Masafumi Ito

Masafumi Ito
Tokyo Metropolitan Institute of Gerontology | TMIG · Research Team for Mechanism of Aging

MD, PhD

About

139
Publications
12,835
Reads
How we measure 'reads'
A 'read' is counted each time someone views a publication summary (such as the title, abstract, and list of authors), clicks on a figure, or views or downloads the full-text. Learn more
8,813
Citations
Citations since 2017
30 Research Items
2849 Citations
20172018201920202021202220230100200300400500
20172018201920202021202220230100200300400500
20172018201920202021202220230100200300400500
20172018201920202021202220230100200300400500

Publications

Publications (139)
Article
Growth differentiation factor 15 [GDF15], a possible biomarker of mitochondrial function related to ageing was reported to be associated an increased risk of cardiovascular events. However, there were no previous data that investigated the relationship between masked hypertensive effect and serum GDF15 level. In outpatients clinic in which evaluate...
Article
Perforin secreted from cytotoxic T cells and natural killer cells play important roles in anti-tumor immunoreaction leading to cancer cell apoptosis. The aim of this study is to investigate whether perforin-rich tumor microenvironment could inhibit tumor growth. Advanced prostate cancer (PC) expresses high amount of prostate-specific antigen (PSA)...
Article
Mitochondria are dysfunctional in post-senescent cells. Therefore, age-dependent impairment of mitochondrial energy production accompanied by excessive mitochondrial reactive oxygen species (ROS) is proposed to be a key driver of cellular senescence, which is a state of irreversible cell cycle arrest. However, it remains to be clarified whether mit...
Article
Full-text available
Perforin secreted from cytotoxic lymphocytes plays a critical role in cancer immunosurveillance. The aim of this study was to investigate the therapeutic potential of liposomes containing perforin expression vector driven by the promotor of prostate-specific antigen (PSA). The anti-tumor effect of perforin was analyzed using prostate cancer (PC) PC...
Article
Molecular hydrogen (H2) is an antioxidant and anti-inflammatory agent; however, the molecular mechanisms underlying its biological effects are largely unknown. Similar to other gaseous molecules such as inhalation anesthetics, H2 is more soluble in lipids than in water. A recent study demonstrated that H2 reduces radical polymerization-induced cell...
Article
Background/aim: De-differentiation is a key step for the progression of cancer cells. This study investigated the anti-tumor effect of kartogenin (KGN), which has the ability to differentiate cells, on prostate cancer (PC) cells. Materials and methods: The effects of KGN on androgen receptor (AR) nuclear localization, prostate-specific antigen (...
Article
Full-text available
We aimed to develop a sandwich ELISA to detect prostate-specific membrane antigen (PSMA) on small extracellular vesicles (EVs) using T-cell immunoglobulin domain and mucin domain-containing protein 4 (Tim4) as a capture molecule for EVs and to evaluate its diagnostic potential in urologic malignancies. First, we optimized the conditions for sandwic...
Article
Aim: To identify novel diagnostic markers for renal cell carcinoma (RCC), we analyzed miRNAs in serum extracellular vesicles (EVs). Materials and methods: EVs were purified from serum of healthy controls and patients with localized and advanced RCC using T-cell immunoglobulin domain and mucin domain-containing protein 4 conjugated to magnetic be...
Article
Background/aim: To identify novel biomarkers for prostate cancer (PC), we evaluated changes of miRNAs contained in serum small extracellular vesicles (EVs) in patients who received low dose rate prostate brachytherapy (BT). Materials and methods: EVs were isolated from the pooled serum of 10 PC patients prior to and 1 month after BT. miRNA profi...
Article
Background: Cabazitaxel (CBZ) is now widely used for prostate cancer (PC) patients resistant to docetaxel (DOC), however, most patients eventually acquire resistance. It will, therefore, be of great benefit to discover novel therapeutic target for the resistance. We aimed to identify candidate therapeutic targets for CBZ-resistance by proteomic an...
Article
Mitochondria are multifunctional organelles that regulate diverse cellular processes. Mitochondrial stress, including stress generated by electron transport chain defects and impaired mitochondrial proteostasis, is intimately involved in various diseases and pathological conditions. Sepsis is a life-threatening condition that occurs when an imbalan...
Article
Full-text available
Aims: Sarcopenia is a serious problem because of its poor prognosis. Growth differentiation factor 15 (GDF15) is associated with mitochondrial dysfunction, inflammation, insulin resistance and oxidative stress, which may play crucial roles for the development of sarcopenia. We aimed to examine whether serum GDF15 level is associated with muscle ma...
