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Apoptosis

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Full-Text Articles in Medicine and Health Sciences

Possible Role Of Tetracyclines On Covid-19: Recycling Well-Known Old Drugs From The Shelf, Martin Gnoni, Raul Vasquez-Gararatti, Angel Mena May 2020

Possible Role Of Tetracyclines On Covid-19: Recycling Well-Known Old Drugs From The Shelf, Martin Gnoni, Raul Vasquez-Gararatti, Angel Mena

The University of Louisville Journal of Respiratory Infections

We are in the midst of a pandemic due to the novel coronavirus SARS-CoV-2. Innovative therapies are in the lookup around the world. Recently, chloroquine and hydroxychloroquine in addition to Azithromycin were proposed to be used in patients with severe disease even though strong evidence is lacking. We propose the use of tetracyclines in addition to anti-virals early in the curse of the disease in order to prevent the Cytokine Storm Syndrome associated with COVID-19 and prevent ARDS. The proposed mechanisms of tetracyclines are: 1) anti-apoptotic properties; 2) decrease the Myeloperoxidase and ROS releaser from immune cells; 3) decrease neutrophil ...


Anticancer Activity Of Thmpp: Downregulation Of Pi3k/ S6k1 In Breast Cancer Cell Line., Suresh Palanivel, Akshaya Murugesan, Olli Yli-Harja, Meenakshisundaram Kandhavelu Apr 2020

Anticancer Activity Of Thmpp: Downregulation Of Pi3k/ S6k1 In Breast Cancer Cell Line., Suresh Palanivel, Akshaya Murugesan, Olli Yli-Harja, Meenakshisundaram Kandhavelu

Articles, Abstracts, and Reports

Breast cancer is the most common cancer that majorly affects female. The present study is focused on exploring the potential anticancer activity of 2-((1, 2, 3, 4-Tetrahydroquinolin-1-yl) (4 methoxyphenyl) methyl) phenol (THMPP), against human breast cancer. The mechanism of action, activation of specific signaling pathways, structural activity relationship and drug-likeness properties of THMPP remains elusive. Cell proliferation and viability assay, caspase enzyme activity, DNA fragmentation and FITC/Annexin V, AO/EtBr staining, RT-PCR, QSAR and ADME analysis were executed to understand the mode of action of the drug. The effect of THMPP on multiple breast cancer cell lines (MCF-7 ...


Evaluating The Anti-Cancer Efficacy Of A Synthetic Curcumin Analog On Human Melanoma Cells And Its Interaction With Standard Chemotherapeutics, Krishan Parashar, Siddhartha Sood, Ali Mehaidli, Colin Curran, Caleb Vegh, Christopher Nguyen, Christopher Pignanelli, Jianzhang Wu, Guang Liang, Yi Wang, Siyaram Pandey Mar 2020

Evaluating The Anti-Cancer Efficacy Of A Synthetic Curcumin Analog On Human Melanoma Cells And Its Interaction With Standard Chemotherapeutics, Krishan Parashar, Siddhartha Sood, Ali Mehaidli, Colin Curran, Caleb Vegh, Christopher Nguyen, Christopher Pignanelli, Jianzhang Wu, Guang Liang, Yi Wang, Siyaram Pandey

Medical Student Research Symposium

Melanoma is the leading cause of skin-cancer related deaths in North America. Metastatic melanoma is difficult to treat and chemotherapies have limited success. Furthermore, chemotherapies lead to toxic side effects due to nonselective targeting of normal cells. Curcumin is a natural product of Curcuma longa (turmeric) and has been shown to possess anti-cancer activity. However, due to its poor bioavailability and stability, natural curcumin is not an effective cancer treatment. We tested synthetic analogs of curcumin that are more stable. One of these derivatives, Compound A, has shown significant anti-cancer efficacy in colon, leukemia, and triple-negative inflammatory breast cancer cells ...


Antiproliferative And Apoptotic Effects Of Proteins From Black Seeds (Nigella Sativa) On Human Breast Mcf-7 Cancer Cell Line, Yamna Khursid, Basir Syed, Shabana U. Simjee, Obaid Beg, Aftab Ahmed Jan 2020

Antiproliferative And Apoptotic Effects Of Proteins From Black Seeds (Nigella Sativa) On Human Breast Mcf-7 Cancer Cell Line, Yamna Khursid, Basir Syed, Shabana U. Simjee, Obaid Beg, Aftab Ahmed

Pharmacy Faculty Articles and Research

Background

Nigella sativa (NS), a member of family Ranunculaceae is commonly known as black seed or kalonji. It has been well studied for its therapeutic role in various diseases, particularly cancer. Literature is full of bioactive compounds from NS seed. However, fewer studies have been reported on the pharmacological activity of proteins. The current study was designed to evaluate the anticancer property of NS seed proteins on the MCF-7 cell line.

