Diseases Commons^™

Geographic Disparities In The Distribution Of The U.S. Gynecologic Oncology Workforce: A Society Of Gynecologic Oncology Study, Stephanie Ricci, Ana Tergas, Kara Roche, Melissa Fairbairn, Kimberly Levinson, Micael Lopez-Acevedo, +Several Additional Authors

Obstetrics and Gynecology Faculty Publications

A recent ASCO workforce study projects a significant shortage of oncologists in the U.S. by 2020, especially in rural/underserved (R/US) areas. The current study aim was to determine the patterns of distribution of U.S. gynecologic oncologists (GO) and to identify provider-based attitudes and barriers that may prevent GOs from practicing in R/US regions. U.S. GOs (n = 743) were electronically solicited to participate in an on-line survey regarding geographic distribution and participation in outreach care. A total of 320 GOs (43%) responded; median age range was 35–45 years and 57% were male. Most practiced in an urban setting (72%) at …

Re:Align, George Washington University Cancer Center

RE:

No abstract provided.

Alcohol, Stem Cells And Cancer., Shoujun Gu, Bao-Ngoc Nguyen, Shuyun Rao, Shulin Li, Kirti Shetty, Asif Rashid, Vivek Shukla, Chu-Xia Deng, Lopa Mishra, Bibhuti Mishra

Surgery Faculty Publications

Dosage, gender, and genetic susceptibility to the effects of alcohol remained only partially elucidated. In this review, we summarize the current knowledge of the mechanisms underlying the role of alcohol in liver and gastrointestinal cancers. In addition, two recent pathways- DNA repair and TGF-β signaling which provide new insights into alcohol in the regulation of cancers and stem cells are also discussed here.

Somatic Vhl Mutation In A Patient With Men1-Associated Metastatic Pancreatic Neuroendocrine Tumor Responding To Sunitinib Treatment: A Case Report., Jasmine Shell, Dhaval Patel, Astin Powers, Martha Quezado, Keith Killian, Paul Meltzer, Jack Zhu, Apostolos Gaitanidis, Fatima Karzai, Vladimir Neychev, Patience Green, Electron Kebebew

Surgery Faculty Publications

Multiple endocrine neoplasia type 1 (MEN1) and von Hippel-Lindau (VHL) are autosomal-dominant diseases caused by germline mutations in tumor-suppressor genes. A patient with a germline MEN1 mutation and a somatic VHL mutation in the tumor has not been reported. Herein, we report on a patient with MEN1 and a metastatic nonfunctioning pancreatic neuroendocrine tumor (PNET) with a somatic VHL mutation. This patient underwent a pancreaticoduodenectomy for a grade 2 PNET obstructing her pancreatic duct. The patient developed liver and regional lymph node metastases as well as growth of a PNET in the remnant pancreas. As part of a clinical trial …

Inhibition Of Post-Transcriptional Steps In Ribosome Biogenesis Confers Cytoprotection Against Chemotherapeutic Agents In A P53-Dependent Manner, Russell T Sapio, Anastasiya N Nezdyur, Matthew Krevetski, Leonid Anikin, Vincent J Manna, Natalie Minkovsky, Dimitri G Pestov

Rowan-Virtua School of Osteopathic Medicine Departmental Research

The p53-mediated nucleolar stress response associated with inhibition of ribosomal RNA transcription was previously shown to potentiate killing of tumor cells. Here, we asked whether targeting of ribosome biogenesis can be used as the basis for selective p53-dependent cytoprotection of nonmalignant cells. Temporary functional inactivation of the 60S ribosome assembly factor Bop1 in a 3T3 cell model markedly increased cell recovery after exposure to camptothecin or methotrexate. This was due, at least in part, to reversible pausing of the cell cycle preventing S phase associated DNA damage. Similar cytoprotective effects were observed after transient shRNA-mediated silencing of Rps19, but not …

Cognitive Issues In Childhood Cancer Survivors And Related Parental Perceptions And Behaviors: An Integrative Review Of Literature, Brian Decant, Joseph Tariman

Grace Peterson Nursing Research Colloquium

Background: Survivorship of childhood cancer is often accompanied by neurocognitive late-effects (NCLE) related to the disease and/or it’s associated treatment regimes.

