宫颈癌CD44v6和MMP-9的表达及其临床意义

目的:探讨宫颈癌组织中CD44v6和MMP9蛋白的表达及临床意义。方法:采用免疫组化SP法分析65例Ⅰ、Ⅱ期术后宫颈癌组织中CD44v6和MMP9蛋白的表达情况。结果:CD44v6和MMP9在伴有淋巴结转移宫颈癌中的阳性表达率为84.6%和92.3%,无淋巴结转移为67.3%和69.2%,两组间差异有显著意义,P<0.05;CD44v6和MMP9表达与病理类型和临床分期无明显相关。结论:检测宫颈癌转移相关基因表达并分析其表达的相互关系有助于判断宫颈癌的转移潜能及指导术后干预治疗。     

Hedgehog及Wnt信号通路交互作用与宫颈癌发生的关系

目的探讨宫颈癌发生的可能机制。方法对2例宫颈癌、2例癌旁组织及1例正常宫颈组织进行人全基因组芯片检测,使用RT-PCR方法验证芯片结果,并分析其中主要的信号传导通路及关键基因、转录因子。结果通过对芯片差异基因筛选及信号通路分析,发现FORKHEAD转录因子家族为差异基因重要调控因子。癌旁组织与正常组织比较中Hedgehog信号通路激活（=0.018,包含7个差异基因）;癌组织和正常组织比较Wnt信号通路出现激活（=0.032,包含7个差异基因）。宫颈癌患者Hedgehog通路中Gli-1表达下调;Wnt信号通路抑制基因SFRP-1基因表达静默,Fra-1基因表达上调。结论Wnt和Hedgehog信号通路差异性激活及两者的信号交互在宫颈癌发生过程中起着重要作用。     

宫颈癌的发病与血管内皮生长因子的相关性研究

目的了解宫颈癌的发病与血管内皮生长因子(VEGF)的相关性研究。方法应用LSAB免疫组织化学技术,检测63例宫颈癌及19例正常宫颈组织标本中VEGF的表达。结果宫颈癌组织中VEGF的阳性表达率为53.9%(34/63),而正常宫颈组织中VEGF均为阴性表达;肿瘤直径≥4cm或间质浸润≥1/2的宫颈癌病人VEGF阳性表达率明显高于肿瘤直径<4cm或间质浸润<1/2者)(χ2=4.52、4.00,P<0.05)。有宫颈旁浸润或盆腔淋巴结转移者VEGF的阳性表达率显著高于无宫颈旁浸润的淋巴结转移者(χ2=4.48、7.27,P<0.05)。结论VEGF表达与宫颈癌的局部浸润和转移有关,可作为判断宫颈癌生物学行为的指标之一。     

宫颈癌巨噬细胞浸润和VEGFR-3表达与淋巴结转移的关系

目的 :探讨宫颈癌组织巨噬细胞浸润与VEGFR-3阳性脉管密度的相关性及其与淋巴结转移的关系。 方法 :采用免疫组化SP法检测59例宫颈癌石蜡标本中CD68及VEGFR-3的蛋白表达,并应用计算机辅助图像分析系统对脉管的密度行定量分析。 结果: 淋巴结转移组巨噬细胞数和VEGFR-3阳性脉管密度明显高于无淋巴结转移组(P<0.05、P<0.01)。随临床分期或病理分级增高,巨噬细胞数和VEGFR-3阳性脉管密度均有增加的趋势,但无统计学差异(P>0.05)。巨噬细胞数和VEGFR-3阳性脉管密度成正相关(r=0.318,P=0.014)。 结论: 宫颈癌中浸润的巨噬细胞通过促进淋巴管生成与宫颈癌的淋巴结转移密切相关。     

Cervical alterations in pregnancy

Spontaneous preterm birth (SPTB), defined as delivery before 37 weeks' gestation, remains a significant obstetric dilemma even after decades of research in this field. Although trends from 2007 to 2014 showed the rate of preterm birth slightly decreased, the CDC recently reported the rate of preterm birth has increased for two consecutive years since 2014. Currently, 1 in 10 pregnancies in the US still end prematurely. In this chapter, we focus on the “compartment” of the cervix. The goal is to outline the current knowledge of normal cervical structure and function in pregnancy and the current knowledge of how the cervix malfunctions lead to SPTB. We review the mechanisms by which our current interventions are hypothesized to work. Finally, we outline gaps in knowledge and future research directions that may lead to novel and effective interventions to prevent premature cervical failure and SPTB.     