Methods

NS seed extract was prepared in phosphate-buffered saline (PBS), and proteins were precipitated using 80% ammonium sulfate. The crude seed proteins were partially purified using gel filtration chromatography ...


Optimal Control With Manf Treatment Of Photoreceptor Degeneration, Erika T. Camacho, Suzanne Lenhart, Luis A. Melara, M. Cristina Villalobos, Stephen Wirkus Jan 2020

Optimal Control With Manf Treatment Of Photoreceptor Degeneration, Erika T. Camacho, Suzanne Lenhart, Luis A. Melara, M. Cristina Villalobos, Stephen Wirkus

Mathematical and Statistical Sciences Faculty Publications and Presentations

People afflicted with diseases such as retinitis pigmentosa and age-related macular degeneration experience a decline in vision due to photoreceptor degeneration, which is currently unstoppable and irreversible. Currently there is no cure for diseases linked to photoreceptor degeneration. Recent experimental work showed that mesencephalic astrocyte-derived neurotrophic factor (MANF) can reduce neuron death and, in particular, photoreceptor death by reducing the number of cells that undergo apoptosis. In this work, we build on an existing system of ordinary differential equations that represent photoreceptor interactions and incorporate MANF treatment for three experimental mouse models having undergone varying degrees of photoreceptor degeneration. Using ...


Perivascular Macrophages In The Neonatal Macaque Brain Undergo Massive Necroptosis After Simian Immunodeficiency Virus Infection, Diana G. Bohannon, Yueying Wang, Colin H. Reinhart, Julian B. Hattler, Jiangtao Luo, Hamid R. Okhravi, Jianshui Zhang, Qingsheng Li, Marcelo J. Kuroda, Woong-Ki Kim Jan 2020

Perivascular Macrophages In The Neonatal Macaque Brain Undergo Massive Necroptosis After Simian Immunodeficiency Virus Infection, Diana G. Bohannon, Yueying Wang, Colin H. Reinhart, Julian B. Hattler, Jiangtao Luo, Hamid R. Okhravi, Jianshui Zhang, Qingsheng Li, Marcelo J. Kuroda, Woong-Ki Kim

Virology Papers

We previously showed that rhesus macaques neonatally infected with simian immunodeficiency virus (SIV) do not develop SIV encephalitis (SIVE) and maintain low brain viral loads despite having similar plasma viral loads compared to SIV-infected adults. We hypothesize that differences in myeloid cell populations that are the known target of SIV and HIV in the brain contribute to the lack of neonatal susceptibility to lentivirus-induced encephalitis. Using immunohistochemistry and immunofluorescence microscopy, we examined the frontal cortices from uninfected and SIV-infected infant and adult macaques (n = 8/ea) as well as adults with SIVE (n = 4) to determine differences in myeloid cell ...


Gasdermins In Apoptosis: New Players In An Old Game., Corey Rogers, Emad S. Alnemri Dec 2019

Gasdermins In Apoptosis: New Players In An Old Game., Corey Rogers, Emad S. Alnemri

Department of Biochemistry and Molecular Biology Faculty Papers

Apoptosis is a form of programmed cell death (PCD) that plays critical physiological roles in removing superfluous or dangerous cell populations that are unneeded or threatening to the health of the host organism. Although the molecular pathways leading to activation of the apoptotic program have been extensively studied and characterized starting in the 1970s, new evidence suggests that members of the gasdermin superfamily are novel pore-forming proteins that augment apoptosis by permeabilizing the mitochondria and participate in the final stages of the apoptotic program by inducing secondary necrosis/pyroptosis. These findings may explain outstanding questions in the field such as ...


Junctophilin-2 Protects Cardiomyocytes Against Palmitate-Induced Injury, Xiaoyun Ji Dec 2019

Junctophilin-2 Protects Cardiomyocytes Against Palmitate-Induced Injury, Xiaoyun Ji

Electronic Thesis and Dissertation Repository

Cardiac lipotoxicity may induce cardiomyocyte apoptosis, eventually leading to myocardial dysfunction and heart failure. This study investigated whether and how junctophilin-2 (JPH2) plays a role in palmitate-induced apoptosis in cardiomyocytes. Here, we found palmitate incubation reduced JPH2 protein levels, increased cytosolic Ca2+ and induced apoptosis in cardiomyocytes. JPH2 over-expression prevented the increased cytosolic Ca2+ and apoptosis in palmitate-stimulated cardiomyocytes. JPH2 over-expression also attenuated palmitate-induced CCAAT-enhancer-binding protein homologous protein (CHOP) expression and CHOP deletion alleviated palmitate-induced apoptosis. Furthermore, blocking Ca2+ release from ryanodine receptor-2 (RyR2) prevented palmitate-stimulated CHOP induction and apoptosis. Additionally, JPH2 silencing elevated cytosolic Ca2 ...


