丙氨瑞林治疗后子宫内膜癌细胞有丝分裂指数、细胞周期及超微结构的变化

目的：研究丙氨瑞林对子宫内膜癌的作用及机理。方法：对诊刮确诊为子宫内膜癌的１７例患者,肌肉注射丙氨瑞林２００μｇ,每天１次×７ｄ。用药结束后３ｄ行手术治疗。检测用药前、后癌细胞有丝分裂指数（ｍｉｔｏｔｉｃ　ｉｎｄｅｘ,ＭＩ）;并运用流式细胞术及透射电镜观察子宫内膜样腺癌８例用药前后癌细胞的细胞周期变化及超微结构变化。结果：内膜样腺癌１３例用药后ＭＩ下降（Ｐ＜０．０１）,８例用药后癌细胞Ｓ期下降（Ｐ＜０．０５）;癌细胞中线粒体、粗面内质网等减少,核内常染色质减少,异染色质增多,核仁固缩或呈圈状。结论：丙氨瑞林短期治疗子宫内膜癌,尤其是子宫内膜样癌,可抑制癌细胞的合成代谢与分裂。     

孕激素对子宫内膜腺癌的治疗作用及对超微结构的影响

孕激素对子宫内膜腺癌的治疗作用及对超微结构的影响董建春综述江森华祖德审校（山东医科大学附属医院，上海第二医科大学瑞金医院）子宫内膜腺癌（内膜癌）是女性生殖道中最常见的恶性肿瘤［１］，对于局限性病变，传统的治疗方法为全子宫加双侧附件切除，或术后加用盆腔...     

持续正压通气治疗儿童阻塞性睡眠呼吸暂停低通气综合征的现状

近年来研究发现胰岛素抵抗和高胰岛素血症与子宫内膜异常增生具有明显的相关性[1]。本研究的目的是通过免疫组化的方法检测胰岛素受体在子宫内膜异常增生及腺癌病变组织的表达情况,以了解胰岛素及其受体在子宫内膜病理改变中的作用。1材料与方法1.1材料研究组标本为1998～2000年山西省肿瘤医院妇科术后病理组织检查确诊为子宫内膜腺癌12例(研究组1),子宫内膜重度异常增生10例(研究组2);对照组标本为山西省妇幼保健院与北京大学第三医院妇科因卵巢及子宫肌瘤因素切除子宫的内膜标本及门诊要求取环的患者(征得其同意)吸取的内膜标本,全部经病…     

子宫内膜息肉的手术治疗及术后复发的预防

目的探讨子宫内膜息肉的宫腔镜手术治疗及术后应用孕激素预防复发的效果。方法选择北京大学深圳医院2001年8月至2007年8月行宫腔镜诊治的子宫内膜息肉86例患者,术后分为激素治疗组和观察组,激素治疗组术后给予安宫黄体酮周期性治疗3个月,观察子宫内膜息肉复发及妊娠情况。结果 86例患者中,宫腔镜检查多发性子宫内膜息肉56例,单发性子宫内膜息肉32例;激素治疗组术后2年,复发率为2.3%,观察组复发率为13.9%,两组比较,差异有统计学意义(P0.05)。32例有生育要求的患者中,术后2年23例自然妊娠,妊娠率为71.9%,但激素治疗组妊娠率(70.6%,12/17)和观察组(73.3%,11/15)比较,差异无统计学意义(P0.05)。结论子宫内膜息肉患者行宫腔镜诊断及治疗效果明确,术后应用孕激素治疗可能有助于预防子宫内膜息肉的复发。     

