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- Title
- Anticancer ativities of topotecan-genistein combination in prostate cancer cells.
- Creator
- Hörmann, Vanessa P., Kumi-Diaka, James, Charles E. Schmidt College of Science, Department of Biological Sciences
- Abstract/Description
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Prostate cancer is one of the leading causes of death in men aged 40-55. Genistein isoflavone (4', 5', 7-trihydroxyisoflavone) is a dietary phytochemical with demonstrated anti-tumor activities in a variety of cancers. Topotecan Hydrochloride (Hycamtin) is an FDA-approved chemotherapy drug, primarily used for secondary treatment of ovarian,cervical and small cell lung cancers. This study was to demonstrate the potential anticancer activities and synergy of topotecan-genistein combination in...
Show moreProstate cancer is one of the leading causes of death in men aged 40-55. Genistein isoflavone (4', 5', 7-trihydroxyisoflavone) is a dietary phytochemical with demonstrated anti-tumor activities in a variety of cancers. Topotecan Hydrochloride (Hycamtin) is an FDA-approved chemotherapy drug, primarily used for secondary treatment of ovarian,cervical and small cell lung cancers. This study was to demonstrate the potential anticancer activities and synergy of topotecan-genistein combination in LNCaP prostate cancer cells. The potential efficacy and mechanism of topotecan/genistein-induced cell death was investigated... Results: The overall data indicated that i) both genistein and topotecan induce cellular death in LNCaP cells, ii) topotecan-genistein combination was significantly more efficacious in reducing LNCaP cell viabiligy compared to either genistein or topotecan alone, iii) in all cases, cell death was primarily through apoptosis, via the activation of the intrinsic pathway, iv) ROS levels were increased and VEGF expression was diminished significantly with the topotecan-genistein combination treatment, v) genetic analysis of topotecan-genistein treatment groups showed changes in genetic expression levels in pathway specific apoptotic genes.... Conclusion: Treatments involving topotecan-genistein combination may prove to be an attractive alternative phytotherapy of adjuvant therapy for prostate cancer.
Show less - Date Issued
- 2012
- PURL
- http://purl.flvc.org/FAU/3358553
- Subject Headings
- Apoptosis, Molecular aspects, Prostate, Cancer, Adjuvant treatment, Prostate, Cancer, Molecular aspects, Phytochemicals, Physiological effect, Antioxidants, Therapeutic use, Topotecan, Therapeutic use, Genistein, Therapeutic use, Cancer, Chemotherapy
- Format
- Document (PDF)
- Title
- Anticarcinogenic effects of genistein and anthocyanin extract in MCF-7 human breast cancer cells.
- Creator
- Stinson, Corine M., Charles E. Schmidt College of Science, Department of Biological Sciences
- Abstract/Description
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This study investigated potential apoptotic and anti-proliferative effects of the phytochemicals, genistein and anthocyanin extract, as single and combined treatments in MCF-7 human breast cancer cells. Cells were exposed to single and combined treatments with the phytochemiclas for 48 and 72 hours. Cell viability was assessed using the MTT bioassay. Apoptosis induction was assessed using acridine orange ethidium bromide and rhodamine 123 ethidium bromide fluorescence assays. Both singe and...
Show moreThis study investigated potential apoptotic and anti-proliferative effects of the phytochemicals, genistein and anthocyanin extract, as single and combined treatments in MCF-7 human breast cancer cells. Cells were exposed to single and combined treatments with the phytochemiclas for 48 and 72 hours. Cell viability was assessed using the MTT bioassay. Apoptosis induction was assessed using acridine orange ethidium bromide and rhodamine 123 ethidium bromide fluorescence assays. Both singe and combination treatments induced dose- and time-dependent apoptotic cell death in MCF-7 cells. The percentage of apoptosis was higher in combination treatments than single treatments with either phytochemical, although the difference was not statistically significant. The combination of genistein and anthocyanin extract peaked in efficacy at 48 hours of treatment, to exhibit significantly greater (P<. O5) dose- and time-dependent cell cytotoxicity than single treatments. This study reveals potential chemopreventive implications for the complementary effects of genistein and anthocyanin extract.
