前列腺癌患者PCA3 mRNA的表达及其临床意义

目的：评价PCA3在前列腺癌诊断、临床分期及Gleason评分中的临床应用价值。方法：选取2005年11月～2006年9月在我院住院的前列腺癌患者56例,其中T2期12例,T3期21例,T4（N0～3,M0～1）期23例;Gleason评分5～7分27例,8～10分29例;BPH患者23例,健康男性9例。分别获取其外周血及前列腺按摩液,采用RT—PCR方法检测两种体液标本中PCA3的表达阳性情况,使用SPSS12．0统计软件包对其结果进行分析。结果：BPH和对照组两种体液标本未见PCA3阳性表达,而PCa患者外周血标本PCA3阳性率为88．9％（48／54）,前列腺按摩液标本PCA3阳性率为81．3%（39／48）,差异均有统计学意义（P〈0．01）。结论：两种体液标本PCA3的阳性表达有明显的前列腺癌特异性,并且随着前列腺癌的临床分期增高,其阳性率越高,有望成为诊断前列腺癌的新肿瘤标志物和判断预后的指标。     

聚集素在前列腺癌中的表达及意义

目的　探讨抗细胞凋亡因子聚集素 (clusterin)在前列腺癌中的表达及意义。　方法　RT PCR方法检测聚集素在前列腺癌组织 (3例 )、癌细胞系 (1株 )及正常前列腺组织 (3例 )中的表达水平。　结果　 3例前列腺癌组织及 1例前列腺癌细胞株中聚集素与内参基因 β actin相比较的相对表达量明显高于 3例正常前列腺组织。　结论　聚集素在前列腺癌中高表达 ,提示聚集素可能通过抗凋亡机制在前列腺癌的生物特性中发挥作用。     

A comparison of prostate cancer detection rates by 12 or 6 core biopsy at different prostate-specific antigen densities in Korean men

OBJECTIVES: To evaluate the diagnostic value of 12 core biopsy versus sextant biopsy at different prostatic-specific antigen densities (PSAD). METHODS: We retrospectively analyzed the records of 1,463 patients who underwent transrectal ultrasound-guided prostate biopsies at our institution. 995 patients underwent 12 core biopsy and 468 sextant biopsy of the prostate. The cancer detection rates achieved by these two methods were analyzed at different PSAD levels. RESULTS: All patients were stratified into 5 groups according to PSAD level; group A: PSAD < 0.1 (n = 290), group B: 0.1 /= 0.4 (n = 231). In group B, 12 core biopsy had a higher detection rate than 6 core biopsy (P = 0.017). CONCLUSIONS: These results demonstrate 12 core biopsy is better able to detect cancer than 6 core biopsy in patients with a PSAD in the range 0.1-0.2, which suggests that PSAD be considered when deciding on the number of prostate biopsy cores required.     

前列腺特异性抗原持续异常患者前列腺重复穿刺活检的临床分析

目的 探讨PSA持续异常患者前列腺重复穿刺活检的诊断价值及适应证. 方法选取2004年1月至2011年9月首次穿刺活检诊断为前列腺良性病变但PSA持续异常的患者90例,其中BPH、正常前列腺组织及前列腺炎症患者组(BPH组)66例,前列腺上皮内瘤变(prostatic intraepithelial neoplasia,PIN)组10例,前列腺不典型小腺泡增生(atypical small acinar proliferation,ASAP)组14例.年龄43～86岁,平均71岁.PSA 3.1～168.0μg/L,平均17.6 μg/L.直肠指检(digital rectal examination,DRE)触及结节26例.采用模板定位经会阴重复穿刺活检. 结果 本组90例根据重复穿刺活检病理结果分为良性组57例,PIN或ASAP组5例,前列腺癌(prostate cancer,PCa)组28例.其中BPH组发现PCa为14例(21.2％),PIN组发现PCa为6例(60.0％),ASAP组发现PCa为8例(57.1％),BPH组与PIN组、ASAP组比较差异均有统计学意义(P＜0.05).BPH组重复穿刺活检诊断为良性组的平均前列腺体积为(65.9±22.6)ml,DRE阳性7例,PCa组为(50.4±20.8) ml,DRE阳性5例,两组间比较差异有统计学意义(P＜0.05).PIN组和ASAP组的患者重复穿刺活检结果显示年龄、PSA值、PSAD值、前列腺体积、DRE阳性例数在重复穿刺后诊断为良性组、PIN或ASAP组和PCa组间差异均无统计学意义(P＞0.05). 结论 对PSA持续异常患者行前列腺重复穿刺活检可以提高PCa的诊断率.首次穿刺诊断为BPH的患者,前列腺体积越小及DRE结果阳性者,若PSA持续升高,应强烈建议重复穿刺活检.首次穿刺诊断为PIN或ASAP的患者,不论年龄、PSA、PSAD、前列腺体积和DRE结果如何,均应建议重复穿刺活检.     

