Immunotherapy for neuroblastoma using syngeneic fibroblasts transfected with IL-2 and IL-12

Cytokine-modified tumour cells have been used in clinical trials for immunotherapy of neuroblastoma, but primary tumour cells from surgical biopsies are difficult to culture. Autologous fibroblasts, however, are straightforward to manipulate in culture and easy to transfect using nonviral or viral vectors. Here we have compared the antitumour effect of fibroblasts and tumour cells transfected ex vivo to coexpress interleukin-2 (IL-2) and IL-12 in a syngeneic mouse model of neuroblastoma. Coinjection of cytokine-modified fibroblasts with Neuro-2A tumour cells abolished their in vivo tumorigenicity. Treatment of established tumours with three intratumoral doses of transfected fibroblasts showed a significant therapeutic effect with reduced growth or complete eradication of tumours in 90% of mice, associated with extensive leukocyte infiltration. Splenocytes recovered from vaccinated mice showed enhanced IL-2 production following Neuro-2A coculture, and increased cytotoxicity against Neuro-2A targets compared with controls. Furthermore, 100% of the tumour-free mice exhibited immune memory against tumour cells when rechallenged three months later. The potency of transfected fibroblasts was equivalent to that of tumour cells in all experiments. We conclude that syngeneic fibroblasts cotransfected with IL-2 and IL-12 mediate therapeutic effects against established disease, and are capable of generating immunological memory. Furthermore, as they are easier to recover and manipulate than autologous tumour cells, fibroblasts provide an attractive alternative immunotherapeutic strategy for the treatment of neuroblastoma

Genome sequences of four cluster P mycobacteriophages

Four bacteriophages infecting Mycobacterium smegmatis mc2155 (three belonging to subcluster P1 and one belonging to subcluster P2) were isolated from soil and sequenced. All four phages are similar in the left arm of their genomes, but the P2 phage differs in the right arm. All four genomes contain features of temperate phages

Neighbourhood immigration, health care utilization and outcomes in patients with diabetes living in the Montreal metropolitan area (Canada): a population health perspective

Abstract: Background: Understanding health care utilization by neighbourhood is essential for optimal allocation of resources, but links between neighbourhood immigration and health have rarely been explored. Our objective was to understand how immigrant composition of neighbourhoods relates to health outcomes and health care utilization of individuals living with diabetes. Methods: This is a secondary analysis of administrative data using a retrospective cohort of 111,556 patients living with diabetes without previous cardiovascular diseases (CVD) and living in the metropolitan region of Montreal (Canada). A score for immigration was calculated at the neighbourhood level using a principal component analysis with six neighbourhood-level variables (% of people with maternal language other than French or English, % of people who do not speak French or English, % of immigrants with different times since immigration (<5 years, 5–10 years, 10–15 years, 15–25 years)). Dependent variables were all-cause death, all-cause hospitalization, CVD event (death or hospitalization), frequent use of emergency departments, frequent use of general practitioner care, frequent use of specialist care, and purchase of at least one antidiabetic drug. For each of these variables, adjusted odds ratios were estimated using a multilevel logistic regression. Results: Compared to patients with diabetes living in neighbourhoods with low immigration scores, those living in neighbourhoods with high immigration scores were less likely to die, to suffer a CVD event, to frequently visit general practitioners, but more likely to visit emergency departments or a specialist and to use an antidiabetic drug. These differences remained after controlling for patient-level variables such as age, sex, and comorbidities, as well as for neighbourhood attributes like material and social deprivation or living in the urban core. Conclusions: In this study, patients with diabetes living in neighbourhoods with high immigration scores had different health outcomes and health care utilizations compared to those living in neighbourhoods with low immigration scores. Although we cannot disentangle the individual versus the area-based effect of immigration, these results may have an important impact for health care planning

Macrosocial determinants of population health in the context of globalization

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/55738/1/florey_globalization_2007.pd

Towards closed form solutions to the multiview constraints of curves and surfaces

Abstract. In this paper we present the theoretical setting for the closed form solutions to the multiview constraints of curves and surfaces observed by the motion of a camera in a scene. We £nd that knowledge of a curve or surface‘s structure can provide matching constraints and thus closed form solutions for the position of a camera in a scene over many images. This is advantageous for the process of Structure From Motion (SFM) as it may negate some of the need for non-linear optimisation (Bundle-Adjustment) of an initial linear solution to the motion of the camera and structure of the scene.