scholarly journals Tumor Microvasculature: Endothelial Leakiness and Endothelial Pore Size Distribution in a Breast Cancer Model

2008 ◽  
Vol 1 ◽  
pp. BCBCR.S481 ◽  
Author(s):  
E.E. Uzgiris
Keyword(s):  
Breast Cancer ◽  
Contrast Agents ◽  
Power Law ◽  
Tumor Model ◽  
Mammary Adenocarcinoma ◽  
Dynamic Contrast Enhancement ◽  
Tumor Microvasculature ◽  
Chemically Induced ◽  
Induced Tumors ◽  
Tumor Types

Tumor endothelial leakiness is quantified in a rat mammary adenocarcinoma model using dynamic contrast enhancement MRI and contrast agents of widely varying sizes. The contrast agents were constructed to be of globular configuration and have their uptake rate into tumor interstitium be driven by the same diffusion process and limited only by the availability of endothelial pores of passable size. It was observed that the endothelial pore distribution has a steep power law dependence on size, r– β, with an exponent of −4.1. The model of large pore dominance in tumor leakiness as reported in some earlier investigation with fluorescent probes and optical chamber methods is rejected for this tumor model and a number of other tumor types including chemically induced tumors. This steep power law dependence on size is also consistent with observations on human breast cancer.

TPEN Exerts Antitumor Efficacy in Murine Mammary Adenocarcinoma Through an H2O2 Signaling Mechanism Dependent on Caspase-3

2019 ◽  
Vol 18 (11) ◽  
pp. 1617-1628 ◽  
Author(s):  
Viviana Soto-Mercado ◽  
Miguel Mendivil-Perez ◽  
Claudia Urueña-Pinzon ◽  
Susana Fiorentino ◽  
Carlos Velez-Pardo ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Cancer Cells ◽  
Caspase 3 ◽  
Tumor Model ◽  
Mammary Adenocarcinoma ◽  
Nuclear Chromatin ◽  
A Cells

Background: Breast cancer is the second most common cancer worldwide. N, N, N’, N’-Tetrakis (2-pyridylmethyl)-ethylenediamine (TPEN) is a lipid-soluble zinc metal chelator that induces apoptosis in cancer cells through oxidative stress (OS). However, the effectiveness and the mechanisms involved in TPENinduced cell death in mammary adenocarcinoma cells in vitro and in vivo are still unclear. Objective: This study aimed to evaluate the cytotoxic effect of TPEN in mouse embryonic fibroblasts (MEFs, as normal control cells) and mammary adenocarcinoma cancer cells (TS/A cells) in vitro and in a mammary tumor model in vivo. Methods: Cells were treated with TPEN (0-3 µM), and changes in nuclear chromatin and DNA, mitochondrial membrane potential (ΔΨm), and intracellular reactive oxygen species (ROS) levels were determined by both fluorescence microscopy and flow cytometry. Cell proliferation and the cell cycle were also analyzed. Cellular markers of apoptosis were evaluated by Western blot. Finally, the effect of TPEN in a mammary adenocarcinoma tumor model in vivo was determined by immunohistological analyses. Results: TPEN induced apoptosis in TS/A cells in a dose-dependent manner, increasing nuclear chromatin condensation, DNA fragmentation, cell cycle arrest and ΔΨm loss. Additionally, TPEN increased dichlorofluorescein fluorescence (DCF+) intensity, indicative of ROS production; increased DJ-1-Cys106-sulfonate expression, a marker of intracellular H2O2 stress; induced p53 and PUMA upregulation; and activated caspase-3. Moreover, TPEN induced mammary cancer cell elimination and tumor size reduction in vivo 48 h after treatment through an OS-induced apoptotic mechanism. Conclusion: TPEN selectively induces apoptosis in TS/A cells through an H2O2-mediated signaling pathway. Our findings support the use of TPEN as a potential treatment for breast cancer.

scholarly journals The MPA mouse breast cancer model: evidence for a role of progesterone receptors in breast cancer

2009 ◽  
Vol 16 (2) ◽  
pp. 333-350 ◽  
Author(s):  
Claudia Lanari ◽  
Caroline A Lamb ◽  
Victoria T Fabris ◽  
Luisa A Helguero ◽  
Rocío Soldati ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Hormone Receptors ◽  
Progesterone Receptors ◽  
Tumor Model ◽  
Cancer Models ◽  
Induced Tumors ◽  
Mouse Breast Cancer ◽  
Tumor Virus ◽  
Ductal Carcinomas

More than 60% of all breast neoplasias are ductal carcinomas expressing estrogen (ER) and progesterone receptors (PR). By contrast, most of the spontaneous, chemically or mouse mammary tumor virus induced tumors, as well as tumors arising in genetically modified mice do not express hormone receptors. We developed a model of breast cancer in which the administration of medroxyprogesterone acetate to BALB/c female mice induces mammary ductal carcinomas with a mean latency of 52 weeks and an incidence of about 80%. These tumors are hormone-dependent (HD), metastatic, express both ER and PR, and are maintained by syngeneic transplants. The model has been further refined to include mammary carcinomas that evolve through different stages of hormone dependence, as well as several hormone-responsive cell lines. In this review, we describe the main features of this tumor model, highlighting the role of PR as a trigger of key signaling pathways mediating tumor growth. In addition, we discuss the relevance of this model in comparison with other presently used breast cancer models pointing out its advantages and limitations and how, this model may be suitable to unravel key questions in breast cancer.

