No abstract

Ce document examine l'évolution des dynamiques touristiques de la ville de Durban dans un contexte post-apartheided. La ville de Durban s’est imposée comme l'une des destinations touristiques les plus populaires d’'Afrique du Sud. En accord avec les diktats de l'apartheid, pour satisfaire les souhaits d’une minorité blanche, l’organisation de la ville avait ignoré les besoin de la majorité noire. Aujourd’hui la ville de Durban se repositionne sur l’échiquier touristique, portée par les changements politiques intérieurs et les opportunités des marchés touristiques internationaux et nationaux. Afin de se positionner avec succèssur ce marché, la ville de Durban renforce son image autour de la promotion son front de mer, des sports nautiques, du tourisme de congrés, et des animations culturelles. La transition démocratique des années 1990 a fourni de nombreux défis et oppportunités dans la première sur le plan touristique fut de se positionner sur le nouveau marché touristique noir. Cal passe aussi par les urgence à résoudre sur le plan de la criminalité, de l’hygiène et de la résorption des disparités  sur le marché du travail, en particulier en termes de race et de l'égalité des sexes dans le secteur du tourisme. Les plus sérieuses limites pour le tourisme à Durban sont le chômage et la marginalisation de la majorité des African people.
This paper examines the changing fortunes of Durban as a tourist city from the apartheid to the post apartheid eras.  Durban has long earned its prime position as one of South Africa’s most popular year‑round tourist destination. In keeping with the dictates of apartheid, the city catered largely for the needs of the white minority, while that of the black majority was largely ignored. With political changes and shifts in both the international and domestic markets, an effort had to be made to reposition tourism in the city.  In order to successfully promote its tourism opportunities, Durban attempted to enhance its image and appeal by promoting its sports, convention and cultural attractions.  The democratic transition of the 1990s provided many challenges, the most enduring of which was the need to cater for the emerging black tourist market.  There was also an urgency to address problems of crime and grime, disparities in the distribution of labour market opportunities, especially in terms of race and gender within the tourism sector. A serious threat to tourism in Durban is unemployment and alienation of the majority of African people from the industry.

The epidermal growth factor receptor (EGFR) is altered in 57% of high grade glioma (HGG) by mutation, rearrangement and/or focal amplification, suggesting it should be a target for therapy. However, attempts to therapeutically target EGFR in HGG patients have failed for reasons that remain largely unknown. We have derived a panel of primary cell lines from HGG patients expressing different forms of the EGFR including the most common mutations: the autoactivating deletion EGFRvIII and the extracellular domain point mutation A289V. Using anti-proliferative assays and cell cycle analysis we screened our HGG cell lines for response to Panitumumab (an EGFR targeting antibody) or Dacomitinib (an irreversible TKI targeting EGFR). The anti-proliferative activity of Panitumumab and Dacomitinib showed a similar profile across the HGG cell lines, but the response to EGFR inhibition ranged from resistant to highly sensitive. In order to improve the anti-tumour response to Panitumumab we tested it in combination with either a MEK inhibitor (Trametinib) or a PI3K inhibitor (BYL719), as both signalling pathways are downstream of EGFR. The combination of Panitumumab and Trametinib showed additive anti-tumour activity against HGG cell lines expressing the wtEGFR, whereas the combination of Panitumumab with BYL719 did not display additivity. In contrast, EGFRvIII cell lines showed an additive anti-tumour response to Panitumumab and BYL719 but not Trametinib. More generally, the activation of the ras/MEK/ERK pathway through either ras mutation or integrin engagement mediated resistance to EGFR-targeted therapeutics. Finally, the SB2 HGG cell line, which contains the A289V mutation, was completely resistant to EGFR therapy due to an activating mutation in PI3KCA. We are currently confirming these in vitro observations in orthotopic xenograft models. The epidermal growth factor receptor (EGFR) is altered in 57% of high grade glioma (HGG) by mutation, rearrangement and/or focal amplification, suggesting it should be a target for therapy. However, attempts to therapeutically target EGFR in HGG patients have failed for reasons that remain largely unknown. We have derived a panel of primary cell lines from HGG patients expressing different forms of the EGFR including the most common mutations: the autoactivating deletion EGFRvIII and the extracellular domain point mutation A289V. Using anti-proliferative assays and cell cycle analysis we screened our HGG cell lines for response to Panitumumab (an EGFR targeting antibody) or Dacomitinib (an irreversible TKI targeting EGFR). The anti-proliferative activity of Panitumumab and Dacomitinib showed a similar profile across the HGG cell lines, but the response to EGFR inhibition ranged from resistant to highly sensitive. In order to improve the anti-tumour response to Panitumumab we tested it in combination with either a MEK inhibitor (Trametinib) or a PI3K inhibitor (BYL719), as both signalling pathways are downstream of EGFR. The combination of Panitumumab and Trametinib showed additive anti-tumour activity against HGG cell lines expressing the wtEGFR, whereas the combination of Panitumumab with BYL719 did not display additivity. In contrast, EGFRvIII cell lines showed an additive anti-tumour response to Panitumumab and BYL719 but not Trametinib. More generally, the activation of the ras/MEK/ERK pathway through either ras mutation or integrin engagement mediated resistance to EGFR-targeted therapeutics. Finally, the SB2 HGG cell line, which contains the A289V mutation, was completely resistant to EGFR therapy due to an activating mutation in PI3KCA. We are currently confirming these in vitro observations in orthotopic xenograft models. This work is providing new insights into the mechanism that control response to EGFR-targeted therapeutics and should lead to therapeutic combinations that have efficacy in HGG patients. Note: This abstract was not presented at the conference. Citation Format: Vino Pillay, Sameer Greenall, Terrance G. Johns. Targeting the EGFR in high-grade glioma. [abstract]. In: Proceedings of the AACR Special Conference: Advances in Brain Cancer Research; May 27-30, 2015; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2015;75(23 Suppl):Abstract nr A29.