Medicine and Health Sciences Commons^™

Acute Hypersensitivity Of Pluripotent Testicular Cancer-Derived Embryonal Carcinoma To Low-Dose 5-Aza Deoxycytidine Is Associated With Global Dna Damage-Associated P53 Activation, Anti-Pluripotency And Dna Demethylation, Bijesh K. Biswal, Maroun J. Beyrouthy, Mary P. Hever-Jardine, David Armstrong, Craig R. Tomlinson, Brock C. Christensen, Carmen J. Marsit, Michael J. Spinella

Dartmouth Scholarship

Human embryonal carcinoma (EC) cells are the stem cells of nonseminoma testicular germ cells tumors (TGCTs) and share remarkable similarities to human embryonic stem (ES) cells. In prior work we found that EC cells are hypersensitive to low nanomolar doses of 5-aza deoxycytidine (5-aza) and that this hypersensitivity partially depended on unusually high levels of the DNA methyltransferase, DNMT3B. We show here that low-dose 5-aza treatment results in DNA damage and induction of p53 in NT2/D1 cells. In addition, low-dose 5-aza results in global and gene specific promoter DNA hypomethylation. Low- dose 5-aza induces a p53 transcriptional signature distinct from …

Anti-Apoptotic Mcl-1 Localizes To The Mitochondrial Matrix And Couples Mitochondrial Fusion To Respiration, Rhonda Perciavalle

Theses and Dissertations (ETD)

MCL-1, an anti-apoptotic BCL-2 family member that is essential for the survival of multiple cell lineages, is also among the most highly amplified genes in cancer. Although MCL-1 is known to oppose cell death, precisely how it functions to promote survival of normal and malignant cells is poorly understood. Here, I report that different forms of MCL-1 reside in distinct mitochondrial locations and exhibit separable functions. On the outer mitochondrial membrane, a MCL-1 isoform acts like other anti-apoptotic BCL-2 molecules to antagonize apoptosis, whereas an amino-terminally truncated isoform of MCL-1 that is imported into the mitochondrial matrix is necessary to …

Effects Of Canola And Corn Oil Mimetic On Jurkat Cells, Gabriela Ion, Kayla Fazio, Juliana A. Akinsete, W. Elaine Hardman

Gabriela Ion

BACKGROUND: The Western diet is high in omega-6 fatty acids and low in omega-3 fatty acids. Canola oil contains a healthier omega 3 to omega 6 ratio than corn oil. Jurkat T leukemia cells were treated with free fatty acids mixtures in ratios mimicking that found in commercially available canola oil (7% α-linolenic, 30% linoleic, 54% oleic) or corn oil (59% linoleic, 24% oleic) to determine the cell survival or cell death and changes in expression levels of inflammatory cytokines and receptors following oil treatment. METHODS: Fatty acid uptake was assessed by gas chromatography. Cell survival and cell death were …

Consumption Of High Ω-3 Fatty Acid Diet Suppressed Prostate Tumorigenesis In C3(1) Tag Mice, Juliana Akinsete, Gabriela Ion, Theodore Witte, W. Hardman

Gabriela Ion

Prostate cancer incidence and mortality are high in the Western world and high ω-6/ω-3 PUFA in the Western diet may be a contributing factor. We investigated whether changing from a diet that approximates ω-6 fat content of the Western diet to a high ω-3 fat diet at adulthood might reduce prostate cancer risk. Female SV 129 mice that had consumed a high ω-6 diet containing corn oil for 2 weeks were bred with homozygous C3(1)Tag transgenic male mice. All male offspring were weaned to the corn oil diet (CO) until postpuberty when half of the male offspring were transferred to …

Thr 163 Phosphorylation Causes Mcl-1 Stabilization When Degradation Is Independent Of The Adjacent Gsk3-Targeted Phosphodegron, Promoting Drug Resistance In Cancer, Shanna K. Nifoussi, Julie A. Vrana, Aaron M. Domina, Alfredo De Biasio, Jingang Gui, Mark A. Gregory, Stephen R. Hann, Ruth W. Craig

