SKP2、p53蛋白在非小细胞肺癌中的表达及其临床意义

目的:研究SKP2、p53蛋白在非小细胞肺癌(NSCLC)组织中的表达特征,探讨它们之间的关系及其对预后的影响.方法:利用组织芯片和免疫组化技术检测SKP2、p53蛋白在89例非小细胞肺癌,10例肺良性病变组织中的表达.结果:NSCLC组织中SKP2、p53蛋白表达阳性率分别为(23.52±13.57)%、( 50.58±24.15)%,均明显高于肺良性病变组织(2.91±1.27)%、(2.83±1.01)%(P=0.000、0.000).SKP2蛋白在NSCLC组织中的表达水平与细胞分化程度,病理类型,TNM分期密切相关(P=0.000,0.000,0.000),而与淋巴转移无统计学联系(P=0.051).p53蛋白在NSCLC组织中的表达水平与病理类型,TNM分期密切相关(P=0.000,0.004),而与细胞分化程度,淋巴转移无统计学联系(P=0.386,0.644).NSCLC组织中SKP2、p53蛋白表达呈正相关(r=0.391,P=0.000),二者同时高表达率20.22%(18/89),与细胞分化程度密切相关(P=0.007),而与病理类型,TNM分期,淋巴转移无统计学联系(P=0.197,0.547,0.302).单因素分析显示SKP2蛋白高表达的NSCLC患者5年生存率较SKP2蛋白低表达的患者降低(P=0.042/0.031);p53蛋白高表达的NSCLC患者5年生存率较p53蛋白低表达的患者无统计学差异(P=0.089/0.154);SKP2、p53蛋白同时高表达的NSCLC患者5年生存率较其他患者明显降低(P=0.015/0.015);多因素分析显示NSCLC患者5年生存率与细胞分化程度,TNM分期,术后放/化疗密切相关.结论:SKP2、p53蛋白在NSCLC的发生发展中起重要作用,且可能存在某种协同作用,但它们对NSCLC患者预后的影响尚需进一步研究.     

肺癌组织SKP2和p53蛋白表达临床意义的探讨

目的:探讨SKP2、p53蛋白在肺癌组织中的表达和关系及其对预后的影响.方法:组织芯片和免疫组化技术检测SKP2、p53蛋白在89例非小细胞肺癌(NSCLC)、13例小细胞肺癌(SCLC)和10例肺良性病变组织中的表达.结果:NSCLC、SCLC及肺良性病变组织中SKP2和p53蛋白的表达差异均有统计学意义,P值均为0.000.SKP2蛋白在肺癌组织中的表达水平与细胞分化程度、病理类型、TNM分期及淋巴转移密切相关,P值均为0.000.p53蛋白在肺癌组织中的表达水平与细胞分化程度、病理类型密切相关(P值均为0.000).肺癌组织中SKP2、p53蛋白表达呈正相关(r=0.448, P=0.000),两者同时高表达与细胞分化程度及病理类型密切相关(P值分别为0.001和0.022).多因素分析显示,肺癌患者5年生存率与SKP2蛋白表达水平、TNM分期、淋巴转移及术后放/化疗密切相关.结论:SKP2和p53蛋白在肺癌的发生发展中可能存在某种协同作用,对肺癌患者的预后可能有一定影响.     

Bax和Bcl-xl蛋白表达与非小细胞肺癌临床病理特征的关系

 目的 探讨凋亡相关基因Bax和Bcl-xl蛋白表达水平与非小细胞肺癌（NSCLC）临床病理特征的关系。方法 应用免疫组化SP法检测了35例NSCLC和7例正常肺组织中bax和bcl-xl蛋白的表达。结果 bax在正常肺组织中高表达率为71.4 %，在NSCLC中表达率为42.9 %，提示bax蛋白在NSCLC中表达过低。bcl-xl在正常肺组织中表达率为14.3 %，在NSCLC中的高表达率为57.1 %。提示NSCLC中存在bcl-xl蛋白高表达。bax与TNM分期（r =-0.475，P =0.002）、淋巴结转移（r = -0.236，P = 0.015）负相关，bcl-xl与TNM分期（r =0.542，P =0.027）、淋巴结转移（r =0.257，P =0.003）、病理分级（r =0.183，P =0.024）正相关。bax和bcl-xl间（r =-0.162，P =0.032）负相关，其他组间未见显著相关。结论 bax和bcl-xl蛋白相互抑制，均与非小细胞肺癌的发生、发展有关，可作为反映非小细胞肺癌生物学行为的指标。     

