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Articles 541 - 570 of 616
Full-Text Articles in Neoplasms
E2f4 Regulatory Program Predicts Patient Survival Prognosis In Breast Cancer, Sari S. Khaleel, Erik H. Andrews, Matthew Ung, James Direnzo, Chao Chung
E2f4 Regulatory Program Predicts Patient Survival Prognosis In Breast Cancer, Sari S. Khaleel, Erik H. Andrews, Matthew Ung, James Direnzo, Chao Chung
Dartmouth Scholarship
Genetic and molecular signatures have been incorporated into cancer prognosis prediction and treatment decisions with good success over the past decade. Clinically, these signatures are usually used in early-stage cancers to evaluate whether they require adjuvant therapy following surgical resection. A molecular signature that is prognostic across more clinical contexts would be a useful addition to current signatures. We defined a signature for the ubiquitous tissue factor, E2F4, based on its shared target genes in multiple tissues. These target genes were identified by chromatin immunoprecipitation sequencing (ChIP-seq) experiments using a probabilistic method. We then computationally calculated the regulatory activity score …
Autoantibodies To The Ny-Eso-1 Tumor Antigen In Metastatic Melanoma: Sialylation Of The Fc Region Of Immunoglobulin G Induces Differential Expression Signatures Of Inflammatory Molecules During Dendritic Cell Differentiation And Maturation, Martin Oaks, Nathaniel Rein, John O. Richards, James Shaffer
Autoantibodies To The Ny-Eso-1 Tumor Antigen In Metastatic Melanoma: Sialylation Of The Fc Region Of Immunoglobulin G Induces Differential Expression Signatures Of Inflammatory Molecules During Dendritic Cell Differentiation And Maturation, Martin Oaks, Nathaniel Rein, John O. Richards, James Shaffer
Journal of Patient-Centered Research and Reviews
Purpose: We tested the hypothesis that different glycoforms of antibodies from patients with metastatic melanoma have different functional effects on human dendritic cell differentiation and maturation.
Methods: Antibodies to the cancer antigen NY-ESO-1 were affinity-purified from patients with melanoma and further fractionated into different glycoforms by lectin chromatography. Sialic acid-rich and sialic acid-poor fractions of these immunoglobulin G antibodies (IgG) were added to dendritic cell cultures during both differentiation and maturation, and the resulting cellular messenger RNA (mRNA) and culture supernatants were tested by microarray and enzyme-linked immunoassay for molecules related to inflammatory pathways.
Results: We identified unique mRNA and …
Role Of A Genetic Variant On The 15q25.1 Lung Cancer Susceptibility Locus In Smoking-Associated Nasopharyngeal Carcinoma, Xuemei Ji, Weidong Zhang, Jiang Gui, Xia Fan, Weiwei Zhang, Yafang Li, Guangyu An, Dakai Zhu, Qiang Hu
Role Of A Genetic Variant On The 15q25.1 Lung Cancer Susceptibility Locus In Smoking-Associated Nasopharyngeal Carcinoma, Xuemei Ji, Weidong Zhang, Jiang Gui, Xia Fan, Weiwei Zhang, Yafang Li, Guangyu An, Dakai Zhu, Qiang Hu
Dartmouth Scholarship
Background: The 15q25.1 lung cancer susceptibility locus, containing CHRNA5, could modify lung cancer susceptibility and multiple smoking related phenotypes. However, no studies have investigated the association between CHRNA5 rs3841324, which has been proven to have the highest association with CHRNA5 mRNA expression, and the risk of other smoking-associated cancers, except lung cancer. In the current study we examined the association between rs3841324 and susceptibility to smoking-associated nasopharyngeal carcinoma (NPC).