Proliferative and Neoplastic Lesions in the Rodent Nasal Cavity

1991 ◽  
Vol 19 (4_part_1) ◽  
pp. 358-372 ◽  
Author(s):  
H. Roger Brown ◽  
Thomas M. Monticello ◽  
Robert R. Maronpot ◽  
Holly W. Randall ◽  
John R. Hotchkiss ◽  
...  
Keyword(s):  
Nasal Cavity ◽  
Squamous Cell ◽  
Strain Differences ◽  
Transitional Region ◽  
Chemically Induced ◽  
Induced Tumors ◽  
Nasal Tumors ◽  
Neoplastic Lesions ◽  
Route Of Exposure ◽  
Tumor Types

Proliferative lesions in the rodent nasal cavity are reviewed; attempt was made to compare species affected, sex differences, strain differences, route of administration and tumor types occurring both spontaneously and after induction by different chemicals. This review is not meant to be all inclusive but to be representative of observed trends. Our general conclusions in this paper are that: 1) spontaneous nasal tumors in rodents are very rare; 2) spontaneous nasal tumors in rats are most often squamous cell tumors, whereas hemangiomas or respiratory adenomas predominate in mice and squamous cell tumors are rare; 3) rats are usually more susceptible to the induction of epithelial tumors of the nasal cavity than mice; 4) chemically-induced hemangiomas and hemangiosarcomas of the nasal cavity have only been reported in mice; 5) tumors of the olfactory epithelium are almost uniformly malignant and invasive, while nonsquamous tumors of the respiratory epithelium are typically less invasive; 6) chemically-induced tumors of the olfactory region, either mesenchymal or epithelial, do not always require an inhalation route of exposure but may occur by systemic targeting of this region; and 7) chemicals inducing tumors in the olfactory region often produce a variety of tumor morphologies in this location as well as squamous and polypoid tumors of the transitional region. More work will be needed to illucidate the mechanisms of nasal carcinogenesis and to further refine the current tumor classification system.

TAp73 opposes tumor angiogenesis by promoting hypoxia-inducible factor 1α degradation

2020 ◽  
Author(s):  
Lungwani Muungo
Keyword(s):  
Cancer Progression ◽  
Hypoxia Inducible Factor ◽  
Tumor Hypoxia ◽  
Human Lung Cancer ◽  
Regulatory Subunit ◽  
Patients With Cancer ◽  
Hypoxia Inducible Factor 1 ◽  
Chemically Induced ◽  
Induced Tumors ◽  
Patient Prognosis

Tumor hypoxia and hypoxia-inducible factor 1 (HIF-1) activationare associated with cancer progression. Here, we demonstrate thatthe transcription factor TAp73 opposes HIF-1 activity through anontranscriptional mechanism, thus affecting tumor angiogenesis.TAp73-deficient mice have an increased incidence of spontaneousand chemically induced tumors that also display enhanced vascularization.Mechanistically, TAp73 interacts with the regulatory subunit(α) of HIF-1 and recruits mouse double minute 2 homolog intothe protein complex, thus promoting HIF-1α polyubiquitination andconsequent proteasomal degradation in an oxygen-independentmanner. In human lung cancer datasets, TAp73 strongly predictsgood patient prognosis, and its expression is associated with lowHIF-1 activation and angiogenesis. Our findings, supported by invivo and clinical evidence, demonstrate a mechanism for oxygenindependentHIF-1 regulation, which has important implicationsfor individualizing therapies in patients with cancer.

Non-invasive immunoPET imaging of PD-L1 using anti-PD-L1-B11 in breast cancer and melanoma tumor model

2021 ◽  
Author(s):  
Aditya Bansal ◽  
Mukesh K. Pandey ◽  
Whitney Barham ◽  
Xin Liu ◽  
Susan M. Harrington ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumor Model ◽  
Melanoma Tumor ◽  
Non Invasive

scholarly journals Antitumor Potential of Lippia citriodora Essential Oil in Breast Tumor-Bearing Mice

Antioxidants ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 875
Author(s):  
Katerina Spyridopoulou ◽  
Tamara Aravidou ◽  
Evangeli Lampri ◽  
Eleni Effraimidou ◽  
Aglaia Pappa ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Antiproliferative Activity ◽  
Folk Medicine ◽  
Tumor Model ◽  
Flowering Plant ◽  
Antitumor Effects ◽  
Lippia Citriodora ◽  
Antitumor Potential ◽  
Apoptotic Marker

