性激素及人前列腺生长因子对人前列腺间质成纤维细胞增殖…

从人胎儿前列腺组织中分离培养间质成纤维细胞，观察雄激素（ＤＨＴ），雌激素（Ｅ２）及部分纯化的人前列腺生长因子（ｈＰＧＦ）对该细胞增殖的影响，结果发现：（１）ＤＨＴ及ｈＰＧＦ对体外培养的人前列腺间质成纤维均具有明业的促增殖作用，但前者表现为延迟反应，后者为即时效应；（２）雌激素对该细胞无刺激增殖作用；（３）Ｅ２与ＤＨＴ联合应用对该细胞增殖刺激作用也无明显影响，实验结果提示：ＤＨＴ对人前列腺间质成纤维     

β射线内照射对人增生前列腺细胞凋亡的影响

目的 探讨β射线内照射对人增生前列腺细胞凋亡的影响.方法 20例前列腺增生(BPH)患者随机分为4组:对照组未行内照射,3组照射组于前列腺切除术前1,4,7 d行90Sr/90Yβ射线内照射,采用TUNEL染色、流式细胞术和琼脂糖凝胶电泳检测前列腺细胞凋亡变化.结果 与对照组比较,β射线内照射后前列腺细胞凋亡增多,并随时间延长而增加(P＜0.01),对照组基因组DNA保持完整,β射线辐射7 d后基因组DNA呈现梯状带凋亡改变.结论 β射线内照射能够有效诱发人增生的前列腺细胞凋亡,进而引起前列腺组织萎缩.     

大豆异黄酮、姜黄素预防良性前列腺增生的实验研究

目的 探讨大豆异黄酮和姜黄素对良性前列腺增生的预防作用。方法 体外试验用药物直接与组织培养前列腺平滑肌细胞作用,噻唑蓝比色法检测药物的抑制率;体内试验以口服给药观察大豆异黄酮、姜黄素对丙酸睾酮诱导的小鼠前列腺增生的对抗作用;RT-PCR法探讨端粒酶逆转录酶(TERT)的mRNA表达。结果 大豆异黄酮和姜黄素可抑制大鼠前列腺平滑肌细胞生长,对抗高雄激素诱导的小鼠前列腺指数增高,降低TERT的mRNA表达。结论 大豆异黄酮和姜黄素对前列腺增生有预防作用。其作用机制可能与下调TERT有关。     

MR导向间质激光治疗前列腺增生的研究进展

前列腺良性增生(BPH)属于常见疾病。前列腺为肌纤维的腺体器官,其结构为外层腺体以及内层腺体围绕尿道,大多发生在内层,累计范围从围绕膀胱颈到精阜的后尿道黏膜腺和尿道黏膜下腺,纤维肌组织增生常发生于腺体增生之前,随后     

性激素及人前列腺生长因子对人前列腺间质成纤维细胞增殖的影响

从人胎儿前列腺组织中分离培养了间质成纤维细胞,观察雄激素(DHT)、雌激素(E_2)及部分纯化的人前列腺生长因子(hPGF)对该细胞增殖的影响。结果发现:(1)DHT及hPGF对体外培养的人前列腺间质成纤维细胞均具有明显的促增殖作用,但前者表现为延迟反应,后者为即时效应;(2)雌激素对该细胞无刺激增殖作用;(3)E_2与DHT联合应用对该细胞增殖刺激作用也无明显影响。实验结果提示:DHT对人前列腺间质成纤维细胞具有间接的刺激增殖作用,可能通过刺激前列腺细胞自分泌或旁分泌作用而调节前列腺生长。     

姜黄素对人肝癌细胞增殖和凋亡的影响

目的 探讨姜黄素对肝癌细胞（QGY）细胞增殖和细胞周期的调控及细胞凋亡的影响。方法 采用MTT法测定姜黄素在不同浓度，不同时间对QGY的抑制作用，流式细胞仪分析细胞周期分布，透射电镜观察细胞的超微结构变化。结果 姜黄素可抑制QGY的抑制作用。流式细胞仪分析细胞周期分布，透射电镜观察细胞的超微结构变化。结果 姜黄素可抑制QGY细胞的生长，其抑瘤率与药物浓度和作用时间呈依赖关系，72h的中效浓度（IC50）为49.50μmol/L，流式细胞仪分析证实姜黄素能使QGY细胞聚积在S期，电镜观察发现姜黄素可导致细胞变性。坏死，诱导细胞凋亡。结论 姜黄素可干扰QGY细胞的周期分布，具有细胞毒作用。抗增殖，诱导细胞凋亡的作用。     