Methods: In this case-control study we genotyped the CHRNA5 rs3841324 polymorphism with 400 NPC cases and 491 healthy controls who were Han Chinese and frequency-matched by age (±5 years), gender, and …
Pathophysiology, Incidence And Implications In Intraductal Papillary Mucinous Neoplasia Of The Pancreas, Ericka Haverick
Pathophysiology, Incidence And Implications In Intraductal Papillary Mucinous Neoplasia Of The Pancreas, Ericka Haverick
Nursing Student Class Projects (Formerly MSN)
Intraductal papillary mucinous neoplasms (IPMN) are uncommon tumors arising from the main pancreatic duct, branching pancreatic ducts, or both. The “overall incidence of invasive carcinoma associated with resected IPMN has been reported to be 20-40%” (Mohri et al., 2011). Due to their malignant potential, these lesions, along with mucinous cystic neoplasms (MCN), are considered more worrisome, and often require surgical resection (Gallucci, Langellotto, De Ritis, & Uomo, 2012). Even after removal of a primary lesion, patients remain under surveillance to monitor for recurrence, the rate of which is approximately 6 % (Gallucci et al., 2012), and patients with main duct …
Inpp4b Suppresses Prostate Cancer Cell Invasion, Myles C. Hodgson, Elena I. Deryugina, Egla Suarez, Sandra M. Lopez, Dong Lin, Hui Xue, Ivan P. Gorlov
Inpp4b Suppresses Prostate Cancer Cell Invasion, Myles C. Hodgson, Elena I. Deryugina, Egla Suarez, Sandra M. Lopez, Dong Lin, Hui Xue, Ivan P. Gorlov
Dartmouth Scholarship
INPP4B and PTEN dual specificity phosphatases are frequently lost during progression of prostate cancer to metastatic disease. We and others have previously shown that loss of INPP4B expression correlates with poor prognosis in multiple malignancies and with metastatic spread in prostate cancer.
We demonstrate that de novo expression of INPP4B in highly invasive human prostate carcinoma PC-3 cells suppresses their invasion both in vitro and in vivo. Using global gene expression analysis, we found that INPP4B regulates a number of genes associated with cell adhesion, the extracellular matrix, and the cytoskeleton. Importantly, de novo expressed INPP4B suppressed the proinflammatory chemokine …
Targeting The Redox System To Overcome Mechanisms Of Drug Resistance In Chronic Lymphocytic Leukemia, Marcia A. Ogasawara
Targeting The Redox System To Overcome Mechanisms Of Drug Resistance In Chronic Lymphocytic Leukemia, Marcia A. Ogasawara
Dissertations and Theses (Open Access)
Chronic Lymphocytic Leukemia (CLL) is the most common form of leukemia diagnosed in Western countries and is characterized by clonal expansion of B cells. The clinical course of CLL is diverse and nearly 50% of patients present with chromosomal abnormalities. Deletion of the short arm on chromosome 17 (del17p) occurs in 5-7% of cases and presents with the shortest median survival time and often respond poorly to therapy. The tumor suppressor gene, TP53 is located on this region and it is well established that the p53 protein regulates multiple functions including: mitochondria biogenesis, response to DNA damage and redox balance. …
Modeling The Adaptive Immune Response To Mutation-Generated Antigens, Rory J. Geyer
Modeling The Adaptive Immune Response To Mutation-Generated Antigens, Rory J. Geyer
University Scholar Projects
Somatic mutations may drive tumorigenesis or lead to new, immunogenic epitopes (neoantigens). The immune system is thought to represses neoplastic growths through the recognition of neoantigens presented only by tumor cells. To study mutations as well as the immune response to mutation-generated antigens, we have created a conditional knockin mouse line with a gene encoding, 5’ to 3’, yellow fluorescent protein (YFP), ovalbumin (which is processed to the immunologically recognizable peptide, SIINFEKL), and cyan fluorescent protein (CFP), or, YFP-ovalbumin-CFP. A frame shift mutation has been created at the 5’ end of the ovalbumin gene, hence YFP should always be expressed, …
Molecular Characterization Of Glioblastoma Cancer Stem Cells, Jo Meagan Garner
Molecular Characterization Of Glioblastoma Cancer Stem Cells, Jo Meagan Garner
Theses and Dissertations (ETD)
Malignant gliomas are locally aggressive, highly vascular tumors that have an overall survival time less than 14 months, and current therapies provide little improvement in the disease course and outcome. While glioblastoma multiforme (GBM) patients present uniform histological phenotypes, the molecular determinants of the disease vary considerably between individual cases resulting in complicated prognosis. The heterogeneity, aggressiveness and rapid tumor relapse of GBM is believed to be sustained by cancer stem-like cell populations that are able to initiate and maintain tumors. Although CSCs represent only a small fraction of cells within a tumor, their high tumor-initiating capacity and therapeutic resistance …
Evaluation Of Current Clinical Criteria For Li-Fraumeni Syndrome In A Diverse Sample Of Tp53 Mutation Carriers, Emily A. Parham
Evaluation Of Current Clinical Criteria For Li-Fraumeni Syndrome In A Diverse Sample Of Tp53 Mutation Carriers, Emily A. Parham
Dissertations and Theses (Open Access)
Li-Fraumeni syndrome (LFS) is a hereditary cancer predisposition syndrome caused by heterozyogous germline mutations in the TP53 gene and characterized by an excess of early-onset cancers, high lifetime risk of cancer, and a wide range of tumor types. Recent studies suggesting a benefit in comprehensive screening protocols for both children and adults make the timely identification of individuals with LFS increasingly important.
