The German National Registry of Primary Immunodeficiencies (2012-2017).

The German PID-NET registry was founded in 2009, serving as the first national registry of patients with primary immunodeficiencies (PID) in Germany. It is part of the European Society for Immunodeficiencies (ESID) registry. The primary purpose of the registry is to gather data on the epidemiology, diagnostic delay, diagnosis, and treatment of PIDs.

Importance of whole-body imaging with complete coverage of hands and feet in alveolar rhabdomyosarcoma staging.

Background: Alveolar rhabdomyosarcoma commonly arises in the extremities and is characterized by aggressive biology and high frequency of metastases. Whole-body imaging is increasingly employed in pediatric oncology but not recommended as standard in the staging of soft-tissue sarcomas.

Objective: After observing patients with a large symptomatic alveolar rhabdomyosarcoma lesion and a smaller silent lesion in the more distal part of an extremity we sought to estimate the frequency of this constellation.

Treatment and outcome of Ganglioneuroma and Ganglioneuroblastoma intermixed.

Background: Ganglioneuroma (GN) and ganglioneuroblastoma intermixed (GNBI) are mature variants of neuroblastic tumors (NT). It is still discussed whether incomplete resection of GN/GNBI impairs the outcome of patients.

Methods: Clinical characteristics and outcome of localized GN/GNBI were retrospectively compared to localized neuroblastoma (NB) and ganglioneuroblastoma-nodular (GNBN) registered in the German neuroblastoma trials between 2000 and 2010.

Stanniocalcin 2 promotes invasion and is associated with metastatic stages in neuroblastoma.

Stanniocalcin 2 (STC2) is a secreted glycoprotein of as yet unknown functions. We investigated STC2 in human neuroblastoma, the most common solid extra-cranial tumor of infancy. In primary tumor samples, we found that expression of STC2 is associated with the metastatic Stages 4 and 4s and MYCN expression.

Embryonic development and malformation of lymphatic vessels.

In the human, malformations of lymphatic vessels can be observed as lymphangiectasia, lymphangioma and lymphangiomatosis, with a prevalence of 1.2-2.8 per thousand.

Keratoepithelin reverts the suppression of tissue factor pathway inhibitor 2 by MYCN in human neuroblastoma: a mechanism to inhibit invasion.

Neuroblastoma is the most frequent solid malignancy of children. The most reliable prognostic factor in neuroblastoma is the amplification status of the MYCN oncogene, but exceptions from this rule have been observed. Recently we have demonstrated that keratoepithelin (BIGH3, TGFBI) expression significantly reduces proliferation and invasion of neuroblastomas in vitro and in vivo.

Elevated expression of VEGFR-3 in lymphatic endothelial cells from lymphangiomas.

Background: Lymphangiomas are neoplasias of childhood. Their etiology is unknown and a causal therapy does not exist. The recent discovery of highly specific markers for lymphatic endothelial cells (LECs) has permitted their isolation and characterization, but expression levels and stability of molecular markers on LECs from healthy and lymphangioma tissues have not been studied yet.

Three reactive compartments in venous malformations.

Vascular malformations affect 3% of neonates. Venous malformations (VMs) are the largest group representing more than 50% of cases. In hereditary forms of VMs gene mutations have been identified, but for the large group of spontaneous forms the primary cause and downstream dysregulated genes are unknown.

The proepicardium delivers hemangioblasts but not lymphangioblasts to the developing heart.

The mass of the myocardium and endocardium of the vertebrate heart derive from the heart-forming fields of the lateral plate mesoderm. Further components of the mature heart such as the epicardium, cardiac interstitium and coronary blood vessels originate from a primarily extracardiac progenitor cell population: the proepicardium (PE). The coronary blood vessels are accompanied by lymph vessels, suggesting a common origin of the two vessel types.

Mesenchymal cells with leukocyte and lymphendothelial characteristics in murine embryos.

The development of lymphatic endothelial cells (LECs) from deep embryonic veins or mesenchymal lymphangioblasts is controversially discussed. Studies employing quail-chick grafting experiments have shown that various mesodermal compartments of the embryo possess lymphangiogenic potential, whereas studies on murine embryos have been in favor of a venous origin of LECs. We have investigated NMRI mice from embryonic day (ED) 9.

