Medical Specialties Commons^™

The Sensitivity Of Cross-Sectional Imaging For Identifying Periampullary Diverticula, Austin Chiang, Md, Mph, Jetmir Vojnika, Md, Alexander Schlachterman, Md, David E. Loren, Md, Thomas E. Kowalski

Division of Gastroenterology and Hepatology Posters

Our aim was to determine the sensitivity of imaging in identifying duodenal diverticula as seen during ERCP.

Cellular Network Modeling And Single Cell Gene Expression Analysis Reveals Novel Hepatic Stellate Cell Phenotypes Controlling Liver Regeneration Dynamics, Daniel Cook, Sirisha Achanta, Jan B. Hoek, Babatunde A. Ogunnaike, Rajanikanth Vadigepalli

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Background: Recent results from single cell gene and protein regulation studies are starting to uncover the previously underappreciated fact that individual cells within a population exhibit high variability in the expression of mRNA and proteins (i.e., molecular variability). By combining cellular network modeling, and high-throughput gene expression measurements in single cells, we seek to reconcile the high molecular variability in single cells with the relatively low variability in tissue-scale gene and protein expression and the highly coordinated functional responses of tissues to physiological challenges. In this study, we focus on relating the dynamic changes in distributions of hepatic stellate cell …

Control Of Ccnd1 Ubiquitylation By The Catalytic Saga Subunit Usp22 Is Essential For Cell Cycle Progression Through G1 In Cancer Cells., Victoria J. Gennaro, Timothy J. Stanek, Amy R. Peck, Yunguang Sun, Feng Wang, Shuo Qie, Karen E. Knudsen, Hallgeir Rui, Tauseef Butt, J. Alan Diehl, Steven B. Mcmahon

Department of Biochemistry and Molecular Biology Faculty Papers

Overexpression of the deubiquitylase ubiquitin-specific peptidase 22 (USP22) is a marker of aggressive cancer phenotypes like metastasis, therapy resistance, and poor survival. Functionally, this overexpression of USP22 actively contributes to tumorigenesis, as USP22 depletion blocks cancer cell cycle progression in vitro, and inhibits tumor progression in animal models of lung, breast, bladder, ovarian, and liver cancer, among others. Current models suggest that USP22 mediates these biological effects via its role in epigenetic regulation as a subunit of the Spt-Ada-Gcn5-acetyltransferase (SAGA) transcriptional cofactor complex. Challenging the dogma, we report here a nontranscriptional role for USP22 via a direct effect on the …

Severe Lumbar Disability Is Associated With Decreased Psoas Cross-Sectional Area In Degenerative Spondylolisthesis, Scott C. Wagner, Arjun S. Sebastian, James C. Mckenzie, Joseph S. Butler, Ian D. Kaye, Patrick B. Morrissey, Alexander R. Vaccaro, Christopher K. Kepler

Rothman Institute Papers

Study Design: Retrospective cohort. Objectives: Alterations in lumbar paraspinal muscle cross-sectional area (CSA) may correlate with lumbar pathology. The purpose of this study was to compare paraspinal CSA in patients with degenerative spondylolisthesis and severe lumbar disability to those with mild or moderate lumbar disability, as determined by the Oswestry Disability Index (ODI). Methods: We retrospectively reviewed the medical records of 101 patients undergoing lumbar fusion for degenerative spondylolisthesis. Patients were divided into ODI score ≤40 (mild/moderate disability, MMD) and ODI score >40 (severe disability, SD) groups. The total CSA of the psoas and paraspinal muscles were measured on preoperative …

Designing The Ideal Perioperative Pain Management Plan Starts With Multimodal Analgesia., Eric S. Schwenk, Edward R. Mariano

Department of Anesthesiology Faculty Papers

Multimodal analgesia is defined as the use of more than one pharmacological class of analgesic medication targeting different receptors along the pain pathway with the goal of improving analgesia while reducing individual class-related side effects. Evidence today supports the routine use of multimodal analgesia in the perioperative period to eliminate the over-reliance on opioids for pain control and to reduce opioid-related adverse events. A multimodal analgesic protocol should be surgery-specific, functioning more like a checklist than a recipe, with options to tailor to the individual patient. Elements of this protocol may include opioids, non-opioid systemic analgesics like acetaminophen, non-steroidal anti-inflammatory …

Three Years Of Growth Hormone Therapy In Children Born Small For Gestational Age: Results From The Answer Program, Robert Rapaport, Peter Lee, Judith L. Ross, Paul Saenger, Vlady Ostrow, Giuseppe Piccoli

