卵巢上皮性肿瘤中溶血磷脂酸受体表达及其生物学意义

目的：探讨3种溶血磷脂酸（lysophosphatidic acid，LPA）受体（LPA1，LPA2及LPA3）mRNA和蛋白在人卵巢肿瘤组织中的表达状况及意义。方法：采用半定量RT—PCR和Western blot检测LPA1、LPA2和LPA3mRNA以及LPA2和LPA3蛋白在人卵巢上皮性肿瘤组织中的表达水平。结果：RT-PCR结果显示，LPA1mRNA在正常卵巢组织、良性卵巢肿瘤及上皮性卵巢癌中表达阳性率分别为100％、100％、95．7％，差异均无显著性（P〉0．05）；上皮性卵巢癌组织LPA2mRNA、LPA3mRNA表达阳性率（95．7％；91．3％）显著高于良性卵巢肿瘤（21．3％；21．3％）及正常卵巢组织（15．4％；15．4％）（P〈0．01）；良性卵巢肿瘤与正常卵巢组织LPA2mRNA、LPA3mRNA表达阳性率差异无显著性（P〉0．05）；上皮性卵巢癌组织中LPA1mRNA表达率和表达水平高于LPA3mRNA（P〈0．05）。Western blot结果显示，上度性卵巢癌组织中LPA2和LPA3蛋白表达阳性率（95．7％；95．7％）均高于良性卵巢肿瘤（50％；42．9％）和正常卵巢组织表达阳性率（38．5％；38．5％）（P〈0．01）；良性卵巢肿瘤与正常卵巢组织中LPA2和LPA3蛋白表达阳性率及表达水平相比差异无显著性（P〉0．05）。病理资料的相关分析显示，上皮性卵巢癌组织中LPA受体mRNA和蛋自表达与临床病理特征无相关性。结论：LPA1、LPA2和LPA3在卵巢上皮性肿瘤中普遍表达，LPA受体可能参与了卵巢癌的发生发展过程。     

卵巢癌中MDR1的表达及其临床意义

目的检测MDR1在卵巢癌中的表达并探讨其在卵巢癌化疗耐药中的作用。方法采用RT-PCR复合定量技术对40例卵巢癌、20例良性卵巢肿瘤、20例正常卵巢组织中MDR1的表达进行检测,分析其表达与临床病理特征及化疗疗效的相关性。结果卵巢癌中MDR1的表达显著高于正常组及良性肿瘤组,且肿瘤分化程度越差其表达越高,P〈0．05。MDR1在术前化疗组中的阳性表达率显著高于术前未化疗组,P〈0．05。MDR1阴性组患者的化疗反应率显著高于阳性组患者（70．6％比43．5％）,P〈0．05,MDR1阴性对化疗有效的预测值为70．6%。结论MDR1可能在卵巢癌获得性耐药的形成中发挥一定作用,MDR1的检测可能有助于卵巢癌化疗方案的制定,并成为预测化疗疗效的有用指标。     

应用组织微阵列技术检测MMP-2和TIMP-2在卵巢肿瘤中的表达

目的探讨基质金属蛋白酶．2（MMP-2）和组织金属蛋白酶抑制剂．2（TIMP-2）在卵巢肿瘤中的表达。方法应用组织微阵列技术结合免疫组化方法检测94例卵巢肿瘤组织中MMP-2和TIMP-2的表达，以胞质出现棕黄色颗粒为阳性。结果卵巢癌组织和卵巢交界性肿瘤组织中MMP-2阳性表达率明显高于卵巢良性肿瘤（P〈0．05），卵巢癌组织中TIMP-2阳性表达率明显高于卵巢良性肿瘤（P〈0．05）；MMP-2在Ⅲ～Ⅳ期卵巢癌中的阳性表达率明显高于Ⅰ～Ⅱ期（P〈0．05），MMP-2在病理分级2-3级阳性表达率明显高于1级（P〈0．05）；TIMP-2在不同临床分期和病理分级的卵巢癌中的阳性表达情况与MMP-2相反。结论MMP-2的表达上调和TIMP-2相对弱表达在卵巢恶性肿瘤的演进发展中具有重要作用。     

