TY - JOUR A1 - Apsemidou, Athanasia A1 - Füller, Miriam Antonie A1 - Idelevich, Evgeny A. A1 - Kurzai, Oliver A1 - Tragiannidis, Athanasios A1 - Groll, Andreas H. T1 - Candida lusitaniae breakthrough fungemia in an immuno-compromised adolescent: case report and review of the literature JF - Journal of Fungi N2 - Candida lusitaniae is a rare cause of candidemia that is known for its unique capability to rapidly acquire resistance to amphotericin B. We report the case of an adolescent with grade IV graft-vs.-host disease after hematopoietic cell transplantation who developed catheter-associated C. lusitaniae candidemia while on therapeutic doses of liposomal amphotericin B. We review the epidemiology of C. lusitaniae bloodstream infections in adult and pediatric patients, the development of resistance, and its role in breakthrough candidemia. Appropriate species identification, in vitro susceptibility testing, and source control are pivotal to optimal management of C. lusitaniae candidemia. Initial antifungal therapy may consist of an echinocandin and be guided by in vitro susceptibility and clinical response. KW - Candida lusitaniae KW - candidemia KW - resistance KW - breakthrough KW - infection KW - transplantation Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-220125 SN - 2309-608X VL - 6 IS - 4 ER - TY - JOUR A1 - Glutsch, Valerie A1 - Kneitz, Hermann A1 - Gesierich, Anja A1 - Goebeler, Matthias A1 - Haferkamp, Sebastian A1 - Becker, Jürgen C. A1 - Ugurel, Selma A1 - Schilling, Bastian T1 - Activity of ipilimumab plus nivolumab in avelumab-refractory Merkel cell carcinoma JF - Cancer Immunology, Immunotherapy N2 - Background Merkel cell carcinoma (MCC) is a rare and aggressive neuroendocrine cutaneous malignancy with poor prognosis. In Europe, approved systemic therapies are limited to the PD-L1 inhibitor avelumab. For avelumab-refractory patients, efficient and safe treatment options are lacking. Methods At three different sites in Germany, clinical and molecular data of patients with metastatic MCC being refractory to the PD-L1 inhibitor avelumab and who were later on treated with combined IPI/NIVO were retrospectively collected and evaluated. Results Five patients treated at three different academic sites in Germany were enrolled. Three out of five patients investigated for this report responded to combined IPI/NIVO according to RECIST 1.1. Combined immunotherapy was well tolerated without any grade II or III immune-related adverse events. Two out of three responders to IPI/NIVO received platinum-based chemotherapy in between avelumab and combined immunotherapy. Conclusion In this small retrospective study, we observed a high response rate and durable responses to subsequent combined immunotherapy with IPI/NIVO in avelumab-refractory metastatic MCC patients. In conclusion, our data suggest a promising activity of second- or third-line PD-1- plus CTLA-4-blockade in patients with anti-PD-L1-refractory MCC. KW - ipilimumab KW - Merkel cell carcinoma KW - resistance KW - avelumab KW - nivolumab Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-265635 SN - 14320851 VL - 70 IS - 7 ER - TY - JOUR A1 - Di Sante, Domenico A1 - Erdmenger, Johanna A1 - Greiter, Martin A1 - Matthaiakakis, Ioannis A1 - Meyer, René A1 - Fernandez, David Rodríguez A1 - Thomale, Ronny A1 - van Loon, Erik A1 - Wehling, Tim T1 - Turbulent hydrodynamics in strongly correlated Kagome metals JF - Nature Communications N2 - A current challenge in condensed matter physics is the realization of strongly correlated, viscous electron fluids. These fluids can be described by holography, that is, by mapping them onto a weakly curved gravitational theory via gauge/gravity duality. The canonical system considered for realizations has been graphene. In this work, we show that Kagome systems with electron fillings adjusted to the Dirac nodes provide a much more compelling platform for realizations of viscous electron fluids, including non-linear effects such as turbulence. In particular, we find that in Scandium Herbertsmithite, the fine-structure constant, which measures the effective Coulomb interaction, is enhanced by a factor of about 3.2 as compared to graphene. We employ holography to estimate the ratio of the shear viscosity over the entropy density in Sc-Herbertsmithite, and find it about three times smaller than in graphene. These findings put the turbulent flow regime described by holography within the reach of experiments. Viscous