{"title":"Report of the AI Pathology Task Force, Non-clinical Evaluation Expert Committee, Japan Pharmaceutical Manufacturers Association: questionnaire survey on AI pathology and utilization of whole slide image database.","authors":"Masaki Yamazaki, Emi Tomikawa, Miyoko Okada, Satoru Kajikawa, Yui Terayama, Shino Kumabe, Tetsuya Sakairi, Akira Inomata, Izumi Matsumoto, Gen Sato, Mutsumi Suzuki","doi":"10.1293/tox.2024-0099","DOIUrl":"10.1293/tox.2024-0099","url":null,"abstract":"<p><p>In recent years, the development of Artificial Intelligence (AI) technology has led to the introduction and use of AI-based histopathological evaluation (AI pathology) by various companies and organizations. The AI Pathology Task Force of the Non-clinical Evaluation Expert Committee within the Drug Evaluation Committee of the Japan Pharmaceutical Manufacturers Association (JPMA) recognizes the importance of understanding the current use and needs surrounding AI pathology in Japan. This includes its role in non-clinical research fields, such as toxicity evaluation, drug efficacy evaluation, and basic research. In addition, assessing needs and challenges related to pathology image databases is essential. Between October and November 2023, with the cooperation of the Japanese Society of Toxicologic Pathology (JSTP), we conducted a questionnaire survey on non-clinical pathology image databases to explore these issues among JPMA-affiliated and JSTP-affiliated organizations. The questionnaire survey consisted of three items: (1) implementation and utilization of whole slide images, (2) use of AI pathology in non-clinical research fields, and (3) needs and feasibility of establishing a precompetitive pathology image database (repository) and AI pathology in the non-clinical pathology field. This report summarizes the survey results and serves as a foundation for guiding future directions in the use of AI pathology in non-clinical studies in Japan.</p>","PeriodicalId":17437,"journal":{"name":"Journal of Toxicologic Pathology","volume":"38 3","pages":"205-211"},"PeriodicalIF":0.9,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12208863/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144553877","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Minkyoung Sung, Joo-Hee Choi, Soo-Eun Sung, Kyung-Ku Kang, Sun Hee Park, Duyeol Kim, Sijoon Lee
{"title":"Spontaneous T-cell lymphoblastic lymphoma in a young ICR mouse: a case report.","authors":"Minkyoung Sung, Joo-Hee Choi, Soo-Eun Sung, Kyung-Ku Kang, Sun Hee Park, Duyeol Kim, Sijoon Lee","doi":"10.1293/tox.2024-0086","DOIUrl":"10.1293/tox.2024-0086","url":null,"abstract":"<p><p>Lymphoblastic lymphoma (LBL) is an aggressive neoplasm characterized by the proliferation of undifferentiated lymphocytes. It primarily spreads to immune organs such as the thymus, spleen, lymph nodes, bone marrow, and liver. Although well-documented in humans, spontaneous LBL cases in laboratory animals are exceedingly rare. This study reports a case of T cell-derived LBL in a young adult ICR mouse, notably without bone marrow metastasis. This case provides valuable insights into the spontaneous occurrence of LBL in laboratory rodents by contributing to comparative oncology and preclinical research.</p>","PeriodicalId":17437,"journal":{"name":"Journal of Toxicologic Pathology","volume":"38 3","pages":"199-203"},"PeriodicalIF":0.9,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12208864/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144553878","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Report of the AI Pathology Task Force, Non-clinical Evaluation Expert Committee, Japan Pharmaceutical Manufacturers Association: an overview of recent publications about AI pathology.","authors":"Emi Tomikawa, Satoshi Sakai, Yoshinori Yamagiwa, Yumi Kangawa, Yusuke Kagawa, Yuki Kato, Kensuke Kojima, Akira Inomata, Izumi Matsumoto, Gen Sato, Mutsumi Suzuki","doi":"10.1293/tox.2024-0100","DOIUrl":"10.1293/tox.2024-0100","url":null,"abstract":"<p><p>The use of artificial intelligence (AI) in non-clinical pathology is rapidly expanding. In this study, we conducted a literature survey of articles published after 2017 that used AI to analyze the histopathological images of experimental animals. We identified 44 articles that used AI for various purposes, including the detection of abnormal sites, determination and quantification of normal tissues, and classification of normal/abnormal images. AI systems or applications were either custom-built, commercially available, or a combination of both. Rats and mice were mainly used, and the liver was the most frequently analyzed organ. Our findings suggest that AI can be useful in non-clinical pathology and that collaboration between pharmaceutical companies or cooperation with IT experts can be a potential approach to further advance the utilization of AI in this field.