Cancer Biology Commons^™

Epidemiology Of Non-Alcoholic Fatty Liver Disease And Risk Of Hepatocellular Carcinoma Progression, Krishna Chaitanya Thandra, Adam Barsouk, Kalyan Saginala, John Sukumar Aluru, Prashanth Rawla, Alexander Barsouk

Kimmel Cancer Center Faculty Papers

Non-alcoholic fatty liver disease (NAFLD) has become the most common chronic liver disease worldwide. Its incidence has grown alongside the increasing global prevalence of type 2 diabetes, obesity, and metabolic syndrome. The risk of progression to hepatocellular carcinoma for nonalcoholic steatohepatitis patients over 5 years is 8%, and despite targeted and immunotherapy treatment advances, HCC maintains a bleak 5-year survival of 19%. NAFLD’s primary risk factors are components of metabolic syndrome as well as possible sleep disturbances. NAFLD is most common among men 50-60 years of age, though incidence in women catches up after menopause. In the US, Hispanics are …

Mechanisms By Which Mnte-2-Pyp Suppresses Prostate Cancer Cell Growth, Yuxiang Zhu

Theses & Dissertations

Prostate cancer patients are often treated with radiotherapy. MnTE-2-PyP, is a superoxide dismutase (SOD) mimic and a known radioprotector of normal tissues. Our recent work demonstrates that MnTE-2-PyP also inhibits prostate cancer progression with radiotherapy; however, the mechanisms remain unclear. In this thesis, we identified that MnTE-2-PyP-induced intracellular H2O2 levels are critical in inhibiting growth of prostate cancer cells. We found that MnTE-2-PyP induced protein oxidations in PC3 cells and one major group of oxidized protein targets were involved in energy metabolism. The oxidative phosphorylation rates were significantly enhanced in both PC3 and LNCaP cells with MnTE-2-PyP treatment, but mitochondrial …

The Cellular Origin And Molecular Drivers Of Claudin-Low Mammary Cancer, Patrick D. Raedler

Theses & Dissertations

Breast cancers of the claudin-low subtype make up a substantial portion of triple-negative breast cancers and have stem cell-like and mesenchymal features. Although it has been recognized for some time that this breast cancer subtype is highly aggressive and difficult to treat, the molecular drivers and cellular origin of claudin-low breast cancer have been poorly defined. The lack of suitable in vivo models has prohibited the study of tumor initiation and progression of this subtype. In this work, we report two novel mouse models that, upon expression of oncogenic RAS in the mammary epithelium, develop highly metastatic triple-negative mammary tumors …

Targeted Therapies In Select Gastrointestinal Cancers And Cancer Cachexia, Scott Mulder

Theses & Dissertations

Hepatocellular carcinomas exhibit metabolic alterations to support their proliferative and biosynthetic needs. We identified that elevated expression of the mitochondrial oxidative carboxylase, malic enzyme 2 (ME2), correlates with poorer hepatocellular carcinoma patient survival. Hepatocellular carcinoma patient tumors with high ME2 expression exhibit transcriptomic alterations indicative of PI3K/AKT/mTOR and c-Myc signaling as well as elevated central carbon, fatty acid, and redox metabolism pathways. Depletion of ME2 in the hepatocellular carcinoma cell line PLC or in the livers of mice treated with diethylnitrosamine to chemically induce hepatocellular carcinomas, results in impaired proliferation and reduced tumor formation. Additionally, the loss of …

Single-Fluorophore Sensors For Mechanical Force In Living Cells, Sarah Kricheff

Honors Scholar Theses

Mechanotransduction is the process by which a mechanical stimulus is converted to a cellular signal. This process is heavily influential of cell morphology, differentiation, and behavior. However, altered levels of mechanical stimuli are also found in many pathological contexts. For example, cancerous cells have stiffer surrounding tissue than healthy cells, and research suggests that this alters cell behavior and promotes metastasis. Despite these findings, the cellular processes behind these signaling alterations remain widely unknown. Understanding these cascades is critical, as involved proteins can give us a deeper understanding of the role of mechanotransduction, and certain proteins can potentially be targeted …

