Thèse 3 cycle--Géographie--Bordeaux III, 1972. / La couv. porte en plus : "les régions littorales" Contient les résumés en français, en anglais et en allemand. Bibliogr. p. 223-234.

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Th. 3e cycle--Hist.--Paris 1, 1977. / Index.

Du XVe au XVII siècle, le Portugal a occupé la première place parmi les Etats les plus avancés de son temps. Et c’est pendant cette époque que les explorateurs de ce pays ont parcouru les océans lors d’expéditions qui les ont amenés en Afrique, en Asie, en Amérique et en Océanie. Or, le contact des peuples et des cultures a toujours été source d’influences réciproques de nature diverse et multiforme. Nous nous proposons d’étudier, dans cette thèse, les empreintes lusitaniennes dans le Golfe de Guinée. La recherche a été menée dans la partie australe de la Côte d’Ivoire, du Ghana, du Togo et du Bénin et elle se fonde sur un corpus composé de quelques centaines d’entrées que nous avons répertoriées à travers une recherche bibliographique et une enquête de huit ans sur le terrain. L’analyse de ces données, se fait selon une méthode qui combine à la fois l’histoire et le structuralisme dans son approche contrastive car, il s’agit, en réalité, de comparer deux systèmes linguistiques : le portugais et des langues Niger-Congo des groupes langues kru et kwa. L’étude se tisse autour de trois parties : la première partie fait un rappel historique des rapports luso-africains puis délimite l’univers géographique cible; la seconde étudie l’emprunt lexical portugais dans les principales langues de la région; enfin, la troisième et dernière partie, aborde la question des emprunts onomastiques portugais dans la région. / From XVth to XVIIth century, Portugal has been ranking first among the most advanced nations of its time. It is during that era that the explorers helped this country to reach out Africa, Asia, America and Oceania. But any contact with peoples and cultures has always been a source of various and multifaceted reciprocal influences. In this thesis, we will study the lusitanian impressions in the Guinea Gulf. The research has been conducted in the southern part of Ivory Coast, Ghana, Togo and Benin and is based on a corpus made up of some hundreds of words that we have listed in a bibliography and an investigation that we have carried out in the field during eight years. The analysis of data is done according to a bipolar method which combines history and structuralism in its contrastive approach because, in reality, we are comparing two linguistic systems: portuguese, kru and kwa languages of the Niger-Congo family. The study includes three parts; the first part deals with the historical background of luso-african relationships then delineates the targeted geographic realms; the second part studies the portuguese lexical borrowings in the main languages of the region; finally, the third and last part touches on the issue of portuguese onomastic borrowings in the region.

Background. VAV interacting Krüppel-like factor (VIK) is a novel transcription factor. Previously our lab reported a series of breast cancer tumour samples where VIK methylation was associated with an increased risk of recurrence in tamoxifen-treated patients, indicating a role for VIK in ER positive breast cancer and endocrine resistance. Additionally VIK has been shown to be involved in cell cycle regulation, interacting with CDK4 and VAV1. The cyclin D-CDK4/6-Rb pathway is frequently dysregulated in ER positive breast cancer. Combined treatment of palbociclib, a highly selective CDK4/6 inhibitor, with endocrine therapy substantially improved outcome of patients with ER positive metastatic breast cancer. Increasing clinical use means acquired resistance to palbociclib is emerging as a major clinical challenge. Results. VIK was confirmed to be subject to regulation by DNA methylation in breast cancer. VIK methylation correlated to transcriptional silencing of mRNA in both cancer cell lines and primary tumours. To determine the functional significance of loss of VIK expression, VIK was knocked down in unmethylated breast cancer cell lines and a normal breast epithelial cell line. Knockdown resulted in cell death via induction of apoptosis. VIK knockdown altered cell cycle progression from G1 to S phase. Expression of multiple regulatory cell cycle proteins was altered, differentially in normal and tumour cells. Treatment with the CDK4/6 inhibitor, palbociclib, in cells with reduced VIK expression resulted in decreased sensitivity to the drug, inducing a shift in IC50 value towards resistance. In a model of acquired resistance, T47D cells were cultured long-term with palbociclib generating resistant clones. VIK was significantly downregulated in all resistant clones to barely detectable mRNA levels, suggesting a role for VIK in resistance to CDK4/6 inhibition. Conclusion. This PhD has confirmed VIK is a novel epigenetically regulated gene in breast cancer. VIK expression is essential to both normal and tumour breast cell survival and is involved in the regulation of the G1/S phase transition in the cell cycle. Loss of VIK expression potentially contributes to the development of acquired resistance to CDK4/6 inhibitors.

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