Consultation multidisciplinaire pour les patients atteints d’une pathologie tumorale (carcinome infiltrant ou lésion précancéreuse) liée à HPV : la consultation multidisciplinaire papillomavirus

Given the recent increase in the number of human papillomavirus (HPV)-induced cancers in other locations than gynaecological, the number of patients with two cancers at distinct sites, and because of the lack of exhaustive data, we decided to create a multidisciplinary network around an HPV consultation at the Georges-Pompidou European Hospital (HEGP). This network aims to set up the best tools for detecting HPV-associated “multisite” precancerous lesions in order to determine the possible impact of dedicated care for this at-risk population. This monthly consultation was created at the HEGP in June 2014. It is currently organized around five consultations: gynaecological, ENT, urological, digestive and immunological. Every patient who has been diagnosed with HPV-related cancer and whose care is provided at the HEGP is offered this particular follow-up: systematically, once the initial lesion has been treated, the patient is convened annually for a day during which it benefits from the consultations mentioned above. A consultation with a psychologist is systematically proposed. Local samples are taken at each site: a cytological examination, the analysis of known predictive and prognostic virological markers are carried out. This study fits more broadly in a theme of clinical and fundamental research around cancers related to HPV.     

Cervical cancer incidence in elderly women-biology or screening history?

AimIn many countries, the age-specific pattern of cervical cancer incidence is currently bipolar with peaks at for instance 45 and 65 years of age. Consequently, a large proportion of cervical cancer cases are presently diagnosed in women above the screening age. The purpose of the study was to determine whether this bipolar pattern in age-specific incidence of cervical cancer reflects underlying biology or can be explained by the fact that the data come from birth cohorts with different screening histories.MethodsCombination of historical data on cervical screening and population-based cancer incidence data from Denmark 1943–2013, Finland and Norway 1953–2013, and Sweden 1958–2013.ResultsSince the implementation of screening, the incidence of cervical cancer has decreased for each successive birth cohort. All birth cohorts showed a unipolar age-specific pattern. In unscreened women in Denmark and Sweden, the incidence peaked around the age of 50; the peak was less marked in Finland; while peak age for unscreened women could not be determined for Norway due to widespread opportunistic screening. The current old-age peak in the incidence of cervical cancer represents residuals from unscreened or underscreened birth cohorts.ConclusionThe current bipolar pattern in age-specific incidence of cervical cancer can largely be explained by the different screening histories of successive birth cohorts. While it is reasonable to offer screening to elderly women today, birth cohort trends in disease burden should be carefully monitored to justify permanent changes in upper screening age.     

Prevention of preterm birth: Novel interventions for the cervix

Preterm birth is the leading cause of neonatal mortality and morbidity worldwide. Spontaneous preterm birth is a complex, multifactorial condition in which cervical dysfunction plays an important role in some women. Current treatment options for cervical dysfunction include cerclage and supplemental progesterone. In addition, cervical pessary is being studied in research protocols. However, cerclage, supplemental progesterone and cervical pessary have well known limitations and there is a strong need for alternate treatment options. In this review, we discuss two novel interventions to treat cervical dysfunction: (1) injectable, silk protein-based biomaterials for cervical tissue augmentation (injectable cerclage) and (2) a patient-specific pessary. Three-dimensional computer simulation of the cervix is performed to provide a biomechanical rationale for the interventions. Further development of these novel interventions could lead to new treatment options for women with cervical dysfunction.     

HPV16 E2基因各区域缺失与宫颈病变相关性的研究

目的:检测湖北地区HPV16阳性宫颈标本E2基因碳端(C)、铰链区(H)、氮端(N)的缺失状态,探讨其与CIN及宫颈癌的关系。方法:将122例宫颈标本按病变程度分为宫颈癌组、CINⅡ~Ⅲ组、对照组。应用多重聚合酶链反应(PCR)将各组HPV16感染标本E2基因的C、H、N分别与E6基因同时扩增,检测E2基因各区域的缺失状态,并应用Scion Image4.0软件半定量分析E2、E6基因条带灰度值,判断HPV DNA的整合状态。结果:宫颈癌组E2基因C、H、N缺失率分别是22.5%,50%,77.5%;CIN组为30.77%,69.23%,92.31%;对照组为9.09%,27.27%,27.27%。E2基因C、H缺失率在3组的任两组间比较无统计学差异(P0.05),而E2基因N端缺失率在宫颈癌组与对照组之间及CIN组与对照组之间差异有统计学意义(P均0.01)。结论:HPV16病毒E2基因N端缺失状态与CIN及宫颈癌有内在关系。在检测HPV感染同时检测E2基因N端缺失状态,对间接判断预后及指导后续治疗有重要意义。