RGD-FasL induces apoptosis of pituitary adenoma cells

This study was to investigate the cytotoxic effects on pituitary adenoma cell lines GH3/MMQ/AtT20 induced by RGD-FasL and the underlying mechanism. Fas/DcR3 mRNAs were detected by RT-PCR and their surface expressions were measured by flow cytometry. Cytotoxicity exerted by RGD-FasL on tumor cells was measured with MTT assay and the induced apoptosis was determined by agarose gel electrophoresis. The cell cycle and apoptosis was assessed by flow cytometry with PI staining. The expressions of caspase8/9/3, Bcl-2, RANKL and JNK2 were detected by Western blotting. Approximately 13.7% of GH3 cells, 25.5% of MMQ cells, 22.2% of AtT20 cells express Fas, while 23.9% of GH3 cells, 24.1% of MMQ cells, 4.6% of AtT20 cells express DcR3. The cytotoxic effects of FasL/RGD-FasL on tumor cells were all taken in a dose-dependent manner. Cell lines MMQ/AtT20 showed the same sensitivity to RGD-FasL as to FasL, while cell line GH3 was less sensitive to RGD-FasL. The cell cycle analysis indicated that RGD-FasL could inhibit cells in G0/G1 phase and G2/M phase. In MMQ and AtT20 cells treated with RGD-FasL, the AI was not significantly different from that treated with FasL, while in GH3 cells treated with RGD-FasL, the AI was lower than that treated with FasL. The expressions of caspase-8/9/3, RANKL and JNK2 were increased while that of Bcl-2 was decreased after treatment with RGD-FasL, suggesting that RGD-FasL induces apoptosis through caspase activation. We concluded that RGD-FasL could possibly be considered as a novel therapeutical candidate for the treatment of pituitary adenomas. Cellular ＆ Molecular Immunology.     

经单鼻孔蝶窦入路垂体腺瘤切除45例分析

目的探讨经单鼻孔蝶窦入路显微手术垂体腺瘤切除的方法和效果。方法对45例垂体腺瘤患者采用经单鼻孔蝶窦入路显微手术切除6例微腺瘤及39例大腺瘤,其中泌乳素(PRL)腺瘤18例,生长激素(GH)腺瘤8例,混合性(PRL GH或PRL ACTH)腺瘤12例,无功能性腺瘤7例。结果显微镜下全切除43例,次全切除2例。术后一过性尿崩症28例,经治疗1周左右恢复。无手术死亡、脑脊液鼻漏、术区出血及脑膜炎等并发症。术后平均住院8 d,全组病例术中未输血;随访1~5年,1例复发。结论单鼻孔经蝶窦入路较传统经蝶入路具有安全、简便、微创、术后并发症少、恢复快、效果满意等优点,是鞍内肿瘤切除的良好径路。     

垂体腺瘤手术入路的解剖学观察

目的为垂体腺瘤的显微外科手术提供解剖学参考依据。方法采用30具成人尸体头颅,按经蝶入路、经额入路、经翼点入路三种手术入路方式逐层解剖入路的邻近血管、神经并进行解剖学观测。结果颈内动脉内口间距(21.73±3.72)mm、视神经管内口间距(11.77±3.34)mm、海绵窦间距(20.92±4.58)mm、鞍底横径(13.57±4.21)mm、鞍底纵径(13.61±3.18)mm、蝶窦前壁至鼻孔的深度(92.91±17.81)mm、眉弓上缘中点到鞍结节的距离(62.24±14.17)mm、眉上缘中点到同侧视神经管内口距离(53.45±16.91)mm、眉上缘中点到对侧视神经管内口距离(62.24±20.80)mm、眉弓上缘中点到同侧颈内动脉入口的距离(69.81±21.96)mm、眉弓上缘中点到对侧颈内动脉入口的距离(78.40±27.46)mm、眉弓上缘中点到同侧颈内动脉膝部的距离(56.43±15.31)mm、眉弓上缘中点到对侧颈内动脉膝部的距离(64.53±17.01)mm、翼点到垂体柄末端距离(59.24±17.17)mm、翼点到前床突的距离(45.51±10.55)mm、翼点到海绵窦的距离(43.72±9.48)mm。结论应用这些解剖学测量结果可指导与鞍区相关的手术,安全显露鞍区解剖结构,不损伤重要的血管和神经。     

Plurihormonal pituitary adenomas: immunostaining of all pituitary hormones is mandatory for correct classification

