Kyoto University · 의학
유지 에소 교수의 연구실은 간세포생식세포암(HCC)과 다양한 암에서의 유전자 안정성 및 DNA 복구 기전에 초점을 맞추고 있으며, 특히 미세위상불안정성(MSI)과 변이 부담(TMB)이 면역검사점 억제제(ICIs) 반응에 미치는 영향을 규명하고 있습니다. 염증이 유전자 이상을 유도하는 메커니즘, 특히 TNFα와 NF-κB 경로를 통해 MSH2 단백질이 억제되는 과정을 밝혀내며 암 발생의 염증 기반 기전을 밝혀내고 있습니다. 또한 레바티닙과 같은 표적항암제의 치료 강도를 정량화하는 신뢰도 있는 지표(예: 2M-DBR) 개발을 통해 개인화된 암 치료 전략을 모색하고 있습니다.
표시된 성과는 수집된 데이터 기준으로 산출되며, 일부 차이가 있을 수 있습니다.
Recent innovations in the next-generation sequencing technologies have unveiled that the accumulation of genetic alterations results in the transformation of normal cells into cancer cells. Accurate and timely repair of DNA is, therefore, essential for maintaining genetic stability. Among various DNA repair pathways, the mismatch repair (MMR) pathway plays a pivotal role. MMR deficiency leads to a molecular feature of microsatellite instability (MSI) and predisposes to cancer. Recent studies rev
Systemic chemotherapy using a multitargeted tyrosine kinase inhibitor is an established treatment for advanced-stage tumors in various organs. Comprehensive genomic analyses using next-generation sequencing technology revealed the intra- and intertumor heterogeneity of human hepatocellular carcinomas (HCCs), and provided evidence for the use of therapeutic agents effective against multiple targets in tumor cells. Recently, the efficacy and safety of a multitargeted tyrosine kinase inhibitor, len
The development of immune checkpoint inhibitors (ICIs) targeting cytotoxic T lymphocyte antigen 4 (CTLA-4), programmed cell death protein 1 (PD-1), or programmed cell death protein ligand 1 (PD-L1) has revolutionized the treatment strategy in various types of cancers. In addition, recent studies have revealed that tumor microsatellite instability (MSI) status and tumor mutation burden (TMB) contribute significantly to the therapeutic response to anti-PD-1 monoclonal antibody (mAb), which led to
The pretreatment NLR value may be a useful predictor of response to Atezo/Bev therapy for HCC.
Inflammation predisposes to tumorigenesis in various organs by potentiating a susceptibility to genetic aberrations. The mechanism underlying the enhanced genetic instability through chronic inflammation, however, is not clear. Here, we demonstrated that TNFα stimulation induced transcriptional downregulation of MSH2, a member of the mismatch repair family, via NF-κB-dependent miR-21 expression in hepatocytes. Liver cancers developed in ALB-MSH2(-) (/) (-)AID(+), ALB-MSH2(-) (/) (-), and ALB-AID
Lenvatinib was recently approved as a novel first-line molecular targeted agent (MTA) for treating hepatocellular carcinoma (HCC). The importance of relative dose intensity (RDI) has been shown in the treatment of various types of cancers. However, RDI may not accurately reflect the treatment intensity of lenvatinib, as it is the first oral MTA where the dose is based on the patient's weight. We aimed to evaluate the utility of 2M-DBR (the delivered dose intensity/body surface area ratio at 60 d
Transarterial chemoembolization (TACE) is the recommended first-line treatment for intermediate-stage hepatocellular carcinoma (HCC). In patients who became refractory to TACE, a treatment switch to tyrosine kinase inhibitors (TKIs) needs to be considered. However, TACE could worsen liver function, thereby narrowing the time window for a switch to TKIs because TKIs are recommended for patients with Child-Pugh grade A (CP-A). We investigated the factors associated with CP grade deterioration afte
SEUS guidance is recommended for more accurate localization of suitable hepatic lesion biopsy areas as it increases conspicuity and differentiates viable areas from denaturalization or necrosis.
Immunotherapy with immune checkpoint inhibitors has been shown to be beneficial for cancers originating from various organs. In May 2020, combination therapy with anti-programmed death-ligand 1 antibody atezolizumab and anti-vascular endothelial growth factor (VEGF) antibody bevacizumab was approved as a novel first-line systemic therapy for hepatocellular carcinoma (HCC). The number of patients with HCC not caused by hepatitis virus infection (non-viral HCC), including non-alcoholic steatohepat
Serum M2BPGi levels are correlated with nutritional status markers in patients with CLD and could be a useful clinical marker of malnutrition.
US-guided polidocanol foam sclerotherapy may be an effective and safe method for the treatment of symptomatic giant hepatic cysts.
Our findings suggest that US-guided liver tumor biopsy is a useful and safe method for obtaining high-quality samples for NGS-based clinical sequencing. In cases with metastatic liver tumors, US-guided biopsy should be considered to provide accurate and optimal sequencing results for patients.
Baseline M2BPGi levels may predict the tolerability and treatment response to lenvatinib. Patients with high M2BPGi levels may less likely to benefit from lenvatinib therapy.
