砷剂对肺腺癌细胞凋亡及LRP、C-myc基因表达的影响

目的:研究三氧化二砷(arsenic trioxide,As2O3)对人肺腺癌的抑制和诱导凋亡作用及对肺耐药蛋白基因(lung resistance protein,LRP)、C-myc基因表达的影响及可能机制.方法:选用人肺腺癌A549细胞株,运用体外细胞培养法,MTT法,流式细胞术检测As2O3对人肺腺癌的抑制和诱导凋亡作用;用反转录-聚合酶链反应(RT-PCR)方法检测LRP、C-myc mRNA的表达.结果:As2O3对人肺腺癌A549细胞具有抑制作用,其抑制率呈时间-剂量依赖关系.不同浓度的As2O3均可诱导凋亡.1.0μmol/L、2.0μmol/L的As2O3可下调LRP的表达.结论:As2O3具有抑制肿瘤细胞增殖作用,主要是通过诱导细胞凋亡实现的,其机制与下调LRP、C-myc表达有密切关系.     

砷剂对肺腺癌细胞凋亡及LRP、C—myc基因表达的影响

目的：研究三氧化二砷（arsenictrioxide,As2O3）对人肺腺癌的抑制和诱导凋亡作用及对肺耐药蛋白基因（1ungresistance protein,LRP）、C—myc基因表达的影响及可能机制。方法：选用人肺腺癌A549细胞株,运用体外细胞培养法,MTF法,流式细胞术检测As2O3,对人肺腺癌的抑制和诱导凋亡作用;用反转录-聚合酶链反应（RT—PCR）方法检测LRP、C—mycmRNA的表达。结果：As2O3对人肺腺癌A549细胞具有抑制作用,其抑制率呈时间-剂量依赖关系。不同浓度的As2O3均可诱导凋亡。1．0μmol／L、2．0μmol／L的As2O3可下调LRP的表达。结论：As2O3具有抑制肿瘤细胞增殖作用,主要是通过诱导细胞凋亡实现的,其机制与下调LRP、C—myc表达有密切关系。     

三氧化二砷对人肾癌细胞A-704的抑制作用研究

目的研究三氧化二砷（Arsenic trioxide，As2O3）对人肾癌细胞系A-704细胞生长的抑制作用。方法采用体外培养A-704细胞株与不同浓度的As2O3进行作用，应用形态学观察、琼脂糖凝胶电泳、MTT法检测观察As2O3对细胞的增殖抑制和诱导凋亡的作用。结果As2O3能够抑制A-704细胞的增殖，出现凋亡的形态学改变和DNA片段化，且呈时间剂量依赖性，在浓度为0．5、1．0、2．0、4．0μmol／L作用96小时，As2O3对A-704细胞的抑制率分别40．01％、43，72％、47．54％、53．61％与未经As2O3处理的细胞相比，均有显著差异（P〈0．05）。结论As2O3对A-704细胞具有显著的增殖抑制作用，并具有浓度和时间依赖性特点。     

三氧化二砷对人肺腺癌A549细胞株生长及对Survivin基因表达的影响

目的:研究三氧化二砷(As2O3)对人肺腺癌细胞株A549的生长抑制作用和对Survivin基因表达的影响,探讨As2O3抑制肺癌细胞增殖的机制。方法:体外培养A549细胞,通过不同剂量的As2O3与A549细胞株共培养,以台盼兰染色后鉴定活细胞计数,计算细胞生长抑制率及存活率;进一步应用Western blot方法检测Survivin表达情况;分析三氧化二砷抑制Survivin的表达水平与A549细胞存活的相关性。结果:As2O3能明显抑制A549细胞株的生长,具有浓度和时间依赖性;As2O3能明显下调Survivin蛋白的表达水平,亦具有浓度和时间依赖性;且Survivin蛋白的表达下调与肿瘤细胞存活率成负相关。结论:As2O3在体外可以明显抑制A549细胞株的生长,并显著抑制Survivin基因的表达。     

低氧条件下三氧化二砷对人肺腺癌A549细胞增殖的影响

目的:对比研究常氧和低氧条件下三氧化二砷（arsenic trioxide,As2O3）对人肺腺癌A549细胞增殖的抑制作用。方法:分别在常氧（21％ O2）和低氧（5％ O2）条件下以1、2、4 μmol/L As2O3处理人肺腺癌A549细胞，12、24、48 h后收集细胞，以MTT法检测细胞增殖抑制率，以Annexin VPI双染色流式细胞术检测细胞凋亡，分析两种条件下As2O3对细胞增殖抑制率及凋亡率的影响。结果: 常氧及低氧条件下，细胞增殖抑制率、细胞早期凋亡率及总凋亡率均随As2O3浓度的增加及作用时间的延长而增加（均P<0.05），晚期凋亡率变化不显著。在As2O3相同浓度、相同处理时间，低氧条件下细胞增殖抑制率及凋亡率较常氧条件下无明显降低。结论: As2O3可促进细胞凋亡，显著抑制A549细胞增殖，且在低氧条件下的上述作用未见减弱。     

