Publications by authors named "Yasuto Takeuchi"

Background And Aims: Methods for predicting therapeutic response to immune checkpoint inhibitors in cancer therapy are in high demand. In patients with advanced hepatocellular carcinoma (HCC), atezolizumab (anti-programmed cell death-ligand 1 [PD-L1]) and bevacizumab (anti-vascular endothelial growth factor) combination therapy (Atezo/Bev therapy) is a first-line treatment. However, no reliable biomarkers are currently available to predict its efficacy.

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Triple-negative breast cancer (TNBC) lacks the expression of hormone and HER2 receptors and is highly malignant with no effective therapeutic targets. In TNBC, the cancer stem-like cell (CSC) population is considered to be the main cause of resistance to treatment. Thus, the therapeutic targeting of this population could substantially improve patient survival.

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  • Durvalumab plus tremelimumab (Durva/Treme) is the first-line immunotherapy option for patients with unresectable hepatocellular carcinoma (HCC), with a reported objective response (OR) rate of 15.5%.
  • The study involved 110 patients and aimed to identify whether changes in tumor markers, specifically alpha-fetoprotein (AFP) and des-gamma-carboxy prothrombin (DCP), could serve as predictive biomarkers for treatment response, using data collected both before and four weeks after treatment.
  • It was found that higher baseline AFP levels (≥ 400 ng/mL) significantly correlated with better OR rates, and a ≥10% reduction in AFP or DCP
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  • Durvalumab plus tremelimumab (Dur/Tre) is approved for first-line treatment of unresectable hepatocellular carcinoma (u-HCC), but its real-world effectiveness is not well understood.
  • A study involving 120 patients found an objective response rate (ORR) of 15.8%, a disease control rate (DCR) of 53.3%, and a median progression-free survival (PFS) of 3.9 months, alongside a high rate of adverse events (AEs).
  • Although there was no significant difference in response and survival rates between those treated as first-line versus later-line, first-line therapy showed better disease control; careful management is needed for older patients or those with
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  • The use of immune checkpoint inhibitors (ICIs) has led to increased incidents of ICI-induced liver injury, making it a significant concern for healthcare providers. !* -
  • Severe liver injuries often require corticosteroid treatment, necessitating thorough evaluations including clinical assessments, blood tests, imaging, and sometimes liver biopsies for accurate diagnosis. !* -
  • Distinguishing between types of liver injury, such as acute hepatitis-like effects and cholangitis, is crucial for effective treatment, with non-hepatocellular injuries often responding poorly to corticosteroids, highlighting the need for interdisciplinary cooperation in diagnosis and management. !*
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The neutrophil -to-lymphocyte ratio (NLR) is useful for predicting the effectiveness of treatment with immune checkpoint inhibitors (ICIs) and immune-related adverse events (irAEs). Because a growing body of evidence has recently shown that the number of lymphocytes that comprise NLR fluctuates according to nutritional status, this study examined whether the usefulness of NLR varies in ICI treatment due to changes in nutritional status. A retrospective analysis was performed on 1234 patients who received ICI treatment for malignant tumors at our hospital.

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Background: To identify predictive factors associated with successful transition to conversion therapy following combination therapy with atezolizumab and bevacizumab in the treatment of unresectable hepatocellular carcinoma (HCC).

Methods: In total, 188 patients with HCC, who received atezolizumab plus bevacizumab combination therapy as the first-line chemotherapy, were studied. Patients who achieved complete response (CR) with systemic chemotherapy alone were excluded.

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In vitro studies using cell culture, including three-dimensional cultures without the involvement of tumor vessels, have limitations in simulating complex intratumoral hypoxic conditions in live subjects. To generate experimental hypoxic conditions closer to those observed in humans in clinical settings, in vivo studies are necessary. In addition, visible light generated via bioluminescence and fluorescence is generally unsuitable for in vivo experiments because of low tissue penetration.

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  • Hypoxia is a key factor in cardiovascular diseases and tumors, triggering various cellular processes like blood formation, new blood vessel growth, and cell death.
  • Hypoxia-inducible factor-1 (HIF-1) activates specific genes by binding to hypoxia response elements (HREs), which are crucial for developing gene therapies targeting hypoxia.
  • Research shows that gene activation linked to HREs varies depending on the cell type and oxygen levels, leading to an in vitro method for studying the effects of different HRE copy numbers on gene expression.
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  • Cancer stem cells (CSCs) show diversity within tumors, making it hard to target treatments effectively, especially in triple-negative breast cancer (TNBC).
  • Through single-cell transcriptomics, researchers identified a specific subpopulation of CSCs characterized by FXYD3, which is linked to drug resistance during chemotherapy.
  • Targeting the Na+/K+ pump with specific inhibitors, such as cardiac glycosides, could potentially improve treatment outcomes by eliminating these resistant CSCs, leading to better TNBC patient prognoses.
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Liver fibrosis is an important phenomenon in non-alcoholic fatty liver disease (NAFLD) progression. Standard markers reflecting liver fibrosis, including the FIB-4 index, increase with age. This study aimed to identify fibrosis progression-related markers that are diagnostically beneficial even in aged individuals.

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Background And Aims: The IMbrave 150 trial revealed the usefulness of atezolizumab plus bevacizumab therapy in patients with unresectable hepatocellular carcinoma (HCC), making it now considered the first-line systemic chemotherapy agent for HCC. The present study investigated factors associated with early tumor progression of atezolizumab plus bevacizumab in patients with advanced HCC in real-world clinical practice.

Methods: A total of 184 HCC patients who received atezolizumab plus bevacizumab therapy were studied.