Vitamin D receptor polymorphism and prostate cancer prognosis

BackgroundProstatic epithelial cells synthesize the active form of vitamin D (1,25-dihydroxyvitamin D₃), which participates in regulating prostate growth. Calcitriol, a synthetic form of vitamin D₃, exhibits antiproliferative and prodifferentiation activities in prostate cancer. The function of 1,25-dihydroxyvitamin D₃ is mediated by its binding to vitamin D receptor (VDR). VDR forms a heterodimer, typically with retinoid X receptor, to regulate vitamin D target genes. We evaluated the relationship between VDR polymorphism and clinical characteristics associated with prostate cancer risk and prognosis among Egyptian men.Materials and methodsThis case-control study included 2 groups of patients: group A, a control group of 50 subjects with benign prostate hyperplasia, and group B, 50 subjects newly diagnosed with prostate cancer. All participants performed complete blood count, liver and kidney function tests, prostate specific antigen measurement, histopathological analysis and immunohistochemistry for Dickkopf Homolog 3. Restriction fragment length polymorphism-polymerase chain reaction as performed to detect VDR polymorphism.ResultsPatients with prostate cancer and controls showed a significantly different CA genotype frequency (p = 0.007). Furthermore, prostate-specific antigen levels were significantly different in different genotypes in patients with prostate cancer (p < 0.001). Finally, T stage and the VDR ApaI C/A polymorphism were significantly associated (p < 0.041).ConclusionThe VDR ApaI C/A polymorphism may be a diagnostic and prognostic marker for prostate cancer in Egyptian men.     

胃癌中人端粒酶逆转录酶mRNA的实时定量检测

目的　建立一种实时荧光定量逆转录 聚合酶链反应 (RT PCR)方法 ,检测胃癌组织中hTERTmRNA的表达 ,探讨hTERT的表达水平与胃癌的关系及其在胃癌诊断中的价值。方法采用Taqman技术与LightCycler荧光定量PCR仪对 3 5例胃癌及其相应切缘组织中hTERTmR NA的表达进行实时定量检测。将hTERT与GAPDH拷贝数之比的 10 0倍作为标准化hTERT(NhTERT)。结果　 (1)胃癌及其相应切缘组织中NhTERT分别为 6.2 7± 0 .89、0 .93± 0 .18,两者之间差异有统计学意义 (t =12 .76,P <0 .0 1)。(2 )胃癌组织中hTERTmRNA的表达水平与组织的分化程度密切相关 (P <0 .0 1) ,而与患者的年龄、性别、肿瘤的大小、定位以及 pTNM分期无相关性。结论　实时荧光定量RT PCR方法能对hTERTmRNA进行准确、高效的定量。hTERTmR NA的实时定量检测可能有助于胃癌的早期诊断。     

前列腺特异性膜抗原新型剪接变异体PSM-E对前列腺癌细胞骨转移的作用

目的 探讨前列腺特异性膜抗原(PSMA)新型剪接变异体PSM-E对前列腺癌细胞(RM-1)骨转移的作用及其机制.方法 脂质体将PSM-E、PSMA基因转染RM-1,构建细胞模型(RM-1-PSM-E、RM-1-PSMA),检测羧肽酶活性;黏附及迁移实验测定不同细胞在骨基质胶模型上的黏附及迁移能力;Western blot检测不同细胞中粘着斑激酶(FAK)的表达及磷酸化水平.结果 与转染空质粒的RM-1比较,RM-1-PSM-E、RM-1-PSMA的羧肽酶活性分别升高1.96倍和2.13倍,而黏附能力分别升高12倍和14倍,加入羧肽酶活性抑制剂后,RM-1-PSM-E、RM-1-PSMA的黏附能力分别降低2.6倍和3.5倍;与转染空质粒的RM-1比较,RM-1-PSM-E、RM-1-PSMA的迁移能力降低,且FAK的磷酸化水平分别升高1.47倍和1.66倍.结论 PSM-E对前列癌细胞骨转移具有调控作用,这与PSM-E的酶活性及FAK磷酸化水平有关.     

