Medicine and Health Sciences Commons^™

Cumulative Exposure To Solar Ultraviolet A & B Increases Apoptosis Of Peripheral Blood Cutaneous Lymphocyte Antigen (Cla)+ T-Lymphocytes In Outdoor Workers, Afif Nurul Hidayati, Saut Sahat Pohan, Widodo J. Pudjirahardjo, Isaac Effendy

Journal of General - Procedural Dermatology & Venereology Indonesia

Background: Exposure to ultraviolet A & B (UVA-UVB) plays a role in the survival of human life, but it may cause negative effects, such as immunosuppression and skin cancer. The effect of solar UVA-UVB exposure on apoptosis (Bax/Bcl-2 ratio) of peripheral blood cutaneous lymphocyte antigen (CLA)+ T-lymphocyte; the immune competent cells in the skin, has not been investigated. Apoptosis of peripheral blood CLA+ Tlymphocyte affects its function; which serves as the skin's resistance and is involved in infectious diseases, skin inflammation, and malignancies. This study observed the effect of solar UVA-UVB to apoptosis (Bax/Bcl2 ratio) of peripheral blood CLA+ …

Targeting The Stat5 Pathway In Ph+ Acute Lymphoblastic Leukemia, Valentina Minieri, Marco De Dominici, Marja T. Nevalainen, Bruno Calabretta

Department of Cancer Biology Faculty Papers

No abstract provided.

Understanding The Role Of Epstein - Barr Virus Encoded Rnas (Ebers) In Ebv Biology, Waqar Ahmed

Medical Education Dissertations

Epstein Barr virus (EBV) is an oncogenic herpesvirus aetiologically linked to several human malignancies of epithelial and lymphoid origins. An accumulating body of data indicates that EBV-infected cells release specific viral components in nano-vesicles called exosomes. Epstein-Barr virus encoded RNAs (EBER1 and EBER2) are two highly abundant, non-protein coding RNAs that are consistently expressed in all EBV latency programs. Conventional in situ hybridization (ISH) studies have indicated that these RNAs are typically found in the nucleus of EBV-infected cells. Recently, it was reported that EBERs are released out of the infected cells. However, the mechanism by which these highly abundant …

Influences Of Porphyromonas Gingivalis On The Viability Of Esophageal Cancer Cells., Muddasir Mohammed

Electronic Theses and Dissertations

A recent study demonstrated an association between the Porphyromonas gingivalis (Pg)infection and the progression of ESCC (Gao et al., 2016). However, how Pg infection affects the nature of ESCC remains unknown. We examined the effects of Pg on the proliferation and chemotherapy drug-induced apoptosis of ESCC cells and elucidated the signaling molecules involved in these processes. Method: Apoptosis and cell proliferation were tested using Flow cytometry and Tetrazolium salt based proliferation assays respectively. Western Blot was utilized to detect the protein expression. CDK2 and Cyclin E were knocked down in the ESCC cells through transfection. Unpaired T-test and …

Il-24 Promotes Apoptosis Through Camp-Dependent Pka Pathways In Human Breast Cancer Cells, Leah Persaud, Jason Mighty, Xuelin Zhong, Ashleigh Francis, Marifer Mendez, Hilal Muharam, Stephen M. Redenti, Dibash Das, Bertal Huseyin Aktas, Moira Sauane

Publications and Research

Interleukin 24 (IL-24) is a tumor-suppressing protein, which inhibits angiogenesis and induces cancer cell-specific apoptosis. We have shown that IL-24 regulates apoptosis through phosphorylated eukaryotic initiation factor 2 alpha (eIF2α) during endoplasmic reticulum (ER) stress in cancer. Although multiple stresses converge on eIF2α phosphorylation, the cellular outcome is not always the same. In particular, ER stress-induced apoptosis is primarily regulated through the extent of eIF2α phosphorylation and activating transcription factor 4 (ATF4) action. Our studies show for the first time that cyclic adenosine monophosphate (cAMP)-dependent protein kinase A (PKA) activation is required for IL-24-induced cell death in a variety of …

A Reversible Carnitine Palmitoyltransferase (Cpt1) Inhibitor Offsets Chronic Lymphocytic Leukemia Cell Proliferation, Elena Gugiatti, Claudya Tenca, Silvia Ravera, Marina Fabbi, Fabio Ghiotto, Zbigniew Darzynkiewicz, Silvia Bruno

NYMC Faculty Publications

No abstract provided.

