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Glucose Metabolism Of Breast Cancer Sub-Clones That Preferentially Metastasize To The Lungs And Bone, Anna G. Skubiz 2020 University of Mississippi

Glucose Metabolism Of Breast Cancer Sub-Clones That Preferentially Metastasize To The Lungs And Bone, Anna G. Skubiz

Honors Theses

Malignant breast cancers exhibit preferential metastasis to bone and lung (1). While changes in gene expression in lung-specific (LM) and bone-specific metastasis (BoM) lines derived from the MDA-MB-231 breast cancer line have been identified, few metabolic genes are differentially expressed; thus it is unknown if tissue-specific metabolic reprogramming occurs. Two hallmarks of cancer cells are an altered metabolic phenotype characterized by enhanced conversion of glucose to lactate in spite of adequate oxygen availability for complete mitochondrial oxidation of this substrate (referred to as aerobic glycolysis or the Warburg effect) and a greater dependence on glutamine. These changes in primary tumor ...


Breast Cancer Sub-Clones That Metastasize To Lung And Bone Exhibit Different Metabolic Preferences, Mollie Merrell 2020 University of Mississippi

Breast Cancer Sub-Clones That Metastasize To Lung And Bone Exhibit Different Metabolic Preferences, Mollie Merrell

Honors Theses

Metastasis is responsible for the majority of cancer related deaths. In breast cancer the lungs and bones are the major sites for metastasis. Previous studies used the metastatic aggressive MDA-MB-231 breast cancer line to isolate sub-clones that preferentially invade the lungs (LM line) or bones (BoM line). While genes associated with the tissue specific metastasis have been identified, it is unknown if metabolic adaptations contribute to the growth of the LM and BoM lines in their respective organs. The goal of this study was to test the hypothesis that the LM and BoM lines exhibit differences in glucose and glutamine ...


Cell Proliferation And Viability Inhibition By Resveratrol On Breast Cancer Cell Lines, Kyle Ford Gordon Jr 2020 University of Mississippi

Cell Proliferation And Viability Inhibition By Resveratrol On Breast Cancer Cell Lines, Kyle Ford Gordon Jr

Honors Theses

Antioxidants are well-known for their various health benefits. They are able to protect cells from being damaged by free radicals that are produced by vital biochemical processes. It has long been known that antioxidants are important in our everyday health, but their potential as disease preventers and potential therapeutic agents is a relatively new field of study. Resveratrol, a natural polyphenol and well-known antioxidant, is found in plants, fruits, and products derived from them, like red wine. Resveratrol has been shown to have various properties, including antiaging, anti-aggregation of platelets, anti-inflammatory, and anticancer activities. Because of their many health benefits ...


Design Of A 3d Printed Bioreactor For Bone Cancer Research, Brooklyn K. VanDerWolde, Katelyn Hillson 2020 South Dakota State University

Design Of A 3d Printed Bioreactor For Bone Cancer Research, Brooklyn K. Vanderwolde, Katelyn Hillson

The Journal of Undergraduate Research

Bone cancer is an aggressive disease and has peak occurrence during physiological stimulation of growth and aging. Astronauts who undergo long-term space missions also acquire an increased risk of bone tissue degeneration and cancer. Few in-vitro models currently exist capable of reproducing the complex microenvironment of bone tissue to support multicellular activity in a three-dimensional structure. This limits the ability to understand disease progression and develop suitable treatment strategies. Therefore, developing a bone tissue model and an associated bioreactor is critical to understand the risks associated with cancer progression and improve treatment and preventions related to those risks. The goal ...


