論文 - 齋藤　義正

Environmental factors in gastric carcinogenesis and preventive intervention strategies

Tan Y., Matsuzaki J., Saito Y., Suzuki H.

Genes and Environment 47 （ 1 ）  2025年12月

ISSN  18807046

　概要を見る

Gastric cancer, a significant global health concern, arises from a complex interplay of genetic and environmental factors. Helicobacter pylori (H. pylori) infection is a major risk factor that can be mitigated through eradication strategies. Epstein-Barr virus (EBV) infection causes a distinct subtype of gastric cancer called EBV-associated gastric cancer. The gastric microbiome, a dynamic ecosystem, is also involved in carcinogenesis, particularly dysbiosis and specific bacterial species such as Streptococcus anginosus. Long-term use of proton pump inhibitors and potassium-competitive acid blockers also increases the risk of gastric cancer, whereas non-steroidal anti-inflammatory drugs including aspirin may have a protective effect. Smoking significantly increases the risk, and cessation can reduce it. Dietary factors such as high intake of salt, processed meats, and red meat may increase the risk, whereas a diet rich in fruits and vegetables may be protective. Extracellular vesicles, which are small membrane-bound structures released by cells, modulate the tumor microenvironment and may serve as biomarkers for risk stratification and as therapeutic targets in gastric cancer. This review highlights the multifaceted etiology of gastric cancer and its risk factors and emphasizes the importance of a multi-pronged approach to prevention including H. pylori eradication and modification of lifestyle factors, as well as the potential of microbiome-based and EV-based interventions. Further research is needed to refine risk stratification and to develop personalized prevention strategies.

• Access to Document (DOI)

Impact of strength training of large muscle groups on quality of life

Takahashi T., Matsuzaki J., Enomoto T., Saito Y.

Journal of Clinical Biochemistry and Nutrition 77 （ 3 ） 264 - 267 2025年11月

ISSN  09120009

　概要を見る

Muscle-strengthening activities reduce the risk of various diseases and promote overall health. Physical activities targeting large muscle groups, such as weightlifting or resistance exercises, provide an additional health benefit. The present study investigated the relationship between strength training and health-related quality of life (HRQOL) through a cross-sectional study of 50 adults participating in large muscle group strengthening activities (LMG) and 50 adults who did not (NLMG). HRQOL was assessed using the SF-12v2 questionnaire, and sleep habits were assessed using the PSQI questionnaire. The LMG group had a significantly higher Role/Social component summary (RCS) score than the NLMG group (50.5 ± 7.2 vs 47.2 ± 8.3; respectively, p = 0.040). The physical component summary (PCS) and mental component summary (MCS) scores also tended to be higher in the LMG group than in the NLMG group (52.6 ± 8.4 vs 49.9 ± 10.2, respectively; p = 0.15 and 59.0 ± 7.9 vs 56.7 ± 6.0, respectively; p = 0.10). Linear regression analysis showed that a higher RCS score was significantly associated with LMG training, whereas higher PCS and MCS scores were associated with better sleep quality. These results suggest that strength training targeting large muscle groups may improve the social aspect of HRQOL, highlighting the potential benefits of incorporating such exercises into regular physical activity regimens.

• Access to Document (DOI)

Association of KRAS variants with survival and therapeutic outcomes in biliary tract cancers

Iida K., Matsui Y., Urabe Y., Muramatsu T., Matsuzaki J., Saito Y.

ESMO Open 10 （ 6 ）  2025年06月

　概要を見る

Background: Biliary tract cancer (BTC) remains a highly aggressive malignancy with limited treatment options and poor prognosis. To explore the association between KRAS variants and survival/therapeutic outcomes of patients with BTC, we analyzed genetic and clinical data obtained from BTC patients who underwent comprehensive genomic profiling (CGP) testing in Japan. Patients and methods: A total of 7773 patients with BTC who were registered in the Center for Cancer Genomics and Advanced Therapeutics (C-CAT) were included in this study. The main outcome was overall survival (OS) in months. For survival analysis, OS was measured from diagnosis to last follow-up or death, and for therapeutic outcomes, from treatment initiation to last follow-up or death. Results: The overall frequency of KRAS mutations in BTC was 23.4%. When classified according to tumor subtype, KRAS mutations were identified in 24.9% of patients with intrahepatic cholangiocarcinoma (IHC), in 32.2% of those with extrahepatic cholangiocarcinoma (EHC), and in 9.4% of those with gall-bladder cancer (GB). Among patients with KRAS mutations, G12D mutation was the most common in IHC (41.5%), EHC (35.9%), and GB (29.8%). In all BTC subtypes (IHC, EHC, and GB), patients with KRAS mutations had worse OS compared to those with wild-type KRAS. By KRAS variant, the G12D, G12V, and Q61H mutations were associated with poor OS in patients with IHC, while the G12D and G12V mutations were associated with poor OS in patients with EHC. Furthermore, in patients with unresectable BTC who received first-line treatment with regimens including gemcitabine, cisplatin, and durvalumab therapy, the G12D mutation was associated with poor OS across all regimens evaluated in this study. Conclusions: KRAS variants were significantly associated with poor prognosis and unfavorable therapeutic outcomes in BTC patients and may serve as potential prognostic and predictive factors.