3,3'-Diindolylmethane Enhances Apoptosis In Docetaxel-Treated Breast Cancer Cells By Generation Of Reactive Oxygen Species., Susan Lanza-Jacoby, Guanjun Cheng

Department of Surgery Faculty Papers

CONTEXT: A major problem in the treatment of cancer is the development of toxic side effects and resistance to chemotherapy. The use of plant compounds to overcome resistance and prevent toxicity is a potential strategy for treatment.

OBJECTIVE: We evaluated whether 3,3'-diindolylmethane (DIM) enhanced the sensitivity of breast cancer cells to docetaxel (DOC).

MATERIALS AND METHODS: MDA-MB231 and Sk-BR-3 cells were treated with and without 25 or 50 µM of DIM and 1 nM of DOC for 48 and 72 h, respectively. MTT assay was used to measure cell survival. Apoptosis and intracellular reactive oxygen species (ROS) were determined by …

Transcriptional Up-Regulation Of Relaxin-3 By Nur77 Attenuates Β-Adrenergic Agonist-Induced Apoptosis In Cardiomyocytes., Xiaohua You, Zhifu Guo, Fang Cheng, Bing Yi, Fan Yang, Xinzhu Liu, Ni Zhu, Xianxian Zhao, Guijun Yan, Xin-Liang Ma, Jianxin Sun

Center for Translational Medicine Faculty Papers

The relaxin family peptides have been shown to exert several beneficial effects on the heart, including anti-apoptosis, anti-fibrosis, and anti-hypertrophy activity. Understanding their regulation might provide new opportunities for therapeutic interventions, but the molecular mechanism(s) coordinating relaxin expression in the heart remain largely obscured. Previous work demonstrated a role for the orphan nuclear receptor Nur77 in regulating cardiomyocyte apoptosis. We therefore investigated Nur77 in the hopes of identifying novel relaxin regulators. Quantitative real-time PCR (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA) data indicated that ectopic expression of orphan nuclear receptor Nur77 markedly increased the expression of latexin-3 (RLN3), but not relaxin-1 …

Evaluation Of Survivin Gene Expression As A Prognostic Biomarker In Pediatric B-Acute Lymphoblastic Leukemia, Ayman Azzam, Fathia Elbassal, Mahmoud A. El-Hawy, Nagwan Y. Saleh, Samar M. Kamal Elden

Menoufia Medical Journal

Objective The aim of this study was to evaluate the level of survivin mRNA expression in Egyptian patients with acute pediatric lymphoblastic leukemia and to outline any significant relation between the level of survivin expression and the clinical and hematological findings in those patients. Background Survivin, a unique member of the inhibitor of apoptosis protein family, plays an important role in regulating both apoptosis and cell division and was found to be highly expressed in various kinds of tumors. Patients and methods Survivin expression was quantitatively determined by real-time (RT) PCR in 30 newly diagnosed acute lymphoblastic leukemia (B-ALL) pediatric …

Imetelstat, A Telomerase Inhibitor, Is Capable Of Depleting Myelofibrosis Stem And Progenitor Cells, Xiaoli Wang, Cing Siang Hu, Bruce Petersen, Jiajing Qiu, Fei Ye, Fei Huang, Ronald Hoffman

