Open Access. Powered by Scholars. Published by Universities.®

Cell Biology Commons

Open Access. Powered by Scholars. Published by Universities.®

Cancer Biology

Institution
Keyword
Publication Year
Publication
Publication Type
File Type

Articles 1 - 30 of 467

Full-Text Articles in Cell Biology

Anti-Cancer Effects Of Oleocanthal And Extra Virgin Olive Oil, Limor Goren Sep 2019

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 ...


Role Of A 19s Proteasome Subunit- Psmd10(Gankyrin) In Neurogenesis Of Human Neuronal Progenitor Cells, Indrajit Sahu, Padma P. Nanaware, Minal Mane, Saim Wasi Mulla, Soumen Roy, Prasanna Venkatraman Aug 2019

Role Of A 19s Proteasome Subunit- Psmd10(Gankyrin) In Neurogenesis Of Human Neuronal Progenitor Cells, Indrajit Sahu, Padma P. Nanaware, Minal Mane, Saim Wasi Mulla, Soumen Roy, Prasanna Venkatraman

Open Access Articles

PSMD10(Gankyrin), a proteasome assembly chaperone, is a widely known oncoprotein which aspects many hall mark properties of cancer. However, except proteasome assembly chaperon function its role in normal cell function remains unknown. To address this issue, we induced PSMD10(Gankyrin) overexpression in HEK293 cells and the resultant large-scale changes in gene expression profile were analyzed. We constituted networks from microarray data of these differentially expressed genes and carried out extensive topological analyses. The overrecurring yet consistent theme that appeared throughout analysis using varied network metrics is that all genes and interactions identified as important would be involved in neurogenesis ...


Modeling Of Cisplatin-Induced Signaling Dynamics In Triple-Negative Breast Cancer Cells Reveals Mediators Of Sensitivity, Anne Margriet Heijink, Marieke Everts, Megan E. Honeywell, Ryan Richards, Yannick P. Kok, Elisabeth G. E. De Vries, Michael J. Lee, Marcel A T M Van Vugt Aug 2019

Modeling Of Cisplatin-Induced Signaling Dynamics In Triple-Negative Breast Cancer Cells Reveals Mediators Of Sensitivity, Anne Margriet Heijink, Marieke Everts, Megan E. Honeywell, Ryan Richards, Yannick P. Kok, Elisabeth G. E. De Vries, Michael J. Lee, Marcel A T M Van Vugt

Open Access Articles

Triple-negative breast cancers (TNBCs) display great diversity in cisplatin sensitivity that cannot be explained solely by cancer-associated DNA repair defects. Differential activation of the DNA damage response (DDR) to cisplatin has been proposed to underlie the observed differential sensitivity, but it has not been investigated systematically. Systems-level analysis-using quantitative time-resolved signaling data and phenotypic responses, in combination with mathematical modeling-identifies that the activation status of cell-cycle checkpoints determines cisplatin sensitivity in TNBC cell lines. Specifically, inactivation of the cell-cycle checkpoint regulator MK2 or G3BP2 sensitizes cisplatin-resistant TNBC cell lines to cisplatin. Dynamic signaling data of five cell cycle-related signals predicts ...


Leptin Promotes Expression Of Emt-Related Transcription Factors And Invasion In A Src And Fak-Dependent Pathway In Mcf10a Mammary Epithelial Cells, Monserrat Olea-Flores, Miriam Zuñiga-Eulogio, Arvey Tacuba-Saavedra, Magdalena Bueno-Salgado, Andrea Sánchez-Carvajal, Yovani Vargas-Santiago, Miguel A. Mendoza-Catalán, Eduardo Pérez Salazar, Alejandra García-Hernández, Teresita Padilla-Benavides, Napoleón Navarro-Tito Aug 2019

