前列腺癌中P53和bcl-2蛋白的表达及意义

应用免疫组化ＬＳＡＢ法，检测１５例良性前列腺增生症（ＢＰＨ）和３５例前列腺癌（Ｐｃａ）组织中Ｐ５３、ｂｃｌ－２蛋白的表达水平。结果发现：（１）ＢＰＨ组与Ｐｃａ组中Ｐ５３、ｂｃｌ－２蛋白的阳性表达率分别为６．７％、１３．３％和３４．３％、４２．９％，显示Ｐｃａ组Ｐ５３、ｂｃｌ－２蛋白阳性率明显高于ＢＰＨ组（分别Ｐ〈０．０５、Ｐ〈０．０５）。（２）Ｐｃａ组中Ｐ５３蛋白阳性１２例，其中Ⅰ、Ⅱ级肿瘤阳性５     

抗凋亡基因bcl—2在膀胱肿瘤中的表达及意义

应用链菌素亲和素－过氧化物酶（ＬＳＡＢ）免疫组织化学技术对４９例膀胱肿瘤石蜡切片ｂｃｌ－２原癌基因蛋白的表达进行研究，结果显示，在各级（期）膀胱肿瘤中均为ｂｃｌ－２基因表达，随着肿瘤分级，分别的增加，ｂｃｌ－２基因表达增多，但无显著性差异（Ｐ〉０．０５），在〉５０岁以上患者中ｂｃｌ－２基因表达率明显高于≤５０岁者（Ｐ〈０．０５）。虽然在复发肿瘤和多发肿瘤及男性患者ｂｃｌ－２基因表达有增加趋势，但其     

膀胱癌中bcl-2和p16基因的表达与预后的关系

目的 探讨ｂｃｌ－２和Ｐ１６基因蛋白在膀胱癌的表达与预后的关系。方法 采用ＳＡＢＣ法对５１例膀胱癌组织和５例正常膀胱粘膜行ｂｃｌ－２和Ｐ１６基因表达的检测。结果 ｂｃｌ－２在膀胱癌的阳性表达率为８０．２％,生存组和死亡组之间比较差异有显著性意义。Ｐ１６在膀胱癌在阳生表达率为５０．９％。５例正常膀胱粘膜均阳性,两者比较有显著性意义。在病理分级、临床分期和预后的总样本率中比较差异有显著性意义;即随病理     

原发性乳腺癌组织中bcl-2基因表达与临床病理联系

目的 探讨原发性乳腺癌组织中ｂｃｌ－２基因的表达与临床病理的关系。方法 应用免疫组织化学方法（Ｓ－Ｐ）研究６３例乳腺癌组织，１５例癌旁正常乳腺组织中的ｂｃｌ－２基因表达率。表达特点及乳腺癌临床病理的联系。结果 乳腺癌ｂｃｌ－２阳性率（４９．２％）明显高于癌旁正常乳朱组织和阳性率（２０％），Ｐ〈０．０５。乳腺癌组织学分级越高，ｂｃｌ－２阳性率越高，Ｐ〈０．０５。三年无复发无转移病例阳性率小于三年内有     

CD15抗原和bcl-2基因蛋白在甲状腺癌中的表达及相关性研究

目的 研究甲状腺癌组织中ＣＤ１５抗原和ｂｃｌ－２基因蛋白的表达与肿瘤发生和转移的关系,并探讨ＣＤ１５与ｂｃｌ－２基因蛋白表达的关系。方法 应用微波－ＬＳＡＢ免疫组织化学法检测５０例甲状腺癌、４５例甲状腺腺瘤和２０例癌旁正常甲状腺组织中ＣＤ１５和ｂｃｌ－２基因蛋白表达。结果 在甲状腺癌组织中ＣＤ１５和ｂｃｌ－２基因蛋白表达阳性率分别为６８．０％和４６．０％,均显著高于甲状腺腺瘤和癌旁正常甲状腺组织（     

凋亡相关基因产物Fas／APO—1和bcl—2蛋白在肾癌组织中的表达及 …

目的 研究凋亡相关基因Ｆａｓ／ＡＰＯ－１和ｂｃｌ－２在肾癌发生发展中的作用。方法 采用免疫组织化学法对３５例肾癌组织和２６例远离肾癌的正常肾组织Ｆａｓ／ＡＰＯ－１和ｂｃｌ－２蛋白的表达进行检测。结果 肾癌组织Ｆａｓ／ＡＰＯ－１蛋白表达率５７．１４％,明显低于正常肾组织中的表达率（８４．６２％,Ｐ〈０．０５）,且表达强度也明显低下;而ｂｃｌ－２蛋白表达率为８０．０％,明显高于正常肾组织中的表达率（５     

