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Full-Text Articles in Cancer Biology

Diffuse Reflectance Spectroscopy To Quantify In Vivo Tissue Optical Properties: Applications In Human Epithelium And Subcutaneous Murine Colon Cancer, Gage Joseph Greening May 2019

Diffuse Reflectance Spectroscopy To Quantify In Vivo Tissue Optical Properties: Applications In Human Epithelium And Subcutaneous Murine Colon Cancer, Gage Joseph Greening

Theses and Dissertations

Colorectal cancer is the 4th most common and 2nd deadliest cancer. Problems exist with predicting which patients will respond best to certain therapy regimens. Diffuse reflectance spectroscopy has been suggested as a candidate to optically monitor a patient’s early response to therapy and has been received favorably in experimentally managing other cancers such as breast and skin. In this dissertation, two diffuse reflectance spectroscopy probes were designed: one with a combined high-resolution microendoscopy modality, and one that was optimized for acquiring data from subcutaneous murine tumors. For both probes, percent errors for estimating tissue optical properties (reduced scattering coefficient ...


Adipocytes Activate Mitochondrial Fatty Acid Oxidation And Autophagy To Promote Tumor Growth In Colon Cancer, Yang-An Wen, Xiaopeng Xing, Jennifer W. Harris, Yekaterina Y. Zaytseva, Mihail I. Mitov, Dana L. Napier, Heidi L. Weiss, B. Mark Evers, Tianyan Gao Feb 2017

Adipocytes Activate Mitochondrial Fatty Acid Oxidation And Autophagy To Promote Tumor Growth In Colon Cancer, Yang-An Wen, Xiaopeng Xing, Jennifer W. Harris, Yekaterina Y. Zaytseva, Mihail I. Mitov, Dana L. Napier, Heidi L. Weiss, B. Mark Evers, Tianyan Gao

Markey Cancer Center Faculty Publications

Obesity has been associated with increased incidence and mortality of a wide variety of human cancers including colorectal cancer. However, the molecular mechanism by which adipocytes regulate the metabolism of colon cancer cells remains elusive. In this study, we showed that adipocytes isolated from adipose tissues of colon cancer patients have an important role in modulating cellular metabolism to support tumor growth and survival. Abundant adipocytes were found in close association with invasive tumor cells in colon cancer patients. Co-culture of adipocytes with colon cancer cells led to a transfer of free fatty acids that released from the adipocytes to ...


Cd4+ T Cell Regulation Of Immune Responses To The Simian Virus 40 Large Tumor Antigen Is Complex And Involves Multiple Layers Of Coordination Dependent On Immune Conditions, Arielle Raugh, Lawrence Mylin Dec 2016

Cd4+ T Cell Regulation Of Immune Responses To The Simian Virus 40 Large Tumor Antigen Is Complex And Involves Multiple Layers Of Coordination Dependent On Immune Conditions, Arielle Raugh, Lawrence Mylin

Honors Projects and Presentations: Undergraduate

Cytotoxic (CD8+) and Helper (CD4+) T lymphocytes play an important role in the immune detection and destruction of tumors. The induction of Cytotoxic T cell responses by multiple CD8 epitopes located within the Simian Virus 40 Large Tumor Antigen (SV40 T ag) oncoprotein has been well characterized, and we have begun to characterize the role(s) of CD4+ Helper T cells in controlling cellular immune responses to the SV40 T ag. The goal of this study was to characterize the cytokines produced by activated SV40T ag-specific Helper T cells in order to identify subset(s) of Helper T cells that ...


Characterizing Monoclonal Antibodies Against The Cholecystokinin 2 Receptor (Cck2r) And A Splice Variant For Use In Pancreatic Cancer Studies, Laura Ritenour May 2016

Characterizing Monoclonal Antibodies Against The Cholecystokinin 2 Receptor (Cck2r) And A Splice Variant For Use In Pancreatic Cancer Studies, Laura Ritenour

Honors Projects and Presentations: Undergraduate

Pancreatic cancer is an extremely aggressive cancer with a five-year survival rate of less than 6%, largely due to the lack of early detection and effective treatment options. A better understanding of the mechanisms leading to malignant transformation is necessary to improve patient outcomes. One known contributor to tumor aggression is the cholecystokinin 2 receptor (CCK2R), a G-protein coupled receptor that binds the gastrointestinal hormones CCK and gastrin. A constitutively-active form of the receptor, the intron 4 splice variant (CCK2i4svR), has also been observed in cancer cells. To facilitate studies of CCK2i4svR, a monoclonal antibody specific to an insertion in ...


