A5068779813- HER2/EGFR in Cancer Research
- Monoclonal and Polyclonal Antibodies Research
- Colorectal Cancer Treatments and Studies
- CAR-T cell therapy research
- Gastric Cancer Management and Outcomes
- Cancer Immunotherapy and Biomarkers
- Radiopharmaceutical Chemistry and Applications
- Cancer Cells and Metastasis
- Gastrointestinal Tumor Research and Treatment
- Colorectal and Anal Carcinomas
- Melanoma and MAPK Pathways
- Cancer Treatment and Pharmacology
- PARP inhibition in cancer therapy
- Cell death mechanisms and regulation
- Pancreatic and Hepatic Oncology Research
- Peptidase Inhibition and Analysis
- Cytokine Signaling Pathways and Interactions
- Neuroblastoma Research and Treatments
- Medical Imaging Techniques and Applications
- Phagocytosis and Immune Regulation
- Fibroblast Growth Factor Research
- Estrogen and related hormone effects
- Advanced Breast Cancer Therapies
- Cancer, Stress, Anesthesia, and Immune Response
- Neutropenia and Cancer Infections
National Cancer Center Hospital East
2017-2025
Keio University
2019
Toranomon Hospital
2015-2017
Abstract HER3 is overexpressed in several cancers, including colorectal cancer. Although therapies with anti-HER3 antibodies have been investigated, significant clinical benefits not reported. U3-1402 a novel HER3-antibody–drug conjugate (ADC) composed of the antibody patritumab and topoisomerase I inhibitor, DX-8951 derivative (DXd). The sensitivity DXd was evaluated by growth inhibition assay. antitumor activity murine xenograft model which its effects on cells, range expression levels,...
The programmed death‐1/programmed death‐ligand 1 ( PD ‐L1) pathway is a negative feedback that suppresses the activity of T cells. Previous studies reported high ‐L1 expression on tumor cells TC ) was associated with poor survival in patients colorectal cancer; however, prognostic evaluation these limited because they included at various disease stages. purpose present study to evaluate relationship between status immune microenvironment and clinicopathological features stage III cancer. Two...
In Japan, the social (medical) health‐care system is on way to being developed advance personalized medicine through implementation of cancer genomic medicine, known as “cancer clinical sequencing,” which uses a next‐generation sequencer. However, no Japanese guidance for testing exists. Gene panel can be carried out help determine patient treatment, confirm diagnosis, and evaluate prognostic predictions patients with mainly solid cancers whom standard treatment available. This describes how...
<p>Immune infiltration in tumors at baseline and association with response to T-DXd therapy. <b>A,</b> Tumoral CD8<sup>+</sup> cell densities, as determined using mIHC, responders nonresponders. <b>B, </b><i>CD8A</i> <i>CD8B</i> mRNA expression levels, RNA-seq, CPM, counts per million. <b>C,</b> Relationship between immune densities for cells expressing CD4, CD68, CD20, CD163, CD208, CD1a, mIHC IHC....
<p>Unsupervised hierarchical clustering analysis based on cell densities of evaluated immune cells at baseline. <b>A,</b> Heatmap depicting unsupervised results and characteristics the three observed groups. <b>B, </b><i>ERBB2</i> expression levels in groups obtained from clustering. <b>C,</b> Kaplan–Meier OS PFS curves 1, 2, 3 grouped by cells. CPM, counts per million; ECOG PS, Eastern Cooperative Oncology Group performance status; I/O,...
<p>Tumor-infiltrating immune cell densities at baseline and in response to T-DXd therapy responders nonresponders. <b>A,</b> Tumor-infiltrating CD8<sup>+</sup> T-cell densities, as determined using mIHC. <b>B,</b> Tumoral <i>CD8A</i> <i>CD8B</i> expression, RNA-seq. <b>C,</b> Percentage of cells CD3<sup>+</sup> baseline, FCM. <b>D,</b> Densities eTregs (Fr2)...
<p>Supplementary Figures and Tables.</p>
<div>Abstract<p>Trastuzumab deruxtecan (T-DXd), an anti-HER2 antibody–drug conjugate with a topoisomerase I inhibitor connected by cleavable linker, has been approved for patients HER2-positive gastric or gastroesophageal junction tumors. This biomarker study assessed HER2 expression and immune cell infiltration in relation to the therapeutic response T-DXd. retrospective analysis included samples from treated T-DXd three clinical trials. We performed RNA sequencing multiplex IHC...
<p>Associations between pretreatment HER2 expression levels and therapy response to T-DXd. <b>A, </b><i>ERBB2</i> mRNA levels, as determined using RNA-seq. <b>B,</b> H-score, IHC. CPM, counts per million; CR, complete response; PD, progressive disease; PR, partial SD, stable disease.</p>
TPS847 Background: B7-H3 is an immune checkpoint protein overexpressed in multiple solid tumors with limited expression normal tissues. GSK’227 (HS-20093), a novel B7-H3-targeted ADC, composed of human anti–B7-H3 monoclonal antibody linked to topoisomerase I inhibitor via protease-cleavable linker, and has shown acceptable safety promising antitumor activity patients Asian origin advanced (NCT05276609; NCT05830123). The current study will evaluate the safety, tolerability, efficacy,...
