13 research outputs found
Public Discourse as Information System: the Use of SSM to Facilitate âHealthierâ Stakeholder Discourse
This paper explores dialogue between the diverse stakeholders affected by the introduction of the BioFuels Sales Obligation policy in New Zealand. The research will use ârich picturesâ within the framework of Soft Systems Methodology (SSM) to evaluate the extent to which such abstract visualization might facilitate the communication of different viewpoints. It will examine whether the act of representation might encourage individuals, organizations and interest groups to reflect upon their beliefs and assumptions thereby contributing to a healthy discourse around the subject of New Zealand biofuels
Epigenetic regulator genes direct lineage switching in MLL/AF4 leukaemia
The fusion gene MLL/AF4 defines a high-risk subtype of pro-B acute lymphoblastic leukaemia. Relapse can be associated with a lineage switch from acute lymphoblastic to acute myeloid leukaemia resulting in poor clinical outcomes due to resistance towards chemo- and immuno-therapies. Here we show that the myeloid relapses share oncogene fusion breakpoints with their matched lymphoid presentations and can originate from varying differentiation stages from immature progenitors through to committed B-cell precursors. Lineage switching is linked to substantial changes in chromatin accessibility and rewiring of transcriptional programmes, including alternative splicing. These findings indicate that the execution and maintenance of lymphoid lineage differentiation is impaired. The relapsed myeloid phenotype is recurrently associated with the altered expression, splicing or mutation of chromatin modifiers, including CHD4 coding for the ATPase/helicase of the nucleosome remodelling and deacetylation complex, NuRD. Perturbation of CHD4 alone or in combination with other mutated epigenetic modifiers induces myeloid gene expression in MLL/AF4-positive cell models indicating that lineage switching in MLL/AF4 leukaemia is driven and maintained by disrupted epigenetic regulation
Isolation and Characterization of a New T-Even Bacteriophage, CEV1, and Determination of Its Potential To Reduce Escherichia coli O157:H7 Levels in Sheep
Bacteriophage CEV1 was isolated from sheep resistant to Escherichia coli O157:H7 colonization. In vitro, CEV1 efficiently infected E. coli O157:H7 grown both aerobically and anaerobically. In vivo, sheep receiving a single oral dose of CEV1 showed a 2-log-unit reduction in intestinal E. coli O157:H7 levels within 2 days compared to levels in the controls
Association between VEGF Splice Isoforms and Progression-Free Survival in Metastatic Colorectal Cancer Patients Treated with Bevacizumab
PURPOSE: Bevacizumab improves survival for metastatic colorectal cancer patients with chemotherapy, but no proven predictive markers exist. The VEGF-A splice form, VEGF(165)b, anti-angiogenic in animal models, binds bevacizumab. We tested the hypothesis that prolonged progression-free survival (PFS) would occur only in patients with low relative VEGF(165)b levels treated with bevacizumab. METHODS: Blinded tumor samples from the phase-III trial of FOLFOX4±bevacizumab were assessed for VEGF(165)b and VEGF(total) by immunohistochemistry and scored relative to normal tissue. A predictive index (PI) was derived from the ratio of VEGF(165)b:VEGF(total) for 44 samples from patients treated with FOLFOX+bevacizumab (Arm A) and 53 samples from patients treated with FOLFOX4 (Arm B), and PFS, and overall survival (OS) analysed based on PI relative to median ratio. RESULTS: Unadjusted analysis of PFS showed significantly better outcome for individuals with VEGF(165)b:VEGF(total) ratio scores below median treated with FOLFOX4+bevacizumab compared to FOLFOX4 alone (median 8.0 months vs 5.2 months, p<0.02), but no effect of bevacizumab on PFS in patients with VEGF(165)b:VEGF(total) ratio >median (5.9 months vs 6.3 months). These findings held after adjustment for other clinical and demographic features. Overall survival (OS) was increased in Arm A (median 13.6 months) compared with Arm B (10.6 months) in the low VEGF(165)b group, but this did not reach statistical significance. There was no difference in the high VEGF(165)b:VEGF(total) group between FOLFOX+bevacizumab (10.8 months) and FOLFOX alone (11.3months). CONCLUSION: Low VEGF(165)b:VEGF(total) ratio may be a predictive marker for bevacizumab in metastatic colorectal cancer, and individuals with high relative levels may not benefit
Predictive value of the antiangiogenic VEGF splice variant expression for bevacizumab efficacy in the phase III trial of bevacizumab and FOLFOX4 versus FOLFOX4 in previously treated patients with advanced colorectal cancer (ECOG E3200T2).
Association between VEGF Splice Isoforms and Progression-Free Survival in Metastatic Colorectal Cancer Patients Treated with Bevacizumab
Epigenetic regulator genes direct lineage switching in MLL/AF4 leukaemia
The fusion gene MLL/AF4 defines a high-risk subtype of pro-B acute lymphoblastic leukaemia. Relapse can be associated with a lineage switch from acute lymphoblastic to acute myeloid leukaemia resulting in poor clinical outcomes due to resistance towards chemo- and immuno-therapies. Here we show that the myeloid relapses share oncogene fusion breakpoints with their matched lymphoid presentations and can originate from varying differentiation stages from immature progenitors through to committed B-cell precursors. Lineage switching is linked to substantial changes in chromatin accessibility and rewiring of transcriptional programmes, including alternative splicing. These findings indicate that the execution and maintenance of lymphoid lineage differentiation is impaired. The relapsed myeloid phenotype is recurrently associated with the altered expression, splicing or mutation of chromatin modifiers, including CHD4 coding for the ATPase/helicase of the nucleosome remodelling and deacetylation complex, NuRD. Perturbation of CHD4 alone or in combination with other mutated epigenetic modifiers induces myeloid gene expression in MLL/AF4-positive cell models indicating that lineage switching in MLL/AF4 leukaemia is driven and maintained by disrupted epigenetic regulation