Nanosecond Pulsed Electric Fields Induce Endoplasmic Reticulum Stress Accompanied By Immunogenic Cell Death In Murine Models Of Lymphoma And Colorectal Cancer, Alessandra Rossi, Olga N. Pakhomova, Peter A. Mollica, Maura Casciola, Uma Mangalanathan, Andrei G. Pakhomov, Claudia Muratori Dec 2019

Nanosecond Pulsed Electric Fields Induce Endoplasmic Reticulum Stress Accompanied By Immunogenic Cell Death In Murine Models Of Lymphoma And Colorectal Cancer, Alessandra Rossi, Olga N. Pakhomova, Peter A. Mollica, Maura Casciola, Uma Mangalanathan, Andrei G. Pakhomov, Claudia Muratori

Bioelectrics Publications

Depending on the initiating stimulus, cancer cell death can be immunogenic or non-immunogenic. Inducers of immunogenic cell death (ICD) rely on endoplasmic reticulum (ER) stress for the trafficking of danger signals such as calreticulin (CRT) and ATP. We found that nanosecond pulsed electric fields (nsPEF), an emerging new modality for tumor ablation, cause the activation of the ER-resident stress sensor PERK in both CT-26 colon carcinoma and EL-4 lymphoma cells. PERK activation correlates with sustained CRT exposure on the cell plasma membrane and apoptosis induction in both nsPEF-treated cell lines. Our results show that, in CT-26 cells, the activity of ...


A Small Peptide Antagonist Of The Fas Receptor Inhibits Neuroinflammation And Prevents Axon Degeneration And Retinal Ganglion Cell Death In An Inducible Mouse Model Of Glaucoma, Anitha Krishnan, Andrew J. Kocab, David N. Zacks, Ann Marshak-Rothstein, Meredith Gregory-Ksander Sep 2019

A Small Peptide Antagonist Of The Fas Receptor Inhibits Neuroinflammation And Prevents Axon Degeneration And Retinal Ganglion Cell Death In An Inducible Mouse Model Of Glaucoma, Anitha Krishnan, Andrew J. Kocab, David N. Zacks, Ann Marshak-Rothstein, Meredith Gregory-Ksander

Open Access Articles

BACKGROUND: Glaucoma is a complex, multifactorial disease where apoptosis, microglia activation, and inflammation have been linked to the death of retinal ganglion cells (RGCs) and axon degeneration. We demonstrated previously that FasL-Fas signaling was required for axon degeneration and death of RGCs in chronic and inducible mouse models of glaucoma and that Fas activation triggered RGC apoptosis, glial activation, and inflammation. Here, we investigated whether targeting the Fas receptor with a small peptide antagonist, ONL1204, has anti-inflammatory and neuroprotective effects in a microbead-induced mouse model of glaucoma.

METHODS: Intracameral injection of microbeads was used to elevate intraocular pressure (IOP) in ...


Expression Of Mitochondrial Membrane-Linked Sab Determines Severity Of Sex-Dependent Acute Liver Injury, Sanda Win, Robert W. M. Min, Christopher Q. Chen, Jun Zhang, Yibu Chen, Meng Li, Ayako Suzuki, Manal F. Abdelmalek, Ying Wang, Mariam Aghajan, Filbert W. M. Aung, Anna Mae Diehl, Roger J. Davis, Tin A. Than, Neil Kaplowitz Sep 2019

Expression Of Mitochondrial Membrane-Linked Sab Determines Severity Of Sex-Dependent Acute Liver Injury, Sanda Win, Robert W. M. Min, Christopher Q. Chen, Jun Zhang, Yibu Chen, Meng Li, Ayako Suzuki, Manal F. Abdelmalek, Ying Wang, Mariam Aghajan, Filbert W. M. Aung, Anna Mae Diehl, Roger J. Davis, Tin A. Than, Neil Kaplowitz

University of Massachusetts Medical School Faculty Publications

SAB is an outer membrane docking protein for JNK mediated impaired mitochondrial function. Deletion of Sab in hepatocytes inhibits sustained JNK activation and cell death. Current work demonstrated that increasing SAB enhanced the severity of APAP liver injury. Female mice were resistant to liver injury and exhibited markedly decreased hepatic SAB protein expression versus males. The mechanism of SAB repression involved a pathway from ERalpha to p53 expression which induced miR34a-5p. miR34a-5p targeted the Sab mRNA coding region, repressing SAB expression. Fulvestrant or p53 knockdown decreased miR34a-5p and increased SAB in females leading to increased injury from APAP and TNF ...