• Access to Document (DOI)

Upper gastrointestinal triple stenosis in a patient with trisomy 17p syndrome: Case report and literature review

Ando H., Mori H., Takabayashi K., Matsuura N., Masaoka T., Matsuzaki J., Saito Y., Kato M., Kosaki K., Kanai T.

DEN Open 5 （ 1 ）  2025年04月

ISSN  2692-4609

　概要を見る

Upper gastrointestinal stenosis, which can be congenital or acquired, can lead to dysphagia. The association between trisomy 17p syndrome, a rare chromosomal abnormality, and upper gastrointestinal stenosis is unclear. A 20-year-old man diagnosed with trisomy 17p syndrome was referred to our department due to recurrent vomiting. Esophagogastroduodenoscopy revealed stenotic areas in the esophagus, stomach, and duodenum. The congenital gastrointestinal stenosis present in both the duodenum and esophagus suggested that the stasis and reflux of digestive fluids exacerbated stenosis in the stomach and esophagus. Gastric acid suppression therapy and endoscopic dilation of the esophagus and duodenum effectively resolved the patient's vomiting symptoms.

• Access to Document (DOI)

Clinical applications of human organoids

Verstegen M.M.A., Coppes R.P., Beghin A., De Coppi P., Gerli M.F.M., de Graeff N., Pan Q., Saito Y., Shi S., Zadpoor A.A., van der Laan L.J.W.

Nature Medicine 31 （ 2 ） 409 - 421 2025年02月

ISSN  10788956

　概要を見る

Organoids are innovative three-dimensional and self-organizing cell cultures of various lineages that can be used to study diverse tissues and organs. Human organoids have dramatically increased our understanding of developmental and disease biology. They provide a patient-specific model to study known diseases, with advantages over animal models, and can also provide insights into emerging and future health threats related to climate change, zoonotic infections, environmental pollutants or even microgravity during space exploration. Furthermore, organoids show potential for regenerative cell therapies and organ transplantation. Still, several challenges for broad clinical application remain, including inefficiencies in initiation and expansion, increasing model complexity and difficulties with upscaling clinical-grade cultures and developing more organ-specific human tissue microenvironments. To achieve the full potential of organoid technology, interdisciplinary efforts are needed, integrating advances from biology, bioengineering, computational science, ethics and clinical research. In this Review, we showcase pivotal achievements in epithelial organoid research and technologies and provide an outlook for the future of organoids in advancing human health and medicine.

• Access to Document (DOI)

Cholangiocarcinoma organoid-based evaluation of cancer immunotherapy using the Designer extracellular vesicles

Sannomiya, R; Yamano, T; Matsuzaki, J; Matsushita, M; Kanai, Y; Saito, Y

CANCER SCIENCE 116   1160 - 1160 2025年01月

ISSN  1347-9032

Association of miR-155-5p and PD-L1 expression with intertumoral T cell infiltration in mouse pancreatic cancer cells

Asakawa, Y; Matsuzaki, J; Oikawa, C; Koreeda, T; Shibagaki, R; Tan, Y; Oshima, K; Nakamura, M; Imamoto, K; Saito, Y

CANCER SCIENCE 116   834 - 834 2025年01月

ISSN  1347-9032

Contribution of chromosome 19 microRNA cluster to cancer stemness in cholangiocarcinoma

Sakamoto, M; Matsuzaki, J; Ye, ZX; Muramatsu, T; Saito, Y

CANCER SCIENCE 116   1676 - 1676 2025年01月

ISSN  1347-9032

Tracking miRNA variation during pancreatic carcinogenesis

Shibagaki, R; Matsuzaki, J; Oikawa, C; Koreeda, T; Asakawa, Y; Katsuda, T; Ochiya, T; Saito, Y

