c—erbB—2原癌基因产物增强表达与胃癌预后的关系

用ABC酶标法观察c-erbB-2原癌基因产物(190KI))增强表达与 103例胃癌预后的关系及临床应用价值.c-erbB2癌蛋白在正常胃粘膜、癌旁肠化和异型增生为阴性.而在胃癌中增强表达13.6%(14/103例),并与淋巴结转移的关系密切(P<0.05).c-erbB-2癌蛋白表达主要定位于癌细胞膜.生存期分析显示c-erbB-2癌蛋白阳性的胃癌患者预后差,术后生存期短(P<0.05),表明原位检测c-erbB-2癌蛋白有助于判断胃癌预后.     

p53和c-erbB-2表达与胃癌进展的关系

目的探讨p53和c-erbB-2表达与胃癌进展的关系。方法收集139例胃癌手术切除标本,包括黏膜内癌23例、浸润至黏膜下层31例、浸润至肌层47例、浸润至浆膜或浆膜外38例,切片采用免疫组化S-P法染色。结果进展期胃癌中p53和c-erbB-2阳性表达率均明显高于早期胃癌（P值分别为0.010、0.000）。c-erbB-2表达与p53表达存在相关性（P=0.023〈0.05）。c-erbB-2阳性表达是胃癌发展的1个危险因素,p53表达阳性和阴性的OR值比较无统计学意义（P〉0.05）。结论抑癌基因p53突变有利于癌基因c-erbB-2的表达;c-erbB-2阳性表达是胃癌发展的1个危险因素,与胃癌的发展密切相关。     

胃癌组织中p53、PCNA及c-erbB-2表达与淋巴结转移的关系

目的：探讨p53、PCNA及c-erbB-2在胃癌组织中的表达及其与淋巴结转移的关系。方法：应用免疫组织化学方法（S－P法）检测299例胃癌组织中p53、增殖细胞核抗原（PCNA）及c-erbB-2的表达。结果：p53、PCNA及c-erbB-2在有淋巴结转移的胃癌组织中的表达率分别为44．8％、71．7％、71．7％；在无淋巴结转移的胃癌组织中的表达率分别为47．1％，78．2％和47．1％。结论：p53、PCNA的表达与淋巴结转移无相关性（P＞0．05），c-erbB-2的表达与淋巴结转移密切相关（P＜0．01）。c-erbB-2可作为判断胃癌患者预后的1个重要指标。     

HER2基因在胃癌组织中的表达及其临床意义

目的探讨HER2基因表达、扩增与胃癌生物学行为的关系。方法应用FISH技术,检测20例胃癌标本中HER2扩增情况,应用IHC技术检测胃癌组织中HER2表达情况。结果应用FISH技术检测胃癌组织中HER2基因扩增率为35%,IHC技术检测胃癌组织中HER2蛋白阳性表达率为30%;HER2基因扩增及蛋白阳性表达与胃癌浸润深度、淋巴结转移及病理分期有关(P<0.05)。结论 HER2基因表达与胃癌浸润和转移有关,可作为判断胃癌生物学行为和预后的重要指标。     

胃癌组织中c-erbB-2与P-gp表达的相关性研究

目的了解胃癌组织中c-erbB-2表达与多药耐药的相关性及其临床意义。方法采用免疫组化方法检测了98例胃癌组织中c-erbB-2表达,应用流式细胞术(FCM)检测癌细胞P-糖蛋白(P-gp)水平,并对其进行相关性分析。结果胃癌组织中c-erbB-2阳性表达33例,阳性率33.67%;P-gp阳性表达58例,阳性率59.18%。在c-erbB-2表达阴性的病例累及2～3个部位的癌比累及1个部位癌的P-gp表达增多,两组比较有显著性差异(P=0.035)。当c-erbB-2和P-gp表达双阳性时,P-gp表达增多与双阴性组比较有非常显著性差异(P<0.001);当c-erbB-2或P-gp表达单阳性时,P-g表达增多与双阴性组比较有非常显著性差异(P<0.001);胃癌c-erbB-2和P-gp表达与患者年龄、性别、临床分期、胃癌分化程度和3年生存情况分析,均无统计学意义。结论同时检测胃癌c-erbB-2和P-gp表达水平,可为胃癌的综合治疗及化疗药物选择提供临床参考依据。但是不能用来判断胃癌患者预后。     

胃癌组织HER-3和Akt的表达及其临床意义

目的:检测胃癌组织与非肿瘤胃组织(胃黏膜及肌组织)中表皮生长因子受体-3(HER-3)、丝苏氨酸激酶(Akt)的表达及胃癌组织中HER-3、Akt的表达与临床病理参数及预后的关系.方法:免疫组化ElivisionTM二步法检测84例胃癌及15例非肿瘤胃组织中HER-3、Akt的表达,应用SPSS 13.0分析HER-3、Akt的表达与胃癌患者临床病理特征及预后的关系.结果:胃癌组织中HER-3阳性率为56.0%(47/84),过表达率为21.4%(18/84),Akt阳性率为48.3%(54/84),过表达率为31.0%(26/84).HER-3的阳性表达与临床分期、远处转移相关(P值分别为0.038和0.008),Akt的阳性表达与分化程度、淋巴结转移相关(P值分别为0.023和0.028),Akt的过表达与临床分期、肿瘤浸润深度、淋巴结转移相关,P值分别为0.014、0.009和0.034.HER-3阴性的总生存时间(OS)显著优于阳性者(P=0.023),Akt低表达的OS、无进展生存率(PFS)均显著优于高表达者,P＜0.001.结论:HER-3、Akt的表达与细胞的恶变相关.HER-3、Akt可能参与肿瘤细胞的粘附、增殖、浸润及转移的过程,可作为胃癌预后的预测因子.     