A number of criteria have been proposed to identify patients with LFS. The National Comprehensive Cancer Network (NCCN) combines several in its Clinical Practice Guidelines for TP53 genetic testing. Prior studies have shown that the cumulative sensitivity of …
Predicting Targeted Drug Combinations Based On Pareto Optimal Patterns Of Coexpression Network Connectivity, Nadia M. Penrod, Casey S. Greene, Jason H. Moore
Predicting Targeted Drug Combinations Based On Pareto Optimal Patterns Of Coexpression Network Connectivity, Nadia M. Penrod, Casey S. Greene, Jason H. Moore
Dartmouth Scholarship
Molecularly targeted drugs promise a safer and more effective treatment modality than conventional chemotherapy for cancer patients. However, tumors are dynamic systems that readily adapt to these agents activating alternative survival pathways as they evolve resistant phenotypes. Combination therapies can overcome resistance but finding the optimal combinations efficiently presents a formidable challenge. Here we introduce a new paradigm for the design of combination therapy treatment strategies that exploits the tumor adaptive process to identify context-dependent essential genes as druggable targets. We have developed a framework to mine high-throughput transcriptomic data, based on differential coexpression and Pareto optimization, to investigate drug-induced …
Analysis Of The Regulation And Function Of Cip2a To Identify Candidate Biomarkers For Prostate Cancer, Diana Savoly
Analysis Of The Regulation And Function Of Cip2a To Identify Candidate Biomarkers For Prostate Cancer, Diana Savoly
Graduate School of Biomedical Sciences Theses and Dissertations
Protein Phosphatase 2A (PP2A) is a tumor suppressor involved in the regulation of several signaling pathways and the cell cycle. PP2A becomes inactivated by several inhibitors, including Cancerous Inhibitor of PP2A (CIP2A). CIP2A has been identified as an oncogene, which is over-expressed in cancers and inhibits PP2A through direct interaction. CIP2A is recognized as a biomarker for cancer; however, it is not cancer-specific. Therefore, we identified and examined the use of CIP2A-regulated proteins as potential biomarkers in prostate cancer to better diagnose prostate cancer in patients. Currently, Prostate Specific Antigen (PSA) is widely used to detect prostate cancer; however, it …
Microbiota, Oral Microbiome, And Pancreatic Cancer, Dominique S. Michaud, Jacques Izard
Microbiota, Oral Microbiome, And Pancreatic Cancer, Dominique S. Michaud, Jacques Izard
Department of Food Science and Technology: Faculty Publications
Only 30% of patients diagnosed with pancreatic cancer survive one year post-diagnosis. Progress in understanding the causes of pancreatic cancer has been made, including solidifying the associations with obesity and diabetes, and a proportion of cases should be preventable through lifestyle modifications. Unfortunately, identifying reliable biomarkers of early pancreatic cancer has been extremely challenging, and no effective screening modality is currently available for this devastating form of cancer. Recent data suggest the microbiota may play a role in the disease process, but many questions remain. Future studies focusing on the human microbiome, both etiologically and as a marker of disease …
Molecular Pap Biomarkers For Cervical Cancer Risk Assessment In Thinprep® Clinical Specimens, Jennifer Taylor
Molecular Pap Biomarkers For Cervical Cancer Risk Assessment In Thinprep® Clinical Specimens, Jennifer Taylor
Graduate School of Biomedical Sciences Theses and Dissertations
