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

Cancer Biology Commons

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

Articles 1 - 16 of 16

Full-Text Articles in Cancer Biology

Notch1 Inhibition In Vivo Results In Mammary Tumor Regression And Reduced Mammary Tumorsphere-Forming Activity In Vitro, Matthew J. Simmons, Ryan W. Serra, Nicole M. Hermance, Michelle A. Kelliher Sep 2012

Notch1 Inhibition In Vivo Results In Mammary Tumor Regression And Reduced Mammary Tumorsphere-Forming Activity In Vitro, Matthew J. Simmons, Ryan W. Serra, Nicole M. Hermance, Michelle A. Kelliher

Open Access Articles

INTRODUCTION: NOTCH activation has been recently implicated in human breast cancers, associated with a poor prognosis, and tumor-initiating cells are hypothesized to mediate resistance to treatment and disease relapse. To address the role of NOTCH1 in mammary gland development, transformation, and mammary tumor-initiating cell activity, we developed a doxycycline-regulated mouse model of NOTCH1-mediated mammary transformation.

METHODS: Mammary gland development was analyzed by using whole-mount analysis and by flow cytometry in nulliparous transgenic mice maintained in the presence/absence of doxycycline (or intracellular NOTCH1). Mammary tumors were examined histologically and immunophenotyped by staining with antibodies followed by flow cytometry. Tumors were ...


Synergistic Effects Of Nanosecond Pulsed Electric Fields Combined With Low Concentration Of Gemcitabine On Human Oral Squamous Cell Carcinoma In Vitro, Jing Wang, Jinsong Guo, Shan Wu, Hongqing Feng, Shujun Sun, Jie Pan, Jue Zhang, Stephen J. Beebe Aug 2012

Synergistic Effects Of Nanosecond Pulsed Electric Fields Combined With Low Concentration Of Gemcitabine On Human Oral Squamous Cell Carcinoma In Vitro, Jing Wang, Jinsong Guo, Shan Wu, Hongqing Feng, Shujun Sun, Jie Pan, Jue Zhang, Stephen J. Beebe

Bioelectrics Publications

Treatment of cancer often involves uses of multiple therapeutic strategies with different mechanisms of action. In this study we investigated combinations of nanosecond pulsed electric fields (nsPEF) with low concentrations of gemcitabine on human oral cancer cells. Cells (Cal-27) were treated with pulse parameters (20 pulses, 100 ns in duration, intensities of 10, 30 and 60 kV/cm) and then cultured in medium with 0.01 mu g/ml gemcitabine. Proliferation, apoptosis/necrosis, invasion and morphology of those cells were examined using MTT, flow cytometry, clonogenics, transwell migration and TEM assay. Results show that combination treatments of gemcitabine and nsPEFs ...


Mdm2-P53 Signaling In Tissue Homeostasis And The Dna Damage Response: A Dissertation, Hugh S. Gannon Jun 2012

Mdm2-P53 Signaling In Tissue Homeostasis And The Dna Damage Response: A Dissertation, Hugh S. Gannon

GSBS Dissertations and Theses

The p53 transcription factor responds to various cellular stressors by regulating the expression of numerous target genes involved in cellular processes such as cell cycle arrest, apoptosis, and senescence. As these downstream pathways are harmful to the growth and development of normal cells when prolonged or deregulated, p53 activity needs to be under tight regulatory control. The Mdm2 oncoprotein is the chief negative regulator of p53, and many mouse models have demonstrated that absence of Mdm2 expression leads to constitutive p53 activation in a variety of cell types. While unregulated p53 can be deleterious to cells, functional p53 is essential ...


Slow-Cycling Cancer Cells: A Dissertation, Nathan F. Moore Jun 2012

Slow-Cycling Cancer Cells: A Dissertation, Nathan F. Moore

GSBS Dissertations and Theses

Tumor recurrence after chemotherapy is a major cause of patient morbidity and mortality. Recurrences are thought to be due to small subsets of stem-like cancer cells that are able to survive chemotherapy and drive tumor re-growth. A more complete understanding of stem-like cancer cell regulation is required to develop therapies to better target and eliminate these cells.

