Publications by authors named "Miki Fukumoto"

Article Synopsis
  • ATP-dependent chromatin remodeling complexes, specifically non-canonical BAF (ncBAF), play important roles in hematopoietic stem cells (HSCs), but their functions haven't been fully explored.* -
  • The study focuses on BRD9, a key component of ncBAF, finding that its loss increases chromatin accessibility, leading to a preference for myeloid cell development while hindering B cell formation.* -
  • BRD9 is shown to interact with CTCF, which affects gene expression and chromatin structure in HSCs, highlighting ncBAF's crucial role in determining cell fate in both normal and cancerous blood cell development.*
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SETBP1 is a potential epigenetic regulator whose hotspot mutations preventing proteasomal degradation are recurrently detected in myeloid malignancies with poor prognosis. It is believed that the mutant SETBP1 exerts amplified effects of wild-type SETBP1 rather than neomorphic functions. This indicates that dysregulated quantitative control of SETBP1 would result in the transformation of hematopoietic cells.

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Article Synopsis
  • Detailed analysis shows that genetic rearrangements of chromosome 3 drive certain myeloid leukemias by increasing EVI1 transcription through enhancer changes.
  • A novel EVI1 RNA variant, created by mutations in the splicing factor SF3B1, contributes to acute myeloid leukemia transformation and is frequently found in these patients.
  • Mutant SF3B1 promotes abnormal EVI1 splicing, enhancing stem cell self-renewal and accelerating leukemia development in mouse models, highlighting a crucial link between splicing mutations and myeloid leukemia pathogenesis.
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Yes-associated protein 1 (YAP1) and its paralogue PDZ-binding motif (TAZ) play pivotal roles in cell proliferation, migration, and invasion, and abnormal activation of these TEAD transcriptional coactivators is found in diverse cancers in humans and mice. Targeting YAP1/TAZ signaling is thus a promising therapeutic avenue but, to date, few selective YAP1/TAZ inhibitors have been effective against cancer cells either in vitro or in vivo. We screened chemical libraries for potent YAP1/TAZ inhibitors using a highly sensitive luciferase reporter system to monitor YAP1/TAZ-TEAD transcriptional activity in cells.

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Article Synopsis
  • Eukaryotes use two pre-mRNA splicing systems: the major spliceosome for most introns and the minor spliceosome for rare introns, but the role of the minor spliceosome is not well understood.
  • Research shows that losing the minor spliceosome component ZRSR2 can boost the self-renewal of hematopoietic stem cells, indicating its regulatory importance.
  • Mutations in minor introns are linked to various cancers and disorders, such as Noonan syndrome, suggesting that minor intron recognition plays a critical role in blood cell development and cancer progression.
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Objective: To investigate the impact of the number of drugs on rehabilitation outcomes for patients with acute traumatic brain injury.

Design: Retrospective cohort study.

Setting: Hospital-based database created by the Japan Medical Data Center.

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Aim: To test the hypothesis that hip fracture patients who receive occupational therapy (OT) have better functional ability than those who do not.

Methods: This retrospective observational study utilized data from the Japan Rehabilitation Database spanning 2005-2015. In-hospital hip fracture patients admitted to acute hospitals were identified.

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The aim of this review was to determine the utility of home visits by occupational therapists before and after a patient is discharged from an acute care hospital. All relevant published studies were identified by searching the CENTRAL, MEDLINE, EMBASE, Occupational Therapy Systematic Evaluation of Evidence, and WHO International Clinical Trials Registry Platform databases. Randomized controlled trials were included regardless of sex, age, disease, and duration of acute hospitalization.

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Traumatic brain injury (TBI) often causes behavioral problems and difficulties with school work, but the specific factors associated with difficulty in returning to school after TBI still remain unclear. The purpose of this study was to investigate factors associated with difficulty in returning to school within 1 year of injury in students with traumatic brain injury. This study is a secondary analysis of existing data sets.