<p>Concentration of TNF-α in the supernatants THP-1 cells.</p>
<p>Pharmacokinetics of eribulin release from TROP2-eribulin and total concentration in the plasma.</p>
<div>Abstract<p>Antibody–drug conjugates (ADC) are a rapidly advancing category of therapeutic agents with notable anticancer efficacy. However, the emergence interstitial lung disease as severe ADC-associated adverse event highlights need to better understand underlying mechanisms. In this study, xenograft model mice tumors expressing different levels trophoblast antigen 2 (TROP2) were generated by subcutaneously transplanting various TROP2-expressing cancer lines. The received...
Antibody-drug conjugates (ADCs) are a rapidly advancing category of therapeutic agents with notable anti-cancer efficacy. However, the emergence interstitial lung disease (ILD) as severe ADC-associated adverse event highlights need to better understand underlying mechanisms. In this study, xenograft model mice tumors expressing different levels trophoblast antigen 2 (TROP2) were generated by subcutaneously transplanting various TROP2-expression cancer lines. The received doses...
Abstract Background Trastuzumab deruxtecan (T-DXd) is an antibody–drug conjugate targeting HER2-positive gastric cancer or gastroesophageal junction (GC/GEJC). Although effective, T-DXd has notable toxicities, including interstitial lung disease (ILD). This study evaluated the efficacy, safety, and prognostic factors associated with for GC/GEJC. Methods A retrospective observational was conducted at our institution by reviewing medical records of patients treated until September 2023....
Abstract Background: B7-homolog 3 protein (B7-H3) is an immune checkpoint overexpressed in many types of solid tumors, but with limited expression normal tissues [1]. GSK5764227 (GSK’227) a novel antibody-drug conjugate (ADC) composed fully human anti-B7-H3 monoclonal antibody linked to topoisomerase I inhibitor via protease-cleavable linker. GSK’227 (also known as HS-20093) has shown acceptable safety and promising antitumor activity Asian patients advanced tumors (NCT05276609;...
Ewing sarcoma is a rare tumor that occurs commonly in the long bones of children or adolescents can also arise soft tissues including extremities, retroperitoneum, chest wall, and rarely liver as primary sites. We report case arising primarily and, to our knowledge, this fourth reported occurring liver. A 27-year-old Japanese woman was admitted with sudden onset right upper abdominal pain. Clinical examination revealed multilocular cystic mass consisting thickened, irregular septa nodal...
Abstract The PI3K-Akt-mTOR (PAM) pathway is implicated in tumor progression many types, including metastatic gastric cancer (GC). initial promise of PAM inhibitors has been unrealized the clinic, presumably due, part, to up-regulation Akt signaling that occurs when inhibited. Here we present DIACC3010 (formerly M2698), an inhibitor two nodes pathway, p70S6K and 1/3, blocks vitro vivo preclinical models GC while providing a mechanism inhibits from subsequent up-regulation. Utilizing cell...
We conducted a first-in-human, dose-escalation study, to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and activity of TAK-931, cell division cycle 7 inhibitor, in Japanese patients with advanced solid tumors.Patients ages ≥20 years received oral TAK-931: once daily for 14 days 21-day cycles (schedule A; from 30 mg); or twice on, off 28-day B; 60 continuous D; 20 2 5 E; 100 mg) cycles.Of 80 enrolled, all had prior systemic treatment 86% stage IV disease. In schedule...
Intratumour heterogeneity frequently leads to drug resistance, which is a major issue in discovery. Drug distribution one of the key factors for elucidating resistance mechanism; however, quantitative and regional measurement challenging. Here, we developed novel ultra-sensitive analytical method applied it HER3-targeting antibody-drug conjugate patritumab deruxtecan (HER3-DXd), aiming explore its payload (DXd) within heterogeneous tissues.The named LDMS-CE-MS, capillary electrophoresis-mass...
Abstract Background: Antibody-drug conjugates (ADCs) are a new class of therapeutics that combine monoclonal antibody with cytotoxic agent (known as their payloads) via synthetic linker. While ADCs one game changer and the fastest growing classes novel clinical benefits recently, interstitial pneumonia (ILD) is problem fatal adverse event. However, mechanism ADC-induced ILD under investigation. Purpose: We clarify ADC-ILD by analyzing released payload distribution in lung using Trophoblast...
611 Background: Programmed death 1 (PD-1)/ PD-L1 pathway is a negative feedback mechanism that suppresses the activity of T cells. Some previous studies showed positive expression on tumor cells (TC) was poor prognostic factor in patients with colorectal cancer; however, recent suggest IC also play important roles to determine prognosis cancer patients. The aim this study investigate association clinical and pathological features TC IC. Methods: We retrospectively reviewed data consecutive...
3568 Background: The programmed death-1 (PD-1)/PD-L1 pathway is a negative feedback mechanism that suppresses the activity of T cells. PD-L1 was expressed on tumor cells (TCs) or tumor-infiltrating immune (ICs) in several malignancies. We previously reported high expression TCs and ICs were associated with poor better prognosis patients stage IIIb colorectal cancer, respectively. whether these findings validated III cancer. Methods: Formalin-fixed paraffin-embedded (FFPE) blocks specimens...