Journal of Toxicologic Pathology最新文献_第10页

Spontaneous adenocarcinoma with giant cell formation in the accessory sex glands in a male Sprague-Dawley rat. 雄性Sprague-Dawley大鼠副性腺自发性腺癌伴巨细胞形成。

IF 1.2 4区医学

Journal of Toxicologic Pathology Pub Date : 2021-10-01 Epub Date: 2021-07-23 DOI: 10.1293/tox.2021-0019

Shingo Miyazaki, Takashi Ogawa, Tomoya Onozato, Yuji Okuhara, Tatsuya Nagasawa, Morimichi Hayashi

{"title":"Spontaneous adenocarcinoma with giant cell formation in the accessory sex glands in a male Sprague-Dawley rat.","authors":"Shingo Miyazaki, Takashi Ogawa, Tomoya Onozato, Yuji Okuhara, Tatsuya Nagasawa, Morimichi Hayashi","doi":"10.1293/tox.2021-0019","DOIUrl":"https://doi.org/10.1293/tox.2021-0019","url":null,"abstract":"In this study, we report the features of an adenocarcinoma with giant cell formation spontaneously occurring in the accessory sex glands of a male 10-month-old Sprague-Dawley rat. A milky white mass was found in the region corresponding to the left seminal vesicle and the left coagulating gland. Histologically, tumor cells exhibited diverse growth patterns, including glandular/trabecular, cystic, and sheet-like growth areas. The tumor cells were pleomorphic, with round- or oval-shaped nuclei and abundant eosinophilic cytoplasm. Mitotic figures were occasionally observed. Giant cells were also prominent in the sheet-like growth area, with intracytoplasmic vacuoles containing eosinophilic material. The stroma was rich in collagen fibers and fibroblasts. Numerous inflammatory cells were observed in the glandular and cystic lumina and stroma. Immunohistochemically, the tumor cells were positive for cytokeratin AE1/AE3 and proliferating cell nuclear antigen. In the sheet-like growth area, some of the tumor cells and giant cells were positive for vimentin in the cytoplasm adjacent to the nucleus. Electron microscopy revealed that the tumor cells contained a small number of mitochondria and rough endoplasmic reticulum, and had no basement membrane or desmosome. The giant cells occasionally contained variably sized intracytoplasmic lumina and globular filamentous bodies, probably corresponding to vimentin. Considering these morphological features, the tumor was diagnosed as an adenocarcinoma with the formation of giant tumor cells originating from the male accessory sex glands.","PeriodicalId":17437,"journal":{"name":"Journal of Toxicologic Pathology","volume":"34 4","pages":"345-351"},"PeriodicalIF":1.2,"publicationDate":"2021-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/08/70/tox-34-345.PMC8484923.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39527000","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}

引用次数: 0

A case of spontaneous Zymbal's gland carcinoma with lung metastasis in an aged Fischer 344 rat. 老年Fischer 344大鼠自发性淋巴腺癌伴肺转移1例。

IF 1.2 4区医学

Journal of Toxicologic Pathology Pub Date : 2021-10-01 Epub Date: 2021-07-23 DOI: 10.1293/tox.2021-0013

Ai Maeno, Yoshimitsu Sakamoto, Motoki Hojo, Yukie Tada, Jin Suzuki, Akiko Inomata, Takako Moriyasu, Akihiko Hirose, Noriko Kemuriyama, Katsuhiro Miyajima, Dai Nakae

