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Articles 1 - 30 of 47
Full-Text Articles in Cancer Biology
Synergistic Sensitization Of Pancreatic Cancer Cells By Nanosecond Pulsed Electric Fields And Cold Atmospheric Plasma Via Amplifying Ros And Apoptotic Signaling, Zobia Minhas, Edwin A. Oshin, Lifang Yang, Chunqi Jiang, Siqi Guo
Synergistic Sensitization Of Pancreatic Cancer Cells By Nanosecond Pulsed Electric Fields And Cold Atmospheric Plasma Via Amplifying Ros And Apoptotic Signaling, Zobia Minhas, Edwin A. Oshin, Lifang Yang, Chunqi Jiang, Siqi Guo
Bioelectrics Publications
Pancreatic cancer remains a highly lethal malignancy, with standard therapies offering limited benefits in advanced stages; thus, novel strategies that exploit specific cancer cell vulnerabilities are urgently needed. Building on our previous findings that nanosecond pulsed electric fields (nsPEF) combined with cold atmospheric plasma (CAP) produce enhanced cytotoxicity, this study investigates the molecular mechanisms underlying this synergy. Pan02 pancreatic cancer cells were subjected to nsPEF, CAP, or a combination of both. We assessed cell viability, reactive oxygen species (ROS) production, and mitochondrial integrity using metabolic assays, flow cytometry, and fluorescence microscopy. Apoptotic markers were evaluated via Western blotting and caspase …
Global Erk/Mapk Activation Determines Oncogenic Fitness In Kras-Mutant Pancreatic Ductal Adenocarcinoma, Rachel A. Burge
Global Erk/Mapk Activation Determines Oncogenic Fitness In Kras-Mutant Pancreatic Ductal Adenocarcinoma, Rachel A. Burge
MUSC Theses and Dissertations
In pancreatic ductal adenocarcinoma (PDAC), ~95% of cases harbor an activating KRAS mutation. The most common KRAS mutations in PDAC are KRASG12D (42%), KRASG12V (31%), and KRASG12R (15%). Patients harboring KRASG12R mutations have increased overall survival compared to those with KRASG12D/V-mutations. While KRASG12D/Vare common in all KRAS-mutant cancers, KRASG12Ris only common in PDAC.
KRASG12R is unable to activate the lipid kinase PIK3CA, a KRAS effector that is important for tumorigenesis in murine models. To investigate the tumorigenic potential of KRASG12R and the mechanisms that enable this mutation …
The Role Of Ucp2 In Pancreatic Cancer Metabolism And Its Potential As A Radiosensitizer, Emily Rieff
The Role Of Ucp2 In Pancreatic Cancer Metabolism And Its Potential As A Radiosensitizer, Emily Rieff
Dissertations and Theses (Open Access)
Uncoupling protein 2 (UCP2) is a mitochondrial protein that regulates the flow of protons down the gradient established by the electron transport chain (ETC) without generating ATP, thus uncoupling the proton gradient from ATP generation. In tumors, specifically pancreatic cancer (PDAC), the ETC is highly stimulated to generate the copious ATP needed by the tumor to grow. However, extended ETC use increases reactive oxygen species (ROS), and if left unchecked, results in cell death. To evade this, PDAC employs antioxidant strategies, including upregulating UCP2 in tumor cells. In addition to its uncoupling function, UCP2 indirectly controls ROS levels by maintaining …
Bp1003 Decreases Stat3 Expression And Its Pro-Tumorigenic Functions In Solid Tumors And The Tumor Microenvironment, Maria Gagliardi, Rhonda Kean, Bingbing Dai, Jithesh Augustine, Michael Roberts, Jason Fleming, D. Craig Hooper, Ana Ashizawa
Bp1003 Decreases Stat3 Expression And Its Pro-Tumorigenic Functions In Solid Tumors And The Tumor Microenvironment, Maria Gagliardi, Rhonda Kean, Bingbing Dai, Jithesh Augustine, Michael Roberts, Jason Fleming, D. Craig Hooper, Ana Ashizawa
Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers
Overexpression and aberrant activation of signal transducer and activator of transcription 3 (STAT3) contribute to tumorigenesis, drug resistance, and tumor-immune evasion, making it a potential cancer therapeutic target. BP1003 is a neutral liposome incorporated with a nuclease-resistant P-ethoxy antisense oligodeoxynucleotide (ASO) targeting the STAT3 mRNA. Its unique design enhances BP1003 stability, cellular uptake, and target affinity. BP1003 efficiently reduces STAT3 expression and enhances the sensitivity of breast cancer cells (HER2+, triple negative) and ovarian cancer cells (late stage, invasive ovarian cancer) to paclitaxel and 5-fluorouracil (5-FU) in both 2D and 3D cell cultures. Similarly, ex vivo and in …
