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Structurally Related Flavonoids CT1 and CT3 Have Cytotoxic Activity On Triple Negative MDA-MB-231 Breast Cancer Cells By Targeting The MEK-ERK PathwayBelcher, Dewey A, III, Hackworth, Keagan Davis, Hagood, Kendra Lyndsey, Aramburo, Jacqueline, Umeh, chukuwunyere, Michaud, Kristen, Morgan, Cunningham, Garrett, Mudd, Torrenegra, Ruben, Gina, Mendez-Callejas, Palau, Victoria 07 April 2022 (has links)
Breast cancer is the most commonly diagnosed cancer in women with an estimated 287,850 cases in 2022. Approximately 684,000 deaths each year are associated with breast cancer across the world. Risk factors of breast cancer include increased estrogen exposure, family history of breast cancer, and environmental factors. Treatment of breast cancer is highly dependent on the presence of HER2, estrogen, and progesterone receptors. Breast cancers that present with increased receptors for estrogen, progesterone, and HER2 are typically the least aggressive and the easiest to treat. The percentage of cases in the United States associated with hormone receptor positive and HER-2 negative or positive are approximately 82%. Absence of receptors for estrogen, progesterone, and HER2 is known as triple negative breast cancer. In the United States, only about 10% of cases are associated with this form. However, it is considered the most aggressive and difficult to treat. Two emerging flavonoids known as CT1 and CT3 have shown cytotoxic activity against cell lines that represent some of the most common breast cancers: MCF7, MDA-MB-231, and SKBr3. CT1 and CT3 were extracted from the leaves of Chromolaena tacotana using a Soxhlet extractor and the compounds then underwent isolation and purification. The cells were then treated with CT1 or CT3 at concentrations of 5, 10, 20, 40 and 80 µM. MTT assays were then used to determine cell viability. MDA-MB-231, the most aggressive type of breast cancer cells, responded to both CT1 and CT3. The most profound cytotoxic effects of CT1 were seen with MCF7 and MDA-MB-231, while CT3 exhibited a greater toxicity against SKBr3 cells. Preliminary results indicate that CT1 and CT3 target the MEK-ERK signaling pathway. Further studies need to be completed to determine mechanistically how these compounds lead to receptor-independent toxicity.
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CT1 Cytotoxic Effects Against MDA-MB-231 EvasionHarding, Jeanna, Locke, Autumn, Akinbote, Olasunkanmi, Torrenegra, Ruben, Hagood, Kendra, Hackworth, Keagan, Palau, Victoria 25 April 2023 (has links)
Breast cancer is the most commonly occurring cancer worldwide, more than 2.26 million new cases occurred in women in 2020. Treatment for breast cancer is normally individualized to the patient based on the presence of different receptors, these receptors include HER2, progesterone, and estrogen. The presence of these receptors generally comes with an amenable prognosis, and a wide array of available treatments. There are types of breast cancers that do not have any of these receptors and tend to be much more aggressive. This type of cancer is called triple negative and represents about 10 percent of all breast cancer occurrences in the United States. The lack of receptors makes this type of cancer extremely difficult to treat and generally comes with a poor prognosis. In the present study, we used triple negative breast cancer cell line MDA-MB231, which is known to use actin remodeling to evade immunologic response. These cells were treated with two novel, structurally similar flavonoids, CT1 and CT3 derived from an ethnobotanically recognized species of Chromolaena.
CT1 and CT3 are extracted from the leaves of Chromolaena tacotana and then isolated and purified by chromatography. These compounds are used to treat cancer cells, at different concentrations that include 5, 10, 20, 40 and 80mM. MTT assays are used to determine their effect on cell viability, and the mechanism of action was analyzed by immunoblotting and TUNEL..
CT1 has a significantly stronger inhibitory effect on MDA-MB231 cell viability as compared to CT3. Preliminary analysis of the mechanism of action of CT1 has revealed that it neither follows the canonical intrinsic apoptotic pathway nor the extrinsic pathway that involves the activated form of c-JUN.
By up-regulating actin, triple negative breast cancer is able to evade immunologic response and cancer treatment. CT1, a novel flavonoid extracted from the leaves of Chromoleana tacotana has shown cytotoxic effects against triple negative breast cancer cells effectively bypassing the actin response. The mechanism of action is currently under study.
