Medicine and Health Sciences Commons^™

Design And Development Of A Novel Class Of Cell Cycle Cdk Inhibitors Targeting The Cyclin Binding Groove Utilizing The Replace Strategy, Padmavathy Nandha Premnath

Theses and Dissertations

Inhibition of CDK2 activity in G1 and S phases of the cell cycle can promote selective apoptosis of cancer cells through the E2F1 pathway. Currently available CDK inhibitors target the ATP binding pocket and result in lack of specificity for the cell cycle vs. the transcriptional CDKs. It has been shown that a peptide HAKRRLIF derived from the tumor suppressor p21 binds to the cyclin binding groove (CBG) and selectively inhibits cell cycle CDKs (CDK2/Cyclin A, CDK2/Cyclin E and CDK4/Cyclin D). The CBG is unique to cell cycle CDKs hence targeting this site avoids the inhibition of transcriptional CDKs can …

Novel Insights Into The Role Of The Smoothened Cysteine Rich Domain In Hedgehog Signalling, Rajashree Rana

Theses and Dissertations (ETD)

The Hedgehog (Hh) signal transduction pathway functions as one of the key developmental pathways and deranged Hh signalling is associated with numerous cancer and tumor conditions. The Smoothened (Smo) G protein coupled receptor (GPCR) functions as the signal transducer of the Hh pathway and is the most attractive drug target of the pathway. The structure of the Smo receptor includes seven membrane spanning domains, extracellular and intracellular loops connecting the membranous domains and the extracellular cysteine rich domain (CRD). The extracellular CRD of the Smo receptor is homologous to the Frizzled (FzD) CRD. The FzD CRD interacts with the physiological …

Identification Of Cell Signaling Pathway Regulated By Micrornas In Cancer Cells Using A Systems Biological Approach, Sangbae Kim

Dissertations & Theses (Open Access)

MicroRNAs (miRNAs) are single-stranded, non-coding RNA molecules that regulate gene expression via imperfect binding of the miRNA to specific sites in the 3' untranslated region of the mRNAs. Because prediction of miRNA targets is an essential step for understanding the functional roles of miRNAs, many computational approaches have been developed to identify miRNA targets. However, identifying targets remains challenging due to the inherent limitation of current prediction approaches based on imperfect complementarity between miRNA and its target mRNAs. To overcome these current limitations, we developed a novel correlation-based approach that is sequence independence to predict functional targets of miRNAs by …

Lung Cancer Survival Disparities In Nevada, Chima Osuoha

UNLV Theses, Dissertations, Professional Papers, and Capstones

Lung cancer is the leading cause of cancer death in both men and women in the United States. Nevada shows moderate incidence rates of lung cancer for men but high rates for women. Little is known about the lung cancer experience and survival characteristics of the nearly 2000 new cases occurring every year in the State. The purpose of this study was to measure the extent to which geographic area of residency, gender, race, health insurance, social economic status (SES) and stage at diagnosis were associated with survival in patients diagnosed with lung cancer in Nevada. This was a retrospective …

Effect Of Chemotherapeutic Treatment Schedule On A Tissue Transport Model, Dan E. Ganz

Masters Theses

Current chemotherapeutic treatment schedule prediction methods rely heavily on PK/PD-based models and overlook the important contribution of tissue-level transport and binding. Tissue-level transport and binding phenomena are essential to understanding drug delivery and efficacy in tumors. Drugs with desirable PK/PD properties often fail in vivo due to poor tissue-level transport. We developed an in silico method to predict the effect of treatment schedule on efficacy that couples PK/PD with tissue-level transport. Treatment schedules were implemented on theoretical drugs with different PK/PD and transport properties. For each drug with a given clearance rate, diffusivity, and binding, treatment schedules consisting of one …

Role Of Chronic Inflammation On Liver Function During Cachexia Progression In The ApcMin/+ Mouse Model, Aditi Narsale

Theses and Dissertations

Cachexia is a multifactorial syndrome that manifests during the advanced stage of chronic diseases and is characterized by a progressive loss of body mass sustained by underlying inflammation. The ApcMin/+ mouse is an established model of cachexia that exhibits a gradual loss of body mass correlating with increasing tumor burden and plasma IL – 6 levels. Moreover it also mimics other secondary characteristics observed in cachectic patients like splenomegaly, elevated plasma endotoxin levels, gut barrier dysfunction, hypogonadism and an overall hypermetabolic state. Liver controls the energy metabolism in the body by regulating glucose and lipid metabolism, glycogen storage, filtration of …

