Matching Items (24)

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Avastin: Roche Pharmaceutical's Cancer Treatment & The United States Healthcare System

Description

This paper seeks to put a spotlight on much that is wrong in the United States with cancer drug development, pricing, marketing and outcomes. Roche Pharmaceutical's cancer drug, Avastin will

This paper seeks to put a spotlight on much that is wrong in the United States with cancer drug development, pricing, marketing and outcomes. Roche Pharmaceutical's cancer drug, Avastin will be used as an example to highlight these issues. Drug patents, Medicare policies, weak metrics of efficacy and ceaseless demand—allow drug manufacturers to price their oncology treatments as they choose, regardless of results, and with virtually no competition, avenue or institution that serves to lower prices in the United States. Avastin will be established as an oncology drug that is overpriced and poorly evaluated based on its effectiveness. Facts, opinions and study analytics will be offered (from industry experts, insiders, doctors and scientists) that in almost all cases show that patients treated with Avastin receive marginal benefit. Allowing Medicare to negotiate drug prices with manufacturers, reducing conflicts of interest for doctors, setting research & development investment requirements and creating more relevant clinical metrics for use in FDA approvals would help reduce the financial burden on cancer patients and taxpayers.

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Date Created
  • 2017-05

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The Reconceptualization of Palliative Care in Oncology Nursing: A Meta-Synthesis

Description

Often equated with hospice or end-of-life care, palliative care is the expansion of traditional disease-model medical treatments to include the goals of enhancing quality of life, facilitating patient autonomy, and

Often equated with hospice or end-of-life care, palliative care is the expansion of traditional disease-model medical treatments to include the goals of enhancing quality of life, facilitating patient autonomy, and addressing physical or emotional suffering. This interdisciplinary model is essential throughout the cancer continuum and offers the best patient outcomes when initiated at the time of diagnosis. While extensive research exists on the purpose and benefits of palliative care, substantial barriers to early and effective implementation remain. This study aims to examine and integrate current research literature on oncology nurses' perceptions of palliative care, including comparison to evidence-based preferred practice. Synthesis of qualitative findings offers transformative reconceptualization aimed to inform nursing education and improve patient care.

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Date Created
  • 2016-05

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A Retrospective Investigation to Assess the Potential Application of Predictive Machine Learning Algorithms in Oncology Clinical Trials

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The purpose of this investigation is to apply a machine learning algorithm with de-identified, historic oncology clinical trial data to assess the theoretical understanding of predictive modeling to derive potential

The purpose of this investigation is to apply a machine learning algorithm with de-identified, historic oncology clinical trial data to assess the theoretical understanding of predictive modeling to derive potential clinical practice recommendations. Within this study, electronic medical records from the HonorHealth Virginia G. Piper Institute will undergo data visualization to identify potential correlations and trends critical for model creation as well as further identify potential expansions or limitations of scope regarding model purpose. Hypothesis pursued post data visualization was the development of a predictive model for 6-month survival. Current standard is estimated physician accuracy at 56.5% accuracy at 6 months out. This study created supervised learning models using decision trees, KNN, SVM and Ensemble methods using combinations of LASSO Logistic Regression and Know-GRFF Random Forest for feature selection. SVM trained on a combined set of LASSO and Know-GRRF featured produced the highest performing model at 75.5% with an AUC of 0.82. This study demonstrates the potential for applying predictive modeling on readily available EMR records to drive clinical practice recommendations. The models developed could potentially, with further development, be used as an ancillary tool for jumpstarting patient-physician conversations on survival and life expectancy.

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Date Created
  • 2019-05

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Current Trends in the Use of Complementary Medicine in Oncology

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This paper focuses on the current use of complementary medicine in Oncology. First, it reviews the general trends in the rise of complementary therapies in the United States and look

This paper focuses on the current use of complementary medicine in Oncology. First, it reviews the general trends in the rise of complementary therapies in the United States and look at the organizations responsible for the advancement of research. Next reviewed is the specific use of complementary medicine in cancer prevention, during treatment, and post-treatment therapy for increased quality of life. There are many modalities used in the management of this disease including yoga, tai chi chuan, botanicals, probiotics and meditation practices. Each of these therapies has their own unique benefits and are used at different stages of disease prevention and treatment.

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Date Created
  • 2013-05

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Evaluating and controlling glioblastoma infiltration

Description

Glioblastoma (GBM) is the most common primary brain tumor with an incidence of approximately 11,000 Americans. Despite decades of research, average survival for GBM patients is a modest 15 months.

Glioblastoma (GBM) is the most common primary brain tumor with an incidence of approximately 11,000 Americans. Despite decades of research, average survival for GBM patients is a modest 15 months. Increasing the extent of GBM resection increases patient survival. However, extending neurosurgical margins also threatens the removal of eloquent brain. For this reason, the infiltrative nature of GBM is an obstacle to its complete resection. We hypothesize that targeting genes and proteins that regulate GBM motility, and developing techniques that safely enhance extent of surgical resection, will improve GBM patient survival by decreasing infiltration into eloquent brain regions and enhancing tumor cytoreduction during surgery. Chapter 2 of this dissertation describes a gene and protein we identified; aquaporin-1 (aqp1) that enhances infiltration of GBM. In chapter 3, we describe a method for enhancing the diagnostic yield of GBM patient biopsies which will assist in identifying future molecular targets for GBM therapies. In chapter 4 we develop an intraoperative optical imaging technique that will assist identifying GBM and its infiltrative margins during surgical resection. The topic of this dissertation aims to target glioblastoma infiltration from molecular and cellular biology and neurosurgical disciplines. In the introduction we; 1. Provide a background of GBM and current therapies. 2. Discuss a protein we found that decreases GBM survival. 3. Describe an imaging modality we utilized for improving the quality of accrued patient GBM samples. 4. We provide an overview of intraoperative contrast agents available for neurosurgical resection of GBM, and discuss a new agent we studied for intraoperative visualization of GBM.

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Date Created
  • 2014

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Fabrication and Characterization of Panobinostat Loaded PLA-PEG Nanoparticles

Description

Medulloblastoma is the most common malignant pediatric brain cancer and is classified into four different subgroups based on genetic profiling: sonic hedgehog (SHH), WNT, Group 3 and 4. Changes in

Medulloblastoma is the most common malignant pediatric brain cancer and is classified into four different subgroups based on genetic profiling: sonic hedgehog (SHH), WNT, Group 3 and 4. Changes in gene expression often alter the progression and development of cancers. One way to control gene expression is through the acetylation and deacetylation of histones. More specifically in medulloblastoma SHH and Group 3, there is an increased deacetylation, and histone deacetylase inhibitors (HDACi) can be used to target this change. Not only can HDACi target increases in deacetylation, they are also known to induce cell cycle arrest and apoptosis. The combination of these factors has made HDACi a promising cancer therapeutic. Panobinostat, a hydrophobic, small molecule HDACi was recently identified as a potent molecule of interest for the treatment of medulloblastoma. Furthermore, panobinostat has already been FDA approved for treatment in multiple myeloma and is being explored in clinical trials against various solid tumors. The laboratory is interested in developing strategies to encapsulate panobinostat within nanoparticles composed of the biodegradable and biocompatible polymer poly(lactic acid)-poly(ethylene glycol) (PLA-PEG). Nanoparticles are formed by single emulsion, a process in which hydrophobic drugs can be trapped within the hydrophobic nanoparticle core. The goal was to determine if the molecular weight of the hydrophobic portion of the polymer, PLA, has an impact on loading of panobinostat in PLA-PEG nanoparticles. Nanoparticles formulated with PLA of varying molecular weight were characterized for loading, size, zeta potential, controlled release, and in vivo tolerability. The results of this work demonstrate that panobinostat loaded nanoparticles are optimally formulated with a 20:5kDa PLA-PEG, enabling loading of ~3.2 % w/w panobinostat within nanoparticles possessing an average diameter of 102 nm and surface charge of -8.04 mV. Panobinostat was released from nanoparticles in a potentially biphasic fashion over 72 hours. Nanoparticles were well tolerated by intrathecal injection, although a cell culture assay suggesting reduced bioactivity of encapsulated drug warrants further study. These experiments demonstrate that the molecular weight of PLA influences loading of panobinostat into PLA-PEG nanoparticles and provide basic characterization of nanoparticle properties to enable future in vivo evaluation.

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Date Created
  • 2019

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Characterization of the Role of Necroptosis for Oncolytic Vaccinia Efficacy

Description

Since the molecular biology revolution in the 1980s, ease of gene editing had led to the resurgence of Oncolytic Virotherapy. Countless viruses have been engineered yet only three are approved

Since the molecular biology revolution in the 1980s, ease of gene editing had led to the resurgence of Oncolytic Virotherapy. Countless viruses have been engineered yet only three are approved for clinical use worldwide, with only one being approved by the U.S Food and Drug Administration (FDA). Vaccinia virus (VACV) has a large genome, contains many immune evasion genes and has been thoroughly studied, making it a popular candidate for an oncolytic platform. VACV mutants with deletions in the E3 immune evasion protein have been shown to have oncolytic efficacy but the mechanism of tumor selectivity has not been fully elucidated. These mutants have been shown to be regulated by the necroptosis pathway, a pathway that has been shown to be deficient in certain cancers. Using a pan-cancer screening method that combines dye exclusion assays, western blot analysis, and viral growth curve, the role of necroptosis in regulating VACV replication and oncolytic efficacy in cancer was further characterized. Results demonstrate a preliminary correlation between necroptosis, viral replication, and oncolytic efficacy. This correlation is clearest in breast cancer and melanomas yet may apply to other cancer subgroups. This data was also used to guide the development of a receptor-interacting protein kinase 3 (RIP3) matched pair mouse model in the E0771 mouse breast cancer line which can be used to further study the role of necroptosis and oncolytic efficacy in vivo. Understanding the contribution necroptosis plays in oncolytic efficacy can guide to design enhance the design of clinical trials to test VACV E3L mutants and may lead to better efficacy in humans and an improvement in clinical oncology.

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Date Created
  • 2020

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Pathogenic peptides to enhance treatment of glioblastoma: evaluation of RVG-29 from rabies virus and chlorotoxin from scorpion venom

Description

Glioblastoma (GBM) is a highly invasive and deadly late stage tumor that develops from abnormal astrocytes in the brain. With few improvements in treatment over many decades, median patient survival

Glioblastoma (GBM) is a highly invasive and deadly late stage tumor that develops from abnormal astrocytes in the brain. With few improvements in treatment over many decades, median patient survival is only 15 months and the 5-year survival rate hovers at 6%. Numerous challenges are encountered in the development of treatments for GBM. The blood-brain barrier (BBB) serves as a primary obstacle due to its innate ability to prevent unwanted molecules, such as most chemotherapeutics, from entering the brain tissue and reaching malignant cells. The GBM cells themselves serve as a second obstacle, having a high level of genetic and phenotypic heterogeneity. This characteristic improves the probability of a population of cells to have resistance to treatment, which ensures the survival of the tumor. Here, the development and testing of two different modes of therapy for treating GBM is described. These therapeutics were enhanced by pathogenic peptides known to improve entry into brain tissue or to bind GBM cells to overcome the BBB and/or tumor cell heterogeneity. The first therapeutic utilizes a small peptide, RVG-29, derived from the rabies virus glycoprotein to improve brain-specific delivery of nanoparticles encapsulated with a small molecule payload. RVG-29-targeted nanoparticles were observed to reach the brain of healthy mice in higher concentrations 2 hours following intravenous injection compared to control particles. However, targeted camptothecin-loaded nanoparticles were not capable of producing significant treatment benefits compared to non-targeted particles in an orthotopic mouse model of GBM. Peptide degradation following injection was shown to be a likely cause for reduced treatment benefit. The second therapeutic utilizes chlorotoxin, a non-toxic 36-amino acid peptide found in the venom of the deathstalker scorpion, expressed as a fusion to antibody fragments to enhance T cell recognition and killing of GBM. This candidate biologic, known as anti-CD3/chlorotoxin (ACDClx) is expressed as an insoluble protein in Nicotiana benthamiana and Escherichia coli and must be purified in denaturing and reducing conditions prior to being refolded. ACDClx was shown to selectively activate T cells only in the presence of GBM cells, providing evidence that further preclinical development of ACDClx as a GBM immunotherapy is warranted.