前列腺癌细胞凋亡与bcl-2蛋白表达及其意义

目的：探讨细胞凋亡及ｂｃｌ－２蛋白表达在前列腺癌（ＰＣａ）中的意义及前二者之间的相互关系。方法：采用原位细胞凋亡标记及免疫组织化学法对２５例ＰＣａ、１８例前列腺增生症 （ＢＰＨ）及１０例正常列腺的前列腺组织石蜡切片行ｂｃｌ－２蛋白及细胞凋亡检测。结果：ＰＣａ组的细胞凋亡充显著高于ＢＰＨ组及正常组,且ＰＣａ的细胞凋亡率与其分化程度呈显著负相关。ｂｃｌ－２蛋白在ＰＣａ组中表达率为３２％,与分化程度无关     

前列腺增生组织中细胞凋亡调控基因的表达

目的：搪塞细胞凋亡调控基因在良性前列腺增生（ＢＰＨ）发病中作用。方法：免疫组织化学结合计算机图像分析方法检测１８例正常前列腺（ＮＰ）和６２例ＢＰＨ组织中ｂｃｌ－２、ｂａｘ、Ｆａｓ和白介素－１β转化酶（ＩＣＥ）表达。结果：上述４种蛋白均主要２于上皮细胞,ＢＰＨ上皮细胞的ｂｃｌ－２表达显著高于ＮＰ,而其他３种蛋白表达均显著低于ＮＰ、ＢＰＨ的上皮面积百分比与ｂａｘ和ＩＣＥ表达之间均呈负相关,而与ｂｃｌ－     

前列腺增生症各区细胞增殖与凋亡特征的研究

目的 探讨良性前列腺增生症（ＢＰＨ）各区细胞增殖和凋亡特征及其与ＢＰＨ发病的关系。方法 采用流式细胞术对３３例ＢＰＨ病人前列腺各区细胞表皮生长因子（ＥＧＦ）,表皮生长因子受体（ＥＧＦ－Ｒ）,碱性纤维细胞生长因子和转化生长因子－β１（ＴＧＦ－β１）表达,细胞ＤＮＡ含量和细胞凋亡情况进行定量对比分析。结果 ＥＧＦ和ＥＧＦ－Ｒ的标记率和表达量在移行区（ＴＺ）明显高于周边区（ＰＺ）和中央区（ＣＺ）。     

结直肠腺瘤细胞凋亡和增殖与bcl—2和P53蛋白表达的关系

目的 探讨结直肠腺瘤中细胞凋亡和增殖与ｂｃｌ－２和Ｐ５３蛋白表达的关系。方法 对４５例结直肠腺瘤用原位末端标记（ＴＵＮＥＬ）法检测细胞凋亡;以增殖细胞核抗原标记增殖检测其增殖活性;用免疫组织化学检测ｂｃｌ－２和Ｐ５３蛋白表达,另选结直肠高分化腺癌和五常黏膜各１０例作对照检测。结果 ４５例结直肠腺瘤细胞的凋亡指数（ＡＩ）为（９０．８５&;#177;０．２４）％,结直肠腺癌细胞的ＡＩ为（１．８６&;#177;０．１５）％,两者ＡＩ均高于正常结直肠黏膜（Ｐ〈０．０１）,而腺瘤与腺癌ＡＩ值差异也有显著性（Ｐ〈０．０５）;ｂｃｌ－２和Ｐ５３蛋白的表达率与细胞ＡＩ呈显著互相关（ｒｓ＝－０．６５和ｒｓ＝－０．６０）,Ｐ５３蛋白表达与细胞增殖活性呈正相关（ｒｓ＝０．８６）,而ｂｃｌ－２蛋白表达与细胞增殖无相关性,结论ｂｃｌ－２和Ｐ５３蛋白过度表达与细     