Discovery And Elucidation Of The Fgfr3-Tacc3 Recurrent Fusion In Glioblastoma, Brittany C. Parker Kerrigan

Dissertations & Theses (Open Access)

Fusion genes occur due to chromosomal instability where two previously separate genes rearrange and fuse together, forming a hybrid gene. The first fusions were reported in leukemias; however, with the advent of more powerful sequencing technologies, fusions have recently been reported in several solid tumors. Using next-generation deep sequencing approaches, we discovered a fusion gene connecting the fibroblast growth factor receptor 3 (FGFR3) gene to the transforming coiled-coil containing protein 3 (TACC3) gene in glioblastoma multiforme. The fusion occurred in 8.3% of patient samples, but not in low grade or normal samples. FGFR3-TACC3 produced an in-frame …

Women's Stories Of Breast Cancer: Sharing Information Through Youtube Video Blogs, Jenna Kressler

Electronic Thesis and Dissertation Repository

Breast cancer is one of the most prevalent chronic diseases among North American women. Individuals need accessible and reliable health information for self-care and self-health promotion. Increasingly, individuals are contributing to and accessing information about cancer, using interactive online resources such as YouTube. The purpose of this research was to investigate the personal YouTube video blogs of women with breast cancer and their portrayed messages. This study used a narrative inquiry to examine the video blogs of four women with breast cancer. The women talked about having cancer as a transformative experience. Information about breast cancer from healthcare providers was …

Individual, Disease, And Work-Related Factors Associated With Work Patterns, Presenteeism And Sick Pay Policy Of The Colorectal Cancer Survivor After Treatment, Kristin A. Roper

Graduate Doctoral Dissertations

Participation of colorectal cancer survivors (CRC) in the workforce has been described by clinicians, survivors, and researchers as a way to improve mood, quality of life (QOL), and survival. Maintaining self-esteem and financial independence have also been attributed to continued employment of the CRC survivor. The purpose of this cross-sectional survey was to describe patterns of employment of the CRC survivor and to examine the individual, disease, and work-related factors that influence presenteeism and perceived adequacy of sick pay (ASP) policy. The Conceptual Model of Nursing and Health Policy and the Pathways to Work Life Recovery guided the design, selection …

The Role Of Lipocalin 2 In Early Stage Colon Cancer Metastasis To The Liver, Fides Elamparo

Senior Theses

Metastasis, frequently from the colon to the liver, is the major cause of death with colorectal cancer, reducing the five-year survival to less than 6%. Metastasis occurs due to productive collaborations between tumor cells and host-derived cells in the tumor microenvironment, where a pre-metastatic niche is created to prime for cancer cell invasion into the target organ. In a highly metastatic colorectal cancer cell line implanted into the cecum of Balb/c mice, microarray analysis showed lipocalin 2 (Lcn2) is one of the most highly expressed proteins in the liver of tumor-bearing mice prior to metastasis.

When RT-PCR was performed, greater …

Health Literacy And Cancer Prevention: A Qualitative Exploration Of The Health Communication Needs Of Hispanics Residing In Northeast Texas, Jessica R. Hyde

Health and Kinesiology Theses

Introduction: Limited health literacy can impede adherence to cancer screening guidelines. This problem transcends sociocultural boundaries; however, Hispanics are more likely to have limited health literacy than other racial/ethnic groups in the U.S. The purpose of this study is to explore health literacy at a conceptual level in Hispanic adults residing in Northeast Texas in order to better understand this population's communication needs related to cancer prevention. Methods: Focus group methodology and the Spanish-language version of the Newest Vital Sign (NVS-S) were used to gather data. Results: Of the 18 individuals who sat for the NVS-S, 6 were classified as …

The Effect Of Patient Education On Anxiety Levels In Patients Receiving Chemotherapy For The First Time, Sarah Garcia

Evidence-Based Practice Project Reports

Cancer affects approximately 1.5 million people every year throughout the United States.Comprehensive care that includes psychosocial aspects is important to help patients effectively adapt to their diagnosis and treatment plan. Improper prevention and management of anxiety can lead to poor psychosocial outcomes, dissatisfaction with care, and decreased adherence to treatment. Current evidence suggests that education is effective at helping reduce anxiety in patients receiving chemotherapy for the first time. The purpose of this evidenced based practice project was to determine if nurse-led patient education regarding chemotherapy side effects, side-effect management, and orientation to the infusion center was effective at decreasing …

Cancer Diagnosis During Pregnancy: Evaluating The Challenges Faced By Oncologists, Shannon Kaye Mulligan

Dissertations & Theses (Open Access)

