A randomised phase II study of pegylated arginine deiminase (ADI-PEG 20) in Asian advanced hepatocellular carcinoma patients

[[abstract]]Background:Human hepatocellular carcinoma (HCC) cells are largely deficient of argininosuccinate synthetase and thus auxotrophic for arginine. This study aims to investigate the efficacy and pharmacodynamics of pegylated arginine deiminase (ADI-PEG 20), a systemic arginine deprivation agent, in Asian HCC patients. Methods:Patients with advanced HCC who were not candidates for local therapy were eligible and randomly assigned to receive weekly intramuscular injections of ADI-PEG 20 at doses of 160 or 320 IU m-2. The primary end point was disease-control rate (DCR). Results:Of the 71 accruals, 43.6% had failed previous systemic treatment. There were no objective responders. The DCR and the median overall survival (OS) of the intent-to-treat population were 31.0% (95% confidence interval (CI): 20.5-43.1) and 7.3 (95% CI: 4.7-9.9) months respectively. Both efficacy parameters were comparable between the two study arms. The median OS of patients with undetectable circulating arginine for more than or equal to and <4 weeks was 10.0 (95% CI: 2.1-17.9) and 5.8 (95% CI: 1.4-10.1) months respectively (P=0.251, log-rank test). The major treatment-related adverse events were grades 1-2 local and/or allergic reactions. Conclusions:ADI-PEG 20 is safe and efficacious in stabilising the progression of heavily pretreated advanced HCC in an Asian population, and deserves further exploration.British Journal of Cancer advance online publication, 31 August 2010; doi:10.1038/sj.bjc.6605856 www.bjcancer.com

Gene therapy for carcinoma of the breast: Pro-apoptotic gene therapy

The dysregulation of apoptosis contributes in a variety of ways to the malignant phenotype. It is increasingly recognized that the alteration of pro-apoptotic and anti-apoptotic molecules determines not only escape from mechanisms that control cell cycle and DNA damage, but also endows the cancer cells with the capacity to survive in the presence of a metabolically adverse milieu, to resist the attack of the immune system, to locally invade and survive despite a lack of tissue anchorage, and to evade the otherwise lethal insults induced by drugs and radiotherapy. A multitude of apoptosis mediators has been identified in the past decade, and the roles of several of them in breast cancer have been delineated by studying the clinical correlates of pathologically documented abnormalities. Using this information, attempts are being made to correct the fundamental anomalies at the genetic level. Fundamental to this end are the design of more efficient and selective gene transfer systems, and the employment of complex interventions that are tailored to breast cancer and that are aimed concomitantly towards different components of the redundant regulatory pathways. The combination of such genetic modifications is most likely to be effective when combined with conventional treatments, thus robustly activating several pro-apoptotic pathways

Relationship between serum leptin immunoreactivity and body fat mass as estimated by use of a novel gas-phase Fourier transform infrared spectroscopy deuterium dilution method in cats.

ObjectiveTo validate a recently developed commercially available leptin radioimmunoassay (RIA) for use with feline serum and evaluate the relationship between serum leptin concentrations and body fat mass in domestic cats.Animals19 sexually intact male specific-pathogen-free domestic cats that weighed 3.8 to 7.1 kg and were 1.1 to 3.5 years old.ProcedureSpecificity for feline leptin was evaluated by use of gel filtration chromatography and reverse-phase high-performance liquid chromatography fractionation of serum. Body fat mass was determined by use of the deuterium oxide (D2O) dilution method. Serum water D2O enrichment was measured by use of gas-phase Fourier transform infrared spectroscopy.ResultsBody fat mass and percentage body fat ranged from 0.3 to 2.3 kg and 7.5 to 34.9%, respectively. Serum leptin concentrations were lower in the unfed versus the fed state and ranged between 1.6 and 4.9 ng/ml human equivalent (HE); mean +/- SD value was 2.9 +/- 0.2 ng/ml HE. Leptin concentrations increased with increasing body fat mass and percentage of body fat.ConclusionsLeptin is in the serum of domestic cats in free (&gt; 78%) and apparently bound forms. The relationship between body fat and serum leptin concentration was similar to that observed in humans and rodents and indicative of a lipostatic role for leptin in cats. Cats that have an overabundance of body fat appear to be less sensitive to the weight-normalizing action of leptin than cats of ideal body condition

Drivers and facilitators of hunting behaviour in domestic cats and options for management

This is the final version. Available on open access from Wiley via the DOI in this recordDomestic cats Felis catus are distinct from other domesticated animals because their phenotype and genotype are relatively unchanged. While they live with people as pets or pest controllers, they retain capacity for survival independent of human support and readily persist as feral animals. Most cats retain some propensity to express hunting behaviours, even if hunting is not required for nutrition. In some settings, depredation by cats is a threat to biodiversity conservation, leading to attempts to mitigate their impacts. We characterise drivers and facilitators of the hunting behaviour of domestic cats: evolutionary origins, diet, life history, personality and environment. Hunting is driven particularly by evolutionary constraints and associated physiological and nutritional requirements. Proximate causes of variation in hunting behaviours relate to prey availability, husbandry and degree of domestication, while early life history and personality play further roles. We review cat management approaches in terms of effectiveness, feasibility and welfare. Amongst lethal, large-scale methods of population control, poisoning is most frequently used in cat eradications from islands. Because poisoning is challenged on welfare grounds, euthanasia is used at smaller scales and in inhabited, mainland settings. Non-lethal approaches, primarily surgical sterilisation, are favoured by cat advocates but entail challenging logistics and scale. In attempts to inhibit predation of wild species by pet cats, owners restrict outdoor access and use collar-mounted devices, including bells, sonic devices, collar covers and bibs. Other individual-level interventions, such as dietary and behavioural enrichment, some of which may improve cat welfare, have potential, but effects on hunting remain untested. Understanding and managing the hunting behaviour of cats are complex challenges. We highlight drivers and facilitators of this behaviour, representing starting points for formulating solutions that might be acceptable to cat owners and wider groups of people who value cat welfare, while also being effective for wildlife conservation.SongBird SurvivalUniversity of Exete

Descrição de dieta purificada para indução de quadro de desnutrição protéica em ratos

No presente trabalho é descrita a composição de dieta hipoprotéica (6% de proteína) purificada para indução de quadro de desnutrição em roedores. A referida dieta foi padronizada em laboratório a partir de modificação da AIN-93 (documento do American Institute of Nutrition que estabelece os padrões nutricionais para roedores de laboratório), visando a obtenção de animais desnutridos para estudar as alterações metabólicas decorrentes da desnutrição protéica associada a situações como exercício físico, gestação e diabetes. A dieta em questão contém os seguintes componentes (g/ kg): amido de milho (480), caseína (71,5), dextrina de milho (159), sacarose (121), óleo de soja (70), microcelulose (50), mistura mineral AIN-93-G-MX (35), mistura de vitaminas AIN-93-G-VX, (10), L-cistina (1), cloridrato de colina (2,5). Ratos alimentados cronicamente com a dieta apresentaram sinais comumente presentes na desnutrição protéica humana e de animais de laboratório: redução do ganho de peso, hipoproteinemia, hipoalbuminemia, elevação dos ácidos graxos livres séricos e do glicogênio hepático