Molecular Mechanisms Of Squamous Cell Carcinoma Tumor Stem Cell Creation Via High Nitric Oxide (Hno) Adaptation, Niresh T. Kuganeswaran '16, Krishi Korrapati '17, Thomas Wan '16, Timothy Tamas, James A. Radosevich Mar 2016

Molecular Mechanisms Of Squamous Cell Carcinoma Tumor Stem Cell Creation Via High Nitric Oxide (Hno) Adaptation, Niresh T. Kuganeswaran '16, Krishi Korrapati '17, Thomas Wan '16, Timothy Tamas, James A. Radosevich

Student Publications & Research

Cancer relapse or recurrence is defined as the return of cancer or its signs/symptoms after a period of improvement. Surgery may not remove all cancer cells and leave behind a few which cannot be detected by scans or other tests. It is also possible that some tumor cells are resistant to chemotherapy or radiation. Although many cancer cells are killed by these treatments, there may exist a few which contain a different genetic makeup which allows them to survive. These hypermalignant cancer cells, or cancer stem cells (CSCs), have been associated with causing cancer relapse. It has also been ...


Role Of Pseudogenes In Cancer Stem Creation Via High Nitric Oxide (Hno) Adaptation, Krishi Korrapati '17, Niresh T. Kuganeswaran '16, Thomas Wan '16, Timothy Tamas, James A. Radosevich Mar 2016

Role Of Pseudogenes In Cancer Stem Creation Via High Nitric Oxide (Hno) Adaptation, Krishi Korrapati '17, Niresh T. Kuganeswaran '16, Thomas Wan '16, Timothy Tamas, James A. Radosevich

Student Publications & Research

Gene chip analysis of ten HNO adapted cell lines (Squamous cells: SCC-016, SCC-040, SCC-056, SCC-114, SCC-116; Adenocarcinomas: A549, BT20, Hs578, MCF7, and T47D) was carried out. Known pseudogenes were identified in each line, as well as their coding counterparts.

The adenocarcinoma cell lines had no up regulated pseudogenes, while they had the following down regulated pseudogenes: RP6-159A1.2, RP11-255N24.3, AC004490.1, LDHBP, RP11-572H4.2. The squamous cell carcinomas (SCCs) had the following up regulated pseudogenes: RPL37AP1, AC138972.1, RP11-641D5.1, AC005534.6, AC022431.1, RPL26P12, and they had these down regulated pseudogenes: RP6-159A1.2, RP11-255N24.3, RBMXP1, RP11-20O23.1 ...


Increasing The Stability And Expression Of Green Fluorescent Protein In Pancreatic Cancer Cells For Metastasis Assays, Holly M. Ross, John F. Harms Jan 2016

Increasing The Stability And Expression Of Green Fluorescent Protein In Pancreatic Cancer Cells For Metastasis Assays, Holly M. Ross, John F. Harms

Honors Projects and Presentations: Undergraduate

Pancreatic cancer is the fourth leading cause of cancer death in the United States, with only 11% of patients diagnosed with metastatic disease surviving the first year. Even so, few studies exist to characterize the mechanism of metastasis in this highly aggressive form of cancer. Consequently, it is imperative that techniques, such as tagging cells with green fluorescent protein (GFP), are developed to track cancerous cells over the course of their spread. Unfortunately, the existing GFP vector contains a cytomegalovirus promotor, which is readily silenced by cells and decreases the vector’s usefulness for long-term studies in vivo. It was ...


Investigating Cellular Immunity Using The Sv40 Large Tumor Antigen, Matthew Lauver, Caitlin Mason, Stephanie Schell, Lawrence Mylin Jan 2015

Investigating Cellular Immunity Using The Sv40 Large Tumor Antigen, Matthew Lauver, Caitlin Mason, Stephanie Schell, Lawrence Mylin

Honors Projects and Presentations: Undergraduate

The Simian Virus 40 Large Tumor antigen (SV40 T ag) is a viral oncoprotein that is capable of inducing tumors and serving as the target for anti-tumor T cell responses. Because of this, the SV40 T ag has been studied extensively as a model to better understand immune control of solid tumors. Our laboratory has recently identified three CD4+ epitopes within the T ag and is conducting studies to characterize their role(s) in regulating cellular immunity to the SV40 T ag. Towards this goal, we have generated a cell line (C2a) that expresses a derivative of the T ag ...


