Medicine and Health Sciences Commons^™

Contribution Of Ectodomain Mutations In Epidermal Growth Factor Receptor To Signaling In Glioblastoma Multiforme, Marta L. Rojas

Dissertations & Theses (Open Access)

CONTRIBUTION OF ECTODOMAIN MUTATIONS IN EPIDERMAL GROWTH FACTOR RECEPTOR TO SIGNALING IN GLIOBLASTOMA MULTIFORME

Publication No._________

Marta Rojas, M.S.

Supervisory Professor: Oliver Bögler, Ph.D.

The Cancer Genome Atlas (TCGA) has conducted a comprehensive analysis of a large tumor cohort and has cataloged genetic alterations involving primary sequence variations and copy number aberrations of genes involved in key signaling pathways in glioblastoma (GBM). This dataset revealed missense ectodomain point mutations in epidermal growth factor receptor (EGFR), but the biological and clinical significance of these mutations is not well defined in the context of gliomas.

In our study, we focused on understanding …

Novel Amino Acid Transporter-Targeted Radiotracers For Breast Cancer Imaging, Fanlin Kong

Dissertations & Theses (Open Access)

Breast cancer is the most common malignancy among women in the world. Its 5-year survival rate ranges from 23.4% in patients with stage IV to 98% in stage I disease, highlighting the importance of early detection and diagnosis. ¹⁸F-2-Fluoro-2-deoxy-glucose (¹⁸F-FDG), using positron emission tomography (PET), is the most common functional imaging tool for breast cancer diagnosis currently. Unfortunately, ¹⁸F-FDG-PET has several limitations such as poorly differentiating tumor tissues from inflammatory and normal brain tissues. Therefore, ¹⁸F-labeled amino acid-based radiotracers have been reported as an alternative, which is based on the fact that tumor cells uptake …

Adaptive Intensity Modulated Radiation Therapy Planning Optimization With Changing Tumor Geometry And Biology Enforcing Both Cumulative And Fraction Size Dose Constraints, Behlul Saka

Graduate Theses and Dissertations

Intensity Modulated Radiation Therapy (IMRT) is a modern technique of delivering radiation treatments to cancer patients. In IMRT technology, intensities must be chosen for the many small unit grids into which the beams are divided to produce a desired distribution of dose at points throughout the body with the goal of maximizing dose delivered to the tumor while sparing healthy tissues from excessive radiation and keeping dose homogeneous across the tumor. Although IMRT plans are optimized as a single overall treatment plan, they are delivered over 30-50 treatment sessions (fractions) and both cumulative and per-fraction dose constraints apply. The extended …

Optimizing Heart Dose Reduction For Deep Inspiration Left Breast Radiotherapy, Ronald James Harder

UNLV Theses, Dissertations, Professional Papers, and Capstones

Multiple studies have shown that an increased risk of late injury cardiac abnormalities including congestive heart failure (CHF), ischemia, and coronary artery disease (CAD) can be associated with common left breast radiation therapy (RT) techniques. Many radiation therapy clinics have adopted the Deep Inspiration Breath Hold (DIBH) technique for the treatment of the left breast with external beam therapy based on studies showing a decrease in the dose received by the heart. A common technology used to monitor inhalation during DIBH is the Real-Time Position Management (RPM) system (Varian Medical Systems, Palo Alto, CA). This study analyzes if there is …

Strategies For Reducing The Impact Of Tumour Motion During Helical Tomotherapy, Bryan Kim

Electronic Thesis and Dissertation Repository

Tumour motion presents a significant limitation for effective radiotherapy of lung cancer, and more specifically for helical tomotherapy. The simultaneous and continuous movements of tomotherapy subsystems (gantry, couch, and binary multi-leaf collimator) can lead to inaccurate dose delivery, when combined with tumour motion. In this thesis, we have investigated the impact of tumour motion and strategies to reduce the resulting dose discrepancies for helical tomotherapy, through computer simulations and film measurements performed in a dynamic body phantom. Three distinctively different types of dose discrepancies have been isolated: dose rounding, dose rippling, and the intensity-modulated radiation therapy (IMRT) asynchronization effect. Each …

The Development And Implementation Of An Anthropomorphic Head Phantom For The Assessment Of Proton Therapy Treatment Procedures, Paige A. Summers

Dissertations & Theses (Open Access)

