卵巢癌组织中LncRNA UCA1的表达及意义

目的探讨长链非编码RNA(long non-coding RNAs,LncRNA)尿路上皮癌胚抗原1(urothelial carcinoma associated gene 1,UCA1)在卵巢癌组织中的表达及临床病理意义。方法回顾性分析皖南医学院第一附属医院/弋矶山医院2015年1月~2018年3月收治的48例卵巢癌患者的临床病理资料,同时与15例卵巢交界性肿瘤组织、20例卵巢良性肿瘤组织、20例正常卵巢组织进行比较分析。采用qRT-PCR检测卵巢癌组织、卵巢交界性肿瘤组织、卵巢良性肿瘤组织、正常卵巢组织中UCA1的表达量,并分析UCA1表达与卵巢癌临床病理特征的关系。结果48例卵巢癌组织中UCA1的平均表达量(12.90±2.60)均明显高于卵巢交界性肿瘤组织(4.73±1.10)、卵巢良性肿瘤(2.85±0.99)、卵巢正常组织(2.30±1.13)(P<0.05);UCA1在卵巢交界性肿瘤组织中的表达高于卵巢良性肿瘤、正常卵巢组织(P<0.05);卵巢良性肿瘤与正常卵巢组织中UCA1的表达差异无统计学意义(P>0.05)。结论LncRNA UCA1在卵巢癌组织中高表达,可能促进卵巢癌细胞的侵袭及转移,可作为卵巢癌临床治疗的潜在靶向和预后不良的分子标志物。     

C-erbB-2基因表达与卵巢肿瘤的关系研究

目的研究卵巢肿瘤中C-erbB-2基因的表达,探讨C-erbB-2基因在卵巢肿瘤发生发展中的作用及作为一种肿瘤标记物用于临床筛查和判断预后的临床意义。方法应用免疫组织化学的方法检测20例正常卵巢组织、30例卵巢恶性肿瘤、20例卵巢良性肿瘤中C-erbB-2的基因表达情况。用卡方检验（Chi-Square Test）检测C-erbB-2在卵巢肿瘤组织中的表达。结果卵巢恶性肿瘤组织中C-erbB-2基因阳性表达率为73.3%,卵巢良性肿瘤组织为15%,正常卵巢组织中为0%,无C-erbB-2过表达。在临床分期中,Ⅰ～Ⅱ期卵巢癌C-erbB-2基因阳性表达率为33.3%,Ⅲ～Ⅳ期为90.5%。结论 1.在卵巢恶性肿瘤组织中C-erbB-2基因表达异常或扩增。2.C-erbB-2作为影响细胞凋亡因子,基因过表达与卵巢肿瘤的发生发展有关,其检测为判断卵巢肿瘤的预后提供重要的理论依据。     

Follow-up of ovarian function post-chemotherapy following ovarian cryopreservation and transplantation

BACKGROUND: The purpose of this study was to assess the ovarian function after treatment of a malignant disease in women who previously had cortical tissue from an entire ovary cryopreserved prior to chemotherapy, and to assess ovarian function after autotransplantation of cryopreserved ovarian tissue. All were treated with chemotherapeutic drugs with an estimated high risk of inducing ovarian failure. METHODS: Twenty-two women with breast cancer (n = 8), Hodgkin's disease (n = 6), non-Hodgkin's (n = 2), leukaemia (n = 5) or brain tumour (n = 1) underwent a clinical examination >18 months after cryopreservation. Three patients with premature ovarian failure had ovarian tissue autotransplanted orthotopically and heterotopically. Ovarian function was assessed by ultrasonography of the remaining ovary and hormone measurements. RESULTS: Nine of 22 women (41%) had sonographic and hormonal signs of ovarian failure with ovarian volumes <1.3 cm3, no antral follicles and high FSH levels (median 57.1 IU/l). Thirteen of the 22 women (59%) still menstruated and 10 had a seemingly normal ovarian function, with a median ovarian volume of 6.8 cm3, a median number of antral follicles of six, FSH <15 IU/l and normal estradiol levels. All three patients with autotransplanted ovarian tissue regained ovarian function as confirmed by return of menses, follicles on ultrasonography and normalized hormone levels. Two embryos were created from the crypreserved tissue after IVF. CONCLUSIONS: Treatment with bone-marrow transplantation and/or high doses of alkylating agents led to ovarian failure in all patients. Autotransplantation of ovarian tissue led to return of ovarian function.     