Neurocognitive Risk Factors And Current Intervention Strategies For Survivors Of Pediatric Acute Lymphoblastic Leukemia, Abigail Taber 2020 Liberty University

Neurocognitive Risk Factors And Current Intervention Strategies For Survivors Of Pediatric Acute Lymphoblastic Leukemia, Abigail Taber

Senior Honors Theses

The improved survival rate for pediatric cancer patients is one of the greatest triumphs of recent medicine, but the late effects faced by these survivors have been uncovered through this new population of survivors. Many survivors of pediatric acute lymphoblastic leukemia (ALL) experience cognitive deficits in areas such as attention, memory, processing speed, and academic achievement following cancer treatment. Recent research has pointed to chemotherapeutic agents, host risk factors, and genetic predispositions as perpetrators of these deficits, although other factors are also under investigation. Consequently, the search for appropriate interventions for the amelioration of these deficits has dominated the literature ...


Exploring Occupational Disruption In Newly Diagnosed Individuals With Cancer With Minor (Dependent) Children, Riley S. Harrold 2020 University of St. Augustine for Health Sciences

Exploring Occupational Disruption In Newly Diagnosed Individuals With Cancer With Minor (Dependent) Children, Riley S. Harrold

Student Capstone Projects

Background: According to the American Cancer Society (2019), there were more than 1.7 million new cases of cancer in 2019 alone. Individuals are being diagnosed at a young age with 22.4% of cases occurring in individuals 22-55 years old and whom are childrearing age (Shah et al., 2017). There are an estimated 2.85 million children under the age of 18 who are living with a parent who has cancer (Shah et al., 2017). Newly diagnosed individuals face changes in daily life, the threat of possible death, and fear of dying (Compas et al., 1994). Changes in shared ...


365— Clobetasol-Induced Quiescence In The Vulvar Carcinoma Cell Line Umscv-4 Can Be Overcome By Repeated Removal And Re-Exposure To This Ultrapotent Corticosteroid, Nolberto Jaramillo Jr., Nina Mustico 2020 SUNY Geneseo

365— Clobetasol-Induced Quiescence In The Vulvar Carcinoma Cell Line Umscv-4 Can Be Overcome By Repeated Removal And Re-Exposure To This Ultrapotent Corticosteroid, Nolberto Jaramillo Jr., Nina Mustico

GREAT Day

Vulvar cancer is rare, mostly afflicting women aged 60 and older. The cancer is often preceded by a common vulvar rash, Lichen sclerosis, that is usually treated with the ultra-potent corticosteroid, clobetasol propionate. This treatment may, in turn, be associated with vulvar carcinogenesis. Quiescence, a common characteristic of stem cells, is a reversible state of growth arrest. Our results suggest that clobetasol is causing UMSCV-4 vulvar carcinoma cells to enter quiescence, and may allow them to evade the standard treatments that target rapidly proliferating populations. Furthermore, when these cells are removed from clobetasol and re-exposed, they proliferate at higher levels ...


147— The Effect Of A Histone Deacetylase Inhibitor On Pd-L1, Hla-Abc, Hla-E, And Hla-G On Human Breast Cancer Cell Lines, Nikhil Reddy, Alec Toufexis 2020 SUNY Geneseo

147— The Effect Of A Histone Deacetylase Inhibitor On Pd-L1, Hla-Abc, Hla-E, And Hla-G On Human Breast Cancer Cell Lines, Nikhil Reddy, Alec Toufexis

GREAT Day

Increased expression of human leukocyte antigen (HLA) allows tumor cells to be more easily detected by the immune system. In previous research, epigenetic modifiers including the histone deacetylase inhibitor 3 (HDAC3), RGFP966, has been shown to decrease PD-L1 expression. PD-L1 expression inhibits T cell cytotoxicity, and decreasing it can enhance the immune response. We hope to elucidate whether or not HLA-ABC expression similarly decreases upon exposure to the HDAC3 inhibitor which would be detrimental to immune detection. Two breast cancer cell lines that express HLA-ABC are MCF-7 and MDA-MB-231. Our initial results show that HLA-ABC is expressed on the MDA-MB-231 ...