{"title":"A case of spontaneous Zymbal's gland carcinoma with lung metastasis in an aged Fischer 344 rat.","authors":"Ai Maeno, Yoshimitsu Sakamoto, Motoki Hojo, Yukie Tada, Jin Suzuki, Akiko Inomata, Takako Moriyasu, Akihiko Hirose, Noriko Kemuriyama, Katsuhiro Miyajima, Dai Nakae","doi":"10.1293/tox.2021-0013","DOIUrl":"https://doi.org/10.1293/tox.2021-0013","url":null,"abstract":"Zymbal's gland neoplasms are induced in rats through the administration of various carcinogens, but spontaneous neoplasia is rare. This report describes a spontaneous Zymbal's gland carcinoma with lung metastasis found in an aged male Fischer 344 rat. Macroscopically, the dome-like tumor nodule, approximately 30 mm in diameter with ulceration, was located near the ear canal of the rat. No healthy tissue or structure of Zymbal's gland was identified on the corresponding side, while the normal salivary glands and a lacrimal gland were observed. Histologically, a large part of the tumor mass was occupied by poorly differentiated neoplastic cells, the shapes of which were oval to polygonal or fusiform. Additionally, clusters of sebaceous-like foamy cells and squamous metaplasia with prominent keratinization were observed. Tumor cells were found to metastasize to the lung; these cells displayed histological similarities, including a sebaceous gland-like pattern, to those in the primary site. The tumor cells were immunohistochemically positive for cytokeratin AE1/AE3 or vimentin but negative for CD68, S100, α-smooth muscle actin, von Willebrand factor, and desmin. Our results indicate that the tumor was a poorly differentiated Zymbal's gland carcinoma with lung metastasis.","PeriodicalId":17437,"journal":{"name":"Journal of Toxicologic Pathology","volume":"34 4","pages":"353-358"},"PeriodicalIF":1.2,"publicationDate":"2021-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/47/e9/tox-34-353.PMC8484931.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39519982","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}

引用次数: 1

Application of humanized mice to toxicology studies: Evaluation of the human relevance of the mode of action for rodent liver tumor formation by activators of the constitutive androstane receptor (CAR). 将人源化小鼠应用于毒理学研究：评估构成性雄甾烷受体 (CAR) 激活剂对啮齿动物肝脏肿瘤形成的作用模式与人类的相关性。

IF 1.2 4区医学

Journal of Toxicologic Pathology Pub Date : 2021-10-01 Epub Date: 2021-06-27 DOI: 10.1293/tox.2021-0027

Tomoya Yamada

{"title":"Application of humanized mice to toxicology studies: Evaluation of the human relevance of the mode of action for rodent liver tumor formation by activators of the constitutive androstane receptor (CAR).","authors":"Tomoya Yamada","doi":"10.1293/tox.2021-0027","DOIUrl":"10.1293/tox.2021-0027","url":null,"abstract":"The constitutive androstane receptor (CAR)-mediated mode of action (MOA) for phenobarbital (PB)-induced rodent liver tumor formation has been established, with increased hepatocyte proliferation, which is a key event in tumor formation. Previous studies have demonstrated that PB and other CAR-activators stimulate proliferation in cultured rodent hepatocytes, but not in cultured human hepatocytes. However, in the genetically humanized CAR and pregnane X receptor (PXR) mouse (hCAR/hPXR mouse, downstream genes are still mouse), PB increased hepatocyte proliferation and tumor production in vivo. In contrast to the hCAR/hPXR mouse, studies with chimeric mice with human hepatocytes (PXB-mouse, both receptor and downstream genes are human) demonstrated that PB did not increase human hepatocyte proliferation in vivo. PB increased hepatocyte proliferation in a chimeric mouse model with rat hepatocytes, indicating that the lack of human hepatocyte proliferation is not due to any functional defect in the chimeric mouse liver environment. Gene expression analysis demonstrated that the downstream genes of CAR/PXR activation were similar in hCAR/hPXR and CD-1 mice, but differed from those observed in chimeric mice with human hepatocytes. These findings strongly support the conclusion that the MOA for CAR-mediated rodent liver tumor formation is qualitatively implausible for humans. Indeed, epidemiological studies have found no causal link between PB and human liver tumors. There are many similarities with respect to hepatic effects and species differences between rodent CAR and peroxisome proliferator-activated receptor α activators. Based on our research, the chimeric mouse with human hepatocytes (PXB-mouse) is reliable for human cancer risk assessment of test chemicals.","PeriodicalId":17437,"journal":{"name":"Journal of Toxicologic Pathology","volume":"34 4","pages":"283-297"},"PeriodicalIF":1.2,"publicationDate":"2021-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/f4/75/tox-34-283.PMC8484926.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39526547","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}