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Background: Adjuvant therapy for colorectal cancer (CRC) in patients aged ≥75 years is supported by inadequate evidence, although such patients are increasing in number worldwide.

Patients And Methods: We assessed the influence of age and comorbidities on the prognosis of CRC in elderly patients using pooled data by the Japanese Study Group for Postoperative Follow-up of Colorectal Cancer. In total, 4598 patients (3304 with colon cancer and 1294 with rectal cancer) who underwent curative surgery from 2004 to 2006 were analysed with respect to age, Charlson comorbidity score (CS), tumour marker positivity, adjuvant therapy and prognosis.

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Phosphoinositides play pivotal roles in the regulation of cancer cell phenotypes. Among them, phosphatidylinositol 3,4-bisphosphate (PI(3,4)P ) localizes to the invadopodia, and positively regulates tumor cell invasion. In this study, we examined the effect of PI(3,4)P on focal adhesion dynamics in MDA-MB-231 basal breast cancer cells.

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Cancer vaccine application is limited to specific cancer types because few cancer-associated antigens are known to induce tumor rejection. Accordingly, we assessed the utility of Ad881, an oncolytic adenovirus in which viral replication was strictly regulated by the cancer-specific midkine promoter, as a cancer vaccine in a murine colorectal cancer model lacking specific cancer-associated antigens. In CT26 and CMT93 cells, Ad881 (multiplicity of infection: 100 or 1,000) showed stronger cytotoxicity and oncolysis than its equivalent replication-defective adenovirus, Ad884.

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Lynch syndrome (LS) and familial adenomatous polyposis (FAP) are major sources of hereditary colorectal cancer (CRC) and are associated with other malignancies. There is some heterogeneity in management strategies in Japan. We undertook a survey of management of hereditary CRC in hospitals that are members of the Japan Society of Colorectal Cancer Research.

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CD44, a transmembrane receptor, is expressed in the standard or variant form and plays a critical role in tumor progression and metastasis. This protein regulates cell adhesion and migration in breast cancer cells. We previously reported that phosphatidylinositol-4-phosphate (PI(4)P) at the Golgi regulates cell migration and invasion in breast cancer cell lines.

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α-Actinins (ACTNs) are known to crosslink actin filaments at focal adhesions in migrating cells. Among the four isoforms of mammalian ACTNs, ACTN1 and ACTN4 are ubiquitously expressed. Recently, ACTN4 was reported to enhance cancer cell motility, invasion, and metastasis.

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Downregulation of cell-cell adhesion and upregulation of cell migration play critical roles in the conversion of benign tumors to aggressive invasive cancers. In this study, we show that changes in cell-cell adhesion and cancer cell migration/invasion capacity depend on the level of phosphatidylinositol 4-phosphate [PI(4)P] in the Golgi apparatus in breast cancer cells. Attenuating SAC1, a PI(4)P phosphatase localized in the Golgi apparatus, resulted in decreased cell-cell adhesion and increased cell migration in weakly invasive cells.

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Success in islet transplantation-based therapies for type 1 diabetes mellitus and an extreme shortage of pancreatic islets have motivated recent efforts to develop renewable sources of islet-replacement tissue. Although pancreatic progenitor cells hold a promising potential, only a few attempts have been made at the prospective isolation of pancreatic stem/progenitor cells, because of the lack of specific markers and the development of effective cell culture methods. We found that prominin1 (also known as CD133) recognized the undifferentiated epithelial cells, whereas platelet-derived growth factor receptor beta (PDGFRbeta) was expressed on the mesenchymal cells in the mouse embryonic pancreas.

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Nodal signaling induces the formation of the endoderm and mesoderm during gastrulation. Nodal expression persists until the definitive endoderm progenitor has completely formed, and disappears thereafter. A tightly regulated Nodal expression system is essential for the differentiation of embryonic stem (ES) cells into distinct tissue lineages.

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