NYMC Faculty Publications

Clinical trials of imetelstat therapy have indicated that this telomerase inhibitor might have disease-modifying effects in a subset of patients with myelofibrosis (MF). The mechanism by which imetelstat induces such clinical responses has not been clearly elucidated. Using in vitro hematopoietic progenitor cell (HPC) assays and in vivo hematopoietic stem cell (HSC) assays, we examined the effects of imetelstat on primary normal and MF HSCs/HPCs. Treatment of CD34(+) cells with imetelstat reduced the numbers of MF but not cord blood HPCs (colony-forming unit-granulocyte/macrophage, burst-forming unit-erythroid, and colony-forming unit-granulocyte/erythroid/macrophage/megakaryocyte) as well as MF but not normal CD34(+)ALDH(+) cells irrespective of the …

The Comparison Of Effects Of Synthetic And Natural Arachidin-3 On Rotavirus Infected Cells, Rebekah Napier-Jameson

Electronic Theses and Dissertations

Rotavirus (RV) causes severe, life-threatening diarrhea, in infants, young children and immunocompromised adults. There are several effective vaccines for young children, however they are strain specific and are not protective against many RV strains in developing countries. Therefore, it is important to investigate anti-RV therapeutic agents. Our laboratory has shown arachidin-1 (A1) and arachadin-3 (A3) significantly inhibit RV replication in two cell lines, however the molecular mechanism(s) of action are not known. A synthetic molecule of A3 (sA3) has been produced, but its’ antiviral effects have not been examined. Our hypothesis is that sA3 produces the same effects on RV-infected …

A Novel Fas-Binding Outer Membrane Protein And Lipopolysaccharide Of Leptospira Interrogans Induce Macrophage Apoptosis Through The Fas/Fasl-Caspase-8/-3 Pathway., Peng Du, Shi-Jun Li, David M. Ojcius, Kai-Xuan Li, Wei-Lin Hu, Xu'ai Lin, Ai-Hua Sun, Jie Yan

All Dugoni School of Dentistry Faculty Articles

Leptospira interrogans is the major causative agent of leptospirosis, an emerging, globally spreading zoonotic infectious disease. The pathogen induces macrophage apoptosis, but the molecular basis and mechanism remain unknown. In the present study, we found that L. interrogans caused apoptosis of phagocytosis-inhibited macrophages, and the product of the L. interrogans LB047 gene (Lep-OMP047) was the unique protein captured by mouse and human Fas proteins. The recombinant expressed Lep-OMP047 (rLep-OMP047) strongly bound mouse and human Fas proteins with equilibrium association constant (K

Complement Factor D Protects Mice From Ethanol-Induced Inflammation And Liver Injury., Rebecca L Mccullough, Megan R Mcmullen, Megan M Sheehan, Kyle L Poulsen, Sanjoy Roychowdhury, Dian J Chiang, Michele T Pritchard, Juan Caballeria, Laura E Nagy

Articles, Abstracts, and Reports

Complement plays a crucial role in microbial defense and clearance of apoptotic cells. Emerging evidence suggests complement is an important contributor to alcoholic liver disease. While complement component 1, Q subcomponent (C1q)-dependent complement activation contributes to ethanol-induced liver injury, the role of the alternative pathway in ethanol-induced injury is unknown. Activation of complement via the classical and alternative pathways was detected in alcoholic hepatitis patients. Female C57BL/6J [wild type (WT)], C1q-deficient ( C1qa

Luteolin Decreases Egfr-Mediated Cell Proliferation And Induces Apoptosis In Glioblastoma Cell Lines., David M. Anson, Rachel M. Wilcox, Eric Huseman, Trevor Stump, Robert L. Paris, Belinda O. Darkwah, Stacy Lin, Andrea O Adegoke, Rebecca J. Gryka, Denise Simpson, Samson Amos

Pharmaceutical Sciences Faculty Publications

Glioblastomas are a subtype of gliomas, which are the most aggressive and deadly form of brain tumours. The epidermal growth factor receptor (EGFR) is over-expressed and amplified in glioblastomas. Luteolin is a common bioflavonoid found in a variety of fruits and vegetables. The aim of the present study was to explore the molecular and biological effects of luteolin on EGF-induced cell proliferation and the potential of luteolin to induce apoptosis in glioblastoma cells. In vitro cell viability assays demonstrated that luteolin decreased cell proliferation in the presence or absence of EGF. Immunoblots revealed that luteolin decreased the protein expression levels …

