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Articles 1 - 30 of 7032

Full-Text Articles in Medicine and Health Sciences

Effect Of Differences In Metabolic Activity Of Melanoma Models On Response To Lonidamine Plus Doxorubicin., Kavindra Nath, Jeffrey Roman, David S. Nelson, Lili Guo, Seung-Cheol Lee, Stepan Orlovskiy, Kevin Muriuki, Daniel F. Heitjan, Stephen Pickup, Dennis B. Leeper, Ian A. Blair, Mary E. Putt, Jerry D. Glickson Dec 2018

Effect Of Differences In Metabolic Activity Of Melanoma Models On Response To Lonidamine Plus Doxorubicin., Kavindra Nath, Jeffrey Roman, David S. Nelson, Lili Guo, Seung-Cheol Lee, Stepan Orlovskiy, Kevin Muriuki, Daniel F. Heitjan, Stephen Pickup, Dennis B. Leeper, Ian A. Blair, Mary E. Putt, Jerry D. Glickson

Department of Radiation Oncology Faculty Papers

Lonidamine (LND), a metabolic modulator, sensitizes DB-1 human melanoma to doxorubicin (DOX) chemotherapy by acidifying and de-energizing the tumor. This report compares the effects of LND on two human melanoma lines, DB-1 and WM983B, which exhibit different metabolic properties. Using liquid chromatography mass spectrometry and Seahorse analysis, we show that DB-1 was more glycolytic than WM983B in vitro. 31P magnetic resonance spectroscopy (MRS) indicates that LND (100 mg/kg, i.p.) induces similar selective acidification and de-energization of WM983B xenografts in immunosuppressed mice. Over three hours, intracellular pH (pHi) of WM983B decreased from 6.91 ± 0.03 to 6 ...


Levels Of Par-1 Kinase Determine The Localization Of Bruchpilot At The Drosophila Neuromuscular Junction Synapses., Kara R. Barber, Martin Hruska, Keegan M. Bush, Jade A. Martinez, Hong Fei, Irwin B. Levitan, Matthew B. Dalva, Yogesh P. Wairkar Dec 2018

Levels Of Par-1 Kinase Determine The Localization Of Bruchpilot At The Drosophila Neuromuscular Junction Synapses., Kara R. Barber, Martin Hruska, Keegan M. Bush, Jade A. Martinez, Hong Fei, Irwin B. Levitan, Matthew B. Dalva, Yogesh P. Wairkar

Farber Institute for Neurosciences Faculty Papers

Functional synaptic networks are compromised in many neurodevelopmental and neurodegenerative diseases. While the mechanisms of axonal transport and localization of synaptic vesicles and mitochondria are relatively well studied, little is known about the mechanisms that regulate the localization of proteins that localize to active zones. Recent finding suggests that mechanisms involved in transporting proteins destined to active zones are distinct from those that transport synaptic vesicles or mitochondria. Here we report that localization of BRP-an essential active zone scaffolding protein in Drosophila, depends on the precise balance of neuronal Par-1 kinase. Disruption of Par-1 levels leads to excess accumulation of ...


Loss-Of-Function Mutations In Atp6ap1 And Atp6ap2 In Granular Cell Tumors., Fresia Pareja, Alissa H. Brandes, Thais Basili, Pier Selenica, Felipe C. Geyer, Dan Fan, Arnaud Da Cruz Paula, Rahul Kumar, David N. Brown, Rodrigo Gularte-Mérida, Barbara Alemar, Rui Bi, Raymond S. Lim, Ino De Bruijn, Sho Fujisawa, Rui Gardner, Elvin Feng, Anqi Li, Edaise M. Da Silva, John R. Lozada, Pedro Blecua, Leona Cohen-Gould, Achim A. Jungbluth, Emad A. Rakha, Ian O. Ellis, Maria I.A. Edelweiss, Juan P. Palazzo, Larry Norton, Travis Hollmann, Marcia Edelweiss, Brian P. Rubin, Britta Weigelt, Jorge S. Reis-Filho Dec 2018

Loss-Of-Function Mutations In Atp6ap1 And Atp6ap2 In Granular Cell Tumors., Fresia Pareja, Alissa H. Brandes, Thais Basili, Pier Selenica, Felipe C. Geyer, Dan Fan, Arnaud Da Cruz Paula, Rahul Kumar, David N. Brown, Rodrigo Gularte-Mérida, Barbara Alemar, Rui Bi, Raymond S. Lim, Ino De Bruijn, Sho Fujisawa, Rui Gardner, Elvin Feng, Anqi Li, Edaise M. Da Silva, John R. Lozada, Pedro Blecua, Leona Cohen-Gould, Achim A. Jungbluth, Emad A. Rakha, Ian O. Ellis, Maria I.A. Edelweiss, Juan P. Palazzo, Larry Norton, Travis Hollmann, Marcia Edelweiss, Brian P. Rubin, Britta Weigelt, Jorge S. Reis-Filho