上皮性卵巢癌Survivin蛋白的表达及拓扑替康对其表达的影响

目的研究上皮性卵巢癌组织中Survivin蛋白表达的差异和不同浓度拓扑替康（TPT）对卵巢癌细胞株SKOV3 Survivin蛋白表达的影响。方法应用免疫组化法检测54例上皮性卵巢癌、25例良性卵巢肿瘤及20例正常卵巢组织中Survivin蛋白的表达，分析其表达与卵巢癌恶性程度及临床病理特征的关系，用不同浓度的TPT作用于对数生长期的SKOV3细胞，检测Survivin蛋白的表达。结果Survivin蛋白在上皮性卵巢癌与良性上皮性卵巢肿瘤及正常卵巢组织中的表达差异具有显著意义（P〈0.01）。Survivin蛋白的表达与临床病理特征有关，Ⅲ-Ⅳ期的表达率（78．4％）明显高于Ⅰ-Ⅱ期（41．2％）（P=0．007），且肿瘤的分化程度越低，Survivin蛋白表达越强（P=0．027），伴有淋巴结转移者（96，7％）明显高于无淋巴结转移者（29．2％）（P〈0．01），伴有腹水转移者（94．7％）明显高于无腹水转移者（51．4％）（P〈0．001），但是与卵巢的组织学类型无荚（P=0．977）。随着TPT浓度的增加，SKOV3中Survivin蛋白表达减少（P〈0．001），各组Survivin蛋白表达差异具有统计学意义。结论Survivin蛋白的表达与卵巢癌的恶性程度有关，恶性程度越高Survivin蛋白的表达越多．而TPT作用于SKOV3细胞可以抑制其Survivin蛋白的表达。     

检测NFκB/p65蛋白在卵巢上皮癌表达的临床意义

目的探讨核转录因子（NFκB）家族蛋白在卵巢癌组织中的表达及其临床意义。方法通过免疫组化方法检测卵巢良性上皮性肿瘤、卵巢交界性上皮性肿瘤和卵巢癌中NFκB／p65的表达。结果NFκB／p65蛋白呈现棕黄色、细颗粒状物，在卵巢良性上皮性肿瘤、卵巢交界性上皮性肿瘤和卵巢癌中NFκB的阳性表达率分别为：26．7％、37．5％和72．5％；在卵巢癌中，p65核染色阳性与分化程度、淋巴结转移、临床分期及肿瘤大小明显相关（P〈0．05）。结论NFκB与分化程度、淋巴结转移、临床分期及肿瘤大小关系密切，可望和其他指标一起作为判断卵巢癌预后的标志物。     

Notch1信号蛋白在卵巢肿瘤中的表达及其临床意义

目的探讨Notch1在卵巢肿瘤的形成和转化中的表达特点及其与卵巢癌的临床病理学参数的关系。方法于2006年7月至2007年1月采用免疫组织化学SP染色法，检测34例卵巢癌、6例卵巢交界性瘤、23例卵巢良性肿瘤和13例正常卵巢组织中Notch1的表达，并采用SPSS12．0软件的卡方检验统计方法进行分析。结果①Notch1在卵巢癌、卵巢交界性瘤、卵巢良性肿瘤和正常卵巢组织中的表达分别为74％（25／34）、67％（4／6）、30％（7／23）和23％（3／13），Notch1在卵巢癌中的表达与其在卵巢交界性瘤、卵巢良性肿瘤和正常卵巢组织中的表达差异有显著性（P〈0．01），而后三者比较差异无显著性（P〉0．05）。②Notch1在卵巢癌中的表达与手术病理分期、周围组织浸润、淋巴结转移、病理类型差异无显著性（P〉0．05），与卵巢癌病理分化程度有关（P〈0．01），而且分化程度越低，Notch1的表达越低。结论①Notch1在卵巢的癌变转化过程中表达逐渐增加，可能与早期卵巢癌变的启动有关。②Notch1在卵巢癌中的表达与其病理分化程度有关，分化程度越低，Notch1的表达越低，可能与其恶性程度有关并为临床手术和术后治疗提供相关依据。     

