Journal of Toxicologic Pathology最新文献

{"title":"Regarding \"A concise review of veterinary forensic medicine in Japan: current status and perspectives\".","authors":"Jiayi Chen","doi":"10.1293/tox.2026-0004","DOIUrl":"10.1293/tox.2026-0004","url":null,"abstract":"","PeriodicalId":17437,"journal":{"name":"Journal of Toxicologic Pathology","volume":"39 3","pages":"123"},"PeriodicalIF":1.1,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13342310/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148412199","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":"Spontaneous malignant myoepithelioma in the parotid gland of an aged female Crl:CD (SD) rat.","authors":"Takuro Endo, Osamu Hashiguchi, Moeko Aoki, Nobuaki Sato, Teppei Yamashita, Tsubasa Saito, Kohji Tanaka","doi":"10.1293/tox.2025-0130","DOIUrl":"10.1293/tox.2025-0130","url":null,"abstract":"<p><p>An aged female Crl:CD (SD) rat developed a subcutaneous tumor in the left occipital region. Histologically, the tumor was predominantly composed of spindle-shaped cells proliferating in a loosely cohesive fascicular arrangement in a basophilic myxoid matrix with a minor population of epithelioid cells. Metastases were detected in the cervical lymph nodes, kidneys, lungs, and the pleural cavity. Duct-like structures, considered to be entrapped normal salivary ducts, were scattered within the tumor. Immunohistochemically, the tumor cells were diffusely positive for vimentin, focally positive for alpha-smooth muscle actin and p63 in the spindle-shaped population, and positive for cytokeratin AE1/AE3, exclusive to the epithelioid cell population, whereas S100, chromogranin A, and myoglobin were not expressed in any of the tumor cells. Ultrastructurally, spindle-shaped tumor cells exhibited microfilaments, desmosome-like junctions, and cytoplasmic processes. These features were consistent with the diagnosis of malignant myoepithelioma, most likely originating from the parotid gland.</p>","PeriodicalId":17437,"journal":{"name":"Journal of Toxicologic Pathology","volume":"39 3","pages":"111-116"},"PeriodicalIF":1.1,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13342317/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148412192","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":"Evaluation of the skin carcinogenicity of the TRPV1 antagonist motugivatrep (SJP-0132) using an ultra-short-term two-stage skin carcinogenesis assay in Tg-rasH2 mice.","authors":"Yoshinori Yamagiwa, Mayumi Kawabe, Yuko Doi, Shingo Nemoto, Ikuyo Atsumi","doi":"10.1293/tox.2026-0011","DOIUrl":"10.1293/tox.2026-0011","url":null,"abstract":"<p><p>Motugivatrep (SJP-0132), a transient receptor potential cation channel subfamily V member 1 (TRPV1) antagonist, is being developed as an ophthalmic drug for dry eye disease. Since the role of TRPV1 antagonists in skin carcinogenesis remains controversial, this study aimed to investigate whether motugivatrep promotes skin tumorigenesis using an ultra-short-term two-stage skin carcinogenesis model with Tg-rasH2 mice. Following initiation with a single dermal application of 7,12-dimethylbenz[<i>a</i>]anthracene, motugivatrep was applied topically at doses of 0, 150, 300, or 750 µg/50 µL/animal once a day to mouse skin for 7 weeks. The positive control group received 12-<i>O</i>-tetradecanoylphorbol-13-acetate (TPA) once weekly. No skin tumors or preneoplastic lesions were observed in any animals treated with motugivatrep. In contrast, treatment with TPA significantly increased skin tumor formation, confirming the validity of the assay. These results indicated that motugivatrep lacked skin tumor promotion activity in this Tg-rasH2 mice model, providing safety information regarding dermal exposure to motugivatrep.</p>","PeriodicalId":17437,"journal":{"name":"Journal of Toxicologic Pathology","volume":"39 3","pages":"117-122"},"PeriodicalIF":1.1,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13342311/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148412155","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":"Multinucleation and cytotoxicity induced by multikinase inhibition in highly proliferative cells.","authors":"Emi Tomikawa, Kei Takahashi, Haruhiko Hattori, Tadamasa Arai, Masakatsu Kawai, Kazumi Nishimura, Yasufumi Goto, Ryotaro Yagi, Yohei Miyamoto, Tomoya Miyoshi","doi":"10.1293/tox.2025-0083","DOIUrl":"10.1293/tox.2025-0083","url":null,"abstract":"<p><p>Phenotypic screening using motor neurons derived from the induced pluripotent stem (iPS) cell of a patient with amyotrophic lateral sclerosis led to the