非小细胞肺癌中Skp2的表达及其与p27蛋白表达的关系

背景与目的 S期激酶相关蛋白2(Skp2)是细胞周期正性调节因子之一,它能促进周期蛋白依赖性激酶抑制剂p27的泛索化蛋白水解,在肿瘤中过表达,本研究旨在探讨非小细胞肺癌(non-small cell lung cancerNSCLC)中Skp2表达的临床意义及其与p27蛋白表达的关系.方法应用组织芯片和免疫组织化学方法检测Skp2和p27在68例NSCLC组织和17例正常支气管上皮细胞中的表达.结果 Skp2仅在肺癌组织中表达,且与患者的组织学类型(P=0.039),肿瘤细胞的分化程度(P=0.016),性别(P=0.012)和吸烟与否(P=0.026)显著相关,而与患者的年龄和TNM分期无关.p27在正常支气管上皮细胞中均有表达,在肺癌组织中表达降低;Skp2阳性表达的患者中p27表达明显降低,两者呈负相关(P=0.021).结论 在NSCLC中,Skp2蛋白表达的增高与p27泛素化依赖的蛋白降解有关,提示Skp2蛋白过表达在NSCLC的发生和发展中可能起霞要作用.     

HER-2/neu过度表达与晚期非小细胞肺癌患者预后的关系

目的:探讨晚期非小细胞肺癌(NSCC)患者HER-2蛋白的表达情况以及与预后关系. 方法: 应用免疫组织化学技术(MaxvisionTM快捷免疫组化法)检测68例NSCLC患者病理蜡块 HER-2蛋白的表达情况. 结果: 全组HER-2蛋白阳性率为32.4%.HER-2蛋白阳性和阴性表达患者的生存时间差异没有统计学意义(P=0.13). 结论: HER-2过度表达与晚期非小细胞肺癌患者预后的关系有待进一步研究.     

雌激素受体α和β及表皮生长因子受体的表达与非小细胞肺癌临床病理特点关系

目的:研究雌激素受体(ER)α和β与表皮生长因子受体(EGFR)在非小细胞肺癌(NSCLC)患者的表达情况及其与临床病理特点的关系.方法:收集有组织学病理诊断的164例非小细胞肺癌患者的肺癌组织及其相关临床资料,免疫组化方法检测ERα和ERβ与EGFR的表达情况,分析其表达与临床病理特点的关系.结果:164例非小细胞肺癌患者中,ERα表达阳性率为8.5％ (14/164),ERβ表达阳性率89.0％(146/164),表皮生长因子受体阳性率为57.9％ (95/164).ERα的阳性表达与NSCLC患者的年龄和疾病的分期有关,＜60岁的年轻患者(14.1％,P=0.043)和Ⅰ、Ⅱ期的患者(17.3％,P＜0.001)的表达率更高;ERβ的表达在年轻患者(95.3％,P=0.039)和疾病分期较晚的患者(95.2％,P=0.011)中有更高阳性率表达,在肺腺癌(67.6％,P =0.032)和高分化肺癌(83.3％,P=0.001)的患者ERβ(++)-(+++)高表达率更高;EGFR阳性率在女性(69.8％,P=0.033)和不吸烟的患者(68.9％,P=0.01)更高.结论:ERα、β和EGFR在非小细胞肺癌患者的表达情况与患者的临床病理特点具有相关性,提示雌激素受体的表达可能与非小细胞肺癌的发生、发展有着密切关系,有可能成为非小细胞肺癌治疗的新靶点.     