Leptin Promotes Expression Of Emt-Related Transcription Factors And Invasion In A Src And Fak-Dependent Pathway In Mcf10a Mammary Epithelial Cells, Monserrat Olea-Flores, Miriam Zuñiga-Eulogio, Arvey Tacuba-Saavedra, Magdalena Bueno-Salgado, Andrea Sánchez-Carvajal, Yovani Vargas-Santiago, Miguel A. Mendoza-Catalán, Eduardo Pérez Salazar, Alejandra García-Hernández, Teresita Padilla-Benavides, Napoleón Navarro-Tito

University of Massachusetts Medical School Faculty Publications

Leptin is one of the main adipokines secreted in breast tissue, and has been associated with epithelial-mesenchymal transition (EMT) and tumor progression in breast cancer. Leptin promotes EMT, cell migration and invasion in epithelial breast cells, leading to tumor progression. However, the molecular mechanism that underlies these events is not fully understood; however, the activation of different signaling pathways appears to be essential. In this sense, the effect of leptin on the activation of kinases like Src and FAK, which regulate signaling pathways that activate the EMT program, has not been completely described. Therefore, we investigated the involvement of these ...


Multimodal Quantitative Imaging Of Brain Cancer In Cultured Cells, Xin Feng, Alona Muzikansky, Alonzo H. Ross, Michael R. Hamblin, Peter R. Jermain, Anna N. Yaroslavsky Jul 2019

Multimodal Quantitative Imaging Of Brain Cancer In Cultured Cells, Xin Feng, Alona Muzikansky, Alonzo H. Ross, Michael R. Hamblin, Peter R. Jermain, Anna N. Yaroslavsky

Open Access Articles

Fluorescence emission, polarization and subcellular localization of methylene blue (MB) were studied in four cancerous and two normal human brain cell lines. Fluorescence emission and polarization images were acquired and analyzed. The co-localization of MB with mitochondria, lysosomes and nuclei of the cells was evaluated. Glioblastoma cells exhibited significantly higher MB fluorescence polarization compared to normal astrocytes. Preferential accumulation of MB in mitochondria of glioblastoma cells may explain higher fluorescence polarization values in cancer cells as compared to normal. These findings may lead to the development of a quantitative method for the detection of brain cancer in single cells.


F-Box Protein Fbxo16 Functions As A Tumor Suppressor By Attenuating Nuclear Beta-Catenin Function, Debasish Paul, Sehbanul Islam, Rajesh Kumar. Manne, U. S. Dinesh, Sunil K. Malonia, Biswanath Maity, Ramanamurthy Boppana, Srikanth Rapole, Praveen Kumar Shetty, Manas Kumar Santra Jul 2019

F-Box Protein Fbxo16 Functions As A Tumor Suppressor By Attenuating Nuclear Beta-Catenin Function, Debasish Paul, Sehbanul Islam, Rajesh Kumar. Manne, U. S. Dinesh, Sunil K. Malonia, Biswanath Maity, Ramanamurthy Boppana, Srikanth Rapole, Praveen Kumar Shetty, Manas Kumar Santra

Open Access Articles

Aberrant activation of beta-catenin has been implicated in a variety of human diseases, including cancer. In spite of significant progress, the regulation of active Wnt/beta-catenin-signaling pathways is still poorly understood. In this study, we show that F-box protein 16 (FBXO16) is a putative tumor suppressor. It is a component of the SCF (SKP1-Cullin1-F-box protein) complex, which targets the nuclear beta-catenin protein to facilitate proteasomal degradation through the 26S proteasome. FBXO16 interacts physically with the C-terminal domain of beta-catenin and promotes its lysine 48-linked polyubiquitination. In addition, it inhibits epithelial-to-mesenchymal transition (EMT) by attenuating the level of beta-catenin. Therefore, depletion ...


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 Jun 2019

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 Jun 2019

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 ...


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

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 May 2019

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 ...


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

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 May 2019

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 May 2019

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 ...


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 May 2019

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 ...