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The Cytotoxic Effects of Novel Flavonoids CT1 and CT3 on Breast Cancer Cells are Independent of the Presence of ER, PR, and HER2 ReceptorsHagood, Kendra, Hackworth, Keagan Davis, Umeh, Chukwunyere Ifeanyichukwu, Mudd, Garret, Michaud, Kristen, Cunningham, Morgan, Torrenegra, Ruben, Palau, Victoria 18 March 2021 (has links)
Introduction: Breast cancer is the most frequently diagnosed cancer found in women across the world, with an estimated 2.3 million new cases occurring in 2020. Additionally, over 684,000 deaths annually are attributed to breast cancer across the globe, making it the most common cause of cancer-related death in women. Further, treatment of breast cancer relies heavily on whether or not the cancer cells express estrogen, progesterone, and HER 2 receptors and this expression profile is often related to how quickly the cells grow and spread. In the United States, breast cancer cells that are hormone receptor positive and HER-2 negative make up about 73% of breast cancer cases, and cells that do not express any receptor and are known as triple negative, make up around 12% of cases (American Cancer Society, 2019). With that being said, CT1 and CT3 are novel compounds that have a cytotoxic effect on cell lines representing up to 85% of all breast cancer subtypes in the United States.
Methods: The leaves of Chromolaena tacotana that contains the flavonoids CT1 and CT3 were dried and placed in a soxhlet extractor using dichloromethane (CH2Cl2) to extract the chlorophyll. The flavonoids were extracted using a column chromatography eluted with trichloromethane (CHCl3), a 1:1 dilution of CHCl3:methanol and methanol, followed by isolation and purification of the compounds. Human breast cancer cell lines MCF7, MDA-MB-231, and SKBr3 were treated with CT1 and CT3 at concentrations of 5, 10, 20, 40 and 80 µM, followed by incubation for 24 hours. To assess cell viability an MTT assay was conducted by adding a 5-diphenyl-tetrazolium bromide reagent. The purple-colored formazan crystals were solubilized with acidified isopropanol, then analyzed by spectrophotometry.
Results: CT1 appeared to have the most cytotoxic effects compared to CT3 on MCF7. The opposite effect was observed for SKBr3 with CT3 showing the most effects as compared to CT1. No differential effect was observed on MDA-MB-231 since both CT1 and CT3 showed similar inhibition of cell viability.
Conclusions: The results from the different breast cancer cell lines SKBr3, MCF7, and MDA-MB-231 vary based on how they responded to CT1 and CT3. CT3 was more effective on SKBr3 than CT1. CT1 was more effective on MCF7 than CT3. For MDA-MB-231, both CT1 and CT3 showed similar significant cytotoxic effects. The antiproliferative effects of CT1 and CT3 appear to be concentration dependent on all cells studied. In view of the results from MDA-MB-231 triple negative breast cancer cell line, the cytotoxic effect of the flavonoids is not dependent on the presence of estrogen, progesterone, or HER2 receptors on breast cancer cells. Further studies on the mechanism of action are necessary to elucidate the molecular targets of CT1 and CT3.
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Vyobrazení Korejského poloostrova ve zpravodajství České televize v letech 2015-2020 / Representation of the Korean Peninsula in the news of Czech Television in years 2015-2020Kymličková, Petra January 2021 (has links)
The diploma thesis introduces the media image of Korean Peninsula within the news of Czech Television from 2015 to 2020. Korean Peninsula is an incredibly interesting area in terms of history, politics, economics, culture and international relations, including relations between the two Koreas and the Czech Republic. Czech Television was chosen to depict the two state units existing on the Korean Peninsula, which should - due to its specific position as a public service medium - provide viewers objective and impartial news. The theoretical part introduces the basic concepts and theories, focusing on the media public service broadcasting, media construction of reality, gatekeeping and agenda-setting. Considerable attention is also given to Czech Television itself and the Korean Peninsula, where among the other things, the key historical moments of this region are briefly explained and the media environment of both Koreas is overviewed closely. In the practical part, the collected data is analyzed, both quantitative and qualitative methods. Within the content analysis, the data are sorted by frequency, order, topic or tone of the content. It includes an analysis of the most frequent terms and their possible change during the time. The results and finding are summarized at the end of the work and...
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