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Identifying Genetic Regulators Of Cancer Stem Cell Differentiation For Glioblastoma Therapy, Ann Chen, Yang Xiao, Rong Fan, Jiangbing Zhou 2019 Yale University

Identifying Genetic Regulators Of Cancer Stem Cell Differentiation For Glioblastoma Therapy, Ann Chen, Yang Xiao, Rong Fan, Jiangbing Zhou

Yale Day of Data

Glioblastoma multiforme (GBM) is the most common and aggressive type of primary brain cancer. Even with treatment, GBM patients have a median survival rate of less than 15 months and a five-year survival rate of 2%. Poor therapeutic outcomes may be attributed to the presence of a subpopulation of cells within tumors, known as cancer stem cells (CSCs), which are resistant to conventional radiotherapy and chemotherapy. CSCs are capable of tumor initiation, sustained self-renewal, and differentiation into terminal cell types. These terminally differentiated cells make up the bulk of the tumor and are sensitive to GBM therapies. Therefore, CSC-directed therapies ...


The Role Of Kras In Mechanosensing In Non-Small Cell Lung Cancer, Krista M. Powell 2019 Virginia Commonwealth University

The Role Of Kras In Mechanosensing In Non-Small Cell Lung Cancer, Krista M. Powell

Theses and Dissertations

Lung cancer is the number one cause of cancer related death worldwide, with more than 1.6 million fatalities each year. Non-small cell lung cancer (NSCLC) accounts for 80-85% of all lung cancers, with KRAS being one of the most prevalent oncogenic driver mutations. Therapeutic approaches for KRAS-mutated NSCLC have been extensively explored due to the US National Cancer Institute RAS Initiative, but methods of directly targeting KRAS or downstream effectors, such as MEK, still have poor results. Previous reports have shown that KRAS-mutated NSCLC activate distinct receptor tyrosine kinases (RTKs) depending on the epithelial or mesenchymal state. Epithelial-to-mesenchymal transition ...


Mechanisms And Immunogenicity Of Nspef-Induced Cell Death In B16f10 Melanoma Tumors, Alessandra Rossi, Olga N. Pakhomova, Andrei G. Pakhomov, Samantha Weygandt, Anna A. Bulysheva, Len E. Murray, Peter A. Mollica, Claudia Muratori 2019 Old Dominion University

Mechanisms And Immunogenicity Of Nspef-Induced Cell Death In B16f10 Melanoma Tumors, Alessandra Rossi, Olga N. Pakhomova, Andrei G. Pakhomov, Samantha Weygandt, Anna A. Bulysheva, Len E. Murray, Peter A. Mollica, Claudia Muratori

Bioelectrics Publications

Accumulating data indicates that some cancer treatments can restore anticancer immunosurveillance through the induction of tumor immunogenic cell death (ICD). Nanosecond pulsed electric fields (nsPEF) have been shown to efficiently ablate melanoma tumors. In this study we investigated the mechanisms and immunogenicity of nsPEF-induced cell death in B16F10 melanoma tumors. Our data show that in vitro nsPEF (20-200, 200-ns pulses, 7 kV/cm, 2 Hz) caused a rapid dose-dependent cell death which was not accompanied by caspase activation or PARP cleavage. The lack of nsPEF-induced apoptosis was confirmed in vivo in B16F10 tumors. NsPEF also failed to trigger ICD-linked responses ...


Regulation Of The Long Non-Coding Rna Fam83h-As1 By Human Papillomavirus In Cervical Cancer, Jamie Ann Barr Ph.D. 2019 West Virginia University

Regulation Of The Long Non-Coding Rna Fam83h-As1 By Human Papillomavirus In Cervical Cancer, Jamie Ann Barr Ph.D.

Graduate Theses, Dissertations, and Problem Reports

Non-coding RNAs (NcRNAs), such as long non-coding RNAs (lncRNAs) and microRNAs (miRNAs), have been found to be involved in a variety of critical biological processes, and dysregulation of ncRNAs have been involved with several human diseases including cancer.

