Journal of Toxicologic Pathology最新文献_第7页

Lobular distribution of enhanced expression levels of heat shock proteins using in-situ hybridization in the mouse liver treated with a single administration of CCl4 使用in-situ</i&gt观察热休克蛋白表达水平增强的小叶分布单次给药CCl4处理小鼠肝脏的杂交

4区医学

Journal of Toxicologic Pathology Pub Date : 2023-01-01 DOI: 10.1293/tox.2023-0053

Hitoshi KANDORI, Masami AOKI, Yumiko MIYAMOTO, Sayuri NAKAMURA, Ryosuke KOBAYASHI, Mitsuharu MATSUMOTO, Kotaro YOKOYAMA

引用次数: 0

Two cases of cartilaginous metaplasia in the sclera of Japanese White rabbits. 日本大白兔巩膜软骨化生2例。

IF 1.2 4区医学

Journal of Toxicologic Pathology Pub Date : 2023-01-01 DOI: 10.1293/tox.2022-0062

Kotaro Yamada, Yoshinori Yamagiwa, Miki Masatsugu, Yu Haranosono

{"title":"Two cases of cartilaginous metaplasia in the sclera of Japanese White rabbits.","authors":"Kotaro Yamada, Yoshinori Yamagiwa, Miki Masatsugu, Yu Haranosono","doi":"10.1293/tox.2022-0062","DOIUrl":"https://doi.org/10.1293/tox.2022-0062","url":null,"abstract":"Spontaneous cartilaginous metaplasia of the sclera has not been reported in rabbits. Herein, we report two cases of spontaneous cartilaginous metaplasia in the sclera of Japanese White (JW) rabbits. Case 1 was noted in a 14-week-old male Kbs:JW rabbit that received a single ocular instillation of 20% isoproterenol (IP) a day before necropsy, and showed no abnormalities in clinical signs, ophthalmological assessments, and necropsy. Case 2 was noted in a 38-week-old male Kbs:JW rabbit that was housed under light-emitting diode (LED) lighting for 26 weeks and showed no effects of LED on clinical signs, ophthalmological assessments, and necropsy. Histological sections of the eyes of both animals were prepared and stained with hematoxylin and eosin (H&E) and Alcian blue, and immunohistochemical staining for vimentin was performed. The H&E-stained specimens showed focal hyaline cartilage-like tissues distributed between the scleral fibers at the posterior pole in both cases. The surrounding scleral fibers were compressed and/or partially destroyed by the cartilage-like tissue. The cartilage-like matrix was stained blue by Alcian blue, and immunohistochemistry showed that chondrocyte-like cells were positive for vimentin. Based on these findings, we diagnosed cartilaginous metaplasia in the sclera of Kbs:JW rabbits. The lesion was farther from the IP administration site in Case 1 and was not accompanied by other ophthalmological or histopathological abnormalities in either of the cases. This implies that the lesions occurred spontaneously owing to the abnormal differentiation of neural crest-derived cells.","PeriodicalId":17437,"journal":{"name":"Journal of Toxicologic Pathology","volume":"36 1","pages":"45-48"},"PeriodicalIF":1.2,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/f0/de/tox-36-045.PMC9837471.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10585370","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

Effects of Siraitia grosvenorii extract on nonalcoholic steatohepatitis-like lesions in Sprague Dawley rats fed a choline-deficient, methionine-lowered, l-amino acid-defined diet. 罗汉果提取物对饲喂胆碱缺乏、蛋氨酸降低、l-氨基酸限定饮食的Sprague Dawley大鼠非酒精性脂肪性肝炎样病变的影响

IF 1.2 4区医学

Journal of Toxicologic Pathology Pub Date : 2023-01-01 DOI: 10.1293/tox.2022-0043