Massives Ovarialödem bei einem 13-jährigen Mädchen

Massive ovarian edema is a rare tumor-like condition found in young women resulting from accumulation of fluid mostly due to partial or intermittent torsion of the ovary or secondary, to a preexisting ovarian lesion. We report a case of a 13-year-old girl presenting with an ovarian mass measuring 16 cm. CA-12-5 levels were slightly elevated. Concerns regarding underlying malignancy led to salpingo-oophorectomy. Pathological evaluation revealed a massive ovarian edema and multiple thromboses of ovarian veins. Differentiating massive ovarian edema from malignant ovarian tumor is crucial to prevent patients from undergoing unnecessary surgery.     

The origin of the extrinsic adrenergic innervation to the rat ovary

Cutting the suspensory ligament reduced the ovarian content of norepinephrine (NE) to less than half that of controls and only a few blood vessels had perivascular fibers and an occasional nerve remained in the interstitial gland. Cutting the ovarian plexus had a less drastic, but similar effect on the ovarian content of NE and on the pattern of ovarian adrenergic nerves. Cutting both the suspensory ligament and ovarian plexus eliminated visualization of ovarian adrenergic nerves, but some ovarian NE was still measurable. Fluorescence and electron microscopic studies of the suspensory liagament revealed a large adrenergic nerve embedded in smooth muscle of the ligament. The nerve was also acetylcholinesterase-positive. Cutting the celiac plexus or incising a small nerve lateral to the plexus and medial to the origin of the suspensory ligament, had the same effect on the ovarian adrenergic nerves as cutting the suspensory ligament. It is concluded that the extrinsic adrenergic nerves to the rat ovary reach the organ by two routes: one via the nerve in the suspensory ligament (superior ovarian nerve), and one via the traditionally described ovarian plexus along the ovarian artery.     

Predictors of IVF outcome by three-dimensional ultrasound

BACKGROUND: Our study was designed to evaluate whether ovarian antral follicle number, ovarian volume, stromal area and ovarian stromal blood flow are predictive of ovarian response and IVF outcome. A total of 56 women with normal basal serum FSH concentrations who had no history of ovarian surgery, no ovarian and/or uterine pathology, were non-smokers and undergoing their first IVF cycle using a standard long GnRH agonist protocol were examined. METHODS: Total ovarian antral follicle number, total ovarian volume, total stromal area and mean flow index (FI) of the ovarian stromal blood flow were determined by three-dimensional (3D) and power Doppler ultrasound after pituitary suppression. Pretreatment 3D ultrasound ovarian measurements were compared with subsequent ovulation induction parameters [peak estradiol (E2) on HCG administration day and number of oocytes] and cycle outcome (fertilization and pregnancy rates). RESULTS: The total antral follicle number achieved the best predictive value for favourable IVF outcome, followed by ovarian stromal FI, peak E2 on HCG administration day, total ovarian volume, total ovarian stromal area and age. Using these six parameters, we were able to predict a favourable IVF outcome in 50% (11/22) of patients and poor outcome in 85% (29/34) of patients. CONCLUSIONS: Three-dimensional ultrasound facilitates determination of the antral follicle number, ovarian volume calculation, evaluation of the ovarian stroma and analysis of the intensity of ovarian stromal blood flow in a short time without increasing the patient's discomfort.     

Detection of antibodies to ovarian antigens in women with premature ovarian failure.

Premature ovarian failure is a common condition of uncertain aetiology in most cases, although autoimmunity is thought to play a role in a proportion of cases. The frequency of ovarian antibodies, which may be markers for an autoimmune aetiology in this condition, remains unclear. To define this further, we have examined the sera of 45 women with premature ovarian failure (five with iatrogenic ovarian failure, nine with an associated autoimmune disease, and 27 with idiopathic ovarian failure), as well as four women with infertility due to Turner's syndrome and 41 pre- and post-menopausal controls. Using two human ovarian antigen preparations, 24% and 60% of the ovarian failure patients reacted in an ELISA (P < 0.05 and P < 0.001 compared with controls), but frequent cross-reactivity was found with fallopian tube antigens. The apparent aetiology of ovarian failure did not correlate with the presence of ovarian antibodies. Using bovine ovary as an antigen, there was a significant overall increase in binding by the ovarian failure patients, but this was almost identical to binding in an ELISA with bovine fallopian tube. In contrast to a previous report, there was no significant increase of binding to soluble or Triton-extracted membrane fractions of bovine corpora lutea containing the LH/hCG receptor by the patients with ovarian failure. These results suggest that ovarian antibodies are common in premature ovarian failure, but their specificity and pathogenic role are questionable.     

