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Article ; Online: Keeping Score: Semiquantitative and Quantitative Scoring Approaches to Genetically Engineered and Xenograft Mouse Models of Cancer.

Knoblaugh, Sue E / Himmel, Lauren E

2018 Volume 56, Issue 1, Page(s) 24–32

Abstract: There is a growing need to quantitate or "score" lesions in mouse models of human disease, for correlation with human disease and to establish their clinical relevance. Several standard semiquantitative scoring schemes have been adapted for nonneoplastic ...

Abstract	There is a growing need to quantitate or "score" lesions in mouse models of human disease, for correlation with human disease and to establish their clinical relevance. Several standard semiquantitative scoring schemes have been adapted for nonneoplastic lesions; similarly, the pathologist must carefully select an approach to score mouse models of cancer. Genetically engineered mouse models with a continuum of precancerous and cancerous lesions and xenogeneic models of various derivations present unique challenges for the pathologist. Important considerations include experimental design, understanding of the human disease being modeled, standardized classification of lesions, and approaches for semiquantitative and/or quantitative scoring in the model being evaluated. Quantification should be considered for measuring the extent of neoplasia and expression of tumor biomarkers. Semiquantitative scoring schemes have been devised that include severity, frequency, and distribution of lesions. Although labor-intensive, scoring mouse models of cancer provides numerical data that enable statistical analysis and greater translational impact.
MeSH term(s)	Animals ; Biomarkers, Tumor ; Disease Models, Animal ; Genetic Engineering/veterinary ; Heterografts ; Humans ; Image Processing, Computer-Assisted ; Mice ; Neoplasms, Experimental/pathology
Chemical Substances	Biomarkers, Tumor
Language	English
Publishing date	2018-10-31
Publishing country	United States
Document type	Journal Article
ZDB-ID	188012-3
ISSN	1544-2217 ; 0300-9858
ISSN (online)	1544-2217
ISSN	0300-9858
DOI	10.1177/0300985818808526
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Mitochondrial diabetes in mice expressing a dominant-negative allele of nuclear respiratory factor-1 (

Morrish, Fionnuala / Gingras, Helene / Noonan, Joanna / Huang, Li / Sweet, Ian R / Kuok, Iok Teng / Knoblaugh, Sue E / Hockenbery, David M

bioRxiv : the preprint server for biology

2023

Abstract: Genetic polymorphisms in nuclear respiratory factor-1 ( ...

Abstract	Genetic polymorphisms in nuclear respiratory factor-1 (
Language	English
Publishing date	2023-11-13
Publishing country	United States
Document type	Preprint
DOI	10.1101/2023.01.22.524153
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Keeping Score: Semiquantitative and Quantitative Scoring Approaches to Genetically Engineered and Xenograft Mouse Models of Cancer

Knoblaugh, Sue E. / Himmel, Lauren E.

Veterinary Pathology. 2019 Jan., v. 56, no. 1 p.24-32

2019

Abstract: There is a growing need to quantitate or “score” lesions in mouse models of human disease, for correlation with human disease and to establish their clinical relevance. Several standard semiquantitative scoring schemes have been adapted for nonneoplastic ...

Abstract	There is a growing need to quantitate or “score” lesions in mouse models of human disease, for correlation with human disease and to establish their clinical relevance. Several standard semiquantitative scoring schemes have been adapted for nonneoplastic lesions; similarly, the pathologist must carefully select an approach to score mouse models of cancer. Genetically engineered mouse models with a continuum of precancerous and cancerous lesions and xenogeneic models of various derivations present unique challenges for the pathologist. Important considerations include experimental design, understanding of the human disease being modeled, standardized classification of lesions, and approaches for semiquantitative and/or quantitative scoring in the model being evaluated. Quantification should be considered for measuring the extent of neoplasia and expression of tumor biomarkers. Semiquantitative scoring schemes have been devised that include severity, frequency, and distribution of lesions. Although labor-intensive, scoring mouse models of cancer provides numerical data that enable statistical analysis and greater translational impact.
Keywords	animal pathology ; biomarkers ; experimental design ; genetic engineering ; human diseases ; mice ; neoplasms ; statistical analysis ; xenotransplantation ; animal models ; cancer ; classification ; image analysis ; neoplasia ; quantification ; scoring ; grading ; semiquantitative ; xenografts
Language	English
Dates of publication	2019-01
Size	p. 24-32.
Publishing place	SAGE Publications
Document type	Article ; Online
ZDB-ID	188012-3
ISSN	1544-2217 ; 0300-9858
ISSN (online)	1544-2217
ISSN	0300-9858
DOI	10.1177/0300985818808526
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Pathological Analysis of Lung Metastasis Following Lateral Tail-Vein Injection of Tumor Cells.