托盘根乙醇提取物的抗癌作用研究

目的　观察托盘根乙醇提取物 ( ERC)对肿瘤生长的影响。方法　用 MTT法观察 ERC体外对人肿瘤SPC- A- 1细胞的影响 ,体内抑瘤实验观察 ERC对 L ewis肺癌的作用。结果　 ERC体外明显抑制 SPC- A- 1细胞的生长 ,体内明显抑制 L ewis癌块增大 ,减少 L ewis肺转移结节数。结论　 ERC对肺癌细胞系有明显抗肿瘤作用     

丙戊酸钠和亚砷酸对Molt-4细胞的协同抑制作用

目的 观察丙戊酸钠(VPA)以及亚砷酸(As2O3)对人类急性T细胞白血病细胞株Molt-4增生、分化和细胞周期的影响以及二者的协同作用.方法 用MTT法观察细胞生长曲线及药物对细胞增生的抑制作用,流式细胞仪检测给药前后DNA含量变化等方法,观察了As2O3和VPA对Molt-4细胞体外抗癌的协同作用.结果 VPA和As2O3均可明显抑制细胞增生,VPA对Molt-4细胞抑制率为50%的浓度即JC50卯为4.904 mmol/L;As2O3的IC50为9.925μmol/L;当二者联用时在体外有相加作用(Q值均＞0.85),在5 mmol/L VPA与10 μmol/L As2O3联用时抑制率达(70.31±2.54)%.流式细胞术检测示经不同浓度VPA处理后G1期细胞由28.21%增加至71.89%,S期细胞由71.75%减低至9.49%.结论 VPA和As2O3均可明显抑制细胞增生,两者合用有协同相加作用,其机制有待进一步研究.     

As2O3联用IFN-α诱导肾癌细胞株789-0凋亡的实验研究

目的:研究不同浓度As2O3对肾癌细胞株789-0的凋亡影响及联用IFN-α有无协同作用,并探讨其作用机制.方法:采用MTT法检测As2O3单用及联用IFN-α对细胞增殖的影响,流式细胞仪检测其对细胞周期和凋亡的影响.结果:(0.5-4)μmol/L的As2O3对肾癌789-0细胞的增殖均有一定抑制作用,且随浓度增加呈增强趋势.联用1000IU的IFN-α后,肾癌细胞的增殖抑制率明显高于相应浓度的单用As2O3组,具协同作用.2.83μmol/L.(IC50)的As2O3作用于肾癌789-0细胞48h后呈现G2/M期阻滞,凋亡特征明显;联用IFN-α后呈现Go/C1期、G2/M期阻滞,凋亡率显著增高.结论:As2O3能抑制肾癌789-0细胞的增殖并诱导细胞凋亡,联用IFN-α可产生协同作用.其机制可能与干扰细胞周期的不同时相有关.     

唑来膦酸对肺癌细胞生长抑制的观察及机制的初步研究

目的:研究唑来膦酸对非小细胞肺癌(NSCLC)细胞株A-549生长抑制及诱导凋亡的作用。方法:用MTT法测定唑来膦酸、泰索帝及二药联合对肺癌细胞A-549的生长抑制率,流式细胞仪检测细胞周期、细胞凋亡率。结果:0·1~100μmol/L的唑来膦酸对肺癌细胞A-549均有抑制作用,首先表现为G1期阻滞,继而出现细胞凋亡,呈剂量、时间依赖性,并且与泰索帝联用可以提高细胞凋亡率。结论:唑来膦酸对肺癌细胞A-549具有明显抑制作用,且与泰索帝联用有协同作用,其作用机制可能是通过诱导细胞凋亡来实现的。     

As2O3对人膀胱癌细胞凋亡和MDR1表达及细胞周期的影响

目的 :观察三氧化二砷 (As2 O3 )对人膀胱癌细胞株BIU 87的凋亡诱导作用及对多药耐药基因 (MDR1)蛋白表达、细胞周期的影响。方法 :采用四氮唑蓝 (MTT)法检测As2 O3 不同浓度、不同作用时间对BIU 87细胞的生长抑制率 ;流式细胞术(FCM )检测不同浓度As2 O3 作用 72h后细胞中与凋亡有关蛋白Fas、bcl 2及MDR1蛋白表达、细胞周期变化。结果 :As2 O3 可有效抑制BIU 87细胞的生长增殖 ,与浓度、时间相关 ,P <0 0 5 ;Fas、bcl 2的表达分别与浓度增高呈正、负相关 ,P <0 0 5 ,且二者随浓度增高呈负相关 ,P <0 0 5 ;MDR1蛋白表达与对照组相比As2 O3 1μmol/L作用后升高 ,P <0 0 5 ,2、5 μmol/L作用后降低 ,P <0 0 5 ;随As2 O3 浓度升高 ,细胞周期被阻滞在G0 /G1期。结论 :As2 O3 可有效抑制人膀胱癌细胞的生长增殖 ,诱导细胞凋亡及阻滞细胞周期可能起了重要作用     

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.