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Co-Targeting Plk1 And Dnmt3a In Advanced Prostate Cancer, Zhuangzhuang Zhang, Lijun Cheng, Qiongsi Zhang, Yifan Kong, Daheng He, Kunyu Li, Matthew Rea, Jianlin Wang, Ruixin Wang, Jinghui Liu, Zhiguo Li, Chongli Yuan, Enze Liu, Yvonne N. Fondufe-Mittendorf, Lang Li, Tao Han, Chi Wang, Xiaoqi Liu 2021 University of Kentucky

Co-Targeting Plk1 And Dnmt3a In Advanced Prostate Cancer, Zhuangzhuang Zhang, Lijun Cheng, Qiongsi Zhang, Yifan Kong, Daheng He, Kunyu Li, Matthew Rea, Jianlin Wang, Ruixin Wang, Jinghui Liu, Zhiguo Li, Chongli Yuan, Enze Liu, Yvonne N. Fondufe-Mittendorf, Lang Li, Tao Han, Chi Wang, Xiaoqi Liu

Toxicology and Cancer Biology Faculty Publications

Because there is no effective treatment for late-stage prostate cancer (PCa) at this moment, identifying novel targets for therapy of advanced PCa is urgently needed. A new network-based systems biology approach, XDeath, is developed to detect crosstalk of signaling pathways associated with PCa progression. This unique integrated network merges gene causal regulation networks and protein-protein interactions to identify novel co-targets for PCa treatment. The results show that polo-like kinase 1 (Plk1) and DNA methyltransferase 3A (DNMT3a)-related signaling pathways are robustly enhanced during PCa progression and together they regulate autophagy as a common death mode. Mechanistically, it is shown that ...


Cancer Salt Nostalgia, Aashish S. Allu, Venkataswarup Tiriveedhi 2021 Lafayette High School

Cancer Salt Nostalgia, Aashish S. Allu, Venkataswarup Tiriveedhi

Biology Faculty Research

High-salt (sodium chloride) diets have been strongly associated with disease states and poor health outcomes. Traditionally, the impact of salt intake is primarily studied in cardiovascular diseases, hypertension and renal diseases; however, recently there has been increasing evidence demonstrating the role of salt in autoimmune diseases. Salt has been shown to modulate the inflammatory activation of immune cells leading to chronic inflammation-related ailments. To date, there is minimal evidence showing a direct correlation of salt with cancer incidence and/or cancer-related adverse clinical outcomes. In this review article, we will discuss the recent understanding of the molecular role of salt ...


Identifying The Cell Composition And Clonal Diversity Of Supratentorial Ependymoma Using Single Cell Rna-Sequencing, James He 2021 University of Connecticut

Identifying The Cell Composition And Clonal Diversity Of Supratentorial Ependymoma Using Single Cell Rna-Sequencing, James He

University Scholar Projects

Ependymoma is a primary solid tumor of the central nervous system. Supratentorial ependymoma (ST-EPN), a subtype of ependymomas, is driven by an oncogenic fusion between the ZFTA and RELA genes in 70% of cases. We introduced this fusion into neural progenitor cells of mice embryos via in utero electroporation of a non-viral binary piggyBac transposon system containing ZFTA-RELA. From preliminary data in the LoTurco lab, inducing the expression of ZFTA-RELA into different neural progenitor cells produces tumors of varying lethality and cellular composition. To define the cellular composition and subclonal diversity of ST-EPN tumors, we used single cell RNA-sequencing to ...


Identifying The Cell Composition And Clonal Diversity Of Supratentorial Ependymoma Using Single Cell Rna-Sequencing, James He 2021 University of Connecticut

Identifying The Cell Composition And Clonal Diversity Of Supratentorial Ependymoma Using Single Cell Rna-Sequencing, James He

Honors Scholar Theses

Ependymoma is a primary solid tumor of the central nervous system. Supratentorial ependymoma (ST-EPN), a subtype of ependymomas, is driven by an oncogenic fusion between the ZFTA and RELA genes in 70% of cases. We introduced this fusion into neural progenitor cells of mice embryos via in utero electroporation of a non-viral binary piggyBac transposon system containing ZFTA-RELA. From preliminary data in the LoTurco lab, inducing the expression of ZFTA-RELA into different neural progenitor cells produces tumors of varying lethality and cellular composition. To define the cellular composition and subclonal diversity of ST-EPN tumors, we used single cell RNA-sequencing to ...


