Digital Commons Network^™

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 …

Chemotherapy-Induced Cognitive Impairment Is Associated With Decreases In Cell Proliferation And Histone Modifications, Teresita L. Briones, Julie Woods

Wayne State University Associated BioMed Central Scholarship

Abstract

Background

In this study, we examined the effects of cyclophosphamide, methothrexate, and 5-Fluorouracil (CMF) drug combination on various aspects of learning and memory. We also examined the effects of CMF on cell proliferation and chromatin remodeling as possible underlying mechanisms to explain chemotherapy-associated cognitive dysfunction. Twenty-four adult female Wistar rats were included in the study and had minimitter implantation for continuous activity monitoring two weeks before the chemotherapy regimen was started. Once baseline activity data were collected, rats were randomly assigned to receive either CMF or saline injections given intraperitoneally. Treatments were given once a week for a total …

Unilateral Thalamic Infarction Presenting As Vertical Gaze Palsy: A Case Report, Muhib Khan, Christos Sidiropoulos, Panayiotis Mitsias

Wayne State University Associated BioMed Central Scholarship

Abstract

Introduction

Vertical gaze palsy is a recognized manifestation of midbrain lesions. It rarely is a consequence of unilateral thalamic infarction.

Case presentation

We report the case of a 48-year-old African-American woman who presented to our facility with vertical gaze palsy and evidence of left medial thalamic infarct on diffusion-weighted imaging without coexisting midbrain ischemia. The etiology of infarct was determined to be small vessel disease after extensive investigation.

Conclusions

This report suggests a possible role of the thalamus as a vertical gaze control center. Clinicoradiological studies are needed to further define the role of the thalamus in vertical gaze …

Lack Of An Association Of Mir-938 Snp In Iddm10 With Human Type 1 Diabetes, Xiaofan Mi, Hongzhi He, Yangxin Deng, Abert M. Levin, Jin-Xiong She, Qing-Sheng Mi, Li Zhou

Wayne State University Associated BioMed Central Scholarship

Abstract

MicroRNAs (miRNAs) are a newly discovered type of small non-protein coding RNA that function in the inhibition of effective mRNA translation, and may serve as susceptibility genes for various disease developments. The SNP rs12416605, located in human type 1 diabetes IDDM10 locus, changes the seeding sequence (UGU[G/A]CCC) of miRNA miR-938 and potentially alters miR-938 targets, including IL-16 and IL-17A. In an attempt to test whether miR-938 may be a susceptibility gene for IDDM10, we assessed the possible association of the miR-938 SNP with T1D in an American Caucasian cohort of 622 patients and 723 healthy controls by TaqMan assay. …

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 …

Event-Related Potential Studies Of Post-Traumatic Stress Disorder: A Critical Review And Synthesis, Arash Javanbakht, Israel Liberzon, Alireza Amirsadri, Klevest Gjini, Nash N. Boutros

Wayne State University Associated BioMed Central Scholarship

Abstract

Despite the sparseness of the currently available data, there is accumulating evidence of information processing impairment in post-traumatic stress disorder (PTSD). Studies of event-related potentials (ERPs) are the main tool in real time examination of information processing. In this paper, we sought to critically review the ERP evidence of information processing abnormalities in patients with PTSD. We also examined the evidence supporting the existence of a relationship between ERP abnormalities and symptom profiles or severity in PTSD patients. An extensive Medline search was performed. Keywords included PTSD or post-traumatic stress disorder, electrophysiology or EEG, electrophysiology, P50, P100, N100, P2, …

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 …

High-Frequency Ultrasound For Intraoperative Margin Assessments In Breast Conservation Surgery: A Feasibility Study, Timothy E. Doyle, Rachel E. Factor, Christina L. Ellefson, Kristina M. Sorensen, Brady J. Ambrose, Jeffrey B. Goodrich, Vern P. Hart, Scott C. Jensen, Hemang Patel, Leigh A. Neumayer

Wayne State University Associated BioMed Central Scholarship

Abstract

Background

In addition to breast imaging, ultrasound offers the potential for characterizing and distinguishing between benign and malignant breast tissues due to their different microstructures and material properties. The aim of this study was to determine if high-frequency ultrasound (20-80 MHz) can provide pathology sensitive measurements for the ex vivo detection of cancer in margins during breast conservation surgery.

Methods

Ultrasonic tests were performed on resected margins and other tissues obtained from 17 patients, resulting in 34 specimens that were classified into 15 pathology categories. Pulse-echo and through-transmission measurements were acquired from a total of 57 sites on the …

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 …}

Clue: A Randomized Comparative Effectiveness Trial Of Iv Nicardipine Versus Labetalol Use In The Emergency Department, W Peacock, Joseph Varon, Brigitte M. Baumann, Pierre Borczuk, Chad M. Cannon, Abhinav Chandra, David M. Cline, Deborah Diercks, Brian Hiestand, A Hsu, Preeti Jois-Bilowich, Brian Kaminski, Philip Levy, Richard M. Nowak, Jon W. Schrock

Wayne State University Associated BioMed Central Scholarship

Abstract

Introduction

Our purpose was to compare the safety and efficacy of food and drug administration (FDA) recommended dosing of IV nicardipine versus IV labetalol for the management of acute hypertension.

Methods

Multicenter randomized clinical trial. Eligible patients had 2 systolic blood pressure (SBP) measures ≥180 mmHg and no contraindications to nicardipine or labetalol. Before randomization, the physician specified a target SBP ± 20 mmHg (the target range: TR). The primary endpoint was the percent of subjects meeting TR during the initial 30 minutes of treatment.

Results

Of 226 randomized patients, 110 received nicardipine and 116 labetalol. End organ damage …

Fetal Erap2 Variation Is Associated With Preeclampsia In African Americans In A Case-Control Study, Lori D. Hill, Dashaunda D. Hilliard, Timothy P. York, Sindhu Srinivas, Juan P. Kusanovic, Ricardo Gomez, Michal A. Elovitz, Roberto Romero, Jerome F. Strauss Iii

Wayne State University Associated BioMed Central Scholarship

Abstract

Background

Preeclampsia affects 3-8% of pregnancies and is a major cause of maternal and perinatal morbidity and mortality worldwide. This complex disorder is characterized by alterations in the immune and vascular systems and involves multiple organs. There is strong evidence for a genetic contribution to preeclampsia. Two different single nucleotide polymorphisms (SNPs) in the endoplasmic reticulum aminopeptidase 2 (ERAP2) gene were recently reported to be associated with increased risk for preeclampsia in two different populations. ERAP2 is expressed in placental tissue and it is involved in immune responses, inflammation, and blood pressure regulation; making it is an attractive preeclampsia …

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 …

The Cns Microvascular Pericyte: Pericyte-Astrocyte Crosstalk In The Regulation Of Tissue Survival, Drew Bonkowski, Vladimir Katyshev, Roumen D. Balabanov, Andre Borisov, Paula Dore-Duffy

Wayne State University Associated BioMed Central Scholarship

Abstract

The French scientist Charles Benjamin Rouget identified the pericyte nearly 140 years ago. Since that time the role of the pericyte in vascular function has been difficult to elucidate. It was not until the development of techniques to isolate and culture pericytes that scientists have begun to understand the true impact of this unique cell in the maintenance of tissue homeostasis. In the brain the pericyte is an integral cellular component of the blood-brain barrier and, together with other cells of the neurovascular unit (endothelial cells, astrocytes and neurons) the pericyte makes fine-tuned regulatory adjustments and adaptations to promote …

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 …

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 …