Publications by authors named "Masatoshi Kusuhara"

Background: A methodology to assess the immune microenvironment (IME) of non-small cell lung cancer (NSCLC) has not been established, and the prognostic impact of IME factors is not yet clear.

Aims: This study aimed to assess the IME factors and evaluate their prognostic values.

Methods And Results: We assessed CD8 tumor-infiltrating lymphocyte (TIL) density, forkhead box protein P3 (Foxp3 ) TIL density, and programmed death receptor ligand-1 (PD-L1) tumor proportion score (TPS) using a machine-learning algorithm in whole-slide imaging (WSI).

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Background: Research on whole genome/exome sequencing is increasing worldwide. However, challenges are emerging in relation to receiving germline pathogenic variant results and sharing them with relatives.

Objective: The aim of this study was to investigate the occurrence of and reasoning related to regret among patients with cancer who shared single-gene testing results and whole exome sequencing with family members.

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Article Synopsis
  • The study investigated how Japanese cancer patients communicate their hereditary cancer test results to family members, focusing on germline pathogenic variants.
  • Out of 21 patients, all shared their results with at least one relative, with 85.7% sharing with first-degree relatives; children were the most common recipients of this information.
  • The findings showed a tendency for patients to prioritize sharing results with immediate family, indicating a desire to enhance their relatives' health awareness and well-being.
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  • Despite the presence of KRAS mutations in colorectal cancer (CRC) patients, no effective treatments specifically targeting these mutations have been developed yet.
  • The study analyzed gene expression differences between CRC patients with wild-type KRAS and those with mutations in codon 12, identifying at least 11 candidate molecules with significant expression changes.
  • Three particular genes (BMP4, PHLDA1, and GJB5) showed increased expression in cell lines with KRAS G12 mutations, suggesting potential pathways for developing new treatments for KRAS-driven CRC.
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Recent studies have revealed that colorectal cancer (CRC) displays intratumor genetic heterogeneity, and that the cancer microenvironment plays an important role in the proliferation, invasion and metastasis of CRC. The present study performed genomic analysis on paired primary CRC and synchronous colorectal liver metastasis (CRLM) tissues collected from 22 patients using whole-exome sequencing, cancer gene panels and microarray gene expression profiling. In addition, immunohistochemical analysis was used to confirm the protein expression levels of genes identified as highly expressed in CRLM by DNA microarray analysis.

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Article Synopsis
  • Multiple endocrine neoplasia type 1 (MEN1) is a hereditary cancer syndrome caused by variants in the MEN1 gene, identified in two patients via whole exome sequencing.
  • Analysis of tumors from these patients showed loss of the normal MEN1 allele, chromosomal changes, and low somatic variants, leading to insights about tumorigenesis.
  • The findings suggest that the second hit in the MEN1 tumor suppressor might arise from large genomic rearrangements rather than smaller mutations or epigenetic changes.
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Purpose: The adhesion molecule cluster of differentiation 44v9 interacts with and stabilizes the cystine/glutamate exchanger protein, which functions as a transporter of cystine. Stabilized cystine/glutamate exchanger increases extracellular cystine uptake and enhances glutathione production. Augmented levels of reduced glutathione mitigate reactive oxygen species and protect cancer cells from apoptosis.

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High-throughput sequencing has greatly contributed to precision medicine. However, challenges remain in reporting secondary findings (SFs) of germline pathogenic variants and managing the affected patients. The aim of this study was to examine the incidence of SFs in Japanese cancer patients using whole exome sequencing (WES) and to understand patient preferences regarding SF disclosure.

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Rationale: Pleomorphic adenoma (PA) is the most common benign tumor of salivary glands. PAs have the potential for regional and distant metastases that preserve their benign phenotype; they also have the potential for malignant transformation. The molecular pathogenesis of malignant neoplasms has been studied extensively in recent years, unlike that of benign tumors, such as PA.

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The aim of the study was to investigate the effect of chemo-radiation on the genetic and immunological status of rectal cancer patients who were treated with preoperative chemoradiotherapy (CRT). The expression of immune response-associated genes was compared between rectal cancer patients treated (n = 9) and not-treated (n = 10) with preoperative CRT using volcano plot analysis. Apoptosis and epithelial-to-mesenchymal transition (EMT) marker genes were analysed by quantitative PCR (qPCR).

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Background: It is unclear whether clinical factors and immune microenvironment (IME) factors are associated with tumor mutation burden (TMB) in patients with nonsmall cell lung cancer (NSCLC).