Dual origin of avian lymphatics.

The earliest signs of the lymphatic vascular system are the lymph sacs, which develop adjacent to specific embryonic veins. It has been suggested that sprouts from the lymph sacs form the complete lymphatic vascular system. We have studied the origin of the jugular lymph sacs (JLS), the dermal lymphatics and the lymph hearts of avian embryos.

The neurotrophin receptor TrkB cooperates with c-Met in enhancing neuroblastoma invasiveness.

Neuroblastoma is the most frequent extracranial solid malignancy of childhood with a high mortality in advanced tumour stages. The hallmark of neuroblastoma is its clinical and biological heterogeneity. The molecular mechanisms leading to favourable or unfavourable tumour behaviour are still speculative.

Sublethal irradiation promotes invasiveness of neuroblastoma cells.

Neuroblastoma is the most frequent extracranial solid tumour of childhood. Despite multiple clinical efforts, clinical outcome has remained poor. Neuroblastoma is considered to be radiosensitive, but some clinical studies including the German trial NB90 failed to show a clinical benefit of radiation therapy.

Altered expression patterns of EphrinB2 and EphB2 in human umbilical vessels and congenital venous malformations.

Vascular malformations cause discomfort and pain in children and are often associated with skeletal hypertrophy. Their molecular basis is poorly understood. Ephrin ligands and Eph receptor tyrosine kinases are involved in embryonic vascular development.

Microarray analysis reveals differential gene expression patterns and regulation of single target genes contributing to the opposing phenotype of TrkA- and TrkB-expressing neuroblastomas.

Expression of neurotrophin receptors of the tyrosine kinase receptor (Trk) family is an important prognostic factor in solid tumors including neuroblastoma. High expression of TrkA (NTRK1) is associated with a favorable biology and outcome of neuroblastoma, whereas TrkB (NTRK2) is expressed on aggressive neuroblastomas with unfavorable outcome. To gain new insights into the global gene expression program resulting in these divergent biological phenotypes, we stably expressed either TrkA or TrkB in the human SH-SY5Y neuroblastoma cell line.

Lymphangioblasts in embryonic lymphangiogenesis.

Background: The origin of the lymphatic endothelium, either from the venous system or mesenchymal lymphangioblasts, presents as a persistent controversy. Recently, highly specific markers of the lymphatic endothelium have been found, enabling us to reinvestigate the embryonic origin of the lymphatics.

Methods And Results: The homeobox transcription factor, Prox1, is expressed in lymphatic, but not in blood vascular, endothelial cells throughout murine and avian development and in adult human tissues.

High activin A-expression in human neuroblastoma: suppression of malignant potential and correlation with favourable clinical outcome.

Amplification of the MYCN oncogene contributes to the malignant progression of human neuroblastomas, but the mechanisms have remained unclear. We have previously demonstrated that N-Myc facilitates angiogenesis by downregulating an angiogenesis inhibitor identified as the inhibin betaA homodimer activin A. Here, we have sought to define the molecular, biological and clinical consequences of activin A expression in human neuroblastoma.

Hypoxia-induced erythropoietin expression in human neuroblastoma requires a methylation free HIF-1 binding site.

The glycoprotein hormone Erythropoietin (EPO) stimulates red cell production and maturation. EPO is produced by the kidneys and the fetal liver in response to hypoxia (HOX). Recently, EPO expression has also been observed in the central nervous system where it may be neuroprotective.

Hepatocyte growth factor/c-Met signaling promotes the progression of experimental human neuroblastomas.

Neuroblastoma is the most frequent solid childhood malignancy. Despite aggressive therapy, mortality is high due to rapid tumor progression to advanced stages. The molecules and mechanisms underlying poor prognosis are not well understood.

Development and engineering of lymphatic endothelial cells: clinical implications.

Studies on the lymphatic endothelium have been hampered by the difficulty to identify lymphatic endothelial cells (LECs) and to distinguish them from blood vascular endothelial cells (BECs). The situation was greatly improved by the identification of molecules with high specificity for LECs. A great deal of progress in the field of lymphangiogenesis research has been due to the detection of lymphangiogenic growth factors and their receptors, and there is growing evidence that these molecules are also involved in tumor-induced lymphangiogenesis and lymphatic dissemination of tumor cells.