DNA与AgNOR在甲状腺良、恶性病变中的定量研究

本研究采用Ｆｅｕｌｇｅｎ染色和ＡｇＮＯＲ银染色，检测ＤＮＡ及ＡｇＮＯＲ物质，发现：ＤＮＡ含量Ⅲ级为甲状腺癌组＞非典型结节组＞结甲肿组＞对照组，而Ⅰ级则反之；ＡｇＮＯＲ均数为甲状腺癌组（９．２７±２：７２）＞非典型结节组（４．７８±１．６６）＞结甲肿组（３．１６±１．３８）＞对照组（３．０８±０．４１）；甲状腺癌组与各组间差异有显著意义（Ｐ＜０．０１），非典型结节组与结甲肿组、对照组间差异也有显著意义（Ｐ＜０．０１），而结甲肿组与对照组间则无差异（Ｐ＞０．０５）。作者认为Ⅲ级ＤＡＮ含量的细胞出现频率越高或／和ＡｇＮＯＲ均数越高，恶性的可能性就越大或分化程度越低；本研究提示ＡｇＮＯＲ的均数与ＤＮＡ含量具有显著的相关性，并与细胞增生的程度呈正比，故对鉴别良、恶性肿瘤及交界性病变有肯定价值。     

甲状腺滤泡性肿瘤DNA含量与AgNOR计数研究

目的：探讨ＤＮＡ含量与ＡｇＮＯＲ对甲状腺良恶性滤泡性肿瘤的鉴别诊断价值。方法：应用流式细胞术和胶体银染技术对９例正常甲状腺组织和３６例滤泡生肿瘤（２２例腺瘤和１４例腺癌）进行ＤＮＡ含量分析和ＡｇＮＯＲ计数。结果：１４例滤泡性癌中，１１例为ＤＮＡ异倍体，而２２例滤泡性腺瘤仅１例为ＤＮＡ异倍体，且伴有不典型增生。ＡｇＮＯＲ由正常甲状腺组织、滤泡性腺瘤至滤泡性癌逐渐增加，相互之间有显著性差异（Ｐ〈０．０     

血卟啉衍生物对鼠肿瘤细胞DNA含量,AgNORs的影响

应用图像分析技术测定大鼠移植Ｗ２５６肿瘤单纯放射治疗组（对照组）和血卟啉衍生物并放射治疗组（实验组）肿瘤细胞的ＤＮＡ含量及ＡｇＮＯＲｓ计数，探讨血卟啉衍生物对恶性肿瘤放射治疗的增敏作用。结果显示实验组大鼠肿瘤细胞ＤＮＡ含量为（５．８４±１．２２）Ｃ，ＡｇＮＯＲｓ计数为２．４２±０．７３；对照组大鼠肿瘤细胞ＤＮＡ含量为（７．８３±０．６８）Ｃ，ＡｇＮＯＲｓ计数为５．３５±０．８４；前者ＤＮＡ含量及ＡｇＮＯＲｓ计数显著低于后者（ｔ＝６．３７，ｔ＝１１．７７，Ｐ＜０．０１）。表明血卟啉衍生物对恶性肿瘤放射治疗有明显的增敏作用     

大肠癌细胞DNA、AgNORs定量研究──两者相关性及预后意义的探讨

应用ＡｇＮＯＲｓ染色技术，对６３例大肠癌的ＡｇＮＯＲｓ颗粒进行了计数研究。其中３８例同时进行肿瘤细胞核ＤＮＡ含量静态测定。结果表明，大肠癌细胞ＡｇＮＯＲｓ数量与其ＤＮＡ含量之间有明显相关性（Ｐ＜０．０ｌ）。ＤＮＡ含量和ＡｇＮＯＲｓ计数愈低，肿瘤分化愈好，患者预后愈好；反之，ＤＮＡ含量和Ａｇ－ＮＯＲｓ计数愈高、肝瘤分化愈差，患者预后愈差。表明ＡｇＮＯＲｓ计数，ＤＮＡ含量检测均可作为大肠癌分级、判断预后的参考指标。     

紫外光血液辐照疗法对放射治疗鼠肿瘤细胞DNA含量、AgNORs计数的影响

应用多功能图像分析仪，检测了鼠Ｗ２５６移植性肿瘤细胞ＤＮＡ含量，并同时测定细胞ＡｇＮＯＲｓ计数，探讨紫外光血液辐照疗法（ＵＢＩ）对放射治疗的增敏作用。结果表明；光量＋放疗组肿瘤细胞ＤＮＡ含量为５．３４±１．０９Ｃ，ＡｇＮＯＲｓ计数为２．２４±０．４３；单纯放疗组肿瘤细胞ＤＮＡ含量为７．８３±０．８６Ｃ，ＡｇＮＯＲｓ计数为５．３５±０．８４；前者ＤＮＡ含量及ＡｇＮＯＲｓ计数显著小于后者（Ｐ＜０．０５）。表明ＵＢＩ对放疗恶性肿瘤有明显的增敏作用。     

前列腺癌AgNOR计数与DNA含量测定的意义

作者应用银染色技术对３０例前列腺癌、２０例前列腺增生症组织中的核仁组成区相关嗜银蛋白（ＡｇＮＯＲ）进行检测，并采用图像分析技术测定其ＤＮＡ含量。结果显示，在前列腺癌组织中，ＡｇＮＯＲ计数与ＤＮＡ含量均明显高于前列腺增生症组织（Ｐ＜０．００１）；肿瘤分化越差，ＡｇＮＯＲ计数和ＤＮＡ含量越高，并且与患者预后相关（Ｐ＜０．００１）；ＡｇＮＯＲ计数与ＤＮＡ含量呈明显的正相关（Ｐ＜０．０１）。结果提示ＡｇＮＯＲ计数与ＤＮＡ含量可作为反映前列腺癌生物学行为的指标。     