Article
Full-text available
Background: There has been no clinically useful diagnostic or prognostic biomarker for renal cell carcinoma (RCC). Serum γ-glutamyltransferase (GGT) activity has been reported to be a prognostic marker for several types of cancer including RCC. Exosomes or small extracellular vesicles present in body fluids have potential as a biomarker. We have r...
Article
Full-text available
Background Docetaxel is first-line chemotherapy for castration-resistant prostate cancer (CRPC), but most patients acquire docetaxel resistance. CD44 has been shown to be involved in drug resistance of cancers including prostate cancer. We hypothesized that CD44 in serum exosomes could be a diagnostic marker for docetaxel resistance in CRPC patient...
Conference Paper
Introduction: Antibody therapy has been successfully used for several caners, but the efficacy is still limited. To select patients that respond well to the therapy, development of companion diagnostics is essential. Although D-L1 expression determined by immunohistochemistry has been shown to be a marker to select patients with non-small-cell lung...
Article
Background: Exosomes or small extracellular vesicles secreted from cells are nanovesicles with a diameter of 40-150 nm, which play a number of roles in both physiologic and pathologic processes. In Graves' disease (GD), autoantibodies bind to the thyrotropin receptor (TSHR) on the surface of thyroid follicular epithelial cells and stimulate thyroid...
Article
Unlike urinary tract infection (UTI), asymptomatic bacteriuria (ABU) should not be treated with some exceptions such as pregnant women and patients who will undergo traumatic urologic interventions. However, there has been no clinically available marker for their differential diagnosis. Exosomes or small extracellular vesicles carry proteins contai...
Article
p>Purposes of the study: Clear renal cell carcinoma (ccRCC) is one of the most lethal malignant tumors. Molecular targeted therapies have been used to improve outcomes for metastatic or advanced ccRCC. However, currently approved therapies have limited success and a cure remains elusive. Since ccRCC could be curable if diagnosed at the early stage,...
Article
Full-text available
We investigated age-related changes in in vivo and in vitro functions and gene expression of the bladder of male and female mice. Mature and aged (12 and 27-30 month old) C57BL/6 mice of both sexes were used. Frequency volume, conscious free-moving cystometry and detrusor contractile and relaxant properties in in vitro organ bath were evaluated. mR...
Article
We isolated a cryptic genospecies of Haemophilus influenzae referred to as 'Haemophilus quentini' in the urethra of 3 men complaining of urethritis symptoms. H. influenzae strains, which had been isolated from the urethra in 77 of 1518 men complaining of urethritis symptoms, identified by the conventional test, and stored, were re-cultured for this...
Article
Exosomes or microvesicles that are secreted from cells are considered to play important roles in tumor microenvironment. Carbonic anhydrase 9 (CA9), which is induced by hypoxia-inducible factor 1 (HIF1) in response to hypoxia, is overexpressed in many types of cancer including renal cell carcinoma (RCC). We examined the expression level of CA9 in s...
Article
Purposes of the study: Exosome has been demonstrated to be a useful non-invasive biomarker for several cancers including prostate cancer. For better understanding cancer-derived exosome, their proteomic analysis is necessary. The aim of this study is to establish the method for isolation and analysis of prostate cancer-related exosomes. Experimenta...
Article
Full-text available
Background Exosomes or extracellular vesicles have the potential as a diagnostic marker for various diseases including cancer. In order to identify novel exosomal markers for prostate cancer (PC), we performed proteomic analysis of exosomes isolated from PC cell lines and examined the usefulness of the marker in patients. Methods Exosomes isolated...
Article
Full-text available
Inhalation of molecular hydrogen (H2) gas ameliorates oxidative stress-induced acute injuries in the brain. Consumption of water nearly saturated with H2 also prevents chronic neurodegenerative diseases including Parkinson's disease in animal and clinical studies. However, the molecular mechanisms underlying the remarkable effect of a small amount...
Article
Advanced bladder cancer is treated mainly with gemcitabine and cisplatin, but most patients eventually become resistance. Androgen receptor (AR) signaling has been implicated in bladder cancer as well as other types of cancer including prostate cancer. In this study, we investigated the expression and role of AR in gemcitabine-resistant bladder can...
Article
Purpose: We evaluated aging-related bladder dysfunctions and biological changes in the bladder and dorsal root ganglia (DRG) in rats, and investigated whether long-term caloric restriction (CR) may have preventive effects on these changes. Materials and methods: Male Fischer 344 rats were divided into young (6 months-old) fed ad libitum (Y), old...