引用次数: 0

Histopathological changes of the spinal cord and motor neuron dynamics in SOD1 Tg mice SOD1-Tg小鼠脊髓组织病理学变化及运动神经元动力学

IF 1.2 4区医学

Journal of Toxicologic Pathology Pub Date : 2021-10-01 DOI: 10.1293/tox.2021-0056

Masaharu Tanaka, Kengo Homma, A. Soejima

引用次数: 1

Contribution of toxicologic pathologists for the safety of human health in biomedical research-past, present, and future of the JSTP. 毒理学病理学家对生物医学研究中人类健康安全的贡献——JSTP的过去、现在和未来。

IF 1.2 4区医学

Journal of Toxicologic Pathology Pub Date : 2021-10-01 Epub Date: 2021-05-23 DOI: 10.1293/tox.2021-0028

Makoto Enomoto, Hijiri Iwata, Mari Iida

{"title":"Contribution of toxicologic pathologists for the safety of human health in biomedical research-past, present, and future of the JSTP.","authors":"Makoto Enomoto, Hijiri Iwata, Mari Iida","doi":"10.1293/tox.2021-0028","DOIUrl":"https://doi.org/10.1293/tox.2021-0028","url":null,"abstract":"The research field of \"Toxicologic Pathology\" evaluates potentially toxic chemical exposures and chemically mediated illnesses in humans and experimental animals. Comparative studies of chemical exposures between model organisms and humans are essential for the risk assessment of chemicals and human health. Here we review the development and activities of the Japanese Society of Toxicologic Pathology (JSTP) during its 37-year history. Toxicological pathology studies provide many interesting and valuable findings. Rodent cancer bioassay data demonstrate the importance of dose levels, times, and duration of exposures to chemicals that possibly cause human cancers. Studies of toxic injuries in the nasal cavity demonstrate that specific chemical compounds affect different target cells and tissues. These observations are relevant for current air pollution studies in the preventive medicine field. Future toxicological pathology studies will be enhanced by applying molecular pathology with advanced observation techniques. In addition to the nasal cavity, another sense organ such as the tongue should be a potential next program of our mission for risk assessment of inhaled and ingested chemicals. As a message to the younger members of the JSTP, interdisciplinary and global cooperation should be emphasized. Elucidating the mechanisms of toxicologic pathology with a combination of advanced expertise in genetics and molecular biology offers promise for future advances by JSTP members.","PeriodicalId":17437,"journal":{"name":"Journal of Toxicologic Pathology","volume":"34 4","pages":"275-282"},"PeriodicalIF":1.2,"publicationDate":"2021-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/94/36/tox-34-275.PMC8484924.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39526545","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}

引用次数: 1

Genome editing of Nf1, Pten, and Trp53 in neonatal mice induces glioblastomas positive for oligodendrocyte lineage transcription factor 2. 新生小鼠中Nf1、Pten和Trp53的基因组编辑可诱导少突胶质细胞谱系转录因子2阳性的胶质母细胞瘤。

IF 1.2 4区医学

Journal of Toxicologic Pathology Pub Date : 2021-10-01 Epub Date: 2021-07-23 DOI: 10.1293/tox.2021-0029

Hiromi Yamamoto, Keisuke Yamamura, Haruka Nagasaki, Takamasa Suzuki, Fumiko Ninomiya, Kenji Matsubara, Naomoto Harada, Shuichi Ohkubo

