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Cancer Biology Commons

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2012

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Articles 1 - 30 of 44

Full-Text Articles in Cancer Biology

A Synthetic Interaction Screen Identifies Factors Selectively Required For Proliferation And Tert Transcription In P53-Deficient Human Cancer Cells, Li Xie, Claude Gazin, Sung Mi Park, Lihua Julie Zhu, Marie-Anne Debily, Ellen L. W. Kittler, Maria L. Zapp, David S. Lapointe, Stephane Gobeil, Ching-Man A. Virbasius, Michael R. Green Dec 2012

A Synthetic Interaction Screen Identifies Factors Selectively Required For Proliferation And Tert Transcription In P53-Deficient Human Cancer Cells, Li Xie, Claude Gazin, Sung Mi Park, Lihua Julie Zhu, Marie-Anne Debily, Ellen L. W. Kittler, Maria L. Zapp, David S. Lapointe, Stephane Gobeil, Ching-Man A. Virbasius, Michael R. Green

Open Access Articles

Numerous genetic and epigenetic alterations render cancer cells selectively dependent on specific genes and regulatory pathways, and represent potential vulnerabilities that can be therapeutically exploited. Here we describe an RNA interference (RNAi)-based synthetic interaction screen to identify genes preferentially required for proliferation of p53-deficient (p53-) human cancer cells. We find that compared to p53-competent (p53+) human cancer cell lines, diverse p53- human cancer cell lines are preferentially sensitive to loss of the transcription factor ETV1 and the DNA damage kinase ATR. In p53- cells, RNAi-mediated knockdown of ETV1 or ATR results in decreased expression of the telomerase catalytic subunit ...


Large Scale Matrix Degradation By Stromal Cells Independent Of Invadopodia, Hong Cao, Robbin Eppinga, Eugene W. Krueger, Jing Chen, Mark A. Mcniven Dec 2012

Large Scale Matrix Degradation By Stromal Cells Independent Of Invadopodia, Hong Cao, Robbin Eppinga, Eugene W. Krueger, Jing Chen, Mark A. Mcniven

Faculty Work Comprehensive List

Invadopodia are actin-rich structures at the base of many neoplastic cells that sequester matrix metalloproteases that act to degrade the surrounding stroma to facilitate the invasive process. Conventional invadopodia are dependent upon Src kinase and the large GTPase dynamin 2 (Dyn 2). Whether invadopodia are the only mechanism by which cells degrade matrix is unclear. We have observed that cells of mesenchymal origin degrade matrix in an unique way different from tumor cells. The HYPOTHESIS of this study is that fibroblasts, and other cells of mesenchymal origin, degrade matrix by a mechanism distinct from that of epithelial-based tumor cells. The ...


Nuclear Pore Component Nup98 Is A Potential Tumor Suppressor And Regulates Posttranscriptional Expression Of Select P53 Target Genes, Stephan Singer, Ruiying Zhao, Anthony M. Barsotti, Anette Ouwehand, Mina Fazollahi, Elias Coutavas, Kai Breuhahn, Olaf Neumann, Thomas Longerich, Tobias Pusterla, Maureen A. Powers, Keith M. Giles, Peter J. Leedman, Jochen Hess, David Grunwald, Harmen J. Bussemaker, Robert H. Singer, Peter Schirmacher, Carol Prives Dec 2012

Nuclear Pore Component Nup98 Is A Potential Tumor Suppressor And Regulates Posttranscriptional Expression Of Select P53 Target Genes, Stephan Singer, Ruiying Zhao, Anthony M. Barsotti, Anette Ouwehand, Mina Fazollahi, Elias Coutavas, Kai Breuhahn, Olaf Neumann, Thomas Longerich, Tobias Pusterla, Maureen A. Powers, Keith M. Giles, Peter J. Leedman, Jochen Hess, David Grunwald, Harmen J. Bussemaker, Robert H. Singer, Peter Schirmacher, Carol Prives

Biochemistry and Molecular Pharmacology Publications and Presentations

The p53 tumor suppressor utilizes multiple mechanisms to selectively regulate its myriad target genes, which in turn mediate diverse cellular processes. Here, using conventional and single-molecule mRNA analyses, we demonstrate that the nucleoporin Nup98 is required for full expression of p21, a key effector of the p53 pathway, but not several other p53 target genes. Nup98 regulates p21 mRNA levels by a posttranscriptional mechanism in which a complex containing Nup98 and the p21 mRNA 3'UTR protects p21 mRNA from degradation by the exosome. An in silico approach revealed another p53 target (14-3-3sigma) to be similarly regulated by Nup98. The ...


