18 research outputs found
Local and systemic effect of transfection-reagent formulated DNA vectors on equine melanoma
Background Equine melanoma has a high incidence in grey horses. Xenogenic DNA
vaccination may represent a promising therapeutic approach against equine
melanoma as it successfully induced an immunological response in other species
suffering from melanoma and in healthy horses. In a clinical study, twenty-
seven, grey, melanoma-bearing, horses were assigned to three groups (n = 9)
and vaccinated on days 1, 22, and 78 with DNA vectors encoding for equine (eq)
IL-12 and IL-18 alone or in combination with either human glycoprotein (hgp)
100 or human tyrosinase (htyr). Horses were vaccinated intramuscularly, and
one selected melanoma was locally treated by intradermal peritumoral
injection. Prior to each injection and on day 120, the sizes of up to nine
melanoma lesions per horse were measured by caliper and ultrasound. Specific
serum antibodies against hgp100 and htyr were measured using cell based flow-
cytometric assays. An Analysis of Variance (ANOVA) for repeated measurements
was performed to identify statistically significant influences on the relative
tumor volume. For post-hoc testing a Tukey-Kramer Multiple-Comparison Test was
performed to compare the relative volumes on the different examination days.
An ANOVA for repeated measurements was performed to analyse changes in body
temperature over time. A one-way ANOVA was used to evaluate differences in
body temperature between the groups. A p–value < 0.05 was considered
significant for all statistical tests applied. Results In all groups, the
relative tumor volume decreased significantly to 79.1 ± 26.91% by day 120 (p <
0.0001, Tukey-Kramer Multiple-Comparison Test). Affiliation to treatment
group, local treatment and examination modality had no significant influence
on the results (ANOVA for repeated measurements). Neither a cellular nor a
humoral immune response directed against htyr or hgp100 was detected. Horses
had an increased body temperature on the day after vaccination. Conclusions
This is the first clinical report on a systemic effect against equine melanoma
following treatment with DNA vectors encoding eqIL12 and eqIL18 and formulated
with a transfection reagent. Addition of DNA vectors encoding hgp100
respectively htyr did not potentiate this effect
Critical questions in ovarian cancer research and treatment: Report of an American Association for Cancer Research Special Conference.
Substantial progress has been made in understanding ovarian cancer at the molecular and cellular level. Significant improvement in 5-year survival has been achieved through cytoreductive surgery, combination platinum-based chemotherapy, and more effective treatment of recurrent cancer, and there are now more than 280,000 ovarian cancer survivors in the United States. Despite these advances, long-term survival in late-stage disease has improved little over the last 4 decades. Poor outcomes relate, in part, to late stage at initial diagnosis, intrinsic drug resistance, and the persistence of dormant drug-resistant cancer cells after primary surgery and chemotherapy. Our ability to accelerate progress in the clinic will depend on the ability to answer several critical questions regarding this disease. To assess current answers, an American Association for Cancer Research Special Conference on "Critical Questions in Ovarian Cancer Research and Treatment" was held in Pittsburgh, Pennsylvania, on October 1-3, 2017. Although clinical, translational, and basic investigators conducted much of the discussion, advocates participated in the meeting, and many presentations were directly relevant to patient care, including treatment with poly adenosine diphosphate ribose polymerase (PARP) inhibitors, attempts to improve immunotherapy by overcoming the immune suppressive effects of the microenvironment, and a better understanding of the heterogeneity of the disease