Dartmouth Scholarship

The antiapoptotic Bcl-2 family member Mcl-1 is a PEST protein (containing sequences enriched in proline, glutamic acid, serine, and threonine) and is subject to rapid degradation via multiple pathways. Impaired degradation leading to the maintenance of Mcl-1 expression is an important determinant of drug resistance in cancer. Phosphorylation at Thr 163 in the PEST region, stimulated by 12-O-tetradecanoylphorbol acetic acid (TPA)-induced activation of extracellular signal-regulated kinase (ERK), is associated with Mcl-1 stabilization in BL41-3 Burkitt lymphoma cells. This contrasts with the observation that Thr 163 phosphorylation in normal fibroblasts primes glycogen synthase kinase (GSK3)-induced phosphorylation at Ser 159, producing a …

Latexin Is Down-Regulated In Hematopoietic Malignancies And Restoration Of Expression Inhibits Lymphoma Growth, Yi Liu, Dianna Howard, Kyle Rector, Carol Swiderski, Jason Brandon, Lawrence Schook, Jayesh Mehta, J. Scott Bryson, Subbarao Bondada, Ying Liang

Internal Medicine Faculty Publications

Latexin is a negative regulator of hematopoietic stem cell number in mice. Its dysregulated expression in other tumors led us to hypothesize that latexin may have tumor suppressor properties in hematological malignancies. We found that latexin was down-regulated in a variety of leukemia and lymphoma cell lines as well as in CD34+ cells from the blood and marrow of patients with these malignancies. 5-aza-2'-deoxycytodine treatment and bisulfite sequencing revealed hypermethylation of latexin promoter in tumor cells. Retrovirus-mediated latexin overexpression in A20 mouse lymphoma cells inhibited their in vitro growth by 16 fold and in vivo tumor volume by 2 fold. …

Immunologic Effects Of Gliotoxin In Rats: Mechanisms For Prevention Of Autoimmune Diabetes Mellitus, Honggang Liu, Susan H. Jackman, Henry Driscoll, Bryan Larsen

Susan H. Jackman

Various fungal products, such as gliotoxin (GT), have immunomodulating activity, a fact exploited previously by our group for prevention of autoimmune diabetes mellitus in BB/Wor rats. To understand better the immunologic effects in GT-treated rats, splenocytes from 65-day-old prediabetic diabetes-prone rats were phenotypically characterized after chronic treatment with GT. A parallel study examined the direct effects of GT on splenocyte preparations incubated with the mycotoxin. In vitro treatment of splenocytes with GT revealed relative decreases in CD4+ and increases in CD8+ T-cell subsets, whereas in vivo treatment with GT did not result in detectable alterations in relative CD4+ and CD8+ …

Immunologic Effects Of Gliotoxin In Rats: Mechanisms For Prevention Of Autoimmune Diabetes Mellitus, Honggang Liu, Susan H. Jackman, Henry Driscoll, Bryan Larsen

Henry Driscoll

Various fungal products, such as gliotoxin (GT), have immunomodulating activity, a fact exploited previously by our group for prevention of autoimmune diabetes mellitus in BB/Wor rats. To understand better the immunologic effects in GT-treated rats, splenocytes from 65-day-old prediabetic diabetes-prone rats were phenotypically characterized after chronic treatment with GT. A parallel study examined the direct effects of GT on splenocyte preparations incubated with the mycotoxin. In vitro treatment of splenocytes with GT revealed relative decreases in CD4+ and increases in CD8+ T-cell subsets, whereas in vivo treatment with GT did not result in detectable alterations in relative CD4+ and CD8+ …

Effects Of Canola And Corn Oil Mimetic On Jurkat Cells, Gabriela Ion, Kayla Fazio, Juliana A. Akinsete, W. Elaine Hardman

Elaine Hardman Ph.D.

