Digital Commons Network^™

A Forward Genetic Screen Reveals Novel Independent Regulators Of Ulbp1, An Activating Ligand For Natural Killer Cells, Benjamin G Gowen, Bryan Chim, Caleb D. Marceau, Trever T Greene, Patrick Burr, Jeanmarie R. Gonzalez, Charles Hesser, Peter A. Dietzen, Teal Russell, Alexandre Iannello, Laurent Coscoy, Charles L. Sentman

Dartmouth Scholarship

Recognition and elimination of tumor cells by the immune system is crucial for limiting tumor growth. Natural killer (NK) cells become activated when the receptor NKG2D is engaged by ligands that are frequently upregulated in primary tumors and on cancer cell lines. However, the molecular mechanisms driving NKG2D ligand expression on tumor cells are not well defined. Using a forward genetic screen in a tumor-derived human cell line, we identified several novel factors supporting expression of the NKG2D ligand ULBP1. Our results show stepwise contributions of independent pathways working at multiple stages of ULBP1 biogenesis. Deeper investigation of selected hits …

A Cytosolic Multiprotein Complex Containing P85Α Is Required For Β-Catenin Activation In Colitis And Colitis-Associated Cancer, Tatiana Goretsky, Emily M. Bradford, Hyunji Ryu, Maryam Tahir, Mary Pat Moyer, Tianyan Gao, Linheng Li, Terrence A. Barrett

Internal Medicine Faculty Publications

Wnt/β-catenin signaling is required for crypt structure maintenance. We previously observed nuclear accumulation of Ser-552 phosphorylated β-catenin (pβ-Cat^Ser-552) in intestinal epithelial cells (IEC) during colitis and colitis-associated cancer. Data here delineate a novel multiprotein cytosolic complex (MCC) involved in β-catenin signaling in the intestine. The MCC contains p85α, the class IA subunit of PI3K, along with β-catenin, 14-3-3ζ, Akt, and p110α. MCC levels in IEC increase in colitis and colitis-associated cancer patients. IEC-specific p85α-deficient (p85^ΔIEC) mice develop more severe dextran sodium …

Critical Shortage Of African American Medical Oncologists In The United States, Lauren M. Hamel, Robert Chapman, Mary Malloy, Susan Eggly, Louis A. Penner, Anthony F. Shields, Michael S. Simon, Justin F. Klamerus, Charles Schiffer, Terrence L. Albrecht

Hematology/Oncology Articles

No abstract provided.

Monomethylarsonous Acid (Mmaiii) Has An Adverse Effect On The Innate Immune Response Of Human Bronchial Epithelial Cells To Pseudomonas Aeruginosa, Emily G. Notch, Britton C. Goodale, Roxanna Barnaby, Bonita Coutermarsh, Brent Berwin, Vivien F. Taylor, Brian P. Jackson, Bruce A. Stanton

Dartmouth Scholarship

Arsenic is the number one contaminant of concern with regard to human health according to the World Health Organization. Epidemiological studies on Asian and South American populations have linked arsenic exposure with an increased incidence of lung disease, including pneumonia, and chronic obstructive pulmonary disease, both of which are associated with bacterial infection. However, little is known about the effects of low dose arsenic exposure, or the contributions of organic arsenic to the innate immune response to bacterial infection. This study examined the effects on Pseudomonas aeruginosa (P. aeruginosa) induced cytokine secretion by human bronchial epithelial cells (HBEC) …

Serum Iron Level Is Associated With Time To Antibiotics In Cystic Fibrosis, Alex H. Gifford, Dana B. Dorman, Lisa A. Moulton, Jennifer E. Helm, Mary M. Griffin, Todd A. Mackenzie

Dartmouth Scholarship

Background:

Serum levels of hepcidin‐25, a peptide hormone that reduces blood iron content, are elevated when patients with cystic fibrosis (CF) develop pulmonary exacerbation (PEx). Because hepcidin‐25 is unavailable as a clinical laboratory test, we questioned whether a one‐time serum iron level was associated with the subsequent number of days until PEx, as defined by the need to receive systemic antibiotics (ABX) for health deterioration.

