scholarly journals Atovaquone Suppresses the Growth of Metastatic Triple-Negative Breast Tumors in Lungs and Brain by Inhibiting Integrin/FAK Signaling Axis

2021 ◽  
Vol 14 (6) ◽  
pp. 521
Author(s):  
Nehal Gupta ◽  
Sanjay K. Srivastava
Keyword(s):  
Tumor Cells ◽  
Breast Tumor ◽  
Triple Negative ◽  
Malignant Neoplasm ◽  
Tumor Model ◽  
Metastatic Tumor ◽  
Mouse Heart ◽  
Breast Tumor Cells

Triple-negative breast cancer (TNBC) is considered to be the most aggressive and malignant neoplasm and is highly metastatic in nature. In the current study, we investigated the anti-metastatic potential of atovaquone, a protozoal drug prescribed for Pneumocystis pneumonia. We showed that atovaquone induced apoptosis and reduced the survival of several aggressive metastatic TNBC cell lines including metastatic patient-derived cells by reducing the expression of integrin α6, integrin β4, FAK, Src, and Vimentin. In order to study the efficacy of atovaquone in suppressing metastasized breast tumor cells in brain and lungs, we performed three in vivo experiments. We demonstrated that oral administration of 50 mg/kg of atovaquone suppressed MDA-MB-231 breast tumor growth by 90% in lungs in an intravenous metastatic tumor model. Anti-metastatic effect of atovaquone was further determined by intracardiac injection of 4T1-luc breast tumor cells into the left ventricle of mouse heart. Our results showed that atovaquone treatment suppressed the growth of metastatic tumors in lungs, liver and brain by 70%, 50% and 30% respectively. In an intracranial model, the growth of HCC1806-luc brain tumors in atovaquone treated mice was about 55% less than that of control. Taken together, our results indicate the anti-metastatic effects of atovaquone in vitro and in vivo in various breast tumor metastasis models.

scholarly journals TGFBI expression reduces in vitro and in vivo metastatic potential of lung and breast tumor cells

2011 ◽  
Vol 308 (1) ◽  
pp. 23-32 ◽  
Author(s):  
Gengyun Wen ◽  
Michael A. Partridge ◽  
Bingyan Li ◽  
Mei Hong ◽  
Wupeng Liao ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Breast Tumor ◽  
Metastatic Potential ◽  
Breast Tumor Cells

Breast tumor cells isolated from in vitro resistance to trastuzumab remain sensitive to trastuzumab anti-tumor effects in vivo and to ADCC killing

2009 ◽  
Vol 58 (11) ◽  
pp. 1887-1896 ◽  
Author(s):  
Timothy E. Kute ◽  
Lori Savage ◽  
John R. Stehle ◽  
Jung W. Kim-Shapiro ◽  
Michael J. Blanks ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Breast Tumor ◽  
Breast Tumor Cells

Trehalose liposomes induce apoptosis of breast tumor cells in vitro and in vivo

2020 ◽  
Vol 532 (4) ◽  
pp. 505-512
Author(s):  
Hideaki Ichihara ◽  
Keiji Kuwabara ◽  
Yoko Matsumoto
Keyword(s):  
Tumor Cells ◽  
Breast Tumor ◽  
Breast Tumor Cells

scholarly journals Bispecific antibody targeting TROP2xCD3 suppresses tumor growth of triple negative breast cancer

2021 ◽  
Vol 9 (10) ◽  
pp. e003468
Author(s):  
Huicheng Liu ◽  
Lili Bai ◽  
Liu Huang ◽  
Na Ning ◽  
Lin Li ◽  
...  
Keyword(s):  
Breast Cancer ◽  
T Cells ◽  
Tumor Cells ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Bispecific Antibody ◽  
Tumor Model ◽  
Tnbc Cell

