、嫌色细胞癌、未分化癌有效,对淋巴结转移及肺转移者的疗效相对较好.