Translating Evidence-Based Guidelines Into Practice—Are We Getting It Right? A Multi-Centre Prospective International Audit Of Nutrition Care In Patients With Foregut Tumors (Inform), Merran Findlay, Judith D. Bauer, Rupinder Dhaliwal, Marian De Van Der Schueren, Alessandro Laviano, Adrianne Widaman, Lisa Martin, Andrew G. Day, Leah M. Gramlich

Faculty Research, Scholarly, and Creative Activity

Malnutrition is highly prevalent in patients with foregut tumors comprising head and neck (HNC) and esophageal (EC) cancers, negatively impacting outcomes. International evidence-based guidelines (EBGs) for nutrition care exist; however, translation of research evidence into practice commonly presents considerable challenges and consequently lags. This study aimed to describe and evaluate current international nutrition care practices compared with the best-available evidence for patients with foregut tumors who are at high risk of malnutrition. A multi-centre prospective cohort study enrolled 170 patients commencing treatment of curative intent for HNC (n = 119) or EC (n = 51) in 11 cancer …

Pd-L1 Expression On Circulating Tumor Cells May Be Predictive Of Response To Pembrolizumab In Advanced Melanoma: Results From A Pilot Study, Muhammad K. Khattak, Anna L. Reid, James Freeman, Michelle Pereira, Ashleigh Mcevoy, Johnny Lo, Markus Frank, Tarek Meniawy, Ali Didan, Isaac Spencer, Benhur Amanuel, Michael Millward, Mel Ziman, Elin Gray

Research outputs 2014 to 2021

BACKGROUND: PD-1 inhibitors are routinely used for the treatment of advanced melanoma. This study sought to determine whether PD-L1 expression on circulating tumor cells (CTCs) can serve as a predictive biomarker of clinical benefit and response to treatment with the PD-1 inhibitor pembrolizumab.

METHODS: Blood samples were collected from patients with metastatic melanoma receiving pembrolizumab, prior to treatment and 6-12 weeks after initiation of therapy. Multiparametric flow cytometry was used to identify CTCs and evaluate the expression of PD-L1.

RESULTS: CTCs were detected in 25 of 40 patients (63%). Patients with detectable PD-L1

CONCLUSION: Our results reveal the potential of …

Structural Characterization And In Vitro Lipid Binding Studies Of Non-Specific Lipid Transfer Protein 1 (Nsltp1) From Fennel (Foeniculum Vulgare) Seeds, Mekdes Megeressa, Bushra Siraj, Shamshad Zarina, Aftab Ahmed

Pharmacy Faculty Articles and Research

Non-specific lipid transfer proteins (nsLTPs) are cationic proteins involved in intracellular lipid shuttling in growth and reproduction, as well as in defense against pathogenic microbes. Even though the primary and spatial structures of some nsLTPs from different plants indicate their similar features, they exhibit distinct lipid-binding specificities signifying their various biological roles that dictate further structural study. The present study determined the complete amino acid sequence, in silico 3D structure modeling, and the antiproliferative activity of nsLTP1 from fennel (Foeniculum vulgare) seeds. Fennel is a member of the family Umbelliferae (Apiaceae) native to southern Europe and the Mediterranean …

Assessment Of The Potential Anti-Tumour Effect Of Salvia Triloba And The Combination Of Salvia Triloba And Paclitaxel On Ovarian Cancer: Skov3 Cell Line, Naela Adel Mohammed

Archived Theses and Dissertations

No abstract provided.

Subclonal Evolution Of Chronic Lymphocytic Leukemia After Allogeneic T Cell Therapies, Haven Garber

Dissertations & Theses (Open Access)

Subclonal evolution of chronic lymphocytic leukemia after allogeneic T-cell therapies

Haven Garber, MD

Advisory Professor: Jeffrey Molldrem, MD

Intratumoral genetic heterogeneity describes the molecular differences among subclones within a tumor and is a major barrier to effective therapy in many solid and liquid cancers, including chronic lymphocytic leukemia (CLL). Rare, treatment-resistant subclones can expand to compose relapsed disease during tumor evolution. Examination of malignant evolution in the context of specific treatment provides insight into the molecular lesions that mediate therapeutic response and resistance. Both chemotherapy and targeted therapy were shown to precipitate CLL subclonal evolution. We hypothesized that allogeneic T-cell …

