Publications by authors named "Fumitaka Takeshita"

Background: Oral hypofunction is the stage before oral dysfunction. The subjective symptoms of poor oral function and the decline in oral health-related quality of life (OHRQoL) that occur in the oral hypofunction stage can be missed.

Objective: This multicentre cross-sectional study was performed to examine the relationships between the test results for oral hypofunction, subjective frailty symptoms and OHRQoL of outpatients in dental clinics.

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  • - This study analyzed the impact of different dental prosthetic methods on patients with Kennedy Class I partial edentulism, focusing on aspects like oral function, frailty symptoms, and quality of life.
  • - 348 patients were divided into three groups: those with natural teeth (NT), those using removable partial dentures (RPD), and those with implant-supported fixed prostheses (ISFP), and their oral health was evaluated through various tests and questionnaires.
  • - Results indicated that the RPD group experienced poorer oral hygiene, reduced chewing ability, and higher rates of frailty symptoms compared to the ISFP group, suggesting that the type of prosthetic method significantly influences patients' oral health outcomes.
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Background: Noninvasive detection of early stage cancers with accurate prediction of tumor tissue-of-origin could improve patient prognosis. Because miRNA profiles differ between organs, circulating miRNomics represent a promising method for early detection of cancers, but this has not been shown conclusively.

Methods: A serum miRNA profile (miRNomes)-based classifier was evaluated for its ability to discriminate cancer types using advanced machine learning.

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  • Genetic changes in Rho GTPase-activating proteins, specifically ARHGAP6 and ARHGAP26, are commonly seen in diffuse-type gastric cancer, highlighting their importance in understanding the disease.
  • Researchers identified that these genetic alterations often occur together with mutations in the RhoA gene in cancers that have spread to the peritoneum, particularly in gastric and pancreatic cancers.
  • The study unveils that these mutations impair RhoA-ROCK-MLC2 signaling, leading to enhanced cell death through mechanisms involving cell adhesion and lysosomal dysfunction, suggesting potential new treatments targeting this pathway.
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Recurrence is one of the major issues in bladder cancer (BCa). Novel technologies, such as the detection of microRNAs carried by extracellular vesicles (EVs) in urine, have been proposed as biomarkers for detecting recurrence in BCa. Although the usefulness of microRNAs in body fluids from cancer patients has been reported, it is also known that they play essential roles in cancer progression.

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Urothelial carcinoma (UC) is an umbrella term for bladder cancers (BCa) and upper-tract urothelial carcinoma (UTUC), with BCa and UTUC sometimes detected concomitantly. The methods of detection for UC are often inaccurate or highly invasive, and, therefore, are thought to be unsatisfactory. Previously, we reported seven serum miRNAs as diagnostic markers for BCa.

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Oncogenic signalling confers tumour-progression advantages; thus, its pharmacological blockade is the best strategy for cancer chemotherapy. However, drug resistance and heterogeneous dependency of tumour hamper their therapeutic potential, suggesting the necessity for a new ubiquitous modality based on evading drug resistance. Here, we proposed a de novo addiction to oncogenic signalling (Dead-On) concept, wherein specific blockade of target molecules forces cancer cells to develop dependency on an oncogenic signalling.

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Spindle cell/sclerosing rhabdomyosarcoma (ssRMS) is a rare subtype of rhabdomyosarcoma (RMS) that has fascicular spindle cell and/or sclerosing morphology. SsRMS has a diverse molecular background and is categorized into three groups: congenital/infantile ssRMS with a gene fusion involving the NCOA2 and VGLL2, ssRMS with the MYOD1 mutation, and ssRMS with no recurrent identifiable genetic alterations. Because ssRMS is a newly defined disease concept of RMS, the optimal treatment methods have not been determined.

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Myxofibrosarcoma (MFS) is one of the most aggressive sarcomas with highly complex karyotypes and genomic profiles. Although a complete resection is required in the treatment of MFS, it is often not achieved due to its strong invasive nature. Additionally, MFS is refractory to conventional chemotherapy, leading to poor prognosis.

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  • The study aimed to identify serum miRNAs that can distinguish early gastric cancer (EGC) from non-cancer controls, involving 1417 patients and controls from a large cohort in Tokyo.
  • Using sensitive DNA chip technology, researchers evaluated miRNA profiles and developed diagnostic models based on the levels of specific miRNAs in two sets of samples.
  • The findings indicated high accuracy for detecting EGC, with the developed diagnostic index showing very high sensitivity and specificity, suggesting that these miRNAs could serve as effective non-invasive biomarkers for EGC detection.
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Dedifferentiated liposarcoma (DDLPS) is a highly malignant subtype of liposarcoma, with characteristic amplification of MDM2 and CDK4 (12q14-15). It is caused by the dedifferentiation of well-differentiated liposarcoma. DDLPS is refractory to conventional chemotherapy; thus, surgical resection is the primary treatment modality.

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Synovial sarcoma (SS) is defined as a monomorphic blue spindle cell sarcoma showing variable epithelial differentiation, and is characterized by a specific fusion gene, SS18-SSX. Although SS is rare, it accounts for approximately 8% of all soft tissue sarcomas, which occupies a significant proportion of soft tissue tumors. The prognosis of SS is unfavorable, with 5-year survival rate of 50-60%, and only a few anti-cancer agents are recommended for its treatment.