Targeting Sec61Α By Ipomoeassin F Leads To Highly Cytotoxic Effect, Zhijian Hu May 2019

Targeting Sec61Α By Ipomoeassin F Leads To Highly Cytotoxic Effect, Zhijian Hu

Theses and Dissertations

Ipomoeassin F is a flagship congener of a resin glycoside family that inhibits growth of many tumor cell lines with only single-digital nanomolar IC50 values. However, biological and pharmacological mechanisms of ipomoeassin F have been undefined. To facilitate exploration of the biological and pharmacological properties, we performed sophisticate SAR (Structure–activity relationship) studies of ipomoeassin F to understand its pharmacophore and structure properties so that we can design favorable probes for further biological investigation. By applying appropriate deviates that possess fluorescent groups and similar bio-activity, the target protein was found to be localized in endoplasmic reticulum (ER). Through biotin affinity ...


The Signaling Pathways Of Metallothionein-Mediated Chemotaxis In Breast Cancer, Jennifer Messina May 2019

The Signaling Pathways Of Metallothionein-Mediated Chemotaxis In Breast Cancer, Jennifer Messina

University Scholar Projects

Metallothionein (MT) is a small, thiol rich protein released into the extracellular environment in response to stress. Elevated expression of MT has been linked to many inflammatory diseases including inflammatory bowel diseases, diabetes, and cancer. In breast cancer, high expression of MT has been associated with poor patient prognosis. Previous studies have shown that MT acts as a chemoattractant in lymphocytes, and that UC1MT, a monoclonal anti-MT antibody, can block this chemotactic response. In addition, it has been shown that both Cholera toxin and Pertussis toxin, which are known antagonists of G-protein coupled receptors, can inhibit MT-mediated chemotaxis. Here, I ...


The Signaling Pathways Of Metallothionein-Mediated Chemotaxis In Breast Cancer, Jennifer Messina May 2019

The Signaling Pathways Of Metallothionein-Mediated Chemotaxis In Breast Cancer, Jennifer Messina

Honors Scholar Theses

Metallothionein (MT) is a small, thiol rich protein released into the extracellular environment in response to stress. Elevated expression of MT has been linked to many inflammatory diseases including inflammatory bowel diseases, diabetes, and cancer. In breast cancer, high expression of MT has been associated with poor patient prognosis. Previous studies have shown that MT acts as a chemoattractant in lymphocytes, and that UC1MT, a monoclonal anti-MT antibody, can block this chemotactic response. In addition, it has been shown that both Cholera toxin and Pertussis toxin, which are known antagonists of G-protein coupled receptors, can inhibit MT-mediated chemotaxis. Here, I ...


Study Of Alpha Mangostin As A Chemoprotective Agent For Breast Cancer Via Activation Of The P53 Pathway, Vanessa Van Oost May 2019

Study Of Alpha Mangostin As A Chemoprotective Agent For Breast Cancer Via Activation Of The P53 Pathway, Vanessa Van Oost

Honors Program Projects

Breast carcinoma is the most frequently diagnosed cancer among women and causes over 400,000 deaths each year worldwide. Current treatments such as chemotherapy are not selective for cancerous tissues but are destructive to normal tissues as well. This causes a range of side effects including pain, nausea, hair loss, weakness, and more. Inactivation of p53 is a very common mutation within human cancer cells. The ability to activate the p53 pathway which protects cells from tumor formation is lost in 50% of cancers. Due to the prevalence of this mutation, p53 is a uniquely valuable target for applied research ...


The Molecular Mechanisms Underlying The Cancer Killing Effect Of Interleukin-24, Leah Eshanie Persaud May 2019

The Molecular Mechanisms Underlying The Cancer Killing Effect Of Interleukin-24, Leah Eshanie Persaud

All Dissertations, Theses, and Capstone Projects

Interleukin-24 (IL-24) is an immunomodulatory cytokine that also displays specific anti-tumor effects across many cancer cell types. The tumor suppressor activities of IL-24 include inhibition of angiogenesis, metastasis, toxic autophagy, cancer-specific apoptosis, and sensitization to traditional cancer treatments like chemotherapy and radiation. Overexpression of IL-24 can selectively induce apoptosis in various cancer cells while having no adverse effects on normal cells. Due to this favorable killing effect, IL-24 is currently in phase II clinical trials. There is accumulating evidence that IL-24’s anti-cancer activity is primarily through the endoplasmic reticulum (ER) stress pathway but other pathways leading to cell death ...