BACKGROUND: The Western diet is high in omega-6 fatty acids and low in omega-3 fatty acids. Canola oil contains a healthier omega 3 to omega 6 ratio than corn oil. Jurkat T leukemia cells were treated with free fatty acids mixtures in ratios mimicking that found in commercially available canola oil (7% α-linolenic, 30% linoleic, 54% oleic) or corn oil (59% linoleic, 24% oleic) to determine the cell survival or cell death and changes in expression levels of inflammatory cytokines and receptors following oil treatment. METHODS: Fatty acid uptake was assessed by gas chromatography. Cell survival and cell death were …

Consumption Of High Ω-3 Fatty Acid Diet Suppressed Prostate Tumorigenesis In C3(1) Tag Mice, Juliana A. Akinsete, Gabriela Ion, Theodore R. Witte, W. Elaine Hardman

Elaine Hardman Ph.D.

Prostate cancer incidence and mortality are high in the Western world and high ω-6/ω-3 PUFA in the Western diet may be a contributing factor. We investigated whether changing from a diet that approximates ω-6 fat content of the Western diet to a high ω-3 fat diet at adulthood might reduce prostate cancer risk. Female SV 129 mice that had consumed a high ω-6 diet containing corn oil for 2 weeks were bred with homozygous C3(1)Tag transgenic male mice. All male offspring were weaned to the corn oil diet (CO) until postpuberty when half of the male offspring were transferred to …

Retinoic Acid Decreases Atf-2 Phosphorylation And Sensitizes Melanoma Cells To Taxol-Mediated Growth Inhibition, Ying Huang, Jennifer Minigh, Sarah Miles, Richard N. Niles

Richard M. Niles

Cutaneous melanoma is often resistant to chemo- and radiotherapy. This resistance has recently been demonstrated to be due, at least in part, to high activating transcription factor 2 (ATF-2) activity in these tumors. In concordance with these reports, we found that B16 mouse melanoma cells had higher levels of ATF-2 than immortalized, but non-malignant mouse melanocytes. In addition, the melanoma cells had a much higher amount of phosphorylated (active) ATF-2 than the immortalized melanocytes. In the course of determining how retinoic acid (RA) stimulates activating protein-1 (AP-1) activity in B16 melanoma, we discovered that this retinoid decreased the phosphorylation of …

Exogenous Alpha-Synuclein Induces Cell Death Related Proteins In C6 Oligodendrocyte-Like Cells Corresponding To Protein Expression Observed In Multiple System Atrophy, Derrick Samuel Hilton

Dissertations

Multiple System Atrophy (MSA) consists of three disorders; Autonomic Dysfunction, Cerebellar Ataxia, and Parkinsonism. In MSA, the protein Alpha-Synuclein (SNCA) appears in the central nervous system as misfolded protein aggregates primarily in oligodendrocytes. This dissertation reports the results from studies examining the effect of exogenous SNCA has on a cell model: C6 oligodendrocyte-like cells. Treated cells were evaluated using western blot and DNA microarray. In addition the expression of proteins was evaluated using immunocytochemistry in MSA patient tissue.

C6 cells were shown to take up SNCA when added to the media. SNCA also underwent a truncation when taken up by …

Visualizing Spatiotemporal Dynamics Of Apoptosis After G1 Arrest By Human T Cell Leukemia Virus Type 1 Tax And Insights Into Gene Expression Changes Using Microarray-Based Gene Expression Analysis., Mariluz Araínga, Hironobu Murakami, Yoko Aida

Journal Articles: Pharmacology & Experimental Neuroscience

BACKGROUND: Human T cell leukemia virus type 1 (HTLV-1) Tax is a potent activator of viral and cellular gene expression that interacts with a number of cellular proteins. Many reports show that Tax is capable of regulating cell cycle progression and apoptosis both positively and negatively. However, it still remains to understand why the Tax oncoprotein induces cell cycle arrest and apoptosis, or whether Tax-induced apoptosis is dependent upon its ability to induce G1 arrest. The present study used time-lapse imaging to explore the spatiotemporal patterns of cell cycle dynamics in Tax-expressing HeLa cells containing the fluorescent ubiquitination-based cell cycle …

