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Anti-Cancer Effects Of Oleocanthal And Extra Virgin Olive Oil, Limor Goren 2019 The Graduate Center, City University of New York

Anti-Cancer Effects Of Oleocanthal And Extra Virgin Olive Oil, Limor Goren

All Dissertations, Theses, and Capstone Projects

Oleocanthal is a phenolic compound found in varying concentrations in extra virgin olive oil. Oleocanthal has been shown to be active physiologically, benefiting several diseased states by conferring anti-inflammatory and neuroprotective benefits. Recently, we and other groups have demonstrated its specific and selective toxicity toward cancer cells; however, the mechanism leading to cancer cell death is still disputed. The current study demonstrates that oleocanthal induced damage to cancer cells’ lysosomes leading to cellular toxicity in vitro. Non-cancer cells were significantly less affected. Lysosomal membrane permeabilization following oleocanthal treatment in various cell lines was assayed via three complementary methods. Additionally, we ...


Tumor Cell-Organized Fibronectin Is Required To Maintain 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 2019 University of Massachusetts Amherst

Tumor Cell-Organized Fibronectin Is Required To Maintain 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

Arthur M. Mercurio

Tumors can undergo long periods of dormancy, with cancer cells entering a largely quiescent, non-proliferative state before reactivation and outgrowth. For a patient, these post-remission tumors are often drug resistant and highly aggressive, resulting in poor prognosis. To understand the role of the extracellular matrix (ECM) in regulating tumor dormancy, we created an in vitro cell culture system that combines carefully controlled ECM substrates with nutrient deprivation 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 ...


Identification Of Essential Genes In Hepatocellular Carcinomas Using Crispr Screening, Ankur Sheel 2019 University of Massachusetts Medical School

Identification Of Essential Genes In Hepatocellular Carcinomas Using Crispr Screening, Ankur Sheel

GSBS Dissertations and Theses

Hepatocellular carcinoma (HCC) is an aggressive subtype of liver cancer with a poor prognosis. Currently, prognosis for HCC patients remains poor as few therapies are available. The clinical need for more effective HCC treatments remains unmet partially because HCC is genetically heterogeneous and HCC driver genes amenable to targeted therapy are largely unknown. Mutations in the TP53 gene are found in ~30% of HCC patients and confer poor prognosis to patients. Identifying genes whose depletion can inhibit HCC growth, and determining the mechanisms involved, will aid the development of targeted therapies for HCC patients. Therefore, the first half of this ...


Edb-Fn Targeted Peptide–Drug Conjugates For Use Against Prostate Cancer, Shang Eun Park, Kiumars Shamloo, Timothy A. Kristedja, Shaban Darwish, Marco Bisoffi, Keykavous Parang, Rakesh Tiwari 2019 Chapman University

Edb-Fn Targeted Peptide–Drug Conjugates For Use Against Prostate Cancer, Shang Eun Park, Kiumars Shamloo, Timothy A. Kristedja, Shaban Darwish, Marco Bisoffi, Keykavous Parang, Rakesh Tiwari

Pharmacy Faculty Articles and Research

Prostate cancer (PCa) is the most common malignancy in men and is the leading cause of cancer-related male mortality. A disulfide cyclic peptide ligand [CTVRTSADC] 1 has been previously found to target extra domain B of fibronectin (EDB-FN) in the extracellular matrix that can dierentiate aggressive PCa from benign prostatic hyperplasia. We synthesized and optimized the stability of ligand 1 by amide cyclization to obtain [KTVRTSADE] 8 using Fmoc/tBu solid-phase chemistry. Optimized targeting ligand 8 was found to be stable in phosphate buered saline (PBS, pH 6.5, 7.0, and 7.5) and under redox conditions, with a ...