BackgroundTriple negative breast cancer (TNBC) is a subtype of breast cancers with poor prognosis and targeted drug therapies are limited. To develop novel and efficacious therapies for TNBC, we developed a bispecific antibody F7AK3 that recognizes both trophoblast cell surface antigen 2 (TROP2) and CD3 and evaluated its antitumor activities both in vitro and in vivo.MethodsThe binding affinities of F7AK3 to the two targets, TROP2 and CD3, were evaluated by surface plasmon resonance. Binding of F7AK3 to TNBC cells and T cells were evaluated by flow cytometry. Immunofluorescent staining was performed to demonstrate the interactions between T cells with TNBC cells. The cytotoxicity of T cells against TNBC cell lines and primary tumor cells mediated by F7AK3 were determined in vitro. In vivo antitumor activity of F7AK3 was investigated in a xenograft TNBC tumor model, using immunodeficient mice that were reconstituted with human peripheral blood mononuclear cells.ResultsWe demonstrated that F7AK3 binds specifically to human TROP2 and CD3 antigens, as well as TNBC cell lines and primary tumor cells. Human T cells can only be activated by F7AK3 in the presence of target tumor cells. F7AK3 recruits T cells to TROP2+ tumor cells in vitro and into tumor tissues in vivo. Antitumor growth activity of F7AK3 is observed in a xenograft TNBC tumor model.ConclusionThis study showed the antitumor potential of an anti-TROP2xCD3 bispecific antibody F7AK3 to TNBC tumor cells both in vitro and in vivo. These data demonstrate that F7AK3 has the potential to treat TNBC patients, which warrants further preclinical and clinical evaluation of the F7AK3 in advanced or metastatic TNBC patients.

scholarly journals Antiproliferative Effect of Electric Fields on Breast Tumor Cells In Vitro and In Vivo

2017 ◽  
Vol 6 (3) ◽  
pp. 71 ◽  
Author(s):  
Firman Alamsyah ◽  
Izzatun Niswah Ajrina ◽  
Fitriya Nur Annisa Dewi ◽  
Diah Iskandriati ◽  
Silvia Arin Prabandari ◽  
...  
Keyword(s):  
Growth Inhibition ◽  
Tumor Cells ◽  
Breast Tumor ◽  
Breast Tissue ◽  
In Vitro Study ◽  
Mammary Glands ◽  
Breast Tumor Cells ◽  
Mcf 7

Our research focused on the antiproliferative effect of low intensity (18 Vpp) and intermediate frequency (100 KHz) electrostatic wave between two capacitive electrodes on breast tumor cells in vitro and in vivo. In vitro study has been conducted by using MCF-7 cell lines treated with external electrostatic for 24, 48, and 72 hours of treatment and the cells number were calculated during treatment by using hemocytometer and presented as Growth Inhibition (GI)% efficacy. For in vivo, we used female mice (Mus musculus) strain C3H as animal model. The mice were injected with either MCF-7 cells, mammary tumor cells from C3H donor, or NaCl 0.9% (placebo) subcutaneously into the axilla area and exposed by external electrostatic in each cage for 12 hours in 2 weeks before necropsied. The adjacent and breast tissue were collected and stained with Hematoxylin – Eosin then analyzed for histopathological profile. In vitro study revealed the number of exposed cells decreased with lower proliferation rate than the non-exposed cells. Moreover, the external electrostatic caused 28-39% growth inhibition efficacy of MCF-7 cells. After 2 weeks of exposure, placebo mice were physically normal, whereas the tumor undergone significant shrinkage of more than 67% in size. Histopathological analysis of the mammary glands indicated infiltration of macrophages into the tumor area through the blood vessel. No abnormality was found in the skin layer and mammary glands of the breast tissue of placebo mice. Here, we present new knowledge of electro-capacitive cancer therapy (ECCT) as a novel treatment modality.Keywords : ECCT, tumor, in vitro, in vivo, breast cancer cells, antiproliferative

Monoclonal antibody 2C5-mediated binding of liposomes to brain tumor cells in vitro and in subcutaneous tumor model in vivo

2005 ◽  
Vol 13 (6) ◽  
pp. 337-343 ◽  
Author(s):  
Bhawna Gupta ◽  
Tatiana S. Levchenko ◽  
Dmitry A. Mongayt ◽  
Vladimir P. Torchilin
Keyword(s):  
Monoclonal Antibody ◽  
Brain Tumor ◽  
Tumor Cells ◽  
Tumor Model ◽  
Subcutaneous Tumor ◽  
Brain Tumor Cells

scholarly journals Biochemical and Anti-Triple Negative Metastatic Breast Tumor Cell Properties of Psammaplins

