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Metastatic canine mammary carcinomas can be identified by a gene expression profile that partly overlaps with human breast cancer profiles
Robert Klopfleisch, Dido Lenze, Michael Hummel, Achim D Gruber
BMC Cancer , 2010, DOI: 10.1186/1471-2407-10-618
Abstract: Messenger RNA expression profiles of twenty-seven lymph node metastasis positive or negative canine mammary carcinomas were established by microarray analysis. Differentially expressed genes were functionally characterized and associated with molecular pathways. The findings were also correlated with published data on human breast cancer.Metastatic canine mammary carcinomas had 1,011 significantly differentially expressed genes when compared to non-metastatic carcinomas. Metastatic carcinomas had a significant up-regulation of genes associated with cell cycle regulation, matrix modulation, protein folding and proteasomal degradation whereas cell differentiation genes, growth factor pathway genes and regulators of actin organization were significantly down-regulated. Interestingly, 265 of the 1,011 differentially expressed canine genes are also related to human breast cancer and, vice versa, parts of a human prognostic gene signature were identified in the expression profiles of the metastatic canine tumors.Metastatic canine mammary carcinomas can be discriminated from non-metastatic carcinomas by their gene expression profiles. More than one third of the differentially expressed genes are also described of relevance for human breast cancer. Many of the differentially expressed genes are linked to functions and pathways which appear to be relevant for the induction and maintenance of metastatic progression and may represent new therapeutic targets. Furthermore, dogs are in some aspects suitable as a translational model for human breast tumors in order to identify prognostic molecular signatures and potential therapeutic targets.Canine mammary tumor (CMT) is the most common cancer among female dogs and often becomes fatal due to the development of distant metastases [1-3]. Metastasis to the regional lymph node is an early step in metastasis and one of the most important prognostic factors in the diagnosis of CMT, a criterion that is also valid for human breast cancer
DZNep-mediated apoptosis in B-cell lymphoma is independent of the lymphoma type, EZH2 mutation status and MYC, BCL2 or BCL6 translocations
Chidimma Agatha Akpa,Dido Lenze,Elisabeth Oker,Karsten Kleo,Lora Dimitrova,Michael Hummel
- , 2019, DOI: 10.1371/journal.pone.0220681
Abstract:
Transcriptome and proteome analysis of tyrosine kinase inhibitor treated canine mast cell tumour cells identifies potentially kit signaling-dependent genes
Robert Klopfleisch, Anja Meyer, Patricia Schlieben, Angelika Bondzio, Chris Weise, Dido Lenze, Michael Hummel, Ralf Einspanier, Achim D Gruber
BMC Veterinary Research , 2012, DOI: 10.1186/1746-6148-8-96
Abstract: Transcriptome analysis of the canine mast cell tumour cell line C2 treated for up to 72 hours with the tyrosine kinase inhibitor masitinib identified significant changes in the expression levels of approximately 3500 genes or 16% of the canine genome. Approximately 40% of these genes had increased mRNA expression levels including genes associated with the pro-proliferative pathways of B- and T-cell receptors, chemokine receptors, steroid hormone receptors and EPO-, RAS and MAP kinase signaling. Proteome analysis of C2 cells treated for 72 hours identified 24 proteins with changed expression levels, most of which being involved in gene transcription, e.g. EIA3, EIA4, TARDBP, protein folding, e.g. HSP90, UCHL3, PDIA3 and protection from oxidative stress, GSTT3, SELENBP1.Transcriptome and proteome analysis of neoplastic canine mast cells treated with masitinib confirmed the strong important and complex role of KIT in these cells. Approximately 16% of the total canine genome and thus the majority of the active genes were significantly transcriptionally regulated. Most of these changes were associated with reduced proliferation and metabolism of treated cells. Interestingly, several pro-proliferative pathways were up-regulated, which may represent attempts of masitinib treated cells to activate alternative pro-proliferative pathways. These