Sensitization Of Human Cancer Cells To Gemcitabine By The Chk1 Inhibitor Mk-8776: Cell Cycle Perturbation And Impact Of Administration Schedule In Vitro And In Vivo, Ryan Montano, Ruth Thompson, Injae Chung, Huagang Hou, Nadeem Khan, Alan Eastman Dec 2013

Sensitization Of Human Cancer Cells To Gemcitabine By The Chk1 Inhibitor Mk-8776: Cell Cycle Perturbation And Impact Of Administration Schedule In Vitro And In Vivo, Ryan Montano, Ruth Thompson, Injae Chung, Huagang Hou, Nadeem Khan, Alan Eastman

Open Dartmouth: Faculty Open Access Scholarship

Chk1 inhibitors have emerged as promising anticancer therapeutic agents particularly when combined with antimetabolites such as gemcitabine, cytarabine or hydroxyurea. Here, we address the importance of appropriate drug scheduling when gemcitabine is combined with the Chk1 inhibitor MK-8776, and the mechanisms involved in the schedule dependence.


Killerflip: A Novel Lytic Peptide Specifically Inducing Cancer Cell Death, B Pennarun, G. Gaidos, O Bucur, A Tinari Oct 2013

Killerflip: A Novel Lytic Peptide Specifically Inducing Cancer Cell Death, B Pennarun, G. Gaidos, O Bucur, A Tinari

Open Dartmouth: Faculty Open Access Scholarship

One of the objectives in the development of effective cancer therapy is induction of tumor-selective cell death. Toward this end, we have identified a small peptide that, when introduced into cells via a TAT cell-delivery system, shows a remarkably potent cytoxicity in a variety of cancer cell lines and inhibits tumor growth in vivo, whereas sparing normal cells and tissues. This fusion peptide was named killer FLIP as its sequence was derived from the C-terminal domain of c-FLIP, an anti-apoptotic protein. Using structure activity analysis, we determined the minimal bioactive core of killerFLIP, namely killerFLIP-E. Structural analysis of cells using ...


Expression Of The Human Gastrin Receptors Cckbr And Cckcr In Panco2 Murine Pancreatic Cancer Cells, Shannon V. Sell, Glenn R. Jones, Gail L. Matters, John F. Harms Jan 2013

Expression Of The Human Gastrin Receptors Cckbr And Cckcr In Panco2 Murine Pancreatic Cancer Cells, Shannon V. Sell, Glenn R. Jones, Gail L. Matters, John F. Harms

Honors Projects and Presentations: Undergraduate

Pancreatic cancer is the fourth leading cause of cancer mortality. The gastrointestinal hormone, gastrin, stimulates human pancreatic cancer growth via its receptor, CCKBR, and a splice-variant of CCKBR (termed CCKCR) detected only in cancer cells. This cancer-associated variant retains the fourth intron and exhibits increased cell signaling. Recently, a single nucleotide polymorphism (SNP; C>A) in the fourth intron was identified. Presence of SNP(A) was correlated with CCKCR protein expression in pancreatic cancer specimens and decreased patient survival. We hypothesize expression of human CCKCR in murine pancreatic cancer cells will increase tumor growth and metastasis relative to expression of ...


A Physical Sciences Network Characterization Of Non-Tumorigenic And Metastatic Cells, Abigail Hielscher, D. Wirtz, Et Al. Jan 2013

A Physical Sciences Network Characterization Of Non-Tumorigenic And Metastatic Cells, Abigail Hielscher, D. Wirtz, Et Al.

PCOM Scholarly Papers

To investigate the transition from non-cancerous to metastatic from a physical sciences perspective, the Physical Sciences-Oncology Centers (PS-OC) Network performed molecular and biophysical comparative studies of the non-tumorigenic MCF-10A and metastatic MDA-MB-231 breast epithelial cell lines, commonly used as models of cancer metastasis. Experiments were performed in 20 laboratories from 12 PS-OCs. Each laboratory was supplied with identical aliquots and common reagents and culture protocols. Analyses of these measurements revealed dramatic differences in their mechanics, migration, adhesion, oxygen response, and proteomic profiles. Model-based multi-omics approaches identified key differences between these cells' regulatory networks involved in morphology and survival. These results ...


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 ...