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Granular cell tumors (GCTs) are rare tumors that can arise in multiple anatomical locations, and are characterized by abundant intracytoplasmic granules. The genetic drivers of GCTs are currently unknown. Here, we apply whole-exome sequencing and targeted sequencing analysis to reveal mutually exclusive, clonal, inactivating somatic mutations in the endosomal pH regulators ATP6AP1 or ATP6AP2 in 72% of GCTs. Silencing of these genes in vitro results in impaired vesicle acidification, redistribution of endosomal compartments, and accumulation of intracytoplasmic granules, recapitulating the cardinal phenotypic characteristics of GCTs and providing a novel genotypic-phenotypic correlation. In addition, depletion of ATP6AP1 or ATP6AP2 results in ...


A Learning Community Approach To Identifying Interventions In Health Systems To Reduce Colorectal Cancer Screening Disparities., Lillian C. Man, Melissa Dicarlo, Emily Lambert, Randa Sifri, Martha Romney, Linda Fleisher, Ronald Myers Dec 2018

A Learning Community Approach To Identifying Interventions In Health Systems To Reduce Colorectal Cancer Screening Disparities., Lillian C. Man, Melissa Dicarlo, Emily Lambert, Randa Sifri, Martha Romney, Linda Fleisher, Ronald Myers

Department of Medical Oncology Faculty Papers

Although colorectal cancer (CRC) screening in the United States has been increasing, screening rates are not optimal, and there are persistent disparities in CRC screening and mortality, particularly among minority patients. As most CRC screening takes place in primary care, health systems are well-positioned to address this important population health problem. However, most health systems have not actively engaged in identifying and implementing effective evidence-based intervention strategies that can raise CRC screening rates and reduce disparities. Drawing on the Collective Impact Model and the Interactive Systems Framework for Dissemination and Implementation, our project team applied a learning community strategy to ...


Non-Neutralizing Antibodies Elicited By Recombinant Lassa-Rabies Vaccine Are Critical For Protection Against Lassa Fever., Tiago Abreu-Mota, Katie R. Hagen, Kurt Cooper, Peter B. Jahrling, Gene Tan, Christoph Wirblich, Reed F. Johnson, Matthias J. Schnell Dec 2018

Non-Neutralizing Antibodies Elicited By Recombinant Lassa-Rabies Vaccine Are Critical For Protection Against Lassa Fever., Tiago Abreu-Mota, Katie R. Hagen, Kurt Cooper, Peter B. Jahrling, Gene Tan, Christoph Wirblich, Reed F. Johnson, Matthias J. Schnell

Department of Microbiology and Immunology Faculty Papers

Lassa fever (LF), caused by Lassa virus (LASV), is a viral hemorrhagic fever for which no approved vaccine or potent antiviral treatment is available. LF is a WHO priority disease and, together with rabies, a major health burden in West Africa. Here we present the development and characterization of an inactivated recombinant LASV and rabies vaccine candidate (LASSARAB) that expresses a codon-optimized LASV glycoprotein (coGPC) and is adjuvanted by a TLR-4 agonist (GLA-SE). LASSARAB elicits lasting humoral response against LASV and RABV in both mouse and guinea pig models, and it protects both guinea pigs and mice against LF. We ...


Medial Temporal Lobe Functional Connectivity Predicts Stimulation-Induced Theta Power., E. A. Solomon, J. E. Kragel, R. Gross, B. Lega, M. R. Sperling, G. Worrell, S. A. Sheth, K. A. Zaghloul, B. C. Jobst, J. M. Stein, S. Das, R. Gorniak, C. S. Inman, S. Seger, D. S. Rizzuto, M. J. Kahana Dec 2018

Medial Temporal Lobe Functional Connectivity Predicts Stimulation-Induced Theta Power., E. A. Solomon, J. E. Kragel, R. Gross, B. Lega, M. R. Sperling, G. Worrell, S. A. Sheth, K. A. Zaghloul, B. C. Jobst, J. M. Stein, S. Das, R. Gorniak, C. S. Inman, S. Seger, D. S. Rizzuto, M. J. Kahana

Department of Neurology Faculty Papers

Focal electrical stimulation of the brain incites a cascade of neural activity that propagates from the stimulated region to both nearby and remote areas, offering the potential to control the activity of brain networks. Understanding how exogenous electrical signals perturb such networks in humans is key to its clinical translation. To investigate this, we applied electrical stimulation to subregions of the medial temporal lobe in 26 neurosurgical patients fitted with indwelling electrodes. Networks of low-frequency (5-13 Hz) spectral coherence predicted stimulation-evoked increases in theta (5-8 Hz) power, particularly when stimulation was applied in or adjacent to white matter. Stimulation tended ...