Cordycepin Induces Apoptosis Of Human Ovarian Cancer Cells By Inhibiting Ccl5-Mediated Akt/Nf-Κb Signaling Pathway, Zhen Yang Cui, Soo Jung Park, Eunbi Jo, In-Hu Hwang, Kyung-Bok Lee, Sung-Woo Kim, Dae Joon Kim, Jong Chun Joo, Seok Hoon Hong, Min-Goo Lee, Ik-Soon Jang

School of Medicine Publications and Presentations

The chemokine, CCL5, is a key mediator for the recruitment of immune cells into tumors and tissues. Akt/NF-κB signaling is significantly activated by CCL5. However, the role of NF-κB inactivation in apoptosis induced by negative regulation of CCL5 remains unclear. Here, we analyzed the effect of cordycepin on NF-κB activity in SKOV-3 cells and found that cordycepin-mediated inhibition of NF-κB signaling induced apoptosis in SKOV-3 cells via the serial activation of caspases. In addition, immune-blotting analysis showed that CCL5 is highly expressed in SKOV-3 cells. In addition to activating caspases, we show that, cordycepin prevents TNF-α-induced increase in CCL5, Akt, …

Till Death Do Us Part: The Marriage Of Autophagy And Apoptosis., Katrina F Cooper

Rowan-Virtua School of Osteopathic Medicine Departmental Research

Autophagy is a widely conserved catabolic process that is necessary for maintaining cellular homeostasis under normal physiological conditions and driving the cell to switch back to this status quo under times of starvation, hypoxia, and oxidative stress. The potential similarities and differences between basal autophagy and stimulus-induced autophagy are still largely unknown. Both act by clearing aberrant or unnecessary cytoplasmic material, such as misfolded proteins, supernumerary and defective organelles. The relationship between reactive oxygen species (ROS) and autophagy is complex. Cellular ROS is predominantly derived from mitochondria. Autophagy is triggered by this event, and by clearing the defective organelles effectively, …

The State Of The Translational Chaperone Icd-1 During Apoptosis In Caenorhabditis Elegans, Kyle Cicalese

Senior Honors Projects, 2010-2019

The unfolded protein response (UPR) is a signal transduction cascade that mitigates low levels of misfolded protein stress in the endoplasmic reticulum (ER) in an effort to save the affected cell, while prolonged and/or acute ER stress leads to UPR-initiated apoptosis (programmed cell death). One putative step driving apoptosis is the cleavage of chaperones, proteins tasked to help misfolded proteins refold, by caspases, proteases essential to the execution of apoptosis. We are studying the nascent polypeptide-associated complex (NAC), a heterodimeric chaperone complex essential for viability, to determine if its beta subunit is cleaved by caspases during apoptosis to prevent the …

Kaempferol Induces G2/M Cell Cycle Arrest Via Checkpoint Kinase 2 And Promotes Apoptosis Via Death Receptors In Human Ovarian Carcinoma A2780/Cp70 Cells, Ying Gao, Junfeng Yin, Gary O. Rankin, Yi Charlie Chen

Clinical and Translational Science Institute

Kaempferol is a widely distributed dietary flavonoid. Epidemiological studies have demonstrated kaempferol consumption lowers the risk of ovarian cancer. Our previous research proved that kaempferol suppresses human ovarian cancer cells by inhibiting tumor angiogenesis. However, the effects of kaempferol on the cell cycle and extrinsic apoptosis of ovarian cancer cells have not yet been studied. In the present study, we demonstrated that kaempferol induced G2/M cell cycle arrest via the Chk2/Cdc25C/Cdc2 pathway and Chk2/p21/Cdc2 pathway in human ovarian cancer A2780/CP70 cells. Chk2 was not responsible for kaempferol-induced apoptosis and up-regulation of p53. Kaempferol stimulated extrinsic apoptosis via death receptors/FADD/Caspase-8 pathway. …