Approximately 500,000 patients are diagnosed with cervical cancer worldwide each year, thus making it the second most common cause of cancer-related deaths in women. Persistent high-risk human papillomavirus (HR-HPV) infections induce cervical dysplasia by increasing the expression of two viral oncogenes, E6 and E7. Utilization of the Papanicolaous smear test (Pap test) has contributed to a decrease in morbidity and mortality of cervical cancer; however, subjective analysis of cell morphology with a limited amount of cells has led to a substantial rate of false positive and false negative diagnoses. A more objective and sensitive diagnostic tool for the detection of …
Parp Inhibition: A Method Of Treating And Preventing Certain Cancers, Chana Tropper
Parp Inhibition: A Method Of Treating And Preventing Certain Cancers, Chana Tropper
The Science Journal of the Lander College of Arts and Sciences
Breast cancer is one of the largest causes of cancer related deaths in women. Less than 5% of breast cancer cases are genetically inherited and most often develop after menopause. The BRCA gene mutation is a genetic inheritance which increases ones chances of developing breast cancer at a young age tenfold. Recent research has proposed a method of treatment in genetically inherited breast cancers by taking advantage of the impaired DNA repair pathway caused by the BRCA mutation. The combination of a BRCA mutation, which leads to deficient double strand DNA repair, and PARP inhibition, which leads to deficient single …
Immunotherapy As A Treatment Option For Patients With Pancreatic Cancer, Yehuda Lehrfield
Immunotherapy As A Treatment Option For Patients With Pancreatic Cancer, Yehuda Lehrfield
The Science Journal of the Lander College of Arts and Sciences
Pancreatic cancer is one of the worst forms of cancer that can develop in an individual. Traditionally, chemotherapy is administered but it has very limited success. Using the immune system to treat the cancer is very enticing and many studies have been conducted to attempt to harness the body’s own mechanisms to defeat the cancer. It seems that in order to properly treat the tumor a two pronged approach must be used. First, the immune system must be stimulated to react to the tumor and attack it. A possible cytokine that can be utilized is interferon alpha, which could result …
Chemopreventive Effects Of Pterostilbene In Metastatic Prostate Cancer Cells, Phillip A. Zook
Chemopreventive Effects Of Pterostilbene In Metastatic Prostate Cancer Cells, Phillip A. Zook
PCOM Biomedical Studies Student Scholarship
Recent studies find that pterostilbene (PTS) exhibits more favorable drug properties and similar chemopreventive effects to its structural analogue resveratrol (RSV). However, few studies describe the activity of PTS in prostate cancer (PCa). Here, we conducted cell count experiments to assess the effects of PTS on metastatic PCa cell viability and to compare the potency of PTS to RSV in this respect. We also performed experiments to assess the effects of PTS on the androgen receptor (AR) and AR-mediated events. We used qPCR to measure the mRNA levels of the androgenresponsive gene (ARG), prostate-specific antigen (PSA), and Western blots to …
Effect Of Heme Oxygenase-1 On Matrix Metalloproteinase-3 Expression In Human Fibroblasts, Theresa A. Stangl
Effect Of Heme Oxygenase-1 On Matrix Metalloproteinase-3 Expression In Human Fibroblasts, Theresa A. Stangl
PCOM Biomedical Studies Student Scholarship