Show less - Date Issued
- 2011
- PURL
- http://purl.flvc.org/FAU/3320108
- Subject Headings
- Phytochemicals, Therapeutic use, Phytoestrogens, Physiological effect, Breast, Cancer, Risk factors, Breast, Cancer, Treatment, Probiotics, Cancer, Chemoprevention, Antioxidants, Therapeutic use
- Format
- Document (PDF)
- Title
- Biomonitoring of hypoxia and sulfide stress in three sub-tropical seagrasses.
- Creator
- Irwin, Connor., Charles E. Schmidt College of Science, Department of Biological Sciences
- Abstract/Description
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Hypoxia and sulfide exposure, increased using glucose, are considered major environmental stressors in seagrass communities. Quantum efficiency, total soluble protein and catalase activity were quantified to evaluate the applicability of each of these bioindicators to detect environmental stress in three tropical seagrass species, Thalassia testudinum (Banks ex Kèoenig), Halodule wrightii (Ascherson) and Syringodium filiforme (Kuetz). Hypoxia + sulfide treatments significantly decreased the...
Show moreHypoxia and sulfide exposure, increased using glucose, are considered major environmental stressors in seagrass communities. Quantum efficiency, total soluble protein and catalase activity were quantified to evaluate the applicability of each of these bioindicators to detect environmental stress in three tropical seagrass species, Thalassia testudinum (Banks ex Kèoenig), Halodule wrightii (Ascherson) and Syringodium filiforme (Kuetz). Hypoxia + sulfide treatments significantly decreased the quantum efficiency of all three species, but showed no response in protein and catalase activity. Although no treatment effect was found, catalase activity was enhanced in T. testudinum leaves and H. wrightii roots relative to other tissues, while S. filiforme showed no location-specific catalase activity. These results indicate that quantum efficiency is a more sensitive indicator than protein and catalase activity to hypoxia and sulfide stress in seagrasses.
Show less - Date Issued
- 2010
- PURL
- http://purl.flvc.org/FAU/2976445
- Subject Headings
- Plant physiology, Environmental management, Seagrasses, Habitat, Environmental aspects, Sulfites, Physiological effect, Marine ecology
- Format
- Document (PDF)
- Title
- Investigating maternal health and hatchling mortality in leatherback sea turtles (Dermochelys coriacea v.).
- Creator
- Perrault, Justin R., Charles E. Schmidt College of Science, Department of Biological Sciences
- Abstract/Description
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The reproductive success of leatherback turtles (Dermochelys coriacea) is typically the lowest of the seven sea turtle species. Why this vital rate is decreased has remained unanswered for nearly a century. Recently, detailed postmortem examination of leatherback hatchlings identified muscular pathologies that suggested possible selenium deficiency. High bodily burdens of mercury compounds are associated with selenium depletion. Selenium is a necessary detoxifying nutrient that itself can be...
Show moreThe reproductive success of leatherback turtles (Dermochelys coriacea) is typically the lowest of the seven sea turtle species. Why this vital rate is decreased has remained unanswered for nearly a century. Recently, detailed postmortem examination of leatherback hatchlings identified muscular pathologies that suggested possible selenium deficiency. High bodily burdens of mercury compounds are associated with selenium depletion. Selenium is a necessary detoxifying nutrient that itself can be toxic at elevated concentrations. Mercury compounds are toxicants with no known biological function. High bodily concentrations of mercury can be detrimental to marine organismal health, reproduction and survival, both directly and indirectly through inducing selenium depletion. The goals of this dissertation are to evaluate several related hypotheses to explain low leatherback nest success. ... Because leatherbacks take in high volumes of prey, high tissue concentrations of mercury and selenium can result. This study provides the first evidence that chemical contaminants may explain low reproductive success in leatherback sea turtles.
Show less - Date Issued
- 2013
- PURL
- http://purl.flvc.org/fcla/dt/3362575
- Subject Headings
- Selenium, Physiological effect, Predation (Biology), Leatherback turtle, Mortality, Sea turtles, Mortality, Wildlife conservation
- Format
- Document (PDF)
- Title
- Methionine sulfoxide reductase A (MsrA) and aging in the anoxia-tolerant freshwater turtle (Trachemys scripta).
- Creator
- Bruce, Lynsey Erin., Charles E. Schmidt College of Science, Department of Biological Sciences
- Abstract/Description
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The enzyme Methionine sulfoxide reductase A (MsrA) repairs oxidized proteins, and may act as a scavenger of reactive oxygen species (ROS), making it a potential therapeutic target for age-related neurodegenerative diseases. The anoxia-tolerant turtle offers a unique model to observe the effects of oxidative stress on a system that maintains neuronal function following anoxia and reoxygenation, and that ages without senescence. MsrA is present in both the mitochondria and cytosol, with protein...