Lippia citriodora is a flowering plant cultivated for its lemon-scented leaves and used in folk medicine for the preparation of tea for the alleviation of symptoms of gastrointestinal disorders, cold, and asthma. The oil extracted from the plant leaves was shown to possess antioxidant potential and to exert antiproliferative activity against breast cancer. The aim of this study was to further investigate potential antitumor effects of L. citriodora oil (LCO) on breast cancer. The in vitro antiproliferative activity of LCO was examined against murine DA3 breast cancer cells by the sulforhodamine B assay. We further explored the LCO’s pro-apoptotic potential with the Annexin-PI method. The LCO’s anti-migratory effect was assessed by the wound-healing assay. LCO was found to inhibit the growth of DA3 cells in vitro, attenuate their migration, and induce apoptosis. Finally, oral administration of LCO for 14 days in mice inhibited by 55% the size of developing tumors in the DA3 murine tumor model. Noteworthy, in the tumor tissue of LCO-treated mice the apoptotic marker cleaved caspase-3 was elevated, while a reduced protein expression of survivin was observed. These results indicate that LCO, as a source of bioactive compounds, has a very interesting nutraceutical potential.

scholarly journals Metformin induces Ferroptosis by inhibiting UFMylation of SLC7A11 in breast cancer

2021 ◽  
Vol 40 (1) ◽  
Author(s):  
Jingjing Yang ◽  
Yulu Zhou ◽  
Shuduo Xie ◽  
Ji Wang ◽  
Zhaoqing Li ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Treatment ◽  
Morphological Changes ◽  
Tumor Model ◽  
Independent Manner ◽  
Regulated Cell Death ◽  
Anti Cancer ◽  
Cancer Agent ◽  
Approved Drugs

Abstract Background Ferroptosis is a newly defined form of regulated cell death characterized by the iron-dependent accumulation of lipid peroxidation and is involved in various pathophysiological conditions, including cancer. Targeting ferroptosis is considered to be a novel anti-cancer strategy. The identification of FDA-approved drugs as ferroptosis inducers is proposed to be a new promising approach for cancer treatment. Despite a growing body of evidence indicating the potential efficacy of the anti-diabetic metformin as an anti-cancer agent, the exact mechanism underlying this efficacy has not yet been fully elucidated. Methods The UFMylation of SLC7A11 is detected by immunoprecipitation and the expression of UFM1 and SLC7A11 in tumor tissues was detected by immunohistochemical staining. The level of ferroptosis is determined by the level of free iron, total/lipid Ros and GSH in the cells and the morphological changes of mitochondria are observed by transmission electron microscope. The mechanism in vivo was verified by in situ implantation tumor model in nude mice. Results Metformin induces ferroptosis in an AMPK-independent manner to suppress tumor growth. Mechanistically, we demonstrate that metformin increases the intracellular Fe2+ and lipid ROS levels. Specifically, metformin reduces the protein stability of SLC7A11, which is a critical ferroptosis regulator, by inhibiting its UFMylation process. Furthermore, metformin combined with sulfasalazine, the system xc− inhibitor, can work in a synergistic manner to induce ferroptosis and inhibit the proliferation of breast cancer cells. Conclusions This study is the first to demonstrate that the ability of metformin to induce ferroptosis may be a novel mechanism underlying its anti-cancer effect. In addition, we identified SLC7A11 as a new UFMylation substrate and found that targeting the UFM1/SLC7A11 pathway could be a promising cancer treatment strategy.

scholarly journals Spontaneous Fusion of MSC with Breast Cancer Cells Can Generate Tumor Dormancy

2021 ◽  
Vol 22 (11) ◽  
pp. 5930
Author(s):  
Catharina Melzer ◽  
Juliane von der Ohe ◽  
Tianjiao Luo ◽  
Ralf Hass
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Tumor Development ◽  
Cellular Interactions ◽  
Hybrid Cells ◽  
Induced Tumors ◽  
Culture Model ◽  
Gene Expression Levels

Direct cellular interactions of MDA-MB-231cherry breast cancer cells with GFP-transduced human mesenchymal stroma/stem-like cells (MSCGFP) in a co-culture model resulted in spontaneous cell fusion by the generation of MDA-MSC-hyb5cherry GFP breast cancer hybrid cells. The proliferative capacity of MDA-MSC-hyb5 cells was enhanced about 1.8-fold when compared to the parental MDA-MB-231cherry breast cancer cells. In contrast to a spontaneous MDA-MB-231cherry induced tumor development in vivo within 18.8 days, the MDA-MSC-hyb5 cells initially remained quiescent in a dormancy-like state. At distinct time points after injection, NODscid mice started to develop MDA-MSC-hyb5 cell-induced tumors up to about a half year later. Following tumor initiation, however, tumor growth and formation of metastases in various different organs occurred rapidly within about 10.5 days. Changes in gene expression levels were evaluated by RNA-microarray analysis and revealed certain increase in dormancy-associated transcripts in MDA-MSC-hyb5. Chemotherapeutic responsiveness of MDA-MSC-hyb5 cells was partially enhanced when compared to MDA-MB-231 cells. However, some resistance, e.g., for taxol was detectable in cancer hybrid cells. Moreover, drug response partially changed during the tumor development of MDA-MSC-hyb5 cells; this suggests the presence of unstable in vivo phenotypes of MDA-hyb5 cells with increased tumor heterogeneity.

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