Sumo-Mediated Regulation Of Nlrp3 Modulates Inflammasome Activity., Rachael Barry, Sidonie Wicky John, Gianmaria Liccardi, Tencho Tenev, Isabel Jaco, Chih-Hong Chen, Justin Choi, Paulina Kasperkiewicz, Teresa Fernandes-Alnemri, Emad S Alnemri, Marcin Drag, Yuan Chen, Pascal Meier Dec 2018

Sumo-Mediated Regulation Of Nlrp3 Modulates Inflammasome Activity., Rachael Barry, Sidonie Wicky John, Gianmaria Liccardi, Tencho Tenev, Isabel Jaco, Chih-Hong Chen, Justin Choi, Paulina Kasperkiewicz, Teresa Fernandes-Alnemri, Emad S Alnemri, Marcin Drag, Yuan Chen, Pascal Meier

Department of Biochemistry and Molecular Biology Faculty Papers

The NLRP3 inflammasome responds to infection and tissue damage, and rapidly escalates the intensity of inflammation by activating interleukin (IL)-1β, IL-18 and cell death by pyroptosis. How the NLRP3 inflammasome is negatively regulated is poorly understood. Here we show that NLRP3 inflammasome activation is suppressed by sumoylation. NLRP3 is sumoylated by the SUMO E3-ligase MAPL, and stimulation-dependent NLRP3 desumoylation by the SUMO-specific proteases SENP6 and SENP7 promotes NLRP3 activation. Defective NLRP3 sumoylation, either by NLRP3 mutation of SUMO acceptor lysines or depletion of MAPL, results in enhanced caspase-1 activation and IL-1β release. Conversely, depletion of SENP7 suppresses NLRP3-dependent ASC ...


Nkx2-1-As1 Negatively Regulates Cd274/Pd-L1, Cell-Cell Interaction Genes, And Limits Human Lung Carcinoma Cell Migration., Hasmeena Kathuria, Guetchyn Millien, Liam Mcnally, Adam C. Gower, Jean-Bosco Tagne, Yuxia Cao, Maria I. Ramirez Dec 2018

Nkx2-1-As1 Negatively Regulates Cd274/Pd-L1, Cell-Cell Interaction Genes, And Limits Human Lung Carcinoma Cell Migration., Hasmeena Kathuria, Guetchyn Millien, Liam Mcnally, Adam C. Gower, Jean-Bosco Tagne, Yuxia Cao, Maria I. Ramirez

Center for Translational Medicine Faculty Papers

The function of most long noncoding RNAs (lncRNAs) is unknown. However, recent studies reveal important roles of lncRNAs in regulating cancer-related pathways. Human antisense lncRNA-NKX2-1-AS1 partially overlaps the NKX2-1/TTF1 gene within chromosomal region 14q13.3. Amplification of this region and/or differential expression of genes therein are associated with cancer progression. Herein we show higher levels of NKX2-AS1 and NKX2-1 in lung adenocarcinomas relative to non-tumor controls but no correlation between NKX2-1-AS1 and NKX2-1 levels across specimens, or with amplification of the 14q13.3 region, suggesting that NKX2-1-AS1 and NKX2-1 are independently regulated. Loss-and-gain of function experiments showed that ...


Emt- And Stroma-Related Gene Expression And Resistance To Pd-1 Blockade In Urothelial Cancer., Li Wang, Abdel Saci, Peter M. Szabo, Scott D. Chasalow, Mireia Castillo-Martin, Josep Domingo-Domenech, Arlene Siefker-Radtke, Padmanee Sharma, John P. Sfakianos, Yixuan Gong, Ana Dominguez-Andres, William K. Oh, David Mulholland, Alex Azrilevich, Liangyuan Hu, Carlos Cordon-Cardo, Hélène Salmon, Nina Bhardwaj, Jun Zhu, Matthew D. Galsky Dec 2018

Emt- And Stroma-Related Gene Expression And Resistance To Pd-1 Blockade In Urothelial Cancer., Li Wang, Abdel Saci, Peter M. Szabo, Scott D. Chasalow, Mireia Castillo-Martin, Josep Domingo-Domenech, Arlene Siefker-Radtke, Padmanee Sharma, John P. Sfakianos, Yixuan Gong, Ana Dominguez-Andres, William K. Oh, David Mulholland, Alex Azrilevich, Liangyuan Hu, Carlos Cordon-Cardo, Hélène Salmon, Nina Bhardwaj, Jun Zhu, Matthew D. Galsky

