肿瘤混合粘液核芯肽诱导的人肿瘤引流区淋巴结细胞毒反应

我们采用凝胶过滤和密度梯度离心技术从胰腺癌细胞株SW1990细胞匀浆和细胞培养上清中提取了肿瘤粘液，用无水氢氟酸去掉糖链后，经鉴定为不含糖的肿瘤混合粘液核芯肽(MUC)，主要成份为MU-C1、MUC2和MUC3。动物实验表明具有诱发细胞免疫反应作用，本研究进一步观察其诱导人肿瘤引流区淋巴结细胞的体外扩增及溶瘤的作用。     

胃周淋巴结淋巴因子激活的杀伤细胞抗肿瘤研究

淋巴细胞经白细胞介素-2(Interleukin-2,IL-2)体外诱导培养后,可产生明显的杀伤肿瘤细胞活性,此杀伤细胞称为LAK细胞(lymphokine activated killer cells)。本实验取19例胃癌患者胃引流区淋巴结淋巴细胞(gastric drainage lymphnode lymphocytes,GDLNL),在体外经重组白细胞介素-2诱导培养若干天后,对高分化胃腺癌细胞MNK_(28)进行体外杀伤实验。结果提示,无癌转移的淋巴结淋巴细胞在诱导培养3天～2周内,LAK活性较高;而有癌转移的淋巴结淋巴细胞在2周内亦有明显的LAK活性,但较低,以后逐渐升高,3周最高,且至5周时,仍有杀伤肿瘤活性。     

人癌相关粘蛋白前体诱发小鼠抗肿瘤免疫反应的研究

从胰腺癌细胞株ＳＷ１９９０提取粘蛋白核心肽，加佐剂ＤＥＴＯＸ免疫ＢＡＬＢ／Ｃ小鼠，观察其诱发小鼠的抗肿瘤免疫反应。六次免疫后，产生了皮肤迟发超敏反应，其脾细胞在体外可杀伤种种瘤细胞，包括胃癌，结肠癌，胰腺癌；对急性料细胞白血病Ｋ５６２也有弱杀伤。     

胰、脾

树突细胞负载K-ras突变多肽诱导抗胰腺癌免疫反应；HIF-1α、VEGF在胰腺癌组织中的表达及其与血管新生的关系；胰头癌根治术联合血管切除的术中评估和操作要点；2cm以下的胰头癌的临床特点和外科治疗；K-ras突变多肽诱导胰腺癌免疫治疗的实验研究；外围血γδT细胞在胰腺癌裸鼠过继免疫治疗中的作用；细针穿刺细胞学检查在胰腺及壶腹周围肿瘤手术中的应用；无症状胰腺肿瘤的诊断与治疗。[编者按]     

人胰腺癌相关粘蛋白核芯多肽的提取与特性

应用分子筛层析及氯化铯密度梯度离心从人胰腺癌细胞株SW1990提取、纯化获得粘蛋白,再用氟氢酸去除粘蛋白的碳水化合物而获得核芯肽。对粘蛋白核芯肽进行了氨基酸组份分析,并以免疫印迹及ELISA法进行免疫原分析,结果表明所提取的核芯肽至少含有Muc-1,Muc-2,及Muc-3三种不同氨基酸序列的多肽,免疫印迹表明此核芯肽含有从28至大于90KD的多条肽。在此基础上,制备了抗此核芯肽的单克隆抗体,5株单克隆抗体与多种癌细胞起反应,但多不与正常组织起反应,仅一株单克隆抗体MY-5与部分正常组织反应。这为进一步观察癌相关核芯肽病理生理功能打下了基础。     