Methods:

Clinical, biochemical, and microbiological parameters were simultaneously checked in 54 adults with CF. Charts were reviewed to determine when they first experienced a PEx after these parameters were assessed. Time to ABX was compared …

Antioncogenic And Oncogenic Properties Of Nrf2 In Arsenic-Induced Carcinogenesis, Young-Ok Son, Poyil Pratheeshkumar, Ram Vinod Roy, Andrew Hitron, Lei Wang, Sasidharan Padmaja Divya, Mei Xu, Jia Luo, Gang Chen, Zhuo Zhang, Xianglin Shi

Center for Research on Environmental Disease Faculty Publications

Arsenic (As³⁺) is a carcinogen with considerable environmental and occupational relevancy. The present study shows that As³⁺-transformed human lung bronchial epithelial BEAS-2B cells (AsT cells) exhibit the property of apoptosis resistance. The level of basal reactive oxygen species (ROS) is very low in AsT cells in correlation with elevated expressions of both antioxidant enzymes and antiapoptotic proteins. Nuclear factor erythroid 2-related factor (Nrf2) and p62 are constitutively expressed. These two proteins up-regulate antioxidant enzymes and antiapoptotic proteins. The knockdown of Nrf2 or p62 by small interfering RNA (siRNA) enhanced both ROS levels and As³⁺-induced …

Integrin Α6Β4 Promotes Autocrine Epidermal Growth Factor Receptor (Egfr) Signaling To Stimulate Migration And Invasion Toward Hepatocyte Growth Factor (Hgf), Brittany L. Carpenter, Min Chen, Teresa Knifley, Kelley A. Davis, Susan M.W. Harrison, Rachel L. Stewart, Kathleen O'Connor

Markey Cancer Center Faculty Publications

Integrin α6β4 is up-regulated in pancreatic adenocarcinomas where it contributes to carcinoma cell invasion by altering the transcriptome. In this study, we found that integrin α6β4 up-regulates several genes in the epidermal growth factor receptor (EGFR) pathway, including amphiregulin (AREG), epiregulin (EREG), and ectodomain cleavage protease MMP1, which is mediated by promoter demethylation and NFAT5. The correlation of these genes with integrin α6β4 was confirmed in The Cancer Genome Atlas Pancreatic Cancer Database. Based on previous observations that integrin α6β4 cooperates with c-Met in pancreatic cancers, we examined the impact of EGFR signaling on hepatocyte growth factor (HGF)-stimulated migration and …

Pleiotropic Effects Of Immune Responses Explain Variation In The Prevalence Of Fibroproliferative Diseases, Shirley B. Russell, Joan C. Smith, Minjun Huang, Joel S. Trupin, Scott M. Williams

Dartmouth Scholarship

Many diseases are differentially distributed among human populations. Differential selection on genetic variants in ancestral environments that coincidentally predispose to disease can be an underlying cause of these unequal prevalence patterns. Selected genes may be pleiotropic, affecting multiple phenotypes and resulting in more than one disease or trait. Patterns of pleiotropy may be helpful in understanding the underlying causes of an array of conditions in a population. For example, several fibroproliferative diseases are more prevalent and severe in populations of sub-Saharan ancestry. We propose that this disparity is due to selection for an enhanced Th2 response that confers resistance to …

‘The Thing Is Not Knowing’: Patients' Perspectives On Surveillance Of An Indeterminate Pulmonary Nodule, Renda Soylemez Wiener, Michael K. Gould, Steven Woloshin, Lisa M. Schwartz, Jack Clark

Dartmouth Scholarship

Background: The hundreds of thousands of patients found to have a potentially malignant pulmonary nodule each year are faced with tremendous uncertainty regarding what the nodule is and how it should be evaluated.

Objective: To explore patients' responses to the detection and evaluation of a pulmonary nodule.

Effect Of A Cognitive-Behavioral Prevention Program On Depression 6 Years After Implementation Among At-Risk Adolescents: A Randomized Clinical Trial., David A Brent, Steven M. Brunwasser Phd, Steven D Hollon, V Robin Weersing, Gregory N Clarke, John F Dickerson, William R Beardslee, Tracy R G Gladstone, Giovanna Porta, Frances L Lynch, Satish Iyengar, Judy Garber

College of Science & Mathematics Departmental Research

IMPORTANCE: Adolescents whose parents have a history of depression are at risk for developing depression and functional impairment. The long-term effects of prevention programs on adolescent depression and functioning are not known.

OBJECTIVE: To determine whether a cognitive-behavioral prevention (CBP) program reduced the incidence of depressive episodes, increased depression-free days, and improved developmental competence 6 years after implementation.