Kinuko Uno, Katsuhiro Miyajima, Shuji Ogawa, Noriko Suzuki-Kemuriyama, Dai Nakae

{"title":"Effects of Siraitia grosvenorii extract on nonalcoholic steatohepatitis-like lesions in Sprague Dawley rats fed a choline-deficient, methionine-lowered, l-amino acid-defined diet.","authors":"Kinuko Uno, Katsuhiro Miyajima, Shuji Ogawa, Noriko Suzuki-Kemuriyama, Dai Nakae","doi":"10.1293/tox.2022-0043","DOIUrl":"https://doi.org/10.1293/tox.2022-0043","url":null,"abstract":"Siraitia grosvenorii is the fruit of a cucurbitaceous vine endemic to China. Its extract has been used as a sweetener and exhibits various anti-inflammatory and anticarcinogenic effects mediated via its antioxidant properties. In the present study, we aimed to clarify the preventive or ameliorative effects of S. grosvenorii extract (SGE) on nonalcoholic steatohepatitis-like lesions induced in male Hsd: Sprague Dawley rats fed a choline-deficient, methionine-lowered, l-amino acid-defined diet for 13 weeks. This diet increased hepatotoxicity parameters and upregulated the expression of inflammation- and fibrosis-related genes in the liver, resulting in the progression of hepatic lesions, oxidative stress, hepatocellular apoptosis, and fibrosis. Furthermore, this diet upregulated the expression of phosphorylated nuclear factor-κB (NF-κB) and CD44. SGE administration inhibited these lesions, similar to CD44, a factor that controls hepatic inflammation and fibrosis. These results revealed that SGE impacts the disease stage via antioxidative effects and regulation of CD44 expression. SGE was found to be useful for preventing and treating steatohepatitis.","PeriodicalId":17437,"journal":{"name":"Journal of Toxicologic Pathology","volume":"36 1","pages":"1-10"},"PeriodicalIF":1.2,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/b7/35/tox-36-001.PMC9837469.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10585374","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 convolutional neural network for analyzing hepatic fibrosis in mice. 卷积神经网络在小鼠肝纤维化分析中的应用。

IF 1.2 4区医学

Journal of Toxicologic Pathology Pub Date : 2023-01-01 DOI: 10.1293/tox.2022-0066

Hyun-Ji Kim, Eun Bok Baek, Ji-Hee Hwang, Minyoung Lim, Won Hoon Jung, Myung Ae Bae, Hwa-Young Son, Jae-Woo Cho

{"title":"Application of convolutional neural network for analyzing hepatic fibrosis in mice.","authors":"Hyun-Ji Kim, Eun Bok Baek, Ji-Hee Hwang, Minyoung Lim, Won Hoon Jung, Myung Ae Bae, Hwa-Young Son, Jae-Woo Cho","doi":"10.1293/tox.2022-0066","DOIUrl":"https://doi.org/10.1293/tox.2022-0066","url":null,"abstract":"Recently, with the development of computer vision using artificial intelligence (AI), clinical research on diagnosis and prediction using medical image data has increased. In this study, we applied AI methods to analyze hepatic fibrosis in mice to determine whether an AI algorithm can be used to analyze lesions. Whole slide image (WSI) Sirius Red staining was used to examine hepatic fibrosis. The Xception network, an AI algorithm, was used to train normal and fibrotic lesion identification. We compared the results from two analyses, that is, pathologists' grades and researchers' annotations, to observe whether the automated algorithm can support toxicological pathologists efficiently as a new apparatus. The accuracies of the trained model computed from the training and validation datasets were greater than 99%, and that obtained by testing the model was 100%. In the comparison between analyses, all analyses showed significant differences in the results for each group. Furthermore, both normalized fibrosis grades inferred from the trained model annotated the fibrosis area, and the grades assigned by the pathologists showed significant correlations. Notably, the deep learning algorithm derived the highest correlation with the pathologists' average grade. Owing to the correlation outcomes, we conclude that the trained model might produce results comparable to those of the pathologists' grading of the Sirius Red-stained WSI fibrosis. This study illustrates that the deep learning algorithm can potentially be used for analyzing fibrotic lesions in combination with Sirius Red-stained WSIs as a second opinion tool in non-clinical research.","PeriodicalId":17437,"journal":{"name":"Journal of Toxicologic Pathology","volume":"36 1","pages":"21-30"},"PeriodicalIF":1.2,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/c2/9e/tox-36-021.PMC9837472.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10585372","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