肿瘤疫苗(Lipostn)诱导肿瘤引流区淋巴结淋巴细胞的体外溶瘤作用

从12例胃癌患者，6例结肠癌患者引流区淋巴结中分离淋巴细胞，与肿瘤疫苗(Lipostn)中非佐剂部分在体外共培养扩增．借助MTT比色法及^61Cr释放实验研究了淋巴结淋巴细胞在Lipostn的刺激后对抗原表达阳性和阴性的传代肿瘤细胞系的杀伤效应。实验结果表明：(1)．肿瘤引流区淋巴细胞与在无分裂原的刺激下被Lipostn刺激，     

粘蛋白核芯肽MUC1的基因结构及其在肿瘤生物治疗中的意义

MUC~1是一系列粘蛋白核芯肽(apomucin)分子的一员,存在于正常的导管上皮细胞及某些肿瘤细胞表面,在维持正常细胞的生理功能及肿瘤发生、发展、转移等病理过程中起重要作用。随着MUC~1的克隆,粘蛋白核芯肽的其它成员的结构及生物学意义相继被阐明,针对它们不同的表位制成不同的疫苗,为肿瘤的主动特异性免疫治疗提供了一个新途径。     

自体可溶性肿瘤抗原协同IL-2诱导外周血单个核细胞体外增殖及杀瘤作用的研究

本研究观察了胃癌自体可溶性肿瘤抗原协同IL-2诱导外周血单个核细胞(peripheral blood monoclear cells,PBMC)体外增殖及杀瘤作用.我们以生化方法提取胃癌自体可溶性抗原(rumor soluible antigen,TSA),协同IL-2体外培养淋巴细胞,MTT法测定增殖及杀瘤作用,APAAF法检测细胞表型变化.结果表明,一定剂量TSA可协同IL-2诱导PBMC增殖及杀瘤,单独TSA无此效应.促增殖效应呈时间剂量依赖特征.E/T为80:1时,TSA协同诱导的PBMC杀瘤活性为86.3%,单独IL-2诱导时为48.6%.表型测定表明,TSA协同诱导的PBMC其CD25及CD8表达均显著增高.由此可见,粗提自体胃癌抗原具有诱导T细胞增殖及杀伤肿瘤作用,提示增殖的T细胞可望用于肿瘤的临床过继免疫治疗.     

胰、脾

联合应用双自杀基因对SW1990细胞的杀伤作用//逆转录病毒介导的CD／5-FC对胰腺癌细胞的杀伤作用//胰头癌淋巴结转移的临床研究//胰岛素瘤的诊断与治疗//高强度聚焦超声治疗晚期胰腺癌//常规分村立体定向适形放射治疗晚期胰腺癌28例临床观察//^125I种子檀入内照射联合化疗治疗胰腺癌临床疗效的初步评价。     

树突细胞负载K-ras突变多肽诱导抗胰腺癌免疫反应

背景与目的:由于大多数肿瘤抗原尚未确定,所以肿瘤的免疫治疗还处于临床探索阶段。k-ras原癌基因在胰腺癌中有特异性的表达,突变位点恒定,不失为一个良好的免疫靶位。本研究探讨以k-ras基因为靶点体外诱导胰腺癌被动免疫治疗的可行性,为临床进行胰腺癌个体化治疗提供实验依据。方法:利用RT-PCR法扩增k-ras基因,通过流式细胞术检测k-ras癌基因突变类型。合成含突变位点的多肽,负载外周血单核细胞来源的树突细胞(dendritic cell,DC),检测其表达率,对T细胞进行激发活化,M TT法检测肿瘤特异性T细胞对胰腺癌细胞Patu8988的杀伤作用。结果:Patu8988胰腺癌细胞株12位密码子点突变为GGT→GTT,12位氨基酸突变为缬氨酸。合成突变多肽能有效地在树突细胞表达突变位点,激发的肿瘤特异性T细胞(cytotoxic T lym phocytes,CTLs)能有效地杀伤相应的肿瘤细胞。结论:突变多肽能有效地诱导免疫细胞杀伤含k-ras突变基因的胰腺癌细胞,从而为胰腺癌的免疫治疗提供实验依据。     

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.