雌激素对前列腺增生症移行区细胞Bcl-2、Bax和c-myc基因表达的影响

目的　探讨大剂量外源性雌激素对良性前列腺增生症 (BPH )移行区 (TZ)细胞Bcl 2、Bax和c myc基因表达的影响 ,籍此了解雌激素对BPH的治疗机制。 方法　对 3 0例经服用已烯雌酚的BPH患者 (处理组 )和 3 0例空白对照患者 (对照组 )的标本 ,采用免疫流式细胞光度术检测上述 3种基因在TZ的标记率和表达量。结果　雌激素处理后 ,TZ细胞Bcl 2的标记率和表达量分别由对照组的 2 5 .5 0 %和 73 .0 0降低为 13 .3 5 %和 44 .46(P <0 .0 1) ,Bax的表达量则由对照组的48.0 0升高为 5 6.97(P <0 .0 1)。结论　大剂量雌激素对BPH治疗作用可能与其抑制TZ细胞Bcl 2的表达和促进Bax的表达进而提高细胞凋亡率有关。     

Does benign prostatic hyperplasia originate from the peripheral zone of the prostate? A preliminary study

OBJECTIVE: To compare the histological characteristics, cell proliferation, apoptosis and biological features in benign prostatic hyperplasia (BPH) in the peripheral (PZ) and transition zone (TZ) of the prostate. PATIENTS AND METHODS: Tissue from BPH in TZ and PZ was obtained from 68 patients undergoing transrectal ultrasonography-guided biopsy and used for both morphometric analysis and immunohistochemical studies. The epithelial, stromal and luminal composition of the tissue was determined using a computer-assisted method for quantitative morphometric analysis. Apoptosis was detected as the apoptotic index (AI) using the TdT dUTP nick-end labelling assay. Cell proliferation was determined as the proliferation index (PI) using Ki-67 immunostaining. The expression of epidermal growth factor receptor (EGFR), transforming growth factor beta1 (TGFbeta1), androgen receptor (AR) and bcl-2 were assessed immunohistochemically. RESULTS: There was no difference in the stroma/epithelium ratio between PZ and TZ hyperplastic nodules (P > 0.05). The mean AI in epithelium was almost identical to the corresponding PI. In stroma, no apoptotic cells were detectable. There was a significantly higher PI and AI in the glandular epithelial cells in PZ hyperplastic than in TZ hyperplastic nodules, but no difference in PI of the stromal cells between PZ and TZ hyperplastic nodules. There was significantly higher expression of TGFbeta1 and lower expression of EGFR and bcl-2 in PZ than TZ hyperplastic nodules (P < 0.05). There was no difference in AR expression between PZ and TZ hyperplastic nodules (P > 0.05). CONCLUSIONS: These results indicate that some hyperplastic nodules in PZ might originate from the PZ, and the formation of these nodules might be modulated in a different way from that in the TZ.     

前列腺增生症各区细胞超微结构研究

目的：研究前列腺增生组织三个区细胞超微结构的变化。方法：采用透射电镜对10例良性前列腺增生症（BPH）患者前列腺组织不同区域的30份标本进行超微结构观察。结果：移行区腺上皮层次增多，间质可见多量具有功能旺盛表现的平滑肌细胞，同时有大量的成纤维细胞，并可见典型的肥大细胞和淋巴细胞，细胞膜接触处似有融合现象；中央区和周边区平滑肌细胞可见变性表现，如核固缩、核周间隙扩张、胞质空泡化、成纤维细胞成分较少。结论：前列腺增生症三个区域细胞超微结构存在一定差异。     

Tumour grade, proliferation, apoptosis, microvessel density, p53, and bcl-2 in prostate cancers: differences between tumours located in the transition zone and in the peripheral zone

OBJECTIVES: Transition zone (TZ) carcinomas of the prostate are thought to have less malignant potential than tumours that arise in the peripheral zone (PZ). It is unclear, however, whether this can be put down to anatomical reasons alone, or if there are further differences between tumours of both zones. METHODS: We examined Gleason scores, proliferation and apoptosis rates, microvessel density (MVD), p53 expression and bcl-2 expression in 76 paraffin-embedded radical prostatectomy specimens, containing 54 tumour foci in the TZ and 58 tumour foci in the PZ, matched for volume. The terminal deoxynucleotidyl transferase mediated dUTP-biotin nick end labelling (TUNEL) method was applied to detect apoptotic cells. Proliferation, MVD, p53, and bcl-2 were investigated by immunohistochemistry. RESULTS: There were significant differences between TZ tumours and PZ tumours in terms of the median Gleason scores (5 versus 7; P < 0.0001), the proliferation rate (3.2% versus 5.2%; P = 0.0003), and the MVD (68.5 versus 104; P = 0.0002), but the median apoptosis rate was quite similar (0.8% versus 0.9%). The p53 and bcl-2 expression were more frequent in PZ cancers as compared to TZ carcinomas (11% versus 2% and 27% versus 6%, respectively). CONCLUSION: There is evidence for lower Gleason scores as well as lower expression of markers related to tumour growth in TZ carcinomas of the prostate, which might contribute to a less malignant clinical behaviour as compared to PZ cancers.     

