泌乳素瘤血清泌乳素水平的相关影响因素

目的探讨泌乳素瘤患者血清泌乳素（PRL）水平升高的相关影响因素。方法泌乳素腺瘤61例,分析其术前泌乳素水平与年龄、性别、侵袭性、肿瘤大小、免疫组化PRL染色强度的关系。结果将所有病例按血清泌乳素水平分为≤100μg/L、〉100μg/L两组,进行二项分类logistic回归分析,入选变量为年龄、侵袭性、免疫组织化学PRL染色强度,OR值分别为0.933、12.034和2.666。结论泌乳素腺瘤患者血清泌乳素水平与年龄、肿瘤侵袭性和免疫组织化学PRL染色强度有关,但压迫丘脑和垂体柄导致泌乳素释放抑制因子释放减少有可能参与影响了泌乳素的释放。     

ESR1及其亚型△5-Del-ESR1 mRNA在泌乳素腺瘤中的表达

目的：研究ESR及其亚型mRNA在泌乳素腺瘤中的表达.方法：应用RT-PCR测定20例泌乳素腺瘤标本ESRI、ESR2及△5-Del-ESR1 mRNA的表达,研究其表达水平与患者性别、肿瘤体积、侵袭性及PRL水平的关系.结果：男性和绝经后女性患者肿瘤ESR1 mRNA表达高于育龄女性患者（P=0.08）;侵袭性泌乳素腺瘤高于非侵袭性肿瘤（P=0.01）;表达水平与PRL的对数值呈正相关,R2=0.665（P=0.00）.PRL≥1000ng/ml的患者△5-Del-ESR1 mRNA表达水平较PRL〈1000ng/ml的患者明显增高（P=0.031）.结论：ESR1及其亚型A5-Del-ESRI mRNA表达与泌乳素腺瘤PRL分泌及肿瘤侵袭有关.     

ESR1及其亚型△5-Del-ESR1 mRNA在泌乳素腺瘤中的表达

目的:研究ESR及其亚型mRNA在泌乳素腺瘤中的表达.方法:应用RT-PCR测定20例泌乳素腺瘤标本ESRI、ESR2及△5-Del-ESR1 mRNA的表达,研究其表达水平与患者性别、肿瘤体积、侵袭性及PRL水平的关系.结果:男性和绝经后女性患者肿瘤ESR1 mRNA表达高于育龄女性患者(P=0.08);侵袭性泌乳素腺瘤高于非侵袭性肿瘤(P=0.01);表达水平与PRL的对数值呈正相关,R2=0.665(P=0.00).PRL≥1000ng/ml的患者△5-Del-ESR1 mRNA表达水平较PRL<1000ng/ml的患者明显增高(P=0.031).结论:ESR1及其亚型A5-Del-ESRI mRNA表达与泌乳素腺瘤PRL分泌及肿瘤侵袭有关.     

垂体泌乳素腺瘤中雌激素、雄激素的表达与临床特点的相关性研究

目的研究雌激素(ER)和雄激素(AR)受体与泌乳素腺瘤临床表现之间的相关关系,探讨泌乳素腺瘤发病机理中ER和AR表达可能存在的性别差异。方法搜集同济医院2000年12月～2001年12月期间经蝶窦手术的30例泌乳素腺瘤病例,实验分为两部分。第一部分：回顾性分析了病人性别、年龄、血浆泌乳素水平、肿瘤的大小、侵袭性、CT和MRI以及手术发现、术前使用溴隐亭情况和肿瘤复发等临床资料,第二部分：选取30例中的20例泌乳素腺瘤标本,用免疫组化技术检测了ER和AR的表达。运用卡方检测行统计学分析泌乳素腺瘤的各种临床特点和ER、AR表达间的关系。结果统计分析结果显示ER和AR的表达与泌乳素腺瘤的特征如：性别、年龄、肿瘤体积、肿瘤的侵袭性无关(P＞0.05)。结论泌乳素腺瘤的性别、年龄、肿瘤体积、肿瘤的侵袭性程度不会影响ER和AR的表达。男性泌乳素腺瘤较女性患者更具侵袭性。单纯手术治疗巨大腺瘤或血浆泌乳素＞200ng／mL的肿瘤疗效并不理想。手术后溴隐亭治疗的应用与患者的性别无关,但与手术前肿瘤的体积和泌乳素水平相关。     

