HIF-1alpha role in oxygen-dependent radio- and chemosensitivity

Poor oxygenation (hypoxia) is a common characteristic of human solid tumours, and is associated with cell survival, metastasis and resistance to radio- and chemotherapies. Hypoxia-induced stabilisation of hypoxia-inducible factor-1α (HIF-1α) leads to changes in expression of various genes associated with growth, vascularisation and metabolism. However whether HIF-1α plays a causal role in promoting hypoxic resistance to antitumour therapies remains unclear. In this study we used pharmacological and genetic methods to investigate the HIF-1α contribution to radio- and chemoresistance in four cancer cell lines derived from cervical, breast, prostate and melanoma human tumours. Under normoxia or hypoxia (<0.2% or 0.5% oxygen) the cells were exposed to either a standard irradiation dose (6.2 Gy) or chemotherapeutic drug (cisplatin), and subsequent cell proliferation (after 7 days) was measured in terms of resazurin reduction. Oxygen-dependent radio- and chemosensitivity was evident in all wild type whereas it was reduced or abolished in HIF-1α (siRNA) knockdown cells. The effects of HIF-1α-modulating drugs (EDHB, CoCl2, deferoxamine to stabilise and R59949 to destabilise it) reflected both HIF-1α-dependent and independent mechanisms. Collectively the data show that HIF-1α played a causal role in our in vitro model of hypoxia-induced radioresistance whereas its contribution to oxygendependent sensitivity to cisplatin was less clear-cut. Although this behavior is likely to be conditioned by further biological and physical factors operating in vivo, it is consistent with the hypothesis that interventions directed at HIF-1α may improve the clinical effectiveness of tumour treatments.

Urbanization effects on welfare and income diversification strategies of peri-urban farm households in Tigray, Northern Ethiopia: An empirical analysis

Urban areas in many developing countries are expanding rapidly by incorporating nearby subsistence farming communities. This has a direct effect on the consumption and production behaviours of the farm households but empirical evidence is sparse. This thesis investigated the effects of rapid urbanization and the associated policies on welfare of subsistence farm households in peri-urban areas using a panel dataset from Tigray, Ethiopia. The study revealed a number of important issues emerging with the rapid urban expansion. Firstly, private asset holdings and consumption expenditure of farm households, that have been incorporated into urban administration, has decreased. Secondly, factors that influence the farm households’ welfare and vulnerability depend on the administration they belong to, urban or rural. Gender and literacy of the household head have significant roles for the urban farm households to fall back into and/or move out of poverty. However, livestock holding and share of farm income are the most important factors for rural households. Thirdly, the study discloses that farming continues to be important source of income and income diversification is the principal strategy. Participation in nonfarm employment is less for farm households in urban than rural areas. Adult labour, size of the local market and past experience in the nonfarm sector improves the likelihood of engaging in skilled nonfarm employment opportunities. But money, given as compensation for the land taken away, is not crucial for the household to engage in better paying nonfarm employments. Production behaviour of the better-off farm households is the same, regardless of the administration they belong to. However, the urban poor participate less in nonfarm employment compared to the rural poor. These findings signify the gradual development of urban-induced poverty in peri-urban areas. In the case of labour poor households, introducing urban safety net programmes could improve asset productivity and provide further protection.