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Programmed cell death ligand-1 (PD-L1) overexpressed on cancer cells has emerged as a key inhibitor that maintains the immunosuppressive microenvironment through its interaction with the PD-1 receptor in cancer. Here, we demonstrated that miR-424-5p delivery via extracellular vesicles (EVs) derived from adipose tissue-mesenchymal stromal cells (AT-MSCs) partly promotes proinflammation and enhances antitumor cytotoxicity in vitro and in vivo. Triple negative breast cancer (TNBC) exhibits increased expression of , and is positively correlated with the overall survival of patients with TNBC.

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Background: Metastasis is the primary cause of death in cancer patients, and its management is still a major challenge. Epithelial to mesenchymal transition (EMT) has been implicated in the process of cancer metastasis, and its pharmacological interference holds therapeutic promise.

Methods: Traf2- and Nck-interacting kinase (TNIK) functions as a transcriptional coregulator of Wnt target genes.

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Dedifferentiated liposarcoma (DDLPS) is one of the four subtypes of liposarcomas; it is characterized by the amplification of the 12q13-15 region, which includes MDM2 and CDK4 genes. DDLPS has an extremely high local recurrence rate and is refractory to chemotherapy and radiation, which leads to poor prognosis. Therefore, a novel therapeutic strategy should be urgently established for improving the prognosis of DDLPS.

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The tenacity of late recurrence of estrogen receptor (ER)-positive breast cancer remains a major clinical issue to overcome. The administration of endocrine therapies within the first 5 years substantially minimizes the risk of relapse; however, some tumors reappear 10-20 years after the initial diagnosis. Accumulating evidence has strengthened the notion that long noncoding RNAs (lncRNAs) are associated with cancer in various respects.

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  • The SWI/SNF chromatin remodeling complex, especially the SMARCA4 protein, is vital for regulating chromatin structure and transcription, and its mutations are commonly found in lung adenocarcinoma (LADC) patients.
  • Mutations in SMARCA4 often lead to loss-of-function, resulting in increased DNA replication stress and making LADC cells more sensitive to ATR inhibitors (ATRi).
  • The study reveals that SMARCA4 loss heightens heterochromatin formation, causing stalled DNA replication and single-stranded DNA issues, which together increase vulnerability to ATRi, potentially serving as a biomarker for treatment efficacy.
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Hepatocellular carcinoma (HCC) is the fourth leading cause of cancer deaths worldwide. The high mortality rate in HCC is largely due to the difficulty of early detection. In this study, to improve patient outcomes, serum samples from 345 patients with HCC, 46 patients with chronic hepatitis (CH), 93 patients with liver cirrhosis (LC), and 1,033 healthy individuals were analyzed with microRNA (miRNA) microarrays.

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The role of microRNAs (miRNAs) during mouse early development, especially in endoderm germ layer formation, is largely unknown. Here, via miRNA profiling during endoderm differentiation, we discovered that miR-124a negatively regulates endoderm lineage commitment in mouse embryonic stem cells (mESCs). To further investigate the functional role of miR-124a in early stages of differentiation, transfection of embryoid bodies with miR-124a mimic was performed.

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Importance: Patients with late-stage esophageal squamous cell carcinoma (ESCC) have a poor prognosis. Noninvasive screening tests using serum microRNAs (miRNAs) to accurately detect early-stage ESCC are needed to improve mortality.

Objective: To establish a model using serum miRNAs to distinguish patients with ESCC from noncancer controls.

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  • This study investigates the role of the p53 tumor-suppressor pathway and its connection to miR-101 in lung cancer, aiming to improve chemotherapy strategies.
  • Researchers used microarray analysis to find that miR-101 is activated by p53 under nucleolar stress, contributing to cancer cell regulation and affecting tumor growth.
  • Findings highlight that low levels of miR-101 correlate with worse outcomes in lung cancer patients with functional p53, suggesting that activating the p53-miR-101 circuit could enhance cancer treatment effectiveness.
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Since comprehensive analysis of the mammalian genome revealed that the majority of genomic products are transcribed in long non-coding RNA (lncRNA), increasing attention has been paid to these transcripts. The applied next-generation sequencing technologies have provided accumulating evidence of dysregulated lncRNA in cancer. The implication of this finding can be seen in many forms and at multiple levels.

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Advanced ovarian cancers are highly metastatic due to frequent peritoneal dissemination, resulting in dismal prognosis. Here we report the functions of cancer-derived extracellular vesicles (EVs), which are emerging as important mediators of tumour metastasis. The EVs from highly metastatic cells strongly induce metastatic behaviour in moderately metastatic tumours.

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Metastasis is the main cause of cancer mortality for many types of cancer; however, difficulties remain in effectively preventing metastasis. It has been recently and widely reported that cancer-derived extracellular vesicles (EVs) contribute to cancer metastasis. Thus, therapeutic strategies targeting cancer-derived EVs hold great promise because of the possibility of EVs driving the cancer microenvironment toward metastasis.

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Osteosarcoma is the most common primary malignancy in bone. Patients who respond poorly to induction chemotherapy are at higher risk of adverse prognosis. The molecular basis for such poor prognosis remains unclear.

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