Several laboratories have reported marked tumor inhibition when the cytokine interleukin-10 (IL-10) is overexpressed as a transgene in a variety of tumor cells. To identify critical effector molecules, we compared the expression of the chemokine crg-2, the murine homolog of human inducible protein 10 (human IP-10) in murine mammary tumors derived from the transplantation of six IL-10 expressing clones of tumor cell line 66.1, parental 66.1, or 66-neo-cells. We observed increased levels of IP-10 mRNA in all IL-10-expressing tumors examined in comparison to 66-neo. IP-10 mRNA was not detected in parental 66.1 tumors. The closely related chemokine Mig (monokine induced by interferon-gamma [IFN-gamma]) was also induced in all IL-10-expressing tumors. Studies of cultured tumor cells in vitro show that mammary epithelial tumor cells, in the absence of host elements, can express IP-10 and Mig in response to induction with either lipopolysaccharide (LPS) or IFN-gamma alone. The combination of LPS plus IFN-gamma resulted in even greater induction of IP-10 RNA. The kinetics of induction differ somewhat for the two chemokines, with IP-10 showing slower induction and less rapid decline. Because both Mig and IP-10 are chemotactic for tumor-infiltrating lymphocytes, we examined the presence of CD4+ and CD8+ lymphocytes in these tumors. Consistent with the upregulation of Mig and IP-10, we saw significantly increased numbers of CD8+ cells and a lesser increase in CD4+ cells in tumors with elevated levels of both chemokines.
David Bruce is a principal lecturer in tourism at UWE, Bristol, leader of the ECfunded Marine Ecotourism in the Atlantic Area project and academic adviser to the Walled Towns Friendship Circle. A town planner and transport economist, he researches the impacts of tourism. Marlon Jackson is a principal lecturer in economics at UWE, Bristol, head of the Local Economy Research Unit and convener of the Bristol Group for TOINism Research. Her research and consultancy is in the economic impacts of tourism and tourism's role in local/regional economic development. Dr Antoni Serra Cantallops is a senior lecturer in tourism marketing and marketing management at the University of the Balearic Islands. An economist, he holds an MBA from Middlesex University, London. His research is in tourism marketing and tourism destination planning. ABSTRACT KEYWORDS: sustainable tourism, urban tourism, heritage tourism, environmental audit, tourism policy, Local Agenda 21 The PREPARe wheelis a dynamic model showing how a systematic environmental audit system could be applied to the development and management of tourism. The model was derived during research onfour European historic walled towns characterised as destinations for heritage and urban tourism. Embracing the approach implied by Local Agenda 21 and'bestvalue' reviews, the paper illustrates how such towns can be assessed for levels of compliance with defined actiotIS and policies set out as the necessary elements of an overall programme to move towards less unsustainable tourism in these destinations. This involves six successive stages: Policy, Responsibility, Eco-awareness, Programme, Audit and Review. Local stakeholders were involved at each stage, from defining objectives for tourism development lo~ally to assessing the levels of compliance with expected policies and actions, although this brought a degree of subjectivity to the results. Turning the PREPARe wheel illustrates the continuous repetition of this process, which is necessary to stimulate ongoing improvements in levels of compliance with policies to move towards less unsustainable tourism. Developments in tourism policy in Alcudi« (one of the original study towns) since 1993 have been analysedto illustrate theprocess in practice.
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