Department of Pediatrics Faculty Papers

Growth hormone (GH) is used to treat short stature and growth failure associated with growth disorders. Birth size and GH status variably modulate response to GH therapy. The aim of this study was to determine the effect of birth size on response to GH therapy, and to determine the impact of GH status in patients born small for gestational age (SGA) on response to GH therapy. Data from the prospective, non-interventional American Norditropin® Studies: Web-Enabled Research (ANSWER) Program were analyzed for several growth outcomes in response to GH therapy over 3 years. GH-naïve children from the ANSWER Program were included …

A Systematic Review Of Treating Recurrent Head And Neck Cancer: A Reintroduction Of Brachytherapy With Or Without Surgery., Julianna Rodin, Voichita Bar-Ad, David Cognetti, Joseph Curry, Jennifer Johnson, Chad Zender, Laura Doyle, David Kutler, Benjamin E. Leiby, William M. Keane, Adam J. Luginbuhl

Department of Otolaryngology - Head and Neck Surgery Faculty Papers

Purpose: To review brachytherapy use in recurrent head and neck carcinoma (RHNC) with focus on its efficacy and complication rates.

Material and methods: A literature search of PubMed, Ovid, Google Scholar, and Scopus was conducted from 1990 to 2017. Publications describing treatment of RHNC with brachytherapy with or without surgery were included. The focus of this review is on oncologic outcomes and the safety of brachytherapy in the recurrent setting.

Results: Thirty studies involving RHNC treatment with brachytherapy were reviewed. Brachytherapy as adjunctive treatment to surgical resection appears to be associated with an improved local regional control and overall survival, …

Synthetic Dna Immunotherapy In Biochemically Relapsed Prostate Cancer, N. Shore, E. I. Heath, L. T. Nordquist, H. Cheng, K. Bhatt, M. Morrow, T. Mcmullan, K. Kraynyak, J. Lee, B. Sacchetta, L. Liu, S. Rosencranz, S. T. Tagawa, L. J. Appleman, R. Tutrone, J. Garcia, Y. Whang, W. Kelly, I. Csiki, M. L. Bagarazzi

Department of Medical Oncology Faculty Papers

Background: INO-5150 (PSA and PSMA) +/- INO-9012 (IL-12), a synthetic DNA immunotherapy, was assessed for safety, immunogenicity and efficacy in biochemically recurrent prostate cancer patients (pts).

Methods: Phase I, open-label, multi-center study in the US included pts with rising PSA after surgery and/or RT, PSA doubling time (PSADT) >3 months (mos), testosterone >150 ng/dL and no concurrent ADT. Safety, immunogenicity and efficacy (PSA kinetics, PFS) were evaluated in 4 treatment arms of 15 pts each. Arms A: 2mg INO-5150, B: 8.5 mg INO-5150, C: 2mg INO-5150 + 1mg INO-9012 and D: 8.5mg INO-5150 + 1mg INO-9012. Pts received 4 IM …

Complications Associated With Volar Locking Plate Fixation Of Distal Radial Fractures., Todd H. Alter, Asif M. Ilyas

Rothman Institute Papers

• Volar locked plating is the most frequently utilized method for internal fixation of distal radial fractures.
• The overall complication rate for volar plating of distal radial fractures appears to be relatively low compared with other operative fixation methods.
• Carpal tunnel syndrome is the most commonly reported complication.
• However, this may occur after a distal radial fracture regardless of treatment method, with reported rates ranging from 0% to 20% with conservative management and 0% to 14% with volar plating.
• Extensor tendon rupture has been reported at rates of 0% to 4% and is the most frequent complication requiring plate removal.
• Variable-angle …

Bath-Related Headache, Aliza Kumpinsky, Stephanie J. Nahas

Department of Neurology Faculty Papers

PURPOSE OF REVIEW: The purpose of this review is to summarize the most up-to-date literature on bath-related headache, a rare disorder.

RECENT FINDINGS: Initially described in middle-aged Asian women, it is now reported in a wider demographic. More information is available about the pathophysiology of bath-related headache, including its classification as a subtype of reversible cerebral vasoconstriction syndrome (RCVS). Nimodipine can be effective in patients both with and without vasospasm. Bath-related headache is a rare form of thunderclap headache. Although its mechanism is still unclear, it is associated with vasospasm and RCVS. Controlled trials investigating the use of nimodipine and …

Stress Fractures Of The Elbow In The Throwing Athlete: A Systematic Review., Shelby R. Smith, Nirav K. Patel, Alex E. White, Christopher J Hadley, Christopher C. Dodson

Rothman Institute Papers

Background: Stress fractures of the elbow are rare in throwing athletes and present a challenge from both a management and rehabilitation perspective. Although the incidence of stress fractures of the elbow is increasing, there is a lack of data in the literature focused on throwers.

