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14. The role of notch signalling in colorectal cancer

Author

Rees, Philip

Abstract

Colorectal cancer (CRC) continues to be a leading cause of death in the western world and the molecular basis of this disease remains the focus of intensive research. Notch is a highly conserved embryogenic pathway, which is essential for homeostasis in adult tissues and is increasingly implicated in human malignancies, including CRC. Analysis in murine epithelium strongly suggests a central role for these factors in intestinal tumorigenesis; however, the expression and function of N1 in the human colorectal epithelium and CRC remains poorly defined. The aim of this study was to define the expression of N1 in these tissues and to describe possible changes in expression with malignant progression. This study also aimed to model these changes in vitro and to evaluate a functional role for Notch in the human CRC phenotype. From in vivo analysis, it was found that N1 is expressed in the normal colorectal epithelium and expression is frequently altered in human colorectal tumours; N1 is significantly increased in adenocarcinoma tissues and correlates strongly with malignant progression. These findings were closely reflected using colorectal tumour cell lines in vitro where N1 expression increases with cell cycle progression and tumour de-differentiation. Although a causal role for N1 was not established, these findings suggest a complex and context-dependent basis for the Notch pathway in these tissues. Moreover, this study highlights several important but unappreciated roles for N1 in the non-neoplastic colorectal epithelium. Namely, N1 was found to be expressed in both differentiating cells of the normal colonic crypt and in regions of active tissue repair in inflammatory bowel disease. In summary, the results of this study confirm that altered N1 expression represents important changes in the human colorectal epithelium, including colorectal carcinogenesis, but also that Notch signalling may be responsible for more functions in these tissues than currently described.

Published
2010

25. MOONS – multi object spectroscopy for the VLT: overview and instrument integration update

Author

Gonzalez, Oscar, primary, Cirasuolo, Michele, additional, Taylor, William, additional, Black, Martin, additional, Rees, Philip, additional, Bryson, Ian, additional, Chittick, Stephen, additional, Afonso, Jose, additional, Lilly, Simon, additional, Flores, Hector, additional, Maiolino, Roberto, additional, Oliva, Ernesto, additional, Paltani, Stephane, additional, Vanzi, Leonardo, additional, Abreu, Manuel, additional, Amans, Jean-Philippe, additional, Atkinson, David, additional, Beard, Steven, additional, Belfiore, Andrea, additional, Breen, Ciaran, additional, Bayo, Amelia, additional, Born, Andy, additional, Cabral, Alexandre, additional, Chapman, Lee, additional, Cochrane, William, additional, Coelho, João, additional, Colling, Miriam, additional, Conzelmann, Ralf, additional, Dalessio, Francesco, additional, Davidson, George, additional, Delplancke-Ströbele, Françoise, additional, Fisher, Martin, additional, Forchi, Vincenzo, additional, Franzetti, Paolo, additional, Garilli, Bianca, additional, Gargiulo, Adriana, additional, Guinouard, Isabelle, additional, Gutierrez, Pablo, additional, Haigron, Régis, additional, Hammersley, Peter, additional, Ivanov, Valentin, additional, Ives, Derek, additional, Iwert, Olaf, additional, King, David, additional, Kovacz, Suzanne, additional, Laporte, Philippe, additional, Lee, David, additional, Li Causi, Gianluca, additional, Macleod, Alastair, additional, Alvarez Mendez, Domingo, additional, Oliveira, António, additional, Palsa, Ralf, additional, Parra, Manuel, additional, Pedichini, Fernando, additional, Peña, Vicente, additional, Petr-Gotzens, Monika, additional, Rodrigues, Myriam, additional, Royer, Frédéric, additional, Santos, Pedro, additional, Sepulveda, Jorge, additional, Sharman, Robyn, additional, Shen, Tzu-Chiang, additional, Sordet, Michael, additional, Strachan, Jonathan, additional, Tait, Graham, additional, Tejeda, Alexis, additional, Tozzi, Andrea, additional, O'Malley, Norman, additional, Waring, Chris, additional, Watson, Stephen, additional, Willemse, Bart, additional, Xiaofeng, Gao, additional, Yang, Yanbin, additional, and Zoccali, Manuela, additional

Published
2022
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26. MOONS – multi object spectroscopy for the VLT: integration and tests of the field corrector and the rotating front end

Author

Cabral, Alexandre, primary, Abreu, Manuel, additional, Coelho, João M. P., additional, Santos, Pedro, additional, Oliveira, António, additional, Leite, Inês, additional, Afonso, José, additional, Rees, Philip, additional, Artan, Raziye, additional, Lee, David, additional, González, Oscar, additional, Watson, Stephen, additional, Taylor, William, additional, Chittick, Stephen, additional, Bryson, Ian, additional, Guinouard, Isabelle, additional, Cirasuolo, Michele, additional, and Spanò, Paolo, additional

Published
2022
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48. Ravenstein Revisited: The Analysis of Migration, Then and Now

Author

Rees, Philip, Lomax, Nik, Rees, Philip, and Lomax, Nik

Abstract

In 1876, 1885 and 1889, Ernst Ravenstein, an Anglo-German geographer, published papers on internal and international migration in Britain, Europe and North America. He generalized his findings as "laws of migration", which have informed subsequent migration research. This paper aims to compare Ravenstein’s approach to investigating migration with how researchers have studied the phenomenon more recently. Ravenstein used lifetime migrant tables for counties from the 1871 and 1881 censuses of the British Isles. Data on lifetime migrants are still routinely collected but, because of the indeterminate time interval, they are rarely used to study internal migration. Today, internal migration measures from alternative sources are used to measure internal migration: fixed interval migrant data from censuses and surveys, continuous records of migrations from registers, and "big data" from telecommunications and internet companies. Ravenstein described and mapped county-level lifetime migration patterns, using the concepts of "absorption" and "dispersion", using migration rates and net balances. Recently, researchers have used lifetime migrant stocks from consecutive censuses to estimate country to country flows for the world. In the last decade, an Australian-led team has built an international database of internal migration flow data and summary measures. Methods were developed to investigate the modifiable areal unit problem (MAUP), in order to design summary internal migration measures comparable across countries. Indicators of internal migration were produced for countries covering 80 percent of the world’s population. Ravenstein observed that most migrants moved only short distances, anticipating the development of "gravity" models of migration. Recent studies calibrated the relationship between migration and distance, using gravity models. For mid-19th century Britain, Ravenstein found the dominant direction of internal migration to be towards the "centres of commerce

Published
2020

50. Trends in local and small area mortality and morbidity in Yorkshire and the Humber: monitoring health inequalities

Author

Brown, Dominic and Rees, Philip

Subjects
Regional disparities -- Forecasts and trends, Mortality -- Forecasts and trends, Mortality -- Comparative analysis, Mortality -- England, Morbidity -- Forecasts and trends, Morbidity -- Comparative analysis, Market trend/market analysis, Regional focus/area studies
Abstract

Regional disparities in mortality and morbidity rates of Yorkshire and Humber, during 1990's are examined.

Published
2006

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