Current Search: Breast -- Cancer -- Molecular aspects (x)
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- Title
- Inflammatory response in stress and the role of autophagy in breast cancer.
- Creator
- Onwuha-Ekpete, Lillian C., Charles E. Schmidt College of Medicine, Department of Biomedical Science
- Abstract/Description
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We attempted to understand the molecular regulators that impact inflammation using a rat model of human sensation-seeking/risk-taking trait for drug and stress vulnerability, based on their exploratory behavior displaying high rates (HRs) or low rates of locomotor reactivity (LRs) to environmental stress. We found that HRs have a pro-inflammatory phenotype as indicated by increased protein expression of the inflammatory cytokine TNF-(Sa(B. Furthermore, we found that HRs have a lower gene...
Show moreWe attempted to understand the molecular regulators that impact inflammation using a rat model of human sensation-seeking/risk-taking trait for drug and stress vulnerability, based on their exploratory behavior displaying high rates (HRs) or low rates of locomotor reactivity (LRs) to environmental stress. We found that HRs have a pro-inflammatory phenotype as indicated by increased protein expression of the inflammatory cytokine TNF-(Sa(B. Furthermore, we found that HRs have a lower gene expression of the glucocorticoid receptor and histone deacetylase 2 which are known to play an immunosuppressive role. Autophagy (macroautophagy) is a homeostatic process needed for cell maintenance, growth and proliferation and known to assist in tumor survival. FYVE and coiled-coil domain containing 1 (FYCO1) is a novel protein implicated to assist in the plus-end directed trafficking and fusion of autophagosomes. In these studies, we show that FYCO1 gene expression among human breast cell lines of varying degrees of malignancy.
Show less - Date Issued
- 2012
- PURL
- http://purl.flvc.org/fcla/dt/3362042
- Subject Headings
- Breast, Cancer, Genetic aspects, Cancer, Molecular aspects, Carcinogenesis, Cellular signal transduction, Stress (Physiology)
- Format
- Document (PDF)
- Title
- A Study on Reversing the Immunosuppressive Phenotype of Tumor Associated Macrophages.
- Creator
- Liddle, Genevieve M., Hartmann, James X., Florida Atlantic University, Charles E. Schmidt College of Science, Department of Biological Sciences
- Abstract/Description
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Extracellular stimuli may influence the M1/M2 phenotypic polarization of macrophages. We examined M1/M2 biomarkers, phagocytic activity, and tumoricidal activity in RAW 264.7 mouse macrophages. Macrophages were treated with conditioned media (CM) from 4T1 breast cancer cells, curcumin, 22-oxacalcitriol, LPS, or a combination of the previously listed. Arginase activity, a M2 phenotypic biomarker, was upregulated by the treatment of macrophages with conditioned media. Curcumin, 22-...
Show moreExtracellular stimuli may influence the M1/M2 phenotypic polarization of macrophages. We examined M1/M2 biomarkers, phagocytic activity, and tumoricidal activity in RAW 264.7 mouse macrophages. Macrophages were treated with conditioned media (CM) from 4T1 breast cancer cells, curcumin, 22-oxacalcitriol, LPS, or a combination of the previously listed. Arginase activity, a M2 phenotypic biomarker, was upregulated by the treatment of macrophages with conditioned media. Curcumin, 22- oxacalcitriol, and LPS partially inhibited RAW 264.7 arginase activity in the presence of 4T1 breast cancer media. 22-oxacalcitriol increased the phagocytic ability of RAW 264.7 macrophages in the presence of M2 polarizing substances produced by the 4T1 breast cancer cells. Also, LPS increased RAW 264.7 phagocytic ability in the presence of 4T1 breast cancer CM. This study looked at the potential substances that would possibly reverse the M2 tumor promoting macrophage phenotype seen in the breast cancer tumor environment.
Show less - Date Issued
- 2017
- PURL
- http://purl.flvc.org/fau/fd/FA00004867
- Subject Headings
- Macrophages., Breast--Cancer--Treatment., Tumors--Immunological aspects., Cancer--Immunological aspects., Biological response modifiers., Cancer--Molecular aspects.
- Format
- Document (PDF)
- Title
- Investigating the Role of CHI3L1 in Promoting Tumor Growth and Metastasis Using Mammary Tumor Models.