Materials And Methods: We assessed TMB in surgical tumor specimens by performing whole exome sequencing. IME profiles, including PD-L1 tumor proportion score (TPS), stromal CD8 tumor-infiltrating lymphocyte (TIL) density, and stromal Foxp3 TIL density, were quantified by digital pathology using a machine learning algorithm.

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Background: Metabolomics is useful for analyzing the nutrients necessary for cancer progression, as the proliferation is regulated by available nutrients. We studied the metabolomic profile of gastric cancer (GC) tissue to elucidate the associations between metabolism and recurrence.

Methods: Cancer and adjacent non-cancerous tissues were obtained in a pair-wise manner from 140 patients with GC who underwent gastrectomy.

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This study aimed to establish the Japanese Cancer Genome Atlas (JCGA) using data from fresh frozen tumor tissues obtained from 5143 Japanese cancer patients, including those with colorectal cancer (31.6%), lung cancer (16.5%), gastric cancer (10.

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Background And Objective: The efficacy expectation of immune checkpoint inhibitors against NSCLC in patients with ILD seems to be high because these populations are supposed to have high TMB. However, information about the characterization of TMB in patients with NSCLC and ILD is limited. Therefore, this study aimed to evaluate TMB in samples of NSCLC with ILD and clarify factors that influence TMB values.

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Mutually exclusive KIT and PDGFRA mutations are considered to be the earliest events in gastrointestinal stromal tumors (GIST), but insufficient for their malignant progression. Herein, we aimed to identify driver genes and signaling pathways relevant to GIST progression. We investigated genetic profiles of 707 driver genes, including mutations, gene fusions, copy number gain or loss, and gene expression for 65 clinical specimens of surgically dissected GIST, consisting of six metastatic tumors and 59 primary tumors from stomach, small intestine, rectum, and esophagus.

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Background: Lynch syndrome (LS) is the commonest inherited cancer syndrome caused by pathogenic variants of germline DNA mismatch repair (g.MMR) genes. Genome-wide sequencing is now increasingly applied for tumor characterization, but not for g.

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Objectives: To evaluate the relationships between adenine-thymine-rich interactive domain 1A (ARID1A) expression and the clinicopathologic features in T1 colorectal cancer (CRC) and to investigate whether the presence of ARID1A protein is related to genetic changes.

Methods: We retrospectively studied 219 surgically resected T1 CRCs. ARID1A expression was assessed by immunohistochemical methods, and the correlation between ARID1A expression and clinicopathologic features was evaluated.

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Here, we investigated the clinicopathological and mutation profiles of colorectal cancer (CRC) with POLE mutations. Whole-exome sequencing was performed in 910 surgically resected primary CRCs. Tumors exceeding 500 counts of nonsynonymous single nucleotide variants (SNVs) were classified as hypermutators, whereas the remaining were classified as nonhypermutators.

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The effect of direct oral anticoagulants (DOACs) on cancer-associated cerebral infarction (CI) is unclear. We present the clinical course of 20 consecutive patients with cancer-associated CI that developed during treatment with DOACs. The incidence rate of cancer-associated CI during the treatment with DOACs was 3.

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Tumor mutational burden (TMB) and mutational signatures reflect the process of mutation accumulation in cancer. However, the significance of these emerging characteristics remains unclear. In the present study, we used whole-exome sequencing to analyze the TMB and mutational signature in solid tumors of 4046 Japanese patients.

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Article Synopsis
  • The study explores how a fragrant environment (FE) containing α-pinene affects tumor growth in melanoma mice, revealing a ~40% reduction in tumor size.
  • Exposure to the FE led to decreased leptin levels and increased sympathetic nervous activity, while certain immune cells (B cells, CD4 T cells, CD8 T cells, and natural killer cells) were found to be more abundant.
  • These findings suggest that the FE may enhance immune response and activate key neurohormonal pathways, potentially offering a mechanism for how environmental factors can influence cancer outcomes.
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Recent advances in next-generation sequencing have enabled rapid and efficient evaluation of the mutational landscape of cancers. As a result, many cancer-specific neoantigens, which can generate antitumor cytotoxic T-cells inside tumors, have been identified. Previously, we reported a metastatic melanoma case with high tumor mutation burden, who obtained complete remission after anti-PD-1 therapy and surgical resection.

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Background: The efficacy of direct oral anti-coagulants (DOACs) for the treatment of venous thromboembolism (VTE) in Japanese patients with advanced cancer is largely unknown.

Methods: This prospective single-center observational study enrolled Japanese patients with unresectable advanced cancer who started DOAC treatment for new-onset VTE between December 2015 and May 2018. Patients were followed for 3 months to evaluate bleeding and VTE recurrences.

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