pathways may contain hypothetical targets for a combination therapy with masitinib to further improve its therapeutic effect.Canine mast cell tumours (MCT) are currently treated with one or a combination of four different therapeutic approaches: surgical, radiation, classical chemotherapy and the recently introduced tyrosine kinase inhibitors (TKI) [1-3]. The latter mainly act by inhibiting the stem cell factor receptor KIT, the activation of which is one of the most important proliferation stimuli of normal and neoplastic mast cells [1,4].KIT is constitutively expressed on normal and neoplastic canine mast cells [5]. Due to its centra
Deep Sequencing of MYC DNA-Binding Sites in Burkitt Lymphoma
Volkhard Seitz, Peter Butzhammer, Burkhard Hirsch, Jochen Hecht, Ines Gütgemann, Anke Ehlers, Dido Lenze, Elisabeth Oker, Anke Sommerfeld, Edda von der Wall, Christoph K？nig, Christian Zinser, Rainer Spang, Michael Hummel
PLOS ONE , 2011, DOI: 10.1371/journal.pone.0026837
Abstract: Background MYC is a key transcription factor involved in central cellular processes such as regulation of the cell cycle, histone acetylation and ribosomal biogenesis. It is overexpressed in the majority of human tumors including aggressive B-cell lymphoma. Especially Burkitt lymphoma (BL) is a highlight example for MYC overexpression due to a chromosomal translocation involving the c-MYC gene. However, no genome-wide analysis of MYC-binding sites by chromatin immunoprecipitation (ChIP) followed by next generation sequencing (ChIP-Seq) has been conducted in BL so far. Methodology/Principal Findings ChIP-Seq was performed on 5 BL cell lines with a MYC-specific antibody giving rise to 7,054 MYC-binding sites after bioinformatics analysis of a total of approx. 19 million sequence reads. In line with previous findings, binding sites accumulate in gene sets known to be involved in the cell cycle, ribosomal biogenesis, histone acetyltransferase and methyltransferase complexes demonstrating a regulatory role of MYC in these processes. Unexpectedly, MYC-binding sites also accumulate in many B-cell relevant genes. To assess the functional consequences of MYC binding, the ChIP-Seq data were supplemented with siRNA- mediated knock-downs of MYC in BL cell lines followed by gene expression profiling. Interestingly, amongst others, genes involved in the B-cell function were up-regulated in response to MYC silencing. Conclusion/Significance The 7,054 MYC-binding sites identified by our ChIP-Seq approach greatly extend the knowledge regarding MYC binding in BL and shed further light on the enormous complexity of the MYC regulatory network. Especially our observations that (i) many B-cell relevant genes are targeted by MYC and (ii) that MYC down-regulation leads to an up-regulation of B-cell genes highlight an interesting aspect of BL biology.
Global gene expression changes of in vitro stimulated human transformed germinal centre B cells as surrogate for oncogenic pathway activation in individual aggressive B cell lymphomas
Alexandra Schrader, Katharina Meyer, Frederike von Bonin, Martina Vockerodt, Neele Walther, Elisabeth Hand, Antje Ulrich, Kamila Matulewicz, Dido Lenze, Michael Hummel, Arnd Kieser, Michael Engelke, Lorenz Trümper, Dieter Kube
Cell Communication and Signaling , 2012, DOI: 10.1186/1478-811x-10-43
Abstract: The B cell receptor (BCR), CD40, B-cell activating factor (BAFF)-receptors and Interleukin (IL) 21 receptor and Toll like receptor 4 (TLR4) were stimulated in human transformed germinal centre B cells by treatment with anti IgM F(ab)2-fragments, CD40L, BAFF, IL21 and LPS respectively. The changes in gene expression following the activation of Jak/STAT, NF-кB, MAPK, Ca2+ and PI3K signalling triggered by these stimuli was assessed using microarray analysis. The expression of top 100 genes which had a change in gene expression following stimulation was investigated in gene expression profiles of patients with Aggressive non-Hodgkin Lymphoma (NHL).