环氧化酶-2基因和蛋白在人胃癌组织中的表达及临床意义

目的:研究环氧化酶-2(COX-2)基因和蛋白在人胃癌组织中的表达及其与临床病理特征之间的关系.方法:应用逆转录-聚合酶链反应(RT-PCR)技术,检测了47例胃癌患者的癌组织及配对的癌旁组织、11例远离肿瘤的正常胃粘膜组织中COX-2 mRNA的表达,同时应用免疫组织化学技术检测COX-2蛋白的表达.结果:COX-2mRNA在72.3%(34/47)的胃癌组织中表达显著增高(0.619±0.033),癌旁组织表达也增高(0.175±0.084),在正常胃粘膜组织中几乎不表达,癌组织与癌旁组织、正常胃粘膜组织COX-2 mRNA的表达差异有显著性意义.免疫组织化学结果显示70.2%(33/47)的胃癌组织COX-2蛋白呈阳性表达,58.3%(27/47)癌旁组织COX-2蛋白呈不同程度阳性表达,两者比较差异有显著意义,正常胃粘膜组织未见COX-2蛋白表达.胃癌的COX-2过度表达与其淋巴结的转移和临床分期密切相关,而与组织学类型和浸润深度无明显相关.结论:COX-2 mRNA和蛋白表达在人胃癌组织中明显增高,并与胃癌淋巴结的转移和临床分期等临床病理特征密切相关.COX-2的过度表达在人胃癌发生发展和转移中起重要作用.     

FAK和VEGF在胃癌中的表达及其相互关系

目的检测粘着斑激酶(FAK)和血管内皮生长因子(VEGF)在胃癌中的表达及其与侵袭和转移的关系,并探讨二者的相关性.方法采用免疫组织化学sABC法,观察86例胃癌及30例非胃癌组织中FAK和VEGF的表达情况.结果FAK和VEGF在胃癌中的阳性率分别为80%和59%.在非胃癌组织中的阳性表达率分别为10%和13%.FAK和VEGF在侵及浆膜层胃癌病例中的表达明显高于未侵及浆膜层者,二者之间有显著差异性(P＜0.05);有淋巴结转移组与无淋巴结转移组比较有明显差异(P＜0.05),FAK与VEGF阳性表达呈正相关(P＜0.01).结论FAK、VEGF在胃癌的侵袭和转移中起重要作用,二者在胃癌中表达升高可以作预测胃癌侵袭和转移的指标.     

脆性组氨三联体在胃癌中的表达缺失

目的研究胃癌组织中脆性组氨三联体蛋白(FHIT)的表达情况并探讨FHIT基因与胃癌临床病理学指标的关系.方法用免疫组化法检测60例胃癌及癌旁组织中FHIT的表达情况.结果60例胃癌和癌旁组织中FHIT的阳性表达率分别为75%和100%.胃癌组织中FHIT表达强度和阳性细胞数量均低于癌旁组织为32例(53.33%).结果有显著性差异(P＜0.05).在高、中、低分化组胃癌中FHIT表达率分别为80%(16/20)、70%(14/20)、75%(15/20).FHIT在早期胃癌和进展期胃癌中的表达率分别为83.33%(15/18)、71.43%(30/42).FHIT在无淋巴结转移组中表达率为81.82%(18/22),有淋巴结转移组中表达率为71.05%(27/38).结果均无显著性差异(P＞0.05).结论FHIT在胃癌组织中表达水平明显低于癌旁组织.FHIT表达与组织学分级、胃癌病理学分期以及有无淋巴结转移无显著相关性.     

β-catenin的表达与胃癌临床病理特征的关系

目的 探讨胃癌组织中β-catenin的表达与胃癌临床病理特征的关系.方法 应用EnVision法检测60例早期胃癌、60例进展期胃癌组织中β-catenin表达情况,并比较β-catenin在不同临床病理特征的胃癌组织中的表达差异.结果 早期胃癌组织中β-catenin阳性表达率为63.3%,不同组织学类型（肠型和弥漫型）、不同分化程度（高、中、低）、有无淋巴结转移的早期胃癌,其组织中β-catenin阳性表达率相互比较,均存在显著性差异（P＜0.05）,但与浸润深度无显著性相关（P＞0.05）.进展期胃癌组织中β-catenin的阳性表达率为55.0%,不同分化程度及有无淋巴结转移的进展期胃癌,其组织中β-catenin的阳性表达率相互比较存在非常显著性差异（P＜0.01）,但与组织学类型、腹膜转移及远处转移无显著性相关（P＞0.05）.结论 β-catenin表达减低与胃癌的发生、发展有关.     

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.