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Date Created
  • 2019

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Necroptosis: Role in Poxvirus Pathogenesis and Oncolytic Virotherapy

Description

Necroptosis is a pro-inflammatory mechanism of programmed cell death. It has been implicated in many diseases such as inflammatory diseases, neurodegenerative diseases, cancer and during viral infections. The focus of

Necroptosis is a pro-inflammatory mechanism of programmed cell death. It has been implicated in many diseases such as inflammatory diseases, neurodegenerative diseases, cancer and during viral infections. The focus of this research work was to establish the relationship between poxvirus pathogenesis and necroptosis, and the translation implications of necroptosis in oncolytic virotherapy. Vaccinia virus (VACV) is the currently used vaccine for smallpox and it has also been developed as a vaccine vector for several pathogens. E3L is one of the key innate immune evasion genes of VACV and it encodes E3 protein composed of dsRNA binding domain in the C-terminus and Z-NA-binding domain (Z-NA BD) in the N terminus. Both domains are necessary for type 1 interferon resistance and pathogenesis. Recently, it has been shown that in in vitro, the N-terminus of E3 is necessary to inhibit necroptosis occurring through the host-encoded cellular proteins RIP3 and Z-NA-binding protein DAI interaction leading to phosphorylation of MLKL, the key executioner step in the pathway. The research work presented here clearly demonstrates that in a mouse model, the N-terminus of VACV E3 is necessary to inhibit necroptosis during pathogenesis in mice. Another poxvirus belonging to the same family as VACV is monkeypox virus (MPXV) and is an emerging human pathogen. MPXV contains a natural truncation in the N-terminus of its E3 homologue, F3. The results indicate that during MPXV infection in mice, pathogenesis was higher only in DAI knockout mice and not in MLKL knockout mice, suggesting that DAI is possibly activating other proteins not leading to necroptosis. The characterization of VACV as an oncolytic virus was carried out with a focus on future clinical trials. In this study, a pan screening was conducted in various cancer cell lines as many cancers downregulate necroptotic proteins. The results reveal that the N-terminal deletion mutant of VACV selectively replicates in cancer cell lines with a deficient necroptotic pathway and thus, can be used as a potential treatment against specific tumors and evidently, provides abundant scope for future studies.

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Date Created
  • 2020

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Mathematical Simulation of Glioblastoma Multiform Under Treatment

Description

The analysis focuses on a two-population, three-dimensional model that attempts to accurately model the growth and diffusion of glioblastoma multiforme (GBM), a highly invasive brain cancer, throughout the brain. Analysis

The analysis focuses on a two-population, three-dimensional model that attempts to accurately model the growth and diffusion of glioblastoma multiforme (GBM), a highly invasive brain cancer, throughout the brain. Analysis into the sensitivity of the model to

changes in the diffusion, growth, and death parameters was performed, in order to find a set of parameter values that accurately model observed tumor growth for a given patient. Additional changes were made to the diffusion parameters to account for the arrangement of nerve tracts in the brain, resulting in varying rates of diffusion. In general, small changes in the growth rates had a large impact on the outcome of the simulations, and for each patient there exists a set of parameters that allow the model to simulate a tumor that matches observed tumor growth in the patient over a period of two or three months. Furthermore, these results are more accurate with anisotropic diffusion, rather than isotropic diffusion. However, these parameters lead to inaccurate results for patients with tumors that undergo no observable growth over the given time interval. While it is possible to simulate long-term tumor growth, the simulation requires multiple comparisons to available MRI scans in order to find a set of parameters that provide an accurate prognosis.

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Date Created
  • 2020