Article
Background/Aim: Advanced renal cell carcinoma is treated with mammalian target of rapamycin (mTOR) inhibitors or tyrosine kinase inhibitors (TKIs). The effects of these drugs are, however, limited and novel treatment strategies are required. Clear-cell type renal cell carcinoma (ccRCC) is chemo-resistant, in part, due to expression of multidrug res...
Article
Full-text available
Therapeutic effects of molecular hydrogen for a wide range of disease models and human diseases have been investigated since 2007. A total of 321 original articles have been published from 2007 to June 2015. Most studies have been conducted in Japan, China, and the USA. About three-quarters of the articles show the effects in mice and rats. The num...
Article
Objective: The diagnosis of mitochondrial disorders (MDs) is occasionally difficult because patients often present with solitary, or a combination of, symptoms caused by each organ insufficiency, which may be the result of respiratory chain enzyme deficiency. Growth differentiation factor 15 (GDF-15) has been reported to be elevated in serum of pa...
Article
The acquisition of drug resistance is one of the most malignant phenotypes of cancer and identification of its therapeutic target is a prerequisite for the development of novel therapy. MicroRNAs (miRNAs) have been implicated in various types of cancer and proposed as potential therapeutic targets for patients. In the present study, we aimed to ide...
Article
Docetaxel is used as the first-line chemotherapy for castration-resistant prostate cancer (CRPC), but docetaxel resistance occurs in part owing to induction of P-glycoprotein (P-gp) encoded by multidrug resistance protein 1 (MDR1) gene. A recently developed taxane-cabazitaxel-has poor affinity for P-gp and is thereby effective in docetaxel-resistan...
Article
Treatment with taxanes for castration-resistant prostate cancer often leads to the development of resistance. It has been recently demonstrated that exosomes present in the body fluids contain proteins and RNAs in the cells from which they are derived and could serve as a diagnostic marker for various diseases. In the present study, we aimed to ide...
Article
Molecular hydrogen (H2) is an agent with potential applications in oxidative stress-related and/or inflammatory disorders. H2 is usually administered by inhaling H2-containing air (HCA) or by oral intake of H2-rich water (HRW). Despite mounting evidence, the molecular mechanism underlying the therapeutic effects and the optimal method of H2 adminis...
Article
Full-text available
Royal jelly (RJ) produced by honeybees has been reported to possess diverse health-beneficial properties and has been implicated to have a function in longevity across diverse species as well as honeybees. 10-Hydroxy-2-decenoic acid (10-HDA), the major lipid component of RJ produced by honeybees, was previously shown to increase the lifespan of Cae...
Article
Bladder function is often impaired with aging. In other organs, caloric restriction (CR) has been shown to have a prophylactic effect on biological changes associated with aging. We aimed to test the hypothesis that long-term CR can prevent age-related impairment of bladder function in the rat. Fischer 344 male rats were divided into three groups:...
Article
Pyruvate therapy is a promising approach for the treatment of mitochondrial diseases. To identify novel biomarkers for diagnosis and to evaluate therapeutic efficacy, we performed microarray analysis of 2SD cybrid cells harboring a MELAS-causing mutation and control cells treated with either lactate or pyruvate. We found that expression and secreti...
Article
Background/aim: Exosomes have been demonstrated to be useful non-invasive biomarkers for several cancers including prostate cancer. Since normal cells also secrete exosomes, isolation of cancer-derived exosomes from blood is a prerequisite for their better understanding. The aim of this study is to establish the method for isolation of prostate ca...
Article
Full-text available
Objective Mitochondrial respiratory chain disorder (MRCD) is an intractable disease of infants with variable clinical symptoms. Our goal was to identify the causative mutations in MRCD patients.Methods The subjects were 90 children diagnosed with MRCD by enzyme assay. We analyzed whole mitochondrial DNA (mtDNA) sequences. A cybrid study was perform...
Article
We sought to elucidate the effect of an ascorbic acid (AA) deficiency on gene expression, because the water soluble antioxidant AA is an important bioactive substance in vivo. We performed microarray analyses of the transcriptome in the liver from senescence marker protein-30 (SMP30)/gluconolactonase (GNL) knockout (KO) mice, which are unable to sy...
Article
Castration-refractory prostate cancer (CRPC) is treated with taxane-based chemotherapy, but eventually becomes drug resistant. It is thus essential to identify novel therapeutic targets for taxane resistance in CRPC patients. We investigated the role of the chemokine (C-C motif) receptor 1 (CCR1) and its ligand, chemokine (C-C motif) ligand 5 (CCL5...