P53 Drives A Transcriptional Program That Elicits A Non-Cell-Autonomous Response And Alters Cell State In Vivo, Sydney Moyer

Dissertations & Theses (Open Access)

Cell stress and DNA damage activate the tumor suppressor p53, triggering transcriptional activation of a myriad of target genes. The molecular, morphological, and physiological consequences of this activation remain poorly understood in vivo. We activated a p53 transcriptional program in mice by deletion of Mdm2, a gene which encodes the major p53 inhibitor. By overlaying tissue-specific RNA-sequencing data from pancreas, small intestine, ovary, kidney, and heart with existing p53 ChIP-sequencing, we identified a large repertoire of tissue-specific p53 genes and a common p53 transcriptional signature of seven genes which included Mdm2 but not p21. Global p53 activation …

A Functional Three-Dimensional Microphysiological Model Of Myeloma Bone Disease, Richard Visconti

Seton Hall University Dissertations and Theses (ETDs)

Multiple myeloma (MM) is a hematologic cancer caused by a mature B cell neoplasm, or plasmacytoma, that infiltrates the skeleton at several sites. The disease is characterized by uninhibited transformed plasma cell proliferation that disrupts skeletal homeostasis leading to decreased bone modeling and increased bone resorption. Osteolytic lesions (OL) or voids left in the bone, remain long after the treatment of the cancer and indicate disease progression to myeloma bone disease (MBD). Current combinatorial MM therapies inhibit malignant plasma cell proliferation, slow the progression towards MBD, and increase the mean five-year survival rate, but do little to improve osteoblastic function …

Micrornas Associated With Melanoma Inflammation And Response To Pd-1 Inhibition, Robert Szczepaniak Sloane

Dissertations & Theses (Open Access)

Melanoma is an aggressive malignancy of melanocytes with historically poor outcomes. Melanoma therapy has improved markedly over the past decade with advances in molecularly targeted agents and immunotherapies. Immune checkpoint inhibitors achieve T-cell mediated anti-tumor efficacy by blocking engagement of inhibitory checkpoints on T-cells to overcome immunosuppressive signals from tumor cells and the broader microenvironment. Despite these advances, there are a significant proportion of patients who do not benefit from existing immunotherapy strategies making it a priority to identify and target the mechanisms that confer resistance to therapy. We demonstrate that microRNAs are accurate markers of microenvironment composition with prognostic …

Fibroblast Heterogeneity In Pancreatic Cancer Immunity, Josephine Darpolor

Dissertations & Theses (Open Access)

Fibroblasts are a unique cell type defined by their mesenchymal phenotype and exclusion from epithelial, immune, and endothelial cell subsets. Although well studied in wound healing, cancer associated fibroblasts (CAFs) are incredibly heterogeneous, leading to contradictions as to the roles CAFs play in the tumor microenvironment (TME). CAFs were thought to be a barrier to treatment of pancreatic ductal adenocarcinoma (PDAC). However, general stromal targeting strategies have largely failed in the clinic likely due to the heterogeneity of CAFs in the TME. Therefore, our groups and others have worked to unravel the heterogeneity of CAFs in PDAC. In the works …

Conditional Distance Correlation Test For Gene Expression Level, Dna Methylation Level And Copy Number, Shanshan Zhang

Graduate Theses and Dissertations

Over the past years, efforts have been devoted to the genome-wide analysis of genetic and epigenetic profiles to better understand the underlying biological mechanisms of complex diseases such as cancer. It is of great importance to unravel the complex dependence structure between biological factors, and many conditional dependence tests have been developed to meet this need. The traditional partial correlation method can only capture the linear partial correlation, but not the nonlinear correlation. To overcome this limitation, we propose to use the innovative conditional distance correlation (CDC), which measures the conditional dependence between random vectors and detect nonlinear relations. In …

Immunohistochemical Localization Of Prolactin Receptor (Prlr) To Hodgkin's And Reed-Sternberg Cells Of Hodgkin's Lymphoma, Rajendra Gharbaran, Onyekwere Onwumere, Naomi Codrington, Latchman Somenarian, Stephen Redenti

