绝经前乳腺疾病患者性腺轴系激素水平量化分析及其临床意义

目的:研究绝经前(滤泡期或称卵泡前期)的女性乳腺增生和乳腺癌患者HPO轴系激素表达,包括激素雌二醇(E2)、促卵泡激素(FSH)、促黄体激素(LH)、孕酮(P)、睾酮(T)和促催乳素(PRL)6种,为乳腺增生和乳腺癌提供诊断依据。方法:采用放射免疫法检测正常人、乳腺增生和乳腺癌患者各62例血浆E2、FSH、P、T和PRL水平(E2、P和T单位为μg/L,FSH和LH单位为I U/L,PRL单位为g/L),并应用逻辑回归与判别分析等方法进行统计分析。结果:乳腺癌、乳腺增生症和正常人3组人群的激素分布不同,乳腺癌患者的E2(192.59)、FSH水平增高(24.25),LH(30.235 3)与E2、FSH存在协同性增高,Logistic回归分析和聚类分析发现,T水平乳腺癌组低于乳腺增生与正常人群组,差异有统计学意义,P<0.05。P和PRL水平越高,患乳腺癌的危险度上升。结论:通过回归分析和聚类分析,可能提高临床应用性激素检测判别疾病的能力及危险度预测,判别准确率为91.2%。     

大剂量甲地孕酮治疗晚期乳腺癌的内分泌激素改变

目的：了解大剂量甲地孕酮治疗晚期乳腺癌后体内内分泌激素水平改变可能存在的临床意义。方法：选择女性晚期乳腺癌病例共24例以大剂量甲地孕酮（HDMA）治疗（1200mg/d);并测定治疗前后尿17－羟类固醇和17－酮类固醇和血清LH、FSH、E2、PRL、TSH和孕酮（P）水平。结果：LH和FSH降低有显统计意义;E2升高一倍,但没有统计学意义,而PRL升高则有显统计学意义;孕酮轻微下降和TSH轻微升高,无统计意义;24小时尿17－羟类固醇和17－酮类固醇排出量显增加。结论：HDMA可能是通过下丘脑－垂体－肾上腺（性腺）轴的负反馈抑制作用,使LH和FSH分泌下降;体内E2和PRL升高尽管未见与HDMA的临床疗效有确切相关性,但其高泌乳素和高雌激素水平可能对患的预后不利。     

绝经后乳腺癌雌、孕激素受体状态与血清性激素水平的关系

目的探讨绝经后乳腺癌雌激素受体(ER)、孕激素受体(PR)状态与患者血清性激素水平的关系及意义。方法使用全自动免疫分析仪化学发光分析法检测41例乳腺癌患者血清性激素六项(LH、FSH、PRL、E2、P、T)水平,免疫组化EnVision二步法检测乳腺癌ER、PR表达状态。结果绝经后乳腺癌PR阴性组与PR阳性组比较,患者血清LH、FSH水平显著增高(P值分别为0.005和0.031),PRL、E2、P、T水平在二组间差异无统计学意义;在ER阴性组与ER阳性组之间所测性激素水平差异无统计学意义。结论绝经后乳腺癌PR表达状态可能与垂体激素LH、FSH水平有关。     

PTTG 在垂体腺瘤各亚型中的表达与分析

目的:研究PTTG与垂体瘤的各亚型的相关性.方法:用免疫组化方法检测92例垂体肿瘤病人PTTG.其中29例GH,20例PRL,10例ACTH,11例FSH/LH,9例TSH和13例无功能腺瘤.结果:PTTG在细胞质内显著表达,各亚型中GH型是表达最高,PRL腺瘤表达最低,各亚型的阳性表达率与PRL亚型阳性表达率对比均有统计学意义.结论:重体腺瘤不同垂体亚型中PTTG的表达阳性率及表达强度不同,PTTG检测,可为早期诊断垂体腺瘤( GH、PRL、ACTH、FSH/LH、TSH)亚型和无功能型提供参考.     