巨大侵袭性泌乳素腺瘤综合治疗的初步探讨

背景与目的：由于溴隐亭的临床成功应用，泌乳素腺瘤的治疗方式近年有所改变，本文探讨巨大侵袭性泌乳素腺瘤的综合治疗方法及临床治疗效果。方法：对8例随访的巨大侵袭性泌乳素腺瘤进行回顾性分析，1例给以手术切除后辅以药物和放射治疗，6例给以药物和放射治疗，1例单纯给以药物治疗。结果：1例手术切除后辅以药物和放疗者随访49个月达到临床治愈。未手术者7例在平均随访的22个月内体积平均缩小96％，PRL控制在正常水平者2例，余5例仍有不同程度的偏高。结论：对巨大侵袭性泌乳素腺瘤，PRL水平高于200ng／ml者，可考虑先给以药物和／或放疗，部分病例可以避免手术风险，是一种安全、有效的治疗方法。     

人垂体腺瘤细胞原代培养的纯化

背景与目的：较纯的人垂体腺瘤细胞对垂体腺瘤的生物学特性、病因、发病机制等的研究非常重要，本文探讨原代培养垂体腺瘤的细胞纯化方法。方法：采用三种原代培养方法对垂体腺瘤细胞进行培养，方法Ⅰ为目前常用的垂体瘤细胞培养方法，方法Ⅱ结合使用右旋颉氨酸（D-valine）替代左旋颉氨酸（L-valine）的DMEM D-valine培养液，方法Ⅲ采用反复贴壁法结合DMEM D-valine培养液培养。观察其细胞形态变化和生长特征。免疫组织化学染色法检测培养细胞生长激素（growth hormone，GH）、泌乳素（prolactin，PRL）的表达。结果：3种方法均能成功培养出垂体腺瘤细胞，呈圆形或椭圆形，其纯度随培养时间的延长逐渐下降，培养第20天其平均纯度分别为40％、46％、96％。方法Ⅲ明显高于方法Ⅰ和方法Ⅱ，差异具有显著性意义（P〈0．01）：腺瘤细胞分别呈GH、PRL阳性表达，成纤维细胞表达Ⅰ型胶原。结论：反复贴壁法结合DMEM D-valine培养液培养法可得到纯度达95％以上的人垂体腺瘤细胞，纯化后的细胞可分别呈GH和PRL阳性表达，为进一步研究人垂体腺瘤的发病机理、药物治疗和颅外移植等方面奠定了实验基础。     

侵袭性垂体腺瘤的基因研究

垂体腺瘤约占颅内肿瘤的10％，每年发病率为0．5／10万-8．2／10万，而临床上静息的微腺瘤在无选择尸解中高达23％。大部分垂体腺瘤是良性的，而文献报道远处转移几乎是垂体腺癌唯一的诊断证据。介于良性腺瘤和腺癌二者之间的、具有恶性肿瘤生物学行为的肿瘤，称为侵袭性垂体腺瘤，其生长特征是垂体瘤呈侵袭性生长，发病率高（33％-35％），治愈率低（17％）。据文献报道，侵袭性垂体腺瘤的发生率占垂体腺瘤的6％-85％，如何在术前诊断侵袭性垂体腺瘤目前仍是一个难题。临床上对于有以下情况时，一般考虑垂体     

人垂体腺瘤组织p16基因表达临床意义的研究

目的：探讨垂体腺瘤组织中p16基因表达与临床病理特征及肿瘤侵袭性之间的关系。方法：应用免疫组化SP法和RT-PCR检测48例垂体腺瘤组织p16的表达情况。结果：48例肿瘤标本中有11例（22．9％）存在p16蛋白表达，侵袭性腺瘤表达缺失明显高于非侵袭性腺瘤，P〈0．01；p16阴性表达腺瘤直径明显大于阳性表达腺瘤，P〈0．01；p16蛋白表达与患者年龄、性别及垂体腺瘤分泌功能无关。结论：p16基因表达缺失与腺瘤大小有关，p16基因缺失通常是在垂体腺瘤生长过程中逐渐出现的晚期事件。     

