Medicine and Health Sciences Commons^™

Quantitative Measures Of Estrogen Receptor Expression In Relation To Breast Cancer-Specific Mortality Risk Among White Women And Black Women, Huiyan Ma, Yani Lu, Polly A. Marchbanks, Suzanne G. Folger, Brian L. Strom, Jill A. Mcdonald, Michael S. Simon, Linda K. Weiss, Kathleen E. Malone, Ronald T. Burkman, Jane Sullivan-Halley, Dennis M. Deapen, Michael F. Press, Leslie Bernstein

Wayne State University Associated BioMed Central Scholarship

Abstract

Introduction

The association of breast cancer patients’ mortality with estrogen receptor (ER) status (ER + versus ER-) has been well studied. However, little attention has been paid to the relationship between the quantitative measures of ER expression and mortality.

Methods

We evaluated the association between semi-quantitative, immunohistochemical staining of ER in formalin-fixed paraffin-embedded breast carcinomas and breast cancer-specific mortality risk in an observational cohort of invasive breast cancer in 681 white women and 523 black women ages 35-64 years at first diagnosis of invasive breast cancer, who were followed for a median of 10 years. The quantitative measures of …

Characterizing Inflammatory Breast Cancer Among Arab Americans In The California, Detroit And New Jersey Surveillance, Epidemiology And End Results (Seer) Registries (1988–2008), Kelly A. Hirko, Amr S. Soliman, Mousumi Banerjee, Julie Ruterbusch, Joe B. Harford, Robert M. Chamberlain, John J. Graff, Sofia D. Merajver, Kendra Schwartz

Wayne State University Associated BioMed Central Scholarship

Abstract

Introduction

Inflammatory breast cancer (IBC) is characterized by an apparent geographical distribution in incidence, being more common in North Africa than other parts of the world. Despite the rapid growth of immigrants to the United States from Arab nations, little is known about disease patterns among Arab Americans because a racial category is rarely considered for this group. The aim of this study was to advance our understanding of the burden of IBC in Arab ethnic populations by describing the proportion of IBC among different racial groups, including Arab Americans from the Detroit, New Jersey and California Surveillance, Epidemiology …

Microenvironment Generated During Egfr Targeted Killing Of Pancreatic Tumor Cells By Atc Inhibits Myeloid-Derived Suppressor Cells Through Cox2 And Pge2 Dependent Pathway, Archana Thakur, Dana Schalk, Elyse Tomaszewski, Sri Kondadasula, Hiroshi Yano, Fazlul H. Sarkar, Lawrence G. Lum

Wayne State University Associated BioMed Central Scholarship

Abstract

Background

Myeloid-derived suppressor cells (MDSCs) are one of the major components of the immune-suppressive network, play key roles in tumor progression and limit therapeutic responses. Recently, we reported that tumor spheres formed by breast cancer cell lines were visibly smaller in a Th₁ enriched microenvironment with significantly reduced differentiation of MDSC populations in 3D culture. In this study, we investigated the mechanism(s) of bispecific antibody armed ATC mediated inhibition of MDSC in the presence or absence of Th₁ microenvironment.

Methods

We used 3D co-culture model of peripheral blood mononuclear cells (PBMC) with pancreatic cancer cells MiaPaCa-2 [MiaE] …

Pten Loss Mediated Akt Activation Promotes Prostate Tumor Growth And Metastasis Via Cxcl12/Cxcr4 Signaling, M Conley-Lacomb, Allen Saliganan, Pridvi Kandagatla, Yong Q. Chen, Michael L. Cher, Sreenivasa R. Chinni

Wayne State University Associated BioMed Central Scholarship

Abstract

Introduction

The chemokine CXCL12, also known as SDF-1, and its receptor, CXCR4, are overexpressed in prostate cancers and in animal models of prostate-specific PTEN deletion, but their regulation is poorly understood. Loss of the tumor suppressor PTEN (phosphatase and tensin homolog) is frequently observed in cancer, resulting in the deregulation of cell survival, growth, and proliferation. We hypothesize that loss of PTEN and subsequent activation of Akt, frequent occurrences in prostate cancer, regulate the CXCL12/CXCR4 signaling axis in tumor growth and bone metastasis.

Methods

Murine prostate epithelial cells from PTEN^+/+, PTEN ^+/− , and PTEN^−/− (prostate …

Intronic Non-Cg Dna Hydroxymethylation And Alternative Mrna Splicing In Honey Bees, Pablo Cingolani, Xiaoyi Cao, Radhika S. Khetani, Chieh-Chun Chen, Melissa Coon, Alya'a Sammak, Aliccia Bollig-Fischer, Susan Land, Yun Huang, Matthew E. Hudson, Mark D. Garfinkel, Sheng Zhong, Gene E. Robinson, Douglas M. Ruden

