42 research outputs found
The SAURON project. II. Sample and early results
Early results are reported from the SAURON survey of the kinematics and
stellar populations of a representative sample of nearby E, S0 and Sa galaxies.
The survey is aimed at determining the intrinsic shape of the galaxies, their
orbital structure, the mass-to-light ratio as a function of radius, the age and
metallicity of the stellar populations, and the frequency of kinematically
decoupled cores and nuclear black holes. The construction of the representative
sample is described, and its properties are illustrated. A comparison with
long-slit spectroscopic data establishes that the SAURON measurements are
comparable to, or better than, the highest-quality determinations. Comparisons
are presented for NGC 3384 and NGC 4365 where stellar velocities and velocity
dispersions are determined to a precision of 6 km/s, and the h3 and h4
parameters of the line-of-sight velocity distribution to a precision of better
than 0.02. Extraction of accurate gas emission-line intensities, velocities and
line widths from the datacubes is illustrated for NGC 5813. Comparisons with
published line-strengths for NGC 3384 and NGC 5813 reveal uncertainties of <
0.1 A on the measurements of the Hbeta, Mgb and Fe5270 indices. Integral-field
mapping uniquely connects measurements of the kinematics and stellar
populations to the galaxy morphology. The maps presented here illustrate the
rich stellar kinematics, gaseous kinematics, and line-strength distributions of
early-type galaxies. The results include the discovery of a thin, edge-on, disk
in NGC 3623, confirm the axisymmetric shape of the central region of M32,
illustrate the LINER nucleus and surrounding counter-rotating star-forming ring
in NGC 7742, and suggest a uniform stellar population in the decoupled core
galaxy NGC 5813.Comment: 20 pages, 17 figures. To be published in MNRAS. Version with full
resolution images available at
http://www.strw.leidenuniv.nl/~dynamics/Instruments/Sauron/pub_list.htm
Docosahexaenoic acid inhibits Helicobacter pylori growth in vitro and mice gastric mucosa colonization
H. pylori drug-resistant strains and non-compliance to therapy are the major causes of H. pylori eradication failure. For some bacterial species it has been demonstrated that fatty acids have a growth inhibitory effect. Our main aim was to assess the ability of docosahexaenoic acid (DHA) to inhibit H. pylori growth both in vitro and in a mouse model. The effectiveness of standard therapy (ST) in combination with DHA on H. pylori eradication and recurrence prevention success was also investigated. The effects of DHA on H. pylori growth were analyzed in an in vitro dose-response study and n in vivo model. We analized the ability of H. pylori to colonize mice gastric mucosa following DHA, ST or a combination of both treatments. Our data demonstrate that DHA decreases H. pylori growth in vitro in a dose-dependent manner. Furthermore, DHA inhibits H. pylori gastric colonization in vivo as well as decreases mouse gastric mucosa inflammation. Addition of DHA to ST was also associated with lower H. pylori infection recurrence in the mouse model. In conclusion, DHA is an inhibitor of H. pylori growth and its ability to colonize mouse stomach. DHA treatment is also associated with a lower recurrence of H. pylori infection in combination with ST. These observations pave the way to consider DHA as an adjunct agent in H. pylori eradication treatment.publishe
31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two
Background
The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd.
Methods
We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background.
Results
First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001).
Conclusions
In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival