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Multifactorial Effects of Biological...
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Texas Southern University.
Multifactorial Effects of Biological Response Modifiers and Anti-Neoplastic Induced Immune Cell Activation and Triple Negative Breast Cancer Cell Inhibition.
紀錄類型:
書目-語言資料,手稿 : Monograph/item
正題名/作者:
Multifactorial Effects of Biological Response Modifiers and Anti-Neoplastic Induced Immune Cell Activation and Triple Negative Breast Cancer Cell Inhibition./
作者:
Olamigoke, Loretta T.
面頁冊數:
1 online resource (223 pages)
附註:
Source: Dissertation Abstracts International, Volume: 78-12(E), Section: B.
標題:
Environmental science. -
電子資源:
click for full text (PQDT)
ISBN:
9780355063707
Multifactorial Effects of Biological Response Modifiers and Anti-Neoplastic Induced Immune Cell Activation and Triple Negative Breast Cancer Cell Inhibition.
Olamigoke, Loretta T.
Multifactorial Effects of Biological Response Modifiers and Anti-Neoplastic Induced Immune Cell Activation and Triple Negative Breast Cancer Cell Inhibition.
- 1 online resource (223 pages)
Source: Dissertation Abstracts International, Volume: 78-12(E), Section: B.
Thesis (Ph.D.)--Texas Southern University, 2017.
Includes bibliographical references
Active Hexose Correlated Compound (AHCC) is a fermented mushroom extract and immune supplement that has been used to treat a wide range of health conditions such as cancers and also infectious diseases. It is a therapeutic tool for non-specific active immunotherapy and combination chemotherapy. It helps in augmentation of the natural immune response and affects immune cell activation and outcomes. Breast cancer is the most commonly diagnosed cancer among women, accounting for more than 1 in 4 cancers. After lung cancer breast cancer ranks as the most common form of cancer amongst American women, it is also the second leading cause of deaths in females in the United States of America with more than 230,000 new cases diagnosed every year. Taxanes are amongst the most active drugs in the treatment of metastatic breast cancer (MBC) and are established as the standard of care either as monotherapy or in combination with other cytotoxic agents. Paclitaxel is a mitotic inhibitor, isolated from Taxus brevifolia, inducing the assembly of tubulin subunits, thus disrupting the normal microtubule reorganization.
Electronic reproduction.
Ann Arbor, Mich. :
ProQuest,
2018
Mode of access: World Wide Web
ISBN: 9780355063707Subjects--Topical Terms:
1179128
Environmental science.
Index Terms--Genre/Form:
554714
Electronic books.
Multifactorial Effects of Biological Response Modifiers and Anti-Neoplastic Induced Immune Cell Activation and Triple Negative Breast Cancer Cell Inhibition.
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Multifactorial Effects of Biological Response Modifiers and Anti-Neoplastic Induced Immune Cell Activation and Triple Negative Breast Cancer Cell Inhibition.
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Source: Dissertation Abstracts International, Volume: 78-12(E), Section: B.
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Adviser: Alamelu Sundaresan.
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Thesis (Ph.D.)--Texas Southern University, 2017.
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Includes bibliographical references
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Active Hexose Correlated Compound (AHCC) is a fermented mushroom extract and immune supplement that has been used to treat a wide range of health conditions such as cancers and also infectious diseases. It is a therapeutic tool for non-specific active immunotherapy and combination chemotherapy. It helps in augmentation of the natural immune response and affects immune cell activation and outcomes. Breast cancer is the most commonly diagnosed cancer among women, accounting for more than 1 in 4 cancers. After lung cancer breast cancer ranks as the most common form of cancer amongst American women, it is also the second leading cause of deaths in females in the United States of America with more than 230,000 new cases diagnosed every year. Taxanes are amongst the most active drugs in the treatment of metastatic breast cancer (MBC) and are established as the standard of care either as monotherapy or in combination with other cytotoxic agents. Paclitaxel is a mitotic inhibitor, isolated from Taxus brevifolia, inducing the assembly of tubulin subunits, thus disrupting the normal microtubule reorganization.
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The goal of this project is twofold. The first major goal was to study and understand the role and mechanisms of AHCC supplementation alone and in combination with mitogens Phytohemagglutinin (PHA), Phorbol Myristate Acetate (PMA) and a calcium ionophore (Ionomycin) in the prevention of immunosuppression through Peripheral Blood Mononuclear cell (PBMC) activation. We analyzed the effects of these on pro-inflammatory and anti-inflammatory cytokine release as well as Transcription factor activation. The method described here involves "in vitro" culturing of PBMCs and exposing them to different concentrations of AHCC (0, 50, 100, 250, 500, 1,000 mug/mL), PHA(0, 1, 3, 5, 7, 10 mug/mL), PMA (0, 0.5, 1, 5, 10, 20, 25 ng/ml) and Ionomycin (0, 0.2, 0.5, 1, 2, 2.5 mug/mL) for a total period of 96 hours. A proliferative assay was performed every 12 hours to determine the proliferative effect that different concentrations of AHCC, PHA, PMA, Ionomycin and AHCC in combination with each of the mitogens and ionophore has on the PBMC population. Supernatants were extracted at early and late time points and analyzed for effects on cytokine production, protein extraction and quantification was carried out and western analysis was performed to evaluate effect on transcription factor genes -- NFkB and NFAT. We found that AHCC increased activation and proliferation of G0 PBMCs in a dose dependent manner. There was synergism of the response with specific doses of the mitogens used, AHCC was seen to cause the secretion of anti-inflammatory cytokine responsible for regulating pro-inflammatory cytokines, and it also led to activation of transcription factors NFkB & NFAT as early as 30 minutes post treatment. The second major goal of this study was to investigate the cytotoxic effects of a chemotherapy drug Paclitaxel at different concentrations of 0.046, 0.23, 0.46, 0.92, 1.4, 2.3, 4.6 microM and a biological response modifier AHCC at concentrations of 500 and 1,000microg/ml (alone and in combination) on cell proliferation and apoptosis in triple negative breast cancer cells MDA-MB-231. The methodology used in this study involved determination of the doubling time of MDA-MB-231 breast cancer cells, carrying out multiple cytotoxicity assays, which involved culturing of the breast cancer cells in 96 well plates, 6 wells plates and chambered slides and treating the cells with selected concentrations of paclitaxel, AHCC and Paclitaxel in combination with AHCC to study enhanced and synergistic effects that led to increased apoptosis of the cancer cell. A 7 day Cytotoxicity assay was performed with the cells seeded into the 96well plate, with one plate terminated each day and this assay was performed so as to evaluate effect of the treatment on cell growth. Tubulin and actin staining were performed on cells grown in the chamber slides so as to study the effect of the drug on the cytoskeleton of the cell. From the results obtained, increased cytotoxicity was observed from the treatment with paclitaxel, AHCC and a combination of these two therapeutic measures.
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2018
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Mode of access: World Wide Web
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