Irisin Functions To Inhibit Malignant Growth Of Human Pancreatic Cancer Cells Via Downregulation Of The Pi3k/Akt Signaling Pathway., Deguo Zhang, Ping Zhang, Luan Li, Nan Tang, Fei Huang, Xianguo Kong, Xueying Tan, Guangjun Shi Sep 2019

Irisin Functions To Inhibit Malignant Growth Of Human Pancreatic Cancer Cells Via Downregulation Of The Pi3k/Akt Signaling Pathway., Deguo Zhang, Ping Zhang, Luan Li, Nan Tang, Fei Huang, Xianguo Kong, Xueying Tan, Guangjun Shi

Department of Medicine Faculty Papers

Introduction: Irisin is a newly identified cytokine that has gained increasing attention because of its potential therapeutic applications in metabolic diseases and human cancers. Recently, accumulating evidence indicates that irisin plays an important role in the development and metastasis of various tumors. The aim of this study was to evaluate the effects and underlying mechanisms of irisin on malignant growth of pancreatic cancer cells.

Materials and methods: The anti-proliferative effect of irisin was examined using the CCK-8 assay. Irisin-induced apoptosis was determined by the annexin V-FITC/PI staining assay. The effects of irisin on cell migration and invasion were assessed ...


Atf6alpha Impacts Cell Number By Influencing Survival, Death And Proliferation, Rohit B. Sharma, Jarin T. Snyder, Laura C. Alonso Sep 2019

Atf6alpha Impacts Cell Number By Influencing Survival, Death And Proliferation, Rohit B. Sharma, Jarin T. Snyder, Laura C. Alonso

Open Access Articles

BACKGROUND: A growing body of literature suggests the cell-intrinsic activity of Atf6alpha during ER stress responses has implications for tissue cell number during growth and development, as well as in adult biology and tumorigenesis [1]. This concept is important, linking the cellular processes of secretory protein synthesis and endoplasmic reticulum stress response with functional tissue capacity and organ size. However, the field contains conflicting observations, especially notable in secretory cell types like the pancreatic beta cell.

SCOPE OF REVIEW: Here we summarize current knowledge of the basic biology of Atf6alpha, along with the pleiotropic roles Atf6alpha plays in cell life ...


The Role Of Atf4 In Amyloid-Beta-Induced Neuronal Death., Gillian Petroff Aug 2019

The Role Of Atf4 In Amyloid-Beta-Induced Neuronal Death., Gillian Petroff

Electronic Thesis and Dissertation Repository

Alzheimer’s disease (AD) is partially characterized by excessive accumulation of amyloid-b (Ab) in the brain. Ab oligomers have greater toxicity than Ab fibrils and induce neuronal stress. The Integrated Stress Response (ISR) is activated in response to cellular stress and increases expression of activating transcription factor 4 (ATF4) and its target genes. Prolonged activation has been shown to induce aberrant cell death, and increased markers of the ISR have been found in the brains of AD patients. However, the exact mechanism of amyloid-b-induced death is largely unknown. We aimed to determine if Ab-induced neuronal death occurs through ATF4-mediated upregulation ...


The Effect Of Saturated Fatty Acid On The Expression Of Apoptotic And Fibrotic Proteins In Renal Tubular Epithelial Cells, Joya Sims, Xeuying Zhao, Doctor Of Physiology In Cardiology, Alyssa Cobbs Aug 2019

The Effect Of Saturated Fatty Acid On The Expression Of Apoptotic And Fibrotic Proteins In Renal Tubular Epithelial Cells, Joya Sims, Xeuying Zhao, Doctor Of Physiology In Cardiology, Alyssa Cobbs

Journal of Health Disparities Research and Practice

Diabetic Nephropathy, triggered by diabetes, is a kidney disease with severe health consequences and is a high economic burden. Literature suggests that the deterioration of kidney function correlates best with the degree of renal tubulointerstitial fibrosis. Proximal tubule epithelial cells can orchestrate renal fibrosis, as a result of fatty acid accumulation, also known as lipotoxicity. The objective of the study is to evaluate the effect of saturated fatty acid on renal tubular epithelial cells. Human kidney proximal tubule cells (HK-2) were cultured in 5% FBS/DMEM/streptomycin/Hepes and incubated at 37°C until cells are 90% confluent. Palmitic acid ...


