Digital Commons Network^™

Human Genome-Wide Association And Mouse Knockout Approaches Identify Platelet Supervillin As An Inhibitor Of Thrombus Formation Under Shear Stress., Leonard C. Edelstein, Elizabeth J. Luna, Ian B. Gibson, Molly Bray, Ying Jin, Altaf Kondkar, Srikanth Nagalla, Nacima Hadjout-Rabi, Tara C. Smith, Daniel Covarrubias, Stephen N. Jones, Firdos Ahmad, Moritz Stolla, Xianguo Kong, Zhiyou Fang, Wolfgang Bergmeier, Chad Shaw, Suzanne M. Leal, Paul Bray

Department of Medicine Faculty Papers

BACKGROUND: High shear force critically regulates platelet adhesion and thrombus formation during ischemic vascular events. To identify genetic factors that influence platelet thrombus formation under high shear stress, we performed a genome-wide association study and confirmatory experiments in human and animal platelets.

METHODS AND RESULTS: Closure times in the shear-dependent platelet function analyzer (PFA)-100 were measured on healthy, nondiabetic European Americans (n=125) and blacks (n=116). A genome-wide association (P

CONCLUSIONS: We show for the first time that (1) platelets contain supervillin; (2) platelet thrombus formation in the PFA-100 is associated with human SVIL variants and low SVIL expression; and (3) …

Effect Of Oxidative Stress On Protein Tyrosine Phosphatase 1b In Scleroderma Dermal Fibroblasts., Pei-Suen Tsou, Nadine N. Talia, Adam J. Pinney, Ann Kendzicky, Sonsoles Piera-Velazquez, Sergio A. Jimenez, James R. Seibold, Kristine Phillips, Alisa E Koch

Department of Dermatology and Cutaneous Biology Faculty Papers

OBJECTIVE: Platelet-derived growth factor (PDGF) and its receptor, PDGFR, promote fibrosis in systemic sclerosis (SSc; scleroderma) dermal fibroblasts, and such cells in scleroderma skin lesions produce excessive reactive oxygen species (ROS). PDGFR is phosphorylated upon PDGF stimulation, and is dephosphorylated by protein tyrosine phosphatases (PTPs), including PTP1B. This study was undertaken to determine whether the thiol-sensitive PTP1B is affected by ROS in SSc dermal fibroblasts, thereby enhancing the phosphorylation of PDGFR and synthesis of type I collagen. This study also sought to investigate the effect of a thiol antioxidant, N-acetylcysteine (NAC), in SSc.

METHODS: Fibroblasts were isolated from the skin …

Perspectives On: Sgp Symposium On Mitochondrial Physiology And Medicine: Mitochondria Take Center Stage., Shey-Shing Sheu, Robert T Dirksen, Edward N Pugh

Center for Translational Medicine Faculty Papers

No abstract provided.

Perspectives On: Sgp Symposium On Mitochondrial Physiology And Medicine: Molecular Identities Of Mitochondrial Ca2+ Influx Mechanism: Updated Passwords For Accessing Mitochondrial Ca2+-Linked Health And Disease., Jin O-Uchi, Shi Pan, Shey-Shing Sheu

Center for Translational Medicine Faculty Papers

No abstract provided.

Cdc42-Dependent Activation Of Nadph Oxidase Is Involved In Ethanol-Induced Neuronal Oxidative Stress, Xin Wang, Zunji Ke, Gang Chen, Mei Xu, Kimberly A. Bower, Jacqueline A. Frank, Zhuo Zhang, Xianglin Shi, Jia Luo

Pharmacology and Nutritional Sciences Faculty Publications

It has been suggested that excessive reactive oxygen species (ROS) and oxidative stress play an important role in ethanol-induced damage to both the developing and mature central nervous system (CNS). The mechanisms underlying ethanol-induced neuronal ROS, however, remain unclear. In this study, we investigated the role of NADPH oxidase (NOX) in ethanol-induced ROS generation. We demonstrated that ethanol activated NOX and inhibition of NOX reduced ethanol-promoted ROS generation. Ethanol significantly increased the expression of p47^phox and p67^phox, the essential subunits for NOX activation in cultured neuronal cells and the cerebral cortex of infant mice. Ethanol caused serine …

