Tomio Arai

Tomio Arai
Tokyo Metropolitan Institute of Gerontology | TMIG · Department of Pathology

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636
Publications
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Introduction
Skills and Expertise

Publications

Publications (636)
Article
Full-text available
Epithelial–mesenchymal transition (EMT) plays a pivotal role in cancer progression and metastasis in many types of malignancies, including colorectal cancer. Although the importance of EMT is also considered in colorectal neuroendocrine carcinoma (NEC), its regulatory mechanisms have not been elucidated. We recently established a human colorectal N...
Article
Full-text available
Pancreatic ductal adenocarcinoma (PDAC) is an intractable cancer that is difficult to diagnose early, and there is no cure other than surgery. PDAC is classified as an adenocarcinoma that has limited effective anticancer drug and molecular-targeted therapies compared to adenocarcinoma found in other organs. A large number of cancer cell lines have...
Article
Aim: Diabetic kidney disease (DKD), a chronic kidney disease caused by diabetes and other comorbidities, is the leading cause of end-stage renal disease. The pathogenesis of DKD is diverse and influenced by various causes, some but not all of which cause proteinuria. Some factors such as hypertension can modify DKD. Therefore, the spectrum of DKD...
Article
Full-text available
Background and Objectives ¹²³ I-meta-iodobenzyl-guanidine ( ¹²³ I-MIBG) myocardial scintigraphy is employed as a diagnostic imaging test to differentiate Lewy body diseases (LBDs), including Parkinson’s disease and dementia with Lewy bodies, from other similar diseases. However, its diagnostic accuracy lacks validation compared with that of the gol...
Article
Background: The aim of this autopsy study was to clarify the differences of renal histopathology between non-chronic kidney disease (CKD) and CKD caused by hypertensive-nephrosclerosis in the elderly and during the aging process. Methods: We examined autopsy specimens from 105 elderly patients (53 male subjects; mean age, 86.2 years) including 4...
Article
Background: Anorectal melanoma is a rare disease with poor prognosis and nonspecific symptoms, leading to difficulties in preoperative diagnosis. Here, we describe the establishment of MELS, a novel anorectal melanoma cell line derived from tumor resection of the rectum in a 40-year-old Japanese man. Methods: Histological, electron microscopic,...
Article
Accumulation of phosphorylated α‐synuclein in the central and peripheral nervous systems is a histological hallmark of Lewy body disease (LBD), including Parkinson's disease (PD), dementia with Lewy bodies (DLB), and LB‐related pure autonomic failure. The submandibular gland is employed as a biopsy site for detecting Lewy pathology; however, the in...
Article
Background We have reported that precancerous conditions and lesions invariably have shorter telomeres and associated chromosomal instability relative to normal tissue.Methods Using the Q-FISH method and our original software, Tissue Telo, we estimated telomere lengths in cardiac- and intestinal-type mucosae in 48 cases of Barrett’s esophagus (shor...
Article
Background The prevalence of Lynch syndrome (LS)-associated DNA mismatch repair (MMR)-deficient bladder cancer (BC) has scarcely been investigated.Methods Immunohistochemistry for four MMR proteins (MLH1, MSH2, MSH6, and PMS2) was performed in formalin-fixed paraffin-embedded (FFPE) sections prepared from the resected specimens of 618 consecutive n...
Article
Aim Heart failure is increasing in Japan, in particular that with preserved ejection fraction (HFpEF) prevalent in older-aged patients. The purpose of this study was to investigate the pathophysiology during the early stage of left ventricular (LV) diastolic dysfunction by the quantitative proteome analysis of human myocardium. Methods Among 331 p...
Article
Background As esophageal gastrointestinal stromal tumors (GISTs) are very rare, their clinicopathological features remain obscure. We conducted a nationwide survey to clarify the characteristics of these tumors and to establish a consensus on their diagnosis and treatment.Methods The clinicopathological information of patients with esophageal GISTs...
Article
Full-text available
Obtaining a correct intraosseous epidermal cyst diagnosis is difficult due to the extreme rarity of this cyst. Further, the clinical manifestations and radiographic findings are very similar to those of a malignancy or infection. Early histopathological analysis is required for accurate diagnosis and for avoiding unnecessary antibiotic administrati...
