EMBO/sd-character-level-ner huggingface dataset:
Figure 5a, Circos plot summary of the stromal ligand-receptor interactions. Outer sectors are weighted according to the number of annotated ligand receptor interactions per cell type. Links between sectors are weighted according to the 'Interaction Strength', calculated as a product of ligand and receptor expression. Links are coloured by the respective stromal subsets; myCAFs (red), iCAFs (orange), dPVL cells (blue) and imPVL cells (light blue) b, Summary of the total ligands and receptors annotated per cell type. c-e, Imputed gene expression of selected candidate signalling molecules identified between the four stromal subsets and malignant (c) epithelial, (d) myeloid and (e) T-cells. Expression of ligands in stromal clusters are represented on the left, with cognate receptors on target cells on the right.
Identification of NCOA5 as an LXR repressorProtein–protein interaction network showing connectivity between the putative ligand‐stimulated and LXR binding‐dependent transcriptional regulators of Abca1 (shown in orange).Figure 2Protein-protein interaction network showing connectivity between the putative ligand‐stimulated and LXR binding‐dependent transcriptional regulators of Abca1 (shown in orange). Edges represent protein-protein interactions. NCOA5 node and edge are outlined red to indicate that this physical association is found in mouse interaction networks. Luciferase reporter assays from RAW 264.7 macrophages expressing reporter alone, or together with full‐length SND1, SART1, or HMBOX1. LXR ligand stimulations with 1 μM T0901317 were performed for 18 h. A diagram of the reporter construct is shown above. Fold changes are shown relative to vehicle‐stimulated reporter alone (first lane). Error bars represent ± SEM for n = 9 (**P = 0.001, *P = 0.011 for SND1, *P = 0.046 for SART1). Luciferase reporter assays from RAW 264.7 macrophages expressing reporter alone, or together with full‐length NCOA5 or an NCOA5 mutant lacking the NH2‐terminus. LXR ligand stimulations with 1 μM T0901317 were performed for 18 h. Diagrams of the reporter constructs are shown above. Fold changes are shown relative to vehicle‐stimulated reporter alone (first lane). Error bars represent ± SEM for n = 6-12 (**P 0.001, *P = 0.035). RT-qPCR of Abca1 transcripts following infection of primary BMMs with Ncoa5 or control retrovirus. LXR ligand stimulations were performed with 1 μM T0901317 for 18 h. Fold changes are shown relative to vehicle‐stimulated control. Error bars represent ± SEM for n = 4 (*P = 0.029).
Figure 4Mdm2-/-Trp53-/- (double knock-out, DKO) MEFs were transduced with pInducer20-p53EE lentivirus to enable tetracyclin (Tet)-inducible expression of mouse p53EE. Induction of p53EE sensitized cells to apoptosis induced by 24 hour treatment with 1 µg/ml doxorubicin (Doxo) as detected by flow cytometry for Annexin V. mRNA expression of p53 target genes was measured in cells from (A) relative to β-actin by RTqPCR following treatment with Tet ± 1 µg/ml Doxo. Expression of the pro-apoptotic p53 target genes Bbc3 (Puma) and Bax is not significantly induced. n=6. Proliferation of MEFs with indicated genotypes was analyzed by live-cell imaging in the presence of 10 µM nutlin-3a (Nutlin) and/or 0.05 µg/ml doxorubicin (Doxo). Shown is the median confluence ±SEM (n=12). Cell viability assays for MEFs with indicated genotypes treated with Mdm2 inhibitors ± 0.4 µg/ml Doxo. n=3. Cell viability assays for MEFs with indicated genotypes treated with Mdm2 inhibitors ± 0.4 µg/ml Doxo. n=3. Western blot of E1A-MEFs with indicated genotypes treated with 10 µM Nutlin ± 0.4 µg/ml Doxo for 18 hours reveals induction of apoptosis (cCasp-3, cleaved caspase-3; cParp, cleaved Parp) in double-treated p53EE/EE MEFs in the absence of p53 target gene (p21, Mdm2) activation. *, 10 hours 0.4 µg/ml Doxo; **, 10 hours 0.2 µg/ml Doxo. mRNA expression of p53 target genes was measured in E1A MEFs of indicated genotype relative to β-actin by RTqPCR following combined treatment with 10 µM Nutlin and 1 µg/ml Doxo. n=12. Western blot of p53EE/EE E1A-MEFs with indicated genotypes treated for 18 hours with 10 µM Nutlin, 0.4 µg/ml Doxo and 30-100-500 nM Ganetespib as indicated. Comb, combined treatment with 3 drugs for 18 hours. Pre, pre-treatment with ganetespib for 24 hours followed by combined treatment with Nutlin and Doxorubicin for 18 hours. Western blot of cellular fractions from unstressed and Doxo-treated MEFs of indicated genotype identifies p53EE protein in the mitochondrial fraction. PCNA, Tom20/Bak are shown as nuclear and mitochondrial marker proteins.
