Sphingosine Kinase 1 Promotes Malignant Progression in Colon Cancer and Independently Predicts Survival of Patients With Colon Cancer by Competing Risk Approach in South Asian Population

OBJECTIVES: Sphingosine kinase 1 (SphK1) phosphorylates the membrane sphingolipid, sphingosine, to sphingosine-1-phosphate (S1P), an oncogenic mediator, which drives tumor cell growth and survival. Although SphK1 has gained increasing prominence as an oncogenic determinant in several cancers, its potential as a therapeutic target in colon cancer remains uncertain. We investigated the clinical relevance of SphK1 expression in colon cancer as well as its inhibitory effects in vitro.

METHODS: SphK1 expression in human colon tumor tissues was determined by immunohistochemistry and its clinicopathological significance was ascertained in 303 colon cancer cases. The effects of SphK1 inhibition on colon cancer cell viability and the phosphoinositide 3-kinase (PI3K)/Akt cell survival pathway were investigated using a SphK1-selective inhibitor-compound 5c (5c). The cytotoxicity of a novel combination using SphK1 inhibition with the chemotherapeutic drug, 5-fluorouracil (5-FU), was also determined.

RESULTS: High SphK1 expression correlated with advanced tumor stages (AJCC classification). Using a competing risk analysis model to take into account disease recurrence, we found that SphK1 is a significant independent predictor for mortality in colon cancer patients. In vitro, the inhibition of SphK1 induced cell death in colon cancer cell lines and attenuated the serum-dependent PI3K/Akt signaling. Inhibition of SphK1 also enhanced the sensitivity of colon cancer cells to 5-FU.

CONCLUSION: Our findings highlight the impact of SphK1 in colon cancer progression and patient survival, and provide evidence supportive of further development in combination strategies that incorporate SphK1 inhibition with current chemotherapeutic agents to improve colon cancer outcomes.

Human Adaptation in Asian Palaeolithic:Hominin Dispersal and Behaviour during the Late Quaternary

This book examines the first human colonization of Asia and particularly the tropical environments of Southeast Asia during the Upper Pleistocene. In studyexamining the unique character of the Asian archaeological record, it reassesses long-accepted propositions about the development of human ‘modernity.’ Ryan J. Rabett reveals an evolutionarily relationship between colonization, the challenges encountered during this process – especially in relation to climatic and environmental change – and the forms of behaviour that emerged. This book argues that human ‘modernity’ is not something achieved in the remote past in one part of the world, but rather is a diverse, flexible, responsive, and on-going process of adaptation, one that continues to this day.

The early exploitation of Southeast Asian mangroves:Bone technology from caves and open sites

This paper focuses on the contribution that the study of bone technology is making to the understanding of early tropical subsistence in Southeast Asia. Newly completed research suggests that during the period from the terminal Pleistocene to mid Holocene, bone tools may have featured prominently in coastal subsistence. There are indications that this technology may have had a particular association with hunting and gathering in the mangrove forests that proliferated along many coasts during this period. The study of these tools thus represents a rare chance to examine prehistoric extractive technologies, which are generally agreed to have been predominantly made on organic, nonpreserving media. The evidence presented also suggests that prehistoric foragers from this region possessed a good working understanding of the mechanical properties of bone and used bone implements where conditions and needs suited the parameters of this material. © 2005 by the University of Hawai'i Press.

Shakespeare and World Cinema

Review of the field

Cinema-going at the Southampton Odeon: Exhibition Data and Popular Taste

Cinemagoing data from the 1970s. A case study of the data from the Southampton Odeon

'When I Land in Islamabad I Feel Home and When I Land in Heathrow I Feel Home': Gendered Belonging and Diasporic Identities of South Asian British Citizens in London, in Leicester and in North England

According to Deleuze and Guattari (1987) ‘de-territorialization’ is followed by a moment of re-territorialization. This moment, however, has to be regarded as a continuing educational process that becomes a different spatial site of social practices. It is argued in this chapter that regional, local as well as global identification override national and mono-ethno cultural identities, while shaping particular notions of gendered belonging and creating specific diasporic practices. Based on a sample of interviews with professional and academic South Asian British citizens in London, in Leicester, and in a number of Northern English cities gendered and generational patterns in terms of local diasporic identities are explored. Apart from multiple cultural belonging, foremost, territorial bonds and notions of group loyalty collapse at a point where temporary migration and settlement alternate in individual biographies.

Retro, faux-vintage, and anachronism: When cinema looks back at Its Analogue Past

This article explores the definition of ‘vintage cinema’ and specifically re-evaluates the fetishism for the past and its regurgitation in the present by providing a taxonomy of the phenomenon in recent film production. Our contribution identifies three aesthetic categories: the faux-vintage, the retro and the anachronistic and by illustrating their overlapping and discrepancies, it argues that the past remains a powerful negotiator of meaning for the present and the future. Drawing on studies of memory and digital nostalgia, this article focuses on the latter category: anachronism and unravel the persistence of and the filmic fascination for obsolete analogue objects through an analysis of Only Lovers Left Alive (Jim Jarmusch, 2013).