Show moreThe enzyme Methionine sulfoxide reductase A (MsrA) repairs oxidized proteins, and may act as a scavenger of reactive oxygen species (ROS), making it a potential therapeutic target for age-related neurodegenerative diseases. The anoxia-tolerant turtle offers a unique model to observe the effects of oxidative stress on a system that maintains neuronal function following anoxia and reoxygenation, and that ages without senescence. MsrA is present in both the mitochondria and cytosol, with protein levels increasing respectively 3- and 4-fold over 4 hours of anoxia, and remaining 2-fold higher than basal upon reoxygenation. MsrA was knocked down in neuronally-enriched cell cultures via RNAi transfection. Propidium iodide staining showed no significant cell death during anoxia, but this increased 7-fold upon reoxygenation, suggesting a role for MsrA in ROS suppression during reperfusion. This is the first report in any system of MsrA transcript and protein levels being regulated by oxygen levels.
Show less - Date Issued
- 2010
- PURL
- http://purl.flvc.org/FAU/2683139
- Subject Headings
- Oxidation-reduction reaction, Proteins, Chemical modification, Turtles, Physiology, Oxygen, Physiological effect, Aging, Molecular aspects
- Format
- Document (PDF)
- Title
- Molecular mechanisms of neuroprotection in the anoxia tolerant freshwater turtle.
- Creator
- Kesaraju, Shailaja., Charles E. Schmidt College of Science, Department of Biological Sciences
- Abstract/Description
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Cardiac ischemia, stroke and some neurodegenerative disorders are all characterized by cell damage and death due to low oxygen levels. Comparative studies show that anoxia tolerant model systems present a unique opportunity to study "survival" instead of death in the complete absence of oxygen. The freshwater turtle (Trachemys scripta elegans) is unique in its ability to survive total oxygen deprivation for hours to days, as well as reoxygenation insult after anoxia. The broad objective of...
Show moreCardiac ischemia, stroke and some neurodegenerative disorders are all characterized by cell damage and death due to low oxygen levels. Comparative studies show that anoxia tolerant model systems present a unique opportunity to study "survival" instead of death in the complete absence of oxygen. The freshwater turtle (Trachemys scripta elegans) is unique in its ability to survive total oxygen deprivation for hours to days, as well as reoxygenation insult after anoxia. The broad objective of this study is to understand the modulation of key molecular mechanisms involving stress proteins and VEGF that offer neuroprotection and enhance cell survival in the freshwater turtle through anoxia and reoxygenation. In vivo analyses have shown that anoxia induced stress proteins (Hsp72, Hsp60, Grp94, Hsp60, Hsp27, HO-1); modest changes in the Bcl2/Bax ratio and no change in cleaved caspase-3 expression suggesting resistance to neuronal damage. These results were corroborated with immunohistochemical evidence indicating no damage in turtle brain when subjected to the stress of anoxia and A/R. To understand the functional role of Hsp72, siRNA against Hsp72 was utilized to knockdown Hsp72 in vitro (neuronally enriched primary cell cultures established from the turtle). Knockdown cultures were characterized by increased cell death associated with elevated ROS levels. Silencing of Hsp72 knocks down the expression of Bcl2 and increases the expression of Bax, thereby decreasing the Bcl2/Bax ratio. However, there was no increase in cytosolic Cytochrome c or the expression levels of cleaved Caspase-3. Significant increase in AIF was observed in the knockdown cultures that increase through anoxia and reoxygenation, suggesting a caspase independent pathway of cell death., Expression of the master regulator of hypoxia, HIF1 alpha and its target gene, VEGF, were analyzed at the mRNA and protein levels. The results showed no significant increase in HIF-1 alpha levels but anoxia VE GF The levels of stress proteins and VEGF returned to control levels during reoxygenation suggesting robust ROS protection mechanisms through reoxygenation. The present study thereby emphasizes Trachemys scripta as an advantageous model to examine anoxia and reoxygenation survival without major damage to the brain due to it's modulation of molecular mechanisms.
