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Development Of A Biosensor-Based Rapid Urine Test For Detection Of Urogenital Schistosomiasis., Kathleen E Mach, Ruchika Mohan, Shailja Patel, Pak Kin Wong, Michael Hsieh, Joseph C Liao

Urology Faculty Publications

No abstract provided.

Targeting Il13ralpha2 Activates Stat6-Tp63 Pathway To Suppress Breast Cancer Lung Metastasis, Panagiotis Papageorgis, Sait Ozturk, Arthur W. Lambert, Christiana M. Neophytou, Alexandros Tzatsos, Chen K. Wong, Sam Thiagalingam, Andreas I. Constantinou

Anatomy and Regenerative Biology Faculty Publications

Introduction

Basal-like breast cancer (BLBC) is an aggressive subtype often characterized by distant metastasis, poor patient prognosis, and limited treatment options. Therefore, the discovery of alternative targets to restrain its metastatic potential is urgently needed. In this study, we aimed to identify novel genes that drive metastasis of BLBC and to elucidate the underlying mechanisms of action.

Methods

An unbiased approach using gene expression profiling of a BLBC progression model and in silicoleveraging of pre-existing tumor transcriptomes were used to uncover metastasis-promoting genes. Lentiviral-mediated knockdown of interleukin-13 receptor alpha 2 (IL13Ralpha2) coupled with whole-body in vivo bioluminescence imaging was …

Differences In Health-Related Behaviors And Attitudes Between Urban, Rural, And Isolated Households In Western West Virginia, Michael Newsome Phd, Tim Hazelett, Monika Sawhney Phd, Msw

Economics Faculty Research

This study uses data from a 2013 survey of 275 randomly sampled households across nine counties in western West Virginia to examine the significant differences between the health behaviors and attitudes of rural and isolated populations. The results show that age, education, and income are significant factors in explaining differences in health-related behaviors and attitudes for all urban, rural and isolated respondents. However, after controlling for socio-demographic differences, isolation is found to have only a few significant effects, and some of the effects run counter to stereotypes of isolated populations. Rural respondents are significantly more likely than isolated respondents to …

Role Of Non-Selective Beta Blockers In Hepatocellular Carcinoma: An Analysis In Patients With Cirrhosis And Portal Hypertension, Hiren Patel, Abhishek Kumar, Nihar Shah Md, Ela Eris, Michael Maroules, Walid J. Baddoura, Vincent A. Debari

Gastroenterology

There are many different biochemical processes responsible for the hepatocelluar carcinoma (HCC) development that can be targeted for the prevention or halt progression of the HCC. Non-selective betablockers (NSBB) affects a multitude of intracellular biochemical and signaling pathways involved in carcinogenesis. Aim: To determine if NSBB may be protective for HCC in patients with cirrhosis and portal hypertension. Methods: We retrospectively enrolled 200 patients from medical records diagnosed with cirrhosis and portal hypertension between January 2001 and December 2013. Eighteen patients were excluded (taking selective beta-blocker and/or unavailable medical records). The etiology of cirrhosis, use of NSBB, demographics and the …

Nitrate And Nitrite Ingestion And Risk Of Ovarian Cancer Among Postmenopausal Women In Iowa, Maki Inoue-Choi, Rena R. Jones, Kristin E. Anderson, Kenneth P. Cantor, James R. Cerhan, Stuart Krasner, Kimberly Robien, Peter J. Weyer, Mary H. Ward

Epidemiology Faculty Publications

Nitrate and nitrite are precursors in the endogenous formation of N-nitroso compounds (NOC), potential human carcinogens. We evaluated the association of nitrate and nitrite ingestion with postmenopausal ovarian cancer risk in the Iowa Women's Health Study. Among 28,555 postmenopausal women, we identified 315 incident epithelial ovarian cancers from 1986 to 2010. Dietary nitrate and nitrite intakes were assessed at baseline using food frequency questionnaire data. Drinking water source at home was obtained in a 1989 follow-up survey. Nitrate-nitrogen (NO₃-N) and total trihalomethane (TTHM) levels for Iowa public water utilities were linked to residences and average levels were …