血清性激素的水平对男性肺癌患者诊断的意义

背景与目的研究表明内分泌激素失调在肿瘤的发生发展过程中有重要的作用。本研究拟探讨检测男性肺癌患者血清性激素水平的临床意义。方法采用放射免疫法和免疫放射法测定男性肺癌患者（62例）、肺良性疾病患者（30例）及正常健康人（30例）血清雌二醇（E2）、睾酮（T）、泌乳素（PRL）、生长激素（GH）、黄体生成素（LH）、卵泡刺激素（FSH）、促甲状腺激素（TSH）水平。结果男性肺癌组与正常对照组比较T水平显著降低（t=0．348，P〈0．01），E2、PRL、FSH水平显著升高（t=0．362，P〈0．01；t=2．913，P〈0．05；t=2．739，P〈0．01）；男性肺癌组与肺良性疾病组比较T水平显著降低（t=3．903，P〈0．05）；鳞癌组和腺癌组与小细胞肺癌组比较T水平显著降低（t=0．358，P〈0．01；t=3．902，P〈0．05），鳞癌组与腺癌组比较FSH及TSH显著升高（F3．918，P〈0．01；t=2．912，P〈0．05）。有淋巴结转移组与无淋巴结转移组比较T水平显著降低（t=3．914，P〈0．01），其它激素无明显差异。结论肺癌患者血清中性激素水平紊乱，检测血清中E2、T、PRL及FSH对肺癌的诊断有一定的价值，并可作为判断患者病情的指标。     

用ROC曲线评价雌激素、卵泡刺激素、黄体生成素判断乳腺癌患者绝经状态

目的应用ROC曲线评价雌二醇（estradiol,E2）、卵泡刺激素（follicle stimulating hormone,FSH）和黄体生成素（luteinizing hormone,LH）3项性激素对浸润性乳腺癌患者绝经状态的判断能力。方法分析本院128例绝经前及204例已绝经浸润性乳腺癌患者的性激素检测结果。应用ROC曲线评价单项性激素及它们联合的判断能力和判断点（Cut-offPoint）。结果单项E2、FSH和LH的ROC曲线下面积分别为0.9395（95%CI：0.9110～0.9679）、0.9714（95%CI：0.9514～0.9914）和0.9053（95%CI：0.8681～0.9424）;Youden指数最大时的判断点分别为49.52pg/ml、21.96mU/ml和13.25mU/ml。FSH的ROC曲线下面积分别和E2（P=0.036）、LH相比（P〈0.001）,差别均具有统计学意义。经计算E2和FSH进入联合判断模型,联合判断的曲线下面积为0.9774（95%CI：0.9597～0.9952）,Youden指数最大时的判断点的绝经概率（P绝经）=0.46。结论单项E2、FSH和LH均可判断乳腺癌患者的绝经状态,其中FSH的能力好于E2和LH。而E2和FSH的联合判断好于单项指标。由于LH的ROC曲线下面积最小,经计算没能进入联合判断模型,故不推荐用其判断乳腺癌患者的绝经状态。可根据临床需要,调整ROC曲线的绝经概率,选择判断点,并了解在该判断点下的误诊率或漏诊率的大小。     

胃癌、大肠癌患者血清性激素水平测定的临床意义

目的：探讨胃肠癌患者血清性激素水平及其临床意义。方法：采用放射免疫法，测定116例胃肠癌患者血清黄体生成素（LH），卵泡刺激素（FSH），催乳素（PRL），睾酮（T）及雌二醇（E2）水平。结果：胃癌患者LH，FSH，PRL水平均高于对照组（P＞0．05），T，E2水平均低于对照组，男性胃癌患者T水平显著低于对照组（P＜0．05），年龄小于60岁的男性胃癌患者血清T水平随肿瘤恶性程度的增加而明显下降（P＜0．01），结直肠癌患者TH，FSH，PRL，T水平与正常人比较，无显著性差异（P＞0．05），男性患者血清E2水平在正常值范围，女性患者E2水平显著低于正常人（P＜0．05），并在绝经期前随肿瘤恶性程度的增加而明显下降（P＜0．01），结论：男性胃癌患者血清T水平和女性结直肠癌患者血清E2水平，可作为判断患者病情的指标之一。     

国内乳腺癌患者性激素三项指标测定现状及应注意的问题

性激素三项指标包括雌二醇（estradiol,E2）、促卵泡刺激素（follicle—stimulatinghormone,FSH）和促黄体生成素（1uteinizinghormone,LH）。对于激素反应性乳腺癌患者,内分泌治疗是重要治疗措施之一。第三代芳香化酶抑制剂（aromataseinhibitors,AIs）作为初始治疗、辅助治疗均可显著降低乳癌复发率、远处转移,提高无病生存期及总生存期。因此,AIs已经成为绝经后、激素反应性乳腺癌患者的重要治疗选择。     

