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5. The EphA2 Receptor Regulates Invasiveness and Drug Sensitivity in Canine and Human Osteosarcoma Cells.

Author

Harris, Evelyn D., Sharpe, Jessica C., Strozen, Timothy, Abdi, Shabnam, Kliewer, Maya, Sanchez, Malkon G., Hogan, Natacha S., MacDonald-Dickinson, Valerie, Vizeacoumar, Franco J., and Toosi, Behzad M.

Subjects
COMPARATIVE method, COMBINATION drug therapy, BONE cancer, OSTEOSARCOMA, CELL survival
Abstract

Osteosarcoma is an aggressive bone cancer affecting both humans and dogs, often leading to pulmonary metastasis. Despite surgery and chemotherapy being the primary treatment modalities, survival rates remain low in both species, underscoring the urgent need for more efficacious therapeutic options. Accumulating evidence indicates numerous biological and clinical similarities between human and canine osteosarcoma, making it an ideal choice for comparative oncological research that should benefit both species. The EphA2 receptor has been implicated in controlling invasive responses across different human malignancies, and its expression is associated with poor prognosis. In this study, we utilized a comparative approach to match EphA2 functions in human and canine osteosarcoma models. Our objectives were to assess EphA2 levels and its pro-malignant action in osteosarcoma cells of both species. We found that EphA2 is overexpressed in most of both canine and human osteosarcoma cell lines, while its silencing significantly reduced cell viability, migration, and invasion. Moreover, EphA2 silencing enhanced the sensitivity of osteosarcoma cells to cisplatin, a drug commonly used for treating this cancer. Furthermore, inhibition of EphA2 expression led to a significant reduction in tumor development capability of canine osteosarcoma cells. Our data suggest that these EphA2 effects are likely mediated through various signaling mechanisms, including the SRC, AKT, and ERK–MAPK pathways. Collectively, our findings indicate that EphA2 promotes malignant behaviors in both human and canine osteosarcoma and that targeting EphA2, either alone or in combination with chemotherapy, could offer potential benefits to osteosarcoma patients. [ABSTRACT FROM AUTHOR]

Published
2024
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12. Maternal Transfer and Apical and Physiological Effects of Dietary Hexabromocyclododecane Exposure in Parental Fathead Minnows (Pimephales promelas)

Author

Malala Irugal Bandaralage, Susari, primary, Ignacio Bertucci, Juan, additional, Park, Brad, additional, Green, Derek, additional, Brinkmann, Markus, additional, Masse, Anita, additional, Crump, Doug, additional, Basu, Niladri, additional, Hogan, Natacha, additional, and Hecker, Markus, additional

Published
2022
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14. Target organ toxicity in rats after subchronic oral exposure to soil extracts containing a complex mixture of contaminants

Author

Boamah, Bright, primary, Barnsley, Sarah, additional, Finch, Lian, additional, Briens, Jennifer, additional, Siciliano, Steven, additional, Hogan, Natacha, additional, Hecker, Markus, additional, Hanson, Mark, additional, Campbell, Patrick, additional, Peters, Rachel, additional, Manek, Aditya, additional, Al-Dissi, Ahmad N., additional, and Weber, Lynn, additional

Published
2022
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16. Maternal Transfer and Apical and Physiological Effects of Dietary Hexabromocyclododecane Exposure in Parental Fathead Minnows (Pimephales promelas).

Author

Malala Irugal Bandaralage, Susari, Ignacio Bertucci, Juan, Park, Brad, Green, Derek, Brinkmann, Markus, Masse, Anita, Crump, Doug, Basu, Niladri, Hogan, Natacha, and Hecker, Markus

Subjects
HEXABROMOCYCLODODECANE, FATHEAD minnow, PERSISTENT pollutants, ENDOCRINE disruptors
Abstract

Hexabromocyclododecane (HBCD) is a persistent organic pollutant that has been characterized as an endocrine disruptor, undergoes maternal transfer, and hinders development and growth in oviparous organisms. The present study examined the apical effects of dietary HBCD (11.5, 36.4, 106 mg/kg, wet wt) on adult fathead minnow exposed for 49 days and the subsequent accumulation and maternal transfer kinetics in adult tissue and eggs, respectively. Exposed adults displayed a significant increase in egg production in the medium treatment group, but no other significant effects were noted. Maternal transfer of dietary HBCD had a similar egg‐to‐muscle ratios (EMR) in the low and medium treatment groups (1.65 and 1.27 [wet wt], respectively). However, the high treatment group deviated from other treatments with an EMR of 4.2 (wet wt), potentially due to differences in total lipid content in food and/or reaching diffusion/lipid saturation limits in adult tissue, resulting in lower accumulation in the adult muscle tissue. A positive correlation was observed between egg HBCD concentration and time of exposure, which indicates that maternal transfer of HBCD is of concern in fish, and further studies should be conducted to fully elucidate the potential adverse effects that may be observed in the early life stage of oviparous organisms. Environ Toxicol Chem 2023;42:143–153. © 2022 SETAC [ABSTRACT FROM AUTHOR]

