IRAK-M Expression in Tumor Cells Supports Colorectal Cancer Progression through Reduction of Antimicrobial Defense and Stabilization of STAT3.

Colorectal cancer (CRC) is associated with loss of epithelial barrier integrity, which facilitates the interaction of the immunological microenvironment with the luminal microbiome, eliciting tumor-supportive inflammation. An important regulator of intestinal inflammatory responses is IRAK-M, a negative regulator of TLR signaling. Here we investigate the compartment-specific impact of IRAK-M on colorectal carcinogenesis using a mouse model.

The minimum required level of donor chimerism in hereditary hemophagocytic lymphohistiocytosis.

Reduced-intensity conditioning has improved survival after hematopoietic stem cell transplantation (HSCT) for hemophagocytic lymphohistiocytosis (HLH) at the cost of more frequent mixed chimerism. The minimum level of donor chimerism (DC) required to prevent HLH reactivation in humans remains to be determined. In a multicenter retrospective study, 103 patients transplanted for hereditary HLH (2000-2013) and DC permanently or transiently <75% (overall, CD3(+), CD56(+)) were analyzed regarding DC, specific immunologic function, occurrence of systemic reactivations (≥5/8 HLH criteria), partial systemic flares (<5 criteria and HLH-directed treatment), isolated central nervous system reactivations, and management.

High fat diet increases melanoma cell growth in the bone marrow by inducing osteopontin and interleukin 6.

The impact of metabolic stress induced by obesity on the bone marrow melanoma niche is largely unknown. Here we employed diet induced obese mice model, where mice received high-fat (HFD) or normal diet (ND) for 6 weeks before challenge with B16F10 melanoma cells. Tumor size, bone loss and osteoclasts numbers were assessed histologically in the tibial bones.

Correlation of Observed-to-Expected MRI Fetal Lung Volume and Ultrasound Lung-to-Head Ratio at Different Gestational Times in Fetuses With Congenital Diaphragmatic Hernia.

Objective: The purpose of this study is to compare the observed-to-expected MRI fetal lung volume and the observed-to-expected ultrasound lung-to-head ratio intraindividually for prediction of survival, the need for extracorporeal membrane oxygenation (ECMO) therapy, and the development of chronic lung disease (CLD) at different times of gestation (< 28, 28-32, and > 32 weeks) in fetuses with congenital diaphragmatic hernia (CDH), and to analyze the intraindividual correlation of observed-to-expected MRI fetal lung volume and observed-to-expected ultrasound lung-to-head ratio.

Materials And Methods: Two hundred one fetuses were included in our study. Observed-to-expected MRI fetal lung volume and observed-to-expected ultrasound lung-to-head ratio were calculated for 270 MRI and ultrasound examinations performed within 72 hours of each other.

Retrospective analysis of survival after resection of pancreatic renal cell carcinoma metastases.

Introduction: Previous reports showed an excellent survival for patients after resection of pancreatic metastases from renal cell cancer (pRCC) and reported several predictive factors. This study aims to give more evidence to reported risk factors by analyzing a large cohort of patients with pancreatic resection due to pRCC.

Patients And Methods: We retrospectively analyzed all pancreatic resections due to pRCC between January 1993 and October 2014 in two German pancreatic surgery centers.

The marine triterpene glycoside frondoside A exhibits activity in vitro and in vivo in prostate cancer.

Despite recent advances in the treatment of metastatic castration-resistant prostate cancer (CRPC), outcome of patients remains poor due to the development of drug resistance. Thus, new drugs are urgently needed. We investigated efficacy, toxicity and mechanism of action of marine triterpene glycoside frondoside A (FrA) using CRPC cell lines in vitro and in vivo.

Inhibition of cGAS DNA Sensing by a Herpesvirus Virion Protein.

Invading viral DNA can be recognized by the host cytosolic DNA sensor, cyclic GMP-AMP (cGAMP) synthase (cGAS), resulting in production of the second messenger cGAMP, which directs the adaptor protein STING to stimulate production of type I interferons (IFNs). Although several DNA viruses are sensed by cGAS, viral strategies targeting cGAS are virtually unknown. We report here that Kaposi's sarcoma-associated herpesvirus (KSHV) ORF52, an abundant gammaherpesvirus-specific tegument protein, subverts cytosolic DNA sensing by directly inhibiting cGAS enzymatic activity through a mechanism involving both cGAS binding and DNA binding.

Interferon Gamma Counteracts the Angiogenic Switch and Induces Vascular Permeability in Dextran Sulfate Sodium Colitis in Mice.

