垂体腺瘤的受体靶向性基因治疗研究

目的构建并评价受体靶向性基因导入系统对垂体腺瘤的靶向性治疗作用.方法构建GE7系统介导的基因治疗系统,通过垂体腺瘤GH3细胞及对照细胞的体外基因转染实验,观察其对垂体腺瘤的转染能力和靶向性.结果成功构建GE7基因治疗系统;基因转染后,GH3细胞特异性表达报告基因,并被治疗基因特异性杀伤.结论GE7基因治疗系统能够达到靶向性治疗垂体腺瘤的目的.     

垂体生长激素腺瘤基因治疗的动物实验研究

目的利用GE7系统介导的生长激素启动子调控毒性基因治疗裸鼠垂体生长激素腺瘤,评价该系统的治疗效果.方法构建GE7系统介导的生长激素启动子调控基因治疗系统,对垂体生长激素腺瘤裸鼠模型进行治疗,并观察其治疗效果.结果治疗组裸鼠肿瘤体积缩小,而各对照组肿瘤体积均有不同程度的增加;基因治疗后荷瘤裸鼠生存期超过120 d,明显超过对照组的40 d左右(P＜0.01).结论GE7系统介导的生长激素启动子调控自杀基因治疗系统能有效治疗垂体腺瘤动物模型.     

垂体腺瘤双重靶向性基因治疗的实验研究

本研究选择GE7基因导入系统，与人生长激素启动子(human growth hormone promoter，hGHp)调控的单纯疱疹病毒-胸苷激酶(herpes simplex virus thymidine kinase，HSV-TK)基因组成基因治疗系统，实验观察对垂体腺瘤细胞的治疗作用。     

GHS-R基因5 侧翼区萤火虫荧光素酶报告基因增强子载体的构建和鉴定

目的构建生长激素释放剂受体(GHS-R)基因5'侧翼区萤火虫荧光素酶报告基因增强子载体。方法以原代培养的人生长激素(GH)腺瘤细胞基因组DNA为模板,PCR扩增GHS-R基因5'侧翼转录调控区不同长度片段(A～F)克隆,再定向克隆到pGL3-Enhancer载体中。结果通过酶切鉴定和基因测序,证明成功地构建了pGL3-Enhancer A～F克隆重组体。结论本载体的成功构建为体外研究GHS-R基因的转录调节提供了新的手段,为下一步在人垂体GH腺瘤中GHS-R基因启动子的干预研究奠定了基础。     

垂体生长激素腺瘤细胞表皮生长因子受体的表达

目的了解大鼠垂体生长激素腺瘤(GH3)细胞的表皮生长因子受体(EGFR)的表达情况.方法应用免疫组化的方法检测GH3细胞及阴性对照U-2OS细胞和阳性对照HO8910PM细胞的EGFR表达情况.结果 GH3细胞和HO8910PM细胞明显黄染,U-2OS细胞无明显染色;GH3、U-2OS和HO8910细胞表达EGFR的阳性细胞率分别为90.57%、4.84%和93.33%.结论垂体生长激素腺瘤细胞中存在着广泛的EGFR表达,而且具有较高的表达强度.     

慢病毒介导的shRNA沉默PTTG基因表达对人生长激素型垂体腺瘤细胞生长的影响

目的观察慢病毒介导shRNA沉默PTTG基因表达对人生长激素型垂体腺瘤细胞生长的影响。方法原代培养人生长激素型垂体腺瘤细胞,分为正常对照组、阴性对照组和实验组。实验组构建PTTG-shRNA的慢病毒表达载体并转染肿瘤细胞,阴性对照组转染空慢病毒载体,正常对照组细胞不转染。流式细胞仪分析细胞转染效率,RT-PCR和Western blot检测肿瘤细胞PTTG mRNA和蛋白的表达水平,MTT检测细胞增殖情况,流式细胞仪检测细胞周期变化。结果与正常对照组和阴性对照组比较,实验组细胞转染PTTG-shRNA慢病毒载体后,PTTG mRNA和蛋白表达显著下降(均P<0.01),细胞生长显著变慢(均P<0.05),G0/G1期细胞比例显著增高(均P<0.05),凋亡率明显增加(均P<0.05)。结论慢病毒介导shRNA沉默PTTG基因表达可显著抑制人生长激素型垂体腺瘤细胞的生长,为进一步研究垂体腺瘤的发病机制和肿瘤的基因治疗提供实验基础。     