Gene Expression Of Selected Apoptotic Markers In Human Oral Squamous Carcinoma Hsc-3 Cell Line Treated With Myrmecodia Pendans Plant Extract, Widya Lestari, Wan N A W Yusry, Siti H. Iskandar, Solachuddin J A Ichwan, Nining I. Irfan, Wastuti H. Suriyah Aug 2019

Gene Expression Of Selected Apoptotic Markers In Human Oral Squamous Carcinoma Hsc-3 Cell Line Treated With Myrmecodia Pendans Plant Extract, Widya Lestari, Wan N A W Yusry, Siti H. Iskandar, Solachuddin J A Ichwan, Nining I. Irfan, Wastuti H. Suriyah

Makara Journal of Health Research

Background: Myrmecodia pendans (M. pendans), or Sarang Semut, is an epiphyte with anticancer potential. It was recently reported that it induces apoptotic activity in the human oral squamous carcinoma (HSC-3) cell line. This study aimed to investigate the effect of M. pendans treated samples on the expression of apoptotic markers, Bax and Bcl-2. Methods: M. pendans was purchased from West Papua, Indonesia. The hypocotyl was dried thoroughly and then extracted aqueously. The apoptotic activity was detected via flow cytometry. Bax and Bcl-2 expression was analyzed by quantitative real-time polymerase chain reaction. Results: Results of our cell cycle analysis reveal that ...


Identifying Important Parameters In The Inflammatory Process With A Mathematical Model Of Immune Cell Influx And Macrophage Polarization, Marcella Torres, Jing Wang, Paul J. Yannie, Shobha Ghosh, Rebecca A. Segal, Angela M. Reynolds Jul 2019

Identifying Important Parameters In The Inflammatory Process With A Mathematical Model Of Immune Cell Influx And Macrophage Polarization, Marcella Torres, Jing Wang, Paul J. Yannie, Shobha Ghosh, Rebecca A. Segal, Angela M. Reynolds

Math and Computer Science Faculty Publications

In an inflammatory setting, macrophages can be polarized to an inflammatory M1 phenotype or to an anti-inflammatory M2 phenotype, as well as existing on a spectrum between these two extremes. Dysfunction of this phenotypic switch can result in a population imbalance that leads to chronic wounds or disease due to unresolved inflammation. Therapeutic interventions that target macrophages have therefore been proposed and implemented in diseases that feature chronic inflammation such as diabetes mellitus and atherosclerosis. We have developed a model for the sequential influx of immune cells in the peritoneal cavity in response to a bacterial stimulus that includes macrophage ...


Disruption Of Telomere Integrity And Dna Repair Machineries By Kml001 Induces T Cell Senescence, Apoptosis, And Cellular Dysfunctions, Dechao Cao, Juan Zhao, Lan N. Nguyen, Lam N. T. Nguyen, Sushant Khanal, Xindi Dang, Madison Schank, Bal K. Chand Thakuri, Xiao Y. Wu, Zheng D. Morrison, Mohamed El Gazzar, Yue Zou, Shunbin Ning, Ling Wang, Jonathan P. Moorman, Zhi Q. Yao May 2019

Disruption Of Telomere Integrity And Dna Repair Machineries By Kml001 Induces T Cell Senescence, Apoptosis, And Cellular Dysfunctions, Dechao Cao, Juan Zhao, Lan N. Nguyen, Lam N. T. Nguyen, Sushant Khanal, Xindi Dang, Madison Schank, Bal K. Chand Thakuri, Xiao Y. Wu, Zheng D. Morrison, Mohamed El Gazzar, Yue Zou, Shunbin Ning, Ling Wang, Jonathan P. Moorman, Zhi Q. Yao

ETSU Faculty Works

T cells in chronic viral infections are featured by premature aging with accelerated telomere erosion, but the mechanisms underlying telomere attrition remain unclear. Here, we employed human CD4 T cells treated with KML001 (a telomere-targeting drug) as a model to investigate the role of telomere integrity in remodeling T cell senescence. We demonstrated that KML001 could inhibit cell proliferation, cytokine production, and promote apoptosis via disrupting telomere integrity and DNA repair machineries. Specifically, KML001-treated T cells increased dysfunctional telomere-induced foci (TIF), DNA damage marker γH2AX, and topoisomerase cleavage complex (TOPcc) accumulation, leading to telomere attrition. Mechanistically, KML001 compromised telomere integrity ...