Article
Full-text available
Background Senescence-accelerated mice (SAM) are a series of mouse strains originally derived from unexpected crosses between AKR/J and unknown mice, from which phenotypically distinct senescence-prone (SAMP) and -resistant (SAMR) inbred strains were subsequently established. Although SAMP strains have been widely used for aging research focusing o...
Article
Full-text available
Background There is accumulating evidence that obesity is closely associated with an impaired free fatty acid metabolism as well as with insulin resistance and inflammation. Excessive fatty acid uptake mediated by fatty acid translocase CD36 plays an important role in hepatic steatosis. Molecular hydrogen has been shown to attenuate oxidative stres...
Article
Neuroinflammation and oxidative stress are involved in the pathogenesis of neurodegenerative diseases such as Alzheimer's diseases and Parkinson's disease. Naturally derived kavalactones isolated from Piper methysticum (Piperaceae) have been shown to exhibit neuroprotective effects. We have previously reported that a chemically synthesized kavalact...
Article
Pyruvate treatment was found to alleviate clinical symptoms of mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome and is highly promising therapeutic. Using capillary electrophoresis time-of-flight mass spectrometry (CE-TOFMS), we measured time-changes of 161 intracellular and 85 medium metabolites to...
Article
Full-text available
Effects of molecular hydrogen on various diseases have been documented for 63 disease models and human diseases in the past four and a half years. Most studies have been performed on rodents including two models of Parkinson's disease and three models of Alzheimer's disease. Prominent effects are observed especially in oxidative stress-mediated dis...
Article
Full-text available
Lactulose is a synthetic disaccharide that can be catalyzed only by intestinal bacteria in humans and rodents, and a large amount of hydrogen is produced by bacterial catalysis of lactulose. We previously reported marked effects of ad libitum administration of hydrogen water on prevention of a rat model of Parkinson's disease (PD). End-alveolar bre...
Article
Full-text available
Hepatitis B virus X (HBX) protein has been reported to induce upregulation of β-catenin, a known proto-oncogene, in p53-knockout and p53-mutant hepatic cell lines both in a GSK-3β-dependent manner and via interaction with adenomatous polyposis coli, which results in protection from β-catenin degradation. In this study, we describe a novel mechanism...
Article
MicroRNAs (miRNAs) are small non-coding RNAs that control protein expression through translational inhibition or mRNA degradation. MiRNAs have been implicated in diverse biological processes such as development, proliferation, apoptosis and differentiation. Upon treatment with nerve growth factor (NGF), rat pheochromocytoma PC12 cells elicit neurit...
Article
ABCA1, a member of the ATP-binding cassette transporter family, regulates high-density lipoprotein (HDL) metabolism and cholesterol transport. Its expression is upregulated mainly by the activation of the liver X receptor (LXR). Since ABCA1 plays a pivotal role in cholesterol and HDL metabolism, identification of a compound capable of increasing it...
Article
The ATP-binding cassette transporter A1 (ABCA1) is a membrane transporter that directly contributes to high-density lipoprotein (HDL) biogenesis by regulating the cellular efflux of cholesterol. Since ABCA1 plays a pivotal role in cholesterol homeostasis and HDL metabolism, identification of a novel substance that is capable of increasing its expre...
Article
ETS1, which belongs to the ETS transcription factor family, plays important roles in diverse aspects of cancer such as drug resistance and metastasis. In the present study, we examined the functional roles of ETS1 in paclitaxel resistance and invasion using human prostate cancer PC3 cells and paclitaxel-resistant PC3PR cells established from PC3 ce...
Article
Cortactin is overexpressed in various types of cancer and enhances cell motility. It has been recently reported that silent mating type information regulation 2 homolog 1 interacts with cortactin and promotes cell migration. Here, we examined the role of cortactin and silent mating type information regulation 2 homolog 1 in migration and invasion o...
Article
Full-text available
Molecular hydrogen has prominent effects on more than 30 animal models especially of oxidative stress-mediated diseases and inflammatory diseases. In addition, hydrogen effects on humans have been reported in diabetes mellitus type 2, hemodialysis, metabolic syndrome, radiotherapy for liver cancer, and brain stem infarction. Hydrogen effects are as...
Data
Effects of 10-HDA and/or pRJ-Fr.5 on the lifespan. (XLSX)
Data
The effect of RJ-Fr.1 on the lifespan of C. elegans. The survival curves of N2 hermaphrodites incubated with RJ-Fr.1 (0 (control), 10, 25 or 100 µg/ml) are shown. The RJ-Fr.1 was given at 20°C from 0-day adult until death. Day 0 corresponds to the L4 molt. The percentage of live worms is plotted against adult age. Detailed parameters are presented...