Primary epididymis squamous cell carcinoma in a CB6F1-Tg rasH2 mouse. CB6F1-Tg rasH2小鼠原发性附睾鳞状细胞癌。

IF 1.2 4区医学

Journal of Toxicologic Pathology Pub Date : 2022-10-01 Epub Date: 2022-06-30 DOI: 10.1293/tox.2022-0047

Manabu Ikeda, Toshihisa Fujiwara, Junko Fujishima, Airo Yukawa, Kinji Kobayashi

{"title":"Primary epididymis squamous cell carcinoma in a CB6F1-Tg rasH2 mouse.","authors":"Manabu Ikeda, Toshihisa Fujiwara, Junko Fujishima, Airo Yukawa, Kinji Kobayashi","doi":"10.1293/tox.2022-0047","DOIUrl":"https://doi.org/10.1293/tox.2022-0047","url":null,"abstract":"In a 26-week carcinogenicity study in rasH2-Tg mice, squamous cell carcinoma on the epididymis was observed in a male mouse in the positive control group treated with N-methyl-N-nitrosourea. A 29-week-old male rasH2-Tg mouse that was euthanized 21 weeks after the administration of N-methyl-N-nitrosourea had a white-grayish mass on the left caput epididymis. The mass was nodular and consisted of pleomorphic tumor cells forming alveolar, sheeted, and trabecular structures suggesting epithelial tumor growth. These cells presented a cobblestone-like arrangement and formed intercellular bridges. Keratinization was infrequently observed. Periodic acid-methenamine-silver staining revealed argyrophilic fibrous structures around the alveolar structure of the tumor cells. Immunohistochemically, the tumor cells were positive for cytokeratin AE1/AE3 and cytokeratin 14 and negative for cytokeratin 5, p63, uroplakin III, vimentin, desmin, and αSMA. These immunohistochemical results suggested the tumor cells originated from the epididymal ducts. Metastatic lesions were observed in the mesenteric, inguinal, and pancreaticoduodenal lymph nodes. Based on these results, this tumor was diagnosed to be a primary squamous cell carcinoma of the epididymis. This is the first report of primary squamous cell carcinoma of the epididymis in a rasH2-Tg mouse.","PeriodicalId":17437,"journal":{"name":"Journal of Toxicologic Pathology","volume":"35 4","pages":"349-353"},"PeriodicalIF":1.2,"publicationDate":"2022-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/4d/60/tox-35-349.PMC9647212.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40475883","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

Changes in 5-Fluorouracil-induced external granular cell damage during the time-course of the developing cerebellum of infant rats. 5-氟尿嘧啶诱导的幼鼠小脑外颗粒细胞损伤在时间过程中的变化。

IF 1.2 4区医学

Journal of Toxicologic Pathology Pub Date : 2022-10-01 Epub Date: 2022-05-30 DOI: 10.1293/tox.2022-0003