Chemotherapy-Induced Modulation Of Tumor Antigen Presentation, Alaina C. Larson
Chemotherapy-Induced Modulation Of Tumor Antigen Presentation, Alaina C. Larson
Theses & Dissertations
Pancreatic cancer is a lethal malignancy, with a five-year overall survival rate of just 13%. Current treatment approaches thus require modification and attention has shifted towards improving immunotherapy efficacy. Select chemotherapy drugs possess inherent immunomodulatory activity and could be used to initiate immunotherapeutic success, thereby restoring anti-tumor immunity in pancreatic cancer. In this work, I evaluated the impact of the chemotherapy drug gemcitabine on tumor antigen presentation by human leukocyte antigen class I (HLA-I). Gemcitabine regulated HLA-I expression on multiple levels, increasing pancreatic cancer cells’ HLA-I mRNA transcripts, total protein and surface expression, as well as surface stability. Temperature-dependent assay …
Identification Of Mitotic Phosphatases And Cyclin K As Novel Molecular Targets In Pancreatic Cancer, Yi Xiao
Identification Of Mitotic Phosphatases And Cyclin K As Novel Molecular Targets In Pancreatic Cancer, Yi Xiao
Theses & Dissertations
Pancreatic cancer is a highly lethal disease worldwide. Given the limited effectiveness of current regimens in restricting tumor progression, it is imperative that potential molecular targets be identified to offer valuable insights into alternative therapeutics. By using a phosphate-binding tag (Phos-tag) technique, previous studies have identified several Hippo pathway-related proteins and kinases required for cancer growth or paclitaxel resistance. This work has screened various phosphatases and cyclins/cyclin-dependent kinases (CDKs) as potential cancer targets, but specifically focuses on characterizing the roles of carboxy-terminal domain small phosphatase like 2 (CTDSPL2), apoptosis-stimulating protein of p53-2 (ASPP2), and Cyclin K in pancreatic cancer.
CTDSPL2 …
Trip13’S Crucial Role In Pancreatic Cancer Progression, Swati Dhasmana, Anupam Dhasmana, Stella Rios, Iris A. Enriquez-Perez, Sheema Khan, Farrukh Afaq, Upender Manne, Murali M. Yallapu, Subhash Chauhan
Trip13’S Crucial Role In Pancreatic Cancer Progression, Swati Dhasmana, Anupam Dhasmana, Stella Rios, Iris A. Enriquez-Perez, Sheema Khan, Farrukh Afaq, Upender Manne, Murali M. Yallapu, Subhash Chauhan
Research Symposium
Background: Pancreatic cancer, characterized by its high mortality rate, stands as one of the most aggressive cancer forms. The projected surge in pancreatic cancer-related deaths, making it the second leading cause in the United States by 2030, underscores the urgency for effective early screening tools. This study employs data mining methods to scrutinize bioinformatic data surrounding TRIP13. Examining differential expression across various cancers, correlating TRIP13 expression with pancreatic cancer stages, exploring associations with common cancer genes, and analyzing overall survival rates constitute the core investigations. Integrated with molecular biology techniques, the study further quantifies TRIP13 expression in progressive pancreatic cancer …
Oncolytic Tanapoxvirus Recombinants Expressing Mil-2, Flagellin-C, And Mccl2 Regress Human Cancer Xenografts In Immune Deficient Nude Mice And Immune Cell Reconstituted Balb/C Nude Mice., Michael Leonard Monaco
Oncolytic Tanapoxvirus Recombinants Expressing Mil-2, Flagellin-C, And Mccl2 Regress Human Cancer Xenografts In Immune Deficient Nude Mice And Immune Cell Reconstituted Balb/C Nude Mice., Michael Leonard Monaco
Dissertations
Tanapoxvirus (TPV) is a double stranded DNA virus from the genus Yatapoxvirus which has been engineered for the purpose of potentially treating a number of human cancers. Previous studies have shown TPV recombinants are capable of inducing tumor inhibition and even regression in athymic nude mice bearing human cancer xenografts of colorectal, melanoma and triple negative breast cancer (TNBC). However, TPV is host-restricted to humans and monkeys, including cancerous cells, which has provided a unique obstacle in its development as an oncolytic virus (OV). Namely, standard syngeneic mouse models cannot be used as test systems to evaluate TPV’s efficacy against …
