Publications by authors named "Shigehiro Yagishita"

Patient-derived xenografts (PDX) and organoids (PDO) are widely used to model cancer and predict treatment response in matched patients. However, their predictive accuracy has not been systematically studied nor compared. We conducted a systematic review and meta-analysis of studies using PDX or PDO from solid tumors treated with identical anti-cancer agents as the matched patient, identifying 411 patient-model pairs (267 PDX, 144 PDO).

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Unlabelled: Retroperitoneal sarcoma (RPS) is a biologically heterogeneous tumor and rare malignant mesenchymal soft-tissue neoplasm. Although the 5-year overall survival rate for RPS is approximately 60%-70%, it is quite low for unresectable tumors. Surgery is a standard treatment for RPS.

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Endometrial cancer (EC) represents a significant health burden globally, particularly in postmenopausal women. Current treatment options for advanced-stage EC remain limited, emphasizing the need for novel therapeutic strategies. This study aimed to investigate farletuzumab ecteribulin (FZEC), an antibody-drug conjugate (ADC) targeting folate receptor alpha (FRα), as a potential new therapeutic agent for EC.

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Background: High-grade endometrial cancer (EC) has a poor prognosis, but molecular classification-based treatments present new therapeutic opportunities. Antibody-drug conjugates (ADC) emerge as promising tools, yet a deeper understanding of antigen dynamics, optimal therapeutic sequencing, and resistance mechanisms is essential. This study investigates the utility of patient-derived xenograft (PDX) models for EC as preclinical platforms, evaluating molecular subtypes and the ADC targets expression of patient and PDX tumors.

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Background: In EGFR-mutated lung adenocarcinoma (EGFRm LUAD), EGFR mutations do not necessarily result in increased EGFR expression (EGFR-exp), which differs among patients. However, the factors influencing EGFR-exp and the impact of EGFR-exp on tumor characteristics in patients with EGFRm LUAD remain unclear.

Patients And Methods: Whole-exome and RNA sequencing were performed for patients with early- and advanced-stage EGFRm LUAD.

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Background: Asthma involves variable airflow limitation and persistent airway inflammation. Eosinophilic asthma, characterized by cytokine-mediated type 2 inflammation, is generally treated with inhaled corticosteroids. However, patients with severe asthma may require biologics, such as mepolizumab, which targets IL-5 and can manage uncontrolled eosinophilic asthma.

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Background: Human epidermal growth factor receptor 3 (HER3), a tyrosine kinase belonging to the HER family, is a known target for cancer therapy; recently, an anti-HER3 antibody-drug conjugate (ADC) is developing. To understand HER3 expression in epithelial ovarian cancer (EOC), this study was conducted.

Methods: We investigated the expression of HER3 in 202 patients with EOC using immunohistochemistry (IHC), and the association between HER3 expression, clinicopathological features, prognosis, and treatment timing.

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Chemoradiotherapy (CRT) followed by durvalumab is standard for unresectable locally advanced non-small-cell lung cancer (LA-NSCLC). This study assesses how CRT alters the T-cell receptor (TCR) repertoire in CD8 + PD-1 + T-cells and its impact on clinical outcomes. This prospective study, conducted from November 2019 to May 2021 at three institutions in Japan, evaluated the diversity of TCR repertoire (DE50) in PD-1 + CD8 + T-cells and CD8 + T-cell phenotypes in peripheral blood before and after CRT.

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KRAS inhibitors sotorasib and adagrasib have been approved for the treatment of KRAS-mutant non-small cell lung cancer (NSCLC). However, the efficacy of single-agent treatments is limited, presumably due to multiple resistance mechanisms. To overcome these therapeutic limitations, combination strategies that potentiate the antitumor efficacy of KRAS inhibitors must be developed.

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Article Synopsis
  • Patient-derived xenograft (PDX) models involve transplanting human tumor tissues into immunocompromised mice, and are considered reliable models for studying cancer due to their accurate representation of real tumors.
  • There are significant ethical concerns surrounding PDX models, including the need to respect the dignity of human tissues, prevent commercialization of human parts, and ensure adherence to animal ethics.
  • The study outlines four essential ethical considerations and advocates for the development of governance policies to ensure that PDX models are used responsibly in research, complying with both national and international regulations.
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  • This study analyzed pharmacokinetic (PK) data for atezolizumab, an immunotherapy drug, in Japanese patients with non-small cell lung cancer (NSCLC), focusing on a dosing regimen of 1200 mg every three weeks.
  • Researchers evaluated data from 262 patients, measuring plasma drug levels before the third treatment cycle and examining how these levels correlated with treatment effectiveness and the occurrence of adverse events (AEs).
  • Findings indicated that lower plasma levels of atezolizumab were linked to shorter overall survival, while higher drug concentrations were associated with increased AEs, suggesting the importance of monitoring PK levels for better treatment outcomes.
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Pembrolizumab is a major treatment for recurrent or advanced non-small-cell lung cancer (NSCLC). However, data on its use and pharmacokinetics (PK) in older patients are limited. This open-label, multicenter, observational study evaluated real-world data on the safety, efficacy, and PK of pembrolizumab in older patients with NSCLC.

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Despite widespread adoption of tissue clearing techniques in recent years, poor access to suitable light-sheet fluorescence microscopes remains a major obstacle for biomedical end-users. Here, we present descSPIM (desktop-equipped SPIM for cleared specimens), a low-cost ($20,000-50,000), low-expertise (one-day installation by a non-expert), yet practical do-it-yourself light-sheet microscope as a solution for this bottleneck. Even the most fundamental configuration of descSPIM enables multi-color imaging of whole mouse brains and a cancer cell line-derived xenograft tumor mass for the visualization of neurocircuitry, assessment of drug distribution, and pathological examination by false-colored hematoxylin and eosin staining in a three-dimensional manner.

