A5042674032- Renal cell carcinoma treatment
- Cancer, Hypoxia, and Metabolism
- Renal and related cancers
- Total Knee Arthroplasty Outcomes
- Cancer Genomics and Diagnostics
- Glycosylation and Glycoproteins Research
- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Orthopaedic implants and arthroplasty
- Epigenetics and DNA Methylation
- RNA modifications and cancer
- Orthopedic Infections and Treatments
- Genetic and Kidney Cyst Diseases
- Peptidase Inhibition and Analysis
- Bladder and Urothelial Cancer Treatments
- Medical Imaging and Pathology Studies
- Adipose Tissue and Metabolism
- Cancer-related Molecular Pathways
- Multiple and Secondary Primary Cancers
- Knee injuries and reconstruction techniques
- Cancer Research and Treatments
- Cancer Immunotherapy and Biomarkers
- Gastrointestinal Tumor Research and Treatment
- Multiple Myeloma Research and Treatments
- Cancer Diagnosis and Treatment
- Neuroendocrine Tumor Research Advances
Yokohama City University
2014-2024
Kurume University
2021-2022
Yokohama City University Hospital
2017-2022
Japan Meteorological Agency
2022
Meteorological Research Institute
2021-2022
RIKEN Center for Computational Science
2022
Azumi Hospital
2010-2022
National Hospital Organization
2022
Tohoku University Hospital
2020
Tohoku University
2010-2019
HIF (hypoxia-inducible factor) is a transcription factor that plays pivotal role in cellular adaptation to changes oxygen availability. In the presence of oxygen, targeted for destruction by an E3 ubiquitin ligase containing von Hippel–Lindau tumor suppressor protein (pVHL). We found human pVHL binds short HIF-derived peptide when conserved proline residue at core this hydroxylated. Because hydroxylation requires molecular and Fe2+, modification may play key mammalian sensing.
Biallelic inactivation of the von Hippel-Lindau tumor suppressor gene (VHL) is linked to development hereditary (VHL-associated) and sporadic clear-cell renal carcinomas as well other abnormalities. The VHL product, pVHL, part an E3 ubiquitin ligase complex that targets alpha subunits heterodimeric transcription factor HIF (hypoxia-inducible factor) for degradation in presence oxygen. Here we report a HIF2alpha variant lacking both its two prolyl hydroxylation/pVHL-binding sites prevents...
The product of the von Hippel-Lindau gene, pVHL, targets alpha subunits heterodimeric transcription factor hypoxia-inducible (HIF) for polyubiquitination in presence oxygen. binding pVHL to HIF is governed by enzymatic hydroxylation conserved prolyl residues within peptidic motifs present HIFalpha family members. By using a biochemical purification strategy, we have identified human homolog Caenorhabditis elegans Egl9 as hydroxylase. In addition, studied activity structurally diverse...
KL-6, surfactant protein (SP)-A, SP-D, and monocyte chemoattractant protein-1 (MCP-1) are reported to be sensitive markers for interstitial lung diseases (ILD). However, each marker has been studied independently. The aim of this study was a comparative analysis the diagnostic values these markers. Subjects consisted 33 patients with ILD (21 cases idiopathic pulmonary fibrosis 12 associated collagen vascular diseases) 82 control subjects (12 bacterial pneumonia 70 healthy volunteers)....
Circulating levels of KL-6, a high MW glycoprotein (MUC1 mucin), are elevated in majority patients with number interstitial lung diseases, including idiopathic pulmonary fibrosis (IPF). However, KL-6 vary from patient to patient. The aim the present study was determine whether serum level at time diagnosis predicts prognosis IPF.The relationship between clinical variables and 27 IPF were analysed retrospectively. made by histological examination (n = 16) or on findings high-resolution CT...
Searching for early predictive markers of the therapeutic effects high-dose corticosteroids ("pulse therapy") on patients with rapidly progressing idiopathic pulmonary fibrosis (IPF), we evaluated 14 such patients, who had received weekly pulse therapy at least 3 wk. Eight responded to treatment and survived. However, six failed respond, all them died within mo after treatment. Serum levels KL-6 (MUC1 mucin), neutrophil elastase (NE), lactate dehydrogenase (LDH) were measured before, 1 wk...