The Principal Genetic Determinants For Nasopharyngeal Carcinoma In China Involve The Hla Class I Antigen Recognition Groove, Minzhong Tang, J. A. Lautenberger, Xiaojiang Gao, Efe Sezgin, Sher L. Hendrickson, Jennifer L. Troyer, Victor A. David, Li Guan, Carl Mcintosh, Xiuchan Guo, Yuming Zheng, Jian Liao, Hong Deng, Michael Malasky, Bailey Kessing, Cheryl Winkler, Mary Carrington, Guy De The, Yi Zeng, Stephen J. O'Brien Nov 2012

The Principal Genetic Determinants For Nasopharyngeal Carcinoma In China Involve The Hla Class I Antigen Recognition Groove, Minzhong Tang, J. A. Lautenberger, Xiaojiang Gao, Efe Sezgin, Sher L. Hendrickson, Jennifer L. Troyer, Victor A. David, Li Guan, Carl Mcintosh, Xiuchan Guo, Yuming Zheng, Jian Liao, Hong Deng, Michael Malasky, Bailey Kessing, Cheryl Winkler, Mary Carrington, Guy De The, Yi Zeng, Stephen J. O'Brien

Biology Faculty Articles

Nasopharyngeal carcinoma (NPC) is an epithelial malignancy facilitated by Epstein-Barr Virus infection. Here we resolve the major genetic influences for NPC incidence using a genome-wide association study (GWAS), independent cohort replication, and high-resolution molecular HLA class I gene typing including 4,055 study participants from the Guangxi Zhuang Autonomous Region and Guangdong province of southern China. We detect and replicate strong association signals involving SNPs, HLA alleles, and amino acid (aa) variants across the major histocompatibility complex-HLA-A, HLA –B, and HLA -C class I genes (PHLA-A-aa-site-62 = 7.4×10−29; P HLA-B-aa-site-116 = 6.5×10−19; P HLA-C-aa-site-156 = 6 ...


Screening For Melanoma Modifiers Using A Zebrafish Autochthonous Tumor Model, Sharanya Iyengar, Yariv Houvras, Craig J. Ceol Nov 2012

Screening For Melanoma Modifiers Using A Zebrafish Autochthonous Tumor Model, Sharanya Iyengar, Yariv Houvras, Craig J. Ceol

GSBS Student Publications

Genomic studies of human cancers have yielded a wealth of information about genes that are altered in tumors. A challenge arising from these studies is that many genes are altered, and it can be difficult to distinguish genetic alterations that drove tumorigenesis from that those arose incidentally during transformation. To draw this distinction it is beneficial to have an assay that can quantitatively measure the effect of an altered gene on tumor initiation and other processes that enable tumors to persist and disseminate. Here we present a rapid means to screen large numbers of candidate melanoma modifiers in zebrafish using ...


Slow-Cycling Therapy-Resistant Cancer Cells, Nathan F. Moore, Jeanmarie Houghton, Stephen Lyle Nov 2012

Slow-Cycling Therapy-Resistant Cancer Cells, Nathan F. Moore, Jeanmarie Houghton, Stephen Lyle

GSBS Student Publications

Tumor recurrence after chemotherapy is a major cause of patient morbidity and mortality. Recurrences are thought to be secondary to small subsets of cancer cells that are better able to survive traditional forms of chemotherapy and thus drive tumor regrowth. The ability to isolate and better characterize these therapy-resistant cells is critical for the future development of targeted therapies aimed at achieving more robust and long-lasting responses. Using a novel application for the proliferation marker carboxyfluorescein diacetate, succinimidyl ester (CFSE), we have identified a population of slow-cycling, label-retaining tumor cells in both in vitro sphere cultures and in vivo xenograft ...