Purpose: To evaluate studies regarding the management and outcomes of stress fractures of the elbow in throwing athletes.

Study Design: Systematic review; Level of evidence, 4.

Methods: A systematic review was conducted by searching the Scopus, PubMed, and Cochrane Library electronic databases to identify studies reporting on the management and outcomes of stress fractures in …

Era Of Direct Acting Anti-Viral Agents For The Treatment Of Hepatitis C., Monjur Ahmed

Division of Gastroenterology and Hepatology Faculty Papers

Hepatitis C infection is universal and the most common indication of liver transplantation in the United States. The period of less effective interferon therapy with intolerable side effects has gone. Now we have stepped into the era of direct acting anti-viral agents (DAAs) against hepatitis C virus. Treatment of hepatitis C is now extremely effective, tolerable and requires a short duration of intake of oral agents. Less monitoring is required with the current therapy and drug-drug interactions are less than the previous regimen. The current treatment options of chronic hepatitis C with various DAAs are discussed in this article.

Clinical Framework For Quality Improvement Of Cancer Cachexia., Clara Granda-Cameron, Mary Pat Lynch

College of Nursing Faculty Papers & Presentations

The objective of this article is to introduce the Clinical Framework for Quality Improvement of Cancer Cachexia (Cachexia Care Framework) as a tool to demonstrate the relevance of integrating the clinical components of cancer cachexia and the organizational strategies of a cancer institution on the quality of patient care and delivery of services throughout the cancer cachexia continuum. The data sources included peer-reviewed literature relevant to cancer cachexia and quality cancer care, and the authors' expertise. The Cachexia Care Framework results from a combination of the international consensus definition of cancer cachexia, the Institute of Medicine report Ensuring Quality Cancer …

Treatment-Related Decisional Conflict, Quality Of Life, And Comorbidity In Older Adults With Cancer., Jeannette M. Kates

College of Nursing Faculty Papers & Presentations

Objective: The present study aims to examine the relationships between and among cancer treatment-related decisional conflict, quality of life, and comorbidity in older adults with cancer.

Methods: A convenience sample of 200 older adults was recruited from outpatient medical oncology and radiation oncology practices in the northeastern United States. A cross-sectional, descriptive, correlational study design was used employing a survey method. Survey instruments included the Decisional Conflict scale (DCS) (with five subscales, including informed, values clarity, support, uncertainty, and effective decision); Self-administered comorbidity questionnaire (SCQ); European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (including five function …

Larotrectinib Efficacy And Safety In Trk Fusion Cancer: An Expanded Clinical Dataset Showing Consistency In An Age And Tumor Agnostic Approach, U. N. Lassen, C. M. Albert, S. Kummar, C. M. Van Tilburg, S. G. Dubois, B. Geoerger, L. Mascarenhas, N. Federman, R. J. Schilder, F. Doz, J. D. Berlin, D. Y. Oh, S. S. Bielack, R. Mcdermott, D. S. Tan, S. Cruickshank, N. C. Ku, M. C. Cox, A. Drilon, D. S. Hong

Department of Medical Oncology Faculty Papers

Background: TRK fusion cancer results from gene fusions involving NTRK1, NTRK2 or NTRK3. Larotrectinib, the first selective TRK inhibitor, has demonstrated an overall response rate (ORR) of 75% with a favorable safety profile in the first 55 consecutively enrolled adult and pediatric patients with TRK fusion cancer (Drilon et al.,NEJM2018). Here, we report the clinical activity of larotrectinib in an additional 35 TRK fusion cancer patients and provide updated follow-up of the primary analysis set (PAS) of 55 patients as of 19^thFeb 2018.