Tumor Cell-Organized Fibronectin Is Required To Maintain 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 2019 University of Massachusetts Amherst

Tumor Cell-Organized Fibronectin Is Required To Maintain 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

University of Massachusetts Medical School Faculty Publications

Tumors can undergo long periods of dormancy, with cancer cells entering a largely quiescent, non-proliferative state before reactivation and outgrowth. For a patient, these post-remission tumors are often drug resistant and highly aggressive, resulting in poor prognosis. To understand the role of the extracellular matrix (ECM) in regulating tumor dormancy, we created an in vitro cell culture system that combines carefully controlled ECM substrates with nutrient deprivation 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 ...


Aryl Hydrocarbon Receptor Nuclear Translocator-Like (Arntl/Bmal1) Is Associated With Bevacizumab Resistance In Colorectal Cancer Via Regulation Of Vascular Endothelial Growth Factor A., Elke Burgermeister, Francesca Battaglin, Fagr Eladly, Wen Wu, Frank Herweck, Nadine Schulte, Johannes Betge, Nicolai Härtel, Jakob N. Kather, Cleo-Aron Weis, Timo Gaiser, Alexander Marx, Christel Weiss, Ralf Hofheinz, Ian S. Miller, Fotios Loupakis, Heinz-Josef Lenz, Annette T. Byrne, Matthias P. Ebert 2019 University of Heidelberg

Aryl Hydrocarbon Receptor Nuclear Translocator-Like (Arntl/Bmal1) Is Associated With Bevacizumab Resistance In Colorectal Cancer Via Regulation Of Vascular Endothelial Growth Factor A., Elke Burgermeister, Francesca Battaglin, Fagr Eladly, Wen Wu, Frank Herweck, Nadine Schulte, Johannes Betge, Nicolai Härtel, Jakob N. Kather, Cleo-Aron Weis, Timo Gaiser, Alexander Marx, Christel Weiss, Ralf Hofheinz, Ian S. Miller, Fotios Loupakis, Heinz-Josef Lenz, Annette T. Byrne, Matthias P. Ebert

Physiology and Medical Physics Articles

BACKGROUND: The identification of new biomarkers and the development of novel, targetable contexts of vulnerability are of urgent clinical need in drug-resistant metastatic colorectal cancer (mCRC). Aryl-Hydrocarbon-Receptor-Nuclear-Translocator-Like (ARNTL/BMAL1) is a circadian clock-regulated transcription factor promoting expression of genes involved in angiogenesis and tumour progression. We hypothesised that BMAL1 increases expression of the vascular endothelial growth factor A VEGFA gene and, thereby, confers resistance to anti-angiogenic therapy with bevacizumab (Beva), a clinically used antibody for neutralization of VEGFA.

METHODS: PCR and immunohistochemistry were employed to assess BMAL1 expression in mice (C57BL/6 J

FINDINGS: In murine CRCs, high BMAL1 expression ...


Gene Expression Signature Of Atypical Breast Hyperplasia And Regulation By Sfrp1, Kelly J. Gregory, Giovanna M. Crisi, Brooke A. Bentley, Grace Makari-Judson, Holly S. Mason, Jun Yu, Lihua Julie Zhu, Karl J. Simin, Jacob P. S. Johnson, Ashraf Khan, Sallie S. Schneider, D. Joseph Jerry 2019 Pioneer Valley Life Sciences Institute

Gene Expression Signature Of Atypical Breast Hyperplasia And Regulation By Sfrp1, Kelly J. Gregory, Giovanna M. Crisi, Brooke A. Bentley, Grace Makari-Judson, Holly S. Mason, Jun Yu, Lihua Julie Zhu, Karl J. Simin, Jacob P. S. Johnson, Ashraf Khan, Sallie S. Schneider, D. Joseph Jerry

Open Access Articles

BACKGROUND: Atypical breast hyperplasias (AH) have a 10-year risk of progression to invasive cancer estimated at 4-7%, with the overall risk of developing breast cancer increased by ~ 4-fold. AH lesions are estrogen receptor alpha positive (ERalpha+) and represent risk indicators and/or precursor lesions to low grade ERalpha+ tumors. Therefore, molecular profiles of AH lesions offer insights into the earliest changes in the breast epithelium, rendering it susceptible to oncogenic transformation.