Background: Interferon (IFN)-γ is a central pathogenesis factor in inflammatory bowel disease (IBD) with pleiotropic effects on many different cell types. However, as yet, the immune modulatory functions of IFN-γ in IBD have been predominantly investigated. Based on previous studies showing that IFN-γ acts antiangiogenic in colorectal carcinoma, we investigated the effects of IFN-γ on the vascular system in IBD.

Marine alkaloid Monanchocidin a overcomes drug resistance by induction of autophagy and lysosomal membrane permeabilization.

Monanchocidin A (MonA) is a novel alkaloid recently isolated from the marine sponge Monanchora pulchra. The compound reveals cytotoxic activity in genitourinary cancers including cisplatin-sensitive and -resistant germ cell tumor (GCT) cell lines, hormone-sensitive and castration-resistant prostate carcinoma cell lines and different bladder carcinoma cell lines. In contrast, non-malignant cells were significantly less sensitive.

Altered patterns of heartbeat-evoked potentials in depersonalization/derealization disorder: neurophysiological evidence for impaired cortical representation of bodily signals.

Objective: Core features of depersonalization/derealization disorder (DPD) are emotional numbing and feelings of disembodiment. Although there are several neurophysiological findings supporting subjective emotional numbing, the psychobiology of disembodiment remains unclear.

Methods: Heartbeat-evoked potentials (HEPs), which are considered psychophysiological indicators for the cortical representation of afferent signals originating from the cardiovascular system, were assessed in 23 patients with DPD and 24 healthy control individuals during rest and while performing a heartbeat perception task.

Diffusion-weighted imaging and dynamic contrast-enhanced MRI of experimental breast cancer bone metastases--a correlation study with histology.

Purpose: To validate imaging parameters from diffusion-weighted imaging and dynamic contrast-enhanced MRI with immunohistology and to non-invasively assess microstructure of experimental breast cancer bone metastases.

Materials And Methods: Animals bearing breast cancer bone metastases were imaged in a clinical 1.5 T MRI scanner.

Small changes in bone structure of female α7 nicotinic acetylcholine receptor knockout mice.

Background: Recently, analysis of bone from knockout mice identified muscarinic acetylcholine receptor subtype M3 (mAChR M3) and nicotinic acetylcholine receptor (nAChR) subunit α2 as positive regulator of bone mass accrual whereas of male mice deficient for α7-nAChR (α7KO) did not reveal impact in regulation of bone remodeling. Since female sex hormones are involved in fair coordination of osteoblast bone formation and osteoclast bone degradation we assigned the current study to analyze bone strength, composition and microarchitecture of female α7KO compared to their corresponding wild-type mice (α7WT).

Methods: Vertebrae and long bones of female 16-week-old α7KO (n = 10) and α7WT (n = 8) were extracted and analyzed by means of histological, radiological, biomechanical, cell- and molecular methods as well as time of flight secondary ion mass spectrometry (ToF-SIMS) and transmission electron microscopy (TEM).

Spreader flaps for middle vault contour and stabilization.

Nasal hump excision is common during septorhinoplasty. Without appropriate restoration of the middle nasal vault, cosmetic and functional problems may ensue. Recently, spreader flaps have become an established alternative to traditional spreader grafts.

Current trends in patch testing - new data from the German Contact Dermatitis Research Group (DKG) and the Information Network of Departments of Dermatology (IVDK).

Background And Objectives: The relevance of contact allergens is subject to constant change due to changing exposures according to consumers' preferences and legal requirements. The objective of this paper is to present trends in contact sensitization from the DKG and IVDK patch test clinics, which have led to changes in the DKG standard series (as of 1.1.

A microsurgical procedure for middle cerebral artery occlusion by intraluminal monofilament insertion technique in the rat: a special emphasis on the methodology.

Introduction: Although there are many experimental studies describing the methodology of the middle cerebral artery occlusion (MCAO) in the literature, only limited data on these distinct anatomical structures and the details of the surgical procedure in a step by step manner. The aim of the present study simply is to examine the surgical anatomy of MCAO model and its modifications in the rat.

Materials And Methods: Forty Sprague-Dawley rats were used; 20 during the training phase and 20 for the main study.

Granulocyte colony-stimulating factor does not promote neurogenesis after experimental intracerebral haemorrhage.

Background: Hematopoietic growth factors have been suggested to induce neuroprotective and regenerative effects in various animal models of cerebral injury. However, the pathways involved remain widely unexplored.

Aims: This study aimed to investigate effects of local and systemic administration of granulocyte colony-stimulating factor on brain damage, functional recovery, and cerebral neurogenesis in an intracerebral haemorrhage whole blood injection model in rats.

Structural proteins of Kaposi's sarcoma-associated herpesvirus antagonize p53-mediated apoptosis.