Plant Based Compounds Inhibit Proliferation, Alter Cytomorphology And Decrease Migration Of Human Adenocarcinoma Cells, Devapriya Segaran 2021 Pittsburg State University

Plant Based Compounds Inhibit Proliferation, Alter Cytomorphology And Decrease Migration Of Human Adenocarcinoma Cells, Devapriya Segaran

Electronic Theses & Dissertations

Adenocarcinoma is an aggressive form of lung cancer that has a high risk of recurrence with a survival rate of 33%. In recent years, there has been much interest in the ability of naturally occurring plant derived phenols to inhibit specific type of cancers. Compounds like curcumin derived from turmeric, rutin derived from citrus fruits and resveratrol derived from blueberries have been of particular interest. In this thesis I studied the anti-cancer effects of the above-mentioned compounds on a human a549 adenocarcinoma cell line. Inverted phase contrast microscopy was used to observe alterations to the cytomorphology of cells. An MTT ...


Novel Hsp40/J-Domain Protein Inhibitors To Deplete Misfolded Mutant P53, Shigeto Nishikawa 2021 Department of Hematology & Oncology, Children’s Mercy Research Institute, MO

Novel Hsp40/J-Domain Protein Inhibitors To Deplete Misfolded Mutant P53, Shigeto Nishikawa

Research Days

Background: Accumulation of oncogenic mutant p53 (mutp53) greatly contributes to cancer progression. Heat shock protein 40 (HSP40), also known as J-domain proteins (JDPs), has been implicated in stabilization of misfolded forms of mutp53. Specifically, we demonstrate that DNAJA1, a member of HSP40/JDPs, binds to and stabilizes misfolded mutp53, while knockdown of DNAJA1 results in CHIP ubiquitin ligase-mediated degradation of misfolded mutp53 and inhibition of tumor growth. Since no HSP40/JDPs inhibitors are currently available in clinics, these findings prompted us to identify inhibitors for DNAJA1 or HSP40/JDPs.

Objectives/Goal: The goal of this study is to identify and ...


The Effects Of Mapk Signaling On The Development Of Cerebellar Granule Cells, Kerry Morgan 2021 University of Connecticut

The Effects Of Mapk Signaling On The Development Of Cerebellar Granule Cells, Kerry Morgan

University Scholar Projects

The granule cells are the most abundant neuronal type in the human brain. Rapid proliferation of granule cell progenitors results in dramatic expansion and folding of the cerebellar cortex during postnatal development. Mis-regulation of this proliferation process causes medulloblastoma, the most prevalent childhood brain tumor. In the developing cerebellum, granule cells are derived from Atoh1-expressing cells, which arise from the upper rhombic lip (the interface between the roof plate and neuroepithelium). In addition to granule cells, the Atoh1 lineage also gives rise to different types of neurons including cerebellar nuclei neurons. In the current study, I have investigated the ...


The Effects Of Mapk Signaling On The Development Of Cerebellar Granule Cells, Kerry Morgan 2021 University of Connecticut

The Effects Of Mapk Signaling On The Development Of Cerebellar Granule Cells, Kerry Morgan

Honors Scholar Theses

The granule cells are the most abundant neuronal type in the human brain. Rapid proliferation of granule cell progenitors results in dramatic expansion and folding of the cerebellar cortex during postnatal development. Mis-regulation of this proliferation process causes medulloblastoma, the most prevalent childhood brain tumor. In the developing cerebellum, granule cells are derived from Atoh1-expressing cells, which arise from the upper rhombic lip (the interface between the roof plate and neuroepithelium). In addition to granule cells, the Atoh1 lineage also gives rise to different types of neurons including cerebellar nuclei neurons. In the current study, I have investigated the ...


