前列腺癌中神经营养因子及其受体的表达

目的:研究神经营养因子(NTFs)及其受体在前列腺癌中的表达。方法:采用免疫印迹法检测35例前列腺癌患者前列腺组织中神经生长因子(NGF)、脑源性神经营养因子(BDNF)以及其受体TrkA、TrkB、p75的表达,并以10例意外死亡年轻人正常前列腺组织中表达水平作对照。结果:与对照组相比,癌组织中NGF表达下降,而BDNF表达上调,差异均具有显著性(P<0.01);另外,癌组织中p75表达下调,但TrkA、TrkB表达均上调,且差异都具有显著性(P<0.05)。结论:NGF、BDNF及其受体表达变化与前列腺癌发生发展有关,可作为诊断前列腺癌的参考指标。     

脑源性神经营养因子及酪氨酸激酶受体B可能成为治疗膀胱肿瘤的新靶点

神经营养因子是一类对神经元的生长、发育和维持其基本功能起着重要作用的蛋白质。近来研究发现,神经营养因子在多种人体肿瘤中也有异常表达,这提示神经营养因子不仅在神经系统中发挥作用,在肿瘤中也扮演着重要角色,而其中对脑源性神经营养因子(brain derived neurotrophic factor,BDNF)及其受体酪氨酸激酶受体B(Tyrosine kinase receptor B,TrkB)的研究最为广泛,但BDNF/TrkB信号通路在各类肿瘤中的具体作用机制仍没有统一的认识。这篇综述主要对BDNF/TrkB在肿瘤中的不同作用并结合在膀胱肿瘤中的表达情况,推论BDNF/TrkB信号通路有可能成为治疗膀胱肿瘤的新靶点。     

神经营养因子与周围神经的损伤和修复

神经营养因子可由多种组织的细胞表达。周围神经损伤后,神经营养因子的表达和逆行运输发生显著变化,提示机体对神经营养因子的需求。神经营养因子能影响多种细胞的基因表达和功能,起到保护损伤神经元、促进神经再生和保护靶器官的作用,展示良好的应用前景。     

雪旺细胞源神经营养因子的神经营养活性及其抗NO神经毒性 …

目的：研究雪旺细胞源神经营养因子对脊髓前角神经元的神经营养活性及对抗一氧化氮（ＮＯ）神经细胞毒性的作用。方法：分４组进行神经元培养：（１）营养因子组：加入不同浓度的雪旺细胞源神经营养因子；（２）ＮＯ组，加入ＮＯ体外供体硝普钠；（３）营养因子＋ＮＯ组；同时加入雪旺细胞源神经营养因子和硝普钠；（４）对照组：加Ｄ－Ｈａｎｋ，培养２天后，ＭＴＴ法观察各组细胞情况。结果：营养因子组ＯＤ值均明显高于对照组；Ｎ     

脑源性神经营养因子在急性脊髓损伤后神经修复中作用的研究进展

脑源性神经营养因子（brainderivedneurotrophicfactor,BDNF）是在脑内合成的一种蛋白质,并且广泛分布于中枢神经系统内。它属于神经营养因子的一种,对神经系统的生长发育和成熟有重要的影响。本文就BDNF及其受体的分子结构、功能、影响因素及在急性脊髓损伤后神经修复方面的研究现状和应用前景做一综述。     

BDNF及TrKB可能成为肿瘤治疗的新希望

脑源性神经营养因子是酪氨酸蛋白激酶受体B的配体,两者结合促进酪氨酸蛋白激酶受体同源二聚体形成,激活酪氨酸激酶受体B活性,促进受体酪氨酸残基磷酸化,活化的酪氨酸蛋白激酶受体B顺序激活多种蛋白酶,将脑源性神经营养因子信号传至细胞核,产生各种生物学效应.越来越多的研究发现,脑源性神经营养因子和酪氨酸蛋白激酶受体B在恶性肿瘤中的表达高于肿瘤旁组织及正常组织,它们通过促进肿瘤的血管形成,抑制肿瘤的失巢凋亡,抵抗抗肿瘤因子等各种方式,促进肿瘤的生长、分化和转移.脑源性神经营养因子及酪氨酸蛋白激酶受体B与肿瘤的密切联系,为临床治疗提供了一个新的治疗策略,那就是通过靶向抑制脑源性神经营养因子及酪氨酸蛋白激酶受体B的表达,从而促进肿瘤细胞失巢凋亡,抑制生长,分化和转移,达到治疗肿瘤的目的.从目前的基础和临床的研究看来,这种治疗策略有很大的应用前景.     