The tumor suppressor p53 is a central regulatory molecule of apoptosis and is commonly mutated in tumors. Kaposi's sarcoma-associated herpesvirus (KSHV)-related malignancies express wild-type p53. Accordingly, KSHV encodes proteins that counteract the cell death-inducing effects of p53.

Validation of the reliability of computational O-GlcNAc prediction.

O-GlcNAcylation is an inducible, highly dynamic and reversible posttranslational modification, which regulates numerous cellular processes such as gene expression, translation, immune reactions, protein degradation, protein-protein interaction, apoptosis, and signal transduction. In contrast to N-linked glycosylation, O-GlcNAcylation does not display a strict amino acid consensus sequence, although serine or threonine residues flanked by proline and valine are preferred sites of O-GlcNAcylation. Based on this information, computational prediction tools of O-GlcNAc sites have been developed.

Hematopoietic stem cell transplantation in children and young adults with secondary myelodysplastic syndrome and acute myelogenous leukemia after aplastic anemia.

Secondary myelodysplastic syndrome and acute myelogenous leukemia (sMDS/sAML) are the most serious secondary events occurring after immunosuppressive therapy in patients with aplastic anemia. Here we evaluate the outcome of hematopoietic stem cell transplantation (HSCT) in 17 children and young adults with sMDS/sAML after childhood aplastic anemia. The median interval between the diagnosis of aplastic anemia and the development of sMDS/sAML was 2.

Tumor-associated fibroblasts isolated from colorectal cancer tissues exhibit increased ICAM-1 expression and affinity for monocytes.

Progression of colorectal cancer (CRC) is strongly associated with inflammation and other desmoplastic reactions in the tumor cell-surrounding tissue. We successfully isolated fibroblasts from the desmoplastic stroma of human CRC specimens and uninvolved colon tissue of patients treated surgically for CRC and investigated potential functional capacities. All of the isolated fibroblasts were vimentin-positive and CK-20/CD45-negative confirming the fibroblast phenotype.

Gamma interferon-induced guanylate binding protein 1 is a novel actin cytoskeleton remodeling factor.

Gamma interferon (IFN-γ) regulates immune defenses against viruses, intracellular pathogens, and tumors by modulating cell proliferation, migration, invasion, and vesicle trafficking processes. The large GTPase guanylate binding protein 1 (GBP-1) is among the cellular proteins that is the most abundantly induced by IFN-γ and mediates its cell biologic effects. As yet, the molecular mechanisms of action of GBP-1 remain unknown.

IFN-γ-driven intratumoral microenvironment exhibits superior prognostic effect compared with an IFN-α-driven microenvironment in patients with colon carcinoma.

Interferon (IFN)-α and IFN-γ are cytokines with potent immunomodulating and anti-tumor activities. It is unknown which of the two IFNs may be more potent in the regulation of an anti-tumorigenic response in colorectal carcinoma or whether both cytokines cooperate. We, therefore, established human myxovirus resistance protein A and human guanylate-binding protein-1 as markers for the differential detection of IFN-α- and IFN-γ-driven tumor micromilieus, respectively.

Expression and localization of axin 2 in colorectal carcinoma and its clinical implication.

Purpose: Aberrant activation of the Wnt/β-catenin pathway plays a major role in the development of colorectal carcinoma (CRC). Axin 2 is a key protein of this pathway and is upregulated in CRC. Here, we investigated RNA- and protein expression of axin 2 in CRC tissues at the single cell level.

O-GlcNAc transferase inhibits KSHV propagation and modifies replication relevant viral proteins as detected by systematic O-GlcNAcylation analysis.

O-GlcNAcylation is an inducible, highly dynamic and reversible post-translational modification, mediated by a unique enzyme named O-linked N-acetyl-d-glucosamine (O-GlcNAc) transferase (OGT). In response to nutrients, O-GlcNAc levels are differentially regulated on many cellular proteins involved in gene expression, translation, immune reactions, protein degradation, protein-protein interaction, apoptosis and signal transduction. In contrast to eukaryotic cells, little is known about the role of O-GlcNAcylation in the viral life cycle.

GBP-1 acts as a tumor suppressor in colorectal cancer cells.

The human guanylate-binding protein 1 (GBP-1) is among the proteins the most highly induced by interferon-γ (IFN-γ) in every cell type investigated as yet. In vivo, GBP-1 expression is associated with the presence of inflammation and has been observed in autoimmune diseases, inflammatory bowel diseases (IBD) and cancer. In colorectal carcinoma (CRC), the expression of GBP-1 in the desmoplastic stroma has been previously reported to correlate with the presence of an IFN-γ-dominated T helper type 1 (Th1) micromilieu and with an increased cancer-related 5-year survival.