DKK3在上皮性卵巢癌中表达的初步探索

目的:探讨DKK3表达与卵巢上皮性癌的关系。方法:采用免疫组化法检测不同卵巢组织DKK3蛋白表达水平,其中88例卵巢上皮性癌组织(以下简称卵巢癌组织)、39例卵巢良性肿瘤组织及46例正常卵巢组织。结果:DKK3在正常卵巢组织、卵巢良性肿瘤及卵巢癌组织的表达有明显差异,差异有统计学意义(P0.05)。而DKK3表达与上皮性卵巢癌的临床病理分期及分化程度无关(P0.05)。结论:DKK3表达水平下降与卵巢癌有关,DKK3可作为预测卵巢癌的指标。     

Ovarian Cancer and Body Size: Individual Participant Meta-Analysis Including 25,157 Women with Ovarian Cancer from 47 Epidemiological Studies

Background

Only about half the studies that have collected information on the relevance of women''s height and body mass index to their risk of developing ovarian cancer have published their results, and findings are inconsistent. Here, we bring together the worldwide evidence, published and unpublished, and describe these relationships.

Methods and Findings

Individual data on 25,157 women with ovarian cancer and 81,311 women without ovarian cancer from 47 epidemiological studies were collected, checked, and analysed centrally. Adjusted relative risks of ovarian cancer were calculated, by height and by body mass index.Ovarian cancer risk increased significantly with height and with body mass index, except in studies using hospital controls. For other study designs, the relative risk of ovarian cancer per 5 cm increase in height was 1.07 (95% confidence interval [CI], 1.05–1.09; p<0.001); this relationship did not vary significantly by women''s age, year of birth, education, age at menarche, parity, menopausal status, smoking, alcohol consumption, having had a hysterectomy, having first degree relatives with ovarian or breast cancer, use of oral contraceptives, or use of menopausal hormone therapy. For body mass index, there was significant heterogeneity (p<0.001) in the findings between ever-users and never-users of menopausal hormone therapy, but not by the 11 other factors listed above. The relative risk for ovarian cancer per 5 kg/m² increase in body mass index was 1.10 (95% CI, 1.07–1.13; p<0.001) in never-users and 0.95 (95% CI, 0.92–0.99; p = 0.02) in ever-users of hormone therapy.

Conclusions

Ovarian cancer is associated with height and, among never-users of hormone therapy, with body mass index. In high-income countries, both height and body mass index have been increasing in birth cohorts now developing the disease. If all other relevant factors had remained constant, then these increases in height and weight would be associated with a 3% increase in ovarian cancer incidence per decade. Please see later in the article for the Editors'' Summary     

Psychophysiological Patterns During Cell Phone Text Messaging: A Preliminary Study

This study investigated the psychohysiological patterns associated with cell phone text messaging (texting). Twelve college students who were very familiar with texting were monitored with surface electromyography (SEMG) from the shoulder (upper trapezius) and thumb (abductor pollicis brevis/opponens pollicis); blood volume pulse (BVP) from the middle finger, temperature from the index finger, and skin conductance (SC) from the palm of the non-texting hand; and respiration from the thorax and abdomen. The counter-balanced procedure consisted of a 2 min pre-baseline, 1 min receiving text messages, 2 min middle baseline, 1 min sending text messages and 2 min post-baseline. The results indicated that all subjects showed significant increases in respiration rate, heart rate, SC, and shoulder and thumb SEMG as compared to baseline measures. Eighty-three percentage of the participants reported hand and neck pain during texting, and held their breath and experienced arousal when receiving text messages. Subjectively, most subjects were unaware of their physiological changes. The study suggests that frequent triggering of these physiological patterns (freezing for stability and shallow breathing) may increase muscle discomfort symptoms. Thus, participants should be trained to inhibit these responses to prevent illness and discomfort.     

Development and Preliminary Evaluation of a Multivariate Index Assay for Ovarian Cancer

Background

Most women with a clinical presentation consistent with ovarian cancer have benign conditions. Therefore methods to distinguish women with ovarian cancer from those with benign conditions would be beneficial. We describe the development and preliminary evaluation of a serum-based multivariate assay for ovarian cancer. This hypothesis-driven study examined whether an informative pattern could be detected in stage I disease that persists through later stages.