486— Cell Cycle Effect On Hla Expression In Htb-4 And Mrc-5, Nick Turnquist, Andrew Kareeparampil 2020 SUNY Geneseo

486— Cell Cycle Effect On Hla Expression In Htb-4 And Mrc-5, Nick Turnquist, Andrew Kareeparampil

GREAT Day

Human Leukocyte Antigen (HLA) is a gene that codes for cell-surface proteins that are the basis of our bodies’ immune response. We observed two cell lines, HTB-4 and a non-cancerous cell line known as MRC-5. Our purpose for this experiment was to observe the effect of the cell cycle on HLA expression for these cell lines. Two flasks were prepared for each cell line: one confluent and one non-confluent. Flow cytometry analysis was performed for each of the four flasks. The flow cytometry results of the MRC-5 cells indicate increased HLA expression in the confluent flask, in the G1 phase ...


Analysis Of Cyclin E In Fibrolamellar Hepatocellular Carcinoma, Hannah Gustafson, Katrina Vang, Tim Vogt, Sara Stickler 2020 Concordia University St. Paul

Analysis Of Cyclin E In Fibrolamellar Hepatocellular Carcinoma, Hannah Gustafson, Katrina Vang, Tim Vogt, Sara Stickler

Research and Scholarship Symposium Posters

Fibrolamellar Hepatocellular Carcinoma (FL-HCC), a rare primary liver cancer, differs from the most common liver cancer, hepatocellular carcinoma, as FL-HCC is not correlated with chronic liver diseases. Mayo Clinic conducted a proteomic screening and found the proline biosynthetic pathway to be dysregulated in FL-HCC patients. In liver cells, free proline has been shown to induce the mTOR pathway, which stimulates cell proliferation through upregulation of full-length Cyclin E (FL-E). In addition, FL-E can be partially cleaved by an enzyme called serine protease neutrophil elastase, creating low molecular weight cyclin E (LMW-E) that has been linked to tumorigenesis. To further investigate ...


Microrna Expression Profiling Of Normal And Malignant Human Colonic Stem Cells Identifies, Vignesh Viswanathan, Lynn Opdenaker, Shirin Modarai, Jeremy Z Fields, Gregory Gonye, Bruce M Boman 2020 Helen F Graham Cancer Center and Research Institute

Microrna Expression Profiling Of Normal And Malignant Human Colonic Stem Cells Identifies, Vignesh Viswanathan, Lynn Opdenaker, Shirin Modarai, Jeremy Z Fields, Gregory Gonye, Bruce M Boman

Department of Pharmacology and Experimental Therapeutics Faculty Papers

MicroRNAs (miRNAs) have a critical role in regulating stem cells (SCs) during development, and because aberrant expression of miRNAs occurs in various cancers, our goal was to determine if dysregulation of miRNAs is involved in the SC origin of colorectal cancer (CRC). We previously reported that aldehyde dehydrogenase (ALDH) is a marker for normal and malignant human colonic SCs and tracks SC overpopulation during colon tumorigenesis. MicroRNA expression was studied in ALDH-positive SCs from normal and malignant human colon tissues by Nanostring miRNA profiling. Our findings show that: (1) A unique miRNA signature distinguishes ALDH-positive CRC cells from ALDH-positive normal ...


Computational Chemistry - Ulk 101, Michaela Montpas 2020 Olivet Nazarene University

Computational Chemistry - Ulk 101, Michaela Montpas

Scholar Week 2016 - present

Autophagy is a process that generates the necessary building components for cells by cytoplasmic breakdown of unnecessary materials (Martin, Celano, Solitro, Gunaydin, Scott, et. al., 2018). This is a survival technique for cells in times of stress, especially during periods of nutrient starvation. Cancer cells, unfortunately, benefit from this process due to their ability to flourish in nutrient-starved environments, becoming resistant to therapy. The primary protein in mammals responsible for this process is a serine/threonine kinase called ULK 1 (unc-51 like autophagy initiating kinase 1). As such, inhibitors of ULK 1 can be used in cancer therapies in order ...


