Induced mammary cancer in rat models: pathogenesis, genetics, and relevance to female breast cancer

Miller, James L.; Bartlett, Arianna P.; Harman, Rebecca M.; Majhi, Prabin D.; Jerry, D. Joseph; Walle, Gerlinde R. Van de

doi:10.1007/s10911-022-09522-w

Cited by 10 publications

(25 citation statements)

References 247 publications

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“…With the successful generation of equine and canine xenografts, we are now able to confirm and extend this work in vivo . For example, and similar to induced carcinogenesis studies in rodent models, host mice containing equine and canine mammary xenografts could be treated with progestins (e.g., medroxyprogesterone acetate), followed by exposure to mammary carcinogens (e.g., 7,12-dimethylbenz(a)anthracene (DMBA) [ 101 – 103 ] or high levels of estrogens (e.g., 17-β-estradiol) [ 5 , 13 , 96 ], and their xenografts could then be assessed for neoplastic features or other indications of early induced malignancy at the molecular level ( S6 Fig ). Additionally, host mice containing mammary xenografts may also be adequate models for assessing variations in lactation strategy and developmental processes via hormone supplements or relevant pharmaceuticals ( S6 Fig ).…”

Section: Discussionmentioning

confidence: 99%

A xenotransplantation mouse model to study physiology of the mammary gland from large mammals

Miller,

Reddy,

Harman

et al. 2024

PLoS ONE

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Although highly conserved in structure and function, many (patho)physiological processes of the mammary gland vary drastically between mammals, with mechanisms regulating these differences not well understood. Large mammals display variable lactation strategies and mammary cancer incidence, however, research into these variations is often limited to in vitro analysis due to logistical limitations. Validating a model with functional mammary xenografts from cryopreserved tissue fragments would allow for in vivo comparative analysis of mammary glands from large and/or rare mammals and would improve our understanding of postnatal development, lactation, and premalignancy across mammals. To this end, we generated functional mammary xenografts using mammary tissue fragments containing mammary stroma and parenchyma isolated via an antibody-independent approach from healthy, nulliparous equine and canine donor tissues to study these species in vivo. Cryopreserved mammary tissue fragments were xenotransplanted into de-epithelialized fat pads of immunodeficient mice and resulting xenografts were structurally and functionally assessed. Preimplantation of mammary stromal fibroblasts was performed to promote ductal morphogenesis. Xenografts recapitulated mammary lobule architecture and contained donor-derived stromal components. Mammatropic hormone stimulation resulted in (i) upregulation of lactation-associated genes, (ii) altered proliferation index, and (iii) morphological changes, indicating functionality. Preimplantation of mammary stromal fibroblasts did not promote ductal morphogenesis. This model presents the opportunity to study novel mechanisms regulating unique lactation strategies and mammary cancer induction in vivo. Due to the universal applicability of this approach, this model serves as proof-of-concept for developing mammary xenografts for in vivo analysis of virtually any mammals, including large and rare mammals.

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Section: Discussionmentioning

confidence: 99%

A xenotransplantation mouse model to study physiology of the mammary gland from large mammals

Miller,

Reddy,

Harman

et al. 2024

PLoS ONE

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“…Demecolcine, a classic inhibitor of spindle fibre formation during M phase, finds widespread application as a mitotic inhibitor and apoptosis inducer [ 33 ]. DMBA treatment can result in differential expression of immune-related genes in mammary gland tissues from Wistar-Kyoto and Wistar-Furth rats [ 34 ]. While Tetradioxin hasn't been directly employed for therapeutic purposes, recent studies have unveiled its considerable potential in regulating immune systems among HIV-infected individuals as well as those afflicted by COVID-19 [ 35 , 36 ].…”

Section: Discussionmentioning

confidence: 99%

Developing neural network diagnostic models and potential drugs based on novel identified immune-related biomarkers for celiac disease