Slow-cycling stem cells are integral components of adult epithelial tissues and may give rise to cancer stem cell populations that share similar characteristics. These slow-cycling adult stem cells are inherently resistant to traditional forms of chemotherapy and transference of this characteristic may help ...


Antagonistic Pleiotropy: The Role Of Smurf2 In Cancer And Aging: A Dissertation, Charusheila Ramkumar Jun 2012

Antagonistic Pleiotropy: The Role Of Smurf2 In Cancer And Aging: A Dissertation, Charusheila Ramkumar

GSBS Dissertations and Theses

In response to telomere shortening, oxidative stress, DNA damage or aberrant activation of oncogenes, normal somatic cells exit the cell cycle and enter an irreversible growth arrest termed senescence. The limited proliferative capacity imposed by senescence on cells impedes the accumulation of mutations necessary for tumorigenesis and prevents proliferation of cells at risk of neoplastic transformation. Opposite to the tumor suppressor function, accumulation of senescent cells in adult organisms is thought to contribute to aging by depleting the renewal capacity of tissues and stem/progenitor cells, and by interfering with tissue homeostasis and functions. The Antagonistic Pleiotropy Theory of senescence ...


Mechanisms Of Kras-Mediated Pancreatic Tumor Formation And Progression: A Dissertation, Victoria A. Appleman May 2012

Mechanisms Of Kras-Mediated Pancreatic Tumor Formation And Progression: A Dissertation, Victoria A. Appleman

GSBS Dissertations and Theses

Pancreatic cancer is the 4th leading cause of cancer related death in the United States with a median survival time of less than 6 months. Pancreatic ductal adenocarcinoma (PDAC) accounts for greater than 85% of all pancreatic cancers, and is marked by early and frequent mutation of the KRAS oncogene, with activating KRAS mutations present in over 90% of PDAC. To date, though, targeting activated KRAS for cancer treatment has been very difficult, and targeted therapies are currently being sought for the downstream effectors of activated KRAS. Activation of KRAS stimulates multiple signaling pathways, including the MEK-ERK and PI3K-AKT signaling ...


The Molecular Mechanisms For Maintenance Of Cancer Stem Cells In Chronic Myeloid Leukemia: A Dissertation, Haojian Zhang May 2012

The Molecular Mechanisms For Maintenance Of Cancer Stem Cells In Chronic Myeloid Leukemia: A Dissertation, Haojian Zhang

GSBS Dissertations and Theses

Chronic myeloid leukemia (CML) is a clonal hematopoietic stem cell disorder associated with the Philadelphia chromosome (Ph) that arises from a reciprocal translocation between chromosomes 9 and 22, thereby resulting in the formation of the chimeric BCR-ABL oncogene encoding a constitutively activated tyrosine kinase. BCR-ABL tyrosine kinase inhibitors (TKIs) induce a complete hematologic and cytogenetic response in the majority of chronic phrase CML patients. However, TKIs cannot efficiently eradicate leukemia stem cells (LSCs) because of the insensitivity of LSCs to TKIs. Therefore, developing new strategies to target LSCs is necessary and critical for curing CML, and success of this approach ...


Interleukin-1Β Mediates Metalloproteinase-Dependent Renal Cell Carcinoma Tumor Cell Invasion Through The Activation Of Ccaat Enhancer Binding Protein Β, Brenda L. Petrella, Matthew P. P. Vincenti May 2012

Interleukin-1Β Mediates Metalloproteinase-Dependent Renal Cell Carcinoma Tumor Cell Invasion Through The Activation Of Ccaat Enhancer Binding Protein Β, Brenda L. Petrella, Matthew P. P. Vincenti

Open Dartmouth: Faculty Open Access Scholarship

Effective treatment of metastatic renal cell carcinoma (RCC) remains a major medical concern, as these tumors are refractory to standard therapies and prognosis is poor. Although molecularly targeted therapies have shown some promise in the treatment of this disease, advanced RCC tumors often develop resistance to these drugs. Dissecting the molecular mechanisms underlying the progression to advanced disease is necessary to design alternative and improved treatment strategies. Tumor-associated macrophages (TAMs) found in aggressive RCC tumors produce a variety of inflammatory cytokines, including interleukin-1 b (IL-1b). Moreover, the presence of TAMs and high serum levels of IL-1b in RCC patients correlate ...


