Le pronostic sombre de l'adenocarcinome pancreatique est principalement du a la resistance ra... more Le pronostic sombre de l'adenocarcinome pancreatique est principalement du a la resistance rapidement acquise a tous les traitements conventionnels. Malgre les mecanismes de resistance specifiques aux medicaments, aucun n’explique comment ces cellules resistent a tous types de stress induit par tous types de traitements anticancereux. L'activation des voies de reponse au stress repose sur les modifications post-traductionnelles (PTM) des proteines impliquees. Parmi toutes les PTMs, celles mediees par la famille de proteines ubiquitine jouent un role central dans le processus. Notre objectif etait d'identifier les alterations de l'ubiquitination, de la neddylation et de la sumoylation associees au phenotype multi-resistant et de demontrer leur implication dans la survie des cellules cancereuse pancreatique en cours de traitement. Cette approche a mis en evidence une modification de la sumoylation de la proteine PML (Promyelocytic leukemia) associee a la resistance a l...
The capacity of cancer to adapt to treatment and evolve is a major limitation for targeted therap... more The capacity of cancer to adapt to treatment and evolve is a major limitation for targeted therapies. While the role of new acquired mutations is well-established, recent findings indicate that resistance can also arise from subpopulations of tolerant/persister cells that survive in the presence of the treatment. Different processes contribute to the emergence of these cells, including pathway rebound through the release of negative feedback loops, transcriptional rewiring mediated by chromatin remodeling and autocrine/paracrine communication among tumor cells and within the tumor microenvironment. In this review, we discuss the non-genetic mechanisms that eventually result in cancer resistance to targeted therapies, with a special focus on those involving changes in gene expression.
e14035 Background: The immune response to melanoma has been shown to be locally affected by prese... more e14035 Background: The immune response to melanoma has been shown to be locally affected by presence of tumor-infiltrating lymphocytes (TILs), generally divided into brisk (infiltrating the entire base of the invasive tumor), non-brisk (infiltrating only focally) and absent. Several studies showed that greater presence of TILs, especially brisk, in primary melanoma is associated with a better prognosis and a higher survival rate. Since recent studies revealed an association between PD-1/PD-L1 expression levels and tumor response, the aim of our study was to investigate the correlation between plasma PD-1 and presence/absence/class of TILs in metastatic melanoma patients. Methods: The plasma PD-1 levels were analyzed in 28 patients with metastatic melanoma using a specific ELISA assay. The characterization of TILs in tumor tissue was performed by immunohistochemistry. Statistical analysis was assessed using t-Student and ANOVA tests. Survival curves were estimated by using the Kaplan...
Background: The immune response in melanoma patients is locally affected by presence of tumor-inf... more Background: The immune response in melanoma patients is locally affected by presence of tumor-infiltrating lymphocytes (TILs), generally divided into brisk, nonbrisk, and absent. Several studies have shown that a greater presence of TILs, especially brisk, in primary melanoma is associated with a better prognosis and higher survival rate. Patients and Methods: We investigated by enzyme-linked immunosorbent assay (ELISA) the correlation between PD-1 levels in plasma and the presence/absence of TILs in 28 patients with metastatic melanoma. Results: Low plasma PD-1 levels were correlated with brisk TILs in primary melanoma, whereas intermediate values correlated with the nonbrisk TILs, and high PD-1 levels with absent TILs. Although the low number of samples did not allow us to obtain a statistically significant correlation between the plasma PD-1 levels and the patients’ overall survival depending on the absence/presence of TILs, the median survival of patients having brisk type TILs ...
Le pronostic sombre de l'adenocarcinome pancreatique est principalement du a la resistance ra... more Le pronostic sombre de l'adenocarcinome pancreatique est principalement du a la resistance rapidement acquise a tous les traitements conventionnels. Malgre les mecanismes de resistance specifiques aux medicaments, aucun n’explique comment ces cellules resistent a tous types de stress induit par tous types de traitements anticancereux. L'activation des voies de reponse au stress repose sur les modifications post-traductionnelles (PTM) des proteines impliquees. Parmi toutes les PTMs, celles mediees par la famille de proteines ubiquitine jouent un role central dans le processus. Notre objectif etait d'identifier les alterations de l'ubiquitination, de la neddylation et de la sumoylation associees au phenotype multi-resistant et de demontrer leur implication dans la survie des cellules cancereuse pancreatique en cours de traitement. Cette approche a mis en evidence une modification de la sumoylation de la proteine PML (Promyelocytic leukemia) associee a la resistance a l...
The capacity of cancer to adapt to treatment and evolve is a major limitation for targeted therap... more The capacity of cancer to adapt to treatment and evolve is a major limitation for targeted therapies. While the role of new acquired mutations is well-established, recent findings indicate that resistance can also arise from subpopulations of tolerant/persister cells that survive in the presence of the treatment. Different processes contribute to the emergence of these cells, including pathway rebound through the release of negative feedback loops, transcriptional rewiring mediated by chromatin remodeling and autocrine/paracrine communication among tumor cells and within the tumor microenvironment. In this review, we discuss the non-genetic mechanisms that eventually result in cancer resistance to targeted therapies, with a special focus on those involving changes in gene expression.
e14035 Background: The immune response to melanoma has been shown to be locally affected by prese... more e14035 Background: The immune response to melanoma has been shown to be locally affected by presence of tumor-infiltrating lymphocytes (TILs), generally divided into brisk (infiltrating the entire base of the invasive tumor), non-brisk (infiltrating only focally) and absent. Several studies showed that greater presence of TILs, especially brisk, in primary melanoma is associated with a better prognosis and a higher survival rate. Since recent studies revealed an association between PD-1/PD-L1 expression levels and tumor response, the aim of our study was to investigate the correlation between plasma PD-1 and presence/absence/class of TILs in metastatic melanoma patients. Methods: The plasma PD-1 levels were analyzed in 28 patients with metastatic melanoma using a specific ELISA assay. The characterization of TILs in tumor tissue was performed by immunohistochemistry. Statistical analysis was assessed using t-Student and ANOVA tests. Survival curves were estimated by using the Kaplan...
Background: The immune response in melanoma patients is locally affected by presence of tumor-inf... more Background: The immune response in melanoma patients is locally affected by presence of tumor-infiltrating lymphocytes (TILs), generally divided into brisk, nonbrisk, and absent. Several studies have shown that a greater presence of TILs, especially brisk, in primary melanoma is associated with a better prognosis and higher survival rate. Patients and Methods: We investigated by enzyme-linked immunosorbent assay (ELISA) the correlation between PD-1 levels in plasma and the presence/absence of TILs in 28 patients with metastatic melanoma. Results: Low plasma PD-1 levels were correlated with brisk TILs in primary melanoma, whereas intermediate values correlated with the nonbrisk TILs, and high PD-1 levels with absent TILs. Although the low number of samples did not allow us to obtain a statistically significant correlation between the plasma PD-1 levels and the patients’ overall survival depending on the absence/presence of TILs, the median survival of patients having brisk type TILs ...
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Papers by Mirna Swayden