Small Molecule Kras Agonist For Mutant Kras Cancer Therapy., Ke Xu, Dongkyoo Park, Andrew T Magis, Jun Zhang, Wei Zhou, Gabriel L Sica, Suresh S Ramalingam, Walter J Curran, Xingming Deng Apr 2019

Small Molecule Kras Agonist For Mutant Kras Cancer Therapy., Ke Xu, Dongkyoo Park, Andrew T Magis, Jun Zhang, Wei Zhou, Gabriel L Sica, Suresh S Ramalingam, Walter J Curran, Xingming Deng

Articles, Abstracts, and Reports

BACKGROUND: Lung cancer patients with KRAS mutation(s) have a poor prognosis due in part to the development of resistance to currently available therapeutic interventions. Development of a new class of anticancer agents that directly targets KRAS may provide a more attractive option for the treatment of KRAS-mutant lung cancer.

RESULTS: Here we identified a small molecule KRAS agonist, KRA-533, that binds the GTP/GDP-binding pocket of KRAS. In vitro GDP/GTP exchange assay reveals that KRA-533 activates KRAS by preventing the cleavage of GTP into GDP, leading to the accumulation of GTP-KRAS, an active form of KRAS. Treatment of ...


Interaction Between The Bag1s Isoform And Hsp70 Mediates The Stability Of Anti-Apoptotic Proteins And The Survival Of Osteosarcoma Cells Expressing Oncogenic Myc., Victoria J. Gennaro, Helen Wedegaertner, Steven B. Mcmahon Mar 2019

Interaction Between The Bag1s Isoform And Hsp70 Mediates The Stability Of Anti-Apoptotic Proteins And The Survival Of Osteosarcoma Cells Expressing Oncogenic Myc., Victoria J. Gennaro, Helen Wedegaertner, Steven B. Mcmahon

Department of Biochemistry and Molecular Biology Faculty Papers

BACKGROUND: The oncoprotein MYC has the dual capacity to drive cell cycle progression or induce apoptosis, depending on the cellular context. BAG1 was previously identified as a transcriptional target of MYC that functions as a critical determinant of this cell fate decision. The BAG1 protein is expressed as multiple isoforms, each having an array of distinct biochemical functions; however, the specific effector function of BAG1 that directs MYC-dependent cell survival has not been defined.

METHODS: In our studies the human osteosarcoma line U2OS expressing a conditional MYC-ER allele was used to induce oncogenic levels of MYC. We interrogated MYC-driven survival ...


Induction Of Ampk Activation By N,N'-Diarylurea Fnd-4b Decreases Growth And Increases Apoptosis In Triple Negative And Estrogen-Receptor Positive Breast Cancers, Jeremy Johnson, Piotr G. Rychahou, Vitaliy M. Sviripa, Heidi L. Weiss, Chunming Liu, David S. Watt, B. Mark Evers Mar 2019

Induction Of Ampk Activation By N,N'-Diarylurea Fnd-4b Decreases Growth And Increases Apoptosis In Triple Negative And Estrogen-Receptor Positive Breast Cancers, Jeremy Johnson, Piotr G. Rychahou, Vitaliy M. Sviripa, Heidi L. Weiss, Chunming Liu, David S. Watt, B. Mark Evers

Markey Cancer Center Faculty Publications

Purpose

Triple negative breast cancer (TNBC) is the most lethal and aggressive subtype of breast cancer. AMP-activated protein kinase (AMPK) is a major energy regulator that suppresses tumor growth, and 1-(3-chloro-4-((trifluoromethyl)thio)phenyl)-3-(4-(trifluoromethoxy)phenyl)urea (FND-4b) is a novel AMPK activator that inhibits growth and induces apoptosis in colon cancer. The purpose of this project was to test the effects of FND-4b on AMPK activation, proliferation, and apoptosis in breast cancer with a particular emphasis on TNBC.

Materials and methods

(i) Estrogen-receptor positive breast cancer (ER+BC; MCF-7, and T-47D), TNBC (MDA-MB-231 and HCC-1806), and ...