Proton therapy has become an increasingly more common method of radiation therapy, with the dose sparing to distal tissue making it an appealing option, particularly for treatment of brain tumors. This study sought to develop a head phantom for the Radiological Physics Center (RPC), the first to be used for credentialing of institutions wishing to participate in clinical trials involving brain tumor treatment of proton therapy. It was hypothesized that a head phantom could be created for the evaluation of proton therapy treatment procedures (treatment simulation, planning, and delivery) to assure agreement between the measured dose and calculated dose within …

The Role Of Acidic Fibroblast Growth Factor And Fibroblast Growth Factor Receptor 4 In High Grade Serous Carcinoma, Tarrik Zaid

Dissertations & Theses (Open Access)

Background: High grade serous carcinoma whether ovarian, tubal or primary peritoneal, continues to be the most lethal gynecologic malignancy in the USA. Although combination chemotherapy and aggressive surgical resection has improved survival in the past decade the majority of patients still succumb to chemo-resistant disease recurrence. It has recently been reported that amplification of 5q31-5q35.3 is associated with poor prognosis in patients with high grade serous ovarian carcinoma. Although the amplicon contains over 50 genes, it is notable for the presence of several members of the fibroblast growth factor signaling axis. In particular acidic fibroblast growth factor (FGF1) …

Role Of Prostaglandin E2 In The Regulation Of Pancreatic Stellate Cells Hyper Activity Associated With Pancreatic Cancer, Chantale Charo

Dissertations & Theses (Open Access)

Pancreatic cancer is one of the most lethal type of cancer due to its high metastasis rate and resistance to chemotherapy. Pancreatic fibrosis is a constant pathological feature of chronic pancreatitis and the hyperactive stroma associated with pancreatic cancer. Strong evidence supports an important role of cyclooxygenase-2 (COX-2) and COX-2 generated prostaglandin E2 (PGE2) during pancreatic fibrosis. Pancreatic stellate cells (PSC) are the predominant source of extracellular matrix production (ECM), thus being the key players in both diseases. Given this background, the primary objective is to delineate the role of PGE2 on human pancreatic stellate cells (PSC) hyper activation associated …

Tp53 As A Biomarker In Head And Neck Squamous Cell Carcinoma, Thomas J. Ow Md

Dissertations & Theses (Open Access)

Currently, there are no molecular biomarkers that guide treatment decisions for patients with head and neck squamous cell carcinoma (HNSCC). Several retrospective studies have evaluated TP53 in HNSCC, and results have suggested that specific mutations are associated with poor outcome. However, there exists heterogeneity among these studies in the site and stage of disease of the patients reviewed, the treatments rendered, and methods of evaluating TP53 mutation. Thus, it remains unclear as to which patients and in which clinical settings TP53 mutation is most useful in predicting treatment failure.

In the current study, we reviewed the records of a cohort …

Impact Of An Online Support System On Health Related Quality Of Life Among Men Diagnosed With Prostate Cancer, Daniel K. Osei

Loma Linda University Electronic Theses, Dissertations & Projects

Prostate cancer is a major public health issue worldwide and a significant cause of male cancer death in the USA. Though early screening and treatment has greatly enhanced the outcome, men diagnosed with prostate cancer face problems that compromise quality of life after treatment. Online support for prostate cancer clients is a convenient way to help because it is anonymous, inexpensive, and can be used at clients’ convenience. Yet few studies have explored how these supports impact these clients. This study used a longitudinal randomized experimental design to examine the impact of online services on quality of life of prostate …

A Comparison Of Spatio-Temporal Prediction Methods Of Cancer Incidence In The U.S, Michelle Hamlyn

UNLV Theses, Dissertations, Professional Papers, and Capstones

Cancer is the cause of one out of four deaths in the United States, and in 2009, researchers expected over 1.5 million new patients to be diagnosed with some form of cancer. People diagnosed with cancer, whether a common or rare type, need to undergo treatments, the amount and kind of which will depend on the severity of the cancer. So how do healthcare providers know how much funding is needed for treatment? What would better enable a pharmaceutical company to determine how much to allocate for research and development of drugs, the amount of each drug to manufacture, or …

Clinical Impact Of Couch Top And Rails On Imrt And Arc Therapy, Kiley B. Pulliam

Dissertations & Theses (Open Access)

Purpose: To evaluate the clinical impact of the Varian Exact Couch on dose and volume coverage to targets and critical structures and tumor control probability (TCP) for 6-MV IMRT and Arc Therapy.