Yuko Yamaguchi, Tsubasa Saito, Mizuho Takagi, Tomomi Nakazawa, Kazutoshi Tamura

{"title":"Changes in 5-Fluorouracil-induced external granular cell damage during the time-course of the developing cerebellum of infant rats.","authors":"Yuko Yamaguchi, Tsubasa Saito, Mizuho Takagi, Tomomi Nakazawa, Kazutoshi Tamura","doi":"10.1293/tox.2022-0003","DOIUrl":"https://doi.org/10.1293/tox.2022-0003","url":null,"abstract":"5-Fluorouracil (5-FU) is widely used as a chemotherapeutic agent that blocks DNA synthesis and replication by inhibiting thymidylate synthetase. This study aimed to elucidate 5-FU-induced changes in the external granular cells (EGCs) in the cerebellum of infant rats and the possible underlying mechanism. Six-day-old infant rats were injected subcutaneously with 40 mg/kg of 5-FU, and their cerebellums were examined at 6, 9, 12, and 24 h after treatment (HAT), and 2, 4, and 10 d after treatment (DAT). The width of the external granular layer (EGL) decreased from 24 HAT to 4 DAT in the 5-FU group compared to that in the control group. However, the width in the 5-FU group was comparable to that of the control group at 10 DAT. The number of apoptotic cells, cleaved caspase 3-labeling index (LI%), p21cip1-LI%, and expression levels of p53, p21cip1, and Fas mRNAs increased at 24 HAT. However, no changes were detected in the expression levels of Puma and Bax mRNAs at any time point. BrdU-LI% increased at 6 and 12 HAT but decreased at 24 HAT. The phospho-histone H3-LI% decreased from 6 HAT to 2 DAT. The width of the molecular layer decreased compared to that of the control group at 10 DAT. No differences were observed in Purkinje cell development. These results indicate that 5-FU inhibited cell proliferation by inducing apoptosis of EGCs via activation of Fas and caspase-3 without the involvement of the mitochondrial pathway and induced p53-dependent G1-S and G2-M phase arrest.","PeriodicalId":17437,"journal":{"name":"Journal of Toxicologic Pathology","volume":"35 4","pages":"299-311"},"PeriodicalIF":1.2,"publicationDate":"2022-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/51/f3/tox-35-299.PMC9647215.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40475884","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

Kidney organoid derived from renal tissue stem cells is a useful tool for histopathological assessment of nephrotoxicity in a cisplatin-induced acute renal tubular injury model. 来源于肾组织干细胞的肾类器官是对顺铂诱导的急性肾小管损伤模型肾毒性进行组织病理学评估的有用工具。

IF 1.2 4区医学

Journal of Toxicologic Pathology Pub Date : 2022-10-01 Epub Date: 2022-07-18 DOI: 10.1293/tox.2022-0006

Shota Ueno, Kenji Kokura, Yasushi Kuromi, Mitsuhiko Osaki, Futoshi Okada, Shinji Kitamura, Tetsuya Ohbayashi

{"title":"Kidney organoid derived from renal tissue stem cells is a useful tool for histopathological assessment of nephrotoxicity in a cisplatin-induced acute renal tubular injury model.","authors":"Shota Ueno, Kenji Kokura, Yasushi Kuromi, Mitsuhiko Osaki, Futoshi Okada, Shinji Kitamura, Tetsuya Ohbayashi","doi":"10.1293/tox.2022-0006","DOIUrl":"https://doi.org/10.1293/tox.2022-0006","url":null,"abstract":"Organoids derived from renal tissue stem cells (KS cells) isolated from the S3 segment of adult rat nephrons have previously been developed and evaluated. However, data regarding the histopathological evaluation of these organoids are limited. Therefore, in this study, we performed histopathological examinations of the properties of these organoids and evaluated the nephrotoxicity changes induced by cisplatin treatment. We observe that the tubular structure of the organoids was generally lined by a single layer of cells, in concordance with previous findings. Microvilli were exclusively observed under electron microscopy on the luminal side of this tubular structure. Moreover, the luminal side of the tubular structure was positive for aquaporin-1 (Aqp1), a marker of the proximal renal tubule. Cisplatin treatment induced cell death and degeneration, including cytoplasmic vacuolation, in cells within the tubular structure of the organoids. Cisplatin toxicity is associated with the induction of γ-H2AX (a marker of DNA damage) and the drop of phospho-histone H3 (a marker of cell division) levels. During the nephrotoxicity assessment, the kidney organoids displayed various features similar to those of the natural kidney, suggesting that it is possible to use these organoids in predicting nephrotoxicity. The histological evaluation of the organoids in this study provides insights into the mechanisms underlying nephrotoxicity.","PeriodicalId":17437,"journal":{"name":"Journal of Toxicologic Pathology","volume":"35 4","pages":"333-343"},"PeriodicalIF":1.2,"publicationDate":"2022-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/dd/b8/tox-35-333.PMC9647211.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40478341","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