Department of Cancer Biology Faculty Papers

Cancers infiltrated with T-cells are associated with a higher likelihood of response to PD-1/PD-L1 blockade. Counterintuitively, a correlation between epithelial-mesenchymal transition (EMT)-related gene expression and T-cell infiltration has been observed across tumor types. Here we demonstrate, using The Cancer Genome Atlas (TCGA) urothelial cancer dataset, that although a gene expression-based measure of infiltrating T-cell abundance and EMT-related gene expression are positively correlated, these signatures convey disparate prognostic information. We further demonstrate that non-hematopoietic stromal cells are a major source of EMT-related gene expression in bulk urothelial cancer transcriptomes. Finally, using a cohort of patients with metastatic urothelial cancer ...


The Genomic Landscape Of Cutaneous Scc Reveals Drivers And A Novel Azathioprine Associated Mutational Signature., Gareth J. Inman, Jun Wang, Ai Nagano, Ludmil B. Alexandrov, Karin J. Purdie, Richard G. Taylor, Victoria Sherwood, Jason Thomson, Sarah Hogan, Lindsay C. Spender, Andrew P. South, Michael Stratton, Claude Chelala, Catherine A. Harwood, Charlotte M. Proby, Irene M. Leigh Dec 2018

The Genomic Landscape Of Cutaneous Scc Reveals Drivers And A Novel Azathioprine Associated Mutational Signature., Gareth J. Inman, Jun Wang, Ai Nagano, Ludmil B. Alexandrov, Karin J. Purdie, Richard G. Taylor, Victoria Sherwood, Jason Thomson, Sarah Hogan, Lindsay C. Spender, Andrew P. South, Michael Stratton, Claude Chelala, Catherine A. Harwood, Charlotte M. Proby, Irene M. Leigh

Department of Dermatology and Cutaneous Biology Faculty Papers

Cutaneous squamous cell carcinoma (cSCC) has a high tumour mutational burden (50 mutations per megabase DNA pair). Here, we combine whole-exome analyses from 40 primary cSCC tumours, comprising 20 well-differentiated and 20 moderately/poorly differentiated tumours, with accompanying clinical data from a longitudinal study of immunosuppressed and immunocompetent patients and integrate this analysis with independent gene expression studies. We identify commonly mutated genes, copy number changes and altered pathways and processes. Comparisons with tumour differentiation status suggest events which may drive disease progression. Mutational signature analysis reveals the presence of a novel signature (signature 32), whose incidence correlates with chronic ...


Perioperative Aspirin And Long-Term Survival In Patients Undergoing Coronary Artery Bypass Graft., Qian Ding, Hong Liu, Zugui Zhang, Jordan E. Goldhammer, Eric Yuen, Zhongmin Li, Linong Yao, Nilas Young, Douglas Boyd, William Weintraub, Rohinton Morris, Jianzhong Sun Dec 2018

Perioperative Aspirin And Long-Term Survival In Patients Undergoing Coronary Artery Bypass Graft., Qian Ding, Hong Liu, Zugui Zhang, Jordan E. Goldhammer, Eric Yuen, Zhongmin Li, Linong Yao, Nilas Young, Douglas Boyd, William Weintraub, Rohinton Morris, Jianzhong Sun

Department of Anesthesiology Faculty Papers

This study aimed to examine association between perioperative uses of aspirin and long-term survival in patients undergoing CABG. A retrospective cohort study was performed in 9,584 consecutive patients receiving cardiac surgery from three tertiary hospitals. Of all the patients, 4,132 patients undergoing CABG met inclusion criteria and were divided into four groups: with or without preoperative or postoperative aspirin respectively. 30-day postoperative and long-term mortality were compared with the use of propensity scores and inverse probability weighting adjustment to reduce the treatment-selection bias. The patients taking preoperative aspirin presented significantly more with comorbidities. However, the results of this ...


Bilateral Mastectomy, Choroidal Mass: A Curve Ball., Phillip Gordon, Carol L. Shields Dec 2018

Bilateral Mastectomy, Choroidal Mass: A Curve Ball., Phillip Gordon, Carol L. Shields

Wills Eye Hospital Papers

No abstract provided.


