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Full-Text Articles in Life Sciences
Targeting The Brd4/Foxo3a/Cdk6 Axis Sensitizes Akt Inhibition In Luminal Breast Cancer, Jingyi Liu, Weijie Guo, Zhibing Duan, Lei Zeng, Yadi Wu, Yule Chen, Fang Tai, Yifan Wang, Yiwei Lin, Qiang Zhang, Yanling He, Jiong Deng, Rachel L. Stewart, Chi Wang, Pengnian Charles Lin, Saghi Ghaffari, B. Mark Evers, Suling Liu, Ming-Ming Zhou, Binhua P. Zhou, Jian Shi
Targeting The Brd4/Foxo3a/Cdk6 Axis Sensitizes Akt Inhibition In Luminal Breast Cancer, Jingyi Liu, Weijie Guo, Zhibing Duan, Lei Zeng, Yadi Wu, Yule Chen, Fang Tai, Yifan Wang, Yiwei Lin, Qiang Zhang, Yanling He, Jiong Deng, Rachel L. Stewart, Chi Wang, Pengnian Charles Lin, Saghi Ghaffari, B. Mark Evers, Suling Liu, Ming-Ming Zhou, Binhua P. Zhou, Jian Shi
Molecular and Cellular Biochemistry Faculty Publications
BRD4 assembles transcriptional machinery at gene super-enhancer regions and governs the expression of genes that are critical for cancer progression. However, it remains unclear whether BRD4-mediated gene transcription is required for tumor cells to develop drug resistance. Our data show that prolonged treatment of luminal breast cancer cells with AKT inhibitors induces FOXO3a dephosphorylation, nuclear translocation, and disrupts its association with SirT6, eventually leading to FOXO3a acetylation as well as BRD4 recognition. Acetylated FOXO3a recognizes the BD2 domain of BRD4, recruits the BRD4/RNAPII complex to the CDK6 gene promoter, and induces its transcription. Pharmacological inhibition of either BRD4/FOXO3a association or …
Collagen Prolyl 4-Hydroxylase 1 Is Essential For Hif-1Α Stabilization And Tnbc Chemoresistance, Gaofeng Xiong, Rachel L. Stewart, Jie Chen, Tianyan Gao, Timothy L. Scott, Luis M. Samayoa, Kathleen L. O'Connor, Andrew N. Lane, Ren Xu
Collagen Prolyl 4-Hydroxylase 1 Is Essential For Hif-1Α Stabilization And Tnbc Chemoresistance, Gaofeng Xiong, Rachel L. Stewart, Jie Chen, Tianyan Gao, Timothy L. Scott, Luis M. Samayoa, Kathleen L. O'Connor, Andrew N. Lane, Ren Xu
Markey Cancer Center Faculty Publications
Collagen prolyl 4-hydroxylase (P4H) expression and collagen hydroxylation in cancer cells are necessary for breast cancer progression. Here, we show that P4H alpha 1 subunit (P4HA1) protein expression is induced in triple-negative breast cancer (TNBC) and HER2 positive breast cancer. By modulating alpha ketoglutarate (α-KG) and succinate levels P4HA1 expression reduces proline hydroxylation on hypoxia-inducible factor (HIF) 1α, enhancing its stability in cancer cells. Activation of the P4HA/HIF-1 axis enhances cancer cell stemness, accompanied by decreased oxidative phosphorylation and reactive oxygen species (ROS) levels. Inhibition of P4HA1 sensitizes TNBC to the chemotherapeutic agent docetaxel and doxorubicin in xenografts and patient-derived …
“Do We Know Jack” About Jak? A Closer Look At Jak/Stat Signaling Pathway, Emira Bousoik, Hamidreza Montazeri Aliabadi
“Do We Know Jack” About Jak? A Closer Look At Jak/Stat Signaling Pathway, Emira Bousoik, Hamidreza Montazeri Aliabadi
Pharmacy Faculty Articles and Research
Janus tyrosine kinase (JAK) family of proteins have been identified as crucial proteins in signal transduction initiated by a wide range of membrane receptors. Among the proteins in this family JAK2 has been associated with important downstream proteins, including signal transducers and activators of transcription (STATs), which in turn regulate the expression of a variety of proteins involved in induction or prevention of apoptosis. Therefore, the JAK/STAT signaling axis plays a major role in the proliferation and survival of different cancer cells, and may even be involved in resistance mechanisms against molecularly targeted drugs. Despite extensive research focused on the …