Publications and Research

Prolactin receptor (PRLR), a type-1 cytokine receptor, is overexpressed in a number of cancer types. It has attracted much attention for putative pro-oncogenic roles, which however, remains controversial in some malignancies. In this study, we reported the localization of PRLR to the Hodgkin's and Reed-Sternberg (HRS) cells of Hodgkin's lymphoma (HL), a neoplasm of predominantly B cell origin. Immunohistochemistry performed on 5-μm thick FFPE sections revealed expression of PRLR in HRS cells. Cellular immunofluorescence experiments showed that the HL-derived cell lines, Hs445, KMH2 and L428 overexpressed PRLR. The PRLR immunofluorescent signal was depleted after treating the cell lines with 10 …

Hpv Mediated Antagonism Of The Il-18 Proinflammatory Pathway In Head And Neck Cancer, Wyatt W. Anderson

Electronic Thesis and Dissertation Repository

In this thesis, I examined the effect of human papillomavirus (HPV) on the proinflammatory IL-18 cytokine pathway in head and neck cancers. I investigated the expression and methylation of genes associated with this pathway using The Cancer Genome Atlas (TCGA) data. In HPV+ cancers, IL18, CASP1, and AIM2 were downregulated, while IL18BP was upregulated compared to HPV- cancers and adjacent non-cancerous tissues, and IL18’s promoter was significantly more methylated. I compared HPV+ and HPV- head and neck cancer cell lines for expression of RNA and protein levels of IL-18 and IL-18BP by qPCR, western blot, and ELISA. IL-18 …

Heavy Is The Head That Wears The Crown: Black Men’S Perspective On Harmful Effects Of Hair Product Use And Breast Cancer Risk, Dede K. Teteh, Marissa Chan, Bing Turner, Brian Hedgeman, Marissa Ericson, Phyllis Clark, Eudora Mitchell, Emily Barrett, Adana Llanos, Rick Kittles, Susanne Montgomery

Health Sciences and Kinesiology Faculty Articles

Racial disparities in breast cancer are well-documented, and Black women assume a disproportionate burden of breast cancer mortality. Black women also commonly use hair products containing endocrine disrupting chemicals (EDCs) more often at an increased rate, as compared to other racial/ethnic groups. Emerging findings have reported the use of hair and other personal care products containing EDCs may contribute to breast cancer risk. While some sociocultural perspectives about hair and identity have been explored, the role of beauty expectations upheld by males has not been studied. Through a community-based participatory methodology, we explored perceptions and beliefs held by Black men …

Hitting The Bullseye: Are Extracellular Vesicles On Target?, Nicole Noren Hooten, María Yáñez-Mó, Rachel M. Derita, Ashley Russell, Peter Quesenberry, Bharat Ramratnam, Paul D Robbins, Dolores Di Vizio, Sicheng Wen, Kenneth W Witwer, Lucia R Languino

Department of Cancer Biology Faculty Papers

No abstract provided.

Kdm5b Is Essential For The Hyperactivation Of Pi3k/Akt Signaling In Prostate Tumorigenesis, Guoliang Li, Thanigaivelan Kanagasabai, Wenfu Lu, Mike R. Zou, Shang-Min Zhang, Sherly I. Celada, Michael G. Izban, Qi Liu, Tao Lu, Billy R. Ballard, Xinchun Zhou, Samuel E. Adunyah, Robert J. Matusik, Qin Yan, Zhenbang Chen

Biology Student Research

KDM5B (lysine[K]-specific demethylase 5B) is frequently upregulated in various human cancers including prostate cancer. KDM5B controls H3K4me3/2 levels and regulates gene transcription and cell differentiation, yet the contributions of KDM5B to prostate cancer tumorigenesis remain unknown. In this study, we investigated the functional role of KDM5B in epigenetic dysregulation and prostate cancer progression in cultured cells and in mouse models of prostate epithelium–specific mutant Pten/Kdm5b. Kdm5b deficiency resulted in a significant delay in the onset of prostate cancer in Pten-null mice, whereas Kdm5b loss alone caused no morphologic abnormalities in mouse prostates. At 6 months of age, the prostate weight …

Biomechanical And Biophysical Properties Of Breast Cancer Cells Under Varying Glycemic Regimens, Diganta Dutta, Xavier-Lewis Palmer, Jose Ortega-Rodas, Vasundhara Balraj, Indrani Ghosh Dastider, Surabhi Chandra

