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Articles 1 - 26 of 26
Full-Text Articles in Biochemistry, Biophysics, and Structural Biology
Apoptosis Induction In Jurkat T-Lymphocytes By Proton Pump Inhibitors (Ppis), Shreya Murali, Randall Reif
Apoptosis Induction In Jurkat T-Lymphocytes By Proton Pump Inhibitors (Ppis), Shreya Murali, Randall Reif
Student Research Submissions
Apoptosis, commonly known as programmed cell death, constantly occurs in humans. As a cancer cell increases in acidity, apoptosis is induced. In healthy cells, proton pump proteins allow for H+ ions to permeate cellular membranes, regulating pH. However, proton pump inhibitors (PPIs), such as omeprazole, prevent proton movement. In previous studies, omeprazole induced cell death in Jurkat T lymphocytes; however, there was no confirmation of whether the cells died through apoptosis, or through necrosis, where the cell bursts. By using Annexin-V staining, the effects of omeprazole, dexlansoprazole, and esomeprazole on apoptosis induction can be measured. Cell death was observed …
The Role Of Myocardin In The Progression Of Non-Small Cell Lung Cancer, Soromidayo Akinsiku
The Role Of Myocardin In The Progression Of Non-Small Cell Lung Cancer, Soromidayo Akinsiku
Biotechnology Theses
Lung cancer is the leading cause of cancer-related mortality in the world and NSCLC accounts for 85% of all lung cancer cases. The mainstay of treatment for patients with stage I, II and IIIA NSCLC is surgery, followed by post-operative cisplatin-based chemotherapy. Additional adjuvant therapy involving targeted tyrosine kinase inhibitors has been in use, however even for the targeted therapy, resistance eventually develops. Therefore, there is a need for identifying novel targets for this life-threatening disease. Given that preliminary studies in Ikebe lab revealed that myocardin knockdown significantly promoted caspase-3 degradation, in this study, using myocardin siRNA, we investigated the …
Bis-Indolyl Compounds And The Induction Of Apoptosis In T98g Glioblastoma Multiforme Cells, Margot C. Brown
Bis-Indolyl Compounds And The Induction Of Apoptosis In T98g Glioblastoma Multiforme Cells, Margot C. Brown
Seton Hall University Dissertations and Theses (ETDs)
1,1-bis(3’idolyl)-1(aryl)methane compounds (BIM compounds) have been shown to have anti-cancer properties in colon cancer, bladder cancer, and leukemia cells. The purpose of this work was to determine if BIM compounds could be an effective treatment of glioblastoma multiforme. Sulforhodamine B (SRB) assays showed that 20µM of the BIM compounds could inhibit cellular proliferation of the T98G glioblastoma multiforme cell line over 72 hours. Then immunoblotting was used to analyze the molecular pathway induced by BIM compounds. An increase in the expression of both BAX and cleaved caspase 3 suggest BIM compounds activate programmed cell death, or apoptosis in glioblastoma cells. …
Exploring The Anticancer Mechanism Of Thienopyrazole Derivative Tpz-1 In Acute Myeloid Leukemia, Jessica Dyanne Hess
Exploring The Anticancer Mechanism Of Thienopyrazole Derivative Tpz-1 In Acute Myeloid Leukemia, Jessica Dyanne Hess
Open Access Theses & Dissertations
Anticancer drug discovery is a time and resource-consuming process for which exceedingly reliable and efficient modern approaches are needed. Phenotypic drug screenings can generate highly potent and innovative drug candidates; however, deconvolution of the drugâ??s target often presents significant barriers to drug development. To overcome this hurdle, we have originally combined in vitro and in silico analyses to uncover the molecular mechanism(s) driving the anticancer activity of the uniquely structured small molecule drug candidate, Tpz-1. Our study revealed that Tpz-1 is a multitargeted agent which induces the programmed death of HL-60 acute myeloid leukemia cells primarily through disruption of microtubule …
Investigative Mechanisms To Exploit Caspase-Induced Apoptosis Using Polymeric Nanogels, Francesca Edith Anson
Investigative Mechanisms To Exploit Caspase-Induced Apoptosis Using Polymeric Nanogels, Francesca Edith Anson
Doctoral Dissertations