Cooperativity Of Rb, Brca1, And P53 In Malignant Breast Cancer Evolution, Prashant Kumar, Malini Mukherjee, Jacob P. S. Johnson, Milan Patel, Bing Huey, Donna G. Albertson, Karl Simin Nov 2012

Cooperativity Of Rb, Brca1, And P53 In Malignant Breast Cancer Evolution, Prashant Kumar, Malini Mukherjee, Jacob P. S. Johnson, Milan Patel, Bing Huey, Donna G. Albertson, Karl Simin

Open Access Articles

Breast cancers that are "triple-negative" for the clinical markers ESR1, PGR, and HER2 typically belong to the Basal-like molecular subtype. Defective Rb, p53, and Brca1 pathways are each associated with triple-negative and Basal-like subtypes. Our mouse genetic studies demonstrate that the combined inactivation of Rb and p53 pathways is sufficient to suppress the physiological cell death of mammary involution. Furthermore, concomitant inactivation of all three pathways in mammary epithelium has an additive effect on tumor latency and predisposes highly penetrant, metastatic adenocarcinomas. The tumors are poorly differentiated and have histologic features that are common among human Brca1-mutated tumors, including heterogeneous ...


Identification Of Padi2 As A Potential Breast Cancer Biomarker And Therapeutic Target., John L. Mcelwee, Sunish Mohanan, Obi L. Griffith, Heike C. Breuer, Lynne J. Anguish, Brian D. Cherrington, Ashley M. Palmer, Louise R. Howe, Venkataraman Subramanian, Corey P. Causey, Paul R. Thompson, Joe W. Gray, Scott A. Coonrod Oct 2012

Identification Of Padi2 As A Potential Breast Cancer Biomarker And Therapeutic Target., John L. Mcelwee, Sunish Mohanan, Obi L. Griffith, Heike C. Breuer, Lynne J. Anguish, Brian D. Cherrington, Ashley M. Palmer, Louise R. Howe, Venkataraman Subramanian, Corey P. Causey, Paul R. Thompson, Joe W. Gray, Scott A. Coonrod

Thompson Lab Publications

BACKGROUND: We have recently reported that the expression of peptidylarginine deiminase 2 (PADI2) is regulated by EGF in mammary cancer cells and appears to play a role in the proliferation of normal mammary epithelium; however, the role of PADI2 in the pathogenesis of human breast cancer has yet to be investigated. Thus, the goals of this study were to examine whether PADI2 plays a role in mammary tumor progression, and whether the inhibition of PADI activity has anti-tumor effects.

METHODS: RNA-seq data from a collection of 57 breast cancer cell lines was queried for PADI2 levels, and correlations with known ...


The Cancer Stem Cell Conundrum In Multiple Myeloma, Robert G. Hawley Oct 2012

The Cancer Stem Cell Conundrum In Multiple Myeloma, Robert G. Hawley

Anatomy and Regenerative Biology Faculty Publications

No abstract provided.


Activation Of Amp-Activated Protein Kinase By 3,39-Diindolylmethane (Dim) Is Associated With Human Prostate Cancer Cell Death In Vitro And In Vivo, Di Chen, Sanjeev Banerjee, Qiuzhi C. Cui, Dejuan Kong, Fazlul H. Sarkar, Q. Ping Dou Oct 2012

Activation Of Amp-Activated Protein Kinase By 3,39-Diindolylmethane (Dim) Is Associated With Human Prostate Cancer Cell Death In Vitro And In Vivo, Di Chen, Sanjeev Banerjee, Qiuzhi C. Cui, Dejuan Kong, Fazlul H. Sarkar, Q. Ping Dou

Oncology Faculty Publications

There is a large body of scientific evidence suggesting that 3,39-Diindolylmethane (DIM), a compound derived from the digestion of indole-3-carbinol, which is abundant in cruciferous vegetables, harbors anti-tumor activity in vitro and in vivo. Accumulating evidence suggests that AMP-activated protein kinase (AMPK) plays an essential role in cellular energy homeostasis and tumor development and that targeting AMPK may be a promising therapeutic option for cancer treatment in the clinic. We previously reported that a formulated DIM (BR-DIM; hereafter referred as B-DIM) with higher bioavailability was able to induce apoptosis and inhibit cell growth, angiogenesis, and invasion of prostate cancer ...