Marine Drugs ◽  
2018 ◽  
Vol 16 (11) ◽  
pp. 442 ◽  
Author(s):  
Yu-Dong Zhou ◽  
Jun Li ◽  
Lin Du ◽  
Fakhri Mahdi ◽  
Thuy Le ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumor Cell ◽  
Tumor Cells ◽  
Breast Tumor ◽  
Triple Negative ◽  
Hdac Inhibitors ◽  
Metastatic Breast ◽  
Dependent Manner ◽  
Breast Tumor Cells ◽  
Metastatic Breast Tumor

Breast tumors reprogram their cellular metabolism, nutrient uptake, and utilization-associated biochemical processes. These processes become further transformed as genetically predisposed metastatic breast tumor cells colonize specific organs. Breast tumor cells often metastasize to the brain, bone, lung and liver. Massagué and colleagues isolated organotropic subclones and established organ-specific gene signatures associated with lung-, bone-, and brain-specific metastatic triple-negative breast cancer (TNBC) MDA-MB-231 cells. Using these genetically characterized metastatic subclones specific to lung (LM4175), bone (BoM1833), and brain (BrM-2a), we evaluated marine natural products for the ability to differentially suppress metastatic breast cancer cells in a target organ-dependent manner. Psammaplin-based histone deacetylase (HDAC) inhibitors were found to differentially inhibit HDAC activity, induce activation of hypoxia-inducible factor-1 (HIF-1), and disrupt organotropic metastatic TNBC subclone growth. Further, psammaplins distinctly suppressed the outgrowth of BoM1833 tumor spheroids in 3D-culture systems. Similar results were observed with the prototypical HDAC inhibitor trichostatin A (TSA). These organotropic tumor cell-based studies suggest the potential application of HDAC inhibitors that may yield new directions for anti-metastatic breast tumor research and drug discovery.

scholarly journals Promising potential of [177Lu]Lu-DOTA-folate to enhance tumor response to immunotherapy—a preclinical study using a syngeneic breast cancer model

2020 ◽  
Author(s):  
Patrycja Guzik ◽  
Klaudia Siwowska ◽  
Hsin-Yu Fang ◽  
Susan Cohrs ◽  
Peter Bernhardt ◽  
...  
Keyword(s):  
Tumor Growth ◽  
Survival Time ◽  
Tumor Cells ◽  
Median Survival ◽  
Breast Tumor ◽  
Median Survival Time ◽  
Therapy Outcome ◽  
Minor Effect

Abstract Purpose It was previously demonstrated that radiation effects can enhance the therapy outcome of immune checkpoint inhibitors. In this study, a syngeneic breast tumor mouse model was used to investigate the effect of [177Lu]Lu-DOTA-folate as an immune stimulus to enhance anti-CTLA-4 immunotherapy. Methods In vitro and in vivo studies were performed to characterize NF9006 breast tumor cells with regard to folate receptor (FR) expression and the possibility of tumor targeting using [177Lu]Lu-DOTA-folate. A preclinical therapy study was performed over 70 days with NF9006 tumor-bearing mice that received vehicle only (group A); [177Lu]Lu-DOTA-folate (5 MBq; 3.5 Gy absorbed tumor dose; group B); anti-CTLA-4 antibody (3 × 200 μg; group C), or both agents (group D). The mice were monitored regarding tumor growth over time and signs indicating adverse events of the treatment. Results [177Lu]Lu-DOTA-folate bound specifically to NF9006 tumor cells and tissue in vitro and accumulated in NF9006 tumors in vivo. The treatment with [177Lu]Lu-DOTA-folate or an anti-CTLA-4 antibody had only a minor effect on NF9006 tumor growth and did not substantially increase the median survival time of mice (23 day and 19 days, respectively) as compared with untreated controls (12 days). [177Lu]Lu-DOTA-folate sensitized, however, the tumors to anti-CTLA-4 immunotherapy, which became obvious by reduced tumor growth and, hence, a significantly improved median survival time of mice (> 70 days). No obvious signs of adverse effects were observed in treated mice as compared with untreated controls. Conclusion Application of [177Lu]Lu-DOTA-folate had a positive effect on the therapy outcome of anti-CTLA-4 immunotherapy. The results of this study may open new perspectives for future clinical translation of folate radioconjugates.

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