Publications by authors named "Kazunori Aoki"

Article Synopsis
  • The study investigates sex differences in the outcomes of advanced renal cell carcinoma (RCC) patients treated with immune checkpoint inhibitors (ICIs) and their tumor-infiltrating immune cell profiles.
  • Female patients exhibited shorter progression-free survival (PFS) compared to males when treated with first-line dual ICI combinations and nivolumab monotherapy, while no significant differences were found in other treatment groups.
  • The lower effectiveness of ICIs in females might be attributed to differences in immune microenvironments, particularly the reduced presence of CD8+ T cells in female patients.
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Background: Multisystem inflammatory syndrome in children (MIS-C) presents some clinical overlap with Kawasaki disease (KD). Although KD is common in Japan, the clinical characteristics of MIS-C in Japan remain unknown. Therefore, we aimed to determine the epidemiological and clinical features of MIS-C in Japan.

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Background: Gastric cancer (GC) is one of the most common and deadly malignant diseases worldwide. Despite revolutionary advances, the therapeutic efficacy of anti-PD1/PDL1 monoclonal antibodies in advanced GC is still low due to the emergence of innate and acquired resistance to treatment. Myeloid cells represent the majority of human immune cells.

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Background: Mediastinal tumors in children may be misdiagnosed as bronchial asthma, resulting in delayed diagnosis and airway obstruction leading to cardiac arrest.

Purpose: This study aimed to identify factors for early diagnosis of mediastinal tumors in children to avoid a life-threatening situation.

Methods: We retrospectively reviewed the medical records of 14 children with airway compressions caused by mediastinal tumors who visited the Hyogo Prefectural Kobe Children's Hospital between April 2016 and September 2023.

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Objectives: Despite the recommendation for lung-protective mechanical ventilation (LPMV) in pediatric acute respiratory distress syndrome (PARDS), there is a lack of robust supporting data and variable adherence in clinical practice. This study evaluates the impact of an LPMV protocol vs. standard care and adherence to LPMV elements on mortality.

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Purpose: Visualizing mitochondria in cancer cells from human pathological specimens may improve our understanding of cancer biology. However, using immunohistochemistry to evaluate mitochondria remains difficult because almost all cells contain mitochondria and the number of mitochondria per cell may have important effects on mitochondrial function. Herein, we established an objective system (Mito-score) for evaluating mitochondria using machine-based processing of hue, saturation, and value color spaces.

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Article Synopsis
  • Overcoming resistance to immune checkpoint inhibitors is critical for treating non-small-cell lung cancer (NSCLC), which includes different molecular subtypes with distinct immune landscapes.
  • The study identifies three adenocarcinoma subtypes (TRU, PP, PI) and their immune responses, finding that the PI subtype has a stronger immune activation while the PP subtype shows features that suppress the immune response.
  • Understanding these immune characteristics can guide personalized treatment strategies, suggesting that immune checkpoint inhibitors may work well for the PI subtype and that targeting glycolysis could help improve the immune response in the PP subtype.
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Inflammatory factors in the peripheral blood, such as the C-reactive protein level and neutrophil-to-lymphocyte ratio (NLR), are prognostic markers in multiple types of cancer, including non-small cell lung cancer (NSCLC). However, the association between inflammatory factors and prognosis based on histological types has not been adequately reported. In addition, the relationship between these factors and the immune condition of the tumor microenvironment (TME) is unclear.

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Interleukin-6 (IL-6)/signal transducer and activator of transcription 3 (STAT3) pathway inhibition may overcome chemoresistance of metastatic pancreatic cancer (MPC). We sought to determine the safety and recommended dose of tocilizumab (TCZ), an IL-6 receptor monoclonal antibody, and biological correlates of tumor shrinkage in patients with gemcitabine (GEM)/nanoparticle albumin-bound paclitaxel (nab-PTX)-refractory MPC. This phase 1 study enrolled 10 patients with MPC who had progressed after GEM/nab-PTX.

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Background: Phenotyping analysis that includes time course is useful for understanding the mechanisms and clinical management of postoperative delirium. However, postoperative delirium has not been fully phenotyped. Hypothesis-free categorization of heterogeneous symptoms may be useful for understanding the mechanisms underlying delirium, although evidence is currently lacking.

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Unlabelled: Resistance to immune checkpoint blockade remains challenging in patients with non-small cell lung cancer (NSCLC). Tumor-infiltrating leukocyte (TIL) quantity, composition, and activation status profoundly influence responsiveness to cancer immunotherapy. This study examined the immune landscape in the NSCLC tumor microenvironment by analyzing TIL profiles of 281 fresh resected NSCLC tissues.