Tip60 Regulation Of Δnp63Α Is Associated With Cisplatin Resistance, Akshay Hira, Andrew Stacy, Jin Zhang, Michael P. Craig, Madhavi Kadakia 2020 Wright State University - Main Campus

Tip60 Regulation Of Δnp63Α Is Associated With Cisplatin Resistance, Akshay Hira, Andrew Stacy, Jin Zhang, Michael P. Craig, Madhavi Kadakia

Symposium of Student Research, Scholarship, and Creative Activities Materials

About 5.4 million basal and squamous cell skin cancers are diagnosed every year in the US. ΔNp63a, a member of the p53 transcription factor family, is overexpressed in non-melanoma skin cancer and regulates cell survival, migration and invasion. TIP60 is histone acetyltransferase (HAT) which mediates cellular processes such as transcription and the DNA damage response (DDR). Previous studies in our lab have shown that overexpression of TIP60 induces ΔNp63a protein stabilization in a catalytic-dependent manner. Since ΔNp63a is known to transcriptionally regulate several DDR genes and promote cisplatin resistance, its stabilization by TIP60 may contribute to the failure of ...


Functional Blockade Of E-Selectin In Tumor-Associated Vessels Enhances Anti-Tumor Effect Of Doxorubicin In Breast Cancer, Yoshihiro Morita, Macall Leslie, Hiroyasu Kameyama, Ganesh L R Lokesh, Norihisa Ichimura, Rachel Davis, Natalie Hills, Nafis Hasan, Roy Zhang, Yuji Kondo, David G Gorenstein, David E Volk, Inna Chervoneva, Hallgeir Rui, Takemi Tanaka 2020 University of Oklahoma Health Sciences Center

Functional Blockade Of E-Selectin In Tumor-Associated Vessels Enhances Anti-Tumor Effect Of Doxorubicin In Breast Cancer, Yoshihiro Morita, Macall Leslie, Hiroyasu Kameyama, Ganesh L R Lokesh, Norihisa Ichimura, Rachel Davis, Natalie Hills, Nafis Hasan, Roy Zhang, Yuji Kondo, David G Gorenstein, David E Volk, Inna Chervoneva, Hallgeir Rui, Takemi Tanaka

Department of Pharmacology and Experimental Therapeutics Faculty Papers

Chemotherapy is a mainstay of treatment for solid tumors. However, little is known about how therapy-induced immune cell infiltration may affect therapy response. We found substantial CD45+ immune cell density adjacent to E-selectin expressing inflamed vessels in doxorubicin (DOX)-treated residual human breast tumors. While CD45 level was significantly elevated in DOX-treated wildtype mice, it remained unchanged in DOX-treated tumors from E-selectin null mice. Similarly, intravenous administration of anti-E-selectin aptamer (ESTA) resulted in a significant reduction in CD45+ immune cell density in DOX-treated residual tumors, which coincided with a delay in tumor growth and lung metastasis in MMTV-pyMT mice. Additionally ...


Tumor Cell-Organized Fibronectin Maintenance Of A Dormant Breast Cancer Population, Lauren E. Barney, Christopher L. Hall, Alyssa D. Schwartz, Akia N. Parks, Christopher Sparages, Sualyneth Galarza, Manu O. Platt, Arthur M. Mercurio, Shelly R. Peyton 2020 University of Massachusetts Amherst

Tumor Cell-Organized Fibronectin Maintenance Of A Dormant Breast Cancer Population, Lauren E. Barney, Christopher L. Hall, Alyssa D. Schwartz, Akia N. Parks, Christopher Sparages, Sualyneth Galarza, Manu O. Platt, Arthur M. Mercurio, Shelly R. Peyton

Open Access Articles

Tumors can undergo long periods of dormancy, with cancer cells entering a largely quiescent, nonproliferative state before reactivation and outgrowth. To understand the role of the extracellular matrix (ECM) in regulating tumor dormancy, we created an in vitro cell culture system with carefully controlled ECM substrates to observe entrance into and exit from dormancy with live imaging. We saw that cell populations capable of surviving entrance into long-term dormancy were heterogeneous, containing quiescent, cell cycle-arrested, and actively proliferating cells. Cell populations capable of entering dormancy formed an organized, fibrillar fibronectin matrix via alphavbeta3 and alpha5beta1 integrin adhesion, ROCK-generated tension, and ...


