A5036477513- Cancer Research and Treatments
- Peptidase Inhibition and Analysis
- Liver physiology and pathology
- Virus-based gene therapy research
- Neuroendocrine Tumor Research Advances
- Lung Cancer Treatments and Mutations
- Cancer-related Molecular Pathways
- Adenosine and Purinergic Signaling
- Cancer, Hypoxia, and Metabolism
- Ubiquitin and proteasome pathways
- Advanced biosensing and bioanalysis techniques
- Cancer Cells and Metastasis
- Hepatocellular Carcinoma Treatment and Prognosis
- RNA Interference and Gene Delivery
- Pancreatic and Hepatic Oncology Research
- RNA modifications and cancer
- Multiple Myeloma Research and Treatments
- Lung Cancer Research Studies
- Cancer therapeutics and mechanisms
- bioluminescence and chemiluminescence research
- Chromatin Remodeling and Cancer
- Neuropeptides and Animal Physiology
- Pharmacogenetics and Drug Metabolism
- Lung Cancer Diagnosis and Treatment
- Cancer Mechanisms and Therapy
Merck (Germany)
2014-2024
Merck Serono (Italy)
2015
University of Toronto
2005-2006
Abstract Purpose: The mesenchymal–epithelial transition factor (c-Met) receptor, also known as hepatocyte growth receptor (HGFR), controls morphogenesis, a process that is physiologically required for embryonic development and tissue repair. Aberrant c-Met activation associated with variety of human malignancies including cancers the lung, kidney, stomach, liver, brain. In this study, we investigated properties two novel compounds developed to selectively inhibit in antitumor therapeutic...
Tepotinib is an oral, potent, highly selective MET inhibitor. This first-in-man phase I trial investigated the MTD of tepotinib to determine recommended II dose (RP2D).Patients received orally according one three escalation regimens (R) on a 21-day cycle: R1, 30-400 mg once daily for 14 days; R2, 30-315 3 times/week; or R3, 300-1,400 daily. After two cycles, treatment could continue in patients with stable disease until progression unacceptable toxicity. The primary endpoint was incidence...
The mesenchymal-epithelial transition factor (c-Met) is a receptor tyrosine kinase with hepatocyte growth (HGF) as its only high-affinity ligand. Aberrant activation of c-Met associated many human malignancies, including hepatocellular carcinoma (HCC). We investigated the in vivo antitumor and antimetastatic efficacy inhibitor MSC2156119J (EMD 1214063) patient-derived tumor explants. BALB/c nude mice were inoculated MHCC97H cells or fragments 10 primary liver cancer explants selected...
Proteasomes are broadly expressed key components of the ubiquitin-dependent protein degradation pathway containing catalytically active subunits (β1, β2, and β5). LMP7 (β5i) is a subunit immunoproteasome, an inducible isoform that predominantly in hematopoietic cells. Clinically effective pan-proteasome inhibitors for treatment multiple myeloma (MM) nonselectively target other constitutive proteasome immunoproteasome with comparable potency, which can limit therapeutic applicability these...
Abstract Large multifunctional peptidase 7 (LMP7/β5i/PSMB8) is a proteolytic subunit of the immunoproteasome, which predominantly expressed in normal and malignant hematolymphoid cells, including multiple myeloma, contributes to degradation ubiquitinated proteins. Described herein for first time preclinical profile M3258; an orally bioavailable, potent, reversible highly selective LMP7 inhibitor. M3258 demonstrated strong antitumor efficacy myeloma xenograft models, novel model human bone...
<p>Summary of the significance analysis for survival analyses.</p>
<p>Supplementations with nucleosides and hypoxanthine: (A) Proliferation of GTL-16 EBC-1 cells upon supplementation or hypoxanthine. (B) Apoptosis (caspase-3 activation) in nucleosides, hypoxanthine their combination.</p>
<p>GART and E2F1 mRNA levels following METi combined with IR: of GART (left) (right) (50nM, 24 hr), IR (10 Gy, 1 hr) their combination in GTL-16 EBC-1 cells.</p>
<p>Differential expression analysis of the GTL-16 and EBC-1 transcriptomics data.</p>
<p>Suppementary metabolomics data: (A) Heat map determining top hits of metabolite ions in all cell lines at 24 hrs time-point post METi (|log2FC| > 0.5; adj.<i>P</i> value < 0.01). (B) Differences (dots) abundance METi-treated (24 hrs) and control cells. Statistically significant differences <i>P</i> 0.01) are highlighted dark blue. (C) Enrichment analysis the data for GTL-16 EBC-1 cells after 50 nM hrs, focusing on purine-related pathways.</p>
<p>Differential abundance analysis and ion annotation matches for non-targeted metabolomics measurements.</p>
<p>Supplementations with glutamine, serine, and folic acid: (A) Proliferation of GTL-16 EBC-1 cells upon supplementation serine or acid. (B) Apoptosis (caspase-3 activation) in acid.</p>
<p>Basic statistics of the downloaded TCGA data.</p>
<p>GART protein expression upon MAPK and PI3K targeting: GART levels in untreated GTL-16 EBC-1 cells after (AZD6244) (LY294002) pathways inhibition. ß Actin was used as a loading control.</p>
<p>p4E-BP1 protein levels upon MET inhibition: Whole-cell lysates were subjected to Western blotting using a specific antibody against p4E-BP1 following the treatment either with vehicle or 50nM tepotinib (EMD1214063, shortly EMD) for 4 24h as indicated. blots representative of <i>N</i>=3 independent experiments are shown.</p>
<p>Differential abundance analysis and ion annotation matches for non-targeted metabolomics measurements.</p>
<p>Differential expression analysis of the GTL-16 and EBC-1 transcriptomics data.</p>
<p>Basic statistics of the downloaded TCGA data.</p>
<p>GART protein expression upon MAPK and PI3K targeting: GART levels in untreated GTL-16 EBC-1 cells after (AZD6244) (LY294002) pathways inhibition. ß Actin was used as a loading control.</p>
<p>p4E-BP1 protein levels upon MET inhibition: Whole-cell lysates were subjected to Western blotting using a specific antibody against p4E-BP1 following the treatment either with vehicle or 50nM tepotinib (EMD1214063, shortly EMD) for 4 24h as indicated. blots representative of <i>N</i>=3 independent experiments are shown.</p>
<p>Summary of the significance analysis for survival analyses.</p>
<p>Supplementations with nucleosides and hypoxanthine: (A) Proliferation of GTL-16 EBC-1 cells upon supplementation or hypoxanthine. (B) Apoptosis (caspase-3 activation) in nucleosides, hypoxanthine their combination.</p>