Pigmented Villonodular Synovitis Does Not Influence The Outcome Following Cementless Total Hip Arthroplasty Using Ceramic-On-Ceramic Articulation: A Case-Control Study With Middle-Term Follow-Up., Chi Xu, Heng Guo, Kerri L. Bell, Feng-Chih Kuo, Ji-Ying Chen Nov 2018

Pigmented Villonodular Synovitis Does Not Influence The Outcome Following Cementless Total Hip Arthroplasty Using Ceramic-On-Ceramic Articulation: A Case-Control Study With Middle-Term Follow-Up., Chi Xu, Heng Guo, Kerri L. Bell, Feng-Chih Kuo, Ji-Ying Chen

Rothman Institute

BACKGROUND: Pigmented villonodular synovitis (PVNS) is a relatively rare, locally aggressive, and potentially recurrent synovial disease of large joints. The purpose of this study was to investigate (1) the disease recurrence rate and (2) the treatment outcomes including Harris hip scores, complications, and revision following cementless total hip arthroplasty (THA) with ceramic-on-ceramic (CoC) articulation in patients with PVNS.

METHODS: Twenty-two patients (14 females and 8 males) with histologically confirmed PVNS underwent cementless THA using CoC bearings between 2000 and 2013. Three patients with less than 5-year follow-up were excluded. The mean age was 35.2 years (range, 22-58 years) with ...


Semaphorin 5a Drives Melanoma Progression: Role Of Bcl-2, Mir-204 And C-Myb., Simona D'Aguanno, Elisabetta Valentini, Maria Grazia Tupone, Marianna Desideri, Marta Di Martile, Manuela Spagnuolo, Simonetta Buglioni, Cristiana Ercolani, Italia Falcone, Marco De Dominici, Michele Milella, Maria Giulia Rizzo, Bruno Calabretta, Carlo Cota, Andrea Anichini, Daniela Trisciuoglio, Donatella Del Bufalo Nov 2018

Semaphorin 5a Drives Melanoma Progression: Role Of Bcl-2, Mir-204 And C-Myb., Simona D'Aguanno, Elisabetta Valentini, Maria Grazia Tupone, Marianna Desideri, Marta Di Martile, Manuela Spagnuolo, Simonetta Buglioni, Cristiana Ercolani, Italia Falcone, Marco De Dominici, Michele Milella, Maria Giulia Rizzo, Bruno Calabretta, Carlo Cota, Andrea Anichini, Daniela Trisciuoglio, Donatella Del Bufalo

Department of Cancer Biology Faculty Papers

BACKGROUND: Melanoma, the most aggressive form of skin cancer, is characterized by high rates of metastasis, drug resistance and mortality. Here we investigated the role of Semaphorin 5A (Sema5A) on the properties associated with melanoma progression and the factors involved in Sema5A regulation.

METHODS: Western blotting, qRT-PCR, Chromatin immunoprecipitation (ChIP) assay, immunohistochemistry of melanoma patient specimens and xenograft tissues, in vitro Transwell assay for cell migration and invasion evaluation, in vitro capillary-like structure formation analysis.

RESULTS: A significant correlation of Sema5A mRNA expression and melanoma progression was observed by analyzing GEO profile dataset. Endogenous Sema5A protein was detected in 95 ...


Distinct Role Of Il-27 In Immature And Lps-Induced Mature Dendritic Cell-Mediated Development Of Cd4, Fang Zhou, Guang-Xian Zhang, A. M. Rostami Nov 2018

Distinct Role Of Il-27 In Immature And Lps-Induced Mature Dendritic Cell-Mediated Development Of Cd4, Fang Zhou, Guang-Xian Zhang, A. M. Rostami

Department of Neurology Faculty Papers

Interleukin-27 (IL-27) plays an important role in regulation of anti-inflammatory responses and autoimmunity; however, the molecular mechanisms of IL-27 in modulation of immune tolerance and autoimmunity have not been fully elucidated. Dendritic cells (DCs) play a central role in regulating immune responses mediated by innate and adaptive immune systems, but regulatory mechanisms of DCs in CD4+ T cell-mediated immune responses have not yet been elucidated. Here we show that IL-27 treated mature DCs induced by LPS inhibit immune tolerance mediated by LPS-stimulated DCs. IL-27 treatment facilitates development of the CD4+ CD127+3G11+ regulatory T cell subset in vitro and in ...


Scientific Collaborations In Pancreatic Cancer And What's On The Horizon For Research/Clinical Trials, Jonathan R. Brody, Phd, Elda Grabocka, Phd, Michael J. Pishvaian, Md, Phd, James A. Poser, Iii, Md Nov 2018

Scientific Collaborations In Pancreatic Cancer And What's On The Horizon For Research/Clinical Trials, Jonathan R. Brody, Phd, Elda Grabocka, Phd, Michael J. Pishvaian, Md, Phd, James A. Poser, Iii, Md

Pancreatic Cancer & Related Diseases Symposium

No abstract provided.