Methodology/Principal Findings

Sera, collected under uniform protocols from multiple institutions, representing 176 cases and 187 controls from women presenting for surgery were examined using high-throughput, multiplexed immunoassays. All stages and common subtypes of epithelial ovarian cancer, and the most common benign ovarian conditions were represented. A panel of 104 antigens, 44 autoimmune and 56 infectious disease markers were assayed and informative combinations identified. Using a training set of 91 stage I data sets, representing 61 individual samples, and an equivalent number of controls, an 11-analyte profile, composed of CA-125, CA 19-9, EGF-R, C-reactive protein, myoglobin, apolipoprotein A1, apolipoprotein CIII, MIP-1α, IL-6, IL-18 and tenascin C was identified and appears informative for all stages and common subtypes of ovarian cancer. Using a testing set of 245 samples, approximately twice the size of the model building set, the classifier had 91.3% sensitivity and 88.5% specificity. While these preliminary results are promising, further refinement and extensive validation of the classifier in a clinical trial is necessary to determine if the test has clinical value.

Conclusions/Significance

We describe a blood-based assay using 11 analytes that can distinguish women with ovarian cancer from those with benign conditions. Preliminary evaluation of the classifier suggests it has the potential to offer approximately 90% sensitivity and 90% specificity. While promising, the performance needs to be assessed in a blinded clinical validation study.     

Ovarian Function,Not Age,Predicts the Benefit from Ovarian Suppression or Ablation for Premenopausal Women with Breast Cancer

The role of adjuvant ovarian suppression or ablation (OS/OA) in premenopausal women with hormone receptor-positive breast cancer remains controversial. The purpose of our study was to examine which patients might benefit from the addition of OS/OA to tamoxifen. We analyzed the data of 2065 premenopausal patients with hormone receptor-positive invasive ductal carcinomas who were treated at Sun Yat-Sen University Cancer Center from 2000 to 2008. The five-year disease-free survival rate (DFSR) and overall survival rate (OSR) were compared by menstrual status and treatment. Compared with patients older than forty years of age, patients younger than forty years old had significant lower DFSRs and OSRs. The addition of OS/OA to tamoxifen increased the DFSR and OSR of patients with normal menstrual cycles after chemotherapy, regardless of their age at diagnosis. Patients with normal menstrual cycles after chemotherapy are the main beneficiaries of an adjuvant OS/OA.     

Antibody-Targeted Liposomes to Deliver Doxorubicin to Ovarian Cancer Cells

Abstract

Ovarian cancer is the leading cause of death in women with a gynecologic malignancy. The main reason for the high mortality is the late occurrence of symptoms, resulting in an advanced diseased state at the time of diagnosis. Since ovarian cancer remains confined to the peritoneal cavity virtually throughout its entire clinical course, this type of cancer is an attractive candidate for intraperitoneal chemotherapy. Local instillation of anticancer agents has been used with some success, although systemic absorption of drug, as well as local drug effects, can produce substantial toxicity. This contribution deals with the use of antibody-targeted liposomes (immunoliposomes) for the delivery of doxorubicin to ovarian cancer cells. After a brief discussion of pharmaceutical aspects of the preparation, characterization and stability of OV-17L3 immunoliposomes (anti-ovarian carcinoma Fab' liposomes), me in vitro and in vivo interaction between these specific immunoliposomes and ovarian carcinoma cells are described. A rapid, highly efficient and long-lasting adherence of i.p. administered specific immunoliposomes to i.p. located target cells was observed in a xenograft model of i.p. growing human ovarian carcinoma. However, our preliminary findings on the antitumor activity of doxorubicin-containing immunoliposomes in this xenograft model do not show a therapeutic advantage of specific immunoliposomes over nonspecific liposomes containing doxorubicin. The last part of the article is devoted to an evaluation of the results and discusses potential research directions in the near future.     