Heme oxygenase-1(HO-1) is an enzyme that plays a very important role in the resolution of inflammation. HO-1-based therapies are effective in a number of disease conditions. However, HO-1 also increases tumor growth, angiogenesis, metastasis and chemoresistance. Matrix metalloproteinase-3 (MMP-3) is an enzyme involved in physiological and pathophysiological tissue remodeling. Unbalanced expression of MMPs is a key feature of connective tissue destruction in chronic inflammatory conditions. Previously shown in this laboratory, the HO-1 inducer, hemin, increased MMP-3 mRNA expression in some HGF cultures. To assess whether HO-1 and/or its products regulate expression of MMP-3 in human fibroblasts, the effect of HO-1 …
Conformational Changes And Translocation Of Tissue-Transglutaminase To The Plasma Membranes: Role In Cancer Cell Migration, Ambrish Kumar, Jianjun Hu, Holly A. Lavoie, Kenneth B. Walsh, Donald J. Dipette, Ugra S. Singh
Conformational Changes And Translocation Of Tissue-Transglutaminase To The Plasma Membranes: Role In Cancer Cell Migration, Ambrish Kumar, Jianjun Hu, Holly A. Lavoie, Kenneth B. Walsh, Donald J. Dipette, Ugra S. Singh
Faculty Publications
Background
Tissue-transglutaminase (TG2), a dual function G-protein, plays key roles in cell differentiation and migration. In our previous studies we reported the mechanism of TG2-induced cell differentiation. In present study, we explored the mechanism of how TG2 may be involved in cell migration.
Methods
To study the mechanism of TG2-mediated cell migration, we used neuroblastoma cells (SH-SY5Y) which do not express TG2, neuroblastoma cells expressing exogenous TG2 (SHYTG2), and pancreatic cancer cells which express high levels of endogenous TG2. Resveratrol, a natural compound previously shown to inhibit neuroblastoma and pancreatic cancer in the animal models, was utilized to …
Novel Therapeutic Strategies For Pancreatic Cancer, Bridget A. Quinn
Novel Therapeutic Strategies For Pancreatic Cancer, Bridget A. Quinn
Theses and Dissertations
Pancreatic cancer is a devastating disease that leaves patients with a very poor prognosis and few therapeutic options. Many of the treatment options available are the same that have been used for almost 2 decades. There is a dire need for both novel treatments for this disease as well as novel strategies of treatment. This body of work will introduce and provide evidence in support of a novel combination therapy for pancreatic cancer treatment, a novel strategy of modifying currently used chemotherapeutics for pancreatic cancer therapy, and a novel transgenic preclinical mouse model of pancreatic cancer. Sabutoclax, an antagonist of …
Radiosensitization Of Head & Neck Carcinoma Cells By Linifanib, A Receptor Tyrosine Kinase Inhibitor, Heng-Wei Hsu
Radiosensitization Of Head & Neck Carcinoma Cells By Linifanib, A Receptor Tyrosine Kinase Inhibitor, Heng-Wei Hsu
Loma Linda University Electronic Theses, Dissertations & Projects
Tumor angiogenesis is a hallmark of advanced cancers and promotes invasion and metastasis. Over 90% of head and neck squamous cell carcinomas (HNSCC) express angiogenic factors such as vascular endothelial growth factor (VEGF). Since radiotherapy is one of the most commonly used treatments for HNSCC, it is imperative to identify the interactions between antiangiogenic therapy and radiotherapy, and to develop combination therapy to improve clinical outcome. The mechanisms between antiangiogenic agents and ionizing radiation are complicated and involve many interactions between the vasculature, tumor stroma and tumor cells. The proliferation and metastasis of tumor cells rely on angiogenesis/blood vessel formation. …
Nkg2d Ligands In Cancer, Neha Das Gupta
Nkg2d Ligands In Cancer, Neha Das Gupta
Theses and Dissertations (ETD)
