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Dopamine Levels In The Brain Of Rat Models Of Human Rheumatoid Arthritis, Amelia Stinson

Theses & Dissertations

Research Focus. Rheumatoid arthritis (RA) is a chronic, debilitating, autoimmune disease that causes the destruction of bone tissue and the articular structures of joints. At least 30% of RA patient populations have cognitive impairment. Acidic dopamine (DA) is the principal neuroimmunotransmitter that links the central nervous system and peripheral nervous system together. The aim of the present study was to determine the levels of DA and its two acidic metabolites: 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in arthritic induced rats, and whether their levels vary across four different parts of the brain: amygdala (AMG), front cerebral cortex (CX), hippocampus …

Subanesthetic Ketamine For Postoperative Analgesia: An Evidenced-Based Project, Jeremy Vance

Doctoral Projects

Roughly 100 million surgical procedures are performed in the United States (U.S.) each year and more than 80% of these patients experience acute postoperative pain. Pain costs the U.S. an estimated $560 to $635 billion annually and is a significant contributor to national rates of mortality, morbidity, and disability. Despite these findings, patients continue to receive suboptimal postoperative pain relief.

The adjunct administration of subanesthetic ketamine is opioid-sparing and can improve the effectiveness of a multimodal pain management approach. This project used an exploratory descriptive design to examine how an evidence-based presentation impacted the clinical practice of certified registered nurse …

Incidence Of Cognitively Defined Late-Onset Alzheimer's Dementia Subgroups From A Prospective Cohort Study., Paul K Crane, Emily Trittschuh, Shubhabrata Mukherjee, Andrew J Saykin, R Elizabeth Sanders, Eric B Larson, Susan M Mccurry, Wayne Mccormick, J D Bowen, Thomas Grabowski, Mackenzie Moore, Julianna Bauman, Alden L Gross, C Dirk Keene, Thomas D Bird, Laura E Gibbons, Jesse Mez

Articles, Abstracts, and Reports

INTRODUCTION: There may be biologically relevant heterogeneity within typical late-onset Alzheimer's dementia.

METHODS: We analyzed cognitive data from people with incident late-onset Alzheimer's dementia from a prospective cohort study. We determined individual averages across memory, visuospatial functioning, language, and executive functioning. We identified domains with substantial impairments relative to that average. We compared demographic, neuropathology, and genetic findings across groups defined by relative impairments.

RESULTS: During 32,286 person-years of follow-up, 869 people developed Alzheimer's dementia. There were 393 (48%) with no domain with substantial relative impairments. Some participants had isolated relative impairments in memory (148, 18%), visuospatial functioning (117, 14%), …

Depression In Stroke Patients; A Cross Sectional Study Highlighting The Association Of Stroke On Age And Gender Basis., Saira Abbas, Naila Naeem Shahbaz, Muhammad Amir Umer, Sumera Rafat Umer, Asfia Irfan, Adnan Anwar

Pakistan Journal of Neurological Sciences (PJNS)

Stroke is the second leading cause of death. Depressive disorder is characterized by period of sad mood and anhedonia occurring for two consecutive weeks. Among stroke survivors, the consequence of physical and psychological changes can be devastating. One of those psychological changes is post-stroke depression (PSD). Stroke itself has debilitating morbidity and superimposed PSD further decreases the quality of life of patients and impairs recovery. This study leads us to know the magnitude of post stroke depression.

A Rare Case Of Becker Disease In A 7 Year Old Boy, Prem Chand, Rozmeen Badruddin Husein, Fazal M. Arain

Pakistan Journal of Neurological Sciences (PJNS)

Becker Disease is an autosomal recessive version of the rare congenital disorder called Myotonia Congenita. Due to the rarity of Becker Disease, the genetic and pathological basis of this disease have not been studied well and possible diagnostic methods and techniques are yet to be explored. The existing method of diagnosis of such a case is predominantly dependent on the clinical examination. More work and studies need to be done on the diagnostic aspect of this disease to discover newer diagnostic methods for this disease, which are more reliable and specific. In order to develop better diagnostic methods for the …

Epidemiological Data Of Neurological Disorders In Pakistan And Neighboring Countries: A Review, Ghulam Hussain, Azhar Rasul, Haseeb Anwar, Muhammad Umar Sohail, Syed Kashif Shahid Kamran, Shahid Mahmood Baig, Asghar Shabbir, Javed Iqbal

Pakistan Journal of Neurological Sciences (PJNS)