Shoc2 Is Targeted To Late Endosomes And Required For Erk1/2 Activation In Egf-Stimulated Cells, Emilia Galperin, Lina Abdelmoti, Alexander Sorkin

Molecular and Cellular Biochemistry Faculty Publications

Shoc2 is the putative scaffold protein that interacts with RAS and RAF, and positively regulates signaling to extracellular signal-regulated protein kinases 1 and 2 (ERK1/2). To elucidate the mechanism by which Shoc2 regulates ERK1/2 activation by the epidermal growth factor (EGF) receptor (EGFR), we studied subcellular localization of Shoc2. Upon EGFR activation, endogenous Shoc2 and red fluorescent protein tagged Shoc2 were translocated from the cytosol to a subset of late endosomes containing Rab7. The endosomal recruitment of Shoc2 was blocked by overexpression of a GDP-bound H-RAS (N17S) mutant and RNAi knockdown of clathrin, suggesting the requirement of RAS activity and …

Between Utopia And Dystopia, Zhe Ren

Student Theses and Dissertations

I watch the city. I am fascinated by the swift change and goings on of metropolitan life. I think of it as a collective performance and exemplary of basic human nature. The urban space also frightens me because it is expanding so fast that it disrupts the relationship between human civilization and the natural balance. My work is an exploration of this coexistence between humans and nature. As populations continue to expand and energy becomes rare, we find new ways to cohabitate. While creating new life forms both naturally and scientifically, humans become parasitic to their surroundings. Population growth is …

Deciphering Mechanisms Of Staphylococcal Biofilm Evasion Of Host Immunity., Mark L. Hanke, Tammy Kielian

Journal Articles: Pathology and Microbiology

Biofilms are adherent communities of bacteria contained within a complex matrix. Although host immune responses to planktonic staphylococcal species have been relatively well-characterized, less is known regarding immunity to staphylococcal biofilms and how they modulate anti-bacterial effector mechanisms when organized in this protective milieu. Previously, staphylococcal biofilms were thought to escape immune recognition on the basis of their chronic and indolent nature. Instead, we have proposed that staphylococcal biofilms skew the host immune response away from a proinflammatory bactericidal phenotype toward an anti-inflammatory, pro-fibrotic response that favors bacterial persistence. This possibility is supported by recent studies from our laboratory using …

Improved Tumor Contrast Achieved By Single Time Point Dual-Reporter Fluorescence Imaging, Kenneth M. Tichauer, Kimberley S. Samkoe, Kristian J. Sexton, Jason R. Gunn, Tayyaba Hasan, Brian W. Pogue

Dartmouth Scholarship

In this study, we demonstrate a method to quantify biomarker expression that uses an exogenous dual-reporter imaging approach to improve tumor signal detection. The uptake of two fluorophores, one nonspecific and one targeted to the epidermal growth factor receptor (EGFR), were imaged at 1 h in three types of xenograft tumors spanning a range of EGFR expression levels (n  =  6 in each group). Using this dual-reporter imaging methodology, tumor contrast-to-noise ratio was amplified by >6 times at 1 h postinjection and >2 times at 24 h. Furthermore, by as early as 20 min postinjection, the dual-reporter imaging signal …

Pv1 Down-Regulation Via Shrna Inhibits The Growth Of Pancreatic Adenocarcinoma Xenografts, Sophie J. Deharvengt, Dan Tse, Olga Sideleva, Caitlin Mcgarry, Jason R. Gunn, Daniel S. Longnecker, Catherine Carriere, Radu V. Stan

Dartmouth Scholarship

PV1 is an endothelial-specific protein with structural roles in the formation of diaphragms in endothelial cells of normal vessels. PV1 is also highly expressed on endothelial cells of many solid tumours. On the basis of in vitro data, PV1 is thought to actively participate in angiogenesis. To test whether or not PV1 has a function in tumour angiogenesis and in tumour growth in vivo, we have treated pancreatic tumour-bearing mice by single-dose intratumoural delivery of lentiviruses encoding for two different shRNAs targeting murine PV1. We find that PV1 down-regulation by shRNAs inhibits the growth of established tumours derived from two …

Arsenic, Organic Foods, And Brown Rice Syrup, Brian P. Jackson, Vivien F. Taylor, Margaret R. Karagas, Tracy Punshon, Kathryn L. Cottingham

Dartmouth Scholarship

Background: Rice can be a major source of inorganic arsenic (As_i) for many sub-populations. Rice products are also used as ingredients in prepared foods, some of which may not be obviously rice based. Organic brown rice syrup (OBRS) is used as a sweetener in organic food products as an alternative to high-fructose corn syrup. We hypothesized that OBRS introduces As into these products.