METHODS: In this study, women were selected who were diagnosed with ductal or lobular AH, but no breast cancer prior to or within the 2-year follow-up. Paired AH and ...


Pathognomonic And Epistatic Genetic Alterations In B-Cell Non-Hodgkin Lymphoma, Man Chun John Ma, Benjamin J. Chen, Michael R. Green 2019 The University of Texas MD Anderson Cancer Center

Pathognomonic And Epistatic Genetic Alterations In B-Cell Non-Hodgkin Lymphoma, Man Chun John Ma, Benjamin J. Chen, Michael R. Green

University of Massachusetts Medical School Faculty Publications

B-cell non-Hodgkin lymphoma (B-NHL) encompasses multiple clinically and phenotypically distinct subtypes of malignancy with unique molecular etiologies. Common subtypes of B-NHL such as diffuse large B-cell lymphoma (DLBCL) have been comprehensively interrogated at the genomic level, but other less common subtypes such as mantle cell lymphoma (MCL) remain sparsely characterized. Furthermore, multiple B-NHL subtypes have thus far not been comprehensively compared to identify conserved or subtype-specific patterns of genomic alterations. Here, we employed a large targeted hybrid-capture sequencing approach encompassing 380 genes to interrogate the genomic landscapes of 755 B-NHL tumors at high depth; primarily including DLBCL, MCL, follicular lymphoma ...


Somatic Molecular Analysis Augments Cytologic Evaluation Of Pancreatic Cyst Fluids As A Diagnostic Tool, Ali Sakhdari, Parnian Ahmadi Moghaddam, Chi Young Ok, Otto Walter, Keith Tomaszewicz, Mandi-Lee Caporelli, Xiuling Meng, Jennifer LaFemina, Giles F. Whalen, Edward Belkin, Jaroslav Zivny, Wahid Y. Wassef, Bruce A. Woda, Lloyd Hutchinson, Ediz F. Cosar 2019 University of Massachusetts Medical School

Somatic Molecular Analysis Augments Cytologic Evaluation Of Pancreatic Cyst Fluids As A Diagnostic Tool, Ali Sakhdari, Parnian Ahmadi Moghaddam, Chi Young Ok, Otto Walter, Keith Tomaszewicz, Mandi-Lee Caporelli, Xiuling Meng, Jennifer Lafemina, Giles F. Whalen, Edward Belkin, Jaroslav Zivny, Wahid Y. Wassef, Bruce A. Woda, Lloyd Hutchinson, Ediz F. Cosar

Open Access Articles

Objective: Better tools are needed for early diagnosis and classification of pancreatic cystic lesions (PCL) to trigger intervention before neoplastic precursor lesions progress to adenocarcinoma. We evaluated the capacity of molecular analysis to improve the accuracy of cytologic diagnosis for PCL with an emphasis on non-diagnostic/negative specimens.

Design: In a span of 7 years, at a tertiary care hospital, 318 PCL endoscopic ultrasound-guided fine needle aspirations (EUS-FNA) were evaluated by cytologic examination and molecular analysis. Mucinous PCL were identified based on a clinical algorithm and 46 surgical resections were used to verify this approach. The mutation allele frequency (MAF ...