Loss Of The Na+/H+ Exchange Regulatory Factor 1 Results In Increased Susceptibility To Cisplatin-Induced Acute Kidney Injury., Adrienne M. Bushau-Sprinkle

Electronic Theses and Dissertations

Background. Acute kidney injury (AKI), an abrupt loss of kidney function which carries a high mortality and confers an increased risk of chronic kidney disease, develops in 30% of patients who receive cisplatin, a widely used chemotherapeutic agent [1], [2], [3]. The sodium hydrogen exchange regulatory factor isoform 1 (NHERF1) is a scaffolding protein that anchors multiple membrane proteins, in renal proximal tubules [4]. NHERF-1 deficient mice have aberrant localization of BBM proteins in intracellular compartments [5]. The investigators have recently demonstrated NHERF1 deficient proximal tubule cells have an underlying …

Induction Of Apoptosis By Streptomyces Strain Ch54-4 Extract Through Activation Of Caspase-3 In Human Nasopharyngeal Cells, Chantarawan Saengkhae, Ekkachai Khongkhaduead, Rattanaporn Srivibool

Chulalongkorn Medical Journal

Background ; Streptomycetes serves as an incessant source of novel compounds withthe ability to produce bioactive secondary metabolites, such as,antimicrobial, antiviral, and especially anticancer compounds. In the caseof screening for new anticancer agents, a soil sample was collected fromthe tropical mangrove area in Chantaburi Province, Thailand which mayhave potential effects to induce apoptosis on nasopharyngeal cancer.Objectives ; To study the anticancer and apoptosis induction mechanisms ofStreptomyces strain CH54-4 extract on human nasopharyngeal (KB) cellline.Methods : Streptomyces strain CH54-4 was maintained in ISP2 broth. The cells andmedium were extracted with methanol and ethyl acetate (1:1) and treatedon KB cells. The cell …

Tannic Acid Induces Endoplasmic Reticulum Stress-Mediated Apoptosis In Prostate Cancer, Prashanth K.B. Nagesh, Elham Hatami, Pallabita Chowdhury, Vivek Kumar Kashyap, Sheema Khan, Bilal B. Hafeez, Subhash C. Chauhan, Meena Jaggi, Murali M. Yallapu

School of Medicine Publications and Presentations

Endoplasmic reticulum (ER) stress is an intriguing target with significant clinical importance in chemotherapy. Interference with ER functions can lead to the accumulation of unfolded proteins, as detected by transmembrane sensors that instigate the unfolded protein response (UPR). Therefore, controlling induced UPR via ER stress with natural compounds could be a novel therapeutic strategy for the management of prostate cancer. Tannic acid (a naturally occurring polyphenol) was used to examine the ER stress mediated UPR pathway in prostate cancer cells. Tannic acid treatment inhibited the growth, clonogenic, invasive, and migratory potential of prostate cancer cells. Tannic acid demonstrated activation of …

Targeting Cdk6 And Bcl2 Exploits The "Myb Addiction" Of Ph+ Acute Lymphoblastic Leukemia, Marco De Dominici, Patrizia Porazzi, Angela Rachele Soliera, Samanta A. Mariani, Sankar Addya, Paolo Fortina, Luke F. Peterson, Orietta Spinelli, Alessandro Rambaldi, Giovanni Martinelli, Anna Ferrari, Ilaria Iacobucci, Bruno Calabretta

