PSA"灰区"值时前列腺癌组织中Trp-p8的表达及意义

目的 研究Trp-p8蛋白在PSA"灰区"前列腺组织中的表达规律,探讨其在前列腺癌(PCa)早期诊断中的作用.方法 通过免疫组织化学的方法研究了28例PSA"灰区"前列腺组织中Trp-p8蛋白的表达情况,其中前列腺增生症(BPH)和PCa标本各14例,采用图文数据成像分析系统判定各组织中Trp-p8蛋白的表达强度,分析其差异性.结果 BPH中Trp-p8蛋白的表达强度较弱,呈不表达或微量表达.在PCa组织中Trp-p8蛋白均呈不同程度的阳性表达,这种表达差异具有统计学意义.结论 Trp-p8在PSA"灰区"前列腺组织中的表达存在差异,在PCa组织中Trp-p8蛋白的表达强度高于BPH组织,这种差异性表达对于早期PCa诊断具有重要意义.     

Association between leptin receptor gene polymorphisms and early-onset prostate cancer

OBJECTIVE: To report a case-control study examining the relationship between polymorphisms in the leptin receptor (OBR) gene and the development of young-onset prostate cancer, because epidemiological studies report that prostate cancer risk is associated with animal fat intake, and thus we investigated if this association occurs via this genetic mechanism. PATIENTS, SUBJECTS AND METHODS: The Lys109Arg (OBR1) and Gln223Arg (OBR2) polymorphisms in the coding region of OBR were studied in blood DNA from 271 patients with prostate cancer aged < 56 years at diagnosis and 277 geographically matched control subjects. Cases were collected through the Cancer Research UK/British Prostate Group Familial Prostate Cancer Study. Blood DNA was genotyped using the polymerase chain reaction and a restriction enzyme digest. RESULTS: There was no statistically significant association between the OBR genotype and prostate cancer risk; men homozygous for 109Arg genotype had a slightly increased risk for prostate cancer, with a relative risk (95% confidence interval) of 1.36 (0.65-2.85), and those homozygous for the 223Arg allele had some reduction in prostate cancer risk, at 0.82 (0.58-1.26), but neither was statistically significant. CONCLUSION: This case-control study showed no significant association between leptin receptor gene polymorphisms and the risk of young-onset prostate cancer, suggesting that genetic variations in OBR are unlikely to have a major role in the development of early-onset prostate cancer in the UK.     

脂肪酸合成酶在前列腺癌中的表达及临床意义

目的 研究前列腺癌中脂肪酸合成酶（fatty acid synthase，FASE）的表达及其临床意义。方法对68例前列腺癌手术或穿刺活检患者的石蜡标本进行FASE的免疫组织化学染色和半定量分析，并与良性前列腺增生进行对照。结果FASE在良性前列腺增生组织中的阳性表达率（12.8％）明显低于前列腺癌组织（47．1％，P〈0．05）。FASE表达与临床分期、病理分级、骨转移有关（P〈0．05）；与年龄、淋巴结转移、远处转移无关（P〉0．05）。FASE阳性和阴性患者的生存率有显著性差异（P=0．002）。结论FASE在前列腺癌组织中表达增高，酶活性增强；FASE在前列腺癌组织中表达增高有提示不良预后的作用。     

Expression of leptin and leptin receptor in the testis of fertile and infertile patients

The aim of our study was to investigate the relationships between the expression of leptin, leptin receptor in the testis and spermatogenesis, and testosterone (T) concentration in infertile men. Testicular tissue samples were collected from the testes of five fertile volunteers, eight patients with obstructive azoospermia (OA), six patients with Sertoli cell-only syndrome (SCO) and 32 oligospermic patients with varicocele testis. In testicular tissue, leptin and leptin receptor were identified by staining with polyclonal antibodies. Serum follicle stimulating hormone, lutenising hormone (LH), and T were determined by chemiluminescence assays. Leptin was expressed on germ cells, mainly on spermatocytes. The ratio of immunostained germ cells to total germ cells was inversely correlated with the concentration of T (r = -0.32, P = 0.01), sperm concentration (r = -0.51, P = 0.002) and Johnsen's score (r = -0.44,P = 0.005). In contrast, leptin receptor immunostained cells were found in the interstitium, primarily in Leydig cells. Leptin receptor expression on Leydig cells was inversely correlated with serum T concentration (r = -0.50, P < 0.001). The dysfunction of spermatogenesis is associated with an increase in leptin and leptin receptor expression in the testis.     