Extracellular-Signal Regulated Kinase: A Central Molecule Driving Epithelial-Mesenchymal Transition In Cancer, Monserrat Olea-Flores, Miriam Daniela Zuniga-Eulogio, Miguel Angel Mendoza-Catalan, Hugo Alberto Rodriguez-Ruiz, Eduardo Castaneda-Saucedo, Carlos Ortuno-Pineda, Teresita Padilla-Benavides, Napoleon Navarro-Tito 2019 Autonomous University of Guerrero

Extracellular-Signal Regulated Kinase: A Central Molecule Driving Epithelial-Mesenchymal Transition In Cancer, Monserrat Olea-Flores, Miriam Daniela Zuniga-Eulogio, Miguel Angel Mendoza-Catalan, Hugo Alberto Rodriguez-Ruiz, Eduardo Castaneda-Saucedo, Carlos Ortuno-Pineda, Teresita Padilla-Benavides, Napoleon Navarro-Tito

Open Access Articles

Epithelial-mesenchymal transition (EMT) is a reversible cellular process, characterized by changes in gene expression and activation of proteins, favoring the trans-differentiation of the epithelial phenotype to a mesenchymal phenotype. This process increases cell migration and invasion of tumor cells, progression of the cell cycle, and resistance to apoptosis and chemotherapy, all of which support tumor progression. One of the signaling pathways involved in tumor progression is the MAPK pathway. Within this family, the ERK subfamily of proteins is known for its contributions to EMT. The ERK subfamily is divided into typical (ERK 1/2/5), and atypical (ERK 3/4 ...


Integration Of Random Forest Classifiers And Deep Convolutional Neural Networks For Classification And Biomolecular Modeling Of Cancer Driver Mutations, Steve Agajanian, Odeyemi Oluyemi, Gennady M. Verkhivker 2019 Chapman University

Integration Of Random Forest Classifiers And Deep Convolutional Neural Networks For Classification And Biomolecular Modeling Of Cancer Driver Mutations, Steve Agajanian, Odeyemi Oluyemi, Gennady M. Verkhivker

Mathematics, Physics, and Computer Science Faculty Articles and Research

Development of machine learning solutions for prediction of functional and clinical significance of cancer driver genes and mutations are paramount in modern biomedical research and have gained a significant momentum in a recent decade. In this work, we integrate different machine learning approaches, including tree based methods, random forest and gradient boosted tree (GBT) classifiers along with deep convolutional neural networks (CNN) for prediction of cancer driver mutations in the genomic datasets. The feasibility of CNN in using raw nucleotide sequences for classification of cancer driver mutations was initially explored by employing label encoding, one hot encoding, and embedding to ...


Differential Roles Of Mammalian Target Of Rapamycin Complexes 1 And 2 In Migration Of Prostate Cancer Cells, Smrruthi Vaidegi Venugopal 2019 Clark Atlanta University

Differential Roles Of Mammalian Target Of Rapamycin Complexes 1 And 2 In Migration Of Prostate Cancer Cells, Smrruthi Vaidegi Venugopal

Electronic Theses & Dissertations Collection for Atlanta University & Clark Atlanta University

In this study, we investigated differential activation and the role of two mTOR complexes in cell migration of prostate cancer cells. Specific knock-down of endogenous RAPTOR and RICTOR by siRNA resulted in decreased cell migration in LNCaP, DU145, and PC3 cells indicating that both mTORC1 and mTORC2 are required for cell migration. EGF treatment induced the activation of both mTORC1 and mTORC2 as determined by complex-specific phosphorylation of mTOR protein. Specific knock-down or inhibition of Rac1 activity in PC3 cells blocked EGF-induced activation of mTORC2, but had no effect on mTORC1 activation. Furthermore, the over-expression of constitutively active Rac1 (Rac1Q61L ...