Objective: We determined the concentration and speciation of As in commercially available brown rice syrups and in products containing OBRS, including toddler formula, cereal/energy bars, and high-energy foods used by endurance athletes.

Methods: We used …

Mitochondrial Lysyl-Trna Synthetase Independent Import Of Trna Lysine Into Yeast Mitochondria., Naresh Babu V Sepuri, Madhavi Gorla, Michael P King

Department of Biochemistry and Molecular Biology Faculty Papers

Aminoacyl tRNA synthetases play a central role in protein synthesis by charging tRNAs with amino acids. Yeast mitochondrial lysyl tRNA synthetase (Msk1), in addition to the aminoacylation of mitochondrial tRNA, also functions as a chaperone to facilitate the import of cytosolic lysyl tRNA. In this report, we show that human mitochondrial Kars (lysyl tRNA synthetase) can complement the growth defect associated with the loss of yeast Msk1 and can additionally facilitate the in vitro import of tRNA into mitochondria. Surprisingly, the import of lysyl tRNA can occur independent of Msk1 in vivo. This suggests that an alternative mechanism is present …

Retinoids Regulate The Formation And Degradation Of Gap Junctions In Androgen-Responsive Human Prostate Cancer Cells., Linda Kelsey, Parul Katoch, Kristen E. Johnson, Surinder K. Batra, Parmender P. Mehta

Journal Articles: Biochemistry & Molecular Biology

The retinoids, the natural or synthetic derivatives of Vitamin A (retinol), are essential for the normal development of prostate and have been shown to modulate prostate cancer progression in vivo as well as to modulate growth of several prostate cancer cell lines. 9-cis-retinoic acid and all-trans-retinoic acid are the two most important metabolites of retinol. Gap junctions, formed of proteins called connexins, are ensembles of intercellular channels that permit the exchange of small growth regulatory molecules between adjoining cells. Gap junctional communication is instrumental in the control of cell growth. We examined the effect of 9-cis-retinoic acid and all-trans retinoic …

Prostate Cancer-Specific And Potent Antitumor Effect Of A Dd3-Controlled Oncolytic Virus Harboring The Pten Gene, Miao Ding, Xin Cao, Hai-Neng Xu, Jun-Kai Fan, Hong-Ling Huang, Dong-Qin Yang, Yu-Hua Li, Jian Wang, Runsheng Li, Xin-Yuan Liu

Molecular and Cellular Biochemistry Faculty Publications

Prostate cancer is a major health problem for men in Western societies. Here we report a Prostate Cancer-Specific Targeting Gene-Viro-Therapy (CTGVT-PCa), in which PTEN was inserted into a DD3-controlled oncolytic viral vector (OV) to form Ad.DD3.E1A.E1B(Δ55)-(PTEN) or, briefly, Ad.DD3.D55-PTEN. The woodchuck post-transcriptional element (WPRE) was also introduced at the downstream of the E1A coding sequence, resulting in much higher expression of the E1A gene. DD3 is one of the most prostate cancer-specific genes and has been used as a clinical bio-diagnostic marker. PTEN is frequently inactivated in primary prostate cancers, which is crucial for prostate cancer progression. Therefore, the Ad.DD3.D55-PTEN …

Chromosomal Instability And Cancer: A Complex Relationship With Therapeutic Potential, Samuel F. Bakhoum, Duane A. Compton

Dartmouth Scholarship

Chromosomal instability (CIN) is a hallmark of human neoplasms. Despite its widespread prevalence, knowledge of the mechanisms and contributions of CIN in cancer has been elusive. It is now evident that the role of CIN in tumor initiation and growth is more complex than previously thought. Furthermore, distinguishing CIN, which consists of elevated rates of chromosome missegregation, from aneuploidy, which is a state of abnormal chromosome number, is crucial to understanding their respective contributions in cancer. Collectively, experimental evidence suggests that CIN enables tumor adaptation by allowing tumors to constantly sample the aneuploid fitness landscape. This complex relationship, together with …

