Toxicologic Pathology最新文献_第2页

Spontaneous Abdominal Hemangiosarcoma With Metastases to the Lungs in a Control Sprague-Dawley Rat. Sprague-Dawley大鼠自发性腹腔血管肉瘤伴肺转移。

IF 1.8 4区医学

Toxicologic Pathology Pub Date : 2026-04-01 Epub Date: 2026-02-25 DOI: 10.1177/01926233261419482

Gayle Hennig, Jean-Guy Bienvenu, Muthafar Al-Haddawi

{"title":"Spontaneous Abdominal Hemangiosarcoma With Metastases to the Lungs in a Control Sprague-Dawley Rat.","authors":"Gayle Hennig, Jean-Guy Bienvenu, Muthafar Al-Haddawi","doi":"10.1177/01926233261419482","DOIUrl":"10.1177/01926233261419482","url":null,"abstract":"This short communication describes a spontaneous hemangiosarcoma within the abdomen, which appeared to have originated from the prostate gland area with infiltration, and that metastasized to the lungs in a 46-week-old male Sprague-Dawley rat. At necropsy, a 90 mm × 60 mm × 50 mm dark cystic neoplastic mass was present in the abdomen and the lung lobes had multiple dark cystic neoplastic structures. The abdominal mass was necrotic with a few peripheral areas of plump oval cells and frond-like structures lined by spindle-shaped cells. The lung neoplastic cysts were filled with blood and there were foci of plump oval cells within and peripheral to the cysts, as well as multiple small clusters throughout the lung parenchyma. Neoplastic cells of the abdominal mass and lung cysts stained positively for von Willebrand Factor by immunohistochemistry, indicating a vascular endothelial cell origin and consistent with a diagnosis of hemangiosarcoma. The lung hemangiosarcomas were considered metastases from the abdominal hemangiosarcoma based on their similar cellular morphology and multiple foci throughout the lung lobes.","PeriodicalId":23113,"journal":{"name":"Toxicologic Pathology","volume":" ","pages":"267-271"},"PeriodicalIF":1.8,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147285182","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

Toxicologic Pathology Forum*: Summary of the 2024 Society of Toxicologic Pathology Town Hall and 2025 STP Member Survey on Determining and Communicating Adversity. 毒物病理学论坛*:2024年毒物病理学学会市政厅和2025年STP成员关于确定和沟通逆境的调查总结。

IF 1.8 4区医学

Toxicologic Pathology Pub Date : 2026-04-01 Epub Date: 2025-12-09 DOI: 10.1177/01926233251395000

Kathleen A Funk, Lyn M Wancket, Brad Bolon, Sabine Francke, Renee R Hukkanen, Lila Ramaiah

{"title":"Toxicologic Pathology Forum*: Summary of the 2024 Society of Toxicologic Pathology Town Hall and 2025 STP Member Survey on Determining and Communicating Adversity.","authors":"Kathleen A Funk, Lyn M Wancket, Brad Bolon, Sabine Francke, Renee R Hukkanen, Lila Ramaiah","doi":"10.1177/01926233251395000","DOIUrl":"10.1177/01926233251395000","url":null,"abstract":"In 2016, the publication of the Society of Toxicologic Pathology's (STP) \"best practice\" recommendations on determining and communicating adversity and the European Society of Toxicologic Pathology's (ESTP) expert working group report on adversity were key milestones in addressing adversity determinations for nonclinical studies as translational tools for assessing human risk. Since then, many publications attest to the ongoing difficulty in adversity decision-making posed by unique context-specific challenges. The STP gathered input on current adversity practices from Society members via an open discussion at the 2024 STP Town Hall session (held at the STP 43rd Annual Symposium) and by a subsequent online survey. Most STP pathologists make adversity determinations by applying the STP and/or ESTP recommendations at their discretion. Adversity decisions are generally made for pivotal toxicity studies but occasionally may be assigned for other study types. Adversity determinations are difficult for certain organ systems (immune, reproductive, and endocrine) and product classes (eg, cell and gene therapies, proteins, and small molecules). Most pathologists assign adversity based on direct effects of the test article, but other factors (eg, secondary pharmacology, species relevance, adaptive responses) are also considered. Procedural adversity (eg, effects of administration/implantation) is a key factor in some circumstances.","PeriodicalId":23113,"journal":{"name":"Toxicologic Pathology","volume":" ","pages":"214-223"},"PeriodicalIF":1.8,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145709358","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

Toxicologic Pathology Forum*: Opinion on Remote Digital Toxicologic Pathology in Practice-Lessons From a Digital Team and Approach to Scientific Quality, Flexibility, and Well-Being. 毒理学病理学论坛*：关于远程数字毒理学病理学实践的意见——来自数字团队的经验教训和科学质量、灵活性和福祉的方法。

IF 1.8 4区医学

Toxicologic Pathology Pub Date : 2026-04-01 Epub Date: 2026-02-18 DOI: 10.1177/01926233261416818

Frederic Gervais, Malgorzata Ciurkiewicz, Anna Domenech-Fontanals, Begonya Garcia, Monica Ronderos Herrera