Electrical & Computer Engineering Faculty Publications

Diabetes accelerates cancer cell proliferation and metastasis, particularly for cancers of the pancreas, liver, breast, colon, and skin. While pathways linking the 2 disease conditions have been explored extensively, there is a lack of information on whether there could be cytoarchitectural changes induced by glucose which predispose cancer cells to aggressive phenotypes. It was thus hypothesized that exposure to diabetes/high glucose alters the biomechanical and biophysical properties of cancer cells more than the normal cells, which aids in advancing the cancer. For this study, atomic force microscopy indentation was used through microscale probing of multiple human breast cancer cells (MCF-7, …

Pan-Cancer Analysis Of Telomerase Reverse Transcriptase (Tert) Isoforms, Mathushan Subasri

Electronic Thesis and Dissertation Repository

Reactivation of the multi-subunit ribonucleoprotein telomerase is the primary telomere maintenance mechanism in cancer, but it is rate-limited by the enzymatic component, telomerase reverse transcriptase (TERT). While regulatory in nature, TERT alternative splice variant/isoform regulation and functions are not fully elucidated and are further complicated by their highly diverse expression. In this thesis, I characterized TERT expression across normal and neoplastic tissues using TCGA and GTEx RNA-sequencing data. In doing so, I demonstrated the global overexpression and splicing shift towards full-length TERT in neoplastic tissue. Furthermore, my studies identified tumour subtype expression differences possibly regulated by subtype-specific characteristics, detailed heterogeneity …

Effects Of Germline And Somatic Events In Candidate Brca-Like Genes On Breast-Tumor Signatures, Weston R. Bodily, Brian H. Shirts, Tom Walsh, Suleyman Gulsuner, Mary-Claire King, Alyssa Parker, Moom Roosan, Stephen R. Piccolo

Pharmacy Faculty Articles and Research

Mutations in BRCA1 and BRCA2 cause deficiencies in homologous recombination repair (HR), resulting in repair of DNA double-strand breaks by the alternative non-homologous end-joining pathway, which is more error prone. HR deficiency of breast tumors is important because it is associated with better responses to platinum salt therapies and PARP inhibitors. Among other consequences of HR deficiency are characteristic somatic-mutation signatures and gene-expression patterns. The term “BRCA-like” (or “BRCAness”) describes tumors that harbor an HR defect but have no detectable germline mutation in BRCA1 or BRCA2. A better understanding of the genes and molecular events associated with tumors being …

Rho Gtpases: Big Players In Breast Cancer Initiation, Metastasis And Therapeutic Responses, Brock Humphries, Zhishan Wang, Chengfeng Yang

Toxicology and Cancer Biology Faculty Publications

Rho GTPases, a family of the Ras GTPase superfamily, are key regulators of the actin cytoskeleton. They were originally thought to primarily affect cell migration and invasion; however, recent advances in our understanding of the biology and function of Rho GTPases have demonstrated their diverse roles within the cell, including membrane trafficking, gene transcription, migration, invasion, adhesion, survival and growth. As these processes are critically involved in cancer initiation, metastasis and therapeutic responses, it is not surprising that studies have demonstrated important roles of Rho GTPases in cancer. Although the majority of data indicates an oncogenic role of Rho GTPases, …

Upregulation Of Cpt1a Is Essential For The Tumor-Promoting Effect Of Adipocytes In Colon Cancer, Xiaopeng Xiong, Yang-An Wen, Rachelle Fairchild, Yekaterina Y. Zaytseva, Heidi L. Weiss, B. Mark Evers, Tianyan Gao

Markey Cancer Center Faculty Publications

Colon tumors grow in an adipose tissue-enriched microenvironment. Locally advanced colon cancers often invade into surrounding adipose tissue with a direct contact with adipocytes. We have previously shown that adipocytes promote tumor growth by modulating cellular metabolism. Here we demonstrate that carnitine palmitoyltransferase I (CPT1A), a key enzyme controlling fatty acid oxidation (FAO), was upregulated in colon cancer cells upon exposure to adipocytes or fatty acids. In addition, CPT1A expression was increased in invasive tumor cells within the adipose tissue compared to tumors without direct contact with adipocytes. Silencing CPT1A abolished the protective effect provided by fatty acids against nutrient …