G9a Interacts With Snail And Is Critical For Snail-Mediated E-Cadherin Repression In Human Breast Cancer, Chenfang Dong, Yadi Wu, Jun Yao, Yifan Wang, Yinhua Yu, Piotr G. Rychahou, B. Mark Evers, Binhua P. Zhou

Molecular and Cellular Biochemistry Faculty Publications

Breast cancers are highly heterogeneous but can be grouped into subtypes based on several criteria, including level of expression of certain markers. Claudin-low breast cancer (CLBC) is associated with early metastasis and resistance to chemotherapy, while gene profiling indicates it is characterized by the expression of markers of epithelial-mesenchymal transition (EMT) - a phenotypic conversion linked with metastasis. Although the epigenetic program controlling the phenotypic and cellular plasticity of EMT remains unclear, one contributor may be methylation of the E-cadherin promoter, resulting in decreased E-cadherin expression, a hallmark of EMT. Indeed, reduced E-cadherin often occurs in CLBC and may contribute …

Rituximab Induces Sustained Reduction Of Pathogenic B Cells In Patients With Peripheral Nervous System Autoimmunity., Michael A Maurer, Goran Rakocevic, Carol S Leung, Isaak Quast, Martin Lukačišin, Norbert Goebels, Christian Münz, Hedda Wardemann, Marinos Dalakas, Jan D Lünemann

Department of Neurology Faculty Papers

The B cell-depleting IgG1 monoclonal antibody rituximab can persistently suppress disease progression in some patients with autoimmune diseases. However, the mechanism underlying these long-term beneficial effects has remained unclear. Here, we evaluated Ig gene usage in patients with anti-myelin-associated glycoprotein (anti-MAG) neuropathy, an autoimmune disease of the peripheral nervous system that is mediated by IgM autoantibodies binding to MAG antigen. Patients with anti-MAG neuropathy showed substantial clonal expansions of blood IgM memory B cells that recognized MAG antigen. The group of patients showing no clinical improvement after rituximab therapy were distinguished from clinical responders by a higher load of clonal …

Glycosylation Of Human Cyclooxygenase-2 (Cox-2) Decreases The Efficacy Of Certain Cox-2 Inhibitors., Mary B. Sevigny, Kamara Graham, Esmeralda Ponce, Maggie Louie, Kylie Mitchell

Natural Sciences and Mathematics | Faculty Scholarship

Prostanoids play an important role in a variety of physiological and pathophysiological processes including inflammation and cancer. The rate-limiting step in the prostanoid biosynthesis pathway is catalyzed by cyclooxygenase-2 (COX-2). COX-2 exists as two glycoforms, 72 and 74 kDa, the latter resulting from an additional glycosylation at Asn(580). In this study, Asn(580) was mutated, and the mutant and wild-type COX-2 genes were expressed in COS-1 cells to determine how glycosylation affects the inhibition of COX-2 activity by aspirin, flurbiprofen, ibuprofen, celecoxib, and etoricoxib. Results indicate that certain inhibitors were 2-5 times more effective at inhibiting COX-2 activity when the glycosylation …

Dyschronic, A Drosophila Homolog Of A Deaf-Blindness Gene, Regulates Circadian Output And Slowpoke Channels., James E C Jepson, Mohammad Shahidullah, Angelique Lamaze, Drew Peterson, Huihui Pan, Kyunghee Koh

Farber Institute for Neuroscience Faculty Papers

Many aspects of behavior and physiology are under circadian control. In Drosophila, the molecular clock that regulates rhythmic patterns of behavior has been extensively characterized. In contrast, genetic loci involved in linking the clock to alterations in motor activity have remained elusive. In a forward-genetic screen, we uncovered a new component of the circadian output pathway, which we have termed dyschronic (dysc). dysc mutants exhibit arrhythmic locomotor behavior, yet their eclosion rhythms are normal and clock protein cycling remains intact. Intriguingly, dysc is the closest Drosophila homolog of whirlin, a gene linked to type II Usher syndrome, the leading cause …

