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Jeffrey Ira Everitt

Professor Emeritus in Pathology
Pathology

Selected Publications


Targeting glutamine dependence with DRP-104 inhibits proliferation and tumor growth of castration-resistant prostate cancer.

Journal Article Prostate · March 2024 BACKGROUND: Prostate cancer (PCa) continues to be one of the leading causes of cancer deaths in men. While androgen deprivation therapy is initially effective, castration-resistant PCa (CRPC) often recurs and has limited treatment options. Our previous stu ... Full text Link to item Cite

Spontaneous episodic inflammation in the intestines of mice lacking HNF4A is driven by microbiota and associated with early life microbiota alterations.

Journal Article mBio · August 31, 2023 The inflammatory bowel diseases (IBD) occur in genetically susceptible individuals who mount inappropriate immune responses to their microbiota leading to chronic intestinal inflammation. Whereas IBD clinical presentation is well described, how interaction ... Full text Link to item Cite

KeyLoop retractor for global gasless laparoscopy: evaluation of safety and feasibility in a porcine model.

Journal Article Surg Endosc · August 2023 BACKGROUND: Many surgeons in low- and middle-income countries have described performing surgery using gasless (lift) laparoscopy due to inaccessibility of carbon dioxide and reliable electricity, but the safety and feasibility of the technique has not been ... Full text Link to item Cite

Genome editing using Staphylococcus aureus Cas9 in a canine model of glycogen storage disease Ia.

Journal Article Mol Ther Methods Clin Dev · June 8, 2023 Glycogen storage disease type Ia (GSD Ia) is the inherited deficiency of glucose-6-phosphatase (G6Pase), associated with life-threatening hypoglycemia and long-term complications, including hepatocellular carcinoma formation. Gene replacement therapy fails ... Full text Link to item Cite

Rescue of glutaric aciduria type I in mice by liver-directed therapies.

Journal Article Sci Transl Med · April 19, 2023 Glutaric aciduria type I (GA-1) is an inborn error of metabolism with a severe neurological phenotype caused by the deficiency of glutaryl-coenzyme A dehydrogenase (GCDH), the last enzyme of lysine catabolism. Current literature suggests that toxic catabol ... Full text Link to item Cite

Movie 1 from HER2 Isoforms Uniquely Program Intratumor Heterogeneity and Predetermine Breast Cancer Trajectories During the Occult Tumorigenic Phase

Other · April 3, 2023 <p>p95HER2 labelled sidebuds. p95HER2 shown in magenta. Krt14 antibody staining shown in green.</p><p></p> ... Full text Cite

Movie 3 from HER2 Isoforms Uniquely Program Intratumor Heterogeneity and Predetermine Breast Cancer Trajectories During the Occult Tumorigenic Phase

Other · April 3, 2023 <p>p95HER2 invasive carcinoma. p95HER2 shown in magenta. Krt14 antibody staining shown in green.</p> ... Full text Cite

Movie 4 from HER2 Isoforms Uniquely Program Intratumor Heterogeneity and Predetermine Breast Cancer Trajectories During the Occult Tumorigenic Phase

Other · April 3, 2023 <p>p95HER2 microinvasive carcinoma. p95HER2 shown in magenta. Krt14 antibody staining shown in green.</p> ... Full text Cite

Movie 5 from HER2 Isoforms Uniquely Program Intratumor Heterogeneity and Predetermine Breast Cancer Trajectories During the Occult Tumorigenic Phase

Other · April 3, 2023 <p>d16HER2 mammary intraepithelial neoplasm. d16HER2 shown in magenta. Krt14 antibody staining shown in green.</p> ... Full text Cite

Movie 2 from HER2 Isoforms Uniquely Program Intratumor Heterogeneity and Predetermine Breast Cancer Trajectories During the Occult Tumorigenic Phase

Other · April 3, 2023 <p>d16HER2 labelled sidebuds. d16HER2 shown in yellow. Krt14 antibody staining shown in green.</p> ... Full text Cite

Targeting glutamine dependence with DRP-104 inhibits proliferation and tumor growth of castration-resistant prostate cancer.

Journal Article Prostate · March 2024 BACKGROUND: Prostate cancer (PCa) continues to be one of the leading causes of cancer deaths in men. While androgen deprivation therapy is initially effective, castration-resistant PCa (CRPC) often recurs and has limited treatment options. Our previous stu ... Full text Link to item Cite

Spontaneous episodic inflammation in the intestines of mice lacking HNF4A is driven by microbiota and associated with early life microbiota alterations.

Journal Article mBio · August 31, 2023 The inflammatory bowel diseases (IBD) occur in genetically susceptible individuals who mount inappropriate immune responses to their microbiota leading to chronic intestinal inflammation. Whereas IBD clinical presentation is well described, how interaction ... Full text Link to item Cite

KeyLoop retractor for global gasless laparoscopy: evaluation of safety and feasibility in a porcine model.

Journal Article Surg Endosc · August 2023 BACKGROUND: Many surgeons in low- and middle-income countries have described performing surgery using gasless (lift) laparoscopy due to inaccessibility of carbon dioxide and reliable electricity, but the safety and feasibility of the technique has not been ... Full text Link to item Cite

Genome editing using Staphylococcus aureus Cas9 in a canine model of glycogen storage disease Ia.

Journal Article Mol Ther Methods Clin Dev · June 8, 2023 Glycogen storage disease type Ia (GSD Ia) is the inherited deficiency of glucose-6-phosphatase (G6Pase), associated with life-threatening hypoglycemia and long-term complications, including hepatocellular carcinoma formation. Gene replacement therapy fails ... Full text Link to item Cite

Rescue of glutaric aciduria type I in mice by liver-directed therapies.

Journal Article Sci Transl Med · April 19, 2023 Glutaric aciduria type I (GA-1) is an inborn error of metabolism with a severe neurological phenotype caused by the deficiency of glutaryl-coenzyme A dehydrogenase (GCDH), the last enzyme of lysine catabolism. Current literature suggests that toxic catabol ... Full text Link to item Cite

Movie 1 from HER2 Isoforms Uniquely Program Intratumor Heterogeneity and Predetermine Breast Cancer Trajectories During the Occult Tumorigenic Phase

Other · April 3, 2023 <p>p95HER2 labelled sidebuds. p95HER2 shown in magenta. Krt14 antibody staining shown in green.</p><p></p> ... Full text Cite

Movie 3 from HER2 Isoforms Uniquely Program Intratumor Heterogeneity and Predetermine Breast Cancer Trajectories During the Occult Tumorigenic Phase

Other · April 3, 2023 <p>p95HER2 invasive carcinoma. p95HER2 shown in magenta. Krt14 antibody staining shown in green.</p> ... Full text Cite

Movie 4 from HER2 Isoforms Uniquely Program Intratumor Heterogeneity and Predetermine Breast Cancer Trajectories During the Occult Tumorigenic Phase

Other · April 3, 2023 <p>p95HER2 microinvasive carcinoma. p95HER2 shown in magenta. Krt14 antibody staining shown in green.</p> ... Full text Cite

Movie 5 from HER2 Isoforms Uniquely Program Intratumor Heterogeneity and Predetermine Breast Cancer Trajectories During the Occult Tumorigenic Phase

Other · April 3, 2023 <p>d16HER2 mammary intraepithelial neoplasm. d16HER2 shown in magenta. Krt14 antibody staining shown in green.</p> ... Full text Cite

Movie 2 from HER2 Isoforms Uniquely Program Intratumor Heterogeneity and Predetermine Breast Cancer Trajectories During the Occult Tumorigenic Phase

Other · April 3, 2023 <p>d16HER2 labelled sidebuds. d16HER2 shown in yellow. Krt14 antibody staining shown in green.</p> ... Full text Cite

Movie 4 from HER2 Isoforms Uniquely Program Intratumor Heterogeneity and Predetermine Breast Cancer Trajectories During the Occult Tumorigenic Phase

Other · April 3, 2023 <p>p95HER2 microinvasive carcinoma. p95HER2 shown in magenta. Krt14 antibody staining shown in green.</p> ... Full text Cite

Supplementary Tables 1-5 for scRNAseq marker genes from HER2 Isoforms Uniquely Program Intratumor Heterogeneity and Predetermine Breast Cancer Trajectories During the Occult Tumorigenic Phase

Other · April 3, 2023 <p>Supplementary Table 1: Cluster-specific markers from all cells (8,486 cells) Supplementary Table 2: Cluster-specific markers from all epithelial cells (3,843 cells) Supplementary Table 3: Cluster-specific markers from all immune cells (1,8 ... Full text Cite

Movie 5 from HER2 Isoforms Uniquely Program Intratumor Heterogeneity and Predetermine Breast Cancer Trajectories During the Occult Tumorigenic Phase

Other · April 3, 2023 <p>d16HER2 mammary intraepithelial neoplasm. d16HER2 shown in magenta. Krt14 antibody staining shown in green.</p> ... Full text Cite

Movie 1 from HER2 Isoforms Uniquely Program Intratumor Heterogeneity and Predetermine Breast Cancer Trajectories During the Occult Tumorigenic Phase

Other · April 3, 2023 <p>p95HER2 labelled sidebuds. p95HER2 shown in magenta. Krt14 antibody staining shown in green.</p><p></p> ... Full text Cite

Data from HER2 Isoforms Uniquely Program Intratumor Heterogeneity and Predetermine Breast Cancer Trajectories During the Occult Tumorigenic Phase

Other · April 3, 2023 <div>Abstract<p>HER2-positive breast cancers are among the most heterogeneous breast cancer subtypes. The early amplification of HER2 and its known oncogenic isoforms provide a plausible mechanism in which distinct programs of tumor het ... Full text Cite

Movie 3 from HER2 Isoforms Uniquely Program Intratumor Heterogeneity and Predetermine Breast Cancer Trajectories During the Occult Tumorigenic Phase

Other · April 3, 2023 <p>p95HER2 invasive carcinoma. p95HER2 shown in magenta. Krt14 antibody staining shown in green.</p> ... Full text Cite

Supplementary Tables 1-5 for scRNAseq marker genes from HER2 Isoforms Uniquely Program Intratumor Heterogeneity and Predetermine Breast Cancer Trajectories During the Occult Tumorigenic Phase

Other · April 3, 2023 <p>Supplementary Table 1: Cluster-specific markers from all cells (8,486 cells) Supplementary Table 2: Cluster-specific markers from all epithelial cells (3,843 cells) Supplementary Table 3: Cluster-specific markers from all immune cells (1,8 ... Full text Cite

Movie 2 from HER2 Isoforms Uniquely Program Intratumor Heterogeneity and Predetermine Breast Cancer Trajectories During the Occult Tumorigenic Phase

Other · April 3, 2023 <p>d16HER2 labelled sidebuds. d16HER2 shown in yellow. Krt14 antibody staining shown in green.</p> ... Full text Cite

Supplementary figure FS4 from Neoadjuvant Radiation Therapy and Surgery Improves Metastasis-Free Survival over Surgery Alone in a Primary Mouse Model of Soft Tissue Sarcoma

Other · April 3, 2023 <p>Long-term metastases study of an autochthonous p53/MCA mouse model of STS induced by Cre-LoxP technology using TRP53 fl/fl mice</p> ... Full text Cite

Supplementary figure FS4 from Neoadjuvant Radiation Therapy and Surgery Improves Metastasis-Free Survival over Surgery Alone in a Primary Mouse Model of Soft Tissue Sarcoma

Other · April 3, 2023 <p>Long-term metastases study of an autochthonous p53/MCA mouse model of STS induced by Cre-LoxP technology using TRP53 fl/fl mice</p> ... Full text Cite

Supplementary figure FS3 from Neoadjuvant Radiation Therapy and Surgery Improves Metastasis-Free Survival over Surgery Alone in a Primary Mouse Model of Soft Tissue Sarcoma

Other · April 3, 2023 <p>Long-term survival of an autochthonous p53/MCA mouse model in immunocompetent 129/SvJae wild-type mice induced by CRISPR/Cas9</p> ... Full text Cite

Supplementary figure FS3 from Neoadjuvant Radiation Therapy and Surgery Improves Metastasis-Free Survival over Surgery Alone in a Primary Mouse Model of Soft Tissue Sarcoma

Other · April 3, 2023 <p>Long-term survival of an autochthonous p53/MCA mouse model in immunocompetent 129/SvJae wild-type mice induced by CRISPR/Cas9</p> ... Full text Cite

An injectable PEG-like conjugate forms a subcutaneous depot and enables sustained delivery of a peptide drug.