Develop A High-Throughput Screening Method To Identify C-P4h1 (Collagen Prolyl 4-Hydroxylase 1) Inhibitors From Fda-Approved Chemicals, Shike Wang, Kuo-Hao Lee, Nathália Victoria Araujo, Chang-Guo Zhan, Vivek M. Rangnekar, Ren Xu

Pharmaceutical Sciences Faculty Publications

Collagen prolyl 4-hydroxylase 1 (C-P4H1) is an α-ketoglutarate (α-KG)-dependent dioxygenase that catalyzes 4-hydroxylation of proline on collagen. C-P4H1-induced prolyl hydroxylation is required for proper collagen deposition and cancer metastasis. Therefore, targeting C-P4H1 is considered a potential therapeutic strategy for collagen-related cancer progression and metastasis. However, no C-P4H1 inhibitors are available for clinical testing, and the high content assay is currently not available for C-P4H1 inhibitor screening. In the present study, we developed a high-throughput screening assay by quantifying succinate, a byproduct of C-P4H-catalyzed hydroxylation. C-P4H1 is the major isoform of collagen prolyl 4-hydroxylases (CP4Hs) that contributes the majority prolyl 4-hydroxylase …

Expression And Localization Of The 14-3-3 (Ywha) Protein Family Within Mammals, Neha Kumrah, Santanu De

Mako: NSU Undergraduate Student Journal

The 14-3-3 (YWHA) are a family of homologous, acidic, and highly conserved proteins expressed abundantly and ubiquitously in a wide array of organisms ranging from plants to animals, including humans, which regulate important cellular events. Within mammals, seven isoforms of 14-3-3 exist: β, γ, ε, ζ, η, τ, and σ (stratifin), each of which is encoded by a unique gene. Studies have shown similar expression patterns among mammalian species. The 14-3-3 proteins are commonly expressed and have proven to play critical roles in proper cellular localization, function, and homeostatic regulation. Numerous researchers have investigated the expression and localization patterns of …

Luteolin Induces Cytotoxicity In Mix Cellularity Classical Hodgkin's Lymphoma Via Caspase Activated-Cell Death, Rajendra Gharbaran, Enyuan Shang, Onyekwere Onwumere, Naomi Codrington, Evangelina Dankwa Sarpong, Stephen M. Redenti

Publications and Research

Background/aim: We investigated the effects of luteolin (LUT) on classical Hodgkin's lymphoma (cHL), since such studies in malignant lymphomas are lacking.

Materials and methods: Effect of LUT on cell growth was assessed with water-soluble tetrazolium 1 (WST-1) cell proliferation assay and automated hemocytometry on trypan blue-exclusion assay. Cell death was investigated with acridine orange/ethidium bromide live-dead assay, propidium iodide (PI) flow cytometry, and Annexin-V-PI microscopy. Caspase activation was studied using CellEvent Caspase-3/7 Green detection reagent. High resolution immunofluorescence microscopy was used to detect cleaved-PARP-1.

Results: LUT induced a dose-dependent decrease in the growth of KMH2 and L428 cells, cellular models …

Eating Broccoli: Can It Protect Cancer Patients From Radiation Skin Damage?, Huong Pham

The Journal of Purdue Undergraduate Research

No abstract provided.

Igf-1r Inhibition Induces Mek Phosphorylation To Promote Survival In Colon Carcinomas, Qing Wang, Yan Zhang, Jiang Zhu, Honggang Zheng, Shuntai Chen, Li Chen, Hsin-Sheng Yang

Toxicology and Cancer Biology Faculty Publications

The insulin-like growth factor 1 receptor (IGF-1R) governs several signaling pathways for cell proliferation, survival, and anti-apoptosis. Thus, targeting IGF-1R appears as a reasonable rationale for tumor treatment. However, clinical studies showed that inhibition of IGF-1R has very limited efficacy due to the development of resistance to IGF-1R blockade in tumor cells. Here, we discovered that prolonged treatment of colon cancer cells with IGF-1R inhibitors (BMS-754807 and GSK1838705A) stimulates p70 KDa ribosomal protein S6 kinase 1 (p70S6K1) activation, a well-known kinase signaling for cell survival. We also found that p70S6K1 activation by IGF-1R inhibition is independent of K-Ras and PIK3CA …