Development Of Targeted Drug Delivery System To Improve Immunotherapy In Pancreatic Cancer, Poornima Devi Shaji, Ana Martinez Bulnes, Nirnoy Dan, Subhash C. Chauhan, Sheema Khan, Murali M. Yallapu
Development Of Targeted Drug Delivery System To Improve Immunotherapy In Pancreatic Cancer, Poornima Devi Shaji, Ana Martinez Bulnes, Nirnoy Dan, Subhash C. Chauhan, Sheema Khan, Murali M. Yallapu
Research Colloquium
Introduction: About 95% of tumor arises from epithelial cell lining ducts known to be pancreatic ductal adenocarcinomas, with less than 5-7% survival rate. Unfortunately, little progress has been seen in the outcomes of patients with PDAC as tumor develops high desmoplasia and chemo-resistance to chemotherapeutic drugs, such as gemcitabine (Gem). Immunotherapy has shown promising results in other cancers but limited response in pancreatic cancer due to desmoplasia and fibrotic tumor microenvironment. A recently identified mucin, MUC13 is aberrantly expressed in pancreatic tumors but not in normal pancreas. Due to its high membrane expression, MUC13 may serve as an excellent target …
Microrna-145 Replacement As A Therapeutic Tool To Improve Trail Therapy, Sheema Khan, Saini Setua, Nirnoy Dan, Melida Flores Cantu, Ana Martinez Bulnes, Murali M. Yallapu, Stephen W. Behrman, Meena Jaggi, Subhash C. Chauhan, Sheema Khan
Microrna-145 Replacement As A Therapeutic Tool To Improve Trail Therapy, Sheema Khan, Saini Setua, Nirnoy Dan, Melida Flores Cantu, Ana Martinez Bulnes, Murali M. Yallapu, Stephen W. Behrman, Meena Jaggi, Subhash C. Chauhan, Sheema Khan
Research Symposium
Pancreatic cancer (PanCa) is a third leading cause of cancer related deaths in US. Unlike other cancers, PanCa is highly resistant to TNF-related apoptosis-inducing ligand (TRAIL) that emerges as one of the most-promising therapy in clinical trials. Our group has previously identified microRNA-145 (miR-145) is downregulated in PanCa, the restoration of which inhibits tumor growth and enhances gemcitabine sensitivity. In this study, we have observed that miR-145 restoration in PanCa cells renders them sensitive to TRAIL treatment. Therefore, we have engineered unique superparamagnetic nanoparticles (SPs) for co-delivering miR-145 and TRAIL in PanCa for improving their therapeutic response to TRAIL. The …
Microrna-145 Replacement As A Therapeutic Tool To Improve Trail Therapy, Saini Setua, Nirnoy Dan, Melida Flores Cantu, Ana Martinez Bulnes, Murali M. Yallapu, Stephen W. Behrman, Meena Jaggi, Subhash C. Chauhan, Sheema Khan
Microrna-145 Replacement As A Therapeutic Tool To Improve Trail Therapy, Saini Setua, Nirnoy Dan, Melida Flores Cantu, Ana Martinez Bulnes, Murali M. Yallapu, Stephen W. Behrman, Meena Jaggi, Subhash C. Chauhan, Sheema Khan
Research Symposium
Pancreatic cancer (PanCa) is a third leading cause of cancer related deaths in US. Unlike other cancers, PanCa is highly resistant to TNF-related apoptosis-inducing ligand (TRAIL) that emerges as one of the most-promising therapy in clinical trials. Our group has previously identified microRNA-145 (miR-145) is downregulated in PanCa, the restoration of which inhibits tumor growth and enhances gemcitabine sensitivity. In this study, we have observed that miR-145 restoration in PanCa cells renders them sensitive to TRAIL treatment. Therefore, we have engineered unique superparamagnetic nanoparticles (SPs) for co-delivering miR-145 and TRAIL in PanCa for improving their therapeutic response to TRAIL. The …
Dissecting The Role Of Selenoprotein P And Thioredoxin Reductase In Pancreatic Cancer Metabolism, Alyssa A. Abbas
Dissecting The Role Of Selenoprotein P And Thioredoxin Reductase In Pancreatic Cancer Metabolism, Alyssa A. Abbas
Dissertations, Master's Theses and Master's Reports
Pancreatic ductal adenocarcinoma (PDAC), the fourth leading cause of US cancer-related deaths, has a stark 5-year survival rate of 9%, emphasizing an urgent need for effective therapies. A well-established characteristic of cancer, metabolic dysregulation, presents an opportunity for developing therapies that target specific metabolic susceptibilities inherent in cancer cells. Our recent studies have discovered a susceptibility in PDAC; deprivation of cystine or blocking its uptake by erastin (a cystine transport inhibitor) triggers significant lipid peroxidation, thereby inducing ferroptosis specifically in the mesenchymal subtype of PDAC, but not in the epithelial subtype. This study aims to elucidate the roles of Selenoprotein …