Objectives: The primary purpose of this integrative literature review was to examine NCLE in pediatric cancer survivors and identify parental perceptions and behaviors that correlated to cognitive dysfunction in their children.

Method: An integrative literature review was completed utilizing searches in PubMed, CINAHL Complete, and PsycINFO. Some search terms included “childhood cancer”, “survivor”, “cognition”, “cognitive disorder”, “neurocognitive”, “late-effects”, “child(ren)”, “parent(s)”, and “perception”.

Results: Analysis of ten predominant methods of neurocognitive evaluation yielded five major cognitive deficit measures in pediatric …

Dnmt3a Haploinsufficiency Provokes Hematologic Malignancy Of B-Lymphoid, T-Lymphoid, And Myeloid Lineage In Mice, Garland Michael Upchurch

Theses & Dissertations

DNA methyltransferase 3A (DNMT3A) is a master epigenetic regulator of benign and malignant hematopoiesis. To dissect the biological consequences of homozygous and heterozygous Dnmt3a inactivation in malignant hematopoiesis, we generated Dnmt3a homozygous null (Dnmt3a^Δ/Δ) and Dnmt3a heterozygous (Dnmt3a^+/–) mice and compared the presentations of hematologic malignancies between cohorts. Bi-allelic inactivation of Dnmt3a results in the presentation of mature lymphoid neoplasms resembling chronic lymphocytic leukemia (CLL; B220⁺CD19⁺CD5⁺; 88% penetrance (37/42)) and CD8+ peripheral T-cell lymphoma (PTCL; TCRβ⁺CD3⁺CD8⁺CD4^—; 40% penetrance (17/42)). …

Developing A Peer Cancer Support Group Evaluation, Glenda Kith

Master's Projects and Capstones

Introduction: For many years, health care organizations have offered peer cancer support groups to cancer survivors, but peer cancer support group evaluation is not standardized. Without a clear and consistent evaluation, it may be difficult to understand the efficacy of and gain support for peer cancer support groups. In this paper, I discuss how an evaluation was created for a peer cancer support group called Cancer Awareness Resource and Education (CARE).

Methods: In-depth interviews with CARE participants were conducted and pre-survey and a post-survey were developed. The in-depth interviews included a convenience sample of eight individuals, two individuals from the …

Multiple Myeloma Baseline Immunoglobulin G Level And Pneumococcal Vaccination Antibody Response, Michael A. Thompson, Martin K. Oaks, Maharaj Singh, Karen M. Michel, Michael P. Mullane, Husam S. Tarawneh, Angi Kraut, Kayla J. Hamm

Journal of Patient-Centered Research and Reviews

Infections are a major cause of morbidity and mortality in multiple myeloma (MM), a cancer of the immune system. Vaccination clinical efficacy endpoints have not been demonstrated, and there are limited data on surrogate markers of efficacy. This pilot study evaluated sequential immunologic markers after standard pneumococcal vaccination (PV) in patients with MM and non-MM controls. Vaccination was standard for PV (PCV13 or PPV23), with laboratory testing at baseline and at 2, 4, 12 and 24 weeks after vaccination. Immunoglobulin G (IgG) antibodies to pneumococcal antigens were detected by ELISA. Prevaccination total IgG levels and IgG subclass levels were also …

Diffuse Pulmonary Infiltrates: A Guise Of Adenocarcinoma, Mourad Ismail, Raminderjit Sekhon

NYMC Faculty Publications

Small and non-small cell lung cancer present in a variety of radiologic and clinical patterns, and have been linked to smoking. Primary adenocarcinoma of the lung has been increasingly recognized in females and nonsmokers, often presenting a diagnostic challenge. In the absence of smoking history, these radiographic patterns may be initially misdiagnosed as an infectious or inflammatory condition, often delaying the diagnosis of malignancy. We report two cases of female patients with relatively short or no smoking history presenting with diffuse pulmonary infiltrates not typically seen in primary lung cancer, which created a diagnostic challenge, ultimately diagnosed as primary lung …

