A5056184964- Polyamine Metabolism and Applications
- Amino Acid Enzymes and Metabolism
- Axon Guidance and Neuronal Signaling
- Chemical Synthesis and Analysis
- Microtubule and mitosis dynamics
- Cannabis and Cannabinoid Research
- Cancer-related Molecular Pathways
- Hedgehog Signaling Pathway Studies
- Biopolymer Synthesis and Applications
- Epigenetics and DNA Methylation
- Cancer therapeutics and mechanisms
- Boron Compounds in Chemistry
- Monoclonal and Polyclonal Antibodies Research
- Cancer Research and Treatments
- Ubiquitin and proteasome pathways
- Synthesis and Biological Evaluation
- Microbial Natural Products and Biosynthesis
- DNA and Nucleic Acid Chemistry
- Organoboron and organosilicon chemistry
- Luminescence and Fluorescent Materials
- Protein Kinase Regulation and GTPase Signaling
- Cell death mechanisms and regulation
- Angiogenesis and VEGF in Cancer
- Hippo pathway signaling and YAP/TAZ
- Blood properties and coagulation
Université Claude Bernard Lyon 1
2009-2025
Centre de Recherche en Cancérologie de Lyon
2014-2025
Centre National de la Recherche Scientifique
2013-2024
Centre Léon Bérard
2013-2024
Inserm
2013-2024
Laboratoire de Vectorologie et Thérapeutiques Anticancéreuses
1998-2018
Université Européenne de Bretagne
2010
Institut de génétique et de développement de Rennes
2010
Université de Rennes
1998-2008
University of Central Florida
2003-2008
Cyclin‐dependent kinases (cdk) play an essential role in the intracellular control of cell division cycle (cdc). These and their regulators are frequently deregulated human tumours. Enzymatic screening has recently led to discovery specific inhibitors cyclin‐dependent kinases, such as butyrolactone I, flavopiridol purine olomoucine. Among a series C2, N 6 , N9‐substituted ade‐nines tested on purified cdc2/cylin B, 2‐(1‐ethyl‐2‐hydroxyethylamino)‐6‐benzylamino‐9‐isopropylpu‐rine (roscovitine)...
Netrins, a family of laminin-related molecules, have been proposed to act as guidance cues either during nervous system development or the establishment vascular system. This was clearly demonstrated for netrin-1 via its interaction with receptors DCC and UNC5s. However, mainly based on shared homologies netrin-1, netrin-4 also play role in neuronal outgrowth developmental/pathological angiogenesis interactions receptors. Here, we present high-resolution structure netrin-4, which shows...
The serine/threonine protein kinase CK2, a tetramer composed of regulatory dimer (CK2β2) bound to two catalytic subunits CK2α, is well‐established therapeutic target for various pathologies, including cancer and viral infections. Several types CK2 inhibitors have been developed, that bind the ATP‐site, bivalent occupy both CK2α ATP‐site αD pocket, CK2α/CK2β interface. Interestingly, inhibitor AB668 shares similar chemical structure with interface CCH507. In this study, we designed analogs...
Polyamines (putrescine, spermidine, and spermine) are essential for growth survival of all cells. When polyamine biosynthesis is inhibited, there up-regulation import. The mammalian transport system unknown. We have previously shown that the heparan sulfate (HS) side chains recycling glypican-1 (Gpc-1) can sequester spermine, intracellular depletion increases number NO-sensitive N-unsubstituted glucosamines in HS, NO-dependent cleavage HS at these sites required spermine uptake. NO derived...
Chronic inflammation and cancer are intimately associated. This is particularly true for inflammatory bowel diseases (IBD), such as ulcerative colitis Crohn's disease, which show a major increased risk colorectal cancer. While the understanding of molecular pathogenesis IBD has recently improved, mechanisms that link these chronic states to development in large part unknown. One NF-κB pathway activation turn may contribute tumor formation by providing anti-apoptotic survival signals...
Several N1-substituted polyamines containing various spacer units between nitrogen centers were synthesized as their respective HCl salts. The N1-substituents included benzyl, naphthalen-1-ylmethyl, anthracen-9-ylmethyl, and pyren-1-ylmethyl. polyamine ranged from generic (4,4-triamine, 4,3-triamine, diaminooctane) spacers to more exotic [2-(ethoxy)ethanoxy-containing diamine, hydroxylated cyclohexylene-containing triamine] spacers. Two control compounds also evaluated:...
The polyamine transport system (PTS) is an energy-dependent machinery frequently overactivated in cancer cells with a high demand for polyamines. We have exploited the PTS to selectively deliver polyamine-containing drug cells. F14512 combines epipodophyllotoxin core-targeting topoisomerase II spermine moiety introduced as cell delivery vector. tail supports three complementary functions: (a) facilitate formulation of water-soluble compound, (b) increase DNA binding reinforce inhibition, and...
