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, After 24 hours of treatment, the medium containing docetaxel was removed; observed that apoptosis and particularly Caspase-3 dependent apoptosis correlated with increased neo-vessel formation and vasculature stabilization, apoptosis (Figure S1G), nor in cell growth (Figure S1H) between both cell lines

, Our results could be in accordance with different studies. Indeed, PKC? was shown to induce stabilization of VEGFA translation without impacting its transcription (42). Moreover, AKT was

, As once cleaved, Caspase-3 translocates into the nucleus, we wondered whether the induction of proangiogenic genes could be due to an unexpected transcriptional function of cleaved

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, Caspase-3-subcutaneous injection of CT-26 cells followed by IP injection of FU (50mg/kg) and irinotecan (40mg/kg) with weekly IP injection of Z-FA-FMK control inhibitor or of Z-DEVD-FMK Caspase-3 RT-PCR analysis of VEGFA expression. Data are presented as mean ± SD. Figure 5: Cleaved Caspase-3 could down-regulate anti-apoptotic genes. A. RNA sequencing analysis of MCF-7 Caspase-3 +/+ downregulated genes with Enrichr NCI-Nature pathway database, (50mg/kg) (FU) and irinotecan (40mg/kg) with or without injections of

+. , RNA sequencing analysis of the 36 genes in common in B with Enrichr NCI-Nature pathway database. D. Fold change of enriched genes in A showing RNA sequencing data of Caspase-3 +/+ and -/-MCF-7 cells. E. Venn diagram of A enriched genes in Caspase-3 +/+ MCF-7 cells and Caspase-3 interacted genes. F. RNA sequencing analysis Caspase-3 non-interacted genes in MCF-7 Caspase-3 +/+ cells with Enrichr ENCODE and ChEA Consensus TFs from ChIP

, Rev: TTCTTTGCAGCTCCTTCGTT), human ?-actin an emission scan to evaluate tumor metabolism after 18F-FDG uptake (30min static acquisition, tumor-centered, ATGGAGGGGAATACAGCCC

, Cell culture supernatants were assayed by ELISA for human VEGFA (Invitrogen), according to the manufacturer's protocol

, Western blot analyses were conducted as described previously [2] with the following primary antibodies: Cleaved Caspase-3, Cleaved Caspase-7, Cleaved Caspase-8, Cleaved Caspase-9, Procaspase-3, Procaspase-6, Procaspase-7

, Caspase-3 -/-MCF-7 cells were transiently transfected with procaspase-3-GFP plasmid for 48 h. Then, cells were treated or not with docetaxel, Fluorescence microscopy

, For transfection experiments, cells were transfected with 2 different siRNA specific for human NF-?B (GGATCCTTCTTTGACTCAT and CCACCTTCATTCTCAACTT), PKC (GCAAGAAGAACAATGGCAA and GCATGAATGTGCACCATAA), Pro-caspase-3 (GGGAAACATTCAGAAACTT and GCACCTGGTTATTATTCTT), Pro-caspase-6 (GCAGATAGAGACAATCTTA and GCGAAGGCAATCACATTTA)

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, Caspase-3. Firefly luciferase assay with various combinations of Caspase-3 small subunit plasmid, siRNA against Caspase-3, -6 or -7 transfection and docetaxel (10 nM) treatment during 24h

S. Figure, Pharmacological inhibition of Caspase-3 blocks VEGFA induction in mouse cells. RT-PCR analysis of VEGFA expression in 4T1 and CT-26 cells treated or not with docetaxel (10 nM) and with Z-FA-FMK control inhibitor or with Z-DEVD-FMK Caspase-3 inhibitor. B. Targeting Caspase-6 and

, Tumor growth in BALB/c mice after subcutaneous injection of CT-26 cells followed by intraperitoneal (IP) injections of 5-fluorouracile (FU) (50 mg/kg) and irinotecan (40mg/kg) with or without weekly injections of Caspase-6 or -7-specific siRNA into the tumor

, Il est maintenant clairement établi que le système immunitaire peut influencer la réponse du cancer au traitement. Cependant, l'influence du microenvironnement tumoral sur les cellules immunitaires n'est pas complètement comprise

. Dans, nous avons montré que le microenvironnement tumoral, en augmentant les événements d'épissage alternatif, induisait l'expression d'une isoforme alternative du facteur de transcription IRF1 dans les cellules Th1. En outre, nous avons également montré, chez la souris comme chez l'homme, que l'isoforme alternative d'IRF1 altère l'activité transcriptionnelle d'IRF1 sur le promoteur de Il12rb1, entraînant une diminution de la sécrétion

, Ainsi, l'expression de l'isoforme courte d'IRF1 augmente au sein du microenvironnement tumoral, et bloquer son apparition pourrait potentialiser l'effet anti-tumoral des cellules Th1