Primary tumor dependent inhibition of tumor growth, angiogenesis, and perfusion of secondary breast cancer in bone

2011 ◽  
Vol 29 (8) ◽  
pp. 1251-1258 ◽  
Author(s):  
Christian Schaefer ◽  
Malte Schroeder ◽  
Ina Fuhrhop ◽  
Lennart Viezens ◽  
Jasmin Otten ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumor Growth ◽  
Primary Tumor ◽  
Dependent Inhibition ◽  
Inhibition Of Tumor Growth ◽  
Secondary Breast Cancer

scholarly journals Host deficiency in ephrin-A1 inhibits breast cancer metastasis

F1000Research ◽  
2020 ◽  
Vol 9 ◽  
pp. 217 ◽  
Author(s):  
Eileen Shiuan ◽  
Ashwin Inala ◽  
Shan Wang ◽  
Wenqiang Song ◽  
Victoria Youngblood ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumor Growth ◽  
Cancer Cell ◽  
Lung Metastasis ◽  
Primary Tumor ◽  
Tumor Recurrence ◽  
Cancer Metastasis ◽  
Primary Tumor Growth ◽  
Primary Tumors ◽  
4T1 Cells

Background: The conventional dogma of treating cancer by focusing on the elimination of tumor cells has been recently refined to include consideration of the tumor microenvironment, which includes host stromal cells. Ephrin-A1, a cell surface protein involved in adhesion and migration, has been shown to be tumor suppressive in the context of the cancer cell. However, its role in the host has not been fully investigated. Here, we examine how ephrin-A1 host deficiency affects cancer growth and metastasis in a murine model of breast cancer. Methods: 4T1 cells were orthotopically implanted into the mammary fat pads or injected into the tail veins of ephrin-A1 wild-type (Efna1+/+), heterozygous (Efna1+/-), or knockout (Efna1-/-) mice. Tumor growth, lung metastasis, and tumor recurrence after surgical resection were measured. Flow cytometry and immunohistochemistry (IHC) were used to analyze various cell populations in primary tumors and tumor-bearing lungs. Results: While primary tumor growth did not differ between Efna1+/+, Efna1+/-, and Efna1-/- mice, lung metastasis and primary tumor recurrence were significantly decreased in knockout mice. Efna1-/- mice had reduced lung colonization of 4T1 cells compared to Efna1+/+ littermate controls as early as 24 hours after tail vein injection. Furthermore, established lung lesions in Efna1-/- mice had reduced proliferation compared to those in Efna1+/+ controls. Conclusions: Our studies demonstrate that host deficiency of ephrin-A1 does not impact primary tumor growth but does affect metastasis by providing a less favorable metastatic niche for cancer cell colonization and growth. Elucidating the mechanisms by which host ephrin-A1 impacts cancer relapse and metastasis may shed new light on novel therapeutic strategies.

scholarly journals TIMP-2 suppresses tumor growth and metastasis in murine model of triple-negative breast cancer

2019 ◽  
Vol 41 (3) ◽  
pp. 313-325 ◽  
Author(s):  
David Peeney ◽  
Sandra M Jensen ◽  
Nadia P Castro ◽  
Sarvesh Kumar ◽  
Silvia Noonan ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumor Growth ◽  
Signaling Pathways ◽  
Triple Negative Breast Cancer ◽  
Primary Tumor ◽  
Epithelial To Mesenchymal Transition ◽  
Triple Negative ◽  
Metastasis Suppressor ◽  
Mesenchymal Transition ◽  
Tumor Growth And Metastasis

Abstract Metastasis is the primary cause of treatment failures and mortality in most cancers. Triple-negative breast cancer (TNBC) is refractory to treatment and rapidly progresses to disseminated disease. We utilized an orthotopic mouse model that molecularly and phenotypically resembles human TNBC to study the effects of exogenous, daily tissue inhibitor of metalloproteinase-2 (TIMP-2) treatment on tumor growth and metastasis. Our results demonstrated that TIMP-2 treatment maximally suppressed primary tumor growth by ~36–50% and pulmonary metastasis by >92%. Immunostaining assays confirmed disruption of the epithelial to mesenchymal transition (EMT) and promotion of vascular integrity in primary tumor tissues. Immunostaining and RNA sequencing analysis of lung tissue lysates from tumor-bearing mice identified significant changes associated with metastatic colony formation. Specifically, TIMP-2 treatment disrupts periostin localization and critical cell-signaling pathways, including canonical Wnt signaling involved in EMT, as well as PI3K signaling, which modulates proliferative and metastatic behavior through p27 phosphorylation/localization. In conclusion, our study provides evidence in support of a role for TIMP-2 in suppression of triple-negative breast cancer growth and metastasis through modulation of the epithelial to mesenchymal transition, vascular normalization, and signaling pathways associated with metastatic outgrowth. Our findings suggest that TIMP-2, a constituent of the extracellular matrix in normal tissues, may have both direct and systemic antitumor and metastasis suppressor effects, suggesting potential utility in the clinical management of breast cancer progression.