The Mouse That Trolled: The Long And Tortuous History Of A Gene Mutation Patent That Became An Expensive Impediment To Alzheimer's Research, Tania M. Bubela, Saurabh Vishnubhakat, Robert Cook-Deegan

Office of the Provost

This case study presents the tale of the academic discovery of a rare mutation for early-onset Alzheimer's disease that was patented by a sole inventor and licensed to a non-practicing entity (NPE), the Alzheimer's Institute of America (AIA). Our aims are (1) to relate this story about patents, research tools, and impediments to medical progress, and (2) to inform ongoing debates about how patents affect research, disposition of university inventions, and the distribution of benefits from publicly funded research. We present an account of the hunt for Alzheimer's genes, their patenting, assignment, and enforcement based on literature, litigation records and …

Multiple Cerebral Hydatid Cysts In 8-Year-Old Boy: A Case Report And Literature Review Of A Rare Presentation, Muhammad Baba Khan, Muhammad Riaz, Muhammad Ehsan Bari

Section of Neurosurgery

Background: Multiple cerebral hydatid cysts are very rare with only a few reports in the literature detailing diagnostic workup, medical management, surgical techniques, possible complications, and outcomes.
Case description: We present the case of an 8-year-old boy who presented with progressively worsening headaches, vomiting, and intermittent fever since 20 days. Diagnostic workup was performed, and magnetic resonance imaging revealed multiple intracranial cysts predominantly in the right frontal region with significant mass effect. A total of 19 intracranial cysts were removed surgically, and the child recovered uneventfully.
Conclusions: Neurosurgeons should keep hydatidosis in the list of differentials when evaluating patients with …

Paracrine Effect Of Nrg1 And Hgf Drives Resistance To Mek Inhibitors In Metastatic Uveal Melanoma., Hanyin Cheng, Mizue Terai, Ken Kageyama, Shinji Ozaki, Peter Mccue, Takami Sato, Andrew E. Aplin

Department of Cancer Biology Faculty Papers

Uveal melanoma patients with metastatic disease usually die within one year, emphasizing an urgent need to develop new treatment strategies for this cancer. MEK inhibitors improve survival in cutaneous melanoma patients but show only modest efficacy in metastatic uveal melanoma patients. In this study, we screened for growth factors that elicited resistance in newly characterized metastatic uveal melanoma cell lines to clinical-grade MEK inhibitors, trametinib and selumetinib. We show that neuregulin 1 (NRG1) and hepatocyte growth factor (HGF) provide resistance to MEK inhibition. Mechanistically, trametinib enhances the responsiveness to NRG1 and sustained HGF-mediated activation of AKT. Individually targeting ERBB3 and …

Glanzmann's Thrombasthenia: Pathogenesis, Diagnosis, And Current And Emerging Treatment Options, Tia Solh, Ashley Botsford, Melhem Solh

PCOM Scholarly Works

Glanzmann’s thrombasthenia (GT) is a genetic platelet surface receptor disorder of GPIIb/IIIa (ITG αIIbβ3), either qualitative or quantitative, which results in faulty platelet aggregation and diminished clot retraction. Spontaneous mucocutaneous bleeding is common and can lead to fatal bleeding episodes. Control and prevention of bleeding among patients with GT is imperative, and remains challenging. Local measures, including anti-fibrinolytic therapy, with or without platelet transfusions, used to be the mainstay of therapy. However, in recent years the use of recombinant factor VIIa (rFVIIa) has increased significantly, with excellent response rates in treating and preventing hemorrhage among GT patients. Gene therapy and …

Development And Implementation Of A Clinical Pathway Approach To Simulation-Based Training For Foregut Surgery., Kiyoyuki W. Miyasaka, Joseph Buchholz, Denise Lamarra, Giorgos C. Karakousis, Rajesh Aggarwal

Student Papers, Posters & Projects

INTRODUCTION: Contemporary demands on resident education call for integration of simulation. We designed and implemented a simulation-based curriculum for Post Graduate Year 1 surgery residents to teach technical and nontechnical skills within a clinical pathway approach for a foregut surgery patient, from outpatient visit through surgery and postoperative follow-up.