{"title":"Genome editing of Nf1, Pten, and Trp53 in neonatal mice induces glioblastomas positive for oligodendrocyte lineage transcription factor 2.","authors":"Hiromi Yamamoto, Keisuke Yamamura, Haruka Nagasaki, Takamasa Suzuki, Fumiko Ninomiya, Kenji Matsubara, Naomoto Harada, Shuichi Ohkubo","doi":"10.1293/tox.2021-0029","DOIUrl":"https://doi.org/10.1293/tox.2021-0029","url":null,"abstract":"To generate a mouse glioblastoma model by genome editing, we introduced Cas9 protein and guide RNAs specific for Nf1, Pten, and Trp53 into the neonatal mouse forebrain by electroporation. We found a high incidence (approximately 90%) of glial tumor development, including glioblastomas, 15 weeks later. The histological features of the tumors were similar to those of diffuse gliomas and, in some cases, similar to human glioblastomas, with microvascular proliferation (glomeruloid structure). In addition, unlike glial fibrillary acidic protein (GFAP)-positive glioblastomas generated using a similar method in a previous model, the majority of tumor cells were positive for oligodendrocyte lineage transcription factor 2, but negative for GFAP and neurofilaments. One base pair insertions identical to those seen in a previous model were found around the target sequences in Nf1, Pten, and Trp53, and additional deletions were found only in Pten. Considering that the histological characteristics were different from those seen in the previous model, our new model provides an additional research tool to investigate the early stages of glioblastoma development.","PeriodicalId":17437,"journal":{"name":"Journal of Toxicologic Pathology","volume":"34 4","pages":"359-365"},"PeriodicalIF":1.2,"publicationDate":"2021-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/d7/01/tox-34-359.PMC8484922.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39504621","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}

引用次数: 1

A possible critical dosing period of p-cumylphenol for development of cystic kidneys in rat neonates 对枯基苯酚对大鼠新生儿囊性肾发育的可能临界给药期

IF 1.2 4区医学

Journal of Toxicologic Pathology Pub Date : 2021-09-24 DOI: 10.1293/tox.2021-0010

T. Nakazawa, Y. Yamaguchi, Yachiyo Fukunaga, K. Tamura

{"title":"A possible critical dosing period of p-cumylphenol for development of cystic kidneys in rat neonates","authors":"T. Nakazawa, Y. Yamaguchi, Yachiyo Fukunaga, K. Tamura","doi":"10.1293/tox.2021-0010","DOIUrl":"https://doi.org/10.1293/tox.2021-0010","url":null,"abstract":"In accordance with a previous report on cystic kidneys induced in rat neonates when dosed with p-cumylphenol (PCP) for 18 days from postnatal day (PND) 4, 3 rat neonates were dosed with PCP once a day for 14 days, either from PND 14, 21, 28, 35, or 42 as W2, W3, W4, W5, and W6 groups, respectively, to investigate whether dosing periods in different PNDs influenced the development of cystic renal tubules. The lesion was striking in the W2 group and at a lesser magnitude in the W3 group, whereas either kidney was unaffected when dosing was initiated beyond PND 28. These findings, together with the results from the previous study, suggested that PND 14-28 is a critical dosing period for PCP to develop cystic kidneys in rat neonates. The lining epithelium of the cystic tubules was immunohistochemically positive for AQP2. This finding and the anatomical location indicated that the cystic tubules were of collecting duct origin. Either obstruction, fluid accumulation, or reparative hyperplasia of the lining epithelium was unlikely to be involved in the formation of cystic tubules lined with a monolayer of cuboidal or columnar epithelium with a high nuclear density. Thus, the follow-up investigation on PCP suggested a critical dosing period of PND 14-28 in rat neonates for the development of cystic dilation of renal collecting ducts. This study further supports that additive hyperplasia of the lining epithelium is a fundamental basis of this unique lesion.","PeriodicalId":17437,"journal":{"name":"Journal of Toxicologic Pathology","volume":"35 1","pages":"123 - 127"},"PeriodicalIF":1.2,"publicationDate":"2021-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43844256","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Effects of testosterone on rat placental development 睾酮对大鼠胎盘发育的影响

IF 1.2 4区医学

Journal of Toxicologic Pathology Pub Date : 2021-09-16 DOI: 10.1293/tox.2021-0035