Autophagic Flux Modulation By Wnt/Β-Catenin Pathway Inhibition In Hepatocellular Carcinoma, Lilia Turcios, Heather E. Chacon, Catherine Garcia, Pedro Eman, Virgilius Cornea, Jieyun Jiang, Brett T. Spear, Chunming Liu, David S. Watt, Francesc Marti, Roberto Gedaly Feb 2019

Autophagic Flux Modulation By Wnt/Β-Catenin Pathway Inhibition In Hepatocellular Carcinoma, Lilia Turcios, Heather E. Chacon, Catherine Garcia, Pedro Eman, Virgilius Cornea, Jieyun Jiang, Brett T. Spear, Chunming Liu, David S. Watt, Francesc Marti, Roberto Gedaly

Surgery Faculty Publications

Autophagy targets cellular components for lysosomal-dependent degradation in which the products of degradation may be recycled for protein synthesis and utilized for energy production. Autophagy also plays a critical role in cell homeostasis and the regulation of many physiological and pathological processes and prompts this investigation of new agents to effect abnormal autophagy in hepatocellular carcinoma (HCC). 2,5-Dichloro-N-(2-methyl-4-nitrophenyl) benzenesulfonamide (FH535) is a synthetic inhibitor of the Wnt/β-catenin pathway that exhibits anti-proliferative and anti-angiogenic effects on different types of cancer cells. The combination of FH535 with sorafenib promotes a synergistic inhibition of HCC and liver cancer stem ...


The Loss Of Atrx Increases Susceptibility To Pancreatic Injury And Oncogenic Kras In Female But Not Male Mice., Claire C Young, Ryan M Baker, Christopher J Howlett, Todd Hryciw, Joshua E Herman, Douglas Higgs, Richard Gibbons, Howard Crawford, Arthur Brown, Christopher L Pin Jan 2019

The Loss Of Atrx Increases Susceptibility To Pancreatic Injury And Oncogenic Kras In Female But Not Male Mice., Claire C Young, Ryan M Baker, Christopher J Howlett, Todd Hryciw, Joshua E Herman, Douglas Higgs, Richard Gibbons, Howard Crawford, Arthur Brown, Christopher L Pin

Paediatrics Publications

Background

Pancreatic ductal adenocarcinoma (PDAC) is the third leading cause of cancer death in North America, accounting for >30,000 deaths annually. Although somatic activating mutations in KRAS appear in 97% of PDAC patients, additional factors are required to initiate PDAC. Because mutations in genes encoding chromatin remodelling proteins have been implicated in KRAS-mediated PDAC, we investigated whether loss of chromatin remodeler ɑ-thalassemia, mental-retardation, X-linked (ATRX) affects oncogenic KRAS’s ability to promote PDAC. ATRX affects DNA replication, repair, and gene expression and is implicated in other cancers including glioblastomas and pancreatic neuroendocrine tumors. The hypothesis was that deletion of ...


Inflammatory Serine Proteases Play A Critical Role In The Early Pathogenesis Of Diabetic Cardiomyopathy., Mikhail A Kolpakov, Kunal Sikder, Amrita Sarkar, Shaswati Chaki, Sanket K Shukla, Xinji Guo, Zhao Qi, Carlos Barbery, Abdelkarim Sabri, Khadija Rafiq Jan 2019

Inflammatory Serine Proteases Play A Critical Role In The Early Pathogenesis Of Diabetic Cardiomyopathy., Mikhail A Kolpakov, Kunal Sikder, Amrita Sarkar, Shaswati Chaki, Sanket K Shukla, Xinji Guo, Zhao Qi, Carlos Barbery, Abdelkarim Sabri, Khadija Rafiq

Center for Translational Medicine Faculty Papers

BACKGROUND/AIMS: Diabetic cardiomyopathy (DCM) is characterized by structural and functional alterations that can lead to heart failure. Several mechanisms are known to be involved in the pathogenesis of DCM, however, the molecular mechanism that links inflammation to DCM is incompletely understood. To learn about this mechanism, we investigated the role of inflammatory serine proteases (ISPs) during the development of DCM.

METHODS: Eight weeks old mice with deletion of dipeptidyl peptidase I (DPPI), an enzyme involved in the maturation of major ISPs, and wild type (WT) mice controls were injected with streptozotocin (50 mg/kg for 5 days intraperitoneally) and ...


Targeting The Bcl-2 Family In B Cell Lymphoma., Clare M. Adams, Sean Clark-Garvey, Pierluigi Porcu, Christine M. Eischen Jan 2019

Targeting The Bcl-2 Family In B Cell Lymphoma., Clare M. Adams, Sean Clark-Garvey, Pierluigi Porcu, Christine M. Eischen

Department of Medical Oncology Faculty Papers

Although lymphoma is a very heterogeneous group of biologically complex malignancies, tumor cells across all B cell lymphoma subtypes share a set of underlying traits that promote the development and sustain malignant B cells. One of these traits, the ability to evade apoptosis, is essential for lymphoma development. Alterations in the Bcl-2 family of proteins, the key regulators of apoptosis, is a hallmark of B cell lymphoma. Significant efforts have been made over the last 30 years to advance knowledge of the biology, molecular mechanisms, and therapeutic potential of targeting Bcl-2 family members. In this review, we will highlight the ...