An Outlook on Ovarian Cancer and Borderline Ovarian Tumors: Focus on Genomic and Proteomic Findings

Among the gynaecological malignancies, ovarian cancer is one of the neoplastic forms with the poorest prognosis and with the bad overall and disease-free survival rates than other gynaecological cancers. Ovarian tumors can be classified on the basis of the cells of origin in epithelial, stromal and germ cell tumors. Epithelial ovarian tumors display great histological heterogeneity and can be further subdivided into benign, intermediate or borderline, and invasive tumors. Several studies on ovarian tumors, have focused on the identification of both diagnostic and prognostic markers for applications in clinical practice. High-throughput technologies have accelerated the process of biomolecular study and genomic discovery; unfortunately, validity of these should be still demonstrated by extensive researches on sensibility and sensitivity of ovarian cancer novel biomarkers, determining whether gene profiling and proteomics could help differentiate between patients with metastatic ovarian cancer and primary ovarian carcinomas, and their potential impact on management. Therefore, considerable interest lies in identifying molecular and protein biomarkers and indicators to guide treatment decisions and clinical follow up. In this review, the current state of knowledge about the genoproteomic and potential clinical value of gene expression profiling in ovarian cancer and ovarian borderline tumors is discussed, focusing on three main areas: distinguishing normal ovarian tissue from ovarian cancers and borderline tumors, identifying different genotypes of ovarian tissue and identifying proteins linked to cancer or tumor development. By these targets, authors focus on the use of novel molecules, developed on the proteomics and genomics researches, as potential protein biomarkers in the management of ovarian cancer or borderline tumor, overlooking on current state of the art and on future perspectives of researches.Key Words: Ovarian cancer, borderline ovarian tumors, markers, genomics, proteomics, oncogenes.     

Modeling Resistance to Pathway-Targeted Therapy in Ovarian Cancer

A detailed understanding of the biochemical pathways that are responsible for cancer initiation and maintenance is critical to designing targeted cancer therapy. Although we have accumulated knowledge about individual molecular changes that underlie cancer development, we are still learning how multiple biochemical pathways cooperate in cancer. This cooperation and cross-talk between redundant biochemical pathways appear to be the main reasons for the failure of therapeutic agents that are designed to interfere with a specific molecular target. In order to simulate the cooperation of several biochemical pathways in cancer development, we have engineered mouse ovarian cancer cell lines and tumors with different combinations of defined genetic alterations. We have used this system to determine the functional contributions of individual pathways that are necessary for cell proliferation and tumor maintenance, as well as to test the molecular mechanisms of tumor resistance to pathway-targeted therapy.     

Insecurities of Women Regarding Breast Cancer Research: A Qualitative Study

Objectives

Only 1.2%–11% of all potential study participants participate in cancer studies. Low participation rates can result in bias or in a failure to obtain data saturation. Subject-scientific psychology assumes that reasons for acting are based on individual premises. The objective of this study was to render reproducible individual reasons of female breast cancer patients to participate or not participate in breast cancer studies using a qualitative approach.

Methods

Problem-based interviews were conducted with female breast cancer patients. The selection of interview partners continued until theoretical data saturation was achieved.

Results

As main arguments against participation emotional overload and too many medication side-effects were stated. Improvement of health-related values, long-term protection and comprehensive follow-up exams were stated as arguments for participation. Trust in the attending physician was mentioned as influencing both participation and non-participation.

Conclusions

A significant influential factor determining willingness to participate in studies was one''s contentment with patient-physician communication. In order to guarantee an adequate patient decision-making process, keeping existing standards for patient briefings is absolutely mandatory.     

VEGF靶向分子探针的制备及对卵巢癌细胞SKOV3体外成像的初步研究

目的:制备分子探针VEGF-USPIO和研究其在体外对卵巢癌细胞的靶向成像作用。方法:采用化学偶联法将VEGF抗体与USPIO连接,构建成具有免疫活性的靶向分子探针VEGF-USPIO。用CCK-8法检测该探针对卵巢癌细胞株SKOV3细胞活性的影响;普鲁士蓝染色法检测细胞磁性标记情况,并对经过标记的细胞进行体外磁共振成像,观察其对磁共振信号强度的影响。结果:成功合成了分子靶向探针VEGF-USPIO;当探针浓度在60μg/mL及以下时对细胞活性无影响(P0.05);细胞普鲁士蓝染色结果显示标记了靶向探针VEGF-USPIO的细胞其胞膜及胞浆含铁颗粒沉积较多;细胞体外磁共振成像结果显示经靶向探针标记的细胞,T2WI信号强度较未标记探针的对照组细胞降低(P0.05)。结论:所合成的VEGF-USPIO通过磁共振信号强度的变化实现MRI成像。     