S. Furukawa, Naho Tsuji, Seigo Hayashi, Yusuke Kuroda, M. Kimura, Chisato Hayakawa, Kazuya Takeuchi, A. Sugiyama

{"title":"Effects of testosterone on rat placental development","authors":"S. Furukawa, Naho Tsuji, Seigo Hayashi, Yusuke Kuroda, M. Kimura, Chisato Hayakawa, Kazuya Takeuchi, A. Sugiyama","doi":"10.1293/tox.2021-0035","DOIUrl":"https://doi.org/10.1293/tox.2021-0035","url":null,"abstract":"We investigated the morphological effects of testosterone on placental development in a rat model of polycystic ovarian syndrome (PCOS). Testosterone propionate (TP), which was subcutaneously administered to pregnant rats with 5 mg/animal from gestation day (GD) 14 to GD 18, induced a maternal weight reduction without mortality or clinical signs from GD 19 onwards. A decrease in fetal and placental weight, an increase in intrauterine growth retardation (IUGR) rates, and histological changes in the placenta were observed on GD 21 but not on GD15 or 17. Histopathologically, on GD 21, the trophoblast septa thickened, and the maternal sinusoids were narrowed in the labyrinth zone, resulting in a small placenta. Additionally, the placental weight, thickness, and histological morphology in the labyrinth zone on GD 21 in the TP-treated group were nearly identical to those on GD 17 in the control and TP-treated groups. Therefore, it was assumed that the testosterone-induced small placenta was induced in association with the developmental inhibition of the fetal part of the placentas from GD 17 onwards.","PeriodicalId":17437,"journal":{"name":"Journal of Toxicologic Pathology","volume":"35 1","pages":"37 - 44"},"PeriodicalIF":1.2,"publicationDate":"2021-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45033509","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 1

Spontaneous seminoma in medaka (Oryzias latipes) 水稻自发性精原细胞瘤

IF 1.2 4区医学

Journal of Toxicologic Pathology Pub Date : 2021-09-08 DOI: 10.1293/tox.2021-0024

Yusuke Kuroda, Yumiko Hoshikawa, Kota Irie, M. Kimura, Kazuya Takeuchi, S. Furukawa

引用次数: 2

Chronic otitis externa with heat shock protein 70-positive intranuclear inclusion bodies in the ceruminous gland epithelium of a Chihuahua dog 吉娃娃犬耳蜗上皮慢性外耳炎伴热休克蛋白70阳性核内包涵体

IF 1.2 4区医学

Journal of Toxicologic Pathology Pub Date : 2021-08-28 DOI: 10.1293/tox.2021-0033

Takeru Kiuchi, Kenichi Watanabe, S. Nakagun, K. Miyahara, N. Horiuchi, Y. Kobayashi

{"title":"Chronic otitis externa with heat shock protein 70-positive intranuclear inclusion bodies in the ceruminous gland epithelium of a Chihuahua dog","authors":"Takeru Kiuchi, Kenichi Watanabe, S. Nakagun, K. Miyahara, N. Horiuchi, Y. Kobayashi","doi":"10.1293/tox.2021-0033","DOIUrl":"https://doi.org/10.1293/tox.2021-0033","url":null,"abstract":"A Chihuahua dog showed persistent itching in the right ear canal. Anti-inflammatory medicines and prednisolone were ineffective and total ear canal ablation was performed. Histological diagnosis was chronic otitis externa. Eosinophilic intranuclear inclusion bodies (Cowdry type A and full-type) were occasionally observed in the ceruminous gland epithelium. The inclusion bodies were negative for nucleic acid and ultrastructurally composed of fibrous structures (approximately 10 nm in width). Viral infection was initially suspected, but polymelase chain reaction tests did not detect the expected viral genes. Immunohistochemistry revealed that the inclusion bodies were positive for heat shock protein 70 (HSP70), suggesting that these bodies could be protein aggregates including HSP70. The etiology of this lesion has not been elucidated, but chronic inflammation may influence the cytoplasm-to-nuclear transportation of HSP70. To the best of our knowledge, this is the first report of canine chronic otitis externa with HSP70-positive intranuclear inclusion bodies.","PeriodicalId":17437,"journal":{"name":"Journal of Toxicologic Pathology","volume":"35 1","pages":"83 - 87"},"PeriodicalIF":1.2,"publicationDate":"2021-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41412802","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0