AIMS: We studied the clinicopathological characteristics of plurihormonal pituitary adenomas. METHODS AND RESULTS: The study material included 167 plurihormonal adenomas, which consisted of 31% of the surgically removed pituitary adenomas that we collected during a 12-year period. The mean age of patients with plurihormonal adenoma was 45.7 years (range 13-75 years). There were 86 men and 81 women. All tumours were fully classified by immunohistochemical staining for seven pituitary hormones or subunits. Thirty immunohistochemical subtypes of plurihormonal adenomas were recognized. Hormonal symptoms were present in 70% of patients, while serum hormonal levels were increased in 89% of patients. Most patients had symptoms related to only one of the hormones and only 7% of patients had symptoms related to two hormones. The most common hormonal symptom was acromegaly (50%); symptoms related to hyperprolactinaemia ranked second (20%). Double immunostaining of all the possible combinations of the hormones was performed in 30 selected tumours, and they all showed mixtures of hormones in individual adenoma cells in any hormonal combinations studied. The latter finding supported the view that plurihormonal adenomas are monomorphous adenomas. CONCLUSIONS: Plurihormonal adenomas are common pituitary adenomas. Immunohistochemical staining of all pituitary hormones is mandatory for correct classification.     

Unusual double pituitary adenoma: a case report

We report the case of a 60-year-old woman with Cushing disease. Magnetic resonance imaging (MRI) revealed a large sellar and suprasellar mass involving the right cavernous sinus, consistent with pituitary macroadenoma. It was resected by transsphenoidal surgery. Light microscopy revealed two separate pituitary adenomas with different histologic and immunohistochemical features. One was amphophilic and strongly Periodic Acid-Schiff (PAS) positive, the other chromophobic and PAS negative. The former tumor was immunopositive for adrenocorticotropic hormone (ACTH); approximately 30% tumor cells were immunopositive for MGMT (O6-Methylguanine-DNA Methyl-Transferase). The second tumor was a PAS negative, luteinizing hormone (LH) and alpha subunit immunopositive gonadotroph adenoma. In this tumor, about 90% of the cells were immunopositive for MGMT. The Ki-67 nuclear indices of the two tumors were 6% and 2%. Our case represents a rare combination of two morphologically different pituitary adenomas, one producing ACTH and the other LH and alpha subunit. The two tumors differed not only in Ki-67 labeling indices but in MGMT immunoexpression as well.     

蝶窦垂体腺瘤的临床病理学观察

目的 探讨蝶窦垂体腺瘤(sphenoid sinus pituitary adenoma,SSPA)的临床病理特征,提高对蝶窦垂体腺瘤的认识和病理诊断水平.方法 对12例SSPA进行临床、组织病理学和SP法免疫组化染色(PRL、hGH、ACTH、LH、TSH、FSH等).结果 12例SSPA,男5例,女7例,年龄39～66岁,平均48.4岁,中位年龄55.5岁.其中原发于蝶窦和原发于垂体窝侵至蝶窦者各6例,原发于蝶窦者年龄较原发于垂体窝者偏大.临床症状多样.镜下,原发于蝶窦的垂体腺瘤的形态学与蝶鞍垂体腺瘤相同;SSPA可伴有较明显的慢性炎症细胞浸润(2/12,16.67%).10例行免疫组织化学染色的结果,瘤细胞PRL阳性6例;瘤细胞各项标记物均阴性2例;瘤细胞ACTH阳性、hGH阳性各1例.结论原发于蝶窦的垂体腺瘤比较少见,主要根据光镜及免疫组化确诊,应注意与慢性蝶窦炎和浆细胞瘤鉴别.     

Impact of sex hormones on immune function and multiple sclerosis development

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS) affecting young people and leading to demyelination and neurodegeneration. The disease is clearly more common in women, in whom incidence has been rising. Gender differences include: earlier disease onset and more frequent relapses in women; and faster progression and worse outcomes in men. Hormone-related physiological conditions in women such as puberty, pregnancy, puerperium, and menopause also exert significant influence both on disease prevalence as well as on outcomes. Hormonal and/or genetic factors are therefore believed to be involved in regulating the course of disease. In this review, we discuss clinical evidence for the impact of sex hormones (estrogens, progesterone, prolactin, and testosterone) on MS and attempt to elucidate the hormonal and immunological mechanisms potentially underlying these changes. We also review current knowledge on the relationship between sex hormones and resident CNS cells and provide new insights in the context of MS. Understanding these molecular mechanisms may contribute to the development of new and safer treatments for both men and women.     