Abstract To delineate more precisely the somatic von Hippel‐Lindau disease (VHL) gene alteration as well to elucidate its etiologic role in renal tumorigenesis, we examined a total of 240 sporadic cell carcinomas (RCCs) for VHL alterations by DNA‐SSCP followed sequencing, methylation‐specific PCR assay, microsatellite LOH study, and Southern blot analysis. Intragenic mutation was found exclusively clear‐cell or variant‐type RCCs at frequency 51% (104/202). Hypermethylation promoter region...
Obesity represents chronic inflammatory states promoted by pro-inflammatory M1-macrophage infiltration into white adipose tissue (WAT), thereby inducing insulin resistance. Herein, we demonstrate the importance of an ER stress protein, CHOP, in determining macrophage (ATM) polarity and systemic sensitivity. A high-fat diet (HFD) enhances with CHOP upregulation adipocytes. deficiency prevents HFD-induced resistance glucose intolerance ATM M2 predomination Th2 cytokine WAT. Whereas suppresses...
A great deal of attention has been focused on the antitumor effects anti-MUC1 humoral and cellular responses. We examined whether antibody is present in patients with lung cancer, evaluated its prognostic value. Serum was obtained from 30 nonresectable, non–small cell cancer (NSCLC) 60 healthy volunteers. The presence determined by enzyme-linked immunosorbent assay. were observed for a median follow-up time 54.0 mo. Overall survival estimated Kaplan-Meier method. Multivariate analyses...
Background— The processes of arteriosclerosis, including atherosclerosis and vascular remodeling, are affected by interactions among numerous biological pathways such as responses to inflammation, oxidative stress, endoplasmic reticulum stress. C/EBP homologous protein (CHOP), which is well known induce cellular apoptosis in response severe reportedly upregulated plaque lesions. Methods Results— We examined the effects CHOP deficiency on 2 types arteriosclerosis: cuff injury–induced...
Various molecular-targeting therapies have become available for the treatment of advanced renal cell carcinoma (RCC). Accurate prognostication is desirable choosing appropriate individual patients. 18F-2-fluoro-2-deoxyglucose positron-emission tomography/computed tomography (FDG PET/CT) a non-invasive tool evaluating glucose accumulation, which can be an index biological characteristics cancer. We prospectively evaluated FDG PET/CT as prognostic indicator in patients with RCC. A total 101...
Bladder cancers have been characterized as a tumor group in which the immunological response is relatively well preserved. Programmed death ligand 1 (PD-L1, B7-H1, CD274) has shown to be expressed several malignancies, including bladder cancer. However, clinicopathological impact of this biomarker not yet established. In present study, quantitative real-time polymerase chain reaction (qPCR) was performed using paired normal and cancerous cancer tissue investigate PD-1/PD-L1 gene expression....
Extensive allelotyping studies have implicated several tumor-suppressor loci on chromosomes 3p, 5q, 6q, 8p, 9pq, 10q, 11q, 14q, 17p, 18q and 19p in human kidney tumorigenesis. The PTEN (also called MMAC1 TEP1) gene, a candidate tumor suppressor located at chromosome 10q23.3, is mutated variety of sporadic malignancies as well patients with Cowden disease. To investigate the potential role gene renal tumorigenesis, we searched for abnormalities 68 primary renal-cell carcinomas (RCCs) 17...
We examined the biogenesis of von Hippel-Lindau (VHL) tumor suppressor protein (pVHL) in vitro and vivo. pVHL formed a complex with cytosolic chaperonin containing TCP-1 (CCT or TRiC) en route to assembly elongin B/C subsequent formation VCB-Cul2 ubiquitin ligase. Blocking interaction resulted accumulation within CCT complex. present purified VHL-CCT complexes, when added rabbit reticulocyte lysate, proceeded form VCB VCB-Cul2. Thus, likely functions, at least part, by retaining VHL chains...