The Adar-Mavs Pathway Is A Critical Mediator Of The Innate Immune System In Pancreatic Development And Cancer, Dhwani Rupani
The Adar-Mavs Pathway Is A Critical Mediator Of The Innate Immune System In Pancreatic Development And Cancer, Dhwani Rupani
Dissertations and Theses (Open Access)
Adenosine deaminase acting on RNA (ADAR) is an RNA-binding protein that deaminates adenosine (A) to inosine (I). A-to-I editing is an important post-transcriptional mechanism to prevent recognition of endogenous RNA by MDA5, a cytosolic RNA sensor. Activation of MDA5 by viral RNA can stimulate the innate immune system. Thus, ADAR-mediated RNA editing is crucial to distinguish “self” from “non-self”. ADAR has an important role in gene regulation as A-to-I editing alters RNA processing affecting both RNA and protein abundance. Given its importance in regulating innate immunity and transcript abundance, aberrations in Adar expression are implicated in developmental deformities and carcinogenesis. …
Investigating The Role Of Splenic Macrophages In Pancreatic Cancer, Daisy V. Gonzalez
Investigating The Role Of Splenic Macrophages In Pancreatic Cancer, Daisy V. Gonzalez
Theses & Dissertations
Pancreatic cancer is currently the 3rd leading cause of all cancer-related deaths, with a 5-year survival rate remaining at 10%. The current standard treatment of care and a lack of effective diagnostic markers leaves patients with a dismal prognosis at advanced stages of the disease. This thesis research evaluated the effect of ApoE-expressing macrophages in the spleen. First, we aimed to assess the ApoE expression in the spleen of pancreatic tumor-bearing mice. Results showed that ApoE expression in splenic macrophages increased as the disease progressed. In addition, we saw a significant increase in marginal zone metallophilic macrophages and red pulp …
Complex Role Of Microbiome In Pancreatic Tumorigenesis: Potential Therapeutic Implications, Suneetha Amara, Li V. Yang, Venkataswarup Tiriveedhi, Mahvish Muzaffar
Complex Role Of Microbiome In Pancreatic Tumorigenesis: Potential Therapeutic Implications, Suneetha Amara, Li V. Yang, Venkataswarup Tiriveedhi, Mahvish Muzaffar
Biology Faculty Research
Pancreatic cancer (PC) is the fourth leading cause of cancer-related mortality with limited diagnostic and therapeutic options. Although immunotherapy has shown promise in the treatment of several cancers, its role in pancreatic cancer is rather limited. Several studies have focused on determining the role of the tumor microenvironment with cancer-cell-intrinsic events and tumor-infiltrating immune cellular properties. However, in the past decade, there has been emerging research aimed at delineating the role of the host microbiome, including the metabolites from microbes and host responses, on pancreatic tumorigenesis. Importantly, there is emerging evidence suggesting the beneficial role of a gut microbiome transplant …
Oncolytic Tanapoxvirus Variants Expressing Mil-2 And Mccl-2 Regress Human Pancreatic Cancer Xenografts In Immunocompromised And Immunocompetent Cann.Cg-Foxn1Nu/Crl Nude Mice, Scott David Haller
Oncolytic Tanapoxvirus Variants Expressing Mil-2 And Mccl-2 Regress Human Pancreatic Cancer Xenografts In Immunocompromised And Immunocompetent Cann.Cg-Foxn1Nu/Crl Nude Mice, Scott David Haller
Dissertations
Pancreatic ductal adenocarcinoma (PDAC) is the fifth leading cause of cancer-related death in Western countries. The incidence of PDAC has increased over the last 40 years and is projected to be the second leading cause of cancer death by 2030. Despite aggressive treatment regimens, prognosis for patients diagnosed with PDAC is very poor; PDAC has the lowest 5-year survival rate for any form of cancer in the United States (US). PDAC cases are rarely detected in early stage when surgical resection can be performed and few, approximately 20%, are suitable for surgical resection which remains the only curative treatment when …