Extraction, Purification And Evaluation Of Prmt5-Inhibitory Phytochemical Compounds For The Treatment Of Prostate Adenocarcinoma, Oliver H. Richmond III 2019 Clark Atlanta University

Extraction, Purification And Evaluation Of Prmt5-Inhibitory Phytochemical Compounds For The Treatment Of Prostate Adenocarcinoma, Oliver H. Richmond Iii

Electronic Theses & Dissertations Collection for Atlanta University & Clark Atlanta University

The development and advancement of prostate cancer is supported by a plethora of genetic and proteomic abnormalities, including events of post-translational modifications. The protein arginine methyltransferase 5 (PRMT5) enzyme regulates epigenetic events of histone modifications and protein post-translational modifications within protein signaling pathways. PRMT5 functions by catalyzing the symmetric dimethylation of terminal arginine residues on target protein substrates. Under abnormal conditions of overexpression and upregulation, PRMT5 methyltransferase activity constitutively drives the growth and proliferation of dysregulated cells. Overexpression or upregulation of PRMT5 correlates with disease progression as observed among numerous cancer types, including breast, colorectal, leukemia, lung, melanoma and prostate ...


Loss Of Id4 Promotes Stemness In Prostate Cancer Cells, Dhanushka Hewabostanthirige 2019 Atlanta University Center

Loss Of Id4 Promotes Stemness In Prostate Cancer Cells, Dhanushka Hewabostanthirige

Electronic Theses & Dissertations Collection for Atlanta University & Clark Atlanta University

Inhibitor of differentiation 4 (ID4), a member of the helix-loop-helix family of transcriptional regulators has emerged as a tumor suppressor in prostate cancer (PCa). Recent studies have shown that Id4 is highly expressed in the normal prostate and decreases in prostate cancer due to epigenetic silencing. Id4 knockdown in androgen sensitive LNCaP cells has been shown to lead to castration resistant prostate cancer (CRPC) in vitro and in vivo. Id4-/- mice leads to underdeveloped prostate with PIN like lesions without the loss of Androgen Receptor (AR) expression. In this study we demonstrate that the loss of ID4 expression in PCa ...


Establishment Of Crispr/Cas-9 Aided Knockout Of The Zic2 Gene In The African-American Prostate Cancer Cell Line E006aa-Pr, Janelle Moore 2019 Atlanta University Center

Establishment Of Crispr/Cas-9 Aided Knockout Of The Zic2 Gene In The African-American Prostate Cancer Cell Line E006aa-Pr, Janelle Moore

Electronic Theses & Dissertations Collection for Atlanta University & Clark Atlanta University

The largest U.S. cancer health disparity exists in prostate cancer, with African American men having the highest incidence and mortality rates. The present study evaluated the effects of ZIC2 and the underlying mechanisms in the E006 parental African-American cell line that produces tumors at accelerated growth rates because of the increase of ZIC2 genes in African-American males. We analyzed the experimental research that the overexpression of ZIC2 contributes to progression of prostate cancer. E006AA cells with overexpressed or suppressed ZIC2 were analyzed to determine phenotypic differences, PCR, cell proliferation and immunoblot assays. The expression levels of ZIC2 were analyzed ...


Reversal Of P-Glycoprotein And Breast Cancer Resistance Protein Mediated Multidrug Resistance In Vitro Using In Silico Identified Novel Compounds, Amila Nanayakkara 2019 Southern Methodist University

Reversal Of P-Glycoprotein And Breast Cancer Resistance Protein Mediated Multidrug Resistance In Vitro Using In Silico Identified Novel Compounds, Amila Nanayakkara

Biological Sciences Theses and Dissertations

Multidrug resistance (MDR) is a major cause of chemotherapy failure. Overexpression of ATP-binding cassette (ABC) transporters, P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) are two well-studied drug transporters which are associated with MDR. These two transporters also act as a major functional unit of the blood brain barrier to protect the brain from xenobiotics and toxins. Lack of clinically approved P-gp and BCRP inhibitors renders chemotherapy treatments of many MDR cancers ineffective and obstructs drug uptake into the brain.

Using computational methods, we have identified new compounds that inhibit P-gp (Brewer et al., Mol. Pharmacol. 2014). Several of these ...