Exploiting Unique Biological Features Of Leukemia Stem Cells For Therapeutic Benefit, Haojian Zhang, Shaoguang Li Apr 2019

Exploiting Unique Biological Features Of Leukemia Stem Cells For Therapeutic Benefit, Haojian Zhang, Shaoguang Li

Open Access Articles

Cancer stem cells play a critical role in disease initiation and insensitivity to chemotherapy in numerous hematologic malignancies and some solid tumors, and these stem cells need to be eradicated to achieve a cure. Key to successful targeting of cancer stem cells is to identify and functionally test critical target genes and to fully understand their associated molecular network in these stem cells. Human chronic myeloid leukemia (CML) is well accepted as one of the typical types of hematopoietic malignancies that are derived from leukemia stem cells (LSCs), serving as an excellent model disease for understanding the biology of LSCs ...


Amphiphilic Peptides For Efficient Sirna Delivery, Saghar Mozaffari, Emira Bousoik, Farideh Amirrad, Robert Lamboy, Melissa Coyle, Ryley Hall, Abdulaziz Alasmari, Parvin Mahdipoor, Keykavous Parang, Hamidreza Montazeri Aliabadi Apr 2019

Amphiphilic Peptides For Efficient Sirna Delivery, Saghar Mozaffari, Emira Bousoik, Farideh Amirrad, Robert Lamboy, Melissa Coyle, Ryley Hall, Abdulaziz Alasmari, Parvin Mahdipoor, Keykavous Parang, Hamidreza Montazeri Aliabadi

Pharmacy Faculty Articles and Research

A number of amphiphilic cyclic peptides—[FR]4, [WR]5, and [WK]5—containing hydrophobic and positively-charged amino acids were synthesized by Fmoc/tBu solid-phase peptide methods and evaluated for their efficiency in intracellular delivery of siRNA to triple-negative breast cancer cell lines, MDA-MB-231 and MDA-MB-468, in the presence and absence of 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE). Among the peptides, [WR]5, which contains alternate tryptophan (W) and arginine (R) residues, was found to be the most efficient in the delivery of siRNA by improving the delivery by more than 3-fold when compared to other synthesized cyclic peptides that were not efficient ...


Mechanisms Of Oriented Cell Division And Their Roles In Tissue Development, Evan Blake Dewey Apr 2019

Mechanisms Of Oriented Cell Division And Their Roles In Tissue Development, Evan Blake Dewey

Biology ETDs

Properly executed cell division is crucial to development, maintenance, and longevity of multicellular organisms. Defects in both symmetric and asymmetric divisions can lead to improper developmental patterning, as well as genomic instability, disruption of tissue homeostasis, and cancer. Our research focuses on how regulators orchestrate proper cell divisions. Mushroom Body Defect (Mud) is one such regulator, and here we describe how Mud is regulated via the Hippo signaling pathway kinase Warts (Wts), showing Wts phosphorylates Mud to enhance interaction with the polarity protein Partner of Inscuteable, promoting spindle orientation activity. We next focus on another regulator, Shortstop (Shot), describing a ...


Alpha Mangostin As A Chemoprotective Agent Via Activation Of The P53 Pathway For Breast Cancer, Vanessa Van Oost Apr 2019

Alpha Mangostin As A Chemoprotective Agent Via Activation Of The P53 Pathway For Breast Cancer, Vanessa Van Oost

Scholar Week 2016 - present

Breast carcinoma is the most frequently diagnosed cancer among women and causes over 400,000 deaths yearly worldwide. Current treatments such as chemotherapy are not selective for cancerous tissues but are destructive to normal tissues as well. This causes a range of side effects including pain, nausea, hair loss, weakness, and more. Inactivation of p53 is an almost universal mutation within human cancer cells. The ability to activate the p53 pathway which protects cells from tumor formation is lost in 50% of cancers. Due to the prevalence of this mutation, p53 is a uniquely valuable target for applied research. Alpha ...


