Digital Commons Network^™

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, …

Statistical Analysis Plan (Sap) For The Very Early Rehabilitation In Speech (Verse) After Stroke Trial: An International 3-Arm Clinical Trial To Determine The Effectiveness Of Early, Intensive, Prescribed, Direct Aphasia Therapy, Erin Godecke, Tapan Rai, Dominique A Cadilhac, Elizabeth Armstrong, Sandy Middleton, Natalie Ciccone, Anne Whitworth, Miranda L Rose, Audrey Holland, Fiona Ellery, Graeme J Hankey, Julie Bernhardt

Research outputs 2014 to 2021

Background Limited evidence exists to support very early intensive aphasia rehabilitation after stroke. VERSE is a PROBE trial designed to determine whether two types of intensive aphasia therapy, beginning within 14 days of acute stroke, provide greater therapeutic and cost-effectiveness than usual care. Objective To publish the detailed statistical analysis plan for the VERSE trial prior to unblinding. This statistical analysis plan was based on the published and registered VERSE trial protocol and was developed by the blinded steering committee and management team, led by the trial statistician. This plan was developed using outcome measures and trial data collection forms. …

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 …

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 …

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 …

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.

Faith C. S. Ho, Western Medicine For Chinese: How The Hong Kong College Of Medicine Achieved A Breakthrough, Jack Greatrex

Research Collection College of Integrative Studies

The Hong Kong College of Medicine for Chinese was founded in 1887 with expansive ambitions: the adoption of western medicine and science by the Chinese population of colonial Hong Kong and China more broadly.

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 …

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) …

Implementation Of A Sustainable Peer Mentor Program In Student Registered Nurse Anesthetists (Srnas)”, Kristin Cox

Doctoral Projects

Evidence has shown that Student Registered Nurse Anesthetist’s (SRNAs) stress is perceived as above average and is correlated with substandard patient care during clinical courses (Chipas et al., 2012). Some studies have indicated SRNAs experience low self-efficacy during clinical, which could lead to difficulty in thinking clearly or responding to clinical situations (Imus, Burns, & Weglarz, 2017). Peer mentoring has shown to result in stress reduction and improvement in self-efficacy in students (Barker et al., 2012; Giordana & Wedin, 2010). Despite the current evidence, a nurse anesthesia program in the southeastern United States did not have an organized peer mentor …

Continuous Epidural Analgesia For Postoperative Pain Management: A Policy Analysis, Madison Nowell

Doctoral Projects

Postoperative pain management is a necessary component of the care of every surgical patient. Epidural analgesia is a widely used method to provide excellent postoperative pain relief and enhance postoperative recovery (Sawhney, 2012). Epidural analgesia is associated with fewer side effects than alternative pain management techniques; however, when epidural catheters are managed improperly, or pain is inadequately assessed, epidural analgesia fails to provide adequate pain relief (Deni et al., 2016). More than 80% of surgical patients experience moderate to severe postoperative pain, and 28 to 50% of these patients have a pain score greater than 6 out of 10 at …

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 …

Nanoparticles As Multimodal Photon Transducers Of Ionizing Radiation, Edwin C. Pratt, Travis M. Shaffer, Qize Zhang, Charles Michael Drain, Jan Grimm

Publications and Research

In biomedical imaging, nanoparticles combined with radionuclides that generate Cerenkov luminescence are used in diagnostic imaging, photon-induced therapies, and as activatable probes. In these applications, the nanoparticle is often viewed as a carrier inert to ionizing radiation from the radionuclide. However, certain phenomena such as enhanced nanoparticle luminescence and generation of reactive oxygen species cannot be explained by only Cerenkov luminescence interactions with nanoparticles. Herein, we report methods to examine the mechanisms of nanoparticle excitation by radionuclides, including interactions with Cerenkov luminescence, β particles, and γ radiation. We demonstrate that β scintillation contributes appreciably to excitation and reactivity in certain …