Study Of Alpha Mangostin As A Chemoprotective Agent For Breast Cancer Via Activation Of The P53 Pathway, Vanessa Van Oost
Study Of Alpha Mangostin As A Chemoprotective Agent For Breast Cancer Via Activation Of The P53 Pathway, Vanessa Van Oost
Pence-Boyce STEM Student Scholarship
Breast carcinoma is the most frequently diagnosed cancer among women and causes over 400,000 deaths yearly worldwide. Current treatments such as chemotherapy are not selective for cancerous tissues but are destructive to normal tissues as well. This causes a range of side effects including pain, nausea, hair loss, weakness, and more. Inactivation of p53 is an almost universal mutation within human cancer cells. The ability to activate the p53 pathway which protects cells from tumor formation is lost in 50% of cancers. Due to the prevalence of this mutation, p53 is a uniquely valuable target for applied research. Alpha mangostin …
Tumors Interrupt Irf8-Mediated Dendritic Cell Development To Overcome Immune Surveillance, Melissa Ann Meyer
Tumors Interrupt Irf8-Mediated Dendritic Cell Development To Overcome Immune Surveillance, Melissa Ann Meyer
Arts & Sciences Electronic Theses and Dissertations
Tumors employ multiple mechanisms to evade immune surveillance. One mechanism is tumor-induced myelopoiesis, which expands immune suppressive granulocytes and monocytes to create a protective tumor niche shielding even antigenic tumors. As myeloid cells and immune-stimulatory conventional dendritic cells (cDCs) are derived from the same progenitors, it is logical that tumor-induced myelopoiesis might also impact cDC development. The cDC subset cDC1 is marked by CD141 in humans and CD103 or CD8α in mice. cDC1s act by cross presenting antigen and activating CD8+ T cells. Given these functions, CD103+ cDC1s can support anti-tumor CD8+ T cell responses. However, CD103+ cDC1 numbers are …
Electrophysiological Biomarkers Of Chemotherapy-Related Cognitive Impairment In Hematological Malignancy Patients, David E. Anderson
Electrophysiological Biomarkers Of Chemotherapy-Related Cognitive Impairment In Hematological Malignancy Patients, David E. Anderson
Theses & Dissertations
Multiple cancer populations frequently report cognitive impairment following treatment with chemotherapy agents (“chemo-brain”). Impaired neuropsychological performance is commonly reported in cognitive domains of attention and executive function. Understanding neural mechanisms underlying cognitive impairments is essential to developing prevention and rehabilitation strategies. Brain imaging studies frequently show chemotherapy-related impairments within the attentional control network, which is comprised of a constellation of cortical regions that govern reportedly impaired cognitive functions. In the current dissertation research, I developed a novel electrophysiology battery aimed at recording near-instantaneous neural activity within the attentional control network during cognitive task performance. Cancer patients diagnosed with hematological malignancy …
Investigating The Synergistic Effects Of Two Curcuminoids And Cisplatin On Cancer Cell Migration, Blaine Patty
Investigating The Synergistic Effects Of Two Curcuminoids And Cisplatin On Cancer Cell Migration, Blaine Patty
Mahurin Honors College Capstone Experience/Thesis Projects
Cisplatin is a common chemotherapy drug used to treat various cancers; however, it is relatively ineffective against many cancers, including several types of lung cancer. One approach that could improve cisplatin’s effect is to combine it with another drug that produces a synergistic response greater than either drug alone. Curcumin, a naturally occurring plant compound, has been investigated for synergisms in conjunction with cisplatin chemotherapy, but curcumin use is hampered by its low bioavailability. This project investigated whether two synthetic curcumin analogs, EF-24 and CLEFMA (curcuminoids), which have greater solubility than curcumin, could, when combined with cisplatin, decrease the migration …