Visceral Adipose Tissue Remodeling In Pancreatic Ductal Adenocarcinoma Cachexia: The Role Of Activin A Signaling, Pauline Xu
Theses & Dissertations
Pancreatic ductal adenocarcinoma (PDAC) is currently the third leading cause of cancer death in the United States and is projected to become the second leading cause by the year 2030. Prognosis for patients with metastatic disease remains dismal, with cachexia as a main contributor to the low survival rate. Emerging reports indicate that PDAC patients display distinct phenotypes of cachexia development, with either adipose tissue loss preceding skeletal muscle wasting or loss of only adipose tissue. While muscle wasting has been the most frequently studied mechanism in cachexia research, changes in adipose tissue are increasingly understood as important components of …
Evaluating Targets And Therapeutics For The Treatment Of Pancreatic Cancer, Shelby M. Knoche
Evaluating Targets And Therapeutics For The Treatment Of Pancreatic Cancer, Shelby M. Knoche
Theses & Dissertations
Pancreatic cancer has a dismally low survival rate, due to inadequate understanding of the processes that are involved in disease development and progression. Despite the identification of oncogenic drivers such as KRAS and p53, there is a need for the identification of molecular targets to improve and develop novel therapeutic approaches for the treatment of pancreatic cancer. Studies from our laboratory have identified and evaluated targets and therapeutic approaches that can aid in our understanding of pancreatic cancer disease progression and improve patient outcomes. Through the use of epidermal growth factor receptor (EGFR) ligands (EGF and TGF-α) and small molecule …
Phos-Tag-Based Screens Identify Novel Therapeutic Targets In Ovarian Cancer And Pancreatic Cancer, Renya Zeng
Phos-Tag-Based Screens Identify Novel Therapeutic Targets In Ovarian Cancer And Pancreatic Cancer, Renya Zeng
Theses & Dissertations
Multiple Phos-tag-based screens were conducted in anti-tubulin drug (paclitaxel and nocodazole)-treated cells to explore novel targets implicated in cell cycle regulation, resistance against paclitaxel, and yes-associated protein (YAP) nucleocytoplasmic transport. The Phos-tag-based screen of protein kinases identified that several proteins were degraded or phosphorylated in response to anti-tubulin drug treatment. A tyrosine kinase, fibroblast growth factor receptor 4 (FGFR4), was significantly degraded upon anti-tubulin drug treatment, suggesting its potential role in cell response to paclitaxel. Further functional investigations identified that FGFR4 mediated paclitaxel resistance in ovarian cancer, and specific inhibitors targeting FGFR4 could sensitize ovarian cancer cells to paclitaxel. Mechanistically, …
Development Of A Muc16-Targeted Near-Infrared Antibody Probe For Fluorescence-Guided Surgery Of Pancreatic Cancer, Madeline T. Olson
Development Of A Muc16-Targeted Near-Infrared Antibody Probe For Fluorescence-Guided Surgery Of Pancreatic Cancer, Madeline T. Olson
Theses & Dissertations
Pancreatic cancer (PDAC) is an extremely lethal disease with an overall survival rate of 10%. Surgery remains the only potentially curative treatment option, but resections are complicated by infiltrative disease, proximity of critical vasculature, peritumoral inflammation, and dense stroma. Surgeons are limited to tactile and visual cues to differentiate cancerous tissue from normal tissue. Furthermore, translating preoperative images to the intraoperative setting poses additional challenges for tumor detection, and can result in undetected and unresected lesions. Thus, PDAC has high rates of incomplete resections, and subsequently, disease recurrence. Fluorescence-guided surgery (FGS) has emerged as a method to improve intraoperative detection …
Mutant Kras Alters Extracellular Vesicle Microrna Sorting In Pancreatic Cystic Neoplasms, Rachel L. Dittmar
Mutant Kras Alters Extracellular Vesicle Microrna Sorting In Pancreatic Cystic Neoplasms, Rachel L. Dittmar
Dissertations and Theses (Open Access)