Neurological disorders are the impairments of nervous system and are an important and growing cause of morbidity, mortality, and disability. In addition to health costs, those suffering from these conditions are also frequently victimized of stigmatization and discrimination. Stigmatization further minimizes the patients' access to treatment and social activities. These disorders, therefore, require special attention particularly in developing countries where unfortunately, the burden of these disorders remains largely unrecognized. Moreover, the burden imposed by such chronic neurological conditions in general can be expected to be particularly devastating in poor populations. These conditions are emerging as severe public health concerns in …

Management Of Undernutrition And Failure To Thrive In Children With Congenital Heart Disease In Low- And Middle-Income Countries, Andrew C. Argent, Rakhi Balachandran, Balu Vaidyanathan, Amina Khan, R. Krishna Kumar

Section of Cardiology

Poor growth with underweight for age, decreased length/height for age, and underweight-for-height are all relatively common in children with CHD. The underlying causes of this failure to thrive may be multifactorial, including innate growth potential, severity of cardiac disease, increased energy requirements, decreased nutritional intake, malabsorption, and poor utilisation of absorbed nutrition. These factors are particularly common and severe in low- and middle-income countries. Although nutrition should be carefully assessed in all patients, failure of growth is not a contraindication to surgical repair, and patients should receive surgical repair where indicated as soon as possible. Close attention should be paid …

Decoding Critical Long Non-Coding Rna In Ovarian Cancer Epithelial-To-Mesenchymal Transition., Ramkrishna Mitra, Xi Chen, Evan J. Greenawalt, Ujjwal Maulik, Wei Jiang, Zhongming Zhao, Christine M. Eischen

Department of Cancer Biology Faculty Papers

Long non-coding RNA (lncRNA) are emerging as contributors to malignancies. Little is understood about the contribution of lncRNA to epithelial-to-mesenchymal transition (EMT), which correlates with metastasis. Ovarian cancer is usually diagnosed after metastasis. Here we report an integrated analysis of >700 ovarian cancer molecular profiles, including genomic data sets, from four patient cohorts identifying lncRNA DNM3OS, MEG3, and MIAT overexpression and their reproducible gene regulation in ovarian cancer EMT. Genome-wide mapping shows 73% of MEG3-regulated EMT-linked pathway genes contain MEG3 binding sites. DNM3OS overexpression, but not MEG3 or MIAT, significantly correlates to worse overall patient survival. DNM3OS knockdown results in …

Implementing Evidence-Based Opioid Prescription Practices In A Primary Care Setting, Cyril Gaiennie

Doctor of Nursing Practice

The use and misuse of opioid pain medication has reached epidemic proportions in the United States. More than 16,000 people die each year due to the misuse or abuse of prescription opioid medications, which is more than from heroin, cocaine, and benzodiazepines combined. The purpose of this evidence-based practice project is to establish processes enabling a primary care clinic to implement and adhere to the 2016 Centers for Disease Control’s guidelines for opioid prescription practices in the primary care setting. A retrospective chart review conducted prior to implementation of the guidelines demonstrated that four of six of the CDC’s recommendations …

Nadph Oxidase 5 (Nox5)-Induced Reactive Oxygen Signaling Modulates Normoxic Hif-1Α And P27, Smitha Antony, Guojian Jiang, Yongzhong Wu, Jennifer L Meitzler, Hala R Makhlouf, Diana C Haines, Donna Butcher, Dave S B Hoon, Jiuping Ji, Yiping Zhang, Agnes Juhasz, Jiamo Lu, Han Liu, Iris Dahan, Mariam Konate, Krishnendu K Roy, James H Doroshow

Articles, Abstracts, and Reports

NADPH oxidase 5 (NOX5) generated reactive oxygen species (ROS) have been implicated in signaling cascades that regulate cancer cell proliferation. To evaluate and validate NOX5 expression in human tumors, we screened a broad range of tissue microarrays (TMAs), and report substantial overexpression of NOX5 in malignant melanoma and cancers of the prostate, breast, and ovary. In human UACC-257 melanoma cells that possesses high levels of functional endogenous NOX5, overexpression of NOX5 resulted in enhanced cell growth, increased numbers of BrdU positive cells, and increased γ-H2AX levels. Additionally, NOX5-overexpressing (stable and inducible) UACC-257 cells demonstrated increased normoxic HIF-1α expression and decreased …

The Effect Of Superparamagnetic Iron Oxide Nanoparticle Surface Charge On Antigen Cross-Presentation., Yongbin Mou, Yun Xing, Hongyan Ren, Zhihua Cui, Yu Zhang, Guangjie Yu, Walter J Urba, Qingang Hu, Hongming Hu