Journal Article Biomaterials · March 2023 Many biologics have a short plasma half-life, and their conjugation to polyethylene glycol (PEG) is commonly used to solve this problem. However, the improvement in the plasma half-life of PEGylated drugs' is at an asymptote because the development of bran ... Full text Link to item Cite

Maternal exposure to perfluorobutane sulfonate (PFBS) during pregnancy: evidence of adverse maternal and fetoplacental effects in New Zealand White (NZW) rabbits.

Journal Article Toxicol Sci · February 17, 2023 Perfluorobutanesulfonic acid (PFBS) is a replacement for perfluorooctanesulfonic acid (PFOS) that is increasingly detected in drinking water and human serum. Higher PFBS exposure is associated with risk for preeclampsia, the leading cause of maternal and i ... Full text Link to item Cite

Whole-Slide Cytometric Feature Mapping for Distinguishing Tumor Genomic Subtypes in Head and Neck Squamous Cell Carcinoma Whole-Slide Images.

Journal Article Am J Pathol · February 2023 Head and neck squamous cell carcinoma (HNSCC) is a heterogeneous disease where, in advanced stages, clinical and pathologic stages do not correlate with outcome. Molecular and genomic biomarkers for HNSCC classification have shown promise for prognostic an ... Full text Open Access Link to item Cite

Neoadjuvant Radiation Therapy and Surgery Improves Metastasis-Free Survival over Surgery Alone in a Primary Mouse Model of Soft Tissue Sarcoma.

Journal Article Mol Cancer Ther · January 3, 2023 This study aims to investigate whether adding neoadjuvant radiotherapy (RT), anti-programmed cell death protein-1 (PD-1) antibody (anti-PD-1), or RT + anti-PD-1 to surgical resection improves disease-free survival for mice with soft tissue sarcomas (STS). ... Full text Open Access Link to item Cite

Anti-adhesive bioresorbable elastomer-coated composite hernia mesh that reduce intraperitoneal adhesions.

Journal Article Biomaterials · January 2023 Intraperitoneal adhesions (IAs) are a major complication arising from abdominal repair surgeries, including hernia repair procedures. Herein, we fabricated a composite mesh device using a macroporous monofilament polypropylene mesh and a degradable elastom ... Full text Link to item Cite

Pathologists' perspective on the study design, analysis, and interpretation of proliferative lesions in lifetime and prenatal rodent carcinogenicity bioassays of aspartame.

Journal Article Food Chem Toxicol · January 2023 Aspartame, an artificial sweetener commonly used as a sugar substitute, is currently authorized for use in more than 100 countries. Hundreds of studies, conducted in various countries dating back to the 1970s, have shown that aspartame is safe at real-worl ... Full text Link to item Cite

Mixed-surface polyamidoamine polymer variants retain nucleic acid-scavenger ability with reduced toxicity.

Journal Article iScience · December 22, 2022 Nucleic acid-binding polymers can have anti-inflammatory properties and beneficial effects in animal models of infection, trauma, cancer, and autoimmunity. PAMAM G3, a polyamidoamine dendrimer, is fully cationic bearing 32 protonable surface amines. Howeve ... Full text Link to item Cite

Veterinary Management of Harderian Gland Tumors in Cancer Rainbow (crainbow) HER2-Positive Mice.

Journal Article Comp Med · December 1, 2022 A Cancer Rainbow mouse line that expresses 3 fluorescently labeled isoforms of the tumor-driver gene HER2 (HER2BOW) was developed recently for the study of tumorigenesis in the mammary gland. The expression of 1 of the 3 HER2 isoforms in HER2BOW mice is in ... Full text Link to item Cite

A Non-Invasive Deep Photoablation Technique to Inhibit DCIS Progression and Induce Antitumor Immunity.

Journal Article Cancers (Basel) · November 23, 2022 Ductal carcinoma in situ (DCIS) of the breast is often managed by lumpectomy and radiation or mastectomy, despite its indolent features. Effective non-invasive treatment strategies could reduce the morbidity of DCIS treatment. We have exploited the high he ... Full text Link to item Cite

Cas13d knockdown of lung protease Ctsl prevents and treats SARS-CoV-2 infection.

Journal Article Nat Chem Biol · October 2022 SARS-CoV-2 entry into cells requires specific host proteases; however, no successful in vivo applications of host protease inhibitors have yet been reported for treatment of SARS-CoV-2 pathogenesis. Here we describe a chemically engineered nanosystem encap ... Full text Link to item Cite

Proceedings of the 2022 National Toxicology Program Satellite Symposium.

Journal Article Toxicol Pathol · October 2022 The 2022 annual National Toxicology Program Satellite Symposium, entitled "Pathology Potpourri," was held in Austin, Texas at the Society of Toxicologic Pathology's 40th annual meeting during a half-day session on Sunday, June 19. The goal of this symposiu ... Full text Link to item Cite

Evaluating maternal exposure to an environmental per and polyfluoroalkyl substances (PFAS) mixture during pregnancy: Adverse maternal and fetoplacental effects in a New Zealand White (NZW) rabbit model.

Journal Article Sci Total Environ · September 10, 2022 Mixtures of per- and polyfluoroalkyl substances (PFAS) are often found in drinking water, and serum PFAS are detected in up to 99% of the population. However, very little is known about how exposure to mixtures of PFAS affects maternal and fetal health. Th ... Full text Link to item Cite

Genetically manipulating endogenous Kras levels and oncogenic mutations in vivo influences tissue patterning of murine tumorigenesis.

Journal Article Elife · September 7, 2022 Despite multiple possible oncogenic mutations in the proto-oncogene KRAS, unique subsets of these mutations are detected in different cancer types. As KRAS mutations occur early, if not being the initiating event, these mutational biases are ostensibly a p ... Full text Link to item Cite

Automated Nuclear Segmentation in Head and Neck Squamous Cell Carcinoma Pathology Reveals Relationships between Cytometric Features and ESTIMATE Stromal and Immune Scores.

Journal Article Am J Pathol · September 2022 The tumor microenvironment (TME) plays an important role in the progression of head and neck squamous cell carcinoma (HNSCC). Currently, pathologic assessment of TME is nonstandardized and subject to observer bias. Genome-wide transcriptomic approaches to ... Full text Link to item Cite

Selected Resources for Pathology Evaluation of Nonhuman Primates in Nonclinical Safety Assessment.

Journal Article Toxicol Pathol · July 2022 Humans and nonhuman primates (NHPs) share numerous anatomical and physiological characteristics, thereby explaining the importance of NHPs as essential animal models for translational medicine and nonclinical toxicity testing. Researchers, toxicologic path ... Full text Link to item Cite

Safety evaluation of carbon tetrafluoride as an inert hyperbaric breathing gas in Sprague-Dawley rats.

Journal Article Toxicol Appl Pharmacol · June 1, 2022 Carbon tetrafluoride (CF4) is an inert gas with higher molecular weight and lower water solubility than commonly used hyperbaric breathing gases. These inert gas properties decrease time required to decompress and avoid decompression sickness after deep di ... Full text Link to item Cite

Epigenetic basis of oncogenic-Kras-mediated epithelial-cellular proliferation and plasticity.

Journal Article Dev Cell · February 7, 2022 Oncogenic Kras induces a hyper-proliferative state that permits cells to progress to neoplasms in diverse epithelial tissues. Depending on the cell of origin, this also involves lineage transformation. Although a multitude of downstream factors have been i ... Full text Open Access Link to item Cite

β-Cyclodextrin-containing polymer treatment of cutaneous lupus and influenza improves outcomes.

Journal Article Mol Ther · February 2, 2022 Nucleic acid (NA)-containing damage- and pathogen-associated molecular patterns (DAMPs and PAMPs, respectively) are implicated in numerous pathological conditions from infectious diseases to autoimmune disorders. Nucleic acid-binding polymers, including po ... Full text Link to item Cite

Kidney and Urinary Bladder

Chapter · February 2, 2022 This chapter reviews the mouse kidney and lower urinary tract as models for human diseases. Many mouse strains develop spontaneous strain-specific lesions, which can be confused with outcomes or complications of particular experiments. Inspection of pathol ... Full text Cite

The Role of Machine Learning in Cardiovascular Pathology.

Journal Article Can J Cardiol · February 2022 Machine learning has seen slow but steady uptake in diagnostic pathology over the past decade to assess digital whole-slide images. Machine learning tools have incredible potential to standardise, and likely even improve, histopathologic diagnoses, but the ... Full text Link to item Cite

Update on the Features and Measurements of Experimental Acute Lung Injury in Animals: An Official American Thoracic Society Workshop Report.

Journal Article Am J Respir Cell Mol Biol · February 2022 Advancements in methods, technology, and our understanding of the pathobiology of lung injury have created the need to update the definition of experimental acute lung injury (ALI). We queried 50 participants with expertise in ALI and acute respiratory dis ... Full text Link to item Cite

Exome sequencing of hepatocellular carcinoma in lemurs identifies potential cancer drivers: A pilot study.

Journal Article Evol Med Public Health · 2022 BACKGROUND AND OBJECTIVES: Hepatocellular carcinoma occurs frequently in prosimians, but the cause of these liver cancers in this group is unknown. Characterizing the genetic changes associated with hepatocellular carcinoma in prosimians may point to possi ... Full text Link to item Cite

Bioethical, Reproducibility, and Translational Challenges of Animal Models.

Journal Article ILAR J · December 31, 2021 There is no prescribed stage or standardized point at which an animal model protocol is reviewed for reproducibility and translatability. The method of review for a reproducible and translatable study is not consistently documented in peer literature, and ... Full text Link to item Cite

Poly(lactide-co-ε-caprolactone) scaffold promotes equivalent tissue integration and supports skin grafts compared to a predicate collagen scaffold.

Journal Article Wound Repair Regen · November 2021 Dermal scarring from motor vehicle accidents, severe burns, military blasts, etc. is a major problem affecting over 80 million people worldwide annually, many of whom suffer from debilitating hypertrophic scar contractures. These stiff, shrunken scars limi ... Full text Link to item Cite

Radiologic-pathologic analysis of increased ethanol localization and ablative extent achieved by ethyl cellulose.

Journal Article Sci Rep · October 19, 2021 Ethanol provides a rapid, low-cost ablative solution for liver tumors with a small technological footprint but suffers from uncontrolled diffusion in target tissue, limiting treatment precision and accuracy. Incorporating the gel-forming polymer ethyl cell ... Full text Link to item Cite

HER2 Isoforms Uniquely Program Intratumor Heterogeneity and Predetermine Breast Cancer Trajectories During the Occult Tumorigenic Phase.