Methods: Five clinical prostate patients were planned with both, 6-MV 8-field IMRT and 6-MV 2-field RapidArc using the Eclipse treatment planning system (TPS). These plans neglected treatment couch attenuation, as is standard clinical practice. Dose distributions were then recalculated in Eclipse with the inclusion of the Varian Exact Couch (imaging couch top) and the rails in varying configurations. The changes in dose and coverage were evaluated using the …

Metastatic Disease: Interactions Between Tumor Cells And Host Environment During Cancer Cell Spread, Jennifer M. Maclean

Electronic Thesis and Dissertation Repository

Tumor and metastasis formation are not cell autonomous phenomena, but rather an evolution of disease within and responding to the host environment. Metastatic spread from a primary tumor occurs as a result of a complex interplay between tumor cells and the host, wherein tumor cells must escape the primary tumor, enter the host vasculature, travel to and arrest in a distant tissue and survive and grow in that new organ. It is known that cells that progress through these stages must both escape and exploit host systems, yet the mechanisms used are not fully understood. Therefore, the goal of this …

Risk Of Second Malignant Neoplasms Following Proton Arc Therapy And Volumetric Modulated Arc Therapy For Prostate Cancer, Laura A. Rechner

Dissertations & Theses (Open Access)

The risk of second malignant neoplasms (SMNs) following prostate radiotherapy is a concern due to the large population of survivors and decreasing age at diagnosis. It is known that parallel-opposed beam proton therapy carries a lower risk than photon IMRT. However, a comparison of SMN risk following proton and photon arc therapies has not previously been reported. The purpose of this study was to predict the ratio of excess relative risk (RRR) of SMN incidence following proton arc therapy to that after volumetric modulated arc therapy (VMAT). Additionally, we investigated the impact of margin size and the effect …

Patient Characteristics And Outcomes Of Gastrointestinal Stromal Tumor Patients Undergoing Imatinib Plasma Level Testing, Laura Nolden

Dissertations & Theses (Open Access)

Although gastrointestinal stromal tumor (GIST) is effectively treated with imatinib, there are a number of clinical challenges in the optimal treatment of these patients. The plasma steady-state trough level of imatinib has been proposed to correlate with clinical outcome. Plasma imatinib level may be affected by a number of patient characteristics. Additionally, the ideal plasma trough concentration of imatinib is likely to vary based on the KIT genotype (genotype determines imatinib binding affinity) of the individual patient. Patients’ genotype or plasma imatinib level may influence the type and duration of response that is appreciable by clinical evaluation.

The objectives of …

The Association Between Cancer-Related-Fatigue, Response To Fatigue Treatment, And Cytokines And Their Receptors, In Patients With Advanced Cancer, Sriram Yennu

Dissertations & Theses (Open Access)

Background: Inflammation is implicated in the development of cancer related fatigue (CRF). However there is limited literature on the mediators of inflammation (namely), cytokines and their receptors, associated with clinically significant fatigue and response to treatment.

Methods: We reviewed 37 advanced cancer patients with fatigue (≥4/10), who participated in two Randomized Controlled Trials, of anti-inflammatory agents (Thalidomide and Dexamethasone) for CRF. Responders showed improvement in FACIT-F subscale at the end of study (Day 15). Baseline patient characteristics and symptoms were assessed by FACIT-F, ESAS; serum cytokines [IL-1β and receptor antagonist (IL-1RA), IL-6, IL-6R, TNF-α and sTNF-R1 and R2, IL-8, …

Modeling Mortality Rates For Leukemia Between Men And Women In The United States, Blessed Quansah

UNLV Theses, Dissertations, Professional Papers, and Capstones

Leukemia related deaths increased dramatically over the last forty years. Leukemia is a malignant disease or cancer of the bone marrow and blood. It is characterized by the uncontrolled accumulation of blood cells. Leukemia is divided into two categories: myelogenous or lymphocytic, each of which can be acute or chronic. The terms, myelogenous or lymphocytic denote the cell type involved.