Articles, Abstracts, and Reports

Magnetic nanoparticles (NPs) of superparamagnetic iron oxide (SPIO) have been explored for different kinds of applications in biomedicine, mechanics, and information. Here, we explored the synthetic SPIO NPs as an adjuvant on antigen cross-presentation ability by enhancing the intracellular delivery of antigens into antigen presenting cells (APCs). Particles with different chemical modifications and surface charges were used to study the mechanism of action of antigen delivery. Specifically, two types of magnetic NPs, γFe

Labrad : Vol 43, Issue 3 - December 2017, Aga Khan University Hospital, Karachi

LABRAD - Departments of Pathology & Laboratory Medicine and Radiology Archives

• Levey Jennings Chart and Guide to use Westgard Rules
• Quality Assurance in Frozen Section Studies
• Performance Improvement Monitors in Histology
• Quality Assurance in Immunohistochemistry: The Way We Do It
• Quality Assurance in Laboratory Biosafety
• Quality Control of Culture Media Used in Clinical Microbiology
• Quality Assurance (QA) in Qualitative Tests in the Clinical Laboratory
• Radiology Pathology Correlation
• Quality Requirements for Reporting Sickle Haemoglobin
• Meeting Report of International Federation of Clinical Chemistry (IFCC) Conferences- 2017

Hmgcs2 Is A Key Ketogenic Enzyme Potentially Involved In Type 1 Diabetes With High Cardiovascular Risk., Sanket Kumar Shukla, Weijing Liu, Kunal Sikder, Sankar Addya, Amrita Sarkar, Yidong Wei, Khadija Rafiq

Center for Translational Medicine Faculty Papers

Diabetes increases the risk of Cardio-vascular disease (CVD). CVD is more prevalent in type 2 diabetes (T2D) than type 1 diabetes (T1D), but the mortality risk is higher in T1D than in T2D. The pathophysiology of CVD in T1D is poorly defined. To learn more about biological pathways that are potentially involved in T1D with cardiac dysfunction, we sought to identify differentially expressed genes in the T1D heart. Our study used T1D mice with severe hyperglycemia along with significant deficits in echocardiographic measurements. Microarray analysis of heart tissue RNA revealed that the T1D mice differentially expressed 10 genes compared to …

Cognitive Trajectory Changes Over 20 Years Before Dementia Diagnosis: A Large Cohort Study., Ge Li, Eric B Larson, Jane B Shofer, Paul K Crane, Laura E Gibbons, Wayne Mccormick, J D Bowen, Mary Lou Thompson

Articles, Abstracts, and Reports

BACKGROUND/OBJECTIVES: Longitudinal studies have shown an increase in cognitive decline many years before clinical diagnosis of dementia. We sought to estimate changes, relative to "normal" aging, in the trajectory of scores on a global cognitive function test-the Cognitive Abilities Screening Instrument (CASI).

DESIGN: A prospective cohort study.

SETTING: Community-dwelling members of a U.S. health maintenance organization.

PARTICIPANTS: Individuals aged 65 and older who had no dementia diagnosis at baseline and had at least two visits with valid CASI test score (N = 4,315).

MEASUREMENTS: Average longitudinal trajectories, including changes in trajectory before clinical diagnosis in those who would be diagnosed …

Single Nucleotide Polymorphisms In Efflux Pumps Genes In Extensively Drug Resistant Mycobacterium Tuberculosis Isolates From Pakistan, Akbar Kanji, Rumina Hasan, Asho Ali, Ambreen Zaver, Ying Zhang, Kehkashan Imtiaz, Wanliang Shi, Taane G. Clark, Ruth Mcnerney, Jody Phelan

Department of Pathology and Laboratory Medicine

It is challenging to understand mechanisms of drug resistance in Mycobacterium tuberculosis (MTB) due to the large variability in resistance associated genes. Efflux pump genes contribute to drug resistance and thus add to this complexity. Efflux pump gene protein superfamilies have been characterized by genome analysis of drug resistant strains and through invitro transcriptional studies. However, there is limited information regarding efflux pump genes in extensively drug resistant (XDR) tuberculosis (TB) isolates. Whole genome sequencing (WGS) based analysis of 37 extensively drug resistant (XDR) and five drug sensitive (DS) MTB clinical isolates was performed. Single nucleotide polymorphisms (SNPs) in efflux …