632例垂体腺瘤放射治疗的回顾性分析

背景与目的：放射治疗作为垂体腺瘤的辅助治疗，常用于不适宜手术或者手术未彻底切尽的患者。尽管各类腺瘤所用放射治疗的剂量在文献报告中无大区别，但是放射治疗对各类腺瘤的疗效不全一致，本文回顾性分析632例垂体腺瘤放射治疗的结果，探讨放射治疗剂量在垂体腺瘤治疗中与疗效、并发症以及复发之间的关系。方法：回顾性分析我院放射治疗科1954～1989年间收治的632例垂体腺瘤病例，其中男性302例，女性330例，中位年龄41岁。手术后病理证实的垂体生长激素腺瘤158例，垂体泌乳素腺瘤130例，垂体促肾上腺皮质细胞腺瘤93例。手术后加放疗381例，单纯放疗251例。放射治疗中位剂量49．24 Gy。结果：随访5年后接受放射治疗的垂体生长激素腺瘤、垂体泌乳素腺瘤和垂体促肾上腺皮质细胞腺瘤的总有效率分别为95．5％、86．6％和83-3％，放疗剂量在垂体腺瘤治疗中与疗效、并发症以及复发之间均有相关性。结论：垂体腺瘤放疗剂量控制在45～50 Gy，既可以取得较好的疗效，又能够避免并发症的发生。     

侵袭性垂体腺瘤的组织学与临床预后的关系(英文)

目的分析经蝶窦入路切除的侵袭性垂体腺瘤的组织学侵袭性与临床预后的关系。方法我科自2000年1月～2003年5月行经蝶手术切除的具有完整影像学、病理学和随访资料的侵袭性垂体腺瘤82例,其中 PRL腺瘤39例,GH 腺瘤13例,ACTH 腺瘤6例,无功能腺瘤24例,随访时间5～30个月。结果侵袭性垂体腺瘤 MRI 影像学特点为鞍底受侵下陷,部分肿瘤突入蝶窦;颈内动脉包绕;海绵窦受累,鞍隔突破等,病理检查以鞍底硬膜浸润的发生率最高,并有20例(24.4%)发现有肿瘤内卒中或出血。PRL 腺瘤的全切率明显低于无功能腺瘤(P<0.01),而无功能腺瘤、GH 腺瘤与 ACTH 腺瘤之间相差不明显。PRL 腺瘤的复发率较无功能腺瘤和 GH 腺瘤高(P<0.05)。结论侵袭性垂体腺瘤中,无功能腺瘤与 GH 腺瘤的治疗效果优于 PRL 腺瘤,垂体腺瘤的侵袭性生物学行为导致手术全切机率下降,是术后复发的主要原因。     

垂体泌乳素腺癌的诊断与治疗(附124例临床分析)

ObjectiveTo study the diagnostic and therapeutic features of prolactinoma.Methods124 patients with prolactinoma were studied in clinical manifestation,pathologic,endocrinological,radiographic and therapeutic features.ResultsThe average age of the male patients was 41.6 years,32.3 years of females.The major clinical manifestation in males were sexual and visual disfunction.In females,disfunction of menstruates and galactorrhea.Average serum prolactin was 1875.22 in males,376.6 ng/mL in females.Average diameter of the tumors was 38.05 mm in males,and 83.3% of the tumors were invasive,in females were 15.25 mm and 49%.After surgery,the average serum prolactin decreased to 385.84 ng/mL (P＜0.05),13 of 15 patients improved in sexual function,82.6% patients improved in eyesight and visual field.In females prolactin decreased to 23.93 ng/mL (P＜0.05),and 81 25% infertility with microprolactinoma got pregnancy,higher than controls of drugtherapy (P＜0.05).ConclusionIn males,the tumors were usually larger and more invasive,and serum prolactin levels were higher.The patients were elder.But in females,much younger than males,most of the tumors were microadenoma,and after operation the prolactin usually decrease to normal level and more chance of pregnancy.Results of a single therapy were with less satisfaction,we advocate integrated therapy around operation.     

