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Oevermann L.,University Hospital of Tuebingen
Pediatric research | Year: 2012

Haploidentical transplantation in children opens the possibility to offer this treatment to every child with an otherwise incurable disease, such as some hematological or oncological malignancies, inborn or acquired bone marrow-failure syndromes, hemoglobinopathies, immunodeficiencies, or other genetic diseases. Although initial attempts at haploidentical transplantation were associated with a high transplant-related mortality, recent insights into the biology of haploidentical transplantation, the availability of effective in vivo large-scale graft-manipulation technology, and improved supportive care strategies have led to and are still leading to significantly better outcomes of haploidentical transplantation as compared with previous decades. In addition, expensive and time-consuming searches for matched unrelated donors (MUDs) as well as the expensive establishment and maintenance of cord blood banks are not necessary. Moreover, the worldwide donor registries comprise mainly donors of Caucasian origin and patients of non-Caucasian origin have a lower chance of finding a MUD. Therefore, haploidentical transplantation allows the treatment of children independently of their ethnic background in a timely fashion according to the status of their underlying disease. Source


Handgretinger R.,University Hospital of Tuebingen
Blood | Year: 2014

In this issue of Blood, Wang et al suggest an algorithm for the selection of the best donor in HLA haplotype-mismatched transplantation of T-replete granulocyte colony-stimulating factor (G-CSF)-mobilized bone marrow and peripheral blood stem cells.1 © 2014 by The American Society of Hematology. Source


Cholangiocacinoma (CC) is a cancer disease with rising incidence. Notch signaling has been shown to be deregulated in many cancers. However, the role of this signaling pathway in the carcinogenesis of CC is still not fully explored. In this study, we investigated the effects of Notch inhibition by γ-secretase inhibitor IX (GSI IX) in cultured human CC cell lines and we established a transgenic mouse model with liver specific expression of the intracellular domain of Notch (Notch-ICD) and inactivation of tumor suppressor p53. GSI IX treatment effectively impaired cell proliferation, migration, invasion, epithelial to mesenchymal transition and growth of softagar colonies. In vivo overexpression of Notch-ICD together with an inactivation of p53 significantly increased tumor burden and showed CC characteristics. Our study highlights the importance of Notch signaling in the tumorigenesis of CC and demonstrates that additional inactivation of p53 in vivo. Source


Poets C.F.,University Hospital of Tuebingen
Sleep Medicine | Year: 2010

Apnea of prematurity (AOP) is a developmental sleep disorder which is yet to be completely understood. Although there is some evidence of brainstem immaturity, there is nothing to suggest that infants with AOP have gross deficits in respiratory control. It appears, however, that the early (and frequent) occurrence of hypoxemia during apnea in preterm infants is related to their low expiratory lung volume, which falls even further during apnea, while the accompanying bradycardia results from this combination of apnea and hypoxemia. Feeding is an important trigger for AOP. While hypoxemia during feeding is most likely related to an immature coordination between sucking, swallowing and breathing and potentially also to an immature laryngeal chemoreflex, hypoxemia after feeding may be caused by diaphragmatic fatigue; gastro-esophageal reflux only rarely plays a role. The time course of AOP, i.e., its increased occurrence during the second and third rather than the first week of life, together with data from physiological studies, also suggests a role for diaphragmatic fatigue. Additional factors include upper airway obstruction, persistence of the fetal response to hypoxia, i.e., ventilatory depression, and the close proximity between the eupneic and apneic CO2 thresholds in neonates. Observational data cannot provide definite answers on cause-and-effect issues but may provide a starting point for further studies into mechanisms involved in AOP and for the development of new therapeutic interventions. First, however, we need to better define how much AOP can be tolerated in an infant without endangering neurodevelopment. © 2010 Elsevier B.V. Source


Handgretinger R.,University Hospital of Tuebingen
Seminars in Oncology | Year: 2012

Haploidentical transplantation opens the possibility to offer this treatment to a large number of patients with an otherwise incurable disease, such as some hematologic or oncologic malignancies, inborn or acquired bone marrow failure syndromes, hemoglobinopathies, immunodeficiencies, or other genetic diseases. Initial attempts at haploidentical transplantation using unmanipulated bone marrow were associated with a high transplant-related mortality. However, recent insights into the biology of haploidentical transplantation, the availability of effective in vivo large-scale graft-manipulation technology, and improved supportive care strategies have led to and are still leading to significantly better outcomes compared to previous decades. Methods for the in vitro depletion of T lymphocytes from mobilized peripheral blood stem cells (PBSC) to prevent graft-versus-host disease (GvHD) have facilitated the wider use and acceptance of haploidentical transplantation in children and adult patients. Besides in vitro T-cell depletion techniques, other methods, such as the isolation of alloreactive natural killer (NK) cells, virus-specific T lymphocytes, and other effector or regulatory cells are nowadays available to rapidly rebuild the immune system after haploidentical transplantation for the prevention of severe infections or relapses of the underlying diseases. © 2012 Elsevier Inc. All rights reserved. Source

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