Wayne State University Associated BioMed Central Scholarship

Abstract

Background

Previous whole-genome shotgun bisulfite sequencing experiments showed that DNA cytosine methylation in the honey bee (Apis mellifera) is almost exclusively at CG dinucleotides in exons. However, the most commonly used method, bisulfite sequencing, cannot distinguish 5-methylcytosine from 5-hydroxymethylcytosine, an oxidized form of 5-methylcytosine that is catalyzed by the TET family of dioxygenases. Furthermore, some analysis software programs under-represent non-CG DNA methylation and hydryoxymethylation for a variety of reasons. Therefore, we used an unbiased analysis of bisulfite sequencing data combined with molecular and bioinformatics approaches to distinguish 5-methylcytosine from 5-hydroxymethylcytosine. By doing this, we have performed the first whole …

Systems Analysis Reveals A Transcriptional Reversal Of The Mesenchymal Phenotype Induced By Snail-Inhibitor Gn-25, Asfar S. Azmi, Aliccia Bollig-Fischer, Bin Bao, Bum-Joon Park, Sun-Hye Lee, Gyu Yong-Song, Gregory Dyson, Chandan K. Reddy, Fazlul H. Sarkar, Ramzi M. Mohammad

Wayne State University Associated BioMed Central Scholarship

Abstract

Background

HMLEs (HMLE-SNAIL and Kras-HMLE, Kras-HMLE-SNAIL pairs) serve as excellent model system to interrogate the effect of SNAIL targeted agents that reverse epithelial-to-mesenchymal transition (EMT). We had earlier developed a SNAIL-p53 interaction inhibitor (GN-25) that was shown to suppress SNAIL function. In this report, using systems biology and pathway network analysis, we show that GN-25 could cause reversal of EMT leading to mesenchymal-to-epithelial transition (MET) in a well-recognized HMLE-SNAIL and Kras-HMLE-SNAIL models.

Results

GN-25 induced MET was found to be consistent with growth inhibition, suppression of spheroid forming capacity and induction of apoptosis. Pathway network analysis of mRNA expression …

A Novel Community-Based Study To Address Disparities In Hypertension And Colorectal Cancer: A Study Protocol For A Randomized Control Trial, Joseph Ravenell, Hayley Thompson, Helen Cole, Jordan Plumhoff, Gia Cobb, Lola Afolabi, Carla Boutin-Foster, Martin Wells, Marian Scott, Gbenga Ogedegbe

Wayne State University Associated BioMed Central Scholarship

Abstract

Background

Black men have the greatest burden of premature death and disability from hypertension (HTN) in the United States, and the highest incidence and mortality from colorectal cancer (CRC). While several clinical trials have reported beneficial effects of lifestyle changes on blood pressure (BP) reduction, and improved CRC screening with patient navigation (PN), the effectiveness of these approaches in community-based settings remains understudied, particularly among Black men.

Methods/design

MISTER B is a two-parallel-arm randomized controlled trial that will compare the effect of a motivational interviewing tailored lifestyle intervention (MINT) versus a culturally targeted PN intervention on improvement of BP …

Inhibition Of Hedgehog Signaling Sensitizes Nsclc Cells To Standard Therapies Through Modulation Of Emt-Regulating Mirnas, Aamir Ahmad, Ma'in Y. Maitah, Kevin R. Ginnebaugh, Yiwei Li, Bin Bao, Shirish M. Gadgeel, Fazlul H. Sarkar

Wayne State University Associated BioMed Central Scholarship

Abstract

Background

Epidermal growth factor receptor- tyrosine kinase inhibitors (EGFR-TKIs) benefit Non-small cell lung cancer (NSCLC) patients, and an EGFR-TKIi erlotinib, is approved for patients with recurrent NSCLC. However, resistance to erlotinib is a major clinical problem. Earlier we have demonstrated the role of Hedgehog (Hh) signaling in Epithelial-to-Mesenchymal transition (EMT) of NSCLC cells, leading to increased proliferation and invasion. Here, we investigated the role of Hh signaling in erlotinib resistance of TGF-β1-induced NSCLC cells that are reminiscent of EMT cells.

Methods

Hh signaling was inhibited by specific siRNA and by GDC-0449, a small molecule antagonist of G protein coupled …

Targeting And Killing Of Glioblastoma With Activated T Cells Armed With Bispecific Antibodies, Ian M. Zitron, Archana Thakur, Oxana Norkina, Geoffrey R. Barger, Lawrence G. Lum, Sandeep Mittal

Wayne State University Associated BioMed Central Scholarship

Abstract

Background

Since most glioblastomas express both wild-type EGFR and EGFRvIII as well as HER2/neu, they are excellent targets for activated T cells (ATC) armed with bispecific antibodies (BiAbs) that target EGFR and HER2.

Methods

ATC were generated from PBMC activated for 14 days with anti-CD3 monoclonal antibody in the presence of interleukin-2 and armed with chemically heteroconjugated anti-CD3×anti-HER2/neu (HER2Bi) and/or anti-CD3×anti-EGFR (EGFRBi). HER2Bi- and/or EGFRBi-armed ATC were examined for in vitro cytotoxicity using MTT and ⁵¹Cr-release assays against malignant glioma lines (U87MG, U118MG, and U251MG) and primary glioblastoma lines.

Results

EGFRBi-armed ATC killed up to 85% of U87, …