ingenol mebutate

Ingenol mebutate, which docks excellently with DDX5, reverses ADAM10-mediated gene expression changes, thereby effectively suppressing compensatory VM formation and metastasis and improving prognosis. Collectively, these findings provide insights into the clinical application of AATs.

This study elucidates that evaluating GS is essential for comprehending the heterogeneity of glioma, which is pivotal for predicting immune cell infiltration (ICI) characterization, prognosis, and personalized immunotherapy regimens. We also explored the glycolysis-related genes ADM and IM to develop a theoretical framework for anti-tumor strategies targeting glycolysis.

P2, N=20, Completed, Centre Hospitalier Universitaire de Nice | Unknown status --> Completed

The main forms of immunotherapy used are imiquimod and, to a lesser extent, intralesional interferon-α (IL-INF-α) and ingenol mebutate (IM). Also, its use as a neoadjuvant therapy before surgery was shown to reduce the final surgical defect size required to confirm negative histologic margins. In conclusion, local immunotherapy is frequently used in clinical practice and experience confirms it to be an excellent option for certain patients.

P2, N=24, Completed, Centre Hospitalier Universitaire de Nice | Unknown status --> Completed

There are reports of successful use of topical imiquimod, photodynamic therapy (PDT) and topical 5-fluorouracil with recurrence when treatment is discontinued...He previously applied topical imiquimod, discontinued due to systemic reaction, ingenol mebutate, 5-fluorouracil, and performed PDT with low benefits...For these reasons, we used tirbanibulin ointment on the area of previous surgery and on the peripheral area (right hemi- frontal), applying it once a day for 2 cycles of 5 days with 14 days of break between the 2 cycles...Tirbanibulin has a selective action against cells that most express microtubules and its action is, ideally, to be considered more effective the greater the number of mitoses. Based on this reasoning, we used tirbanibulin in the treatment of iSCC, not as an alternative to the surgical proposal, which always remains the first-line of therapy, but as an adjuvant approach in a selected patient to reduce the risk of progression, waiting for a possible wide local excision.

Co-exposure of IM and STING inhibitor, H-151, to Panc-1 or MIA PaCa-2 cell lines canceled the growth-inhibitory effects of IM alone. In conclusion, IM may have an efficacy comparable to that of existing pancreatic cancer therapeutic agents on the less drug-sensitive Panc-1 cell line and the immune-related molecule STING plays a role in the mechanism of action of IM.

In addition, CRC cells with higher S100A4 expressions and/or the wild-type p53 gene were more sensitive to ingenol mebutate, and their migration and invasion were inhibited by ingenol mebutate. Therefore, our results suggest the repurposing of ingenol mebutate for treating CRC by targeting S100A4.

In this study, we investigated the effect of PKC agonists PEP005 and prostratin on MDSC expansion, differentiation, and recruitment to the tumor microenvironment...Finally, combination of PKC agonism with agonistic CD40 mAb resulted in a marked reduction in tumor growth with a significant increase in intratumoral activated CD8 T cells and tissue-resident memory CD8 T cells in a syngeneic breast cancer mouse model. In sum, this work proposes a novel promising strategy to simultaneously target MDSCs and promote APC function that may have highly impactful clinical relevance in cancer patients.

Methods Using in vitro, ex vivo, in vivo and adoptive transfer systems, we investigated the effect of PKC agonists PEP005 and prostratin on MDSC expansion, differentiation to APC-like cells and recruitment to the TME...Finally, combination of PKC agonism with agonistic CD40 mAb resulted in a marked reduction in tumor growth while synergistically increased intratumoral activated CD8+ T cells and tissue-resident memory CD8+ T cells. Conclusions In sum, we propose a novel promising strategy to simultaneously target MDSCs and promote APC function that may have potential clinical relevance in cancer patients.

Finally, PEP005 resulted in the activation of proapoptotic PKCδ, and the PKC inhibitor bisindolylmaleimide I reduced apoptosis, caspase-3 processing and ROS production, as well as restored cell viability. In conclusion, PKCδ appeared as a central player in apoptosis regulation in CTCL cells, also suggesting its therapeutic targeting.

Finally, treatment of TNBC-bearing C57BL/6J mice with PKC agonist PEP005 markedly reduced tumor burden by decreasing the frequencies of M-MDSCs in tumor, spleen, and bone marrow while increasing cDC1 frequencies in tumors. These findings propose PKCδ as a novel target in myeloid cells to tip the balance from immune suppression to effective antitumor immunity.