Vegf/Neuropilin Signaling In Cancer Stem Cells, Arthur M. Mercurio Mar 2019

Vegf/Neuropilin Signaling In Cancer Stem Cells, Arthur M. Mercurio

Arthur M. Mercurio

The function of vascular endothelial growth factor (VEGF) in cancer extends beyond angiogenesis and vascular permeability. Specifically, VEGF-mediated signaling occurs in tumor cells and this signaling contributes to key aspects of tumorigenesis including the self-renewal and survival of cancer stem cells (CSCs). In addition to VEGF receptor tyrosine kinases, the neuropilins (NRPs) are critical for mediating the effects of VEGF on CSCs, primarily because of their ability to impact the function of growth factor receptors and integrins. VEGF/NRP signaling can regulate the expression and function of key molecules that have been implicated in CSC function including Rho family guanosine ...


Unified Methods For Feature Selection In Large-Scale Genomic Studies With Censored Survival Outcomes, Lauren Spirko-Burns, Karthik Devarajan Mar 2019

Unified Methods For Feature Selection In Large-Scale Genomic Studies With Censored Survival Outcomes, Lauren Spirko-Burns, Karthik Devarajan

COBRA Preprint Series

One of the major goals in large-scale genomic studies is to identify genes with a prognostic impact on time-to-event outcomes which provide insight into the disease's process. With rapid developments in high-throughput genomic technologies in the past two decades, the scientific community is able to monitor the expression levels of tens of thousands of genes and proteins resulting in enormous data sets where the number of genomic features is far greater than the number of subjects. Methods based on univariate Cox regression are often used to select genomic features related to survival outcome; however, the Cox model assumes proportional ...


Induction Of Ampk Activation By N,N'-Diarylurea Fnd-4b Decreases Growth And Increases Apoptosis In Triple Negative And Estrogen-Receptor Positive Breast Cancers, Jeremy Johnson, Piotr G. Rychahou, Vitaliy M. Sviripa, Heidi L. Weiss, Chunming Liu, David S. Watt, B. Mark Evers Mar 2019

Induction Of Ampk Activation By N,N'-Diarylurea Fnd-4b Decreases Growth And Increases Apoptosis In Triple Negative And Estrogen-Receptor Positive Breast Cancers, Jeremy Johnson, Piotr G. Rychahou, Vitaliy M. Sviripa, Heidi L. Weiss, Chunming Liu, David S. Watt, B. Mark Evers

Markey Cancer Center Faculty Publications

Purpose

Triple negative breast cancer (TNBC) is the most lethal and aggressive subtype of breast cancer. AMP-activated protein kinase (AMPK) is a major energy regulator that suppresses tumor growth, and 1-(3-chloro-4-((trifluoromethyl)thio)phenyl)-3-(4-(trifluoromethoxy)phenyl)urea (FND-4b) is a novel AMPK activator that inhibits growth and induces apoptosis in colon cancer. The purpose of this project was to test the effects of FND-4b on AMPK activation, proliferation, and apoptosis in breast cancer with a particular emphasis on TNBC.

Materials and methods

(i) Estrogen-receptor positive breast cancer (ER+BC; MCF-7, and T-47D), TNBC (MDA-MB-231 and HCC-1806), and ...


Vegf/Neuropilin Signaling In Cancer Stem Cells, Arthur M. Mercurio Jan 2019

Vegf/Neuropilin Signaling In Cancer Stem Cells, Arthur M. Mercurio

Open Access Articles

The function of vascular endothelial growth factor (VEGF) in cancer extends beyond angiogenesis and vascular permeability. Specifically, VEGF-mediated signaling occurs in tumor cells and this signaling contributes to key aspects of tumorigenesis including the self-renewal and survival of cancer stem cells (CSCs). In addition to VEGF receptor tyrosine kinases, the neuropilins (NRPs) are critical for mediating the effects of VEGF on CSCs, primarily because of their ability to impact the function of growth factor receptors and integrins. VEGF/NRP signaling can regulate the expression and function of key molecules that have been implicated in CSC function including Rho family guanosine ...


