scholarly journals Effects of Jaeumkanghwa-tang on tamoxifen responsiveness in preclinical ER+ breast cancer model

2019 ◽  
Vol 26 (3) ◽  
pp. 339-353
Author(s):  
Fabia De Oliveira Andrade ◽  
Wei Yu ◽  
Xiyuan Zhang ◽  
Elissa Carney ◽  
Rong Hu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Control Group ◽  
Cancer Model ◽  
Sprague Dawley ◽  
T Regulatory Cell ◽  
Sprague Dawley Rats ◽  
Breast Cancer Model ◽  
Estrogen Receptor Positive ◽  
Treatment Control Group

Resistance to endocrine therapy remains a clinical challenge in the treatment of estrogen receptor-positive (ER+) breast cancer. We investigated if adding a traditional Asian herbal mixture consisting of 12 herbs, called Jaeumkanghwa-tang (JEKHT), to tamoxifen (TAM) therapy might prevent resistance and recurrence in the ER+ breast cancer model of 7,12-dimethylbenz[a]anthracene (DMBA)-exposed Sprague–Dawley rats. Rats were divided into four groups treated as follows: 15 mg/kg TAM administered via diet as TAM citrate (TAM only); 500 mg/kg JEKHT administered via drinking water (JEKHT only group); TAM + JEKHT and no treatment control group. The study was replicated using two different batches of JEKHT. In both studies, a significantly higher proportion of ER+ mammary tumors responded to TAM if animals also were treated with JEKHT (experiment 1: 47% vs 65%, P = 0.015; experiment 2: 43% vs 77%, P < 0.001). The risk of local recurrence also was reduced (31% vs 12%, P = 0.002). JEKHT alone was mostly ineffective. In addition, JEKHT prevented the development of premalignant endometrial lesions in TAM-treated rats (20% in TAM only vs 0% in TAM + JEKHT). Co-treatment of antiestrogen-resistant LCC9 human breast cancer cells with 1.6 mg/mL JEKHT reversed their TAM resistance in dose–response studies in vitro. Several traditional herbal medicine preparations can exhibit anti-inflammatory properties and may increase anti-tumor immune activities in the tumor microenvironment. In the tumors of rats treated with both JEKHT and TAM, expression of Il-6 (P = 0.03), Foxp3/T regulatory cell (Treg) marker (P = 0.033) and Tgfβ1 that activates Tregs (P < 0.001) were significantly downregulated compared with TAM only group. These findings indicate that JEKHT may prevent TAM-induced evasion of tumor immune responses.

scholarly journals Anticancer Potential of Ethyl Acetate Extract Fractions of Ipomoea horsfalliae Hook on DMBA- Induced Breast Cancer Model

2021 ◽  
Vol 12 (5) ◽  
pp. 6447-6459
Keyword(s):  
Breast Cancer ◽  
Ethyl Acetate ◽  
Blood Parameters ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Breast Cancer Model ◽  
Antioxidant Characteristics ◽  
Nitrate And Nitrite ◽  
Breast Tissues

The genus Ipomoea is distributed globally and honored as the largest genus of the family Convolvulaceae. Several varieties of this family have been shown to be effective in treating various diseases, including cancer. This research aimed to explore the anticancer activity of ethyl acetate fractions of Ipomoea horsfalliae Hook (EAIH) in female Sprague-Dawley rats. 7, 12-dimethylbenz (a) anthracene (DMBA) was used to produce breast cancer. The Fractions were selected based on the cytotoxicity analysis in vitro, which was reported in our earlier studies. The study employed two dosages of EAIH (25 and 50 mg/kg). Biochemical, hematological, and antioxidant characteristics were investigated. A decrease in mean tumor volume and tumor weight was detected in EAIH treated groups. The blood parameters were seen as normal. In both DMBA and doxorubicin groups, malondialdehyde was increased, and the level was significantly reduced in EAIH-treated groups. The effect of catalase was shown to be diminished in the groups given DMBA and doxorubicin but normal in the EAIH groups. Nitrate and nitrite levels increased in the DMBA control groups but were normal in the others. There was less necrosis and infiltration in breast tissues treated with doxorubicin as well as in EAIH. In animals treated with EAIH, the therapeutic effect was found to be dose-dependent. The therapies helped to repair some of the altered breast patterns. The study concludes that I. horsfolliae may be a potential anticancer candidate and need to explore further.

