血管内皮生长因子在肝细胞癌血清中的表达意义

目的研究血管内皮生长因子(vascularendothelialgrowthfactor,VEGF)在肝细胞癌(HCC)患者周围血血清中的表达水平与肝癌临床病理特征及肝癌转移复发之间的关系.方法运用sandwich酶联免疫吸附测定法定量检测115例HCC、40例肝脏良性疾病患者和30例健康人血清中VEGF的含量.结果HCC组血清VEGF表达水平[(465.62±336.24)pg/ml]与肝脏良性疾病组[(159.54±120.58)pg/ml]、与健康人组[(123.53±51.84)pg/ml]比较,差异均有显著性(P值均=0.0001);VEGF表达阳性率分别为77.4%、25.0%和3.3%.HCC转移组患者血清VEGF表达水平与未转移组相比,差异有显著性(P=0.001).血清VEGF表达水平还与HCC合并门静脉瘤栓、肿瘤大小和TNM分期密切相关,VEGF含量随TNM分期升高而逐步升高.结论疗前HCC患者的血清VEGF表达水平,是反映HCC侵袭生长及转移潜能的有效生物学指标.     

NSCLC微波消融前后血清VEGF、Arg-1、iNOS水平变化及其相关性

目的 探讨微波消融治疗非小细胞肺癌(NSCLC)的疗效,分析微波消融前后NSCLC患者血清血管内皮生长因子(VEGF)、精氨酸酶-1(Arg-1)、诱导型一氧化氮合酶(iNOS)浓度的变化及三者之间的关系.方法 选取30例健康体检者作为对照组,30例晚期NSCLC患者为试验组,用酶联免疫吸附试验(ELISA)法检测健康体检者、晚期NSCLC患者微波消融术前及术后第1天、第3天、1个月血清VEGF、Arg-1、iNOS浓度.结果 微波消融治疗晚期NSCLC的有效率为33.3％ (10/30),疾病控制率为70.0％(21/30).微波消融术前NSCLC患者血清VEGF、Arg-1、iNOS浓度分别为(816.56±13.26)pg/ml、(5.17±0.20) ng/ml、(544.18±13.93) pg/ml,明显高于对照组的(93.43±9.93) pg/ml、(1.08±0.05) ng/ml、(8.08-±0.33) pg/ml,差异均有统计学意义(t=239.093,P＜0.001;t=110.359,P＜0.001;t=210.792,P＜0.001).晚期NSCLC患者微波消融术后第1天、第3天、1个月血清VEGF浓度分别为(708.41±10.49)pg/ml、(592.63±7.25) pg/ml、(521.91±8.32) pg/ml,均较治疗前明显降低(均P ＜0.05);Arg-1浓度分别为(5.95±0.10) ng/ml、(7.02±0.13) ng/ml、(7.67±0.92) ng/ml,均较治疗前明显升高(均P ＜0.05);iNOS浓度分别为(453.01±9.48)pg/ml、(393.21±9.42) pg/ml、(352.60±8.31)pg/ml,均较治疗前明显降低(均P＜0.05).NSCLC患者治疗前血清iNOS与VEGF表达呈正相关(r =0.379,P=0.039),Arg-1与VEGF表达呈负相关(r=-0.556,P=0.001),iNOS与Arg-1表达无关(r=-0.238,P=0.205).结论 微波消融是一种有效的NSCLC局部治疗手段,除可直接杀灭癌细胞外,亦可影响VEGF、Arg-1、iNOS表达水平,VEGF与iNOS和Arg-1有一定相关性,而iNOS与Arg-1无关.微波消融可在一定程度上改变肿瘤微环境,刺激机体产生抗肿瘤免疫.     

50例肺癌患者血清VEGF、p53含量的分析

目的研究肺癌患者血清血管内皮生长因子(VEGF)与p53含量的变化,探讨VEGF与p53在血清中的协同表达与肺癌的相互关系。方法标本采用ELISA法测定VEGF及p53水平。结果血清VEGF含量正常对照组为108.42±20.94pg/m l,肺癌组为3 8 3.3 9±1 5 7.4 5 pg/m l,二组比较有显著性差异(t=125.946,P<0.001),血清p53含量正常对照组为0.24±0.041 U/m l,肺癌组为0.82±0.283 U/m l,二组比较有显著性差异(t=6.92,P<0.001)。结论通过对肺癌患者血清VEGF与p53含量的研究,可以为肺癌的诊断、治疗提供依据。     