Brg1 Is A Prognostic Indicator And A Potential Therapeutic Target For Prostate Cancer, Rohini Muthuswami, Leeann Bailey, Radhakrishnan Rakesh, Anthony N. Imbalzano, Jeffrey A. Nickerson, Joel W. Hockensmith Jan 2019

Brg1 Is A Prognostic Indicator And A Potential Therapeutic Target For Prostate Cancer, Rohini Muthuswami, Leeann Bailey, Radhakrishnan Rakesh, Anthony N. Imbalzano, Jeffrey A. Nickerson, Joel W. Hockensmith

University of Massachusetts Medical School Faculty Publications

Brahma-related gene 1 (BRG1) is one of two mutually exclusive ATPases that function as the catalytic subunit of human SWItch/Sucrose NonFermentable (SWI/SNF) chromatin remodeling enzymes. BRG1 has been identified as a tumor suppressor in some cancer types but has been shown to be expressed at elevated levels, relative to normal tissue, in other cancers. Using TCGA (The Cancer Genome Atlas) prostate cancer database, we determined that BRG1 mRNA and protein expression is elevated in prostate tumors relative to normal prostate tissue. Only 3 of 491 (0.6%) sequenced tumors showed amplification of the locus or mutation in the ...


Mechanisms And Immunogenicity Of Nspef-Induced Cell Death In B16f10 Melanoma Tumors, Alessandra Rossi, Olga N. Pakhomova, Andrei G. Pakhomov, Samantha Weygandt, Anna A. Bulysheva, Len E. Murray, Peter A. Mollica, Claudia Muratori Jan 2019

Mechanisms And Immunogenicity Of Nspef-Induced Cell Death In B16f10 Melanoma Tumors, Alessandra Rossi, Olga N. Pakhomova, Andrei G. Pakhomov, Samantha Weygandt, Anna A. Bulysheva, Len E. Murray, Peter A. Mollica, Claudia Muratori

Bioelectrics Publications

Accumulating data indicates that some cancer treatments can restore anticancer immunosurveillance through the induction of tumor immunogenic cell death (ICD). Nanosecond pulsed electric fields (nsPEF) have been shown to efficiently ablate melanoma tumors. In this study we investigated the mechanisms and immunogenicity of nsPEF-induced cell death in B16F10 melanoma tumors. Our data show that in vitro nsPEF (20-200, 200-ns pulses, 7 kV/cm, 2 Hz) caused a rapid dose-dependent cell death which was not accompanied by caspase activation or PARP cleavage. The lack of nsPEF-induced apoptosis was confirmed in vivo in B16F10 tumors. NsPEF also failed to trigger ICD-linked responses ...


Eralpha Isoforms Modulate The Tumorigenicity Of 24r,25(Oh)2d3 In Estrogen-Responsive Cancer, Anjali Verma Jan 2019

Eralpha Isoforms Modulate The Tumorigenicity Of 24r,25(Oh)2d3 In Estrogen-Responsive Cancer, Anjali Verma

Theses and Dissertations

Over 200,000 cases of breast cancer are diagnosed every year. Nearly 20% of these patients supplement their diets with some form of vitamin D. This high frequency of vitamin D supplement use may be due in part to research suggesting that cancer patients with higher serum vitamin D3 levels have better prognoses than patients with low serum vitamin D3. However, double-blind clinical trials on the efficacy of vitamin D3 supplementation in breast cancer have been inconclusive. A recent meta-analysis showed evidence of reduced cancer recurrence in patients taking vitamin D3 supplements who had ‘estrogen receptor ...