瘦素及其受体在精索静脉曲张模型大鼠附睾组织的表达及意义

目的:探讨瘦素及其受体在精索静脉曲张模型大鼠附睾组织的表达及其意义。方法:将40只SD大鼠随机分为精索静脉曲张(EV)持续4、8周组(EV4、EV8组,每组12只)和相应的假手术对照组(Control 4、Control 8组,每组8只)。采用左肾静脉部分结扎的方法建立精索静脉曲张模型。采用免疫组织化学法检测大鼠附睾组织中瘦素及瘦素受体表达情况,采用实时定量PCR法检测大鼠附睾组织中瘦素及瘦素受体mRNA表达量。结果:EV4组、EV8组附睾上皮细胞瘦素及瘦素受体表达分别比Control 4组、Control 8组显著增强(P<0.01);而EV4组附睾上皮细胞瘦素及瘦素受体表达与EV8组比较无显著性差异(P>0.05)。EV4组、EV8组附睾上皮细胞瘦素及瘦素受体mRNA的表达分别比Control 4组、Control 8组显著增加(P<0.01);而EV4组瘦素及瘦素受体mRNA的表达与EV8组比较无显著性差异(P>0.05)。结论:精索静脉曲张大鼠附睾组织中瘦素及瘦素受体的表达明显增加,瘦素可能参与了精索静脉曲张引起男性不育的机制。     

LRIG1在前列腺癌和前列腺增生组织中的表达及临床意义

目的 探讨LRIG1在前列腺癌和前列腺增生组织中的表达及临床意义.方法 采用免疫组织化学SP法检测LRIG1蛋白在23例前列腺癌和26例前列腺增生组织中的表达情况,并结合临床进行分析.结果 LRIG1蛋白在前列腺癌组织中和前列腺增生组织中阳性表达率分别为13.04%(3/23)和96.15%(25/26),差异有统计学意义(P<0.05).结论 与前列腺增生组织相比,LRIG1在前列腺癌中表达水平较低,该基因的表达可作为前列腺癌诊断的参考指标.     

不同能量平衡状态下瘦素及瘦素受体在小鼠肝细胞损伤中的作用机制

目的 探讨在不同能量平衡状态下瘦素(leptin)及瘦素受体(leptin receptor,LEPR)参与肝细胞损伤的作用机制研究.方法 选取4周龄FVB/N雌性小鼠18只,分为3组:Mex3c+/-突变组(文中简称Mex3c+/-组,n=6),HFD组(给予高脂饮食,n=6)和Control组(给予普通饲料,n=6...     

Leptin influences cellular differentiation and progression in prostate cancer

PURPOSE: Several studies have shown a positive association of dietary fat with prostate cancer. Leptin, a peptide hormone that has a role in the regulation of body weight, currently serves as a more accurate biomarker for total body fat. We designed a study to determine whether leptin influences cellular differentiation and the progression of prostate cancer. MATERIALS AND METHODS: In this study we investigated serum leptin in 21 patients with prostate cancer, 50 with benign prostatic obstruction and 50 healthy individuals matched for sex, body mass index and age. Patients with cancer were stratified into 2 groups by the disease spread, including groups 1--organ confined and 2--advanced disease, and into 3 groups by the differentiation degree, including groups 3--Gleason sum 2 to 4 or well differentiated, 4--Gleason sum 5 to 7 or moderately differentiated and 5--Gleason sum 8 to 10 or poorly differentiated. RESULTS: We noted significant differences in serum leptin in the cancer versus control and cancer versus benign prostatic obstruction groups. In addition, in the prostate cancer group serum leptin correlated with prostate specific antigen and biopsy Gleason score. We also observed significant differences in serum leptin in groups 1 versus 2, 3 versus 5 and 4 versus 5. CONCLUSION: Leptin may have roles in the development of prostate cancer through testosterone and factors related to obesity. It influences cellular differentiation and the progression of prostate cancer.     