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Background/purpose: Primary sclerosing cholangitis (PSC) is a rare chronic liver disease. The mechanisms and prediction of PSC progression are unclear. Recent investigations have shown that general conditions, such as oxidative stress, affect the course of chronic diseases.

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  • Mitochondrial one-carbon metabolism is important for both embryonic growth and cancer development, providing essential units for making nucleotides and supporting quick cell growth.
  • A study focused on mammary gland development during pregnancy revealed that the enzyme MTHFD2 is crucial for promoting rapid cell proliferation, with its levels increasing during this time.
  • Mice with a mutation in the Mthfd2 gene showed delayed mammary gland expansion during pregnancy, suggesting that MTHFD2 plays a key role in normal tissue development in adults.
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Background: Accurate diagnosis of the lateral extent of early gastric cancer during endoscopic submucosal dissection (ESD) is crucial to achieve negative resection margins. Similar to intraoperative consultation with a frozen section in surgery, rapid frozen section diagnosis with endoscopic forceps biopsy may be useful in assessing tumor margins during ESD. This study aimed to evaluate the diagnostic accuracy of frozen section biopsy.

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As the incidence of breast cancer continues to increase, it is critical to develop prevention strategies for this disease. Inflammation underlies the onset of the disease, and NF-κB is a master transcription factor for inflammation. Nuclear factor-κB (NF-κB) is activated in a variety of cell types, including normal epithelial cells, cancer cells, cancer-associated fibroblasts (CAFs), and immune cells.

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Cryopreservation of tissues is a tough challenge. Cryopreservation is categorized into slow-freezing and vitrification, and vitrification has recently been recognized as a suitable method for tissue cryopreservation. On the contrary, some researchers have reported that slow-freezing also has potential for tissue cryopreservation.

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This study sought to identify factors that are predictive of a therapeutic response to hepatic arterial infusion chemotherapy (HAIC) by focusing on the number of prior transcatheter arterial chemoembolization (TACE) sessions. To determine the parameters predicting a good response to HAIC, we retrospectively analyzed 170 patients with hepatocellular carcinoma (HCC) who received HAIC regimens comprising low-dose cisplatin combined with 5-fluorouracil (LFP) or cisplatin (CDDP) for the first time. In both the LFP and CDDP regimens, the response rates were significantly lower in patients with three or more prior TACE sessions than in those with two or fewer prior TACE sessions (LFP 57% versus 28%; p=0.

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Background: The number of patients with non-functional neuroendocrine tumors (NETs) has increased recently, and the rate of liver metastasis of NETs is about 20% in patients at the first diagnosis. Transcatheter arterial embolization (TAE) and everolimus are therapies with reported efficacy, but few reports have described their combined treatment. We therefore aim to evaluate the efficacy and safety of combination therapy with everolimus and TAE in patients with liver metastasis of gastroenteropancreatic neuroendocrine tumors (GEP-NETs) in a prospective study.

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Anorexia nervosa (AN) can cause severe protein energy malnutrition and the consequent development of various organ disorders. AN is known to cause hepatic complications. We report two cases of starvation and refeeding-induced liver injury in patients with AN, and review the literature on the hepatic complications of AN.

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Recent advances in genome editing technology are accompanied by increasing public expectations on its potential clinical application, but there are still scientific, ethical, and social considerations that require resolution. In Japan, discussions pertaining to the clinical use of genome editing in human embryos are underway. However, understanding of the public's sentiment and attitude towards this technology is limited which is important to help guide the debate for prioritizing policies and regulatory necessities.

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Focal nodular hyperplasia (FNH) is a benign nodular lesion, but because of its feature of portal tract vessel abnormality, it may induce portal hypertension. A 27-year-old woman was admitted with a fever. A large nodule with satellite lesions was found in the liver and cotton wool-like feature of arteries were detected on angiography.

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Although it is held that proinflammatory changes precede the onset of breast cancer, the underlying mechanisms remain obscure. Here, we demonstrate that FRS2β, an adaptor protein expressed in a small subset of epithelial cells, triggers the proinflammatory changes that induce stroma in premalignant mammary tissues and is responsible for the disease onset. FRS2β deficiency in mouse mammary tumor virus (MMTV)-ErbB2 mice markedly attenuated tumorigenesis.

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Article Synopsis
  • EGFR-TKIs are effective for treating non-small-cell lung cancer (NSCLC) with EGFR mutations, but patients often develop resistance to these drugs, leading to poor outcomes.
  • The study identifies the RNA-binding protein MUSASHI-2 (MSI2) as a new factor that contributes to this resistance by enhancing cancer stem-like properties and increasing the expression of the stemness protein Nanog.
  • Targeting the MSI2-Nanog pathway could enhance the effectiveness of EGFR-TKIs and help overcome resistance in NSCLC patients.
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Synopsis of recent research by authors named "Yasuto Takeuchi"

  • - Yasuto Takeuchi's recent research emphasizes the role of RNA-binding proteins and specific tumor markers in enhancing treatment strategies for aggressive cancers like triple-negative breast cancer (TNBC) and hepatocellular carcinoma (HCC), highlighting the therapeutic potential of targeting cancer stem-like cells (CSCs) and utilizing biomarkers for treatment efficacy predictions.
  • - He has conducted multi-center studies on the efficacy and safety of combination immunotherapy (durvalumab plus tremelimumab) for unresectable HCC, shedding light on real-world clinical outcomes and the importance of predictive factors for treatment responses.
  • - Takeuchi's work also explores the impact of nutritional status on immune checkpoint inhibitors' effectiveness and adverse effects, along with pioneering techniques like radionuclide reporter imaging and luciferase assays to better understand tumor hypoxia dynamics in cancer pathology.