In this thesis, the proposed modeling techniques are applied to leukemia deaths data from the Surveillance Epidemiology and End Results (SEER). In particular, annual deaths data from 1969 to 2007 are used in the data analysis, which includes three major …

From Isolated Tumour Cells To Overt Lymph Node Metastases: Biological And Imaging Studies On The Development Of Experimental Lymph Node Metastases, Michael M. Lizardo

Electronic Thesis and Dissertation Repository

Metastatic colonization and establishment of overt lymph node (LN) tumours indicates poor prognosis for cancer patients. However, the basic biology that influences the development of LN metastasis is poorly understood due to the lack of basic animal models. The following work provides a new lymph node experimental metastasis assay (LEMA) that permits the assessment of tumour cell fate after they arrest in draining LNs. In using this new model, we discovered that only 8% of the tumour cells that arrive in the LN are successful in forming overt tumours. This work also explored the use of imaging approaches to monitor …

Hedgehog Signaling: A Potential Therapeutic Target For Non-Small Cell Lung Cancer, Ma'in Yehya Maitah

Wayne State University Dissertations

The American Cancer Society estimated that 222,520 Americans were diagnosed with lung cancer and 157,300 died of lung cancer in 2010 (Jemal et al. 2009, 225-249;Jemal et al. 2011, 69-90). The clinical outcome of patients diagnosed with non-small cell lung cancer (NSCLC), the major lung cancer sub-types, is very poor, which calls for innovative research for finding novel therapeutic targets and agents for better treatment outcome.

Emerging evidences have suggested that a phenomenon called Epithelial-to-Mesenchymal Transition (EMT), which shares similar molecular characteristics with cancer stem-like cells, contributes to lung cancer treatment failure. In view of the fact that EMT process …

Dietary Interventions Against Mammary Glands And Prostate Cancers, Juliana Adedayo Akinsete

Theses, Dissertations and Capstones

Dietary components modulate normal cellular functions and, in cancer cells, alter processes that lead to cancer and/or its progression. The change in the patterns of human food production and consumption over time has contributed to increasing risk for diseases including cancer. Omega-3 and omega-6 fatty acids are classes of essential polyunsaturated fatty acids in the human diet and are required for normal growth and development. Omega-3 and omega-6 fats are thought to be required in the ratio of 1:1 to 1:4 on which humans are thought to have evolved. However, the Western diet has greatly shifted from this ratio. The …

Pitx2 Is Overexpressed In Follicular Cell-Derived Thyroid Cancer And Promotes Thyroid Cancer Proliferation By Regulating Cell Cycle, Yue Huang

Theses, Dissertations and Capstones

Thyroid cancer is the most prevailing malignancy of the endocrine system. Its incidence is rapidly rising at the second fastest rate of all malignancies in the United States, making it a significant health problem. Although the majority of thyroid cancer is slowly-growing and well-differentiated, available treatment options are very limited, and most of them require complete removal of the thyroid gland and surrounding tissues. Patients who have undergone thyroid removal have to take life-long hormone replacement therapy, which is very inconvenient and costly. Therefore, there is an urgent need to develop new treatments for this disease. As a prerequisite for …

Cancer Cachexia And Cardiac Atrophy In The Apcmin/+ Mice Model Of Colon Cancer, Nandini Durga Prasanna Kumar Manne

Theses, Dissertations and Capstones

Cancer cachexia is a muscle wasting condition that occurs in response to a malignant growth in the body. Cachexia is associated with heart failure and is estimated to be the immediate cause of death in about a third of all cancer patients. The purpose of this study was to investigate cardiac atrophy in the APCmin/+ mouse model of colorectal cancer. Compared to age matched C57BL/6 (BL6) mice, APCmin/+ body mass and heart mass were lower at 12 (11.1 Ѡ4.5% and 7.6 Ѡ2.8%, respectively) and 20-weeks (26.1 Ѡ2.5% and 6.0 Ѡ3.8%, respectively) of age (P < 0.05). Immunoblot analysis revealed that these changes in mass were accompanied by increased activation of protein kinase B (Akt Thr 473: 74.4 Ѡ10.9% and 216.0 Ѡ19.6% ; Akt Ser 308: 161.6 Ѡ31.7% and 367.4 Ѡ41.6% at 12- and 20-weeks, respectively, (P < 0.05)), mammalian target of rapamycin (mTOR Ser2448: 23.2 Ѡ13.2% and 44.0 Ѡ16.4% at 12- and 20-weeks, respectively, (P < 0.05)), 5' adenosine monophosphate-activated protein kinase (AMPK: 19.6 Ѡ5.2% and 22.5 Ѡ5.5% at 12- and 20-weeks, respectively, (P < 0.05)) and elevated levels of the autophagy regulator beclin1 (4.7 Ѡ3.3% and 9.5 Ѡ3.0% at 12- and 20-weeks, respectively, (P < 0.05)). No evidence of increased cardiac apoptosis, protein ubiquitination or activation of cardiac caspases or calpains was noted. Taken together, these data suggest that the cardiac atrophy that occurs in the 12- and 20-week old APCmin/+ mouse is relatively modest compared to that seen with other tumor models [1] and is associated with evidence of increased cardiac autophagy.

