Journal: Journal of Experimental & Clinical Cancer Research : CR

Article Title: Therapeutic impact of Nintedanib with paclitaxel and/or a PD-L1 antibody in preclinical models of orthotopic primary or metastatic triple negative breast cancer

doi: 10.1186/s13046-018-0999-5

Figure Lengend Snippet: Paclitaxel and its combination with nintedanib increased median survival in the advanced metastatic breast cancer LM2–4 model. a ) Kaplan-Meier survival curves and median survival values. Paclitaxel (PTX) significantly increased median survival compared to the control group ( p = 0.033; Log-rank (Mantel Cox) Test, n = 8–10). Combination therapy increased median survival (81 days vs 60.5 days, control group) but it did not reach significance. Treatment started around 40 days after cell implantation. b) Effect of sunitinib alone and when combined with PTX in the advanced metastatic LM2–4 breast cancer model. Kaplan-Meier survival curves and median survival values. Modified from Guerin et al., 2013 . PTX alone increased survival whereas sunitinib alone did not, and adding sunitinib to PTX did not result in increased efficacy

Article Snippet: The EMT-6 (ATCC® CRL-2755TM) mouse breast cancer cell line and the derived variant EMT-6/CDDP -selected in vivo for acquired resistance to cisplatin [ ]-, were cultured in DMEM medium with 5% FBS at 37 °C in 5% CO 2.

Techniques: Control, Modification

Journal: Journal of Experimental & Clinical Cancer Research : CR

Article Title: Therapeutic impact of Nintedanib with paclitaxel and/or a PD-L1 antibody in preclinical models of orthotopic primary or metastatic triple negative breast cancer

doi: 10.1186/s13046-018-0999-5

Figure Lengend Snippet: Improvement of immunotherapy efficacy when treating primary tumors with nintedanib combination therapy . a ) Tumor growth in the primary EMT-6 breast cancer model. Treatment was started when average tumor volume was 120mm 3 , around 7 days after cell implantation. Statistical analysis on day 27. ANOVA followed by Tukey’s Multiple Comparison Test * p < 0.05, ** p < 0.01. Data are presented as means ± SD, n = 6. Region of flat line in the curves means that tumor in remaining mice had regressed, and in the case of mice treated with PD-L1 antibody, tumors grew back. Mice were treated with nintedanib and/or paclitaxel (PTX) for 70 days, and then treatment stopped. b) Tumor growth in the primary EMT-6/CDDP model. Treatment was started when average tumor volume was 120mm 3 , 7 days after cell implantation. Statistical analysis on day 27. Kruskal-Wallis test followed by Dunn’s Multiple Comparison Test, ** p < 0.01. Data are presented as means ± SD, n = 9–12. c-f) Effect of nintedanib, paclitaxel, anti-PD-L1 and the drug combinations on c) Vascularity; d) Proliferation; e) CD8+ tumor infiltrating cells; and f) Level of Necrosis. Histology and immunohistochemistry analyses were performed on tumor samples obtained from mice implanted with EMT-6/CDDP cells. Treatment was started when average tumor volume was 120mm 3 and all mice were sacrificed after 10 days of treatment. The Mann-Whitney test was used for statistical analyses. Data are presented as means ± SD, n = 6–7

Article Snippet: The EMT-6 (ATCC® CRL-2755TM) mouse breast cancer cell line and the derived variant EMT-6/CDDP -selected in vivo for acquired resistance to cisplatin [ ]-, were cultured in DMEM medium with 5% FBS at 37 °C in 5% CO 2.

Techniques: Comparison, Immunohistochemistry, MANN-WHITNEY

Journal: Science Advances

Article Title: Integration of 3D genome topology and local chromatin features uncovers enhancers underlying craniofacial-specific cartilage defects

doi: 10.1126/sciadv.abo3648

Figure Lengend Snippet: ( A ) The PRS region (shaded) was defined by the overlaps among deletions ( , , – ) (red) or translocations ( , ) (blue) detected in multiple PRS patients. SRO, the smallest region of overlap; TBC, translocation breakpoint cluster. ( B ) The 278-kb region in mouse (chr11: 111,555,526 to 111,833,944, mm10) orthologous of the human PRS region is zoomed and highlighted. Sequence conservation between mouse and human is shown. Arrow, the Peak16 enhancer. ( C ) 3D reconstruction of mandibles from E18.5 Peak16 −/− , Peak16 +/− , and wild-type (WT) embryos using MicroCT scans. Scale bars, 500 μm. ( D ) Boxplots summarizing the morphological changes in the mandible in Peak16 deletion embryos. Mandibular body length (2 to 13 and 4 to 9, the numbers correspond to the anatomic landmarks used for quantifying mandibular morphology as indicated in fig. S1B) and coronoid length (7 to 8) remained unchanged in Peak16 −/− embryos ( n = 4) compared to Peak16 +/− ( n = 6) and WT ( n = 2) embryos, while condylar width (12 to 13) showed a significant decrease in Peak16 −/− embryos. ( E ) 3D reconstruction of mandibles from PRS −/− , PRS +/− , and WT mice. Note the visible shortening of the mandible in PRS −/− mice compared to the mandible in WT as indicated by the dashed lines. ( F ) Boxplots summarizing the morphological changes in the mandible in PRS region deletion mice. Homozygous deletion of PRS region (PRS −/− , n = 3) resulted in a significant reduction in mandible length, hypoplasia of coronoid process, and reduced condylar width compared to PRS +/− ( n = 3) and WT ( n = 2). For all boxplots in (D) and (F): center line, median; box limits, upper and lower quartiles; whiskers, 1.5× interquartile range. P values (two-tailed t tests): ns, not significant, * P < 0.05, *** P < 0.001, and **** P < 0.0001.

Article Snippet: Both the Peak16 enhancer deletion (Peak16 −/− ) and PRS region deletion (PRS −/− ) mouse models were generated in C56BL/6 background by Cyagen Biosciences Inc. (Guangzhou, China) using CRISPR-Cas9 technology.

Techniques: Translocation Assay, Sequencing, Two Tailed Test

Journal: Science Advances

Article Title: Integration of 3D genome topology and local chromatin features uncovers enhancers underlying craniofacial-specific cartilage defects

doi: 10.1126/sciadv.abo3648

Figure Lengend Snippet: ( A ) Line graphs summarize the temporal expression changes of Sox9 in facial prominences, limb, and liver during murine embryonic development. The murine transcriptome data are taken from ENCODE. ( B to F ) RT-qPCR quantification of Sox9 transcripts in different tissues and developmental stages. Data are from three independently replicated experiments. * P < 0.05 and **** P < 0.0001. (B) The Peak16 deletion causes moderate down-regulation of Sox9 in E11.5 mandible tissues. (C) The deletion of the entire PRS region results in down-regulation of Sox9 in E10.5 mandible tissues. Both the E10.5 and E11.5 mandibles are composed of largely undifferentiated ectomesenchyme, while the MC has not emerged. (D) The Peak16 deletion does not affect Sox9 expression in E14.5 MC. (E and F) The deletion of the PRS region causes significant down-regulation of Sox9 in E14.5 MC (E) but not in E14.5 FLs (F).

Article Snippet: Both the Peak16 enhancer deletion (Peak16 −/− ) and PRS region deletion (PRS −/− ) mouse models were generated in C56BL/6 background by Cyagen Biosciences Inc. (Guangzhou, China) using CRISPR-Cas9 technology.

Techniques: Expressing, Quantitative RT-PCR