High-risk human papillomavirus (HPV) infection is one of the first events in the process of carcinogenesis in cervical and a subset of head and neck cancers. The expression of the viral oncoproteins E6 and E7 is essential in this process by inactivating the tumor suppressor proteins p53 and Rb, respectively, in addition to their interactions with other host proteins and regulation of ...


Eralpha Isoforms Modulate The Tumorigenicity Of 24r,25(Oh)2d3 In Estrogen-Responsive Cancer, Anjali Verma 2019 Virginia Commonwealth University

Eralpha Isoforms Modulate The Tumorigenicity Of 24r,25(Oh)2d3 In Estrogen-Responsive Cancer, Anjali Verma

Theses and Dissertations

Over 200,000 cases of breast cancer are diagnosed every year. Nearly 20% of these patients supplement their diets with some form of vitamin D. This high frequency of vitamin D supplement use may be due in part to research suggesting that cancer patients with higher serum vitamin D3 levels have better prognoses than patients with low serum vitamin D3. However, double-blind clinical trials on the efficacy of vitamin D3 supplementation in breast cancer have been inconclusive. A recent meta-analysis showed evidence of reduced cancer recurrence in patients taking vitamin D3 supplements who had ‘estrogen receptor ...


Regorafenib Enhances Lethality Of Sildenafil And Curcumin In Colorectal Cancer Cells, Kervin Benjamin Owusu 2019 Virginia Commonwealth University

Regorafenib Enhances Lethality Of Sildenafil And Curcumin In Colorectal Cancer Cells, Kervin Benjamin Owusu

Theses and Dissertations

In the United States, more than 130,000 people will be diagnosed with colorectal cancer (CRC) each year and an estimated 50,000 people will die from the disease. Standard of care (SOC) therapies for CRC combine multiple cytotoxic chemotherapeutic drugs. These combinations have varying degrees of effectiveness and can often result in significant patient morbidity. For second recurrence patients, the multi-kinase inhibitor, regorafenib, is an approved agent, but is often poorly tolerated at current doses. In the current study, we propose to develop therapeutic regime of combining agents with modest toxicity profiles: curcumin and sildenafil with regorafenib. Using clinically ...


Sarcoid-Like Reaction Associated With Renal Cell Carcinoma - A Case Report., Asma Iftikhar, Muhammad A I Cheema, Preethi Ramachandran, Sonu Sahni 2019 Touro College of Osteopathic Medicine (New York)

Sarcoid-Like Reaction Associated With Renal Cell Carcinoma - A Case Report., Asma Iftikhar, Muhammad A I Cheema, Preethi Ramachandran, Sonu Sahni

Touro College of Osteopathic Medicine (New York) Publications and Research

Renal cell carcinoma (RCC) is a highly vascular tumor, which may spread to the lungs and other organs. It often presents with localized or systemic manifestation, including paraneoplastic syndromes. Sarcoidosis is a systemic granulomatous inflammatory disease characterized by non-caseating granulomas that typically afflicts the respiratory system. In the absence of any evidence of systemic sarcoidosis they are referred to as sarcoid-like reactions. Non-caseating epithelioid granulomas, also regarded to sarcoid-like granulomas have been described in association with certain malignancies such as carcinomas of the breast, colon, seminoma, and Hodgkin's lymphoma. However, sarcoid like reaction associated with renal cell carcinoma is ...


Effects Of Pag1 On Src-Family Kinase Trafficking In Neuroblastoma Cells, Makenzie E. Mayfield 2019 University of Montana, Missoula

Effects Of Pag1 On Src-Family Kinase Trafficking In Neuroblastoma Cells, Makenzie E. Mayfield

Undergraduate Theses and Professional Papers

The receptor tyrosine kinases (RTKs) are known to help regulate cell behaviors including differentiation, proliferation and migration during embryonic development of the neural crest. RTKs are believed to initiate signaling cascades in response to extracellular cues in part by controlling localization of Src-family kinases (SFKs). The scaffolding protein PAG1 binds SFKs and is believed to influence SFK activity and location within the cell by promoting interaction of SFKs with regulatory proteins and by drawing SFKs into different components of the endocytic pathway. By targeting the PAG1 gene in SH-SY5Y neuroblastoma cells with CRISPR/Cas9 plasmids, we created PAG1-mutant cell-lines in ...