人类组织激肽释放酶6在卵巢上皮性癌中的表达及临床意义

[目的]研究人类组织激肽释放酶（kallikrein,KLK）6蛋白在卵巢上皮性癌组织及腹膜后淋巴结中的表达,探讨其在卵巢上皮性癌中的临床意义。[方法]回顾性分析卵巢肿瘤患者的临床病理资料,采用免疫组化检测72例卵巢癌、16例卵巢交界性肿瘤、20例良性卵巢上皮性肿瘤组织KLK6蛋白的表达;并采用配对设计研究KLK6蛋白在卵巢癌患者腹膜后淋巴结中的表达．探讨KLK6在卵巢上皮性癌发生、发展中的作用。[结果]KLK6在卵巢癌及交界性卵巢肿瘤中的阳性表达分别为52．8％（38／72）、25．O％（4／16）,均显著强于良性上皮性卵巢肿瘤15．0％（3／20）f19〈0．05）。KLK6阳性表达与卵巢癌的临床分期、组织学分级及淋巴结转移有关fP〈0．05）,与组织学类型无相关性（P〉0．05）;KLK6在卵巢癌原发灶与腹膜后转移淋巴结组织中的表达呈正相关（r=8．91,P=0．003）;KLK6阳性与阴性患者的平均生存时间分别为25．9个月和49．2个月（P〈O．051。[结论]KLK6高表达可能在卵巢上皮性癌的发生发展中起潜在作用,KLK6可能与卵巢上皮性癌的浸润、转移有关,KLK6是卵巢癌的不良预后因素之一。     

CD44v6 和MRP 在卵巢癌中的表达

 目的 探讨CD44v6和MRP在上皮性卵巢癌组织中表达与化疗疗效和预后的关系。方法 采用免疫组织化学S-P法，检测10例正常卵巢组织、20例卵巢良性肿瘤和50例卵巢恶性肿瘤上皮性组织中CD44v6和MRP的表达。结果 ①CD44v6和MRP在卵巢恶性肿瘤中的表达明显高于在良性及正常组织中的表达（P〈0．05）；②CD44v6和MRP强阳性率与卵巢癌的临床分期、组织学分级和淋巴结转移有关（P〈0．05）；③卵巢癌中CD44v6和MRP的表达呈正相关（r=0．557，P〈0．05）；④CD44v6和MRP阳性表达的病例，化疗疗效和预后差。结论 检测卵巢癌中的CD44v6和MRP表达可反映肿瘤细胞的化疗疗效及预测预后。     

Le^y抗原在卵巢上皮性肿瘤中的表达及意义

目的：探讨卵巢癌组织Le^y抗原的表达及其临床意义。方法：采用免疫组织化学SP法检测恶性、交界性、良性卵巢上皮肿瘤及正常卵巢组织中Le^y抗原的表达，并分析其与卵巢癌生物学特性之间的关系。结果：Le^y抗原在恶性卵巢上皮性癌中的阳性表达率为75．47％（40／53），明显高于交界性卵巢上皮性肿瘤（47．06％）及良性卵巢上皮性肿瘤（42．86％）（P均〈0．05）。正常卵巢组织中未检出Le^y抗原的表达。晚期卵巢上皮性癌的Le^y抗原的阳性表达率为84．21％，明显高于早期卵巢上皮性癌（53．33％），（P〈0.05）。结论：Le^y抗原与卵巢上皮性癌的发生、发展相关。Le^y抗原的表达可作为反映卵巢癌恶性潜能的一项新的指标。     