electron fluids are predicted in strongly correlated systems but remain challenging to realize. Here, the authors predict enhanced effective Coulomb interaction and reduced ratio of the shear viscosity over entropy density in a Kagome metal, inferring turbulent flow of viscous electron fluids. KW - coupling-constant dependence KW - shear viscosity KW - electron KW - resistance Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-230380 VL - 11 ER - TY - JOUR A1 - Feldheim, Jonas A1 - Kessler, Almuth F. A1 - Monoranu, Camelia M. A1 - Ernestus, Ralf-Ingo A1 - Löhr, Mario A1 - Hagemann, Carsten T1 - Changes of O\(^6\)-Methylguanine DNA Methyltransferase (MGMT) promoter methylation in glioblastoma relapse—a meta-analysis type literature review JF - Cancers N2 - Methylation of the O6-methylguanine DNA methyltransferase (MGMT) promoter has emerged as strong prognostic factor in the therapy of glioblastoma multiforme. It is associated with an improved response to chemotherapy with temozolomide and longer overall survival. MGMT promoter methylation has implications for the clinical course of patients. In recent years, there have been observations of patients changing their MGMT promoter methylation from primary tumor to relapse. Still, data on this topic are scarce. Studies often consist of only few patients and provide rather contrasting results, making it hard to draw a clear conclusion on clinical implications. Here, we summarize the previous publications on this topic, add new cases of changing MGMT status in relapse and finally combine all reports of more than ten patients in a statistical analysis based on the Wilson score interval. MGMT promoter methylation changes are seen in 115 of 476 analyzed patients (24%; CI: 0.21–0.28). We discuss potential reasons like technical issues, intratumoral heterogeneity and selective pressure of therapy. The clinical implications are still ambiguous and do not yet support a change in clinical practice. However, retesting MGMT methylation might be useful for future treatment decisions and we encourage clinical studies to address this topic KW - glioblastoma multiforme (GBM) KW - glioma KW - relapse KW - temozolomide KW - MGMT promoter methylation KW - therapy KW - resistance KW - recurrence Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-193040 SN - 2072-6694 VL - 11 IS - 12 ER - TY - JOUR A1 - Firdessa, Rebuma A1 - Good, Liam A1 - Amstalden, Maria Cecilia A1 - Chindera, Kantaraja A1 - Kamaruzzaman, Nor Fadhilah A1 - Schultheis, Martina A1 - Röger, Bianca A1 - Hecht, Nina A1 - Oelschlaeger, Tobias A. A1 - Meinel, Lorenz A1 - Lühmann, Tessa A1 - Moll, Heidrun T1 - Pathogen- and host-directed antileishmanial effects mediated by polyhexanide (PHMB) JF - PLoS Neglected Tropical Diseases N2 - Background Cutaneous leishmaniasis (CL) is a neglected tropical disease caused by protozoan parasites of the genus Leishmania. CL causes enormous suffering in many countries worldwide. There is no licensed vaccine against CL, and the chemotherapy options show limited efficacy and high toxicity. Localization of the parasites inside host cells is a barrier to most standard chemo- and immune-based interventions. Hence, novel drugs, which are safe, effective and readily accessible to third-world countries and/or drug delivery technologies for effective CL treatments are desperately needed. Methodology/Principal Findings Here we evaluated the antileishmanial properties and delivery potential of polyhexamethylene biguanide (PHMB; polyhexanide), a widely used antimicrobial and wound antiseptic, in the Leishmania model. PHMB showed an inherent antileishmanial activity at submicromolar concentrations. Our data revealed that PHMB kills Leishmania major (L. major) via a dual mechanism involving disruption of membrane integrity and selective chromosome condensation and damage. PHMB's DNA binding and host cell entry properties were further exploited to improve the delivery and immunomodulatory activities of unmethylated cytosine-phosphate-guanine oligodeoxynucleotides (CpG ODN). PHMB spontaneously bound CpG ODN, forming stable nanopolyplexes that enhanced uptake of CpG ODN, potentiated antimicrobial killing and reduced host cell toxicity of PHMB. Conclusions Given its low cost and long history of safe topical use, PHMB holds promise as a drug for CL therapy and delivery vehicle for nucleic acid immunomodulators. KW - resistance KW - activation KW - dendritic cells KW - Cutaneous