identification of Compound X, a novel agent with potent neuroprotective activity that is hypothesized to act by inhibiting hematopoietic progenitor kinase/germinal center kinase-like kinase (HGK). Unlike known HGK inhibitors, including Prostetin and GNE-495, Compound X and related Compounds Y and Z exhibited broader multi-kinase-inhibition profiles, including the strong inhibition of Aurora B kinase and strong-to-moderate inhibition of Src-family kinases in kinase panel screening. Owing to their roles in cytokinesis, we performed <i>in vitro</i> micronucleus tests to assess their genotoxicity. Compounds X, Y, and Z induced the multinucleation of cells at rates of 88.8, 71.5, and 91.8%, respectively, whereas Prostetin and GNE-495 resulted in rates of 0.5 and 1.3%, respectively, which were comparable to the control. A 5-day repeated-dose oral toxicity study of Compound X using mice, at doses of 125, 250, and 500 mg/kg/day, revealed decreased locomotor activity, hypothermia, and mortality at 500 mg/kg/day. Histopathology showed necrosis/hemorrhage in bone marrow cells; single-cell necrosis in the thymus, spleen, and mesenteric lymph nodes; nuclear pleomorphism and single-cell necrosis/necrosis in the gastrointestinal mucosa; and karyomegaly and a reduction in testicular germ cells. These toxicopathological findings suggest that Compound X induces nuclear pleomorphism and necrosis in highly proliferative cells. Although Compound X strongly suppressed HGK, its toxicity may be associated with broader multikinase inhibition, which is consistent with the finding that Prostetin and GNE-495 do not induce multinucleation <i>in vitro</i>.</p>","PeriodicalId":17437,"journal":{"name":"Journal of Toxicologic Pathology","volume":"39 3","pages":"93-101"},"PeriodicalIF":1.1,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13342316/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148412178","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":"<i>N</i>-methyl-<i>N</i>-nitrosourea-induced forestomach neoplastic lesions formed by week 13 following a single intraperitoneal administration in rasH2 mice.","authors":"Takamasa Numano, Ryo Inoue, Tatsuya Miyake, Masahiko Yasuda, Misa Mochizuki, Takashi Katsumata, Izumi Owada, Chiyoko Nishime, Taichi Yamamoto, Masami Suzuki","doi":"10.1293/tox.2025-0107","DOIUrl":"10.1293/tox.2025-0107","url":null,"abstract":"<p><p>CByB6F1-Tg (HRAS)2Jic mice (rasH2 mice) are widely used in 26-week short-term carcinogenicity assessments. To ensure phenotypic stability and carcinogenic sensitivity, a 26-week <i>N</i>-methyl-<i>N</i>-nitrosourea (MNU)-induced carcinogenic susceptibility monitoring study was conducted for quality assurance. The study included (i) comprehensive whole-organ monitoring after colony renewal, and (ii) simplified annual monitoring on production colonies focusing on forestomach tumor formation as the most sensitive endpoint. Retrospective analysis of our 26-week historical data indicated a high incidence of forestomach tumors in mice that were moribund or sacrificed before 13 weeks. Therefore, we compared the 13- and 26-week observation periods to evaluate whether 13 weeks was sufficient for simple carcinogenicity monitoring. RasH2 mice were intraperitoneally administered MNU (75 mg/kg) and observed for 13 and 26 weeks. Both groups exhibited small and large forestomach nodules, including hemorrhagic lesions. The corresponding histopathological features were squamous cell papillomas and carcinomas. The incidence of squamous cell papilloma or carcinoma was 100.0% in both sexes at 13 weeks, which was comparable to that at 26 weeks (100.0% in males and 93.3% in females). These results demonstrated that MNU-induced forestomach tumor can be reliably detected within 13 weeks, indicating that a shortened monitoring period of 13 weeks is sufficient to monitor carcinogenic susceptibility for quality assurance using genotoxic carcinogens in rasH2 mice.