Computational Drug Design: A Multitargeted Approach In Bladder Cancer, Travis C. Lantz, Joydeb Majumder, Gaurav Chopra

The Summer Undergraduate Research Fellowship (SURF) Symposium

Cancer is a complex, robust disease with multiple redundant disease pathways which lead to tumor development, growth, and eventually even death. Despite known redundancies, cancer therapeutics continue to be developed against a single protein target. Initial disease regression occurs followed by relapse in a drug resistant disease state. In response, combinational drug clinical trial targeting multiple pathways began, and have failed due to increased toxicity caused by adverse drug interactions. Development of a single drug that differentially targets multiple disease pathways will result in a more potent therapeutic while inducing minimal toxicity. This was done computationally through in-lab software packages, …

Molecular Mechanisms Of Dna Replication Initiation In Hpvs With Genetic Variations Leading To Cellular Carcinogenesis, Gulden Yilmaz

Graduate School of Biomedical Sciences Theses and Dissertations

Human papillomaviruses are a vast family of double-stranded DNA viruses containing non-carcinogenic and carcinogenic types, whose crucial differences remain unknown, except for the difference in the frequency of DNA replication. The human papillomavirus (HPV) E2 protein regulates the initiation of viral DNA replication and transcription. Its recognition and binding to four 12 bp palindromic sequences in the viral origin is essential for its function. Little is known about the DNA binding mechanism of the E2 protein found in HPV types that have low risk for oncogenicity (low-risk) as well as the roles of various elements of the individual binding sites. …

Metabolic Regulation Of Cellular Signaling, Rashid John Darbandi

Theses and Dissertations (ETD)

Using the biochemically tractable Xenopus oocyte model system, we have previously characterized a novel metabolic regulation of cell death. We found that glucose-6-phosphate (G6P) via the pentose phosphate pathway leads to increased nicotinamide adenine dinucleotide phosphate (NADPH) levels, a subsequent increase in cytosolic acetyl-coenzyme A and activation of Ca2+/calmodulin-dependent protein kinase II (CaMKII). We recently identified coenzyme A (CoA), derived from the breakdown of acetyl-CoA, as the key metabolic signal that mediates a novel mechanism of calmodulindependent activation of CaMKII. CoA binds directly to the calmodulin (CaM) binding domain (CaMBD) of CaMKII resulting in its activation and downstream inhibitory phosphorylation …

Discovery Of Novel Tubulin Inhibitors And Selective Survivin Inhibitors For Advanced Melanoma And Total Synthesis Of Bioactive 20s-Hydroxyvitamin D3, Qinghui Wang

Theses and Dissertations (ETD)

According to the statistics from American Cancer Society, the 5-year survival rate for patients with advanced melanoma is as low as 5%. Treatment of advanced melanoma, therefore, represents an unmet medical need. In this dissertation, I will show the effort to develop new generations of bioavailable tubulin inhibitors targeting the colchicine binding site and selective small-molecule survivin inhibitors for treating advanced melanoma. Extensive structure-activity relationship (SAR) studies of lead molecules ABI-231 and UC-112 have been performed.

Chapter 1 will introduce the current situation of advanced or metastatic melanoma, its clinical drug treatments, as well as problems in current drug treatments. …

Towards A Personalized Cancer Gene Therapy: A Case Of Clear Cell Renal Cell Carcinoma, Dumitru Iacobas, Sanda Iacobas

NYMC Faculty Publications

No abstract provided.