子宫内膜腺癌中孕激素受体亚型的表达

目的 研究子宫内膜癌中孕激素受体A、B、C三种亚型的表达,探讨其在子宫内膜癌发生、发展中的作用。方法 选取子宫内膜腺癌标本23例,其中高分化腺癌9例,中分化腺癌12例,低分化腺癌2例。另外选取绝经后子宫内膜标本5例。分别提取内膜或癌组织蛋白质,采用Western印迹法进行孕激素受体A、B、C三种亚型(hPRA、hPRB、hPRC)表达的半定量分析。结果 子宫内膜中、低分化腺癌与绝经后内膜对照相比,hPRB表达显著性降低(P=0.045);高分化腺癌和绝经后内膜hPRB差异无显著性(P>0.05)。中、低分化腺癌的hPRA、hPRB及hPRC低于高分化腺癌,但差异无显著性(P>0.05)。结论 子宫内膜中、低分化腺癌与绝经后内膜对照相比,hPRB显著下调,而高分化腺癌与绝经后内膜差异无显著性,提示hPBB可能与肿瘤的发生及分化程度有关。     

对高分化子宫内膜腺癌和／或子宫内膜复杂性非典型性增生患者应用保守治疗及ART的研究

子宫内膜腺癌和子宫内膜复杂性非典型性增生多见于绝经后妇女，较少发生于40岁以前，治疗常采用子宫切除手术，但随着妇女因工作或个人原因推迟妊娠、分娩年龄．需保留生育能力的子宫内膜复杂性增生及高分化子宫内膜癌患者数量增加。对高分化子宫内膜腺癌及子宫内膜复杂性非典型性增生患者给予孕激素治疗及辅助生殖技术(ART)治疗的情况进行研究。     

米非司酮治疗绝经过渡期功血的子宫内膜改变

目的探讨米非司酮治疗绝经过渡期功血对子宫内膜的影响。方法选择绝经过渡期功血患者50例,诊断性刮宫后每日口服米非司酮10mg,6个月一疗程。观察治疗前后子宫内膜厚度、子宫内膜病理变化、子宫内膜组织中雌激素受体(ER)、孕激素受体(PR)及ki-67的表达情况。结果米非司酮治疗期间所有患者均出现闭经,根据B超检查结果,米非司酮治疗前子宫内膜厚度为(8.58±1.77)mm,治疗后为(3.82±0.71)mm,两者相比,差异有显著性意义(P<0.01)。子宫内膜转化良好。米非司酮治疗后子宫内膜组织中ER、PR及ki-67的表达均较治疗前降低,差异有显著性。结论米非司酮能明显抑制子宫内膜增殖,降低子宫内膜组织中雌、孕激素受体表达,对细胞周期有明显抑制作用,从而发挥其对绝经过渡期功血的治疗作用。     

长期应用孕激素制剂治疗后对人子宫内膜形态学影响

本文检查了应用低剂量孕激素避孕2到38个月的11名妇女的子宫内膜.标本取材于8例子宫切除术及3例子宫内膜活检.取材后立即进行组织学及扫描电子显微镜检查.结果:每天连续应用一种孕激素2个月以后,子宫内膜腺体上皮的有丝分裂数目减少,继而腺体弯曲度消失,但仍然保持了分泌早期的形态特征.腺上皮有明显的"假复层",很多横切面显示假复层形式,并随孕激素治疗持续时     

宫腔镜下治疗子宫内膜息肉22例临床分析

目的：对宫腔镜下治疗子宫内膜息肉的临床治疗效果进行分析。方法：从我院2013年5月至2014年5月收治的子宫内膜息肉患者中随机选取22例作为研究对象,对其在宫腔镜下进行子宫内膜息肉切除手术,并在术后对患者实施孕激素治疗,将患者在术前和术后的月经量和月经天数进行对比分析。结果：22例患者全部顺利完成手术,平均手术时间为（18．21±5．12）min;术中平均出血量为（30．89±9．43）ml,术后患者均未出现严重并发症。另外,和术前相比,术后所有患者的月经量和月经期都明显减少,差异具有统计学意义（P〈0．05）。结论：对子宫内膜息肉患者在宫腔镜下实施切除术具有非常显著的临床效果。同时,在术后对患者进行孕激素的辅助治疗可以进一步提升治疗效果,具有临床推广的价值。     