Ovarian reserve testing and the use of prognostic models in patients with subfertility.

The decline in fecundity with female age is a well-known phenomenon for clinicians dealing with subfertility patients. Diminishing ovarian reserve seems to be the reason for declining fecundity. Since age is only a rough estimate of ovarian reserve, many tests have been developed to predict ovarian reserve more precisely. This review focuses on these ovarian reserve tests and their clinical role in predicting response to ovarian stimulation and pregnancy chances. According to our analysis, the clomiphene citrate challenge test has the strongest correlation in predicting ovarian reserve, and is the only test that is validated in the general infertility population. The antral follicle count by ultrasound is promising and may offer clinical use. It is not known whether a combination of tests can provide more accurate information of ovarian reserve. It is not yet clear to which extent the results of ovarian reserve tests can be incorporated into the available prognostic models. There is a need for prospective cohort studies that focus on prognostic factors among which are the results of ovarian reserve tests. Only then can the qualitative and quantitative relevance of ovarian reserve testing in the context of the prognosis for couples with subfertility be established.     

Assessment of ovarian reserve. Is there still a role for ovarian biopsy? First do no harm!

Multiple endocrine, ultrasound-based and dynamic tests have been proposed for the assessment of ovarian reserve. Lately, ovarian biopsy has been proposed as a more representative functional test of ovarian reserve, and has been recommended as an early step in the investigation of infertility. Central to this hypothesis is the idea that a random biopsy of the ovarian cortex is reflective of the actual ovarian follicular pool. Recent studies have shown a wide variation in the number and distribution of ovarian follicles even from the same ovary and in the same patient. Coupled with the invasiveness of performing the biopsy and the risk of adhesion formation, we believe that there should not be a role for ovarian biopsy in ovarian reserve testing.     

Expression of Rsf-1, a chromatin-remodeling gene, in ovarian and breast carcinoma

Rsf-1 protein is a member of a chromatin-remodeling complex that plays an important role in regulating gene expression and cell proliferation. Our previous study showed that Rsf-1 was an amplified gene that participated in the development of ovarian serous carcinoma. To further elucidate the role of Rsf-1 in ovarian cancer, we studied Rsf-1 immunoreactivity in 294 ovarian tumors of various histologic types. Because the Rsf-1 amplicon overlaps an amplified region reported in breast cancer, we included 782 neoplastic and normal breast tissues for comparison. Immunohistochemistry was performed on tissue microarrays using a 4-tiered scoring system. Overexpression of Rsf-1 was defined as a nuclear immunointensity of 3+ to 4+ because of a strong correlation between 3+ and 4+ immunointensity and Rsf-1 gene amplification, based on our previous fluorescence in situ hybridization analysis. Rsf-1 overexpression was observed in 25% of high-grade ovarian serous carcinomas and in only rare cases (<7%) of low-grade ovarian serous, ovarian endometrioid, and invasive breast carcinomas but not in any ovarian serous borderline tumors, ovarian clear cell carcinomas, ovarian mucinous carcinomas, intraductal carcinomas of the breast, and normal ovaries and breast tissues. Thus, overexpression of Rsf-1 was significantly associated with high-grade ovarian serous carcinoma (P < .05), as compared with other types of ovarian tumors and breast carcinomas. Our results provide evidence that Rsf-1 expression is primarily confined to high-grade serous carcinoma, the most aggressive ovarian cancer. Because Rsf-1 overexpression occurs in only a small number of breast carcinomas, it is unlikely that Rsf-1 is a critical gene in the development of breast carcinoma.     