Thies, Katie A / Steck, Sarah / Knoblaugh, Sue E / Sizemore, Steven T

Journal of visualized experiments : JoVE

2020 , Issue 159

Abstract: Metastasis, the primary cause of morbidity and mortality for most cancer patients, can be challenging to model preclinically in mice. Few spontaneous metastasis models are available. Thus, the experimental metastasis model involving tail-vein injection ... ...

Abstract	Metastasis, the primary cause of morbidity and mortality for most cancer patients, can be challenging to model preclinically in mice. Few spontaneous metastasis models are available. Thus, the experimental metastasis model involving tail-vein injection of suitable cell lines is a mainstay of metastasis research. When cancer cells are injected into the lateral tail-vein, the lung is their preferred site of colonization. A potential limitation of this technique is the accurate quantification of the metastatic lung tumor burden. While some investigators count macrometastases of a pre-defined size and/or include micrometastases following sectioning of tissue, others determine the area of metastatic lesions relative to normal tissue area. Both of these quantification methods can be exceedingly difficult when the metastatic burden is high. Herein, we demonstrate an intravenous injection model of lung metastasis followed by an advanced method for quantifying metastatic tumor burden using image analysis software. This process allows for investigation of multiple end-point parameters, including average metastasis size, total number of metastases, and total metastasis area, to provide a comprehensive analysis. Furthermore, this method has been reviewed by a veterinary pathologist board-certified by the American College of Veterinary Pathologists (SEK) to ensure accuracy.
MeSH term(s)	Animals ; Cell Count ; Cell Line, Tumor ; Cell Transformation, Neoplastic ; Humans ; Image Processing, Computer-Assisted ; Injections, Intravenous ; Lung Neoplasms/pathology ; Mice ; Neoplasm Metastasis ; Pathology/methods ; Tail
Language	English
Publishing date	2020-05-20
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Video-Audio Media
ZDB-ID	2259946-0
ISSN	1940-087X ; 1940-087X
ISSN (online)	1940-087X
ISSN	1940-087X
DOI	10.3791/61270
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Pathological analysis of lung metastasis following lateral tail-vein injection of tumor cells

Thies, Katie A / Steck, Sarah / Knoblaugh, Sue E / Sizemore, Steven T

Journal of visualized experiments. 2020 May 20, , no. 159

2020

Abstract	Metastasis, the primary cause of morbidity and mortality for most cancer patients, can be challenging to model preclinically in mice. Few spontaneous metastasis models are available. Thus, the experimental metastasis model involving tail-vein injection of suitable cell lines is a mainstay of metastasis research. When cancer cells are injected into the lateral tail-vein, the lung is their preferred site of colonization. A potential limitation of this technique is the accurate quantification of the metastatic lung tumor burden. While some investigators count macrometastases of a pre-defined size and/or include micrometastases following sectioning of tissue, others determine the area of metastatic lesions relative to normal tissue area. Both of these quantification methods can be exceedingly difficult when the metastatic burden is high. Herein, we demonstrate an intravenous injection model of lung metastasis followed by an advanced method for quantifying metastatic tumor burden using image analysis software. This process allows for investigation of multiple end-point parameters, including average metastasis size, total number of metastases, and total metastasis area, to provide a comprehensive analysis. Furthermore, this method has been reviewed by a veterinary pathologist board-certified by the American College of Veterinary Pathologists (SEK) to ensure accuracy.
Keywords	caudal vein ; computer software ; image analysis ; intravenous injection ; lung neoplasms ; lungs ; metastasis ; models ; morbidity ; mortality
Language	English
Dates of publication	2020-0520
Size	p. e61270.
Publishing place	Journal of Visualized Experiments
Document type	Article
ZDB-ID	2259946-0
ISSN	1940-087X
ISSN	1940-087X
DOI	10.3791/61270
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Pathology Principles and Practices for Analysis of Animal Models.