Purification Of Pcbp2 And Its Effect On The Formation Of Dna I-Motifs And Secondary Structures, Nathan Redden 2021 University of Mississippi

Purification Of Pcbp2 And Its Effect On The Formation Of Dna I-Motifs And Secondary Structures, Nathan Redden

Honors Theses

Several secondary, non-B forms of DNA are associated with the promoter regions of many oncogenes, including the intensely studied c-MYC gene that codes for a transcription factor. Two such secondary structures, G-quadruplexes, and i-motifs, have become topics of interest due to their prevalence within oncogenic promoters, as well as their potential accessibility for drug targeting. B-form DNA can adopt alternative structures under certain conditions. These alternative structures are favored when there is an asymmetric distribution of guanosine and cytosine on complimentary DNA strands. The strand rich in guanosine is able to form a quadruple stranded DNA complex termed a G-quadruplex ...


The Role Of Pag1 In The Activated B-Cell Subtype Of Diffuse Large B-Cell Lymphoma, Jared Henderson 2021 The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences

The Role Of Pag1 In The Activated B-Cell Subtype Of Diffuse Large B-Cell Lymphoma, Jared Henderson

The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences Dissertations and Theses (Open Access)

Diffuse Large B Cell Lymphoma (DLBCL) is the most common aggressive hematologic malignancy in adults, but despite recent advances in treatment, many patients today still face poor outcomes. Of the two types of DLBCL, activated B-cell (ABC) and germinal center B-cell (GCB), patients diagnosed with the ABC subtype especially face a lack of effective treatment options. Unlike GCB-DLBCL, ABC-DLBCL is characterized by chronic antigen-driven signaling by the B-cell receptor (BCR), indicating an escape from immunologic tolerance mechanisms that normally regulate self-reactive B cells. While recent therapies have focused on inhibiting the kinases that propagate BCR signaling with mixed success, we ...


Effects Of Heme Oxygenase 1 Inducer, T-Bhq On Growth Of Multiple Myeloma Cell Lines, And On Osteoblast And Osteoclast Differention, Alyaa Alansari 2021 University of Arkansas, Fayetteville

Effects Of Heme Oxygenase 1 Inducer, T-Bhq On Growth Of Multiple Myeloma Cell Lines, And On Osteoblast And Osteoclast Differention, Alyaa Alansari

Graduate Theses and Dissertations

Expansion of plasma cells within the bone marrow constitutes the onset of multiple myeloma (MM). This disease manifests clinically primarily through the formation of osteolytic bone lesions that can lead to osteoporosis. The reason for the development of such lesions is the disruption of the equilibrium between bone resorption and bone formation as a result of proliferation of osteoclasts and reduction in the number of osteoblasts in the process of differentiation of mesenchymal stem cells (MSCs). The maintenance of bone architecture is critically dependent on osteoblasts and osteoclasts, the activity of which is underpinned by a range of soluble factors ...


The Biochemical Characterization Of Aza197 And A Ras Related Protein Cdc42, Alix Montoya-Beltran 2021 University of Arkansas, Fayetteville

The Biochemical Characterization Of Aza197 And A Ras Related Protein Cdc42, Alix Montoya-Beltran

Graduate Theses and Dissertations

Eukaryotic cells contain an extensive amount of GTP/GDP binding proteins. Proteins known as Ras GTPase primary function as a binary switch, where they cycle from an on and off state when GTP or GDP are bound, respectively. They are known to play a critical role in many cellular functions where a dysregulation could potentially lead to oncogenic behavior or other malignancies. In our laboratory, our focus is the study of a Ras related protein Cell division control 42 homolog (Cdc42) which belongs to the Rho subfamily. Cdc42 plays a critical role in many biological signaling processes; therefore, its uncontrol ...