Common Tdp1 Polymorphisms In Relation To Survival Among Small Cell Lung Cancer Patients: A Multicenter Study From The International Lung Cancer Consortium, Pawadee Lohavanichbutr, Lori C. Sakoda, Christopher I. Amos, Susanne M. Arnold, David C. Christiani, Michael P. A. Davies, John K. Field, Eric B. Haura, Rayjean J Hung, Takashi Kohno, Maria Teresa Landi, Geoffrey Liu, Yi Liu, Michael W. Marcus, Grainne M. O'Kane, Matthew B. Schabath, Kouya Shiraishi, Stacey A. Slone, Adonina Tardón, Ping Yang, Kazushi Yoshida, Ruyang Zhang, Xuchen Zong, Gary E. Goodman, Noel S. Weiss, Chu Chen

Internal Medicine Faculty Publications

Background—DNA topoisomerase inhibitors are commonly used for treating small-cell lung cancer (SCLC). Tyrosyl-DNA phosphodiesterase (TDP1) repairs DNA damage caused by this class of drugs and may therefore influence treatment outcome. In this study, we investigated whether common TDP1 single-nucleotide polymorphisms (SNP) are associated with overall survival among SCLC patients.

Methods—Two TDP1 SNPs (rs942190 and rs2401863) were analyzed in 890 patients from 10 studies in the International Lung Cancer Consortium (ILCCO). The Kaplan–Meier method and Cox regression analyses were used to evaluate genotype associations with overall mortality at 36 months postdiagnosis, adjusting for age, sex, race, and tumor stage. …

Cerebrovascular Pathology In Down Syndrome And Alzheimer Disease, Elizabeth Head, Michael J. Phelan, Eric Doran, Ronald C. Kim, Wayne W. Poon, Frederick A. Schmitt, Ira T. Lott

Sanders-Brown Center on Aging Faculty Publications

People with Down syndrome (DS) are at high risk for developing Alzheimer disease (AD) with age. Typically, by age 40 years, most people with DS have sufficient neuropathology for an AD diagnosis. Interestingly, atherosclerosis and hypertension are atypical in DS with age, suggesting the lack of these vascular risk factors may be associated with reduced cerebrovascular pathology. However, because the extra copy of APP leads to increased beta-amyloid peptide (Aβ) accumulation in DS, we hypothesized that there would be more extensive and widespread cerebral amyloid angiopathy (CAA) with age in DS relative to sporadic AD. To test this hypothesis CAA, …

A Customized Quantitative Pcr Microrna Panel Provides A Technically Robust Context For Studying Neurodegenerative Disease Biomarkers And Indicates A High Correlation Between Cerebrospinal Fluid And Choroid Plexus Microrna Expression, Wang-Xia Wang, David W. Fardo, Gregory A. Jicha, Peter T. Nelson

Sanders-Brown Center on Aging Faculty Publications

MicroRNA (miRNA) expression varies in association with different tissue types and in diseases. Having been found in body fluids including blood and cerebrospinal fluid (CSF), miRNAs constitute potential biomarkers. CSF miRNAs have been proposed as biomarkers for neurodegenerative diseases; however, there is a lack of consensus about the best candidate miRNA biomarkers and there has been variability in results from different research centers, perhaps due to technical factors. Here, we sought to optimize technical parameters for CSF miRNA studies. We examined different RNA isolation methods and performed miRNA expression profiling with TaqMan® miRNA Arrays. More specifically, we developed a customized …

Ecog-Acrin (E4805) Randomized Phase Ii Study To Determine The Effect Of 2 Different Doses Of Aflibercept In Patients With Metastatic Renal Cell Carcinoma, Roberto Pili, Opeyemi Jegede, Michael A. Carducci, Judith Manola, David L. Groteluschen, Leonard L. Appleman, Glenn Liu, James C. Shanks, Shaker R. Dakhil, Janice Dutcher, Robert S. Dipaola

Internal Medicine Faculty Publications

Background—Aflibercept is a recombinantly-produced fusion protein that has potent anti-VEGF activity. We tested whether aflibercept has clinical activity in clear cell renal cell carcinoma (ccRCC). The recommended Phase 2 dose was 4 mg/kg but several patients treated at 1 mg/kg demonstrated prolonged progression-free survival (PFS). We therefore tested both doses in a parallel group randomized trial.