Cancer during pregnancy is occurring more often than in the past, and it is estimated that cancer is diagnosed in approximately 1/1000 pregnancies. A consensus exists that management of these patients should prioritize survival of the mother and minimize teratogenic effects to the fetus, and utilize a multidisciplinary approach, involving medical oncology, surgical oncology, radiation oncology, radiology, and a maternal fetal medicine specialist. In spite of this consensus, there is not a standardized approach for treating cancer in women diagnosed during pregnancy. Due to the relative infrequency of this situation in the oncologic setting, the aims of this study were …

Comprehensive Cancer Care: An Outpatient Treatment Facility, Braden Abrams Reid

All Theses

A cancer diagnosis can result in a loss of decision-making and control for patients. The majority of clinical treatments fail to adequately address corollary symptoms and needs that arise both from treatment and from the disease itself. Thus, the architectural problem identified in this thesis inquiry is how can an outpatient cancer centre treat the whole patient comprehensively, while at the same time instilling control and re-empowering the patient? This thesis project proposes a patient-centered environment designed to support the myriad and nuanced needs of the cancer patient, as well as a site-specific proposal for a comprehensive outpatient cancer treatment …

Indoleamine 2,3-Dioxygenase Confers Resistance To Chemotherapy And Γ Radiation To Cancer Cells, Independent Of Direct Immune Involvement, Saman Maleki Vareki

Electronic Thesis and Dissertation Repository

Indoleamine 2,3-dioxygenase-1 (IDO) is an immunosuppressive molecule expressed by most human tumours. IDO levels correlate with poor prognosis in cancer patients and IDO inhibitors are under investigation to enhance endogenous anticancer immunosurveillance. Little is known regarding the immune-independent functions of IDO relevant to cancer therapy. In this thesis I show, for the first time, that IDO mediates human tumour cell resistance, in a cell-autonomous fashion, to single and combination treatment with a diverse group of chemotherapy drugs and g radiation. These drugs include a PARP inhibitor (olaparib), a DNA cross-linking agent (cisplatin), a folate antimetabolite (pemetrexed), a nucleoside analogue (gemcitabine), …

Patient Navigator's Role Definition, Joann Smith

Nursing Theses and Capstone Projects

Patient navigation as a care coordination model continues to evolve. Early programs focused on access to care for the underserved and uninsured. With no standard credentials, title, training or job descriptions, navigator programs are as varied as the people who perform these duties. The nurse navigator provides a holistic approach to care delivery and focuses on care coordination, education, and physical, social and emotional aspects of care. Workload for the navigators is increasing as a result of patient, facility, departmental, and national accreditation demands. The goal of this capstone project was to redefine the job descriptions of the Oncology Nurse …

Mechanoregulation Of Leading Edge Pka Activity During Ovarian Cancer Cell Migration, Andrew J. Mckenzie

Graduate College Dissertations and Theses

Ovarian cancer is the deadliest of all the gynecologic cancers and is known for its clinically occult and asymptomatic dissemination. Most ovarian malignancies are diagnosed in the late stages of the disease and the high rate of morbidity is thought to be due, in part, to the highly metastatic nature of ovarian carcinomas. Cancer metastasis relies on the ability of cells to migrate away from primary tumors and invade into target tissues. Though the processes are distinct, cancer cell invasion relies on the underlying migration machinery to invade target tissues.

Cell migration requires the coordinated effort of numerous spatially-regulated signaling …

Identification And Characterization Of Downstream Effector Protein(S) Regulated By P53 And Prb, Miranda B. Carper

Theses, Dissertations and Capstones

A commonality among cancer types is the high frequency of mutations that inhibit or alter signaling of the p53 and pRb (Retinoblastoma) tumor suppressors. These genes regulate processes vital for cancer suppression such as apoptosis, senescence, and cell cycle arrest among others. Loss of both p53 and pRb promotes processes that support cancer progression and is associated with decreased patient survival and increased rates of tumor reoccurrence. Although data points to the ability of p53 and pRb to collaborate and to inhibit tumorigenesis, it remains unclear how p53 and pRb cooperate toward this task. Using RNA expression profiling, 179 p53 …

Is Massage Therapy An Effective Treatment For Improving Sleep Quality In Women Age 50-80 Diagnosed With Cancer?, Alexander M. Chase

PCOM Physician Assistant Studies Student Scholarship

OBJECTIVE: The objective of this selective EBM review is to determine whether or not massage therapy is an effective treatment in improving sleep quality among women age 50-80 diagnosed with cancer.

STUDY DESIGN: Review of two English language randomized control trials published in 2004 and 2011 and one English language quasiexperimental pretest-posttest comparison study publishEd in 2002.