Breakfast With The Experts, Tbd Nov 2018

Breakfast With The Experts, Tbd

Pancreatic Cancer & Related Diseases Symposium

Continental Breakfast, Informational Tables & Scientific Poster Presentations


Mutant Ubqln2p497h In Motor Neurons Leads To Als-Like Phenotypes And Defective Autophagy In Rats, Tianhong Chen, Bo Huang, Xinglong Shi, Limo Gao, Cao Huang Nov 2018

Mutant Ubqln2p497h In Motor Neurons Leads To Als-Like Phenotypes And Defective Autophagy In Rats, Tianhong Chen, Bo Huang, Xinglong Shi, Limo Gao, Cao Huang

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Mutations in ubiquilin2 (UBQLN2) have been linked to abnormal protein aggregation in amyotrophic lateral sclerosis (ALS). The mechanisms underlying UBQLN2-related neurodegenerative diseases remain unclear. Using a tetracycline-regulated gene expression system, the ALS-linked UBQLN2P497H mutant was selectively expressed in either the spinal motor neurons or astrocytes in rats. We found that selectively expressing mutant UBQLN2P497H in the spinal motor neurons caused several core features of ALS, including the progressive degeneration of motor neurons, the denervation atrophy of skeletal muscles, and the abnormal protein accumulation. Furthermore, mutant UBQLN2P497H accumulation was associated with an age-dependent decrease in several core autophagy-related proteins. ALS-like phenotypes ...


Human-Like Hyperplastic Prostate With Low Zip1 Induced Solely By Zn Deficiency In Rats., Louise Y. Fong, Ruiyan Jing, Karl J. Smalley, Zi-Xuan Wang, Cristian Taccioli, Sili Fan, Hongping Chen, Hansjuerg Alder, Kay Huebner, John L. Farber, Oliver Fiehn, Carlo M. Croce Nov 2018

Human-Like Hyperplastic Prostate With Low Zip1 Induced Solely By Zn Deficiency In Rats., Louise Y. Fong, Ruiyan Jing, Karl J. Smalley, Zi-Xuan Wang, Cristian Taccioli, Sili Fan, Hongping Chen, Hansjuerg Alder, Kay Huebner, John L. Farber, Oliver Fiehn, Carlo M. Croce

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Prostate cancer is a leading cause of cancer death in men over 50 years of age, and there is a characteristic marked decrease in Zn content in the malignant prostate cells. The cause and consequences of this loss have thus far been unknown. We found that in middle-aged rats a Zn-deficient diet reduces prostatic Zn levels (P = 0.025), increases cellular proliferation, and induces an inflammatory phenotype with COX-2 overexpression. This hyperplastic/inflammatory prostate has a human prostate cancer-like microRNA profile, with up-regulation of the Zn-homeostasis-regulating miR-183-96-182 cluster (fold change = 1.41-2.38; P = 0.029-0.0003) and down-regulation of ...


Performance Of Prostate Cancer Recurrence Nomograms By Obesity Status: A Retrospective Analysis Of A Radical Prostatectomy Cohort., Charnita Zeigler-Johnson, Aaron Hudson, Karen Glanz, Elaine Spangler, Knashawn H Morales Nov 2018

Performance Of Prostate Cancer Recurrence Nomograms By Obesity Status: A Retrospective Analysis Of A Radical Prostatectomy Cohort., Charnita Zeigler-Johnson, Aaron Hudson, Karen Glanz, Elaine Spangler, Knashawn H Morales

Department of Medical Oncology Faculty Papers

BACKGROUND: Obesity has been associated with aggressive prostate cancer and poor outcomes. It is important to understand how prognostic tools for that guide prostate cancer treatment may be impacted by obesity. The goal of this study was to evaluate the predicting abilities of two prostate cancer (PCa) nomograms by obesity status.

METHODS: We examined 1576 radical prostatectomy patients categorized into standard body mass index (BMI) groups. Patients were categorized into low, medium, and high risk groups for the Kattan and CaPSURE/CPDR scores, which are based on PSA value, Gleason score, tumor stage, and other patient data. Time to PCa ...


Unilateral Macular Drusen In A Young Female., Kareem Sioufi, Katherine E Talcott, Marc J Spirn Nov 2018

Unilateral Macular Drusen In A Young Female., Kareem Sioufi, Katherine E Talcott, Marc J Spirn

Wills Eye Hospital Papers

No abstract provided.