METHODS: The 3-day curriculum for groups of 6 residents comprises a combination of standardized patient encounters, didactic sessions, and hands-on training. The curriculum is underpinned by a summative simulation "pathway" repeated on days 1 and 3. The "pathway" is a series of simulated preoperative, intraoperative, and postoperative encounters in following up …

Is The Geriatric Impact Ipad Test A Valid Measurement Of Cognitive Function In Older Adults?, Heather Elise O'Dell

Graduate Theses and Dissertations

The number of older adults will rapidly increase within the next generation (Brookmeyer, Johnson, Ziegler-Graham, & Arrighi, 2007). Alzheimer’s disease risk increases with age, especially after age 60 (NIA, n.d.). Aging leads to a decrease in functional independence, and this side effect is exacerbated by cognitive decline (Johnson, Lui, & Yaffe, 2007). Executive function is a predictor of Alzheimer’s disease onset and progression (Zhang, Han, Verhaeghen, & Nilsson, 2007). The Geriatric ImPACTTM test is a potential new and more convenient testing methods than traditional methods used. The purpose of this research is to validate the Geriatric ImPACTTM test by comparing …

Effect Of Sirna Pre-Exposure On Subsequent Response To Sirna Therapy, Hamidreza Montazeri Aliabadi, Parvin Mahdipoor, Cezary Kucharski, Nicole Chan, Hasan Uludag

Pharmacy Faculty Articles and Research

PURPOSE. An alternative cancer therapy based on RNA interference (RNAi) has shown considerable promise but the possibility of resistance development is not known. This study explored the possibility of therapeutic resistance against siRNA nanoparticles in human cancer cells. METHODS. Two approaches to siRNA treatment were undertaken using lipid-modified polyethylenimines, a single high concentration (shock) and repeated increasing concentrations (gradual). The targets were Mcl-1, RPS6KA5 and KSP in MDA-MB-435 cells. RESULTS. There was no evidence of resistance development in shock-treated cells, while the decrease in mRNA levels of targeted proteins was not as robust in naïve cells in gradual treatment. However, …

Pain Management Strategies In Hand Surgery., Constantinos Ketonis, Md, Phd, Asif M Ilyas, Frederic Liss

Department of Orthopaedic Surgery Faculty Papers

Modern anesthetic agents have allowed for the rapid expansion of ambulatory surgery, particularly in hand surgery. The choice between general anesthesia, peripheral regional blocks, regional intravenous anesthesia (Bier block), local block with sedation, and the recently popularized wide-awake hand surgery depends on several variables, including the type and duration of the procedure and patient characteristics, coexisting conditions, location, and expected length of the procedure. This article discusses the various perioperative and postoperative analgesic options to optimize the hand surgical patients' experience.

Epidermal Growth Factor Mediated Healing In Stem Cell-Derived Vocal Fold Mucosa, Liliana Palencia, Amritava Das, Sean P. Palecek, Susan L. Thibeault, Ciara Leydon

Communication Disorders Faculty Publications

Background: The goal of vocal fold wound healing is the reconstitution of functional tissue, including a structurally and functionally intact epithelium. Mechanisms underlying reepithelialization in vocal folds are not known, although it is suspected that healing involves the interplay between several growth factors. We used a three-dimensional human embryonic stem cell-derived model of vocal fold mucosa to examine the effects of one growth factor, exogenous epidermal growth factor (EGF), on wound healing. Materials and methods: A scratch wound was created in the in vitro model. Rate of wound healing, epidermal growth factor receptor (EGFR) activation, and cell proliferation after injury …

Functional Neuroimaging Distinguishes Posttraumatic Stress Disorder From Traumatic Brain Injury In Focused And Large Community Datasets., Daniel G Amen, Cyrus A Raji, Kristen Willeumier, Derek Taylor, Robert Tarzwell, Andrew B. Newberg, Md, Theodore A Henderson

Department of Radiology Faculty Papers

BACKGROUND: Traumatic brain injury (TBI) and posttraumatic stress disorder (PTSD) are highly heterogeneous and often present with overlapping symptomology, providing challenges in reliable classification and treatment. Single photon emission computed tomography (SPECT) may be advantageous in the diagnostic separation of these disorders when comorbid or clinically indistinct.