引用次数: 0

Oligonucleotides: Evolution of Carcinogenicity and Risk Assessment Strategy. 寡核苷酸：致癌性的演变和风险评估策略。

IF 1.8 4区医学

Toxicologic Pathology Pub Date : 2026-03-30 DOI: 10.1177/01926233261427650

Tae-Won Kim

{"title":"Oligonucleotides: Evolution of Carcinogenicity and Risk Assessment Strategy.","authors":"Tae-Won Kim","doi":"10.1177/01926233261427650","DOIUrl":"https://doi.org/10.1177/01926233261427650","url":null,"abstract":"Since 2006, the carcinogenic potential of antisense oligonucleotides (ASOs) has primarily been evaluated using standard 2-year rodent bioassays. To date, no human-relevant tumor findings have been identified across nonclinical ASO studies. As the field matures and more therapeutics advance into development, there is increasing support for carcinogenicity strategies that built on prior data, leverage platform-based risk assessments, and align with evolving regulatory guidance. In several programs, traditional 2-year mouse studies have been replaced by short-term assessments, such as the 6-month study in transgenic rasH2 mouse study, often conducted alongside a 2-year rat study in accordance with ICH S1B(R1). Historically, deviations from the standard two-species approach have been uncommon and typically limited to severe neurological indications or cases lacking an endogenous rodent target. Nevertheless, for eplontersen and olezarsen, carcinogenicity assessment was limited to a single Tg.rasH2 mouse study or fully waived, supported by prior two-species carcinogenicity data from inotersen and volanesorsen. With the recent ICH S1B(R1) addendum, sponsors now have a defined pathway to pursue carcinogenicity strategies, including potential waivers of the 2-year rat study when supported by the totality of evidence. This article reviews the evolving landscape of ASO carcinogenicity testing and highlights opportunities to reduce or waive long-term studies.","PeriodicalId":23113,"journal":{"name":"Toxicologic Pathology","volume":" ","pages":"1926233261427650"},"PeriodicalIF":1.8,"publicationDate":"2026-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147582021","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

Mini Review: Carcinogenicity Statistics. 小型综述：致癌性统计。

IF 1.8 4区医学

Toxicologic Pathology Pub Date : 2026-03-29 DOI: 10.1177/01926233261432174

Jim Saul

引用次数: 0

Carcinogenicity in the 21st Century: Challenges of New Methodologies, Strategies, and Their Impact on Pathologists-Session 1. 21世纪的致癌性：新方法、新策略的挑战及其对病理学家的影响

IF 1.8 4区医学

Toxicologic Pathology Pub Date : 2026-03-27 DOI: 10.1177/01926233261430673

Dirk Schaudien, Samuel M Cohen, Helen-Marie Dunmore, Leslie Bosseler, Matthias Rinke, Torrie A Crabbs

{"title":"Carcinogenicity in the 21st Century: Challenges of New Methodologies, Strategies, and Their Impact on Pathologists-Session 1.","authors":"Dirk Schaudien, Samuel M Cohen, Helen-Marie Dunmore, Leslie Bosseler, Matthias Rinke, Torrie A Crabbs","doi":"10.1177/01926233261430673","DOIUrl":"https://doi.org/10.1177/01926233261430673","url":null,"abstract":"The 2025 joint British and European Society of Toxicologic Pathology Congress commenced with a thought-provoking keynote lecture detailing the history, learnings, and limitations of the 2-year rodent bioassay. Animal carcinogenicity studies and the implementation of the Ames test for mutagenicity have enhanced our understanding of carcinogenesis, toxicokinetics, metabolism, and carcinogenic modes of action. These learnings have challenged the relevance of the 2-year bioassay for the determination of human risk and have raised questions about the need for its continued use. The first session was dedicated to carcinogenesis and Best Practice concepts with three presentations providing an introduction and general overview of rodent carcinogenicity studies: a toxicologist's perspective on the complexities of carcinogenicity studies pertaining to study design, data interpretation, and determination of human safety relevance; an experienced pathologist's overview regarding the intricacies and challenges of histopathological evaluation of carcinogenicity studies, the harmonization of nomenclature, and the data interpretation challenges; and a CRO (contract research organization) pathologist's perspective on the evolution of carcinogenicity studies with an emphasis on peer-review nuances. A case study presentation on hepatocellular foci in rodents advocated for the need to record all foci of cellular alterations with recommended implementation of size/lower threshold criteria for small lesions.","PeriodicalId":23113,"journal":{"name":"Toxicologic Pathology","volume":" ","pages":"1926233261430673"},"PeriodicalIF":1.8,"publicationDate":"2026-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147522073","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

Toxicologic Pathology Forum: Opinion on Considerations for Determination of Adverse Versus Nonadverse Nerve Fiber Degeneration in Nonclinical Toxicity Studies of Oligonucleotides Delivered Directly Into the Intrathecal Space. 毒理学病理论坛：在直接注入鞘内间隙的寡核苷酸的非临床毒性研究中，对不良与非不良神经纤维变性测定的考虑。