Abstract The Aurora kinases are involved in the regulation of cell cycle progression, and alterations their expression have been shown to associate with malignant transformation. In present study, we demonstrated that human thyrocytes express all 3 (A, B C) at both protein mRNA level this is cycle‐regulated. An increase was found, respect normal (HTU5), lines derived from follicular (FTC‐133), papillary (B‐CPAP) anaplastic (8305C) thyroid carcinomas, but not cells a adenoma (HTU42). These...
Tropomyosin-related kinase receptor C (TrkC) is a neurotrophin with tyrosine activity that was expected to be oncogenic. However, it has several characteristics of tumor suppressor: its expression in tumors often been associated good prognosis; and recently demonstrated dependence receptor, transducing different positive signals the presence ligand but inducing apoptosis absence ligand. Here we show TrkC neurotrophin-3 (NT-3) upregulated large fraction aggressive human neuroblastomas (NBs)...
CDON is a novel Sonic Hedgehog (SHH) dependence receptor and targeting the SHH-CDON interaction could represent an alternative therapeutic strategy for patients suffering from tumors that express high SHH levels.
Abstract Targeted radionuclide therapy is a revolutionary tool for the treatment of highly spread metastatic cancers. Most current approaches rely on use vectors to deliver radionuclides tumor cells, targeting membrane‐bound cancer‐specific moieties. Here, we report embryonic navigation cue netrin‐1 as an unanticipated target vectorized radiotherapy. While netrin‐1, known be re‐expressed in tumoral cells promote cancer progression, usually characterized diffusible ligand, demonstrate here...
An efficient modular synthesis of N1-substituted triamines containing different tether lengths between nitrogen centers was developed. A series N1-(9-anthracenylmethyl)triamines were evaluated for biological activity in L1210 (murine leukemia), α-difluoromethylornithine (DFMO)-treated L1210, Chinese hamster ovary (CHO), and CHO-MG cell lines. All 8 had increased potency DFMO-treated cells. The 4,4- 5,4-triamine systems the highest affinity polyamine transporter (PAT) with Ki values 1.8 1.7...
A series of nine N1-(9-anthracenylmethyl)tetraamines (e.g., Ant-4,4,4-tetraamine) were synthesized and evaluated for cytotoxicity in L1210, α-difluoromethylornithine (DFMO)-treated Chinese hamster ovary (CHO), CHO-MG cell lines. Surprisingly, the 3,3,4- 3,4,3-tetraamine motifs had same or decreased DFMO-treated L1210 cells, whereas rest tetraamine systems usually more cytotoxic gave lower IC50 values this treated line. The most sensitive derivatives to DFMO treatment Ant-4,4,3-...
Polyamines are believed to be potent vectors for the selective delivery of chemotherapeutic agents into cancer cells. In this paper, we report effect spermine conjugation on cytotoxic and transport properties acridine. Six derivatives, composed a chain attached at its N1 position an acridine via aliphatic chain, were synthesized. The linker, comprised 3−5 methylene units, was connected position-9 heterocycle through either amide (amidoacridines 8−10) or amine (aminoacridines 11−13) linkage....
Abstract Notch signalling is a causal determinant of cancer and efforts have been made to develop targeted therapies inhibit the so-called canonical pathway. Here we describe an unexpected pro-apoptotic role Notch3 in regulating tumour angiogenesis independently The ligand Jagged-1 upregulated fraction human our data support view that Jagged-1, produced by cells, inhibiting apoptosis induced aberrant expression vasculature. We thus present as dependence receptor inducing endothelial cell...
The navigation cue netrin-1 is well-documented for its key role in cancer development and represents a promising therapeutic target currently under clinical investigation. Phase 1 2 trials are ongoing with NP137, humanized monoclonal antibody against netrin-1. Interestingly, the epitope recognized by NP137 shares 90% homology counterpart netrin-3, closest member to humans, which little known field of cancer. Here, we unveiled that netrin-3 appears be expressed specifically human...
Several N(1)-arylalkylpolyamines containing various aromatic ring systems were synthesized as their respective HCl salts. The N(1)-substituents evaluated ranged in size from N(1)-benzyl, N(1)-naphthalen-1-ylmethyl, N(1)-2-(naphthalen-1-yl)ethyl, N(1)-3-(naphthalen-1-yl)propyl, N(1)-anthracen-9-ylmethyl, N(1)-2-(anthracen-9-yl)ethyl, N(1)-3-(anthracen-9-yl)propyl, and pyren-1-ylmethyl. polyamine architecture was also altered diamine to triamine tetraamine systems. Biological activities L1210...
Anaplastic thyroid cancers (ATC) are aggressive tumors, which exhibit cell cycle misregulations leading to uncontrolled cellular proliferation and genomic instability. They fail respond chemotherapeutic agents radiation therapy, most patients die within a few months of diagnosis. In the present study, we evaluated in vitro effects on ATC cells VX-680, an inhibitor Aurora serine/threonine kinases involved regulation multiple aspects chromosome segregation cytokinesis. The VX-680...