A5015177508- Cancer Treatment and Pharmacology
- Glycosylation and Glycoproteins Research
- Phytochemical Studies and Bioactivities
- HER2/EGFR in Cancer Research
- Chromatography in Natural Products
- Radiomics and Machine Learning in Medical Imaging
- Nanoplatforms for cancer theranostics
- Nanoparticle-Based Drug Delivery
- Angiogenesis and VEGF in Cancer
- Monoclonal and Polyclonal Antibodies Research
- Lung Cancer Research Studies
- Cancer Cells and Metastasis
- Cancer Immunotherapy and Biomarkers
- Flavonoids in Medical Research
- Cell Adhesion Molecules Research
- Bioactive natural compounds
- Cancer, Hypoxia, and Metabolism
- Cancer-related gene regulation
- Natural product bioactivities and synthesis
- Peptidase Inhibition and Analysis
- Colorectal Cancer Treatments and Studies
- Wnt/β-catenin signaling in development and cancer
- Brain Metastases and Treatment
- Gastric Cancer Management and Outcomes
- Caveolin-1 and cellular processes
Eisai (Japan)
2004-2024
Eisai (United Kingdom)
2011
Osaka University
1974-1990
Lenvatinib is an oral inhibitor of multiple receptor tyrosine kinases (RTKs) targeting vascular endothelial growth factor (VEGFR1-3), fibroblast (FGFR1-4), platelet α (PDGFR α), RET and KIT. Antiangiogenesis activity lenvatinib in VEGF- FGF-driven angiogenesis models both vitro vivo was determined. Roles tumor vasculature (microvessel density (MVD) pericyte coverage) as biomarkers for were also examined this study.We evaluated antiangiogenesis against proliferation tube formation HUVECs...
Eribulin mesylate is a synthetic macrocyclic ketone analog of the marine sponge natural product halichondrin B and an inhibitor microtubule dynamics. Some tubulin-binding drugs are known to have antivascular (antiangiogenesis or vascular-disrupting) activities that can target abnormal tumor vessels. Using dynamic contrast-enhanced MRI analyses, here we show eribulin induces remodeling vasculature through novel activity in MX-1 MDA-MB-231 human breast cancer xenograft models. Vascular...
Abstract The Wnt/β-catenin signaling pathway plays crucial roles in embryonic development and the of multiple types cancer, its aberrant activation provides cancer cells with escape mechanisms from immune checkpoint inhibitors. E7386, an orally active selective inhibitor interaction between β-catenin CREB binding protein, which is part pathway, disrupts HEK293 adenomatous polyposis coli (APC)-mutated human gastric ECC10 cells. It also inhibited tumor growth xenograft model suppressed polyp...
We reported previously that an angiogenesis inhibitor, E7820, inhibits in vitro tube formation of human umbilical vein endothelial cell through the suppression integrin alpha2 expression. Here we describe antiangiogenic and antitumor effects E7820 mice discuss feasibility using platelet expression on platelets as a biological marker efficacy E7820. Oral administration significantly inhibited basic fibroblast growth factor-induced Matrigel implants colon WiDr tumor-induced dorsal air sac...
Vascular endothelial growth factor receptor (VEGFR) inhibitors are approved for the treatment of several tumor types; however, some tumors show intrinsic resistance to VEGFR inhibitors, and patients develop acquired these inhibitors. Therefore, a strategy overcome inhibitor is urgently required. Recent reports suggest that activation hepatocyte (HGF) pathway through its cognate receptor, Met, contributes resistance. Here, we explored effect HGF/Met signaling on lenvatinib, inhibitor. In in...
Abstract Eribulin is a microtubule dynamics inhibitor with tumor microenvironment modulation activity such as vascular remodeling activity. Here, we investigated antitumor and immunomodulatory activities of eribulin its liposomal formulation (eribulin-LF) monotherapies or in combination anti–programmed death 1 (PD-1) Ab. The eribulin-LF monotherapy anti–PD-1 Ab was examined P-glycoprotein–knockout 4T1 model. showed stronger immunocompetent mice compared immunodeficient mice, indicating that...
