@article{SchmittKellerNourkamiTutdibietal.2011, author = {Schmitt, Jana and Keller, Andreas and Nourkami-Tutdibi, Nasenien and Heisel, Sabrina and Habel, Nunja and Leidinger, Petra and Ludwig, Nicole and Gessler, Manfred and Graf, Norbert and Berthold, Frank and Lenhof, Hans-Peter and Meese, Eckart}, title = {Autoantibody Signature Differentiates Wilms Tumor Patients from Neuroblastoma Patients}, series = {PLoS ONE}, volume = {6}, journal = {PLoS ONE}, number = {12}, doi = {10.1371/journal.pone.0028951}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-133794}, pages = {e28951}, year = {2011}, abstract = {Several studies report autoantibody signatures in cancer. The majority of these studies analyzed adult tumors and compared the seroreactivity pattern of tumor patients with the pattern in healthy controls. Here, we compared the autoimmune response in patients with neuroblastoma and patients with Wilms tumor representing two different childhood tumors. We were able to differentiate untreated neuroblastoma patients from untreated Wilms tumor patients with an accuracy of 86.8\%, a sensitivity of 87.0\% and a specificity of 86.7\%. The separation of treated neuroblastoma patients from treated Wilms tumor patients' yielded comparable results with an accuracy of 83.8\%. We furthermore identified the antigens that contribute most to the differentiation between both tumor types. The analysis of these antigens revealed that neuroblastoma was considerably more immunogenic than Wilms tumor. The reported antigens have not been found to be relevant for comparative analyses between other tumors and controls. In summary, neuroblastoma appears as a highly immunogenic tumor as demonstrated by the extended number of antigens that separate this tumor from Wilms tumor.}, language = {en} } @article{HaddadChenZhangetal.2011, author = {Haddad, Dana and Chen, Nanhai G. and Zhang, Qian and Chen, Chun-Hao and Yu, Yong A. and Gonzalez, Lorena and Carpenter, Susanne G. and Carson, Joshua and Au, Joyce and Mittra, Arjun and Gonen, Mithat and Zanzonico, Pat B. and Fong, Yuman and Szalay, Aladar A.}, title = {Insertion of the human sodium iodide symporter to facilitate deep tissue imaging does not alter oncolytic or replication capability of a novel vaccinia virus}, series = {Journal of Translational Medicine}, volume = {9}, journal = {Journal of Translational Medicine}, number = {36}, doi = {10.1186/1479-5876-9-36}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-140847}, pages = {1-14}, year = {2011}, abstract = {Introduction: Oncolytic viruses show promise for treating cancer. However, to assess therapeutic efficacy and potential toxicity, a noninvasive imaging modality is needed. This study aimed to determine if insertion of the human sodium iodide symporter (hNIS) cDNA as a marker for non-invasive imaging of virotherapy alters the replication and oncolytic capability of a novel vaccinia virus, GLV-1h153. Methods: GLV-1h153 was modified from parental vaccinia virus GLV-1h68 to carry hNIS via homologous recombination. GLV-1h153 was tested against human pancreatic cancer cell line PANC-1 for replication via viral plaque assays and flow cytometry. Expression and transportation of hNIS in infected cells was evaluated using Westernblot and immunofluorescence. Intracellular uptake of radioiodide was assessed using radiouptake assays. Viral cytotoxicity and tumor regression of treated PANC-1tumor xenografts in nude mice was also determined. Finally, tumor radiouptake in xenografts was assessed via positron emission tomography (PET) utilizing carrier-free (124)I radiotracer. Results: GLV-1h153 infected, replicated within, and killed PANC-1 cells as efficiently as GLV-1h68. GLV-1h153 provided dose-dependent levels of hNIS expression in infected cells. Immunofluorescence detected transport of the protein to the cell membrane prior to cell lysis, enhancing hNIS-specific radiouptake (P < 0.001). In vivo, GLV-1h153 was as safe and effective as GLV-1h68 in regressing pancreatic cancer xenografts (P < 0.001). Finally, intratumoral injection of GLV-1h153 facilitated imaging of virus replication in tumors via (124)I-PET. Conclusion: Insertion of the hNIS gene does not hinder replication or oncolytic capability of GLV-1h153, rendering this novel virus a promising new candidate for the noninvasive imaging and tracking of oncolytic viral therapy.}, language = {en} } @article{HillStritzkerScadengetal.2011, author = {Hill, Philip J. and Stritzker, Jochen and Scadeng, Miriam and Geissinger, Ulrike and Haddad, Daniel and Basse-L{\"u}sebrink, Thomas C. and Gbureck, Uwe and Jakob, Peter and Szalay, Aladar A.}, title = {Magnetic Resonance Imaging of Tumors Colonized with Bacterial Ferritin-Expressing \(Escherichia\) \(coli\)}, series = {PLoS ONE}, volume = {6}, journal = {PLoS ONE}, number = {10}, doi = {10.1371/journal.pone.0025409}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-140920}, pages = {e25409}, year = {2011}, abstract = {Background: Recent studies have shown that human ferritin can be used as a reporter of gene expression for magnetic resonance imaging (MRI). Bacteria also encode three classes of ferritin-type molecules with iron accumulation properties. Methods and Findings: Here, we investigated whether these bacterial ferritins can also be used as MRI reporter genes and which of the bacterial ferritins is the most suitable reporter. Bacterial ferritins were overexpressed in probiotic E. coli Nissle 1917. Cultures of these bacteria were analyzed and those generating highest MRI contrast were further investigated in tumor bearing mice. Among members of three classes of bacterial ferritin tested, bacterioferritin showed the most promise as a reporter gene. Although all three proteins accumulated similar amounts of iron when overexpressed individually, bacterioferritin showed the highest contrast change. By site-directed mutagenesis we also show that the heme iron, a unique part of the bacterioferritin molecule, is not critical for MRI contrast change. Tumor-specific induction of bacterioferritin-expression in colonized tumors resulted in contrast changes within the bacteria-colonized tumors. Conclusions: Our data suggest that colonization and gene expression by live vectors expressing bacterioferritin can be monitored by MRI due to contrast changes.