αIgM stimulation led to the largest number of changes in gene expression, affecting overall 6596 genes. While CD40L stimulation changed the expression of 1194 genes and IL21 stimulation affected 902 genes, only 283 and 129 genes were modulated by lipopolysaccharide or BAFF receptor stimulation, respectively. Interestingly, genes associated with a Burkitt-like phenotype, such as MYC, BCL6 or LEF1, were affected by αIgM. Unique and shared gene expression was delineated. NHL-patients were sorted according to their similarity in the expression of TOP100 affected genes to stimulated transformed germinal centre B cells The αIgM gene module discriminated individual DLBCL in a similar manner to CD40L or IL21 gene modules. DLBCLs with low module activation often carry chromosomal MYC aberrations. DLBCLs with high module activation show strong expression of genes involved in cell-cell communication, immune responses or negative feedback loops. Using chemical inhibitors for selected kinases we show that mitogen activated protein kinase- and phosphoinositide 3 kinase-signalling are dominantly involved in regulating genes included in the αIgM gene module.We provide an in vitro model system to investigate pathway activation in lymphomas. We defined the extent to which different immune response associated pathways are responsible for differe
Estudo da demanda de atendimento na educa？？o especial do Rio Grande do Sul
Alexandre Dido Balbinot
- , 2017, DOI: http://dx.doi.org/10.17058/cinergis.v18i2.8766
Abstract: Objetivo: analisar a demanda da educa？？o especial no Rio Grande do Sul por categoria diagnóstica que caracterizou a matrícula no ano de 2015. Método: trata-se de um estudo do tipo ecológico, que foi baseado em série histórica de dados secundários. A coleta de dados ocorreu durante o mês de agosto de 2016. A análise inferencial foi composta pelo teste T de Student. O nível de significancia empregado foi de p<0,05. Resultados: observou-se diferen？a estatisticamente significativa (p<0,001) na distribui？？o da quantidade de matrículas entre as diferentes categorias diagnósticas; na distribui？？o das matrículas para os diferentes territórios abordados (p=0,002); e, diferen？a na distribui？？o das matrículas para as diferentes modalidades de atendimento disponibilizadas (p = 0,017). Considera？？es finais: a formata？？o da educa？？o especial no Rio Grande do Sul está, em parte, em consonancia com o preconizado, ainda assim, é importante o conhecimento das características desta popula？？o atendida, tanto para o planejamento da estrutura？？o dos servi？os, quanto para forma？？o acadêmica e continuada dos profissionais
A Educa？？o Especial no Ceará: um estudo da evolu？？o dos indicadores entre 2005 e 2014
Alexandre Dido Balbinot
- , 2016, DOI: http://dx.doi.org/10.17058/cinergis.v17i1.7147
Abstract: O cenário da educa？？o especial tem sofrido importantes modifica？？es, principalmente na última década, sendo assim necessária a análise da evolu？？o deste processo. Objetivo: analisar a evolu？？o da educa？？o especial e da inclus？o de portadores de necessidades especiais entre 2005 e 2014 no Estado do Ceará/ Brasil. Método: estudo de caráter ecológico com uso de dados provenientes dos Censos Educacionais. A análise foi realizada no programa Stata 11.0 e empregou-se: Correla？？o de Spearman, Regress？o de Poisson robusta. O nível de significancia empregado foi de p<0,05 e Intervalo de Confian？a de 95%. Resultados: analisou-se 25.591.084 matriculas da educa？？o básica, sendo 268.266 da educa？？o especial. As escolas exclusivamente especializadas representaram 16,04% das matrículas da educa？？o especial e em média, foram 4.303,3 (DP= 2517,47) matrículas anuais. As classes especiais representaram 8,02% das matrículas com média anual de 2.151,8 (DP= 1.162,53). Já as classes comuns do ensino regular contemplaram 75,93% das matrículas e foram em média 20.367,5 (DP= 10.427,4) matrículas anuais. Observou-se redu？？o nas matrículas da educa？？o básica em 3% e aumento na educa？？o especial em 9%. Para as escolas exclusivamente especializadas houve redu？？o de 18% (20% em privadas e 11% em públicas). As classes especiais apresentaram redu？？o de 15%, idêntico as institui？？es públicas. A educa？？o privada n？o apresentou modifica？？o significativa (p=0,129). As classes comuns apresentaram aumento de 19% (13% na rede pública e 11% na privada). Considera？？es finais: a educa？？o no Estado do Ceará está passando por um processo de modifica？？o no seu paradigma de atendimento corroborando com o que é preconizado internacionalmente. Todavia, ainda há uma demanda reprimida de atendimento