In vivo screening of subcutaneous tolerability for the development of novel excipients. 为开发新的赋形剂进行皮下耐受性的体内筛选。

IF 1.2 4区医学

Journal of Toxicologic Pathology Pub Date : 2022-10-01 Epub Date: 2022-06-10 DOI: 10.1293/tox.2022-0035

Yuichi Takai, Stephanie Powlin, Yasuyuki Awasaki, Toshiaki Yamauchi, Tomoya Sano, Haruyuki Takahashi, Abdul-Hackam Ranneh, Yuta Arai

{"title":"In vivo screening of subcutaneous tolerability for the development of novel excipients.","authors":"Yuichi Takai, Stephanie Powlin, Yasuyuki Awasaki, Toshiaki Yamauchi, Tomoya Sano, Haruyuki Takahashi, Abdul-Hackam Ranneh, Yuta Arai","doi":"10.1293/tox.2022-0035","DOIUrl":"https://doi.org/10.1293/tox.2022-0035","url":null,"abstract":"To develop safe subcutaneous formulations and minimize the risk of local irritation, it is essential to optimize the composition of active pharmaceutical ingredients and excipients. Depending on the physicochemical properties of the active pharmaceutical ingredient, additional excipients may be required to improve the stability and solubility of the active pharmaceutical ingredient. However, some of these excipients may not have been previously used in injectable drugs. Owing to the lack of safety data for such excipients, especially those used in subcutaneous dosing, it is important to evaluate their potential for local irritation during the early stages of formulation development. We evaluated the tolerability of 44 formulations with 24 candidate novel excipients, such as surfactants, polymers, and lipids, in a single subcutaneous dose in rats. Excipient formulations were administered as single bolus subcutaneous injections with an injection volume of 1 mL. The injection sites were observed for 2 days, and macroscopic and microscopic examinations were conducted. Local tolerability was evaluated on the basis of severity, incidence, and pathophysiology of each finding. Formulations that caused tissue degeneration or necrosis, which is indicative of tissue injury, were determined to be irritative and poorly tolerated. A single-dose subcutaneous screening study in rats was considered effective in ranking the safety of candidate excipients during the formulation optimization phase.","PeriodicalId":17437,"journal":{"name":"Journal of Toxicologic Pathology","volume":"35 4","pages":"355-360"},"PeriodicalIF":1.2,"publicationDate":"2022-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/75/bd/tox-35-355.PMC9647210.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40475882","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

Inflammation of the cardiac coronary artery in ICR mice. ICR小鼠心脏冠状动脉炎症。

IF 1.2 4区医学

Journal of Toxicologic Pathology Pub Date : 2022-10-01 Epub Date: 2022-06-11 DOI: 10.1293/tox.2022-0022

Kyohei Yasuno, Masako Imaoka, Tetsuya Ohsawa, Keiko Okado, Kiyonori Kai, Yoshimi Tsuchiya

