黏附分子与卵巢肿瘤侵袭及转移之间的相关性研究

细胞黏附分子是一种参与细胞-细胞、细胞-细胞外基质间相互作用的跨膜蛋白，具有多种生物功能，它们通常以配体和受体相结合的方式来发挥作用。近几年研究发现：细胞黏附分子在具有广泛种植性转移等特点的卵巢肿瘤的侵袭及转移等过程中具有重要的作用，本文主要从各种黏附分子在卵巢癌侵袭转移过程中表达的差异以及其在卵巢癌恶变中的作用进行综述。     

p27kip1蛋白在心血管疾病中的作用研究进展

p27蛋白广泛抑制各种Cyclin和细胞周期蛋白依赖激酶（CDK）的活性,具有参与细胞周期调控、诱导凋亡、促进细胞分化等多种生物学功能。心血管疾病中大多以细胞增殖为基础,尤其是心室肥厚为其形态学表现。研究发现p27与这些疾病的发生、发展密切相关。因此,进一步研究阐明p27蛋白的作用机制,有望找到治疗某些心血管疾病的新靶点。     

肾细胞癌组织中CDK4、CyclinD1的表达及其意义

目的 探讨肾细胞癌组织中CDK4、CyclinD1的表达水平及意义。方法 应用实时荧光定量PCR法检测30例人肾细胞癌组织及癌旁肾组织中CDK4、CyclinD1的表达水平。结果 CDK4和CyclinD1在肾癌细胞中的表达水平均明显高于癌旁肾组织，但CyclinD1的表达升高水平和比例高于CDK4表达的升高。CyclinD1／CDK4的比值，在肾癌组织中高于癌旁肾组织。结论 CDK4和CyelinD1的过度表达可能引起细胞异常增殖、分化失控。CDK4和CyclinD1基因在肾细胞的发生、发展中可能起重要作用。     

2 Gy X射线对EL-4细胞p16、CyclinD、CDK4基因转录和蛋白表达影响

目的研究电离辐射对EL-4细胞p16、CyclinD、CDK4基因转录及蛋白表达的影响.探讨p16/CyclinD/CDK4负向调控通路在辐射诱导G1期阻滞中的作用.方法采用半定量RT-PCR方法检测2 GyX射线照射后EL-4细胞p16 mRNA水平变化,采用Northern blot方法检测CyclinD、CDK4基因转录变化,应用免疫细胞化学方法(ICC)检测3种蛋白表达的变化.结果2 Gy X射线照射后2～48 h EL-4细胞p16 mRNA水平增高,48 h恢复至正常水平.p16蛋白表达照射后2h开始增高,12h达到峰值(P＜0.01),72 h恢复至正常水平.EL-4细胞周期蛋白CyclinD mRNA水平于照射后1 h开始明显降低,照射后8 h降至最低值.CyclinD蛋白表达于照射后8 h开始明显减少,持续至照射后48 h(P＜0.05～P＜0.01).EL-4细胞CDK4 mRNA水平于照射后1h明显降低,照射后4 h～12 h保持较低水平,72 h恢复至正常水平.CDK4蛋白表达于照射后4 h明显下降,12 h降至最低,72 h仍低于正常水平(P＜0.01).结论2 Gy X射线照射可诱导EL-4细胞p16表达增高,CyclinD和CDK4表达降低.提示p16/CyclinD/CDK4负向调控通路可能在电离辐射诱导EL-4细胞G1期阻滞中发挥重要作用.     

18F-FDG PET显像在监测卵巢癌复发和转移中的作用

目的　探讨PET显像在监测卵巢癌复发和转移中的作用。方法　 38例卵巢癌术后患者 ,共行 5 5次1 8F 脱氧葡萄糖 (FDG)PET检查。图像分析采用视觉和半定量 [标准摄取值 (SUV)和病灶总葡萄糖酵解量 (TLG) ]方法 ,并与近期血CA12 5值、CT和MRI等比较。结果　①PET显像监测卵巢癌复发和转移的灵敏度、特异性和准确性分别为 92 .0 %、10 0 .0 %和 94 .7%。② 37例次患者有近期CT和 (或 )MRI对照 ,其中 5 9.5 % (2 2例次 )PET显像发现了前者未发现的新病灶。③ 2 1例患者血CA12 5值高于正常 ,但临床未能准确定位病灶 ,PET显像发现了病灶。PET检查还检测出 2例血CA12 5值正常的病灶。卵巢浆液性乳头状癌患者TLG与血CA12 5值呈正相关 (P <0 .0 0 1)。结论　FDGPET显像可早于其他影像学检查发现卵巢癌的转移和复发 ,卵巢浆液性乳头状癌PET显像TLG与血CA12 5值呈正相关。     