A Study of Cervical Cancer In Ethiopian Women

In common with many African countries, Ethiopia has a very limited cytological service, smears are only taken in a hospital or clinic setting and until very recently most had to be sent abroad for analysis. We describe the results of a clinical and cytological investigation of 2111 women attending hospitals and clinics in Addis Ababa: 33 invasive or microinvasive cancers and 10 dysplasias (CIN) were detected. The prevalence of invasive cervical cancer in that population was 15.6/1000. Risk factors were shown to be age over 35 (especially over 50), parity over six (especially more than 10), very low income or subsistence economy, particularly in those from the rural areas, and prostitution. Less significant factors, possibly related to age, were sexual activity of more than 20 years and first coitus before the age of 15; and more than five sexual partners. Most (66%) of women with invasive cancer were at stage 3 or 4.     

Psychophysiological Assessment of Compulsive Gamblers' Arousal to Gambling Cues: A Pilot Study

Psychophysiological assessments measuring heart rate, systolic and diastolic blood pressure, and skin resistance level were conducted on 7 male compulsive gamblers and on 7 age and gender matched controls while both groups performed mental arithmetic and listened to individualized tapes of the gamblers' preferred form of gambling and an individualized fear tape. Heart rate responses of the gamblers to the 2 gambling audiotapes were significantly greater than those found for the controls whereas the groups did not differ on mental arithmetic or the fear provoking scene, confirming some degree of cue-specific arousal in gamblers. The other physical responses did not yield such strong results. If physiological arousal provides the motivational basis for gambling and is maintained on an intermittent schedule of reinforcement, the findings may have implications for the treatment of compulsive gambling.     

卵巢癌患者血清的拉曼光谱研究初探

目的:探究拉曼光谱技术应用于卵巢癌研究的可能性。方法:收集卵巢癌患者血清及健康人血清各20例,用激光共聚焦显微拉曼光谱仪进行检测。结果:两组血清的平均拉曼光谱形态和谱峰基本相似,但在约1010、1158、1283、1520、1646、2307和2661cm-17个拉曼频移附近,卵巢癌患者血清的拉曼光谱谱峰强度明显低于健康对照组,而在其余大部分波段,卵巢癌患者血清的拉曼光谱强度均高于健康对照组。结论:拉曼光谱技术可以初步区分卵巢癌及健康人血清,值得进一步研究和探讨其临床应用价值。     

上海市区女性肺癌的家族聚集性研究

我们利用在上海市区所开展的一项关于女性肺癌的较大规模人群基础上的病例对照研究资料,分析和评价了一级亲属患肺癌史者其在肺癌发生中的作用。文中重点分析了女性非吸烟者肺癌的材料。结果表明,先证者家系一级亲属患肺癌的风险性是对照组家系一级亲属的近3倍(OR=2.80,95% CI1.68-4.67)。对非吸烟先证者家系而言,比数比为2.62(95%CI1.52-4.5 2)。其中,腺癌、鳞癌、其他类和不明分类的肺癌的OR分别为2.79(95%CI 1.53-5.10)、3.88 (95%CI1.42-10.63)、1.26(95%CI0.27-6.01)、2.52 (95%CI1.16-5.49)。按年龄组分层分析的结果显示,35-59岁组与60-69岁组的比数比分别为4.01 (95%CI1.71-8.97)、 1.89(95%CI0.89-3.98)。非吸烟女性研究对象经多因素非条件logistic回归模型的分析后,比数比OR为2.71(95%CI1.54-4.76),有高度统计学意义。在该多变量回归模型的基础上估计的调整人群归因风险度为5.31%。 Abstract:The data set of a large population-based case-control study of female lung cancer conducted in Shanghai urban was used to investigate the contribution of lung cancer in first-degree relatives to lung cancer risk.The analysis in the paper is emphasized on non-smoking women.The results indicates that the risk of first-degree relatives with lung cancer is increased about 30fold(OR=2.80,95% CI:1.68-4.67),and for non-smoking probands the OR is 2.62(95% CI:1.52-4.52).The odds ratios of adeno-carcinoma,squamous cell carcinoma,others unknown of lung cancer are 2.79(95% CI:1.53-5.10),3.88(95% CI:1.42-10.63),1.26(95% CI:0.27-6.01),2.52(95% CI:1.16-5.49),respectively.For cases of age groups of 35 to 59 and 60 to 69 years of probands,with ORs of 4.01(95% CI:1.79-8.97)and 1.89(95% CI:0.89-3.98)respectively.The odds ratio from multivariable unconditional logistic regression is 2.71(95% CI:1.54-4.76).The estimation of adjusted population attributable risk is 5.31% based on the multivariable logistic regression model analysis.     

