RESUMO
The potential utility of tumour-selective 5-fluorouracil treatment using attenuated Salmonella serovar typhimurium recombinant for cytosine deaminase (TAPET-CD) has been documented in experimental settings. The present data demonstrate that in vivo (19)F-magnetic resonance spectroscopy measurements allow the outcome prediction of this prokaryotic-based therapy, demonstrating the necessity of non-invasive real-time imaging techniques for treatment monitoring.
Assuntos
Antineoplásicos/metabolismo , Citosina Desaminase/uso terapêutico , Flucitosina/metabolismo , Fluoruracila/metabolismo , Terapia Genética/métodos , Neoplasias Experimentais/terapia , Animais , Antineoplásicos/análise , Antineoplásicos/uso terapêutico , Western Blotting , Cromatografia em Camada Fina , Citosina Desaminase/genética , Feminino , Flucitosina/análise , Flucitosina/uso terapêutico , Fluoruracila/análise , Fluoruracila/uso terapêutico , Vetores Genéticos , Humanos , Espectroscopia de Ressonância Magnética , Camundongos , Pró-Fármacos/análise , Pró-Fármacos/metabolismo , Pró-Fármacos/uso terapêutico , Salmonella typhimurium/genética , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Introduction: This cross sectional study was done in Gaborone City Council clinics in Botswana. Objective: The aim of the study was to determine the prevalence of hyperten- sion and related cardiovascular risk factors among DM patients. Methods: A total of 401 patients were included in a cross sectional study during a three-month period between December 1; 2003 and February 28; 2004. Results: During the study it was found out that 61.2of DM patients had hypertension; 56.4obesity; 33.5hypercholesterolemia and 38.9hypertriglyceredemia. In the study; hypertension was associated with age; sex; type of DM; body mass index (BMI) and hypertriglyceredemia. Conclusion: The study found out that most of DM patients suffer from co-existing hypertension and related cardiovascular risk factors
Assuntos
Diabetes Mellitus , Hipertensão/epidemiologiaRESUMO
The unique properties of the tumour microenvironment can be exploited by using recombinant anaerobic clostridial spores as highly selective gene delivery vectors. Although several recombinant Clostridium species have been generated during the past decade, their efficacy has been limited. Our goal was to substantially improve the prospects of clostridia as a gene delivery vector. Therefore, we have assessed a series of nitroreductase (NTR) enzymes for their capacity to convert the innocuous CB1954 prodrug to its toxic derivative. Among the enzymes tested, one showed superior prodrug turnover characteristics. In addition, we established an efficient gene transfer procedure, based on conjugation, which allows for the first time genetic engineering of Clostridium strains with superior tumour colonisation properties with high success rates. This conjugation procedure was subsequently used to create a recombinant C. sporogenes overexpressing the isolated NTR enzyme. Finally, analogous to a clinical setting situation, we have tested the effect of multiple consecutive treatment cycles, with antibiotic bacterial clearance between cycles. Importantly, this regimen demonstrated that intravenously administered spores of NTR-recombinant C. sporogenes produced significant antitumour efficacy when combined with prodrug administration.