Clarifying The Connection Between Oncgenic Kras And Gastrin/Cck2r Signaling In Pancreatic Tumorigensis, Andrew LaRow, John F. Harms 2019 Messiah College

Clarifying The Connection Between Oncgenic Kras And Gastrin/Cck2r Signaling In Pancreatic Tumorigensis, Andrew Larow, John F. Harms

Honors Projects and Presentations: Undergraduate

Pancreatic ductal adenocarcinoma (PDAC) is an extremely deadly cancer: the overall five-year survival rate is 8%. This is mainly due to the difficulty of diagnosing PDAC in its early stage: only 9% of patients are diagnosed with localized cancer. Cancer cells display rapid growth and cell division, due in part to oncogene activation and stimulation of mitogenic pathways. In PDAC, mutant K-ras, an oncogene and intracellular signaling protein, is present in 90% of all cases. Because of this high correlation and the role of mutant K-ras in PDAC, it has been repeatedly targeted for cancer therapy, but with little success ...


Regulation Of Canonical And Non-Canonical Hippo Pathway Components In Mitosis And Cancer, Seth Stauffer 2018 University of Nebraska Medical Center

Regulation Of Canonical And Non-Canonical Hippo Pathway Components In Mitosis And Cancer, Seth Stauffer

Theses & Dissertations

The Hippo pathway is conserved regulator of organ size through control of proliferation, apoptosis, and stem-cell self-renewal. In addition to this important function, many of the canonical signaling members have also been shown to be regulated during mitosis. Importantly, Hippo pathway components are frequently dysregulated in cancers and have attracted attention as possible targets for improved cancer therapeutics. Further exploration of Hippo-YAP (yes-associated protein) signaling has revealed new regulators and effectors outside the canonical signaling network and has revealed a larger non-canonical network of signaling proteins in which canonical Hippo pathway components crosstalk with important cellular homeostasis and apoptosis signaling ...


Frost450, A Novel Microtubule Targeting Agent: Resistance And Cross-Resistance In An Ovarian Cancer Cell Line, Jonathan Chancellor Fox 2018 Brigham Young University

Frost450, A Novel Microtubule Targeting Agent: Resistance And Cross-Resistance In An Ovarian Cancer Cell Line, Jonathan Chancellor Fox

Undergraduate Honors Theses

Drug resistance remains problematic for chemotherapy treatments. As primary treatment strategies tend to lose potency against cancer, there is a need for treatment options that overcome drug resistance mechanisms. FROST450, a novel microtubule destabilizing agent, has proven anticancer effects that overcome taxane and multidrug resistance. However, to better understand the clinical potential of FROST450, in this study we examine the mechanisms and implications of acquired FROST450 resistance in an A2780 ovarian cancer cell line. Results indicate FROST450 resistance is associated with increased mitochondrial respiration and with changes in gene sequence or expression level of proteins associated with microtubules, and that ...


Role Of P300 Zz Domain In Chromatin Association And Histone Acetylation, Yongming Xue 2018 The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences

Role Of P300 Zz Domain In Chromatin Association And Histone Acetylation, Yongming Xue

UT GSBS Dissertations and Theses (Open Access)

Transcription is strictly regulated by numerous factors including transcription coactivators. The p300 protein and its close paralogue CREB-binding protein (CREBBP, aka CBP) are well-known transcriptional coactivators that have intrinsic lysine acetyltransferase activity. The functions of p300/CBP largely rely on their capabilities to bind to chromatin and to acetylate the histone substrates. However, the molecular mechanisms underlying the regulation of these processes are not fully understood.

Through combination of various biochemical, biophysical and molecular approaches, we show that the ZZ-type zinc finger (ZZ) domain of p300 functions as a histone reader that specifically binds the N-terminal tail of histone H3 ...


