A5074049671- Cancer-related Molecular Pathways
- Growth Hormone and Insulin-like Growth Factors
- Pancreatic function and diabetes
- Ultrasound and Hyperthermia Applications
- Liver physiology and pathology
- Metabolism, Diabetes, and Cancer
- Cancer Research and Treatments
- Biomedical Research and Pathophysiology
- Liver Disease Diagnosis and Treatment
- Infrared Thermography in Medicine
- TGF-β signaling in diseases
- Retinal Diseases and Treatments
- Thermal Regulation in Medicine
- Glaucoma and retinal disorders
- Neonatal Health and Biochemistry
- Endoplasmic Reticulum Stress and Disease
- Liver Diseases and Immunity
- DNA Repair Mechanisms
- Protein Interaction Studies and Fluorescence Analysis
- Cell death mechanisms and regulation
- Angiogenesis and VEGF in Cancer
- Cancer-related gene regulation
- Pancreatitis Pathology and Treatment
- Corneal surgery and disorders
- Regulation of Appetite and Obesity
Rode Kruis-Vlaanderen
2021-2022
Isarna Therapeutics (Germany)
2014-2019
Janssen (Belgium)
2006-2011
Johnson & Johnson (Brazil)
2004-2011
HistoGeneX (Belgium)
2008
Johnson & Johnson (Israel)
2003
Johns Hopkins University
1989-1998
Johns Hopkins Medicine
1989-1998
Inserm
1988-1992
Hôpital Necker-Enfants Malades
1990-1992
The Chk2 kinase is a tumor suppressor and key component of the DNA damage checkpoint response that encompasses cell cycle arrest, apoptosis, repair. It has also been shown to have role in replicative senescence resulting from dysfunctional telomeres. Some these functions are at least partially exerted through activation p53 transcription factor. High-level expression virally transduced A549 human lung carcinoma cells led arrested proliferation, senescence. These were accompanied by various...
Purpose To evaluate the safety and tolerability of intravitreal ISTH0036, an antisense oligonucleotide selectively targeting transforming growth factor beta 2 (TGF-β2), in patients with primary open angle glaucoma (POAG) undergoing trabeculectomy (TE; filtration surgery). Methods In this prospective phase I trial scheduled for TE mitomycin C (MMC) received a single injection ISTH0036 at end surgery escalating total doses 6.75 μg, 22.5 67.5 μg or 225 resulting calculated intraocular...
We investigated the binding properties of type I insulin-like growth factor (IGF) receptor expressed in NIH-3T3 fibroblasts transfected with a human cDNA. Cell surface receptors bound IGF-I KD = 1 nM as predicted. Although recent studies have suggested that and IGF-II bind to near-equal affinity, this system much lower affinity (KD 15-20 nM). When from cells were solubilized immunopurified, however, both 125I-IGF-I 125I-IGF-II purified extremely high relatively similar affinities 8 17 pM...
Xenopus laevis oocytes possess a glucose transport system that is activated 3- to 5-fold by insulin-like growth factor I (Ka = 3 nM) and insulin 200-250 nM), properties suggesting activation mediated an receptor. This increases the Vmax of hexose uptake has little or no effect on Km for deoxyglucose (Km 1-2 mM). Activation hormone requires about 60 min inhibited cytochalasin B but not cycloheximide. The dependence rate concentration exhibits cooperativity with Hill coefficients 1.8 1.4 basal...
Competitive hormone bindingstudies with membrane and partially purified receptors from Xenopus laevis oocytes revealed that the oocyte possesses high affinity (KO = 1-3 nM) binding sites for both insulin growth factors 1 2 (IGF-1 IGF-2), but not insulin.Consistent these findings, IGF-1 activates hexose uptake by a KA (3 identical its KO, while IGF-2 activate values of 50 nM 200-250 nM, respectively, suggesting activation mediated through an receptor.Both receptor &subunit autophosphorylation...
In vivo transfer of wild-type (wt) p53 gene via a recombinant adenovirus has been proposed to induce apoptosis and increase radiosensitivity in several human carcinoma models. the context combining irradiation, we investigated consequences adenoviral-mediated wtp53 on cell cycle head neck squamous line (SCC97) with mutated phenotype. We showed that ectopic expression SCC97 cells resulted prolonged G1 arrest, associated an increased cyclin-dependent kinase inhibitor WAF1/p21 target gene. A...