Figure 5Representative PET image of the upper body of a human subject who received the PDE10A radioligand [18F]-MNI-1869. Supraclavicular brown adipose tissue (BAT) is highlighted by the crosshairs. The mean standardized uptake value (SUV) of [18F]-MNI-1869 in supraclavicular BAT and skeletal muscle was calculated in human subjects (n = 5). ** P = 0.00210 (5 mins), **** P < 0.0001 (15 mins), **** P < 0.0001 (30 mins), **** P < 0.0001 (50 mins) and ** P = 0.00462 (75 mins) using unpaired 2-tailed Student's t tests.
Figure 4BAX peptide array to define interaction-site with DRP1. A) Schematic representation of the peptide array corresponding to BAX secondary structure with boxes indicating BAX α-helices 1-9. BAX sequence was divided in peptides of 15 amino acids (aa) preceded by a biotin head. The last 5 aa of each peptide overlapped with the first 5 aa of the next peptide. B) Graphical representation of the DRP1 binding assay. Biotin-containing BAX peptides were attached to GUVs using biotinylated lipids and streptavidin. Binding between BAX peptides and DRP1-AF488 results in a recruitment of DRP1-AF488 to the GUV membrane indicated by AF488 fluoresce detected at the rim of the GUV. BAX peptide array to define interaction-site with DRP1. C) Representative images of GUVs incubated with DRP1-AF488, streptavidin and the corresponding BAX peptides (#3, #4, #12, #15). Scale bar 10 µm. BAX peptide array to define interaction-site with DRP1. D) Quantification of the relative fluorescence intensity of DRP1-AF488 at the rim of the GUVs for each BAX peptide of n=3 individual experiments (with n=100 vesicles each). Black lines indicate the mean value. Interacting BAX peptides are highlighted in beige. E-F) Protein crosslinking coupled with mass spectrometry of BAX and DRP1 in liposomes. E) BAX/DRP1 crosslinking analysis workflow. After incubation with crosslinking reagents, proteins were digested using trypsin subjected to LC-MS/MS analysis. F) Schematic representation of BAX and DRP1 with detected cross-linked residues connected by dash lines using DSS and EDC cross-linkers as indicated.
Fig.Figure 4(A) Gpr56 is deleted in CKO microglia. RNAscope shows Gpr56 transcripts co-localize with microglia (arrow) in controls, but not in CKO, and is absent in all cell types in the global Gpr56 KO (Gpr56 null). Arrowhead indicates non-microglia cells expressing Gpr56. RNAscope was performed in the prefrontal cortex of P30 mice. Scale bar, 20 µm. (B) Quantification of Gpr56 fluorescence signals in (A). N = 20-50 cells for each. (C) Confocal images of vGlut2 (green) labeling retinal ganglion cell (RGC) presynaptic terminals and Homer1 (red) for post-synapses in the dLGN of CKO and controls at P10. Overlapped vGlut2 and Homer1 are quantified as synapses, indicated by white circles. Arrows pointing to the synapse enlarged in the upper right-hand inset. (D) A time course of dLGN synapse density (vGlut2+/Homer1+) between WT and controls. (E) Representative super-resolution images and 3D-reconstructed images of vGlut2 and Homer1 staining of P8 dLGN. Green objects represent surface rendering of vGlut2+ presynaptic terminals. Red spots are rendered Homer1+ post-synapses. Magenta spots represent Homer1+ post-synapses within a distance of 300nm from the nearest vGlut2+ surface. (F) Quantification of Homer1+ spots adjacent to vGlut2 surface within 100nm, 200nm, and 300nm, respectively. N = 3. (G) Western blot of vGlut2 and Homer1 using microdissected dLGN tissue from P8 mice. (H, I) Quantification of vGlut2 and Homer1 expression in CKOs and controls. N = 3, *p = 0.027. (J) Quantification of synapse density (vGlut2+/Homer1+) in the dLGN of both male and female iCKO mice at P10. N = 3 for male, N = 4 for female. (K) An overview of vGlut1 and Homer1 staining in dLGN at P10. The yellow outline indicates the dLGN core, and the dotted boxes show where synapses are quantified. (L) Representative images of vGlut1+ (green) presynaptic terminals and Homer1+ (red) postsynapses in the dLGN of CKO and controls at P10. Arrows pointing to the synapse enlarged in inset. (M) Quantification of synapse density (vGlut1/homer1) at P10 in the dLGN of CKO mice and controls. N=3 (WT), N=5 (CKO), p = 0.053.