Cysteine aspartate proteases (caspases) act as the molecular scissors of cell death, disintegrating diverse cellular components necessary for survival and growth via proteolysis. Caspases are tightly regulated through a myriad of mechanisms including proteolytic processing, structural changes, post-translational modifications and metal binding. Correspondingly, cancers have evolved numerous resistance and desensitization mechanisms upstream or within the caspase pathway to avoid death signals. These mechanisms are extremely diverse and are not fully understood however, the field overwhelming suggests caspase activity and caspase inhibition antagonism to be critical for efficacious cancer therapies. Accordingly, exploiting the role of caspases in apoptosis has become an …
A Noncanonical Function Of The Telomerase Rna Component In Human Embryonic Stem Cells, Kirsten Ann Brenner
A Noncanonical Function Of The Telomerase Rna Component In Human Embryonic Stem Cells, Kirsten Ann Brenner
Arts & Sciences Electronic Theses and Dissertations
Telomeres are stretches of TTAGGG nucleotide repeats located at the ends of linear chromosomes that shorten with progressive cell division and prevent genomic instability at the cost of limiting a cell’s capacity to proliferate. This limitation can be overcome by telomerase, a ribonucleoprotein complex that elongates telomeres via reverse-transcription of the template telomerase RNA component (TERC). Recent studies have reported potential functions of TERC outside of its role in telomere maintenance. These noncanonical functions of TERC are however poorly defined, and the molecular mechanisms and biological relevance behind such functions remain elusive. Here, we generated conditional TERC knock-out human embryonic …
Mechanisms Of Oriented Cell Division And Their Roles In Tissue Development, Evan Blake Dewey
Mechanisms Of Oriented Cell Division And Their Roles In Tissue Development, Evan Blake Dewey
Biology ETDs
Properly executed cell division is crucial to development, maintenance, and longevity of multicellular organisms. Defects in both symmetric and asymmetric divisions can lead to improper developmental patterning, as well as genomic instability, disruption of tissue homeostasis, and cancer. Our research focuses on how regulators orchestrate proper cell divisions. Mushroom Body Defect (Mud) is one such regulator, and here we describe how Mud is regulated via the Hippo signaling pathway kinase Warts (Wts), showing Wts phosphorylates Mud to enhance interaction with the polarity protein Partner of Inscuteable, promoting spindle orientation activity. We next focus on another regulator, Shortstop (Shot), describing a …
The Role Of The Cell-Surface Protease Tmprss13 In Colorectal Cancer, Fausto Alexander Varela
The Role Of The Cell-Surface Protease Tmprss13 In Colorectal Cancer, Fausto Alexander Varela
Wayne State University Dissertations
Colorectal cancer (CRC) is one of the most common and deadly cancers in both men and women in the United States. Extracellular proteolysis is often dysregulated in cancer including (CRC), resulting in degradation of extracellular matrix, as well as cleavage, processing, or shedding of cell adhesion molecules, growth factors, and cytokines. Several members of the type II transmembrane serine protease (TTSP) family have been shown to play critical roles in cancer progression; however, many family members have not yet been characterized in malignancy. We identified TMPRSS13 transcript to be upregulated in CRC compared to normal colon. This increase was confirmed …
The Caspase Cascade During Hibernation In The Golden-Mantled Ground Squirrel, Spermophilus Lateralis, Michael David Treat
The Caspase Cascade During Hibernation In The Golden-Mantled Ground Squirrel, Spermophilus Lateralis, Michael David Treat
UNLV Theses, Dissertations, Professional Papers, and Capstones
In several human pathologies like heart attack, stroke, neurodegenerative diseases, and autoimmune disorders, widespread cell death, or apoptosis, is a major cause of organ dysfunction and death. Hibernating golden-mantled ground squirrels, Spermophilus lateralis, experience numerous conditions during the winter that are known to be pro-apoptotic in other mammal systems (e.g. extreme hypothermia, ischemia and reperfusion, acidosis, increased reactive oxygen species, bone and muscle disuse). However, studies suggest that hibernators may invoke a protective phenotype to limit widespread cell damage and loss during the hibernation season. Could regulating apoptosis provide protection against the harmful conditions experienced during the hibernation season? Could …