Análise de indicadores de evolu？？o da educa？？o especial no estado do Espírito Santo entre 2005 e 2013
Alexandre Dido Balbinot
- , 2017, DOI: http://dx.doi.org/10.17058/cinergis.v18i4.9627
Abstract: Objetivo: analisar, através das matrículas na educa？？o básica e na Educa？？o Especial, a evolu？？o do processo de inclus？o de portadores de necessidades educacionais especiais na educa？？o do Estado do Espírito Santo. Método: estudo do tipo ecológico, que utilizou dados secundários, oriundos dos Censos Educacionais. Foram incluídas, no estudo, as matrículas entre 2005 e 2013 realizadas em estabelecimentos de educa？？o do Estado do Espírito Santo - Brasil. Foram analisadas 8.397.364 matrículas da educa？？o básica, sendo 143.927 da Educa？？o Especial. Resultados: foi evidenciada retra？？o de 1% nas matrículas da educa？？o básica, entretanto n？o houve varia？？o nas matrículas da Educa？？o Especial. Referente às modalidades de atendimento, observou-se redu？？o nas matrículas para escola exclusivamente especializada em 30%, enquanto que para o atendimento em classe comum com atendimento educacional especializado (AEE), houve aumento de 16%. Considera？？es finais: a Educa？？o Especial no Estado do Espírito Santo apresentou mudan？a em seu paradigma de atendimento sendo evidente a evolu？？o em consonancia com os ideais preconizados pela Declara？？o de Salamanca e dos direitos garantidos pela legisla？？o vigente
Study of the Effect of Methyl Jasmonate Concentration on Aflatoxin Biosynthesis by Aspergillus parasiticus in Yeast Extract Sucrose Medium
Dido Maria Meimaroglou,Dia Galanopoulou,Panagiota Markaki
International Journal of Microbiology , 2009, DOI: 10.1155/2009/842626
Abstract: Aflatoxin B1 (AFB1) is a carcinogenic metabolite produced by certain Aspergillus species on agricultural commodities. AFB1 biosynthesis is affected by jasmonic acid and also by its methylester (MeJA), a plant growth regulator derived from linoleic acid. This study reports the effect of MeJA on the growth of A. parasiticus and AFB1 output in yeast extract sucrose (YES) medium when added at three different concentrations; namely, 10−2 M, 10−4 M, and 10−6 M. AFB1 determination was performed by immunoaffinity and HPLC. MeJA at 10−4 and 10−6 M concentrations had no significant effect on mycelial growth but did affect AFB1 production after the 7th day of incubation; on the 12th day, AFB1 production was increased by 212.7% and 141.6% compared to the control samples (addition of 10−6 M and 10−4 M MeJA, resp.). Treatment of A. parasiticus cultures with 10−2 M MeJA inhibited mycelial growth and AFB1 production as well. These results suggest that the effect of MeJA on AFB1 biosynthesis by A. parasiticus depends on the MeJA concentration used.
Antibiotic resistant profile of Streptococcus pneumoniae from the nasopharynx.
YT Kandakai-Olukemi, MS Dido
Annals of African Medicine , 2009,
Abstract: Background: Antimicrobial resistance in Streptococcus pneumoniae has compromised the effectiveness of therapy for pneumococcal diseases and asymptomatic nasopharyngeal carriers play an important role in transmission of resistant strains. Method: Eighty-eight volunteer students attending 2 secondary schools in Jos, Nigeria were involved in this study to determine the antimicrobial resistant profile of Streptococcus pneumoniae isolated from the nasopharynx. The study population consisted of males and females between the ages of 15 – 25 years. Nasopharyngeal swab samples were analyzed for the presence of S. pneumoniae using standard bacteriological methods. The isolates were subjected to antimicrobial susceptibility testing using the disc diffusion method. Results: S. pneumoniae was isolated from 37(42.04%) of the 88 samples. Isolates showed the highest resistance of 12 (32.43%) to erythromycin and lowest resistance of 4(10.81%) to ciprofloxacin. The resistance profiles for the 26(70.27%) penicillin-sensitive and 11(29.72%) penicillin-resistant isolates were similar. Both exhibited varying degrees of resistance to several groups of antimicrobials. However, isolates found to be resistant to penicillin showed a higher degree of resistance to other antimicrobial agents. Conclusion: This study has shown that some secondary school students are carriers of multiple antibiotic-resistant S. pneumoniae.
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