Department of Cancer Biology Faculty Papers

Philadelphia chromosome–positive acute lymphoblastic leukemia (Ph^þ ALL) is currently treated with BCR-ABL1 tyrosine kinase inhibitors (TKI) in combination with chemotherapy. However, most patients develop resistance to TKI through BCR-ABL1–dependent and –independent mechanisms. Newly developed TKI can target Ph^þ ALL cells with BCR-ABL1–dependent resistance; however, overcoming BCR-ABL1–independent mechanisms of resistance remains challenging because transcription factors, which are difficult to inhibit, are often involved. We show here that (i) the growth of Ph^þ ALL cell lines and primary cells is highly dependent on MYB-mediated transcriptional upregulation of CDK6, cyclin D3, and BCL2, and (ii) restoring their expression in MYB-silenced …

Cell-Cycle-Specific Function Of P53 In Fanconi Anemia Hematopoietic Stem And Progenitor Cell Proliferation, Xiaoli Li, Andrew F. Wilson, Wei Du, Qishen Pang

Clinical and Translational Science Institute

Overactive p53 has been proposed as an important pathophysiological factor for bone marrow failure syndromes, including Fanconi anemia (FA). Here, we report a p53-dependent effect on hematopoietic stem and progenitor cell (HSPC) proliferation in mice deficient for the FA gene Fanca. Deletion of p53 in Fanca−/− mice leads to replicative exhaustion of the hematopoietic stem cell (HSC) in transplant recipients. Using Fanca−/− HSCs expressing the separation-of-function mutant p53515C transgene, which selectively impairs the p53 function in apoptosis but keeps its cell-cycle checkpoint activities intact, we show that the p53 cell-cycle function is specifically required for the regulation of Fanca−/− HSC …

Neurotensin Receptor 3/Sortilin Contributes To Tumorigenesis Of Neuroendocrine Tumors Through Augmentation Of Cell Adhesion And Migration, Ji Tae Kim, Dana L. Napier, Heidi L. Weiss, Eun Y. Lee, Courtney M. Townsend, B. Mark Evers

Markey Cancer Center Faculty Publications

Neurotensin (NTS), a 13–amino acid peptide which is distributed predominantly along gastrointestinal tract, has multiple physiologic and pathologic functions, and its effects are mediated by three distinct NTS receptors (NTSRs). Overexpression and activation of NTS signaling components, especially NTS and/or NTSR1, are closely linked with cancer progression and metastasis in various types of cancers including neuroendocrine tumors (NETs). Although deregulation of NTSR3/sortilin has been implicated in a variety of human diseases, the expression and role of NTSR3/sortilin in NETs have not been elucidated. In this study, we investigated the expression and oncogenic effect of NTSR3/sortilin in NETs. Increased protein levels …

Minocycline Protects Developing Brain Against Ethanol-Induced Damage, Xin Wang, Kai Zhang, Fanmuyi Yang, Zhenhua Ren, Mei Xu, Jacqueline A. Frank, Zun-Ji Ke, Jia Luo

Pharmacology and Nutritional Sciences Faculty Publications

Fetal alcohol spectrum disorders (FASD) are caused by ethanol exposure during the pregnancy and is the leading cause of mental retardation. Ethanol exposure during the development results in the loss of neurons in the developing brain, which may underlie many neurobehavioral deficits associated with FASD. It is important to understand the mechanisms underlying ethanol-induced neuronal loss and develop appropriate therapeutic strategies. One of the potential mechanisms involves neuroimmune activation. Using a third trimester equivalent mouse model of ethanol exposure, we demonstrated that ethanol induced a wide-spread neuroapoptosis, microglial activation, and neuroinflammation in C57BL/6 mice. Minocycline is an antibiotic that inhibits …

Novel Docosahexaenoic Acid Ester Of Phloridzin Inhibits Proliferation And Triggers Apoptosis In An In Vitro Model Of Skin Cancer, Theodora Mantso, Dimitrios T. Trafalis, Sotiris Botaitis, Rodrigo Franco, Aglaia Pappa, H. P. Vasantha Rupasinghe, Mihalis I. Panayiotidis

