At the annual prestigious International Symposium of the Fritz-Bender Foundation, Munich, 18-20 May, 2016, researchers, clinicians, and students discussed the state of the art and future perspectives of genomic medicine in cancer. Genomic medicine (also known as precision medicine/oncology) should help clinicians to provide a more precise diagnosis and therapy in oncology for individual patients. The meeting focused on next-generation sequencing methods, analytical computational analysis of big data, and data mining on the way to translational and evidence-based medicine. The meeting covered the social and ethical impact of genomic medicine as well as news and views on antibody targeting of intracellular proteins, on the architecture of intracellular proteins and their impact on carcinogenesis, and on the adaptation of tumor therapy in due consideration of tumor evolution. Subheadings like “Genetic Profiling of Patients and Risk Prediction,” “Molecular Profiling of Tumors and Metastases,” “Tumor-Host Microenvironment Interaction and Metabolism,” and “Targeted Therapy” were subsumed under the main heading of “Personalized Cancer Care.”

The Oslo University Hospital (Norway), the K.G. Jebsen Centre for Breast Cancer Research (Norway), The Radiumhospital Foundation (Norway) and the Fritz-Bender-Foundation (Germany) designed under the conference chairmen (E. Mihich, K.S. Zänker, A.L. Borresen-Dale) and advisory committee (A. Borg, Z. Szallasi, O. Kallioniemi, H.P. Huber) a program at the cutting edge of “PERSONALIZED CANCER CARE: Risk prediction, early diagnosis, progression and therapy resistance.” The conference was held in Oslo from September 7 to 9, 2012 and the science-based presentations concerned six scientific areas: (1) Genetic profiling of patients, prediction of risk, late side effects; (2) Molecular profiling of tumors and metastases; (3) Tumor-host microenvironment interaction and metabolism; (4) Targeted therapy; (5) Translation and (6) Informed consent, ethical challenges and communication. Two satellite workshops on (i) Ion Ampliseq—a novel tool for large scale mutation detection; and (ii) Multiplex RNA ISH and tissue homogenate assays for cancer biomarker validation were additionally organized. The report concludes that individual risk prediction in carcinogenesis and/or metastatogenesis based on polygenic profiling may be useful for intervention strategies for health care and therapy planning in the future. To detect distinct and overlapping DNA sequence alterations in tumor samples and adjacent normal tissues, including point mutations, small insertions or deletions, copy number changes and chromosomal rearrangements will eventually make it possible to design personalized management plans for individualized patients. However, large individualized datasets need a new approach in bio-information technology to reduce this enormous data dimensionally to simply working hypotheses about health and disease for each individual.

In acute respiratory distress syndrome of term newborn infants, surfactant replacement may be effective because endogenous surfactant is decreased and structurally changed. Inflammation is central to acute respiratory distress syndrome, and hence, attenuation of proinflammatory transcription factor nuclear factor (NF)-[kappa]B activation in the lung might prevent secondary loss of surfactant function. In this study, we tested the hypothesis that the topical use of a NF-[kappa]B inhibitor (I[kappa]B kinase-NF-[kappa]B essential modulator binding domain [IKK-NBD] peptide), together with surfactant as a carrier substance, improves surfactant function by attenuation of pulmonary inflammation during 24 hrs of mechanical ventilation in a neonatal piglet model of acute respiratory distress syndrome by repeated airway lavage. Prospective, randomized, controlled study. Research laboratory of a university children's hospital. A total of 24 anesthetized, mechanically ventilated newborn piglets. After 20 +/- 6 (mean +/- sd) lavages to induce lung failure and inflammation, a porcine surfactant (100 mg/kg) with (S+IKK) or without (S) 1.25 mg of IKK-NBD peptide, or an air bolus (control) was administered into the airways. Lung function was monitored throughout 24 hrs of mechanical ventilation and completed by ex vivo analyses. Pao2 (S+IKK, 125 +/- 16 mm Hg; S, 105 +/- 33; control, 61 +/- 20), ventilation efficiency index, functional residual capacity, compliance of the respiratory system, and extravascular lung water (S+IKK, 24 +/- 2 mL/kg; S, 30 +/- 7; control, 34 +/- 8) were all significantly improved in S+IKK piglets after 24 hrs. Decreased leukocyte concentrations in bronchoalveolar lavage (S+IKK, 152 +/- 94 cells/microL; S, 202 +/- 100; control, 276 +/- 57) were observed together with reduced acid sphingomyelinase activity, lowered ceramide concentrations, improved surfactant function (minimum surface tension: S+IKK, 10.8 +/- 6.1 mN/m; S, 13.2 +/- 3.9; control, 20.9 +/- 8.5), and decreased NF-[kappa]B activation in lung tissue. Supplementation of exogenous surfactant with a NF-[kappa]B inhibitor to create a "fortified" surfactant improves gas exchange, lung function, and pulmonary edema during 24 hrs of mechanical ventilation, without a secondary functional relapse. Inhibition of NF-[kappa]B suppressed acid sphingomyelinase activity and ceramide generation, indicating a novel proinflammatory link of NF-[kappa]B.

Lipopolysaccharide (LPS) can activate human and murine T cells in vivo and in vitro. Here we analysed the effects of LPS on T cells with defined specificities in T-cell receptor (TCR)-transgenic systems. LPS rapidly induced high amounts of interferon (IFN)-gamma in a subpopulation of purified T cells from DO11.10 (OVA323-339/H2-Ad) and OT-1 (OVA257-264/H2-Kb) mice when coincubated with antigen-pulsed peritoneal exudate cells (PECs). LPS induced IFN-gamma in T cell cultures even when the number of antigenic major histocompatibility complex (MHC) class-I complexes was too small to stimulate the T cells. LPS, thus, overruled the unresponsiveness of the otherwise 'antigen-ignorant' T cells. The release of IFN-gamma strictly correlates with the PECs' ability to produce interleukin (IL)-12. In contrast to the induction of IFN-gamma, antigen-specific IL-2 secretion and proliferation of T cells were rather decreased in the presence of LPS. Only very few IFN-gamma-secreting natural killer (NK) cells and natural killer T (NKT) cells in the given experimental system could be detected using intracellular fluorescence-activated cell sorter (FACS) staining. Taken together, our results indicate that LPS has the potential to activate quiescent T cells and to specifically induce IFN-gamma in CD4 and CD8 T cells. This may have direct consequences for the activation of autoreactive T cells following bacterial infections.