肿瘤-睾丸抗原在胃癌组织中的表达

目的 检测8种肿瘤-睾丸抗原(CTA)基因mRNA在胃癌组织及相应癌旁组织中的表达.方法 用逆转录-聚合酶链反应(RT-PCR)方法检测55例胃癌患者的癌组织和相应癌旁组织中8种CTA基因mRNA的表达,30例非肿瘤患者胃黏膜组织作为对照.结果 55例胃癌组织中,表达MAGE-A1、MAGE-A3、CT9、CT10、NY-ESO-1、SSX-1、SSX-2、SXX-4基因的阳性率分别是60.0%(33/55)、30.9%(17/55)、34.5%(19/55)、12.7%(7/55)、10.9%(6/55)、23.6%(13/55)、3.6%(2/55)和27.3%(15/55),而相应的癌旁组织均为阴性.非肿瘤患者胃黏膜组织未见此8种CTA基因的表达.8种CTA基因的表达与患者年龄、性别、肿瘤大小、分化程度、幽门螺旋杆菌感染及TNM分期无明显相关(P>0.05).结论 多种CTA基因在胃癌中呈特异性高表达,为胃癌的免疫治疗提供了新的潜在的靶位.     

Screening for prostate cancer using prostate-specific antigen testing in Japanese men on hemodialysis

Objectives The objectives of this study were to evaluate the usefulness of serum prostate-specific antigen (PSA) screening in detecting prostate cancer in Japanese men on hemodialysis, and to analyze features of prostate cancer detected in these patients. Materials and methods This study included 115 male hemodialysis patients aged >55 years who agreed to the measurement of serum PSA value (group A) and 7529 men aged >55 years participating in a PSA mass screening test in Kobe City (group B) between April 2005 and March 2006. Prostate biopsy was recommended in men with serum PSA > 4.0 ng/ml in both groups. Seventy-eight patients with normal renal function aged >55 years diagnosed as having prostate cancer during the same time period as groups A and B were also included as a comparison group (group C). Results There was no significant difference in the distribution of serum PSA values between groups A and B. Prostate biopsy was performed in 8 and 205 men in groups A and B, respectively, and prostate cancer was detected in 5 and 68 in groups A and B, respectively; that is, there was no significant difference in the rate of positive prostate biopsy between these two groups (group A, 62.5%; group B, 33.2%), while the cancer detection rate in group A (4.3%) was significantly greater than that in group B (0.90%). In addition, there was no evident metastasis in five patients on hemodialysis who were diagnosed as having prostate cancer, and their serum PSA, clinical T stage and biopsy Gleason score were similar to those in group C. However, the percent of positive biopsy cores in these five was significantly greater than that in group C. All five were treated by maximal androgen blockade therapy, and all are currently alive without emergence of hormone-refractory diseases. Conclusions These findings indicate that hemodialysis patients may have an increased risk of prostate cancer, and that prostate cancer detected in such patients tends to be relatively advanced. Therefore, it would be recommended for hemodialysis patients to undergo PSA testing to screen for prostate cancer.     

SPECT与PSA联合检测诊断前列腺癌的临床意义

目的：探讨放射性核素骨显像与血清前列腺特异抗原联合检测在前列腺癌诊断中的临床意义。方法;采用单光子发射型计算机断层摄影术骨显像及血清ＰＳＡ浓度检测诊断ＰＣａ患者６３例。结果：６３例ＰＣａ患者中,血清ＰＳＡ测定阳性率为９６．８３％,ＳＰＥＣＴ骨显像转移率为５７．１４％。结论：ＳＰＥＣＴ骨显像与血清ＰＳＡ浓度联合检测对于ＰＣａ患者的临床诊断及治疗具有重要的指导意义。     

大肠癌患者门静脉血癌细胞的检测及临床意义

目的 探讨门静脉血管癌细胞与大肠癌肝转移的关系。方法 以非核素ＲＴ－ＰＣＲ方法,对５４例大肠癌患者门静脉血中结肠癌细胞的标志物细胞角质蛋白２０（ＣＫ２０）进行了检测。结果 ５４例中,４１例门静脉血中检出ＣＫ２０阳性表达,阳性率７５．９％,ＣＫ２０阳性检出与Ｄｕｋｅｓ分期,肝转移存在显著性相关,随着Ｄｕｋｅｓ分期的进展ＣＫ２０阳性率显著增加,随访发现,门静脉血ＣＫ２０扩增阳性者,术后发生肝转移机会增     