Characterization Of The Ossn Microbiome In Hiv-1 Infected Patients, Kenneth O. Simbiri, Erle S. Robertson May 2012

Characterization Of The Ossn Microbiome In Hiv-1 Infected Patients, Kenneth O. Simbiri, Erle S. Robertson

Botswana-UPenn Scholarly Publications

Purpose: Ocular surface squamous neoplasia (OSSN) is a rare cancer previously seen in elderly men. In Botswana there is an increase in OSSN and pterygia among young HIV-1 infected patients. Factors that determine the course of this cancer have not been characterized. Recent studies identified HPV, EBV, KSHV, HSV-1/2, and CMV in patient samples. We now characterize the microbiome associated with the disease that may contribute to its course.

Results: Pyrosequencing identified viruses, bacteria, fungus and parasites. Analysis of shotgun cloning sequences showed a majority of infectious agents identified by pyrosequencing.

Conclusion: HIV patients with OSSN in Botswana are ...


Increased Geranylgeranylated K-Ras Contributes To Antineoplastic Effects Of Farnesyltransferase Inhibitors., Mandy A. Hall May 2012

Increased Geranylgeranylated K-Ras Contributes To Antineoplastic Effects Of Farnesyltransferase Inhibitors., Mandy A. Hall

UT GSBS Dissertations and Theses (Open Access)

The Ras family of small GTPases (N-, H-, and K-Ras) is a group of important signaling mediators. Ras is frequently activated in some cancers, while others maintain low level activity to achieve optimal cell growth. In cells with endogenously low levels of active Ras, increasing Ras signaling through the ERK and p38 MAPK pathways can cause growth arrest or cell death. Ras requires prenylation – the addition of a 15-carbon (farnesyl) or 20-carbon (geranylgeranyl) group – to keep the protein anchored into membranes for effective signaling. N- and K-Ras can be alternatively geranylgeranylated (GG’d) if farnesylation is inhibited but are preferentially ...


Identifying Purification And Storage Techniques For The Human Papillomavirus Type 16 Major Capsid Protein L1, Stephanie Anderson Apr 2012

Identifying Purification And Storage Techniques For The Human Papillomavirus Type 16 Major Capsid Protein L1, Stephanie Anderson

Molecular, Cellular, and Developmental Biology Undergraduate Contributions

Expression of human papillomavirus (HPV) major capsid protein L1 in Escherichia coli produces L1 proteins that can self­assemble into pentamers, with 72 pentamers forming a capsomere. With effective purification and storage techniques, these L1 pentamers could provide a more economic alternative for manufacturing HPV vaccines. Various techniques were evaluated in order to develop the most efficient method for L1 protein purification. Primary purification of L1 protein fused to Glutathione S­ transferase (GST) was accomplished by GST affinity chromatography. DEAE anion exchange chromatography and heparin affinity chromatography were then tested as secondary purification techniques. Results showed heparin chromatography removed L1 ...


Analysis Of Integrin Α6Β4 Function In Breast Carcinoma: A Dissertation, Kristin D. Gerson Apr 2012

Analysis Of Integrin Α6Β4 Function In Breast Carcinoma: A Dissertation, Kristin D. Gerson

GSBS Dissertations and Theses

The development and survival of multicellular organisms depends upon the ability of cells to move. Embryogenesis, immune surveillance, wound healing, and metastatic disease are all processes that necessitate effective cellular locomotion. Central to the process of cell motility is the family of integrins, transmembrane cell surface receptors that mediate stable adhesions between cells and their extracellular environment. Many human diseases are associated with aberrant integrin function. Carcinoma cells in particular can hijack integrins, harnessing their mechanical and signaling potential to propagate cell invasion and metastatic disease, one example being integrin α6β4. This integrin, often referred to simply as β4, is ...