Pancreatic ductal adenocarcinoma (PDAC) is among the deadliest cancers by organ site with a 5-year survival rate of just 10.8%. This is largely because most patients do not experience symptoms until the disease has already metastasized. The best hope to cure PDAC is surgery, which can only be done with a curative intent at an early stage when the disease is localized. There are no reliable circulating, body-fluid-based biomarkers to detect early stage PDAC or its precursor lesions in a timely manner for effective surgical intervention. When potential PDAC precursor lesions, such as mucinous pancreatic cysts are found, there are …
Targeted Therapies In Select Gastrointestinal Cancers And Cancer Cachexia, Scott Mulder
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 …
Longitudinal Clonal Lineage Dynamics And Functional Characterization Of Pancreatic Cancer Chemo-Resistance And Metastasization, Chieh-Yuan Li
Longitudinal Clonal Lineage Dynamics And Functional Characterization Of Pancreatic Cancer Chemo-Resistance And Metastasization, Chieh-Yuan Li
Dissertations and Theses (Open Access)
In recent years, technological advancements, such as next-generation sequencing and single-cell interrogation techniques, have enriched our understanding in tumor heterogeneity. By dissecting tumors and characterizing clonal lineages, we are better understanding the intricacies of tumor evolution. Tumors are represented by the presence of and dynamic interactions amongst clonal lineages. Each lineage and each cell contributes to tumor dynamics through intrinsic and extrinsic mechanisms, and the variable responses of clones to perturbations in the environment, especially therapeutics, underlie disease progression and relapse. Thus, there exists a pressing need to understand the molecular mechanisms that determine the functional heterogeneity of tumor sub-clones …
Molecular Insights Into Paf-1 Mediated Pancreatic Homeostasis, Stemness, And Cancer Progression, Saswati Karmakar
Molecular Insights Into Paf-1 Mediated Pancreatic Homeostasis, Stemness, And Cancer Progression, Saswati Karmakar
Theses & Dissertations
Pancreatic ductal adenocarcinoma (PDAC) is a lethal disease that has one of the lowest 5-year survival rates among cancers, at just 9%. This grim prognosis is primarily due to the extensive metastatic spread of tumor cells beyond the pancreas at diagnosis and the inability of current therapeutic modalities to treat this aggressive disease effectively. Given that the cancer cells in pancreatic tumors are heterogeneous, the major culprit for cancer initiation, progression, and metastasis remains elusive. Recent studies provide evidence for the existence of highly tumorigenic and drug-resistant cells that are capable of tumor initiation, known as the cancer stem cells …
The Cxcr2-Dependent Role Of Cancer-Associated Fibroblasts In Pancreatic Ductal Adenocarcinoma, Mohammad Awaji
The Cxcr2-Dependent Role Of Cancer-Associated Fibroblasts In Pancreatic Ductal Adenocarcinoma, Mohammad Awaji
Theses & Dissertations
Pancreatic ductal adenocarcinoma (PDAC) is the most common type of pancreatic cancer, the fourth leading cause of cancer-related deaths in the USA with over 40,000 deaths per year. Unlike other major cancer types, the progress in dealing with PDAC is plodding, attributed mainly to the asymptomatic nature of the disease, the late diagnosis and the ineffectiveness of current therapies. A better understanding of the biology of the disease could permit the discovery of novel diagnostic and therapeutic tools. With that in mind, we present this dissertation that investigates the tumor-stromal interaction underlined by genetic alterations and inflammation. PDAC develop as …
Induction And Metastasis Of Cancer Stem Cells In Pancreatic Cancer, Rama Krishna Nimmakayala
Induction And Metastasis Of Cancer Stem Cells In Pancreatic Cancer, Rama Krishna Nimmakayala
Theses & Dissertations
Pancreatic cancer is one of the most lethal of all types of cancer with an overall 5-year survival rate of less than 8%. Cancer cells in pancreatic tumor are heterogeneous, and it is poorly understood which population is most responsible for the cancer initiation, progression and metastasis. Recent studies provide evidence for the existence of a highly tumorigenic and metastatic cells within a heterogeneous tumor known as the cancer stem cells (CSCs). Studies also provided ample evidence for the existence of distinct types of CSC populations in a heterogeneous tumor with type specific genotypic, phenotypic and functional characteristics. But, it …