Diabetes Mellitus Type 2 Is Associated With Increased Tumor Expression Of Programmed Death-Ligand 1 (Pd-L1) In Surgically Resected Non-Small Cell Lung Cancer - A Matched Case-Control Study, Christopher A. Febres-Aldana, Robert Poppiti, John M. Varlotto, Rick Voland, Michael Zaleski, Setareh Sharzehi, Negar Rassaei 2020 Mount Sinai Medical Center

Diabetes Mellitus Type 2 Is Associated With Increased Tumor Expression Of Programmed Death-Ligand 1 (Pd-L1) In Surgically Resected Non-Small Cell Lung Cancer - A Matched Case-Control Study, Christopher A. Febres-Aldana, Robert Poppiti, John M. Varlotto, Rick Voland, Michael Zaleski, Setareh Sharzehi, Negar Rassaei

Open Access Articles

OBJECTIVES: Programmed death-ligand 1 (PD-L1) expression is a biomarker for cancer immunotherapy. Diabetes mellitus type-2 is a comorbid disease associated with adverse outcomes in Non-Small Cell Lung Cancer (NSCLC). We aimed to investigate the differences in PD-L1 expression in diabetics.

METHODS: A matched case-control cohort of surgically-resected NSCLC was assembled from an early multicenter study (PMID: 19152440). PD-L1 immunohistochemistry (Clone 22C3) was graded by a tumor positive score (TPS) system (TPS0: no staining; TPS1: < 1%; TPS2: 1-49%; TPS3: > /=50%). Variables showing significance at univariate survival analysis were fit in a Cox regression survival model.

RESULTS: Diabetics (n=40) and nondiabetics (n=39) showed no ...


Methylation Of Srd5a2 Promoter Predicts A Better Outcome For Castration-Resistant Prostate Cancer Patients Undergoing Androgen Deprivation Therapy, Zongwei Wang, Tuo Deng, Xingbo Long, Xueming Lin, Shulin Wu, Hongbo Wang, Rongbin Ge, Zhenwei Zhang, Chin-Lee Wu, Mary-Ellen Taplin, Aria F. Olumi 2020 Harvard Medical School

Methylation Of Srd5a2 Promoter Predicts A Better Outcome For Castration-Resistant Prostate Cancer Patients Undergoing Androgen Deprivation Therapy, Zongwei Wang, Tuo Deng, Xingbo Long, Xueming Lin, Shulin Wu, Hongbo Wang, Rongbin Ge, Zhenwei Zhang, Chin-Lee Wu, Mary-Ellen Taplin, Aria F. Olumi

Open Access Articles

PURPOSE: To determine whether SRD5A2 promoter methylation is associated with cancer progression during androgen deprivation therapy (ADT) in CRPC.

PATIENTS AND METHODS: In a Local CRPC cohort, 42 prostatic specimens were collected from patients who were diagnosed as CRPC and underwent transurethral resection of the prostate (TURP) at Massachusetts General Hospital (MGH). In a metastatic CRPC (Met CRPC) cohort, 12 metastatic biopsies were collected from CRPC patients who would be treated with abiraterone plus dutasteride (Clinical Trial NCT01393730). As controls, 36 benign prostatic specimens were collected from patients undergoing prostate reduction surgery for symptoms of bladder outlet obstruction secondary to ...


