THE CHRONOBIOLOGICAL HYPOTHESIS AND PSYCHOSOCIAL AND CULTURAL GENOMIC THERAPIES: FROM THE EXAMPLE OF PARKINSON’S DISEASE AND NEURODEGENERATIVE PROCESS

Recent research on Parkinson’s Disease (PD) revealed some common etiopathogenic mechanisms underlying a large range of chronic diseases, and more specifically the deregulation of chronobiological rhythms that may start in the very beginning of such pathological development. Contrary to the bottom-up tradition, the post-genomic biology provides now a much favorable zeitgeist to integrate holistic interventions in both biomedical research and mainstream medical practice. Such integrative efforts may not only improve our understanding of system-level dynamics about health and disease, but also opens larger possibilities for new clinical options that bring positive pathological evolutions while globally increasing quality of life of patients, caregivers, and their families. To facilitate the transition, we renew the invitation to join our international open source research project in widely testing the Creative Psychosocial Genomic Healing Experience (CPGHE), an evidence-based construction of a holistic and naturalist intervention with its standardized version specially designed to offer easy adaption for scientific investigation towards an evidence-based integration of holistic intervention possibilities

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

Pressure dependence of the near-band-edge photoluminescence from ZnO microrods at low temperature

The temperature and pressure dependences of band-edge photo luminescence from ZnO microrods have been investigated. The energy separation between the free exciton (FX) and its first order phonon replica (FX-1LO) decreases at a rate of k(B)T with increasing temperature. The intensity ratio of the FX-1LO to the bound exciton (BX) emission is found to decrease slightly with increasing pressure. All of the exciton emission peaks show a blue shift with increasing pressure. The pressure coefficient of the FX transition, longitudinal optical (LO) phonon energy, and binding energy of BX are estimated to be 21.4, 0.5, and 0.9 meV/GPa, respectively. (c) 2006 Elsevier Ltd. All rights reserved