许旺细胞源神经营养因子受体在外周神经组织中的分布研究

目的探讨许旺细胞源神经营养因子(SDNF)受体在外周神经的分布状况.方法应用放射性受体结合法检测外周神经组织中125I-SDNF的特异性结合.结果外周神经组织中存在许旺细胞源神经营养因子的特异性结合位点,且该特异性结合位点具有如下特点(1)高亲和力,Kd为(93.11±0.52)pmol/L;(2)低结合容量,Bmax为(8.91±0.26)fmol/mg;(3)可饱和性,饱和曲线呈双曲线型,Scatchard分析的回归线呈直线;(4)可逆性,结合常数K1为(3.91±0.63)×107M-1×min,解离常数K-1为(3.38±0.54)×10-3min-1;(5)特异性.结论外周神经组织中存在许旺细胞源神经营养因子的高亲和力受体,故为许旺细胞源神经营养因子发挥神经营养作用的靶组织.     

神经营养因子与糖尿病性勃起功能障碍

目前研究表明,神经营养因子在各类神经的发育、分化和再生过程中发挥了重要作用。局部神经营养因子的异常变化是糖尿病性周围神经病变的发病机制之一。糖尿病性勃起功能障碍发病原因众多,而其中重要的一点就是勃起神经的损伤。神经营养因子对于勃起神经损伤导致的勃起功能障碍有明确的治疗作用,最近发现其对糖尿病性勃起功能障碍实验动物也有类似效果。神经营养因子对治疗糖尿病性勃起功能障碍开辟了一条新的思路。     

周围神经损伤及其转基因治疗

修复周围神经损伤的技术迄今已得到很大的改进,但神经功能仍停留在部分恢复的状态,人们对神经损伤修复中所涉及的神经、化学因素及其相互作用的复杂关系所知尚少。已经证明许多神经营养因子在神经功能的发育、维持和调节等作用中至关重要,这些因子包括神经生长因子和近年来分离鉴定出的神经营养因子家族成员。本文综述了周围神经损伤和再生的过程及雪旺细胞和各种营养因子的作用．并展望病毒载体及细胞介导的DNA链技术在周围神经损伤治疗中的潜在用途。     

许旺细胞源神经营养因子对脊髓前角运动神经元的保护作用

目的 了解许旺细胞源神经营养因子对神经损伤所致脊髓前角运动神经元死亡的保护作用。方法 选用出生３周ＳＤ鼠切断坐骨神经,神经近侧行旺细胞源神经营养因子或生理盐水,４周后观察腰４－５节段脊髓前角运动神经元的存活率和一氧化氮合成酶表达情况。结果术后４周,营养因子组神经元的存活率是９３．４％,生理盐一是５９．６％,两组一氧化氮合酶表达均未见增加。结论 许旺细胞源神经营养因子对员的俏髓前角运动神经元有明显     

血管内皮生长因子在甲状腺癌的表达及意义

血管内皮生长因子特异性作用于血管内皮细胞,通过促进内皮细胞的增生,增加血管通透性,以诱导肿瘤血管及淋巴管生成,在肿瘤的发生发展中起到关键作用.研究表明,VEGF及其受体的表达与甲状腺癌的发生,淋巴结转移,预后密切相关,抑制VEGF及其受体的表达在甲状腺未分化癌及髓样癌的治疗中有一定的应用前景.     

Overexpression of the EphA2 tyrosine kinase in prostate cancer.