Use of microdose GnRH agonist protocol in women with low ovarian volumes undergoing IVF

Ovarian volume measurements have been recently shown to be predictive of response to ovarian stimulation. Women with small ovarian volumes, i.e. <3 cm(3), have a higher incidence of cycle cancellation, together with a lower peak oestradiol concentration, lower number of retrieved oocytes, and lower pregnancy rates, compared with women with larger ovarian volumes. We prospectively investigated whether a higher dose, microdose flare gonadotrophin-releasing hormone (GnRH) agonist protocol, can improve IVF outcome in women with a small ovarian volume. Only the first IVF cycle was reviewed. In total, 109 women aged <40 years undergoing 109 cycles were prospectively evaluated. Women with an ovarian volume of < or =3 cm(3) noted on the day of luteal GnRH agonist administration had their stimulation regimen changed to a more aggressive microdose flare GnRH agonist protocol. In all, 30 women (27.5%) with an ovarian volume of <3 cm(3), and 79 women (72.5%) with an ovarian volume of >3 cm(3) were compared. Women with an ovarian volume of <3 cm(3) had a significantly higher incidence of unexplained infertility as their presenting aetiology, compared with women with a larger ovarian volume (33 and 8.6%, P = 0.0036). There was a significant negative correlation between age and ovarian volume, and between day 3 FSH concentration and ovarian volume. We also report a significant positive correlation between body mass index and ovarian volume. There was also a significant positive correlation between ovarian volume and the number of oocytes retrieved. Despite a trend towards higher day 3 FSH concentrations, a significantly longer duration of stimulation, higher gonadotrophin requirements, and lower oocyte yield, the implantation and pregnancy rates were comparable between the two groups. Women with a small ovarian volume noted at baseline ultrasound can have comparable implantation and pregnancy rates to those with larger ovarian volumes with the use of a higher dose gonadotrophin, microdose GnRH agonist stimulation.     

A case for combined ovarian and breast cancer prevention

Targeted prevention of ovarian cancer is hindered by the inaccessibility of ovarian tissue, lack of accepted biomarkers and low disease incidence. However, ovarian cancer has common risk factors and shared etiologies with breast cancer. Chemoprevention of ovarian cancer has been demonstrated incidentally during testing of novel breast cancer prevention drugs. Here it is hypothesized that the development of combined ovarian and breast cancer prevention strategies is a preferable strategy for ovarian cancer prevention.     

Cutaneous Mechanical Stimulation Regulates Ovarian Blood Flow via Activation of Spinal and Supraspinal Reflex Pathways in Anesthetized Rats

The reflex effects of noxious mechanical stimulation of a hindpaw or abdominal skin on ovarian blood flow, and the reflex pathways involved in those responses were examined in anesthetized rats. Blood flow in the left ovary was measured using a laser Doppler flowmeter, and the activity of the left ovarian sympathetic nerve and mean arterial pressure (MAP) of the common carotid artery were recorded. Stimulation of the left or right hindpaw for 30 s produced marked increases in ovarian sympathetic nerve activity and MAP. Ovarian blood flow slightly decreased during the stimulation and then slightly increased after the stimulation. After the left ovarian sympathetic nerves were severed, the same stimulus produced a remarkable monophasic increase in ovarian blood flow that was explained by passive vasodilation due to a marked increase in MAP. After spinal transection at the third thoracic (T3) level, the responses of MAP, ovarian sympathetic nerve activity, and ovarian blood flow to hindpaw stimulation were nearly abolished. Stimulation of the abdomen at the right or left side for 30 s produced slight increases in ovarian sympathetic nerve activity and MAP. Ovarian blood flow slightly decreased during the stimulation and then slightly increased after the stimulation. After the ovarian sympathetic nerves were severed, the response of the ovarian blood flow changed to a monophasic increase due to an increase in MAP. After spinal transection, stimulation of the left abdomen produced a moderate increase in MAP, a remarkable increase in ovarian sympathetic nerve activity and a slight decrease in ovarian blood flow during the stimulation. In contrast, stimulation of the right abdomen produced a smaller response in ovarian sympathetic nerve activity during the stimulation while it increased the MAP to a similar degree. Ovarian blood flow slightly increased after the end of stimulation, which was explained as passive vasodilation due to the increase in MAP. In conclusion, stimulation of somatic afferents affects ovarian blood flow by inducing changes in ovarian sympathetic nerve activities and blood pressure. When stimulation was applied to a hindpaw whose segment of afferent input is far from the segment of the ovarian sympathetic nerves, it took a supraspinal reflex pathway. However, when stimulation was applied to the abdomen whose spinal segment of the afferent is close to the segment of the ovarian sympathetic nerve output, there are spinal segmental reflex pathways. The present results demonstrate that spinal reflexes depend on the laterality of the stimulus, while supraspinal reflexes do not depend on the laterality of the stimulus.     

