A5077450352- Heat shock proteins research
- Hormonal Regulation and Hypertension
- Immune Cell Function and Interaction
- Cancer Immunotherapy and Biomarkers
- Immunotherapy and Immune Responses
- Lung Cancer Treatments and Mutations
- Endoplasmic Reticulum Stress and Disease
- Lung Cancer Research Studies
- CAR-T cell therapy research
- Colorectal Cancer Treatments and Studies
- Toxin Mechanisms and Immunotoxins
- Esophageal Cancer Research and Treatment
- Radiomics and Machine Learning in Medical Imaging
- PARP inhibition in cancer therapy
- Cancer Genomics and Diagnostics
- Brain Metastases and Treatment
- Peptidase Inhibition and Analysis
- T-cell and B-cell Immunology
- Lung Cancer Diagnosis and Treatment
- Gastric Cancer Management and Outcomes
- Genetic factors in colorectal cancer
- Statistical Methods in Clinical Trials
- Helicobacter pylori-related gastroenterology studies
- Urinary and Genital Oncology Studies
- Chemokine receptors and signaling
National Cancer Center Hospital East
2017-2025
Chiba Cancer Center
2020-2024
National Cancer Centre Japan
2024
Tokyo National Hospital
2017-2018
Kanto Central Hospital
2014
PD-1 blockade exerts antitumor effects by reinvigorating tumor antigen–specific CD8+ T cells. Whereas neoantigens arising from gene alterations in cancer cells comprise critical antigens immunity, a subset of non–small cell lung cancers (NSCLCs) harboring substantial mutation burden (TMB) lack the microenvironment (TME), which results resistance to therapy. To overcome this resistance, clarifying mechanism(s) impairing immunity highly mutated NSCLCs is an urgent issue. Here, we showed that...
Regulatory T (T reg ) cells suppress effective antitumor immunity in tumor-bearing hosts, thereby becoming promising targets cancer immunotherapy. Despite the importance of tumor immunity, little is known about their differentiation process and epigenetic profiles microenvironment (TME). Here, we showed that TME human lung cancers harbored a completely different open chromatin profile compared with CD8 + cells, conventional CD4 TME, peripheral cells. The integrative sequencing analyses...
Abstract Purpose: This is a phase Ib trial of TAS-116, an oral HSP90 inhibitor, plus nivolumab for colorectal cancer and other solid tumors. Patients Methods: Enrolled patients received TAS-116 in dose-finding part to estimate the recommended dose. Additional were enrolled dose-expansion part. monotherapy (orally once daily, 80–160 mg) was administered 2 weeks followed by combination with (intravenously every weeks, 3 mg/kg). The primary endpoint dose-limiting toxicities (DLT). We also...
Abstract Regulatory T (Treg) cells are important negative regulators of immune homeostasis, but in cancers they tone down the anti-tumor response. They distinguished by high expression levels chemokine receptor CCR4, hence their targeting anti-CCR4 monoclonal antibody mogamulizumab holds therapeutic promise. Here we show that despite a significant reduction peripheral effector Treg cells, clinical responses minimal cohort patients with advanced CCR4-negative solid cancer phase Ib study...
<p>Antibodies used for flow cytometry.</p>
<p>Antigen-specific CD8+ T cells are significantly increased after pimitespib treatment. (A–C). Antigen-specific T-cell induction in the presence or absence of pimitespib. Representative flow cytometry staining antigen-specific (left) and summaries frequency (right). For vitro sensitization cells, 1.5–2.0 × 106 were cultured with antigen-presenting pulsed various peptides (Melan-A/MART-1, A; influenza, B; CMV, C) without (1 μM). Seven to ten days later, pre-sensitized stained...
<p>Pimitespib–induced reduction in FOXP3 expression depends on STAT5 degradation MJ cells. (A). Immunoprecipitation of HSP90 and STAT5. cell lysates were incubated with normal rabbit IgG, anti-HSP90 mAb, or anti-STAT5 immunocomplexes purified, separated, blotted. (B, C). The effect STAT5B knockdown expression. siRNA was used for (B). cells after cultured the indicated concentrations pimitespib 48 hours. examined (C). (D). mock transduced to develop an STAT5b overexpression (OE)....
