A5021421264- Cancer Genomics and Diagnostics
- Gastric Cancer Management and Outcomes
- Gastrointestinal Tumor Research and Treatment
- Colorectal Cancer Treatments and Studies
- Monoclonal and Polyclonal Antibodies Research
- HER2/EGFR in Cancer Research
- Genomics and Chromatin Dynamics
- Olfactory and Sensory Function Studies
- Neurobiology and Insect Physiology Research
- Biochemical Analysis and Sensing Techniques
- Histone Deacetylase Inhibitors Research
- Genomic variations and chromosomal abnormalities
- Lung Cancer Treatments and Mutations
- Cell Adhesion Molecules Research
- Cancer Mechanisms and Therapy
- Cancer-related gene regulation
- Phagocytosis and Immune Regulation
- Pancreatic and Hepatic Oncology Research
- Metastasis and carcinoma case studies
- Microtubule and mitosis dynamics
- Multiple Myeloma Research and Treatments
- DNA Repair Mechanisms
- RNA modifications and cancer
- Signaling Pathways in Disease
- Advanced Biosensing Techniques and Applications
Daiichi-Sankyo (Japan)
2017-2025
Translational Research Informatics Center (Japan)
2022
Daiichi Sankyo (United States)
2019
Daiichi Sankyo (Germany)
2017
Jackson Laboratory
2012-2016
Genome Institute of Singapore
2011-2014
University Hospital Olomouc
2012
Palacký University Olomouc
2012
Agency for Science, Technology and Research
2011
RIKEN Center for Brain Science
2004
Trastuzumab deruxtecan (T-DXd) showed statistically significant clinical improvement in patients with human epidermal growth factor receptor 2-positive (HER2
The vertebrate olfactory system discriminates a wide variety of odorants by relaying coded information from sensory neurons in the epithelium to cortical areas brain. Recent studies have shown that first step odor discrimination is mediated approximately 1000 distinct receptors, which comprise largest family G-protein-coupled receptors. In present study, we used Ca(2+) imaging and single-cell reverse transcription-PCR techniques identify mouse responding an odorant subsequently clone...
The olfactory system is remarkable in its capacity to discriminate a wide range of odorants through series transduction events initiated receptor neurons. Each neuron expected express only single odorant gene that belongs the G protein coupled family. ligand–receptor interaction, however, has not been clearly characterized. This study demonstrates functional identification receptor(s) for specific odorant(s) from neurons by combination Ca 2+ -imaging and reverse transcription–coupled PCR...
Significance In this study, we provide the first detailed molecular characterization, to our knowledge, of a distinct cancer genomic configuration, tandem duplicator phenotype (TDP), that is significantly enriched in molecularly related triple-negative breast, serous ovarian, and endometrial carcinomas. We show here TDP represents an oncogenic configuration featuring ( i ) genome-wide disruption genes, ii loss cell cycle control DNA damage repair, iii increased sensitivity cisplatin...
Using a long-span, paired-end deep sequencing strategy, we have comprehensively identified cancer genome rearrangements in eight breast genomes. Herein, show that 40%–54% of these structural genomic result different forms fusion transcripts and 44% are potentially translated. We find single segmental tandem duplication spanning several genes is major source the gene both cell lines primary tumors involving adjacent placed reverse-order position by event. Certain other mutations, however,...
Somatic genome rearrangements are thought to play important roles in cancer development. We optimized a long-span paired-end-tag (PET) sequencing approach using 10-Kb genomic DNA inserts study human structural variations (SVs). The use of insert size allows the identification breakpoints within repetitive or homology-containing regions few kilobases and results higher physical coverage compared with small libraries same effort. have applied this comprehensively characterize SVs 15 two...
Currently, the only approved treatments for gastrointestinal stromal tumor (GIST) are tyrosine kinase inhibitors (TKI), which eventually lead to development of secondary resistance mutations in KIT or PDGFRA and disease progression. Herein, we identified G protein-coupled receptor 20 (GPR20) as a novel non-tyrosine target GIST, developed new GPR20 IHC, assessed expression cell lines, patient-derived xenografts, clinical samples from two institutes (United States Japan). We studied stratified...
Single-cell level analysis is powerful tool to assess the heterogeneity of cellular components in tumor microenvironments (TME). In this study, we investigated immune-profiles using single-cell analyses endoscopically- or surgically-resected tumors, and peripheral blood mononuclear cells from gastric cancer patients. Furthermore, technically characterized two distinct platforms analysis; RNA-seq-based (scRNA-seq), mass cytometry-based (CyTOF), both which are broadly embraced technologies....