Article
Background The attention on mismatch repair-deficient (dMMR) gastric cancer has increased in this era of anti-PD-1 blockade therapy; however, the prevalence and molecular genetics of patients with dMMR gastric cancer have not been completely investigated. Methods Immunohistochemistry of MMR proteins (MLH1, MSH2, MSH6 and PMS2) was performed on for...
Article
Background/aim: DNA mismatch repair (MMR) deficiency has received increasing attention as a biomarker of anti-PD-1 treatments of solid tumors including gastric cancer (GC). However, efficient screening has not been established. Patients and methods: A total of 513 patients were tested for the expression of MMR proteins by immunohistochemistry to...
Article
Full-text available
Gastric cancer is prevalent in the Asian population. Genetic predisposition to gastric cancer is not fully understood. Recent studies have demonstrated that D-amino acid oxidase (DAO), a multifunctional enzyme, protects the mucosa of gastrointestinal (GI) tracts by generating hydrogen sulfide (H2S) in the stomach of rodents. The present study surve...
Article
Full-text available
Lewy body disease (LBD) is a spectrum of progressive neurodegenerative disorders characterized by the wide distribution of Lewy bodies and neurites in the central and peripheral nervous system (CNS, PNS). Clinical diagnoses include Parkinson’s disease (PD), dementia with Lewy bodies, or pure autonomic failure. All types of LBD are accompanied by no...
Article
Background The prevalence and molecular characteristics of deficient mismatch repair prostate cancer in the Japanese population have scarcely been investigated. Methods Immunohistochemistry for mismatch repair proteins (MLH1, MSH2, MSH6 and PMS2) was performed in formalin-fixed paraffin-embedded sections prepared from resected primary prostate can...
Preprint
Full-text available
Background: Cytological diagnosis of pancreatic specimens obtained by endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) is often challenging because of the small amount of sample or well-differentiated adenocarcinoma with weak cytological atypia. Therefore, the sensitivity and specificity of cytological diagnosis for pancreatic cancer s...
Article
Background: The prevalence and molecular characteristics of defective DNA mismatch repair endometrial cancers in the Japanese population have been underexplored. Data supporting clinical management of patients with Lynch-like syndrome and germline variant of uncertain significance of mismatch repair genes are still lacking. Methods: Immunohistoc...
Article
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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
Alcohol consumption is an established risk factor for cancer, but little is known regarding the effect of genetic polymorphisms in alcohol metabolism genes on alcohol-related cancer risk in the Japanese population. Associations between the ADH1B gene (alcohol dehydrogenase 1B), single nucleotide polymorphism (SNP) rs1229984 and cancer have been ext...
Article
Full-text available
Background: CYP2A6 is an enzyme involved in oxidation of a number of environmental chemicals, including nicotine, pro-carcinogenic nitrosamines and polycyclic aromatic hydrocarbons (PAHs). The whole gene deletion of CYP2A6 (CYP2A6*4) is prevalent in East Asian population. Whether or not CYP2A6*4 associates with cancer is still controversial. Meth...
Preprint
Full-text available
Background CYP2A6 is an enzyme involved in oxidation of a number of environmental chemicals, including nicotine, pro-carcinogenic nitrosamines and polycyclic aromatic hydrocarbons (PAHs). The whole gene deletion of CYP2A6 (CYP2A6*4) is prevalent in East Asian population. Whether or not CYP2A6*4 associates with cancer is still controversial. Methods...
Preprint
Full-text available
Background CYP2A6 is an enzyme involved in oxidation of a number of environmental chemicals, including nicotine, pro-carcinogenic nitrosamines and polycyclic aromatic hydrocarbons (PAHs). The whole gene deletion of CYP2A6 (CYP2A6*4) is prevalent in East Asian population. Whether or not CYP2A6*4 associates with cancer is still controversial. Methods...
Article
Gastrointestinal melanoma (GM) is a rare but aggressive type of malignant melanoma arising in the gastrointestinal tract. An anti-programmed cell death protein 1 (PD-1) antibody markedly improves prognosis in patients with melanoma. However, little is known regarding the expression of immune-oncology biomarkers in GM compared with skin melanoma (SM...