恶性肿瘤中Yes相关蛋白与p73作用关联的研究进展

Yes相关蛋白(Yes associated protein,YAP)是Hippo信号通路最主要的调控因子,具有促进细胞增殖、抑制细胞凋亡的作用。在人类乳腺癌、肺癌、结直肠癌、胃癌、卵巢癌等多种肿瘤中YAP表达明显上调。而在另一方面,当DNA损伤时,作为转录辅助激活因子的YAP增强p73相关凋亡基因的转录,具有促进凋亡作用。在细胞内环境的维持与调控过程中,YAP所发挥的作用截然不同。本文主要介绍Hippo信号通路、YAP、p73在恶性肿瘤中的作用,以及YAP与p73在肿瘤细胞中的具体调控机制和作用。     

卵巢癌循环肿瘤细胞的生物学特性及其临床应用进展

卵巢癌病死率在妇科生殖系统恶性肿瘤中位居第一位, 卵巢癌早期无特异性症状, 就诊时多数已为晚期, 卵巢癌患者高病死率的主要原因是复发和转移。外周血循环肿瘤细胞在肿瘤的复发和转移过程中起重要作用。近年来, 循环肿瘤细胞已广泛应用于多种恶性肿瘤的诊断和预后评估。笔者就卵巢癌患者外周血循环肿瘤细胞的生物学特性和应用进展作一综述。     

PET/CT新型分子显像剂在肿瘤个体化药物治疗中的应用

分子成像等多学科的发展以及肿瘤细胞增殖过程中许多新的分子靶点和基因表达的发现为肿瘤个体化药物治疗奠定了基础。PET/CT作为目前最成熟的分子成像检查设备,实现了功能与形态影像的有机融合,近年来,多种新型分子显像剂的出现,推动了PET/CT在临床肿瘤个体化治疗中的应用。就新型分子显像剂在肿瘤个体化药物治疗中的应用现状做一综述。     

PET/CT新型分子显像剂在肿瘤个体化药物治疗中的应用

分子成像等多学科的发展以及肿瘤细胞增殖过程中许多新的分子靶点和基因表达的发现为肿瘤个体化药物治疗奠定了基础。PET/CT作为目前最成熟的分子成像检查设备,实现了功能与形态影像的有机融合,近年来,多种新型分子显像剂的出现,推动了PET/CT在临床肿瘤个体化治疗中的应用。就新型分子显像剂在肿瘤个体化药物治疗中的应用现状做一综述。     

顺铂在卵巢癌治疗中的应用

卵巢癌的发病率在女性生殖器恶性肿瘤中占第三位,但其死亡率却居首位。20世纪70年代以来,顺铂（cisplatin）以及它的同类物卡铂（carboplatin）和草酸铂（oxaliplatin）已被临床广泛用于治疗多种恶性肿瘤。由于顺铂是一种以浓度决定疗效的抗肿瘤药物,短时间内每次给药浓度越高,疗效越好。但顺铂本身所具有的耳毒性、肾毒性、神经毒性、消化道反应则限制其大剂量使用,影响其疗效。另外,肿瘤细胞的耐药性也给顺铂的应用带来阻碍。现将目前顺铂在卵巢癌治疗中的应用情况作一综述。     

Cancer surveillance based on imaging techniques in carriers of BRCA1/2 gene mutations: a systematic review

We have systematically reviewed the literature focusing on the performance of surveillance programmes and imaging techniques for the early diagnosis of breast and ovarian cancer in women carrying mutations in BRCA1/2 genes. A search for relevant articles published between 1996 and 2005 (inclusive) was run on Medline, Embase and other databases. Of the 749 articles retrieved, only 13 met the inclusion criteria. Of these, 12 provided information on breast cancer surveillance, 1 on ovarian cancer surveillance and a further study addressed both cancer types. A critical appraisal of the studies was performed using a tool for the quality assessment of diagnostic accuracy studies (QUADAS). The synthesis of results is qualitative. All studies on imaging techniques for the diagnosis of breast cancer indicated that screening MRI had the highest sensitivity (between 77% and 100%). Breast cancer surveillance programmes, including MRI, achieved the highest diagnostic performance (between 83% and 95%) for all women. However, it must be taken into account that biases that may affect the validity of the outcomes were seen in the evaluated studies. Also, MRI is an expensive test with a low positive predictive value and, to date, MRI screening has not been proven to reduce mortality rates in women carrying BRCA1/2 gene mutations. As a result of the scant information and low quality of the papers reviewed, no definitive conclusion could be drawn on the performance of ovarian cancer surveillance in women carrying BRCA1/2 mutations.     