Molecular Dynamics Of P21 And Fluorescent Sphingomyelin In Keratinocytes Exposed To Uvb, Tyler Malcolm Fraser 2018 California Polytechnic State University - San Luis Obispo

Molecular Dynamics Of P21 And Fluorescent Sphingomyelin In Keratinocytes Exposed To Uvb, Tyler Malcolm Fraser

Master's Theses and Project Reports

Non-melanoma skin cancer (NMSC) is the most common malignant tumor, representing more than a third of all malignant tumors combined and the incidence is increasing every year. Ultraviolet (UV) radiation from the sun is the most dominant factor contributing to tumor initiation and progression. The condition is most prevalent in populations with lighter skin and older age. Current pharmaceutical molecular research targets the inhibition of the Epidermal Growth Factor Receptor (EGFR), a receptor which is commonly over-expressed or dysregulated in skin malignancies. This study evaluates the content and location of the damage marker p21 within keratinocytes that were incubated in ...


Hdl In Endocrine Carcinomas: Biomarker, Drug Carrier, And Potential Therapeutic, Emily E. Morin, Xiang-An Li, Anna Schwendeman 2018 University of Michigan

Hdl In Endocrine Carcinomas: Biomarker, Drug Carrier, And Potential Therapeutic, Emily E. Morin, Xiang-An Li, Anna Schwendeman

Physiology Faculty Publications

High-density lipoprotein (HDL) have long been studied for their protective role against cardiovascular diseases, however recently relationship between HDL and cancer came into focus. Several epidemiological studies have shown an inverse correlation between HDL-cholesterol (HDL-C) and cancer risk, and some have even implied that HDL-C can be used as a predictive measure for survival prognosis in for specific sub-population of certain types of cancer. HDL itself is an endogenous nanoparticle capable of removing excess cholesterol from the periphery and returning it to the liver for excretion. One of the main receptors for HDL, scavenger receptor type B-I (SR-BI), is highly ...


A Crispr Platform For Rapid And Inducible Genome Editing In Human Non-Small Cell Lung Cancer Cells, Lloyd Bartley 2018 Murray State University

A Crispr Platform For Rapid And Inducible Genome Editing In Human Non-Small Cell Lung Cancer Cells, Lloyd Bartley

Posters-at-the-Capitol

Non-small cell lung cancer (NSCLC) accounts for about 85% of lung cancer, which is the leading cause of cancer death in the world. High mortality rate associated with NSCLC is partially attributed to the limited understanding of NSCLC as well as ineffective therapeutic treatments. The initiation and progression of NSCLC involves genetic changes leading to alterations in the control of tissue development and homeostatic maintenance. Better knowledge about these genetic abnormalities is imperative for developing new chemotherapeutic drugs for NSCLC. Recent research demonstrates that the expression of paraoxonase 2 (PON2), a lactonase/arylesterase with anti-oxidant properties, are markedly enhanced in ...


Characterization Of A Basement Membrane Associated Protein Encoding Gene In Drosophila Melanogaster, Aref Ranjbar, Ajay Srivastava 2018 Western Kentucky University

Characterization Of A Basement Membrane Associated Protein Encoding Gene In Drosophila Melanogaster, Aref Ranjbar, Ajay Srivastava

Posters-at-the-Capitol

Title: Characterization of a Basement Membrane Associated Protein Encoding Gene in Drosophila melanogaster

Authors: Aref Ranjbar, Mayank Kapadia, Ajay Srivastava, PhD(faculty member, mentor)

Basement Membranes (BM) are important for normal development and tumor progression. In order to get a better understanding of BM dynamics we identified genes that encoded BM interacting proteins. One such gene is predicted to be involved in vesicle-mediated transport in Drosophila melanogaster. Here we characterize this gene by utilizing molecular biology techniques like immunohistochemistry, RNA in situ hybridization, and Western blot analysis utilizing antibodies generated in the laboratory. Western blot analysis identified this protein to ...