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 ...


Stat5 Signaling Specifies Basal Versus Stress Erythropoietic Responses Through Distinct Binary And Graded Dynamic Modalities, Ermelinda Porpiglia, Daniel Hidalgo, Miroslav Koulnis, Abraham R. Tzafriri, Merav Socolovsky Aug 2012

Stat5 Signaling Specifies Basal Versus Stress Erythropoietic Responses Through Distinct Binary And Graded Dynamic Modalities, Ermelinda Porpiglia, Daniel Hidalgo, Miroslav Koulnis, Abraham R. Tzafriri, Merav Socolovsky

Pediatric Publications and Presentations

Erythropoietin (Epo)-induced Stat5 phosphorylation (p-Stat5) is essential for both basal erythropoiesis and for its acceleration during hypoxic stress. A key challenge lies in understanding how Stat5 signaling elicits distinct functions during basal and stress erythropoiesis. Here we asked whether these distinct functions might be specified by the dynamic behavior of the Stat5 signal. We used flow cytometry to analyze Stat5 phosphorylation dynamics in primary erythropoietic tissue in vivo and in vitro, identifying two signaling modalities. In later (basophilic) erythroblasts, Epo stimulation triggers a low intensity but decisive, binary (digital) p-Stat5 signal. In early erythroblasts the binary signal is superseded ...


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 ...


Jnk And Pten Cooperatively Control The Development Of Invasive Adenocarcinoma Of The Prostate, Anette Hubner, David J. Mulholland, Claire L. Standen, Maria Karasarides, Julie Cavanagh-Kyros, Tamera Barrett, Hongbo Chi, Dale Greiner, Cathy Tournier, Charles L. Sawyers, Richard A. Flavell, Hong Wu, Roger J. Davis Jul 2012

Jnk And Pten Cooperatively Control The Development Of Invasive Adenocarcinoma Of The Prostate, Anette Hubner, David J. Mulholland, Claire L. Standen, Maria Karasarides, Julie Cavanagh-Kyros, Tamera Barrett, Hongbo Chi, Dale Greiner, Cathy Tournier, Charles L. Sawyers, Richard A. Flavell, Hong Wu, Roger J. Davis

Davis Lab Publications

The c-Jun NH(2)-terminal kinase (JNK) signal transduction pathway is implicated in cancer, but the role of JNK in tumorigenesis is poorly understood. Here, we demonstrate that the JNK signaling pathway reduces the development of invasive adenocarcinoma in the phosphatase and tensin homolog (Pten) conditional deletion model of prostate cancer. Mice with JNK deficiency in the prostate epithelium (DeltaJnk DeltaPten mice) develop androgen-independent metastatic prostate cancer more rapidly than control (DeltaPten) mice. Similarly, prevention of JNK activation in the prostate epithelium (DeltaMkk4 DeltaMkk7 DeltaPten mice) causes rapid development of invasive adenocarcinoma. We found that JNK signaling defects cause an ...


Fancj/Bach1 Acetylation At Lysine 1249 Regulates The Dna Damage Response, Jenny X. Xie, Min Peng, Shawna Guillemette, Steven Quan, Stephanie Maniatis, Yuliang Wu, Aditya Venkatesh, Scott A. Shaffer, Robert M. Brosh Jr., Sharon B. Cantor Jul 2012

Fancj/Bach1 Acetylation At Lysine 1249 Regulates The Dna Damage Response, Jenny X. Xie, Min Peng, Shawna Guillemette, Steven Quan, Stephanie Maniatis, Yuliang Wu, Aditya Venkatesh, Scott A. Shaffer, Robert M. Brosh Jr., Sharon B. Cantor

Open Access Articles

BRCA1 promotes DNA repair through interactions with multiple proteins, including CtIP and FANCJ (also known as BRIP1/BACH1). While CtIP facilitates DNA end resection when de-acetylated, the function of FANCJ in repair processing is less well defined. Here, we report that FANCJ is also acetylated. Preventing FANCJ acetylation at lysine 1249 does not interfere with the ability of cells to survive DNA interstrand crosslinks (ICLs). However, resistance is achieved with reduced reliance on recombination. Mechanistically, FANCJ acetylation facilitates DNA end processing required for repair and checkpoint signaling. This conclusion was based on the finding that FANCJ and its acetylation were ...


