Toxicologic Pathology最新文献_第10页

Causes of Mortality and Profile of Spontaneous Tumors in Young CD-1 Mice. 年轻CD-1小鼠自发性肿瘤的死亡原因和特征。

IF 1.5 4区医学

Toxicologic Pathology Pub Date : 2022-08-01 Epub Date: 2022-07-08 DOI: 10.1177/01926233221105391

Ancuta Apreutese, Michela Levi, Ian Taylor, Radu Apreutese, Sydney Mukaratirwa, Vasanthi Mowat

{"title":"Causes of Mortality and Profile of Spontaneous Tumors in Young CD-1 Mice.","authors":"Ancuta Apreutese, Michela Levi, Ian Taylor, Radu Apreutese, Sydney Mukaratirwa, Vasanthi Mowat","doi":"10.1177/01926233221105391","DOIUrl":"https://doi.org/10.1177/01926233221105391","url":null,"abstract":"A retrospective study was performed to establish the causes of mortality and incidence patterns of tumors in young (<50 weeks) control CD-1® mice from Charles River Laboratories. Tumor incidences (fatal and nonfatal) and nonneoplastic causes of death observed during the first 50 weeks of the study were collected from 48 thirteen-week toxicity studies conducted between 2009 and 2018 and from 43 carcinogenicity studies conducted between 2005 and 2018. Thirteen-week studies had a mortality rate of 8/620 (1.3%) in males and 4/620 (0.65%) in females. The major factors contributing to death were integument lesions in males (3/8) and experimental procedure-related injuries in females (3/4). All tumors recorded were nonfatal. Bronchiolo-alveolar adenoma was the commonest tumor with the same incidence in both males and females (4/620, 0.65%); a single lymphoma (0.16%) and uterine leiomyosarcoma (1/620 0.16%) were reported in females. The mortality rates of males and females that died or were euthanized during the first 50 weeks in carcinogenicity studies were 192/2830 (6.8%) and 198/2830 (7%), respectively. The most common fatal tumor in this age group was lymphoma in both sexes, with an incidence of 18/192 (9.3%) and 41/198 (20.7%) in males and females, respectively. In males tumors were responsible for fewer deaths than in females (17% vs. 32.3%). The major nonneoplastic causes of death or moribundity were cutaneous lesions (44/192, 22.9%), and obstructive uropathy (39/192, 20.3%) in males, and chronic progressive nephropathy (40/198, 20.2%) in females. Only minor differences were evident compared to a similar study performed 15 years ago; these might reflect changes in terminology and diagnostic criteria, and stricter animal welfare endpoints.","PeriodicalId":23113,"journal":{"name":"Toxicologic Pathology","volume":null,"pages":null},"PeriodicalIF":1.5,"publicationDate":"2022-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40570606","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

Deep Learning-Based Segmentation of Morphologically Distinct Rat Hippocampal Reactive Astrocytes After Trimethyltin Exposure. 三甲基锡暴露后大鼠海马反应性星形胶质细胞的深度学习分割。

IF 1.5 4区医学

Toxicologic Pathology Pub Date : 2022-08-01 Epub Date: 2022-09-20 DOI: 10.1177/01926233221124497

Miika Vuorimaa, Ilona Kareinen, Petri Toivanen, Stefan Karlsson, Saku Ruohonen

{"title":"Deep Learning-Based Segmentation of Morphologically Distinct Rat Hippocampal Reactive Astrocytes After Trimethyltin Exposure.","authors":"Miika Vuorimaa, Ilona Kareinen, Petri Toivanen, Stefan Karlsson, Saku Ruohonen","doi":"10.1177/01926233221124497","DOIUrl":"https://doi.org/10.1177/01926233221124497","url":null,"abstract":"As regulators of homeostasis, astrocytes undergo morphological changes after injury to limit the insult in central nervous system (CNS). Trimethyltin (TMT) is a known neurotoxicant that induces reactive astrogliosis in rat CNS. To evaluate the degree of reactive astrogliosis, the assessment relies on manual counting or semiquantitative scoring. We hypothesized that deep learning algorithm could be used to identify the grade of reactive astrogliosis in immunoperoxidase-stained sections in a quantitative manner. The astrocyte algorithm was created using a commercial supervised deep learning platform and the used training set consisted of 940 astrocytes manually annotated from hippocampus and cortex. Glial fibrillary acidic protein-labeled brain sections of rat TMT model were analyzed for astrocytes with the trained algorithm. Algorithm was able to count the number of individual cells, cell areas, and circumferences. The astrocyte algorithm identified astrocytes with varying sizes from immunostained sections with high confidence. Algorithm analysis data revealed a novel morphometric marker based on cell area and circumference. This marker correlated with the time-dependent progression of the neurotoxic profile of TMT. This study highlights the potential of using novel deep learning-based image analysis tools in neurotoxicity and pharmacology studies.","PeriodicalId":23113,"journal":{"name":"Toxicologic Pathology","volume":null,"pages":null},"PeriodicalIF":1.5,"publicationDate":"2022-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40371117","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