BACKGROUND: Molecules that are highly expressed by human prostate cancers may serve as therapeutically relevant targets or tumor markers. Tyrosine kinases are frequently overexpressed in metastatic tumor cells and this prompted us to screen for tyrosine kinases that are overexpressed in prostate cancer cells. METHODS: Expression levels of the EphA2 receptor tyrosine kinase were determined by Western blot analysis in canine and human prostate cancer cell lines and in immortalized and transformed variants of 267B1 prostatic epithelial cells. EphA2 levels in benign human prostate and prostate cancers were also determined in formalin-fixed, paraffin-embedded tissues using immunohistochemical staining. RESULTS: Metastatic prostate cancer cells overexpressed EphA2 by 10-100 fold as compared with non-invasive prostatic epithelial cells. EphA2 immunoreactivity in vivo was also significantly greater in human prostate cancers as compared with benign prostate epithelium. CONCLUSIONS: The EphA2 receptor tyrosine kinase is differentially expressed in human and canine prostate cancer cell lines and overexpressed in human prostate cancers as compared with benign prostate tissues. Metastasis-derived canine prostate carcinoma cell lines overexpress EphA2 and may provide pre-clinical models to further evaluate the role of EphA2 in prostate carcinogenesis. Further investigations are needed to determine the utility of EphA2 as a tumor marker and a novel target in human prostate cancer.     

转化生长因子调控表皮生长因子受体在雄激素非依赖型前列腺癌细胞中表达的意义

目的 :探讨转化生长因子 (TGF)α对前列腺癌雄激素非依赖型细胞系中表皮生长因子受体 (EGFR)表达的调控。　方法 :采用逆转录 多聚酶链式反应和Western印迹法对TGFα刺激前列腺癌雄激素非依赖型细胞系PC3、ARCaP后EGFRmRNA表达及其蛋白水平进行定量分析。　结果 :TGFα引起PC3、ARCaP的EGFRmRNA表达升高 ,分别为 5 .0 1± 0 .4 5和 9.0 5± 0 .6 3,明显高于对照组 (P <0 .0 5 )。PC3细胞系TGFα治疗后EGFR蛋白水平为 2 .2 8±0 .5 3,明显高于对照组 (P <0 .0 5 ) ;而ARCaP细胞系TGFα治疗后EGFR仅为 1 .2 4± 0 .2 2 ,和对照组比较无差别 (P >0 .0 5 )。　结论 :TGFα可以明显提高前列腺癌细胞的EGFR表达量 ;TGFα EGFR自分泌环参与雄激素非依赖型前列腺癌的形成     

TRAIL受体在前列腺癌中的表达

目的　探讨肿瘤坏死因子相关诱导凋亡配体 (TRAIL)受体在前列腺癌组织中的表达及其与前列腺癌恶性度的关系。方法　采用免疫组织化学方法检测前列腺癌组织及良性前列腺增生组织中DR4、DR5及DcR1的表达。结果　前列腺癌组织DcR1表达水平显著低于良性前列腺增生组织 (P <0 .0 1) ,DR4、DR5的表达水平两者无显著性差异。前列腺癌组织中DR4、DR5及DcR1的表达程度与前列腺癌组织的病理分级和临床分期无关 (P >0 .0 5 )。结论　TRAIL基因受体DcR1在前列腺癌凋亡机制中可能发挥重要作用     

RANKL acts directly on RANK-expressing prostate tumor cells and mediates migration and expression of tumor metastasis genes

BACKGROUND: Metastases to bone are a frequent complication of human prostate cancer and result in the development of osteoblastic lesions that include an underlying osteoclastic component. Previous studies in rodent models of breast and prostate cancer have established that receptor activator of NF-kappaB ligand (RANKL) inhibition decreases bone lesion development and tumor growth in bone. RANK is essential for osteoclast differentiation, activation, and survival via its expression on osteoclasts and their precursors. RANK expression has also been observed in some tumor cell types such as breast and colon, suggesting that RANKL may play a direct role on tumor cells. METHODS: Male CB17 severe combined immunodeficient (SCID) mice were injected with PC3 cells intratibially and treated with either PBS or human osteprotegerin (OPG)-Fc, a RANKL antagonist. The formation of osteolytic lesions was analyzed by X-ray, and local and systemic levels of RANKL and OPG were analyzed. RANK mRNA and protein expression were assessed on multiple prostate cancer cell lines, and events downstream of RANK activation were studied in PC3 cells in vitro. RESULTS: OPG-Fc treatment of PC3 tumor-bearing mice decreased lesion formation and tumor burden. Systemic and local levels of RANKL expression were increased in PC3 tumor bearing mice. PC3 cells responded to RANKL by activating multiple signaling pathways which resulted in significant changes in expression of genes involved in osteolysis and migration. RANK activation via RANKL resulted in increased invasion of PC3 cells through a collagen matrix. CONCLUSION: These data demonstrate that host stromal RANKL is induced systemically and locally as a result of PC3 prostate tumor growth within the skeleton. RANK is expressed on prostate cancer cells and promotes invasion in a RANKL-dependent manner.     