</p>","PeriodicalId":17437,"journal":{"name":"Journal of Toxicologic Pathology","volume":"38 3","pages":"191-198"},"PeriodicalIF":0.9,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12208865/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144553876","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Novel three-dimensional analysis method for accurate evaluation of cutaneous small sensory nerve fibers in mice.","authors":"Minori Inanaga- Kojima, Tetsuro Matsuura, Kiyokazu Ozaki","doi":"10.1293/tox.2024-0085","DOIUrl":"10.1293/tox.2024-0085","url":null,"abstract":"<p><p>Intraepidermal nerve fiber (IENF) density is commonly evaluated to diagnose peripheral neuropathy. However, conventional two-dimensional (2D) analysis using rodent models shows high interstudy variability. Three-dimensional (3D) IENF analysis has been proposed for human skin biopsies because the spatial location of each nerve can be easily determined. However, no studies have compared 2D and 3D analyses of mouse cutaneous nerve fibers under the same conditions. We aimed to establish a more accurate analysis method for mouse cutaneous nerve fibers. We used the glabrous plantar metatarsal skin of male C57BL/6J mice. The middle area of the plantar skin was used for 2D and 3D analyses, and the marginal area was also investigated in the 3D analysis. Tissue transparency, nerve fiber-specific antibodies, confocal microscopy, and IMARIS software were used for the 3D analysis. The 3D analysis clearly defined branching points and continuity, allowing accurate IENF density measurement. Conversely, the 2D analysis could not accurately determine IENF density because it could not detect the continuity of the nerve from the dermis to epidermis. Thus, the actual IENF density from the 3D analysis was significantly less than that from the 2D analysis. In addition, the density and length of IENFs in the middle area were significantly higher than those in the marginal area. This 3D approach enables the precise capture of IENF trajectories with various parameters, establishing a standard method for evaluating peripheral neuropathy models. Furthermore, our findings indicate that comparative studies aiming to analyze mouse IENF need to consider the site of skin sampling.</p>","PeriodicalId":17437,"journal":{"name":"Journal of Toxicologic Pathology","volume":"38 2","pages":"167-175"},"PeriodicalIF":0.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11966124/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143796014","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Masaki Fujioka, Shugo Suzuki, Min Gi, Ikue Noura, Arpamas Vachiraarunwong, Anna Kakehashi, Hideki Wanibuchi
{"title":"Nicotine promotes the development of invasive bladder carcinoma in rats.","authors":"Masaki Fujioka, Shugo Suzuki, Min Gi, Ikue Noura, Arpamas Vachiraarunwong, Anna Kakehashi, Hideki Wanibuchi","doi":"10.1293/tox.2024-0087","DOIUrl":"10.1293/tox.2024-0087","url":null,"abstract":"<p><p>Tobacco smoking is a major risk factor for human cancers including urinary bladder carcinoma. In a previous study, nicotine was shown to enhance rat urinary bladder carcinogenesis in a two-stage carcinogenesis model. In this study, we examined the progressive effects of nicotine on bladder carcinogenesis in F344 rats treated with N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN). Nicotine, administered in drinking water for 52 weeks following 4 weeks of BBN treatment, significantly increased the incidence and multiplicity of invasive urothelial carcinoma in a dose-dependent manner. The Ki67 labeling index of bladder papillomas was significantly increased by nicotine in a dose-dependent manner. However, nicotine treatment did not affect the incidence or total number of tumors, and nicotine administration alone for 52 weeks did not result in any neoplastic lesions. These data suggest that while nicotine does not initiate carcinogenesis, it has the potential to promote invasive urinary cancers.</p>","PeriodicalId":17437,"journal":{"name":"Journal of Toxicologic Pathology","volume":"38 2","pages":"161-165"},"PeriodicalIF":0.