Transvaginal sonographic appearance of functional ovarian cysts

Knowledge of the nature of ovarian lesions is important in order to establish the correct treatment and, especially, to detect ovarian cysts that do not require surgical treatment. With the purpose of demonstrating the utility of transvaginal sonography with colour Doppler of ovarian functional ovarian cysts, 378 ovarian tumours were studied, comparing sonographic diagnosis with pathological findings. Sensitivity and specificity of colour Doppler transvaginal sonography to detect functional ovarian cysts were 84.6 and 99.2% respectively. Positive and negative predictive values were 98 and 93.5% respectively. In our experience, transvaginal sonography with colour Doppler is a useful technique in the diagnosis of ovarian pathology.      

应用荧光原位杂交技术检测卵巢浆液性囊腺癌中ZNF217基因拷贝数

目的探讨锌指蛋白217（zinc finger protein 217，ZNF217）基因在卵巢浆液性囊腺癌中20号染色体基因拷贝数改变情况及其临床意义。方法应用荧光原位杂交技术及LSI ZNF217探针对2种卵巢癌细胞株SKOV3、HO-8910和23例卵巢浆液性囊腺癌、10例浆液性囊腺瘤及7份正常卵巢组织进行检测。结果两种卵巢癌细胞株及12例卵巢癌出现ZNF217基因扩增，浆液性囊腺瘤有1例发生了基因的扩增，其余的及正常卵巢组织未出现基因扩增，卵巢癌与卵巢浆液性囊腺瘤、正常卵巢细胞相比较，ZNF217基因拷贝数改变差异有统计学意义（P〈0．05），而低分化的卵巢癌比高分化发生ZNF217基因扩增的几率明显增高（P〈0．05），Ⅲ～Ⅳ期比Ⅰ期的卵巢癌ZNF217基因拷贝数明显增多（P〈0．05）。结论ZNF217基因很可能是卵巢癌发生的促进因子之一，并与卵巢癌分化及预后不良有关。     

CK7单克隆抗体在鉴别卵巢原发性与胃肠道源性转移癌中的意义

目的研究ＣＫ７单克隆抗体在鉴别卵巢原发性癌和来源于胃肠道的卵巢转移性癌中的意义。方法采用免疫组织化学ＡＢＣ方法对４６例卵巢原发性癌、３４例原发灶在胃的卵巢转移性癌和３０例原发灶在肠的卵巢转移性癌进行了ＣＫ７单克隆抗体表达的检测。结果４６例卵巢原发性癌ＣＫ７均呈阳性表达,而３０例来源于肠的卵巢转移性癌ＣＫ７均为阴性,３４例来源于胃的卵巢转移性癌５０％呈ＣＫ７阳性表达。两组卵巢转移性癌的ＣＫ７阳性率与原发癌相比均有显著性差异（Ｐ＜０００１）。结论ＣＫ７单克隆抗体作为一个原发性卵巢癌的特异性标记,对鉴别卵巢原发性癌和来源于胃肠道的卵巢转移癌有重要意义     

Ovarian stimulation and ovarian tumours: a critical reappraisal

Increased interest has arisen recently about the possible associationbetween ovarian stimulation and ovarian tumours. In this article,the current knowledge on the epidemiology, pathogenesis andaetiology of ovarian tumours is extensively reviewed in relationto the existing literature on the relationship between ovulationinduction and ovarian neoplasia. The available data from epidemiologicalstudies and case reports do not support a direct causa] relationshipbetween ovarian stimulation and ovarian cancer. However, itis possible that ovarian stimulants may have an augmenting rolefor special categories of tumours, e.g. sex-cord stromal tumours.A definite answer to this important issue may be reached throughlarge prospective epidemiological studies or large retrospectivewell-designed case-control studies.     