CANCER SCIENCE 116   1204 - 1204 2025年01月

ISSN  1347-9032

Ionizing radiation upregulation immune gene expression in a patient-derived biliary tract carcinoma organoid

Okuda, K; Haruna, S; Tateno, K; Okumura, H; Suzuki, R; Miyazaki, K; Uchihara, Y; Kato, Y; Saito, Y; Shibata, A

CANCER SCIENCE 116   1643 - 1643 2025年01月

ISSN  1347-9032

Investigation of miRNAs involved in T cell infiltration in mouse pancreatic cancer

Koreeda, T; Matsuzaki, J; Oikawa, C; Nakamura, M; Shibagaki, R; Saito, Y

CANCER SCIENCE 116   152 - 152 2025年01月

ISSN  1347-9032

Investigation of cholangiocarcinoma growth and stemness inhibitory factors secreted by vascular endothelial cells

Takeshita, Y; Semba, M; Yamashita, T; Saito, Y; Sudo, R

CANCER SCIENCE 116   1645 - 1645 2025年01月

ISSN  1347-9032

Elucidation of the effect of bacterial RNA in blood on the carcinogenesis of hepatocellular carcinoma.

Oshima, K; Matsuzaki, J; Nakayama, J; Yamamoto, Y; Tsugawa, H; Kato, K; Ochiya, T; Saito, Y

CANCER SCIENCE 116   1893 - 1893 2025年01月

ISSN  1347-9032

Correction of IDH1 mutations by genome editing for human intrahepatic cholangiocarcinoma organoids

Suzuki, S; Matsuzaki, J; Muramatsu, T; Saito, Y

CANCER SCIENCE 116   1326 - 1326 2025年01月

ISSN  1347-9032

Intestinal metabolites predict treatment resistance of patients with depression and anxiety

Matsuzaki J., Kurokawa S., Iwamoto C., Miyaho K., Takamiya A., Ishii C., Hirayama A., Sanada K., Fukuda S., Mimura M., Kishimoto T., Saito Y.

Gut Pathogens 16 （ 1 ）  2024年12月

研究論文（学術雑誌）, 共著, 最終著者, 査読有り,  ISSN  1757-4749

　概要を見る

Background: The impact of the gut microbiota on neuropsychiatric disorders has gained much attention in recent years; however, comprehensive data on the relationship between the gut microbiome and its metabolites and resistance to treatment for depression and anxiety is lacking. Here, we investigated intestinal metabolites in patients with depression and anxiety disorders, and their possible roles in treatment resistance. Results: We analyzed fecal metabolites and microbiomes in 34 participants with depression and anxiety disorders. Fecal samples were obtained three times for each participant during the treatment. Propensity score matching led us to analyze data from nine treatment responders and nine non-responders, and the results were validated in the residual sample sets. Using elastic net regression analysis, we identified several metabolites, including N-ε-acetyllysine; baseline levels of the former were low in responders (AUC = 0.86; 95% confidence interval, 0.69–1). In addition, fecal levels of N-ε-acetyllysine were negatively associated with the abundance of Odoribacter. N-ε-acetyllysine levels increased as symptoms improved with treatment. Conclusion: Fecal N-ε-acetyllysine levels before treatment may be a predictive biomarker of treatment-refractory depression and anxiety. Odoribacter may play a role in the homeostasis of intestinal L-lysine levels. More attention should be paid to the importance of L-lysine metabolism in those with depression and anxiety.

• Access to Document (DOI)

Plasma extracellular vesicle microRNAs reflecting the therapeutic effect of the CBP/β-catenin inhibitor PRI-724 in patients with liver cirrhosis

Yoshida M., Matsuzaki J., Fujita K., Kimura M., Umezu T., Tokuda N., Yamaguchi T., Kuroda M., Ochiya T., Saito Y., Kimura K.