Perk-Dependent Repression Of Mir-106b-25 Cluster Is Required For Er Stress-Induced Apoptosis., S. Gupta, D. E. Read, A. Deepti, K. Cawley, A. Gupta, D. Oommen, T. Verfaillie, S. Matus, Mary A. Smith, Justin L. Mott, P. Agostinis, C. Hetz, A. Samali

Journal Articles: Biochemistry & Molecular Biology

Activation of the unfolded protein response sensor PKR-like endoplasmic reticulum kinase (Perk) attenuates endoplasmic reticulum (ER) stress levels. Conversantly, if the damage is too severe and ER function cannot be restored, this signaling branch triggers apoptosis. Bcl-2 homology 3-only family member Bim is essential for ER stress-induced apoptosis. However, the regulatory mechanisms controlling Bim activation under ER stress conditions are not well understood. Here, we show that downregulation of the miR-106b-25 cluster contributes to ER stress-induced apoptosis and the upregulation of Bim. Hypericin-mediated photo-oxidative ER damage induced Perk-dependent cell death and led to a significant decrease in the levels of …

Proline-Rich Tyrosine Kinase 2 (Pyk2) Regulates Igf-I-Induced Cell Motility And Invasion Of Urothelial Carcinoma Cells, Marco Genua, Shi-Qiong Xu, Simone Buraschi, Stephen C. Peiper, Leonard G. Gomella, Antonio Belfiore, Renato V. Iozzo, Andrea Morrione

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

The insulin-like growth factor receptor I (IGF-IR) plays an essential role in transformation by promoting cell growth and protecting cancer cells from apoptosis. We have recently demonstrated that the IGF-IR is overexpressed in invasive bladder cancer tissues and promotes motility and invasion of urothelial carcinoma cells. These effects require IGF-I-induced Akt- and MAPK-dependent activation of paxillin. The latter co-localizes with focal adhesion kinases (FAK) at dynamic focal adhesions and is critical for promoting motility of urothelial cancer cells. FAK and its homolog Proline-rich tyrosine kinase 2 (Pyk2) modulate paxillin activation; however, their role in regulating IGF-IR-dependent signaling and motility in …

Function Of Insulin-Like Growth Factor Binding Protein 7 (Igfbp7) In Hepatocellular Carcinoma, Dong Chen

Theses and Dissertations

Title of Dissertation: FUNCTION OF INSULIN-LIKE GROWTH FACTOR BINDING PROTEIN 7(IGFBP7) IN HEPATOCELLULAR CARCINOMA By Dong Chen. Purpose: Hepatocellular carcinoma (HCC) is a highly virulent malignancy with no effective treatment, thus requiring the development of innovative and effective targeted therapies. The oncogene Astrocyte Elevated Gene-1 (AEG-1) plays a seminal role in hepatocarcinogenesis and profoundly downregulates Insulin-like Growth Factor Binding Protein-7 (IGFBP7). The present study focuses on analyzing potential tumor suppressor functions of IGFBP7 in HCC and the relevance of IGFBP7 downregulation in mediating AEG-1 function. Experimental Design: IGFBP7 expression was detected by immunohistochemistry in HCC tissue microarrays by real-time PCR …

Bim Mediates Imatinib-Induced Apoptosis Of Gastrointestinal Stromal Tumors: Translational Implications, David Reynoso

Dissertations & Theses (Open Access)

Gastrointestinal stromal tumors (GISTs) are oncogene-addicted cancers driven by activating mutations in the genes encoding receptor tyrosine kinases KIT and PDGFR-α. Imatinib mesylate, a specific inhibitor of KIT and PDGFR-α signaling, delays progression of GIST, but is incapable of achieving cure. Thus, most patients who initially respond to imatinib therapy eventually experience tumor progression, and have limited therapeutic options thereafter. To address imatinib-resistance and tumor progression, these studies sought to understand the molecular mechanisms that regulate apoptosis in GIST, and evaluate combination therapies that kill GISTs cells via complementary, but independent, mechanisms. BIM (Bcl-2 interacting mediator …

