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Contexte Des travaux antérieurs ont montré que l'interleukine-6 circulante (IL-6) était un facteur prédicteur significatif de la survenue de seconds cancers primaires (SCP) chez les patients atteints d'un cancer de la sphère oto-rhino-laryngologique (ORL). Objectif Le but de cette étude était d'identifier les facteurs associés aux niveaux sériques d'IL-6 chez les patients atteints de cancer ORL de stade I-II. Méthodes Cette étude a été réalisée dans le cadre d'un essai de chimioprévention de phase III. Un échantillon de sérum a été obtenu avant tout traitement auprès de 527 des 540 patients présentant un cancer ORL recrutés pour participer à l'essai clinique. L'IL-6 a été mesurée par immunométrie chimioluminescente. Les caractéristiques sociodémographiques et cliniques des patients, leurs habitudes de vie et les caractéristiques de leur tumeur ont été évaluées. Les facteurs indépendamment associés aux niveaux sériques d'IL-6 ont été identifiés en utilisant un modèle de régression linéaire multiple. Résultats La concentration médiane d'IL-6 dans le sérum était de 3,1 ng/L (intervalle interquartile : 2,20-4,40). L'analyse multivariée a permis d’identifier huit facteurs significativement associés à l'IL-6 (P ≤ 0,05) : l’âge, le sexe, le statut matrimonial, l’indice de masse corporelle, le tabagisme, l’indice de comorbidités, le score de performance de Karnofsky et le site tumoral. Chez les fumeurs, les taux sériques d'IL-6 augmentaient de façon dose-dépendante avec la durée du tabagisme (p de tendance = 0,03) et avec le nombre de paquets-années consommés (p de tendance = 0,03). Conclusion Ces résultats ont montré que plusieurs facteurs de risque standards de SCP sont aussi associés aux taux circulants d'IL-6. Ceci suggère que l'effet de ces facteurs sur la survenue de SCP pourrait être médié par un processus inflammatoire. De plus, nous avons montré une relation doseréponse avec la quantité ou la durée du tabagisme, suggérant un rôle causal du tabac dans la production d'IL-6. / Background In a previous work, we reported that circulating interleukin-6 (IL-6) significantly improves outcome prediction for second primary cancer (SPC) in head and neck cancer (HNC) patients. Objective The purpose of this study was to identify factors associated with IL-6 serum levels in patients with stage I or II HNC. Methods This study was conducted as part of a phase III chemoprevention trial. A pretreatment serum sample was obtained from 527 of the 540 HNC patients recruited in the trial. IL-6 was measured on an Immulite analyzer with chemiluminescent immunometric assay (Siemens Diagnostics). Patients’ sociodemographic and medical characteristics, lifestyle habits and cancer characteristics were evaluated before radiation therapy. Factors independently associated with IL-6 levels were identified using the multiple linear regression. Results The median of IL-6 serum level was 3.1 ng/L (Interquartile range: 2.20-4.40). In the multivariate analysis, eight factors were significantly associated with IL-6 (P ≤ 0.05): age, sex, marital status, body mass index (BMI), smoking, comorbidity index, Karnofsky performance status, and cancer site. In cigarette smokers, IL-6 serum levels increased with longer durations of cigarette smoking (p-value for trend = 0.03) and with the number of pack-years consumed (p-value for trend = 0.03). Conclusion These results showed that several standard risk factors of SPC, such as age, BMI and smoking status, are associated with circulating IL-6 levels. This suggests that the effect of these factors on the occurrence of SPC might be mediated by an inflammatory process. Moreover, we have shown a dose-response relationship with the quantity smoked or the duration of smoking suggesting a causal role of tobacco in IL-6 production.

Mémoire d'orthophonie : Médecine : Nancy 1 : 2009. / Titre provenant de l'écran-titre. Bibliogr.

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To personalize treatment for cancer, correct staging of the primary tumor, nodal disease and metastatic disease is of essence. By targeting tumor specific receptors with radiolabeled antibodies, specificity and accuracy of imaging may be improved. Radio-immunodiagnostics can potentially detect small volume disease, occult metastasis and recurrent cancer in treated tissue. This thesis focuses on evaluation of radio-immunoconjugates directed towards CD44v6, which is a surface receptor overexpressed in many head and neck squamous cell carcinomas. At the outset, the monoclonal chimeric antibody cMab U36 and its cleavage products Fab’ and F(ab’)2 were labeled with 125I and assessed in vitro and in vivo (paper I). The best distribution pattern and tumor to organ ratio was achieved with F(ab’)2. Due to the immunological responses humans can develop towards chimeric antibodies, they are not optimal for clinical use, and subsequently fully human antibody fragments were developed. AbD15179, which is a monovalent fragment, was labeled with 111In and 125I and evaluated in vitro and in mice bearing CD44v6-expressing tumors. Tumor to organ ratios were improved compared to cMab U36 derived fragments, and 111In-AbD15179 displayed a more favorable distribution compared to 125I-AbD15179 (Paper II). A bivalent Fab-dHXL, AbD19384 derived from AbD15179, was then constructed and labeled with 125I and evaluated in cell- and biodistribution studies. Furthermore, an imaging study in a small animal PET was performed with 124I-AbD19384 (Paper III). Uptake in kidneys was reduced and liver uptake increased compared to AbD15179 reflecting the larger molecule. The high CD44v6 expressing tumor was clearly visualized with maximum uptake at 48 hours post injection.In paper IV human single chain fragments towards CD44v6v were selected, and the top candidates A11 and H12 were further evaluated in vitro and in vivo. Single chain fragments are small molecules exhibiting fast clearance and high affinity to the target. The study proved this by demonstrating superior tumor to blood ratios of radiolabeled A11 and H12 compared to previously studied molecules.

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Dementia means significant cognitive decline in language, memory and executive functions. Dementia is associated with progressive communication difficulties, which can result in reduced quality of life. To promote quality of life, the communicative environment, participation in group activities and cognitive stimulation have great significance. Cognitive stimulation can delay, slow or prevent symptoms of dementia. Furthermore, information and communication technology (ICT) has promising results in relation to dementia. However, research including psychosocial intervention are limited, which motivates present study. The present study is the first Swedish study which purpose was to promote social interaction for people with dementia through conversational sessions as a group activity when using the communication aid CIRCA (Computer Interactive Reminiscence and Communication Aid). Further purpose was to contribute to the understanding of high technological communication aids’ potential to facilitate and support communication for people with dementia. Five individuals with dementia were recruited from a residential care home. The study comprises a seven-session CIRCA-based group activity, and the material consist of seven hours and fifteen minutes recordings. The analysis included mapping of conversational topics where particularly interesting interactive phenomena were selected that were considered representative of the interaction. The results showed that the conversational sequences could relate to the content of CIRCA, the management of the tablet or were as a result of the content in CIRCA. Characteristic interactional phenomena were enjoyable group dynamics with laughter, humour, singing and social inclusion where participants contributed with information, personal experiences and asked each other questions. Furthermore, a symmetric interaction emerged between participants and between participants and the facilitator. The participants considered the group sessions in use of CIRCA to be enjoyable, amusing, informative and provided conversational topics and simplified the conversations in comparison to without communication aid. The results indicate that CIRCA has promising potential to be utilized as a group activity for people with dementia. CIRCA could be applicable in residential care homes where caregivers’ opportunities to socialize one-to-one is limited. Furthermore, the multimedia of CIRCA can offer a variation that may cater to several individuals interests. CIRCA could constitute a group intervention to promote activity, interaction and social relationships, that could improve the quality of life of people with dementia.