METHODS: Subjects were selected from a multisite database, where rest and on-task SPECT scans were obtained on a large group of neuropsychiatric patients. Two groups were analyzed: Group 1 with TBI (n=104), PTSD (n=104) or both (n=73) closely matched for demographics and comorbidity, compared to each other and healthy controls (N=116); Group 2 …

Landscape Analysis Of Multi-Sectoral Initiatives For Under-Nutrition In Pakistan, Zulfiqar Ahmed Bhutta, Albertha Nyaku, Jane Keylock, Shehla Zaidi, Jai Das

Community Health Sciences

Mapping of Multi-Sectoral Initiatives for Nutrition in Pakistan, Challenges faced, Opportunities, and potential for Cross- Sectoral Synergies.

Inhaled Nitric Oxide As An Adjunctive Treatment For Cerebral Malaria In Children: A Phase Ii Randomized Open-Label Clinical Trial, Juliet Mwanga-Amumpaire, Ryan W. Carroll, Elisabeth Baudin, Elisabeth Kemigisha, Dorah Nampijjah, Kenneth Mworozi, Data Santorino, Dan Nyehangane, Daniel I. Nathan, Pierre De Beaudrap, Jean-Francois Etard, Martin Feelish, Bernadette O. Fernandez, Annie Berssenbrugge, David Bangsberg, Kenneth D. Bloch, Yap Boum Ii, Warren M. Zapol

OHSU-PSU School of Public Health Faculty Publications and Presentations

Background. Children with cerebral malaria (CM) have high rates of mortality and neurologic sequelae. Nitric oxide (NO) metabolite levels in plasma and urine are reduced in CM.

Methods. This randomized trial assessed the efficacy of inhaled NO versus nitrogen (N2) as an adjunctive treatment for CM patients receiving intravenous artesunate.We hypothesized that patients treated with NO would have a greater increase of the malaria biomarker, plasma angiopoietin-1 (Ang-1) after 48 hours of treatment.

Results. Ninety-two children with CM were randomized to receive either inhaled 80 part per million NO or N₂ for 48 or more hours. Plasma Ang-1 levels …

Selective Impact Of Cdk4/6 Suppression On Patient-Derived Models Of Pancreatic Cancer., Agnieszka K Witkiewicz, Nicholas A Borja, Jorge Franco, Jonathan Brody, Md, Charles Yeo, John Mansour, Michael A Choti, Peter Mccue, Erik S Knudsen

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Pancreatic ductal adenocarcinoma (PDA) harbors an exceedingly poor prognosis, and is generally considered a therapy-recalcitrant disease due to poor response to conventional chemotherapy coupled with non-actionable genetic drivers (e.g. KRAS mutations). However, PDA frequently loses p16ink4a, thereby leading to deregulation of CDK4/6. Surprisingly, in established cell models and xenografts, CDK4/6 inhibition has a modest effect on proliferation and resistance develops rapidly. To determine if such weak response was an intrinsic feature of PDA, we developed primary tumor explants that maintain the tumor environment and recapitulate feuture of primary PDA. The CDK4/6 inhibitor PD-0332991 was highly efficient at suppressing proliferation in …

Novel Cross Talk Between Igf-Ir And Ddr1 Regulates Igf-Ir Trafficking, Signaling And Biological Responses., Roberta Malaguarnera, Maria Luisa Nicolosi, Antonella Sacco, Alaide Morcavallo, Veronica Vella, Concetta Voci, Michela Spatuzza, Shi-Qiong Xu, Renato V Iozzo, Riccardo Vigneri, Andrea Morrione, Antonino Belfiore