Scientific Reports 14 （ 1 ）  2024年12月

研究論文（学術雑誌）, 共著, 査読有り,  ISSN  2045-2322

　概要を見る

There is an unmet need for antifibrotic therapies to prevent the progression of liver cirrhosis. Previously, we conducted an exploratory trial to assess the safety and antifibrotic efficacy of PRI-724, a selective CBP/β-catenin inhibitor, in patients with liver cirrhosis. PRI-724 was well tolerated and exerted a potential antifibrotic effect. Here, we investigated whether the profiles of circulating microRNAs packaged in extracellular vesicles (EV-miRNAs) are associated with responses to liver fibrosis treatments. Eighteen patients who received PRI-724 for 12 weeks in a phase 1/2a study were classified as responders (n = 10) or non-responders (n = 8) based on changes in liver stiffness. Plasma samples were obtained before and after PRI-724 administration and the levels of EV-miRNAs were analyzed. Three miRNAs (miR-6510-5p, miR-6772-5p, and miR-4261) were identified as predictors of response or non-response to PRI-724, and the levels of three other miRNAs (miR-939-3p, miR-887-3p, and miR-7112-5p) correlated with the efficacy of treatment. Expression of miR-887-3p was detected in hepatocytes and was decreased significantly in liver tissue following PRI-724 treatment. In addition, transfection of a miR-887-3p mimic activated hepatic stellate cells. Thus, decreases in the miR-887-3p level in blood may reflect recovery from liver fibroses in patients with liver cirrhosis treated with PRI-724, although further validation studies are warranted to confirm this.

• Access to Document (DOI)

A comparative study on dietary diversity and gut microbial diversity in children with autism spectrum disorder, attention-deficit hyperactivity disorder, their neurotypical siblings, and non-related neurotypical volunteers: a cross-sectional study

Kurokawa S., Nomura K., Sanada K., Miyaho K., Ishii C., Fukuda S., Iwamoto C., Naraoka M., Yoneda S., Imafuku M., Matsuzaki J., Saito Y., Mimura M., Kishimoto T.

Journal of Child Psychology and Psychiatry and Allied Disciplines 65 （ 9 ） 1184 - 1195 2024年09月

研究論文（学術雑誌）, 共著, 査読有り,  ISSN  00219630

　概要を見る

Background: Previous research has shown a significant link between gut microbiota in children with autism spectrum disorder (ASD) and attention-deficit hyperactivity disorder (ADHD). However, much remains unknown because of the heterogeneity of disorders and the potential confounders such as dietary patterns and control group variations. Methods: Children aged 6–12 years who had been clinically diagnosed with ASD and/or ADHD, their unaffected neurotypical siblings, and non-related neurotypical volunteers were recruited cross-sectionally. The ASD diagnosis was confirmed using the Autism Diagnostic Observation Schedule-2 (ADOS-2) in all patients, including those with ADHD. Standardized DNA extraction and sequencing methods were used to compare gut microbial alpha-diversity among the groups. Dietary diversity was calculated from a standardized dietary questionnaire form. We compared the difference in gut microbiome between patients with ASD and/or ADHD with neurotypical siblings and non-related neurotypical controls. Results: Ninety-eight subjects were included in the study (18 with ASD, 19 with ADHD, 20 with both ASD and ADHD, 13 neurotypical siblings, and 28 non-related neurotypical controls). The alpha-diversity indices, such as Chao 1 and Shannon index, showed a significant difference between the groups in a Linear mixed-effect model (F(4, 93) = 4.539, p =.02), (F(4, 93) = 3.185, p =.017), respectively. In a post-hoc pairwise comparison, patients with ASD had lower alpha-diversity compared with non-related controls after Bonferroni correction. Dietary diversity shown in Shannon index did not differ among the groups (F(4, 84) = 1.494, p =.211). Conclusions: Our study indicates disorder-specific microbiome differences in patients with ASD. In future research on gut microbiota in neurodevelopmental disorders, it is necessary to consider the impact of ASD and ADHD co-occurrence, and strictly control for background information such as diet, to elucidate the gut–microbiota interaction in ASD and ADHD for exploring the potential of therapeutic interventions.

• Access to Document (DOI)

Association between driver gene mutations in pancreatic epithelial cells and engraftment ability / survival in mice

Shibagaki, R; Matsuzaki, J; Ochiya, T; Saito, Y

CANCER SCIENCE 115   1997 - 1997 2024年03月

ISSN  1347-9032

Bacteria-derived RNAs can be detected in the blood and altered in patients with hepatocellular carcinoma

Oshima, K; Matsuzaki, J; Nakayama, J; Tsugawa, H; Yamamoto, Y; Kato, K; Ochiya, T; Saito, Y

CANCER SCIENCE 115   1912 - 1912 2024年03月

ISSN  1347-9032

Distinct intercellular trafficking of COPB2 in lung cancer cells

Tan, YZ; Matsuzaki, J; Fujita, Y; Yamaguchi, T; Oikawa, C; Ochiya, T; Saito, Y

CANCER SCIENCE 115   1592 - 1592 2024年03月

ISSN  1347-9032