22 research outputs found
Laryngeal Mask Airway for neonatal resuscitation in a developing country: evaluation of an educational intervention. Neonatal LMA: an educational intervention in DRC
Tumor-Infiltrating T Cells Correlate with NY-ESO-1-Specific Autoantibodies in Ovarian Cancer
BACKGROUND: Tumor-infiltrating CD8+ T cells are correlated with prolonged progression-free and overall survival in epithelial ovarian cancer (EOC). A significant fraction of EOC patients mount autoantibody responses to various tumor antigens, however the relationship between autoantibodies and tumor-infiltrating T cells has not been investigated in EOC or any other human cancer. We hypothesized that autoantibody and T cell responses may be correlated in EOC and directed toward the same antigens. METHODOLOGY AND PRINCIPAL FINDINGS: We obtained matched serum and tumor tissue from 35 patients with high-grade serous ovarian cancer. Serum samples were assessed by ELISA for autoantibodies to the common tumor antigen NY-ESO-1. Tumor tissue was examined by immunohistochemistry for expression of NY-ESO-1, various T cell markers (CD3, CD4, CD8, CD25, FoxP3, TIA-1 and Granzyme B) and other immunological markers (CD20, MHC class I and MHC class II). Lymphocytic infiltrates varied widely among tumors and included cells positive for CD3, CD8, TIA-1, CD25, FoxP3 and CD4. Twenty-six percent (9/35) of patients demonstrated serum IgG autoantibodies to NY-ESO-1, which were positively correlated with expression of NY-ESO-1 antigen by tumor cells (r = 0.57, p = 0.0004). Autoantibodies to NY-ESO-1 were associated with increased tumor-infiltrating CD8+, CD4+ and FoxP3+ cells. In an individual HLA-A2+ patient with autoantibodies to NY-ESO-1, CD8+ T cells isolated from solid tumor and ascites were reactive to NY-ESO-1 by IFN-gamma ELISPOT and MHC class I pentamer staining. CONCLUSION AND SIGNIFICANCE: We demonstrate that tumor-specific autoantibodies and tumor-infiltrating T cells are correlated in human cancer and can be directed against the same target antigen. This implies that autoantibodies may collaborate with tumor-infiltrating T cells to influence clinical outcomes in EOC. Furthermore, serological screening methods may prove useful for identifying clinically relevant T cell antigens for immunotherapy
Low vitamin D status is associated with systemic and gastrointestinal inflammation in dogs with a chronic enteropathy
Vitamin D is traditionally known for its role in calcium homeostasis and bone metabolism.
However, it has been demonstrated that numerous types of cells express the vitamin D
receptor and it is now clear that the physiological roles of vitamin D extend beyond the
maintenance of skeletal health. Vitamin D insufficiency, which is typically assessed by
measuring the major circulating form of vitamin D, 25 hydroxyvitamin D (25(OH)D), has
been associated with a number of disorders in people including hypertension, diabetes,
cardiovascular diseases, cancer, autoimmune conditions and infectious diseases. Meta-analyses
have demonstrated that serum 25(OH)D concentrations are an important predictor
of survival in people with a wide variety of illnesses and have been linked to all-cause
mortality in the general human population.
The role of vitamin D in non-skeletal disorders in cats and dogs is poorly understood. This is
surprising since cats and dogs could act as excellent models for probing the biology of
vitamin D. Vitamin D status in people is largely dependent on cutaneous production of
vitamin D. This is influenced by many factors such as season, latitude and exposure to
ultraviolet (UV) radiation. The interpretation of human studies investigating the effects
vitamin D status on disease outcomes are therefore influenced by a number of confounding
variables. Unlike humans, domesticated cats and dogs do not produce vitamin D cutaneously
and obtain vitamin D only from their diet. The physiological functions and regulation of
vitamin D are otherwise similar to humans. Most pets are fed commercial diets containing a
relatively standard amount of vitamin D. Consequently, companion animals are attractive
model systems in which to examine the relationship vitamin D status and health outcomes.
Furthermore, spontaneously occurring model systems which did not require disease to be
induced in healthy animals would allow the numbers of animals used in scientist research to
be reduced.
This thesis aimed to define vitamin D homeostasis in companion animals in three disease
settings; in cats with feline immunodeficiency virus (FIV) infection, dogs with chronic
enteropathies (CE) and in hospitalised ill cats. Additional aims were to assess the prognostic
significance of serum 25(OH)D concentrations in companion animals and the relationship
between serum 25(OH)D concentrations and markers of inflammation. The hypothesis of
this thesis was that vitamin status D would negatively correlate with presence of disease,
markers of inflammation and disease outcomes. As similar findings have been demonstrated
in human medicine, the hypothesis was that cats and dogs would be suitable models to
investigate the role of vitamin D in human disease.
This thesis demonstrates that in dogs with a CE serum 25(OH)D concentrations are
negatively correlated with inflammation and are predictive of clinical outcomes. Vitamin D
status was also lower in cats with FIV and importantly vitamin D status was predictive of
short term mortality in hospitalised ill cats. This research will be of interest to veterinary
surgeons and opens the possibility for clinical trials which examine if low vitamin D status is
causally associated with ill health and whether vitamin D supplementation results in superior
treatment outcomes in companion animals. This thesis also demonstrates the potential of cats
and dogs as model systems in which to examine the role of vitamin D in human health