Religious Coping And Types And Sources Of Information Used In Making Prostate Cancer Treatment Decisions., Janice V Bowie, Caryn N Bell, Altovise Ewing, Ballington Kinlock, Ashley Ezema, Roland J Thorpe, Thomas A Laveist

Health Policy and Management Faculty Publications

Treatment experiences for prostate cancer survivors can be challenging and dependent on many clinical and psychosocial factors. One area that is less understood is the information needs and sources men utilize. Among these is the influence of religion as a valid typology and the value it may have on treatment decisions. The objective of this study was to assess the relationship between race, religion, and cancer treatment decisions in African American men compared with White men. Data were from the Diagnosis and Decisions in Prostate Cancer Treatment Outcomes Study that consisted of 877 African American and White men. The main …

Praja Is Overexpressed In Glioblastoma And Contributes To Neural Precursor Development, Joshua Shin, Viveka Mishra, Eric Glasgow, Sobia Zaidi, Kazufumi Ohshiro, Lopa Mishra, Shuyun Rao, +Several Additional Authors

Medicine Faculty Publications

PRAJA, a RING-H2 E3 ligase, is abundantly expressed in brain tissues such as the cerebellum and frontal cortex, amongst others, and more specifically in neural progenitor cells as well as in multiple cancers that include glioblastomas. However, the specific role that Praja plays in neural development and gliomas remains unclear. In this investigation, we performed bioinformatic analyses to examine Praja1 and Praja2 expression across 29 cancer types, and observed raised levels of Praja1 and Praja2 in gliomas with an inverse relationship between Praja1 and apoptotic genes and Praja substrates such as Smad3. We analyzed the role of Praja in the …

Managing Renal Cell Carcinoma Associated Paraneoplastic Syndrome With Nephron-Sparing Surgery In A Patient With Von Hippel-Lindau., John M Dibianco, Julie Y An, Sally Tanakchi, Zachary Stanik, Aidan Mcgowan, Mahir Maruf, Abhinav Sidana, Amit Lodha Jain, Akhil Muthigi, Arvin K George, Christopher Bayne, W Marston Linehan, Shawna L Boyle, Adam R Metwalli

Urology Faculty Publications

A patient with germline von Hippel-Lindau (VHL) gene alteration and history of multiple tumors present with classical paraneoplastic syndrome (PNS) associated with renal cell carcinoma (RCC). She underwent open nephron sparing surgery with resolution of symptoms. She remained without recurrence of RCC for the initial 2 years of her follow-up. To the best of our knowledge, this case represents the first in which PNS was specifically resolved using a partial nephrectomy in a patient with VHL. This case report provides initial evidence for the potential role of nephron sparing surgery in the management of paraneoplastic symptoms associated with hereditary RCC.

Alternative Splicing Promotes Tumour Aggressiveness And Drug Resistance In African American Prostate Cancer., Bi-Dar Wang, Kristin Ceniccola, Sujin Hwang, Ramez Andrawis, Anelia Horvath, Jennifer A Freedman, Jacqueline Olender, Stefan Knapp, Travers Ching, Lana Garmire, Vyomesh Patel, Mariano A Garcia-Blanco, Steven R Patierno, Norman H Lee

Pharmacology and Physiology Faculty Publications

linical challenges exist in reducing prostate cancer (PCa) disparities. The RNA splicing landscape of PCa across racial populations has not been fully explored as a potential molecular mechanism contributing to race-related tumour aggressiveness. Here, we identify novel genome-wide, race-specific RNA splicing events as critical drivers of PCa aggressiveness and therapeutic resistance in African American (AA) men. AA-enriched splice variants of PIK3CD, FGFR3, TSC2 and RASGRP2 contribute to greater oncogenic potential compared with corresponding European American (EA)-expressing variants. Ectopic overexpression of the newly cloned AA-enriched variant, PIK3CD-S, in EA PCa cell lines enhances AKT/mTOR signalling and increases proliferative …

African-American Esophageal Squamous Cell Carcinoma Expression Profile Reveals Dysregulation Of Stress Response And Detox Networks., Hayriye Verda Erkizan, Kory Johnson, Svetlana Ghimbovschi, Deepa Karkera, Gregory Trachiotis, Houtan Adib, Eric P Hoffman, Robert G Wadleigh

Genomics and Precision Medicine Faculty Publications

BACKGROUND: Esophageal carcinoma is the third most common gastrointestinal malignancy worldwide and is largely unresponsive to therapy. African-Americans have an increased risk for esophageal squamous cell carcinoma (ESCC), the subtype that shows marked variation in geographic frequency. The molecular architecture of African-American ESCC is still poorly understood. It is unclear why African-American ESCC is more aggressive and the survival rate in these patients is worse than those of other ethnic groups.