子宫内膜电切除术后创面组织病理学改变及再次治疗的原因分析

目的 探讨宫腔镜下子宫内膜电切除术(TCRE)后创面组织病理学改变及再次治疗的原因。方法 对1991年3月至2002年9月,行TCRE后仍有少量出血、腹痛进行再次治疗的患者38例为研究对象,其中行子宫切除13例、二次TCRE3例和宫腔镜下刮宫22例,将手术获取的组织标本,通过病理学和免疫组织化学方法,观察行TCRE后宫腔创面的组织病理学改变,并分析再次治疗的原因。结果 (1)TCRE后,早期(术后21d内)创面表层组织坏死,肉芽组织增生;晚期(术后5个月以上)创面以胶原纤维为主、厚薄不一的瘢痕组织;(2)增生的肉芽组织表面有子宫内膜柱状上皮细胞覆盖,瘢痕组织下方平滑肌细胞增生,细胞核呈增殖细胞核抗原阳性反应;(3)肉芽或瘢痕组织中残存内膜基底层腺体,其边缘可见局灶性或弥漫性子宫内膜增生,部分瘢痕组织内显示淋巴细胞浸润及大量异物巨细胞反应;(4)部分患者子宫内膜异位于子宫肌层,刮宫可见破碎的内膜及炎性肉芽组织。结论 行TCRE后创面修复以肉芽组织增生、瘢痕形成为主,内膜腺体与平滑肌细胞增生参与创面修复;残存内膜再生、子宫内膜异位和术后感染,是导致再次治疗的原因。     

Effects of tamoxifen on steroid hormone receptors and hormone concentration and the results of DNA analysis by flow cytometry in endometrial carcinoma

OBJECTIVES: Tamoxifen is a nonsteroidal triphenylethylene derivate with a predominant antiestrogen activity, used in the endocrine treatment of breast and endometrial cancer. It is not known which endometrial carcinomas will respond favorably to tamoxifen and which ones will not. The aim of this study was to find out whether tamoxifen has an effect on hormone steroid receptors, hormone concentration, DNA content, and proliferative activity in endometrial cancer and to correlate the tamoxifen-induced changes with pathologic parameters such as clinical stage, tumor differentiation, depth of invasion, and histologic type. METHODS: Thirty postmenopausal women with endometrial carcinoma were treated with 30 mg of tamoxifen daily for 7-10 days after curettage. Steroid hormone receptors (estrogen and progesterone receptors), levels of follicle-stimulating hormone, luteinizing hormone, prolactin, estradiol, progesterone, testosterone, dehydroepiandrosterone sulfate, sex hormone binding globulin, and DNA ploidy and proliferative activity were determined before and after therapy. The patients were also divided into favorable and unfavorable prognosis groups according to classical histological parameters. The patients in the favorable group consisted of patients with stage I disease, well and moderately differentiated tumors, favorable histologic type, and a depth of myometrial invasion of less than (1/3). The patients with only one of the unfavorable parameters (clinical stage II or III, poorly differentiated tumors, unfavorable histologic types, and deeper invasion of myometrium) were included in the unfavorable prognosis group. RESULTS: After the treatment, there was a net increase in the progesterone receptors and sex hormone binding globulin and a significant decrease in the estrogen receptors. The increase in progesterone receptors and decrease in estrogen receptors occurred in the patient group with favorable prognosis regarding histologic type, degree of differentiation, and clinical stage, but also in the unfavorable prognosis group regarding the depth of myometrial invasion. Statistically significant decrease in the follicle-stimulating hormone concentration was observed in the groups with favorable prognosis regarding histologic type, depth of myometrial invasion, and grade of differentiation. Concentration of sex hormone binding globulin was significantly increased in groups with favorable prognosis if histologic type and grade of differentiation were taken into account. On the other hand, there was a significant decrease in the concentration of luteinizing hormone in the group with unfavorable histologic type and also a decrease in progesterone concentration in patients with unfavorable prognosis regarding the grade of differentiation. There was no statistical significance either in the concentrations of other hormones measured or in the DNA analysis by flow cytometry. CONCLUSIONS: Our results revealed that tamoxifen can increase progesterone receptors and decrease estrogen receptors in endometrial cancer. The effect was most pronounced in tumors with favorable clinicopathologic parameters. We conclude that tamoxifen therapy can induce progesterone receptor synthesis even in tumors with low initial progesterone receptor levels, making such tumors potentially responsive to additional hormonal therapy with progesterone.     