- Creator
- Libreros, Stephania, Iragavarapu-Charyulu, Vijaya, Florida Atlantic University, Charles E. Schmidt College of Medicine, Department of Biomedical Science
- Abstract/Description
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Metastasis is the primary cause of mortality in women with breast cancer. Recently, elevated serum levels of a glycoprotein known as chitinase-3 likeprotein- 1 (CHI3L1) has been correlated with poor prognosis and shorter survival of patients with cancer and inflammatory diseases. The biological and physiological functions of CHI3L1 in tumor progression have not yet been elucidated. In this document, we describe the role of CHI3L1 in tumor growth and metastasis and its relationship with...
Show moreMetastasis is the primary cause of mortality in women with breast cancer. Recently, elevated serum levels of a glycoprotein known as chitinase-3 likeprotein- 1 (CHI3L1) has been correlated with poor prognosis and shorter survival of patients with cancer and inflammatory diseases. The biological and physiological functions of CHI3L1 in tumor progression have not yet been elucidated. In this document, we describe the role of CHI3L1 in tumor growth and metastasis and its relationship with inflammation. Using well-established models of breast cancer, we show that CHI3L1 is increased in the serum of tumor bearing mice. We found that CHI3L1 levels are increased at both the “pre-metastatic” and “metastatic stage” and that tumor cells, splenic, alveolar and interstitial macrophages; and myeloid derived population produce CHI3L1. Furthermore, we demonstrated that CHI3L1 has an inhibitory role on the expression of interferon-gamma (IFN γ) by T cells, while enhancing the production of pro-inflammatory mediators by macrophages such as Cchemokine ligand 2 (CCL2/MCP-1), Chemokine CX motif ligand 2 (CXCL2/IL-8) and matrix metalloproteinase-9 (MMP-9), all of which promote tumor growth and metastasis. We demonstrated that in vivo treatment of tumor-bearing mice with chitin microparticles, a TH1 adjuvant and a substrate for CHI3L1, promoted immune effector functions with increased production of IFN-γ but decreased CCL2/MCP-1, CXCL2/IL-8 and MMP-9 expression by splenic and pulmonary macrophages. Significantly, in vivo administration of chitin microparticles decreased tumor growth and pulmonary metastasis in mammary tumor bearing mice. These results suggest that CHI3L1 may play a role in tumor progression. Inflammation plays a pivotal role during tumor progression and metastasis by promoting the production of pro-inflammatory molecules such as CHI3L1. However, little is known about how CHI3L1 expression can affect secondary sites to enhance metastasis. In these studies, we demonstrated that CHI3L1 alters the cellular composition and inflammatory mediators that aid in the establishment of a metastatic niche for the support of infiltrating tumor cells leading to accelerated tumor progression. Since previous studies showed that CHI3L1 modulates inflammation, we determined the role of CHI3L1 in the context of pre-existing inflammation and metastasis. We found that CHI3L1 deficient mice with preexisting inflammation had decreased pro-inflammatory mediators, and significant reduction in tumor volume and metastasis compared to wild type controls. Preexisting inflammation and CHI3L1 may be driving the establishment of a premetastatic milieu in the lungs and aiding in the establishment of metastasis. Understanding the role of CHI3L1 in inflammation during tumor progression could result in the design of targeted therapies for breast cancer patients.
Show less - Date Issued
- 2015
- PURL
- http://purl.flvc.org/fau/fd/FA00004517, http://purl.flvc.org/fau/fd/FA00004517
- Subject Headings
- Biopharmaceutics, Breast -- Cancer -- Etiology, Breast -- Cancer -- Molecular aspects, Cell differentiation, Chitinase, Glycoproteins -- Metabolism, Inflammation, Mice as laboratory animals
- Format
- Document (PDF)
- Title
- Therapeutic potential of pomegranate and genistein for human breast cancer.
- Creator
- Louis Jeune, Marie Adeline, Florida Atlantic University, Kumi-Diaka, James
- Abstract/Description
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The therapeutic potential of pomegranate and genistein on growth inhibition of human breast cancer cells was investigated. Methods. Cells (MCF-7) were initially cultured for 48 hr to achieve 80% confluence; and then exposed to the agents in single and combination treatments. Post-treatment analysis was done by using a series of bioassays, including LDH, MTS, AcrO-EthBr, Annexin-FITC and TUNEL assays for growth inhibition and apoptosis detection; and Caspase-3 and NQO1 for molecular pathways...
