Medicine and Health Sciences Commons^™

Unfolded Protein Response In Cancer: The Physician's Perspective, Xuemei Li, Kezhong Zhang, Zihai Li

Wayne State University Associated BioMed Central Scholarship

Abstract

The unfolded protein response (UPR) is a cascade of intracellular stress signaling events in response to an accumulation of unfolded or misfolded proteins in the lumen of the endoplasmic reticulum (ER). Cancer cells are often exposed to hypoxia, nutrient starvation, oxidative stress and other metabolic dysregulation that cause ER stress and activation of the UPR. Depending on the duration and degree of ER stress, the UPR can provide either survival signals by activating adaptive and antiapoptotic pathways, or death signals by inducing cell death programs. Sustained induction or repression of UPR pharmacologically may thus have beneficial and therapeutic …

Combination Of Dasatinib And Curcumin Eliminates Chemo-Resistant Colon Cancer Cells, Jyoti Nautiyal, Shailender S. Kanwar, Yingjie Yu, Adhip Pn Majumdar

Wayne State University Associated BioMed Central Scholarship

Abstract

Metastatic colorectal cancer remains a serious health concern with poor patient survival. Although 5-Fluorouracil (5-FU) or 5-FU plus oxaliplatin (FOLFOX) is the standard therapy for colorectal cancer, it has met with limited success. Recurrence of the tumor after chemotherapy could partly be explained by the enrichment of the chemo-resistant sub-population of cancer stem cells (CSCs) that possess the ability for self-renewal and differentiation into different lineages in the tumor. Therefore development of therapeutic strategies that target CSCs for successful treatment of this malignancy is warranted. The current investigation was undertaken to examine the effectiveness of the combination therapy of …

Activating Mutation In Met Oncogene In Familial Colorectal Cancer, Deborah W. Neklason, Michelle W. Done, Nykole R. Sargent, Ann G. Schwartz, Hoda Anton-Culver, Constance A. Griffin, Dennis J. Ahnen, Joellen M. Schildkraut, Gail E. Tomlinson, Louise C. Strong, Alexander R. Miller, Jill E. Stopfer, Randall W. Burt

Wayne State University Associated BioMed Central Scholarship

Abstract

Background

In developed countries, the lifetime risk of developing colorectal cancer (CRC) is 5%, and it is the second leading cause of death from cancer. The presence of family history is a well established risk factor with 25-35% of CRCs attributable to inherited and/or familial factors. The highly penetrant inherited colon cancer syndromes account for approximately 5%, leaving greater than 20% without clear genetic definition. Familial colorectal cancer has been linked to chromosome 7q31 by multiple affected relative pair studies. The MET proto-oncogene which resides in this chromosomal region is considered a candidate for genetic susceptibility.

Methods

MET exons …

Rad6b Acts Downstream Of Wnt Signaling To Stabilize Β-Catenin: Implications For A Novel Wnt/Β-Catenin Target, Brigitte Gerard, Larry Tait, Pratima Nangia-Makker, Malathy Pv Shekhar

Wayne State University Associated BioMed Central Scholarship

Abstract

Background

Aberrant Wnt/β-catenin signaling is associated with breast cancer even though genetic mutations in Wnt signaling components are rare. We have previously demonstrated that Rad6B, an ubiquitin conjugating enzyme, stabilizes β-catenin via polyubiqutin modifications that render β-catenin insensitive to proteasomal degradation. Rad6B is a transcriptional target of β-catenin, creating a positive feedback loop between Rad6B expression and β-catenin activation.

Methods

To isolate subpopulations expressing high or low Rad6B levels, we transfected MDA-MB-231 or WS-15 human breast cancer cells with ZsGreen fluorescent reporter vector in which the expression of ZsGreen was placed under the control of Rad6B promoter. ZsGreen^{high …}

Histone Deacetylases (Hdacs) In Xpc Gene Silencing And Bladder Cancer, Xiaoxin S. Xu, Le Wang, Judith Abrams, Gan Wang

Wayne State University Associated BioMed Central Scholarship

Abstract

Bladder cancer is one of the most common malignancies and causes hundreds of thousands of deaths worldwide each year. Bladder cancer is strongly associated with exposure to environmental carcinogens. It is believed that DNA damage generated by environmental carcinogens and their metabolites causes development of bladder cancer. Nucleotide excision repair (NER) is the major DNA repair pathway for repairing bulk DNA damage generated by most environmental carcinogens, and XPC is a DNA damage recognition protein required for initiation of the NER process. Recent studies demonstrate reduced levels of XPC protein in tumors for a majority of bladder cancer patients. …