67例结肠癌DNA倍体和Ag—NOR计数分析对判断患者预后价值的初步探讨

对６７例结肠癌石蜡包埋组织材料做ＤＮＡ倍体水平分析和Ａｇ—ＮＯＲ计数。结果见：ＤＮＡ二倍体肿瘤５年、７年生存率分别为７８．０％（３２／４１）、３９．０％（１６／４１）；非二倍体肿瘤则为２６．９％（７／２６）、１１．５％（３／２６）（ｐ＜０．０１、ｐ＜０．０５）；Ａｇ─ＮＯＲ计数小于均值（６．９±１．０）组５年、７年生存率为８０．０％（２８／３５）、４０．０（１４／３５），大于均值组则为３４．４％（１１／３２）、１５．６％（５／３２）（ｐ＜０．０１、ｐ＜０．０５）。Ａｇ－ＮＯＲ计数小于均值组ＤＮＡ二倍体肿瘤占９７．１％（３４／３５）；大于均值组二倍体肿瘤占２１．９％（７／３２）（ｐ＜０．０１）。结果表明：ＤＮＡ倍体水平和Ａｇ－ＮＯＲ计数具有一致性，可以做为判断结肠癌预后指标。     

67例结肠癌DNA倍体和Ag—NOR计数分析对判断患者预后价值的初步探讨

对６７例结肠癌石蜡包埋组织材料做ＤＮＡ倍体水平分析和Ａｇ—ＮＯＲ计数。结果见：ＤＮＡ二倍体肿瘤５年、７年生存率分别为７８．０％（３２／４１）、３９．０％（１６／４１）；非二倍体肿瘤则为２６．９％（７／２６）、１１．５％（３／２６）（ｐ＜０．０１、ｐ＜０．０５）；Ａｇ─ＮＯＲ计数小于均值（６．９±１．０）组５年、７年生存率为８０．０％（２８／３５）、４０．０（１４／３５），大于均值组则为３４．４％（１１／３２）、１５．６％（５／３２）（ｐ＜０．０１、ｐ＜０．０５）。Ａｇ－ＮＯＲ计数小于均值组ＤＮＡ二倍体肿瘤占９７．１％（３４／３５）；大于均值组二倍体肿瘤占２１．９％（７／３２）（ｐ＜０．０１）。结果表明：ＤＮＡ倍体水平和Ａｇ－ＮＯＲ计数具有一致性，可以做为判断结肠癌预后指标。     

食管鳞癌DNA和RNA测定及其预后关系的研究

目的　探讨食管鳞癌ＤＮＡ异倍体和ＲＮＡ含量变化与预后的关系。方法　应用流式细胞技术对６２例随访患者的石蜡标本进行研究。结果　术后生存５年以上患者的ＤＮＡ异倍体７８．１％（２５／３２）,ＲＮＡ含量为２０．５３±４．２１。术后半年内死亡者ＤＮＡ为９３．３％ （２８／３０）,ＲＮＡ含量为２４．８４±６．３５,两者均有显著性差异。ＤＮＡ异倍体和ＲＮＡ含量与病期、恶性程度和淋巴结转移有关。结论　ＤＮＡ和ＲＮＡ测定是判断食管鳞癌病期、恶性程度、有无淋巴结转移和预后的重要指标。表２　食管癌不同病期与ＤＮＡ和ＲＮＡ含量的关系生存时间（年） 病期 例数 ＤＮＡ２Ｃ Ａｎ ％ＲＮＡ含量（ｘ±ｓ）＞ ５ Ⅰ ３ ２ １ ５０ １０．６１±０．２４Ⅱ １９ ４ １５ ７８．９ ２１．５６±３．４１Ⅲ ８ １ ７ ８７．５ ２３．９８±２．１１Ⅳ ２ ０ ２ １００ ２６．１２±１．５６＜ ０．５ Ⅰ ０ ０ ０Ⅱ １１ １ １０ ９０．９ ２３．４５±４．２７Ⅲ １３ １ １２ ９２．３ ２４．７６±２．８７Ⅳ ６ ０ ６ １００ ２７．３１±２．５６表３　食管鳞病分化程度与ＤＮＡ和ＲＮＡ含量的关系生存时间（年） 分化 例数 ＤＮＡ２Ｃ Ａｎ ％ＲＮＡ含量（ｘ±ｓ）＞ ５ Ⅰ ５ ３     

宫颈良、恶性病变核仁组成区蛋白定量与宫颈癌预后的研究

应用核仁组成区蛋白嗜银（ＡｇＮＯＲ）技术，对１０９例宫颈良、恶性病变进行了ＡｇＮＯＲ定量研究。结果表明：１．慢性宜颈炎、宫颈非典型增生、宫颈鳞癌三种病变的ＡｓＮＯＲ均值有显著差异（Ｐ＜０．０１）。２．宫颈鳞癌组织学１级ＡｇＮＯＲ计数低于组织学Ⅱ级（Ｐ＜０．００１）。３．随访１０年以上的７３例宫颈鳞癌患者，核仁组成区蛋白高均值组（≥５）的患者生存时间显著短于低均值组（＜５）（Ｐ＜０．０５），１０年生存率分别为１８％与４６％。作者认为，ＡｇＮＯＲ计数可作为一种新的肿瘤定量指标，在宫颈良、恶性病变的鉴别诊断、选择最佳治疗方案、推测宫颈癌预后等方面具有重要的临床价值。     

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.