Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 4 de 4
Filter
Add more filters










Database
Language
Publication year range
1.
Ann Hematol ; 94(2): 283-7, 2015 Feb.
Article in English | MEDLINE | ID: mdl-25138222

ABSTRACT

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare hematodermic neoplasm which typically presents with skin infiltrates with or without lymphadenopathy and bone marrow involvement. No standard of care exists for this aggressive disease and prognosis is particularly poor. Here, we present our experience with nine BPDCN patients diagnosed at our institution between 2005 and 2012. BPDCN patients were identified in the databases at the Department of Hematology and Oncology, the Department of Dermatology, and the Institute of Pathology at the Otto-von-Guericke-University Magdeburg. There were six male and three female patients with a median age at diagnosis of 66 years. Sites involved were skin (five cases), lymph nodes (five cases), and bone marrow (five cases). Treatments varied from single agent chemotherapy to polychemotherapy and allogeneic stem cell transplantation for consolidation. The three patients that were treated with acute leukemia-type induction therapy followed by allogeneic stem cell transplantation (one after standard conditioning and two after reduced intensity conditioning using fludarabine in combination with thiotepa) achieved sustained remissions and are alive with a follow-up of 8, 35, and 41 months. In contrast, median survival in the less intensively treated patients was only 9.5 (range 1 to 29) months.


Subject(s)
Dendritic Cells/pathology , Hematologic Neoplasms/therapy , Hematopoietic Stem Cell Transplantation/methods , Skin Neoplasms/therapy , Unrelated Donors , Aged , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Chemoradiotherapy/methods , Combined Modality Therapy , Female , Humans , Male , Middle Aged , Remission Induction , Retrospective Studies , Survival Analysis , Transplantation, Homologous , Treatment Outcome , Young Adult
2.
Acta Neuropathol ; 129(2): 259-77, 2015 Feb.
Article in English | MEDLINE | ID: mdl-25391494

ABSTRACT

Neuronal injury from ischemic stroke is aggravated by invading peripheral immune cells. Early infiltrates of neutrophil granulocytes and T-cells influence the outcome of stroke. So far, however, neither the timing nor the cellular dynamics of neutrophil entry, its consequences for the invaded brain area, or the relative importance of T-cells has been extensively studied in an intravital setting. Here, we have used intravital two-photon microscopy to document neutrophils and brain-resident microglia in mice after induction of experimental stroke. We demonstrated that neutrophils immediately rolled, firmly adhered, and transmigrated at sites of endothelial activation in stroke-affected brain areas. The ensuing neutrophil invasion was associated with local blood-brain barrier breakdown and infarct formation. Brain-resident microglia recognized both endothelial damage and neutrophil invasion. In a cooperative manner, they formed cytoplasmic processes to physically shield activated endothelia and trap infiltrating neutrophils. Interestingly, the systemic blockade of very-late-antigen-4 immediately and very effectively inhibited the endothelial interaction and brain entry of neutrophils. This treatment thereby strongly reduced the ischemic tissue injury and effectively protected the mice from stroke-associated behavioral impairment. Behavioral preservation was also equally well achieved with the antibody-mediated depletion of myeloid cells or specifically neutrophils. In contrast, T-cell depletion more effectively reduced the infarct volume without improving the behavioral performance. Thus, neutrophil invasion of the ischemic brain is rapid, massive, and a key mediator of functional impairment, while peripheral T-cells promote brain damage. Acutely depleting T-cells and inhibiting brain infiltration of neutrophils might, therefore, be a powerful early stroke treatment.