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Article Synopsis
  • Excessive stress may worsen tumor growth, with the paraventricular nucleus (PVN) in the hypothalamus playing a key role in stress response by activating the HPA axis through corticotropin-releasing hormone (CRH).
  • In this study, activating CRH neurons led to increased plasma corticosterone levels and significantly promoted tumor growth, indicating a direct link between stress responses and cancer progression.
  • The activation of CRH neurons decreased cytotoxic CD8 T cells in tumors and upregulated various factors associated with tumor progression, suggesting that stress can negatively impact the immune environment supporting cancer development.
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Hepatocellular adenomas are rare diseases, defined as benign liver neoplasms composed of cells with hepatocellular differentiation. Differential diagnosis of hepatocellular adenoma from other lesions, including focal nodular hyperplasia and hepatocellular carcinoma, is crucial to determine treatment strategy. We describe a case of β-catenin-activated inflammatory hepatocellular adenoma with malignant transformation.

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Article Synopsis
  • The study investigates how cytokine levels change over 72 hours in children diagnosed with acute encephalopathy (AE) and febrile seizures (FS), focusing on their potential as biomarkers for differentiating the two conditions.
  • Researchers measured levels of 13 different cytokines in serum samples from seven children and found that most cytokines peaked within the first 12-24 hours after onset.
  • The results suggest that cytokine levels are generally higher in AE compared to FS, and highlight the importance of monitoring these levels to guide anti-inflammatory treatment decisions within the first day after symptoms appear.
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The occurrence of immune-related adverse events (irAEs) after immune checkpoint inhibitors (ICIs) is unpredictable. Profiles of peripheral blood mononuclear cells (PBMCs) represent the host immune system and have the potential to predict irAEs. We analyzed PBMC subsets using multicolor flow cytometry before and at weeks 2 and 8 after the start of ICIs in patients with non-small cell lung cancer.

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Important roles of humoral tumor immunity are often pointed out; however, precise profiles of dominant antigens and developmental mechanisms remain elusive. We systematically investigated the humoral antigens of dominant intratumor immunoglobulin clones found in human cancers. We found that approximately half of the corresponding antigens were restricted to strongly and densely negatively charged polymers, resulting in simultaneous reactivities of the antibodies to both densely sulfated glycosaminoglycans (dsGAGs) and nucleic acids (NAs).

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Background: Although serum lactate levels are widely accepted markers of haemodynamic instability, an alternative method to evaluate haemodynamic stability/instability continuously and non-invasively may assist in improving the standard of patient care. We hypothesise that blood lactate in paediatric ICU patients can be predicted using machine learning applied to arterial waveforms and perioperative characteristics.

Methods: Forty-eight post-operative children, median age 4 months (2.

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Background: Conversion surgery, which is defined as chemotherapy or chemoradiotherapy followed by radical surgery, may improve survival of patients with initially unresectable advanced biliary tract cancer, including gallbladder cancer. However, there are few reports on conversion surgery for advanced gallbladder cancer.

Case Presentation: A 69-year-old woman was referred to our hospital with initially unresectable gallbladder cancer with peritoneal carcinomatosis.

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Imatinib mesylate is a potent tyrosine kinase inhibitor that may induce immunological effects, such as inhibition of immune suppressive cells; but, how it modulates the immune system remains to be completely elucidated. In this study, we showed that cell proliferation of CT26 colon cancer and Lewis lung carcinoma (3LL) lung cancer cells was not inhibited by imatinib in vitro, although its administration significantly suppressed the growth of CT26, but not 3LL, subcutaneous tumors, and prolonged survival in CT26 tumor-bearing mice. Further, we examined the expression of immune cell-related molecules in the tumors to elucidate the differences in imatinib-mediated antitumor effects between CT26 and 3LL tumors.

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Cervical adenocarcinoma (ADC) is the second most common pathological subtype of cervical cancer after squamous cell carcinoma. It accounts for approximately 20% of cervical cancers, and the incidence has increased in the past few decades, particularly among young patients. The persistent infection of high-risk human papillomavirus (HPV) is responsible for most cervical ADC.

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Background: Perioperative management of congenital tracheal stenosis (CTS) is challenging. In the present study, compared the effect of closed-pediatric intensive care unit (PICU) perioperative management by pediatric intensivists and open-PICU management by surgeons. Outcomes in terms of ventilator-free days (VFD) and length of postoperative PICU stay in children with CTS were evaluated.

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