Show less - Date Issued
- 2008
- PURL
- http://purl.flvc.org/FAU/165943
- Subject Headings
- Turtles, Physiology, Anoxemia, Proteins, Chemical modification, Oxygen, Physiological effect, Molecular neurobiology
- Format
- Document (PDF)
- Title
- Neuropeptidergic and neuromorphological adaptations induced by behavioral sensitization to nicotine in a rodent model of vulnerability to nicotine relapse: abstinence-related negative effect.
- Creator
- Aydin, Cigdem., Charles E. Schmidt College of Science, Department of Biological Sciences
- Abstract/Description
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A rat model of novelty-seeking phenotype predicts vulnerability to nicotine relapse where locomotor reactivity to novelty is used to rank high (HR) versus low (LR) responders. This dissertation examines the neuropeptidergic and structural substrates of the expression of locomotor sensitization to a low dose nicotine challenge and associated social anxiety-like behavior following chronic intermittent nicotine exposure during adolescence in the LRHR phenotype. Data show the long-lasting nature...
Show moreA rat model of novelty-seeking phenotype predicts vulnerability to nicotine relapse where locomotor reactivity to novelty is used to rank high (HR) versus low (LR) responders. This dissertation examines the neuropeptidergic and structural substrates of the expression of locomotor sensitization to a low dose nicotine challenge and associated social anxiety-like behavior following chronic intermittent nicotine exposure during adolescence in the LRHR phenotype. Data show the long-lasting nature of behavioral sensitization to nicotine and abstinence-related social anxiety-like behavior in nicotine pre-trained HRs compared to saline pre-trained controls. Moreover, this behavior is accompanied by an imbalance between the brain antistress/antianxiety, i.e., neuropeptide Y (NPY), and stress, i.e., corticotrophin releasing factor (CRF) systems in the amygdala. Moreover, a deficit in NPY signaling marked with decreased NPY and increased NPY Y2 receptor (Y2R) mRNA levels is observed in the hip pocampus, along with mossy fiber reorganization in nicotine pre-trained HRs. Furthermore, a Y2R antagonist administered 1 wk of abstinence reverses these behavioral, molecular and morphological effects in nicotine-exposed HRs. Additionally, the role of amygdalar synaptic plasticity in longlasting social withdrawal is also investigated by assessing brain-derived neurotrophic factor (BDNF) and spinophilin mRNA levels in HRs following a behaviorally-sensitizing nicotine regimen. A persistent increase in BDNF and spinophilin mRNA levels in the basolateral amygdala (BLA) is observed in nicotine pre-trained HRs even across a long (3-wk) abstinence spanning into young adulthood. This strongly suggests BDNFmediated long-lasting neuroplasticity within the BLA that may regulate abstinence-related negative affect in HRs., Moreover, a cannabinoid receptor 1 (CB1R) antagonist, AM251 treatment during a short (1-wk) abstinence is ineffective in reversing social anxiety, nicotine-induced neuroplasticity and the neuropeptidergic changes in the amygdala, although it is effective in reversing the expression of locomotor sensitization to challenge nicotine even following a long (3-wks) abstinence. Furthermore, the identical AM251 treatment given during the late phase of a long (3-wk) abstinence further augments social withdrawal and associated BLA plasticity in nicotine pre-trained HRs. These findings implicate neuropeptidergic and neuroplastic changes in the hippocampus and the amygdala in vulnerability to the long-lasting behavioral effects of nicotine in the novelty-seeking phenotype.
Show less - Date Issued
- 2011
- PURL
- http://purl.flvc.org/FAU/3329828
- Subject Headings
- Rats as laboratory animals, Nicotine, Physiological effect, Habituation (Neuropsychology)
- Format
- Document (PDF)
- Title
- Novel molecular targets for genistein in prostate cancer cells.
- Creator
- Merchant, Kendra T., Charles E. Schmidt College of Science, Department of Biological Sciences
- Abstract/Description
-
Prostate cancer is the most common form of non-skin cancer and the second leading cause of cancer deaths within the United States. The five year survival rate has increased from 69% to 99% over the last 25 years for the local and regional disease, but has remained fairly low (approximately 34%) for the advanced disease. Therefore, current research is aimed at finding complementary or alternative treatments that will specifically target components of the signal transduction, cell-cycle and...