Summary An assay system for fusion activity of envelope particles Sendai virus, reassembled from NP40-solubilized envelopes, was established and conditions the artificial assembly virus with haemolytic activities were investigated. Large (GP1) small (GP2) glycoproteins lipids seemed to be required expression particles. Potential haemolysin associated GP2. A relatively high proportion GP1 formation a activity. When top lipid fraction (Hosaka & Shimizu, 1972a) used reassembly, usually...
Abstract Purpose: E7389-LF is a liposomal formulation of eribulin that contributes to tumor vascular remodeling. The phase II part this Ib/II study assessed the efficacy/safety in combination with nivolumab several disease cohorts; herein, we report results from small cell lung cancer (SCLC) cohort. Experimental Design: Patients unresectable/measurable SCLC and progression first-line platinum-based chemotherapy with/without an immune checkpoint inhibitor (ICI) were enrolled receive 2.1 mg/m2...
Abstract Purpose: E7389-LF is a liposomal formulation of the microtubule dynamics inhibitor eribulin and has shown preliminary efficacy in treatment gastric cancer. Study 120, phase Ib/II open-label study, assessed safety combination with nivolumab, programmed cell death (PD)-1 inhibitor. This report focuses on cancer cohort within expansion phase. Patients Methods: Eligible patients had unresectable, measurable cancer, progression following platinum drug plus fluoropyrimidine (1L),...
Nuclear proteins contain a signal, termed the nuclear transport that specifies their selective into nucleus. Previously we reported antibodies to Asp-Asp-Asp-Glu-Asp (DDDED) inhibited of in vivo. We therefore tried detect cellular receptor signals as protein reacted with both anti-DDDED antibody and signal sequences. Using two steps affinity chromatography, anti-DDDED-Sepharose nucleoplasmin-Sepharose, obtained 69 kDa (p69) from pore fraction showed these characters. This p69 recognized by...
We report the dose-escalation part of a phase I study liposomal eribulin (E7389-LF) in Japanese patients with advanced solid tumors and no alternative standard therapy.
Most non-small-cell lung cancers (NSCLCs) harboring activating mutations in the epidermal growth factor receptor (EGFR) are initially responsive to EGFR tyrosine kinase inhibitors (EGFR-TKIs); however, they invariably develop resistance these drugs. E7820 is an angiogenesis inhibitor that decreases integrin-α2 expression and currently undergoing clinical trials. We investigated whether combination with erlotinib, EGFR-TKI, could overcome EGFR-TKI-resistance NSCLC cell lines A549 (KRAS;...
E7820 is an orally active inhibitor of α(2)-integrin mRNA expression, currently tested in phases I and II. We aimed to evaluate what levels inhibition integrin expression are needed achieve tumor stasis mice, compare this the level achieved humans. Tumor growth was measured mice bearing a pancreatic KP-1 tumor, dosed at 12.5-200 mg/kg over 21 days. In phase study, administered daily for 28 days range 0-200 mg, followed by 7-day washout period. PK-PD models were developed NONMEM....
BackgroundA liposomal formulation of eribulin, E7389-LF, may provide improved pharmacokinetics and allow increased access to tumour tissues. This expansion a phase 1 study assessed the safety efficacy E7389-LF in patients with human epidermal growth factor receptor type 2-negative metastatic breast cancer.MethodsPatients received 2.0 mg/m2 every three weeks. Tumour assessments were conducted six weeks by investigator Response Evaluation Criteria Solid Tumours v1.1. All adverse events...
Abstract Purpose: In the dose-expansion part of this open-label, phase I study, we explored efficacy and safety E7389-LF (liposomal formulation eribulin) in Japanese patients with advanced gastric cancer. Patients Methods: cancer who had been previously treated ≥2 lines chemotherapy received 2.0 mg/m2 every 3 weeks (the determined maximum tolerated dose, primary objective Study 114). Secondary objectives included response rate (ORR), progression-free survival (PFS), safety; exploratory...