METHODS: To begin to define genetic alterations that occur in African-American ESCC we conducted microarray expression profiling in pairs of esophageal squamous cell tumors and matched control tissues.

RESULTS: …

Clinicians’ Perspectives On Adopting A Lung Cancer Palliative Care Intervention, Shaunna Siler

Loma Linda University Electronic Theses, Dissertations & Projects

Despite the significant progress in implementing palliative care interventions for cancer patients, few intervention studies seek healthcare clinicians’ input prior to implementation. The purpose of this research was then to explore palliative care and oncology clinicians’ (e.g., physicians, nurses, social workers, and chaplains) perspectives on current challenges and useful practices in meeting the quality of life needs of lung cancer patients and family caregivers, and to increase the likelihood of the adoption of a palliative care intervention based on understanding current trends in palliative care delivery at three outpatient oncology sites. The conceptual framework used for this study was the …

Coping As A Mediator Between Symptom Burden And Distress In Lung Cancer Patients, Spring F. Gehring

Loma Linda University Electronic Theses, Dissertations & Projects

Lung cancer is considered the leading cause of cancer death worldwide. An estimated 224,390 new cases of lung cancer are expected to be diagnosed and 158,080 Americans are expected to die from lung cancer in 2016 (National Institutes of Health, 2016; Siegel, Miller, & Jemal, 2016). Lung cancer patients also report the highest levels of psychological distress and symptom burden than any other forms of cancer (Linden, Vodermaier, MacKenzie, & Greig, 2012). Given the prevalence and impact of lung cancer, it is imperative to address the emotional toll this diagnosis can have on those suffering with the disease to develop …

Cancer Center Regional Benchmarks For Psychosocial Care, Desiree R. Azizoddin

Loma Linda University Electronic Theses, Dissertations & Projects

The American College of Surgeons (ACoS) Commissions on Cancer (CoC) formulated and implemented standard 3.2 for Psychosocial Distress Screening. This standard requires that all accredited cancer centers evaluate psychosocial distress and provide appropriate triage and intervention for all cancer patients. Over the past decade, Loma Linda University Medical Oncology Center (LLUMOC) administration, physicians, nurses, psychosocial care staff, and chaplaincy collaborated to implement a psychosocial screening and referral program throughout cancer patient services. This current research includes qualitative analysis assessing strengths and barriers of the psychosocial program at LLUMOC from the perspective of LLUMOC providers and two directors of Supportive Care …

Targeting Ledgf/P75 To Sensitize Chemoresistant Prostate Cancer Cells To Taxanes, Leslimar Rios-Colón

Loma Linda University Electronic Theses, Dissertations & Projects

Prostate cancer (PCa) is the second most diagnosed cancer in males. This disease disproportionately affects African American men, with a higher incidence and mortality compared to other ethnic/racial groups. An aging male population and the complexity of addressing the health disparities associated with this disease puts PCa into the spotlight due to its serious public health implications and the imminent fiscal challenge over the next decades. Chronic prostate inflammation resulting in activation of stress and prosurvival pathways contribute to disease progression and the development of chemoresistance. Lens epithelium-derived growth factor p75 (LEDGF/p75) is a stressresponse protein that promotes cellular survival …

Clinical Applications Of Pd-L1 Bioassays For Cancer Immunotherapy, Delong Liu, Shuhang Wang, Wendy Bindeman

NYMC Faculty Publications

Programmed death ligand 1 (PD-L1) has emerged as a biomarker that can help to predict responses to immunotherapies targeted against PD-L1 and its receptor (PD-1). Companion tests for evaluating PD-L1 expression as a biomarker of response have been developed for many cancer immunotherapy agents. These assays use a variety of detection platforms at different levels (protein, mRNA), employ diverse biopsy and surgical samples, and have disparate positivity cutoff points and scoring systems, all of which complicate the standardization of clinical decision-making. This review summarizes the current understanding and ongoing investigations regarding PD-L1 expression as a potential biomarker for clinical outcomes …

Cancer-Specific Mortality, Cure Fraction, And Noncancer Causes Of Death Among Diffuse Large B-Cell Lymphoma Patients In The Immunochemotherapy Era., Nadia Howlader, Angela B Mariotto, Caroline Besson, Gita Suneja, Kim Robien, Naji Younes, Eric A Engels

Epidemiology Faculty Publications

BACKGROUND

Survival after the diagnosis of diffuse large B-cell lymphoma (DLBCL) has been increasing since 2002 because of improved therapies; however, long-term outcomes for these patients in the modern treatment era are still unknown.