Investigating The Synergistic Effects Of Two Curcuminoids And Cisplatin On Cancer Cell Reactive Oxygen Species, Matthew Millay
Investigating The Synergistic Effects Of Two Curcuminoids And Cisplatin On Cancer Cell Reactive Oxygen Species, Matthew Millay
Mahurin Honors College Capstone Experience/Thesis Projects
Cisplatin is an anticancer drug which can cause the production of reactive oxygen species (ROS) that kill cancer cells. Curcumin is a naturally occurring plant compound that can increase ROS levels in cancer cells and enhance the activity of cisplatin against cancer, but it exhibits poor bioavailability. We investigated whether two synthetic curcumin analogs (curcuminoids), EF-24 and CLEFMA, with anti-cancer activity and improved bioavailability, increased cisplatin’s effect against cancer. A spectrophotometric fluorescent ROS assay was used to determine if cisplatin, the curcuminoids or combinations of cisplatin with a curcuminoid affected the level of ROS in the A549 non-small cell lung …
Inhibition Of Insulin‐Like Growth Factor 1 Receptor Enhances The Efficacy Of Sorafenib In Inhibiting Hepatocellular Carcinoma Cell Growth And Survival, Fang Wang, Thomas Bank, George Malnassy, Maribel Arteaga, Na Shang, Annika Dalheim, Xianzhong Ding, Scott J. Cotler, Mitchell F. Denning, Michael I. Nishimura, Peter Breslin, Wei Qiu
Inhibition Of Insulin‐Like Growth Factor 1 Receptor Enhances The Efficacy Of Sorafenib In Inhibiting Hepatocellular Carcinoma Cell Growth And Survival, Fang Wang, Thomas Bank, George Malnassy, Maribel Arteaga, Na Shang, Annika Dalheim, Xianzhong Ding, Scott J. Cotler, Mitchell F. Denning, Michael I. Nishimura, Peter Breslin, Wei Qiu
Biology: Faculty Publications and Other Works
Hepatocellular carcinoma (HCC) is the fifth most common primary cancer and second largest cause of cancer‐related death worldwide. The first‐line oral chemotherapeutic agent sorafenib only increases survival in patients with advanced HCC by less than 3 months. Most patients with advanced HCC have shown limited response rates and survival benefits with sorafenib. Although sorafenib is an inhibitor of multiple kinases, including serine/threonine‐protein kinase c‐Raf, serine/threonine‐protein kinase B‐Raf, vascular endothelial growth factor receptor (VEGFR)‐1, VEGFR‐2, VEGFR‐3, and platelet‐derived growth factor receptor β, HCC cells are able to escape from sorafenib treatment using other pathways that the drug insufficiently inhibits. The aim …
Evaluation And Adaptation Of Live-Cell Interferometry For Applications In Basic, Translational, And Clinical Research, Kevin A. Leslie
Evaluation And Adaptation Of Live-Cell Interferometry For Applications In Basic, Translational, And Clinical Research, Kevin A. Leslie
Theses and Dissertations
Cell mass is an important indicator of cell health and status. A diverse set of techniques have been developed to precisely measure the masses of single cells, with varying degrees of technical complexity and throughput. Here, the development of a non-invasive, label-free optical technique, termed Live-Cell Interferometry (LCI), is described. Several applications are presented, including an evaluation of LCI’s utility for assessing drug response heterogeneity in patient-derived melanoma lines and the measurement of CD3+ T cell kinetics during hematopoietic stem cell transplantation. The characterization of mast cells during degranulation, the measurement of viral reactivation kinetics in Kaposi’s Sarcoma, and drug …