垂体瘤手术对垂体激素影响的研究

为了解垂体瘤手术治疗对垂体激素的影响，对经手术治疗后的150例垂体瘤进行了血清PRL、GH、T3、T4、TSH、F、ACTH水平的动态观察，现将结果报告如下。材料与方法一、对象：自1996年至1997年在我院接受手术治疗150例垂体瘤，其中男性65例，占43．3％；女性85例，占56．7％。年龄26－67岁，平均44．l岁。病程4个月一14年，平均4．5年。PRL瘤84例（临床上有不同程度的月经紊乱或闭经溢乳及性功能障碍等，血清PRL水平明显高于正常）；GH瘤30例（I％床上均有肢端肥大症表现，血清GH水平明显高于正常）；无功能瘤36例（临床无垂体激素…     

垂体瘤伴腺垂体功能减退诊疗进展

本文综述了垂体瘤手术前后腺垂体功能减退的诊断和治疗,着重讨论生长激素（GH）／胰岛素样生长因子（IGF）轴、催乳素（PRL）、促甲状腺激素（TSH）轴、促肾上腺皮质激素（ACTH）轴（不包括下丘脑一垂体一性腺轴的内容）。目前临床上。存在着不少甲状腺激素替代不充分或糖皮质激素超量使用的现象,一定程度上影响着垂体瘤的治疗效果。手术前后对甲状腺和肾上腺轴功能进行准确评估对于垂体瘤患者的合理治疗显得十分重要。本文全面综述了近年来TSH和ACTH轴功能低下的评估和替代治疗的新观点。此外,GH轴在垂体前叶功能减退时最易受累．临床上常容易忽视GH激素缺乏的评估和治疗．成人GH合理补充治疗能有效改善患者身体组成和骨健康．降低心血管疾病风险,提高生活质量。本文一并讨论了成人GH合理补充的方法,认为长期规范随访和及时调整药物剂量十分必要。     

乳腺增生与乳腺癌组织中雌激素受体、孕激素受体的表达差异及其临床意义

 目的　探讨乳腺增生及乳腺癌组织中雌激素受体（ER）、孕激素受体（PR）的表达差异及其临床意义。方法　采用免疫组织化学方法检测68例乳腺增生和168例乳腺癌标本中ER、PR的表达。结果　 乳腺癌患者ER表达水平明显高于乳腺增生患者（P＜0.05）,而PR在两组中的表达差异无统计学意义。绝经后乳腺癌患者ER表达水平中位值为30 %,明显高于绝经后乳腺增生患者的10 %（P＜0.05）,而在绝经前两组患者ER表达水平差异无统计学意义。浸润性小叶癌组织内PR的表达明显高于浸润性导管癌等其他类型,差异有统计学意义（P＝0.005）。结论　ER、PR的表达能够较好地反映乳腺疾病的病理生物学特征。     

平消胶囊治疗乳腺增生并子宫肌瘤的临床观察

目的:观察平消胶囊治疗乳腺增生并子宫肌瘤的临床疗效。方法:将70例经彩超等检查证实为乳腺增生并子宫肌瘤的患者随机分为治疗组50例和对照组20例。治疗组应用平消胶囊治疗,对照组予桂枝茯苓丸。跟踪观察疗效。结果:治疗组50例,临床治愈18例,有效31例,无效1例,总有效率98%;对照组 20例,临床治愈2例,有效17例,无效1例,总有效率95%。治疗组疼痛感的改善和肿块缩小、伴随症状均好于对照组。结论:平消胶囊对治疗乳腺增生并子宫肌瘤疗效明显,具有显著治疗作用,不良反应小,长期服用无毒副反应, 值得推广。     

Pre-irradiation of mouse mammary gland stimulates cancer cell migration and development of lung metastases

Background:

In most patients with breast cancer, radiotherapy induces inflammation that is characterised by an increase of promigratory factors in healthy tissues surrounding the tumour. However, their role in the emergence of the migration phenotype and formation of metastases is still unclear.

Methods:

A single mammary gland of BALB/c mice was irradiated with four doses of 6 Gy given at a 24-h interval. After the last session of irradiation, treated and control mammary glands were either collected for quantification of promigratory and proinflammatory factors or were implanted with fluorescent ubiquitination-based cell cycle indicator (FUCCI)-expressing mouse mammary cancer D2A1 cells. The migration of cancer cells in the mammary glands was monitored by optical imaging. On day 21, mammary tumours and lungs were collected for histology analyses and the quantification of metastases.