卵巢良恶性肿瘤中TCF4和E－cadherin的表达及临床意义

目的：探讨 TCF4和 E －cadherin 在卵巢癌中的表达意义。方法：采用免疫组化 SP 法检测19例卵巢良性囊腺瘤、19例交界性囊腺瘤、50例恶性肿瘤中 TCF4和 E －cadherin 的表达。结果：TCF4在卵巢癌组织、交界性肿瘤中表达明显高于良性囊腺瘤组织（P ＜0．05）,阳性率分别为76％、63．2％、31．6％。E －cadherin在卵巢良性、交界性肿瘤、卵巢癌中阳性率分别为78．9％、52．6％、36．0％。E －cadherin 在卵巢交界性肿瘤及卵巢癌组织中表达明显低于良性肿瘤组织（P ＜0．05）。E －cadherin 及 TCF4表达与卵巢癌患者年龄无关（P＞0．05）,TCF4表达与卵巢癌病理学分级、FIGO 分期有关（P ＜0．05）。结论：TCF4在卵巢癌中表达高于卵巢良性肿瘤和交界性肿瘤,同时与卵巢癌病理学分级、FIGO 分期成正相关。而 E －cadherin 在卵巢癌中表达低于卵巢良性肿瘤和交界性肿瘤,同时与卵巢癌病理学分级、FIGO 分期负相关。     

Oncogénétique et psycho-oncologie, une collaboration recommandée...

Résumé: La possibilité depuis 1994, de connaître la probabilité individuelle de développer certains cancers a permis de proposer de nouvelles modalités de prévention, de traitements et contribué au développement actuel de loncogénétique. Une meilleure connaissance des répercussions psychologiques tant pour les patients que pour les apparentés est désormais possible et limplication des psycho-oncologues dans ce cadre de la réalisation des tests prédictifs, recommandée. La mission de «messager» qui incombe au «cas-index» doit faire lobjet dune attention particulière. La complexité de linformation et la dimension paradoxale que peut avoir parfois la communication à propos des choix, rend difficile lévaluation de la qualité du consentement. La situation particulièrement délicate dune aide à la décision à légard de la chirurgie prophylactique, exige une collaboration étroite des généticiens et des psycho-oncologues.Les soins de support en oncologie     

The role of papillomaviruses in human cancers

This review comprehensively evaluates the influence of gene-gene, gene-environment and multiple interactions on the risk of colorectal cancer (CRC). Methods of studying these interactions and their limitations have been discussed herein. There is a need to develop biomarkers of exposure and of risk that are sensitive, specific, present in the pathway of the disease, and that have been clinically tested for routine use. The influence of inherited variation (polymorphism) in several genes has been discussed in this review; however, due to study limitations and confounders, it is difficult to conclude which ones are associated with the highest risk (either individually or in combination with environmental factors) to CRC. The majority of the sporadic cancer is believed to be due to modification of mutation risk by other genetic and/or environmental factors. Micronutrient deficiency may explain the association between low consumption of fruit/vegetables and CRC in human studies. Mitochondrial modulation by dietary factors influences the balance between cell renewal and death critical in colon mucosal homeostasis. Both genetic and epigenetic interactions are intricately dependent on each other, and collectively influence the process of colorectal tumorigenesis. The genetic and environmental interactions present a good prospect and a challenge for prevention strategies for CRC because they support the view that this highly prevalent cancer is preventable.     

Antifungal combination therapy in localized candidosis

A mouse model of localized candidosis in air-filled subcutaneous cysts imitating thrush has been developed. We have now tested various antifungal combinations in this animal model. Flucytosine (5-FC) + amphotericin B (Amph B) showed the highest efficacy, a clear additive or even synergistic effect was seen. The combination of 5-FC + imidazole or triazole derivative was less efficacious, an additive effect was rare. The combination of 5-FC + Amph B was also tested against Candida albicans strains showing various degrees of 5-FC-resistance. A significant reduction in 5-FC-resistant mutants was seen after the treatment with the combination.     