The Human Phosphotyrosine Signaling Network: Evolution And Hotspots Of Hijacking In Cancer., Lei Li, Chabane Tibiche, Cong Fu, Tomonori Kaneko, Michael F. Moran, Martin Schiller, Shawn Shun-Cheng Li, Edwin Wang Jul 2012

The Human Phosphotyrosine Signaling Network: Evolution And Hotspots Of Hijacking In Cancer., Lei Li, Chabane Tibiche, Cong Fu, Tomonori Kaneko, Michael F. Moran, Martin Schiller, Shawn Shun-Cheng Li, Edwin Wang

Life Sciences Faculty Publications

Phosphotyrosine (pTyr) signaling, which plays a central role in cell-cell and cell-environment interactions, has been considered to be an evolutionary innovation in multicellular metazoans. However, neither the emergence nor the evolution of the human pTyr signaling system is currently understood. Tyrosine kinase (TK) circuits, each of which consists of a TK writer, a kinase substrate, and a related reader, such as Src homology (SH) 2 domains and pTyr-binding (PTB) domains, comprise the core machinery of the pTyr signaling network. In this study, we analyzed the evolutionary trajectories of 583 literature-derived and 50,000 computationally predicted human TK circuits in 19 ...


Runx2 Mediates Epigenetic Silencing Of The Bone Morphogenetic Protein-3b (Bmp-3b/Gdf10) In Lung Cancer Cells, Manish Tandon, Karthiga Devi Gokul, Syed A. Ali, Zujian Chen, Jane B. Lian, Gary S. Stein, Jitesh Pratap Jun 2012

Runx2 Mediates Epigenetic Silencing Of The Bone Morphogenetic Protein-3b (Bmp-3b/Gdf10) In Lung Cancer Cells, Manish Tandon, Karthiga Devi Gokul, Syed A. Ali, Zujian Chen, Jane B. Lian, Gary S. Stein, Jitesh Pratap

Open Access Articles

BACKGROUND: The Runt-related transcription factor Runx2 is essential for bone development but is also implicated in progression of several cancers of breast, prostate and bone, where it activates cancer-related genes and promotes invasive properties. The transforming growth factor beta (TGF-beta) family member bone morphogenetic protein-3B (BMP-3B/GDF10) is regarded as a tumor growth inhibitor and a gene silenced in lung cancers; however the regulatory mechanisms leading to its silencing have not been identified.

RESULTS: Here we show that Runx2 is highly expressed in lung cancer cells and downregulates BMP-3B. This inverse relationship between Runx2 and BMP-3B expression is further supported ...


Notch Signaling Activates Yorkie Non-Cell Autonomously In Drosophila, Hillary K. Graves, Sarah E. Woodfield, Chih-Chao Yang, Georg Halder, Andreas Bergmann Jun 2012

Notch Signaling Activates Yorkie Non-Cell Autonomously In Drosophila, Hillary K. Graves, Sarah E. Woodfield, Chih-Chao Yang, Georg Halder, Andreas Bergmann

Molecular, Cell and Cancer Biology Publications

In Drosophila imaginal epithelia, cells mutant for the endocytic neoplastic tumor suppressor gene vps25 stimulate nearby untransformed cells to express Drosophila Inhibitor-of-Apoptosis-Protein-1 (DIAP-1), conferring resistance to apoptosis non-cell autonomously. Here, we show that the non-cell autonomous induction of DIAP-1 is mediated by Yorkie, the conserved downstream effector of Hippo signaling. The non-cell autonomous induction of Yorkie is due to Notch signaling from vps25 mutant cells. Moreover, activated Notch in normal cells is sufficient to induce non-cell autonomous Yorkie activity in wing imaginal discs. Our data identify a novel mechanism by which Notch promotes cell survival non-cell autonomously and by which ...


