Malignant cells often demonstrate a proliferative advantage when compared to non-malignant cells. However, the rapid growth and metabolism required for survival can also highlight vulnerabilities specific to these malignant cells. One such vulnerability exhibited by cancer is an increased demand for amino acids (AAs), which often results in a dependency on exogenous sources of AAs or requires upregulation of de novo synthesis. These metabolic alterations can be exploited by therapy, which aims to improve treatment outcome and decrease relapse and reoccurrence. One clinically utilised strategy targeting AA dependency is the use of asparaginase in the treatment of acute lymphoblastic leukaemia (ALL), which results in a depletion of exogenous asparagine and subsequent cancer cell death. Examples of other successful strategies include the exploitation of arginine deiminase and methioninase, nutrient restriction of methionine and the inhibition of glutaminase. In this review, we summarise these treatment strategies into three promising avenues: AA restriction, enzymatic depletion and inhibition of metabolism. This review provides an insight into the complexity of metabolism in cancer, whilst highlighting these three current research avenues that have support in both preclinical and clinical settings.
We describe a technique for nding pixelwise correspondences between two images by using models of objects of the same class to guide the search. The object models are \learned" from example images (also called prototypes) of an object class. The models consist of a linear combination of prototypes. The ow elds giving pixelwise correspondences between a base prototype and each of the other prototypes must be given. A n o v el image of an object of the same class is matched to a model by minimizing an error between the novel image and the current guess for the closest model image. Currently, the algorithm applies to line drawings of objects. An extension to real grey level images is discussed.
Nine ventilated low birthweight babies were treated with dexamethasone (0-6 mg/kg/day). Appreciable suppression of weight gain was accompanied by uraemia and significant increases in the concentration of ali amino acids except phenylalanine, tyrosine, threonine, and glutamate. Ornithine, citrulline, alanine, glutamine, and cystine concentrations increased threefold or more. The findings could not be explained by changes in dietary intake and presumably reflect pronounced catabolism, though the effects of dexamethasone on, intermediary metabolism and membrane transport could also play a part.Dexamethasone is used increasingly to treat infants with bronchopulmonary dysplasia, principally to facilitate the withdrawal of mechanical respiratory support. ' 2 The precise mode of action of this drug in bronchopulmonary dysplasia is not clear, but lung compliance is known to increase, possibly through clearance of interstitial oedema. Treatment, which may be given for six weeks or more,' is usually accompanied by suppression of weight gain and uraemia, indicating the presence of catabolism.3 The metabolic vulnerability of immature infants provided with protein in excess of growth requirements is well known,47 but there are no data about the metabolic effects of high dose corticosteroid treatment in this group of patients. In this study we have measured the effect of dexamethasone on plasma amino acid concentrations.
This paper responds to recent calls in the leadership studies literature for anthropologically informed empirical research on leadership phenomena in non-Western and non-Anglophone settings. The authors have worked extensively on rural development projects in Laos and draw on ethnographic ‘observant-participation’ and interview data to explore how leadership is construed in a contested terrain where traditional concepts intersect with those of official government and international development agencies. A theoretical discussion of linguistic relativity and the socially constitutive nature of language in general is offered as background justification for studying the language of leadership in context. The anthropological distinction between etic and emic operations is also introduced to differentiate between various interpretative positions that can be taken in relation to the fieldwork and data discussed in this paper. The study shows how difficult it can be for native Lao speakers to find words to describe leadership or give designations to ‘leaders’ outside of officially sanctioned semantic and social fields. A key finding of the study is that, viewed from the perspective of the Lao People’s Revolutionary Party, authority and leadership are coextensive. This social fact is reflected in the linguistic restrictions on what can and cannot be described as leadership in Laos.
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