Publications by authors named "Hiroyuki Sakaguchi"

Background/aim: We previously reported the usefulness of detecting aberrant methylation in tumor suppressive microRNAs (miRNAs) in bile and plasma to discriminate pancreaticobiliary cancers from benign pancreaticobiliary diseases. This study analyzed the methylation of miRNAs in pancreatic juice to identify those specific to pancreatic cancer (PC).

Patients And Methods: Pancreatic juice was collected from 20 patients with PC, including eight with intraductal papillary mucinous carcinoma (IPMC), two with low grade-pancreatic intraepithelial neoplasia (LG-PanIN), 32 with LG-intraductal papillary mucinous neoplasm (IPMN), and seven with benign pancreatic lesions.

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  • A glioblastoma patient with high tumor mutation burden and mismatch repair deficiency showed a strong positive response to pembrolizumab, an immune checkpoint inhibitor, despite previous treatment with temozolomide which usually leads to resistance.
  • Despite rapid disease progression, indicated by high Ki67 levels, the patient's condition improved significantly with pembrolizumab.
  • This case highlights the potential of precision oncology in treating GBM and emphasizes the need for thorough genomic profiling to inform treatment strategies.
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Precision medicine has drastically changed cancer treatment strategies including KRAS-mutant cancers which have been undruggable for decades. While intrinsic or acquired treatment resistance remains unresolved in many cases, epigenome-targeted therapy may be an option to overcome. We recently discovered the effectiveness of blocking small ubiquitin-like modifier (SUMO) signaling cascade (SUMOylation) in MYC-expressing KRAS-mutant cancer cells using a SUMO-activating enzyme E inhibitor TAK-981 that results in SUMOylation inhibition.

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  • Immune checkpoint inhibitors (ICIs) can improve cancer treatment but may cause serious side effects, including myocarditis.
  • The report discusses two cases of myocarditis that did not respond to corticosteroids, indicating a severe reaction to ICIs.
  • Additional treatments like intravenous immunoglobulin and tacrolimus were effective in resolving the myocarditis, suggesting that early use of alternative immunosuppressive therapies should be considered when corticosteroids fail.
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  • - The case involves a 59-year-old man with poorly differentiated lung carcinoma and a rare K601E mutation who showed limited response to the targeted drugs dabrafenib and trametinib after failing chemotherapy and immunotherapy.
  • - Although the patient had a significant initial response to the treatment, the tumor's regression lasted only 52 days before progressing, indicating a rapid development of resistance.
  • - A follow-up liquid biopsy revealed additional genetic changes associated with resistance, highlighting the complexities of treating K601E-mutant lung carcinoma and the need for improved molecular diagnostics and personalized therapy strategies.
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Background: KRAS mutations frequently occur in cancers, particularly pancreatic ductal adenocarcinoma, colorectal cancer, and non-small cell lung cancer. Although KRAS inhibitors have recently been approved, effective precision therapies have not yet been established for all KRAS-mutant cancers. Many treatments for KRAS-mutant cancers, including epigenome-targeted drugs, are currently under investigation.

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Electrical muscle stimulation (EMS) has been shown to stimulate the production of myokines (i.e., brain-derived neurotrophic factor (BDNF)), but the most effective EMS parameters for myokine production have not been fully elucidated.

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The clinical development of Kirsten rat sarcoma virus (KRAS)-G12C inhibitors for the treatment of KRAS-mutant lung cancer is limited by the presence of co-mutations, intrinsic resistance, and the emergence of acquired resistance. Therefore, innovative strategies for enhancing apoptosis in KRAS-mutated non-small cell lung cancer (NSCLC) are urgently needed. Through CRISPR-Cas9 knockout screening using a library of 746 crRNAs and drug screening with a custom library of 432 compounds, we discover that WEE1 kinase inhibitors are potent enhancers of apoptosis, particularly in KRAS-mutant NSCLC cells harboring TP53 mutations.

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In the realm of rare cardiac tumors, intimal sarcoma presents a formidable challenge, often requiring innovative treatment approaches. This case report presents a unique instance of primary intimal sarcoma in the left atrium, underscoring the critical role of genomic profiling in guiding treatment. Initial genomic testing unveiled a somatic, active mutation in ( N666K), accompanied by and amplifications.

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Purpose: Electrical muscle stimulation (EMS) is known to be effective at stimulating brain-derived neurotrophic factor (BDNF) levels, but the relationship between the volume of muscle stimulated and BDNF levels is not clear. The purpose of this study was to quantify BDNF as a function of muscle volume stimulated in young adults.

Methods: Twelve young adults (male, n = 9, age = 27.

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  • The study compared the effectiveness of two first-line treatments for inoperable pancreatic cancer: FOLFIRINOX, which includes leucovorin, 5-fluorouracil, irinotecan, and oxaliplatin, versus gemcitabine plus Nab-paclitaxel (GnP).
  • Data from 45 patients treated between 2014 and 2019 were analyzed, revealing that while there was no significant difference in the time until disease progression, patients on FOLFIRINOX had a longer median overall survival (16.7 months) compared to those on GnP (7.2 months).
  • The findings also suggested that patients on GnP were less likely to switch to FOLF
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Primary malignant melanoma (MM) of the mediastinum is rare, and there is a lack of consensus regarding the preferred treatment because non-cutaneous MM demonstrates an inferior response to systemic therapy. Herein, we describe the case of a 73-year-old man with MM of the anterior mediastinum with multiple liver metastases. Even though the size of lesions increased rapidly following diagnosis, nivolumab monotherapy caused remarkable tumor shrinkage.

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Immune checkpoint inhibitors (ICIs) are widely used in both monotherapy and combination chemotherapy for various types of cancers. Nivolumab is the most popular among ICIs, and the number of adapted malignant diseases for nivolumab is increasing. Bronchoesophageal fistula formation is a serious complication of the treatment for esophageal or lung cancer.

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Purpose: Astaxanthin (AST) has a strong antioxidant cellular membrane chaperone protective effect. Recently, a water-soluble nanosized AST (nano-AST) form was produced, which is expected to improve the efficacy of oral intake effects. The purpose of this study was to examine whether oral nano-AST has therapeutic effects on UV-induced photokeratitis in mice.

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Several studies have reported that short sleep duration is a risk factor for obesity and metabolic disease. Moreover, both sleep duration and sleep timing might independently be associated with dietary nutrient intake. In this study, we investigated the associations between self-reported sleep duration and dietary nutrient intake, with and without adjustments for variations in sleep timing (i.

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