垂体瘤复发因素分析及治疗

目的探讨复发性垂体瘤二次手术的效果及并发症。方法回顾分析本院10年间12例复发性垂体瘤的手术,肿瘤大小(2.3cm×2.3cm)~(6.0cm×4.5cm),复发的肿瘤大多为经蝶术后。结果9例肿瘤获全切,3例次全切除。术后2例复发行第3次手术,其余未见复发。结论初步研究结果显示,复发原因多样,复发性垂体瘤应首选手术,全切率高。肿瘤的位置是术式选择的关键,不推荐保守治疗。     

Role of sex hormones in cardiovascular resistance to atropine in rats at rest and during stress

Castration of males and females reduces the sensitivity of cardiac chronotropic function to atropine and potentiates the vascular component in the reaction to atropine in females (during stress) and males (at rest and during stress). Our results show that estrogens and androgens increase the sensitivity of the cardiovascular system to cholinergic influences at rest and during stress. __________ Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 141, No. 3, pp. 270–272, March, 2006     

垂体腺瘤中垂体激素与S-100蛋白免疫组化双重染色观察

目的：探讨滤泡星状细胞在垂体腺瘤分类中的意义及滤泡星状细胞与内分泌细胞之间的关系。方法：应用免疫组化双重染色方法,对４２ 例人重体腺瘤的垂体激素与 Ｓ１００ 蛋白表达进行对照观察。结果：垂体腺瘤组织中的滤泡星状细胞有两种情况,一种为腺瘤组织中可见散在分布的滤泡星状细胞,并可见１ 个瘤细胞既有 Ｓ１００ 蛋白表达,又含激素分泌颗粒;另一种为滤泡星状细胞构成了腺瘤的一种主要的细胞成分。结论：滤泡星状细胞与内分泌细胞的功能密切相关,可能在调整内分泌细胞的产生和激素释放方面起一定的作用;滤泡星状细胞腺瘤应作为垂体无功能腺瘤的一个单独类型。     

眶上锁孔入路治疗垂体瘤的临床解剖学研究

目的 :探讨内窥镜辅助眶上锁孔入路治疗垂体瘤的可行性。方法 :2 1例福尔马林固定尸体头部标本用于鞍区各解剖结构 ,特别是垂体柄、视神经、视交叉及其供血动脉特点的观察 ,总结手术可利用的间隙、应保护的结构 ;在 9例新鲜尸头上模拟进行内窥镜辅助眶上锁孔入路手术 ,进一步验证其可行性及优势。结果 :颈内动脉床突上段长度 (14 .5± 1.3 )mm(8.1～ 18.5mm ) ,发向垂体柄、视神经或视交叉的穿支动脉的支数分别为 :大脑前或前交通动脉 3 .0支 (2～ 6支 ) ,颈内动脉 2 .1支 (1～ 5支 ) ,后交通动脉 3 .2支 (3～ 6支 ) ,基底动脉 1.4支 (1～ 3支 )。视神经颅内段长度为 (11.4± 2 .7)mm (6.1～ 17.6mm ) ,第 1间隙面积为 (4 4 .8± 3 .4)mm2 (7.0～ 10 0 .8mm2 ) ,手术可通过第 1间隙或 /和第 2间隙进行。结论 :通过眶上锁孔入路治疗向鞍上发展的垂体瘤有充足的操作空间 ,具有视神经、视交叉减压充分 ,利于保护其供血动脉的优点。     

Combined pituitary function-test with four hypothalamic releasing hormones

Summary Anterior pituitary function was investigated in ten healthy subjects by administering a combination of 200 µg thyrotropin releasing hormone (TRH), 100 µg gonadotropin releasing hormone (GnRH), 100 µg growth hormone releasing factor (GRF^1–44), and 100 µg human corticotropin releasing factor (CRF). The same test protocol was performed in all subjects after pretreatment with 0.25 mg terguride. Five subjects were tested only with TRH and GnRH, five only with CRF, and six only with GRF. There was a prompt increase in all hormones after the administration of the four releasing hormones (RH). Pretreatment with terguride lowered the prolactin (PRL) increase (p<0.01) as well as the thyrotropin (TSH) peak (p<0.05) compared with the test without dopamine agonist pretreatment. The PRL levels after combined RH administration were significantly higher than after TRH and GnRH alone. Although four of the five subjects had higher TSH levels after combined RH administration than after TRH and GnRH alone, the difference was not significant. Other hormones were not significantly influenced by the combined RH administration or dopamine agonist pretreatment. Despite the fact that the interaction of the different releasing hormones and dopamine agonists influences the pituitary hormone response, combined RH administration seems to be a useful test for evaluating pituitary function also in patients receiving dopamine agonist therapy.Abbreviations ACTH Adrenocorticotropic hormone - CRF Human corticotropin releasing factor - DA Dopamine - FSH Follicle-stimulating hormone - GH Human growth hormone - GnRH Gonadotropin releasing hormone - GRF; GRF^1–44 Growth hormone releasing factor - LH Luteinizing hormone - PRL Prolactin - RH Releasing hormone (s) - RIA Radioimmunoassay - SE Standard error - TRH Thyrotropin releasing hormone - TSH Thyrotropin Supported by Deutsche Forschungsgemeinschaft (We 439/5-1 and Mu 585/2-2).     