<p>Pimitespib treatment does not significantly alter the infiltration of myeloid cell populations in gastric cancers. (A, B). Representative multiple IHC images T subsets (A), and (B) before pimitespib with or without nivolumab. (C). A summary frequencies CD14+ cells (monocyte/macrophage), HLA-DR+ cells, CD14+CD206+ CD14+HLA-DR+ cells. The data are presented as a total six fields per biopsy specimen from five patients. Scale bars, 50 μm.</p>
<p>Antitumor efficacy of combined treatment with anti–PD-1 mAb and pimitespib is not observed in CD8+ T cell–depleted mice. (A). Representative flow cytometry staining PBMCs from C57BL/6 For CD4+ T-cell depletion, anti-CD4 (0.5 mg/body) or anti-CD8β (0.2 mg/body), respectively, was administered intraperitoneally once weekly. depletion confirmed by cytometry. (B). Antitumor A total 2 × 106 MC-38 cells were injected subcutaneously, the cancer size monitored twice weekly (n = 6). After...
<p>MHC/peptide multimers used for antigen-specific T-cell induction and detection.</p>
<div>Abstract<p>Regulatory T (Treg) cells play key roles in cancer immunity by suppressing a range of antitumor immune responses and contributing to resistance PD-1 blockade therapy. Given their critical self-tolerance, local control immunosuppression Treg cells, such as the tumor microenvironment, has been intensively studied. Inhibition HSP90, chaperone with vital regulating proteostasis impedes progression interrupting oncogenic signaling pathways potentially modulating...
<p>Antibodies Used in RPPA Analysis.</p>
<p>Pimitespib augments the antitumor efficacy of anti–PD-1 mAb. (A–C). Antitumor combined treatment with mAb and pimitespib against CMT-93. A total 2 × 106 CMT-93 cells were inoculated subcutaneously, cancer size was monitored twice weekly (n = 6). The mice randomized, some received intraperitoneal administration (0.5 mg/body) on that day (day 0) and/or oral (14 mg/kg/body) five times from 0. Cancer growth (A for summary B each mouse) PFS (C) are shown. defined as time 0 until large...
<p>A schematic summary of the reduction in Treg cells by pimitespib. HSP90 inhibition pimitespib impairs via STAT5 degradation. The IL-2/STAT5 signaling pathway is essential for development and maintenance (left). STAT5, a client protein HSP90, inhibited treatment, resulting FOXP3 transcription. Decreased expression inhibits development, maintenance, immunosuppressive function (right). cell impairment, therefore, mainly caused pimitespib–induced degradation.</p>
<p>Primary antibodies and associated Opal fluorophore applications used for multiplex immunohistochemistry.</p>
Platinum-based definitive chemoradiotherapy (dCRT) is the standard treatment for patients with unresectable locally advanced esophageal squamous cell carcinoma (ESCC) that invades aorta, vertebral body or trachea; however, complete response rates remain low (11–25%), leading to poor survival. To evaluate additive efficacy of anti-PD-L1 antibody drug atezolizumab, we conducted a phase 2, multicenter, single-arm trial 1 year atezolizumab following dCRT in 40 ESCC recruited from seven Japanese...
Background: Oncologists increasingly rely on clinical genome sequencing to pursue effective, molecularly targeted therapies. This study assesses the validity and utility of artificial intelligence Watson for Genomics (WfG) analyzing results. Methods: identified patients with solid tumors who participated in in-house projects at a single cancer specialty hospital between April 2013 October 2016. Targeted results these patients' tumors, previously analyzed by multidisciplinary specialists...
Crizotinib is a standard treatment for advanced ALK ‐positive non‐small‐cell lung cancer ( NSCLC ). We undertook this study to investigate the pharmacokinetics of crizotinib and clinical pharmacogenomic factors that may increase risk adverse events AE s). defined clinically significant s as grade 4 hematological toxicity, ≥3 non‐hematological any interstitial disease. Eight subjects with scheduled receive 250 mg twice daily were studied. Six patients female two male, most had low body weight...
Aim/Background: Growing number of patients with EGFR activating mutation (EGFR M+) treated EGFR-TKIs (tyrosine kinase inhibitors) suffer from metastases to central nervous system (CNS). This is because the prognosis patient M+ has substantially prolonged by EGFR-TKIs, but efficacy in CNS lesion relatively low. By using Matrix Assisted Laser Desorption/Ionization (MALDI) Mass Spectrometry imaging (MSI) and liquid chromatography-tandem mass spectrometry (LC-MS/MS), we analyzed whether...