Knoblaugh, Sue E / Hohl, Tobias M / La Perle, Krista M D

ILAR journal

2019 Volume 59, Issue 1, Page(s) 40–50

Abstract: Over 60% of NIH extramural funding involves animal models, and approximately 80% to 90% of these are mouse models of human disease. It is critical to translational research that animal models are accurately characterized and validated as models of human ... ...

Abstract	Over 60% of NIH extramural funding involves animal models, and approximately 80% to 90% of these are mouse models of human disease. It is critical to translational research that animal models are accurately characterized and validated as models of human disease. Pathology analysis, including histopathology, is essential to animal model studies by providing morphologic context to in vivo, molecular, and biochemical data; however, there are many considerations when incorporating pathology endpoints into an animal study. Mice, and in particular genetically modified models, present unique considerations because these modifications are affected by background strain genetics, husbandry, and experimental conditions. Comparative pathologists recognize normal pathobiology and unique phenotypes that animals, including genetically modified models, may present. Beyond pathology, comparative pathologists with research experience offer expertise in animal model development, experimental design, optimal specimen collection and handling, data interpretation, and reporting. Critical pathology considerations in the design and use of translational studies involving animals are discussed, with an emphasis on mouse models.
MeSH term(s)	Animals ; Disease Models, Animal ; Pathology/methods ; Research Design ; Translational Medical Research/methods
Language	English
Publishing date	2019-04-29
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2192062-X
ISSN	1930-6180 ; 1084-2020
ISSN (online)	1930-6180
ISSN	1084-2020
DOI	10.1093/ilar/ilz001
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Mammary gland development and EDC-driven cancer susceptibility in mesenchymal ERα-knockout mice.

Wormsbaecher, Clarissa / Cumbia, Brittney M / Amurgis, Emma G / Poska, Jillian M / Price, Madeline R / Mo, Xiaokui M / Knoblaugh, Sue E / Kurita, Takeshi / Burd, Craig Joseph

Endocrine-related cancer

2023 Volume 30, Issue 12

Abstract: Development of the mammary gland requires both proper hormone signaling and cross talk between the stroma and epithelium. While estrogen receptor (ERα) expression in the epithelium is essential for normal gland development, the role of this receptor in ... ...

Abstract	Development of the mammary gland requires both proper hormone signaling and cross talk between the stroma and epithelium. While estrogen receptor (ERα) expression in the epithelium is essential for normal gland development, the role of this receptor in the stroma is less clear. Moreover, several lines of evidence suggest that mouse phenotypes of in utero exposure to endocrine disruption act through mesenchymal ERα in the developing fetus. We utilized a Twist2-cre mouse line to knock out mesenchymal ERα. Herein, we assessed mammary gland development in the context of mesenchymal ERα deletion. We also tested the effect of in utero bisphenol A (BPA) exposure to alter the tumor susceptibility in the mouse mammary tumor virus-neu (MMTV-neu) breast cancer mouse model. Mesenchymal ERα deletion resulted in altered reproductive tract development and atypical cytology associated with estrous cycling. The mammary gland demonstrated mature epithelial extension unlike complete ERα-knockout mice, but ductal extension was delayed and reduced compared to ERα-competent mice. Using the MMTV-Neu cancer susceptibility model, ERα-intact mice exposed to BPA had reduced tumor-free survival and overall survival compared to BPA-exposed mice having mesenchymal ERα deletion. This difference is specific for BPA exposure as vehicle-treated animals had no difference in tumor development between mice expressing and not expressing mesenchymal ERα. These data demonstrate that mesenchymal ERα expression is not required for ductal extension, nor does it influence cancer risk in this mouse model but does influence the cancer incidence associated with in utero BPA exposure.
MeSH term(s)	Mice ; Animals ; Receptors, Estrogen/metabolism ; Estrogen Receptor alpha/genetics ; Estrogen Receptor alpha/metabolism ; Mice, Knockout ; Epithelium/metabolism ; Neoplasms/metabolism ; Mammary Glands, Animal/pathology
Chemical Substances	Receptors, Estrogen ; Estrogen Receptor alpha
Language	English
Publishing date	2023-11-14
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
ZDB-ID	1218450-0
ISSN	1479-6821 ; 1351-0088
ISSN (online)	1479-6821
ISSN	1351-0088
DOI	10.1530/ERC-23-0062
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Nonhelical Helicobacter pylori Mutants Show Altered Gland Colonization and Elicit Less Gastric Pathology than Helical Bacteria during Chronic Infection.