Subject(s)
Brain Ischemia/immunology , Integrin alpha4beta1/metabolism , Microglia/physiology , Neutrophil Infiltration/physiology , Neutrophils/physiology , Stroke/immunology , Animals , Blood-Brain Barrier/immunology , Blood-Brain Barrier/pathology , Brain/immunology , Brain/pathology , Brain Ischemia/pathology , Cell Adhesion/physiology , Disease Models, Animal , Male , Mice, Inbred C57BL , Mice, Transgenic , Microglia/pathology , Motor Activity/physiology , Neutrophils/pathology , Random Allocation , Recovery of Function/physiology , Stroke/pathology
3.
PLoS One ; 9(6): e99296, 2014.
Article in English | MEDLINE | ID: mdl-24901233

ABSTRACT

Interleukin (IL)-1 signaling plays an important role in inflammatory processes, but also in malignant processes. The essential downstream event in IL-1 signaling is the activation of nuclear factor (NF)-κB, which leads to the expression of several genes that are involved in cell proliferation, invasion, angiogenesis and metastasis, among them VEGF-A. As microenvironment-derived IL-1ß is required for invasion and angiogenesis in malignant tumors, also in chondrosarcomas, we investigated IL-1ß-induced signal transduction and VEGF-A expression in C3842 and SW1353 chondrosarcoma cells. We additionally performed in vitro angiogenesis assays and NF-κB-related gene expression analyses. Curcumin is a substance which inhibits IL-1 signaling very early by preventing the recruitment of IL-1 receptor associated kinase (IRAK) to the IL-1 receptor. We demonstrate that IL-1 signaling and VEGF-A expression are blocked by Curcumin in chondrosarcoma cells. We further show that Curcumin blocks IL-1ß-induced angiogenesis and NF-κB-related gene expression. We suppose that IL-1 blockade is an additional treatment option in chondrosarcoma, either by Curcumin, its derivatives or other IL-1 blocking agents.


Subject(s)
Curcumin/pharmacology , Interleukin-1/metabolism , Signal Transduction/drug effects , Cell Line, Tumor , Chondrosarcoma/metabolism , Chondrosarcoma/pathology , Gene Expression Regulation/drug effects , Human Umbilical Vein Endothelial Cells , Humans , Interleukin-1/antagonists & inhibitors , Interleukin-1/pharmacology , Interleukin-1 Receptor-Associated Kinases/metabolism , NF-kappa B/metabolism , Neovascularization, Physiologic/drug effects , Phosphorylation/drug effects , Receptors, Interleukin-1/metabolism , Vascular Endothelial Growth Factor A/metabolism
4.
Thromb Haemost ; 102(6): 1274-7, 2009 Dec.
Article in English | MEDLINE | ID: mdl-19967161

ABSTRACT

Transcranial "diagnostic" ultrasound (US) has been shown to accelerate thrombolysis related to recombinant tissue-type plasminogen activator (rt-PA). In this in vitro study, we evaluated the potential of US to increase clot dissolution mediated by Abciximab (Abc) compared to rt-PA. The effect of 1.8-MHz pulsed wave (PW) Doppler US on dissolution of whole venous blood clots (WBC) and platelet-rich clots (PRC) treated with Abc and rt-PA was investigated in an in vitro model. Clot dissolution was measured by weight loss. Abc-related WBC dissolution was enhanced by additional US, but the effect was not any more detectable when the US was attenuated by a human temporal bone (US-tb). In PRC there was no additional effect of US on the Abc-related clot lysis. Rt-PA-related clot dissolution was increased by US in WBC and PRC as well, however, US-tb was only effective in WBC. The effect of insonation on WBC dissolution treated with the combination of Abc plus rt-PA was lower compared with those treated with rt-PA. In this in vitro experiment, the additional effect of "diagnostic" US in combination with Abc was only present in WBC and less strong than with rt-PA. The results do not support the use of Abc for sonothrombolysis targeting both, fibrin-rich and platelet-rich clots. In contrast, US when combined with rt-PA increases dissolution in both, WBC and PRC as well.


Subject(s)
Antibodies, Monoclonal/pharmacology , Fibrinolytic Agents/pharmacology , Immunoglobulin Fab Fragments/pharmacology , Thrombolytic Therapy/methods , Tissue Plasminogen Activator/pharmacology , Ultrasonic Therapy/methods , Abciximab , Blood Coagulation/drug effects , Combined Modality Therapy , Humans , In Vitro Techniques , Recombinant Proteins/pharmacology , Stroke/drug therapy , Stroke/therapy , Thrombosis/drug therapy , Thrombosis/therapy
SELECTION OF CITATIONS
SEARCH DETAIL
...