Prolactin: Its role in advanced tongue cancer

Serum prolactin was measured pretherapeutically and sequentially thereafter using immunoradiometric assay method in 37 male patients with advanced tongue cancer and compared with 23 healthy, age-matched controls. Prolactin levels were correlated with age, various clinicopathologic parameters, overall survival, and patients with response and those with progressive disease. Patients with advanced tongue cancer had higher prolactin levels than controls (P < 0.02), but intergroup variation in prolactin was not observed when considering the age, site of the lesion, disease stage, histologic grade, and keratin. Of the patients, 30% had hyperprolactinemia (prolactin >15.0 ng/ml). To assess the prognostic significance of pretherapeutic prolactin level, the patients were divided according to the cutoff level of prolactin (15.0 ng/ml). Hyperprolactinemic patients had more unfavourable prognosis than patients with prolactin <15.0 ng/ml (X²=2.91, df=1, P < 0.0037). In monitoring disease course, patients who responded to treatments had decreased prolactin levels at the end of 18 months as compared to their pretherapeutic levels (P < 0.01). In patients who subsequently developed progressive disease within 18 months, prolactin levels reduced initially at response, whereas with disease progression, prolactin levels increased significantly (P < 0.05). The positive and negative predictive value of prolactin was 100%. Immunohistochemical localization confirmed the ectopic production of prolactin by tongue tumors. In conclusion, our data indicate that hyperprolactinemia may be an independent predictor of short-term prognosis; circulating prolactin may be used as a marker for monitoring disease course in patients with advanced tongue cancer, and prolactin is produced ectopically by tongue tumors. © 1994 Wiley-Liss, inc.     

Clinicopathologic study of 123 cases of prolactin-secreting pituitary adenomas with special reference to multihormone production and clonality of the adenomas

BACKGROUND: Prolactinoma is the most invasive type of pituitary adenoma and is generally believed to be well-differentiated adenoma and to produce only prolactin (PRL). The factors related to the various biologic behaviors occurring in patients of different ages and sexes await clarification. Since different immunophenotypes of adenoma may show different biologic behaviors and responses to medical agents, the authors examined hormone production and tried to clarify the clonality of plurihormonal prolactinoma. METHODS: Clinicopathologic factors were studied in 123 patients with prolactinomas (40 males and 83 females). The specimens were fixed in either 10% neutral buffered formalin or 70% alcohol and used for light microscopy. Alcohol-fixed tissue was used to extract DNA from 26 samples obtained from female patients for human androgen receptor gene (HUMARA) assay. RESULTS: Sixty one cases (50%) were pure prolactinoma and 62 cases (50%) were plurihormonal prolactinoma. Spearman rank correlation analysis revealed a significant relationship between age and serum PRL level (P = 0.0002), age and tumor volume (P < 0.0001), and tumor volume and serum PRL level (P < 0.0001). Multiple regression analysis showed a significant correlation only between tumor volume and serum PRL level. The Mann-Whitney U test revealed that prolactinomas associated with higher PRL levels, larger adenomas, and higher ages were significantly more invasive to the cavernous sinus and that male patients had significantly higher PRL levels and larger adenomas. The HUMARA assay disclosed that 11 of 13 plurihormonal prolactinomas (85%) were compatible with monoclonal origin. CONCLUSIONS: The current results suggest that not only can various hormones other than PRL be secreted by prolactinoma, but also that most multihormone-producing prolactinomas are monoclonal in origin.     

Serum Levels of Interleukin-8 and Soluble Interleukin-6 Receptor in Patients with Stage-I Multiple Myeloma: A Case-Control Study