Investigation Of Novel Functions For Dna Damage Response And Repair Proteins In Escherichia Coli And Humans, Benjamin A. Hilton
Investigation Of Novel Functions For Dna Damage Response And Repair Proteins In Escherichia Coli And Humans, Benjamin A. Hilton
Electronic Theses and Dissertations
Endogenous and exogenous agents that can damage DNA are a constant threat to genome stability in all living cells. In response, cells have evolved an array of mechanisms to repair DNA damage or to eliminate the cells damaged beyond repair. One of these mechanisms is nucleotide excision repair (NER) which is the major repair pathway responsible for removing a wide variety of bulky DNA lesions. Deficiency, or mutation, in one or several of the NER repair proteins is responsible for many diseases, including cancer. Prokaryotic NER involves only three proteins to recognize and incise a damaged site, while eukaryotic NER …
Rac1 And Ire1 Are Required To Prevent Early Loss Of Intestinal Homeostasis In Drosophila Melanogaster, Mauricio M. Ortega
Rac1 And Ire1 Are Required To Prevent Early Loss Of Intestinal Homeostasis In Drosophila Melanogaster, Mauricio M. Ortega
Dissertations, Masters Theses, Capstones, and Culminating Projects
No abstract available
Modulation Of Cell Death Signaling And Cell Proliferation By The Interaction Of Homoserine Lactones And Paraoxonase 2., Aaron Mackallan Neely
Modulation Of Cell Death Signaling And Cell Proliferation By The Interaction Of Homoserine Lactones And Paraoxonase 2., Aaron Mackallan Neely
Electronic Theses and Dissertations
Pseudomonas aeruginosa produces N-(3-oxododecanoyl)-homoserine lactone (C12) as a quorum-sensing molecule that functions to facilitate bacteria-bacteria communication. C12 has also been reported to affect many aspects of human host cell physiology, including evoking cell death in various types of cells. However, the signaling pathway(s) leading to C12-triggerred cell death remains unclear. To clarify cell death signaling induced by C12, we examined mouse embryonic fibroblasts (MEFs) deficient in one or more caspases. Our data indicate that, unlike most apoptotic inducers, C12 evokes a novel form of apoptosis in cells, probably through the direct induction of mitochondrial membrane permeabilization. Previous studies indicate that …
Direct Regulation Of Apoptosis By Linear Ubiqutin Chain Assembly Complex (Lubac) And Feedback Regulation Of Lubac Function By Caspases, Donghyun Joo
Dissertations & Theses (Open Access)
Tumor Necrosis Factor-alpha (TNF-α) is a cytokine that plays a role in various cellular processes such as proliferation, differentiation (mainly through NF-κB signaling) and death (via apoptosis signaling). Recently, linear ubiquitination by LUBAC (linear ubiquitin chain assembly complex) was reported to have a regulatory function in TNF-α mediated NF-κB activation. Although LUBAC is suggested to control not only NF-kB signaling but also the apoptosis pathway, the precise mechanism of apoptosis regulation remains unknown. Moreover, NF-κB and apoptosis pathways have opposed but fundamental functions for various cellular processes. Although these two pathways actively interplay to balance the death and survival, the …
Elucidating The Signalling Pathway Of Mer Tyrosine Kinase Receptor In Efferocytosis, Ekenedelichukwu Azu
Elucidating The Signalling Pathway Of Mer Tyrosine Kinase Receptor In Efferocytosis, Ekenedelichukwu Azu
Electronic Thesis and Dissertation Repository
Efferocytosis is the clearance of apoptotic cells and is necessary for homeostasis. Mer Tyrosine Kinase (MerTK) is a crucial efferocytic receptor whose loss is associated with chronic inflammatory diseases and autoimmunity. While previous studies have shown that MerTK mediates efferocytosis through a unique mechanism that requires integrins, MerTK signalling pathway remains unknown. Given this unusual internalization mechanism, I hypothesized that MerTK signals and engages integrins through a novel signalling pathway different from that used by other phagocytic receptors. Therefore, this study aimed to identify the signalling pathways activated by MerTK, utilizing conventional cell biology and pharmacological approaches.