Does Venlafaxine (Effexor) Decrease The Frequency Of Hot Flashes In Women With Breast Cancer?, Allison Berneking

PCOM Physician Assistant Studies Student Scholarship

Objective: The objective of this systematic review is to determine whether or not “Does venlafaxine (Effexor) decrease the frequency of hot flashes in women with breast cancer?”

Does Dietary Intervention Have An Effect On The Progression And Ultimately The Treatment Of Prostate Cancer?, Jenna M. Lombardi

PCOM Physician Assistant Studies Student Scholarship

OBJECTIVE: The objective of this systematic review is to determine whether or not dietary intervention has an effect on the progression and ultimately the treatment of Prostate cancer.

Is Acupuncture Effective In Reducing Nausea And Vomiting In Patients Undergoing Chemotherapy?, Kara Meekins

PCOM Physician Assistant Studies Student Scholarship

OBJECTIVE- The objective of this systematic review is to determine whether or not acupuncture effective in reducing nausea and vomiting in patients undergoing chemotherapy.

Is Lenalidomide, In Combination With Dexamethasone, A Safe And Effective Treatment For Relapsed Multiple Myeloma?, Sarah Moncado

PCOM Physician Assistant Studies Student Scholarship

OBJECTIVE: The objective of this systematic review is to determine whether or not lenalidomide, in combination with dexamethasone, is a safe and effective treatment for relapsed multiple myeloma.

Spirituality And Depression In Parents With Children In Oncology Or Hematology Treatment, Kurt D. Soell

Walden Dissertations and Doctoral Studies

The psychological burden of cancer treatment affects not only child patients but also their parents. There is extensive literature on the positive influence of spirituality on the cancer patient. But there is a gap in the literature on the potential healing influence of spirituality on the parent of the cancer or hematology patient. The purpose of this study was to examine the relationship between spirituality and parents' levels of depression and anxiety during their child's hematological or oncology treatment. Using the transtheoretical model of change, a purposive sample of 48 parents of children undergoing cancer or hematology treatment completed a …

Differences In Breast Cancer Tumor Size, Stage, And Survival By Socioeconomic Position In Young Women, Julie Maureen Tomaska

Walden Dissertations and Doctoral Studies

Although the incidence of breast cancer in women under 40 years of age is somewhat rare, young women tend to present with cancer that is more advanced and with poorer prognostic characteristics. This research will be important to providers, women and their families and those seeking to clarify screening guidelines. The purpose of this quantitative, retrospective, cohort study was to evaluate differences in prognostic characteristics by socioeconomic position (SIP). The cohort was comprised of females aged 18 to 39 with a primary diagnosis of breast cancer. Data were obtained from the Surveillance, Epidemiology and End Results registry for all primary …

Case-Control Study Of Sunlight Exposure And Cutaneous Human Papillomavirus Seroreactivity In Basal Cell And Squamous Cell Carcinomas Of The Skin, Michelle R. Iannacone

USF Tampa Graduate Theses and Dissertations

Non-melanoma skin cancer (NMSC), comprised of basal cell carcinoma (BCC) and squamous cell carcinoma (SCC), is the most common cancer in Caucasians. Ultraviolet radiation (UVR) exposure is the most important environmental risk factor for both BCC and SCC development. However, the precise relationship between UVR and the risk of NMSC is complex, and the relationship may differ by skin cancer type. It has been hypothesized that intermittent patterns and childhood sunlight exposure are important for BCC while continuous (chronic) and lifelong (i.e. childhood and adulthood) sunlight exposure is important for SCC. Epidemiologic studies have demonstrated that cutaneous human papillomavirus (HPV) …

The Mediating Role Of Social Support And Fulfillment Of Spiritual Needs In End Of Life Care, Kimberley A. Gryglewicz

USF Tampa Graduate Theses and Dissertations

End of life (EOL) caregiving can be a daunting and challenging endeavor as caregivers adjust to the ever-changing care demands associated with dying. Increased personal care, assisting with symptom and medication management, and attending to the emotional and spiritual needs of the dying person require caregivers to learn new tasks and to assume new roles such as social worker, nurse, and chaplain. As families continue to play an essential role in meeting the health care needs of their dying loved ones, it is imperative for social workers to understand the complexities of the end of life caregiving experience in order …