Colorectal Cancer Liver Metastatic Growth Depends On Pad4-Driven Citrullination Of The Extracellular Matrix, A. E. Yuzhalin, A. N. Gordon-Weeks, M. L. Tognoli, K. Jones, B. Markelc, R. Konietzny, R. Fischer, Aaron Muth, E. O'Neill, Paul R. Thompson, P. J. Venables, B. M. Kessler, S. Y. Lim, R. J. Muschel 2018 University of Oxford

Colorectal Cancer Liver Metastatic Growth Depends On Pad4-Driven Citrullination Of The Extracellular Matrix, A. E. Yuzhalin, A. N. Gordon-Weeks, M. L. Tognoli, K. Jones, B. Markelc, R. Konietzny, R. Fischer, Aaron Muth, E. O'Neill, Paul R. Thompson, P. J. Venables, B. M. Kessler, S. Y. Lim, R. J. Muschel

Open Access Articles

Citrullination of proteins, a post-translational conversion of arginine residues to citrulline, is recognized in rheumatoid arthritis, but largely undocumented in cancer. Here we show that citrullination of the extracellular matrix by cancer cell derived peptidylarginine deiminase 4 (PAD4) is essential for the growth of liver metastases from colorectal cancer (CRC). Using proteomics, we demonstrate that liver metastases exhibit higher levels of citrullination and PAD4 than unaffected liver, primary CRC or adjacent colonic mucosa. Functional significance for citrullination in metastatic growth is evident in murine models where inhibition of citrullination substantially reduces liver metastatic burden. Additionally, citrullination of a key matrix ...


Development Of A Pd-L1 Pet Imaging Biomarker, Caleb Jack Bridgwater 2018 University of Louisville

Development Of A Pd-L1 Pet Imaging Biomarker, Caleb Jack Bridgwater

Posters-at-the-Capitol

Immunotherapy strategies are very promising treatments for cancer patients. Specifically, Immune checkpoint inhibitor therapy focusing on the PD-1/PD-L1 pathway shows long-lasting positive results in many cancer patients. Unfortunately, not all the patients can benefit from this highly effective treatment. Hence, there is a great need for predictive biomarkers. Immunohistochemical (IHC) staining has been used as a way of predicting patient response, yet shows many problems. For example, IHC utilizes an invasive biopsy and sample fixing, which creates an incomplete and delayed picture of the patient’s biochemistry and the tumor microenvironment, consequently ignoring metastases.

The purpose of this study ...


Combined High-Speed Single Particle Tracking Of Membrane Proteins And Super-Resolution Of Membrane-Associated Structures, Hanieh Mazloom Farsibaf, Keith A. Lidke 2018 University of New Mexico

Combined High-Speed Single Particle Tracking Of Membrane Proteins And Super-Resolution Of Membrane-Associated Structures, Hanieh Mazloom Farsibaf, Keith A. Lidke

Shared Knowledge Conference

Many experiments have shown that the diffusive motion of lipids and membrane proteins are slower on the cell surface than those in artificial lipid bilayers or blebs. One hypothesis that may partially explain this mystery is the effect of the cytoskeleton structures on the protein dynamics. A model proposed by Kusumi [1] is the Fence-Picket Model which describes the cell membrane as a set of compartment regions, each ~ 10 to 200 nm in size, created by direct or indirect interaction of lipids and proteins with actin filaments just below the membrane. To test this hypothesis, we have assembled a high-speed ...


Histone Deacetylation Is The Primary Epigenetic Mechanism For Silencing Of Tumor Suppressor Gene - Tissue Factor Pathway Inhibitor-2 In Hepatocellular Carcinoma Cells, Alisha Deshmukh, Shirish Barve 2018 Murray State University

Histone Deacetylation Is The Primary Epigenetic Mechanism For Silencing Of Tumor Suppressor Gene - Tissue Factor Pathway Inhibitor-2 In Hepatocellular Carcinoma Cells, Alisha Deshmukh, Shirish Barve

Posters-at-the-Capitol

Hepatocellular carcinoma (HCC) is the third leading cause of cancer related mortality worldwide. With a survival rate of less than 5 percent, a therapeutic treatment is desperately needed to manage this disease. Many epigenetic mechanisms that underlay HCC are being identified. A frequently silenced pathway tissue factor pathway inhibitor-2 (TFPI-2) is a critical tumor suppressor gene. In HCC, inactivation of TFPI-2 leads to tumor growth. Recent research indicated Fas L plays a major role in apoptosis as part of HCC. For the purposes of this study, the phytochemical Curcumin was explored to observe its possible effects on the epigenetic mechanisms ...


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