腺病毒介导D2S基因联合溴隐亭治疗对GH3细胞生长的抑制作用

目的 探讨腺病毒介导多巴胺2型受体短链亚型基因(D2S)联合溴隐亭对大鼠垂体生长激素腺瘤GH3细胞株体外生长活性的影响.方法 应用携带人D2S基因及增强型绿色荧光蛋白(EGFP)报告基因的复制缺陷型腺病毒载体pAd - D2S - EGFP感染大鼠GH3细胞,RT - PCR、Western - blot法检测转染后细胞D2S mRNA及蛋白的表达,并采用CCK -8法检测转染D2S基因后联合溴隐亭药物干预治疗,对GH3细胞生长抑制及诱导凋亡作用,运用光镜及荧光显微镜检测联合作用后细胞形态变化.结果 GH3细胞转染D2S基因后检测到D2S基因的转录及蛋白表达较对照组增高.腺病毒转染D2S基因联合溴隐亭干预后第2天,体外培养的GH3细胞存活率明显下降(32.76±3.88)％,与单纯加药组的(101.78±2.05)％及空载体组的(91.79±3.80)％相比,差异有统计学意义(P＜0.01).光镜下及荧光显微镜结合Hoechst核染色观察到细胞形态出现皱缩脱落、死亡、核碎片等改变.结论 腺病毒介导D2S基因联合溴隐亭能有效抑制GH3细胞的增殖.     

中华神经外科杂志第21卷(2005年)文题索引

脑肿瘤 鞍隔结外Rosai一D。而1助病一例 (7)442. 王绍天余新光周定标等 鞍内置管引流预防垂体腺瘤经蝶术后瘤床渗血杨义任祖禅 苏长保等(2)103. 鞍区混合型生殖细胞瘤一例邢东风鲍庆华(9) 573. 鞍区Rathke囊肿的诊断和显微外科治疗楼林王天华毛 宇震等(3) 164. 成人第四脑室肿瘤的诊断和外科治疗唐恺于春江(3)171. C6胶质瘤细胞多药耐药基因启动子靶向的双自杀基因表达载体的 构建及鉴定王成伟马道新潘顺等(11) 691. 垂体腺瘤患者血浆神经肤Y与垂体激素水平相关性研究甄自 刚马景锰阎学江(10) 612. 垂体腺瘤双重靶向性基因治疗的实验研究…     

转录因子YY1对垂体瘤侵袭性的影响

目的观察转录因子YY1(Yin-Yang 1)在垂体腺瘤中的表达情况,并进一步分析沉默YY1对大鼠垂体瘤GH3细胞侵袭性的影响。方法运用免疫组化技术观察YY1在不同类型垂体腺瘤组织中的表达情况。Western blot实验检测siRNA沉默大鼠垂体瘤GH3细胞中的基因YY1后,YY1蛋白及基质金属蛋白酶MMP-2、MMP-9的表达水平。采用Transwell chamber细胞侵袭实验观察沉默YY1对GH3细胞侵袭的影响。结果 YY1在侵袭性垂体腺瘤中表达升高;沉默YY1后,GH3细胞侵袭能力下降35.7%(P0.05),MMP-2、MMP-9蛋白表达量下降(P0.05)。结论转录因子YY1在侵袭性垂体腺瘤中的表达升高,并通过上调MMP-2、MMP-9的表达来促进GH3细胞侵袭性。     

Non-surgical management of hormone-secreting pituitary tumors

Hormone-secreting pituitary tumors account for about 30% of all pituitary tumors. Successful long-term management of patients with these tumors frequently requires a multimodality team approach. Given that the role and efficacy of neurosurgical resection of hormone-secreting pituitary tumors is well described, we focus this review on the other important treatment modalities that are becoming increasingly crucial in the management of acromegaly, Cushing’s disease and prolactinomas. Medical management with standard and novel drugs as well as the role and effectiveness of radiation therapy and radiosurgery are discussed in detail.     

Pituitary tumors in children: clinical analysis of 21 cases

Objective The aim of this study is to review the results of surgery for pituitary adenomas in children less than 18 years old. Materials and methods A retrospective review was done of pituitary adenoma patients with the age of less than 18 years who were treated in the period 1979–2003 at Dr. Shariati Hospital. Conclusions Twenty-one patients (12 girls and 9 boys) were identified. The age range (mean) in girls and boys was 9–18 (15.8) and 9–17 (14.8) years, respectively. The duration of follow-up was 1–23 (13.4) years. Eight patients (38.1%) had adrenocorticotropic hormone-secreting tumors, 33.3% had prolactin-secreting tumors, 19% had growth hormone-secreting tumors, and 9.53% had nonfunctioning adenomas. Multidisciplinary management included surgery and, if necessary, reoperation with/without radiotherapy and pharmacotherapy. Eleven patients, mostly with prolactinomas, acromegaly, and nonfunctioning adenomas, needed reoperation and radiotherapy. There were two deaths, one of which was because of apoplexy. The biological behavior of pediatric pituitary adenomas seems more aggressive than adults’ adenomas. The chance of pituitary apoplexy in pediatric invasive pituitary adenoma is high.     