LETM1 is required for mitochondrial translation and respiration.Figure 1 (A) Immunofluorescence analysis of HeLa cells transfected with either a non-target dsRNA (NT) or one of the three siRNAs targeting LETM1 (siR1, siR2 or siR3) and labeled with anti-TOM20 antibody. In siR1 treated cells, the mitochondria formed a 'honeycomb' of swollen distinct organelles; siR3 resulted in giant organelles with a central region distinguished by reduced TOM20; siR2, produced relatively little swelling and the mitochondrial network was generally well preserved. The pronounced swelling induced by siR1 significantly increased circularity (p = 2.32E-58) (ImageJ analysis), siR1 circularity = 0.683 ±0.012 compared with 0.414 ±0.008 for the NT; where 1 = a perfect circle. Over 150 mitochondria were quantified in each cell type; data are means ± SEM. Scale bar represents 12 µm in the main images and 4 µm in offset magnification   (B) 35S labeling of de novo mitochondrial protein synthesis of HeLa cells transfected as in (A). Polypeptide assignments flank the gel images. Coomassie stained gels are used as loading controls and immunoblots indicate the efficiency of LETM1 knockdown   (C) Quantification of the radiolabeled mitochondrial polypeptides in panel (B) and similar gels, expressed relative to protein synthesis of the NT. Data represent the mean ± standard error (SEM) of n=6 independent experiments; 1 or 2 rounds of transfection for siR1 and siR3, but exclusively 2 rounds in the case of siR2  (D) Representative immunoblots for the OXPHOS proteins NDUFB8 and COII of HeLa cells transfected with NT or siLETM1 (siR1, siR2 or siR3). Vinculin and GAPDH are shown as loading controls. The mean relative abundances for respiratory subunits COII and NDUFB8 are shown beneath the blots. Data are expressed as mean ± SEM of n=8 independent experiments   (E) Mitochondrial oxygen consumption rate (OCR) measured using a Seahorse flux analyzer before (basal) and after the addition (maximal) of the uncoupler FCCP, in HeLa cells treated with NT or siLETM1 (siR1 or siR2). Data are means ± SEM of n=5 experiments
Figure 1A, B DNA methylation level of NTN1 (A) and DAPK1 (B) 5' regions (Illumina's HumanMethylation450K Array (HM450) from The Cancer Genome Atlas breast cohort) in paired breast tissues (normal: green circles, tumor: red circles), n = 92, Wilcoxon matched-pairs signed rank test, P = 0.004 and P = 0.0008. C, D NTN1 (C) and DAPK1 (D) gene expression in paired breast tissues (normal: green bars, tumor: red bars, RNAseq from TCGA breast cohort, n = 112 and 114, respectively. E, F Correlation between NTN1 (E) and DAPK1 (F) gene expression and DNA methylation in the breast cancer cohort (TCGA, n = 807). Pearson correlation, P = 6.7.10-5, r = -0.14 for NTN1 (A) and P<10-16, r = -0.32 for DAPK1 (B), respectively.G, H Tumor/Normal DNA methylation ratio of NTN1 (G) and DAPK1 (H) in humanbreasttumors (data extracted from TCGA cohort, paired samples) according to gene expression (downregulated FC ≤ 0.5, down, n = 33, or upregulated FC ≥ 1.3, up, n = 16). P = 3.10-2 and P = 3.10-4 two-sided Mann Whitney test, for NTN1 and DAPK1, respectively.
