Publications by authors named "Tomizawa K"

Ribosome biogenesis is pivotal in the self-replication of life. In Escherichia coli, three ribosomal RNAs and 54 ribosomal proteins are synthesized and subjected to cooperative hierarchical assembly facilitated by numerous accessory factors. Realizing ribosome biogenesis in vitro is a critical milestone for understanding the self-replication of life and creating artificial cells.

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Background/aim: This study aimed to predict the optimal timing for adaptive radiation therapy (ART) using two-dimensional X-ray image-based water equivalent thickness (2DWET).

Patients And Methods: Forty patients with oropharyngeal and hypopharyngeal cancer underwent Computed Tomography (CT) rescanning during treatment. An adaptive score (AS) was proposed to guide ART decisions based on changes in four dose indices: target coverage, spinal cord dose, parotid gland dose, and over-dose volume.

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Bone-modifying agents (BMAs) have been widely used to reduce skeletal-related events, including pathological fractures. Herein, we aimed to clarify the incidence of pathological fractures caused by high-risk femoral bone metastases after palliative radiotherapy (RT) in the BMA era and evaluate the necessity of prophylactic surgical stabilization. We assessed 90 patients with high-risk femoral bone metastases, indicated by Mirels' scores ≥ 8, without pathological fractures and surgical fixations, who received palliative RT at our institution between January 2009 and December 2018.

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Mitochondrial tRNA (mt-tRNA) modifications play pivotal roles in decoding and sustaining tRNA stability, thereby enabling synthesis of essential respiratory complex proteins in mitochondria. Consequently, loss of human mt-tRNA modifications caused by mutations in the mitochondrial or nuclear genome can cause life-threatening mitochondrial diseases such as encephalopathy and cardiomyopathy. In this article, we first provide a comprehensive overview of the functions of mt-tRNA modifications, the responsible modification enzymes, and the diseases caused by loss of mt-tRNA modifications.

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Unlabelled: Over 170 types of chemical modifications have been identified in cellular RNAs across the three domains of life. Modified RNA is eventually degraded to constituent nucleosides, and in mammals, modified nucleosides are released into the extracellular space. By contrast, the fate of modified nucleosides in bacteria remains unknown.

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  • Human tRNA modifications at positions 16 and 17, known as D16/D17, are produced by the enzyme DUS1L, which was identified as essential for these modifications in glioblastoma cells.
  • Knocking out DUS1L leads to a loss of D16/D17 modifications and negatively impacts cell growth while its overexpression disrupts tRNA processing and translation.
  • Higher levels of DUS1L in glioma patients correlate with worse prognoses, highlighting its potential role in cancer biology and the need for further research into its functions.
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  • - This study investigated the acute toxicity of hypo-fractionated radiotherapy in Japanese breast cancer patients post-surgery, focusing on two treatment cohorts: moderately hypo-fractionated (Cohort M) and ultra-hypo-fractionated (Cohort U).
  • - A total of 123 patients were evaluated over 90 days after treatment, with the most common acute adverse events being grade 1 and 2, and no grade 3 or higher events reported.
  • - The study concluded that the rates of acute toxicity from these radiotherapy methods were considered acceptable, with 15% for Cohort M and 10% for Cohort U experiencing grade 2 or higher adverse events.
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In higher eukaryotes, tRNA methyltransferase 10A (TRMT10A) is responsible for N1-methylguanosine modification at position nine of various cytoplasmic tRNAs. Pathogenic mutations in TRMT10A cause intellectual disability, microcephaly, diabetes, and short stature in humans, and generate cytotoxic tRNA fragments in cultured cells; however, it is not clear how TRMT10A supports codon translation or brain functions. Here, we generated Trmt10a null mice and showed that tRNAGln(CUG) and initiator methionine tRNA levels were universally decreased in various tissues; the same was true in a human cell line lacking TRMT10A.

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Background: This study aimed to evaluate the association between spinopelvic alignment parameters and hip osteoarthritis progression after spinal alignment correction surgery for adult spinal deformity, focusing on the preoperative to postoperative change in spinopelvic alignment.

Methods: This retrospective study enrolled 100 adult spinal deformity patients (196 hip joints) who underwent spinal fusion surgery, after excluding four joints with previous total hip arthroplasty. Acetabular roof obliquity (ARO), center edge angle (CE) and Kellgren and Lawrence (KL) grade were measured in the hip joint.

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MTU1 controls intramitochondrial protein synthesis by catalyzing the 2-thiouridine modification of mitochondrial transfer RNAs (mt-tRNAs). Missense mutations in the MTU1 gene are associated with life-threatening reversible infantile hepatic failure. However, the molecular pathogenesis is not well understood.