Genistein induces breast cancer-associated aromatase and stimulates estrogen-dependent tumor cell growth in in vitro breast cancer model

Toxicology ◽  
2011 ◽  
Vol 289 (2-3) ◽  
pp. 67-73 ◽  
Author(s):  
M.B.M. van Duursen ◽  
S.M. Nijmeijer ◽  
E.S. de Morree ◽  
P. Chr. de Jong ◽  
M. van den Berg
Keyword(s):  
Breast Cancer ◽  
Cell Growth ◽  
Tumor Cell ◽  
Tumor Cell Growth ◽  
Cancer Model ◽  
Breast Cancer Model

Therapeutic monoclonal antibodies target phenotypically-differing human breast cancer

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 13510-13510
Author(s):  
S. E. Hahn ◽  
L. A. da Cruz ◽  
D. Sayegh ◽  
A. Ferry ◽  
K. O’Reilly ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Human Breast Cancer ◽  
In Vivo Studies ◽  
Tumor Growth Inhibition ◽  
Cancer Model ◽  
Human Breast ◽  
Breast Cancer Model ◽  
Cancer Tissues

13510 Background: CD44 (an adhesion molecule and stem cell antigen), CD59 (a complement-inhibitory molecule), MCSP (an adhesion and cell-cell interactions), and Trop-2 (EpCam a related signaling molecule) represent a group of biologically-significant cancer proteins acting through distinct mechanisms. We have described Abs with in vitro and in vivo cancer suppressive activity to this group of targets. However, their effectiveness depends on the phenotype of malignant cells; cell response should correlate with expression of its Ag, and tumor cells represent a heterogeneous group of non-synchronous cells. The present study describes the efficacy of those antibodies in breast cancer models and the prevalence of their antigen targets in a survey of human breast cancer tissues. Methods: In vivo activity of antibodies ARH460–16–2 (anti-CD44), AR36A36.11.1 (anti-CD59), AR11BD-2E11–2 (anti-MCSP), and AR47A6.4.2 (anti-Trop-2) in estrogen-dependent and hormone sensitive xenograft models of human breast cancer was examined. In addition, distribution of the antigens in breast cancer was determined by immunohistochemistry using tumor tissue arrays of breast cancer sections from distinct patients. Results: Treatment of an established breast cancer model with ARH460–16–2 resulted in 51% median tumor xenograft suppression (p<0.05), as well as increased survival in an MDA-MB-231 (breast cancer) grafted model. 63% of human breast cancer sections expressed the CD44 antigen. Treatment with anti-CD59 antibody AR36A36.11.1 resulted in 68% xenograft tumor suppression (p<0.005). AR47A6.4.2 anti-Trop-2 antibody bound to 100% of human breast cancer sections tested, and showed efficacy in the estrogen- dependent MCF-7 breast cancer model. Anti-MCSP antibody AR11BD-2E11–2 demonstrated 80% tumor growth inhibition (p<0.001), increased survival in an estrogen-dependent model of breast cancer, and was found to stain 62% of breast cancer tissues examined. Conclusions: The heterogeneity of breast cancer cell phenotypes in in vitro and in vivo studies and variable composite cellular antigen targets is the basis for the therapeutic use of multiple antibodies, each with independent mechanisms of action, and offers a rationale for combined antibody therapy in selected patients. [Table: see text]

scholarly journals Seribantumab, an Anti-ERBB3 Antibody, Delays the Onset of Resistance and Restores Sensitivity to Letrozole in an Estrogen Receptor–Positive Breast Cancer Model

2015 ◽  
Vol 14 (11) ◽  
pp. 2642-2652 ◽  
Author(s):  
Michael D. Curley ◽  
Gauri J. Sabnis ◽  
Lucia Wille ◽  
Bambang S. Adiwijaya ◽  
Gabriela Garcia ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Cancer Model ◽  
Breast Cancer Model ◽  
Estrogen Receptor Positive ◽  
Positive Breast Cancer

Structure-based discovery of a small non-peptidic Neuropilins antagonist exerting in vitro and in vivo anti-tumor activity on breast cancer model