Martínez, Laura E / O'Brien, Valerie P / Leverich, Christina K / Knoblaugh, Sue E / Salama, Nina R

Infection and immunity

2019 Volume 87, Issue 7

Abstract: Half of all humans ... ...

Abstract	Half of all humans harbor
MeSH term(s)	Animals ; Bacterial Adhesion ; Chronic Disease ; Female ; Helicobacter Infections/microbiology ; Helicobacter Infections/pathology ; Helicobacter pylori/cytology ; Helicobacter pylori/genetics ; Helicobacter pylori/growth & development ; Humans ; Mice, Inbred C57BL ; Pyloric Antrum/microbiology ; Pyloric Antrum/pathology ; Stomach/microbiology ; Stomach/pathology
Language	English
Publishing date	2019-06-20
Publishing country	United States
Document type	Comparative Study ; Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	218698-6
ISSN	1098-5522 ; 0019-9567
ISSN (online)	1098-5522
ISSN	0019-9567
DOI	10.1128/IAI.00904-18
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: KMT2D

Dauch, Cara / Shim, Sharon / Cole, Matthew Wyatt / Pollock, Nijole C / Beer, Abigail J / Ramroop, Johnny / Klee, Victoria / Allain, Dawn C / Shakya, Reena / Knoblaugh, Sue E / Kulewsky, Jesse / Toland, Amanda Ewart

American journal of cancer research

2022 Volume 12, Issue 3, Page(s) 1309–1322

Abstract: Cutaneous squamous cell carcinoma (cSCC) is the second most lethal skin cancer. Due to ultraviolet light-induced damage, cSCCs have a high mutation rate, but some genes are more frequently mutated in aggressive cSCCs. Lysine-specific histone ... ...

Abstract	Cutaneous squamous cell carcinoma (cSCC) is the second most lethal skin cancer. Due to ultraviolet light-induced damage, cSCCs have a high mutation rate, but some genes are more frequently mutated in aggressive cSCCs. Lysine-specific histone methyltransferase 2D (
Language	English
Publishing date	2022-03-15
Publishing country	United States
Document type	Journal Article
ZDB-ID	2589522-9
ISSN	2156-6976
ISSN	2156-6976
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Supporting diversity, equity, inclusion, and belonging to strengthen and position the veterinary profession for service, sustainability, excellence, and impact.

Burkhard, Mary Jo / Dawkins, Sandra / Knoblaugh, Sue E / El-Khoury, Caroline / Coble, Dondrae / Malbrue, Raphael A / Read, Emma K / Greenhill, Lisa M / Moore, Rustin M

Journal of the American Veterinary Medical Association

2022 Volume 260, Issue 11, Page(s) 1283–1290

Abstract: Advancing equality and equity in society is creating positive change, and the time has come to critically evaluate veterinary medicine, which, by all metrics, lacks diversity. To keep pace with increasingly diverse demographics and recent surges in pet ... ...

Abstract	Advancing equality and equity in society is creating positive change, and the time has come to critically evaluate veterinary medicine, which, by all metrics, lacks diversity. To keep pace with increasingly diverse demographics and recent surges in pet ownership among all racial/ethnic groups, significant efforts to enhance diversity, equity, inclusion, and belonging (DEIB) must occur in veterinary colleges and the profession. Recruiting more underrepresented students, building pipelines for diverse faculty/staff, and creating inclusive, welcoming environments where all can thrive are critical steps toward enhancing DEIB within our organizations and profession. Our goal is to share experiences and lessons learned from our intentional commitment to strengthen DEIB, with the hope that our journey will be helpful to others. Increasing diversity in the veterinary profession will be facilitated through removing barriers, creating inclusive work environments where all people feel they belong, and ensuring fair and equitable hiring and personnel management practices. These steps should in turn improve access and quality of veterinary care, ensure we are more representative of the communities we serve, increase revenue, and preserve the human-animal bond. "You cannot change any society unless you take responsibility for it, unless you see yourself belonging to it, and responsible for changing it." - Grace Lee Boggs.
MeSH term(s)	Animals ; Cultural Diversity ; Humans
Language	English
Publishing date	2022-05-25
Publishing country	United States
Document type	Journal Article
ZDB-ID	390811-2
ISSN	1943-569X ; 0003-1488
ISSN (online)	1943-569X
ISSN	0003-1488
DOI	10.2460/javma.21.11.0477
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