NK cell transplantation has been increasingly used to treat cancers that are resistant to chemotherapy. However, not all cancers are susceptible to NK cell killing. The prevalence and mechanisms of NK cell resistance have not been well elucidated. Because NKG2D is a major activating receptor on NK cells, we sought to test the hypothesis that NKG2D is the primary pathway in tumor cell recognition. Herein, we comprehensively assessed 20 cancer cell lines representing a broad array of cancer types. In line with our primary hypothesis, no cancer cell lines that expressed low levels of NKG2D ligands were susceptible to NK …
Identification Of Novel Hif1a Target Genes That Regulate Tumor Progression And Metastasis, Danielle L. Peacock
Identification Of Novel Hif1a Target Genes That Regulate Tumor Progression And Metastasis, Danielle L. Peacock
Theses and Dissertations (ETD)
Hypoxia is a hallmark of most solid tumors. In response to hypoxic stress tumor cells adapt by regulating survival, metabolism and angiogenesis. The heterodimeric HypoxiaInducible Factor (HIF) transcription factors are the master regulators of this response. HIFs play key roles in many critical aspects of cancer biology including angiogenesis, stem cell maintenance, metabolic reprogramming, invasion, metastasis and resistance to radiation therapy and chemotherapy. Overexpression of HIF-1α and HIF-2α has been documented in multiple human cancers and HIF-1 protein is over-expressed in ~30% of primary breast tumors and ~70% of metastases, which independently correlates with poor prognosis and decreased survival in …
Plasma Antibodies To Oral Bacteria And Risk Of Pancreatic Cancer In A Large European Prospective Cohort Study, Dominique S. Michaud, Jacques Izard, Charlotte S. Wilhelm-Benartzi, Doo-Ho You, Verena A. Grote, Anne Tjønneland, Christina C. Dahm, Kim Overvad, Mazda Jenab, Veronika Fedirko, Marie Christine Boutron-Ruault, Françoise Clavel- Chapelon, Antoine Racine, Rudolf Kaaks, Heiner Boeing, Jana Foerster, Antonia Trichopoulou, Pagona Lagiou, Dimitrios Trichopoulos, Carlotta Sacerdote, Sabina Sieri, Domenico Palli, Rosario Tumino, Salvatore Panico, Peter Siersema, Petra Hm Peeters, Eiliv Lund, Aurelio Barricarte, José-María Huerta, Esther Molina-Montes, Miren Dorronsoro, J. Ramón Quirós, Eric J. Duell, Weimin Ye, Malin Sund, Björn Lindkvist, Dorthe Johansen, Kay-Tee Khaw, Nick Wareham, Ruth C. Travis, Paolo Vineis, H. Bas Bueno-De-Mesquita, Elio Riboli
Plasma Antibodies To Oral Bacteria And Risk Of Pancreatic Cancer In A Large European Prospective Cohort Study, Dominique S. Michaud, Jacques Izard, Charlotte S. Wilhelm-Benartzi, Doo-Ho You, Verena A. Grote, Anne Tjønneland, Christina C. Dahm, Kim Overvad, Mazda Jenab, Veronika Fedirko, Marie Christine Boutron-Ruault, Françoise Clavel- Chapelon, Antoine Racine, Rudolf Kaaks, Heiner Boeing, Jana Foerster, Antonia Trichopoulou, Pagona Lagiou, Dimitrios Trichopoulos, Carlotta Sacerdote, Sabina Sieri, Domenico Palli, Rosario Tumino, Salvatore Panico, Peter Siersema, Petra Hm Peeters, Eiliv Lund, Aurelio Barricarte, José-María Huerta, Esther Molina-Montes, Miren Dorronsoro, J. Ramón Quirós, Eric J. Duell, Weimin Ye, Malin Sund, Björn Lindkvist, Dorthe Johansen, Kay-Tee Khaw, Nick Wareham, Ruth C. Travis, Paolo Vineis, H. Bas Bueno-De-Mesquita, Elio Riboli
Department of Food Science and Technology: Faculty Publications
Objective: Examine the relationship between antibodies to 25 oral bacteria and pancreatic cancer risk in a prospective cohort study.
Design: We measured antibodies to oral bacteria in prediagnosis blood samples from 405 pancreatic cancer cases and 416 matched controls, nested within the European Prospective Investigation into Cancer and Nutrition study (EPIC). Analyses were conducted using conditional logistic regression and additionally adjusted for smoking status and body mass index.