Published
2023
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18. RNA in Municipal Wastewater Reveals Magnitudes of COVID-19 Outbreaks across Four Waves Driven by SARS-CoV-2 Variants of Concern

Author

Xie, Yuwei, primary, Challis, Jonathan K., additional, Oloye, Femi F., additional, Asadi, Mohsen, additional, Cantin, Jenna, additional, Brinkmann, Markus, additional, McPhedran, Kerry N., additional, Hogan, Natacha, additional, Sadowski, Mike, additional, Jones, Paul D., additional, Landgraff, Chrystal, additional, Mangat, Chand, additional, Servos, Mark R., additional, and Giesy, John P., additional

Published
2022
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19. Comparative analysis of transcriptomic points-of-departure (tPODs) and apical responses in embryo-larval fathead minnows exposed to fluoxetine

Author

Alcaraz, Alper James G., primary, Baraniuk, Shaina, additional, Mikulášek, Kamil, additional, Park, Bradley, additional, Lane, Taylor, additional, Burbridge, Connor, additional, Ewald, Jessica, additional, Potěšil, David, additional, Xia, Jianguo, additional, Zdráhal, Zbyněk, additional, Schneider, David, additional, Crump, Doug, additional, Basu, Niladri, additional, Hogan, Natacha, additional, Brinkmann, Markus, additional, and Hecker, Markus, additional

Published
2022
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20. EcoToxXplorer: Leveraging Design Thinking to Develop a Standardized Web‐Based Transcriptomics Analytics Platform for Diverse Users

Author

Soufan, Othman, primary, Ewald, Jessica, additional, Zhou, Guangyan, additional, Hacariz, Orcun, additional, Boulanger, Emily, additional, Alcaraz, Alper James, additional, Hickey, Gordon, additional, Maguire, Steve, additional, Pain, Guillaume, additional, Hogan, Natacha, additional, Hecker, Markus, additional, Crump, Doug, additional, Head, Jessica, additional, Basu, Niladri, additional, and Xia, Jianguo, additional

Published
2021
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25. Development of a Comprehensive Toxicity Pathway Model for 17α-Ethinylestradiol in Early Life Stage Fathead Minnows (Pimephales promelas)

Author

Alcaraz, Alper James G., primary, Potěšil, David, additional, Mikulášek, Kamil, additional, Green, Derek, additional, Park, Bradley, additional, Burbridge, Connor, additional, Bluhm, Kerstin, additional, Soufan, Othman, additional, Lane, Taylor, additional, Pipal, Marek, additional, Brinkmann, Markus, additional, Xia, Jianguo, additional, Zdráhal, Zbyněk, additional, Schneider, David, additional, Crump, Doug, additional, Basu, Niladri, additional, Hogan, Natacha, additional, and Hecker, Markus, additional

Published
2021
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26. SETAC2017-Basu-EcoToxChip Overview.pdf

Author

EcoToxChip Project, Basu, Niladri, Crump, Doug, Hecker, Markus, Head, Jessica A., Hickey, Gordon M., Hogan, Natacha, Maguire, Steve, and Jianguo Xia

Abstract

This poster provides an overview of the EcoToxChip project (www.ecotoxchip.ca) that aims to develop, test, validate, and commercialize PCR arrays (EcoToxChips) and a data evaluation tool (ecotoxXplorer.ca) for the characterization, prioritization and management of environmental chemicals and complex mixtures of regulatory concern.

Published
2020
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27. EcoToxXplorer: Leveraging Design Thinking to Develop a Standardized Web‐Based Transcriptomics Analytics Platform for Diverse Users.

Author

Soufan, Othman, Ewald, Jessica, Zhou, Guangyan, Hacariz, Orcun, Boulanger, Emily, Alcaraz, Alper James, Hickey, Gordon, Maguire, Steve, Pain, Guillaume, Hogan, Natacha, Hecker, Markus, Crump, Doug, Head, Jessica, Basu, Niladri, and Xia, Jianguo

Subjects
VISUAL analytics, DESIGN thinking, HEALTH risk assessment, METABOLOMICS, ECOLOGICAL risk assessment, GENOME editing
Abstract

To help realize the potential for toxicogenomics data to transform chemical risk assessment, new tools are urgently needed to help novice users translate transcriptomics data efficiently and effectively into meaningful information and actionable knowledge. In this Focus article, we detail EcoToxXplorer, a next-generation bioinformatics tool that is high-performance (i.e., scalable for large data or user traffic), intuitive to use (i.e., enables complex analytics via a simple interface), universally accessible (i.e., web-based, user-friendly), and built to handle transcriptomics data for the purpose of chemical risk assessment and environmental management. The generation and use of transcriptomics data across the life sciences have risen sharply in recent years driven largely by advances in biotechnology and computational biology. Motivated by our team's experiences, the objective of this project was to design EcoToxXplorer as a next-generation bioinformatics tool that is high-performance (i.e., scalable for large data or user traffic), intuitive to use (i.e., enables complex analytics via a simple interface), and universally accessible (i.e., web-based and user-friendly design) to handle transcriptomics data for the purpose of chemical risk assessment and environmental management. [Extracted from the article]