Kimmel Cancer Center Faculty Papers

The insulin-like growth factor-I receptor (IGF-IR), plays a key role in regulating mammalian development and growth, and is frequently deregulated in cancer contributing to tumor initiation and progression. Discoidin domain receptor 1 (DDR1), a collagen receptor tyrosine-kinase, is as well frequently overexpressed in cancer and implicated in cancer progression. Thus, we investigated whether a functional cross-talk between the IGF-IR and DDR1 exists and plays any role in cancer progression.Using human breast cancer cells we found that DDR1 constitutively associated with the IGF-IR. However, this interaction was enhanced by IGF-I stimulation, which promoted rapid DDR1 tyrosine-phosphorylation and co-internalization with the IGF-IR. …

Taranis Functions With Cyclin A And Cdk1 In A Novel Arousal Center To Control Sleep In Drosophila., Dinis J.S. Afonso, Die Liu, Daniel R. Machado, Huihui Pan, James E.C. Jepson, Dragana Rogulja, Kyunghee Koh

Department of Neuroscience Faculty Papers

Sleep is an essential and conserved behavior whose regulation at the molecular and anatomical level remains to be elucidated. Here, we identify TARANIS (TARA), a Drosophila homolog of the Trip-Br (SERTAD) family of transcriptional coregulators, as a molecule that is required for normal sleep patterns. Through a forward-genetic screen, we isolated tara as a novel sleep gene associated with a marked reduction in sleep amount. Targeted knockdown of tara suggests that it functions in cholinergic neurons to promote sleep. tara encodes a conserved cell-cycle protein that contains a Cyclin A (CycA)-binding homology domain. TARA regulates CycA protein levels and genetically …

Deregulation Of Mir-34b/Sox2 Predicts Prostate Cancer Progression., Irene Forno, Stefano Ferrero, Maria Veronica Russo, Giacomo Gazzano, Sara Giangiobbe, Emanuele Montanari, Alberto Del Nero, Bernardo Rocco, Giancarlo Albo, Lucia R Languino, Dario C Altieri, Valentina Vaira, Silvano Bosari

Department of Cancer Biology Faculty Papers

Most men diagnosed with prostate cancer will have an indolent and curable disease, whereas approximately 15% of these patients will rapidly progress to a castrate-resistant and metastatic stage with high morbidity and mortality. Therefore, the identification of molecular signature(s) that detect men at risk of progressing disease remains a pressing and still unmet need for these patients. Here, we used an integrated discovery platform combining prostate cancer cell lines, a Transgenic Adenocarcinoma of the Mouse Prostate (TRAMP) model and clinically-annotated human tissue samples to identify loss of expression of microRNA-34b as consistently associated with prostate cancer relapse. Mechanistically, this was …

Iron Toxicity In The Retina Requires Alu Rna And The Nlrp3 Inflammasome, Bradley D. Gelfand, Charles B. Wright, Younghee Kim, Tetsuhiro Yasuma, Reo Yasuma, Shengjian Li, Benjamin J. Fowler, Ana Bastos-Carvalho, Nagaraj Kerur, Annette Uittenbogaard, Youn Seon Han, Dingyuan Lou, Mark E. Kleinman, W. Hayes Mcdonald, Gabriel Núñez, Philippe Georgel, Joshua L. Dunaief, Jayakrishna Ambati

Ophthalmology and Visual Science Faculty Publications

Excess iron induces tissue damage and is implicated in age-related macular degeneration (AMD). Iron toxicity is widely attributed to hydroxyl radical formation through Fenton's reaction. We report that excess iron, but not other Fenton catalytic metals, induces activation of the NLRP3 inflammasome, a pathway also implicated in AMD. Additionally, iron-induced degeneration of the retinal pigmented epithelium (RPE) is suppressed in mice lacking inflammasome components caspase-1/11 or Nlrp3 or by inhibition of caspase-1. Iron overload increases abundance of RNAs transcribed from short interspersed nuclear elements (SINEs): Alu RNAs and the rodent equivalent B1 and B2 RNAs, which are inflammasome agonists. Targeting …