{"title":"Inflammation of the cardiac coronary artery in ICR mice.","authors":"Kyohei Yasuno, Masako Imaoka, Tetsuya Ohsawa, Keiko Okado, Kiyonori Kai, Yoshimi Tsuchiya","doi":"10.1293/tox.2022-0022","DOIUrl":"https://doi.org/10.1293/tox.2022-0022","url":null,"abstract":"Inflammation of the cardiac coronary artery in ICR mice is occasionally observed in toxicity studies; however, this has not been well explored histologically. Herein, we investigated the detailed histology of the associated lesions in 6-8-week-old ICR mice. Coronary artery inflammation in the right ventricular wall was observed in 10 of 142 mice (7.0%). Histopathological examination revealed hypertrophy of the vascular smooth muscle cells and perivascular infiltration of macrophages in mild cases. In moderate to marked cases, single-cell necrosis of vascular smooth muscle cells, hemorrhage of the tunica media, and fibrinoid necrosis of the vessel wall were observed, in addition to the changes seen in mild cases. Electron microscopic examination of moderate cases revealed a discontinuous internal elastic lamina suggestive of rupture, and vascular smooth muscle cells beneath the elastic lamina showed degeneration and necrosis. These findings suggest that the lesions developed as a rupture of the internal elastic lamina and necrosis of vascular smooth muscle cells, while leaked plasma components caused vascular and perivascular inflammation. In ICR mice, dystrophic calcinosis (DCC) is known to occur rarely in the right ventricle. DCC is defined as focal calcification in necrotic myocardial fibers, the pathogenesis of which is considered to involve ectopic calcification. Since calcification was not observed in any part of the heart, including the inflammation region, the pathophysiology of cardiac arterial inflammation seen in our ICR mice was considered to differ from that of DCC.","PeriodicalId":17437,"journal":{"name":"Journal of Toxicologic Pathology","volume":"35 4","pages":"345-348"},"PeriodicalIF":1.2,"publicationDate":"2022-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/46/f5/tox-35-345.PMC9647214.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40478345","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

Chemical-induced lung tumor in Tg-rasH2 mice: a novel mouse tumor model to assess immune checkpoint inhibitors combined with a chemotherapy drug. 化学物质诱导的 Tg-rasH2 小鼠肺肿瘤：评估免疫检查点抑制剂联合化疗药物的新型小鼠肿瘤模型。

IF 0.9 4区医学

Journal of Toxicologic Pathology Pub Date : 2022-10-01 Epub Date: 2022-06-26 DOI: 10.1293/tox.2022-0040

Teruaki Hagiwara, Takamasa Numano, Tomomi Hara, Taiki Sugiyama, Yukinori Mera, Seiko Tamano, Hiroto Miyata

{"title":"Chemical-induced lung tumor in Tg-rasH2 mice: a novel mouse tumor model to assess immune checkpoint inhibitors combined with a chemotherapy drug.","authors":"Teruaki Hagiwara, Takamasa Numano, Tomomi Hara, Taiki Sugiyama, Yukinori Mera, Seiko Tamano, Hiroto Miyata","doi":"10.1293/tox.2022-0040","DOIUrl":"10.1293/tox.2022-0040","url":null,"abstract":"In subcutaneous tumor models, changes in the tumor microenvironment can lead to differences in therapeutic treatment responses between the subcutaneous and parent tumors. Accordingly, we generated a lung carcinogenesis model that combines genetically modified mice (Tg-rasH2 mice) with two-stage chemical carcinogenesis as an alternative to the subcutaneous tumor model. In this model, Tg-rasH2 mice were treated with 1-ethyl-1-nitrosourea, followed by butylhydroxytoluene. Mice developed lung adenomas five weeks after treatment initiation. Subsequently, anti-mouse PD-1 antibody (α-mPD-1) or isotype control was administered intraperitoneally twice a week for 4 weeks. Tumor growth was examined by measuring the relative tumor area in serially sliced lung histopathological specimens. No statistically significant differences were observed in the relative lung tumor areas between treated and control groups. A second experiment then examined the antitumor efficacy of α-mPD-1 combined with gemcitabine in a mouse model. Mice were treated identically as in Experiment 1, except that the treated group received once-weekly intraperitoneal injections of 10 mg/kg gemcitabine. In contrast to Experiment 1, the combined treatment significantly reduced the relative tumor areas in the lungs. This result also resembles that of a phase III clinical trial (ORIENT-12), showing that patients with non-small-cell lung carcinoma benefited from combination treatment with gemcitabine and the anti-human PD-1 antibody sintilimab. Thus, this mouse model could be a feasible means to preclinically evaluate the antitumor efficacy of different immunotherapy and chemotherapy drug combinations.","PeriodicalId":17437,"journal":{"name":"Journal of Toxicologic Pathology","volume":"35 4","pages":"321-331"},"PeriodicalIF":0.9,"publicationDate":"2022-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/46/20/tox-35-321.PMC9647217.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40475881","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