Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Transcription profiling of mouse CH1 B-cells upon stimulation either with anti-IgM, IL-4 or with a combination of anti-IgM and IL-4

ABSTRACT: We have studied CH1 cells that undergo G1 arrest upon anti-IgM treatment after 16 hrs of stimulation. First we studied the differential gene expression under anti-IgM and IL-4 stimulation condition individually and in combination, and this revealed the affected genes to be directly or indirectly playing a role for arresting the cells in the G1 phase of the cell cycle. We then performed Western blotting experiments for the selected signaling molecule candidates from various pathways, and the phosphorylation kinetic profiles were used to study their role in regulating the gene expression under anti-IgM and/or IL-4 stimulus. Finally, we profiled how the signaling pathways are regulating the activation and deactivation of 345 transcription factors, which are responsible for regulating the anti-IgM and/or IL-4 responsive genes, which in turn leads to the functional output.

ORGANISM(S): Mus musculus

SUBMITTER: Henna JM-drvenpM-dM-d

PROVIDER: E-MTAB-82 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Integration of signals from the B-cell antigen receptor and the IL-4 receptor leads to a cooperative shift in the cellular response axis.

Aflakian Nooshin N Ravichandran Srikanth S Jamal Md Sarwar MS Jarvenpaa Henna H Lahesmaa Riitta R Rao Kanury V S KV

Molecular bioSystems 20090505 12

Although intracellular signaling events activated through individual cell surface receptors have been characterized in detail, cells are often exposed to multiple stimuli simultaneously in physiological situations. The response elicited then is defined through the cooperative interactions between signals activated by these multiple stimuli. Examples of such instances include cooperativity between individual isoforms of G-protein-coupled receptors, between different growth factor receptors, or be ...[more]

PMID: 19452046

Publication: 1/2

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Project description:Purpose: There is evidence that therapeutic cancer vaccines can lengthen survival for some cancer patients, but responses vary widely from one person to another. Methods to predict clinical outcomes will advance the field and provide new insights into critical determinants of in vivo efficacy. This study uses a high-throughput glycan microarray to assess correlations between a subject's overall survival after receiving PROSTVAC-VF and his anti-glycan humoral responses occuring in the first months after treatment with PROSTVAC-VF. Results: Humoral responses to the terminal Forssman disaccharide (Fsdi) were found to have a statistically significant correlation with survival. Long-term survival was approximately doubled in subjects with four-fold or larger anti-Fsdi responses relative to subjects with little or no anti-Fsdi response. This survival correlation was specific to vaccine treatment, as no correlation was observed in control patients immunized with wild-type poxviruses lacking the key tumor antigen, prostate specific antigen (PSA). Moreover, anti-Fsdi humoral responses were not correlated with general measures of disease severity, such as PSA levels, Gleason score, or Halabi predicted survival. Conclusion: In addition to reporting a new biomarker for monitoring benefical responses to PROSTVAC-VF, this study highlights the potential of glycan microarray technology for personalized medicine. The overall study was a retrospective analysis of 141 subjects from phase II trials of PROSTVAC-VF, a poxvirus based cancer vaccine currently in phase III clinical trials for advanced prostate cancer. The subjects were divided into a training set (n=28) and a validation set (n=113). A glycan microarray was used to profile pre-vaccination and post-vaccination anti-glycan antibody populations in sera as potential biomarkers for PROSTVAC-VF. For both the training set and validation set, the anti-glycan profiles were measured using four variations of serum dilution and isotype specific secondary antibody (IgM at 1:50, IgG at 1:50, total Ig at 1:50, and total Ig at 1:200). IgM levels for the validation set measured at serum dilution of 1:50 are detailed here. The screen for response biomarkers identified anti-glycan humoral responses that consistently stratified subjects into groups with different Kaplan Meier survival estimates. Raw data on SuperSeries GSE50410 record.

Project description:Purpose: There is evidence that therapeutic cancer vaccines can lengthen survival for some cancer patients, but responses vary widely from one person to another. Methods to predict clinical outcomes will advance the field and provide new insights into critical determinants of in vivo efficacy. This study uses a high-throughput glycan microarray to assess correlations between a subject's overall survival after receiving PROSTVAC-VF and his anti-glycan humoral responses occuring in the first months after treatment with PROSTVAC-VF. Results: Humoral responses to the terminal Forssman disaccharide (Fsdi) were found to have a statistically significant correlation with survival. Long-term survival was approximately doubled in subjects with four-fold or larger anti-Fsdi responses relative to subjects with little or no anti-Fsdi response. This survival correlation was specific to vaccine treatment, as no correlation was observed in control patients immunized with wild-type poxviruses lacking the key tumor antigen, prostate specific antigen (PSA). Moreover, anti-Fsdi humoral responses were not correlated with general measures of disease severity, such as PSA levels, Gleason score, or Halabi predicted survival. Conclusion: In addition to reporting a new biomarker for monitoring benefical responses to PROSTVAC-VF, this study highlights the potential of glycan microarray technology for personalized medicine. The overall study was a retrospective analysis of 141 subjects from phase II trials of PROSTVAC-VF, a poxvirus based cancer vaccine currently in phase III clinical trials for advanced prostate cancer. The subjects were divided into a training set (n=28) and a validation set (n=113). A glycan microarray was used to profile pre-vaccination and post-vaccination anti-glycan antibody populations in sera as potential biomarkers for PROSTVAC-VF. For both the training set and validation set, the anti-glycan profiles were measured using four variations of serum dilution and isotype specific secondary antibody (IgM at 1:50, IgG at 1:50, total Ig at 1:50, and total Ig at 1:200). IgM levels for the training set measured at serum dilution of 1:50 are detailed here. The screen for response biomarkers identified anti-glycan humoral responses that consistently stratified subjects into groups with different Kaplan Meier survival estimates. Raw data on SuperSeries GSE50410 record.

Dataset Information

Transcription profiling of mouse CH1 B-cells upon stimulation either with anti-IgM, IL-4 or with a combination of anti-IgM and IL-4

Publications

Integration of signals from the B-cell antigen receptor and the IL-4 receptor leads to a cooperative shift in the cellular response axis.

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