Show moreThe therapeutic potential of pomegranate and genistein on growth inhibition of human breast cancer cells was investigated. Methods. Cells (MCF-7) were initially cultured for 48 hr to achieve 80% confluence; and then exposed to the agents in single and combination treatments. Post-treatment analysis was done by using a series of bioassays, including LDH, MTS, AcrO-EthBr, Annexin-FITC and TUNEL assays for growth inhibition and apoptosis detection; and Caspase-3 and NQO1 for molecular pathways of apoptosis. Results. Pomegranate and genistein showed significant dose- and time-dependent cytotoxic and growth inhibition effects as well as apoptosis induction in MCF-7 cancer cells, with significantly higher ( P < 0.01) effects in the combination treatments than in the single treatments. Both drugs induced apoptosis through a caspase-mediated mechanism and independent of NQO1. Discussion and conclusions. Pomegranate and genistein inhibit the growth of MCF-7 breast cancer cells through induction of apoptosis with combination treatment being more efficacious than single treatments.
Show less - Date Issued
- 2004
- PURL
- http://purl.flvc.org/fcla/dt/13130
- Subject Headings
- Phytochemicals--Physiological effect, Breast--Cancer--Molecular aspects, Women--Diseases--Alternative treatment, Apoptosis--Molecular aspects, Breast--Cancer--Treatment
- Format
- Document (PDF)
- Title
- Genistein targets only proliferating but not quiescent cells: Potential therapeutic significance in breast cancer.
- Creator
- Bodepudi, Sreedevi., Florida Atlantic University, Kumi-Diaka, James
- Abstract/Description
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Phytochemicals are biologically active secondary plant metabolites that could mimic biological activities. In this study genistein isoflavone, a phytochemical present in soy was investigated to determine its effect on the growth of human breast cancer cell line GI-101 and normal breast epithelial cells in vitro. The cells were exposed to varying concentrations of genistein isoflavone for 24 and 48 hour time periods and the effect was determined using post-treatment assays: MTT and Trypan Blue...
Show morePhytochemicals are biologically active secondary plant metabolites that could mimic biological activities. In this study genistein isoflavone, a phytochemical present in soy was investigated to determine its effect on the growth of human breast cancer cell line GI-101 and normal breast epithelial cells in vitro. The cells were exposed to varying concentrations of genistein isoflavone for 24 and 48 hour time periods and the effect was determined using post-treatment assays: MTT and Trypan Blue for cell viability; LDH assay for cytotoxicity; Rhodamine 123/Propidium Iodide and Ethidium Bromide/Acridine Orange assays for treatment-induced apoptosis and FAM Poly caspase assay for mechanism of action. The overall results revealed that genistein inhibited cell growth and proliferation through apoptosis in the cells in both time and dose-dependent manner. Normal breast epithelial cells were not significantly affected by genistein at the corresponding dosages. Based on the results obtained, it was concluded that genistein isoflavone could offer therapeutic efficacy in human breast carcinoma without significantly affecting the normal breast epithelial cells.
Show less - Date Issued
- 2006
- PURL
- http://purl.flvc.org/fcla/dt/13315
- Subject Headings
- Phytochemicals--Physiological effect, Breast--Cancer--Molecular aspects, Women--Diseases--Alternative treatment, Breast--Cancer--Treatment, Apoptosis--Molecular aspects
- Format
- Document (PDF)
- Title
- The Impact of Pharmacological Targeting of Abnormal Tumor Metabolism with 3-Bromopyruvate on Dendritic Cell Mediated Tumoral Immunity.
- Creator
- Lang, Kevin, Hartmann, James X., Florida Atlantic University, Charles E. Schmidt College of Science, Department of Biological Sciences
- Abstract/Description
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Studies have shown that tumor cells are susceptible to pharmacological targeting of their altered glycolytic metabolism with a variety of compounds that result in apoptosis. One such compound, 3-bromopyruvate (3-BP), has been shown to eradicate cancer in an animal model. However, no studies have shown whether the apoptotic fragments resulting from 3-BP treatment have the capacity to elicit an immunogenic cell death that activates dendritic cells, the primary antigen presenting cell in the...