Prolactin-producing pituitary adenoma associated with prolactin cell hyperplasia

A 24-yr-old woman with amenorrhea, galactorrhea, hyperprolactinemia, and sellar mass underwent transsphenoidal surgery. Histologic, immunohistochemical, and electron microscopic investigation revealed a well-differentiated, sparsely granulated prolactin (PRL) cell adenoma of the pituitary showing conclusive PRL immunoreactivity. In the nontumorous adenohypophysis PRL cell hyperplasia was noted. Marked differences were evident between the neoplastic and hyperplastic areas. The tumor consisted of sparsely granulated PRL cells immunoreactive only for PRL. As demonstrated by immunoelectron microscopy, the hyperplastic are a comprised monohormonal sparsely granulated PRL cells as well as bihormonal mammosomatotrophs immunoreactive for both PRL and growth hormone. The MIB-1 index was higher whereas microvessel density was lower in the adenoma as compared with the hyperplastic area. In addition, the nontumorous area showed lymphocytic infiltration whereas inflammatory reaction was not seen in the adenoma. This case represents a rare association of a PRL cell adenoma and PRL cell hyperplasia. The fact that these two lesions were contiguous in the surgically removed material raises the possibility that hyperplasia can precede and transform into adenoma.     

混合性节细胞瘤/垂体腺瘤4例临床病理观察

目的探讨混合性节细胞瘤／垂体腺瘤发生机制、临床病理特征、诊断及鉴别诊断。方法复习4例混合性节细胞瘤／垂体腺瘤患者的临床资料，并对其进行组织学观察和免疫组化（EnVision—plus法）标记。结果4例混合性节细胞瘤／垂体腺瘤患者均为女性，年龄10～35岁，平均26．5岁。临床上3例表现内分泌症状，1例有癫痫症状。组织学上肿瘤由两种不同成分组成，一种结构主要由较多神经节细胞组成，节细胞体积大，可见圆形的尼氏小体，核大，核仁突出，免疫组化标记瘤细胞表达CgA、Syn、S-100蛋白，不表达GFAP；另一部分腺瘤细胞大小形态较一致，圆形或卵圆形，胞质丰富，嗜酸性或空淡，间质血窦丰富，瘤细胞表达GH和PRL。结论混合性节细胞瘤／垂体腺瘤是蝶鞍区极少见的肿瘤，好发于青年女性，常合并肢端肥大症。该瘤的诊断主要依靠组织病理学，并辅以免疫组化标记。治疗主要采用单纯手术切除，预后较好。     

RSUME促进小鼠垂体腺瘤细胞AtT-20凋亡

目的探讨小泛素化修饰增强子(RSUME)、核转录因子-κB抑制因子-α(IκB-α)及核转录因子-κB 1(NF-κB1)在小鼠垂体腺瘤中表达及其细胞凋亡的影响。方法用RSUME小干扰RNA(siRNA)转染At T-20细胞后,用蛋白印迹及实时荧光定量PCR检测RSUME、NF-κB1和IκB-α蛋白的表达及mRNA的表达,流式细胞计量术检测细胞凋亡。结果在蛋白水平,RSUME-siRNA转染后RSUME及IκB-α表达下调(P0.05),NF-κB1则上调(P0.05);在mRNA水平,转染后RSUME mRNA表达水平明显低于转染前(P0.05),而IκB-α及NF-κB1 mRNA水平无明显变化;转染后细胞凋亡率明显升高。结论 RSUME可以通过NF-κB1促进小鼠At T-20垂体腺瘤细胞的凋亡。     

ACTH-producing pituitary adenoma in an infant with cysts of the kidneys and lungs

The light microscopical, electron microscopical and immunohistological features of a rare ACTH-producing chromophobe adenoma of the pituitary gland in an 11-month-old infant are presented. An unusual histological feature was the presence of numerous follicles. These follicles may develop secondary to necrosis of individual tumour cells. There is only one previous report in the literature of a pituitary adenoma occurring in infancy and that tumour also produced ACTH and showed a follicular histological pattern. It is of interest that our patient also had a combination of medullary cysts of the kidneys and congenital peripheral cysts of the lungs. The association of cysts in lungs with cysts in kidneys also has been reported only once previously. We conclude that the occurrence of cysts in kidneys and lungs and a pituitary tumour in infancy represents a bizarre coincidence although an unknown common embryonic insult to these organs cannot be ruled out.