A comparison of the biological features between prostate cancers arising in the transition and peripheral zones

OBJECTIVES: To investigate differences in the biological features of prostate cancer according to the zonal origin. PATIENTS AND METHODS: Among 172 consecutive patients who had a radical prostatectomy (RP), the study included 124 diagnosed as having either transition zone (TZ) or peripheral zone (PZ) cancer, defined according to whether there was > 70% of the cancer area in the TZ or PZ, respectively. The clinicopathological features were then compared between these groups. In addition, the RP specimens were stained immunohistochemically with antibodies to Ki-67, Bcl-2, matrix metalloproteinase-2 (MMP-2), MMP-9 and vascular endothelial growth factor (VEGF). RESULTS: Twenty-four patients were diagnosed as having TZ cancer and the remaining 100 as having PZ cancer. Prostate specific antigen (PSA) values in patients with TZ cancer were significantly higher than in those with PZ cancer. Tumour volume in TZ cancer was significantly greater than that in PZ cancer, but there was no significant difference in biochemical recurrence-free survival between the groups. Immunohistochemistry showed that despite there being no differences in Bcl-2 and VEGF expression between TZ and PZ cancers, there was significantly greater expression of Ki-67, MMP-2 and MMP-9 in PZ than TZ cancers. CONCLUSIONS: Despite there being no significant difference in biochemical recurrence-free survival after RP between patients with TZ and PZ cancers, there was less cell proliferation and biomarker levels related to invasive potential in TZ than in PZ cancers.     

Is transition zone biopsy valuable in benign prostatic hyperplasia patients with serum prostate-specific antigen >10 ng/ml and prior negative peripheral zone biopsy?

OBJECTIVES: To evaluate the importance of transition zone (TZ) biopsy in benign prostatic hyperplasia (BPH) patients with serum prostate-specific antigen (PSA) >10 ng/ml and prior negative peripheral zone (PZ) biopsy and to estimate the sensitivity of TZ biopsy. MATERIAL AND METHODS: A total of 273 BPH patients with PSA >10 ng/ml and prior negative PZ biopsy underwent an extended biopsy protocol. In patients with a TZ volume <25 cm(3), four TZ biopsies were taken (two cores per side from the apex and base). In patients with a TZ volume > or =25 cm(3) (n=183), six TZ biopsies were taken (three cores per side from the apex, middle and base). Overall, 215 patients were subjected to either transurethral resection of the prostate (n=162) or open enucleation of the adenoma (n=53). RESULTS: The extended biopsy revealed prostate cancers in 21.2% of cases (58/273). The zonal distribution of the positive cores was as follow: PZ cancers only in 67.2% of cases (39/58), TZ cancers only in 13.8% (8/58) and PZ+TZ cancers in 19% (11/58). Overall, 73.6% (14/19) and 36.8% (7/19) of TZ cancers were detected at the apex and middle of the TZ, respectively, while no TZ cancers at all were detected at the base (p=0.00015). The incidence of carcinoma on definitive pathology was 5.6% (12/215). Consequently, TZ biopsy detected only 61.3% (19/31) of TZ cancers. The incidence of pure TZ cancers was 7.3%. On the chi(2) test, patient age, serum PSA, transrectal ultrasonography findings and PSA density did not correlate significantly with the detection rate of TZ cancer. Prostate volume (p=0.023), TZ volume (p=0.027) and PSA/TZ density (p=0.007) were predictive of TZ cancers. CONCLUSIONS: Although TZ biopsy was the sole site of cancer in only 2.9% of cases (8/273), it improved the cancer detection rate by 14% in this selected group of patients. The majority (74%) of TZ cancers were detected at the apex site. TZ biopsy has a low sensitivity (61%).     