Show moreProstate cancer is the most common form of non-skin cancer and the second leading cause of cancer deaths within the United States. The five year survival rate has increased from 69% to 99% over the last 25 years for the local and regional disease, but has remained fairly low (approximately 34%) for the advanced disease. Therefore, current research is aimed at finding complementary or alternative treatments that will specifically target components of the signal transduction, cell-cycle and apoptosis pathways to induce cell death, with little or no toxic side effects to the patient. In this study we investigated the effect of genistein on expression levels of genes involved in these pathways. Genistein is a (4 , 5 , 7-trihydroxyisoflavone) is a major isoflavone constituent of soy that has been shown to inhibit growth proliferation and induce apoptosis in cancer cells. The mechanism of genistein-induced cell death and potential molecular targets for genistein in LNCaP prostate cancer c ells was investigated using several techniques. The chemosensitivity of genistein towards the prostate cancer cells was investigated using the ATP and MTS assays and apoptosis induction was determined using apoptosis and caspase assays. Several molecular targets were also identified using cDNA microarray and RT-PCR analysis. Our results revealed that genistein induces cell death in a time and dose-dependent manner and regulates expression levels of several genes involved in carcinogenesis and immunogenicity. Several cell cycle genes were down-regulated, including the mitotic kinesins, cyclins and cyclin dependent kinases, indicating that genistein is able to halt cell cycle progression through the regulation of genes involved in this process., Several members of the Bcl-2 family which are involved in apoptosis were also affected and a number of genes involved in immunogenicity were up-regulated including the DefB1 and HLA membrane receptors. The results of this study provide evidence of genistein's ability to inhibit growth proliferation and induce apoptosis and indicates its potential as an adjuvant in chemotherapy and immunotherapy.
Show less - Date Issued
- 2009
- PURL
- http://purl.flvc.org/FAU/192986
- Subject Headings
- Prostate, Cancer, Adjuvant treatment, Prostate, Cancer, Molecular aspects, Apoptosis, Molecular aspects, Phytochemicals, Physiological effect, Cellular signal transduction
- Format
- Document (PDF)
- Title
- Studies on the role of vitamin D in asthma patients from a South Florida pulmonary practice.
- Creator
- Munim, Amjad., Charles E. Schmidt College of Science, Department of Biological Sciences
- Abstract/Description
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Vitamin D insufficiency/deficiency is widespread in asthma, and epidemiological studies point to an association between low serum 25-hydroxyvitamin D level and poor asthma control and increased severity. In humans. Vitamin D is principally derived from sunlight induced cutaneous conversion of 7-dehydrocholesterol to vitamin D and oral supplementation. We sought to determine if established and chronic-persistent adult asthma patients from a South-Florida pulmonary patient population, with...
Show moreVitamin D insufficiency/deficiency is widespread in asthma, and epidemiological studies point to an association between low serum 25-hydroxyvitamin D level and poor asthma control and increased severity. In humans. Vitamin D is principally derived from sunlight induced cutaneous conversion of 7-dehydrocholesterol to vitamin D and oral supplementation. We sought to determine if established and chronic-persistent adult asthma patients from a South-Florida pulmonary patient population, with abundant sunshine availability and oral vitamin D supplementation exhibit vitamin D insufficiency/deficiency. A trend to vitamin D insufficiency was observed in approximately 65% of both adult asthma patients and apparently healthy (non-asthmatic) volunteers. . The transcription factors required for Th9 conversion, PU.1 and IRF-4, were down-regulated by vitamin D. The generation of Th9 cells was inhibited equally by vitamin D and dexamethasone when used alone, but the effect was additive when both steroids were used in combination. Our studies using non-specifically stimulated cells were extended by analyzing the effect of vitamin D on allergen specific stimulation. The response of CD4+ T cells obtained from the blood of house dust mite positive asthmatics was studied. House dust mite allergen elicited a classical Th2 phenotype response (IL-4, IL-5, IL-9, and IL-13 cytokine profile) and vitamin D effectively inhibited those key Th2 cytokines. We conclude that vitamin D appears to be of significant clinical benefit in our cohort of patients, i.e., established chronic adult human asthma, by down-regulating key immune cells including Th9, Th17, and Th2 involved in this disorder.
Show less - Date Issued
- 2013
- PURL
- http://purl.flvc.org/fcla/dt/3360948
- Subject Headings
- Vitamin D, Health aspects, Vitamin D, Physiological effect, Vitamin D, Therapeutic use, Vitamin D, Physiology, Vitamin D in human nutrition, Lungs, Etiology
- Format
- Document (PDF)