A Word From The Writing Team (November 2018), Jennifer Wilson, Ms, Els, Pam Walter, Mfa Nov 2018

A Word From The Writing Team (November 2018), Jennifer Wilson, Ms, Els, Pam Walter, Mfa

A Word From the Writing Team (Newsletter)

This issue includes:

  • New! Open Access Funds Available
  • January Writing Retreat
  • A Thanksgiving Thought


Hypoxia-Mediated Mitochondria Apoptosis Inhibition Induces Temozolomide Treatment Resistance Through Mir-26a/Bad/Bax Axis., Xin Ge, Min-Hong Pan, Lin Wang, Wei Li, Chengfei Jiang, Jun He, Khaled Abouzid, Ling-Zhi Liu, Zhumei Shi, Bing-Hua Jiang Nov 2018

Hypoxia-Mediated Mitochondria Apoptosis Inhibition Induces Temozolomide Treatment Resistance Through Mir-26a/Bad/Bax Axis., Xin Ge, Min-Hong Pan, Lin Wang, Wei Li, Chengfei Jiang, Jun He, Khaled Abouzid, Ling-Zhi Liu, Zhumei Shi, Bing-Hua Jiang

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Glioblastoma multiforme (GBM) is one of the most hypoxic tumors of the central nervous system. Although temozolomide (TMZ) is an effective clinical agent in the GBM therapy, the hypoxic microenvironment remains a major barrier in glioma chemotherapy resistance, and the underlying mechanisms are poorly understood. Here, we find hypoxia can induce the protective response to mitochondrion via HIF-1α-mediated miR-26a upregulation which is associated with TMZ resistance in vitro and in vivo. Further, we demonstrated that HIF-1α/miR-26a axis strengthened the acquisition of TMZ resistance through prevention of Bax and Bad in mitochondria dysfunction in GBM. In addition, miR-26a expression levels ...


Aberrant Arid5b Expression And Its Association With Ikaros Dysfunction In Acute Lymphoblastic Leukemia., Zheng Ge, Qi Han, Yan Gu, Qinyu Ge, Jinlong Ma, Justin Sloane, Guofeng Gao, Kimberly J. Payne, Laszlo Szekely, Chunhua Song, Sinisa Dovat Nov 2018

Aberrant Arid5b Expression And Its Association With Ikaros Dysfunction In Acute Lymphoblastic Leukemia., Zheng Ge, Qi Han, Yan Gu, Qinyu Ge, Jinlong Ma, Justin Sloane, Guofeng Gao, Kimberly J. Payne, Laszlo Szekely, Chunhua Song, Sinisa Dovat

Abington Hospital Papers

Mutations and single nucleotide polymorphisms of AT-rich interactive domain-containing protein 5B (ARID5B) are involved in the oncogenesis of acute lymphoblastic leukemia (ALL) and treatment outcomes. However, ARID5B expression and clinical significance in ALL remain unclear. We found ARID5B is significantly down-regulated in ALL compared to healthy bone marrow controls. ARID5B also interacts with PHD finger protein 2 (PHF2). Low expression of ARID5B (ARID5Blow) or ARID5B and PHF2 (ARID5BlowPHF2low) is correlated with the markers of cell proliferation and poor prognosis in ALL patients. Ikaros directly regulates ARID5B expression in ALL. Restoring Ikaros function by Casein Kinase II ...


Utilizing V-Y Fasciocutaneous Advancement Flaps For Vulvar Reconstruction., Lauren C. Hand, Talia Maas, Nadia Baka, Rebecca J. Mercier, Patrick J. Greaney, Norman G. Rosenblum, Christine H. Kim Nov 2018

Utilizing V-Y Fasciocutaneous Advancement Flaps For Vulvar Reconstruction., Lauren C. Hand, Talia Maas, Nadia Baka, Rebecca J. Mercier, Patrick J. Greaney, Norman G. Rosenblum, Christine H. Kim

Department of Obstetrics and Gynecology Faculty Papers

Objectives: We aimed to analyze the outcomes of patients who underwent vulvectomy with subsequent V-Y fasciocutaneous flap reconstruction.

Methods: All medical records of all patients who underwent vulvectomies with V-Y fasciocutaneous flap reconstruction from January 2007 to June 2016 were retrospectively reviewed. Patient clinical and surgical data, demographics, and outcomes were abstracted.

Results: Of the 27 patients, 42 flaps were transferred. A simple vulvectomy was performed in 8 (30%) patients, partial radical vulvectomy in 15 (56%), and radical vulvectomy in 4 (15%). The median area of defect was 30 cm

Conclusions: The use of a V-Y fasciocutaneous advancement flap for ...