Objective: Multiple myeloma (MM) remains an incurable disease that needs better recognition and further research. Previous studies elucidated the interaction between myeloma cells and showed the necessity of bone marrow stromal cells for the initiation and progression of MM. Many chemokines and their receptors including interleukin-8 (IL-8) and soluble interleukin-6 receptor (sIL-6R) play important roles in this interaction. The main purpose of this study is evaluating the serum level of IL-8 and sIL-6R on stage-I of MM patients and healthy controls. Methods: Serum samples from 30 stage-I MM  patients (13 males and 17 females) and 30 healthy subjects as controls (13 males and 17 females) were examined in this study. The protein concentrations of serum IL-8 and sIL-6R were assessed by enzyme-linked immunosorbent assay (ELISA). Results: The mean level of IL-8 and sIL-6R were significantly elevated in stage-I MM. The mean levels of IL-8 were 1246.57±279.22 ng/ml in stage-I MM and 902.53± 294.61 ng/ml in controls (P<0.001). The mean levels of sIL-6R were 5.39±1.38 ng/ml and 4.1±1.14 ng/ml in stage-I MM and controls, respectively (P<0.001). The mean levels of IL-8 were 1342.18±193.4 ng/ml in patient females and 859± 278.2ng/ml in control females (P <0.001). The mean levels of sIL-6R were 5.21±1.55 ng/ml and 3.91±1.22 ng/ml in patient females and control females, respectively (P=0.01). The mean level of sIL-6R in patient males and control males were 5.63±1.43 ng/ml and 4.34±1.04 ng/ml, respectively (P=0.01). A significant correlation (Pearson’s correlation = 0.45, P=0.008) was observed in the population of females (patients and controls). Conclusion: The results of study suggest the possible involvement of IL-8 and the sIL-6R at stage-I MM and can better characterize the role of chemokines and their receptors in the disease process, especially in the early stages.     

Spontaneous prolactin transplantable tumor in the Wistar/Furth rat (SMtTW): a new animal model of human prolactinoma

Two spontaneous prolactinomas, removed from 28-mo-old female Wistar/Furth rats, were grafted by serial passages under the kidney capsule and the skin in 117 females of the same consanguineous strain. The hosts, aged between 2 and 10 mo, were free of estrogen treatment. These transplantable tumors, named SMtTW1 and SMtTW2, were studied until the fifth serial passage. The percentage of success was 100% under the kidney capsule and 20% under the skin. From the radioimmunoassays of prolactin (PRL), growth hormone, and adrenocorticotropic hormone and the immunocytochemical results, the tumors secrete PRL only. The PRL tumoral secretion was detected after 3 to 5 mo of graft; at 8 mo, mean plasma PRL values reached 5150 ng/ml (normal value, 15.2 ng/ml). Plasma growth hormone and adrenocorticotropic hormone values remained normal. Like the primary tumors, the grafted tumors were benign, grew slowly, and were sparsely granulated well-differentiated prolactinomas with exocytosis. They remained identical during the first serial passages. The secretion and the growth of SMtTW2 were inhibited by bromocriptine. In the light of our knowledge of the human prolactinoma, the spontaneous transplantable prolactinoma of the rat may be considered to be an animal model closer to the human pathology than the estrogen-induced "tumors" and the induced transplantable tumors. It is easier to use than the spontaneous prolactinoma of the rat.     

胃肠胰神经内分泌肿瘤患者血清CgA、PKB的水平及其临床意义

目的 探讨胃肠胰神经内分泌肿瘤患者血清嗜铬粒蛋白A(CgA)、蛋白激酶B(PKB)水平及意义.方法 选取87例胃肠胰神经内分泌肿瘤患者作为观察组,同时选取健康体检者80例作为对照组,检测血清CgA、PKB水平.结果 观察组血清CgA、PKB水平分别为(140.41±43.02)ng/ml和(1.69±0.15)ng/m...     

Clinical significance of serum MMP-2 and MMP-7 in patients with ovarian cancer

Matrix metalloproteinases (MMPs) are frequently expressed in malignant tumors and play an important role in tumor invasion and metastasis. The aim of this study was to evaluate role of serum MMP-2 and MMP-7 levels in patients with ovarian cancer. Serum levels of MMP-2 and MMP-7 were measured in 28 patients with ovarian carcinoma, 2 with borderline ovarian tumors, 10 with non-malignant gynecological disease and 30 healthy women by Enzyme-Linked Immunosorbent Assay (ELISA). Serum MMP-7 level was significantly (10.24 ± 1.35 ng/ml) higher in the patients with ovarian malign tumors than healthy controls (3.29 ± 1.64 ng/ml) (P < 0.05). Postoperative levels of MMP-7 (7.68 ± 1.17 ng/ml) were significantly lower in patients with malign ovarian tumors than those of preoperative level (10.24 ± 1.35 ng/ml) (P < 0.05). Serum MMP-2 levels were significantly lower in the patients with ovarian malign tumors (227.51 ± 9.91 ng/ml) than those in the healthy controls (279.12 ± 73 ng/ml) (P < 0.05). There was no significant difference in serum levels of MMP-2 and MMP-7 in patients with benign ovarian disease when compared to healthy controls and patients with malignant disease (P > 0.05). As a conclusion, MMP-7 can be a useful serum marker to show disease activity in malignant ovarian tumors.     