Figure 6Heatmap of differentially expressed genes obtained from RNAseq analysis of GSC#9 treated for 4 hours with vehicle (DMSO) or MPZ (20 μM), from three biological replicates. Volcano plot of differentially expressed genes in RNAseq analysis of GSC#9, expressed as fold changes between vehicle (DMSO) and MPZ-treated cells. GSEA (gene set enrichment analysis) plot showing enrichment of "Bilanges serum and rapamycin sensitive genes" signature in vehicle (DMSO) versus MPZ-treated triplicates. Table of top differential pathways in DMSO versus MPZ-treated triplicates. Size of each pathway, normalized enrichment scores (NES), p-value and false discovery rate q value (FDR) were indicated. qRT-PCR was performed on total RNA from GSC#9 treated for 4 hours with vehicle (DMSO) or MPZ (20 μM). Histograms showed changes in RNA expression of indicated targets. Data were normalized to two housekeeping genes (ACTB, HPRT1) and are presented as the mean + s.e.m of technical triplicates. Western-blot analysis of LC3B, CSTD and TFEB in total protein lysates from GSC#9 transfected with non-silencing duplexes (sic) or siRNA duplexes targeting TFEB (siTFEB) and treated with vehicle (DMSO) or MPZ (20 μM) for 16 hours. GAPDH served as a loading control. Western-blot analysis of p-ULK1, p-AKT, p-S6, and p-p70S6K in GSC#9 treated for 1 hour with MPZ (20 μM) or rapamycin (RAPA, 50 nM). Total ULK, AKT, S6, and p70S6K served as loading controls. DMSO was used as a vehicle. Western-blot analysis of MALT1, p-AKT, and p-S6 in total protein lysates from GSC#9 transfected with non-silencing duplexes (sic) or MALT1 targeting siRNA duplexes (siMALT1). Total AKT and S6, as well as GAPDH served as loading controls. Western-blot analysis of p-AKT, p-S6, and p-p70S6K in total protein lysates from GSC#9 treated for 1 hour with vehicle (DMSO) or 20 μM of phenothiazine compounds (MPZ, FLU, CHLO, and CYA). Total AKT, total S6 and total p70S6K served as loading controls. Western-blot analysis of p-S6 and FLAG in GSC#9 expressing WT or C464A MALT-FLAG. Total S6 and GAPDH served as loading controls. Confocal analysis of LAMP2 (red) and mTOR (green) staining in GSC#9 treated with vehicle (DMSO) or MPZ (20 μM), Z-VRPR-FMK (75 μM), FLU (20 μM), CHLO (20 μM), and CYA (20 μM). Alternatively, cells were transfected with sic or siMALT1. Nuclei (DAPI) are shown in blue. Arrows point to LAMP2-positive area. Scale bars: 10 μm. Quantification of mTOR colocalization score with LAMP2 is shown. The Coloc2 plug-in from ImageJ was used to measure Mander's tM1 correlation factor in LAMP2-positive ROI, using Costes threshold regression. Data are presented as the mean + s.e.m. on 3 independent experiments. Each dot represents one cell. n>10.
Figure 2A: Inner (IM) and outer (OM) mitochondrial membranes were traced in randomly collected electron micrographs in order to calculate the IM/OM surface area ratio. Multiple micrographs were analyzed per biological replica. B: Abundances of protein complexes were measured by label-free quantitative proteomics. C: Molecular species of CL were quantified by lipidomics. D: The IM protein concentration was calculated by dividing the sum of the abundance ratios (IM complexes/TOM complex) by the surface area ratio (IM/OM). The CL composition was expressed as Euclidean distance from the CL composition in YPD log cells. A linear regression line is drawn.