</p>","PeriodicalId":17437,"journal":{"name":"Journal of Toxicologic Pathology","volume":"39 3","pages":"103-110"},"PeriodicalIF":1.1,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13342314/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148412170","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":"Retrospective and histopathological study on epithelial tumors in the rectum and anal canal of dogs.","authors":"Kento Ishikawa, James K Chambers, Ko Nakashima, Kazuyuki Uchida","doi":"10.1293/tox.2025-0111","DOIUrl":"10.1293/tox.2025-0111","url":null,"abstract":"<p><p>Epithelial components of the rectum and anal canal comprise the rectal mucosa, anal canal mucosa, and anal glands. The clinicopathological characteristics of 111 cases of canine epithelial tumors in these regions were reviewed. Histopathological examination was performed on normal rectal and anal canal tissues and on 64 tumors. All signet-ring cell carcinomas and anal gland adenomas, as well as approximately half of the adenomas, were classified as anal canal tumors and were located within 1.5 cm of the anus. Acinar adenocarcinomas, papillary adenocarcinomas, and mucinous adenocarcinomas were predominantly classified as rectal tumors. Immunohistochemically, rectal adenomas, acinar adenocarcinomas, papillary adenocarcinomas, and mucinous adenocarcinomas frequently exhibited a CDX2⁺CK20⁺SOX2^-CK7^- immunophenotype, consistent with that of the proximal rectal mucosa. In contrast, adenomas in the anal canal frequently showed a CDX2^-CK20^-SOX2⁺CK7^± immunophenotype, consistent with that of the rectal mucosa at the recto-anal junction. Signet-ring cell carcinomas and anal gland adenomas exhibited a CDX2^-CK20^-SOX2⁺CK7⁺ immunophenotype, consistent with that of the anal glands. In a hierarchical cluster analysis of tumor immunophenotypes, Group 1 (mostly anal canal adenomas) and Group 2 (rectal adenomas, acinar adenocarcinomas, papillary adenocarcinomas, and mucinous adenocarcinomas) formed one cluster, whereas Group 3 (signet-ring cell carcinomas) and Group 4 (anal gland adenomas) formed another distinct cluster. Based on these results, canine epithelial tumors in the rectum and anal canal may be categorized into a rectal mucosa-like immunophenotype (including adenomas, acinar adenocarcinomas, papillary adenocarcinomas, and mucinous adenocarcinomas) and anal gland-like immunophenotype (including signet-ring cell carcinomas and anal gland adenomas).</p>","PeriodicalId":17437,"journal":{"name":"Journal of Toxicologic Pathology","volume":"39 2","pages":"75-85"},"PeriodicalIF":1.1,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13102509/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147775234","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":"Effect of single and repeated-dose oral administration of carbon tetrachloride on liver in zebrafish.","authors":"Satoshi Furukawa, Yukiko Nakajima, Naomi Fujiwara, Shiro Toyohisa, Yasushi Misawa, Kazuya Takeuchi","doi":"10.1293/tox.2025-0047","DOIUrl":"10.1293/tox.2025-0047","url":null,"abstract":"<p><p>Acute toxicity and 14-day repeated-dose toxicity studies were performed via oral gavage to elucidate the effects of oral exposure to carbon tetrachloride (CCl₄) on the liver of zebrafish. In the acute toxicity studies, the lethal dose 50% (LD₅₀) was 386 μL/kg (614 mg/kg, based on density conversion) for both males and females when using a 1% Tween aqueous solution vehicle, and 5,045 μL/kg (8,036 mg/kg) for males and 6,419 μL/kg (10,206 mg/kg) for females when using a corn oil vehicle (cf., rats: 10,054 mg/kg; mice: 13,000 mg/kg, according to known LD₅₀ values). The doses in the repeated toxicity study were set at 0, 200, and 300 μL/kg using a 1% Tween aqueous solution as the vehicle. The survival rate was 87% on Day 7 and 50% on Day 14 in the 200 μL/kg CCl₄-treated group, while it was 10% on Day 7 in the 300 μL/kg CCl₄-treated group. Histopathological findings, including focal bile duct proliferation, focal macrophage aggregation, and focal fibrosis, were detected in both acute and repeated-dose toxicity studies. However, no significant differences were observed in the incidence of these lesions between the control and CCl₄-treated groups. Therefore, the present study demonstrates that the acute lethal dose of CCl₄ administered via oral gavage in zebrafish is nearly equivalent to that observed in rodents. However, zebrafish exhibit markedly low sensitivity to CCl₄-induced liver injury in a species-specific manner.</p>","PeriodicalId":17437,"journal":{"name":"Journal of Toxicologic Pathology","volume":"39 1","pages":"65-74"},"PeriodicalIF":1.1,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13102508/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147775091","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":"Melanomas (amelanotic type) in albino rats.","authors":"Tetsuro Kurotaki, Junko Sato, Minoru Tsuchitani","doi":"10.1293/tox.2025-0100","DOIUrl":"10.1293/tox.2025-0100","url":null,"abstract":"<p><p>Albino rats lack melanin production due to a defect in the <i>tyrosinase</i> gene. Melanomas arising in albino rats, which originate from neural crest cells, are non-melanin-producing