Scientific and Regulatory Policy Committee Points to Consider: Integration of Clinical Pathology Data With Anatomic Pathology Data in Nonclinical Toxicology Studies. 科学和监管政策委员会指出:在非临床毒理学研究中整合临床病理数据和解剖病理数据。

IF 1.5 4区医学

Toxicologic Pathology Pub Date : 2022-08-01 Epub Date: 2022-08-17 DOI: 10.1177/01926233221108887

William Siska, Albert Eric Schultze, Daniela Ennulat, Kathleen Biddle, Michael Logan, Adeyemi O Adedeji, Tara Arndt, Adam D Aulbach

{"title":"Scientific and Regulatory Policy Committee Points to Consider: Integration of Clinical Pathology Data With Anatomic Pathology Data in Nonclinical Toxicology Studies.","authors":"William Siska, Albert Eric Schultze, Daniela Ennulat, Kathleen Biddle, Michael Logan, Adeyemi O Adedeji, Tara Arndt, Adam D Aulbach","doi":"10.1177/01926233221108887","DOIUrl":"https://doi.org/10.1177/01926233221108887","url":null,"abstract":"Integrating clinical pathology data with anatomic pathology data is a common practice when reporting findings in the context of nonclinical toxicity studies and aids in understanding and communicating the nonclinical safety profile of test articles in development. Appropriate pathology data integration requires knowledge of analyte and tissue biology, species differences, methods of specimen acquisition and analysis, study procedures, and an understanding of the potential causes and effects of a variety of pathophysiologic processes. Neglecting these factors can lead to inappropriate data integration or a missed opportunity to enhance understanding and communication of observed changes. In such cases, nonclinical safety information relevant to human safety risk assessment may be misrepresented or misunderstood. This \"Points to Consider\" manuscript presents general concepts regarding pathology data integration in nonclinical studies, considerations for avoiding potential oversights and errors in data integration, and focused discussion on topics relevant to data integration for several key organ systems including liver, kidney, and cardiovascular system.","PeriodicalId":23113,"journal":{"name":"Toxicologic Pathology","volume":null,"pages":null},"PeriodicalIF":1.5,"publicationDate":"2022-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40519101","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

The Common Marmoset-Biomedical Research Animal Model Applications and Common Spontaneous Diseases. 普通狨猴--生物医学研究动物模型应用和常见自发性疾病。

IF 1.4 4区医学

Toxicologic Pathology Pub Date : 2022-07-01 Epub Date: 2022-05-10 DOI: 10.1177/01926233221095449

Hyo-Jeong Han, Sarah J Powers, Kathleen L Gabrielson

引用次数: 0

A Comparison of Historical Control Data From Cynomolgus Macaques (Macaca Fascicularis) of Chinese, Cambodian, and Vietnamese Origin. 中国、柬埔寨和越南食蟹猴历史对照数据的比较。

IF 1.5 4区医学

Toxicologic Pathology Pub Date : 2022-07-01 Epub Date: 2022-06-22 DOI: 10.1177/01926233221103181

Molly Liepnieks, Caitlyn Carter, Michael J Caruso, Zac Lloyd, Michael Muzyka, Daniel Patrick