Role Of Raltegravir In Hiv-1 Management, Kristina E. Rokas, P Brandon Bookstaver, Caitlin L. Shamroe, S Scott Sutton, Vanessa E. Millisor, Jacquelyn E. Bryant, Sharon B. Weissman

Faculty Publications

OBJECTIVE: To review the literature concerning the role of raltegravir in the treatment of HIV-1 in antiretroviral (ARV)-experienced and ARV-naïve patients. DATA SOURCES: A PubMed search was conducted for published data through March 2012 using the search terms raltegravir, MK-0518, and integrase strand transfer inhibitor. An additional search of International Pharmaceutical Abstracts for unpublished data, including data from the Infectious Diseases Society of America, the Conference on Retroviruses and Opportunistic Infections, the International AIDS Society, and the Interscience Conference on Antimicrobial Agents and Chemotherapy, was conducted using similar search terms. STUDY SELECTION AND DATA EXTRACTION: In vitro and in vivo …

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 …

Hyccin, The Molecule Mutated In The Leukodystrophy Hypomyelination And Congenital Cataract (Hcc), Is A Neuronal Protein., Elisabetta Gazzerro, Simona Baldassari, Caterina Giacomini, Veronica Musante, Floriana Fruscione, Veronica La Padula, Roberta Biancheri, Sonia Scarfì, Valeria Prada, Federica Sotgia, Ian D Duncan, Federico Zara, Hauke B Werner, Michael P Lisanti, Lucilla Nobbio, Anna Corradi, Carlo Minetti

Kimmel Cancer Center Faculty Papers

"Hypomyelination and Congenital Cataract", HCC (MIM #610532), is an autosomal recessive disorder characterized by congenital cataract and diffuse cerebral and peripheral hypomyelination. HCC is caused by deficiency of Hyccin, a protein whose biological role has not been clarified yet. Since the identification of the cell types expressing a protein of unknown function can contribute to define the physiological context in which the molecule is explicating its function, we analyzed the pattern of Hyccin expression in the central and peripheral nervous system (CNS and PNS). Using heterozygous mice expressing the b-galactosidase (LacZ) gene under control of the Hyccin gene regulatory elements, …

Motor Neuron Apoptosis And Neuromuscular Junction Perturbation Are Prominent Features In A Drosophila Model Of Fus-Mediated Als, Ruohan Xia, Yajuan Liu, Liuqing Yang, Jozsef Gal, Haining Zhu, Jianhang Jia

Markey Cancer Center Faculty Publications

BACKGROUND: Amyotrophic lateral sclerosis (ALS) is progressive neurodegenerative disease characterized by the loss of motor function. Several ALS genes have been identified as their mutations can lead to familial ALS, including the recently reported RNA-binding protein fused in sarcoma (Fus). However, it is not clear how mutations of Fus lead to motor neuron degeneration in ALS. In this study, we present a Drosophila model to examine the toxicity of Fus, its Drosophila orthologue Cabeza (Caz), and the ALS-related Fus mutants.

RESULTS: Our results show that the expression of wild-type Fus/Caz or FusR521G induced progressive toxicity in multiple tissues of the …

Inhibition Of Fatty Acid Synthase Attenuates Cd44-Associated Signaling And Reduces Metastasis In Colorectal Cancer, Yekaterina Y. Zaytseva, Piotr G. Rychahou, Pat Gulhati, Victoria Allison Elliott, William Conan Mustain, Kathleen O'Connor, Andrew J. Morris, Manjula Sunkara, Heidi L. Weiss, Eun Young Lee, B. Mark Evers

Markey Cancer Center Faculty Publications

Fatty acid synthase (FASN) and ATP-citrate lyase, key enzymes of de novo lipogenesis, are significantly upregulated and activated in many cancers and portend poor prognosis. Even though the role of lipogenesis in providing proliferative and survival advantages to cancer cells has been described, the impact of aberrant activation of lipogenic enzymes on cancer progression remains unknown. In this study, we found that elevated expression of FASN is associated with advanced stages of colorectal cancer (CRC) and liver metastasis, suggesting that it may play a role in progression of CRC to metastatic disease. Targeted inhibition of lipogenic enzymes abolished expression of …