I found that …
Branching Into Rnai: Synthesis, Characterization And Biology Of Branch And Hyperbranch Sirnas, Anthony Muriithi Maina
Branching Into Rnai: Synthesis, Characterization And Biology Of Branch And Hyperbranch Sirnas, Anthony Muriithi Maina
Seton Hall University Dissertations and Theses (ETDs)
The cancer epidemic continues to afflict millions of humans world-wide each year and despite a renewed hope with the development of new and improved forms of therapy, a cure for cancer remains an elusive goal. This is partly related to the rise of resilient forms of tumors that have evolved with resistance towards conventional chemotherapy and radiation treatments. Moreover, these non-specific therapeutic regimens are highly toxic, leading to severe immunosuppressive effects which poisons the body and compromises the road towards remission. In an effort to mitigate these limitations, cancer-targeting approaches are currently experiencing a renaissance in the translation of new …
Med13p Prevents Stress-Independent Mitochondrial Hyperfragmentation And Aberrant Apoptosis Activation In Saccharomyces Cerevisiae By Controlling Cyclin C Nuclear Localization, Svetlana Khakhina
Graduate School of Biomedical Sciences Theses and Dissertations
During aging, and as a result of environmental changes, cells are exposed to elevated levels of reactive oxygen species (ROS). High ROS levels induce lipid oxidation, protein aggregation, mitochondrial hyperfragmentation, DNA damage and programmed cell death (PCD), also called apoptosis. PCD is a highly regulated process and its misregulation has been linked to neurodegenerative diseases and cancer development.
Our hypothesis is that cyclin C plays a role in the initiation of apoptosis. During normal conditions, cyclin C represses the transcription of stress response genes (SRG). In response to stress, cyclin C translocates to the cytoplasm where it facilitates mitochondrial hyperfragmentation …
Modulation Of Bax/Bak Dependent Apoptosis By Sirtuin 3 And Mitochondrial Permeability Transition By Sirtuin 4, Manish Verma
Modulation Of Bax/Bak Dependent Apoptosis By Sirtuin 3 And Mitochondrial Permeability Transition By Sirtuin 4, Manish Verma
Graduate School of Biomedical Sciences Theses and Dissertations
Mitochondria are dynamic organelles that regulate a myriad of cellular functions, including energy production and metabolic regulation. Mitochondria are also a critical regulator of cell death signaling cascades modulating both apoptotic and necrotic cell death. However, what determines which cell death pathway is activated is still unclear. The mitochondrial/intrinsic pathway of apoptosis is dependent on the activation of pro-apoptotic proteins, Bax and Bak, which induce mitochondrial outer membrane permeabilization (MOMP). Once the integrity of outer mitochondrial membrane (OMM) is compromised, pro-apoptotic intermembrane space proteins like cytochrome c, Smac/Diablo, Omi/HtrA2 and AIF are released into the cytoplasm, which activates the post-mitochondrial …
Investigating The Interplay Between Protein Kinases And Caspases, Jacob P. Turowec
Investigating The Interplay Between Protein Kinases And Caspases, Jacob P. Turowec
Electronic Thesis and Dissertation Repository
The balance between cell survival and death is a crucial process in human development and tissue homeostasis, but is also misregulated in disease. In large part, apoptosis is controlled by caspases, a hierarchical series of cysteine aspartic acid proteases that demolish the cell by cleaving key structural and enzymatic proteins, but emerging paradigms have highlighted the ability of kinases to regulate caspase activity. One way in which kinases can control the progression of apoptosis is through phosphorylation of caspase substrates, which acts to prevent caspase cleavage of that target.