2014 ◽  
Vol 349 (2) ◽  
pp. 120-127 ◽  
Author(s):  
Lucia Borriello ◽  
Matthieu Montès ◽  
Yves Lepelletier ◽  
Bertrand Leforban ◽  
Wang-Qing Liu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Model ◽  
Breast Cancer Model ◽  
Anti Tumor Activity

scholarly journals Gene Signatures Induced by Ionizing Radiation as Prognostic Tools in an In Vitro Experimental Breast Cancer Model

Cancers ◽  
2021 ◽  
Vol 13 (18) ◽  
pp. 4571
Author(s):  
Gloria M. Calaf ◽  
Leodan A. Crispin ◽  
Debasish Roy ◽  
Francisco Aguayo ◽  
Juan P. Muñoz ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Cell Line ◽  
Cell Lines ◽  
Cancer Progression ◽  
Combined Treatment ◽  
Cancer Model ◽  
Altered Expression ◽  
Breast Cancer Model

This study aimed to analyze the expression of genes involved in radiation, using an Affymetrix system with an in vitro experimental breast cancer model developed by the combined treatment of low doses of high linear energy transfer (LET) radiation α particle radiation and estrogen yielding different stages in a malignantly transformed breast cancer cell model called Alpha model. Altered expression of different molecules was detected in the non-tumorigenic Alpha3, a malignant cell line transformed only by radiation and originally derived from the parental MCF-10F human cell line; that was compared with the Alpha 5 cell line, another cell line exposed to radiation and subsequently grown in the presence 17β-estradiol. This Alpha5, a tumorigenic cell line, originated the Tumor2 cell line. It can be summarized that the Alpha 3 cell line was characterized by greater gene expression of ATM and IL7R than control, Alpha5, and Tumor2 cell lines, it presented higher selenoprotein gene expression than control and Tumor2; epsin 3 gene expression was higher than control; stefin A gene expression was higher than Alpha5; and metallothionein was higher than control and Tumor2 cell line. Therefore, radiation, independently of estrogen, induced increased ATM, IL7R, selenoprotein, GABA receptor, epsin, stefin, and metallothioneins gene expression in comparison with the control. Results showed important findings of genes involved in cancers of the breast, lung, nervous system, and others. Most genes analyzed in these studies can be used for new prognostic tools and future therapies since they affect cancer progression and metastasis. Most of all, it was revealed that in the Alpha model, a breast cancer model developed by the authors, the cell line transformed only by radiation, independently of estrogen, was characterized by greater gene expression than other cell lines. Understanding the effect of radiotherapy in different cells will help us improve the clinical outcome of radiotherapies. Thus, gene signature has been demonstrated to be specific to tumor types, hence cell-dependency must be considered in future treatment planning. Molecular and clinical features affect the results of radiotherapy. Thus, using gene technology and molecular information is possible to improve therapies and reduction of side effects while providing new insights into breast cancer-related fields.

scholarly journals A Novel Strategy to Enhance Microfracture Treatment With Stromal Cell-Derived Factor-1 in a Rat Model

2021 ◽  
Vol 8 ◽  
Author(s):  
Taylor Mustapich ◽  
John Schwartz ◽  
Pablo Palacios ◽  
Haixiang Liang ◽  
Nicholas Sgaglione ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Cartilage Repair ◽  
Osteochondral Defect ◽  
Control Group ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Stromal Cell Derived Factor ◽  
Empty Control

