Thèse (M.Sc.)--Université Laval, 2004. / Bibliogr. Publié aussi en version électronique.

Thèse (Ph. D.) -- Université Laval, 1996. / Bibliogr.: f. 89-110. Publié aussi en version électronique.

Akademisk avhandling- Karolinska institutet. / Extra t.p., with thesis statement, inserted. Includes 6 articles by the author and S.H. From, reprinted from various periodicals. Includes bibliographies.

München, Techn. Univ., Diss., 2001.

The aim of thesis was to study murine melanoma B16- F10 therapy based on the use of TLR agonists combinedwith activation of phagocytosis. Mechanisms of this therapy were studied on the bases of analysis of tumor infiltrating immune cells and evaluationof thein effect on tumor cells.

The aim of the present study was to assess an influence of two different therapeutical concentrations of peracetic acid on selected haematological and biochemical parameters in grass carp (Ctenopharyngodon idella). Fish were radomly distributed to aquaria and exposed to concentrations of 0 mg.l-1 PAA (control group), 1.0 mg.l-1 PAA (P1 group), 3.0 mg.l-1 PAA (P2 group). Almost total mortality of fish was observed in the concentration 3.0 mg.l-1 PAA during the treatment comparing with the P1 group and untreated control where no mortality was observed. After the end of the experimental exposure of fish to peracetic acid, the sampling of blood has been realised. The samples of the blood were examined in order to determine haematological and biochemical parameters. Consequently, there were no significant differences (p<0.05) in a haematological profile of fish exposed to concentration of 1.0 mg.l-1 PAA. Goblet cells count and size have risen, that caused exposure of fish to peracetic acid. In the biochemical profile of fish, significant changes (p<0.01) in three parameters were found after exposure of fish to peracetic acid in concentration 1.0 mg.l-1. Changed parameters were: aspartate aminotransferase, creatine kinase and lactate dehydrogenase. The changes were moderate and it can be supposed that these changes are reversible. No significant change (p<0.05) in haematological parameters points out to the minimum negative influence of recommended therapeutical concntration (1.0 mg.l-1 PAA) to the health of C. idella.

Spleen is the largest secondary lymphatic organ which develops in a short postnatal period. Information on postnatal development of rabbit spleen is minimal in available literary sources. This diploma thesis deals with the weight, morphometric and histological changes of the spleen of rabbits at age 0, 5, 10, 14, 19, 27, 32 and 39 days. During postnatal development of rabbits, a statistically significant (P <0.01) increase in the weight, length and width of the spleen occurred. The spleen of newborn rabbits was a relatively small organ with an average length of 1.03?0.12 cm, a width of 0.2?0.01 cm and a weight of 52.50?9.69 g. At age 39 days the size and shape of spleen of adult individuals (average length 4.97?0.73 cm, width 0.9?0.18 cm and weight 1078.40?143.35 g). Between the weight and morphometric parameters, high correlation coefficients were observed in the range of 0.891 to 0.998. Spleen growth was accompanied by increasing cellularisation of the parenchyma, by strengthening the connective tissue (from 8.04?1.50 m to 31.30?5.51 m) and the progressive occurrence of connective tissue in the parenchyma. In the newborn rabbits, a red pulp with a high level of erythrocytes prevailed in the spleen parenchyma. Lymphatic tissue consisted only of small irregular aggregations of basophilic mononuclear cells around several central arteries. Basophilic and vascularization increased in the course of the age and the white pulp was gradually formed. In 14 day rabbits, the marginal zone was well-known, and primary lymph nodes formed by CD79+ cells were first formed. From 14th to 39th day the spleen gradually increased the frequency and size of the individual compartments, with rare germinal centers observed in the lymph nodes until the 39th day. Throughout the course of the observation, extramedullary haematopoiesis of different intensity was seen in the spleen.