DATA SOURCES: Data sources were articles published in peer reviewed journals found using PubMed and EBSCOhost.

OUTCOMES MEASURED: Sleep quality was measured using the Verran and Snyder-Halpem Sleep Scale and the Richards-Campbell Sleep Questionnaire.

RESULTS: Soden et al …

Stress Management For Cancer Survivors Using A Technologically Adapted Psychosocial Intervention: A Randomized Trial Determining The Effect Of Expressive Writing On Psychoneuroimmunology Based Outcomes, Utkarsh B. Subnis

Theses and Dissertations

Patients with cancer transitioning from completing their final cancer treatments to survivorship are particularly at risk for experiencing psychosocial stress, and the Institute of Medicine (IOM) has referred to these cancer patients as “lost in transition.” In this study, patients with cancer in their transition phase after completing their final radiation treatment were defined as cancer survivors (CS). CS must deal with chronic stressors such as the fear of cancer recurrence as well as the resumption of their roles in their family and work lives. Chronic stress impacts the nervous system and increases secretion of stress hormones (e.g. cortisol) from …

Role Of Physical Exercise In Reducing Depression And Improving Mental Health In Cancer Survivors, Gregory Levin

Theses: Doctorates and Masters

Cancer survivors are more than twice as likely as the general population to suffer the debilitating effects of depression. This comorbid condition is associated with several negative consequences, such as reduction in compliance with cancer treatments, and hastened mortality. Recent research has examined the therapeutic effect of exercise on depression and reported excellent results of similar magnitude to those achieved with pharmacotherapy or psychological intervention. However, no research, to date, has examined the effectiveness of exercise on reducing depression in depressed cancer survivors. In order to address this important question this thesis reviewed previous literature in the area of cancer …

Molecular Studies On The Anti-Tumor Effects Of Metal-Based Complexes: Involvement Of The Ubiquitin-Proteasome And Apoptotic Pathways, Sara M. Schmitt

Wayne State University Dissertations

The ubiquitin-proteasome pathway is crucial to normal cellular function, and as such, has been extensively investigated as a potential target for cancer therapeutics. Many compounds have been tested for their proteasome inhibitory ability, including various small peptide aldehydes, and, following the success of cisplatin, several metal-containing complexes. The efficacy of these compounds in preclinical studies ultimately resulted in the development and approval of the first-in-class proteasome inhibitor bortezomib, the use of which, unfortunately, has been hindered by toxicity and resistance. These limitations have led to a massive push toward designing and developing new, less toxic proteasome inhibitors for clinical use. …

Initiation And Completion Of Adjuvant Chemotherapy Among Colorectal Cancer Patients, Ashar Ata

Legacy Theses & Dissertations (2009 - 2024)

Introduction: For regionally advanced colorectal cancers resection followed by adjuvant chemotherapy (ACT) is the recommended treatment. Despite consensus on benefits, studies have shown that a significant proportion of patients do not initiate it. Among those who initiate the survival benefits of chemotherapy cannot be fully realized without completed treatment. Without supplementing treatment information from insurance claims cancer registries are inadequate for assessment of ACT utilization. This study was aimed at measuring the initiation and completion of ACT among colorectal cancer patients and identifying the associated factors.

Role Of Micro Rna 148/152 Family In Cancer Progression, Anusha Chaparala

Theses and Dissertations

Micro RNA are small single stranded RNA that regulate the expression of various genes. MiRNA guide the mRNA disintegrating RISC complex to the complimentary sequence in the target mRNA. Each micro RNA has multiple targets and can play a different biological role depending on the population of targets at the particular stage of the cell or a physiological state. Several miRNA show elevated or decreased levels of expression in various cancers because of their role in tumor initiation and progression. MiRNA belonging to mir148/152 family are examples of such MicroRNA. This family includes miR148a, miR148b and miR152. MiR148a and miR152 …

The Expression And Function Of Icam-2 In Neuroblastoma, Joseph Feduska

All ETDs from UAB

Neuroblastoma (NB) is the most common extracranial solid tumor in childhood, accounting for 15% of all childhood cancer deaths. At the time of initial diagnosis, the majority of patients present with NB that has already metastasized. While initial remission is often achieved following treatment, roughly 50% of these patients will relapse and die from the development of intractable metastatic progression. Intercellular adhesion molecule-2 (ICAM-2) is a transmembrane glycoprotein, normally expressed only in endothelial cells and subsets of leukocytes. ICAM-2 expression in cancer cells had not been previously investigated, until our lab recently reported the novel finding of endogenous ICAM-2 expression …