Published
2022
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44. Developmental regulation and estrogenic endocrine disruption of metamorphosis in the Northern leopard frog, Rana pipens

Author

Hogan, Natacha Suzanne

Subjects
Biology, Animal Physiology, Biology, Zoology
Abstract

Amphibian metamorphosis is a dramatic larvae-to-adult transformation regulated by temporal changes in thyroid hormones (TH) as well as interactions with other hormone systems. This developmental process is extremely responsive to changes in environmental conditions and susceptible to aquatic contaminants that interfere with hormone-dependent processes. While many of these endocrine disrupting compounds (EDCs) have been studied for their estrogenic effects on reproduction, the plasticity of amphibian metamorphosis provides a unique model for examining the thyroid-mediated effects of developmental exposure to estrogenic EDCs. The first objective of this thesis was to assess the toxicological response and developmental effects of estrogenic EDCs during the larval life-stages of amphibian development. After establishing baseline toxicity data for the test species, Rana pipiens, a developmental exposure was conducted to determine the estrogen-sensitivity of distinct periods during metamorphosis. Stage-specific exposures altered tadpole growth parameters and resulted in lasting effects such as delayed metamorphosis and female-biased sex ratios. Therefore, the second objective was to identify potential mechanisms by which xenoestrogens alter TH-dependent metamorphosis using a targeted gene expression approach. Development of multiplex and simplex real-time PCR assays and subsequent analysis established that thyroid- and estrogen-responsive transcripts in the tadpole brain are differentially regulated by exogenous TH and upon exposure to an estrogenic EDC. A short-term "challenge" assay confirmed that estrogenic exposure suppresses and in some cases blocks the ability of TH to induce the expression of target genes involved in mediating tissue-specific TH sensitivity during metamorphosis. The results of this research (1) provide evidence of cross-regulation between thyroid and estrogen-regulated genes during amphibian development and (2) indicate that developmental exposure to estrogenic EDCs may affect normal TH-responsiveness necessary for proper timing of metamorphosis.

Published
2013
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47. Using near infrared transmittance to generate sorted fractions of Fusarium-infected wheat and their immunological impact on broiler chickens.

Author

Kautzman, Michael E., Hogan, Natacha S., Gomis, Susantha M., Brown, Kaitlyn S., Wickstrom, Mark L., and Plaizier, J.

Subjects
FUSARIUM toxins, WHEAT diseases & pests, BROILER chickens, POULTRY feeding, IMMUNITY, BIRDS
Abstract

Copyright of Canadian Journal of Animal Science is the property of Canadian Science Publishing and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Published
2017
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48. Performance effects of feed-borne Fusariummycotoxins on broiler chickens: Influences of timing and duration of exposure

Author

Wang, Anhao and Hogan, Natacha S.

Abstract

In commercial practice, broiler chickens may be exposed to Fusariummycotoxins either during specific growth stages or throughout the entire production cycle. A 34-day feeding trial was conducted to identify sensitive periods for mycotoxin effects during the growth cycle of broiler chickens. A total of 420 newly-hatched Ross 308 male broilers were randomly assigned to 60 cages with 7 birds/cage. Sources of clean wheat (<0.5 mg/kg deoxynivalenol [DON]) and Fusarium-contaminated wheat (11.4 mg/kg DON) were used to formulate the starter diets (0.41 and 6.62 mg/kg DON) provided from 1 to 21 d of age and the grower diets (0.54 and 7.90 mg/kg DON) provided from 22 to 34 d. Control and DON diets were provided to broilers according to treatments (control, DON 1 to 14 d, DON 15 to 21 d, DON 22 to 34 d and DON 1 to 34 d). Birds were monitored daily for morbidity or mortality. Broiler growth performance (body weight, average daily gain, average daily feed intake and feed to gain ratio) was measured weekly. Segments of duodenum, jejunum and ileum were collected at 21 and 34 d and morphometric parameters (villus height, crypt depth, villus width, muscularis thickness and villi:crypt ratio) were measured. Birds fed the DON starter diet during the first 14 d did not exhibit any changes in growth performance; however, growth performance was suppressed in birds fed DON-contaminated diets during the grower period (22 to 34 d). At 34 d, birds that received the DON grower diet (DON 22 to 34 d and DON 1 to 34 d) were lighter (1,433 vs. 1,695 g) than birds fed the control diet. Feed to gain ratio was higher in birds fed the DON grower diet from 22 to 28 d (1.77 vs. 1.56) and 28 to 34 d (2.24 vs. 1.85) compared with corresponding controls. These results suggest that providing older broiler chicks (22 to 34 d) feed contaminated with Fusariummycotoxins (specifically DON) may result in production losses. Histopathological analysis of the ileum region revealed that birds provided the DON diets throughout the entire trial (1 to 34 d) had shorter villi (506 vs. 680 μm) and shallower crypt (85 vs. 115 μm) than control birds. Taken together, these results indicate that DON-induced growth suppression may be a result of adverse effects on intestinal morphology during later growth phases of broilers.

Published
2019
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