BackgroundMicrofracture is one of the most widely used techniques for the repair of articular cartilage. However, microfracture often results in filling of the chondral defect with fibrocartilage, which exhibits poor durability and sub-optimal mechanical properties. Stromal cell-derived factor-1 (SDF-1) is a potent chemoattractant for mesenchymal stem cells (MSCs) and is expressed at high levels in bone marrow adjacent to developing cartilage during endochondral bone formation. Integrating SDF-1 into an implantable collagen scaffold may provide a chondro-conductive and chondro-inductive milieu via chemotaxis of MSCs and promotion of chondrogenic differentiation, facilitating more robust hyaline cartilage formation following microfracture.ObjectiveThis work aimed to confirm the chemoattractive properties of SDF-1 in vitro and develop a one-step method for incorporating SDF-1 in vivo to enhance cartilage repair using a rat osteochondral defect model.MethodsBone marrow-derived MSCs (BMSCs) were harvested from the femurs of Sprague–Dawley rats and cultured in low-glucose Dulbecco’s modified Eagle’s medium containing 10% fetal bovine serum, with the medium changed every 3 days. Passage 1 MSCs were analyzed by flow cytometry with an S3 Cell Sorter (Bio-Rad). In vitro cell migration assays were performed on MSCs by labeling cells with carboxyfluorescein diacetate, succinimidyl ester (CFDA-SE; Bio-Rad). For the microfracture model, a 1.6-mm-diameter osteochondral defect was created in the femoral trochleae of 20 Sprague–Dawley rats bilaterally until bone marrow spillage was seen under saline irrigation. One knee was chosen at random to receive implantation of the scaffold, and the contralateral knee was left unfilled as an empty control. Type I collagen scaffolds (Kensey Nash) were coated with either gelatin only or gelatin and SDF-1 using a dip coating process. The rats received implantation of either a gelatin-only scaffold (N = 10) or gelatin-and-SDF-1 scaffold (N = 10) at the site of the microfracture. Femurs were collected for histological analyses at 4- and 8-week time points post-operatively, and sections were stained with Safranin O/Fast Green. The samples were graded blindly by two observers using the Modified O’Driscoll score, a validated scoring system for chondral repair. A minimum of 10 separate grading scores were made per sample and averaged. Quantitative comparisons of cell migration in vitro were performed with one-way ANOVA. Cartilage repair in vivo was also compared among groups with one-way ANOVA, and the results were presented as mean ± standard deviation, with P-values &lt; 0.05 considered as statistically significant.ResultsMSC migration showed a dose–response relationship with SDF-1, with an optimal dosage for chemotaxis between 10 and 100 ng/ml. After scaffold implantation, the SDF-1-treated group demonstrated complete filling of the cartilage defect with mature cartilage tissue, exhibiting strong proteoglycan content, smooth borders, and good incorporation into marginal cartilage. Modified O’Driscoll scores after 8 weeks showed a significant improvement of cartilage repair in the SDF-1 group relative to the empty control group (P &lt; 0.01), with a trend toward improvement when compared with the gelatin-only-scaffold group (P &lt; 0.1). No significant differences in scores were found between the empty defect group and gelatin-only group.ConclusionIn this study, we demonstrated a simple method for improving the quality of cartilage defect repair in a rat model of microfracture. We confirmed the chemotactic properties of SDF-1 on rat MSCs and found an optimized dosage range for chemotaxis between 10 and 100 ng/ml. Furthermore, we demonstrated a strategy to incorporate SDF-1 into gelatin–collagen I scaffolds in vivo at the site of an osteochondral defect. SDF-1-treated defects displayed robust hyaline cartilage resurfacing of the defect with minimal fibrous tissue, in contrast to the empty control group. The results of the in vitro and in vivo studies together suggest that SDF-1-mediated signaling may significantly improve the quality of cartilage regeneration in an osteochondral defect.

An Engineered Breast Cancer Model on a Chip to Replicate ECM-Activation In Vitro during Tumor Progression

2016 ◽  
Vol 5 (23) ◽  
pp. 3074-3084 ◽  
Author(s):  
Filomena Gioiella ◽  
Francesco Urciuolo ◽  
Giorgia Imparato ◽  
Virginia Brancato ◽  
Paolo A. Netti
Keyword(s):  
Breast Cancer ◽  
Tumor Progression ◽  
Cancer Model ◽  
Breast Cancer Model

Abstract 4606: An in vitro and in vivo evaluation of novel anticancer agents in a triple negative breast cancer model

2010 ◽  
Author(s):  
Tamorah Hawthorne ◽  
Joseph Gallien ◽  
Lee Gibbs ◽  
Janeque Jones ◽  
Shannon Muir ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Anticancer Agents ◽  
Triple Negative ◽  
Cancer Model ◽  
In Vivo Evaluation ◽  
Breast Cancer Model

Hexachlorobenzene promotes angiogenesis in vivo, in a breast cancer model and neovasculogenesis in vitro, in the human endothelial cell line HMEC-1

2014 ◽  
Vol 229 ◽  
pp. S153
Author(s):  
Carolina Pontillo ◽  
Alejandro Español ◽  
Florencia Chiappini ◽  
Noelia Miret ◽  
Claudia Cocca ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Endothelial Cell ◽  
Cell Line ◽  
Human Endothelial Cell ◽  
Cancer Model ◽  
Endothelial Cell Line ◽  
Breast Cancer Model ◽  
Human Endothelial Cell Line
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