METHODS

Using Surveillance, Epidemiology, and End Results data, this study first assessed factors associated with DLBCL-specific mortality during 2002-2012. An epidemiologic risk profile, based on clinical and demographic characteristics, was used to stratify DLBCL cases into low-, medium-, and high-risk groups. The proportions of DLBCL cases that might be considered cured in these 3 risk groups was estimated. Risks of death due to various noncancer causes …

The E2f4 Prognostic Signature Predicts Pathological Response To Neoadjuvant Chemotherapy In Breast Cancer Patients, Kenneth M. K. Mark, Frederick S. Varn, Matthew H. Ung, Feng Qian, Chao Cheng

Dartmouth Scholarship

Neoadjuvant chemotherapy is a key component of breast cancer treatment regimens and pathologic complete response to this therapy varies among patients. This is presumably due to differences in the molecular mechanisms that underlie each tumor’s disease pathology. Developing genomic clinical assays that accurately categorize responders from non-responders can provide patients with the most effective therapy for their individual disease. We applied our previously developed E2F4 genomic signature to predict neoadjuvant chemotherapy response in breast cancer. E2F4 individual regulatory activity scores were calculated for 1129 patient samples across 5 independent breast cancer neoadjuvant chemotherapy datasets. Accuracy of the E2F4 signature in …

Choriocarcinoma With Brain, Lung And Vaginal Metastases Successfully Treated Without Brain Radiation Or Intrathecal Chemotherapy: A Case Report, Anja Frost, Jonathan Sherman, M. Katayoon Rezaei, Alivia Aron, Micael Lopez-Acevedo

Neurological Surgery Faculty Publications

Highlights:

• • There is no consensus on optimal treatment for GTN and brain metastases.
• • Brain metastasis treated with craniotomy and intravenous, EMA-CO chemotherapy
• • Intravenous high-dose methotrexate may be adequate to treat brain metastases.

Mapping The Interaction Between Lrrc59 And Cip2a Oncoprotein, Tamika C. Reed

Graduate School of Biomedical Sciences Theses and Dissertations

The oncogene cancerous inhibitor of protein phosphatase 2A (CIP2A) has been shown to promote oncogenesis through numerous protein-protein interactions. CIP2A was initially found to be a direct inhibitor of the PP2A tumor suppressor protein; however, new research has demonstrated that CIP2A can act independently of PP2A through protein-protein interactions resulting in deregulation of the cell cycle and the development of therapeutic drug resistance, tumorigenesis, and cell proliferation. It has been shown that leucine rich repeat containing 59 protein (LRRC59) binds to and is required for the nuclear translocation of CIP2A, thereby making this interaction a target for drug therapy. Thus, …

Characterization Of E-Cadherin Regulation In Response To Zeb1 Inhibition In Endometrial Cancer Cell Lines, Chidozie Paul Chukwu

Graduate School of Biomedical Sciences Theses and Dissertations

Epithelial to mesenchymal transition (EMT) is the process in which cells lose their epithelial structure during gastrulation. This process also affects the migration and movement of tumor cells and promotes invasion and metastases of endometrial carcinomas. Down-regulation of E-cadherin (CDH1) by transcription factors is the key target of EMT modulators and is achieved mainly by ZEB1 (zinc finger E-box binding homeobox 1). Current research looking at restoration of E-cadherin expression in vitro involves the use of small molecules such as histone deacetylase (HDAC) inhibitors and DNA methyltransferase inhibitors. Trichostatin A (TSA) and small interfering ribonucleic acid (siRNA) are tools that …