L’incidence des gliomes est estimée à 6.6 pour 100 000 habitants. Les survies varient selon le sous-type de gliomes, avec des taux de survie à 5 ans d’environ 48% pour les astrocytomes diffus selon la classification de l’Organisation Mondiale de la Santé (OMS), 28% pour les astrocytomes anaplasiques, 80% pour les oligodendrogliomes, 52% pour les oligodendrogliomes anaplasiques et 5% pour les glioblastomes, tumeurs cérébrales malignes les plus fréquentes.Une meilleure compréhension des mécanismes et de la biologie de ces tumeurs et de nouvelles pistes thérapeutiques sont essentielles afin d’identifier de nouvelles thérapies pouvant améliorer le pronostic des patients. La classification OMS 2016 des tumeurs du système nerveux central a, pour la première fois, intégré les données de biologie moléculaires aux données histopathologiques, afin d’améliorer la distinction des différents sous-groupes de tumeurs et d’orienter au mieux les choix thérapeutiques pour chaque sous-groupe.Nous nous sommes intéressés dans ce travail à l’apport de l’approche en protéomique par imagerie par matrix-assisted laser desorption/ionization spectrométrie de masse MALDI (MALDI-MSI) couplée à l’analyse en microprotéomique dans les gliomes dans le cadre de l’étude clinique GLIOMIC (NCT02473484) qui a pour but de réaliser une classification moléculaire des gliomes en intégrant les données cliniques et celles obtenues par ces nouvelles approches.La faisabilité de la technique a d’abord été validée sur une série de gliomes anaplasiques. Dans cette première analyse, nous avons pu démontrer que, bien que l’approche protéomique confirmait également l’hétérogénéité tumorale, les analyses histologiques et protéomiques divergent et apportent des informations complémentaires. L’imagerie moléculaire protéomique a mis en évidence trois différents groupes d’expression de protéines : un groupe de protéines associé au cancer, un groupe de protéines impliquées dans l’inflammation et un groupe de protéines impliquées dans la différentiation des cellules nerveuses et la croissance des neurites.Nous nous sommes ensuite intéressés aux glioblastomes. Les premiers résultats ont également confirmés l’existence des 3 régions d’intérêt définies sur le plan moléculaires, apportant de nouvelles informations par rapport aux données histopathologiques. Ces résultats doivent être confirmés dans une cohorte plus large de patients.En conclusion, l’intégration de ces biomarqueurs protéomiques, aux données cliniques, histopathologiques et de biologie moléculaire, pourrait permettre d’améliorer les connaissances sur les gliomes, leur classification et l’identification de nouvelles cibles thérapeutiques potentielles. / The annual incidence of gliomas is estimated at 6.6 per 100,000. Suvival varies profoundly by type of glioma, with 5-year survival rates of 48% for World Health Organization (WHO) grade II diffuse astrocytoma, 28% for WHO grade III anaplastic astrocytomas, 80% for WHO grade II oligodendroglioma, 52% for WHO grade III anaplastic oligodendroglioma and 5% for WHO grade IV glioblastoma, the most frequent primary malignant brain tumor. A better understanding of the molecular pathogenesis and the biology of these tumors is required to design better therapies which can ultimately improve the prognosis of patients. The WHO 2016 classification of central nervous system tumors has for the first time integrated molecular data with the histopathological data, in order to improve the classification of the different subgroups of central nervous system tumors and to allow to derive more specific therapeutic strategies for each of the different subgroups.In the present work, we aimed at evaluating the value of a proteomic approach using matrix-assisted laser desorption/ionization (MALDI) mass spectrometry coupled with microproteomic analysis in gliomas through the GLIOMIC clinical study (NCT02473484), we aimed at obtaining a molecular classification of glioblastomas by integrating clinical data to the ones obtained by such technologies. The feasibility of this approach was first demonstrated in a cohort of anaplastic gliomas. In this first analysis, we showed that although proteomic analysis confirmed the heterogeneity of brain tumors already observed with the histological analysis, the two approaches may lead to different and complementary information. Three different groups of proteins of interest were identified: one involved in neoplasia, one related to glioma with inflammation, and one involved neurogenesis. Then, analyses of glioblastomas confirmed the three proteomic patterns of interest already observed in the anaplastic gliomas, which represents new information as compared to histopathological analysis alone. These results have to be confirmed in a larger cohort of patients.We conclude that MALDI mass spectrometry coupled with microproteomic analysis may provide new diagnostic information and may aid in the identification of new biomarkers. The integration of these proteomic biomarkers into the clinical data, histopathological data and data from molecular biology may improve the knowledge on gliomas, their classification and development of new targeted therapies.

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