Results:

Pre-irradiation of the mammary gland increased by 1.8-fold the migration of cancer cells, by 2-fold the quantity of circulating cancer cells and by 2.4-fold the number of lung metastases. These adverse effects were associated with the induction of interleukin-6 (IL-6) and cyclooxygenase-2 (COX-2).

Conclusion:

The emergence of the metastasis phenotype is believed to be associated with the accumulation of mutations in cancer cells. Our results suggest an alternative mechanism based on promigratory factors from irradiated mammary glands. In clinic, the efficiency of radiotherapy could be improved by anti-inflammatory agents that would prevent the stimulation of cancer cell migration induced by radiation.     

Overexpression of Id1 in transgenic mice promotes mammary basal stem cell activity and breast tumorigenesis

Inhibitor of differentiation/DNA binding (Id)1 is a crucial regulator of mammary development and breast cancer progression. However, its effect on stemness and tumorigenesis in mammary epithelial cells remains undefined. Herein, we demonstrate that Id1 induces mammary tumorigenesis by increasing normal and malignant mammary stem cell (MaSC) activities in transgenic mice. MaSC-enriched basal cell expansion and increased self-renewal and in vivo regenerative capacity of MaSCs are observed in the mammary glands of MMTV-Id1 transgenic mice. Furthermore, MMTV-Id1 mice develop ductal hyperplasia and mammary tumors with highly expressed basal markers. Id1 also increases breast cancer stem cell (CSC) population and activity in human breast cancer lines. Moreover, the effects of Id1 on normal and malignant stem cell activities are mediated by the Wnt/c-Myc pathway. Collectively, these findings provide in vivo genetic evidence of Id1 functions as an oncogene in breast cancer and indicate that Id1 regulates mammary basal stem cells by activating the Wnt/c-Myc pathway, thereby contributing to breast tumor development.     

雄激素对雌性小鼠乳腺发育的影响

目的:观察雄激素(睾酮)对雌性小鼠乳腺生长、发育的影响,为研究雄激素与乳腺疾病的关系奠定基础.方法:对小鼠进行睾酮皮下注射和来曲唑灌胃给药,一段时间后,应用整装切片法和HE染色法,观察小鼠乳腺组织的发育情况.结果:高剂量雄激素主要使雌性小鼠正常乳腺组织的导管二、三级分支、末端终蕾数量减少;低剂量雄激素一定程度上可以促进乳腺的发育.结论:高剂量雄激素可能经过AR及其它信号通路或作用间质细胞产生某种信号分子抑制乳腺的生长.     

雄激素对雌性小鼠乳腺发育的影响

目的：观察雄激素（睾酮）对雌性小鼠乳腺生长、发育的影响,为研究雄激素与乳腺疾病的关系奠定基础。方法：对小鼠进行睾酮皮下注射和来曲唑灌胃给药,一段时间后,应用整装切片法和HE染色法,观察小鼠乳腺组织的发育情况。结果：高剂量雄激素主要使雌性小鼠正常乳腺组织的导管二、三级分支、末端终蕾数量减少;低剂量雄激素一定程度上可以促进乳腺的发育。结论：高剂量雄激素可能经过AR及其它信号通路或作用间质细胞产生某种信号分子抑制乳腺的生长。     

Prepubertal exposure to zearalenone or genistein reduces mammary tumorigenesis.

Prepubertal exposure to a pharmacological dose (500 mg kg(-1)) of the phyto-oestrogen genistein can reduce the incidence and multiplicity of carcinogen-induced mammary tumours in rats. However, such an exposure also disrupts the function of the hypothalamic-pituitary-gonadal axis, making it unsuitable for breast cancer prevention. We studied whether prepubertal exposure to genistein at a total body dose broadly comparable to the level typical of Oriental countries, approximately 1 mg kg(-1) body weight, affects mammary tumorigenesis. We also studied whether prepubertal exposure to zearalenone, a major source for phyto-oestrogens in the USA, influences breast cancer risk. Prepubertal rats were treated between postnatal days 7 and 20, with 20 microg (approximately 1 mg kg(-1) body weight) of either genistein or zearalenone. Zearalenone exposure significantly reduced both the incidence and multiplicity of mammary tumours induced by 7,12-dimethylbenz(a)anthracene (DMBA). Genistein exposure significantly reduced tumour multiplicity, but not tumour incidence, when compared with vehicle-treated animals. Furthermore, 60% of the tumours in the genistein group were not malignant, while all the tumours analysed for histopathology in the vehicle and zearalenone groups were adenocarcinomas. A higher number of differentiated alveolar buds, and lower number of terminal ducts, were present in the DMBA-treated mammary glands of the phyto-oestrogen exposed rats. The concentration of oestrogen receptor (ER) binding sites after the DMBA treatment was low in the mammary glands of all groups but a significantly higher proportion of the glands in the zearalenone exposed rats were ER-positive (i.e. ER levels > or = 5 fmol mg(-1) protein) than the glands of the vehicle controls. Our data suggest that a prepubertal exposure to a low dose of either zearalenone or genistein may protect the mammary gland from carcinogen-induced malignant transformation, possibly by increasing differentiation of the mammary epithelial tree.     