Abstract Background E7130 is a novel anticancer agent created from total synthetic study of norhalichondrin B. The authors report the dose‐escalation part first‐in‐human patients with advanced solid tumors (NCT03444701). Methods Japanese ≥20 years age were enrolled. was administered intravenously in two cycles: day 1 21‐day cycle (Q3W) or days and 15 28‐day (Q2W). Doses escalated 270 to 550 μg/m 2 for Q3W group 25–400 Q2W group. primary end point phase safety tolerability as assessed by...
To determine a recommended dose of liposomal eribulin (E7389-LF) in combination with nivolumab patients advanced solid tumors, and to evaluate the safety, efficacy, pharmacokinetics, biomarker impact this regimen.Japanese advanced, nonresectable, or recurrent tumors no existing alternative standard/effective therapy (except monotherapy) were assigned either E7389-LF 1.7 mg/m2 plus 360 mg every 3 weeks, 2.1 1.1 240 2 1.4 weeks. Primary objectives safety/tolerability each cohort phase II...
Abstract Eribulin is a synthetic analog of halichondrin B, which isolated from the marine sponge natural product, as first class microtubule dynamics inhibitors. Its clinical formulation currently approved for advanced breast cancer (BC) and liposarcoma in numerous countries. shows antitumor activity through cell death induction by an antimitotic effect, modulation tumor microenvironment that include vascular remodeling, reversal EMT some preclinical subcutaneous xenograft models. Effects...
Abstract Carcinogenesis is often accelerated by the aberrant activation of components molecules Wnt signaling pathway, especially, APC and beta-catenin are frequently reported to be mutated in various cancers. Therefore, signal pathway thought one attractive therapeutic targets. PRI-724 generated PRISM Pharma a small molecule inhibitor its transcriptional coactivator CREB binding protein (CBP) thereby specific modulating Wnt/beta-catenin intravenous continuous infusion. Here we firstly...
Background/Aim: There is no established standard chemotherapy after administration of the combination endocrine plus CDK4/6 inhibitor therapy for luminal-type breast cancer. We used patient-derived xenograft (PDX) models to determine antitumor activity eribulin and capecitabine inhibitor. Materials Methods: examined fulvestrant, palbociclib, eribulin, in 4 cancer PDX (OD-BRE-0188, -0438, -0450, -0745). In OD-BRE-0438, we determined fulvestrant–palbociclib treatment. also performed...
Background Dynamic contrast‐enhanced magnetic resonance imaging (DCE‐MRI) can provide insight into tumor perfusion. However, a method that quantitatively measure the intra‐tumor distribution of voxel clusters with distinct range K trans and v e values remains insufficiently explored. Hypothesis Two‐dimensional cluster analysis may quantify subregion in human breast cancer xenografts. Study Type Prospective longitudinal study. Animal Model Twenty‐two female athymic nude mice MCF‐7 xenograft,...
A new cytotoxic substance designated as BS-1 was isolated from the autolysate and culture filtrate of Bacillus stearothermophilus UK563. On basis spectral data, structure determined bis(2-hydroxyethyl) trisulfide confirmed by direct comparison with synthetic compound. exhibited potent cytotoxicity against leukemia P388-D1, P388, mastocytoma P815, lymphoma EL4 MOLT4.
<div>AbstractPurpose:<p>E7389-LF is a liposomal formulation of eribulin that contributes to tumor vascular remodeling. The phase II part this Ib/II study assessed the efficacy/safety E7389-LF in combination with nivolumab several disease cohorts; herein, we report results from small cell lung cancer (SCLC) cohort.</p>Experimental Design:<p>Patients unresectable/measurable SCLC and progression first-line platinum-based chemotherapy with/without an immune checkpoint...