University of Erlangen-Nuremberg

About: University of Erlangen-Nuremberg is a education organization based out in Erlangen, Bayern, Germany. It is known for research contribution in the topics: Population & Immune system. The organization has 42405 authors who have published 85600 publications receiving 2663922 citations.

Characterization of the immunophenotypes and antigenomes of colorectal cancers reveals distinct tumor escape mechanisms and novel targets for immunotherapy

Abstract: Background: While large-scale cancer genomic projects are comprehensively characterizing the mutational spectrum of various cancers, so far little attention has been devoted to either define the antigenicity of these mutations or to characterize the immune responses they elicit. Here we present a strategy to characterize the immunophenotypes and the antigen-ome of human colorectal cancer. Results: We apply our strategy to a large colorectal cancer cohort (n = 598) and show that subpopulations of tumor-infiltrating lymphocytes are associated with distinct molecular phenotypes. The characterization of the antigenome shows that a large number of cancer-germline antigens are expressed in all patients. In contrast, neo-antigens are rarely shared between patients, indicating that cancer vaccination requires individualized strategy. Analysis of the genetic basis of the tumors reveals distinct tumor escape mechanisms for the patient subgroups. Hypermutated tumors are depleted of immunosuppressive cells and show upregulation of immunoinhibitory molecules. Non-hypermutated tumors are enriched with immunosuppressive cells, and the expression of immunoinhibitors and MHC molecules is downregulated. Reconstruction of the interaction network of tumor-infiltrating lymphocytes and immunomodulatory molecules followed by a validation with 11 independent cohorts (n = 1,945) identifies BCMA as a novel druggable target. Finally, linear regression modeling identifies major determinants of tumor immunogenicity, which include well-characterized modulators as well as a novel candidate, CCR8, which is then tested in an orthologous immunodeficient mouse model. Conclusions: The immunophenotypes of the tumors and the cancer antigenome remain widely unexplored, and our findings represent a step toward the development of personalized cancer immunotherapies.

Role of octreotide in the prevention of postoperative complications following pancreatic resection.

Abstract: Though morbidity and mortality rates following pancreatic resection have improved in recent years, they are still around 35% and 5%, respectively. Typical complications, such as pancreatic fistula, abscess, and subsequent sepsis, are chiefly associated with exocrine pancreatic secretion. In order to clarify whether the perioperative inhibition of exocrine pancreatic secretion prevents complications, we assessed the efficacy of octreotide, a long-acting somatostatin analogue. We conducted a randomized, double-blind, placebo-controlled, multicenter trial in 246 patients undergoing major elective pancreatic surgery. Patients were stratified into a high-risk stratum (limited to patients with pancreatic and periampullary tumors) or low-risk stratum (patients with chronic pancreatitis). Patients received octreotide (3 x 100 micrograms) or placebo subcutaneously for 7 days perioperatively. Eleven complications were defined: death, leakage of anastomosis, pancreatic fistula, abscess, fluid collection, shock, sepsis, bleeding, pulmonary insufficiency, renal insufficiency, and postoperative pancreatitis. Two hundred patients underwent pancreatic head resection, 31 patients underwent left resection, and 15 patients had other procedures. The overall mortality rate within 90 days was 4.5%, with 3.2% in the octreotide group and 5.8% in the placebo group. The complication rate was 32% in the patients receiving octreotide (40 of 125 patients) and 55% in patients receiving placebo (67 of 121 patients) (p less than 0.005). In the patients in the high-risk stratum, complications were observed in 26 of the 68 (38%) patients treated with octreotide and in 46 of 71 (65%) patients given placebo (p less than 0.01). Whereas in patients in the low-risk stratum, the complication rate was 25% (14 of 57 patients) in those treated with octreotide and 42% (21 of 50 patients) in patients given placebo (p = NS). The perioperative application of octreotide reduces the occurrence of typical postoperative complications after pancreatic resection, particularly in patients with tumors.

Three-dimensional imaging by a microscope

Abstract: In transmission microscopy, many objects are three dimensional, that is, they are thicker than the depth of focus of the imaging system. The three-dimensional (3-D) image-intensity distribution consists of a series of two-dimensional images (optical slices) with different parts of the object in focus. First, we deal with the fundamental limitations of 3-D imaging with classical optical systems. Second, a transfer theory of 3-D image formation is derived that relates the 3-D object (complex index of refraction) to the 3-D image intensity distribution in first-order Born approximation. This theory applies to weak objects that do not scatter much light. Since, in a microscope, the illumination is neither coherent nor completely incoherent, a theory for partially coherent light is needed, but in this case the object phase distribution and the absorptive parts of the object play different roles. Finally, some experimental results are presented.

Consolidation in banking and financial stability in Europe: Empirical evidence

Abstract: Using aggregate balance sheet data from banks across the EU-25 over the period from 1997 to 2005 we provide empirical evidence that national banking market concentration has a negative impact on European banks’ financial soundness as measured by the Z-score technique while controlling for macroeconomic, bank-specific, regulatory, and institutional factors. Furthermore, our analysis reveals that Eastern European banking markets exhibiting a lower level of competitive pressure, fewer diversification opportunities and a higher fraction of government-owned banks are more prone to financial fragility whereas capital regulations have supported financial stability across the entire European Union.