Endogenous factors in the pathogenesis of vulvar cancer

In 59 patients with cancer of the vulva, levels of ACTH, FSH, thyrotropin, prolactin, somatotropin, cortisol, triiodothyronine, thyroxin, testosterone, progesterone and estradiol were measured in blood whereas those of 17-HOCS, 17-CS and estrogens--in urine. Hormonal imbalance was established at all levels of the endocrine system, viz. increased concentrations of cortisol and 17-HOCS, decreased ACTH level, shift in androgen/estrogen and androgen/progestin ratios towards testosterone, lowered FSH and somatotropin output and elevated blood-prolactin level.     

Gut bacteria require neutrophils to promote mammary tumorigenesis

Recent studies suggest that gastrointestinal tract microbiota modulate cancer development in distant non-intestinal tissues. Here we tested mechanistic hypotheses using a targeted pathogenic gut microbial infection animal model with a predilection to breast cancer. FVB-Tg(C3-1-TAg)cJeg/JegJ female mice were infected by gastric gavage with Helicobacter hepaticus at three-months-of-age putting them at increased risk for mammary tumor development. Tumorigenesis was multifocal and characterized by extensive infiltrates of myeloperoxidase-positive neutrophils otherwise implicated in cancer progression in humans and animal models. To test whether neutrophils were important in etiopathogenesis in this bacteria-triggered model system, we next systemically depleted mice of neutrophils using thrice weekly intraperitoneal injections with anti-Ly-6G antibody. We found that antibody depletion entirely inhibited tumor development in this H. hepaticus-infected model. These data demonstrate that host neutrophil-associated immune responses to intestinal tract microbes significantly impact cancer progression in distal tissues such as mammary glands, and identify gut microbes as novel targets for extra-intestinal cancer therapy.     

Stem cells and the development of mammary cancers in experimental rats and in humans

Evidence based on immunocytochemical staining and ultrastructure suggests that morphological gradations between epithelial and myoepithelial cells, and possibly between epithelial cells and alveolar-like cells occur in terminal ductal structures of rat and human mammary glands. The benign carcinogen-induced rat and benign human mammary tumors can contain epithelial, myoepithelial-like and alveolar-like cells, whereas the malignant counterparts mainly contain only epithelial-like cells. Clonal epithelial cell lines from normal rat mammary glands, benign tumors, and SV40-transformed human mammary glands can differentiate to either myoepithelial-like or alveolar-like cells. In those of the rat, the differentiation processes occur in steps: intermediate cells along the myoepithelial-like pathway resemble intermediates in terminal ductal structures in vivo, and can also generate certain well-differentiated mesenchymal elements of the original tumours. Differentiation of the benign rat cells to alveolar-like cells with mammatrophic hormones and retinoids in vitro leads to a reduction in their tumor-forming ability in vivo. Cell lines from malignant rat mammary tumors of increasing metastatic potential and from human ductal carcinomas largely fail to yield myoepithelial-like or alveolar-like cells and are relatively slow-growing. Growth of the rat mammary epithelial cells in culture is stimulated by a pituitary-derived mammatrophic growth factor (PMGF), prostaglandin E₂, and -transforming growth factor; the response of the malignant cell lines to PMGF is reduced. It is suggested that stem cells exist in the rat and human glands that are capable of differentiating to the other major cell types of the mammary parenchyma, and that during the carcinogenic process they generate genetically unstable cells which lose their ability to differentiate and attempt to maximise their intrinsically slow growth rate.