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 …

Infections In Older Adults: A Case-Based Discussion Series Emphasizing Antibiotic Stewardship, Alyson Michener, Robin L.P. Jump

Faculty Scholarship

Introduction: Compared with younger populations, adults 65 years and older are more likely to suffer infection-related morbidity and mortality, experience antibiotic-related adverse events, and acquire multidrug-resistant organisms. We developed a series of case-based discussions that stressed antibiotic stewardship while addressing management of common infections in older adults. Methods: Five 1-hour case-based discussions address recognition, diagnosis, and management of infections common in older adults, including those living in long-term care settings: urinary tract infections, upper respiratory tract infections, lower respiratory tract infections, skin and soft tissue infections, and Clostridium difficile infection. The education was implemented at the skilled nursing centers at …

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 …

Prostaglandin D2/J2 Signaling Pathway In A Rat Model Of Neuroinflammation Displaying Progressive Parkinsonian-Like Pathology: Potential Novel Therapeutic Targets, Chuhyon Corwin, Anastasia Nikolopoulou, Allen L. Pan, Mariela Nunez-Santos, Shankar Vallabhajosula, Peter A. Serrano, John Babich, Maria E. Figueiredo-Pereira

Publications and Research

Background: Prostaglandins are products of the cyclooxygenase pathway, which is implicated in Parkinson’s disease (PD). Limited knowledge is available on mechanisms by which prostaglandins contribute to PD neurodegeneration. To address this gap, we focused on the prostaglandin PGD2/J2 signaling pathway, because PGD2 is the most abundant prostaglandin in the brain, and the one that increases the most under pathological conditions. Moreover, PGJ2 is spontaneously derived from PGD2.

Methods: In this study, we determined in rats the impact of unilateral nigral PGJ2-microinfusions on COX-2, lipocalin-type PGD2 synthase (L-PGDS), PGD2/J2 receptor 2 (DP2), and 15 hydroxyprostaglandin dehydrogenase (15-PGDH). Nigral dopaminergic (DA) and …

Oxytocin And Cancer: An Emerging Link, Ben Lerman, Trisheena Harricharran, Olorunseun O. Ogunwobi

Publications and Research

The neuropeptide hormone oxytocin, which is released from the posterior pituitary gland, is involved in a number of physiological processes. Understanding of its effects is gradually increasing due to new research in this area. While mostly recognized as a reproductive system hormone, oxytocin also regulates other organ systems such as the brain and cardiovascular system. Recently, research has focused on unraveling its involvement in cancer, and emerging evidence suggests a potential role for oxytocin as a cancer biomarker. This review summarizes observations linking oxytocin and cancer, with a special emphasis on prostate cancer, where it may promote cell proliferation. Research …

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 …

Pregnancy Anxiety Predicts Shorter Gestation In Latina And Non-Latina White Women: The Role Of Placental Corticotrophin-Releasing Hormone, Isabel F. Ramos, Christine M. Guardino, Maxwell Mansolf, Laura M. Glynn, Curt A. Sandman, Calvin J. Hobel, Christine Dunkel Schetter

Psychology Faculty Articles and Research

Objective

Previous research has shown that a woman’s anxiety about her pregnancy predicts gestational length. Placental corticotrophin-releasing hormone (CRH) is a stress-responsive peptide proposed as a mechanism. We examined placental CRH as a physiological mediator of the association between pregnancy anxiety and gestational length in Latina and non-Latina White women to replicate evidence of associations between pregnancy anxiety, placental CRH and gestational length; to test whether placental CRH levels or changes mediate effects of pregnancy anxiety on gestational length; to examine ethnic differences in pregnancy anxiety, placental CRH, and gestational length; and to explore whether the effects of pregnancy anxiety …

"Born Out Of Fear": A Grounded Theory Study Of The Stigma Of Bipolar Disorder For New Mothers, Walker Ladd Ph.D.