Journal Article Mol Cancer Res · October 2021 HER2-positive breast cancers are among the most heterogeneous breast cancer subtypes. The early amplification of HER2 and its known oncogenic isoforms provide a plausible mechanism in which distinct programs of tumor heterogeneity could be traced to the in ... Full text Link to item Cite

Optimizing ethyl cellulose-ethanol delivery towards enabling ablation of cervical dysplasia.

Journal Article Sci Rep · August 19, 2021 In low-income countries, up to 80% of women diagnosed with cervical dysplasia do not return for follow-up care, primarily due to treatment being inaccessible. Here, we describe development of a low-cost, portable treatment suitable for such settings. It is ... Full text Link to item Cite

ARHGEF26 enhances Salmonella invasion and inflammation in cells and mice.

Journal Article PLoS Pathog · July 2021 Salmonella hijack host machinery in order to invade cells and establish infection. While considerable work has described the role of host proteins in invasion, much less is known regarding how natural variation in these invasion-associated host proteins af ... Full text Link to item Cite

Ex Vivo MR Histology and Cytometric Feature Mapping Connect Three-dimensional in Vivo MR Images to Two-dimensional Histopathologic Images of Murine Sarcomas.

Journal Article Radiol Imaging Cancer · May 2021 Purpose To establish a platform for quantitative tissue-based interpretation of cytoarchitecture features from tumor MRI measurements. Materials and Methods In a pilot preclinical study, multicontrast in vivo MRI of murine soft-tissue sarcomas in 10 mice, ... Full text Open Access Link to item Cite

Polymer-assisted intratumoral delivery of ethanol: Preclinical investigation of safety and efficacy in a murine breast cancer model.

Journal Article PLoS One · 2021 Focal tumor ablation with ethanol could provide benefits in low-resource settings because of its low overall cost, minimal imaging technology requirements, and acceptable clinical outcomes. Unfortunately, ethanol ablation is not commonly utilized because o ... Full text Link to item Cite

Injectable non-immunogenic PEG-like conjugate that forms a subcutaneous depot and enables sustained delivery of a peptide drug

Journal Article · 2021 Many biologics have a short plasma half-life, and their conjugation to polyethylene glycol (PEG) is commonly used to solve this problem. Unfortunately, PEG is immunogenic and forms vacuoles, and improvement in PEGylated drugs' half-life is at an asymptote. ... Full text Cite

International Harmonization of Nomenclature and Diagnostic Criteria (INHAND): Non-proliferative and Proliferative Lesions of the Non-human Primate (M. fascicularis).

Journal Article J Toxicol Pathol · 2021 The INHAND (International Harmonization of Nomenclature and Diagnostic Criteria for Lesions Project (www.toxpath.org/inhand.asp) is a joint initiative of the Societies of Toxicologic Pathology from Europe (ESTP), Great Britain (BSTP), Japan (JSTP) and Nort ... Full text Link to item Cite

RAS mutation patterns arise from tissue-specific responses to distinct oncogenic signaling

Journal Article · 2021 Despite multiple possible oncogenic mutations in the proto-oncogene KRAS , unique subsets of these mutations are detected in different cancer types. As KRAS mutations occur early, if not being initiating, these mutational biases are ostensibly a product of ... Full text Cite

Issues in Laboratory Animal Science That Impact Toxicologic Pathology

Chapter · January 1, 2021 Numerous genetic, microbial, environmental, and experimental factors work together to influence the development of lesions studied by the toxicologic pathologist. The pathologist needs to understand how factors associated with the laboratory animal test su ... Full text Cite

A Comparative Oncology Drug Discovery Pipeline to Identify and Validate New Treatments for Osteosarcoma.

Journal Article Cancers (Basel) · November 11, 2020 BACKGROUND: Osteosarcoma is a rare but aggressive bone cancer that occurs primarily in children. Like other rare cancers, treatment advances for osteosarcoma have stagnated, with little improvement in survival for the past several decades. Developing new t ... Full text Link to item Cite

Coagulopathy Characterized by Rotational Thromboelastometry in a Porcine Pediatric ECMO Model.

Journal Article J Extra Corpor Technol · September 2020 Venoarterial extracorporeal membrane oxygenation (VA-ECMO) is used to support patients with reversible cardiopulmonary insufficiency. Although it is a lifesaving technology, bleeding, inflammation, and thrombosis are well-described complications of ECMO. A ... Full text Link to item Cite

Abstract 5243: Averting tumor growth in rodent breast cancer models with a liquid ablation approach

Conference Cancer Research · August 15, 2020 AbstractIn low-resource settings, surgery or radiation are inaccessible to 90% of cancer patients due to inadequate infrastructure and lack of trained personnel. Resource appropriate technologies must be dev ... Full text Cite

Antibiotic eluting poly(ester urea) films for control of a model cardiac implantable electronic device infection.

Journal Article Acta Biomater · July 15, 2020 Cardiac implantable electronic device (CIED) infections acquired during or after surgical procedures are a major complication that are challenging to treat therapeutically, resulting in chronic and sometimes fatal infections. Localized delivery of antibiot ... Full text Link to item Cite

Comparisons of Infant and Adult Mice Reveal Age Effects for Liver Depot Gene Therapy in Pompe Disease.

Journal Article Mol Ther Methods Clin Dev · June 12, 2020 Pompe disease is caused by the deficiency of lysosomal acid α-glucosidase (GAA). It is expected that gene therapy to replace GAA with adeno-associated virus (AAV) vectors will be less effective early in life because of the rapid loss of vector genomes. AAV ... Full text Open Access Link to item Cite

Targeting PD-L1 Initiates Effective Antitumor Immunity in a Murine Model of Cushing Disease.

Journal Article Clin Cancer Res · March 1, 2020 PURPOSE: Although pituitary adenoma is classified as benign, Cushing disease is associated with significant morbidity due to the numerous sequelae of elevated cortisol levels. Successful therapy for Cushing disease remains elusive due to high rates of trea ... Full text Link to item Cite

Subglottic Cryotherapy: A Pilot Study in New Zealand White Rabbits.

Journal Article Otolaryngol Head Neck Surg · March 2020 To describe proof of concept and pilot data for a cryotherapy application in the subglottis in a rabbit airway model. Four New Zealand white rabbits (3 experimental, 1 control) underwent general anesthesia and laryngoscopy and bronchoscopy. Experimental an ... Full text Link to item Cite

Soft Tissue Anchoring Performance, Biomechanical Properties, and Tissue Reaction of a New Hernia Mesh Engineered to Address Hernia Occurrence and Recurrence.

Journal Article J Med Device · December 1, 2019 One opportunity to reduce hernia occurrence and recurrence rates (currently estimated to be 30% at 10 years postoperatively) is by enhancing the ability of hernia meshes to anchor into tissue to prevent mesh migration, mesh contraction, and mesh tearing aw ... Full text Link to item Cite

Salmeterol with Liver Depot Gene Therapy Enhances the Skeletal Muscle Response in Murine Pompe Disease.

Journal Article Hum Gene Ther · July 2019 Gene therapy for Pompe disease with adeno-associated virus (AAV) vectors has advanced into early phase clinical trials; however, the paucity of cation-independent mannose-6-phosphate receptor (CI-MPR) in skeletal muscle, where it is needed to take up acid ... Full text Link to item Cite

Author Correction: Sequestration of T cells in bone marrow in the setting of glioblastoma and other intracranial tumors.

Journal Article Nat Med · March 2019 In the version of this article originally published, the figure callout in this sentence was incorrect: "Furthermore, in S1P1-KI mice themselves, whereas PD-1 blockade was ineffectual as monotherapy, the effects of 4-1BB agonism and checkpoint blockade pro ... Full text Link to item Cite

miR-34a is a microRNA safeguard for Citrobacter-induced inflammatory colon oncogenesis.

Journal Article Elife · December 13, 2018 Inflammation often induces regeneration to repair the tissue damage. However, chronic inflammation can transform temporary hyperplasia into a fertile ground for tumorigenesis. Here, we demonstrate that the microRNA miR-34a acts as a central safeguard to pr ... Full text Link to item Cite

Pathology Study Design, Conduct, and Reporting to Achieve Rigor and Reproducibility in Translational Research Using Animal Models.

Journal Article ILAR J · December 1, 2018 In translational research, animal models are an important tool to aid in decision-making when taking potential therapies into human clinical trials. Recently, there have been a number of papers that have suggested limited concordance of preclinical animal ... Full text Link to item Cite

An Introduction to Pathology in Biomedical Research: A Mission-Critical Specialty for Reproducibility and Rigor in Translational Research.

Journal Article ILAR J · December 1, 2018 This issue of ILAR Journal focusses on pathology and pathologists in biomedical research, more specifically in preclinical translational research involving (nonhuman) animals, emphasizing academic settings. Considerations in study design and planning to ma ... Full text Link to item Cite

Long-term complications of glycogen storage disease type Ia in the canine model treated with gene replacement therapy.

Conference J Inherit Metab Dis · November 2018 BACKGROUND: Glycogen storage disease type Ia (GSD Ia) in dogs closely resembles human GSD Ia. Untreated patients with GSD Ia develop complications associated with glucose-6-phosphatase (G6Pase) deficiency. Survival of human patients on intensive nutritiona ... Full text Link to item Cite

Sequestration of T cells in bone marrow in the setting of glioblastoma and other intracranial tumors.

Journal Article Nat Med · September 2018 T cell dysfunction contributes to tumor immune escape in patients with cancer and is particularly severe amidst glioblastoma (GBM). Among other defects, T cell lymphopenia is characteristic, yet often attributed to treatment. We reveal that even treatment- ... Full text Link to item Cite

Evolutionarily Conserved and Divergent Roles of Unfolded Protein Response (UPR) in the Pathogenic Cryptococcus Species Complex.

Journal Article Sci Rep · May 25, 2018 The unfolded protein response (UPR) pathway, consisting of the evolutionarily conserved Ire1 kinase/endonuclease and the bZIP transcription factor Hxl1, is critical for the pathogenicity of Cryptococcus neoformans; however, its role remains unknown in othe ... Full text Link to item Cite

Animal Care and Use in Toxicity Testing

Chapter · January 1, 2018 Toxicologists involved in toxicity testing must be aware of the important aspects of how animals are cared for and used in the laboratory. They also need to have an understanding of how the laboratory animal itself and the animal care and use environment a ... Full text Cite

The use of the marmoset in toxicity testing and nonclinical safety assessment studies

Chapter · January 1, 2018 The common marmoset (Callithrix jacchus) is an important nonhuman primate (NHP) model that has been used in both chemical toxicity and pharmaceutical safety assessment testing. These NHPs have a number of features that can make them a useful model for toxi ... Full text Cite

Distinct Angiogenic Changes during Carcinogenesis Defined by Novel Label-Free Dark-Field Imaging in a Hamster Cheek Pouch Model.

Journal Article Cancer Res · December 15, 2017 There remain gaps in knowledge concerning how vascular morphology evolves during carcinogenesis. In this study, we imaged neovascularization by label-free dark-field microscopy of a 7,12-Dimethylbenz[a]anthracene (DMBA)-induced hamster cheek pouch model of ... Full text Link to item Cite

The Role of the IACUC in the Design and Conduct of Animal Experiments that Contribute to Translational Success.

Journal Article ILAR J · July 1, 2017 Institutional Animal Care and Use Committees (IACUCs) have a mandated role under the Animal Welfare Act and under Public Health Service Policy to assure the ethical and humane use of research animals in experiments conducted in the United States. The IACUC ... Full text Link to item Cite

Targeting the histone methyltransferase G9a activates imprinted genes and improves survival of a mouse model of Prader-Willi syndrome.