卵巢上皮癌中细胞外信号调节激酶的表达及其与预后的关系

目的: 探讨磷酸化细胞外调节激酶(p-ERK)在卵巢上皮癌组织中的表达及其与肿瘤患者预后之间的关系。方法: 应用Western印迹方法分别测定正常卵巢组织、良性卵巢组织和卵巢上皮癌组织中p-ERK的含量;收集卵巢上皮癌患者的临床资料;应用Kaplan-Meier法和Cox回归对卵巢上皮癌患者进行生存分析。结果: (1)卵巢上皮癌组织中的p-ERK含量明显高于良性卵巢组织和正常卵巢组织(P<0.01),Ⅲ~Ⅳ期卵巢上皮癌组织中p-ERK含量明显高于I~II期(P<0.01),良性卵巢组织中p-ERK含量与正常卵巢组织相比无显著差异(P>0.05);(2)低分化卵巢上皮癌组织中的p-ERK含量高于中、高分化(P<0.01);(3)在不同病理类型卵巢癌中,与浆液性卵巢上皮癌组织相比,未分化腺癌组织中p-ERK含量与其相仿(P>0.05),而黏液性卵巢上皮癌和卵巢子宫内膜样癌组织中p-ERK含量较低(P<0.05);(4)p-ERK含量与生存时间呈负相关,p-ERK含量高的卵巢上皮癌患者生存时间短;(5)卵巢上皮癌患者的生存时间与p-ERK含量、残余灶、肿瘤分期、肿瘤分级以及化疗的疗程有着密切关系(P<0.05),而与肿瘤的病理类型没有相关性(P>0.05)。结论: p-ERK可能是卵巢上皮癌发病机制一个重要的调节激酶;测定p-ERK水平可能对卵巢上皮癌患者预后有预测价值。     

Role of ovarian artery-to-uterine artery anastomoses in uterine artery embolization: initial anatomic and radiologic studies

Purpose

To explore the anatomic features of normal human ovarian artery-to-uterine artery anastomoses and their impact on uterine artery embolization (UAE).

Methods

Using slice computed tomography (CT) scanning and vascular casting; models of the uterine arterial vascular network were constructed using five sets of uterus, bilateral adnexa and vagina from normal adult females. The anatomy and characteristics of these models were then studied.

Results

Both the casting specimen and the CT-reconstructed model showed the ovarian artery-to-uterine artery anastomoses clearly. Each was composed of the ovarian branch of the uterine artery and the ovarian branch of the ovarian artery. All 10 ovarian artery-to-uterine artery anastomoses were formed by direct connection between the ovarian branch of the uterine artery and the ovarian branch of the ovarian artery.

Conclusions

Thin slice CT scanning combined with vascular casting is a useful method to study the small arterial network. The anastomoses between the ovarian branch of the uterine artery and the ovarian branch of the ovarian artery were formed mainly by direct connection. The implications of the ovarian artery-to-uterine artery anastomoses on UAE are unclear; further function assessments are needed.     

血清中人附睾上皮分泌蛋白4的测定与卵巢上皮性肿瘤患者临床病理特征的关系

为探讨卵巢上皮性肿瘤患者血清人附睾上皮分泌蛋白4（HE4）水平的变化,以及与临床病理特征的关系,采用酶联免疫吸附试验（ELISA）检测21例良性卵巢上皮肿瘤患者、12例交界性卵巢上皮肿瘤患者和49例卵巢癌患者血清HE4水平,并分析其水平与临床病理特征的关系。卵巢癌组血清HE4水平（中位数123.00pmol/L）明显高于交界性卵巢上皮肿瘤组（中位数41.20pmol/L）和良性卵巢上皮肿瘤组（中位数32.80pmol/L）;血清HE4水平与卵巢上皮性癌患者是否绝经、年龄及有无淋巴结转移无关（P〉0.05）,而与患者的临床FIGO分期（Ⅰ＋Ⅱ、Ⅲ＋Ⅳ）、病理组织学类型及有无腹水有关（P〈0.05）,浆液性癌（中位数198.50pmol/L）和子宫内膜样癌患者的血清HE4水平（中位数139.25pmol/L）明显高于黏液性癌患者（中位数30.95pmol/L）（U值分别为17.00和2.00,P〈0.01）。血清HE4水平与卵巢上皮性癌临床病理特征密切相关,并有望成为卵巢上皮性肿瘤恶变的标志物。