{"title":"A Comparison of Historical Control Data From Cynomolgus Macaques (Macaca Fascicularis) of Chinese, Cambodian, and Vietnamese Origin.","authors":"Molly Liepnieks, Caitlyn Carter, Michael J Caruso, Zac Lloyd, Michael Muzyka, Daniel Patrick","doi":"10.1177/01926233221103181","DOIUrl":"https://doi.org/10.1177/01926233221103181","url":null,"abstract":"Cynomolgus macaques, the most commonly utilized nonhuman primate in nonclinical toxicology studies, are acquired from purpose-bred colonies across various geographic locations, including China, Cambodia, and Vietnam. Importation challenges and limited availability have restricted animals suitable for inclusion in nonclinical studies. The coronavirus disease 2019 (COVID-19) outbreak further stressed supply chains, reducing the ability to source animals from a singular location to complete a drug development program. These challenges raised concerns of increased variability in study endpoints due to heterogeneity of animals and that this could subsequently impact historical control data and toxicology study interpretation. To investigate the impact of Chinese, Vietnamese, or Cambodian geographic origin on standard nonclinical toxicology study endpoints, historical control data from studies conducted at a single facility from 2005 to 2020 were compiled and evaluated for the following: clinical observations, body weight, ophthalmoscopic examinations, and clinical and anatomic pathology data. Study populations consisted of 2- to 5-year-old cynomolgus macaques sourced from China (n = 750 males/741 females), Cambodia (n = 282 males/271 females), and Vietnam (n = 122 males/120 females). Interpretation of the various data demonstrated no notable differences in standard toxicology study endpoints or background findings among cynomolgus macaques originating from China, Cambodia, or Vietnam.","PeriodicalId":23113,"journal":{"name":"Toxicologic Pathology","volume":null,"pages":null},"PeriodicalIF":1.5,"publicationDate":"2022-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40165201","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

Immunosuppression Profile of CFZ533 (Iscalimab), a Non-Depleting Anti-CD40 Antibody, and the Presence of Opportunistic Infections in a Rhesus Monkey Toxicology Study. 非消耗性抗cd40抗体CFZ533 (Iscalimab)的免疫抑制特征和恒河猴机会性感染的毒理学研究

IF 1.5 4区医学

Toxicologic Pathology Pub Date : 2022-07-01 Epub Date: 2022-06-22 DOI: 10.1177/01926233221100168

Thierry D Flandre, Keith G Mansfield, Pascal J Espié, Tina Rubic-Schneider, Peter Ulrich

{"title":"Immunosuppression Profile of CFZ533 (Iscalimab), a Non-Depleting Anti-CD40 Antibody, and the Presence of Opportunistic Infections in a Rhesus Monkey Toxicology Study.","authors":"Thierry D Flandre, Keith G Mansfield, Pascal J Espié, Tina Rubic-Schneider, Peter Ulrich","doi":"10.1177/01926233221100168","DOIUrl":"https://doi.org/10.1177/01926233221100168","url":null,"abstract":"CFZ533 (iscalimab) is a nondepleting anti-CD40 antibody intended for inhibition of transplant organ rejection and treatment of autoimmune diseases. In a safety assessment in rhesus monkeys, CFZ533 was administered for 13 weeks up to 150 mg/kg/week subcutaneously. CFZ533 was shown previously to completely inhibit primary and secondary T-cell-dependent antibody responses. CD40 is expressed on B cells, antigen-presenting cells, and endothelial and epithelial cells, but is not expressed on T cells. Here, we demonstrate the complete suppression of germinal center formation in lymphoid organs. CFZ533 was well tolerated and did not cause any dose-limiting toxicity. However, the histological evaluation revealed increased numbers of CD4+ and CD8+ T cells in the T-cell-rich areas of lymph nodes enlarged in response to observed adenovirus and Cryptosporidium infections which suggest that T-cell immune function was unaffected. Background infections appear as the condition leading to unraveling the differential immunosuppressive effects by CFZ533. The presence of T cells at lymph nodes draining sites of infections corroborates the immunosuppressive mechanism, which is different from calcineurin-inhibiting drugs. Furthermore, CFZ533 did not show any hematological or microscopic evidence of thromboembolic events in rhesus monkeys, which were previously shown to respond with thromboembolism to treatment with anti-CD154 antibodies.","PeriodicalId":23113,"journal":{"name":"Toxicologic Pathology","volume":null,"pages":null},"PeriodicalIF":1.5,"publicationDate":"2022-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40165204","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: 2

Special Issue on the Pathobiology of Laboratory Nonhuman Primates: A Review of Species, Substrain, Geographical Origin, Age, and Modality-Related Factors. 实验室非人灵长类动物病理生物学特刊:物种、亚品系、地理起源、年龄和形态相关因素综述。

IF 1.5 4区医学

Toxicologic Pathology Pub Date : 2022-07-01 Epub Date: 2022-06-29 DOI: 10.1177/01926233221106695

Ronnie Chamanza, Chidozie J Amuzie, Jennifer Chilton, Jeffery A Engelhardt

引用次数: 0

Common and Not-So-Common Pathologic Findings of the Gastrointestinal Tract of Rhesus and Cynomolgus Macaques. 恒河猴和猕猴胃肠道常见和不常见的病理结果