Download Entire Issue: Gibbon Surgical Review, Volume 1, Issue 2, 2018 Nov 2018

Download Entire Issue: Gibbon Surgical Review, Volume 1, Issue 2, 2018

Gibbon Surgical Review

Download Entire Issue: Gibbon Surgical Review, Volume 1, Number 2, 2018


The Impact Of Depression On Patient Outcomes In Hip Arthroscopic Surgery., Robroy L. Martin, John J. Christoforetti, Ryan Mcgovern, Benjamin R. Kivlan, Andrew B. Wolff, Shane J. Nho, John P. Salvo, Thomas J. Ellis, Geoff Van Thiel, Dean Matsuda, Dominic S. Carreira Nov 2018

The Impact Of Depression On Patient Outcomes In Hip Arthroscopic Surgery., Robroy L. Martin, John J. Christoforetti, Ryan Mcgovern, Benjamin R. Kivlan, Andrew B. Wolff, Shane J. Nho, John P. Salvo, Thomas J. Ellis, Geoff Van Thiel, Dean Matsuda, Dominic S. Carreira

Department of Medicine Faculty Papers

Background: Mental health impairments have been shown to negatively affect preoperative self-reported function in patients with various musculoskeletal disorders, including those with femoroacetabular impingement.

Hypothesis: Those with symptoms of depression will have lower self-reported function, more pain, and less satisfaction on initial assessment and at 2-year follow-up than those without symptoms of depression.

Study Design: Cohort study; Level of evidence, 3.

Methods: Patients who were enrolled in a multicenter hip arthroscopic surgery registry and had 2-year outcome data available were included in the study. Patients completed the 12-item International Hip Outcome Tool (iHOT-12), visual analog scale (VAS) for pain, and ...


Potential Role Of Csf Cytokine Profiles In Discriminating Infectious From Non-Infectious Cns Disorders., Danielle Fortuna, D. Craig Hooper, Amity L. Roberts, Larry A. Harshyne, Michelle Nagurney, Mark T. Curtis Oct 2018

Potential Role Of Csf Cytokine Profiles In Discriminating Infectious From Non-Infectious Cns Disorders., Danielle Fortuna, D. Craig Hooper, Amity L. Roberts, Larry A. Harshyne, Michelle Nagurney, Mark T. Curtis

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Current laboratory testing of cerebrospinal fluid (CSF) does not consistently discriminate between different central nervous system (CNS) disease states. Rapidly distinguishing CNS infections from other brain and spinal cord disorders that share a similar clinical presentation is critical. New approaches focusing on aspects of disease biology, such as immune response profiles that can have stimulus-specific attributes, may be helpful. We undertook this preliminary proof-of-concept study using multiplex ELISA to measure CSF cytokine levels in various CNS disorders (infections, autoimmune/demyelinating diseases, lymphomas, and gliomas) to determine the potential utility of cytokine patterns in differentiating CNS infections from other CNS diseases ...


The Impact Of Disease-Modifying Therapy Access Barriers On People With Multiple Sclerosis: Mixed-Methods Study., Kristina F. Simacek, John J. Ko, Debbie Moreton, Stefan Varga, Kristen Johnson, Bozena J. Katic Oct 2018

The Impact Of Disease-Modifying Therapy Access Barriers On People With Multiple Sclerosis: Mixed-Methods Study., Kristina F. Simacek, John J. Ko, Debbie Moreton, Stefan Varga, Kristen Johnson, Bozena J. Katic

College of Population Health Faculty Papers

BACKGROUND: In the United States, people with relapsing-remitting multiple sclerosis (RRMS) can face difficulty accessing disease-modifying therapies (DMTs) because of insurance, pharmacy, or provider policies. These barriers have been associated with poor adherence and negative health outcomes.

OBJECTIVE: The goals of this study were to describe the overall occurrence of difficulties and delays associated with gaining access to DMTs among people with RRMS, to assess DMT adherence during periods of reduced access, and to contextualize the patients' journey from receipt of a prescription for DMT to obtaining and taking their medication when faced with access barriers.

METHODS: We recruited US-based ...


Bacterial Contamination Of Platelets For Transfusion: Strategies For Prevention., Jerrold H. Levy, Matthew D. Neal, Jay H. Herman Oct 2018

Bacterial Contamination Of Platelets For Transfusion: Strategies For Prevention., Jerrold H. Levy, Matthew D. Neal, Jay H. Herman

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Platelet transfusions carry greater risks of infection, sepsis, and death than any other blood product, owing primarily to bacterial contamination. Many patients may be at particular risk, including critically ill patients in the intensive care unit. This narrative review provides an overview of the problem and an update on strategies for the prevention, detection, and reduction/inactivation of bacterial contaminants in platelets. Bacterial contamination and septic transfusion reactions are major sources of morbidity and mortality. Between 1:1000 and 1:2500 platelet units are bacterially contaminated. The skin bacterial microflora is a primary source of contamination, and enteric contaminants are ...