Abstract JNJ‐26854165 was originally developed as an activator of p53 capable inducing apoptosis in cancer cell lines. In vitro, demonstrated cytotoxic activity. The ALL line panel had a significantly lower median IC 50 (0.85 µM) than the remaining vivo induced significant differences EFS distribution compared to control 18 37 solid tumors and 5 7 evaluable xenografts. Objective responses were observed 4 tumor xenografts, 2 xenografts achieved PR or CR. Responses noted with both mutant...
During the assembly of cell surface receptors, insulin proreceptors are sometimes joined to insulin-like growth factor (IGF) receptor precursors form covalently linked hybrid receptors. To address biological consequences formation, we studied 3T3-L1 cells known undergo a 50-70-fold increase in binding while maintaining nearly constant levels IGF-I during differentiation from preadipocytes into adipocytes. The presence insulin/IGF hybrids adipocytes was demonstrated by immunoprecipitation...
The uptake and processing of glucagon into liver endosomes were studied in vivo by subcellular fractionation. After injection [[125I]iodo-Tyr10]glucagon [[125I]iodo-Tyr13]glucagon to rats, the radioactivity was maximum at 2 min (6% dose/g tissue). On differential centrifugation, homogenate recovered mainly nuclear (N), microsomal (P) supernatant (S) fractions, with maxima 5, 10 40 min, respectively; recovery mitochondrial-lysosomal (ML) fraction did not exceed 6% maximal 20 min....
The major steps in cholera-toxin action, i.e. binding, internalization, generation of A1 peptide and activation adenylate cyclase, were examined isolated hepatocytes. binding toxin involves a single class high-affinity sites (KD congruent to 0.1 nM; Bmax. 10(7) sites/cell). At 37 degrees C, cell-associated is progressively internalized, as judged by the loss its accessibility antibodies against whole toxin, A B subunits (about 50, 75 30% initially bound after 40 min respectively). Two...
The degradation of insulin in isolated liver endosomes and the relationships this process with ATP-dependent endosomal acidification have been studied. Incubation fractions containing 125I-insulin isotonic KCl at 30 degrees C resulted a rapid loss integrity as judged from trichloroacetic acid precipitability, Sephadex G-50 chromatography, immunoreactivity receptor binding ability, maximum pH 5-6 (t1/2: 10, 6 min, respectively). On log/log plot, amount acid-soluble products generated was...
Chez les poissons hébergeant des Cymothoidae (Crustacés, Isopodes, Hématophages), modifications tissulaires sont mises en évidence au niveau du microbiotope parasitaire.
The effect of insulin-like growth factor I (IGF-I) on the activity alcohol dehydrogenase was determined in primary hepatocyte culture from male rats. Continuous exposure hepatocytes to IGF-I (30 nm) resulted increases Days 3–6 culture. increase enzyme preceded by increased mRNA, indicating that at pretranslational level. observed only presence pharmacological concentrations insulin media. Insulin alone had no activity. permissive influence correlated with ability maintain a steady high...
Objective: Thermal treatment (TT), defined as using supra-physiological body temperatures (39–45 C), somewhat resembles fever in terms of temperature range, one the first natural barriers for to fight exposure external pathogens.Methods: Whole-body thermal (WBTT) consists heating up complete a range 39 45 C. Despite recognized therapeutic potential hyperthermia, broad clinical use WBTT has been limited by safety issues related medical devices and procedures used achieve WBTT, particular...
Aim: In oncology, thermal therapy is the application of external heat to fight cancer cells. The goal whole-body treatment (WBTT) raise patient's core temperature 39-42 °C, and represents only modality that can act on both primary tumor distant metastases. However, WBTT carries potential risks for toxicity when applied without accurate thermometry monitoring.Methods: ElmediX has developed a medical device, HyperTherm, deliver long-term controlled (41.5 up 8 h). safety device protocol was...
Purpose: ISARNA Therapeutics is developing highly potent and selective LNA-modified ASO gapmers targeting TGF-β1 TGF-β2 mRNA. In the field of ophthalmology, glaucoma, second leading cause for blindness in US, has been linked to TGF-β activation as a key driver. ISTH0036 14-mer phosphorothioate Locked Nucleic Acid- (LNA) modified antisense oligonucleotide gapmer, sequence mRNA was developed therapeutic intervention ocular diseases. It shown effectively potently downregulate target...
Abstract Transforming growth factor beta (TGF-β represents a family of cytokines, which function as the primary mediators for TGF-β signaling via receptor type II (TβIIR) and both non-canonical canonical downstream pathways. is associated with wide range biological processes in oncology, including tumor cell invasion, migration, angiogenesis, immunosuppression, well regulation stem properties. Hence, optimal preclinical evaluation efficacy antagonists challenging. Isarna Therapeutics has...