Lsk Derived Lsk- Cells Have A High Apoptotic Rate Related To Survival Regulation Of Hematopoietic And Leukemic Stem Cells, Cong Peng, Yaoyu Chen, Yi Shan, Haojian Zhang, Zhiru Guo, Dongguang Li, Shaoguang Li Jun 2012

Lsk Derived Lsk- Cells Have A High Apoptotic Rate Related To Survival Regulation Of Hematopoietic And Leukemic Stem Cells, Cong Peng, Yaoyu Chen, Yi Shan, Haojian Zhang, Zhiru Guo, Dongguang Li, Shaoguang Li

Open Access Articles

A balanced pool of hematopoietic stem cells (HSCs) in bone marrow is tightly regulated, and this regulation is disturbed in hematopoietic malignancies such as chronic myeloid leukemia (CML). The underlying mechanisms are largely unknown. Here we show that the Lin(-)Sca-1(+)c-Kit(-) (LSK(-)) cell population derived from HSC-containing Lin(-)Sca-1(+)c-Kit(+) (LSK) cells has significantly higher numbers of apoptotic cells. Depletion of LSK cells by radiation or the cytotoxic chemical 5-fluorouracil results in an expansion of the LSK(-) population. In contrast, the LSK(-) population is reduced in CML mice, and depletion of leukemia stem cells (LSCs; BCR-ABL-expressing HSCs) by deleting ...


Melanoma Induction By Ultraviolet A But Not Ultraviolet B Radiation Requires Melanin Pigment, Frances P. Noonan, M. Raza Zaidi, Agnieszka Wolnicka-Glubisz, Miriam R. Anver, Jesse Bahn, Anastas Popratiloff, +9 Additional Authors Jun 2012

Melanoma Induction By Ultraviolet A But Not Ultraviolet B Radiation Requires Melanin Pigment, Frances P. Noonan, M. Raza Zaidi, Agnieszka Wolnicka-Glubisz, Miriam R. Anver, Jesse Bahn, Anastas Popratiloff, +9 Additional Authors

Anatomy and Regenerative Biology Faculty Publications

Malignant melanoma of the skin (CMM) is associated with ultraviolet radiation exposure, but the mechanisms and even the wavelengths responsible are unclear. Here we use a mammalian model to investigate melanoma formed in response to precise spectrally defined ultraviolet wavelengths and biologically relevant doses. We show that melanoma induction by ultraviolet A (320–400 nm) requires the presence of melanin pigment and is associated with oxidative DNA damage within melanocytes. In contrast, ultraviolet B radiation (280–320 nm) initiates melanoma in a pigment-independent manner associated with direct ultraviolet B DNA damage. Thus, we identified two ultraviolet wavelength-dependent pathways for the ...


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 ...


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 ...


Oxaliplatin And Oxaliplatin Derivatives: Synthesis, Characterization, And Reactivity With Biologically Relevant Ligands, Amy Poynter May 2012

Oxaliplatin And Oxaliplatin Derivatives: Synthesis, Characterization, And Reactivity With Biologically Relevant Ligands, Amy Poynter

Honors College Capstone Experience/Thesis Projects

Oxaliplatin is a third generation anticancer drug that has proven to be successful in fighting ovarian and testicular cancer. We are interested in determining how oxaliplatin and oxaliplatin derivatives interact with proteins, as well as how that interaction is affected by the size and shape of these platinum compounds. We have synthesized oxaliplatin as it is used in cancer treatment, as well as similar platinum compounds with the same diaminocyclohexane ligand as oxaliplatin but with additional bulk added to the nitrogen atoms. We are reacting oxaliplatin with key amino acids, including methionine, and will be comparing the kinetics of this ...