IF 1.4 4区医学

Toxicologic Pathology Pub Date : 2022-07-01 Epub Date: 2022-04-01 DOI: 10.1177/01926233221084634

Amanda L Johnson, Rebekah I Keesler, Anne D Lewis, J Rachel Reader, Steven T Laing

引用次数: 0

Society of Toxicologic Pathology Neuropathology Interest Group Article: Neuropathologic Findings in Nonhuman Primates Associated With Administration of Biomolecule-Based Test Articles 毒物病理学学会神经病理学兴趣小组文章:非人类灵长类动物的神经病理学发现与基于生物分子的试验品的管理有关

IF 1.5 4区医学

Toxicologic Pathology Pub Date : 2022-06-13 DOI: 10.1177/01926233221101314

D. Bangari, L. Lanigan, F. Goulet, S. Sisó, B. Bolon

{"title":"Society of Toxicologic Pathology Neuropathology Interest Group Article: Neuropathologic Findings in Nonhuman Primates Associated With Administration of Biomolecule-Based Test Articles","authors":"D. Bangari, L. Lanigan, F. Goulet, S. Sisó, B. Bolon","doi":"10.1177/01926233221101314","DOIUrl":"https://doi.org/10.1177/01926233221101314","url":null,"abstract":"The increasing specificity of novel druggable targets coupled with the complexity of emerging therapeutic modalities for treating human diseases has created a growing need for nonhuman primates (NHPs) as models for translational drug discovery and nonclinical safety assessment. In particular, NHPs are critical for investigating potential unexpected/undesired on-target and off-target liabilities associated with administration of candidate biotherapeutics (nucleic acids, proteins, viral gene therapy vectors, etc.) to treat nervous system disorders. Nervous system findings unique to or overrepresented in NHPs administered biomolecule-based (“biologic”) test articles include mononuclear cell infiltration in most neural tissues for all biomolecule classes as well as neuronal necrosis with glial cell proliferation in sensory ganglia for certain viral vectors. Such test article-related findings in NHPs often must be differentiated from procedural effects (e.g., local parenchymal or meningeal reactions associated with an injection site or implanted catheter to administer a test article directly into the central nervous system) or spontaneous background findings (e.g., neuronal autophagy in sensory ganglia).","PeriodicalId":23113,"journal":{"name":"Toxicologic Pathology","volume":null,"pages":null},"PeriodicalIF":1.5,"publicationDate":"2022-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78704210","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: 2

The MNU Plus Testosterone Rat Model of Prostate Carcinogenesis. 前列腺癌发生的 MNU 加睾酮大鼠模型

IF 1.5 4区医学

Toxicologic Pathology Pub Date : 2022-06-01 Epub Date: 2022-05-19 DOI: 10.1177/01926233221096345

Maarten C Bosland, Michael J Schlicht, Lori Horton, David L McCormick

{"title":"The MNU Plus Testosterone Rat Model of Prostate Carcinogenesis.","authors":"Maarten C Bosland, Michael J Schlicht, Lori Horton, David L McCormick","doi":"10.1177/01926233221096345","DOIUrl":"10.1177/01926233221096345","url":null,"abstract":"Animal models of prostate cancer are essential to identify chemopreventive treatments against this major male malignancy. The N-methyl-N-nitrosourea (MNU) plus testosterone rat model of prostate carcinogenesis is a reliable animal model that recapitulates human prostate cancer in many respects and has been used extensively in chemoprevention studies with good predictive value for the results of human clinical trials. The objective of this article is to describe the induction protocol of this model, demonstrate its robustness and reproducibility over time and across rat strains, provide diagnostic criteria for the identification of prostate lesions, and present the current tumor induction protocol so that others can use this model in a reliable manner. The majority of accessory sex gland tumors in this model are adenocarcinomas originating in the anterior and dorsolateral prostate that metastasize to lungs and abdominal structures. The rat strain used is of critical importance, with the commercially available Wistar WU and Fischer F344 strains yielding the highest tumor incidences. Low dose, long-term testosterone treatment is essential for a high tumor incidence, but in advanced stage, large adenocarcinomas do not appear to be androgen dependent. This rat model is a robust and reproducible prostate cancer animal model of human prostate cancer.","PeriodicalId":23113,"journal":{"name":"Toxicologic Pathology","volume":null,"pages":null},"PeriodicalIF":1.5,"publicationDate":"2022-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9347216/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81388699","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