内镜下经鼻蝶入路治疗儿童及青春期垂体腺瘤

目的探讨儿童及青春期垂体腺瘤的临床特点和内镜下手术治疗。方法回顾性分析31例20岁以下垂体腺瘤病人的临床资料,其中泌乳素腺瘤14例,促肾上腺皮质激素腺瘤8例,生长激素腺瘤6例,无功能性腺瘤3例。均行内镜下经鼻蝶入路垂体腺瘤切除术。结果肿瘤全切除28例,次全切除3例。手术并发症：暂时性尿崩症4例,脑脊液漏2例,水电解质紊乱4例。随访6个月～5年,治愈26例,缓解3例,复发2例。结论儿童及青春期垂体腺瘤多为功能性腺瘤,无功能腺瘤仅占少数。内镜下经鼻蝶入路手术是治疗儿童和青春期垂体腺瘤安全、有效的方法。     

Growth hormone secreting pituitary adenoma with admixed gangliocytoma and ganglioglioma

Pituitary adenomas are the most common tumours found in the sellar region and, when both functioning and non-functioning adenomas are combined, account for 7–15% of primary brain tumours in adults. Rarely, admixed or discrete groups of cells comprising two or more tumour subtypes are seen; the so-called ‘collision tumour’. We present a case of a 54-year-old-woman with a growth hormone-secreting pituitary adenoma admixed with both ganglioglioma and gangliocytoma. The possible mechanisms by which this may occur include a pre-existing gangliocytoma promoting the development of pituitary adenoma by hypersecretion of releasing hormones or aberrant migration of hypothalamic neurons in early embryogenesis.     

单鼻腔经蝶入路显微手术切除垂体腺瘤

目的总结单鼻腔经蝶入路显微手术治疗垂体腺瘤的手术经验。方法回顾性分析458例垂体腺瘤病人的临床资料,其中无功能腺瘤167例,混合性腺瘤34例,功能性腺瘤257例。均行单鼻腔经蝶入路显微切除垂体腺瘤。结果肿瘤全切除306例,次全切除117例,部分切除35例。术后临床症状均有不同程度改善,术后发生难治性尿崩3例,脑脊液漏11例,脑出血2例,感染2例,视力下降3例,鼻出血2例。随访3个月～5年,复发58例,复发率12.7%。结论单鼻腔经蝶入路手术是垂体腺瘤的首选治疗方法。     

内窥镜下经鼻腔-蝶窦入路垂体腺瘤切除术

目的:探讨内窥镜单鼻腔入路在切除垂体腺瘤中的临床应用。方法:采用直径4mm的0°、30°硬性鼻内窥镜及配套摄像系统、内窥镜冲水系统、鼻窦钳等设备,内窥镜下切除垂体腺瘤30例,其中微腺瘤2例,大腺瘤25例,巨型腺瘤3例。泌乳素腺瘤18例,生长激素腺瘤4例,无功能腺瘤8例。结果:内窥镜下全切肿瘤27例,近全切肿瘤3例,术后3例出现一过性脑脊液鼻漏,3例出现一过性多尿。术后19例内分泌化验恢复正常。术后6个月随访20例,1例复发,无鼻中隔穿孔、萎缩性鼻炎等并发症。结论:内窥镜下手术创伤小,深部照明好,提供360°全景术野,切除肿瘤彻底,鼻腔结构损伤小。术后并发症少,病人恢复快等优点。     

鼻窦镜辅助下经单鼻孔入路垂体腺瘤显微手术切除

目的总结鼻窦镜辅助下经单鼻孔入路垂体瘤显微手术切除术的经验及初步体会.方法鼻窦镜辅助下,经单侧鼻腔,严格中线入路打开蝶窦前壁,暴露鞍底.然后在神经显微镜下行垂体瘤切除,最后鼻窦镜下鞍底重建.结果 21例患者中16例一次手术全切除,3例次全切除,1例巨大生长激素(growth hormone, GH)腺瘤大部分切除,后经改良翼点入路二次手术切除,1例巨大催乳素(prolactin, PRL)腺瘤分2次经蝶肿瘤切除,术后患者症状均改善.尿崩2例,分别于术后7 d、15 d停止;脑脊液漏1例,保守治疗2周治愈.结论耳鼻喉科医师解剖熟悉,鼻窦镜下显露鞍底准确充分,神经外科医师显微镜下可克服内镜单手操作的不便,二者结合有利于减少经单鼻孔入路垂体瘤切除的创伤,提高安全性,是一种有效的方法.