ABSTRACT
Oncolytic adenoviruses have shown some promise in cancer gene therapy. However, their efficacy in clinical trials is often limited, and additional therapeutic interventions have been proposed to increase their efficacies. In this context, molecular imaging of viral spread in tumours could provide unique information to rationalize the timing of these combinations. Here, we use the human sodium iodide symporter (hNIS) as a reporter gene in wild-type and replication-selective adenoviruses. By design, hNIS cDNA is positioned in the E3 region in a wild-type adenovirus type 5 (AdIP1) and in an adenovirus in which a promoter from the human telomerase gene (RNA component) drives E1 expression (AdAM6). Viruses show functional hNIS expression and replication in vitro and kinetics of spread of the different viruses in tumour xenografts are visualized in vivo using a small animal nano-SPECT/CT camera. The time required to reach maximal spread is 48 h for AdIP1 and 72 h for AdAM6 suggesting that genetic engineering of adenoviruses can affect their kinetics of spread in tumours. Considering that this methodology is potentially clinically applicable, we conclude that hNIS-mediated imaging of viral spread in tumours may be an important tool for combined anticancer therapies involving replicating adenoviruses
Subject(s)
Colonic Neoplasms/diagnostic imaging , Colonic Neoplasms/therapy , Genes, Reporter , Genetic Therapy/methods , Oncolytic Virotherapy/methods , Symporters/genetics , Tomography, Emission-Computed, Single-Photon , Adenoviridae/genetics , Adenoviridae Infections/diagnostic imaging , Animals , Colonic Neoplasms/virology , Gene Expression , Humans , Injections, Intralesional , Mice , Mice, Inbred BALB C , Neoplasm Transplantation , Transduction, Genetic/methods , Transplantation, Heterologous , Virus ReplicationABSTRACT
OBJECTIVE: To obtain information which might guide vascular specialists and their patients in the choice of site for implantation of central venous access devices (CVADs). DESIGN: Questionnaire study. METHODS: Questionnaires were sent to 69 patients with cystic fibrosis and 54 (78%) responded (39 females: age 5-63, median 24 years). They had received a total of 79 CVADs placed in the upper chest (60), lower chest (13), thigh (3) and arm (3). Only 46% patients had been offered a choice of site. RESULTS: Questions about 14 specific areas of disability or concern found problems most frequently with discomfort (54%), wearing a seatbelt (51%), cosmetic appearance (44%), scarring (44%), choice of clothing (42%) and lying in bed or sleeping (42%). There were no significant differences between upper and lower chest CVADs. Patients with upper chest CVADs seldom had any problems with use of their arm (12%). 81% CVADs could not be accessed by the patients, and in 39% of these cases patients would have liked to do so. CONCLUSIONS: Many patients complain of few problems with their CVADs, regardless of site, but half have some persistent discomfort. Cosmetic considerations frequently cause concern and patients should be given choice in the site of their CVADs.
Subject(s)
Catheterization, Central Venous , Patient Satisfaction , Adolescent , Adult , Child , Child, Preschool , Female , Humans , Male , Middle Aged , Surveys and QuestionnairesABSTRACT
The authors report a case of a gastrointestinal stromal tumour (GIST) of the gallbladder. GISTs are rare mesenchymal tumours of the gastrointestinal tract, mesentery and omentum. GISTs are characterized by the expression of the KIT protein, a transmembrane tyrosine kinase receptor for stem-cell factor. Only a few GISTs of the gallbladder have been described in the literature. The behaviour of these tumours is not fully understood but long-term survival is rare. Initial treatment consists of aggressive surgery. Radiotherapy and conventional chemotherapy have been mostly unsuccessful. More recently promising studies have been performed with Imatinib, an orally administered tyrosine kinase inhibitor, in patients with advanced disease.