Data
The effect of pRJ-Fr.5 treatment on DAF-16 nuclear translocation. DAF-16 nuclear translocation was examined in a daf-16::gfp transgenic N2 line (zIs356, TJ356). The animals were treated with pRJ-Fr.5 (0 or 25 µg/ml) for 24 hrs. [A] Images of DAF-16::GFP animals. The arrowheads show the nuclear localization of DAF-16::GFP. [B] The translocation of D...
Data
Effects of RJ or pRJ on the lifespan. (XLSX)
Data
The effect of RJ-Fr.2 on the lifespan of C. elegans. The survival curves of N2 hermaphrodites incubated with RJ-Fr.2 (0 (control), 10, 25 or 100 µg/ml) are shown. The RJ-Fr.2 was given at 20°C from 0-day adult until death. Day 0 corresponds to the L4 molt. The percentage of live worms is plotted against adult age. Detailed parameters are presented...
Data
Differentially regulated genes by pRJ-Fr.5 treatment. (XLSX)
Article
Full-text available
Background: One of the most important challenges in the study of aging is to discover compounds with longevity-promoting activities and to unravel their underlying mechanisms. Royal jelly (RJ) has been reported to possess diverse beneficial properties. Furthermore, protease-treated RJ (pRJ) has additional pharmacological activities. Exactly how RJ...
Article
Molecular hydrogen has been reported to be effective for a variety of disorders and its effects have been ascribed to the reduction of oxidative stress. However, we have recently demonstrated that hydrogen inhibits type I allergy through modulating intracellular signal transduction. In the present study, we examined the hydrogen effects on lipopoly...
Article
This study aimed to examine the roles of reactive oxygen species (ROS) in cisplatin treatment of human prostate cancer cells; hormone-sensitive LNCaP and hormone-refractory PC3 and DU145 cells. Intracellular levels of ROS and H(2)O(2) were measured and visualized using specific fluorescent probes. NADPH oxidase (NOX) activity was detected by lucige...
Article
We found that two distinct flavonoid glycosides isolated from the peel of Japanese persimmon (Diospyros kaki Fuyu), isoquercitrin (Isq) and hyperin (Hyp), are capable of inhibiting antigen-stimulated degranulation in rat basophilic leukaemia RBL-2H3 cells. In order to elucidate the underlying mechanisms, we examined effects of Isq and Hyp on cellul...
Article
Induction of phase II antioxidant enzymes by activation of Nrf2/ARE (antioxidant response element) signaling has been considered as a promising strategy to combat with oxidative stress-related diseases. In the present study, we tested for potential effects of sesamin, a major lignan contained in sesame seeds, its stereoisomer episesamin, and their...
Article
SIRT1, an NAD(+) -dependent histone/protein deacetylase, controls a broad range of cellular functions. We examined if SIRT1 is involved in the regulation of matrix metalloproteinase (MMP) expression in human dermal fibroblasts. We studied the effect of inhibition of SIRT1 by specific inhibitor and small interfering RNA (siRNA) on MMP-1 and MMP-3 ex...
Article
Patients with hormone-refractory prostate cancer are treated with taxane drugs, but eventually become drug resistant. We aimed to elucidate the molecular mechanisms underlying paclitaxel resistance of hormone-refractory prostate cancer with a special focus on the roles of miR-34a and SIRT1. Paclitaxel-resistant cells (PC3PR) were generated from hor...
Article
The process of cancer development consists of three sequential stages termed initiation, promotion, and progression. Oxidative stress damages DNA and introduces mutations into oncogenes or tumor suppressor genes, thus contributing to cancer development. Cancer chemoprevention is defined to prevent or delay the development of cancer by the use of na...
Article
Five new stilbenoids, vatalbinosides A-E (1-5), and 13 known compounds (6-18) were isolated from the stem of Vatica albiramis. The effects of these new compounds on interleukin-1β-induced production of matrix metalloproteinase-1 (MMP-1) in human dermal fibroblasts were examined. Three resveratrol tetramers, (-)-hopeaphenol (6), vaticanol C (13), an...
Article
Whisky is matured in oak casks. Many nonvolatile substances (whisky congeners, WC) seep from the oak cask during the maturing process. In this study, three antiallergic agents (syringaldehyde, SA; lyoniresinol, Lyo; and ellagic acid, EA) were isolated from WC. Treatment with SA, Lyo, and EA reduced the elevation of intracellular free Ca(2+) concent...