非小细胞肺癌组织Livin和Smac蛋白表达及其临床意义的研究

目的:探讨Livin和Smac蛋白在非小细胞肺癌(non-small cell lung cancer, NSCLC)中的表达及其对NSCLC患者预后的影响.方法:用免疫组织化学技术检测Livin和Smac蛋白在89例NSCLC组织和25例癌旁肺组织中的表达.结果:NSCLC组织中Livin和Smac蛋白阳性表达率分别为53.9%(48/89)和58.4%(52/89),高于癌旁肺组织中的8.0%(2/25)和12.0%(3/25),差异有统计学意义,x2值分别为16.723和16.848,P值均为0.000.Livin和Smac蛋白表达密切相关,x2=18.451,P=0.000,r=0.455.Livin蛋白表达水平与淋巴结转移、TNM分期及病理类型密切相关,x2值分别为19.433、17.161和7.772,P值分别为0.000、0.000和0.021;与性别、年龄、分化等无关,P均>0.05.Smac蛋白表达水平与淋巴结转移、TNM分期密切相关.x2值分别为7.748和7.064,P值分别为0.005和0.008;与性别、年龄和病理类型等无关,P均>0.05.Kaplan-Meier法分析显示,Livin蛋白表达阳性组的预后较阴性组差,x2=7.407,P=0.006;而Smac蛋白表达与预后无关,x2=0.945,P=0.331.结论:Livin蛋白表达与NSCLC的发生、发展密切相关,并对患者的预后产生不良影响.Smac蛋白表达与NSCLC的发生、发展相关,但与预后无关.Livin有可能成为评估NSCLC进展和预后的有价值指标.     

非小细胞肺癌组织Survivin和p53蛋白表达临床意义的探讨

目的:探讨Survivin和p53蛋白在非小细胞肺癌(NSCLC)组织中的表达及其临床意义.方法:采用免疫组化SP法检测60例NSCLC和10例肺良性病变组织中Survivin 和p53蛋白的表达.结果:NSCLC组织中Survivin蛋白阳性表达率为61.6%,明显高于正常对照组的0,x2=13.08,P=0.000...     

NEDD9在非小细胞肺癌中的表达及意义

目的:探讨NEDD9在非小细胞肺癌(non-small cell lung cancer,NSCLC)中的表达及意义。方法:应用免疫组化方法检测NEDD9在145例非小细胞肺癌及癌旁正常肺组织中的表达,并分析其表达与肿瘤临床病理因素及预后的相关性。结果:NEDD9在非小细胞肺癌中高表达,在正常肺组织中低表达(P<0.001);在非小细胞肺癌中,NEDD9的高表达与患者的阳性淋巴结转移及高TNM分期正相关(P=0.001和P=0.039);在预后分析中,NEDD9高表达的患者在单因素和多因素分析中均表现出更差的5年累计生存率(P<0.001)。结论:NEDD9促进非小细胞肺癌的侵袭转移,并与较差的预后相关。     

非小细胞肺癌组织FGFRlOP和PTEN表达及其临床意义的研究

目的:探讨FGFRlOP和PTEN蛋白在非小细胞肺癌(NSCLC)中的表达情况.方法:选取58例NSCLC手术切除标本,采用SP法进行免疫组织化学染色.结果:FGFRlOP和PTEN的阳性表达率分别为91.4%(53/58)和44.8%(26/58).FGFRlOP的表达与肿瘤的分化程度和病理类型密切相关,在鳞癌中的表达高于腺癌,P=0.002;肿瘤的分化程度较低时(腺癌P=0.003,鳞癌P=0.001)也呈现高表达.PTEN在肺腺癌中的表达高于在鳞癌中的表达,P=0.031;肿瘤低分化(腺癌P=0.023,鳞癌P=0.015)时,表达显著降低或缺失.FGFRlOP和PTEN在肺腺癌中的表达呈负相关,r=-0.733,P=0.025.结论:FGFRlOP的高表达与PTEN的低表达或表达缺失可能参与肿瘤的生长分化和进展,并提示预后不良.     

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.