Transplanted photoreceptors form PhNT processes with host photoreceptors and transfer cytoplasmic and membrane proteins but transfer of mRNA was not detected.Figure 6a, MIP image of wildtype (wt) retina transplanted with P8 Nrl.Gfp+/+ CD73+ MACS-enriched photoreceptors; dashed box indicates ROI subjected to 3D deconvolution and volume reconstruction (right) and shows PhNT-like connection between donor and host photoreceptor at the level of host inner segment. Additional images show 3D segmentation of z = 0 and z = 38 focal planes, and reveal the PhNT; green = GFP, blue = nuclei; Scale bar = 10 µm in MIP and 5 µm volume reconstruction; b & c, assessment of properties of PhNT-like processes between donor and host photoreceptors (n = 19 PhNT-like processes; N = 10 eyes) showing (b) diameter and (c) length; d, MIP image of wt retina transplanted with P8 Nrl.Gfp+/+ x myrRFP/+ photoreceptors; showing wt host ONL photoreceptor labeled with cGFP (green) but not with myrRFP (red); Scale bar = 50µm; e, quantification and statistical analysis of material transfer events following subretinal transplantation of live (cGFP = 3775 ± 804, myrRFP = 436 ± 145) or UV-treated (cGFP = 1.3 ± 2.5, myrRFP = 4.3 ± 5.7) Nrl.Gfp+/+x myr-Rfp+/+ photoreceptors into wt hosts (N = 8 and N = 4 retinae, respectively); One-way ANOVA, parametric, two tail, Tukey's multiple comparisons; Graph shows mean ± S.D. f-h, Assessment of potential for transfer of donor Gfp and Gnat1 mRNA during transplantation using RNAscopeTM. f, Representative MIP images of Gnat1-/- eyes transplanted with Nrl.Gfp+/+ donor cells and processed in situ for Gfp mRNA (red) and Gnat1 mRNA (magenta); blue = nuclei; ROIs indicated in (f) show GFP+ve donor cell mass (CM) and GFP+ve cells within Gnat1-/- host outer nuclear layer (ONL); g & h, quantification of Gfp and Gnat1 mRNA (mean fluorescence intensity per cell), respectively (N = 3 retinae); One-way ANOVA, non-parametric, two tailed analysis showed no significant differences in signal intensity for either Gnat1 or Gfp mRNA between GFP+ve and GFP-ve host photoreceptors; i, Manipulation of actin signalling alters material transfer in vivo: (far left) MIP image showing GFP+ve host photoreceptor (green) expressing Rod α-transducin (red) after transplantation of retinal cells transduced with lenti-CAG-P2A.Gfp (transduction control) into Gnat1-/- recipient; Scale bar = 10 µm; adjacent images show Gnat1-/- eyes transplanted with P2 retinal cells transduced with (left) plenti-CAG-P2A.GFP (green), or (middle) plenti-CAG-RhoA-P2A.GFP (green), or (right) plenti-CAG-ΔΝRac1-P2A.GFP (green); green = GFP, blue = nuclei; Scale bar = 20 µm; j, quantification of the number of GFP+ cells in Gnat1-/- host ONL, (N = 5 retinae per condition); plenti-CAG-P2A.GFP (2328 ± 234), plenti-CAG-RhoA-P2A.GFP (668 ± 481), plenti-CAG-ΔΝRac1-P2A.GFP (547 ± 306); One-way ANOVA, non-parametric, Dunn's multiple comparisons test. Graph shows mean ± SD.
Figure 6Schematic diagram showing the sites of electroencephalography (EEG) and electromyography (EMG) surgery (frontal [Ch1], parietal [Ch2], EEG reference [RefE], trapezius muscle [EMG] and EMG reference [RefM] probes), and examples of EEG and EMG traces during WAKE, NREM, and REM states. Gr, animal ground. Increased WAKE duration and decreased NREM duration during the first three hours of the light-on period in Emx1-Cre;Ptprdfl/fl mice (2.5-4 months). (n = 9 mice [Emx1-cWT] and 9 mice [Emx1-cKO], mean ± SEM, *p < 0.05, **p < 0.01, ns, not significant, two-way RM ANOVA with Holm-Sidak test). Decreased delta power (normalized to total power) in NREM, but not WAKE, oscillations in Emx1-Cre;Ptprdfl/fl mice (2.5-4 months). Note also the normal theta power (normalized to total power) in REM oscillations in Emx1-Cre;Ptprdfl/fl mice. (n = 9 [Emx1-cWT] and 9 [Emx1-cKO], mean ± SEM, *p < 0.05, **p < 0.01, ns, not significant, two-way RM ANOVA with Holm-Sidak test). (D) Increased WAKE duration and decreased NREM duration during the first three hours of the light-on period and decreased REM duration in the first half of the light-on period in Ptprd-meA-/- mice (2.5-4 months). Note also that Ptprd-meA-/- mice also display increased WAKE duration and decreased NREM duration during the light-off period. (n = 8 [Ptprd-meA+/+] and 8 [Ptprd-meA-/-], mean ± SEM, *p < 0.05, **p < 0.01, ***p < 0.001, ns, not significant, two-way RM ANOVA with Holm-Sidak test). Decreased delta power (normalized to total power) in NREM (both light-off and light-on periods) and WAKE (light-on period) oscillations, and decreased theta power in REM (mainly light-on period) oscillations in Ptprd-meA-/- mice (2.5-4 months). (n = 8 [Ptprd-meA+/+] and 8 [Ptprd-meA-/-], mean ± SEM, *p < 0.05, **p < 0.01, ***p < 0.001, ns, not significant, two-way RM ANOVA with Holm-Sidak test).