辐射对前列腺增生组织中bcl-2和bax表达的影响及临床意义

目的 探讨前列腺增生组织中bcl—2和bax的表达以及β射线内照射对bcl—2和bax表达的影响。方法 应用免疫组织化学法检测9例正常前列腺(NP)、15例良性前列腺增生(BPH)及35例实施^90Sr／^90Yβ射线照射后前列腺增生组织中bcl—2和bax的表达。结果 NP和BPH上皮组织bcl—2阳性表达均高于间质(P＜0．01)；BPH组织上皮和间质中bcl-2表达阳性串高于NP(P＜0．01)；NP上皮细胞中bax表达高于BPH(P＜O．05)；BPH上皮和问质细胞中bcl—2表达高于bax(P＜0．01)；NP上皮和问质中bcl—2与bax表达无显著差异(P＞0．05)。与对照组相比，应用^90Sr／^90Yβ射线内照射4、7、15d后BPH上皮和间质中bcl—2明显下降，bax阳性细胞率明显升高(P＜0．01)。结论 bcl-2和bax与前列腺细胞凋亡的调节有关，β射线能使前列腺组织中bcl—2和bax含量发生变化，促使前列腺细胞凋亡。     

良性前列腺增生患者前列腺增生组织中survivin和p38MAPK的表达

良性前列腺增生(BPH)发生与细胞凋亡减少密切相关.存活素(survivin)是凋亡抑制家族的成员,是迄今为止发现的最强凋亡抑制因子.survivin可通过多种途径抑制细胞凋亡,是凋亡调控过程中的关键因子[1].     

大豆异黄酮对前列腺增生大鼠细胞凋亡与增殖的影响

目的 探讨补充不同剂量大豆异黄酮对前列腺增生大鼠细胞凋亡与增殖的影响.方法 应用丙酸睾酮诱导大鼠前列腺增生,对正常对照组、模型组、低剂量(60 mg·kg~(-1)·d~(-1))、中剂量(120 mg·kg~(-1)·d~(-1))及高剂量(240 mg·kg~(-1)·d~(-1))大豆异黄酮组采用免疫组化和原位末端标记技术方法检测bcl-2、bax、增殖细胞核抗原(PCNA)和细胞凋亡.结果 低、中、高剂量大豆异黄酮组大鼠前列腺湿重及前列腺指数均显著低于模型组;中剂量大豆异黄酮组大鼠前列腺湿重及前列腺指数均显著低于低剂量组,与正常对照组无显著性差异.与模型组相比,中、高剂量大豆异黄酮组大鼠bcl-2表达显著降低,bax表达升高,细胞增殖指数显著性降低,而细胞凋亡指数显著性升高,尤以中剂量组效果最为明显.结论 前列腺增生大鼠前列腺组织bcl-2和bax的表达调控失衡,大豆异黄酮可能通过调节前列腺组织凋亡基因与抗凋亡基因的表达而抑制前列腺增生.     

良性前列腺增生和癌的关系

良性前列腺增生和癌的关系南京大学医学院附属鼓楼医院泌尿外科（２１０００８）周志耀前列腺增生症（ＢＰＨ）与前列腺癌（ＰＣ）共存在一个腺体，是长期有争议的问题。早在１９２２年Ｇｅｒａｐｈｙ就报道ＰＣ中有７５％伴有ＢＰＨ。而在ＢＰＨ中，当今国内外均发现有５...     

Antiproliferative effect of sildenafil on human pulmonary artery smooth muscle cells

Pulmonary arterial hypertension (PAH) is characterized by vasoconstriction and by obstructive changes of the pulmonary vasculature including smooth muscle cell proliferation which leads to medial hypertrophy and subsequent luminal narrowing. Sildenafil, an orally active inhibitor of cGMP phosphodiesterase–type–5, exerts pulmonary vasodilator activity in PAH patients. We evaluated the effects of sildenafil on growth of cultured human pulmonary artery smooth muscle cells (PASMC). The results indicate that sildenafil reduced DNA synthesis stimulated by PDGF and dose dependently inhibited PASMC proliferation. These effects were paralleled by a progressive increase in cGMP content, followed by an accumulation of cAMP. The treatment with 8–bromo–cGMP or dibutyryl–cAMP mimicked all the effects of sildenafil. On the other hand, treatment of PASMC with inhibitors of cGMP–dependent protein kinase (PKG) or cAMP–dependent protein kinase (PKA) reversed the antiproliferative effect of sildenafil. In addition, sildenafil inhibited the phosphorylation of ERK, a converging point for several pathways leading to cell proliferation. This effect was partially reduced by PKG inhibition and completely abolished by PKA inhibition.We conclude that sildenafil exerts an antiproliferative effect on human PASMC that is mediated by an interaction between the cGMP–PKG and the cAMP–PKA activated pathways, leading to inhibition of PDGF–mediated activation of the ERK.     