Essential Role Of Caveolin-3 In Adiponectin Signalsome Formation And Adiponectin Cardioprotection., Yajing Wang, Xiaoliang Wang, Jean-François Jasmin, Wayne Bond Lau, Rong Li, Yuexin Yuan, Wei Yi, Kurt Chuprun, Michael P. Lisanti, Walter J Koch, Erhe Gao, Xin-Liang Ma

Department of Emergency Medicine Faculty Papers

OBJECTIVE: Adiponectin (APN) system malfunction is causatively related to increased cardiovascular morbidity/mortality in diabetic patients. The aim of the current study was to investigate molecular mechanisms responsible for APN transmembrane signaling and cardioprotection.

METHODS AND RESULTS: Compared with wild-type mice, caveolin-3 knockout (Cav-3KO) mice exhibited modestly increased myocardial ischemia/reperfusion injury (increased infarct size, apoptosis, and poorer cardiac function recovery; P

CONCLUSIONS: Taken together, these results demonstrated for the first time that Cav-3 plays an essential role in APN transmembrane signaling and APN anti-ischemic/cardioprotective actions.

Identification Of Bovine Leukemia Virus Tax Function Associated With Host Cell Transcription, Signaling, Stress Response And Immune Response Pathway By Microarray-Based Gene Expression Analysis., Mariluz Araínga, Eri Takeda, Yoko Aida

Journal Articles: Pharmacology & Experimental Neuroscience

BACKGROUND: Bovine leukemia virus (BLV) is associated with enzootic bovine leukosis and is closely related to human T-cell leukemia virus type I. The Tax protein of BLV is a transcriptional activator of viral replication and a key contributor to oncogenic potential. We previously identified interesting mutant forms of Tax with elevated (TaxD247G) or reduced (TaxS240P) transactivation effects on BLV replication and propagation. However, the effects of these mutations on functions other than transcriptional activation are unknown. In this study, to identify genes that play a role in the cascade of signal events regulated by wild-type and mutant Tax proteins, we …

Decorin-Mediated Inhibition Of Colorectal Cancer Growth And Migration Is Associated With E-Cadherin In Vitro And In Mice., Xiuli Bi, Nicole M Pohl, Zhibin Qian, George R Yang, Yuan Gou, Grace Guzman, Andre Kajdacsy-Balla, Renato V Iozzo, Wancai Yang

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Previous studies have shown that decorin expression is significantly reduced in colorectal cancer tissues and cancer cells, and genetic deletion of the decorin gene is sufficient to cause intestinal tumor formation in mice, resulting from a downregulation of p21, p27(kip1) and E-cadherin and an upregulation of β-catenin signaling [Bi,X. et al. (2008) Genetic deficiency of decorin causes intestinal tumor formation through disruption of intestinal cell maturation. Carcinogenesis, 29, 1435-1440]. However, the regulation of E-cadherin by decorin and its implication in cancer formation and metastasis is largely unknown. Using a decorin knockout mouse model (Dcn(-/-) mice) and manipulated expression of decorin …

Mir-25 Targets Tnf-Related Apoptosis Inducing Ligand (Trail) Death Receptor-4 And Promotes Apoptosis Resistance In Cholangiocarcinoma., Nataliya Razumilava, Steve F. Bronk, Rory L. Smoot, Christian D. Fingas, Nathan W. Werneburg, Lewis R. Roberts, Justin L. Mott

Journal Articles: Biochemistry & Molecular Biology

It has been established that microRNA expression and function contribute to phenotypic features of malignant cells, including resistance to apoptosis. Although targets and functional roles for a number of microRNAs have been described in cholangiocarcinoma, many additional microRNAs dysregulated in this tumor have not been assigned functional roles. In this study, we identify elevated miR-25 expression in malignant cholangiocarcinoma cell lines as well as patient samples. In cultured cells, treatment with the Smoothened inhibitor, cyclopamine, reduced miR-25 expression, suggesting Hedgehog signaling stimulates miR-25 production. Functionally, miR-25 was shown to protect cells against TNF-related apoptosis-inducing ligand (TRAIL)-induced apoptosis. Correspondingly, antagonism of …