DESIGN, SETTING, AND PARTICIPANTS: A 4-site randomized clinical trial compared the effect of CBP plus usual care vs usual care, through follow-up 75 months after the intervention (88% retention), with recruitment from August 2003 through February 2006 at a health maintenance organization, …

Identification And Survival Outcomes Of A Cohort Of Patients With Cancer Of Unknown Primary In Ontario, Canada., Chong S Kim, Malek B Hannouf, Sisira Sarma, George B Rodrigues, Peter K Rogan, Salaheddin M Mahmud, Eric Winquist, Muriel Brackstone, Gregory S Zaric

Epidemiology and Biostatistics Publications

BACKGROUND: Cancer of unknown primary origin (CUP) is defined by the presence of pathologically identified metastatic disease without clinical or radiological evidence of a primary tumour. Our objective was to identify incident cases of CUP in Ontario, Canada, and determine the influence of histology and sites of metastases on overall survival (OS).

MATERIAL AND METHODS: We used the Ontario Cancer Registry (OCR) and the Same-Day Surgery and Discharge Abstract Database (SDS/DAD) to identify patients diagnosed with CUP in Ontario between 1 January 2000, and 31 December 2005. Patient diagnostic information, including histology and survival data, was obtained from the OCR. …

Behavioral, Perceptual, And Neural Alterations In Sensory And Multisensory Function In Autism Spectrum Disorder., Sarah H Baum, Ryan A Stevenson, Mark T Wallace

Brain and Mind Institute Researchers' Publications

Although sensory processing challenges have been noted since the first clinical descriptions of autism, it has taken until the release of the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) in 2013 for sensory problems to be included as part of the core symptoms of autism spectrum disorder (ASD) in the diagnostic profile. Because sensory information forms the building blocks for higher-order social and cognitive functions, we argue that sensory processing is not only an additional piece of the puzzle, but rather a critical cornerstone for characterizing and understanding ASD. In this review we discuss what …

Functional Differences Between Statistical Learning With And Without Explicit Training., Laura J Batterink, Paul J Reber, Ken A Paller

Brain and Mind Institute Researchers' Publications

Humans are capable of rapidly extracting regularities from environmental input, a process known as statistical learning. This type of learning typically occurs automatically, through passive exposure to environmental input. The presumed function of statistical learning is to optimize processing, allowing the brain to more accurately predict and prepare for incoming input. In this study, we ask whether the function of statistical learning may be enhanced through supplementary explicit training, in which underlying regularities are explicitly taught rather than simply abstracted through exposure. Learners were randomly assigned either to an explicit group or an implicit group. All learners were exposed to …

Dual Optimization Method Of Radiofrequency And Quasistatic Field Simulations For Reduction Of Eddy Currents Generated On 7t Radiofrequency Coil Shielding., Yujuan Zhao, Tiejun Zhao, Shailesh B Raval, Narayanan Krishnamurthy, Hai Zheng, Chad T Harris, William B Handler, Blaine A Chronik, Tamer S Ibrahim

Brain and Mind Institute Researchers' Publications

PURPOSE: To optimize the design of radiofrequency (RF) shielding of transmit coils at 7T and reduce eddy currents generated on the RF shielding when imaging with rapid gradient waveforms.

METHODS: One set of a four-element, 2 × 2 Tic-Tac-Toe head coil structure was selected and constructed to study eddy currents on the RF coil shielding. The generated eddy currents were quantitatively studied in the time and frequency domains. The RF characteristics were studied using the finite difference time domain method. Five different kinds of RF shielding were tested on a 7T MRI scanner with phantoms and in vivo human subjects. …

Vascular Access: Inukshuk, Jerry Yee

Nephrology Articles

No abstract provided.

Potential Impact Of Prescribing Metformin According To Egfr Rather Than Serum Creatinine, Delphine S. Tuot, Feng Lin, Michael G. Shlipak, Vanessa Grubbs, Chi-Yuan Hsu, Jerry Yee, Vahakn Shahinian, Rajiv Saran, Sharon Saydah, Desmond E. Williams, Neil R. Powe

Nephrology Articles

OBJECTIVE: Many societies recommend using estimated glomerular filtration rate (eGFR) rather than serum creatinine (sCr) to determine metformin eligibility. We examined the potential impact of these recommendations on metformin eligibility among U.S. adults.