Apoptosis may be an early event of progestin therapy for endometrial hyperplasia

OBJECTIVE: The aim of this study was to investigate the role of apoptosis during progestin therapy for the treatment of endometrial hyperplasia. METHODS: Pre- and posttreatment paraffin-embedded endometrial tissue samples from 19 women with endometrial hyperplasia were examined for changes in glandular cellularity and apoptotic activity related to the administration of progestins. Twelve patients were successfully treated with progestin therapy and 7 patients failed treatment. Glandular cellularity was assessed based on calculating the average number of cells per gland obtained on histologic examination of hematoxylin and eosin stained tissue sections. Apoptotic activity was assessed on the same tissue sections by counting the average number of apoptotic cells per 10 high power fields (hpf) using the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling (TUNEL) assay. The effects of progesterone on apoptotic activity in a low-grade endometrial adenocarcinoma cell line (Ishikawa cells) was also examined using an ELISA cell death detection kit. RESULTS: Glandular cellularity significantly decreased with progestin therapy in both treatment outcome groups. The reduction in cells per gland was significantly greater in the group of successfully treated cases compared to the treatment failures (P = 0.005). However, within the successfully treated group, in situ detection of apoptotic cells using the TUNEL assay showed no statistical difference between pre- and posttreatment endometrial samples. Interestingly, a significant decrease in apoptosis was found in posttreatment samples of the group with persistent hyperplasia. The average number of apoptotic cells detected in 10 hpf was reduced from 7.9 prior to treatment to 3.1 after progestin therapy (P = 0.03). In the progesterone-treated Ishikawa cell line, an increase in apoptotic activity started at 24 h, reached a peak at 48 h, and continued up to 72 h of hormone treatment. At 48 h, apoptotic activity was 42.6% greater than in the untreated control (P = 0.04). By 72 h of progesterone treatment, apoptosis was 37.2% greater in the treated cells compared to the noninoculated cells (P = 0.04). CONCLUSIONS: Progestin-induced apoptosis may occur during the early period of treatment for endometrial hyperplasia. Compared to the fully responsive group, persistent endometrial hyperplasia may have intrinsically different molecular mechanisms in response to progestin therapy.     

孕激素及间质细胞培养液对原代培养内膜腺上皮HOXA11基因表达的影响

目的:探讨间质细胞是否参与了孕激素对子宫内膜腺上皮的调控,及其初步的作用机制。方法:将增生期子宫内膜间质细胞经激素处理后进行培养,提取培养液。用浓度为30%的提取培养液对腺上皮细胞进行原代培养,当细胞生长融合时,加入孕酮或孕雌激素培养4h、24h。提取细胞总RNA,用半定量RT-PCR方法检测腺上皮细胞HOXA11基因表达量。结果:当内膜腺上皮细胞中含有30%经孕激素处理的间质细胞培养液时,加入孕激素或孕、雌激素后其HOXA11基因,在培养4h时表达量有下降趋势;24h时,表达量下降明显;而用RU486预处理后再加入孕激素或雌孕激素,腺上皮细胞HOXA11基因表达量与对照组无差异;当上皮细胞中含有30%经RU486预处理后,再加入孕激素处理的间质细胞培养液时,孕激素或孕、雌激素对内膜腺上皮HOXA11表达的负调控作用在4h时消失;24h时,转为正调控(HOXA11基因表达量增加)。结论:孕激素对内膜腺上皮HOXA11基因的负调控作用需要问质细胞分泌的孕激素依赖因子的参与,而且由间质细胞和内膜腺上皮中的孕激素受体共同介导完成这一负调控作用。     