Journal Article Nat Med · February 2017 Prader-Willi syndrome (PWS) is an imprinting disorder caused by a deficiency of paternally expressed gene(s) in the 15q11-q13 chromosomal region. The regulation of imprinted gene expression in this region is coordinated by an imprinting center (PWS-IC). In ... Full text Link to item Cite

HIV-1 Envelope Mimicry of Host Enzyme Kynureninase Does Not Disrupt Tryptophan Metabolism.

Journal Article J Immunol · December 15, 2016 The HIV-1 envelope protein (Env) has evolved to subvert the host immune system, hindering viral control by the host. The tryptophan metabolic enzyme kynureninase (KYNU) is mimicked by a portion of the HIV Env gp41 membrane proximal region (MPER) and is cro ... Full text Link to item Cite

Current concepts of Harm-Benefit Analysis of Animal Experiments - Report from the AALAS-FELASA Working Group on Harm-Benefit Analysis - Part 1.

Journal Article Lab Anim · June 2016 International regulations and guidelines strongly suggest that the use of animal models in scientific research should be initiated only after the authority responsible for the review of animal studies has concluded a well-thought-out harm-benefit analysis ... Full text Link to item Cite

Recommendations for Addressing Harm-Benefit Analysis and Implementation in Ethical Evaluation - Report from the AALAS-FELASA Working Group on Harm-Benefit Analysis - Part 2.

Journal Article Lab Anim · June 2016 International regulations and guidelines strongly suggest that the use of animal models in scientific research should be initiated only after the authority responsible for the review of animal studies has concluded a well-thought-out harm-benefit analysis ... Full text Link to item Cite

Recommendations for minimum information for publication of experimental pathology data: MINPEPA guidelines.

Journal Article J Pathol · January 2016 Featured Publication Animal models are essential research tools in modern biomedical research, but there are concerns about their lack of reproducibility and the failure of animal data to translate into advances in human medical therapy. A major factor in improving experimenta ... Full text Link to item Cite

Isolation and characterization of a novel Helicobacter species, Helicobacter jaachi sp. nov., from common marmosets (Callithrix jaachus).

Journal Article J Med Microbiol · September 2015 Purpose-bred common marmosets from domestic sources housed in a US research facility, and used in multiple drug discovery programmes, were noted to have a high incidence of spontaneous inflammatory bowel disease and sporadic cholecystitis and cholangiohepa ... Full text Link to item Cite

The future of preclinical animal models in pharmaceutical discovery and development: a need to bring in cerebro to the in vivo discussions.

Journal Article Toxicol Pathol · January 2015 Animal models have provided an important tool to help make the decision to take potential therapies from preclinical studies to humans. In the past several years, the strong reliance of the pharmaceutical discovery and development process on the use of ani ... Full text Link to item Cite

the Toxicology Studies of Cobalt Metal (CASRN 7440-48-4) in F344/N Rats and B6C3F1/N Mice and Toxicology and Carcinogenesis Studies of Cobalt Metal in F344/NTac Rats and B6C3F1/N Mice (Inhalation Studies)

Book · January 1, 2014 Widespread exposure to cobalt metal dust occurs occupationally through the production of alloys, in the manufacture of cobalt salts, and in nuclear technology. It is an effective catalyst for many organic reactions, particularly in hydrotreating catalysts, ... Cite

Issues in Laboratory Animal Science

Chapter · August 29, 2013 Numerous genetic, microbial, environmental, and experimental factors work together to influence development of the lesions studied by the toxicologic pathologist. The pathologist needs to understand how factors associated with the laboratory animal, the an ... Full text Cite

ICLAS Working Group on Harmonization: international guidance concerning the production care and use of genetically-altered animals.

Journal Article Lab Anim · July 2013 Replacement, Reduction and Refinement, the ‘Three Rs’ of Russell & Burch, are accepted worldwide as fundamental to the ethics of animal experimentation. The production, care and use of genetically-altered animals can pose particular challenges to the imple ... Full text Link to item Cite

Meeting report: Urinary Pathology; sixth Research Triangle Park Rodent Pathology Course.

Journal Article Vet Pathol · May 2013 Urinary system toxicity is a significant concern to pathologists in the hazard identification, drug and chemical safety evaluation, and diagnostic service industries worldwide. There are myriad known human and animal urinary system toxicants, and investiga ... Full text Link to item Cite

Issues in Laboratory Animal Science

Chapter · January 1, 2013 Numerous genetic, microbial, environmental, and experimental factors work together to influence development of the lesions studied by the toxicologic pathologist. The pathologist needs to understand how factors associated with the laboratory animal, the an ... Full text Cite

Environmental estrogens differentially engage the histone methyltransferase EZH2 to increase risk of uterine tumorigenesis.

Journal Article Mol Cancer Res · April 2012 Environmental exposures during sensitive windows of development can reprogram normal physiologic responses and alter disease susceptibility later in life in a process known as developmental reprogramming. For example, exposure to the xenoestrogen diethylst ... Full text Link to item Cite

Non-neoplastic and neoplastic pleural endpoints following fiber exposure.

Journal Article J Toxicol Environ Health B Crit Rev · 2011 Exposure to asbestos fibers is associated with non-neoplastic pleural diseases including plaques, fibrosis, and benign effusions, as well as with diffuse malignant pleural mesothelioma. Translocation and retention of fibers are fundamental processes in und ... Full text Link to item Cite

Animal Care and Use in Toxicity Testing

Chapter · August 12, 2010 Toxicologists involved in toxicity testing must be aware of the important aspects of how animals are cared for and used in the laboratory. They also need to have an understanding of how the laboratory animal itself and the animal care and use environment a ... Full text Cite

Guidelines for the welfare and use of animals in cancer research.

Journal Article Br J Cancer · May 25, 2010 Animal experiments remain essential to understand the fundamental mechanisms underpinning malignancy and to discover improved methods to prevent, diagnose and treat cancer. Excellent standards of animal care are fully consistent with the conduct of high qu ... Full text Link to item Cite

Pleural effects of indium phosphide in B6C3F1 mice: nonfibrous particulate induced pleural fibrosis.

Journal Article Exp Lung Res · December 2009 The mechanism(s) by which chronic inhalation of indium phosphide (InP) particles causes pleural fibrosis is not known. Few studies of InP pleural toxicity have been conducted because of the challenges in conducting particulate inhalation exposures, and bec ... Full text Link to item Cite

Inhaled carbon nanotubes reach the subpleural tissue in mice.

Journal Article Nat Nanotechnol · November 2009 Carbon nanotubes are shaped like fibres and can stimulate inflammation at the surface of the peritoneum when injected into the abdominal cavity of mice, raising concerns that inhaled nanotubes may cause pleural fibrosis and/or mesothelioma. Here, we show t ... Full text Link to item Cite

Early onset of spontaneous renal preneoplastic and neoplastic lesions in young conventional rats in toxicity studies.

Journal Article Toxicol Pathol · June 2007 Although occurring in aged laboratory rodents, spontaneous renal tumour are unknown in animals younger than 18 weeks. A survey on renal preneoplastic and neoplastic lesions has been performed on Sprague-Dawley rats from general toxicology studies over the ... Full text Link to item Cite

Tumor-specific efficacy of transforming growth factor-beta RI inhibition in Eker rats.

Journal Article Clin Cancer Res · May 15, 2007 PURPOSE: Transforming growth factor beta (TGF-beta), which generally stimulates the growth of mesenchymally derived cells but inhibits the growth of epithelial cells, has been proposed as a possible target for cancer therapy. However, concerns have been ra ... Full text Link to item Cite

NTP Technical Report on the Toxicity Studies of Wy-14,643 (CAS No. 50892-23-4) Administered in Feed to Sprague-Dawley Rats, B6C3F1Mice, and Syrian Hamsters

Book · January 1, 2007 Wy-14,643 was selected for inclusion in a series of studies on peroxisome proliferators because it is known to produce considerable peroxisome proliferation and hepatocarcinogenicity in rats. Male Sprague-Dawley rats were exposed to Wy-14,643 (greater than ... Cite

Neoplastic Disease

Chapter · December 1, 2006 Neoplastic disease in the rat, as in most species, increases dramatically with increasing age. Many genetic and environmental factors influence the development of neoplasia, and attaining an understanding of these factors and their control is critical for ... Full text Cite

Euthanasia and Necropsy

Chapter · December 1, 2006 Recommendations for animal euthanasia are provided by the American Veterinary Medical Association (AVMA) Panel on Euthanasia. Physical, inhalant, and pharmacologic methods of euthanasia all have their place in research studies that employ laboratory rats. ... Full text Cite

Analysis of renal cell transformation following exposure to trichloroethene in vivo and its metabolite S-(dichlorovinyl)-L-cysteine in vitro.

Journal Article Toxicology · July 5, 2006 Trichloroethene (TCE) is classified as a potential human carcinogen although there is a significant debate regarding the mechanism of TCE induced renal tumor formation. This controversy stems in part from the extremely high doses of TCE required to induce ... Full text Link to item Cite

Preparation of animals for use in the laboratory: issues and challenges for the Institutional Animal Care and Use Committee (IACUC).

Journal Article ILAR J · 2006 Preparation of animals is important for optimization of animal welfare as well as to minimize interanimal variation, thereby strengthening the quality of data for in vivo studies. These issues are important in the work of institutional animal care and use ... Full text Link to item Cite

Conditional expression of the mutant Ki-rasG12C allele results in formation of benign lung adenomas: development of a novel mouse lung tumor model.

Journal Article Carcinogenesis · December 2005 To determine the effects of expression of mutant Ki-ras on lung tumorigenesis, we developed a bitransgenic mouse model that expresses the human Ki-ras(G12C) allele in alveolar type II and/or Clara cells in a tetracycline-inducible, lung-specific manner. Ex ... Full text Link to item Cite

Euthanasia and Necropsy

Chapter · January 1, 2005 Recommendations for animal euthanasia are provided by the American Veterinary Medical Association (AVMA) Panel on Euthanasia. Physical, inhalant, and pharmacologic methods of euthanasia all have their place in research studies that employ laboratory rats. ... Full text Cite

Neoplastic Disease

Chapter · January 1, 2005 Neoplastic disease in the rat, as in most species, increases dramatically with increasing age. Many genetic and environmental factors influence the development of neoplasia, and attaining an understanding of these factors and their control is critical for ... Full text Cite

Mimetics of caloric restriction include agonists of lipid-activated nuclear receptors.

Journal Article J Biol Chem · October 29, 2004 The obesity epidemic in industrialized countries is associated with increases in cardiovascular disease (CVD) and certain types of cancer. In animal models, caloric restriction (CR) suppresses these diseases as well as chemical-induced tissue damage. These ... Full text Link to item Cite

Induction of ERK1/2 and histone H3 phosphorylation within the outer stripe of the outer medulla of the Eker rat by 2,3,5-tris-(glutathion-S-yl)hydroquinone.

Journal Article Toxicol Sci · August 2004 2,3,5-tris-(glutathion-S-yl)-hydroquinone (TGHQ), a metabolite of hydroquinone (HQ), generates reactive oxygen species (ROS) in cultured renal epithelial cells and binds to tissue macromolecules within the rat kidney. The potential mechanisms by which TGHQ ... Full text Link to item Cite

Emission-particle-induced ventilatory abnormalities in a rat model of pulmonary hypertension.

Journal Article Environ Health Perspect · June 2004 Preexistent cardiopulmonary disease in humans appears to enhance susceptibility to the adverse effects of ambient particulate matter. Previous studies in this laboratory have demonstrated enhanced inflammation and mortality after intratracheal instillation ... Full text Link to item Cite

Nasal toxicity of manganese sulfate and manganese phosphate in young male rats following subchronic (13-week) inhalation exposure.