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  • E7820 and Indisulam are drugs that work as molecular glues, influencing RNA splicing to target and degrade the splicing factor RBM39, potentially aiding in cancer treatment.
  • In studies using patient-derived xenograft mouse models, E7820 showed a 38.1% overall response rate, particularly effective in tumors with loss-of-function mutations in homologous recombination repair (HRR) genes like ATM.
  • The drug causes DNA damage, leading to synthetic lethality in HRR-deficient cancer cells, and demonstrates synergistic effects when combined with olaparib, suggesting HRR dysfunction as a key predictive biomarker for treatment efficacy.
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Lenvatinib, a multitarget tyrosine kinase inhibitor for c-Kit and other kinases, has exhibited promising efficacy in treating advanced or metastatic thymic carcinoma (TC). Here, we present the case of a patient with metastatic TC harboring a exon 11 deletion and amplification. The patient exhibited a remarkable response to lenvatinib but experienced rapid disease progression after discontinuation of lenvatinib, referred to as a "disease flare.

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Background: Patients with cancer, particularly those undergoing chemotherapy, are at risk from the low immunogenicity of Coronavirus Disease 19 (COVID-19) vaccines.

Methods: This prospective study assessed the seroconversion rate of COVID-19 vaccines among patients with cancer and hospital staff. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein-specific IgG (S-IgG) concentrations were evaluated before the first vaccination, and 1-3 and 4-6 months after the second vaccination.

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  • Philadelphia chromosome (Ph)-like acute lymphoblastic leukemia (ALL) has a high treatment failure rate and is characterized by gene fusions, particularly involving the PDGFRB gene.
  • Researchers identified a new PDGFRB fusion gene, NRIP1::PDGFRB, in a pediatric ALL patient, which encodes a protein with the kinase domain of PDGFRB but lacks the partner peptide.
  • The study confirmed that NRIP1::PDGFRB has oncogenic potential and can be effectively targeted by various ABL1-specific inhibitors like imatinib and dasatinib, highlighting a novel fusion gene pattern in Ph-like ALL.
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  • Most cervical adenocarcinomas are linked to HPV, but gastric-type cervical adenocarcinoma (GAS) is aggressive and HPV-independent, making treatment challenging due to chemotherapy resistance.
  • Researchers created patient-derived xenografts (PDXs) from two GAS patients and analyzed protein biomarkers to explore drug development possibilities.
  • The study found that HER3 was frequently overexpressed in both patient and PDX tumors, indicating potential new treatment avenues targeting HER3 and HER2 for GAS patients.
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Background/aim: Fucoxanthin (Fx), a dietary marine xanthophyll, exerts potent anticancer effects in various colorectal cancer (CRC) animal models. However, therapeutic effects of Fx in human cancer tissues remain unclear. A patient-derived xenograft (PDX) mouse model transplanted with cancer tissues from patients is widely accepted as the best preclinical model for evaluating the anticancer potential of drug candidates.

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  • - The study investigates the role of Delta-like ligand 3 (DLL3) as a therapeutic target in small-cell lung cancer (SCLC) and its impact on the tumor microenvironment (TME) and patient outcomes.
  • - Results show that in limited-stage SCLC, DLL3 expression is associated with more neoantigens but reduced immune activity, leading to lower levels of immune cells like T cells and dendritic cells.
  • - In extensive-stage SCLC, patients with DLL3-expressing tumors experience significantly worse progression-free survival when treated with standard chemotherapy and anti-PD-L1 therapy, indicating resistance linked to suppressed immune responses.
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Background: Risk factors for predicting pneumonitis during durvalumab consolidation after chemoradiotherapy (CRT) in locally advanced non-small cell lung cancer (LA-NSCLC) are still lacking. Extracellular vesicles (EVs) play a crucial role in intercellular communication and are potential diagnostic tools for various diseases.

Methods: We retrospectively collected predurvalumab treatment serum samples from patients treated with durvalumab for LA-NSCLC, isolated EVs using anti-CD9 and anti-CD63 antibodies, and performed proteomic analyses.

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Although circulating tumour DNA (ctDNA)-based next-generation sequencing (NGS) is a less invasive method for assessing mutations that are essential mechanisms of endocrine therapy resistance in patients with oestrogen receptor-positive breast cancer, adequate amounts of DNA are required to assess polyclonal mutations. By combining a peptide nucleic acid and locked nucleic acid polymerase chain reaction (PNA-LNA PCR) clamping assay, we have developed a novel detection system to screen for polyclonal mutations in ctDNA. A validation assay was prospectively performed on clinical samples and compared with the NGS results.

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Article Synopsis
  • Immune checkpoint inhibitors (ICIs), like nivolumab, show potential in treating advanced NSCLC but only a minority of patients achieve long-term, durable responses.
  • A study analyzed 212 patients, finding that 35% responded to treatment, with 39% categorized as long-term responders (LTRs) and 61% as non-LTRs.
  • The LTR group exhibited significantly better outcomes in terms of tumor shrinkage than the non-LTR group, but no predictive factors were identified from PD-L1 expression or blood drug levels.
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Purpose: To investigate the efficacy and safety of trastuzumab deruxtecan, an antibody-drug conjugate targeting human epidermal growth factor receptor 2 (HER2) with a topoisomerase I inhibitor payload, in patients with uterine carcinosarcoma (UCS) expressing HER2.

Patients And Methods: Patients with recurrent UCS with HER2 immunohistochemistry scores ≥1+ previously treated with chemotherapy were included. Patients were assigned to the HER2-high (immunohistochemistry score ≥2+; n = 22) or low (immunohistochemistry score of 1+; n = 10) groups for primary and exploratory analyses, respectively.

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