Intratumoral effects of medroxy-progesterone on proliferation, apoptosis, and sex steroid receptors in endometrioid endometrial adenocarcinoma

OBJECTIVE: The effects of progesterone on proliferation and apoptosis are studied in a scrutinized evaluation of endometrial carcinoma before, during, and after progesterone therapy. The heterogeneity of sex steroid expression as well as proliferation, indicated as Ki-67 index, is considered. METHODS: A total of 29 endometrial carcinomas were studied with in situ evaluation of Ki-67 proliferation marker, estrogen and progesterone receptors (ER and PR), and bcl-2 and p53 immunohistochemistry in the epithelial part of the tumor. In biopsy 1, before the therapy, Ki-67 ER, and PR were studied also in stroma. Apoptotic cells were morphologically identified in hematoxylin- and eosin-stained sections of the tumors and the apoptotic index (apoptotic cells per 1000 cells) was calculated. Chances in feature factors were mainly evaluated by repeated measures ANOVA. RESULTS: Proliferation (Ki-67) was decreased in grade 1 (G1) and grade 2 (G2) tumors during progesterone therapy both in overall evaluation (Ki) and particularly in the areas of maximal proliferation (Ki-max). No change was seen in G3 tumors. A decrease in PR expression in the areas of maximal expression for PR (PR-max) was also observed in G1 and G2 tumors. Apoptosis as well as bcl-2 and ER expression were unchanged during therapy and withdrawal. CONCLUSIONS: The effect of progesterone is seen only on proliferation in low-grade (G1 and G2) tumors. The coexistence of high PR expression in the foci of high proliferation may contribute to the effect in G1 and G2 tumors. No effect of progesterone is seen on apoptosis in tumors of any grade.     

Modulation of endometrial steroid receptors and growth regulatory genes by tamoxifen

OBJECTIVE: We investigated tamoxifen's effects on the expression of growth regulatory genes in the endometrium to identify the mechanism by which tamoxifen induces proliferation. METHODS: Using immunohistochemical techniques, we analyzed 39 endometrial specimens for expression of Ki-67, lactoferrin, transforming growth factor-alpha, tumor necrosis factor receptor-II, adrenomedullin, estrogen receptors, and progesterone receptors. Twenty specimens were obtained from postmenopausal breast cancer patients treated with tamoxifen (20 mg/day) for at least 6 months to include two endometrial adenocarcinoma specimens. Five secretory phase, three proliferative phase, and seven atrophic endometrial specimens were used as controls. In addition, four endometrial adenocarcinoma specimens were reviewed from patients not treated with tamoxifen. Intensity of immunostaining was quantified using digitized imaging techniques. RESULTS: Overexpression of both estrogen receptors and progesterone receptors, and an elevated proliferative index were the most consistent effects observed in benign endometrial specimens from tamoxifen-treated patients compared with atrophic controls (P <. 003). This staining pattern was also evident in adenocarcinomas from patients who received tamoxifen. Benign endometrium from tamoxifen-treated patients also expressed transforming growth factor-alpha, tumor necrosis factor receptor-II, lactoferrin, and adrenomedullin at levels comparable with those found in proliferative endometrial specimens. CONCLUSION: These data provide further documentation that the uterotropic effects of tamoxifen may be due, at least in part, to the induction of estrogen receptors and progesterone receptors, as well as other genes associated with the proliferative phase. Furthermore, analysis of estrogen receptors, progesterone receptors, and Ki-67 may be useful in identifying postmenopausal individuals on tamoxifen, who are at increased risk for developing endometrial cancer.     