RKIP在人前列腺癌组织中的表达及意义

目的检测RKIP(Raf激酶抑制蛋白)在人前列腺癌组织中的表达,并分析其与前列腺癌病理分级、临床分期的关系。方法运用免疫荧光组织化学的定量方法,检测26例PCa组织和14例BPH组织中RKIP的表达情况,并分析其与前列腺癌病理分级、临床分期的关系。结果RKIP在前列腺癌组织中的表达较前列腺增生组织显著下降;在前列腺癌组织Gleason 8～10分的分化不良组中的表达较Gleason 5～7分的分化良好组明显下降;在前列腺癌组织T_2N_0M_0以内的无转移组中的表达较侵袭转移组明显下降。结论RKIP是一种新型的前列腺癌转移抑制基因,其表达的上调能促进前列腺癌的分化,抑制前列腺癌的转移。     

前列腺癌患者血浆纤维蛋白原的测定及临床意义

目的探讨前列腺癌患者血浆纤维蛋白原（Fib）的变化和临床意义。方法采用全自动血凝分析仪测定77例前列腺癌患者、30例前列腺增生患者和30例健康体检者的Fib含量,对测定数据进行统计学分析。结果前列腺癌患者的Fib含量明显高于非前列腺癌组患者（P〈0.001）,有远处转移的前列腺癌患者的Fib含量高于无远处转移的患者（P〈0.001）,晚期前列腺癌患者的Fib含量高于早期前列腺癌患者（P〈0.001）。恶性肿瘤发生高Fib血症的比例远高于非前列腺癌患者,且随着临床分期的增加而增加（P〈0.001）。前列腺癌伴有高Fib血症的患者疗效和预后差于前列腺癌不伴有高fib血症的患者。结论血浆Fib水平与前列腺癌有着密切的关系,血浆Fib水平的检测对于前列腺癌的诊断、疗效及预后判定有一定意义,值得进一步探讨与研究。     

Leptin and leptin receptor in human seminal plasma and in human spermatozoa

Leptin, a 167 amino acid peptide, is known to influence the gonads via direct and indirect effects. Recent studies provide contradictory proposition about the peripheral impact of leptin in the male gonads. Thus, we examined leptin and its receptors in human seminal plasma and in human ejaculated spermatozoa by Western blot technique and fluorescence microscopy. In seminal plasma we found a free leptin band (16 kDa) by an anti-leptin polyclonal antibody. Incubation of seminal plasma with recombinant leptin caused a statistically significant increase in the amount of free leptin (p < 0.01) and supports this finding. Furthermore, a soluble leptin receptor (145 kDa) was found in human seminal plasma in the same specimen. We also detected a 145-kDa leptin receptor isoform in ejaculated spermatozoa as a possible target of leptin action in the male genital tract, which was localized at the tail of spermatozoa by immunofluorescence microscopy only. This receptor was significantly associated with the intactness of sperm plasma membranes. Spermatozoa with deteriorated membranes contained 49.2 +/- 6.9% leptin receptor signal intensity compared with spermatozoa having intact membranes (p < 0.01). This finding is difficult to interpret and may be caused by a leakage of OB-R due to loss of membrane integrity. In conclusion, these data provide further hints for a peripheral role of leptin in the male genital tract, possibly, by an interaction between leptin and spermatozoa via sperm leptin receptors.     

Prognostic significance of the nadir prostate specific antigen level after hormone therapy for prostate cancer

PURPOSE: We determine whether the nadir prostate specific antigen (PSA) level after hormone therapy can be used to predict the progression to hormone refractory prostate cancer. MATERIALS AND METHODS: We reviewed the progressive status and survival of 177 patients with stage C or D prostate cancer who had received hormone therapy at our institution. The overall survival rate, incidence of progression to hormone refractory prostate cancer and interval until progression were analyzed with reference to the nadir PSA level. Multiple regression analysis was used to analyze the predictive factors for progression to hormone refractory prostate cancer, and the relative efficacy of the nadir PSA level in predicting progression was evaluated by receiver operating characteristics analysis. RESULTS: Median followup was 39 months (range 3 to 89) and 85.4% of patients (151) responded to treatment, of whom 77.5% (117) had progression to hormone refractory prostate cancer. Median time until nadir PSA levels were reached after hormone therapy was 8.1 months and median time until hormone refractory prostate cancer was 24.0 months. Nadir PSA levels were less than 0.2 ng./ml. in 31% of respondents, 0.2 to 1.0 ng./ml. in 23%, 1.1 to 10 ng./ml. in 42% and greater than 10 ng./ml. in 5%. These groups had similar clinicopathological characteristics. Nadir PSA levels correlated significantly with pretreatment PSA levels, Gleason scores and progression to hormone refractory prostate cancer (p = 0.01, p <0.01 and p <0.001, respectively), and inversely correlated with the interval to the establishment of hormone refractory prostate cancer (r = -0.465, p <0.05). By univariate analysis bone metastasis, nadir PSA, PSA at 6 months after treatment and pretreatment PSA were significantly associated with progression to hormone refractory prostate cancer. Only the nadir PSA was calculated to be an independent factor by multivariate analysis. Receiver operating characteristics analysis indicated that nadir PSA predicted progression to hormone refractory prostate cancer after 2 years with an accuracy of 86.2%. With the lower limit of the nadir PSA level set to 1.1 ng./ml., sensitivity was 80.3% and specificity was 83.8%, and these levels were deemed the most appropriate. Furthermore, nadir PSA after hormone therapy was an independent prognosticator for survival, as were initial levels of hemoglobin and alkaline phosphatase. CONCLUSIONS: The nadir PSA level after hormone therapy may be the most accurate factor predicting the progression to hormone refractory prostate cancer and is an independent prognostic factor for survival. Furthermore, a lower limit for the nadir PSA level of 1.1 ng./ml. gives optimal sensitivity and specificity.     