Inhibition Of Fatty Acid Synthase Attenuates Cd44-Associated Signaling And Reduces Metastasis In Colorectal Cancer, Yekaterina Y. Zaytseva, Piotr G. Rychahou, Pat Gulhati, Victoria Allison Elliott, William Conan Mustain, Kathleen O'Connor, Andrew J. Morris, Manjula Sunkara, Heidi L. Weiss, Eun Young Lee, B. Mark Evers Mar 2012

Inhibition Of Fatty Acid Synthase Attenuates Cd44-Associated Signaling And Reduces Metastasis In Colorectal Cancer, Yekaterina Y. Zaytseva, Piotr G. Rychahou, Pat Gulhati, Victoria Allison Elliott, William Conan Mustain, Kathleen O'Connor, Andrew J. Morris, Manjula Sunkara, Heidi L. Weiss, Eun Young Lee, B. Mark Evers

Markey Cancer Center Faculty Publications

Fatty acid synthase (FASN) and ATP-citrate lyase, key enzymes of de novo lipogenesis, are significantly upregulated and activated in many cancers and portend poor prognosis. Even though the role of lipogenesis in providing proliferative and survival advantages to cancer cells has been described, the impact of aberrant activation of lipogenic enzymes on cancer progression remains unknown. In this study, we found that elevated expression of FASN is associated with advanced stages of colorectal cancer (CRC) and liver metastasis, suggesting that it may play a role in progression of CRC to metastatic disease. Targeted inhibition of lipogenic enzymes abolished expression of ...


Chip Sequencing Of Cyclin D1 Reveals A Transcriptional Role In Chromosomal Instability In Mice., Mathew C Casimiro, Marco Crosariol, Emanuele Loro, Adam Ertel, Zuoren Yu, William Dampier, Elizabeth A Saria, Alex Papanikolaou, Timothy J Stanek, Zhiping Li, Chenguang Wang, Paolo Fortina, Sankar Addya, Aydin Tozeren, Erik S Knudsen, Andrew Arnold, Richard G Pestell Mar 2012

Chip Sequencing Of Cyclin D1 Reveals A Transcriptional Role In Chromosomal Instability In Mice., Mathew C Casimiro, Marco Crosariol, Emanuele Loro, Adam Ertel, Zuoren Yu, William Dampier, Elizabeth A Saria, Alex Papanikolaou, Timothy J Stanek, Zhiping Li, Chenguang Wang, Paolo Fortina, Sankar Addya, Aydin Tozeren, Erik S Knudsen, Andrew Arnold, Richard G Pestell

Faculty papers Kimmel Cancer Center

Chromosomal instability (CIN) in tumors is characterized by chromosomal abnormalities and an altered gene expression signature; however, the mechanism of CIN is poorly understood. CCND1 (which encodes cyclin D1) is overexpressed in human malignancies and has been shown to play a direct role in transcriptional regulation. Here, we used genome-wide ChIP sequencing and found that the DNA-bound form of cyclin D1 occupied the regulatory region of genes governing chromosomal integrity and mitochondrial biogenesis. Adding cyclin D1 back to Ccnd1-/- mouse embryonic fibroblasts resulted in CIN gene regulatory region occupancy by the DNA-bound form of cyclin D1 and induction of CIN ...


Cytoplasmic Sequestration Of The Tumor Suppressor P53 By A Heat Shock Protein 70 Family Member, Mortalin, In Human Colorectal Adenocarcinoma Cell Lines, Erin E. Gestl, S. Anne Boettger Jan 2012

Cytoplasmic Sequestration Of The Tumor Suppressor P53 By A Heat Shock Protein 70 Family Member, Mortalin, In Human Colorectal Adenocarcinoma Cell Lines, Erin E. Gestl, S. Anne Boettger

Biology Faculty Publications

No abstract provided.


Cancer And You, Diah-Aldeen Judeh Jan 2012

Cancer And You, Diah-Aldeen Judeh

A with Honors Projects

This project discusses ways a person can identify cancer and what to do if cancer is present.


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 ...


Investigating The Mechanism Of Nur77-Induced Apoptosis In T Cells, Heather E. Fogarty Jan 2012

Investigating The Mechanism Of Nur77-Induced Apoptosis In T Cells, Heather E. Fogarty

Masters Theses 1911 - February 2014

Nur77 is a member of the orphan nuclear receptor family, where it is known to play an important role in apoptosis in both negative selection in T cells and in cancer cell lines. In the development of T cells, it is critical for the immune system to discriminate self from non-self by eliminating auto-reactive cells. It was originally thought that Nur77 initiated apoptosis by activating downstream gene targets. However, it is now clear that Nur77 has its own distinct role outside of the nucleus and the precise mechanisms by which Nur77 induces apoptosis in T cells still needs to be ...