Publications by authors named "Toshihiro Uchihashi"

Neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS), present significant challenges owing to their complex pathologies and a lack of curative treatments. Early detection and reliable biomarkers are critical but remain elusive. Artificial intelligence (AI) has emerged as a transformative tool, enabling advancements in biomarker discovery, diagnostic accuracy, and therapeutic development.

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Bacteria in the oral microbiome are poorly identified owing to the lack of established culture methods for them. Thus, this study aimed to use culture-free analysis techniques, including bacterial single-cell genome sequencing, to identify bacterial species and investigate gene distribution in saliva. Saliva samples from the same individual were classified as inactivated or viable and then analyzed using 16S rRNA sequencing, metagenomic shotgun sequencing, and bacterial single-cell sequencing.

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Immune checkpoint inhibitors (ICIs), including anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and anti-programmed death-1 (PD-1) antibodies, have initiated a new era in the treatment of malignant melanoma. ICIs can be used in various settings, including first-line, adjuvant, and neo-adjuvant therapy. In the scope of this review, we examined clinical studies utilizing ICIs in the context of treating oral mucosal melanoma, a rare disease, albeit with an extremely poor prognosis, with a specific focus on unraveling the intricate web of resistance mechanisms.

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Article Synopsis
  • Amyotrophic lateral sclerosis (ALS) is a severe neurodegenerative disease that leads to progressive muscle weakness and paralysis, with no effective treatments currently available.
  • Recent studies show that 30% of ALS patients experience sensory symptoms, and that sensory neurons may also be affected alongside motor neurons, evidenced by nerve conduction issues and biopsies showing abnormalities.
  • The review highlights the role of sensory neuron dysfunction in ALS, including potential networks with motor neurons and the promise of targeting these sensory neurons for new therapeutic approaches.
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Article Synopsis
  • Body weight loss (BWL) is a serious issue after gastrectomy in gastric cancer patients, and current nutritional interventions aren't sufficient to address it.
  • This study involved 60 patients and evaluated their masticatory ability using functional tooth units (FTU), finding that those with fewer than 4 FTU experienced significantly more weight loss after surgery.
  • The research concluded that low FTU counts are an independent risk factor for greater BWL post-gastrectomy, suggesting that improving oral health may enhance nutritional status after surgery.
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In this study, we investigated whether toothbrushing timing affects cardiovascular disease risk. We enrolled 1675 patients aged ≥ 20 years who were hospitalized for surgery, examination, or medical treatment. The participants were categorized as follows based on toothbrushing: Group MN (brushing teeth after waking up and at night, n = 409), Group Night (brushing teeth at night but not upon waking up, n = 751), Group M (brushing teeth after waking up but not at night, n = 164), and Group None (not brushing teeth at all, n = 259).

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Transforming growth factor β (TGF-β) increases epithelial cancer cell migration and metastasis by inducing epithelial-mesenchymal transition (EMT). TGF-β also inhibits cell proliferation by inducing G1 phase cell-cycle arrest. However, the correlation between these tumor-promoting and -suppressing effects remains unclear.

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The epithelial-to-mesenchymal transition (EMT) is a critical process by which cancer cells acquire malignant features. However, the molecular mechanism and functional implications of EMT and the mesenchymal-to-epithelial transition (MET) in tumor progression remain elusive. In this study, we established two aggressive cancer cell lines from the human oral cancer cell line SAS, mesenchymal-like SAS-m4 and epithelial-like SAS-δ.

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Cleft palate is one of the major congenital craniofacial birth defects. The etiology underlying the pathogenesis of cleft palate has yet to be fully elucidated. Dissociation of the medial edge epithelium (MEE) at the contacting region of palatal shelves and subsequent migration or apoptosis of MEE cells is required for proper MEE removal.

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The prognosis of oral squamous cell carcinoma (OSCC) largely depends on the control of lymph node metastases. We evaluate the therapeutic efficacy of G47Δ, a third-generation oncolytic herpes simplex virus type 1 (HSV-1), in mouse tongue cancer models. Intratumoral injection with G47Δ prolonged the survival in all orthotopic models investigated.

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Melanoma is an aggressive type of cancer originating from the skin that arises from neoplastic changes in melanocytes. Transforming growth factor‑β (TGF‑β) is a pleiotropic cytokine and is known to contribute to melanoma progression by inducing the epithelial‑mesenchymal transition (EMT) program and creating an environment that favors tumor progression. There are three TGF‑β isoforms, TGF‑β1, TGF‑β2 and TGF‑β3, all of which engage in pro‑tumorigenic activities by activating SMAD signaling pathways.

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Background: Salivary duct carcinoma (SDC) is a rare, extremely aggressive malignancy that arises in the submandibular gland. It can metastasize locally early and therefore is an important differential diagnosis of metastatic disease in cervical lymph nodes or specific lymphadenitis such as tuberculous cervical lymphadenitis.

Case Summary: We report a case of SDC in the submandibular gland that presented diagnostic difficulty.

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Alveolar soft part sarcoma (ASPS) is a rare soft tissue sarcoma characterized by an alveolar or organoid arrangement of polygonal tumour cells separated by fibrovascular septa. A specific fusion gene [ASPS critical region 1 (ASPSCR1)-TFE3] was detected in ASPS. Despite being a slow-growing tumour without pain and dysfunction, ASPS is characterized by early metastasis, which leads to poor prognosis.

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Clear cell carcinoma (CCC) is a rare low-grade malignant salivary gland carcinoma. EWSR1-ATF1 fusion has been characterized as a consistent finding in CCC, with breakpoints described between EWSR1 exon 11 and ATF1 exon 3. So far, over 100 cases of CCC harboring EWSR1 rearrangement arising from salivary gland of the oral cavity have been reported.

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Clathrin regulates mitotic progression, in addition to membrane trafficking. However, the detailed regulatory mechanisms of clathrin during mitosis remain elusive. Here, we demonstrate novel regulation of clathrin during mitotic phase of the cell cycle.

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Three-dimensional (3D) cell culture systems have been used to obtain multicellular spheroidal cell aggregates, or spheroids, from cancer cells. However, it is difficult to efficiently prepare large tumor-derived spheroids from cancer cells. To circumvent this problem, we here used a tool equipped with removal membrane, called Spheroid Catch, for the selection and enrichment of large-sized and/or size-matched spheroids from human squamous cell carcinoma (SAS cells) without loss of recovery.

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We previously reported that an ELAS1 peptide containing 29 amino acids induces apoptotic death in U2OS human osteosarcoma cells following DNA double-strand break insults. Here, we show that ELAS1 also caused apoptosis in prostate adenocarcinoma DU145 cells and tongue squamous-cell carcinoma SAS cells. ELAS1 appears to be safe because it induced apoptosis only in cancer cells, not in normal KD cells.

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Cyclin G-associated kinase (GAK) harbors a consensus phosphorylation motif (Y412) for c-Src; however, its physiological significance remains elusive. Here, we show that GAK is phosphorylated by c-Src not only at Y412 but also at Y1149. An anti-GAK-pY412 antibody recognized the shifted band of GAK during M phase.

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Cyclin G1 (CycG1) and Cyclin G2 (CycG2) play similar roles during the DNA damage response (DDR), but their detailed roles remain elusive. To investigate their distinct roles, we generated knockout mice deficient in CycG1 (G1KO) or CycG2 (G2KO), as well as double knockout mice (DKO) deficient in both proteins. All knockouts developed normally and were fertile.

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