In this thesis, we develop new strategies to study this regulatory …
Regulation Of The Tumor Suppresser P53 And Survivin By Ras And Ral Gtpases:Implications For Malignant Transformation, Awet G. Tecleab
Regulation Of The Tumor Suppresser P53 And Survivin By Ras And Ral Gtpases:Implications For Malignant Transformation, Awet G. Tecleab
USF Tampa Graduate Theses and Dissertations
Abstract
Although the critical role of the small GTPases Ras and Ral in oncogenesis has been well documented, much remains to be investigated about the molecular mechanism by which these GTPases regulate malignant transformation. The work under this thesis made two major contributions to this field. The first is the discovery that K-Ras, RalA and/or RalB are required for the maintenance of the high levels of the anti-apoptotic protein survivin in some human cancer cells, and the second is the demonstration that down regulation of K-Ras, RalA and/or RalB, but not Raf-1 or Akt1/2, stabilizes the tumor suppressor p53 and …
Hdm2 Small-Molecule Inhibitors For Therapeutic Intervention In B-Cell Lymphoma, Angela Sosin
Hdm2 Small-Molecule Inhibitors For Therapeutic Intervention In B-Cell Lymphoma, Angela Sosin
Wayne State University Dissertations
Lymphomas frequently retain wild-type (wt) p53 function but overexpress HDM2, compromising p53 activity. Therefore, lymphoma is a suitable model for studying therapeutic value of disrupting HDM2-p53 association by small-molecule inhibitors (SMIs). HDM2 SMIs have been developed and are currently under various stages of preclinical and clinical investigation. This study examined various molecular mechanisms associated and biological effects of two different classes of HDM2 SMIs: the spiro-oxindoles (MI-219) and cis-imidazoline (Nutlin-3) in lymphoma cell lines and patient-derived B-lymphoma cells. Surprisingly, results revealed significant quantitative and qualitative differences between these two agents. At the molecular level, effect of Nutlin-3 was generally more …
Downregulation Of Pax2 Suppresses Ovarian Cancer Cell Growth, Huijuan Song
Downregulation Of Pax2 Suppresses Ovarian Cancer Cell Growth, Huijuan Song
Dissertations & Theses (Open Access)
PAX2 is one of nine PAX genes regulating tissue development and cellular differentiation in embryos. PAX2 promotes cell proliferation, oncogenic transformation, cell-lineage specification, migration, and survival. Unattenuated PAX2 has been found in several cancer types. We therefore sought to elucidate the role of PAX2 in ovarian carcinomas. We found that PAX2 was expressed in low-grade serous, clear cell, endometrioid and mucinous cell ovarian carcinomas, which are relatively chemoresistant compared to high grade serous ovarian carcinomas. Four ovarian cancer cell lines, RMUGL (mucinous), TOV21G (clear cell), MDAH-2774 (endometrioid) and IGROV1 (endometrioid), which express high-levels of PAX2, were used to study the …
Nanosecond Pulsed Electric Field Induction Of Programmed Cell Death Is Cell Type Dependent: An In Vitro Study, Wei Ren
Theses and Dissertations in Biomedical Sciences
Nanosecond pulsed electric fields (nsPEFs) present a novel and effective method for cancer ablation by eradicating the ubiquitous cancer hallmark of apoptosis evasion and enforcing cancer programmed cell death. To develop nsPEFs as an anticancer method, a comprehensive understanding of cell death mechanisms is required. The overall objective of this dissertation is to elucidate molecular mechanisms underlying effects of nsPEFs on E4 murine squamous cell carcinoma and human T-cell Jurkat clones that are wildtype, deficient in FADD (ΔFADD) and deficient in caspase-8 (ACas-8). The overall hypothesis is that nsPEFs eliminate cancer cells through activating caspase-dependent and caspase-independent programmed cell death …