Hormonal aspects of endometrial cancer

In summary, endometrial cancer is an estrogen-related neoplasm whose precursor lesion, endometrial hyperplasia, may be successfully treated with progestational agents. Trials of adjunctive progestin therapy have failed to demonstrate benefit, even though the malignancy is sensitive to palliative therapy with progestins as well as tamoxifen. Paradoxically, chronic tamoxifen exposure in postmenopausal women may increase the risk of endometrial cancer, and such women must be followed closely. Progesterone receptor may be measured using competitive binding assays or by immunohistochemical techniques. There is tumor heterogeneity with regard to progesterone receptor. Tissues surrounding the cancer may contain progesterone receptor and produce false-positive results in biochemical assays. Last, the presence of progesterone receptor not only predicts responsiveness to progestational therapy, but also confers a survival advantage in patients with endometrial cancer.     

Endometrial carcinoma remaining after term pregnancy following conservative treatment with medroxyprogesterone acetate

BACKGROUND: Successful pregnancies after conservative progestin treatment to young women with endometrial carcinoma have recently been reported. However, it is not known for certain whether the lesion is completely eradicated in such patients. We present a case of residual endometrial carcinoma after term pregnancy which had been treated conservatively before the pregnancy began. CASE: A 28-year-old woman with endometrial carcinoma received conservative treatment with high-dose medroxyprogesterone acetate (MPA) and then conceived. After delivery at term, atypical cells were found in the endometrial curettage specimen. A hysterectomy was performed 6 months after delivery and revealed the presence of a small focus of intramucosal, grade 1, endometrioid-type adenocarcinoma. Immunohistochemically, the tumor cells were positive for estrogen and progesterone receptors. CONCLUSION: We concluded that while MPA treatment had been effective, it had not completely eradicated the carcinomatous lesion, which remained during and after the term pregnancy.     

雌/孕激素对原代培养的子宫内膜上皮细胞HOXA11和PR基因表达的影响

目的:探讨雌、孕激素（尤其孕激素）对人子宫内膜腺上皮细胞HOXA11基因和孕酮受体（pro-gesterone receptor,PR）基因表达的影响,以及二者表达量变化的相互关系。方法:将6例增生期子宫内膜腺上皮细胞进行原代培养,当细胞生长融合时,加入17β-雌二醇或/和孕酮培养4h、4d、6d、8d,提取细胞总RNA,用半定量RT-PCR法检测HOXA11mRNA和PRmRNA表达量变化。结果:17β-雌二醇使上皮细胞HOXA11和PR基因表达量增加;而孕酮的作用效应则有所不同,当孕酮作用于与间质细胞分离培养的上皮细胞时,其HOXA11的表达增加,当上皮与间质细胞混合培养时,孕酮则降低上皮细胞HOXA11表达;孕酮对PR的影响则显示无论分离培养还是与间质细胞混合培养的上皮细胞,孕酮均可使上皮细胞PRmRNA表达量降低。结论:子宫内膜HOXA11基因表达受雌、孕激素调节,孕激素对内膜腺上皮HOXA11和PR基因均起负调控作用,但二者的发生机制有所不同。     

氨基导眠能与己酸孕酮治疗子宫内膜癌的作用比较

将子宫内膜癌３９例以双盲法随机分为３组，分别用己酸孕酮、氨基导眠能或两药联合治疗。结果：（１）氨基导眠能使雌二醇（Ｅ２）、孕酮（Ｐ）含量下降，己酸孕酮使血中Ｐ含量增加，联合治疗后Ｐ增加、Ｅ２下降（Ｐ〈０．０５￣０．０１）。（２）己酸孕酮使雌激素受体（ＥＲ）、孕激素受体（ＰＲ）阳性率略下降（Ｐ〉０．０５），氨基导眠能及联合用药后ＥＲ阳性率显著下降（Ｐ〈０．０５）。（３）三种不同方法治疗后均出现癌细胞