A5084006774- Cell Adhesion Molecules Research
- Monoclonal and Polyclonal Antibodies Research
- Angiogenesis and VEGF in Cancer
- Protease and Inhibitor Mechanisms
- S100 Proteins and Annexins
- Chemical Synthesis and Analysis
- Photonic and Optical Devices
- Click Chemistry and Applications
- Bioactive Compounds and Antitumor Agents
- Cancer Mechanisms and Therapy
- Biomarkers in Disease Mechanisms
- Oxidative Organic Chemistry Reactions
- Mechanical and Optical Resonators
- Biochemical and Structural Characterization
- HER2/EGFR in Cancer Research
- Cell death mechanisms and regulation
- Advanced Fiber Optic Sensors
- RNA Interference and Gene Delivery
- Glycosylation and Glycoproteins Research
- Acoustic Wave Resonator Technologies
- Cellular Mechanics and Interactions
- Platelet Disorders and Treatments
- CAR-T cell therapy research
- Synthesis and Catalytic Reactions
- Histone Deacetylase Inhibitors Research
Leitat Technological Center
2010-2023
University of Twente
2019
Institute for Research in Biomedicine
2013
Universitat de Barcelona
2013
Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine
2013
Università degli Studi del Piemonte Orientale “Amedeo Avogadro”
2012
Imperial College London
2012
Merck (Spain)
1995-2011
Merck & Co., Inc., Rahway, NJ, USA (United States)
2006
Corporació Sanitària Parc Taulí
2004
Integrin αvβ3 (vitronectin receptor) has been implicated in human malignant melanoma progression and angiogenesis as a receptor that provides survival signals. However, little is known about the therapeutic potential of antagonists αvβ3. In this report, we characterize activities 2 integrins: specific monoclonal antibody (MAb), 17E6, cyclic RGD peptide blocked cell adhesion induced detachment previously substrate-attached cells vitro. vivo, behaved anti-tumor drugs dose- time-dependent...
ABSTRACT A series of murine monoclonal antibodies were raised against purified human αvβ3 integrin and M21 melanoma cells. Five notable hybridomas identified by ELISA on integrins, the isolated bound αv-chain. These antibodies, 17E6, 20A9, 23G5, 14D9.F8 10G2, recognised extracellular domains integrin, shown to be reactive in FACS, immunoprecipitation, ELISA, fixed cells with M21, M21-L4, UCLA-P3, but not αv-deficient M21-L or M21-L-IIb (M21-L transfected GpIIb integrin). One antibody,...
S100A4, a member of the S100 calcium-binding protein family secreted by tumor and stromal cells, supports tumorigenesis stimulating angiogenesis. We demonstrated that S100A4 synergizes with vascular endothelial growth factor (VEGF), via RAGE receptor, in promoting cell migration increasing KDR expression MMP-9 activity. In vivo overexpression led to significant increase vascularization human melanoma xenograft M21 model. Conversely, when silencing shRNA technology, dramatic decrease...
Despite progresses in diagnosis and treatment, pancreatic cancer continues to have the worst prognosis of all solid malignant tumors. Recent evidences suggest that metastasis-promoting protein S100P stimulates tumor proliferation, survival, invasion metastasis progression through extracellular functions. Moreover, its expression is strongly correlated with poor patients several types although entire molecular mechanism responsible for diverse biological functions not fully understood. We...
The antiapoptotic protein survivin is an attractive target in cancer therapy because it expressed differently tumors and normal tissues potentially required for cells to remain viable. Given that also overexpressed endothelial (ECs) of newly formed blood vessels found tumors, its RNA targeting might compromise EC viability interfere with tumor angiogenesis. We used two antisense strategies against expression, oligonucleotides (aODN) small interfering (siRNA), study ECs the contribution...
ABSTRACT We have shown previously that VUP was the only line out of ten human melanoma lines failed to express vit-ronectin receptor αvβ3, but instead expressed αvβ1. Levels αvβ1 expression were low on parental cells so iterative sorting by FACS, using an anti-αv antibody (13C2), utilised derive sublines with 8-to 10-fold higher amounts cell surface There little dif-ference between (V−) and high (V+) αvβ1-expressing regard adherence collagen type I, IV or laminin substrata. However,...
Whispering gallery mode resonator lasers hold the promise of an ultralow intrinsic limit detection. However, widespread use these devices for biosensing applications has been hindered by complexity and lack robustness proposed configurations. In this work, we demonstrate with integrated microdisk laser. Al2O3doped Yb3+ was utilized because its low optical losses as well emission in range 1020-1050 nm, outside absorption band water. Single-mode laser obtained at a wavelength 1024 nm linewidth...
Concentrations down to 3 nM of the rhS100A4 protein, associated with human tumor development, have been detected in undiluted urine using an integrated sensor based on microring resonators emerging Al 2 O photonic platform.The fabricated microrings were designed for operation C-band (λ = 1565 nm) and exhibited a high-quality factor air 3.2 × 10 5 .The bulk refractive index sensitivity devices was ~100 nm/RIU (for TM polarization) limit detection ~10 -6 RIU.A surface functionalization...
Abstract A novel conjugate between a cyclometalated platinum(II) complex with dual antiangiogenic and antitumor activity cyclic peptide containing the RGD sequence (‐Arg‐Gly‐Asp‐) has been synthesized by combining solid‐ solution‐phase methodologies. Although conjugation rendered non‐cytotoxic compound in all tested tumor cell lines (± α V β 3 5 integrin receptors), of Pt‐c(RGDfK) human umbilical vein endothelial cells at sub‐cytotoxic concentrations opens way to design class angiogenesis...
Without affecting the overall 3D structure, amide-to-ester backbone substitution (or ester scan) exerts a pronounced influence on conformational equilibrium of RGD cyclopeptide cilengitide and its derivatives (see figure; RGD=Arg-Gly-Asp). The appropriate substitution, which stabilized receptor-complementary conformations, improved biological activity this integrin antagonist. Detailed facts importance to specialist readers are published as "Supporting Information". Such documents...
Cilengitide is an RGD-peptide of sequence cyclo[RGDfNMeV] that was developed as a highly active and selective ligand for the αvβ3 αvβ5 integrin receptors. We describe synthesis three analogues this peptide in which N-Me group has been replaced by N-oligoethylene glycol (N-OEG) chains increasing size: namely N-OEG2, N-OEG11, N-OEG23, are respectively composed 2, 11, 23 ethylene oxide monomer units. The different N-OEG cyclopeptides original were compared with respect to lipophilicity...
Antibody-Drug Conjugates (ADCs) have been shown to produce clinical benefit in cancer patient thanks their ability target highly cytotoxic small molecules tumor cells. However, the development of these complex faces significant challenges due need combine a large biologic drug with molecule generate desired bioconjugate. We describe here use protein ligation methodology, based on native chemical reaction site-specific Conjugates, which does not require incorporation unnatural modifications...
A robust synthetic strategy for the introduction of N-(4-azidobutyl) linker into peptides using standard SPPS techniques is described. Based on example Cilengitide it shown that group exerts similar conformational restraints as a backbone N-Me and allows conjugation desired molecule either via click chemistry or—after azide reduction—via acylation or reductive alkylation.
Polythiazole amino acids clasp linear peptides to generate cyclic derivatives, however, the resulting species are not merely stapled but bear a complex heterocyclic moiety displaying its intrinsic set of interactions. As proof concept, bisthiazole has been grafted onto an RGD sequence deliver new cilengitide analogue with improved integrin selectivity and remarkable in vivo antiangiogenic activity.