leishmaniasis KW - topical treatment KW - biocide polyhexamethylene biguanide KW - experimental visceral leishmaniasis KW - drug-delivery systems KW - therapy KW - paromomycin Y1 - 2015 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-148162 VL - 9 IS - 10 ER - TY - JOUR A1 - Kaiser, Bettina A1 - Vogg, Gerd A1 - Fürst, Ursula B. A1 - Albert, Markus T1 - Parasitic plants of the genus Cuscuta and their interaction with susceptible and resistant host plants JF - Frontiers in Plant Science N2 - By comparison with plant microbe interaction, little is known about the interaction of parasitic plants with their hosts. Plants of the genus Cuscuta belong to the family of Cuscutaceae and comprise about 200 species, all of which live as stem holoparasites on other plants. Cuscuta spp. possess no roots nor fully expanded leaves and the vegetative portion appears to be a stem only. The parasite winds around plants and penetrates the host stems via haustoria, forming direct connections to the vascular bundles of their hosts to withdraw water, carbohydrates, and other solutes. Besides susceptible hosts, a few plants exist that exhibit an active resistance against infestation by Cuscuta spp. For example, cultivated tomato (Solanum lycopersicum) fends off Cuscuta reflexa by means of a hypersensitive-type response occurring in the early penetration phase. This report on the plant plant dialog between Cuscuta spp. and its host plants focuses on the incompatible interaction of C. reflexa with tomato. KW - incompatible interaction KW - messenger-RNA KW - Reflexa Roxb KW - localization KW - symbiosis KW - parasitic plants KW - plant-plant interaction KW - Cuscuta KW - dodder KW - plant immunity KW - resistance KW - Lycopersicon esculentum KW - phenolic constituents KW - Orobanche crenata KW - weed dodder KW - tomato KW - striga Y1 - 2015 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-144091 VL - 6 IS - 45 ER - TY - JOUR A1 - Dühring, Sybille A1 - Germerodt, Sebastian A1 - Skerka, Christine A1 - Zipfel, Peter F. A1 - Dandekar, Thomas A1 - Schuster, Stefan T1 - Host-pathogen interactions between the human innate immune system and Candida albicans - understanding and modeling defense and evasion strategies JF - Frontiers in Microbiology N2 - The diploid, polymorphic yeast Candida albicans is one of the most important human pathogenic fungi. C. albicans can grow, proliferate and coexist as a commensal on or within the human host for a long time. However, alterations in the host environment can render C. albicans virulent. In this review, we describe the immunological cross-talk between C. albicans and the human innate immune system. We give an overview in form of pairs of human defense strategies including immunological mechanisms as well as general stressors such as nutrient limitation, pH, fever etc. and the corresponding fungal response and evasion mechanisms. Furthermore, Computational Systems Biology approaches to model and investigate these complex interactions are highlighted with a special focus on game-theoretical methods and agent-based models. An outlook on interesting questions to be tackled by Systems Biology regarding entangled defense and evasion mechanisms is given. KW - agent-based model KW - antimicrobial peptides KW - fungal pathogens KW - Candida albicans KW - immunological cross-talk KW - beta-lactamase inhibition KW - in vitro KW - biomaterial surfaces KW - biofilm formation KW - dendritic cells KW - infection KW - resistance KW - human immune system KW - host-pathogen interaction KW - computational systems biology KW - defense and evasion strategies Y1 - 2015 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-151621 VL - 6 IS - 625 ER - TY - JOUR A1 - Masic, Anita A1 - Hurdayal, Ramona A1 - Nieuwenhuizen, Natalie E. A1 - Brombacher, Frank A1 - Moll, Heidrun T1 - Dendritic Cell-Mediated Vaccination Relies on Interleukin-4 Receptor Signaling to Avoid Tissue Damage after Leishmania major Infection of BALB/c Mice JF - PLoS Neglected Tropical Diseases N2 - Prevention of tissue damages at the site of Leishmania major inoculation can be achieved if the BALB/c mice are systemically given L. major antigen (LmAg)-loaded bone marrow-derived dendritic cells (DC) that had been exposed to CpG-containing oligodeoxynucleotides (CpG ODN). As previous studies allowed establishing that interleukin-4 (IL-4) is involved in the redirection of the immune response towards a type 1 profile, we were interested in further