Journal Article Inhal Toxicol · June 2004 Growing evidence suggests that nasal deposition and transport along the olfactory nerve represents a route by which inhaled manganese and certain other metals are delivered to the rodent brain. The toxicological significance of olfactory transport of manga ... Full text Link to item Cite

Susceptibility to vascular neoplasms but no increased susceptibility to renal carcinogenesis in Vhl knockout mice.

Journal Article Carcinogenesis · March 2004 The von Hippel-Lindau (VHL) tumor suppressor gene plays a prominent role in the development of renal cell carcinoma (RCC) in humans. VHL functions as a ubiquitin E3 ligase, controlling the stability of hypoxia inducible factor (HIF) and tumor angiogenesis. ... Full text Link to item Cite

Pulmonary responses of mice, rats, and hamsters to subchronic inhalation of ultrafine titanium dioxide particles.

Journal Article Toxicol Sci · February 2004 A multispecies, subchronic, inhalation study comparing pulmonary responses to ultrafine titanium dioxide (uf-TiO(2)) was performed. Female rats, mice, and hamsters were exposed to aerosol concentrations of 0.5, 2.0, or 10 mg/m(3) uf-TiO(2) particles for 6 ... Full text Link to item Cite

Osteopontin expression in particle-induced lung disease.

Journal Article Exp Lung Res · 2004 Osteopontin (OPN) is a secreted cytokine with cell adhesive and chemoattractive functions whose expression is induced by a variety of environmental toxicants. It has been implicated in the pathogenesis of several pulmonary granulomatous and fibrotic condit ... Full text Link to item Cite

Laboratory animal science issues in the design and conduct of studies with endocrine-active compounds.

Journal Article ILAR J · 2004 The use of rodent models for research and testing on endocrine-active compounds necessitates an awareness of a number of laboratory animal science issues to standardize bioassay methods and facilitate reproducibility of results between laboratories. These ... Full text Link to item Cite

Emmission-particle-induced ventilatory abnormalities in a rat model of pulmonary hypertension

Journal Article Environmental Health Perspectives · January 1, 2004 Preexistent cardiopulmonary disease in humans appears to enhance susceptibility to the adverse effects of ambient particulate matter. Previous studies in this laboratory have demonstrated enhanced inflammation and mortality after intratracheal instillation ... Full text Cite

Uterine leiomyoma in the Eker rat: a unique model for important diseases of women.

Journal Article Genes Chromosomes Cancer · December 2003 Eker rats carry a defect in the Tsc-2 tumor suppressor gene and female Eker rats develop uterine leiomyoma with a high frequency. The presentation, response to hormones and molecular alterations in these mesenchymal smooth muscle tumors, closely resembles ... Full text Link to item Cite

Variations in Prkdc and susceptibility to benzene-induced toxicity in mice.

Journal Article Toxicol Sci · October 2003 Benzene, a carcinogen that induces chromosomal breaks, is strongly associated with leukemias in humans. Possible genetic determinants of benzene susceptibility include proteins involved in repair of benzene-induced DNA damage. The catalytic subunit of DNA- ... Full text Link to item Cite

Soluble ICAM-1, MCP-1, and MIP-2 protein secretion by rat pleural mesothelial cells following exposure to amosite asbestos.

Journal Article Exp Lung Res · July 2003 Pleural inflammation is a sequela of exposure to toxic mineral fibers such as amosite asbestos. This inflammatory response involves the influx of leukocytes from the vasculature into the pleural space. Adhesion molecules such as intercellular adhesion mole ... Full text Link to item Cite

Pleural dosimetry and pathobiological responses in rats and hamsters exposed subchronically to MMVF 10a fiberglass.

Journal Article Toxicol Sci · July 2003 Interspecies differences in pulmonary and pleural responses to the inhalation of natural mineral and synthetic vitreous fibers have been observed in chronic and subchronic studies. However, the reasons for these differences are not clearly understood. Ther ... Full text Link to item Cite

Ultrafine carbon black particles enhance respiratory syncytial virus-induced airway reactivity, pulmonary inflammation, and chemokine expression.

Journal Article Toxicol Sci · April 2003 Exposure to particulate matter (PM) may exacerbate preexisting respiratory diseases such as asthma, chronic obstructive pulmonary disease (COPD), bronchitis, and pneumonia. However, few experimental studies have addressed the effects of PM on lower respira ... Full text Link to item Cite

Male mice deficient in microsomal epoxide hydrolase are not susceptible to benzene-induced toxicity.

Journal Article Toxicol Sci · April 2003 Enzymes involved in benzene metabolism are likely genetic determinants of benzene-induced toxicity. Polymorphisms in human microsomal epoxide hydrolase (mEH) are associated with an increased risk of developing leukemia, specifically those associated with b ... Full text Link to item Cite

Effect of preexposure to ultrafine carbon black on respiratory syncytial virus infection in mice.

Journal Article Toxicol Sci · April 2003 Epidemiological studies have indicated that exposure to elevated levels of particulate matter exacerbates several pulmonary diseases, including asthma, bronchitis, and viral infections. Respiratory syncytial virus (RSV) is the major cause of bronchiolitis ... Full text Link to item Cite

Genetic susceptibility to benzene-induced toxicity: role of NADPH: quinone oxidoreductase-1.

Journal Article Cancer Res · March 1, 2003 Enzymes that activate and detoxify benzene are likely genetic determinants of benzene-induced toxicity.NAD(P)H: quinone oxidoreductase-1 (NQO1) detoxifies benzoquinones, proposed toxic metabolites of benzene. NQO1 deficiency in humans is associated with an ... Link to item Cite

Polycystic kidney disease as a result of loss of the tuberous sclerosis 2 tumor suppressor gene during development.

Journal Article Am J Pathol · February 2003 Somatic loss of function of the tuberous sclerosis 2 (TSC2) tumor suppressor gene leads to the development of benign and malignant lesions of the kidney, brain, uterus, spleen, and liver and germline loss of function of this tumor suppressor gene is embryo ... Full text Link to item Cite

Long-term pulmonary responses of three laboratory rodent species to subchronic inhalation of pigmentary titanium dioxide particles.

Journal Article Toxicol Sci · November 2002 Female mice, rats, and hamsters were exposed to 10, 50, or 250 mg/m(3) pigmentary titanium dioxide (p-TiO(2)) particles for 6 h per day and 5 days per week for 13 weeks with recovery groups held for an additional 4, 13, 26, or 52 weeks postexposure (46 wee ... Full text Link to item Cite

Cell proliferation is insufficient, but loss of tuberin is necessary, for chemically induced nephrocarcinogenicity.

Journal Article Am J Physiol Renal Physiol · August 2002 Although 2,3,5-tris-(glutathion-S-yl)hydroquinone (TGHQ; 2.5 micromol/kg ip) markedly increased cell proliferation within the outer stripe of the outer medulla (OSOM) of the kidney in both wild-type (Tsc2(+/+)) and mutant Eker rats (Tsc2(EK/+)), only TGHQ- ... Full text Link to item Cite

Chloroform inhalation exposure conditions necessary to initiate liver toxicity in female B6C3F1 mice.

Journal Article Toxicol Sci · April 2002 Chloroform is a nongenotoxic-cytotoxic carcinogen in rodent liver and kidney, including the female B6C3F1 mouse liver. Because tumors are secondary to events associated with cytolethality and regenerative cell proliferation, these end points are valid surr ... Full text Link to item Cite

Combined effects of dietary phytoestrogen and synthetic endocrine-active compound on reproductive development in Sprague-Dawley rats: genistein and methoxychlor.

Journal Article Toxicol Sci · March 2002 Humans and wildlife are frequently exposed to mixtures of endocrine active-compounds (EAC). The objective of the present study was to investigate the potential of the phytoestrogen genistein to influence the reproductive developmental toxicity of the endoc ... Full text Link to item Cite

Use of short-term assays to evaluate the potential toxicity of two new biosoluble glasswool fibers.

Journal Article Inhal Toxicol · March 2002 Two new glasswools were developed for optimal biosolubility in the lung: JM 902, for insulation and filtration; and JM 901F, for standard thermal and acoustical insulation. Both were tested for lung biopersistence and their potential to induce persistent p ... Full text Link to item Cite

The effect of chronic progressive nephropathy on the incidence of renal tubule cell neoplasms in control male F344 rats.

Journal Article Toxicol Pathol · 2002 Chronic progressive nephropathy (CPN) is the most frequently diagnosed lesion in the rat kidney. It has many components including degeneration and regeneration of renal tubule (RT) epithelium, glomerular lesions and interstitial inflammation and fibrosis. ... Full text Link to item Cite

Comparison of the pulmonary responses to inhaled pigmentary and ultrafine titanium dioxide particles in the rat, mouse and hamster

Conference Annals of Occupational Hygiene · January 1, 2002 Groups of female rats, mice and hamsters were exposed to 10, 50 or 250 mg/m 3 pigment grade titanium dioxide (PG-TiO 2) or to 0.5, 2 or 10 mg/m 3 ultrafine titanium dioxide (UF-TiO 2) for 6 h/day, 5 days/week for 13 weeks. At the end of the exposure period ... Full text Cite

NTP TECHNICAL REPORT ON THE TOXICOLOGY AND CARCINOGENESIS STUDIES OF o-NITROTOLUENE (CAS NO. 88-72-2) IN F344/N RATS AND B6C3F1 MICE (FEED STUDIES)

Book · January 1, 2002 o-Nitrotoluene is used to synthesize agricultural and rubber chemicals, azo and sulfur dyes, and dyes for cotton, wool, silk, leather, and paper. o-Nitrotoluene was nominated for study by NIOSH and the NTP based on its considerable human exposure as well a ... Cite

Nephrotoxicity and hepatotoxicity induced by inhaled bromodichloromethane in wild-type and p53-heterozygous mice.

Journal Article Toxicol Sci · December 2001 Bromodichloromethane (BDCM) is a common municipal drinking water disinfection by-product, resulting in widespread trace human exposure via ingestion and inhalation. The present studies were designed to define organ-specific, BDCM-induced toxicity in wild t ... Full text Link to item Cite

Use of genetically modified mouse models for evaluation of carcinogenic risk: considerations for the laboratory animal scientist.

Journal Article Comp Med · October 2001 There has been increasing interest in the use of selected genetically modified (GM) mouse models for the testing of chemicals to determine their carcinogenic potential. GM mouse models are believed to be useful tools that offer mechanistically relevant ins ... Link to item Cite

Acute pulmonary toxicity of particulate matter filter extracts in rats: coherence with epidemiologic studies in Utah Valley residents.

Journal Article Environ Health Perspect · June 2001 Epidemiologic reports by C.A. Pope III et. al. demonstrated that in the Utah Valley, closure of an open-hearth steel mill over the winter of 1987 was associated with reductions in respiratory disease and related hospital admissions in valley residents. To ... Full text Link to item Cite

alpha 2u-Globulin nephropathy, renal cell proliferation, and dosimetry of inhaled tert-butyl alcohol in male and female F-344 rats.

Journal Article Toxicol Sci · May 2001 tert-Butyl alcohol (TBA) has been shown to cause kidney tumors in male rats following chronic administration in drinking water. The objective of the present study was to determine whether TBA induces alpha 2u-globulin (alpha 2u) nephropathy (alpha 2u-N) an ... Full text Link to item Cite

Tuberin-dependent membrane localization of polycystin-1: a functional link between polycystic kidney disease and the TSC2 tumor suppressor gene.

