Journal of Toxicologic Pathology最新文献

{"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":"https://doi.org/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":0.9,"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":"https://doi.org/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":0.9,"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":"https://doi.org/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":0.9,"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":"https://doi.org/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":0.9,"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}

{"title":"Influence of rapamycin and chloroquine on chemically-induced liver injury in rats.","authors":"Sho Fujiwara, Takeshi Izawa, Mutsuki Mori, Mitsuru Kuwamura","doi":"10.1293/tox.2024-0104","DOIUrl":"10.1293/tox.2024-0104","url":null,"abstract":"<p><p>Drug-induced liver injury is a major reason for the discontinuation of drug development. Autophagy is a self-digestive process in the cell and can suppress cell death by removing damaged organelle from the cell. It is known that autophagy can modify drug-induced liver injury; however, details of the effects of autophagy modulation on chemically-induced hepatotoxicity are unclear. In this study, we investigated the influence of autophagy induction by rapamycin or inhibition by chloroquine on carbon tetrachloride (CCl₄)- or allyl alcohol (AA)-induced acute liver injury. Ten- to eleven-week-old male F344 rats were administrated with CCl₄ or AA after pretreatment by rapamycin or chloroquine, and were sampled 18 hours after the hepatotoxicant administration. Hepatic expression of the autophagosomal membrane protein LC3-II was significantly suppressed after CCl₄ administration by rapamycin pretreatment, compared with that in vehicle (DMSO) pretreatment. Expression of autophagy cargo protein p62, were significantly decreased after rapamycin treatment with AA administration. Hepatic p62 expression increased by chloroquine pretreatment. Serum AST and ALT were decreased after CCl₄ exposure in both rapamycin- and chloroquine-pretreated rats. On the other hand, regardless of pretreatment, pathological changes were mild in rats with AA exposure. These results showed that pretreatment with rapamycin or chloroquine can attenuate CCl₄-induced acute liver injury in rats.</p>","PeriodicalId":17437,"journal":{"name":"Journal of Toxicologic Pathology","volume":"39 4","pages":"3-14"},"PeriodicalIF":0.9,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12826878/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146052984","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":"Expression and distribution of tribbles pseudokinase 3 in oxidative stress-mediated acute liver and kidney injury models.","authors":"Yukako Shimotsuma, Takeshi Izawa, Mitsuru Kuwamura","doi":"10.1293/tox.2025-0040","DOIUrl":"10.1293/tox.2025-0040","url":null,"abstract":"<p><p>Tribbles pseudokinase 3 (Trib3) is an inactive protein kinase whose expression increases in response to various stresses. Our previous work showed that Trib3 may play a role in myelin destruction induced by oxidative and endoplasmic reticulum stress in demyelination (<i>dmy</i>) rats. The <i>dmy</i> rat exhibits hind limb ataxia and severe myelin breakdown in the central nervous system. To elucidate how Trib3 contributes to oxidative stress-mediated injury in organs other than the central nervous system, we used two models: an acute liver injury model induced by thioacetamide injection and an acute kidney injury model induced by cisplatin injection. Trib3 mRNA expression increased concurrently with tissue injury and declined during the repair phase. TRIB3 was detected in damaged areas, mainly in degenerated cells and infiltrating macrophages. These results suggest that Trib3 is upregulated in tissues damaged by oxidative stress and may serve as an indicator of tissue injury.</p>","PeriodicalId":17437,"journal":{"name":"Journal of Toxicologic Pathology","volume":"39 1","pages":"25-30"},"PeriodicalIF":0.9,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12861684/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146105965","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 tumor clonality with chemical carcinogenesis in a mouse model of visualized X chromosome inactivation.","authors":"Tomomi Maeda-Tateishi, Yuki Nagata, Yasuo Imanishi, Tomoe Hirakawa, Seong-Seng Tan, Masanori Emoto, Min Gi","doi":"10.1293/tox.2025-0075","DOIUrl":"10.1293/tox.2025-0075","url":null,"abstract":"<p><p>Tumor clonality is determined by somatic mutations in genes that regulate cell proliferation, and this can be either monoclonal or multiclonal. Assays based on X-chromosome inactivation that exploit the random inactivation of one of the two X chromosomes in female embryos have been used to evaluate tumor clonality. However, these methods require technically complex procedures and are not easily applicable to various types of tumors. Here, we