Antiproliferative effects of luteinizing hormone-releasing hormone agonists on the human prostatic cancer cell line LNCaP.

Highly potent LH-releasing hormone (LHRH) agonists have been recently introduced in therapy for the treatment of the carcinoma of the prostate, an androgen-dependent pathology. These peptides are believed to act mainly by inhibiting the pituitary-testicular axis and, consequently, by reducing testosterone levels. The recent observation that binding sites for LHRH analogs are present on prostatic tumor tissue suggests that these drugs could also act directly on the tumor. To verify this hypothesis, the effects of two potent LHRH agonists [Zoladex (Z) and Buserelin (B)] have been studied on the proliferation of the human prostatic cancer cell line LNCaP (lymph node carcinoma of the prostate). LNCaP cells were treated for 9 days with different doses of either Z or B (concentrations from 10(-12)-10(-6) M). Both analogs significantly inhibited cell proliferation at doses between 10(-9)-10(-6) M. The antiproliferative action of the two LHRH agonists was shown to be dose dependent, with IC50 values of 0.82 and 1.79 nM for Z and B, respectively. A similar treatment with B was without any significant effect on the proliferation of a mouse embryo fibroblast cell line (Swiss 3T3), which was used as a nontumoral control. The inhibitory action of both LHRH agonists (10(-8) M) on LNCaP cell proliferation was completely antagonized by the simultaneous treatment of the cells with a potent LHRH antagonist (Nal-Arg-LHRH; 10(-8) M); when given alone at the dose selected, the antagonist did not affect cell growth. These results clearly suggest that the antiproliferative effect of LHRH agonists on LNCaP cells may be mediated by specific receptors. The presence of binding sites for [125I]B was consequently demonstrated on the membranes of LNCaP cells cultured in a medium containing charcoal-stripped fetal calf serum, i.e. in the absence of steroids. The affinity of these binding sites for the ligand was lower than that observed for the same receptors on rat pituitary membranes. To clarify the mechanism of the antiproliferative action of the LHRH agonists, the effects of both Z and B on the incorporation of [3H]thymidine and [14C]methionine into LNCaP cells were investigated. During a short incubation period (3 h), the two LHRH agonists rapidly inhibited [3H]thymidine incorporation into the cells. The same treatment did not affect the incorporation of [14C]methionine into proteins.(ABSTRACT TRUNCATED AT 400 WORDS)     

Antiinflammatory effect of androgen receptor activation in human benign prostatic hyperplasia cells

Progression of benign prostatic hyperplasia (BPH) involves chronic inflammation and immune dysregulation. Preclinical studies have demonstrated that prostate inflammation and tissue remodeling are exacerbated by hypogonadism and prevented by testosterone supplementation. We now investigated whether, in humans, hypogonadism was associated with more severe BPH inflammation and the in vitro effect of the selective androgen receptor agonist dihydrotestosterone (DHT) on cultures of stromal cells derived from BPH patients (hBPH). Histological analysis of inflammatory infiltrates in prostatectomy specimens from a cohort of BPH patients and correlation with serum testosterone level was performed. Even after adjusting for confounding factors, hypogonadism was associated with a fivefold increased risk of intraprostatic inflammation, which was also more severe than that observed in eugonadal BPH patients. Triggering hBPH cells by inflammatory stimuli (tumor necrosis factor α, lipopolysaccharide, or CD4(+)T cells) induced abundant secretion of inflammatory/growth factors (interleukin 6 (IL6), IL8, and basic fibroblast growth factor (bFGF)). Co-culture of CD4(+)T cells with hBPH cells induced secretion of Th1 inducer (IL12), Th1-recruiting chemokine (interferon γ inducible protein 10, IP10), and Th2 (IL9)- and Th17 (IL17)-specific cytokines. Pretreatment with DHT inhibited NF-κB activation and suppressed secretion of several inflammatory/growth factors, with the most pronounced effects on IL8, IL6, and bFGF. Reduced inflammatory cytokine production by T-cells, an increase in IL10, and a significant reduction of T cells proliferation suggested that DHT exerted a broad anti inflammatory effect on testosterone cells [corrected]. In conclusion, our data demonstrate that DHT exerts an immune regulatory role on human prostatic stromal cells, inhibiting their potential to actively induce and/or sustain autoimmune and inflammatory responses.     

Antiproliferative effect of antilymphocyte globulins on B cells and B-cell lines.