Methods: Patients with TRK fusion cancer detected by molecular profiling from 3 larotrectinib clinical trials …

Nci-Match Arms N & P: Phase Ii Study Of Pi3k Beta Inhibitor Gsk2636771 In Patients (Pts) With Cancers (Ca) With Pten Mutation/Deletion (Mut/Del) Or Pten Protein Loss, F. Janku, O. Jegede, S. L. Puhalla, P. Konstantinopoulos, F. Meric-Bernstam, E. P. Mitchell, J. A. Zwiebel, L. M. Mcshane, S. Li, L. V. Rubinstein, L. A. Doyle, D. Patton, B. A. Conley, P. J. O'Dwyer, L. N. Harris, C. Arteaga, P. M. Williams, S. R. Hamilton, A. P. Chen, K. T. Flaherty

Department of Medical Oncology Faculty Papers

Background: The NCI-MATCH trial is the largest national study (1173 sites) for ptswith relapsed/ refractory solid tumors, lymphomas and myeloma, which assigns tar-geted therapies based on individual tumor molecular alterations detected using theadapted Oncomine AmpliSeq panel (143 genes) and immunohistochemistry (IHC).We hypothesized that patients with PTEN-deficient cancers enrolled to Arms N and Pmay benefit from treatment with the PI3K beta-selective inhibitor GSK2636771.

Methods: Eligibility: relapsed/refractory ca, good end-organ function, and ECOG PS ≤ 1. Pts were screened for molecular alterations by centralized testing on fresh tumor biopsy and had deleterious PTEN mut/del without loss of expression (Arm N) or complete …

Pan-Squamous Genomic Profiling Stratified By Anatomic Tumor Site And Viral Association, M. Montesion, C. H. Chung, E. S. Sokol, S. A. Khan, H. Kang, L. A. Albacker, J. M. Johnson, G. M. Frampton, V. A. Miller, J. S. Ross, S. M. Ali

Department of Medical Oncology Faculty Papers

Background: Squamous cell carcinomas (SCC) have diverse anatomic etiologies but may share common genomic biomarkers. We profiled 7,871 unique SCCs across nine anatomic sites to investigate commonality in genomic alterations (GA), tumor mutational burden (TMB), human papillomavirus (HPV) association, and mutational signatures.

Methods: Tissue from over 8,100 unique SCC samples originating from nine anatomic sites (anogenital (anus, cervix, penis, vagina, vulva), esophagus, head and neck, lung, and skin) were sequenced by hybrid capture-based comprehensive genomic profiling to evaluate GA and TMB. About 3% of non-cutaneous SCC samples had UV signatures, indicative of potential primary site misdiagnoses, and were filtered from …

Androgen Decline And Outcome In Castration Resistant Prostate Cancer(Mcrpc) Patients Treated With Docetaxel (Doc), Prednisone1/-Bevacizumab (B), C. J. Ryan, S. Dutta, W. Kelly, M. J. Morris, M-E. Taplin, S. Halabi

Department of Medical Oncology Faculty Papers

No abstract provided.

Epidemiology Of Moderate Alcohol Consumption And Breast Cancer: Association Or Causation?, Samir Zakhari, Jan B. Hoek

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Epidemiological studies have been used to show associations between modifiable lifestyle habits and the incidence of breast cancer. Among such factors, a history of alcohol use has been reported in multiple studies and meta-analyses over the past decades. However, associative epidemiological studies that were interpreted as evidence that even moderate alcohol consumption increases breast cancer incidence have been controversial. In this review, we consider the literature on the relationship between moderate or heavy alcohol use, both in possible biological mechanisms and in variations in susceptibility due to genetic or epigenetic factors. We argue that there is a need to incorporate …

In Vitro Transport Of Methotrexate By Drosophila Multidrug Resistance-Associated Protein., Agnes Karasik, András Váradi, Flóra Szeri

Department of Dermatology and Cutaneous Biology Faculty Papers

Methotrexate (MTX) is a widely used chemotherapeutic agent, immune suppressant and antimalarial drug. It is a substrate of several human ABC proteins that confer multidrug resistance to cancer cells and determine compartmentalization of a wide range of physiological metabolites and endo or xenobiotics, by their primary active transport across biological membranes. The substrate specificity and tissue distribution of these promiscuous human ABC transporters show a high degree of redundancy, providing robustness to these key physiological and pharmacological processes, such as the elimination of toxins, e.g. methotrexate from the body. A similar network of proteins capable of transporting methotrexate has been …

Intestinal Barrier Tightening By A Cell-Penetrating Antibody To Bin1, A Candidate Target For Immunotherapy Of Ulcerative Colitis., Sunil Thomas, Kevther Hoxha, Walker Alexander, John Gilligan, Rima Dilbarova, Kelly Whittaker, Andrew Kossenkov, George C. Prendergast, James M. Mullin