Nanosecond Pulsed Electric Fields Induce A Mitochondria-Independent Apoptosis In B16f10 Melanoma Cells In Vitro, Wentia Elissa Ford
Nanosecond Pulsed Electric Fields Induce A Mitochondria-Independent Apoptosis In B16f10 Melanoma Cells In Vitro, Wentia Elissa Ford
Theses and Dissertations in Biomedical Sciences
Nanosecond pulsed electric fields (nsPEFs) are ultra-short pulses that induce direct electric field and biological effects that initiate apoptosis. Here the application of ten 300ns pulses ranging in electric fields from 12kV/cm-60kV/cm was administered to determine the effects on B16F10 melanoma cells evaluated by in vitro studies. Initial application of nsPEFs demonstrated apoptosis induction in an electric field- and pulse number-dependent manner measured by caspase activation that correlated with decrease in cell viability 24hr post pulse. In addition caspase activity was shown to be independent of calcium mobilization though ions may play a part in other aspects of apoptosis. The …
Nanosecond Pulsed Electric Field Effects On Cell Cycle And Apoptosis, Emily H. Hall
Nanosecond Pulsed Electric Field Effects On Cell Cycle And Apoptosis, Emily H. Hall
Theses and Dissertations in Biomedical Sciences
Apoptosis, programmed cell death, is a highly regulated and complex pathway essential for embryonic development, immune-system function and maintenance of tissue homeostasis where cells induce their own cell death. Cells undergoing apoptosis exhibit a distinctive phenotype characterized by maintenance of membrane integrity, cell shrinkage, phosphatidylserine (PS) externalization at the plasma membrane, caspase protease activation, DNA fragmentation, release of cytochrome c from the mitochondrion, and membrane blebbing. An important regulatory protein in the apoptotic pathway is p53. The p53 protein functions to modulate the cell cycle by arresting cells in the G1 and G 2 phases to repair DNA damage, and/or …
The Antitumor Agent, Arglabin-Dma, Preferentially Induces Apoptosis In Human Colon Tumor Cells, Sung Wook Kwon
The Antitumor Agent, Arglabin-Dma, Preferentially Induces Apoptosis In Human Colon Tumor Cells, Sung Wook Kwon
Theses and Dissertations in Biomedical Sciences
Arglabin-DMA, an analog of farnesyl pyrophosphate (FPP), reportedly inhibits farnesyltransferase (FTase) directly by competitively blocking the binding of Ras protein and its posttranslational modification, as suggested in previous studies. But, the mechanisms by which Arglabin-DMA inhibits tumor growth in vivo and in vitro are still relatively poorly characterized. To determine the mechanism by which this drug inhibits tumor growth, the effects of Arglabin-DMA in two human colon tumor cell lines (mutant K-ras HCT 116 and wild-type ras HT-29) were explored on cell proliferation, apoptosis, and cell cycle kinetics in vitro. In cell viability studies, we showed that Arglabin-DMA …
Induction Of Apoptosis In Human Prostate Cancer Cells By Resveratrol, Gary Zulfikar Morris
Induction Of Apoptosis In Human Prostate Cancer Cells By Resveratrol, Gary Zulfikar Morris
Chemistry & Biochemistry Theses & Dissertations
Recently attention has been brought to trans-resveratrol's {TR) anticancer activity, as determined through a number of cultured cancer cell models. This activity was attributed to TR behaving as an estrogen, and the orientation of TR' s hydroxyl groups. Based on this work it was of interest to determine whether TR would also be toxic in prostate cancer cells; if toxic, did TR induce necrosis or apoptosis in the cells; was it toxic through hormone mediated pathways; and were TR's hydroxyl groups responsible for its biological activity. To this end, cellular viability was assessed in two different prostate cancer cell …