Localization Of Insulin Receptor Substrate-2 In Breast Cancer: A Dissertation, Jennifer L. Clark Mar 2012

Localization Of Insulin Receptor Substrate-2 In Breast Cancer: A Dissertation, Jennifer L. Clark

GSBS Dissertations and Theses

The insulin-like growth factor-1 receptor (IGF-1R) and many of its downstream signaling components have long been implicated in tumor progression and resistance to therapy. The insulin receptor substrate-1 (IRS-1) and IRS-2 adaptor proteins are two of the major downstream signaling intermediates of the IGF-1R. Despite their considerable homology, previous work in our lab and others has shown that IRS-1 and IRS-2 play divergent roles in breast cancer cells. Signaling through IRS-1 promotes cell proliferation, whereas signaling through IRS-2 promotes cell motility and invasion, as well as glycolysis. Moreover, using a mouse model of mammary tumorigenesis, our lab demonstrated that IRS-2 ...


Notch Regulation Of Adam12 Expression In Glioblastoma Multiforme, Ala'a S. Alsyaideh Jan 2012

Notch Regulation Of Adam12 Expression In Glioblastoma Multiforme, Ala'a S. Alsyaideh

Masters Theses 1911 - February 2014

Glioblastoma is the most common malignant brain tumor, accounting for 17% of all primary brain tumors in the United States. Despite the available surgical, radiation, and chemical therapeutic options, the invasive and infiltrative nature of the tumor render current treatment options minimally effective. Recent reports have identified multiple regulators of glioblastoma progression and invasiveness. It has been demonstrated that ADAM12, A Disintegrin And Metalloproteinase encoded by ADAM12 gene, is over-expressed in glioblastoma and directly correlated with tumor proliferation. Additionally, dysregulation of the Notch signaling pathway has been implicated in the pathogenesis of many gliomas. Lastly, an evolving role of microRNAs ...


Kshv Infection Of Endothelial Cells Manipulates Cxcr7-Mediated Signaling: Implications For Kaposi’S Sarcoma Progression And Intervention, Jennifer Totonchy, Lisa Clepper, Janet Douglas, Liron Pantanowitz, Klaus Fruh, Ashlee V. Moses Jan 2012

Kshv Infection Of Endothelial Cells Manipulates Cxcr7-Mediated Signaling: Implications For Kaposi’S Sarcoma Progression And Intervention, Jennifer Totonchy, Lisa Clepper, Janet Douglas, Liron Pantanowitz, Klaus Fruh, Ashlee V. Moses

Pharmacy Faculty Articles and Research

"CXCR7 was recently characterized as an alternative receptor for the chemokine CXCL12/SDF-1, previously thought to bind and signal exclusively through CXCR4.We recently identified CXCR7 as a key cellular factor in the endothelial cell (EC) dysfunction associated with KSHV infection. CXCL12 signaling is critically associated with tumor growth, angiogenesis and metastasis in several diverse tumors and is one of the most studied chemokine/chemokine receptor interactions in cancer systems. The tumorigenic activity of the CXCL12 signaling axis offers an attractive target for therapeutic intervention in multiple cancers including Kaposi’s Sarcoma (KS). However, most of the research to date ...


Evaluation Of Daily Oral Kinase Inhibitors In Pediatric Spnet Tumor Xenografts, Greg Heinicke Jan 2012

Evaluation Of Daily Oral Kinase Inhibitors In Pediatric Spnet Tumor Xenografts, Greg Heinicke

Undergraduate Honors Theses

Throughout the human body cells grow and die at different rates. Each tissue has specific cellular requirements that define the growth and death of its cells. For example red blood cells are replaced frequently whereas brain cells slowly die with age and are not replaced. Cancer comes from a fundamental breakdown in the regulation of growth. These new growing cells reach a point when they are too abundant. When they have surpassed the body's need for new cells, they form large masses called tumors. Tumors are deadly when they become malignant. Malignant cells have the ability to invade and ...