Anti-Human Interleukin(Il)-4 Clone 8d4-8 Cross-Reacts With Myosin-9 Associated With Apoptotic Cells And Should Not Be Used For Flow Cytometry Applications Querying Il-4 Expression, Robert Z. Harms, Kiana Borengasser, Vikas Kumar, Nora Sarvetnick Jan 2019

Anti-Human Interleukin(Il)-4 Clone 8d4-8 Cross-Reacts With Myosin-9 Associated With Apoptotic Cells And Should Not Be Used For Flow Cytometry Applications Querying Il-4 Expression, Robert Z. Harms, Kiana Borengasser, Vikas Kumar, Nora Sarvetnick

Journal Articles: Surgery

Interleukin(IL)-4 is produced by T cells and other leukocytes and is a critical mediator of monocyte and B cell responses. During routine flow cytometry panel validation for the investigation of intracellular cytokines, we observed unique IL-4 expression patterns associated with the widely available monoclonal antibody 8D4-8. Namely, IL-4 (8D4-8) expression was observed in the absence of cellular activation and enhanced following staurosporine exposure. Mass spectrometry analysis of immunoprecipitates from peripheral blood lymphocytes (PBL) revealed that 8D4-8 cross-reacts with the ubiquitous cytoskeletal protein myosin-9. We confirmed these results by western blotting immunoprecipitates, using immunofluorescence among staurosporine-treated Caco-2 cells, and ...


Caspases And Cancer: Connections Through Circular Dichroism Spectroscopy, Sarah M. Hethcox Jan 2019

Caspases And Cancer: Connections Through Circular Dichroism Spectroscopy, Sarah M. Hethcox

University Honors Program Theses

While excessive cell death inevitably leads to negative effects, the endurance of damaged cells in the presence of death signals can be equally detrimental to health. Apoptosis, or programmed cell death, is a highly regulated process in which cues from within or from outside a cell can trigger an irreversible sequence of signals that carry out cell destruction known as the apoptotic cascade. A group of enzymes called caspases play a vital role in this cascade with some participating as initiators and others acting as effectors of protein cleavage and intracellular breakdown. Although it is normal for the activity of ...


Neurogenesis In Neurodegenerative Diseases: Role Of Mfg-E8, C. Cheyuo, M. Aziz, P. Wang Jan 2019

Neurogenesis In Neurodegenerative Diseases: Role Of Mfg-E8, C. Cheyuo, M. Aziz, P. Wang

Journal Articles

No abstract provided.


Senecavirus A: Pathogenicity And Interactions With Host Cell Death Pathway, Maureen Hoch Vieira Fernandes Jan 2019

Senecavirus A: Pathogenicity And Interactions With Host Cell Death Pathway, Maureen Hoch Vieira Fernandes

Electronic Theses and Dissertations

Senecavirus A (SVA) is a positive sense single-strand RNA virus of the genus Senecavirus, family Picornaviridae. Senecavirus A is an emerging picornavirus of swine, which causes vesicular disease (VD) in pigs that is clinically indistinguishable from footand- mouth disease and other high consequence VDs of swine. There is evidence that SVA has been circulating in the US swine population since the late eighty’s, however, recently the virus emerged worldwide, and it has been associated with several VD outbreaks in pigs in many of the major swine producing countries. Despite the recent surge in the number of cases of SVA ...


The Effects Of Obesity, Chronic Stress, And Exercise On Pancreatic Health, Abigail Tice Jan 2019

The Effects Of Obesity, Chronic Stress, And Exercise On Pancreatic Health, Abigail Tice

Graduate Theses, Dissertations, and Problem Reports

Obesity is concomitant with hyperglycemic conditions, increased proinflammatory cytokines, and increased oxidative stress. Under hyperglycemia, thioredoxin interacting protein (TXNIP) is increased and causes increased oxidative stress and pancreatic b-cell apoptosis. Chronic stress is associated with increased glucocorticoid levels and a proinflammatory environment. The purpose of this study was to examine the effects of obesity, chronic stress, and exercise on pancreatic health.

Lean Zucker Rats (LZRs) and Obese Zucker Rats (OZRs) were randomly assigned to four groups: 1) sedentary controls (C: n=8 per); 2) unpredictable chronic mild stress (UCMS) (S: n=8); 3) exercise (E: n=8); and 4) combined ...