Evaluation Of The Role Of Oxidative Stress, Inflammation And Apoptosis In The Pulmonary And The Hepatic Toxicity Induced By Cerium Oxide Nanoparticles Following Intratracheal Instillation In Male Sprague-Dawley Rats, Siva Krishna Nalabotu

Theses, Dissertations and Capstones

The field of nanotechnology is rapidly progressing with potential applications in the automobile, healthcare, electronics, cosmetics, textiles, information technology, and environmental sectors. Nanomaterials are engineered structures with at least one dimension of 100 nanometers or less. With increased applications of nanotechnology, there are increased chances of exposure to manufactured nanomaterials. Recent reports on the toxicity of engineered nanomaterials have given scientific and regulatory agencies concerns over the safety of nanomaterials. Specifically, the Organization for Economic Co-operation and Development (OECD) has identified fourteen high priority nanomaterials for study. Cerium oxide (CeO2) nanoparticles are one among the high priority group. Recent data …

Consumption Of High Ω-3 Fatty Acid Diet Suppressed Prostate Tumorigenesis In C3(1) Tag Mice, Juliana A. Akinsete, Gabriela Ion, Theodore R. Witte, W. Elaine Hardman

Biochemistry and Microbiology

Prostate cancer incidence and mortality are high in the Western world and high ω-6/ω-3 PUFA in the Western diet may be a contributing factor. We investigated whether changing from a diet that approximates ω-6 fat content of the Western diet to a high ω-3 fat diet at adulthood might reduce prostate cancer risk. Female SV 129 mice that had consumed a high ω-6 diet containing corn oil for 2 weeks were bred with homozygous C3(1)Tag transgenic male mice. All male offspring were weaned to the corn oil diet (CO) until postpuberty when half of the male offspring were transferred to …

Optical Imaging For Determination Of Apoptosis Medicated Therapeutic Efficacy, Kaijun Zhang, Bishnuhari Paudyal, Neil Mehta, Brian Gray, Koon Y. Pak, Eric Wickstrom, Mathew L Thakur

Department of Radiology Faculty Papers

No abstract provided.

Effects Of Long-Term Passive Smoking On The Vascular Endothelial Growth Factor And Apoptosis Marker Expression In The Retina And Choroid: An Experimental Study, Sema Dündar, Fati̇h Özcura, İbrahi̇m Meteoğlu, Mehmet Erkut Kara

Turkish Journal of Medical Sciences

To investigate the effects of smoking, reported as a risk factor for age related macular degeneration (ARMD), on the vascular endothelial growth factor (VEGF) expression and apoptosis in the retina and choroid of rats. Materials and methods: This experimental study included 38 Sprague-Dawley rats. The rats were randomly assigned into 4 groups. Groups 1 (males) and 2 (females) were exposed to smoke beginning on day 21 after birth, whereas groups 3 (males) and 4 (females) were not exposed to smoke. At the end of the fourth month, the right eyes of all of the rats were enucleated. Immunohistochemical analysis was …

Effect Of Intravitreal Octreotide Acetate Injection On Retinal Neovascularization, Morphology, And Apoptotic Cell Death In An Oxygen-Induced Retinopathy Mouse Model, Fatma Seli̇n Kaya, İmren Akkoyun, Asuman Ni̇han Haberal Reyhan, Atti̇la Dağdevi̇ren, Gürsel Yilmaz, Si̇bel Oto, Yonca Akova