Shen,

Wang,

et al. 2023

Hum Genomics

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Background As one of the most common intestinal inflammatory diseases, celiac disease (CD) is typically characterized by an autoimmune disorder resulting from ingesting gluten proteins. Although the incidence and prevalence of CD have increased over time, the diagnostic methods and treatment options are still limited. Therefore, it is urgent to investigate the potential biomarkers and targeted drugs for CD. Methods Gene expression data was downloaded from GEO datasets. Differential gene expression analysis was performed to identify the dysregulated immune-related genes. Multiple machine algorithms, including randomForest, SVM-RFE, and LASSO, were used to select the hub immune-related genes (HIGs). The immune-related genes score (IG score) and artificial neural network (ANN) were constructed based on HIGs. Potential drugs targeting HIGs were identified by using the Enrichr platform and molecular docking method. Results We identified the dysregulated immune-related genes at a genome-wide level and demonstrated their roles in CD-related immune pathways. The hub genes (MR1, CCL25, and TNFSF13B) were further screened by integrating several machine algorithms. Meanwhile, the CD patients were divided into distinct subtypes with either high- or low-immunoactivity using single-sample gene set enrichment analysis (ssGSEA) and consensus clustering. By constructing IG score based on HIGs, we found that patients with high IG score were mainly attributed to high-immunoactivity subgroups, which suggested a strong link between HIGs and immunoactivity of CD patients. In addition, the novel constructed ANN model showed the sound diagnostic ability of HIGs. Mechanistically, we validated that the HIGs play pivotal roles in regulating CD's immune and inflammatory state. Through targeting the HIGs, we also found potential drugs for anti-CD treatment by using the Enrichr platform and molecular docking method. Conclusions This study unveils the HIGs and elucidates the networks regulated by these genes in the context of CD. It underscores the pivotal significance of HIGs in accurately predicting the presence or absence of CD in patients. Consequently, this research offers promising prospects for the development of diagnostic biomarkers and therapeutic targets for CD.

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“…Tumor yield and size were stabilized after 75 days (approx.) of DMBA treatment. − Rats were kept palpitated, and when tumor size ranged from 5 to 8 mm, they were analyzed for the in vivo anticancer activity. DMBA induced breast tumors are overexpressed with hormonal receptors such as ER and PR, and also the cell line derived from the DMBA induced breast tumors exhibits a similar nature to that of the MCF7 cell line …”

Section: Methodsmentioning

confidence: 99%

Chitosan-g-estrone Nanoparticles of Palbociclib Vanished Hypoxic Breast Tumor after Targeted Delivery: Development and Ultrasound/Photoacoustic Imaging

Mehata

Singh

Vikas

et al. 2023

ACS Appl. Mater. Interfaces

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Breast cancer is the leading cause of death among women globally. Approximately 80% of all breast cancers diagnosed are overexpressed with estrogen receptors (ERs). In this study, we have developed an estrone (Egen)-grafted chitosan-based polymeric nanocarrier for the targeted delivery of palbociclib (PLB) to breast cancer. The nanoparticles (NPs) were prepared by solvent evaporation using the ionic gelation method and characterized for particle size, zeta potential, polydispersity, surface morphology, surface chemistry, drug entrapment efficiency, cytotoxicity assay, cellular uptake, and apoptosis study. The developed PLB-CS NPs and PLB-CS-g-Egen NPs had a particle size of 116.3 ± 1.53 nm and 141.6 ± 1.97 nm, respectively. The zeta potential of PLB-CS NPs and PLB-CS-g-Egen NPs was found to be 18.70 ± 0.416 mV and 12.45 ± 0.574 mV, respectively. The morphological analysis demonstrated that all NPs were spherical in shape and had a smooth surface. An in vitro cytotoxicity assay was performed in estrogen receptor (ER)-expressing MCF7 cells and T47D cells, which suggested that targeted NPs were 57.34-and 30.32-fold more cytotoxic compared to the pure PLB, respectively. Additionally, cell cycle analysis confirmed that cell cycle progression from the G1 into S phase was blocked more efficiently by targeted NPs compared to nontargeted NPs and PLB in MCF7 cells. In vivo pharmacokinetic studies demonstrated that entrapment of the PLB in the NPs improved the half-life and bioavailability by ∼2−3-fold. Further, ultrasound and photoacoustic imaging of DMBA induced breast cancer in the Sprague-Dawley (SD) rat showed that targeted NPs completely vanished breast tumor, reduced hypoxic tumor volume, and suppressed tumor angiogenesis more efficiently compared to the nontargeted NPs and free PLB. Further, in vitro hemocompatibility and histopathology studies suggested that NPs were biocompatible and safe for clinical use.

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Induced mammary cancer in rat models: pathogenesis, genetics, and relevance to female breast cancer

Cited by 10 publications

References 247 publications

A xenotransplantation mouse model to study physiology of the mammary gland from large mammals

A xenotransplantation mouse model to study physiology of the mammary gland from large mammals

Developing neural network diagnostic models and potential drugs based on novel identified immune-related biomarkers for celiac disease

Chitosan-g-estrone Nanoparticles of Palbociclib Vanished Hypoxic Breast Tumor after Targeted Delivery: Development and Ultrasound/Photoacoustic Imaging

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