exploring the role of IL-4. Thus, wild-type (wt) BALB/c mice or DC-specific IL-4 receptor \(\alpha\) (IL-4R \(\alpha\))-deficient (CD11c\(^{cre}\)IL-4R \(\alpha^{-/lox}\) BALB/c mice were given either wt or IL-4R \(\alpha\)-deficient LmAg-loaded bone marrow-derived DC exposed or not to CpG ODN prior to inoculation of 2x10\(^5\) stationary-phase L. major promastigotes into the BALB/c footpad. The results provide evidence that IL4/IL-4R alpha-mediated signaling in the vaccinating DC is required to prevent tissue damage at the site of L. major inoculation, as properly conditioned wt DC but not IL-4R alpha-deficient DC were able to confer resistance. Furthermore, uncontrolled L. major population size expansion was observed in the footpad and the footpad draining lymph nodes of CD11c\(^{cre}\)IL-4R \(\alpha^{-/lox}\) mice immunized with CpG ODN-exposed LmAg-loaded IL-4R \(\alpha\)-deficient DC, indicating the influence of IL-4R \(\alpha\)-mediated signaling in host DC to control parasite replication. In addition, no footpad damage occurred in BALB/c mice that were systemically immunized with LmAg-loaded wt DC doubly exposed to CpG ODN and recombinant IL-4. We discuss these findings and suggest that the IL4/IL4R \(\alpha\) signaling pathway could be a key pathway to trigger when designing vaccines aimed to prevent damaging processes in tissues hosting intracellular microorganisms. KW - cytokines KW - necrosis-factor-alpha KW - T helper cell KW - visceral leishmaniasis KW - intracellular pathogen KW - interferon-gamma KW - IL-12 production KW - deficient mice KW - resistance KW - responses Y1 - 2012 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-133869 VL - 6 IS - 7 ER - TY - JOUR A1 - Naseem, Muhammad A1 - Dandekar, Thomas T1 - The Role of Auxin-Cytokinin Antagonism in Plant-Pathogen Interactions JF - PLOS Pathogens N2 - No abstract available. KW - disease KW - pseudomas-syringae KW - arabidpsis thaliana KW - immunity KW - organogenesis KW - transcription KW - resistance KW - crosstalk Y1 - 2012 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-131901 VL - 8 IS - 11 ER - TY - JOUR A1 - Hofgaard, Peter O. A1 - Jodal, Henriette C. A1 - Bommert, Kurt A1 - Huard, Bertrand A1 - Caers, Jo A1 - Carlsen, Harald A1 - Schwarzer, Rolf A1 - Schünemann, Nicole A1 - Jundt, Franziska A1 - Lindeberg, Mona M. A1 - Bogen, Bjarne T1 - A Novel Mouse Model for Multiple Myeloma (MOPC315.BM) That Allows Noninvasive Spatiotemporal Detection of Osteolytic Disease JF - PLoS One N2 - Multiple myeloma (MM) is a lethal human cancer characterized by a clonal expansion of malignant plasma cells in bone marrow. Mouse models of human MM are technically challenging and do not always recapitulate human disease. Therefore, new mouse models for MM are needed. Mineral-oil induced plasmacytomas (MOPC) develop in the peritoneal cavity of oil-injected BALB/c mice. However, MOPC typically grow extramedullary and are considered poor models of human MM. Here we describe an in vivo-selected MOPC315 variant, called MOPC315.BM, which can be maintained in vitro. When injected i.v. into BALB/c mice, MOPC315.BM cells exhibit tropism for bone marrow. As few as 10\(^4\) MOPC315.BM cells injected i.v. induced paraplegia, a sign of spinal cord compression, in all mice within 3-4 weeks. MOPC315.BM cells were stably transfected with either firefly luciferase (MOPC315.BM.Luc) or DsRed (MOPC315.BM.DsRed) for studies using noninvasive imaging. MOPC315.BM.Luc cells were detected in the tibiofemoral region already 1 hour after i.v. injection. Bone foci developed progressively, and as of day 5, MM cells were detected in multiple sites in the axial skeleton. Additionally, the spleen (a hematopoietic organ in the mouse) was invariably affected. Luminescent signals correlated with serum myeloma protein concentration, allowing for easy tracking of tumor load with noninvasive imaging. Affected mice developed osteolytic lesions. The MOPC315.BM model employs a common strain of immunocompetent mice (BALB/c) and replicates many characteristics of human MM. The model should be suitable for studies of bone marrow tropism, development of osteolytic lesions, drug testing, and immunotherapy in MM. KW - resistance KW - CD4(+) T-cells KW - tumor specific antigen KW - plasma cells KW - B cell KW - C57BL/KALWRIJ mouse KW - bone disease KW - scid mice KW - idiotype KW - differentiation Y1 - 2012 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-131117 VL - 7 IS - 12 ER -