The Qualitative Report

Childbirth is an established trigger for the onset of bipolar disorders (BD) in the postpartum period, causing significant pathology and disability. Research has shown that the stigma of mental illness for new mothers is a powerful obstacle to care, preventing women from accessing critical treatment and social support. However, the majority of research has examined the relationship between the stigma and postpartum depression, leaving a gap in knowledge regarding stigma and postpartum bipolar disorder. The problem addressed in this grounded theory study was the lack of knowledge regarding the stigma of a diagnosis of bipolar disorder (BD) in the first …

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 …

A Systematic Review Of The Efficacy And Safety Of Fecal Microbiota Transplant For Clostridium Difficile Infection In Immunocompromised Patients, Oluwaseun Shogbesan, Dilli Ram Poudel, Samjeris Victor, Asad Jehangir, Opeyemi Fadahunsi, Gbenga Shogbesan, Anthony A. Donato

Reading Hospital Internal Medicine Residency

Background: Fecal microbiota transplantation (FMT) has been shown to be effective in recurrent

Methods: We searched MEDLINE and EMBASE for English language articles published on FMT for treatment of CD infection in immunocompromised patients (including patients on immunosuppressant medications, patients with human immunodeficiency virus (HIV), inherited or primary immunodeficiency syndromes, cancer undergoing chemotherapy, or organ transplant, including-bone marrow transplant) of all ages. We excluded inflammatory bowel disease patients that were not on immunosuppressant medications. Resolution and adverse event rates (including secondary infection, rehospitalization, and death) were calculated.

Results: Forty-four studies were included, none of which were randomized designs. A total …

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 …

Race Analysis In An African American Majority Sample Of Individuals With Serious Mental Illness And Comorbid Diabetes Participating In A Self-Management Research Treatment Trail, Martha Sajatovic, Molly Howland, Douglas Gunzler, Kristin A. Cassidy, Richard Mccormick, Thomas Scheidemantel, Charles Thomas, Carol Blixen, Neal V. Dawson

Faculty Scholarship

Objectives: Targeted Training in Illness Management (TTIM) focuses on enhancing care engagement for people living with serious mental illness and diabetes. This secondary analysis from a 60-week, randomized controlled trial of TTIM versus treatment as usual evaluated racial subgroup outcomes. Method: Demographics, clinical characteristics, and diabetes status were evaluated for those self-identifying as non-Hispanic White, African American, and Hispanic. Longitudinal response to TTIM was evaluated using a multiple domain risk index. Due to their small sample size; those identifying as Hispanic were excluded from this analysis. Results: Non-Hispanic White participants had greater baseline socioeconomic advantages. Baseline risk scores, glycosylated hemoglobin …

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 …

Mir-196b Target Screen Reveals Mechanisms Maintaining Leukemia Stemness With Therapeutic Potential., Sara E. Meyer, David E. Muench, Andrew M. Rogers, Tess J. Newkold, Emily Orr, Eric O'Brien, John P. Perentesis, John G. Doench, Ashish Lal, Patrick J. Morris, Craig J. Thomas, Judy Lieberman, Edwina Mcglinn, Bruce J. Aronow, Nathan Salomonis, H. Leighton Grimes

Department of Cancer Biology Faculty Papers

We have shown that antagomiR inhibition of miRNA miR-21 and miR-196b activity is sufficient to ablate MLL-AF9 leukemia stem cells (LSC) in vivo. Here, we used an shRNA screening approach to mimic miRNA activity on experimentally verified miR-196b targets to identify functionally important and therapeutically relevant pathways downstream of oncogenic miRNA in MLL-r AML. We found Cdkn1b (p27^Kip1) is a direct miR-196b target whose repression enhanced an embryonic stem cell–like signature associated with decreased leukemia latency and increased numbers of leukemia stem cells in vivo. Conversely, elevation of p27^Kip1 significantly reduced MLL-r leukemia self-renewal, promoted monocytic differentiation …