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Preliminary Study: Leucine Supplementation Exacerbates Muscle Wasting Independent Of The Ubiquitin-Proteasome System, Katarina Bejarano 2020 University of Arkansas, Fayetteville

Preliminary Study: Leucine Supplementation Exacerbates Muscle Wasting Independent Of The Ubiquitin-Proteasome System, Katarina Bejarano

Graduate Theses and Dissertations

Cancer cachexia is the rapid, drastic loss of muscle mass associated with cancer and is not reversible by conventional nutritional means (Brown et al., 2018; Brown et al., 2017). It occurs in ~80% of cancer patients and is responsible for 20-40% of cancer-related deaths (Brown et al., 2018; Brown et al., 2017). This condition leaves patients with fatigue, functional impairment, reduced quality of life, and a decrease in survival rates. Cachexia occurs through an imbalance between protein degradation and protein synthesis (Brown et al., 2018), which is associated with inflammation and altered metabolic processes.

Several studies have investigated the effects ...


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 ...


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 ...


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 ...


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 ...


Loss Of C-Jun N-Terminal Kinase 1 And 2 Function In Liver Epithelial Cells Triggers Biliary Hyperproliferation Resembling Cholangiocarcinoma, Francisco Javier Cubero, Mohamed Ramadan Mohamed, Marius M. Woitok, Gang Zhao, Maximilian Hatting, Yulia A. Nevzorova, Chaobo Chen, Johannes Haybaeck, Alain de Bruin, Matias A. Avila, Mark V. Boekschoten, Roger J. Davis, Christian Trautwein 2020 Complutense University of Madrid

Loss Of C-Jun N-Terminal Kinase 1 And 2 Function In Liver Epithelial Cells Triggers Biliary Hyperproliferation Resembling Cholangiocarcinoma, Francisco Javier Cubero, Mohamed Ramadan Mohamed, Marius M. Woitok, Gang Zhao, Maximilian Hatting, Yulia A. Nevzorova, Chaobo Chen, Johannes Haybaeck, Alain De Bruin, Matias A. Avila, Mark V. Boekschoten, Roger J. Davis, Christian Trautwein

University of Massachusetts Medical School Faculty Publications

Targeted inhibition of the c-Jun N-terminal kinases (JNKs) has shown therapeutic potential in intrahepatic cholangiocarcinoma (CCA)-related tumorigenesis. However, the cell-type-specific role and mechanisms triggered by JNK in liver parenchymal cells during CCA remain largely unknown. Here, we aimed to investigate the relevance of JNK1 and JNK2 function in hepatocytes in two different models of experimental carcinogenesis, the dethylnitrosamine (DEN) model and in nuclear factor kappa B essential modulator (NEMO)(hepatocyte-specific knockout (Deltahepa)) mice, focusing on liver damage, cell death, compensatory proliferation, fibrogenesis, and tumor development. Moreover, regulation of essential genes was assessed by reverse transcription polymerase chain reaction, immunoblottings ...


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 ...


Role Of Bet Inhibitors In Triple Negative Breast Cancers, Durga Khandekar, Venkataswarup Tiriveedhi 2020 Tennessee State University

Role Of Bet Inhibitors In Triple Negative Breast Cancers, Durga Khandekar, Venkataswarup Tiriveedhi

Biology Faculty Research

Bromodomain and extraterminal domain (BET) proteins have evolved as key multifunctional super-regulators that control gene expression. These proteins have been shown to upregulate transcriptional machinery leading to over expression of genes involved in cell proliferation and carcinogenesis. Based on favorable preclinical evidence of BET inhibitors in various cancer models; currently, 26 clinical trials are underway in various stages of study on various hematological and solid organ cancers. Unfortunately, preliminary evidence for these clinical studies does not support the application of BET inhibitors as monotherapy in cancer treatment. Furthermore, the combinatorial efficiency of BET inhibitors with other chemo-and immunotherapeutic agents remain ...


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 Publications by UMMS Authors

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 ...