Preprint
Full-text available
Background CYP2A6 is an enzyme involved in oxidation of a number of environmental chemicals, including nicotine, pro-carcinogenic nitrosamines and polycyclic aromatic hydrocarbons (PAHs). The whole gene deletion of CYP2A6 (CYP2A6*4) is prevalent in East Asian population. Whether or not CYP2A6*4 associates with cancer is still controversial. Methods...
Article
Objective : The optimal method for collecting samples by endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA), which is especially significant because only small amounts of samples can be obtained by this procedure, remains under debate. This study was aimed at clarifying how different collection methods can influence the cytological findi...
Article
The clinicopathological significance of carbohydrate antigen 19-9 (CA19-9) in gastric cancer (GC) remains obscure. Therefore, the current study aimed to clarify the clinicopathological value of CA19-9 in GC utilizing autopsy cases. We examined the expression of CA19-9 and mucin core proteins in GC immunohistochemically, and analyzed serum CA19-9 le...
Article
Context Although numerous theories are reported on sex differences in longevity, the underlying biological mechanisms remain unknown. We previously reported that telomere length in the zona reticularis (ZR) cells of the human adrenal cortex was significantly longer in older than that in younger subjects. However, we could not evaluate sex differenc...
Article
Objective: We clarified clinicopathological characteristics of acute pancreatitis in terminal patients. Methods: Pathological changes in the entire pancreas from serial autopsies (N = 183) classified lesions into the following 3 categories: focal neutrophil infiltration, focal necrotizing pancreatitis, and diffuse necrotizing pancreatitis. The f...
Article
The HOTAIR gene encodes a long noncoding RNA (lncRNA), which functions in development and tumorigenesis. A single nucleotide polymorphism (SNP) rs920778 in the HOTAIR gene, has been recurrently studied for susceptibility to many cancers including oesophageal cancer, gastric cancer, lung cancer, and hepatocellular carcinoma. Most of these studies we...
Article
Full-text available
Vancomycin is recommended for treating severe infections caused by Gram-positive cocci, including methicillin-resistant Staphylococcus aureus. However, renal damage often occurs as a side effect because vancomycin is mainly excreted via the kidneys. The mechanism of vancomycin-associated nephrotoxicity is thought to involve the elevation of oxidati...
Article
The function of actin is regulated by various posttranslational modifications. We showed previously that in the kidney of the nonobese type 2 diabetes model Goto-Kakizaki (GK) rat, increased O-GlcNAcylation of β-actin protein is observed. It has also been reported that both O-GlcNAcylation and phosphorylation occur on serine199 of β-actin. However,...
Preprint
Background CYP2A6 is an enzyme involved in oxidation of a number of environmental chemicals, including nicotine, pro-carcinogenic nitrosamines and polycyclic aromatic hydrocarbons (PAHs). The whole gene deletion of CYP2A6 (CYP2A6*4) is prevalent in East Asian population. Whether or not CYP2A6*4 associates with cancer is still controversial. Methods...
Article
Full-text available
Pathological assessments of the treatment effect are critical for predicting patient outcomes after surgery. This study included 82 localized pancreatic cancer, 40 of whom were treated with neoadjuvant therapy (NAT) using four courses of gemcitabine plus nab-paclitaxel (GnP) followed by pancreatectomy (GnP group). The remaining 42 patients were tre...
Article
Lupus nephritis (LN) is the secondary glomerulonephritis (GN) involved in systemic lupus erythematosus (SLE) and a typical immune complex-type GN. Antineutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis (AAV) is an autoimmune disease characterized by systemic vasculitis and pauci-immune-type crescentic glomerulonephritis (CrGN) with AN...
Article
Purpose: A comprehensive molecular analysis was conducted to identify prognostic and predictive markers for adjuvant S-1 chemotherapy in stage II/III Japanese gastric cancer (GC) patients and to evaluate their potential suitability for alternative cytotoxic or targeted drugs. Experimental Design: We investigated genetic polymorphisms of enzymes pot...
Article
Carbohydrate sulfotransferase 15 (CHST15) synthesizes matrix proteoglycan that regulates various pathogenic mediators and contributes to tissue remodeling and fibrosis during injury. CHST15 has been reported to promote tumor growth and invasion in various types of cancer. Our previous study reported the safety and efficacy of EUS-guided fine-needle...