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11966120/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143796013","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Lymphocytic thyroiditis with an oncocytic alteration in a laboratory beagle.","authors":"Osamu Hashiguchi, Kohji Tanaka, Yuko Yamaguchi, Moeko Aoki, Nobuaki Sato, Takuro Endo, Maoko Yamaguchi, Tsubasa Saito","doi":"10.1293/tox.2024-0073","DOIUrl":"10.1293/tox.2024-0073","url":null,"abstract":"<p><p>Histopathological, immunohistochemical, and ultrastructural characteristics of lymphocytic thyroiditis in an untreated four-year-old male beagle were described. Histopathologically, the thyroid glands were composed of two distinct cell types: round to oval cells with eosinophilic granular cytoplasm (Type A), which is consistent with the features of oncocytic oxyphils, and larger round cells with amphophilic or pale cytoplasm (Type B). These cell types extensively and diffusely infiltrated with a mixture of lymphocytes and plasma cells, destroying the follicular structure. Immunohistochemistry revealed that Type A cells were positive for thyroglobulin and cytochrome C, and that Type B cells were positive for calcitonin, synaptophysin, and cytochrome C. These results indicate that Type A and B cells stem from follicular and C cells, respectively. Ultrastructural investigation showed that microfollicles and microvilli were evident in the cytoplasm and along the luminal surface of Type A cells. Thus, the lymphocytic thyroiditis observed in the beagle exhibited a morphology similar to that of Hashimoto thyroiditis in humans, particularly in view of an oncocytic alteration of follicular cells.</p>","PeriodicalId":17437,"journal":{"name":"Journal of Toxicologic Pathology","volume":"38 2","pages":"177-182"},"PeriodicalIF":0.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11966123/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143796012","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ikue Noura, Shugo Suzuki, Min Gi, Masaki Fujioka, Taisuke Matsue, Anna Kakehashi, Hideki Wanibuchi
{"title":"Comparative analysis of the toxic effects on the mouse lung of 4 weeks exposure to the heated tobacco product Ploom TECH+ and 3R4F reference cigarettes.","authors":"Ikue Noura, Shugo Suzuki, Min Gi, Masaki Fujioka, Taisuke Matsue, Anna Kakehashi, Hideki Wanibuchi","doi":"10.1293/tox.2024-0069","DOIUrl":"10.1293/tox.2024-0069","url":null,"abstract":"<p><p>Pulmonary emphysema is primarily attributable to prolonged exposure to cigarette smoke. Novel tobacco substitutes, such as heated tobacco products, have emerged as healthier alternatives to cigarettes. The effects of short-term inhalation of a heated tobacco product, Ploom TECH+ (PT+), on the lungs of mice were compared with those of 3R4F reference cigarettes. Male 10-week-old C57BL mice were exposed to clean air (control), 3R4F, or PT+ for 1 h/d, 5 d/week for two or four weeks. After four weeks of exposure, the number of inflammatory cells and proportion of neutrophils and lymphocytes in the bronchoalveolar lavage fluid and the number of macrophages in the lung tissue increased significantly in mice exposed to 3R4F but not in those exposed to PT+. Changes in the expression of genes related to inflammation-related factors were observed in the lung tissues of mice exposed to 3R4F for two and four weeks. Chemokine (C-C motif) ligand 17, resistin-like alpha, and lipocalin 2 were among the upregulated genes. In our previous short-term tobacco inhalation study, these genes were identified as useful markers of emphysema effects induced by exposure to cigarette smoke from Peace cigarettes, detectable before pulmonary histological changes appeared. These effects were not observed in the PT+-exposed mice. These data suggest that PT+ caused less damage to the lungs of mice than 3R4F, particularly regarding the induction of emphysema.</p>","PeriodicalId":17437,"journal":{"name":"Journal of Toxicologic Pathology","volume":"38 2","pages":"147-154"},"PeriodicalIF":0.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11966118/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143795964","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Comparative anatomy of respiratory bronchioles and lobular structures in mammals.","authors":"Yumi Umeda, Takeshi Izawa, Kei Kazama, Sachiko Arai, Junichi Kamiie, Shinichiro Nakamura, Kazuki Hano, Masaki Takasu, Akihiro Hirata, Susanne Rittinghausen, Shotaro Yamano","doi":"10.1293/tox.2024-0071","DOIUrl":"10.1293/tox.2024-0071","url":null,"abstract":"<p><p>Rodents are widely used to study the toxicity of chemicals; however, differences between species indicate that the results from rodents are not always directly transferable to humans. The health of workers exposed to various chemicals and particulates at high doses or for long periods is at risk. Respiratory bronchioles and lobular structures, which are demarcated by interlobular septa, are key sites for occupational lung diseases such as pneumoconiosis; however, these structures vary among animal