Abstract The projection neurons in the olfactory bulb (mitral and tufted cells) send axons through lateral tract (LOT) onto several structures of cortex. However, little is known molecular cellular mechanisms underlying establishment functional connectivity from to Here, we investigated developmental process LOT formation by observing expression patterns cell recognition molecules embryonic mice. We immunohistochemically identified a dozen expressed developing some them were localized...
Chromosomal structural variations play an important role in determining the transcriptional landscape of human breast cancers. To assess nature these variations, we analyzed eight tumor samples with a focus on regions gene amplification using mate-pair sequencing long-insert genomic DNA matched transcriptome profiling. We found that tandem duplications appear to be early events evolution, especially genesis amplicons. In detailed reconstruction chromosome 17, large unpaired inversions and...
Abstract Individual glomeruli in the mammalian olfactory bulb presumably represent a single type of odourant receptor. Thus, glomerular sheet provides receptor maps at surface bulb. To understand basic spatial organization sensory maps, we first compared distribution odourant‐induced responses measured by optical imaging intrinsic signals with that detected immunohistochemically expressions Zif268, one immediate early gene products juxtaglomerular cells. In dorsal bulb, clear correlation...
Multiple myeloma ( MM ) is an incurable hematological malignancy caused by accumulation of abnormal clonal plasma cells. Despite the recent development novel therapies, relapse eventually occurs as a result remaining population drug‐resistant stem Side SP cells show cancer cell‐like characteristics in ; thus, targeting these promising strategy to completely cure this malignancy. Herein, we showed that expressed higher levels enhancer zeste homolog EZH 1 and 2 , which encode catalytic...
Abstract Mantle cell lymphoma (MCL) is a rare subtype of non‐Hodgkin's lymphoma, which characterized by overexpression cyclin D1. Although novel drugs, such as ibrutinib, show promising clinical outcomes, relapsed MCL often acquires drug resistance. Therefore, alternative approaches for refractory and are needed. Here, we examined whether inhibitor enhancer zeste homologs 1 2 (EZH1/2), OR‐S1 (a close analog the clinical‐stage compound valemetostat), had an antitumor effect on cells. In...
Structural mutations (SMs) play a major role in cancer development. In some cancers, such as breast and ovarian, DNA double-strand breaks (DSBs) occur more frequently transcribed regions, while other types prostate, there is consistent depletion of breakpoints regions. Despite regularity, little understood about the mechanisms driving these effects. A few works have suggested that protein binding may be relevant, e.g. studies androgen receptor active chromatin specific cell types. We...
Molecular and protein biomarker profiling are key to oncology drug development. Antibody-drug conjugates (ADCs) directly deliver chemotherapeutic agents into tumor cells based on unique cancer cell biomarkers. A pan-cancer tissue microarray (TMA) data set gene panel were validated signature analyses conducted normal tissues refine selection of ADC targets. Correlation mRNA levels, human epidermal growth factor receptor (HER) expression patterns assessed. An EdgeSeq (2862 genes) was used...
CD147 is an immunoglobulin-like receptor that highly expressed in various cancers and involved the growth, metastasis, activation of inflammatory pathways via interactions with functional molecules, such as integrins, CD44, monocarboxylate transporters. Through screening CD147-targeting antibodies antitumor efficacy, we discovered a novel rat monoclonal antibody #147D. This humanized IgG4-formatted antibody, h4#147D, showed potent efficacy xenograft mouse models harboring human PDAC cell...
449 Background: Trastuzumab deruxtecan (T-DXd) is an antibody-drug conjugate (ADC) approved for treatment of HER2-positive GC/gastroesophageal junction adenocarcinoma (GEJA) after chemotherapy (Japan) and advanced/metastatic GC/GEJA a trastuzumab-containing regimen (US/Israel/Singapore). Conventional HER2 immunohistochemistry (IHC) scoring identifies potential responders to trastuzumab but may not be suitable next-generation ADCs capable bystander killing, such as T-DXd [Modi NEJM 2022]. Use...
Abstract More than 85% of GISTs are driven by activating mutations in KIT proto-oncogene receptor tyrosine kinase (KIT) or platelet-derived growth factor alpha (PDGFRA). Currently, the only approved treatments for GIST directed inhibitors (TKIs). However, treatment with TKIs eventually results disease progression most often due to development secondary resistance KIT. In addition, these agents have limited activity PDGFRA mutant and KIT/PDGFRA wild type (WT) as primary therapy. Therefore, it...
Background: Milademetan (DS-3032b) is a small-molecule MDM2 inhibitor that activates p53 and induces apoptosis by disrupting the MDM2-p53 interaction. has demonstrated single-agent antileukemic activity in preclinical clinical studies AML. AZA, hypomethylating agent, used to treat AML myelodysplastic syndromes upregulating epigenetically silenced genes cells. We conducted study of milademetan combination with AZA because both agents modulate gene expression related cell growth or apoptosis....