IF 1.8 4区医学

Toxicologic Pathology Pub Date : 2026-03-25 DOI: 10.1177/01926233261430687

Lisa D Berman-Booty, Ingrid D Pardo, Brad Bolon, Kuldeep Singh, James P Morrison, Shelley Patrick, Sarah Cramer, Jessica L Grieves

{"title":"Toxicologic Pathology Forum: Opinion on Considerations for Determination of Adverse Versus Nonadverse Nerve Fiber Degeneration in Nonclinical Toxicity Studies of Oligonucleotides Delivered Directly Into the Intrathecal Space.","authors":"Lisa D Berman-Booty, Ingrid D Pardo, Brad Bolon, Kuldeep Singh, James P Morrison, Shelley Patrick, Sarah Cramer, Jessica L Grieves","doi":"10.1177/01926233261430687","DOIUrl":"https://doi.org/10.1177/01926233261430687","url":null,"abstract":"Determination of adversity and the no observed adverse effect level (NOAEL) in nonclinical toxicity studies are important components in the overall assessment of the potential for human risk during pharmaceutical development. Resources exist to guide adversity decisions in general, for findings in ganglia of the peripheral nervous system (PNS), and for gliosis in the central nervous system (CNS). The objective of this opinion article is to describe considerations that may apply when determining the adversity (or lack thereof) of nerve fiber degeneration (NFD) in either the CNS or PNS following intrathecal (IT) administration of oligonucleotide (ON) therapeutics (such as antisense oligonucleotides and short interfering RNAs). It is important to differentiate IT delivery procedure-related NFD effects from ON-related effects or ON-related exacerbation of procedure-related findings. This article presents evidence-based approaches for deciding whether NFD associated with IT ON administration is an adverse microscopic finding in the brain, spinal cord, spinal nerve roots, ganglia, and/or nerves. In the authors' collective experience, nonextensive (i.e., regionally restricted), minimal or mild NFD unaccompanied by functional or behavioral deficits, neuronal necrosis, or a substantial inflammatory response in neural tissue can be interpreted as nonadverse.","PeriodicalId":23113,"journal":{"name":"Toxicologic Pathology","volume":" ","pages":"1926233261430687"},"PeriodicalIF":1.8,"publicationDate":"2026-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147514952","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

Toxicologic Pathology Forum*: Virtual Staining of Nonclinical Study Slides-A Brief Review of the Current Status and Future Opportunities. 毒理学病理论坛*：非临床研究幻灯片的虚拟染色——现状和未来机会的简要回顾。

IF 1.8 4区医学

Toxicologic Pathology Pub Date : 2026-03-21 DOI: 10.1177/01926233261426348

Esther E V Crouch

{"title":"Toxicologic Pathology Forum*: Virtual Staining of Nonclinical Study Slides-A Brief Review of the Current Status and Future Opportunities.","authors":"Esther E V Crouch","doi":"10.1177/01926233261426348","DOIUrl":"https://doi.org/10.1177/01926233261426348","url":null,"abstract":"Virtual staining of unstained tissue for histologic assessment is the subject of burgeoning research and has been approached using various methodologies. This technology has the potential to reduce laboratory turnaround time, reduce consumption of chemicals and water, and improve occupational health and safety for laboratory personnel. In addition, the technology presents the alluring prospect of non-destructive hematoxylin and eosin histologic examination, allowing unlimited multiplexing on the same section, and improved image analysis techniques that are unimpeded by inter- and intra-laboratory stain variation. Recent advancements in this field and projections of applicability to nonclinical pharmaceutical development and discovery pathology settings warrant a brief review. Virtual staining has been applied most widely to unlabeled (unstained) tissue but has also been used in stain-to-stain transformation. Specimen input varies from conventional formalin-fixed paraffin-embedded tissue to partially processed or intact tissue. Imaging is commonly traditional brightfield or fluorescence, although other modalities are available. Depending on the imaging modality, computational methods such as deep learning neural networks are used to infer the virtual stain that is ultimately viewed as a digitized histologic image. Current barriers to applicability include qualification, histologic quality, generative artificial intelligence concerns, training material acquisition, and infrastructure.","PeriodicalId":23113,"journal":{"name":"Toxicologic Pathology","volume":" ","pages":"1926233261426348"},"PeriodicalIF":1.8,"publicationDate":"2026-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147494512","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

Navigating the Pathology Minefield: Harnessing the Value of Historical Control Data in Rodent Carcinogenicity Studies. 导航病理雷区：利用历史控制数据在啮齿动物致癌性研究中的价值。

IF 1.8 4区医学

Toxicologic Pathology Pub Date : 2026-02-22 DOI: 10.1177/01926233261420213

John R Foster

引用次数: 0

Thank You to Reviewers. 感谢审稿人。

IF 1.8 4区医学

Toxicologic Pathology Pub Date : 2026-02-01 Epub Date: 2026-01-30 DOI: 10.1177/01926233261415667

引用次数: 0