Kimmel Cancer Center Papers, Presentations, and Grand Rounds

Patients afflicted with ulcerative colitis (UC) are at increased risk of colorectal cancer. While its causes are not fully understood, UC is associated with defects in colonic epithelial barriers that sustain inflammation of the colon mucosa caused by recruitment of lymphocytes and neutrophils into the lamina propria. Based on genetic evidence that attenuation of the bridging integrator 1 (Bin1) gene can limit UC pathogenicity in animals, we have explored Bin1 targeting as a therapeutic option. Early feasibility studies in the dextran sodium sulfate mouse model of experimental colitis showed that administration of a cell-penetrating Bin1 monoclonal antibody (Bin1 mAb 99D) …

Neuroprotective Role Of Phytochemicals., Bharath Kumar Velmurugan, Baskaran Rathinasamy, Bharathi Priya Lohanathan, Varadharajan Thiyagarajan, Ching-Feng Weng

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Neurodegenerative diseases are normally distinguished as disorders with loss of neurons. Various compounds are being tested to treat neurodegenerative diseases (NDs) but they possess solitary symptomatic advantages with numerous side effects. Accumulative studies have been conducted to validate the benefit of phytochemicals to treat neurodegenerative diseases including Alzheimer's disease (AD) and Parkinson's disease (PD). In this present review we explored the potential efficacy of phytochemicals such as epigallocatechin-3-galate, berberin, curcumin, resveratrol, quercetin and limonoids against the most common NDs, including Alzheimer's disease (AD) and Parkinson's disease (PD). The beneficial potentials of these phytochemicals have been demonstrated by evidence-based but more …

Pediatric Obesity: Influence On Drug Dosing And Therapeutics, Barbara Ameer Pharmd, Mba, Bcps, Fcp, Michael Weintraub Md

Department of Medicine Faculty Papers

Obesity is an ongoing global health concern and has only recently been recognized as a chronic disease of energy homeostasis and fuel partitioning. Obesity afflicts 17% of US children and adolescents. Severe obesity (³120% of the 95^th percentile of BMI-for-age, or a BMI of ³35 kg/m²) is the fastest growing subgroup and now approaches 6% of all US youth. Health consequences (e.g., type 2 diabetes, coronary heart disease) are related in a dose-dependent manner to severity of obesity. Since therapeutic interventions are less effective in severe obesity, prevention is a high priority.

Treatment plans involving combinations of …

Clinical Perspective On Passive Audio Vocal Measurement In The Evaluation Of Selective Mutism., Helen Y Xu, Jacob Stroud, Renee K. Jozanovic, Jon Clucas, Jake Jungwoo Son, Bonhwang Koo, Juliet Schwarz, Arno Klein, Rachel Busman, Michael P. Milham

Student Papers, Posters & Projects

Selective Mutism (SM) is an anxiety disorder often diagnosed in early childhood and characterized by persistent failure to speak in certain social situations but not others. Diagnosing SM and monitoring treatment response can be quite complex, due in part to changing definitions of and scarcity of research about the disorder. Subjective self-reports and parent/teacher interviews can complicate SM diagnosis and therapy, given that similar speech problems of etiologically heterogeneous origin can be attributed to SM. The present perspective discusses the potential for passive audio capture to help overcome psychiatry's current lack of objective and quantifiable assessments in the context of …

Neurological Complications Of Immune Checkpoint Inhibitors: What Happens When You 'Take The Brakes Off' The Immune System., Marinos Dalakas

Department of Neurology Faculty Papers

Patients with advanced malignancies treated with immune checkpoint inhibitors are at increased risk for developing immune-related neurological complications. It is a phenomenon of immunological twist when immunotherapy against co-stimulatory molecules activates previously normal T cells to kill tumor cells but, in so doing, the T cells become unrestrained, triggering other autoimmune diseases for which conventional immunotherapy is needed. The most common autoimmune neurological diseases, usually occurring within 2-12 weeks after immune checkpoint inhibitor initiation, include: inflammatory myopathies, myasthenia gravis, acute and chronic demyelinating polyradiculoneuropathies, vasculitic neuropathies, isolated cranial neuropathies, aseptic meningitis, autoimmune encephalitis, multiple sclerosis and hypophysitis. The neurological events …

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

Center for Translational Medicine Faculty Papers

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

Fructose 2,6-Bisphosphate In Cancer Cell Metabolism, Ramon Bartrons, Helga Simon-Molas, Ana Rodríguez-García, Esther Castaño, Àurea Navarro-Sabaté, Anna Manzano, Ubaldo E. Martinez-Outshoorn

