Search results for "Cer"

2020

PIK3CA-related overgrowth spectrum is caused by mosaicism mutations in the PIK3CA gene. These mutations, which are also observed in various types of cancer, lead to a constitutive activation of the PI3K/AKT/mTOR pathway, increasing cell proliferation. Heat shock transcription factor 1 (HSF1) is the major stress-responsive transcription factor. Recent findings indicate that AKT phosphorylates and activates HSF1 independently of heat-shock in breast cancer cells. Here, we aimed to investigate the role of HSF1 in PIK3CA-related overgrowth spectrum. We observed a higher rate of proliferation and increased phosphorylation of AKT and p70S6K in mutant fibroblasts than in control cells. We also fou…

Aptamers as smart ligands for nano-carriers targeting

2016

The development of enhanced drug delivery systems is one of the most attractive fields of pharmaceutical sciences, as some of the highly effective chemo/biotherapeutics for cancer treatment can not be administrated due to their high toxicities for normal cells or low stability in physiological media. However, drugs that are currently not administrable will become valuable if specific cell-targeted drug carriers can protect the normal cells from adverse effects and also improve drug pharmacokinetics. Aptamers are attractive and promising biomaterials developed with high affinity and specificity against numerous valuable targets. They could act similar to monoclonal antibodies (mAbs), and off…

FLT3 Ligand as a Molecular Adjuvant for Naked RNA Vaccines

2016

Intranodal immunization with antigen-encoding naked mRNA has proven to be an efficacious and safe approach to induce antitumor immunity. Thanks to its unique characteristics, mRNA can act not only as a source for antigen but also as an adjuvant for activation of the immune system. The search for additional adjuvants that can be combined with mRNA to further improve the potency of the immunization revealed Fms-like tyrosine kinase 3 (FLT3) ligand as a potent candidate. Systemic administration of the dendritic cell-activating FLT3 ligand prior to or along with mRNA immunization-enhanced priming and expansion of antigen-specific CD8(+) T cells in lymphoid organs, T-cell homing into melanoma tu…

NFATc1 releases BCL6-dependent repression of CCR2 agonist expression in peritoneal macrophages fromSaccharomyces cerevisiaeinfected mice

2016

The link between the extensive usage of calcineurin (CN) inhibitors cyclosporin A and tacrolimus (FK506) in transplantation medicine and the increasing rate of opportunistic infections within this segment of patients is alarming. Currently, how peritoneal infections are favored by these drugs, which impair the activity of several signaling pathways including the Ca(++) /CN/NFAT, Ca(++) /CN/cofilin, Ca(++) /CN/BAD, and NF-κB networks, is unknown. Here, we show that Saccharomyces cerevisiae infection of peritoneal resident macrophages triggers the transient nuclear translocation of NFATc1β isoforms, resulting in a coordinated, CN-dependent induction of the Ccl2, Ccl7, and Ccl12 genes, all enc…

Eosinophil depletion suppresses radiation-induced small intestinal fibrosis.

2017

Radiation-induced intestinal fibrosis (RIF) is a serious complication after abdominal radiotherapy for pelvic tumor or peritoneal metastasis. Herein, we show that RIF is mediated by eosinophil interactions with α-smooth muscle actin-positive (α-SMA+) stromal cells. Abdominal irradiation caused RIF especially in the submucosa (SM) of the small intestine, which was associated with the excessive accumulation of eosinophils in both human and mouse. Eosinophil-deficient mice showed markedly ameliorated RIF, suggesting the importance of eosinophils. After abdominal irradiation, chronic crypt cell death caused elevation of extracellular adenosine triphosphate, which in turn activated expression of…

Natural Compounds: Molecular Weapons against Leukemia’s

2017

Nowadays cancer is one of the main reasons of death all over the world and it is estimated that deaths caused by cancer will grow dramatically in the next decades. Even if chemotherapy is the election therapy for solid tumors, as well as leukemias and lymphomas, cancer treatments are in continuous evolution trying to solve the problem of resistance mainly due to low accumulation of the drug in tumor cells (MDR). Natural compounds represent a valid alternative to treat several disease and recently the scientific community focus on these natural compounds and plant metabolites with therapeutic activities and low toxicities compared with synthetic ones. A combination therapy, that join convent…

2020

Immune checkpoint inhibitors (ICPi) have shown their superiority over conventional therapies to treat some cancers. ICPi are effective against immunogenic tumors. However, patients with tumors poorly infiltrated with immune cells do not respond to ICPi. Combining ICPi with other anticancer therapies such as chemotherapy, radiation, or vaccines, which can stimulate the immune system and recruit antitumor T cells into the tumor bed, may be a relevant strategy to increase the proportion of responding patients. Such an approach still raises the following questions: What are the immunological features modulated by immunogenic therapies that can be critical to ensure not only immediate but also l…

2018

Background: Chemotherapy is currently evaluated in order to enhance the efficacy of immune checkpoint blockade (ICB) therapy in colorectal cancer. However, the mechanisms by which these drugs could...

Organization into Higher Ordered Ring Structures Counteracts Membrane Binding of IM30, a Protein Associated with Inner Membranes in Chloroplasts and …

2016

The IM30 (inner membrane-associated protein of 30 kDa), also known as the Vipp1 (vesicle-inducing protein in plastids 1), has a crucial role in thylakoid membrane biogenesis and maintenance. Recent results suggest that the protein binds peripherally to membranes containing negatively charged lipids. However, although IM30 monomers interact and assemble into large oligomeric ring complexes with different numbers of monomers, it is still an open question whether ring formation is crucial for membrane interaction. Here we show that binding of IM30 rings to negatively charged phosphatidylglycerol membrane surfaces results in a higher ordered membrane state, both in the head group and in the inn…

Squalene versus cholesterol: Which is the best nanocarrier for the delivery to cells of the anticancer drug gemcitabine?

2018

Comptes Rendus Chimie - In Press.Proof corrected by the author Available online since jeudi 22 mars 2018