ABSTRACT
The German Nobel Prize winner Otto Warburg discovered the importance of glycolysis in cancer cells in the 1920s. Nearly one century later the inhibition of tumor glycolysis in cancer cells could literally be the Achilles Heel in cancer therapy. Surprisingly, we could show that Natural Killer (NK) cells pursue this strategy. They employ specific metabolic weapons to eliminate cancer cells by targeting tumor glycolysis. In colon cancer cells a specifically modified form of high mobility group box 1 (HMGB1) protein released by NK cells induced a previously unknown form of cell death. This new link between the killing of cancer cells and the innate immune system opened up new perspectives for immunotherapy in oncology.
Subject(s)
Colonic Neoplasms/immunology , Glycolysis/physiology , HMGB1 Protein/physiology , Immunotherapy , Killer Cells, Natural/immunology , Cell Death/immunology , Humans , Immunity, Innate/physiology , Oxygen Consumption/physiology , Prognosis , Tumor Cells, CulturedABSTRACT
During tumorigenesis cancer cells acquire certain features allowing for sustained growth and circumvention of programmed cell death. For decades cancer research has been focused on the molecular mechanisms of apoptosis and how to overcome apoptosis resistance in tumor cells. Meanwhile, novel types of programmed cell death have turned out to be important for both physiological and pathological processes. Recent findings imply that induction of alternative forms of programmed cell death, such as necroptosis, might be used as a therapeutic approach to overcome therapy resistance in cancer.
Subject(s)
Apoptosis/physiology , Neoplasms/pathology , Apoptosis/genetics , Cell Transformation, Neoplastic/genetics , Cell Transformation, Neoplastic/pathology , Humans , Necrosis , Neoplasms/genetics , Neoplasms/therapyABSTRACT
AIMS: Both epithelial barrier dysfunction and apoptosis resistance of immune cells contribute to the pathogenesis of Crohn's disease. The soluble decoy receptor 3 (DcR3) acts in an anti-apoptotic manner by neutralising the death ligand CD95L. Here, we investigated the possible involvement of DcR3 in Crohn's disease. METHODS: The epithelial fraction of human small intestinal mucosa samples was obtained by laser microdissection. Expression of DcR3 was examined by global gene expression profiling, quantitative reverse transcription polymerase chain reaction, immunoblot analysis, and immunohistochemistry. DcR3 concentrations in the serum of patients with Crohn's disease were measured by enzyme-linked immunosorbent assay. Apoptosis assays were performed to study the effects of DcR3 in intestinal epithelial cells and lamina propria T cells. RESULTS: DcR3 is over-expressed in the epithelial layer of ileum specimens in patients with Crohn's disease, both at actively inflamed and non-active sites. DcR3 serum levels are significantly elevated in patients with active and non-active Crohn's disease as compared to healthy controls. The expression of DcR3 in intestinal epithelial cells is induced by tumour necrosis factor alpha. Increased DcR3 expression is associated with activation of nuclear factor kappa B (NF-kappaB) and results in protection of intestinal epithelial cells and lamina propria T cells from CD95L-induced apoptosis. CONCLUSIONS: DcR3 may promote inflammation in Crohn's disease by inhibiting CD95L-induced apoptosis of epithelial and immune cells as well as by inducing NF-kappaB activation.
Subject(s)
Crohn Disease/physiopathology , Receptors, Tumor Necrosis Factor, Member 6b/physiology , Adolescent , Adult , Aged , Aged, 80 and over , Apoptosis/drug effects , Cell Death/drug effects , Cell Death/physiology , Cell Line , Colon/drug effects , Colon/metabolism , Crohn Disease/metabolism , Crohn Disease/pathology , Fas Ligand Protein/antagonists & inhibitors , Fas Ligand Protein/pharmacology , Female , Humans , Intestinal Mucosa/drug effects , Intestinal Mucosa/metabolism , Intestine, Small/metabolism , Male , Microdissection , Middle Aged , NF-kappa B/metabolism , RNA, Messenger/genetics , Receptors, Tumor Necrosis Factor, Member 6b/genetics , Receptors, Tumor Necrosis Factor, Member 6b/metabolism , Receptors, Tumor Necrosis Factor, Member 6b/pharmacology , T-Lymphocytes/drug effects , Tumor Necrosis Factor-alpha/pharmacology , Up-Regulation/drug effects , Young AdultABSTRACT
BACKGROUND: Primary cardiac tumors are rare and often asymptomatic or present with unspecific symptoms. Benign cardiac tumors of vascular origin are especially rare, with only few existing data in the literature. CASE PRESENTATION: A 35-year-old Caucasian female patient presented to our department with an asymptomatic giant intracardiac angioma infiltrating both ventricles. Evaluation of this tumor involved electrocardiography, echocardiography, cardiac magnetic resonance imaging, coronary angiography, an open myocardial biopsy, and histological examination of the resected specimen. Because our patient was asymptomatic, she was managed conservatively with regular follow-up. We discuss the treatment options available in comparison with similar cases. CONCLUSION: Diagnosis and therapy of benign cardiac tumors, especially of asymptomatic lesions, can be a challenge. There is no evidence available to help in the management of such patients. An extensive evaluation is needed with different imaging modalities, and case-specific decisions should be made that involve experts in cardiology, cardio-oncology, and heart surgery.