Recurrent and/or metastatic head and neck squamous cell carcinoma (HNSCC) remains one of the most difficult cancers to treat with limited chemotherapeutic options. Here, we describe a patient with HNSCC who had complete response to methotrexate (MTX) after progressing on multiple cytotoxic agents; cetuximab, a monoclonal antibody (mAb) against Epidermal Growth Factor Receptor (EGFR), and AMG 479, a mAb against Insulin-like Growth Factor-1 Receptor (IGF-1R).
Insulin-like growth factor-1 receptor inhibitor, AMG-479, in cetuximab-refractory head and neck squamous cell carcinoma.
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View SamplesThe role of antibody and B cells in preventing infection is established. In contrast, the role of B cell responses in containing chronic infections remains poorly understood. IgG2a (IgG1 in humans) can prevent acute infections and T-bet promotes IgG2a isotype switching. However, whether IgG2a and B cell-expressed T-bet influence the host-pathogen balance during persisting infections is unclear. Here we demonstrate that B cell specific loss of T-bet prevents control of persisting viral infection. T-bet in B cells not only controlled IgG2a production, but also mucosal localization, proliferation, glycosylation, and a broad transcriptional program. T-bet controlled a broad antiviral program in addition to IgG2a since T-bet in B cells was important even in the presence of virus-specific IgG2a. Our data supports a model in which T-bet is a universal controller of antiviral immunity across multiple immune lineages.
Cutting Edge: B Cell-Intrinsic T-bet Expression Is Required To Control Chronic Viral Infection.
Specimen part
View SamplesForced sustained swimming exercise at optimal speed enhances growth in many fish species, particularly through hypertrophy of the white skeletal muscle. The exact mechanism of this effect has not been resolved yet. To explore the mechanism, we first subjected wild-type zebrafish to an exercise protocol validated for exercise-enhanced growth, and showed that exercised zebrafish, which indeed showed enhanced growth, had higher cortisol levels than the non-exercised controls. A central role was therefore hypothesized for the steroid hormone cortisol acting through the Glucocorticoid receptor (Gr). Second, we subjected wild-type zebrafish and zebrafish with a mutant Gr to exercise at optimal, suboptimal and super-optimal speeds and compared them with non-exercised controls. Exercised zebrafish showed growth enhancement at all speeds, with highest growth at optimal speeds. In the Gr mutant fish, exercise resulted in growth enhancement similar to wild-type zebrafish, indicating that cortisol cannot be considered as a main determinant of exercise-enhanced growth. Finally, the transcriptome of white skeletal muscle tissue was analysed by RNA sequencing. The results of this analysis showed that in the muscle tissue of Gr mutant fish a lower number of genes is regulated by exercise than in wild-type fish (183 versus 351). A cluster of 36 genes was regulated by exercise in both wild-type and mutant fish. In this cluster, genes involved in transcriptional regulation and protein ubiquitination were overrepresented. Since growth was enhanced similarly in both wild-type fish and mutants, these processes may play an important role in exercise-enhanced growth. Overall design: Deep-sequencing transcriptome analysis of white muscle samples derived from wild-type (++) or glucocorticoid receptor (Gr) mutant (--) Danio rerio specimens that were exposed to either a resting (REST) or a swimming (UOPT) regimen: wild-type resting (REST++; n=3), Gr mutant resting (REST--; n=3), wild-type swimming (UOPT++; n=3), Gr mutant swimming (UOPT--; n=3).
Cortisol Acting Through the Glucocorticoid Receptor Is Not Involved in Exercise-Enhanced Growth, But Does Affect the White Skeletal Muscle Transcriptome in Zebrafish (<i>Danio rerio</i>).
Specimen part, Treatment, Subject
View SamplesDuring sexual dimorphism, the loss of one entire X chromosome in Drosophila males is achieved largely via a broad genome-wide aneuploid effect. Exploring how MSL proteins and two large non coding RNAs (roX1 and roX2) modulate trans-acting aneuploid effect for equality to females, we employ a system biology approach (microarray) to investigate the global aneuploid effect of maleless(mle) mutation by disrupting MSL binding. A large number of the genes (144) that encode a broad spectrum of cellular transport proteins and transcription factors are located in the autosomes of Drosophila melanogaster.
Drosophila maleless gene counteracts X global aneuploid effects in males.
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View SamplesCytochrome oxydases and quinol monooxygenase were removed from the E. coli genome resulting in oxygen-independent physiology
Deletion of genes encoding cytochrome oxidases and quinol monooxygenase blocks the aerobic-anaerobic shift in Escherichia coli K-12 MG1655.
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View SamplesThis SuperSeries is composed of the SubSeries listed below.
The PurR regulon in Escherichia coli K-12 MG1655.
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View SamplesExpression profiling of wild type and purR deletion strains of E. coli K-12 MG1655 under both M9 minimal media and addition of adenine.
The PurR regulon in Escherichia coli K-12 MG1655.
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View SamplesThe simultaneous genotyping of tens of thousands of SNP using SNP microarrays is a very important tool that is revolutionizing genetics and molecular biology. In this work, we present a new application of this technique by using it to assess chromatin immunoprecipitation (CHIP) as a means to assess the multiple genomic locations bound by a protein complex recognized by an antibody. We illustrate the use of this technique with an analysis of the change in histone H4 acetylation, a marker of open chromatin and transcriptionally active genomic regions, which occur during the differentiation of human myoblasts into myotubes. Our results are validated by the observation of a significant correlation between the histone modifications detected and the expression of the nearby genes, as measured by DNA microarrays.
ChIP on SNP-chip for genome-wide analysis of human histone H4 hyperacetylation.
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View SamplesGene expression was determined for both myotubes and myoblasts using Affymetrix HG-U133 A/B arrays.
ChIP on SNP-chip for genome-wide analysis of human histone H4 hyperacetylation.
No sample metadata fields
View SamplesThe aim of this study is to investigate the changes of global gene expression in E. coli during a carbon source shift.
Network context and selection in the evolution to enzyme specificity.
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