前列腺体积和前列腺特异抗原密度与前列腺穿刺阳性率的关系

目的:探讨前列腺体积及前列腺特异抗原密度与前列腺穿刺阳性率的关系并分析其原因.方法:选择2004～2007年间于我院行超声引导下经直肠前列腺系统8针穿刺的患者192例.以前列腺体积<30 ml、30～50 ml、>50 ml为界,计算并比较各组问前列腺穿刺的阳性率及PSAD≥0.15时,前列腺穿刺阳性率的变化.结果:前列腺体积与前列腺穿刺阳性率呈负相关(r＝0.237,P<0.01),前列腺体积<30 ml组,穿刺阳性率为39.1%(18/46);30～50 ml组,阳性率为21.7%(13/60);>50 ml组,阳性率为9.3%(8/86).各组间差异有统计学意义(P<0.01,P<0.05).前列腺特异抗原密度≥0.15时,三组间阳性率差异仍有统计学意义(P<0.01).但三组漏诊率分别为11.1%(2/18)、30.8%(4/13)、62.5%(5/8),差异有统计学意义(P<0.01).结论:前列腺体积是前列腺穿刺阳性率的独立影响因素,应根据前列腺体积制定穿刺方案.     

多药耐药基因在泌尿系统肿瘤细胞系中的表达

目的检测泌尿系统肿瘤多药耐药基因及其产物的表达。方法对肾颗粒细胞癌细胞系ＧＲＣ１，肾透明细胞癌细胞系ＲＣＣ９４９，膀胱移行细胞癌细胞系ＢＩＵ８７、Ｔ２４、ＥＪ，前列腺癌细胞系ＰＣ３ｍ和对照的白血病细胞系ＨＬ６０进行免疫细胞化学和逆转录聚合酶链反应（ＲＴＰＣＲ）检测。结果只有ＧＲＣ１同时表达Ｐ糖蛋白（ＰＧＰ）和ＭＤＲ１基因ｍＲＮＡ，其他肿瘤细胞系均无表达。结论泌尿系肿瘤细胞系多数无ＰＧＰ也没有ＭＤＲ１基因ｍＲＮＡ水平的表达，只有ＧＲＣ１例外     

Immunocytochemical detection and phenotypic characterization of micrometastatic tumour cells in bone marrow of patients with prostate cancer

Monoclonal antibodies (mAbs) specific for cytokeratins are potent probes for the identification of disseminated individual epithelial tumour cells in mesenchymal organs such as bone marrow. We have used a monoclonal antibody (mAB) against cytokeratin 18 (CK18) for the detection of individual metastatic tumour cells in bone marrow aspirates from 84 patients with carcinoma of the prostate. CK18+cells were detected in a sensitivity of 1 per 8×10⁵ marrow cells using the alkaline phosphatase anti-alkaline phosphatase (APAAP) system for staining. We were able to detect CK18+tumour cells in the marrow of 33% of patients with stage N0M0 prostate cancers. The incidence of CK18+cells showed a significant correlation with established risk factors, such as local tumour extent, distant metastases and tumour differentiation. For further characterization of such cells in patients with prostate cancer, we developed an immunocytochemical procedure for simultaneous labelling of cytokeratin component no. 18 (CK18) and prostate-specific antigen (PSA). In a first step, cells were incubated with a murine mAb against PSA, followed by goldconjugated goat anti-mouse antibodies. In a second step, a biotinylated mAb to CK18 was applied as primary antibody and subsequently incubated with complexes of streptavidin-conjugated alkaline phosphatase, which were developed with Newfuchsin substrate. The binding of gold-labelled antibodies was visualized by silver enhancement. CK18+cells co-expressing PSA were found in bone marrow aspirates from 5 out of 14 patients with carcinomas of the prostate. The specificity of CK18 for epithelial tumour cells in bone marrow was supported by negative staining of 12 control aspirates from patients with benign prostatic hyperplasia (BPH). Thus the prostatic origin of CK+cells in bone marrow of patients with prostate cancer has been directly demonstrated for the first time in this work. In conclusion, the approaches presented appear to be reliable methods of identifying and phenotyping individual prostatic carcinoma cells and may help to identify those patients with prostate cancer who are at high risk of relapse.     