Methods—Eligible patients (pts) had histologically confirmed advanced or metastatic ccRCC and previous treatments including prior exposure to a VEGF RTKI. Patients received aflibercept (either 1 mg/kg or 4 mg/kg) day 1 of a 14-day cycle until progression. Patients randomized to 1 mg/kg …

Evaluating The Therapeutic Efficacy Of Restoring Wild-Type P53 Activity In P53-Mutant Tumors, Connie A. Larsson

Dissertations and Theses (Open Access)

The p53 transcription factor is the most frequently altered in human cancers usually via missense mutations that undermine its transcriptional activity. Clinically, TP53 mutations have been shown to be remarkably predictive of refractoriness to treatment, resulting in poor outcome. Consequently, the development of p53 pathway activating agents is rapidly evolving and gaining more attention in cancer therapeutics research, with several small molecule compounds currently in preclinical and clinical trials. However, it remains largely unknown what types or proportions of p53-mutant tumors will respond to p53 restoration-based therapies.

Using a mouse model of Li Fraumeni syndrome, we genetically restored wild-type …

Graft And Mesh Use In Vaginal Surgery, Raheela Mohsin Rizvi, Novera G. Chughtai

Department of Obstetrics & Gynaecology

Pelvic organ prolapse and urinary incontinence are among the most common chronic disorders in women. These are common problems whose pathogenesis remains unclear. As life expectancy increases, significantly greater number of women now present with pelvic organ prolapse and urinary incontinence requiring surgical intervention. Currently, the lifetime risk of undergoing prolapse or continence surgery is one in 11, and up to 30% of patients will require repeat reconstructive surgery and repeat surgery for incontinence in 10%. In an attempt to improve surgical outcomes and to preserve vaginal capacity and coital function, a number of synthetic and biological prostheses have been …

Widespread Theta Synchrony And High-Frequency Desynchronization Underlies Enhanced Cognition., E. A. Solomon, J. E. Kragel, Michael R. Sperling, Ashwini Sharan, G. Worrell, M. Kucewicz, C. S. Inman, B. Lega, K. A. Davis, J. M. Stein, B. C. Jobst, K. A. Zaghloul, S. A. Sheth, D. S. Rizzuto, M. J. Kahana

Department of Neurology Faculty Papers

The idea that synchronous neural activity underlies cognition has driven an extensive body of research in human and animal neuroscience. Yet, insufficient data on intracranial electrical connectivity has precluded a direct test of this hypothesis in a whole-brain setting. Through the lens of memory encoding and retrieval processes, we construct whole-brain connectivity maps of fast gamma (30-100 Hz) and slow theta (3-8 Hz) spectral neural activity, based on data from 294 neurosurgical patients fitted with indwelling electrodes. Here we report that gamma networks desynchronize and theta networks synchronize during encoding and retrieval. Furthermore, for nearly all brain regions we studied, …

The Role Of Mucin-Educated Platelet Activation In Tumor Invasiveness: An Unfolding Concern In The Realm Of Cancer Biology, Akbar Shoukat Ali, Arzoo Ajaz

Department of Obstetrics & Gynaecology

Metastasis is a complex and well-coordinated phenotypic transformation of cancer cells governed by aberrant genetic and molecular pathways. It has been approved as the most consistent cause of cancer death. With emerging insight into the genomics, transcriptomics and proteomics, progress has been made and reasonably large number of molecular pathways of metastasis has been forwarded, but our understanding of precise underlying molecular mechanisms remains largely scarce. It has been well-known for around a decade and more that platelets are intriguingly contributing to the cancer metastasis. However, it is only recently that cancer cells can activate platelets have started to become …

Sustained Sensitizing Effects Of Tumor Necrosis Factor Alpha On Sensory Nerves In Lung And Airways, Ruei-Lung Lin, Qihai Gu, Mehdi Khosravi, Lu-Yuan Lee

Physiology Faculty Publications

Tumor necrosis factor alpha (TNFα) plays a significant role in the pathogenesis of airway inflammatory diseases. Inhalation of aerosolized TNFα induced airway hyperresponsiveness accompanied by airway inflammation in healthy human subjects, but the underlying mechanism is not fully understood. We recently reported a series of studies aimed to investigate if TNFα elevates the sensitivity of vagal bronchopulmonary sensory nerves in a mouse model; these studies are summarized in this mini-review. Our results showed that intratracheal instillation of TNFα induced pronounced airway inflammation 24 hours later, as illustrated by infiltration of eosinophils and neutrophils and the release of inflammatory mediators and …

Does Fecal Microbiota Transplantation Cause Clinical Remission In Patients With Ulcerative Colitis?, Amandeep Singh

PCOM Physician Assistant Studies Student Scholarship

Objective: The objective of this selective EBM review is to determine whether or not “Does Fecal Microbiota Transplantation cause Clinical Remission in Patients with Ulcerative Colitis?”