Journal Article Mol Cell · April 2001 The PKD1 gene accounts for 85% of autosomal dominant polycystic kidney disease (ADPKD), the most common human genetic disorder. Rats with a germline inactivation of one allele of the Tsc2 tumor suppressor gene developed early onset severe bilateral polycys ... Full text Link to item Cite

Carcinogenicity of a nephrotoxic metabolite of the "nongenotoxic" carcinogen hydroquinone.

Journal Article Chem Res Toxicol · January 2001 Hydroquinone (HQ) is a potential human carcinogen to which many people are exposed. HQ generally tests negative in standard mutagenicity assays, making it a "nongenotoxic" carcinogen whose mechanism of action remains unknown. HQ is metabolized to 2,3,5-tri ... Full text Link to item Cite

Acute pulmonary toxicity of particulate matter filter extracts in rats: Coherence with epidemiologic studies in Utah valley residents

Journal Article Environmental Health Perspectives · January 1, 2001 Epidemiologic reports by C.A. Pope III et al. demonstrated that in the Utah Valley, closure of an open-hearth steel mill over the winter of 1987 was associated with reductions in respiratory disease and related hospital admissions in valley residents. To b ... Full text Cite

α2u-Globulin nephropathy, renal cell proliferation, and dosimetry of inhaled tert-butyl alcohol in male and female F-344 rats

Journal Article Toxicological Sciences · January 1, 2001 tert-Butyl alcohol (TBA) has been shown to cause kidney tumors in male rats following chronic administration in drinking water. The objective of the present study was to determine whether TBA induces α2u-globulin (α2u) nephropathy (α2u-N) and enhanced rena ... Cite

Advances in uterine leiomyoma research: conference overview, summary, and future research recommendations.

Journal Article Environ Health Perspect · October 2000 Uterine leiomyomas (fibroids, myomas) are the most common tumors occurring in the genital tract of women over 30 years of age. These benign uterine smooth-muscle tumors are estimated to be clinically significant in at least 25% of the American female popul ... Full text Link to item Cite

Promotion by sodium barbital induces early development but does not increase the multiplicity of hereditary renal tumors in Eker rats.

Journal Article Carcinogenesis · August 2000 Induced cell proliferation is important in the mode of action of many non-genotoxic renal carcinogens. Since Tsc2 mutant (Eker) rats are genetically predisposed to the development of renal cell tumors, they provide a useful animal model in which to study t ... Link to item Cite

Preclinical Evidence for Therapeutic Efficacy of Selective Estrogen receptor Modulators for Uterine Leiomyoma

Journal Article Journal of the Society for Gynecologic Investigation · July 2000 Full text Cite

Advances in uterine leiomyoma research: Conference overview, summary, and future research recommendations

Journal Article Environmental Health Perspectives · 2000 Uterine leiomyomas (fibroids, myomas) are the most common tumors occurring in the genital tract of women over 30 years of age. These benign uterine smooth-muscle tumors are estimated to be clinically significant in at least 25% of the American female popul ... Cite

Preclinical evidence for therapeutic efficacy of selective estrogen receptor modulators for uterine leiomyoma.

Journal Article J Soc Gynecol Investig · 2000 OBJECTIVE: Uterine leiomyoma are the most common gynecologic neoplasm and a primary cause of hysterectomy in premenopausal women. Preclinical studies were conducted in the Eker rat model to investigate the potential efficacy of selective estrogen receptor ... Link to item Cite

Protein Carbonyls in Bronchoalveolar Lavage Fluid in Mice, Rats and Hamsters Following Inhalation of Pigmentary Titanium Dioxide Particles.

Journal Article Inhal Toxicol · January 2000 Elevation of protein carbonyls has been implicated in the clinical setting as a result of oxidant damage associated with a number of disease states in both humans and laboratory animals. Protein carbonyls, the product of oxidative modification of amino aci ... Full text Link to item Cite

Comparison of Selected Pulmonary Responses of Rats, Mice, and Syrian Golden Hamsters to Inhaled Pigmentary Titanium Dioxide.

Journal Article Inhal Toxicol · January 2000 We present a preliminary report of a bioassay designed to compare and contrast selected pulmonary responses of female B6C3F1 mice, Fischer 344 rats, and Syrian golden hamsters to inhaled pigmentary titanium dioxide (TiO2). Animals were administered 10, 50, ... Full text Link to item Cite

Mesotheliomas induced in rats by the fibrous mineral erionite are independent from p53 alterations.

Journal Article Cancer Lett · December 1, 1999 The development of human malignant mesothelioma (MM) is strongly associated with occupational or environmental exposure to certain natural mineral fibers, although the genetic mechanisms underlying this malignancy remain unclear. Although the p53 gene is f ... Full text Link to item Cite

Metabolism of chloroform by cytochrome P450 2E1 is required for induction of toxicity in the liver, kidney, and nose of male mice.

Journal Article Toxicol Appl Pharmacol · October 15, 1999 Chloroform is a nongenotoxic-cytotoxic liver and kidney carcinogen and nasal toxicant in some strains and sexes of rodents. Substantial evidence indicates that tumor induction is secondary to events associated with cytolethality and regenerative cell proli ... Full text Link to item Cite

Studies on the inhalation toxicology of two fiberglasses and amosite asbestos in the Syrian golden hamster. Part II. Results of chronic exposure.

Journal Article Inhal Toxicol · September 1999 Fiberglass (FG) is the largest category of man-made mineral fibers (MMVFs). Many types of FG are manufactured for specific uses building insulation, air handling, filtration, and sound absorption. In the United States, > 95% of FG produced is for building ... Full text Link to item Cite

Studies on the inhalation toxicology of two fiberglasses and amosite asbestos in the syrian golden hamster. Part I. Results of a subchronic study and dose selection for a chronic study.

Journal Article Inhal Toxicol · September 1999 A multidose, subchronic inhalation study was used to estimate the maximum tolerated dose (MTD) of 901 fiberglass (MMVF10.1) for a chronic inhalation study using hamsters. Subchronic study results indicated that 30 mg/m(3) [250-300 WHO fibers (>5 microm lon ... Full text Link to item Cite

Comparison of pulmonary and pleural responses of rats and hamsters to inhaled refractory ceramic fibers.

Journal Article Toxicol Sci · May 1999 The present study was designed to determine whether pleural fiber burdens or subchronic pleural fibroproliferative and inflammatory changes can help explain the marked interspecies differences in pleural fibrosis and mesothelioma that are observed followin ... Full text Link to item Cite

NTP TECHNICAL REPORT ON THE TOXICOLOGY AND CARCINOGENESIS STUDIES OF 60-HZ MAGNETIC FIELDS IN F344/N RATS AND B6C3F1 MICE (WHOLE-BODY EXPOSURE STUDIES)

Book · January 1, 1999 Electric and magnetic fields are associated with the production, transmission, and use of electricity; thus, the potential for human exposure is high. These electric and magnetic fields are predominantly of low frequency (60 Hz in the United States and 50 ... Cite

Estrogen treatment enhances hereditary renal tumor development in Eker rats.

Journal Article Carcinogenesis · November 1998 Hormonal influences are known to affect the development of renal cell carcinoma in man and laboratory animal models. We tested the hypothesis that estrogen treatment or ovariectomy of rats modulates renal tumor development using tuberous sclerosis 2 (Tsc2) ... Full text Link to item Cite

Redistribution and enhanced protein kinase C-mediated phosphorylation of alpha- and gamma-adducin during renal tumor progression.

Journal Article Cell Growth Differ · May 1998 Tumor promotion/progression is known to be due in part to increased signaling through a variety of mitogenic pathways, including protein kinase C (PKC). To determine whether increased PKC activity could play a role in promotion and progression of renal can ... Link to item Cite

Long-term mutagenicity studies with chloroform and dimethylnitrosamine in female lacI transgenic B6C3F1 mice.

Journal Article Environ Mol Mutagen · 1998 The weight of evidence indicates that chloroform induces cancer in the female B6C3F1 mouse liver via a nongenotoxic-cytotoxic mode of action. However, it is probable that DNA damage occurs secondary to events associated with cytolethality and regenerative ... Full text Link to item Cite

Comparison of pleural responses of rats and hamsters to subchronic inhalation of refractory ceramic fibers.

Journal Article Environ Health Perspect · September 1997 In the present subchronic study, we compared pleural inflammation, visceral pleural collagen deposition, and visceral and parietal pleural mesothelial cell proliferation in rats and hamsters identically exposed to a kaolin-based refractory ceramic fiber, ( ... Full text Link to item Cite

Chronic inhalation study of fiber glass and amosite asbestos in hamsters: twelve-month preliminary results.

Journal Article Environ Health Perspect · September 1997 The effects of chronic inhalation of glass fibers and amosite asbestos are currently under study in hamsters. The study includes 18 months of inhalation exposure followed by lifetime recovery. Syrian golden hamsters are exposed, nose only, for 6 hr/day, 5 ... Full text Link to item Cite

Effects of immobilization restraint on Syrian golden hamsters.

Journal Article Lab Anim Sci · August 1997 Rodent nose-only inhalation toxicology systems comprise whole-body immobilization in plastic restraint tubes. This method of restraint is known to have a variety of effects on animals. In the studies reported here, two independent toxicology laboratories e ... Link to item Cite

Altered expression of transforming growth factor-alpha: an early event in renal cell carcinoma development.

Journal Article Mol Carcinog · July 1997 Transforming growth factor-alpha (TGF-alpha) is a multifunctional cell regulatory protein with a wide range of effects on cell growth and differentiation and has been implicated in the neoplastic transformation of a variety of cell types. Altered expressio ... Link to item Cite

Pharmacokinetics of methanol and formate in female cynomolgus monkeys exposed to methanol vapors.

Journal Article Res Rep Health Eff Inst · June 1997 The 1990 Clean Air Act Amendments contain mandates for reduced automotive emissions and add new requirements for the use of alternative fuels such as methanol to reduce certain automotive pollutants. Methanol is acutely toxic in humans at relatively low do ... Link to item Cite

Chrysotile asbestos and H2O2 increase permeability of alveolar epithelium.

Journal Article Exp Lung Res · 1997 The alveolar epithelium contains tight junctions and provides a barrier to passage of potentially injurious substances into the pulmonary interstitium. Alveolar epithelial injury is hypothesized to be an important early event in the pathogenesis of asbesto ... Full text Link to item Cite

Use of lung toxicity and lung particle clearance to estimate the maximum tolerated dose (MTD) for a fiber glass chronic inhalation study in the rat.

Journal Article Fundam Appl Toxicol · July 1996 Short-term toxicity and lung clearance were assessed in rats exposed by inhalation to size-selected fibrous glass (FG) for 13 weeks. Results from this study and from a recent FG chronic inhalation study are presented here as guidelines for the selection of ... Full text Link to item Cite

Pulmonary and pleural responses in Fischer 344 rats following short-term inhalation of a synthetic vitreous fiber. I. Quantitation of lung and pleural fiber burdens.

Journal Article Fundam Appl Toxicol · March 1996 The pleura is an important target tissue of fiber-induced disease, although it is not known whether fibers must be in direct contact with pleural cells to exert pathologic effects. In the present study, we determined the kinetics of fiber movement into ple ... Full text Link to item Cite

Pulmonary and pleural responses in Fischer 344 rats following short-term inhalation of a synthetic vitreous fiber. II. Pathobiologic responses.

Journal Article Fundam Appl Toxicol · March 1996 The pleura is a target site for toxic effects induced by a variety of fibrous particulates, including both natural mineral and man-made vitreous fibers. We examined selected cytological and biochemical indicators of inflammation in both the pleural compart ... Full text Link to item Cite

Renal cell carcinoma development in the rat independent of alterations at the VHL gene locus.