RESEARCH DESIGN AND METHODS: Metformin eligibility was assessed among 3,902 adults with diabetes who participated in the 1999-2010 National Health and Nutrition Examination Surveys and reported routine access to health care, using conventional sCr thresholds (eligible if

RESULTS: Among adults with sCr above conventional cutoffs, MDRD eGFR ≥45 mL/min/1.73 m(2) was most common among men (adjusted odds ratio [aOR] 33.3 [95% CI 7.4-151.5] vs. women) and non-Hispanic …

Migrated Avalon Veno-Venous Extracorporeal Membrane Oxygenation Cannula: How To Adjust Without Interruption Of Flow., Daizo Tanaka, Harrsion T. Pitcher, Nicholas C. Cavarocchi, Hitoshi Hirose

Department of Surgery Faculty Papers

The Avalon dual lumen cannula is presently the cannula of choice for veno-venous extracorporeal membrane oxygenation (VV-ECMO) via right internal jugular cannulation. This cannula establishes VV-ECMO with a single cannulation; however, it requires appropriate positioning to gain adequate oxygenation. Malposition of this cannula can cause inadequate ECMO flow, hypoxia, and structural injury. We have experienced two cases of migration: one into the hepatic vein and the other into the right ventricle. The former was repositioned using echocardiographic guidance without using a guidewire. The latter was repositioned using a guidewire from the femoral vein under fluoroscopy, without antegrade wire placement into …

Achieving Optimal En Face Tissue Sections During Staged Lentigo Maligna Excisions: A Novel Technique, Ben J. Friedman, Jason D. Pimentel, David M. Ozog

Dermatology Articles

No abstract provided.

Employment Status And Participation In Cardiac Rehabilitation: Does Encouraging Earlier Enrollment Improve Attendance?, Quinn R. Pack, Ray W. Squires, Claudia Valdez-Lowe, Mouhamad Mansour, Randal J. Thomas, Steven J. Keteyian

Cardiology Articles

PURPOSE: For patients hospitalized for a cardiac event, an earlier appointment to outpatient cardiac rehabilitation (CR) increases participation. However, it is unknown what effect hastening CR enrollment might have among employed patients planning to return to work (RTW).

METHODS: Using 2 complementary data sets from Henry Ford Hospital (HFH) and Mayo Clinic, we assessed when employed patients eligible for CR anticipated a RTW, the impact of an earlier appointment on CR enrollment, and the effect of employment status on the number of CR sessions attended. Patients at HFH attended CR at either 8 or 42 days (through randomization), whereas Mayo …

Abcc9/Sur2 In The Brain: Implications For Hippocampal Sclerosis Of Aging And A Potential Therapeutic Target, Peter T. Nelson, Gregory A. Jicha, Wang-Xia Wang, Eseosa T. Ighodaro, Sergey C. Artiushin, Colin G. Nichols, David W. Fardo

Sanders-Brown Center on Aging Faculty Publications

The ABCC9 gene and its polypeptide product, SUR2, are increasingly implicated in human neurologic disease, including prevalent diseases of the aged brain. SUR2 proteins are a component of the ATP-sensitive potassium (“K _ATP ”) channel, a metabolic sensor for stress and/or hypoxia that has been shown to change in aging. The K _ATP channel also helps regulate the neurovascular unit. Most brain cell types express SUR2, including neurons, astrocytes, oligodendrocytes, microglia, vascular smooth muscle, pericytes, and endothelial cells. Thus it is not surprising that ABCC9 gene variants are associated with risk for human brain diseases. For example, Cantu syndrome is …

Right Ventricular Dysfunction After Resuscitation Predicts Poor Outcomes In Cardiac Arrest Patients Independent Of Left Ventricular Function., Vimal Ramjee, Anne V. Grossestreuer, Yuan Yao, Sarah M. Perman, Marion Leary, James N. Kirkpatrick, Paul R. Forfia, Daniel M. Kolansky, Benjamin S. Abella, David F. Gaieski

Department of Emergency Medicine Faculty Papers

OBJECTIVE: Determination of clinical outcomes following resuscitation from cardiac arrest remains elusive in the immediate post-arrest period. Echocardiographic assessment shortly after resuscitation has largely focused on left ventricular (LV) function. We aimed to determine whether post-arrest right ventricular (RV) dysfunction predicts worse survival and poor neurologic outcome in cardiac arrest patients, independent of LV dysfunction.

METHODS: A single-center, retrospective cohort study at a tertiary care university hospital participating in the Penn Alliance for Therapeutic Hypothermia (PATH) Registry between 2000 and 2012.