Study Design: Review of three English language primary studies published in 2015.

Data Sources: Two randomized control trials and a cohort study determining if fecal microbiota transplantation does lead to clinical remission of Ulcerative Colitis were found by using PubMed and Cochrane databases.

Outcome(s) Measured: The outcomes measured in all three studies were patient oriented evidence that matters which is clinical remission. The outcomes in the Moayyedi et al. was …

Is Mdma-Assisted Psychotherapy An Effective Treatment For Posttraumatic Stress Disorder (Ptsd)?, Joey Rudd

PCOM Physician Assistant Studies Student Scholarship

Objective: The objective of this selective EBM review is to determine whether or not MDMA-assisted psychotherapy is an effective treatment for posttraumatic stress disorder (PTSD).

Study Design: Systematic review of three published, randomized controlled trials (double-blind, placebo-controlled) between 2008-2013.

Data Sources: All articles used were published in English, in peer-reviewed journals, and found using PubMed/MEDLINE and Cochrane Review databases.

Outcomes Measured: The primary outcome measure in all three studies was the severity of PTSD symptoms. The primary outcome measure was assessed using the Clinician-Administered PTSD Scale (CAPS) and the Severity of Symptoms Scale for PTSD (SSSPTSD). …

Social-Ecological Factors Affecting Patient Shield Use Among Radiologic And Computed Tomography Technologists, Megan Housenick-Lee

Electronic Theses and Dissertations

Medical radiation is estimated to contribute to over 200,000 deaths annually. Recent increases in the use of radiation-producing medical imaging examinations have led to increasing cumulative radiation dose to the general public. Multiple measures have been taken to address this alarming trend, including physician education, technologist education on dose reduction, and equipment-facilitated dose reduction techniques. Shield use can reduce the primary beam by up to 95%. Medical imaging technologists are the primary individuals responsible for applying shielding during an examination. Currently, literature shows that technologists are not shielding individuals as often as they should.

After pilot testing, medical imaging technologists …

Memory Potential, Molecular Characterization, And Translational Applications Of The Novel Theo/Tceo T Cell Phenotype, Todd Bartkowiak, Todd Bartkowiak

Dissertations and Theses (Open Access)

T cells comprise a substantial arm of the immune system and are exquisitely adapted to combat pathogens and tumors. The inflammatory environment largely dictates the nature of T cell response. A hallmark of T cell-mediated immunity is formation of immunological memory; the ability to respond more potently to re-encounter with pathogens. The immune system is also capable of recognizing tumors as foreign, much like viral or bacterial pathogens. Tumors have evolved, though, to generate an immunosuppressive environment to avoid destruction. The field of immunotherapy seeks to overcome immune suppression, in part by targeting T cell co-receptors on the cell surface …

Impact Of Kras/Nras Mutational Heterogeneity On Clinical Outcomes In Colorectal Cancer, Jonathan M. Loree

Dissertations and Theses (Open Access)

Introduction: Mutations in KRAS/NRAS (RAS) predict a lack of benefit from anti-EGFR agents in metastatic colorectal cancer (mCRC). As next generation sequencing (NGS) has advanced, we are discovering atypical and low allele frequency mutations. We aimed to evaluate how NGS can optimally define RAS mutant CRC and the role of relative mutant allele frequency (rMAF) as a biomarker.

Methods: Using institutional and public cohorts of mCRC patients with NGS results, we described the prevalence and clinical impact of atypical (not in current guidelines) and low rMAF RAS mutations (RAS MAF by the MAF of the mutated gene with …

Dynamic Assessment Of Nk Cell Interactions With Pediatric Tumor Cells To Predict Response To Immunotherapy, Arianexys Aquino Lopez

Dissertations and Theses (Open Access)

Due to Natural Killer (NK) cells’ capacity to target tumor cells without prior sensitization, adoptive NK cell therapy represents a promising immunotherapy approach for pediatric cancer patients. Our laboratory has developed an NK cell expansion protocol that generates large quantities of NK cells for therapeutic infusion. Given that NK cells are heterogeneous, with variable receptor expression and potential to target tumor cells, the purpose of my study was to determine whether subpopulations of NK cells with enhanced anti-tumor potential could be identified for increased potency of the NK cell infusion product. In addition, we previously showed that our expanded NK …