Article
Background: Progressive telomere shortening with age or chronic inflammation may lead to genomic instability that characterizes the early stage of carcinogenesis. Certain risk factors, such as drinking alcoholic beverages, or smoking, predispose the oral mucosa to squamous cell carcinoma. The ADH1B and ALDH2 genotypes can influence the risk of can...
Article
Objectives: This study aimed to clarify clinicopathological features of pancreatic cysts. Methods: Pancreata from 280 autopsies (median, 83 years; male, 146; female, 134) were sectioned every 5 mm. Cysts (<10 mm) were diagnosed as a simple cyst or low-grade, intermediate-grade, or high-grade dysplasia. Results: We found 236 cysts in 93 patient...
Article
Aim: Human vascular senescence, which mainly occurs in media, is not completely understood. Here, we used proteomic approaches to investigate age-associated changes in human aortic media with the goal of understanding the molecular mechanisms underlying vascular senescence. Method: Cryopreserved autopsy samples of aortic media from older-aged (a...
Article
Full-text available
Pancreatic cancer, composed of heterogeneous cancer cells, alters epithelial to mesenchymal features during growth and metastasis. In this study, we aimed to characterize pancreatic ductal adenocarcinoma (PDAC) cells showing epithelial or mesenchymal features in 3D culture. In 3D culture, PK-1 cells had high E-cadherin and low vimentin expression a...
Conference Paper
The long non-coding RNA is highly expressed and carries out various functions in different types of cancers. Recently, we reported that contributes to the metastasis of pancreatic ductal adenocarcinoma (PDAC) cells and its inhibition reduces metastasis in vivo. However, the molecular mechanisms underlying the metastasis-promoting role of in PDAC ce...
Conference Paper
p>The H19 long non-coding RNA is highly expressed and carries out various functions in different types of cancers. Recently, we reported that H19 contributes to the metastasis of pancreatic ductal adenocarcinoma (PDAC) cells and its inhibition reduces metastasis in vivo . However, the molecular mechanisms underlying the metastasis-promoting role of...
Article
Context: Adrenocortical zonation is associated with a markedly complex developmental process, and the pathogenesis and/or etiology of many disorders of adrenocortical zonal development have remained unknown. Cells from the three adrenocortical zones are morphologically and functionally differentiated, and the mature stage of cell development or se...
Article
In the original publication of this article, Fig. 2 was published incorrectly. The correct Fig. 2 is given in this correction.
Article
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An 84-year-old man with chronic renal failure, anemia, and diabetes was admitted for hemodialysis initiation. His vital signs were stable until the eighteenth hospital day, before having an influenza A virus infection. Three days later, he died of septic shock with severe liver impairment. His leukocyte count, prothrombin time (PT-INR), and liver e...
Article
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Background Gastric cancer (GC) is histologically a very heterogeneous disease, and the temporal development of different histological phenotypes remains unclear. Recent studies in lung and ovarian cancer suggest that KRAS activation (KRASact) can influence histological phenotype. KRASact likely results from KRAS mutation (KRASmut) or KRAS amplifica...
Article
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Abstract A previous study reported that a massive cerebral infarct in the territory of the middle cerebral artery (MCA) may be associated with development of neurofibrillary tangles (NFTs) in the ipsilateral basal nucleus of Meynert (BNM). We analyzed 19 cases of an MCA territory infarct and 12 with a putaminal hemorrhage (mean age 82.5 years; fema...
Article
The intermediate filament nestin is upregulated in stem/progenitor cells and cancers, and regulates cell proliferation, migration, invasion and stemness. The present study comparatively analyzed serial autopsies of Japanese patients (n=2,206; males, 1,225; females, 981; median, 80.7 years old; range, 33-104 years old) with malignant tumors of whole...
Article
Aim Neutrophil extracellular traps play key roles in the necrotizing vasculitis associated with anti‐neutrophil cytoplasmic antibody‐associated vasculitis (AAV). However, the relationships between neutrophil extracellular traps formation and the distribution and phase of vasculitis are not well understood. In the present study, we clarified the cli...