Pv1 Down-Regulation Via Shrna Inhibits The Growth Of Pancreatic Adenocarcinoma Xenografts, Sophie J. Deharvengt, Dan Tse, Olga Sideleva, Caitlin Mcgarry, Jason R. Gunn, Daniel S. Longnecker, Catherine Carriere, Radu V. Stan May 2012

Pv1 Down-Regulation Via Shrna Inhibits The Growth Of Pancreatic Adenocarcinoma Xenografts, Sophie J. Deharvengt, Dan Tse, Olga Sideleva, Caitlin Mcgarry, Jason R. Gunn, Daniel S. Longnecker, Catherine Carriere, Radu V. Stan

Open Dartmouth: Faculty Open Access Scholarship

PV1 is an endothelial-specific protein with structural roles in the formation of diaphragms in endothelial cells of normal vessels. PV1 is also highly expressed on endothelial cells of many solid tumours. On the basis of in vitro data, PV1 is thought to actively participate in angiogenesis. To test whether or not PV1 has a function in tumour angiogenesis and in tumour growth in vivo, we have treated pancreatic tumour-bearing mice by single-dose intratumoural delivery of lentiviruses encoding for two different shRNAs targeting murine PV1. We find that PV1 down-regulation by shRNAs inhibits the growth of established tumours derived from two ...


Cdk1 And Plk1 Mediate A Clasp2 Phospho-Switch That Stabilizes Kinetochore–Microtubule Attachments, Ana R. R. Maia, Zaira Garcia, Lilian Kabeche, Marin Barisic Jan 2012

Cdk1 And Plk1 Mediate A Clasp2 Phospho-Switch That Stabilizes Kinetochore–Microtubule Attachments, Ana R. R. Maia, Zaira Garcia, Lilian Kabeche, Marin Barisic

Open Dartmouth: Faculty Open Access Scholarship

Accurate chromosome segregation during mitosis relies on a dynamic kinetochore (KT)-microtubule (MT) interface that switches from a labile to a stable condition in response to correct MT attachments. This transition is essential to satisfy the spindle-assembly checkpoint (SAC) and couple MT-generated force with chromosome movements, but the underlying regulatory mechanism remains unclear. In this study, we show that during mitosis the MT- and KT-associated protein CLASP2 is progressively and distinctively phosphorylated by Cdk1 and Plk1 kinases, concomitant with the establishment of KT-MT attachments. CLASP2 S1234 was phosphorylated by Cdk1, which primed CLASP2 for association with Plk1. Plk1 recruitment to ...


Variations In Mre11/Rad50/Nbs1 Status And Dna Damage-Induced S-Phase Arrest In The Cell Lines Of The Nci60 Panel, Kristen M. K. Garner, Alan Eastman May 2011

Variations In Mre11/Rad50/Nbs1 Status And Dna Damage-Induced S-Phase Arrest In The Cell Lines Of The Nci60 Panel, Kristen M. K. Garner, Alan Eastman

Open Dartmouth: Faculty Open Access Scholarship

The Mre11/Rad50/Nbs1 (MRN) complex is a regulator of cell cycle checkpoints and DNA repair. Defects in MRN can lead to defective S-phase arrest when cells are damaged. Such defects may elicit sensitivity to selected drugs providing a chemical synthetic lethal interaction that could be used to target therapy to tumors with these defects. The goal of this study was to identify these defects in the NCI60 panel of cell lines and identify compounds that might elicit selective cytotoxicity.


Growth Factor–Induced Shedding Of Syndecan-1 Confers Glypican-1 Dependence On Mitogenic Responses Of Cancer Cells, Kan Ding, Martha Lopez-Burks, José A. Sánchez-Duran, Murray Korc, Arthur D. Lander Nov 2005

Growth Factor–Induced Shedding Of Syndecan-1 Confers Glypican-1 Dependence On Mitogenic Responses Of Cancer Cells, Kan Ding, Martha Lopez-Burks, José A. Sánchez-Duran, Murray Korc, Arthur D. Lander

Open Dartmouth: Faculty Open Access Scholarship

The cell surface heparan sulfate proteoglycan (HSPG) glypican-1 is up-regulated by pancreatic and breast cancer cells, and its removal renders such cells insensitive to many growth factors. We sought to explain why the cell surface HSPG syndecan-1, which is also up-regulated by these cells and is a known growth factor coreceptor, does not compensate for glypican-1 loss. We show that the initial responses of these cells to the growth factor FGF2 are not glypican dependent, but they become so over time as FGF2 induces shedding of syndecan-1. Manipulations that retain syndecan-1 on the cell surface make long-term FGF2 responses glypican ...