Non-Operative Management Of Hip Osteoarthritis, Ray Marks

Publications and Research

This paper reviews several non-operative and non-pharmacologic management strategies advocated for alleviating the pain and disability experienced by people with hip osteoarthritis. It analyzes whether painful debilitating hip osteoarthritis, which has no effective cure and is often progressive, may be affected positively by non-operative interventions designed to control osteoar- thritis pain. Finally, it provides an integrated plan of management for ameliorating hip osteoar- thritis pain and disability in light of this knowledge.

Procollagen C-Endopeptidase Enhancer Protein 2 (Pcpe2) Reduces Atherosclerosis In Mice By Enhancing Scavenger Receptor Class B1 (Sr-Bi)-Mediated High-Density Lipoprotein (Hdl)-Cholesteryl Ester Uptake, Ricquita D. Pollard, Christopher N. Blesso, Manal Zabalawi, Brian Fulp, Mark Gerelus, Xuewei Zhu, Erica W. Lyons, Nebil Nuradin, Omar L. Francone, Xiang-An Li, Daisy Sahoo, Michael J. Thomas, Mary G. Sorci-Thomas

Pediatrics Faculty Publications

Studies in human populations have shown a significant correlation between procollagen C-endopeptidase enhancer protein 2 (PCPE2) single nucleotide polymorphisms and plasma HDL cholesterol concentrations. PCPE2, a 52-kDa glycoprotein located in the extracellular matrix, enhances the cleavage of C-terminal procollagen by bone morphogenetic protein 1 (BMP1). Our studies here focused on investigating the basis for the elevated concentration of enlarged plasma HDL in PCPE2-deficient mice to determine whether they protected against diet-induced atherosclerosis. PCPE2-deficient mice were crossed with LDL receptor-deficient mice to obtain LDLr^-/-, PCPE2^-/- mice, which had elevated HDL levels compared with LDLr^-/- mice with similar …

Chromatin To Clinic: The Molecular Rationale For Parp1 Inhibitor Function., Felix Y. Feng, Johann S. De Bono, Mark A. Rubin, Karen E Knudsen

Department of Cancer Biology Faculty Papers

Poly(ADP-ribose) polymerase 1 (PARP1) inhibitors were recently shown to have potential clinical impact in a number of disease settings, particularly as related to cancer therapy, treatment for cardiovascular dysfunction, and suppression of inflammation. The molecular basis for PARP1 inhibitor function is complex, and appears to depend on the dual roles of PARP1 in DNA damage repair and transcriptional regulation. Here, the mechanisms by which PARP-1 inhibitors elicit clinical response are discussed, and strategies for translating the preclinical elucidation of PARP-1 function into advances in disease management are reviewed.

Telemetric Blood Pressure Assessment In Angiotensin Ii-Infused Apoe-/- Mice: 28 Day Natural History And Comparison To Tail-Cuff Measurements, Christopher M. Haggerty, Andrea C. Mattingly, Ming C. Gong, Wen Su, Alan Daugherty, Brandon K. Fornwalt

Saha Cardiovascular Research Center Faculty Publications

Abdominal aortic aneurysm (AAA) is a disease of the aortic wall, which can progress to catastrophic rupture. Assessment of mechanical characteristics of AAA, such as aortic distensibility, may provide important insights to help identify at-risk patients and understand disease progression. While the majority of studies on this topic have focused on retrospective patient data, recent studies have used mouse models of AAA to prospectively evaluate the evolution of aortic mechanics. Quantification of aortic distensibility requires accurate measurement of arterial blood pressure, particularly pulse pressure, which is challenging to perform accurately in murine models. We hypothesized that volume/pressure tail-cuff measurements of …