Department of Medical Oncology Faculty Papers

For a long time, pioneers in the field of cancer cell metabolism, such as Otto Warburg, have focused on the idea that tumor cells maintain high glycolytic rates even with adequate oxygen supply, in what is known as aerobic glycolysis or the Warburg effect. Recent studies have reported a more complex situation, where the tumor ecosystem plays a more critical role in cancer progression. Cancer cells display extraordinary plasticity in adapting to changes in their tumor microenvironment, developing strategies to survive and proliferate. The proliferation of cancer cells needs a high rate of energy and metabolic substrates for biosynthesis of …

The Human Cib1-Ever1-Ever2 Complex Governs Keratinocyte-Intrinsic Immunity To Β-Papillomaviruses., Sarah Jill De Jong, Amandine Créquer, Irina Matos, David Hum, Vignesh Gunasekharan, Lazaro Lorenzo, Fabienne Jabot-Hanin, Elias Imahorn, Andres A. Arias, Hassan Vahidnezhad, Leila Youssefian, Janet G. Markle, Etienne Patin, Aurelia D'Amico, Claire Q.F. Wang, Florian Full, Armin Ensser, Tina M. Leisner, Leslie V. Parise, Matthieu Bouaziz, Nataly Portilla Maya, Xavier Rueda Cadena, Bayaki Saka, Amir Hossein Saeidian, Nessa Aghazadeh, Sirous Zeinali, Peter Itin, James G. Krueger, Lou Laimins, Laurent Abel, Elaine Fuchs, Jouni Uitto, Jose Luis Franco, Bettina Burger, Gérard Orth, Emmanuelle Jouanguy, Jean-Laurent Casanova

Department of Dermatology and Cutaneous Biology Faculty Papers

Patients with epidermodysplasia verruciformis (EV) and biallelic null mutations of TMC6 (encoding EVER1) or TMC8 (EVER2) are selectively prone to disseminated skin lesions due to keratinocyte-tropic human β-papillomaviruses (β-HPVs), which lack E5 and E8. We describe EV patients homozygous for null mutations of the CIB1 gene encoding calcium- and integrin-binding protein-1 (CIB1). CIB1 is strongly expressed in the skin and cultured keratinocytes of controls but not in those of patients. CIB1 forms a complex with EVER1 and EVER2, and CIB1 proteins are not expressed in EVER1- or EVER2-deficient cells. The known functions of EVER1 and EVER2 in human keratinocytes are …

Mapk Reliance Via Acquired Cdk4/6 Inhibitor Resistance In Cancer., Renée De Leeuw, Christopher Mcnair, Matthew J. Schiewer, Neermala Poudel Neupane, Lucas J. Brand, Michael A. Augello, Zhen Li, Larry C. Cheng, Akihiro Yoshida, Sean M. Courtney, E. Starr Hazard, Gary Hardiman, Maha H. Hussain, J. Alan Diehl, Justin M. Drake, William Kevin Kelly, Karen E. Knudsen

Department of Cancer Biology Faculty Papers

Purpose: Loss of cell-cycle control is a hallmark of cancer, which can be targeted with agents, including cyclin-dependent kinase-4/6 (CDK4/6) kinase inhibitors that impinge upon the G₁-S cell-cycle checkpoint via maintaining activity of the retinoblastoma tumor suppressor (RB). This class of drugs is under clinical investigation for various solid tumor types and has recently been FDA-approved for treatment of breast cancer. However, development of therapeutic resistance is not uncommon.

Experimental Design: In this study, palbociclib (a CDK4/6 inhibitor) resistance was established in models of early stage, RB-positive cancer.

Results: This study demonstrates that acquired palbociclib resistance renders cancer …

Retrospective Evaluation Of Clinical Experience With Intravenous Ascorbic Acid In Patients With Cancer., Anthony J. Bazzan, George Zabrecky, Nancy Wintering, Andrew B. Newberg, Daniel A. Monti

Marcus Institute of Integrative Health Faculty Papers

BACKGROUND: Intravenous ascorbic acid (IV AA) has been used extensively in cancer patients throughout the United States. Currently, there are limited data on the safety and clinical effects of IV AA. The purpose of this study was to expand the current literature using a retrospective analysis of adverse events and symptomatic changes of IV AA in a large sample of cancer patients.

METHODS: We conducted a retrospective chart review of all patients receiving IV AA for cancer at the Thomas Jefferson University Hospital over a 7-year period. We assessed all reports of adverse events, laboratory findings, and hospital or emergency …