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  • The study examined the effects of postoperative radiotherapy (PORT) after salvage neck dissection for patients with cervical lymph node recurrence in oral cavity cancer, focusing on outcomes like survival and recurrence rates.
  • After following 51 patients for about 7.4 years, the results showed a 7-year overall survival rate of 66.3% and a recurrence-free survival rate of 54.6%, with better outcomes for younger patients and those with isolated lymph node recurrence.
  • While PORT was effective, some patients experienced side effects like severe acute mucositis (35%) and less common long-term issues like osteoradionecrosis (4%) and laryngeal stenosis (2%).
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  • - The study evaluated the effectiveness of using anterior oblique portals (AOP) in radiotherapy for early-stage glottic cancer, aiming to minimize radiation exposure to critical areas like the internal carotid arteries and pharyngeal constrictor muscle.
  • - Out of 66 patients treated with radiotherapy, nearly half received AOP, and results showed no significant difference in local failure or survival rates between AOP and standard treatments, but AOP significantly reduced the incidence of severe acute mucositis.
  • - The findings suggest that AOP maintains effective radiation dose coverage to the cancer while reducing harmful exposure to important surrounding structures.
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  • Patients with unresectable pancreatic cancer (PC) can experience gastrointestinal bleeding due to tumor invasion, but there's no standard treatment established for this issue; palliative radiotherapy (PRT) is being explored as a potential option.
  • A study reviewed medical records from patients diagnosed with unresectable PC, identifying those with confirmed tumor bleeding who received PRT, which was given in various doses at the discretion of the doctors.
  • The results showed that 70% of PRT patients achieved hemostasis within about 8.5 days without significant adverse effects, and this treatment allowed 50% of those who stopped also to resume chemotherapy, leading to improved outcomes.
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Background/aim: Synchronous colorectal cancer, which occurs in approximately 4.8-8.4% of all colorectal cancers, has a genetic profile with a higher rate of v-raf murine sarcoma viral oncogene homolog B1 (BRAF) mutation and microsatellite instability-high than solitary colorectal cancer.

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Background: Volumetric modulated arc therapy (VMAT) for locally advanced rectal cancer (LARC) has emerged as a promising technique, but the planning process can be time-consuming and dependent on planner expertise. We aimed to develop a fully automated VMAT planning program for LARC and evaluate its feasibility and efficiency.

Methods: A total of 26 LARC patients who received VMAT treatment and the computed tomography (CT) scans were included in this study.

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  • A retrospective study was conducted on 80 patients receiving whole-brain radiotherapy (WBRT) for leptomeningeal metastasis (LM) from lung adenocarcinoma, focusing on survival outcomes and prognostic factors.
  • The median overall survival (OS) was 6.2 months, with EGFR/ALK mutant patients having significantly better OS (10.4 months) compared to wild-type patients (3.8 months).
  • Key factors associated with better OS included having EGFR/ALK mutations and a good performance status (ECOG PS of 0-1), indicating that these traits may improve survival chances for patients undergoing WBRT.
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Naked mole-rats (NMRs) have exceptional longevity and are resistant to age-related physiological decline and diseases. Given the role of cellular senescence in aging, we postulated that NMRs possess unidentified species-specific mechanisms to prevent senescent cell accumulation. Here, we show that upon induction of cellular senescence, NMR fibroblasts underwent delayed and progressive cell death that required activation of the INK4a-retinoblastoma protein (RB) pathway (termed "INK4a-RB cell death"), a phenomenon not observed in mouse fibroblasts.

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Understanding the physiology of human-induced pluripotent stem cells (iPSCs) is necessary for directed differentiation, mimicking embryonic development, and regenerative medicine applications. Pluripotent stem cells (PSCs) exhibit unique abilities such as self-renewal and pluripotency, but they lack some functions that are associated with normal somatic cells. One such function is the circadian oscillation of clock genes; however, whether or not PSCs demonstrate this capability remains unclear.

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Previous studies have revealed that age-related hearing loss (AHL) in Cdk5 regulatory subunit-associated protein 1 (Cdk5rap1)-knockout mice is associated with pathology in the cochlea. Here, we aimed to identify mitochondrial alterations in the cochlea of Cdk5rap1-knockout mice with AHL. Mitochondria in the spiral ganglion neurons (SGNs) and hair cells (HCs) were normal despite senescence; however, the mitochondria of types I, II, and IV spiral ligament fibrocytes were ballooned, damaged, and ballooned, respectively, in the stria vascularis.

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Background: Carbon-ion radiotherapy (C-ion RT) is effective for head and neck mucosal melanoma (HN-MM), including radioresistant mucosal melanoma. Melanoma also responds effectively to immune checkpoint inhibitors (ICIs). Data on the efficacy and safety of ICIs for HN-MM are insufficient.

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Background/aim: This study pursued two goals: Firstly, to search for anatomical structures strongly correlating with dose deterioration, and secondly to investigate the effectiveness of image registration focusing on critical anatomy by comparing it with a conventional method. The aim was to achieve robust image registration to correct for anatomical changes during treatment.

Patients And Methods: Twenty patients with head and neck cancer were enrolled, and 68 simulation computed tomography (CT) and rescan CT image sets were retrospectively analyzed.

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Article Synopsis
  • In mammalian mitochondria, the translation of the AUA codon relies on a modification of mitochondrial tRNA, which is catalyzed by the NSUN3 methylase.
  • Mutations in the NSUN3 gene are linked to mitochondrial diseases, and a total knockout of Nsun3 in mice leads to embryonic death between E10.5 and E12.5.
  • Heart-specific knockout mice display enlarged mitochondria and fragmented cristae, with enhanced heart contraction but decreased respiratory complex activity in older mice, highlighting the importance of tRNA modification for both development and aging.
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Purpose: This retrospective study aimed to evaluate the safety and efficacy of repeated carbon-ion radiation therapy (CIRT) in patients with intrahepatic recurrent hepatocellular carcinoma (HCC).

Methods And Materials: We reviewed patients who underwent repeated CIRT for intrahepatic recurrent HCC between 2010 and 2020.

Results: Forty-one patients received multiple CIRT courses for HCC.

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Cancer stem-like cells (CSCs) have a unique translation mode, but little is understood about the process of elongation, especially the contribution of tRNA modifications to the maintenance of CSCs properties. Here, it is reported that, contrary to the initial aim, a tRNA-modifying methylthiotransferase CDKAL1 promotes CSC-factor SALL2 synthesis by assembling the eIF4F translation initiation complex. CDKAL1 expression is upregulated in patients with worse prognoses and is essential for maintaining CSCs in rhabdomyosarcoma (RMS) and common cancers.

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