}, language = {en} } @article{WalitzaMelfsenJansetal.2011, author = {Walitza, Susanne and Melfsen, Siebke and Jans, Thomas and Zellmann, Henrike and Wewetzer, Christoph and Warnke, Andreas}, title = {Obsessive-Compulsive Disorder in Children and Adolescents}, series = {Deutsches {\"A}rzteblatt International}, volume = {108}, journal = {Deutsches {\"A}rzteblatt International}, number = {11}, doi = {10.3238/arztebl.2011.0173}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-141214}, pages = {173-I}, year = {2011}, abstract = {Background: Early-onset obsessive-compulsive disorder (OCD) is one of the more common mental illnesses of children and adolescents, with prevalence of 1\% to 3\%. Its manifestations often lead to severe impairment and to conflict in the family. In this review, we summarize the manifestations, comorbidity, pathophysiology, and course of this disease as well as current modes of diagnosis and treatment. Methods: We selectively review the relevant literature and the German-language guidelines for the diagnosis and treatment of mental illnesses in children and adolescents. Results: Obsessive-compulsive manifestations are of many types and cause severe impairment. Comorbid mental disturbances are present in as many as 70\% of patients. The disease takes a chronic course in more than 40\% of patients. Cognitive behavioral therapy is the treatment of first choice, followed by combination pharmacotherapy including selective serotonin reuptake inhibitors (SSRI) and then by SSRI alone. Conclusion: OCD often begins in childhood or adolescence. There are empirically based neurobiological and cognitive-behavioral models of its pathophysiology. Multiaxial diagnostic evaluation permits early diagnosis. Behavioral therapy and medications are highly effective treatments, but the disorder nonetheless takes a chronic course in a large percentage of patients.}, language = {en} } @article{ChenYuZhangetal.2011, author = {Chen, Nanhai G. and Yu, Yong A. and Zhang, Qian and Szalay, Aladar A.}, title = {Replication efficiency of oncolytic vaccinia virus in cell cultures prognosticates the virulence and antitumor efficacy in mice}, series = {Journal of Translational Medicine}, volume = {9}, journal = {Journal of Translational Medicine}, number = {164}, doi = {10.1186/1479-5876-9-164}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-142268}, pages = {1-11}, year = {2011}, abstract = {Background: We have shown that insertion of the three vaccinia virus (VACV) promoter-driven foreign gene expression cassettes encoding Renilla luciferase-Aequorea GFP fusion protein, beta-galactosidase, and beta-glucuronidase into the F14.5L, J2R, and A56R loci of the VACV LIVP genome, respectively, results in a highly attenuated mutant strain GLV 1h68. This strain shows tumor specific replication and is capable of eradicating tumors with little or no virulence in mice. This study aimed to distinguish the contribution of added VACV promoter-driven transcriptional units as inserts from the effects of insertional inactivation of three viral genes, and to determine the correlation between replication efficiency of oncolytic vaccinia virus in cell cultures and the virulence and antitumor efficacy in mice Methods: A series of recombinant VACV strains was generated by replacing one, two, or all three of the expression cassettes in GLV 1h68 with short non coding DNA sequences. The replication efficiency and tumor cell killing capacity of these newly generated VACV strains were compared with those of the parent virus GLV-1h68 in cell cultures. The virus replication efficiency in tumors and antitumor efficacy as well as the virulence were evaluated in nu/nu (nude) mice bearing human breast tumor xenografts. Results: we found that virus replication efficiency increased with removal of each of the expression cassettes. The increase in virus replication efficiency was proportionate to the strength of removed VACV promoters linked to foreign genes. The replication efficiency of the new VACV strains paralleled their cytotoxicity in cell cultures. The increased replication efficiency in tumor xenografts resulted in enhanced antitumor efficacy in nude mice. Similarly, the enhanced virus replication efficiency was indicative of increased virulence in nude mice. Conclusions: These data demonstrated that insertion of VACV promoter-driven transcriptional units into the viral genome for the purpose of insertional mutagenesis did modulate the efficiency of virus replication together with antitumor efficacy as well as virulence. Replication efficiency of oncolytic VACV in cell cultures can predict the virulence and therapeutic efficacy in nude mice. These findings may be essential for rational design of safe and potent VACV strains for vaccination and virotherapy of cancer in humans and animals.}, language = {en} }