School of Veterinary and Biomedical Sciences: Faculty Publications

Skin cancer is among the most common cancer types accompanied by rapidly increasing incidence rates, thus making the development of more efficient therapeutic approaches a necessity. Recent studies have revealed the potential role of decosahexaenoic acid ester of phloridzin (PZDHA) in suppressing proliferation of liver, breast, and blood cancer cell lines. In the present study, we investigated the cytotoxic potential of PZDHA in an in vitro model of skin cancer consisting of melanoma (A375), epidermoid carcinoma (A431), and non-tumorigenic (HaCaT) cell lines. Decosahexaenoic acid ester of phloridzin led to increased cytotoxicity in all cell lines as revealed by cell viability …

The Role Of Apoptosis And The Effect Of Epidermal Growth Factor On Proapoptotic Bnip 3 In An Experimental Rat Priapism Model, Osman Barut, Ahmet Karakeçi̇, Tunç Ozan, Fati̇h Firdolaş, Neci̇p Pi̇ri̇nççi̇, İrfan Orhan

Turkish Journal of Medical Sciences

Background/aim: This study aimed to investigate the effects of apoptosis-inducing Bcl-2/adenovirus E1B 19 kDa-interacting protein 3 (BNIP 3) and antiapoptotic epidermal growth factor (EGF) on the pathophysiology of experimental low-flow priapism. Materials and methods: Twenty-four adult Sprague-Dawley rats were divided into four equal groups. Group I was the control group. Ischemic priapism was induced for 4 h in Group II rats. In Group III, intraperitoneal EGF at 10 µg/kg was given for 7 days before induction of ischemic priapism for 4 h. In Group IV, intraperitoneal EGF at 20 µg/kg was given for 7 days before induction of ischemic priapism …

Understanding The Role Of Phosphoinositide 3-Kinase And Its Function As A Driving Force Behind The Er Stress Response In Fibrostenotic Crohn’S Disease-Affected Ileal Smooth Muscle Cells, Prashant Yadav

Theses and Dissertations

Crohn’s disease (CD) affects about 780,000 people in the United States alone, and it is estimated that 6-15 per 100,000 persons will receive a diagnosis of this disease each year. There currently is no cure for Crohn’s disease, and available medical therapies simply serve to alleviate the inflammation. This does not help treat fibrostenosis that Crohn’s disease patients may develop, which can only be treated surgically. Finding alternatives to treat CD requires an understanding of mechanisms at the biochemical level. In this thesis, we attempted to gain a better understanding of certain pathways found to be active in Crohn’s disease-affected …

Novel Insights Into The Contribution Of Cellular Senescence To Cancer Therapy: Reversibility, Dormancy And Senolysis., Tareq Saleh

Theses and Dissertations

Cellular senescence a specialized form of growth arrest that contributes to the pathogenesis of several aging-related disorders including cancer. While by definition tumor cells are considered immortalized, they can undergo senescence when exposed to conventional and targeted cancer therapy. Therapy-Induced Senescence (TIS) represents a fundamental response to therapy and impacts its outcomes. However, TIS has been considered a positive therapeutic goal since senescent tumor cells are expected to enter a state of permanent growth abrogation. In this work we examined the hypothesis that a subpopulation of senescent cells can re-acquire proliferative potential after a state of senescent dormancy, indicating that …

Post-Transcriptional Regulation Of Myeloid Cell Leukemia 1 In Cancers, Jia Cui

All ETDs from UAB

Apoptosis, a highly regulated process of programmed cell death, is essential for maintaining normal tissue homeostasis. Myeloid cell leukemia 1 (MCL1), an anti-apoptotic BCL-2 family protein, lies at the center of apoptosis regulation. Overexpression of MCL1 has been identified as a key contributor to tumorigenesis and further enables resistance to anti-cancer chemotherapies and radiation. Due to the critical roles of MCL1 in cancer, it is essential to understand the regulatory mechanisms of MCL1 expression in cells. Previous studies have detailed how MCL1 expression is controlled by multiple mechanisms. However, characterization of the post-transcriptional regulation of MCL1 mRNA has been poorly …