B7‐H1 and ICOS‐L play a key role in the inhibition of T‐cell response mediated by EBV in pDCs.Figure 6(A) B7−H1 and ICOS−L surface expression was evaluated by flow cytometry in pDCs treated with EBV for 48 h. Three different experiments were performed and representative profiles are shown. (B) pDCs were left untreated (un) or treated for 24 h with EBV alone or in the presence of either an anti‐B7‐H1 or anti‐ICOS‐L blocking Ab, or their isotype control. The proliferative response of cord blood‐derived allogeneic naïve CD4+ T cells was determined by BrdU incorporation on gated lymphocytes and blasts by flow cytometry. Profiles of one representative experiment out of three performed having comparable results are shown. In each panel percentage of BrdU‐FITC+ cells and MFI are reported. (C) Supernatants from the T−cell/pDC co−cultures were harvested and the production of IFN−γ and IL−2 were measured. Data are shown as mean ± SEM of results pooled from three independent experiments.
Figure 3(A) UMAP plot defining cell clusters. Expression of defining markers for each cluster is presented in Appendix Fig. S1a. (B) UMAP plot of Acta2 (encoding αSMA) expression in the fibroblast cluster (left panel). UMAP plot of fibroblast subclusters (right panel). ( (C) Enrichment plot of genes in αSMA C1 (left panel). Violin plots for genes enriched in αSMA C1 (right panels). (D) Enrichment plot of genes in αSMA C2 (left panel). Violin plots for genes enriched in αSMA C2 (right panels). (E) Enrichment plot of genes in αSMA C3 (left panel). Violin plots of enriched genes in the αSMA C3 cluster (right panels). Raw scRNA-seq data are derived from (Haensel et al., 2020, Data ref: Haensel et al 2020). Da
Figure 1A) Single dose AR-42 plasma and tissue pharmacokinetic study. Tumor-free CD2F1 mice were administered a single dose of 10, 20 or 50 mg/kg AR-42 (n=3) and plasma (dashed) and gastrocnemius (solid) tissue were analyzed for AR-42 content at different times using LC-MS/MS analyses according to the Materials and Methods (Mean±SD). B) AR-42 dose-response. Starting six days after C-26 cell injection, animals received vehicle or AR-42 orally at 1, 3, 10 or 20 mg/kg daily or 50 mg/kg every other day for 13 days. Individual animal terminal (Day 18 post-injection) body weights corrected for tumor mass according to the Materials and Methods are compared to tumor-free controls. Groups: 1mg/kg (n=8), 3mg/kg (n=8), 10mg/kg (n=13), 20mg/kg (n=6), 50mg/kg (n=5). Dashed reference line (100%) represents the mean tumor-free control value, solid line represents non-linear fit of dose-response data. Study 1, tumor-bearing male mice receiving GTx-024 (15 mg/kg; n=5), AR-42 (10 mg/kg; n=5 ), Combination (15 mg/kg GTx-024 and 10 mg/kg AR-42; n=5 ) or Vehicle (n=5) and tumor-free mice receiving GTx-024 (15mg/kg; n=6) or Vehicle (n=6) were treated daily by oral gavage for 13 days starting 6 days post-injection of C-26 cells. C): Terminal (Day 18 post-injection) body weights corrected for tumor mass according to the Materials and Methods compared to tumor-free controls (mean±SD). Study 1, tumor-bearing male mice receiving GTx-024 (15 mg/kg; n=5), AR-42 (10 mg/kg; n=5 ), Combination (15 mg/kg GTx-024 and 10 mg/kg AR-42; n=5 ) or Vehicle (n=5) were treated daily by oral gavage for 13 days starting 6 days post-injection of C-26 cells. D) Terminal tumor volumes (mean±SD). Study 1, tumor-bearing male mice receiving GTx-024 (15 mg/kg; n=5), AR-42 (10 mg/kg; n=5 ), Combination (15 mg/kg GTx-024 and 10 mg/kg AR-42; n=5 ) or Vehicle (n=5) and tumor-free mice receiving GTx-024 (15mg/kg; n=6) or Vehicle (n=6) were treated daily by oral gavage for 13 days starting 6 days post-injection of C-26 cells. E) Terminal gastrocnemius (mean±SD) and F) quadriceps muscle mass (mean±SD) compared to tumor-free controls.