Journal Article Mol Carcinog · February 1996 Germline alterations of the human von Hippel-Lindau (VHL) tumor suppressor gene predispose to renal cell carcinoma and a constellation of other tumor types found in VHL disease. This gene is also mutated or deleted in a high proportion of sporadic nonpapil ... Full text Link to item Cite

TOXICOLOGY AND CARCINOGENESIS STUDIES OF NICKEL SUBSULFIDE (CAS NO. 12035-72-2) IN F344/N RATS AND B6C3F1 MICE (INHALATION STUDIES)

Book · January 1, 1996 Nickel subsulfide is used in the manufacture of lidiium batteries and is a major component in the refining of certain nickel ores. Nickel subsulfide was nominated as part of a class study of nickel compounds, for which there was little information on the t ... Cite

TOXICOLOGY AND CARCINOGENESIS STUDIES OF NICKEL SULFATE HEXAHYDRATE (CAS NO. 10101-97-0) IN F344/N RATS AND B6C3F1 MICE (INHALATION STUDIES)

Book · January 1, 1996 Nickel sulfate hexahydrate is used in nickel plating, as a mordant in dyeing and printing textiles, as a blackening agent for zinc and brass, and in the manufacture of organic nickel salts. Nickel sulfate hexahydrate was nominated by the National Cancer In ... Cite

Hereditary renal cell carcinoma in the Eker rat: a unique animal model for the study of cancer susceptibility.

Journal Article Toxicol Lett · December 1995 A class of genes, the so-called tumor suppressor genes or anti-oncogenes, was originally identified as being responsible for germ-line transmission of cancer susceptibility in humans. Tumor suppressor genes are recessive at the cellular level with respect ... Full text Link to item Cite

Estrogen stimulation and tamoxifen inhibition of leiomyoma cell growth in vitro and in vivo.

Journal Article Endocrinology · November 1995 Uterine leiomyomas (fibroids) are the most common gynecological neoplasms and may be associated with significant morbidity. Recently, we described a rat model (Eker rat) of fibroid development in which reproductive tract leiomyomas develop spontaneously wi ... Full text Link to item Cite

Allelic loss at the tuberous sclerosis 2 locus in spontaneous tumors in the Eker rat.

Journal Article Mol Carcinog · September 1995 Somatic events leading to the inactivation of tumor suppressor genes often involve chromosomal alterations that can be detected as loss of heterozygosity (LOH). In the Eker rat, spontaneous tumors of the kidney, uterus, and spleen develop as a result of a ... Full text Link to item Cite

Expression of insulin-like growth factor II in spontaneously immortalized rat mesothelial and spontaneous mesothelioma cells: a potential autocrine role of insulin-like growth factor II.

Journal Article Cancer Res · August 15, 1995 Insulin-like growth factors (IGFs) are polypeptides that play an important role in cellular proliferation and differentiation. The present study examines the role of IGFs in the growth of mesothelial cells. Cell lines derived from normal rat mesothelium as ... Link to item Cite

Preneoplastic and neoplastic lesions of rat hereditary renal cell tumors express markers of proximal and distal nephron.

Journal Article Vet Pathol · July 1995 Long-Evans (Eker) rats carry a mutation that predisposes them to develop spontaneous renal cell tumors of two morphologic patterns: solid chromophilic masses or cystic lesions lined by eosinophilic cells. Previous studies have suggested that these tumors a ... Full text Link to item Cite

Rodent model of reproductive tract leiomyomata. Clinical and pathological features.

Journal Article Am J Pathol · June 1995 Mesenchymal tumors of the lower reproductive tract of women are poorly understood at the molecular level as a result in part of the lack of relevant animal models. The present study describes a novel model of gynecological smooth muscle tumors in which the ... Link to item Cite

Rodent model of reproductive tract leiomyomata. Establishment and characterization of tumor-derived cell lines.

Journal Article Am J Pathol · June 1995 Uterine myometrial tumors are the most commonly found gynecological neoplasm in women. The underlying causes of uterine leiomyomata are poorly understood, a result in part of the absence of a good animal model system in which to study these tumors. This re ... Link to item Cite

p53 status in spontaneous and dimethylnitrosamine-induced renal cell tumors from rats.

Journal Article Mol Carcinog · April 1995 Rats carrying the Eker tumor-susceptibility mutation (Eker rats) are predisposed to developing renal cell carcinoma. Rats heterozygous for the Eker mutation develop spontaneous multiple bilateral renal cell tumors by the age of 1 yr. In a previous study, E ... Full text Link to item Cite

Autocrine growth stimulation by transforming growth factor alpha in asbestos-transformed rat mesothelial cells.

Journal Article Cancer Res · February 1, 1995 Although the association between asbestos exposure and mesothelioma development has been established for decades, very little is known regarding the molecular mechanism(s) by which asbestos fibers induce this disease. In this series of experiments, the pot ... Link to item Cite

Toxicity Studies of Cadmium Oxide Administered by Inhalation to F344/N Rats and B6C3F1 Mice

Book · January 1, 1995 Three thousand tons of cadmium are imported or produced annually in the United States, an d approximately 90% of this is cadmium oxide. Cadmium oxide is used in batteries, electroplatin g baths, pigments, plastics, synthetic products, and a variety of othe ... Cite

Toxicity Studies of Dibutyl Phthalate Administered in Feed to F344/N Rats and B6C3F1 Mice

Book · January 1, 1995 Dibutyl phthalate is a phthalate ester with extensive use in industry in such products as plastic (PVC) piping, various varnishes and lacquers, safety glass, nail polishes, paper coatings, dental materials, pharmaceuticals, and plastic food wrap. Concomita ... Cite

Mechanisms of fiber-induced diseases: implications for the safety evaluation of synthetic vitreous fibers.

Journal Article Regul Toxicol Pharmacol · December 1994 Inhalation of certain natural mineral fibers, such as amphibole asbestos, is associated with the development of inflammatory, fibroproliferative, and neoplastic diseases in the lung and pleura of man and experimental animals. The mechanisms by which fibers ... Link to item Cite

Mechanisms of fiber-induced diseases: Implications for the safety evaluation of synthetic vitreous fibers

Conference Regulatory Toxicology and Pharmacology · December 1, 1994 Inhalation of certain natural mineral fibers, such as amphibole asbestos, is associated with the development of inflammatory, fibroproliferative, and neoplastic diseases in the lung and pleura of man and experimental animals. The mechanisms by which fibers ... Cite

Increased susceptibility to in vitro transformation of cells carrying the Eker tumor susceptibility mutation.

Journal Article Carcinogenesis · October 1994 Rats carrying the Eker tumor susceptibility mutation are genetically predisposed to renal cell carcinoma. Rats heterozygous for the Eker mutation (Eker carriers) develop multiple bilateral renal cell carcinomas by the age of 1 year. Using an in vitro rat k ... Full text Link to item Cite

Mesothelial cell proliferation induced by intrapleural instillation of man-made fibers in rats and hamsters.

Journal Article Fundam Appl Toxicol · July 1994 Long-term inhalation exposure to a biopersistent man-made ceramic fiber (RCF 1) results in a high incidence of pleural mesotheliomas in Syrian golden hamsters but not in identically exposed rats. To understand better the mechanisms involved in the intraspe ... Full text Link to item Cite

Wilms' tumor suppressor gene expression in rat and human mesothelioma.

Journal Article Cancer Res · June 15, 1994 Induction of mesothelioma in the rat is an important animal model for assessing the carcinogenic potential of fibers and for understanding the molecular basis underlying the development of these tumors. Mesotheliomas and nephroblastoma (Wilms' tumor) have ... Link to item Cite

Carcinogenicity and toxicity of inhaled nitrobenzene in B6C3F1 mice and F344 and CD rats.

Journal Article Fundam Appl Toxicol · April 1994 The potential carcinogenicity and toxicity of inhaled nitrobenzene were evaluated following chronic (2-year) exposure in mice and rats. Male and female B6C3F1 mice were exposed to 0, 5, 25, or 50 ppm nitrobenzene, while male and female F344 rats and male C ... Full text Link to item Cite

Atypical tubule hyperplasia and renal tubule tumors in conventional rats on 90-day toxicity studies.

Journal Article Toxicol Pathol · 1994 Bilateral, multicentric renal tubule tumors were found in 4 rats at the termination of 3 separate 90-day toxicity studies during the safety evaluation of 3 unrelated chemicals. The 3 studies were conducted at 2 separate locations, but the rats used were ob ... Full text Link to item Cite

Pleural lesions in Syrian golden hamsters and Fischer-344 rats following intrapleural instillation of man-made ceramic or glass fibers.

Journal Article Toxicol Pathol · 1994 The mesothelium is a target of the toxic and carcinogenic effects of certain natural mineral and man-made fibers. Long-term inhalation of a ceramic fiber (RCF-1) results in a high incidence of pleural mesotheliomas in Syrian golden hamsters but not in iden ... Full text Link to item Cite

Carcinogenicity of inhaled benzene in CBA mice.

Journal Article Fundam Appl Toxicol · May 1993 This study investigated benzene-induced neoplasia in CBA/Ca mice, with special emphasis on hematopoietic tissues. Ten-week-old male CBA/Ca mice were exposed to 300 ppm benzene via inhalation for 6 hr/day, 5 days/week, for 16 weeks and held 18 months after ... Full text Link to item Cite

Suppression of tumorigenicity of A549 lung adenocarcinoma cells by human chromosomes 3 and 11 introduced via microcell-mediated chromosome transfer.

Journal Article Mol Carcinog · 1993 To map tumor suppressor genes for lung adenocarcinomas, we introduced normal human chromosomes 3, 7, and 11 into the A549 tumor cell line by microcell-mediated chromosome transfer to test which chromosomes had the ability to suppress tumorigenicity. These ... Full text Link to item Cite

Species-specific PDGF expression in mesothelioma

Conference European Respiratory Review · January 1, 1993 Human mesotheliomas aberrantly express platelet-derived growth factor (PDGF), suggesting an autocrine/paracrine role for this growth factor in the development of these tumours. Experiments to investigate the role of PDGF in the development of rat mesotheli ... Cite

Hereditary renal cell carcinoma in the Eker rat: a rodent familial cancer syndrome.

Journal Article J Urol · December 1992 A rodent model of hereditary cancer in which a single gene mutation predisposes rats to bilateral multicentric renal cell carcinoma (RCC) is described. This rat hereditary cancer syndrome shares certain similarities with von Hippel-Lindau disease (VHLD). I ... Full text Link to item Cite

Antioxidant defense mechanisms in cultured pleural mesothelial cells.

Journal Article Am J Respir Cell Mol Biol · July 1992 The role of different antioxidant pathways in cultured rat pleural mesothelial cells was studied by exposing the cells to various hydrogen peroxide (H2O2) concentrations and by measuring H2O2 cell cytotoxicity and the capacity of the cells to scavenge H2O2 ... Full text Link to item Cite

Predisposition to renal cell carcinoma due to alteration of a cancer susceptibility gene.

Journal Article Science · March 27, 1992 A single germ line gene mutation at a tumor susceptibility locus in a rodent model of hereditary human renal cancer caused a 70-fold increase in susceptibility to chemical carcinogenesis. A carcinogen that targeted both renal epithelial and mesenchymal cel ... Full text Link to item Cite

Characterization of platelet-derived growth factor and platelet-derived growth factor receptor expression in asbestos-induced rat mesothelioma.

Journal Article Cancer Res · January 15, 1992 Although altered expression of platelet-derived growth factor (PDGF) is a hallmark of human mesothelioma, expression of PDGF receptors has not been characterized in this cell type. In addition, the expression of this growth factor and its cognate receptor ... Link to item Cite

Oxidants and antioxidants in alveolar epithelial type II cells: in situ, freshly isolated, and cultured cells.