The Beta-Catenin/Muc1.Ct Interaction In Pancreatic Cancer, Edwin Wiest
The Beta-Catenin/Muc1.Ct Interaction In Pancreatic Cancer, Edwin Wiest
Theses & Dissertations
MUC1 is overexpressed in over 90% of pancreatic cancer cases, and its interaction with beta-catenin promotes progression of the disease. Various in vitro and in vivo methods show that beta-catenin and MUC1 interact by way of the cytoplasmic tail of MUC1 (MUC1.CT). This interaction occurs in the membrane of pancreatic cancer cells but is found to a smaller extent in the nucleus as well. Biophysical methods suggest that MUC1 interacts with beta-catenin through a sequence of amino acids in the tail of MUC1 that sit very near the transmembrane domain of MUC1. In pancreatic ductal adenocarcinoma cells, it appears that …
Ketone Bodies And Signaling In Pancreatic Cancer Cell Lines, Kyla B. Buettner, Pankaj K. Singh, Surendra K. Shukla
Ketone Bodies And Signaling In Pancreatic Cancer Cell Lines, Kyla B. Buettner, Pankaj K. Singh, Surendra K. Shukla
Theses/Capstones/Creative Projects
Pancreatic cancer is the fourth leading cause of cancer-related deaths in the United States, and 95% of these cases are caused by PDAC (pancreatic ductal adenocarcinoma). Ketone bodies have previously been shown to decrease cell proliferation and cancer-induced cachexia. The molecular mechanism of ketone body-mediated growth inhibition of pancreatic cancer cells is not well understood. Research conducted thus far has not explored which molecular pathways are affected by ketone body treatment in pancreatic cancer cells. In the current study, the effect of the ketone body sodium hydroxybutyrate on the JAK-STAT and mTOR pathways and cell migration was explored. A decrease …
Enhanced Electric Pulse Technology For The Ablation Of Pancreatic Cancer, Siqi Guo, Niculina I. Burcus, Chelsea M. Edelblute, James Hornef, Chunqi Jiang, Karl Schoenbach, Richard Heller, Stephen J. Beebe
Enhanced Electric Pulse Technology For The Ablation Of Pancreatic Cancer, Siqi Guo, Niculina I. Burcus, Chelsea M. Edelblute, James Hornef, Chunqi Jiang, Karl Schoenbach, Richard Heller, Stephen J. Beebe
Bioelectrics Publications
Electric pulse based technology has been developed and studied as a non-thermal ablation method for local control of pancreatic cancer. Irreversible electroporation (IRE) has shown a significant survival benefit for local advanced pancreatic cancer in clinical trials. However, incomplete ablation with local recurrence and major complications limit the potential of this new technology. We have developed an integrated moderate heating electric pulse delivery system which consists of controllable tumor heating, multi-parameter monitoring and electric pulse delivery. The impedance of tumor is greatly decreased after moderate heating at 42°C for 1–2 min, which does not cause any cell death. Moderate heating …
Novel Survivin Inhibitor For Suppressing Pancreatic Cancer Cells Growth Via Downregulating Sp1 And Sp3 Transciption Factors, Myrna Hurtado, Umesh T. Sankpal, Aboubacar Kaba, Shahela Mahammad, Jaya Chhabra, Deondra T. Brown, Raj K. Gurung, Alvin A. Holder, Jamboor K. Vishwanatha, Riyaz Basha
Novel Survivin Inhibitor For Suppressing Pancreatic Cancer Cells Growth Via Downregulating Sp1 And Sp3 Transciption Factors, Myrna Hurtado, Umesh T. Sankpal, Aboubacar Kaba, Shahela Mahammad, Jaya Chhabra, Deondra T. Brown, Raj K. Gurung, Alvin A. Holder, Jamboor K. Vishwanatha, Riyaz Basha
Chemistry & Biochemistry Faculty Publications
Background/Aims: Targeting survivin, an anti-apoptotic protein and mitotic regulator, is considered as an effective therapeutic option for pancreatic cancer (PaCa). Tolfenamic acid (TA) showed anti-cancer activity in pre-clinical studies. A recent discovery demonstrated a copper(II) complex of TA (Cu-TA) can result in higher activity. In this study, the ability of Cu-TA to inhibit survivin and its transcription factors, Specificity protein (Sp) 1 and 3 in PaCa cell lines and tumor growth in mouse xenograft model were evaluated.
Methods: Cell growth inhibition was measured in MIA PaCa-2 and Panc1 cells for 2 days using CellTiter-Glo kit. Sp1, Sp3 and survivin expression …