PATIENTS: 291 in- and out-of-hospital adult cardiac arrest patients at the University of Pennsylvania who had return of spontaneous …

Clear Cell Renal Cell Carcinoma With Borderline Features Of Clear Cell Papillary Renal Cell Carcinoma: Combined Morphologic, Immunohistochemical, And Cytogenetic Analysis, Sean R. Williamson, Nilesh S. Gupta, John N. Eble, Craig G. Rogers, Susan Michalowski, Shaobo Zhang, Mingsheng Wang, David J. Grignon, Liang Cheng

Pathology and Laboratory Medicine Articles

Clear cell papillary renal cell carcinoma is increasingly recognized as a distinct tumor with unique morphology, immunohistochemistry, and cytogenetics. Histopathology often mimics clear cell renal cell carcinoma; however, metastasis has not been reported, emphasizing the clinical value of recognizing these likely nonaggressive tumors. We studied tumors with borderline morphology of clear cell papillary renal cell carcinoma, utilizing immunohistochemistry and fluorescence in situ hybridization or karyotyping. Tumors from 22 patients (ages 33 to 82 y) were analyzed. Clear cell papillary renal cell carcinoma-like morphology varied from 10% to 90% of the tumor (median 25%). Sources of resemblance included: branched glands (95%), …

Identification Of Regions Of Normal Grey Matter And White Matter From Pathologic Glioblastoma And Necrosis In Frozen Sections Using Raman Imaging, Rachel Kast, Gregory Auner, Sally Yurgelevic, Brandy Broadbent, Aditya Raghunathan, Laila M. Poisson, Tom Mikkelsen, Mark L. Rosenblum, Steven N. Kalkanis

Neurosurgery Articles

In neurosurgical applications, a tool capable of distinguishing grey matter, white matter, and areas of tumor and/or necrosis in near-real time could greatly aid in tumor resection decision making. Raman spectroscopy is a non-destructive spectroscopic technique which provides molecular information about the tissue under examination based on the vibrational properties of the constituent molecules. With careful measurement and data processing, a spatial step and repeat acquisition of Raman spectra can be used to create Raman images. Forty frozen brain tissue sections were imaged in their entirety using a 300-µm-square measurement grid, and two or more regions of interest within each …

Tools For Economic Analysis Of Patient Management Interventions In Heart Failure Cost-Effectiveness Model: A Web-Based Program Designed To Evaluate The Cost-Effectiveness Of Disease Management Programs In Heart Failure., Shelby D. Reed, Matthew P. Neilson, Matthew Gardner, Yanhong Li, Andrew H. Briggs, Daniel E E. Polsky, Felicia L. Graham, Margaret T. Bowers, Sara C. Paul, Bradi B. Granger, Kevin A. Schulman, David J. Whellan, Barbara Riegel, Wayne C. Levy

Department of Medicine Faculty Papers

BACKGROUND: Heart failure disease management programs can influence medical resource use and quality-adjusted survival. Because projecting long-term costs and survival is challenging, a consistent and valid approach to extrapolating short-term outcomes would be valuable.

METHODS: We developed the Tools for Economic Analysis of Patient Management Interventions in Heart Failure Cost-Effectiveness Model, a Web-based simulation tool designed to integrate data on demographic, clinical, and laboratory characteristics; use of evidence-based medications; and costs to generate predicted outcomes. Survival projections are based on a modified Seattle Heart Failure Model. Projections of resource use and quality of life are modeled using relationships with time-varying …

Enos Transfection Of Adipose-Derived Stem Cells Yields Bioactive Nitric Oxide Production And Improved Results In Vascular Tissue Engineering., Stephen Mcilhenny, Ping Zhang, Thomas Tulenko, Jason Comeau, Sarah Fernandez, Aleksandra Policha, Matthew Ferroni, Elizabeth J Faul, Gabor Bagameri, Irving Shapiro, Paul J. Dimuzio

Department of Surgery Faculty Papers

This study evaluates the durability of a novel tissue engineered blood vessel (TEBV) created by seeding a natural vascular tissue scaffold (decellularized human saphenous vein allograft) with autologous adipose-derived stem cells (ASC) differentiated into endothelial-like cells. Previous work with this model revealed the graft to be thrombogenic, likely due to inadequate endothelial differentiation as evidenced by minimal production of nitric oxide (NO). To evaluate the importance of NO expression by the seeded cells, we created TEBV using autologous ASC transfected with the endothelial nitric oxide synthase (eNOS) gene to produce NO. We found that transfected ASC produced NO at levels …

Saving Life And Brain With Extracorporeal Cardiopulmonary Resuscitation: A Single-Center Analysis Of In-Hospital Cardiac Arrests., Graham Peigh, Nicholas C. Cavarocchi, Hitoshi Hirose

Department of Surgery Faculty Papers

OBJECTIVE: Despite advances in medical care, survival to discharge and full neurologic recovery after cardiac arrest remains less than 20% after cardiopulmonary resuscitation. An alternate approach to traditional cardiopulmonary resuscitation is extracorporeal cardiopulmonary resuscitation, which places patients on extracorporeal membrane oxygenation during cardiopulmonary resuscitation and provides immediate cardiopulmonary support when traditional resuscitation has been unsuccessful. We report the results from extracorporeal cardiopulmonary resuscitation at the Thomas Jefferson University.