Combinatorial treatment with CTO and temozolomide in sc-implanted human LOX 1MVI melanoma.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e19006-e19006
Author(s):  
Rashida A. Karmali ◽  
Yulia Maxuitenko ◽  
Greg Gorman
Keyword(s):  
Antitumor Activity ◽  
Tumor Growth ◽  
Calcium Influx ◽  
Dependent Inhibition ◽  
Melanoma Model ◽  
Dose Dependent Inhibition ◽  
Inhibition Of Tumor Growth ◽  
Induction Of Apoptosis ◽  
Oxide Synthase ◽  
Dose Dependent

e19006 Background: Carboxyamidotriazole orotate (CTO) is the orotic acid salt of 5-amino-1.(4-(4-chlorobenzoyl)-3,5-dichlorobenzyl)-1, 2, 3-triazole-4-carboxamide. CTO possesses increased solubility. The antiproliferative and antimetastatic effects of CTO are related to inhibition of receptor –opertated calcium channel- mediated calcium influx. CTO can inhibit calcium sensitive signal transduction in the VEGF and the PI3K pathways, inhibition of FGF-2-induced tyrosine kinase, VEGF-mediated activation of phospholipase Cγ, generation of IP3 and nitric oxide synthase activation, and induction of apoptosis in imatinib mesylate resistant CML cells by downregulating bcr-abl. Methods: Different combinations of CTO and temozolomide (TEM) were first tested in female athymic NCr-nu/nu mice to evaluate tolerance of the combination. The tolerated combinations were then tested to evaluate the antitumor activity against subcutaneously –implanted human LOX 1MVI melanoma xenografts. Results: Oral CTO at doses of 513 or 342 mg/kg/dose Q1Dx14 resulted in inhibition of tumor growth (p<0.001 and p=0.004). Oral TEM at doses of 90 and 60mg/kg/dose Q4Dx3 resulted in dose-dependent inhibition of tumor growth (p<0.001 and p<0.001). Oral CTO at 513 or 342 mg/kg/dose in combination with TEM 90mg/kg/dose resulted in comparable tumor inhibition to TEM alone. However, oral CTO at 513mg/kg/dose in combination with TEM 60mg/kg/dose resulted in additive antitumor activity compared to each drug alone. Also, CTO at 342mg/kg/dose in combination with TEM 60mg/kg/dose had more than additive antitumor activity and was statistically different from the group treated with TEM 60mg/kg/dose alone (p=0.001). Conclusions: These results suggest that CTO enhances the sensitivity of TEM and may permit use of lower doses of TEM to obtain an optimum antitumor effect in combination therapy thus reducing toxicity of high TEM doses in this melanoma model.

scholarly journals Hypoxia-inducible factor 1α promotes primary tumor growth and tumor-initiating cell activity in breast cancer

2012 ◽  
Vol 14 (1) ◽  
Author(s):  
Luciana P Schwab ◽  
Danielle L Peacock ◽  
Debeshi Majumdar ◽  
Jesse F Ingels ◽  
Laura C Jensen ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumor Growth ◽  
Primary Tumor ◽  
Hypoxia Inducible Factor ◽  
Cell Activity ◽  
Primary Tumor Growth ◽  
Hypoxia Inducible Factor 1Α ◽  
Tumor Initiating Cell

scholarly journals Isotype-Dependent Inhibition of Tumor Growth In Vivo by Monoclonal Antibodies to Death Receptor 4

2001 ◽  
Vol 166 (8) ◽  
pp. 4891-4898 ◽  
Author(s):  
Anan Chuntharapai ◽  
Kelly Dodge ◽  
Katharine Grimmer ◽  
Kurt Schroeder ◽  
Scot A. Marsters ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Tumor Growth ◽  
Death Receptor ◽  
Dependent Inhibition ◽  
Inhibition Of Tumor Growth ◽  
Death Receptor 4

scholarly journals Significant Inhibition of Tumor Growth following Single Dose Nanoparticle-Enhanced Photodynamic Therapy

2014 ◽  
Vol 2014 ◽  
pp. 1-11 ◽  
Author(s):  
Shih-Hsun Cheng ◽  
Chia-Hui Chu ◽  
Nai-Tzu Chen ◽  
Jeffrey S. Souris ◽  
Chin-Tu Chen ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Photodynamic Therapy ◽  
Tumor Growth ◽  
Human Breast Cancer ◽  
Significant Inhibition ◽  
Oxygen Species ◽  
Human Breast ◽  
Apoptotic Response ◽  
Inhibition Of Tumor Growth

Photodynamic therapy (PDT) for cancer treatment involves the pathology’s uptake of photosensitizers, which produce cytotoxic reactive oxygen species by photoirradiation. The use of nanoparticles as carriers of photosensitizers is one promising approach to this endeavor, owing to their small size, unique physicochemical properties, and easy/diverse functionalization. In the current work, we report on thein vivoassessment of PDT efficacy of these nanoconstructs in a murine model of human breast cancer, following a single (one-shot) nanoparticle dose and photoirradiation. Palladium-porphyrin (PdTPP) was administered intratumorally via injection of aqueous suspensions of either free PdTPP or MSN-conjugated PdTPP (MSN-PdTPP) at a dose of 50 μg. Mice were then exposed to a single photoirradiation session with total energy of 80 J. One month after one-shot PDT treatment, significantly greater reductions in tumor growth were observed in MSN-Pd treated animals than in PdTPP cohorts. Electron microscopy of tumor specimens harvested at various timepoints revealed excellent MSN-PdTPP uptake by cancer cells while immunohistologic analysis demonstrated marked increases in apoptotic response of MSN-PdTPP treated animals relative to PdTPP controls. Taken together, these findings suggest that considerable improvements in PDT efficacy can readily be achieved via the use of nanoparticle-based photosensitizers.

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