Results: Individuals with high levels of antibodies against Porphyromonas gingivalis ATTC 53978, a pathogenic periodontal bacteria, had a 2-fold higher risk of pancreatic cancer than individuals lower levels of …
The Protumorigenic Role Of Caspase-8 In Neuroblastoma, Devin Drew Twitchell
The Protumorigenic Role Of Caspase-8 In Neuroblastoma, Devin Drew Twitchell
Theses and Dissertations (ETD)
Neuroblastoma (NB), the most common extracranial solid tumor in children, accounts for 15% of cancer-related deaths in pediatric patients. Caspase-8 (casp8), a proapoptotic protein, is silenced in approximately, 50-70% of neuroblastoma patient samples. Loss of casp8 has been suggested to increase NB metastasis and correlated, in some studies, with advanced-stage NB. Furthermore, decreased casp8 expression may facilitate neuroblastoma tumorigenesis by protecting cells from cell death mediated by either integrins or chemotherapeutics. Paradoxically, casp8 expression is maintained in 30-50% of NB patient samples giving rise to the possibility that casp8 may provide selective advantages for NB tumorigenesis. Caspase-8 is shown to …
Id4 Deficiency Attenuates Prostate Development And Promotes Pin-Like Lesions By Regulating Androgen Receptor Activity And Expression Of Nkx3.1 And Pten, Pankaj Sharma, Ashley Knowell, Swathi Chinaranagari, Shravan Komaragiri, Peri Nagappan, Divya Patel, Mathew C. Havrda, Jaideep Chaudhary
Id4 Deficiency Attenuates Prostate Development And Promotes Pin-Like Lesions By Regulating Androgen Receptor Activity And Expression Of Nkx3.1 And Pten, Pankaj Sharma, Ashley Knowell, Swathi Chinaranagari, Shravan Komaragiri, Peri Nagappan, Divya Patel, Mathew C. Havrda, Jaideep Chaudhary
Dartmouth Scholarship
Background: 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. Id4 is expressed in the normal prostate where its expression is also regulated by androgens. In this study we investigated the effect of loss of Id4 (Id4-/-) on adult prostate morphology. Methods: Histological analysis was performed on prostates from 6-8 weeks old Id4-/-, Id4+/- and Id4+/+ mice. Expression of Id1, Sox9, Myc, androgen receptor, Akt, p-Akt, Pten and Nkx3.1 was investigated by immunohistochemistry. Androgen receptor binding on NKX3.1 promoter was studied by chromatin immuno-precipitation. Id4 was …
Functional Study Of Hemogen Knockout Mouse Model, Peng Gao
Functional Study Of Hemogen Knockout Mouse Model, Peng Gao
Theses and Dissertations (ETD)
Mouse Hemogen (Hemgn) is regarded as a homologue of human Erythroid Differentiation Associated Gene (EDAG). EDAG overexpression has been postulated for association with some leukemia cases. Meanwhile, Hemgn has been found to contribute to Hoxb4 mediated hematopoietic stem cell expansion. Based on these postulations and evidences, a Hemgn knockout mouse model has been generated to study its function in normal and stress hematopoiesis. I confirmed the Hemgn expression in hematopoietic organs including bone marrow and spleen, as well as round spematids in testis. Hemgn is expressed in mouse hematopoietic stem cells and erythroid progenitor cells. Moreover, Hemgn was also found …
Characterization Of Differentiation And Prognostic Biomarkers On Cd8+ Tumor-Infiltrating Lymphocytes In Metastatic Melanoma, Richard C. Wu
Characterization Of Differentiation And Prognostic Biomarkers On Cd8+ Tumor-Infiltrating Lymphocytes In Metastatic Melanoma, Richard C. Wu
Dissertations and Theses (Open Access)