visualized the clonality of tumors induced by chemical substances <i>in vivo</i> using X-linked <i>LacZ</i> heterozygous transgenic female mice that displayed a blue or white mosaic pattern of tissue on X-gal staining. In a model of colorectal tumors induced by 1, 2-dimethylhydrazine dihydrochloride and dextran sulfate sodium salt, 18 blue, 20 unstained (white), and seven mixed-colored tumors in intestinal tissues from 20 mice were observed after X-gal staining. Similarly, in a model of diethylnitrosamine-induced liver tumors, multiple blue or white nodules were observed. These findings demonstrated that this is a simple and effective method for visualizing tumor clonality <i>in vivo</i>. This approach may be readily applicable to models of chemically induced carcinogenesis and useful for evaluating the clonality of multifocal lesions.</p>","PeriodicalId":17437,"journal":{"name":"Journal of Toxicologic Pathology","volume":"39 1","pages":"31-38"},"PeriodicalIF":0.9,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12826865/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146053035","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":"Association between spontaneous neurogenic atrophy of the femoral muscle and islet cell tumors in aged F344 rats.","authors":"Mitsutoshi Uchida, Yumi Wako, Takeshi Kanno, Natsumi Shimoyama, Yutaka Nakahara, Takuya Doi, Yuki Tomonari, Junko Sato","doi":"10.1293/tox.2025-0016","DOIUrl":"10.1293/tox.2025-0016","url":null,"abstract":"<p><p>In aged F344/DuCrlCrlj rats, we observed that all animals with group atrophy of the biceps femoris muscle also had islet cell tumors, suggesting that spontaneous islet cell tumors may induce peripheral neuropathy and muscle atrophy. Among 220 aged male F344/DuCrlCrlj rats examined, 12.3% (27/220) had islet cell tumors, and of these, 22.2% (6/27) had neurogenic muscular atrophy. Sciatic nerve degeneration was observed in 3.2% (7/220) of cases, and all animals with neurogenic muscular atrophy had sciatic nerve degeneration. Notably, no neurogenic muscular atrophy was observed in rats without islet cell tumors. In contrast, rats with neurogenic muscular atrophy tended to have larger islet cell tumors. Although spinal nerve root degeneration was prevalent (90.8%, 198/218), two of the six rats with neurogenic muscular atrophy did not exhibit this pathology. Immunohistochemically, insulin was positive in all islet cell tumors, although glucagon- and somatostatin-positive reactions showed no association with neurogenic muscular atrophy. Experimentally induced hyperinsulinemia in rats is a known cause of neurogenic muscular atrophy, and similar associations have been reported in humans and spontaneous cases of pet rats with islet cell tumors. A complete coincidence between the occurrence of neurogenic muscular atrophy and islet cell tumors in our investigation suggests that some islet cell tumors in F344/DuCrlCrlj rats may be functionally active, and that hyperinsulinemia may contribute to the pathogenesis of neurogenic muscular atrophy.</p>","PeriodicalId":17437,"journal":{"name":"Journal of Toxicologic Pathology","volume":"39 1","pages":"15-23"},"PeriodicalIF":0.9,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12826866/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146053060","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 canine insulinoma with amphicrine differentiation: morphological and immunohistochemical characteristics.","authors":"Hisaki Tokuno, Masashi Fujimoto, Makoto Tsuji, Miyuu Tanaka, Takeshi Izawa, Mitsuru Kuwamura","doi":"10.1293/tox.2025-0062","DOIUrl":"10.1293/tox.2025-0062","url":null,"abstract":"<p><p>A 10-year-old male toy poodle presented with hypoglycemia. An insulinoma was suspected and a surgical excision of two pancreatic masses was performed. White-gray, demarcated, soft masses were identified in the pancreas. Histopathologically, two types of growth patterns were observed in the same neoplasm: nest and glandular. To investigate cellular differentiation, we performed immunohistochemical and transmission electron microscopy analyses. Both types of neoplastic cells were immunopositive for INSM1, Nkx2.2 and insulin. However, the neoplastic cells exhibiting the nest pattern contained exocrine granules, whereas those with the glandular pattern were immunopositive for cytokeratin. Both types of neoplastic cells showed not only neuroendocrine but also exocrine differentiation in the same neoplastic cell. To the best of our knowledge, this is the first report describing the morphology and immunophenotype of the canine insulinoma with amphicrine differentiation: showing both neuroendocrine and exocrine features.</p>","PeriodicalId":17437,"journal":{"name":"Journal of Toxicologic Pathology","volume":"39 1","pages":"39-44"},"PeriodicalIF":0.9,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12826864/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146053005","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}