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Additional file 3: Supplementary Table 2. List of the primers used for pyrosequencing and amplicon sequencing (Illumina MiSeq system).

Regionally DE genes list. (XLSX 282Â kb)

Additional file 3: Table S2. Annotation of the M. Tuberculosis genes and clusters. M. tuberculosis genes are represented by gene symbols and the protein RefSeq ID and COG category eggNOG.

Provincial and territorial policy documents and indicator scores; table contains all CHARPP indicator scores from 13 provincial and territorial harm reduction policy report cards. (XLSX 57Â kb)

Library construction chemistry comparison using tumor samples. Two NEB workflows were evaluated. The first has bead clean up after each of the library construction steps (A); the second has the bead cleanup after A-tail removed (B). Input gDNA was from three different clinical samples (Source 1â 3). (JPEG 27Â kb)

Amodiaquine (AQ) is associated with a relatively high incidence of idiosyncratic drug-induced liver injury (IDILI) and agranulocytosis. A previous study reported that a combination of high dose AQ and glutathione (GSH) depletion led to liver injury. However, the characteristics of this toxicity were very different from AQ-induced liver injury in humans. We developed a model of AQ-induced liver injury with characteristics similar to the injury in humans by treating mice with lower doses of AQ for several weeks. In this study we found that not only did GSH depletion not increase AQ covalent binding to hepatic proteins at this lower dose, but also it paradoxically prevented the liver injury. We extended the model to rats and found AQ treatment led to a mild delayed onset liver injury that resolved despite continued treatment with AQ. Immunohistochemistry indicated the presence of Kupffer cell activation, apoptosis and hepatocyte proliferation in the liver. There was also an increase in serum IL-2, IL-5, IL-9, IL-12, MCP-1 and TGFβ, but a decrease in leptin. Coincident with the elevated serum ALT, the number of liver CD4+ T-cells, IL-17 secreting cells and TH17/Treg cells increased at Week 3 and decreased during continued treatment. Increases in NK1.1+ cells and activated M2 macrophages were also observed during liver injury. These results suggest that the outcome of the liver injury was determined by the balance between effector and regulatory cells. Co-treatment with cyclosporin prevented AQ-induced liver injury, which supports an immune mechanism. Retinoic acid (RA), which has been reported to enhance natural killer (NK) cell activity, exacerbated AQ-induced liver injury. These results suggest that AQ-induced IDILI is immune mediated and the subsequent adaptation appears to represent immune tolerance.

Comparison of GO terms classifications of molecular function from the identified secreted proteins grown under Pka1-repressed and Pka1-induced conditions compared to proteins represented in the Fungal Secretome Knowledgebase. (TIFF 1149 kb)

Additional file 5: Figure S5. A) qRT-PCR analysis of Spy1 levels in 8-week-old MMTV-Spy1 mice and their control littermates (cntl) 48 h after DMBA treatment in mice with and without DMBA. Levels of Flag-Spy1 are corrected for total levels of GAPDH. B) Representative western blot for p53 protein levels in MMTV-Spy1 8-week-old mice and their control littermates 48 h after DMBA treatment. Error bars represent SE. ***p

Kernel density curves of the hdPS distribution within the Full Cohort. (TIF 460Â kb)

A common feature of solid tumours that are resistant to therapy is the presence of regions with low oxygen content (i.e., hypoxia). Oxygen electrode studies suggest that localized prostate adenocarcinoma is commonly hypoxic, although conflicting data have been reported between immunohistochemical detection of hypoxia-induced proteins in biopsy specimens and positron emission tomography (PET) imaging of 18F-labeled hypoxia reporters. Although the 2-nitroimidazole 18F-EF5 is well-established to label hypoxic tumour cells in pre-clinical tumour models and clinical trials of multiple primary tumour sites, it has yet to be tested in prostate cancer. The purpose of this study was to evaluate the feasibility of using 18F-EF5 to detect hypoxia in clinical prostate tumours. Patients with localized adenocarcinoma of the prostate were recruited for pre-treatment 18F-EF5 PET scans. Immunohistochemistry was conducted on diagnostic biopsies to assess the expression of glucose transporter 1 (GLUT1), osteopontin (OPN), and carbonic anhydrase IX (CAIX). Immunoreactivity scores of staining intensity and frequency were used to indicate the presence of tumour hypoxia. We found low tumour-to-muscle ratios of 18F-EF5 uptake that were not consistent with tumour hypoxia, causing early termination of the study. However, we observed GLUT1 and OPN expression in all prostate tumour biopsies, indicating the presence of hypoxia in all tumours. Our data do not support the use of 18F-EF5 PET to detect hypoxia in prostate adenocarcinoma, and suggest the use of immunohistochemistry to quantify expression of the hypoxia-inducible proteins GLUT1 and OPN as indications of prostate tumour hypoxia.