Cell-type plasticity within a tumor has recently been suggested to cause a bidirectional conversion between tumor-initiating stem cells and nonstem cells triggered by an inflammatory stroma. NF-κB represents a key transcription factor within the inflammatory tumor microenvironment. However, NF-κB's function in tumor-initiating cells has not been examined yet. Using a genetic model of intestinal epithelial cell (IEC)-restricted constitutive Wnt-activation, which comprises the most common event in the initiation of colon cancer, we demonstrate that NF-κB modulates Wnt signaling and show that IEC-specific ablation of RelA/p65 retards crypt stem cell expansion. In contrast, elevated NF-κB signaling enhances Wnt activation and induces dedifferentiation of nonstem cells that acquire tumor-initiating capacity. Thus, our data support the concept of bidirectional conversion and highlight the importance of inflammatory signaling for dedifferentiation and generation of tumor-initiating cells in vivo.

Although gastrointestinal cancers are frequently associated with chronic inflammation, the underlying molecular links have not been comprehensively deciphered. Using loss- and gain-of-function mice in a colitis-associated cancer model, we establish here a link comprising the gp130/Stat3 transcription factor signaling axis. Mutagen-induced tumor growth and multiplicity are reduced following intestinal epithelial cell (IEC)-specific Stat3 ablation, while its hyperactivation promotes tumor incidence and growth. Conversely, IEC-specific Stat3 deficiency enhances susceptibility to chemically induced epithelial damage and subsequent mucosal inflammation, while excessive Stat3 activation confers resistance to colitis. Stat3 has the capacity to mediate IL-6- and IL-11-dependent IEC survival and to promote proliferation through G1 and G2/M cell-cycle progression as the common tumor cell-autonomous mechanism that bridges chronic inflammation to tumor promotion.

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The recruitment of immune cells into solid tumors is an essential prerequisite of tumor development. Depending on the prevailing polarization profile of these infiltrating leucocytes, tumorigenesis is either promoted or blocked. Here, we identify IκB kinase α (IKKα) as a central regulator of a tumoricidal microenvironment during intestinal carcinogenesis. Mice deficient in IKKα kinase activity are largely protected from intestinal tumor development that is dependent on the enhanced recruitment of interferon γ (IFNγ)-expressing M1-like myeloid cells. In IKKα mutant mice, M1-like polarization is not controlled in a cell-autonomous manner but, rather, depends on the interplay of both IKKα mutant tumor epithelia and immune cells. Because therapies aiming at the tumor microenvironment rather than directly at the mutated cancer cell may circumvent resistance development, we suggest IKKα as a promising target for colorectal cancer (CRC) therapy.

Pretreatment with hydrocortisone ameliorated shedding of heparan sulfate, a major constituent of the endothelial glycocalyx, in patients undergoing cardiac surgery with cardiopulmonary bypass, but had no relevant influence on various clinical parameters or patient mortality. The relatively small number of patients in this pilot study probably precluded detection of positive outcome differences.

Cardiac surgery, especially if it involves cardiopulmonary bypass, is associated with a severe systemic inflammatory response. It is characterized by complement activation and initiation of coagulation, fibrinolysis and kallikrein cascades. Consecutive activation of immunoregulatory cells results in an extensive release of pro- and anti-inflammatory cytokines. This inflammatory storm is related to organ dysfunction or failure and correlates with postoperative morbidity. In order to attenuate this deleterious inflammatory response in the perioperative period alternative surgical techniques, novel extracorporeal circulation devices and immunomodulatory pharmacological strategies are in focus of contemporary research. Since decades corticosteroids have been used and studied in patients undergoing cardiac surgery. Although it could be shown that glucocorticoids seem to change the pro-inflammatory cytokine profile in a favourable manner, it still remains controversial if this effect translates into a better clinical outcome. Several clinical trials have proclaimed an association between this inflammatory response and the incidence of major complications i.e, myocardial infarction and pulmonary complications, but until now they have failed to show conclusive results. This article describes the different types and recommended dose schemes of corticosteroids in the perioperative period of cardiac surgery along with the discussion of few patents. It will comment on potential side effects and review the effect on the postoperative outcome.

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We are presenting the case of a 76-year-old female scheduled for major abdominal surgery. Her past medical history was remarkable for a three-vessel coronary artery disease, with a severely impaired left ventricular function. She had already undergone complex coronary artery bypass surgery. Currently, she presented with the rare constellation of a hemodynamic relevant and interventionally intractable stenosis of the left subclavian artery proximal to a crucial coronary bypass from left internal mammary artery to the left anterior descending. To protect this patient from perioperative myocardial infarction, an intra-aortic balloon pump was successfully used.