胃癌患者血清中MMP-9的水平及其癌组织中MMP-9与VEGF的表达

目的:探讨胃癌患者血清及其癌组织中基质金属蛋白酶-9(MMP-9)的水平,血管内皮生长因子(VEGF)在癌组织中的表达并研究两者与胃癌预后的关系。方法:运用ELISA法检测40例胃癌患者手术前后血清中MMP-9的水平。同时应用免疫组化法检测了40例手术标本中MMP-9、VEGF蛋白的表达,原位杂交技术检测MMP-9mRNA的表达。结果:术前血清MMP-9水平(371.71±61.05ng/ml)与癌组织浸润程度、TNM分期、淋巴结转移关系密切(P<0.05);术前血清MMP-9水平明显高于术后(192.78±42.29ng/ml)及正常对照组(77.43±31.63ng/ml)(P<0.05);MMP-9蛋白在胃癌组织中的阳性表达率为60.0%,与胃癌的浸润程度、TNM分期、分化程度、淋巴结转移有关(P<0.05);原位杂交检测结果与免疫组化一致;血清MMP-9水平与组织MMP-9蛋白表达呈一致性;VEGF蛋白在胃癌组织中的阳性表达率为55.0%,与TNM分期、淋巴结转移关系密切(P<0.05);胃癌组织VEGF蛋白表达与MMP-9蛋白表达具有明显相关性(P<0.05)。结论:MMP-9、VEGF在肿瘤浸润转移中起重要作用;联合检测两者的表达,特别是检测术后血清中MMP-9的水平有助于判断胃癌患者的预后。     

血管内皮生长因子在胃癌血清中的表达意义

目的　探讨血管内皮生长因子 (vascular endothelial growth factor,VEGF)在胃癌患者血清中的含量与胃癌临床病理特征及预后监测的关系。方法　应用酶联免疫双抗夹心法 (EL ISA)定量检测 5 6例胃癌患者 (肿瘤组 )术前、术后及 31例术后随访胃癌患者血清中 VEGF含量 ,并同期检测 16例溃疡患者 (非肿瘤组 )及 4 5例健康人 (对照组 )血清 VEGF浓度。结果　肿瘤组血清 VEGF含量 (2 5 7.5± 10 7.3) pg/ ml明显高于溃疡组 (132 .0±5 6 .3) pg/ ml与正常对照组 (12 1.4± 4 2 .5 ) pg/ ml;三组 VEGF阳性率分别为 6 9.8%、2 5 .0 %和 11.1%。VEGF水平与胃癌的血管浸润、淋巴结受累及肝转移密切相关 ,且其含量随 TNM分期升高而增高 ,而与患者年龄、性别、肿瘤大小及组织分化等因素无关 ;术后随访的肿瘤复发 /转移者血清 VEGF与未复发 /转移者比较 ,则显著升高。结论　术前胃癌患者血清 VEGF表达水平是反映胃癌侵袭生长及转移潜能的生物学指标之一 ,对术后复发和预后的监测有一定的临床价值     

IGF-1在胃癌组织中的表达及其与浸润转移的关系

[目的]探讨胃癌中IGF-1蛋白的表达及其与肿瘤浸润转移的关系。[方法]免疫组织化学技术分析436例胃癌组织及92例邻近正常胃黏膜组织石蜡标本中IGF-1的表达。[结果]IGF-1在正常胃黏膜组织的表达低于胃癌组织(0 vs 49.5%,χ2=77.132,P<0.001);IGF-1表达与胃癌患者肿瘤大小、分化、侵犯深度、分期、淋巴结转移、远处转移、脉管侵犯、Lauren分型相关,而与组织学类型、性别无关。胃癌患者中肿瘤大小≥5cm患者的IGF-1阳性表达率为64.4%,明显高于<5cm的患者(39.1%,χ2=27.238,P<0.001);弥漫型胃癌患者IGF-1的阳性表达率明显高于肠型患者(85.0%vs 15.7%,χ2=209.184,P<0.001);T3、T4期胃癌患者的IGF-1阳性表达率分别为62.7%、92.3%,明显高于T1、T2期的10.5%、30.3%(χ2=86.830,P<0.001);脉管侵犯患者的IGF-1阳性表达率明显高于无脉管侵犯者(71.5%vs 19.1%,χ2=116.710,P<0.001);淋巴结转移患者的IGF-1阳性表达率为70.0%,明显高于无淋巴结转移者(16.3%,χ2=118.740,P<0.001);远处转移患者的IGF-1阳性表达率为95.1%,明显高于无远处转移者(42.1%,χ2=58.841,P<0.001)。[结论]IGF-1与胃癌的发生发展有关,参与胃癌的浸润转移进程。检测IGF-1的表达可作为判断胃癌生物学行为的重要参考指标。     