Editorial: The Role Of Breast Cancer Stem Cells In Clinical Outcomes, Dayanidhi Raman, Amit K. Tiwari, Venkataswarup Tiriveedhi, Julie A. Rhoades 2020 University of Toledo

Editorial: The Role Of Breast Cancer Stem Cells In Clinical Outcomes, Dayanidhi Raman, Amit K. Tiwari, Venkataswarup Tiriveedhi, Julie A. Rhoades

Biology Faculty Research

No abstract provided.


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 Publications by UMMS Authors

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 ...


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 Publications by UMMS Authors

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 ...


The Role Of Type I Interferon In Vitiligo Pathogenesis And Melanoma Immunotherapy, Rebecca L. Riding 2020 University of Massachusetts Medical School

The Role Of Type I Interferon In Vitiligo Pathogenesis And Melanoma Immunotherapy, Rebecca L. Riding

GSBS Dissertations and Theses

Vitiligo is an autoimmune skin disease in which the pigment producing cells of the epidermis, melanocytes, are targeted for destruction by CD8+ T cells specific for melanocyte/melanoma-shared antigens. Previous work has identified IFNg as the central cytokine driving disease pathogenesis in both human patients and in our mouse model of vitiligo. IFNg signaling induces production of the chemokines CXCL9 and CXCL10, which trigger autoreactive T cell migration into the epidermis where effector T cells can target and destroy melanocytes. However, both IFNg and type I IFN signaling through activation of STAT1 proteins can induce transcription of the chemokines CXCL9 ...


Perplexing Role Of P-Glycoprotein In Tumor Microenvironment, Kianna Robinson, Venkataswarup Tiriveedhi 2020 Tennessee State University

Perplexing Role Of P-Glycoprotein In Tumor Microenvironment, Kianna Robinson, Venkataswarup Tiriveedhi

Biology Faculty Research

Development of multidrug resistance (MDR) still remains a major obstacle to the long-term success of cancer therapy. P-glycoprotein (P-gp) is a well-identified membrane transporter with capability to efflux drug molecules out of the cancer cell leading to reduced efficiency of chemotherapy. Cancer cells upregulate P-gp expression as an adaptive response to evade chemotherapy mediated cell death. While several P-gp inhibitors have been discovered by in silico and pre-clinical studies, very few have successfully passed all phases of the clinical trials. Studies show that application of P-gp inhibitors in cancer therapy regimen following development of MDR achieved limited beneficial outcomes. While ...


Modulation Of The Pol Ii Ctd Phosphorylation Code By Rac1 And Cdc42 Small Gtpases In Cultured Human Cancer Cells And Its Implication For Developing A Synthetic-Lethal Cancer Therapy, Bo Zhang, Xuelin Zhong, Moira Sauane, Yihong Zhao, Zhi-Liang Zheng 2020 Wenzhou-Kean University

Modulation Of The Pol Ii Ctd Phosphorylation Code By Rac1 And Cdc42 Small Gtpases In Cultured Human Cancer Cells And Its Implication For Developing A Synthetic-Lethal Cancer Therapy, Bo Zhang, Xuelin Zhong, Moira Sauane, Yihong Zhao, Zhi-Liang Zheng

Publications and Research

Rho GTPases, including Rho, Cdc42, Rac and ROP subfamilies, are key signaling molecules in RNA polymerase II (Pol II) transcriptional control. Our prior work has shown that plant ROP and yeast Cdc42 GTPases similarly modulate Ser2 and Ser5 phosphorylation status of the C-terminal domain (CTD) of the Pol II largest subunit by regulating CTD phosphatase degradation. Here, we present genetic and pharmacological evidence showing that Cdc42 and Rac1 GTPase signaling modulates a similar CTD Ser2 and Ser5 phosphorylation code in cultured human cancer cells. While siRNA knockdown of Cdc42 and Rac1, respectively, in HeLa cells increased the level of CTD ...


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 Publications by UMMS Authors

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 ...


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