METHODS: Between 2010 and June 2014, 107 adult extracorporeal membrane oxygenation procedures were performed at the Thomas Jefferson University. Patient demographics, survival to discharge, and neurologic recovery of patients who underwent extracorporeal …

Sexting Among Married Couples: Who Is Doing It, And Are They More Satisfied?, Brandon T. Mcdaniel Phd, Michelle Drouin

Health Services and Informatics Research

This study examined the prevalence and correlates of sexting (i.e., sending sexual messages via mobile phones) within a sample of married/cohabiting couples (180 wives and 175 husbands). Married adults do sext each other, but it is much less common than within young adult relationships, and consists mainly of sexy or intimate talk (29% reported engaging in sexy talk with partners) rather than sexually explicit photos or videos (12% reported sending nude or nearly-nude photos). Sending sexy talk messages was positively related to relationship satisfaction only among those with high levels of avoidance, and sending sexually explicit pictures was related to …

Beyond The One-Locus-One-Mirna Paradigm: Microrna Isoforms Enable Deeper Insights Into Breast Cancer Heterogeneity., Aristeidis G Telonis, Phillipe Loher, Yi Jing, Eric R Londin, Isidore Rigoutsos

Computational Medicine Center Faculty Papers

Here we describe our study of miRNA isoforms (isomiRs) in breast cancer (BRCA) and normal breast data sets from the Cancer Genome Atlas (TCGA) repository. We report that the full isomiR profiles, from both known and novel human-specific miRNA loci, are particularly rich in information and can distinguish tumor from normal tissue much better than the archetype miRNAs. IsomiR expression is also dependent on the patient's race, exemplified by miR-183-5p, several isomiRs of which are upregulated in triple negative BRCA in white but not black women. Additionally, we find that an isomiR's 5' endpoint and length, but not the genomic …

Dna-Repair Defects And Olaparib In Metastatic Prostate Cancer., Joaquin Mateo, Suzanne Carreira, Shahneen Sandhu, Susana Miranda, Helen Mossop, Raquel Perez-Lopez, Daniel Nava Rodrigues, Dan Robinson, Aurelius Omlin, Nina Tunariu, Gunther Boysen, Nuria Porta, Penny Flohr, Alexa Gillman, Ines Figueiredo, Claire Paulding, George Seed, Suneil Jain, Christy Ralph, Andrew Protheroe, Syed Hussain, Robert Jones, Tony Elliott, Ursula Mcgovern, Diletta Bianchini, Jane Goodall, Zafeiris Zafeiriou, Chris T Williamson, Roberta Ferraldeschi, Ruth Riisnaes, Bernardette Ebbs, Gemma Fowler, Desamparados Roda, Wei Yuan, Yi-Mi Wu, Xuhong Cao, Rachel Brough, Helen Pemberton, Roger A'Hern, Amanda Swain, Lakshmi P Kunju, Rosalind Eeles, Gerhardt Attard, Christopher J Lord, Alan Ashworth, Mark A Rubin, Karen E Knudsen, Felix Y Feng, Arul M Chinnaiyan, Emma Hall, Johann S De Bono

Department of Medicine Faculty Papers

BACKGROUND: Prostate cancer is a heterogeneous disease, but current treatments are not based on molecular stratification. We hypothesized that metastatic, castration-resistant prostate cancers with DNA-repair defects would respond to poly(adenosine diphosphate [ADP]-ribose) polymerase (PARP) inhibition with olaparib.

METHODS: We conducted a phase 2 trial in which patients with metastatic, castration-resistant prostate cancer were treated with olaparib tablets at a dose of 400 mg twice a day. The primary end point was the response rate, defined either as an objective response according to Response Evaluation Criteria in Solid Tumors, version 1.1, or as a reduction of at least 50% in the …

A Piece Of My Mind. A Piece Of My Mind--Actually., Herbert M. Adler

Department of Psychiatry and Human Behavior Faculty Papers

No abstract provided.