Reversal Of P-Glycoprotein And Breast Cancer Resistance Protein Mediated Multidrug Resistance In Vitro Using In Silico Identified Novel Compounds, Amila Nanayakkara 2019 Southern Methodist University

Reversal Of P-Glycoprotein And Breast Cancer Resistance Protein Mediated Multidrug Resistance In Vitro Using In Silico Identified Novel Compounds, Amila Nanayakkara

Biological Sciences Theses and Dissertations

Multidrug resistance (MDR) is a major cause of chemotherapy failure. Overexpression of ATP-binding cassette (ABC) transporters, P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) are two well-studied drug transporters which are associated with MDR. These two transporters also act as a major functional unit of the blood brain barrier to protect the brain from xenobiotics and toxins. Lack of clinically approved P-gp and BCRP inhibitors renders chemotherapy treatments of many MDR cancers ineffective and obstructs drug uptake into the brain.

Using computational methods, we have identified new compounds that inhibit P-gp (Brewer et al., Mol. Pharmacol. 2014). Several of these ...


Prevalence Of A Variant Gastrin Receptor Rna And Correlating Genomic Polymorphism In Human Pancreatic Cancer, Rebekah Jones 2019 Messiah College

Prevalence Of A Variant Gastrin Receptor Rna And Correlating Genomic Polymorphism In Human Pancreatic Cancer, Rebekah Jones

Honors Projects and Presentations: Undergraduate

Currently, the five-year survival rate of pancreatic cancer is an abysmal 5%. Our lab has focused on the etiology of CCK2i4svR, a hyperactive splice variant of the gastrin receptor (CCK2R), which has been associated with increased pancreatic tumor aggressiveness. To determine if a correlation exists between a single nucleotide polymorphism (SNP) in the receptor, and expression of the variant RNA in patients, we aim to genotype human pancreatic tumor samples and quantify CCK2R and CCK2i4svR mRNA. Initial analysis of RNA samples by Real Time RT‐PCR has demonstrated successful quantification of CCK2R expression in both tumor and normal tissue samples ...


Mutant P53 Depletion By Curcumin-Derived Compounds, Mohamed A.A. Alalem 2019 Children's Mercy Hospital

Mutant P53 Depletion By Curcumin-Derived Compounds, Mohamed A.A. Alalem

Research Days

No abstract provided.


Jnk(1/2) Represses Lkb(1)-Deficiency-Induced Lung Squamous Cell Carcinoma Progression, Jian Liu, Tianyuan Wang, Chad J. Creighton, San-Pin Wu, Madhumita Ray, Kyathanahalli S. Janardhan, Cynthia J. Willson, Sung-Nam Cho, Patricia D. Castro, Michael M. Ittmann, Jian-Liang Li, Roger J. Davis, Francesco J. DeMayo 2019 National Institute of Environmental Health Sciences (NIEHS)

Jnk(1/2) Represses Lkb(1)-Deficiency-Induced Lung Squamous Cell Carcinoma Progression, Jian Liu, Tianyuan Wang, Chad J. Creighton, San-Pin Wu, Madhumita Ray, Kyathanahalli S. Janardhan, Cynthia J. Willson, Sung-Nam Cho, Patricia D. Castro, Michael M. Ittmann, Jian-Liang Li, Roger J. Davis, Francesco J. Demayo

Open Access Articles

Mechanisms of lung squamous cell carcinoma (LSCC) development are poorly understood. Here, we report that JNK1/2 activities attenuate Lkb1-deficiency-driven LSCC initiation and progression through repressing DeltaNp63 signaling. In vivo Lkb1 ablation alone is sufficient to induce LSCC development by reducing MKK7 levels and JNK1/2 activities, independent of the AMPKalpha and mTOR pathways. JNK1/2 activities is positively regulated by MKK7 during LSCC development. Pharmaceutically elevated JNK1/2 activities abates Lkb1 dependent LSCC formation while compound mutations of Jnk1/2 and Lkb1 further accelerate LSCC progression. JNK1/2 is inactivated in a substantial proportion of human LSCC and JNK1 ...


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