Effects Of Heme Oxygenase 1 Inducer, T-Bhq On Growth Of Multiple Myeloma Cell Lines, And On Osteoblast And Osteoclast Differention, Alyaa Alansari 2021 University of Arkansas, Fayetteville

Effects Of Heme Oxygenase 1 Inducer, T-Bhq On Growth Of Multiple Myeloma Cell Lines, And On Osteoblast And Osteoclast Differention, Alyaa Alansari

Graduate Theses and Dissertations

Expansion of plasma cells within the bone marrow constitutes the onset of multiple myeloma (MM). This disease manifests clinically primarily through the formation of osteolytic bone lesions that can lead to osteoporosis. The reason for the development of such lesions is the disruption of the equilibrium between bone resorption and bone formation as a result of proliferation of osteoclasts and reduction in the number of osteoblasts in the process of differentiation of mesenchymal stem cells (MSCs). The maintenance of bone architecture is critically dependent on osteoblasts and osteoclasts, the activity of which is underpinned by a range of soluble factors ...


Investigating A Novel Function For Phosphoserine Aminotransferase 1 (Psat1) In Epidermal Growth Factor Receptor (Egfr)-Mediated Lung Tumorigenesis., Rumeysa Biyik-Sit 2021 University of Louisville

Investigating A Novel Function For Phosphoserine Aminotransferase 1 (Psat1) In Epidermal Growth Factor Receptor (Egfr)-Mediated Lung Tumorigenesis., Rumeysa Biyik-Sit

Electronic Theses and Dissertations

Phosphoserine aminotransferase 1 (PSAT1) catalyzes the second enzymatic step within the serine synthetic pathway (SSP) and its expression is elevated in numerous human cancers, including non-small cell lung cancer (NSCLC). Epidermal growth factor receptor (EGFR) mutant NSCLC is characterized by activating mutations within its tyrosine kinase domain and accounts for 17% of lung adenocarcinomas. Although elevated SSP activity has been observed in EGFR-mutant lung cancer cells, the involvement of PSAT1 in EGFR-mediated oncogenesis is still unclear. Here, we explore a putative non-canonical function for PSAT1 using biochemical approaches to elucidate unknown interacting proteins and genomic RNA-seq profiling to identify cellular ...


Assessing The Outcomes Of Blocking Ccl2-Ccr2 Signaling Axis On Breast Cancer Brain Metastasis, Yutao Qi 2021 The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences

Assessing The Outcomes Of Blocking Ccl2-Ccr2 Signaling Axis On Breast Cancer Brain Metastasis, Yutao Qi

The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences Dissertations and Theses (Open Access)

Breast cancer brain metastases have remained one of the most intense challenges for precision cancer therapeutics, but current treatment options are limited and not curative. Recently, our lab reported that adoptive PTEN downregulation in metastatic breast tumor cells activates PI3K/NF-ƙB signaling and increases the secretion of the chemokine CCL2, which enhances the chemotaxis of CCR2+ myeloid cells, a major subpopulation of bone marrow-derived myeloid cells (BMDMs), from peripheral blood into the brain tumor microenvironment (TME), eventually promoting brain metastasis outgrowth by driving immune suppression. Here, in this project we have been aiming to develop effective therapies by immune-modulating the ...


022— Examining P27 Expression And Quiescence In Clobetasol-Exposed Umscv-4 Vulvar Cancer Cells, Nina Mustico, Vincent Scalcione, Jani E. Lewis 2021 SUNY Geneseo

022— Examining P27 Expression And Quiescence In Clobetasol-Exposed Umscv-4 Vulvar Cancer Cells, Nina Mustico, Vincent Scalcione, Jani E. Lewis

GREAT Day

Vulvar cancer is rare, mostly afflicting women aged 60 and older [1]. The cancer is often preceded by a common vulvar rash, lichen sclerosus, that is usually treated with the ultra-potent corticosteroid, clobetasol propionate. This treatment may, in turn, be associated with vulvar carcinogenesis. Our previous findings suggest that clobetasol is causing UMSCV-4 vulvar carcinoma cells to enter a state of quiescence. Quiescence is temporary removal from the cell cycle and can be thought of as a dormant state in which cells are not actively dividing [2]. There is growing evidence suggesting that quiescence may play a role in allowing ...


