组织因子与肿瘤

近年来认为肿瘤的血管生成、侵袭和转移与凝血高度相关,其中一个关键蛋白就是组织因子(TF)。TF可作为细胞内信号传导介质,改变基因表达形式和细胞行为,明确参与肿瘤相关性血管生成,其表达量与多种肿瘤转移相关。抗血管生成和TF靶向治疗阻止肿瘤生长和转移,有望成为一种新的抗肿瘤治疗方法。     

抗肿瘤血管生成的靶向治疗

血管生成与肿瘤生长、浸润密切相关，同时，新生血管又提供了肿瘤细胞的转移通道，是促进转移的重要途径。因此，血管内皮增殖相关的因子可以作为肿瘤治疗的分子靶点。近年来，大量的研究均证实了通过抑制肿瘤血管生成因子，能够抑制肿瘤血管生成和诱导细胞凋亡。针对肿瘤血管生成为靶点的治疗研究为肿瘤治疗提供了有前景的新途径。     

淋巴管与肿瘤转移

肿瘤转移中淋巴转移是其最常见、最基本的途径,在肿瘤生长、侵袭和转移过程中,肿瘤血管和淋巴管的生成是重要的影响因素.随着对血管内皮生长因子(VEGF)家族的深入研究,逐渐发现其在肿瘤淋巴管的生成中起重要调控作用.现综述与肿瘤转移相关的淋巴管解剖特征、肿瘤淋巴管生成、转移中的分子调控机制及治疗策略等.     

淋巴管与肿瘤转移

肿瘤转移中淋巴转移是其最常见、最基本的途径，在肿瘤生长、侵袭和转移过程中，肿瘤血管和淋巴管的生成是重要的影响因素。随着对血管内皮生长因子(VEGF)家族的深入研究，逐渐发现其在肿瘤淋巴管的生成中起重要调控作用。现综述与肿瘤转移相关的淋巴管解剖特征、肿瘤淋巴管生成、转移中的分子调控机制及治疗策略等。     

MiRNA在肿瘤血管生成中的研究进展

摘 要：肿瘤血管生成在肿瘤的生长和转移过程中发挥重要的作用。微小RNA（microRNA,miRNA）是一类内源性单链非编码RNA分子,通过转录后水平调控广泛参与肿瘤相关生物学过程。MiRNA通过调控促血管生成因子、血管生成抑制因子及血管生成相关信号通路来促进或抑制肿瘤血管生成,并介导肿瘤细胞和血管内皮细胞间细胞通讯。全文对miRNA在肿瘤血管生成中的调控作用进行总结,并对miRNA作为抗肿瘤血管生成新的治疗手段及抗血管生成治疗效果生物标志物的临床意义进行讨论。     

恶性肿瘤微血管研究进展

恶性肿瘤生长、转移均依赖新生血管生成,而且肿瘤诱导血管生成的能力与其侵袭能力相关,近年来,在肿瘤领域研究的重大进展之一就是,确立了肿瘤血管生成在肿瘤发展中的重要地位与抗血管生成治疗肿瘤的意义。研究发现,恶性肿瘤微血管表现为形态和结构不均一性,导致其通透性增高,另外多种生物因子参与其生成调控,在恶性肿瘤微血管中,主要表现在促血管生成因子的活性上调和（或）血管生成抑制因子的活性下调,为肿瘤增殖和转移奠定了基础,恰当的计数方法及微血管标志的选择能够更好地反映微血管的特性。目前,阻断肿瘤血管新生已成为抗肿瘤治疗的研究热点,以avastin为代表的抗血管生成药物在肿瘤治疗中起着重要的作用,临床疗效确切,是一类很有希望的药物。     

血管内皮细胞生长因子与肿瘤血管、淋巴管生成

肿瘤的发生、发展和转移与血管的生成密切相关;肿瘤的淋巴转移是最常见、最基本的途径.故在肿瘤生长、侵袭和转移过程中,肿瘤血管和淋巴管的生成是重要的影响因素.随着对血管内皮生长因子(VEGF)家族的深入研究,发现其在肿瘤血管和淋巴管生成中均起着重要的调控作用.现综述VEGF家族分别与肿瘤血管和淋巴管生成的关系,以及抗血管、淋巴转移的治疗进展.     

血管生成相关因子在肿瘤中的表观遗传学变化

在肿瘤的发生、发展和转移过程中,新生血管的生成起着至关重要的作用,此过程受到相关血管生成因子的调控,这种调控既包括遗传学方面的,也包括表观遗传学方面的.与遗传学的变化不同,表观遗传学变化大多是可逆的.研究者正试图应用DNA甲基化转移酶抑制剂和组蛋白去乙酰化酶抑制剂来拮抗肿瘤及其血管的生成,从而指导肿瘤的临床治疗.本文综述了近年来受表观遗传调控的肿瘤血管生成相关因子的研究进展,阐述了其在肿瘤血管新生过程中表观遗传的调控作用.     

抗血管生成药物长期治疗致肿瘤侵袭转移相关机制的研究进展

抗血管生成药物治疗在临床上取得了一定疗效,许多患者因此获益。然而,部分肿瘤患者长期使用抗血管生成药物后会发生肿瘤转移。原因可能是长期抗血管生成药物治疗会造成肿瘤微环境的乏氧,刺激乏氧诱导因子（hypoxia inducible factors ,HIFs ）的产生。HIFs 参与乏氧信号通路调节肿瘤侵袭转移的各个环节,促进肿瘤细胞上皮- 间质转化（epithelial-mesenchymal transition ,EMT ）的形成,改变血管外周细胞及内皮细胞连接之间的特性,使肿瘤细胞更易进入外周血液循环,随血流到达远处器官并形成转移灶。本研究将对抗血管生成药物长期治疗与肿瘤侵袭转移相关机制的研究进展作一综述。      

肿瘤血管生成及抗血管生成基因治疗

肿瘤的侵袭和转移明显影响患者的预后,而肿瘤的血管生成是肿瘤生长、侵袭、转移的基本条件。因而抑制肿瘤血管生成是治疗肿瘤的关键。本文就肿瘤血管生成的调控及抗肿瘤血管生成基因治疗的研究进展作一综述。     

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.