and are referred to as amelanotic melanomas (AM). AM in albino rats represents one of the most challenging tumors to diagnose pathologically using light microscopy, primarily because of the absence of melanin pigment. Although electron microscopy remains the gold standard for AM diagnosis, PNL2 serves as a practical alternative, particularly in toxicologic studies. To date, only eight reports have definitively diagnosed AM in albino rats by confirming the presence of premelanosomes through ultrastructural analysis. This review aims to provide toxicologic pathologists with information to aid in diagnosing melanomas by analyzing eight previous reports along with data from our own case studies.</p>","PeriodicalId":17437,"journal":{"name":"Journal of Toxicologic Pathology","volume":"39 2","pages":"53-63"},"PeriodicalIF":1.1,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13102507/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147775130","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":"An exophytic multinodular chordoma of the cervical spine in a ferret.","authors":"Tamami Suzuki, Rieru Kiyama, Paul Dela Cruz Valcorza, Keisuke Aoshima, Takashi Kimura","doi":"10.1293/tox.2025-0102","DOIUrl":"10.1293/tox.2025-0102","url":null,"abstract":"<p><p>An 8-year-old male ferret was presented with dyspnea and large, palpable cervical masses. Pathological examination revealed multiple exophytic nodular masses arising from the atlas and axis. Those vertebrae were almost completely replaced by neoplastic tissue. Histologically, the masses were composed of physaliferous cells with foamy cytoplasm embedded within a prominent chondro-osseous matrix. The diagnosis of chordoma was confirmed by immunohistochemistry, as tumor cells were positive for pan-cytokeratin, vimentin, S-100, and neuron-specific enolase. Notably, some chondrocytes and osteocytes adjacent to the tumor cells also expressed these markers, suggesting a neoplastic origin rather than a reactive process. Ki-67 labeling was confined to a subset of cytokeratin-positive cells at the periphery of the nodules, indicating that peripheral proliferation contributes to the exophytic growth pattern. This report describes a case of cervical chordoma with a unique exophytic presentation in a ferret.</p>","PeriodicalId":17437,"journal":{"name":"Journal of Toxicologic Pathology","volume":"39 2","pages":"87-92"},"PeriodicalIF":1.1,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13102506/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147775100","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":"Intramuscular collagen accumulation in different types of skeletal muscle fibers in middle-aged male rats.","authors":"Yoshikazu Taketa, Hideaki Takahashi","doi":"10.1293/tox.2025-0072","DOIUrl":"10.1293/tox.2025-0072","url":null,"abstract":"<p><p>This study focused on the histological characterization of age-related intramuscular collagen accumulation in different skeletal muscle fiber types, specifically fast- and slow-twitch fibers, in young and middle-aged male rats, in relation to the number of nuclei between muscle fibers. The extensor digitorum longus (EDL) and soleus (SOL) muscles from male Sprague-Dawley (SD) rats were collected and sectioned. Hematoxylin and eosin staining was performed for histological examination, while Picrosirius Red and hematoxylin staining were used for morphometric analyses. The SOL, a slow-twitch dominant muscle, tended to have a more distinct and thicker interstitium, as well as more collagen fibers and nuclei between muscle fibers, than the EDL, a fast-twitch dominant muscle. The degree of collagen accumulation between muscle fibers was positively correlated with the number of nuclei. Intramuscular collagen fibers increased with age in both the EDL and SOL, particularly in the latter. The number of nuclei remained unchanged with age. These results suggest that the increase in intramuscular collagen fibers with age is due to increased collagen production by existing fibroblasts rather than fibroblast proliferation. Given that middle-aged male SD rats fed <i>ad libitum</i> were obese, their slow-twitch muscles may have become susceptible to sarcopenic obesity accompanied by intramuscular collagen accumulation.</p>","PeriodicalId":17437,"journal":{"name":"Journal of Toxicologic Pathology","volume":"39 1","pages":"45-50"},"PeriodicalIF":0.9,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12826867/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146053002","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}