Usefulness Of Circulating Tumor Dna In Identifying Somatic Mutations And Tracking Tumor Evolution In Patients With Non-Small Cell Lung Cancer, Moom R. Roosan, Isa Mambetsariev, Rebecca Pharaon, Jeremy Fricke, Hatim Husain, Karen L. Reckamp, Marianna Koczywas, Erminia Massarelli, Andrea H. Bild, Ravi Salgia 2021 Chapman University

Usefulness Of Circulating Tumor Dna In Identifying Somatic Mutations And Tracking Tumor Evolution In Patients With Non-Small Cell Lung Cancer, Moom R. Roosan, Isa Mambetsariev, Rebecca Pharaon, Jeremy Fricke, Hatim Husain, Karen L. Reckamp, Marianna Koczywas, Erminia Massarelli, Andrea H. Bild, Ravi Salgia

Pharmacy Faculty Articles and Research

Background

The usefulness of circulating tumor DNA (ctDNA) in detecting mutations and monitoring treatment response has not been well studied beyond a few actionable biomarkers in non-small cell lung cancer (NSCLC).

Research Question

How does the usefulness of ctDNA analysis compare with that of solid tumor biopsy analysis in patients with NSCLC?

Methods

We retrospectively evaluated 370 adult patients with NSCLC treated at the City of Hope between November 2015 and August 2019 to assess the usefulness of ctDNA in mutation identification, survival, concordance with matched tissue samples in 32 genes, and tumor evolution.

Results

A total of 1,688 ...


Defying The Darkness: Countering Cancer With Light, Travis Hankins 2021 Ouachita Baptist University

Defying The Darkness: Countering Cancer With Light, Travis Hankins

Honors Theses

Triple-Negative Breast Cancer (TNBC) accounts for upwards of 15% of reported breast cancer cases. This subtype of breast cancer poses a greater threat to those diagnosed as compared to other types of breast cancer due to the lack of treatment options available. Additionally, TNBC grows and spreads faster, tends to be more aggressive, and has a greater chance of recurrence than its counterparts. Altogether, TNBC cases generally have a worse prognosis over other types of breast cancer. Photodynamic therapy (PDT) is currently being researched as a way to treat TNBC. Photodynamic therapy agents are light-activated materials used for localized disease ...


Role Of Ampk And Akt In Triple Negative Breast Cancer Lung Colonization, Jeremy Johnson, Zeta Chow, Eun Young Lee, Heidi L. Weiss, B. Mark Evers, Piotr G. Rychahou 2021 University of Kentucky

Role Of Ampk And Akt In Triple Negative Breast Cancer Lung Colonization, Jeremy Johnson, Zeta Chow, Eun Young Lee, Heidi L. Weiss, B. Mark Evers, Piotr G. Rychahou

Pathology and Laboratory Medicine Faculty Publications

Triple negative breast cancer (TNBC) is an aggressive disease with a 5-y relative survival rate of 11% after distant metastasis. To survive the metastatic cascade, tumor cells remodel their signaling pathways by regulating energy production and upregulating survival pathways. AMP-activated protein kinase (AMPK) and Akt regulate energy homeostasis and survival, however, the individual or synergistic role of AMPK and Akt isoforms during lung colonization by TNBC cells is unknown. The purpose of this study was to establish whether targeting Akt, AMPKα or both Akt and AMPKα isoforms in circulating cancer cells can suppress TNBC lung colonization. Transient silencing of Akt1 ...


Toxic Effect Of Crotalus Adamanteus Acidic Phospholipase A2 On Mcf-7 Cell Line, Daniel J. Petra 2021 University of South Dakota

Toxic Effect Of Crotalus Adamanteus Acidic Phospholipase A2 On Mcf-7 Cell Line, Daniel J. Petra

Honors Thesis

We are investigating the effect of Crotalus adamanteus acidic phospholipase A2 on MCF-7 cells using the MTS assay. Understanding these interactions and isolated effects is critical to developing new ways to treat envenomation. By understanding the effects of individual toxins within a whole venom, we are set to better understand the effects of the whole venom and investigate synergistic actions between venom toxins. In this paper, we are quantifying the amount of MCF-7 cell death caused by Crotalus adamanteus phospholipase A2 on MCF-7 using the MTS assay. Analysis of the amount of cells death caused by the phospholipase ...


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