Les génériques en cancérologie: à molécule identique, médicaments identiques? Les biosimilaires, des super-génériques?

Résumé: Les biosimilaires vont bientôt voir leur apparition en Europe. Comment un laboratoire peut-il aborder le développement de son dossier dAMM? Quelles sont les bases légales et les recommandations officielles? Comment la similarité et/ou le caractère générique peuvent-ils être démontrés? Les règles sont-elles identiques à celles des produits chimiques conventionnels pour lesquels, notamment en cancérologie, il existe des médicaments génériques? Comment faire pour que la sécurité et lefficacité des médicaments biosimilaires soient assurées pour les patients?     

Cancer immunotherapy

Unprecedented progress has seen made in the last decade in the field of cancer immunotherapy. The recent approval of nivolumab （Opdivo）, the first anti-programmed cell death-1 （PD-1） antibody, for metastatic melanoma in Japan, marked a milestone in the rapidly advancing field of cancer immunotherapy. Nivolumab together with ipilimumab （Yervoy）, the anti-cytotoxic T-lymphocyte-associated antigen-4 （CTLA-4） antibody, are the first 2 drugs in the class of ＂immune checkpoint inhibitors＂ that have delivered impressive responses in patients with metastatic melanoma and renal cell cancer （RCC） as well as a variety of solid tumors.     

Effect of tumor therapeutic irradiation on the mechanical properties of teeth tissue

Tumor irradiation of the head-neck area is accompanied by the development of a so-called radiation caries in the treated patients. In spite of conservative therapeutic measures, the process results in tooth destruction. The present study investigated the effects of irradiation on the demineralization and remineralization of the dental tissue. For this purpose, retained third molars were prepared and assigned either to a test group, which was exposed to fractional irradiation up to 60 Gy, or to a non-irradiated control group. Irradiated and non-irradiated teeth were then demineralized using acidic hydroxyl-cellulose gel; afterwards the teeth were remineralized using either Bifluorid12 or elmex gelee. The nanoindentation technique was used to measure the mechanical properties, hardness and elasticity, of the teeth in each of the conditions. The values were compared to the non-irradiated control group. Irradiation decreased dramatically the mechanical parameters of enamel and dentine. In nonirradiated teeth, demineralization had nearly the same effects of irradiation on the mechanical properties. In irradiated teeth, the effects of demineralization were negligible in comparison to non-irradiated teeth. Remineralization with Bifluorid12 or elmex gelee led to a partial improvement of the mechanical properties of the teeth. The enamel was more positively affected by remineralization than the dentine.     

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.     

Differentiation state and invasiveness of human breast cancer cell lines

Summary Eighteen breast cancer cell lines were examined for expression of markers of epithelial and fibroblastic differentiation: E-cadherin, desmoplakins, ZO-1, vimentin, keratin and ₁ and ₄ integrins. The cell lines were distributed along a spectrum of differentiation from epithelial to fibroblastic phenotypes. The most well-differentiated, epithelioid cell lines contained proteins characteristic of desmosomal, adherens and tight junctions, were adherent to one another on plastic and in the basement membrane matrix Matrigel and were keratin-positive and vimentin-negative. These cell lines were all weakly invasive in anin vitro chemoinvasion assay. The most poorly-differentiated, fibroblastic cell lines were E-cadherin-, desmoplakin- and ZO-1-negative and formed branching structures in Matrigel. They were vimentin-positive, contained only low levels of keratins and were highly invasive in thein vitro chemoinvasion assay. Of all of the markers analyzed, vimentin expression correlated best within vitro invasive ability and fibroblastic differentiation. In a cell line with unstable expression of vimentin, T47D_CO, the cells that were invasive were of the fibroblastic type. The differentiation markers described here may be useful for analysis of clinical specimens and could potentially provide a more precise measure of differentiation grade yielding more power for predicting prognosis.