卵巢恶性肿瘤的MRI诊断与误诊原因分析

目的:通过分析卵巢恶性肿瘤的MRI征象,提高对卵巢恶性肿瘤的诊断水平。方法:搜集经手术病理证实的20例卵巢恶性肿瘤病例,其中卵巢上皮癌12例、卵巢恶性生殖细胞肿瘤2例、小细胞癌3例、淋巴瘤1例、转移瘤2例。所有病例均行MRI平扫及增强,回顾性分析其MRI征象。结果:卵巢恶性肿瘤MRI表现为肿块体积较大、形态不规则,与周围组织结构分界不清;肿块质地不均,其中囊性肿块4例,实性肿块4例,囊实性肿块12例,囊壁、壁结节和实性部分增强扫描均有明显强化。结论:不同病理类型卵巢恶性肿瘤的MRI表现有相似之处,分析其相关征象对卵巢恶性肿瘤的定性诊断具有重要意义。     

Clinical value of positron emission tomography with FDG for recurrent ovarian cancer

OBJECTIVE: Recurrence is often a major problem for patients who have undergone surgery for ovarian cancer. This prospective study was undertaken to evaluate the clinical contribution of positron emission tomography (PET) using (18)F-fluorodeoxyglucose (FDG) for recurrent ovarian cancer. SUBJECTS AND METHODS: Twenty-four women who had undergone surgery or chemoradiotherapy for histopathologically proven ovarian cancer were enrolled in this study. Ovarian cancer was thought to have recurred in 12 of these women because of evidence on conventional imaging modalities or tumor marker measurements (group A). Clinical findings for the remaining 12 women showed them to be disease-free (group B). PET findings for the women were compared with the final diagnoses obtained by histopathology or by clinical follow-up. The clinical contribution of PET was assessed by evaluating whether PET yielded information complementing the findings of conventional modalities and by examining its impact on treatment. RESULTS: PET gave valuable information for seven of 12 patients in group A in addition to the information obtained from findings on conventional imaging, and treatment was affected in five patients. On the other hand, in group B, additional information was obtained in only three of 12 patients, and treatment of only one patient was affected. Overall sensitivity, specificity, and accuracy of conventional imaging modalities were 72.7%, 75.0%, and 73.3%, respectively, and these rates improved to 92.3%, 100.0%, and 94.4%, respectively, by considering both conventional imaging modalities and PET findings. CONCLUSION:Our preliminary data suggest that whole-body PET with FDG can be a complementary modality for following up patients who have had ovarian cancer, especially patients believed to be at risk for recurrence.     

Circulating tumor markers and nuclear medicine imaging modalities: breast, prostate and ovarian cancer.

Clinical oncologists have always shown great interest in circulating tumor markers. There are several markers that in the clinical routine are a signal of particular tumor types; some of them are strictly tissue-specific such as prostatic specific antigen (PSA) for prostatic cancer, AFP and HCG for germ cell tumors of the testis and ovary, others such as CA 15.3, CA125, CEA or cytokeratins are less specific since their elevations can be found in different varieties of cancers even if they are preferentially associated to a certain tumor type, thus are considered markers for breast, ovarian cancer and colon adenocarcinoma. The most useful clinical applications of these parameters is their determination during the follow-up of the treated patients, in order to detect the tumor recurrence early, and also to evaluate the evolution of the disease by monitoring the treatment responses. During follow-up, increasing levels of tumor markers can be observed even several months before the clinical demonstration of cancer recurrence. The association of tumor marker tests with imaging modalities can lead to several advantages: the first is to confirm the diagnosis of relapses, possibly before the appearence of the related clinical symptoms due to tumor growth; the second is to localize the sites of lesions, while tumor markers provide only a general indication of the existence of metastases; the third is to make possible a correct whole body restaging. In the assessment of cancer response tumor markers are often very reliable and their changes are faster than the morphological ones. Among all the imaging modalities, nuclear medicine plays an important role in detecting recurrences and metastatic localizations as it is able to investigate functional rather than morphological aspects of tumors, and provide different information in comparison to morphologic imaging. In addition, the scintigraphic techniques offer the possibility to evaluate treatment responses, confirming or not the information from biochemical changes. This review aims to show some examples (breast, prostate and ovarian cancer) in which the combination of nuclear medicine imaging modalities and tumor marker tests is proposed for clinical practice. The advantages and some critical aspects are discussed on the basis of the clinical findings and the most important clinical indications are described.     