Obesity-Induced Adipokine Imbalance Impairs Mouse Pulmonary Vascular Endothelial Function And Primes The Lung For Injury., Dilip Shah, Freddy Romero, Michelle Duong, Nadan Wang, Bishnuhari Paudyal, Benjamin T Suratt, Caleb B Kallen, Jianxin Sun, Ying Zhu, Kenneth Walsh, Ross Summer

Center for Translational Medicine Faculty Papers

Obesity is a risk factor for the development of acute respiratory distress syndrome (ARDS) but mechanisms mediating this association are unknown. While obesity is known to impair systemic blood vessel function, and predisposes to systemic vascular diseases, its effects on the pulmonary circulation are largely unknown. We hypothesized that the chronic low grade inflammation of obesity impairs pulmonary vascular homeostasis and primes the lung for acute injury. The lung endothelium from obese mice expressed higher levels of leukocyte adhesion markers and lower levels of cell-cell junctional proteins when compared to lean mice. We tested whether systemic factors are responsible for …

Apoε2 And Education In Cognitively Normal Older Subjects With High Levels Of Ad Pathology At Autopsy: Findings From The Nun Study, Diego Iacono, Peter Zandi, Myron Gross, William R. Markesbery, Olga Pletnikova, Gay Rudow, Juan C. Troncoso

Sanders-Brown Center on Aging Faculty Publications

Asymptomatic Alzheimer's disease (ASYMAD) subjects are individuals characterized by preserved cognition before death despite substantial AD pathology at autopsy. ASYMAD subjects show comparable levels of AD pathology, i.e. β-amyloid neuritic plaques (Aβ-NP) and tau-neurofibrillary tangles (NFT), to those observed in mild cognitive impairment (MCI) and some definite AD cases. Previous clinicopathologic studies on ASYMAD subjects have shown specific phenomena of hypertrophy in the cell bodies, nuclei, and nucleoli of hippocampal pyramidal neurons and other cerebral areas. Since it is well established that the allele APOε4 is a major genetic risk factor for AD, we examined whether specific alleles of APOE …

Trop-2 Is Up-Regulated In Invasive Prostate Cancer And Displaces Fak From Focal Contacts., Marco Trerotola, Kirat K Ganguly, Ladan Fazli, Carmine Fedele, Huimin Lu, Anindita Dutta, Qin Liu, Tiziana De Angelis, Luke W Riddell, Natalia A Riobo, Martin E Gleave, Amina Zoubeidi, Richard Pestell, Dario C Altieri, Lucia R Languino

Department of Urology Faculty Papers

In this study, we show that the transmembrane glycoprotein Trop-2 is up-regulated in human prostate cancer (PCa) with extracapsular extension (stages pT3/pT4) as compared to organ-confined (stage pT2) PCa. Consistent with this evidence, Trop-2 expression is found to be increased in metastatic prostate tumors of Transgenic Adenocarcinoma of Mouse Prostate mice and to strongly correlate with α5β1 integrin levels. Using PCa cells, we show that Trop-2 specifically associates with the α5 integrin subunit, as binding to α3 is not observed, and that Trop-2 displaces focal adhesion kinase from focal contacts. In support of the role of Trop-2 as a promoter …

Akt Inhibition Overcomes Rapamycin Resistance By Enhancing The Repressive Function Of Pras40 On Mtorc1/4e-Bp1 Axis, Wenting Mi, Qing Ye, Side Liu, Qing-Bai She

Markey Cancer Center Faculty Publications

The mTORC1 inhibitors, rapamycin and its analogs, are known to show only modest antitumor activity in clinic, but the underlying mechanisms remain largely elusive. Here, we found that activated AKT signaling is associated with rapamycin resistance in breast and colon cancers by sustained phosphorylation of the translational repressor 4E-BP1. Treatment of tumor cells with rapamycin or the AKT inhibitor MK2206 showed a limited activity in inhibiting 4E-BP1 phosphorylation, cap-dependent translation, cell growth and motility. However, treatment with both drugs resulted in profound effects in vitro and in vivo. Mechanistic investigation demonstrated that the combination treatment was required to effectively …