The Cancer Microbiome: Distinguishing Direct And Indirect Effects Requires A Systemic View, Joao B. Xavier, Amir Mitchell 2020 Memorial Sloan-Kettering Cancer Center

The Cancer Microbiome: Distinguishing Direct And Indirect Effects Requires A Systemic View, Joao B. Xavier, Amir Mitchell

Open Access Articles

The collection of microbes that live in and on the human body - the human microbiome - can impact on cancer initiation, progression, and response to therapy, including cancer immunotherapy. The mechanisms by which microbiomes impact on cancers can yield new diagnostics and treatments, but much remains unknown. The interactions between microbes, diet, host factors, drugs, and cell-cell interactions within the cancer itself likely involve intricate feedbacks, and no single component can explain all the behavior of the system. Understanding the role of host-associated microbial communities in cancer systems will require a multidisciplinary approach combining microbial ecology, immunology, cancer cell biology, and ...


Population Modeling Of Tumor Growth Curves And The Reduced Gompertz Model Improve Prediction Of The Age Of Experimental Tumors, Cristina Vaghi, Anne Rodallec, Raphaelle Fanciullin, Joseph Ciccolini, Jonathan P. Mochel, Michalis Mastri, Clair Poignard, John M. L. Ebos, Sebastien Benzekry 2020 Inria Bordeaux Sud-Ouest

Population Modeling Of Tumor Growth Curves And The Reduced Gompertz Model Improve Prediction Of The Age Of Experimental Tumors, Cristina Vaghi, Anne Rodallec, Raphaelle Fanciullin, Joseph Ciccolini, Jonathan P. Mochel, Michalis Mastri, Clair Poignard, John M. L. Ebos, Sebastien Benzekry

Biomedical Sciences Publications

Tumor growth curves are classically modeled by means of ordinary differential equations. In analyzing the Gompertz model several studies have reported a striking correlation between the two parameters of the model, which could be used to reduce the dimensionality and improve predictive power. We analyzed tumor growth kinetics within the statistical framework of nonlinear mixed-effects (population approach). This allowed the simultaneous modeling of tumor dynamics and inter-animal variability. Experimental data comprised three animal models of breast and lung cancers, with 833 measurements in 94 animals. Candidate models of tumor growth included the exponential, logistic and Gompertz models. The exponential and ...


Peptidylarginine Deiminase Isozyme-Specific Pad2, Pad3 And Pad4 Inhibitors Differentially Modulate Extracellular Vesicle Signatures And Cell Invasion In Two Glioblastoma Multiforme Cell Lines, Pinar Uysal-Onganer, Amy MacLatchy, Rayan Mahmoud, Igor Kraev, Paul R. Thompson, Jameel M. Inal, Sigrun Lange 2020 University of Westminster

Peptidylarginine Deiminase Isozyme-Specific Pad2, Pad3 And Pad4 Inhibitors Differentially Modulate Extracellular Vesicle Signatures And Cell Invasion In Two Glioblastoma Multiforme Cell Lines, Pinar Uysal-Onganer, Amy Maclatchy, Rayan Mahmoud, Igor Kraev, Paul R. Thompson, Jameel M. Inal, Sigrun Lange

Open Access Articles

Glioblastoma multiforme (GBM) is an aggressive adult brain tumour with poor prognosis. Roles for peptidylarginine deiminases (PADs) in GBM have recently been highlighted. Here, two GBM cell lines were treated with PAD2, PAD3 and PAD4 isozyme-specific inhibitors. Effects were assessed on extracellular vesicle (EV) signatures, including EV-microRNA cargo (miR21, miR126 and miR210), and on changes in cellular protein expression relevant for mitochondrial housekeeping (prohibitin (PHB)) and cancer progression (stromal interaction molecule 1 (STIM-1) and moesin), as well as assessing cell invasion. Overall, GBM cell-line specific differences for the three PAD isozyme-specific inhibitors were observed on modulation of EV-signatures, PHB, STIM-1 ...


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