Prostate-derived factor as a paracrine and autocrine factor for the proliferation of androgen receptor-positive human prostate cancer cells

BACKGROUND: The expression of prostate-derived factor (PDF) is significantly elevated in human prostate tumors. We investigate the functional role and signaling of PDF in androgen receptor (AR)-positive human prostate cancer cells. METHODS: Transient or stable expression of PDF by cDNA transfection, antisense-mediated gene silencing, media conditioned by PDF-elevated cells, and antibody (Ab) neutralization were employed. RESULTS: Elevated endogenous and exogenous expression of PDF and treatment of PDF-enriched media were associated with increased proliferation and clonogenic growth of the cells. On the contrary, knockdown of PDF or addition of PDF neutralizing Ab resulted in diminished proliferation and reduced anchorage-independent growth. Further, ERK1/2 and p90RSK, but not Smad2/3, were activated in PDF-elevated cells as well as in cells treated with PDF-enriched media, while inhibition of ERK1/2 decreased the growth of those cells. CONCLUSION: PDF promotes AR-positive prostate tumor progression through upregulating cell proliferation via ERK1/2 signal pathway.     

凋亡抑制基因XIAP在前列腺癌细胞中的表达及与临床病理特征的关系

目的 :研究XIAP基因在前列腺癌细胞系和前列腺癌组织的表达情况 ,及其与前列腺癌临床病理特征的关系。　方法 :应用RT PCR检测前列腺癌组织、正常前列腺组织和前列腺癌细胞株PC 3,DU 14 5 ,LNCaP细胞XIAP基因的表达 ,并通过免疫组化SP法检测 5 6例前列腺癌组织标本XIAP蛋白的表达情况。　结果 :XIAP基因在前列腺癌组织和前列腺癌细胞株PC 3,DU 14 5 ,LNCaP细胞高表达 ,正常前列腺组织无表达。在前列腺癌组织和癌旁组织中 ,XIAP蛋白阳性检出率分别为 5 3.6 % (30 / 5 6 )和 2 1.5 % (12 / 5 6 ) (P <0 .0 1) ;不同分期、分级组XIAP阳性检出率相比差异无显著性 (P >0 .0 5 )。　结论 :凋亡抑制基因XIAP与前列腺癌相关 ,在前列腺癌发生过程中具有重要的作用 ,有可能成为前列腺癌治疗的靶标。     

Insulin-like growth factor binding protein-3 induces early apoptosis in malignant prostate cancer cells and inhibits tumor formation in vivo

BACKGROUND: Insulin-like growth factor binding protein (IGFBP-3) levels are significantly reduced in malignant prostate epithelial cells. In this study, we evaluated the role of endogenous IGFBP-3 on prostate cancer cell growth and tumorigenesis. METHODS: IGFBP-3 was re-expressed by stable transfection of human IGFBP-3 cDNA in a model of human prostate cancer, M12, a malignant subline in which IGFBP-3 levels are undetectable in comparison to the parent epithelial cell, P69. Effect of IGFBP-3 re-expression (M12-BP-3) on growth kinetics, morphology, propensity to apoptosis, and in vivo tumor formation were studied. RESULTS: M12-BP-3 cells secreted IGFBP-3 and growth arrested at a cell density that was threefold lower than control cells and this was associated with marked alteration in cell morphology. Control cells when grown in conditioned media secreted by M12-BP-3 also showed altered morphology compared to when cultured in IGFBP-3-immunodepleted conditioned media. The M12-BP-3 clones showed altered mitochondrial membrane potential, increased PARP cleavage, increase in sub-G1 peak, decreased levels of neuron specific enolase, and decreased tumor formation in athymic, nude mice. CONCLUSIONS: These data suggest that IGFBP-3 induces early apoptosis and has potential tumor suppressive effect in prostate cancer. Prostate 51: 141-152, 2002.