与卵巢癌转移有关的microRNA研究进展

卵巢癌是女性生殖系统三大恶性肿瘤之一,其致死率居于各类妇科肿瘤之首,是严重影响妇女生命的重要疾患,卵巢癌的转移则是造成病人死亡的重要因素。近年来随着microRNA（又称miRNA或微RNA）作为一种小分子非编码RNA被发现,证实miRNA的作用与各类肿瘤有着重要的联系,这些肿瘤包括乳腺癌、食管癌、胰癌、口腔癌等。近几年的研究表明,miRNA可以影响卵巢癌的发生与发展,并与其转移也存在着紧密的关系。与卵巢癌转移有关的miRNA作用机制的揭示,将会为转移性卵巢癌的诊断及治疗提供新的途径。本综述在通过检索近年来最新文献的基础上,对于卵巢癌的转移机理进行了详尽的分析,并对miRNA在卵巢癌转移中的重要研究予以了详细的阐述。     

与卵巢癌转移有关的microRNA 研究进展

卵巢癌是女性生殖系统三大恶性肿瘤之一,其致死率居于各类妇科肿瘤之首,是严重影响妇女生命的重要疾患,卵巢癌的转移则是造成病人死亡的重要因素.近年来随着microRNA(又称miRNA或微RNA)作为一种小分子非编码RNA被发现,证实miRNA的作用与各类肿瘤有着重要的联系,这些肿瘤包括乳腺癌、食管癌、胰癌、口腔癌等.近几年的研究表明,miRNA可以影响卵巢癌的发生与发展,并与其转移也存在着紧密的关系.与卵巢癌转移有关的miRNA作用机制的揭示,将会为转移性卵巢癌的诊断及治疗提供新的途径.本综述在通过检索近年来最新文献的基础上,对于卵巢癌的转移机理进行了详尽的分析,并对miRNA在卵巢癌转移中的重要研究予以了详细的阐述.     

MRI对卵巢成熟畸胎瘤术前诊断初步探讨

目的:探讨MRI对卵巢成熟畸胎瘤术前诊断价值及手术方式选择的指导意义.方法:回顾性分析经妇科手术治疗、病理诊断为卵巢成熟畸胎瘤58例,术前均行MRI扫描.采用自旋回波(SE)序列、快速自旋回波(FSE)序列、压脂序列、DWI序列扫描.常规行矢状面、横断面及冠状面扫描.结果:(1)病变位于右侧卵巢30例,左侧卵巢28例,双侧卵巢3例.(2)病变大小为1.2-16.7cm,边缘较清晰,形态多为类圆形.(3)病变为囊性或囊实性.其内成分多样,MRI信号显示混杂,脂肪成分MRI上T1W、T2W为双高信号,脂肪抑制序列为低信号;牙齿、毛发、软骨、纤维成分T1W、T2W为双低信号;肌肉、神经成分T1W、T2W为等信号.(4)病变小于10 cm,其内脂肪成分较多,无腹腔镜手术禁忌症患者行腹腔镜卵巢畸胎瘤切除术;病变大于10 cm,钙化、毛发等实性成分较少时,能耐受膀胱截石位,行阴式卵巢畸胎瘤切除术;病变大于15 cm,或病变较小但以钙化、牙齿、毛发等实行性成分为主,怀疑恶性卵巢畸胎瘤或者不能判断病变性质时行传统方式开腹卵巢畸胎瘤切除术.结论:MRI能较好显示卵巢畸胎瘤内部结构及成分,在临床手术术式选择方面具有指导意义.