CD8+ cytotoxic T lymphocytes (CTL) frequently infiltrate tumors, yet most melanoma patients fail to undergo tumor regression. We studied the differentiation of the CD8+ tumor-infiltrating lymphocytes (TIL) from 44 metastatic melanoma patients using known T-cell differentiation markers. We also compared CD8+ TIL against the T cells from matched melanoma patients’ peripheral blood. We discovered a novel subset of CD8+ TIL co-expressing early-differentiation markers, CD27, CD28, and a late/senescent CTL differentiation marker, CD57. This CD8+CD57+ TIL expressed a cytolytic enzyme, granzyme B (GB), yet did not express another cytolytic pore-forming molecule, perforin (Perf). In …
Pilot Study Of Cyp2b6 Genetic Variation To Explore The Contribution Of Nitrosamine Activation To Lung Carcinogenesis, Catherine Wassenaar, Qiong Dong, Christopher Amos, Margaret Spitz, Rachel F. Tyndale
Pilot Study Of Cyp2b6 Genetic Variation To Explore The Contribution Of Nitrosamine Activation To Lung Carcinogenesis, Catherine Wassenaar, Qiong Dong, Christopher Amos, Margaret Spitz, Rachel F. Tyndale
Dartmouth Scholarship
We explored the contribution of nitrosamine metabolism to lung cancer in a pilot investigation of genetic variation in CYP2B6, a high-affinity enzymatic activator of tobacco-specific nitrosamines with a negligible role in nicotine metabolism. Previously we found that variation in CYP2A6 and CHRNA5-CHRNA3-CHRNB4 combined to increase lung cancer risk in a case-control study in European American ever-smokers (n = 860). However, these genes are involved in the pharmacology of both nicotine, through which they alter smoking behaviours, and carcinogenic nitrosamines. Herein, we separated participants by CYP2B6 genotype into a high- vs. low-risk group (*1/*1 + *1/*6 vs. *6/*6). Odds ratios estimated …
Cd4 And Cd8 T Cells Directly Recognize Murine Gammaherpesvirus 68-Immortalized Cells And Prevent Tumor Outgrowth, Xiaozhan Liang, Rebecca L. Crepeau, Weijun Zhang, Samuel H. Speck, Edward J. Usherwood
Cd4 And Cd8 T Cells Directly Recognize Murine Gammaherpesvirus 68-Immortalized Cells And Prevent Tumor Outgrowth, Xiaozhan Liang, Rebecca L. Crepeau, Weijun Zhang, Samuel H. Speck, Edward J. Usherwood
Dartmouth Scholarship
There has been extensive research regarding T cell recognition of Epstein-Barr virus-transformed cells; however, less is known regarding the recognition of B cells immortalized by gamma-2 herpesviruses. Here we show that B cells immortalized by murine gammaherpesvirus 68 (MHV-68, γHV-68) can be controlled by either CD4 or CD8 T cells in vivo. We present evidence for the direct recognition of infected B cells by CD4 and CD8 T cells. These data will help in the development of immunotherapeutic approaches combating gamma-2 herpesvirus-related disease.
Differential Effects Of Micrornas On Glioblastoma Growth And Migration, Duane Jeansonne, Marco Pacifici, Adam Lassak, Krzysztof Reiss, Giuseppe Russo, Jovanny Zabaleta, Francesca Peruzzi
Differential Effects Of Micrornas On Glioblastoma Growth And Migration, Duane Jeansonne, Marco Pacifici, Adam Lassak, Krzysztof Reiss, Giuseppe Russo, Jovanny Zabaleta, Francesca Peruzzi
School of Medicine Faculty Publications
Glioblastoma multiforme is characterized by rapid proliferation, aggressive metastatic potential, and resistance to radio- and chemotherapy. The matricellular protein CYR61 regulates cellular proliferation and migration and is highly expressed in Glioblastomas. MicroRNAs are 22-nucleotides long RNAs that regulate gene expression post-transcriptionally. Here, we utilized the LN229 glioblastoma cell line and found that CYR61 is a target of miR-136, miR-155, and miR-634. Over-expression of miR-136 and miR-634 miRNAs negatively affected proliferation, but not migration, while expression of miR-155 reduced migration but did not affect the proliferation of LN229 cells. Investigation of the molecular mechanisms affected by expression of miR-634 revealed an …