Journal Article Am J Physiol · January 1992 Antioxidant enzyme activities, H2O2 clearance, and H2O2 generation by rat alveolar epithelial type II cells were compared between in situ, freshly isolated (6 h ex vivo), and cultured cells (48 h ex vivo). Immunocytochemical studies did not show changes in ... Full text Link to item Cite

Cytochrome P-450- and glutathione-associated enzyme activities in freshly isolated enriched lung cell fractions from beta-naphthoflavone-treated male F344 rats.

Journal Article Toxicology · 1992 Xenobiotics metabolized in rat pulmonary tissue are often selectively cytotoxic to individual lung cell populations. A non-homogeneous distribution of xenobiotic biotransformation enzymes, e.g., cytochrome P-450 (P-450)- and glutathione (GSH)-associated en ... Full text Link to item Cite

Possible cellular and molecular mechanisms for asbestos carcinogenicity.

Journal Article Am J Ind Med · 1992 Asbestos fibers may exert their carcinogenic effects on mesothelial cells and bronchial epithelial cells by direct and indirect mechanisms. Direct effects can occur following the physical interaction of fibers with target cells or by the generation of free ... Full text Link to item Cite

Cytogenetic and molecular correlates between rodent and human renal cell carcinoma.

Journal Article Prog Clin Biol Res · 1992 In man, RCC makes up the largest proportion of primary kidney cancers, comprising approximately 85% of renal tumors and accounting for approximately 2% of the cancer deaths each year (Richie and Skinner 1981). As shown in Table 2, there are many similariti ... Link to item Cite

Hereditary renal cell carcinoma in the rat associated with nonrandom loss of chromosomes 5 and 6.

Journal Article Cancer Res · August 15, 1991 A spontaneous form of renal cell carcinoma occurs in rats that arises as the result of the inheritance of a mutation in a single autosomal gene. Cytogenetic analysis was performed on seven cell lines and four primary tumor cell preparations derived from th ... Link to item Cite

Covalent binding of inhaled formaldehyde to DNA in the respiratory tract of rhesus monkeys: pharmacokinetics, rat-to-monkey interspecies scaling, and extrapolation to man.

Journal Article Fundam Appl Toxicol · August 1991 DNA-protein cross-links were formed in the respiratory tract of rhesus monkeys exposed to [14C]formaldehyde (0.7, 2, or 6 ppm; 6 hr). Concentrations of cross-links (pmol/mg DNA) were highest in the mucosa of the middle turbinates; lower concentrations were ... Full text Link to item Cite

Trisomy of rat chromosome 1 associated with mesothelial cell transformation.

Journal Article Cancer Res · August 1, 1991 Identification of specific chromosomal aberrations in transformed mesothelial cells is an important step in elucidating the mechanism of transformation of these cells which are targets for occupational and environmental carcinogens, such as asbestos fibers ... Link to item Cite

Hydrogen peroxide production by alveolar type II cells, alveolar macrophages, and endothelial cells.

Journal Article Am J Physiol · August 1991 Extracellular H2O2 release and intracellular H2O2 production were determined in rat lung alveolar macrophages, rat alveolar type II cells, and cultured bovine aortic endothelial cells. Isolated macrophages (5 h ex vivo) released 3.1 +/- 0.09 nmol H2O2.min- ... Full text Link to item Cite

Altered expression of transforming growth factor-alpha in hereditary rat renal cell carcinoma.

Journal Article Cancer Res · June 1, 1991 A hereditary form of renal cell carcinoma exists in rats that results from a single gene mutation and is histologically similar to that described in humans. Cell lines derived from these rat tumors were shown to express abundant transforming growth factor- ... Link to item Cite

Co-culture of primary pulmonary cells to model alveolar injury and translocation of proteins.

Journal Article In Vitro Cell Dev Biol · December 1990 Primary rat alveolar type II cells and early passage rat lung fibroblasts were co-cultured on opposite sides of a collagen-coated polycarbonate filter. This is an approach to "model", in part, an alveolar wall to study mechanisms of cytotoxicity and transl ... Full text Link to item Cite

Expression of growth factor and growth factor receptor RNA in rat pleural mesothelial cells in culture.

Journal Article Exp Cell Res · September 1990 Mineral fiber-induced pleural mesothelioma in the rat is a suitable model for asbestos-induced mesothelioma in humans. A proposed mechanism for the genesis of mesotheliomas is the initiation of an autocrine pathway leading to unregulated growth of the meso ... Full text Link to item Cite

Infectious diseases of the upper respiratory tract: implications for toxicology studies.

Journal Article Environ Health Perspect · April 1990 The consequences of adventitious infectious agents upon the interpretation of toxicology studies performed in rats and mice are incompletely understood. Several prevalent murine pathogens cause alterations of the respiratory system that can confuse the ass ... Full text Link to item Cite

The use of tracheal implants in toxicology and carcinogenesis research.

Journal Article Toxicology · 1990 Tracheal implants have served as an important experimental pathology tool with which to study the toxic and/or carcinogenic effects of chemicals upon upper respiratory tract epithelium. Initial studies with this method utilized heterotopic rat tracheal tra ... Full text Link to item Cite

Effects of formaldehyde gas on the respiratory tract of rhesus monkeys. Pathology and cell proliferation.

Journal Article Am J Pathol · March 1989 Formaldehyde is a nasal carcinogen in rats but it remains to be determined what cancer risk this chemical poses in humans. Molecular dosimetry studies of formaldehyde and cellular proliferative responses to formaldehyde-induced cytotoxicity have been studi ... Link to item Cite

Development of a tracheal implant xenograft model to expose human bronchial epithelial cells to toxic gases.

Journal Article Toxicol Pathol · 1989 A tracheal implant model was developed which enabled exposure of differentiated normal human bronchial epithelial cells (NHBE) to a single exposure of a model toxic gas (formaldehyde). NHBE cells were grown in vitro in explant culture under defined serum-f ... Full text Link to item Cite

Urologic syndrome associated with wire caging in AKR mice.

Journal Article Lab Anim Sci · October 1988 Individually housed male AKR/NCrlBR mice used in a chronic inhalation experiment were noted to develop a severe obstructive genitourinary condition. The mouse urologic syndrome (MUS) had one or more of the following features: bladder distension; peripreput ... Link to item Cite

Formaldehyde concentrations in the blood of rhesus monkeys after inhalation exposure.

Journal Article Food Chem Toxicol · August 1988 The effect of subchronic exposure to formaldehyde (HCHO; 6 ppm; 6 hr/day, 5 days/wk for 4 wk) on the HCHO concentration in the blood of three rhesus monkeys was investigated. Immediately after the final exposure, the monkeys were sedated, and blood samples ... Full text Link to item Cite

Effect of a purified diet on dystrophic cardiac calcinosis in mice.

Journal Article Lab Anim Sci · August 1988 Male and female C3H/HeNCrl mice were divided into test groups and fed either a purified diet (AIN-76A) or a natural ingredient diet (NIH-07). Lesions of dystrophic cardiac calcinosis (DCC) were found to be more prevalent and more severe in mice fed the pur ... Link to item Cite

Carcinogen-induced unscheduled DNA synthesis in xenotransplanted human tracheobronchial epithelium: comparison with rat tracheal epithelium.

Journal Article Carcinogenesis · March 1988 Extrapolation from rodent genotoxicity data to humans is complicated by variables such as interspecies differences in carcinogen metabolism and DNA repair. A xenograft system containing human bronchial epithelial cells was used to assess the induction of u ... Full text Link to item Cite

High mortality with severe dystrophic cardiac calcinosis in C3H/OUJ mice fed high fat purified diets.

Journal Article Vet Pathol · March 1988 Severe degenerative myocardial disease occurred in female C3H/OUJ mice fed purified diets for 36 weeks; the diet contained 5% or 20% fat as non-hydrogenated soybean oil. Deaths of lactating females of this group (17/35 high fat diet and 7/35 low fat diet a ... Full text Link to item Cite

Pathologic changes associated with fatal Plasmodium falciparum infection in the Bolivian squirrel monkey (Saimiri sciureus boliviensis).

Journal Article Am J Trop Med Hyg · July 1987 Fatal cases of experimental Plasmodium falciparum (Indochina I) in Bolivian squirrel monkeys (Saimiri sciureus boliviensis) were examined by histologic and ultrastructural methods. Gross lesions were characterized by hepatosplenomegaly and interstitial pul ... Full text Link to item Cite

Lymphocyte activation, cell-mediated cytotoxicity and their relationship to dietary fat-enhanced mammary tumorigenesis in C3H/OUJ mice.

Journal Article J Nutr · May 1987 The effects of dietary soybean oil (SBO) concentration (5 vs. 20% by weight) on mammary tumorigenesis, mitogen-induced blastogenesis, cell-mediated cytotoxicity and serum and lymphocyte fatty acid composition were studied in C3H/OUJ female mice. Weanling m ... Full text Link to item Cite

Diagnostic exercise: eye lesions in rats.

Journal Article Lab Anim Sci · April 1987 Link to item Cite

UNSCHEDULED DNA-SYNTHESIS (UDS) IN XENOGRAFTS CONTAINING RAT OR HUMAN RESPIRATORY EPITHELIAL-CELLS

Conference PROCEEDINGS OF THE AMERICAN ASSOCIATION FOR CANCER RESEARCH · March 1, 1987 Link to item Cite

Effects of an insecticidal dip containing d-limonene in the cat.

Journal Article J Am Vet Med Assoc · October 15, 1986 A study was undertaken to determine the effects of a single dermal application of a commercial insecticidal dip containing 78.2% d-limonene in cats. At the manufacturer's recommended concentration of 1.5 oz/gal of water, no clinical signs or lesions of tox ... Link to item Cite

Diagnostic exercise: lingual growths in rabbits.

Journal Article Lab Anim Sci · October 1986 Link to item Cite

Experimental Babesia bovis infection in Holstein calves.

Journal Article Vet Pathol · September 1986 One intact and two splenectomized Holstein calves were infected intravenously with a Mexican strain of Babesia bovis and killed following the onset of severe clinical disease. A light and electron microscopic study was conducted on selected tissues to exam ... Full text Link to item Cite

Multicentric nerve sheath fibrosarcomas of multiple cranial nerve roots in two dogs.

Journal Article J Am Vet Med Assoc · April 1, 1986 Nerve sheath fibrosarcomas of the left 5th through 8th cranial nerve roots were diagnosed in 1 dog and of the left 4th through 8th cranial nerve roots in another dog. Clinical signs in both dogs included head tilt to the left, circling to the left, left he ... Link to item Cite

Sudden death in training and racing Thoroughbred horses.

Journal Article J Am Vet Med Assoc · December 15, 1985 We reviewed case records, necropsy reports, and histologic sections from 25 Thoroughbred racehorses that died suddenly at 3 Chicago racetracks. These were young horses ranging in age from 2 to 5 years. There were more females (n = 16) than males (n = 9), a ... Link to item Cite

Use of in vitro cytotoxicity to rank ocular irritation of six surfactants.

Journal Article Alternative methods in toxicology. · January 1985 Cite

Lymphosarcoma as the cause of ataxia in a horse.

Journal Article J Am Vet Med Assoc · June 15, 1984 Link to item Cite

Cutaneous herpes simplex virus infection of guinea pigs as a model for antiviral chemotherapy.

Journal Article Ann N Y Acad Sci · March 4, 1977 The kinetics of Herpesvirus hominis (Type 1) replication and lesion development in guinea pig skin were determined. The data indicate that lesion scores did not always reflect virus content. Virus replication was detected prior to appearance of lesions and ... Full text Link to item Cite