Clinical implications of introducing a new PSA assay

BACKGROUND: A number of different prostate-specific antigen (PSA) assays are in common use. There has been little consideration of the possible clinical implications of interassay variation. The availability of two assays in the same laboratory provided an opportunity to audit the clinical implications of the interassay variation in PSA levels. METHODS: The same serum samples from patients with prostate cancer on follow-up were analyzed for PSA by the Abbott AxSYM assay and by the Abbott ARCHITECT assays. To assess within-patient reproducibility of the interassay variation, repeat analysis of PSA by both assays was conducted in a second sample obtained at least 1 month after the first. RESULTS: Samples from 156 cases were analyzed. The mean ratio of serum PSA values by the two assays (AxSYM assay/ARCHITECT assay) was 0.89 (range 0.5-2.27). The interassay coefficient of variation was 20%. In a subgroup of 50 cases with repeat samples available, the correlation coefficient, r, of the interassay variation in PSA between the first and second samples was 0.441. CONCLUSIONS: Interassay variation in serum PSA is clinically significant, both between patients and on repeated measurement within the same patient. Clinicians should be aware that simple correction factors may not accurately control for variation between PSA assays. Ideally, patients on follow-up for prostate cancer should be monitored using a single PSA assay.     

肺癌术中血癌胚抗原mRNA的检测及意义

目的探讨肺癌术中有无肿瘤细胞的血行播散及其规律。方法对52例肺癌、5例肺部良性病变手术患者,于开胸时、结扎肺静脉时及结扎后1h取外周静脉血,结扎肺静脉时取肺静脉血,采用巢式逆转录聚合酶链反应(RTPCR)技术检测血中癌胚抗原(CEA)mRNA的表达量(以经内参照校正的紫外灯光下灰度值表示)。取人腺癌细胞系A549作阳性对照并检测该方法的灵敏度。结果CEAmRNA检测阳性率开胸时为31%(16/52),结扎肺静脉时外周血与肺静脉血、结扎肺静脉后1h外周静脉血均为54%(28/52),且病例一致。开胸时的CEAmRNA表达水平最低95±20,结扎肺静脉时肺静脉血最高126±22,结扎肺静脉时外周静脉血与结扎肺静脉后1h的外周静脉间差异无统计学意义(P>0.05)。CEAmRNA的术中阳性率,鳞癌患者为64%(14/22),腺癌患者为47%(14/30),阳性率与肿瘤性质无关(χ2=1.47,P>0.05);中央型肺癌的术中阳性率(80%,20/25)显著高于周围型肺癌(30%,8/27)(χ2=16.81,P=0.000);TNM分期Ⅰ、Ⅱ、Ⅲ、Ⅳ期者阳性率分别为32%(8/25),55%(6/11),93%(14/15)和0(0/1),分期较晚者显著高于分期较早者(χ2=17.93,P=0.000)。5例阴性对照均为阴性。经检验该方法的灵敏度为1×10-6。结论肺癌术中的确存在血行播散,结扎肺静脉的早晚可能对瘤细胞播散量有较大影响;中央型肺癌和     

粘蛋白7在膀胱癌尿脱落细胞中的表达及意义

目的:探讨粘蛋白7(mucin7,MUC7)在膀胱移行细胞癌(TCC)诊断中的意义。方法:采用巢式逆转录聚合酶链反应(nested RT-PCR)方法检测MUC7mRNA在TCC患者尿脱落细胞中的表达。结果:68例TCC患者中有42例尿液MUC7表达阳性,敏感性为62%;MUC7表达与临床分期有关而与病理分级无关。对照组25例中有3例在尿液中MUC7为阳性表达,特异性为88%。结论:用RT-PCR的方法检测尿脱落细胞中的MUC7,具有较高的膀胱癌诊断价值。     

血清PSA联合直肠指诊诊断前列腺癌的价值

目的 探讨前列腺特异性抗原(PSA)及直肠指诊(DRE)在前列腺癌诊断中的作用。方法 回顾性分析268例前列腺疾病患者的临床资料及PSA、DRE的结果。结果 经病理学确诊14例为前列腺癌,其中PSA值为4.0～9.9μg/L时有5例前列腺癌(5/13),PSA值≥10μg/L有5例前列腺癌(5/7);而DRE可疑者有6例前列腺癌(6/41)。如果单独用PSA或DRE对前列腺癌进行筛选,对前列腺癌诊断的漏诊率分别为28.6％(4/14)、57.1％(8/14),联合使用这两种方法仅有2例漏诊。结论 PSA联合DRE是临床上筛选前列腺癌的可靠方法。