Show moreStudies have shown that tumor cells are susceptible to pharmacological targeting of their altered glycolytic metabolism with a variety of compounds that result in apoptosis. One such compound, 3-bromopyruvate (3-BP), has been shown to eradicate cancer in an animal model. However, no studies have shown whether the apoptotic fragments resulting from 3-BP treatment have the capacity to elicit an immunogenic cell death that activates dendritic cells, the primary antigen presenting cell in the immune system. Immunogenic cell death is critical to eliciting an effective adaptive immune response that selectively kills additional target cells and generates immunological memory. We demonstrated that 3-bromopyruvate induced apoptosis in a number of different murine breast cancer cell lines, including the highly metastatic 4T1 line. The dying tumor cells stimulated immature dendritic cells (DCs) of the immortal JAWS II cell line to produce high levels of the pro-inflammatory cytokine IL-12, and increased their expression of key co-stimulatory molecules CD80 and CD86. The activated dendritic cells showed increased uptake of fragments from dying tumor cells that correlated with the increased levels of calreticulin on the surface and release of high group motility box 1 (HMGB1) of the latter following 3-BP treatment. Additionally, the anti-phagocytic signal CD47 present on breast cancer cells was reduced by treatment with 3-bromopyruvate when compared to the levels on untreated 4T1 cells. 3-BP treated breast cancer cells were able to activate dendritic cells through TLR4 signaling. Signaling was dependent on both the expression of surface calreticulin and on the extracellular release of high mobility group box 1 protein (HMGB1) during the process of immunogenic cell death. Killing by 3-BP was compared to mitoxantrone and doxorubicin, among the few chemotherapeutics that induce immunogenic cell death. 3-BP killing was likewise compared to camptothecin, a compound that fails to induce immunogenic cell death. Importantly, 3-BP did not markedly decrease the levels of the key peptide presenting molecule MHC I on DCs that were co-cultivated with dying tumor cells. Treatment of the highly aggressive triple negative BT-20 human breast cancer cell line with 3-BP also induced an immunogenic cell death, activating human dendritic cells in vitro.
Show less - Date Issued
- 2017
- PURL
- http://purl.flvc.org/fau/fd/FA00004834
- Subject Headings
- Apoptosis., Cellular signal transduction., Cell death., Breast--Cancer--Treatment., Carrier proteins., Cancer--Molecular aspects., Biological interfaces.
- Format
- Document (PDF)
- Title
- Therapeutic Options for the Treatment of Breast Cancer: Using Cytoreg and Genistein Isoflavone.
- Creator
- Johnson, Michelle M., Kumi-Diaka, James, Florida Atlantic University, Charles E. Schmidt College of Science, Department of Biological Sciences
- Abstract/Description
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In spite the heavy investments in therapeutic research breast cancer still impacts the lives of women globally. The projected incidence of new cases in USA for 2008 is 67,770, with estimated 40,480 deaths. In this study, we investigated the therapeutic efficacy of Cytoreg®-genistein combination treatment on MCF-7 human breast cancer cells. MCF-7 cells were treated with genistein and Cytoreg® single and combination treatments for 24- 48hr; and the chemosensitivity assessed using bioassays:...
Show moreIn spite the heavy investments in therapeutic research breast cancer still impacts the lives of women globally. The projected incidence of new cases in USA for 2008 is 67,770, with estimated 40,480 deaths. In this study, we investigated the therapeutic efficacy of Cytoreg®-genistein combination treatment on MCF-7 human breast cancer cells. MCF-7 cells were treated with genistein and Cytoreg® single and combination treatments for 24- 48hr; and the chemosensitivity assessed using bioassays: Trypan Blue and MTT for cell viability; Ethidium bromide/Rhodamine 123 to assess apoptosis induction; F AM PolyCaspase binding assay for mechanism of action. The overall data indicated dose- and timedependent cell death in the MCF-cells and that apoptosis was the major means of treatmentinduced growth inhibition. There was evidence of Cytoreg®-induced autophagy in the cells. The overall findings indicated that genistein-Cytoreg® combination was more efficacious than either genistein or Cytoreg® alone. Cytoreg® enhanced the phytosensitivity of MCF-7 cells to genistein isoflavone.
Show less - Date Issued
- 2008
- PURL
- http://purl.flvc.org/fau/fd/FA00000777
- Subject Headings
- Breast--Cancer--Treatment, Phytochemicals--Physiological effect, Apoptosis--Molecular aspects, Phytoestrogens--Health aspects, Outcome assessment (Medical care)
- Format
- Document (PDF)