非小细胞肺癌患者介入治疗前后血清HIF-1α、VEGF的变化及相关性研究

目的:探讨非小细胞肺癌(non-small cell lung cancer,NSCLC)患者介入治疗前后血清缺氧诱导因子-1α(hypoxia-inducible factor 1 alpha,HIF-1α)和血管内皮生长因子(vascular endothelial growth factor,VEGF)水平的动态变化规律及两者间的相关性。方法:采用酶联免疫吸附试验法(enzymelinked immunosor-bent assay,ELISA)检测40例NSCLC患者介入治疗前、后及30例健康体检者血清HIF-1α、VEGF水平。结果:NSCLC患者血清HIF-1α水平(49.03±8.36)ng/L显著高于正常对照组(37.69±3.33)ng/L(P<0.001);介入治疗前、治疗后1天及7天血清HIF-1α水平分别为:(49.03±8.36)ng/L、(53.46±7.66)ng/L、(60.83±9.43)ng/L,组间比较差异具有统计学意义(P<0.02);NSCLC患者血清VEGF水平(742.71±113.09)pg/ml显著高于正常对照组(592.81±71.01)pg/ml(P<0.001);介入治疗前、治疗后1天及7天血清VEGF水平分别为(742.71±113.09)pg/ml、(877.47±164.29)pg/ml、(1119.00±164.27)pg/ml,组间比较差异具有统计学意义(P<0.001)。介入治疗前、介入治疗后1天及7天血清HIF-1α水平与血清VEGF水平均存在正相关性(r=0.506,P<0.01;r=0.406,P<0.01;r=0.525,P<0.01)。结论:NSCLC患者血清HIF-1α及VEGF水平介入治疗后显著升高,且两者存在显著正相关性。     

胃癌病人血清中血管内皮生长因子与胃癌的血管生成

目的:检测胃癌患者术前血清中血管内皮生长因子(VEGF)浓度及胃癌组织中微血管密度(MVD),探讨血清中VEGF浓度与胃癌血管生成之间的关系。方法:应用酶联免疫技术(ELISA法)检测51例胃癌患者血清中VEGF浓度;应用抗人CD_(34)单克隆抗体进行免疫组织化学染色检测胃癌组织中MVD。结果:胃癌组织中MVD与血清中VEGF浓度呈显著性相关(r=0.938,P<0.01)。胃癌患者血清VEGF浓度与胃癌浸润深度(P<0.05)、淋巴结转移(P<0.01)、远处转移(P<0.01)、肿瘤分期(P<0.05)及肿瘤组织学分型(P<0.05)密切相关,与性别无关(P>0.05)。结论:胃癌的血管生成与血清中VEGF浓度密切相关,检测术前胃癌患者血清VEGF浓度可预测胃癌血管生成情况,可能有助于指导临床治疗。     

晚期神经母细胞瘤患者血清VEGF水平的临床意义

[目的]探讨晚期神经母细胞瘤(NB)患者血清血管内皮生长因子(VEGF)水平的意义。[方法]采用ELISA法检测晚期NB患者血清VEGF水平,并取健康儿童血清作为对照。[结果]初治/复发组患者血清VEGF水平[(548.66±295.22)ng/L]明显高于对照组[(300.46±169.14)ng/L]及完全缓解(CR)/良好部分缓解(PR)组[(280.22±179.38)ng/L](P<0.05)。14例CR患者治疗前较治疗后VEGF水平明显降低[(242.67±214.42)ng/Lvs(481.55±250.41)ng/L](P<0.05)。[结论]晚期NB患者血清VEGF水平升高,经有效治疗后可显著降低,可作为监测治疗反应的一项重要指标。     

原发性肝癌患者血清高水平VEGF的意义

目的:研究血清血管内皮生长因子(vascularendothelial growth factor, VEGF)水平与肝癌临床病理及肿瘤病理学之间的关系。方法:应用VEGF 165定量夹心ELISA法测定30 例正常人、30 例肝硬化和45例肝癌患者外周血清中VEGF的水平,并结合临床及肿瘤病理学的特点进行统计学分析。结果:正常人血清VEGF水平为(153±71)pg/mL,分布范围为(6~371) pg/mL;肝硬化患者血清VEGF水平为(158±67)pg/mL,分布范围为(4~352) pg/mL;45例肝癌患者血清VEGF为(312±206) pg/mL,分布范围为(34~968)pg/mL。肝癌患者的外周血VEGF水平显著高于正常人和肝硬化患者,P<0. 01。高水平的血清VEGF与肝癌的大小、包膜的不完整以及转移与复发有关, P<0. 01,而与肿瘤的分化程度无关, P>0 .01。当肿瘤发展到第Ⅳ期,血清VEGF水平显著升高, P<0. 01。结论:血清VEGF高水平是肝细胞肝癌具有血管侵犯和转移潜在危险的指标,预示不良的预后。     

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.