Immunohistochemical characteristics of breast-carcinoma in patients receiving neuroleptic therapy

The immunohistochemical characteristics of 17 cases of breast carcinoma in patients treated with neuroleptics (prolactin-releasing drug) are reported. Sixteen of the patients were female and one was male. Sixteen tumors in thirteen patients were invasive ductal carcinoma, two tumors in two patients were lipid-secreting carcinoma, one tumor was apocrine carcinoma, and two tumors in one patient were mucinous carcinoma. Elevated serum prolactin (Prl) levels (>15.0 ng/ml) were seen in all 7 patients whose preoperative serum prolactin levels had been determined. Immunohistochemical staining showed that 71% (15/21) of the carcinomas reacted positively for prolactin receptor (PrlR), while immunoreactive Prl was totally negative. Fourteen tumors were estrogen receptor (ER)-positive (67%; 14/21), and 12 were progesterone receptor (PgR)-positive (57%; 12/21). These results suggest that Prl secreted from the pituitary gland may interact with PrlR present on the cancer cells, but there was no evidence of de novo synthesis or uptake of Prl by cancer cells. ER and PgR status showed no characteristic immunoreactivity compared with unselected breast carcinoma patients not related to neuroleptic use.     

晚期非小细胞肺癌患者靶向治疗效果及血清肿瘤标志物变化分析

目的 探讨血清肿瘤标志物癌胚抗原(CEA)、细胞角蛋白19片段(CA211)与晚期非小细胞肺癌(NSCLC)患者靶向治疗效果及预后的关系.方法 选取晚期NSCLC患者82例,所有患者均接受靶向药物治疗,治疗结束后评价近期疗效,并在治疗前及治疗后2个月对患者血清CEA与CA211水平进行检测,比较不同组织学类型晚期NSCLC患者血清CEA、CA211水平,分析治疗前后不同疗效晚期NSCLC患者血清CEA、CA211水平,并分析血清CEA、CA211水平与晚期NSCLC患者生存期的关系.结果 82例患者靶向治疗的总有效率为43.90％;腺癌患者血清CEA水平明显高于鳞癌患者(P﹤0.01),CA211水平明显低于鳞癌患者(P﹤0.01);治疗后,PR组患者血清CEA、CA211水平均较治疗前降低(P﹤0.05);治疗后,PR组患者血清CEA、CA211水平均低于治疗后SD、PD组患者(P﹤0.05);治疗后,PD组患者血清CEA、CA211水平均较治疗前升高(P﹤0.05).血清CEA水平﹤15 ng/ml、血清CA211水平﹤5 ng/ml患者的PFS大于血清CEA水平≥15 ng/ml、血清CA211水平≥5 ng/mL的患者(P﹤0.05).结论 不同近期疗效晚期NSCLC患者血清CEA、CA211水平存在较大差异,血清CEA、CA211水平对预测晚期NSCLC患者靶向治疗效果及预后具有重要的参考价值.     

Pituitary adenomas in patients under 20 years old. A clinicopathological study of 12 cases

The clinical manifestations, pathological features and follow-up data on 12 cases of pituitary adenoma in patient less than 20 years old were evaluated. This group represented 8.5% of our 142 cases of pituitary adenoma from all age groups during the period of study. There were five males and seven females whose ages ranged from 13 to 19 years at diagnosis. Immunocytochemical staining demonstrated the presence of prolactin in 10 tumors, ACTH in one tumor and the remaining neoplasm was negative for the five major pituitary hormones (prolactin, hGH, ACTH, TSH, gonadotrophin). The results of the immunocytochemistry correlated appropriately with the clinical manifestations. Extension beyond the sella turcica at presentation was a common feature as evidenced by the high incidence of visual defects (75%). A complete excision was accomplished in only two patients. The aggressive behavior of these tumors was demonstrated by a recurrence rate of 50% and only a single long-term cure. Early detection and therapy, if possible, are essential for the successful management of pituitary adenomas in younger patients as implied by our study and other reports in the literature.