Expression of apoptosis regulatory proteins in tubular epithelium stressed in culture or following acute renal failure

BACKGROUND: While tubular cell death is a characteristic of acute renal failure (ARF), the molecular mechanisms that modulate this cell death are unclear. Cell fate in acute renal failure hinges on a balance of survival and mortality factors in a changing environment. We further explored this issue by studying selected cell death-related proteins in experimental renal failure. METHOD: The expression of genes that promote (c-myc, Bax, BclxS) or protect (Bcl2, BclxL) from cell death was studied by Northern blot, Western blot, and immunohistochemistry in murine kidneys following ARF induced by folic acid or in renal tubular epithelial cells (MCT) stressed in culture. RESULTS: Renal mRNA levels encoding for c-myc and BclxL were elevated in ARF while the Bcl2/Bax ratio was decreased (Bcl2 decreased and Bax increased; P < 0.05). Protein levels of BclxL increased and Bcl2 protein decreased. Expression of tumor necrosis factor (TNF-alpha), a mediator of ARF, was also increased. Immunohistochemistry further demonstrated that BclxL was increased in some tubuli and absent in others, while Bcl2 expression decreased diffusely. Bax staining was also patchy among tubuli and individual cells in the tubular wall and lumen. As a relative deficit of survival factors is present in ARF, MCT epithelium were deprived of serum survival factors. This resulted in apoptosis, decreased Bcl2/Bax and BclxL/Bax ratios (P < 0.05) and sensitization to TNF-alpha-induced apoptosis (P < 0.05). The latter was prevented by enforced overexpression of BclxL (P < 0.01). TNF-alpha increased the mRNA levels encoding for c-myc and decreased BclxL expression. Neither MCT cells nor the kidney expressed BclxS. CONCLUSIONS: A relative deficit of survival factors likely contributes to changes in levels of BclxL and Bax in ARF. These deficits predispose to cell death induced by persistent lethal factors such as TNF-alpha that is increased in ARF and a potential source of increased c-myc, a downstream facilitator of cell death. These findings implicate members of the Bcl2 family of proteins as regulators of tubular cell death in ARF and single them out as potential therapeutic targets.     

反义c-myc寡核苷酸对大鼠自体移植静脉内膜增生的影响

目的 研究反义ｃ－ｍｙｃ寡聚脱氧核苷酸（ＯＤＮ）对大鼠自体移植静脉内膜增生的影响。方法 移植静脉外周涂以加有反义ｃ－ｍｙｃ寡聚脱氧核苷酸的Ｆ１２７凝胶,于术后１、２周测量静脉内膜平均厚度及观察血管内膜内ｃ－ｍｙｃ蛋白表达情况。结果 手术后１、２周,移植静脉内膜的平均厚度、内膜中ｃ－ｍｙｃ蛋白表达在反义ｃ－ｍｙｃ寡聚脱氧核苷酸组均减少,并存在量效关系（Ｐ〈０．０１）。而只用Ｆ１２７胶组及正义寡聚脱氧     

Expression of apoptosis-related genes and proteins in experimental chronic renal scarring

Apoptosis has been proposed to play an important role in the progression of renal scarring. The mechanisms that determine whether a cell enters the apoptotic program are complex. Bax and Bcl-2 are recognized modulators of this event; their relative levels determine the fate of cells. A role for apoptosis in the progression of renal scarring in the remnant kidneys of rats submitted to subtotal nephrectomy (SNx) has been described. This study investigated the expression (protein and mRNA) of Bax and Bcl-2 in remnant kidneys between day 7 and day 120 post-SNx. Northern blot analysis showed that bax mRNA was increased in remnant kidneys from day 7 (150% of control; P: < 0.05), whereas bcl-2 mRNA was decreased from day 15 (23% of control; P: < 0.05) resulting in a 14-fold increase in the ratio of bax to bcl-2 mRNA by day 120. Western blot analysis showed similar changes in Bax and Bcl-2 protein in remnant kidneys, resulting in a 147-fold increase in the ratio of Bax to Bcl-2 on day 120. Immunohistochemistry showed increases in Bax to be located predominantly in tubules in SNx kidneys. Interestingly, Bcl-2 immunostaining increased in some epithelial cells within atrophic tubules despite the overall decrease in Bcl-2 protein and mRNA. The overall renal apoptotic cells correlated closely with the ratio of bax to bcl-2 at both the mRNA and protein levels (r = 0.594 and 0.308, respectively; P: < 0.05). Furthermore, tubular apoptosis correlated positively with the mRNA level of bax (r = 0.471; P: < 0.01) and negatively with the mRNA and protein levels of bcl-2 (r = -0.443 and -0.607, respectively; P: < 0.01). The increase in the ratio of the death inducer (Bax) to the death repressor (Bcl-2) at the mRNA and protein levels may control the apoptosis associated with the progression of tubular atrophy and chronic renal fibrosis within remnant rat kidneys. These observations may have prognostic and therapeutic implications in chronic renal failure.