Snail、PDEF在前列腺癌中的表达及其意义

目的探讨Snail、PDEF在前列腺癌（PCa）中的表达及意义。方法采用免疫组织化学法检测38例PCa组织及20例良性前列腺增生（BPH）组织中Snail、PDEF的表达,分析两者与前列腺癌临床病理因素的关系。结果PCa组织中Snail、PDEF阳性表达率分别为57.8%、60.5%,BPH组织分别为20%和25%。两种蛋白在PCa和BPH中的表达差异均有统计学意义（P〈0.05）。Snail、PDEF表达的升高与PCa不同分化程度、侵袭转移、临床分期和PSAD有关（P〈0.05）。Snail、PDEF两种蛋白在PCa组织中的表达存在正性相关。结论Snail、PDEF与PCa发生、演进及转移相关。联合检测Snail、PDEF及PSAD可以作为PCa发展及预后的重要参考。Snail和PDEF的高表达可能是PCa侵袭转移的重要生物学标志。     

前列腺癌中PTEN蛋白表达与血清PSA水平的相关性

目的探讨前列腺癌(PCa)组织中PTEN蛋白的表达与血清PSA水平的相关性。方法采用免疫组织化学SABC法对32例PCa和10例前列腺增生(BPH)组织中PTEN蛋白的表达进行检测,并比较各组间PTEN蛋白表达水平的差异及其与血清PSA水平、PCa病理分级、临床分期及预后的关系。结果PTEN在PCa、BPH组织中的阳性表达率分别为31.3%和100.0%,二者比较有显著性差异(P<0.05),且PCa组织中PTEN蛋白的表达与血清PSA水平、病理分级、临床分期和肿瘤转移呈负相关(P<0.05)。结论随着肿瘤细胞病理分级、临床分期的增高,PTEN蛋白阳性表达率降低,它的异常表达在PCa的发生、发展中起重要作用,检测PTEN蛋白的表达有助于判断病情及预后。     

前列腺癌组织雄激素受体表达的意义

目的 探讨Pca发生、发展过程中AR的变化及其临床意义。方法 采用免疫组化和图象分析技术检测PCa(N=40)和NP(N=40)中AR相对含量。结果 PCa中AR相对含量显著高于NP组(0.24±0.03 VS 0.13±0.01 P<0.05);随着PCa病理分级增高,AR相对含量有明显降低趋势;AR阳性表达者的生存期明显较阴性者为长(9.3 VS 21.4月,P<0.05)。结论 在前列腺癌发生发展过程中,AR及其基因存在着复杂的变化,检测AR相对含量对判断患者预后有一定意义。     

不同前列腺组织中雄激素受体的表达研究

目的:研究雄激素受体(AR)在正常前列腺、良性前列腺增生(BPH)和前列腺癌(PCa)组织中的表达,探讨AR与BPH和PCa的关系。方法:采用实时定量PCR、免疫荧光和组织蛋白电泳方法,分析15例正常前列腺、20例BPH与40例PCa标本中AR的表达情况。结果:实时定量PCR和组织蛋白电泳检测BPH组织与正常前列腺组织中AR的表达量差异无统计学意义(P>0.05)。但免疫荧光检测发现BPH组织中AR蛋白表达量增高。3种方法检测PCa组织中AR表达量较正常前列腺组织和BPH组织增高(P<0.05)。高分化PCa的AR表达比低分化PCa高(P<0.05)。随着临床分期的增高,AR的表达降低(P<0.05),激素非依赖性前列腺癌(HRPC)组织中AR表达最低。结论:AR在PCa组织中的表达较正常前列腺和BPH组织中增高,AR的表达与PCa的分级、分期相关。