Cyclin D1 Induces Chromosomal Instability., Mathew C Casimiro, Richard Pestell

Department of Cancer Biology Faculty Papers

We developed mouse model systems to investigate the potential for cyclin D1 to induce CIN in vivo. In a mammary gland specific Tet-inducible model the acute expression profile regulated by cyclin D1 after 7 days was enriched in genes that rank highly with CIN. We also used a mammary gland targeted model (MMTV) to continuously express cyclin D1. The mice started to develop mammary gland tumors at 400 days and the tumor-free incidence was 40% in MMTV-cyclin D1. The gene expression profile of the tumors showed enrichment for the CIN signature. We next compared cyclin D1 expression and the highest …

Small Non-Coding Rnas Govern Mammary Gland Tumorigenesis., Zuoren Yu, Richard Pestell

Department of Cancer Biology Faculty Papers

Small non-coding RNAs include siRNA, miRNA, piRNA and snoRNA. The involvement of miRNAs in the regulation of mammary gland tumorigenesis has been widely studied while the role for other small non-coding RNAs remains unclear. Here we summarize the involvement of miRNA in breast cancer onset and progression through regulating the cell cycle and cellular proliferation. The regulation of breast cancer stem cells and tumor regeneration by miRNA is reviewed. In addition, the emerging evidence demonstrating the involvement of piRNA and snoRNA in breast cancer is briefly described.

Robotic Surgery Training With Commercially Available Simulation Systems In 2011: A Current Review And Practice Pattern Survey From The Society Of Urologic Robotic Surgeons., Costas D Lallas, John W Davis And Members Of The Society Of Urologic Robotic Surgeons

Department of Urology Faculty Papers

Abstract Objectives: Virtual reality (VR) simulation has the potential to standardize surgical training for robotic surgery. We sought to evaluate all commercially available VR robotic simulators. Materials and Methods: A MEDLINE(®) literature search was performed of all applicable keywords. Available VR simulators were evaluated with regard to face, content, and construct validation. Additionally, a survey was e-mailed to all members of the Endourological Society, querying the pervasiveness of VR simulators in robotic surgical training. Finally, each company was e-mailed to ask for a price quote for their respective system. Results: There are four VR robotic surgical simulators currently available: RoSS™, …

Interactions Between Antiepileptics And Second-Generation Antipsychotics, Jose De Leon, Vincenza Santoro, Concetta D'Arrigo, Edoardo Spina

Psychiatry Faculty Publications

INTRODUCTION: Pharmacokinetic and pharmacodynamic drug interactions (DIs) can occur between antiepileptics (AEDs) and second-generation antipsychotics (SGAPs). Some AED and SGAP pharmacodynamic mechanisms are poorly understood. AED-SGAP combinations are used for treating comorbid illnesses or increasing efficacy, particularly in bipolar disorder.

AREAS COVERED: This article provides a comprehensive review of the interactions between antiepileptics and second-generation antipsychotics. The authors cover pharmacokinetic AED-SGAP DI studies, the newest drug pharmacokinetics in addition to the limited pharmacodynamic DI studies.

EXPERT OPINION: Dosing correction factors and measuring SGAP levels can help to compensate for the inductive properties of carbamazepine, phenytoin, phenobarbital and primidone. Further studies …

Krüppel-Like Factor 4 Regulates Intestinal Epithelial Cell Morphology And Polarity, Tianxin Yu, Xi Chen, Wen Zhang, Juan Li, Ren Xu, Timothy C Wang, Walden Ai, Chunming Liu

Markey Cancer Center Faculty Publications

Krüppel-like factor 4 (KLF4) is a zinc finger transcription factor that plays a vital role in regulating cell lineage differentiation during development and maintaining epithelial homeostasis in the intestine. In normal intestine, KLF4 is predominantly expressed in the differentiated epithelial cells. It has been identified as a tumor suppressor in colorectal cancer. KLF4 knockout mice demonstrated a decrease in number of goblet cells in the colon, and conditional ablation of KLF4 from the intestinal epithelium led to altered epithelial homeostasis. However, the role of KLF4 in differentiated intestinal cells and colon cancer cells, as well as the mechanism by which …