A disease such as cancer, where a number of alterations to normal cell function accumulate over time, presents several chernopreventive opportunities to inhibit, slow down or even reverse the process. Many of the crucial changes are induced by alterations to cell signalling pathways which regulate proliferation and apoptosis. As our knowledge of these complicated signalling networks improves, it is becoming clear that many molecules, both drugs and naturally occumng dietary constituents can interact beneficially with deregulated pathways. Molecules such as aspirin and other non-steroidal antiinflammatory drugs, as well as many dietary plant components, for example from green vegetables and tea, can inhibit signalling by affecting kinase activity and therefore phosphorylation of key molecules. Examples of pathways which can be modulated by these agents include activation of the transcription factor nuclear factor-* by tumour promoton or cytokines, signalling by growth factors through the epidermal growth factor receptor/mitogen activated protein kinase pathway and the stress activated (SAF'K)/p38 pathways. Evidence exists, at least from in virro experiments, that through targetting signalling pathways, some compounds may be able to restore rates of apoptosis and proliferation to normal levels, thus rendering them relatively non-toxic, an essential requirement for a good chemopreventive agent.c12 Diet and colorectal cancer prevention MRC Dunn Human Nutrition Unit. Hills Road, Cambridge CB2 2DH Colorectal cancer is the second most common cancer in the UK. The majority of cancers are sporadic and epidemiological estimates suggest that up to 80% of colorectal cancer is attributable to diet This means that it is potentially a preventable disease. Epidemiologically, cross sectional comparisons, case control studies and trends in food intakes show high rates of colorectal cancer in populations consuming diets high in meat and far, and low in starch, NSP (non starch polysaccharides. fibre) and vegetables. In general, prospective studies tend to support these findings although estimates of relative risk are not high. Existing prospective studies have however used crude indices of diet subject to substantial measurement error, and interactions with genetic polymorphisms in for example phase I and I1 enzymes have been studied only rarely. The association between meat consumption and colorectal cancer is usually attributed to the formation of heterocyclic amines in meat when it is cooked. In addition, in humans high meat diets increase the level of nitrosatable material entering the colon so that faecal N-nitrosocompounds (NOC) increase in a dose rcponsivc manner following endogenous synthesis in the colon. Some of the mutations and guanine adducts accumulated during colorcctal cancer progression are characteristic of alkylative damage which would be compatible with N O C exposure. To date, NSP, resistant starch and vegetables have not reduced faecal N O C levels. C13 Human metabolism of dietary chemopreventive compounds Gary...

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The Malampaya field development comprises subsea wells in 820 meters water-depth producing via a subsea manifold and two 16 inch diameter inconel clad flowlines to a shallow water platform 30 km distant. Condensate is removed on the platform and the dry gas is then transported via a 504 km long 24 inch export pipeline to an onshore gas plant at Tabangao (Batangas, Luzon Island) for extraction of H2S. The condensate is stored in the platform CGS Caisson prior to export via a short 3 km long 24 inch diameter pipeline and CALM buoy (Fig 11). The Malampaya Deep Water Gas to Power Project in the Philippines has delivered first gas as advertised on October 1st 2001. The gas production is from five high rate deep water subsea gas wells. This paper summarises the delivery of the wells, in particular, the specific challenges that had to be surmounted to deliver high quality wells whilst remaining within the tight Malampaya project schedule. These challenges related to the deployment of leading edge well technology systems in an environmentally pristine and remote area. This within a country with extremely limited petroleum infrastructure and very long supply lines. The definition and management of good performance within this context and the management of the many interfaces with other disciplines working concurrently required unique ways of working to be established. Within the technical arena, many novel solutions were adopted with respect to rig modifications, drilling with losses, management of hydrates, horizontal Xmas trees, monobore well completions, coiled tubing perforating from a semi-sub well test clean-up and extensive/detailed planning. Organisationally, a working atmosphere was developed based on open, detailed and relentless inter-team challenge. This led to drilling and completing, genuinely to the "limit" of what was achievable for Malampaya. INTRODUCTION Malampaya, developed and operated by Shell Philippines Exploration BV (SPEX), is the first and only gas development in the Philippines. The five subsea wells are the first link in a production chain that supplies 30% of the mainland power requirements. In each well, high deliverability and high availability are critical from day one and throughout the full 25 year field life. There are no other fields that can supplement any shortfall in well performance. Planning was initiated in Houston in late 1998 and moved to Singapore and Manila in mid-1999. Offshore execution started in early-2000 and was completed by September 2001. Innovative business processes and technical solutions were employed in "striving for excellence" in an environment characterised by a very short planning time and a multitude of project interfaces. The Malampaya gas wells were handed over to the production team, on time and within budget. They have been proven capable of production rates exceeding 120MMscf/day. Included in this paper are the key highlights from planning, drilling, completing and commissioning the Malampaya gas wells.

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