International Conference On Advances In Radiation Oncology (Icaro): Outcomes Of An Iaea Meeting, Eeva K. Salminen, Krystyna Kiel, Geoffrey S. Ibbott, Michael C. Joiner, Eduardo Rosenblatt, Eduardo Zubizarreta, Jan Wondergem, Ahmed Meghzifene

Wayne State University Associated BioMed Central Scholarship

Abstract

The IAEA held the International Conference on Advances in Radiation Oncology (ICARO) in Vienna on 27-29 April 2009. The Conference dealt with the issues and requirements posed by the transition from conventional radiotherapy to advanced modern technologies, including staffing, training, treatment planning and delivery, quality assurance (QA) and the optimal use of available resources. The current role of advanced technologies (defined as 3-dimensional and/or image guided treatment with photons or particles) in current clinical practice and future scenarios were discussed.

ICARO was organized by the IAEA at the request of the Member States and co-sponsored and supported by other …

Cathepsin B: A Potential Prognostic Marker For Inflammatory Breast Cancer, Mohamed A. Nouh, Mona M. Mohamed, Mohamed El-Shinawi, Mohamed A. Shaalan, Dora Cavallo-Medved, Hussein M. Khaled, Bonnie F. Sloane

Wayne State University Associated BioMed Central Scholarship

Abstract

Background

Inflammatory breast cancer (IBC) is the most aggressive form of breast cancer. In non-IBC, the cysteine protease cathepsin B (CTSB) is known to be involved in cancer progression and invasion; however, very little is known about its role in IBC.

Methods

In this study, we enrolled 23 IBC and 27 non-IBC patients. All patient tissues used for analysis were from untreated patients. Using immunohistochemistry and immunoblotting, we assessed the levels of expression of CTSB in IBC versus non-IBC patient tissues. Previously, we found that CTSB is localized to caveolar membrane microdomains in cancer cell lines including IBC, and …

Hedgehog Signaling: A Potential Therapeutic Target For Non-Small Cell Lung Cancer, Ma'in Yehya Maitah

Wayne State University Dissertations

The American Cancer Society estimated that 222,520 Americans were diagnosed with lung cancer and 157,300 died of lung cancer in 2010 (Jemal et al. 2009, 225-249;Jemal et al. 2011, 69-90). The clinical outcome of patients diagnosed with non-small cell lung cancer (NSCLC), the major lung cancer sub-types, is very poor, which calls for innovative research for finding novel therapeutic targets and agents for better treatment outcome.

Emerging evidences have suggested that a phenomenon called Epithelial-to-Mesenchymal Transition (EMT), which shares similar molecular characteristics with cancer stem-like cells, contributes to lung cancer treatment failure. In view of the fact that EMT process …

Inhibition Of Cathepsin B Activity Attenuates Extracellular Matrix Degradation And Inflammatory Breast Cancer Invasion, Bernadette C. Victor, Arulselvi Anbalagan, Mona M. Mohamed, Bonnie F. Sloane, Dora Cavallo-Medved

Wayne State University Associated BioMed Central Scholarship

Abstract

Introduction

Inflammatory breast cancer (IBC) is an aggressive, metastatic and highly angiogenic form of locally advanced breast cancer with a relatively poor three-year survival rate. Breast cancer invasion has been linked to proteolytic activity at the tumor cell surface. Here we explored a role for active cathepsin B on the cell surface in the invasiveness of IBC.

Methods

We examined expression of the cysteine protease cathepsin B and the serine protease urokinase plasminogen activator (uPA), its receptor uPAR and caveolin-1 in two IBC cell lines: SUM149 and SUM190. We utilized a live cell proteolysis assay to localize in real …

The Role Of The Sparc Acidic Domain And Egf-Like Module In Glioma Migration, Invasion, And Signaling, Heather M. Mcclung

Wayne State University Dissertations

THE ROLE OF THE SPARC ACIDIC DOMAIN AND EGF-LIKE MODULE IN GLIOMA MIGRATION, INVASION, AND SIGNALING

HEATHER M. MCCLUNG

Advisor: Sandra A. Rempel, Ph.D.

Major: Pharmacology

Degree: Doctor of Philosophy

We have previously shown that Secreted Protein Acidic and Rich in Cysteine (SPARC) is upregulated in all astrocytoma grades and increases tumor cell migration and invasion. It is thought that different domains within the protein may regulate SPARC functions, suggesting domain-specific targeting to inhibit invasion. To enhance our understanding of SPARC-mediated invasion, we first confirm, at the protein level, our previous cDNA array results, that SPARC increases expression of the …