Biomedical subjects

Shuhei Noda

Publications and source records attributed to Shuhei Noda.

4 recordsLinked to original sources

PubMed2026

Dual Mechanisms Underlie the Repression of Repressor Element 1-Silencing Transcription Factor Expression in Lung Neuroendocrine Carcinoma Cells.

Recent advances in genetic analysis have led to further subtyping of small-cell lung carcinoma (SCLC). The major subtypes of SCLC are the achaete-scute family bHLH transcription factor 1 (ASCL1)-predominant (SCLC-A), neuronal differentiation 1 (NEUROD1)-predominant (SCLC-N), and POU class 2 homeobox 3 (POU2F3) (SCLC-P) subtypes. SCLC-A and SCLC-N tumors express chromogranin A (CHGA) and synaptophysin (SYP), but SCLC-P tumors do not. Large-cell neuroendocrine carcinoma, another type of neuroendocrine carcinoma (NEC), also frequently expresses CHGA and SYP. Because CHGA and SYP expression is controlled by a transrepressor, repressor element 1-silencing transcription factor (REST), the mechanisms underlying REST suppression in NEC were investigated, with a focus on miRNAs and epigenetics, to determine the causes of the differences in the expression of CHGA and SYP between SCLC-A/N and SCLC-P cells. The results showed that miR-375-3p, which was induced by ASCL1 and NEUROD1, repressed REST expression by binding to the 3'-untranslated region of REST mRNA. Bisulfite sequencing and experiments using a DNA methyltransferase inhibitor, a histone deacetylase inhibitor, and chromatin immunoprecipitation-based quantitative PCR revealed that promoter/enhancer hypermethylation and histone deacetylation causes REST gene inactivation in SCLC-A/N. These phenomena were also observed in a large-cell neuroendocrine carcinoma cell line that expressed high levels of ASCL1 and NEUROD1. Taken together, these findings suggest that NEC has dual repressive effects on REST expression, resulting in strict regulation of the expression of CHGA, SYP, and other REST-controlled neuronal/neuroendocrine-specific genes.

Humans↗

PubMed2003

Gene expression of detoxifying enzymes in AhR and Nrf2 compound null mutant mouse.

The arylhydrocarbon receptor (AhR) regulates the expression of cytochrome P450 (CYP)-1 gene family members which catalyze xenobiotic Phase I metabolism, while Nrf2 exerts the concerted regulation of Phase II enzyme genes. We generated AhR and Nrf2 compound null mutant mice to examine the integrated function of AhR- and Nrf2-regulated enzymes in detoxification. Furthermore, we used this mouse model, by administering three different classes of chemical inducers, to examine how xenobiotic metabolism may be influenced in the absence of signals transduced by AhR or Nrf2. The compound mutant mice responded only weakly to AhR ligand or Phase II inducer, while they displayed a clear response to phenobarbital, an inducer of the CYP2B family through another, unrelated transcription factor. Here, we report an initial characterization of the AhR-Nrf2 double mutant mice, which may serve as a simplified bioassay system to evaluate xenobiotic toxicity and metabolic biotransformation of various drugs and environmental chemicals.

Animals↗

PubMed2003

Different radiation susceptibility among five strains of mice detected by a skin reaction.

Published reports about skin reactions to radiotherapy, especially among breast-cancer patients, suggest that there are interindividual differences in the normal tissue response, and genetic factors are thought to be involved in this variation. An analysis of murine strain differences may reveal the mechanism of genetic factors in the extent of normal tissue damage from irradiation for several endpoints. The variation in the radiation susceptibility was observed when the skin of mice from strains A/J, C3H/HeMs, C57BL/6J, C.B.17/Icr-scid and C3H-scid was irradiated with a single dose ranging from 10 to 60 Gy, using Cs-137 gamma rays. The active skin reaction of A/J mice lasted for months. C3H/HeMs mice showed dose-dependent skin damage, and consequently recovered to a state of mild damage within 40 days after local irradiation. The time course of the response in C57BL/6J mice was shorter than in A/J mice. The 2 strains of scid mice exhibited severe damage after irradiation at any dose from 20 to 50 Gy, and did not show any dose dependency. The variation between murine strains in macroscopic and histopathological changes in skin during the progression and resolution of damage caused by irradiation suggests an inter-strain variation in the expression of genes involved in injury, apoptosis, repair, and remodeling.

Animals↗

PubMed2002

[RadGenomics project].

Human health conditions are largely determined by a complex interplay among genetic susceptibility, environmental factors, and aging. The RadGenomics project, which began in April 2001, promotes analysis of genes in response to irradiation, identification of their allelic variants in the human population, development of an effective procedure for quantitating individual radio-sensitivity, and analysis of the interrelationship between genetic heterogeneity and susceptibility to irradiation. Major groups of genes with which the project will concern itself include DNA repair genes, cell cycle genes, oncogenes, tumor suppressor genes, genes for programmed cell death, genes for signal transduction, and genes for oxidative processes. The outcome of the RadGenomics project should lead to improved protocols for personalized radiotherapy and reduce the possible side effects of treatment. The project will contribute to future research on the molecular mechanisms of radiation sensitivity in humans and stimulate the development of new high-throughput technology for a broader application of the biological and medical sciences. Identification of functionally important polymorphisms in the radiation response genes may determine individual differences in sensitivity to radiation exposure. The staff members, who are specialists in a variety of fields including genome science, radiation biology, medical science, molecular biology, and bioinformatics, have come to the RadGenomics project from various universities, companies, and research institutes.

Animals↗