Article
Full-text available
Vancomycin hydrochloride (VCM) is a glycopeptide antibiotic that is commonly used to eradicate methicillin-resistant gram-positive cocci, despite its nephrotoxic side effects. Elderly people are particularly susceptible to developing VCM-induced nephrotoxicity. However, the precise mechanism by which VCM induces nephrotoxicity in elderly people is...
Article
Background Accurate diagnosis of malignant and benign pancreatic lesions can be challenging, especially in case of endoscopic ultrasound‐guided fine‐needle aspiration (EUS‐FNA) samples that are small and/or degraded. In the present study, we determined how to best evaluate abnormal SMAD4 expression by immunohistochemical staining on cell‐block spec...
Article
Full-text available
Mucin-producing urothelial-type adenocarcinoma of the prostate (MPUAP) is a rare, aggressive neoplasm thought to originate from the prostatic urethral urothelium. Our case is the first reported to show significantly increased serum levels of carcinoembryonic antigen (CEA) and carbohydrate antigen (CA) 19-9 in MPUAP. An autopsy revealed occult MPUAP...
Article
Full-text available
The long non-coding RNA H19 is highly expressed in several cancers, and the functions of H19 vary among cancer cell types. Recently, we reported that H19 contributes to the metastasis of pancreatic ductal adenocarcinoma (PDAC) cells and that inhibition of H19 reduces metastasis in vivo. However, the molecular mechanisms underlying the metastasis-pr...
Article
Full-text available
Background We hypothesized that the relative proportion of tumor (PoT) at the luminal surface can predict gastric cancer (GC) patient survival. Methods We measured the luminal PoT in resection specimens from 231 GC patients with stage II/III disease who had surgery at the Kanagawa Cancer Center, Yokohama, Japan. Tissue microarrays were used to ass...
Article
Aim The telomere is a structure present at the ends of chromosomes, and is known to shorten with aging and successive rounds of cell division. However, very little is known about telomere attrition in post‐mitotic cells, such as neurons. Methods Using our originally developed quantitative fluorescence in situ hybridization method, we analyzed age‐...
Article
Full-text available
Background: Despite predominant microsatellite instability (MSI) in intestinal-type gastric carcinomas, we found the most frequent MSI in solid-type poorly differentiated adenocarcinoma (PDA). Although this tumor is classified as PDA, it is hypothesized to possess peculiar features among PDAs. The present study aimed to clarify the clinicopatholog...
Article
ATP-binding cassette subfamily G member 2 (ABCG2), an important multidrug resistance transporter, can mediate the efflux of various chemotherapy drugs and contribute to drug resistance in cancer cells. The correlation between ABCG2 expression and cancer stem cell (CSC) phenotypes has been examined in hepatocellular carcinoma, as well as in glioma,...
Article
The incidence of malignant melanoma is increasing worldwide. Melanomas are most commonly localized in the skin but can arise anywhere in the body where melanocytes exist. Gastrointestinal melanoma (GM) is a rare form of this disease. The prognosis of GM is poor compared to that of skin melanoma (SM), however GM has not been well characterized. GM i...
Article
A 58-year-old woman with a history of chronic myelogenous leukemia, for which she was taking dasatinib, was admitted to our hospital with diarrhea and bloody stool. Colonoscopic examination showed multiple protruding polyps with white exudates at the top in the ascending and transverse colon. Biopsy specimens showed erosions with exudates on the su...
Article
Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy with a high incidence of distant metastasis and recurrence. Cancer stem cells (CSCs), which are pluripotent, self-renewable, and capable of forming tumors, contribute to PDAC initiation and metastasis and are responsible for resistance to chemotherapy and radiation. Three types of...
Article
The present study examined the differences between gastrointestinal melanoma (GM) and skin melanoma (SM). The clinicopathological characteristics, the expression of melanoma stem cell markers nestin, sex determining region Y-box 2 and ATP-binding cassette sub-family B member 5, and the presence of the BRAFV600E mutation were evaluated in 10 cases o...
Article
In order to investigate the population dynamics of telomere status, we measured the telomere lengths of glandular cells in the adenohypophysis (AH) and pituicytes, a type of glial cell, in the neurohypophysis (NH) of 128 autopsied humans (65 men, 63 women, 0 and 102 years) using our original quantitative fluorescence in situ hybridization (Q-FISH)...