species. Understanding these differences is crucial for studying the pathology of human occupational lung diseases. However, there is a lack of reviews focusing on these structures in different species. This review explores the lung anatomy of various mammals and its functional importance in disease to connect animal studies with human occupational lung diseases. Our results indicate that artiodactyls, especially small pig breeds and goats, are ideal for research because their respiratory bronchioles and lobular structures are similar to those of humans. This review aims to enhance the use of experimental animal data and improve our understanding of human occupational lung diseases, thereby facilitating early disease detection, treatment, and prevention.</p>","PeriodicalId":17437,"journal":{"name":"Journal of Toxicologic Pathology","volume":"38 2","pages":"113-129"},"PeriodicalIF":0.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11966126/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143795977","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Application of humanized mice to toxicology studies: properties of chimeric mice with humanized liver (PXB-mice) for hepatotoxicity.","authors":"Nazneen Sultana, Takeshi Izawa, Tomomi Kamei, Sho Fujiwara, Yuri Ito, Yuki Takami, Mitsuru Kuwamura","doi":"10.1293/tox.2024-0092","DOIUrl":"10.1293/tox.2024-0092","url":null,"abstract":"<p><p>Chimeric mice with humanized liver are considered a useful tool to predict drug pharmacokinetics and <i>in vivo</i> toxicity in humans. The PXB-mouse is one of such chimeric (humanized) mouse models with more than 70% of human hepatocytes in their liver, which can produce human albumin with human-type bile secretion and express human xenobiotic metabolizing enzymes. However, data are limited regarding the properties of such humanized mice in hepatotoxicity studies. This study aimed to explore the distinctive characteristics of chimeric PXB-mice with humanized liver that can influence susceptibility to hepatotoxicity. Morphologically, the PXB-mice have a diffuse hepatic macrovesicular and microvesicular steatosis in the transplanted human hepatocytes, which can be suppressed after human growth hormone treatment. The humanized liver of the PXB-mice has a metabolic zonation of glutamine synthetase, cytochrome P450 2E1, and argininosuccinate synthase 1, similar to normal liver in rodents and humans. The transplanted human hepatocytes in the PXB liver have a markedly decreased N-cadherin expression compared with normal human liver. Scanning electron microscopy revealed formation of septum-like structures encircling the transplanted human hepatocytes in the PXB liver, which consists of an accumulation of fibers in the space of Disse under transmission electron microscopy and is immunolabeled for laminin. Overall, the present report demonstrated the morphological and immunohistochemical characteristics of the PXB-mice with humanized liver along with some abnormalities in the cell adhesion of the transplanted human hepatocytes. These findings would be useful for hepatotoxicity studies using humanized animal models.</p>","PeriodicalId":17437,"journal":{"name":"Journal of Toxicologic Pathology","volume":"38 2","pages":"183-189"},"PeriodicalIF":0.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11966125/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143795962","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"A concise review of veterinary forensic medicine in Japan: current status and perspectives.","authors":"Shin-Ichi Nakamura","doi":"10.1293/tox.2024-0047","DOIUrl":"10.1293/tox.2024-0047","url":null,"abstract":"<p><p>Veterinary forensic medicine has received increasing attention in recent years from the perspectives of animal abuse, veterinary malpractice, wildlife protection, and zoonosis. Veterinary forensic medicine, equivalent to human forensic medicine, is a relatively new field. Compared with Europe and the United States of America, Japan currently lags behind in both the education and practice of veterinary forensic medicine. However, the situation regarding animals in Japan has changed dramatically in recent years, and the need for veterinary forensic medicine is increasing. This manuscript provides an overview of veterinary forensic medicine and a brief description of its current status and prospects in Japan.</p>","PeriodicalId":17437,"journal":{"name":"Journal of Toxicologic Pathology","volume":"38 2","pages":"131-137"},"PeriodicalIF":0.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11966119/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143795960","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}