Antithymocyte and antilymphocyte globulins (ALG) are currently used as immunosuppressive agents in organ transplantation and for the treatment of acute graft-versus-host disease and aplastic anemia. Since any type of immunosuppressive treatment is known to carry the risk of developing B-cell lymphoproliferative disorders, we investigated the in vitro effect of ALG on human B-cell activation and proliferation. The data demonstrate that whatever the source of lymphocytes used for ALG preparation (thymocytes, thoracic duct lymphocytes, B- or T-cell lines), (1) ALG react with both B- and T-cell lines, and (2) ALG contain antibodies specific for B cells (eg, CD21) or common to T and B cells (eg anti-beta 2-microglobulin, anti-HLA-DR, CD18, CD11a) in addition to T-cell-specific antibodies. Unlike all other T-cell mitogens tested (Concanavalin A [Con A], Pokeweek mitogen [PWM], CD3 and CD2 antibodies), ALG do not trigger B-cell differentiation into immunoglobulin-secreting cells at concentrations which induce maximum T-cell proliferation. This effect could be attributed to a direct interaction of ALG with B lymphocytes as shown by the capacity of ALG to block the response of purified B cells to a variety of activators. Furthermore, all the ALG tested were shown to inhibit the proliferation of six of the seven Epstein-Barr virus (EBV)-transformed lymphoblastoid cell lines and six of the seven Burkitt's lymphoma cell lines studied. This selective B-cell antiproliferative property of ALG was not reproduced with CD11a, CD18, CD21, CD24, or anti-HLA-DR monoclonal antibodies (MoAbs). These results suggest that, although suppressing T-cell responses, ALG treatment may directly control B cell proliferation to some extent, in keeping with the relatively low risk of posttransplant lymphoproliferative disorders reported with ALG.     

Trans-differentiation of prostatic stromal cells leads to decreased glycoprotein hormone alpha production

Age-related development of benign prostatic hyperplasia is an important health issue in developed countries. The histopathogenetic hallmark of this disease is the increase in relative and absolute numbers of smooth muscle cells (SMC). Glycoprotein hormone alpha-subunit (GPHalpha) is expressed in the human prostate, and, because of its structural similarities to other cystine knot growth factors, it has been considered to have growth regulatory functions of its own. Primary cell cultures allowing for selective cultivation of prostatic epithelial cells, fibroblasts, and SMC were established. Directed trans-differentiation and cellular homogeneity was pursued by confocal scanning laser microscopy with cell type-specific markers. GPHalpha production by these cells was assessed by immunofluorimetric assays. Its predominant source was young fibroblasts, whereas replicative senescent fibroblasts, SMC, and control fibroblasts from foreskin did not produce significant amounts. Functionally, GPHalpha reduced growth of stromal cells at concentrations of 10 and 100 nmol/liter as shown by cell viability assays. It is concluded that histogenetic reorganization over the adult lifetime, guided by endocrine factors like steroid hormones together with senescence of fibroblasts, leads to a decreased production of growth inhibitors, such as GPHalpha, favoring proliferation and the development of benign prostatic hyperplasia.     

Antiproliferative effects of a c-myc antisense oligonucleotide on human arterial smooth muscle cells

Summary The effects of a c-myc antisense phosphorothioate DNA oligonucleotide were assessed on the proliferation rate of human arterial smooth muscle cells (HSMCs). Compared to a control oligonucleotide the antisense oligonucleotide suppressed the proliferation of HSMCs in a concentration-dependent manner without a major cytotoxic effect. Outgrowth of HSMCs from media explants was significantly inhibited as well. Induction of c-myc expression by serum stimulation of cells was blunted by the antisense oligonucleotide, as shown by immunoblotting.These results demonstrate that c-myc expression is an essential factor for proliferation of HSMCs after growth stimulation, and they show the potential of antisense technology for modulating gene expression of HSMCs in vitro.Supported by a grant fromt the SFB 330Results of the study have been presented at the XIIIth Congress of the European Society of Cardiology (1991) and the 64th Scientific Session of the American Heart Association (1991)     

Contractile activity of human decidual stromal cells

We previously demonstrated that human decidual stromal cells (DSC), the main cellular component of the decidua, are similar in antigen phenotype and structure to myofibroblasts, cells with contractile activity. In this work we isolated and maintained DSC in fibroblast medium, in which these cells show a stable phenotype similar to that of DSC in vivo. Flow cytometric observations showed that most DSC expressed alpha-smooth muscle (alpha-SM) actin, an intermediate filament that is considered a marker of myofibroblasts and is responsible for the contractile activity of these cells. alpha-SM actin mRNA was detected by RT-PCR in these cells. The contractile activity of DSC was determined by the gel contraction assay; we found that TGF beta 1 and platelet-derived-growth factor, cytokines that are known to be inducers of myofibroblast contractility, also induced contractility of DSC. IL-2, a Th1 cytokine-related with spontaneous abortion, also activated DSC contractility. Our results confirmed that DSC are phenotypically and functionally related with myofibroblast.