Turkish Journal of Medical Sciences

To investigate the effect of octreotide acetate on neovascularization, retinal structures, and apoptotic cell death in an oxygen-induced retinopathy (OIR) mouse model. Materials and methods: A total of 26 C57BL/6J mice were exposed to 75 ± 2% oxygen from postnatal day 7 to 12. On day 12, 12 mice (group C) were injected with 0.1 µg intravitreal octreotide acetate (IVOA) and 14 mice (group D) were injected with 0.05 µg IVOA, in the right eye. The contralateral eyes were injected with 1 µL isotonic saline (control group, group B). Four mice were used as negative controls (group A). Neovascularization was …

Proteasome Regulation Of Caspase-8: Significance In Cancer, Michael Vincent Fiandalo

Theses and Dissertations--Molecular and Cellular Biochemistry

Anti-tumor therapeutic strategies based on combinations of chemotherapeutic agents with a death inducing ligand such as TNF-α Related Apoptosis Inducing Ligand (TRAIL), are directed towards selective and effective cancer cell apoptosis and enhanced therapeutic response. We previously demonstrated that proteasome inhibition sensitizes TRAIL resistant prostate cancer cells to TRAIL-mediated apoptosis via stabilization of the active p18 subunit of initiator caspase-8. The present study investigated the functional link between caspase-8 and the proteasome, by analyzing the impact of caspase-8 ubiquitination and proteasomal degradation on the outcomes of the extrinsic apoptosis pathway in cancer cells. Caspase-8 ubiquitination status was assessed by polyubiquitin …

Regulation Of Neuronal Cell Death By Bh3-Only Proteins, Arindam P. Ghosh

All ETDs from UAB

Apoptosis in metazoan organisms plays critical roles in normal development, tissue homeostasis and immunity, and its disturbed regulation leads to many pathological states, including cancer, autoimmunity, infection and degenerative disorders. Apoptosis can be triggered by the engagement of `death receptors' of the tumor necrosis factor receptor family on the cell surface or by diverse intracellular signals that act upon the BCL2 (B-cell CLL/lymphoma 2) protein family, which controls the integrity of the mitochondrial outer membrane through the complex interactions of family members. Both the pathways lead to cellular demolition by dedicated proteases termed caspases. Different BH3-only proteins (or combinations of …

Cross-Talk Between Nfkb And The Pi3-Kinase/Akt Pathway Can Be Targeted In Primary Effusion Lymphoma (Pel) Cell Lines For Efficient Apoptosis, Azhar Hussain, Saeeda O. Ahmed, Maqbool Ahmed, Omar S. Khan, Sally Al Abdul Mohsen, Leonidas C. Platanias, Khawla S. Al-Kuraya, Shahab Uddin

Centre for Regenerative Medicine & Stem Cell Research

Background: A number of constitutively activated signaling pathways play critical roles in the survival and growth of primary effusion lymphoma cells (PELs) including NFkB and PI3/AKT kinase cascades. NFkBis constitutively activated in a number of malignancies, including multiple myeloma, Burkitt’s lymphoma and diffuse large cell B-cell lymphoma. However, its role in primary effusion lymphoma has not been fully explored.
Methodology/Principal Findings: We used pharmacological inhibition and gene silencing to define the role of NFkB in growth and survival of PEL cells. Inhibition of NFkB activity by Bay11-7085 resulted in decreased expression of p65 in the nuclear compartment as detected by …

The Role Of St6gal-I Sialylation In Fas (Cd95) Death Receptor Function And Tumorigenesis, Amanda F. Swindall

All ETDs from UAB

The golgi glycosyltransferase, ST6Gal-I, adds a negatively-charged sialic acid in an alpha-2-6 linkage to N-linked glycans. ST6Gal-I is upregulated in many cancers, and is associated with increased metastasis and poor patient prognosis. ST6Gal-I expression has been shown to be driven by oncogenic-ras signaling. However, mechanistic details of the role ST6Gal-I plays in tumor initiation and progression are not well defined. Historically, studies have focused on contributions of ST6Gal-I to the malignant cell phenotypes of migration and invasion. Emerging evidence including studies contained in this dissertation have begun to elucidate a role for ST6Gal-I as a regulator of apoptotic signaling by …