复发性卵巢癌血清差异表达蛋白分析

目的探讨血清差异表达蛋白对提高复发性卵巢癌的诊断意义。方法采用弱阳离子（WCX）磁珠纯化试剂盒和基质辅助激光解吸电离飞行时间质谱（MALDI-TOF-MS）技术,对21例复发性卵巢癌和18例完全临床缓解期卵巢癌患者（对照组）的血清标本进行检测,筛选出复发性卵巢癌患者与对照组血清中的差异表达质谱峰,并建立诊断模型。结果在Mr1000～12000区段,发现复发性卵巢癌与对照组间差异表达蛋白峰10个（P〈0.05）。其中Mr1944、1980、2080、2661、2993、4450、4659、5359的蛋白峰显著上调,Mr1897、7868则显著下调。结论 MALDI-TOF-MS结合磁珠技术能直接检测出复发性卵巢癌患者血清差异表达蛋白,对提高复发性卵巢癌诊断的敏感性和特异性具有一定的临床意义。     

Comparison of animal models for the evaluation of radiolabeled androgens

Biodistribution of two 18F-labeled androgens and an 124I/125I-labeled androgen were studied in five androgen receptor (prostate) animal models with or lacking sex hormone binding globulin (SHBG). As models for androgen-receptor positive ovarian cancer, xenografts of three human ovarian cancer cell lines were tested in SCID mice. SHBG in the prostate model systems significantly affects the metabolism, clearance, and distribution of the radiolabeled androgens in several tissues, but ovarian cancer animal models were disappointing.     

CT diagnosis of intrasplenic metastasis from ovarian carcinoma

Intrasplenic metastases from ovarian carcinoma cannot be always demonstrated intraoperatively. CT is the most important imaging modality of choice for staging and follow-up ovarian cancer; in this study we searched CT appearances of intrasplenic metastases from ovarian carcinoma. We retrospectively reviewed imaging histories of the patients with ovarian cancer from the radiology information system, and found 12 patients with intrasplenic metastasis. All patients underwent abdominal CT with 16-MDCT. We searched number, density and maximum diameters of splenic metastasis. The growing rate of three lesions, which were followed up by CT, was calculated. Serum cancer antigen (CA) 125 levels were noted. We also evaluated clinical history and pathology reports of all patients. Splenic metastases, solitary or multiple, were detected most frequently during the follow-up (1-14 years after initial diagnosis) and most were associated with other sites of recurrence. The diameters of lesions ranged from 4 to 85mm. All lesions appeared hypodense except for one lesion with dense calcification. Densities of lesions ranged from 12 to 208 Hounsfield units (mean, 49±51HU). Most lesions appeared as solid well-defined nodules; however some lesions had lobulated and irregular contours with an infiltrative pattern. The growing rates of three lesions were 0.72mm/month, 1.75mm/month and 2.70mm/month. Eight patients had elevated serum CA 125 levels (40-1256U/mL). We concluded that CT can demonstrate intraparenchymal and infiltrative splenic metastasis in patients with ovarian cancer even in the absence of increased CA 125 levels.     

泰素联合顺铂治疗老年期卵巢癌16例

目的　老年期卵巢癌的发生率和死亡率均较高 ,探讨其有效的化疗方法 ,以提高患者生存时间和生活质量。方法　 41例卵巢癌患者随机分为泰素加顺铂治疗组和C(H ,F)AP对照组进行临床观察。结果　治疗组有效率为 6 9% ,副反应较轻 ,疗程明显缩短 ;对照组有效率为 32 % ,副反应较重 ,疗程长 ,且易发生药物蓄积中毒 ,二者有效率比较有显著性差异。结论　泰素加顺铂治疗老年期卵巢癌 ,具有疗效好、副反应轻、疗程大大缩短等优点。     

Cerebral metastasis and other cerebral events in women with ovarian cancer

AIM: To determine the incidence, imaging findings and prognostic significance of cerebral metastases and other cerebral events in women with ovarian cancer. METHOD: A 5-year retrospective review of all women with ovarian cancer who had cranial imaging was undertaken at two major gynaecological oncology centers. RESULTS: Of 1222 women under clinical review, 78 underwent cranial imaging and 13 (1.1%) had cerebral metastasis. Computed tomography (CT) was diagnostic of parenchymal disease in 12 and magnetic resonance imaging (MRI) showed leptomeningeal disease in two. The women were aged between 23 and 73 years and all had stage III or IV disease at presentation. Cerebral metastasis occurred at 6-60 months from initial diagnosis, with death occurring predominantly within 12 months, but with five survivors at 4-45 months. Of the remaining 65 women, 10 had cerebrovascular disease and three had unrelated lesions. CONCLUSION: Cerebral metastasis remains a rare event in women with ovarian cancer but may be an isolated late event associated with survival beyond a year after neurosurgery and chemotherapy. CT should be the first investigation as the incidence of cerebrovascular disease is similar to that of metastatic disease.