Women's Health 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 …

Fibroblast-Secreted Hepatocyte Growth Factor Mediates Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor Resistance In Triple-Negative Breast Cancers Through Paracrine Activation Of Met, Kelly L. Mueller, Julie M. Madden, Gina L. Zoratti, Charlotte Kuperwasser, Karin List, Julie L. Boerner

Wayne State University Associated BioMed Central Scholarship

Abstract

Introduction

Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) have shown clinical efficacy in lung, colon, and pancreatic cancers. In lung cancer, resistance to EGFR TKIs correlates with amplification of the hepatocyte growth factor (HGF) receptor tyrosine kinase Met. Breast cancers do not respond to EGFR TKIs, even though EGFR is overexpressed. This intrinsic resistance to EGFR TKIs in breast cancer does not correlate with Met amplification. In several tissue monoculture models of human breast cancer, Met, although expressed, is not phosphorylated, suggesting a requirement for a paracrine-produced ligand. In fact, HGF, the ligand for Met, is not …

The Cyclin-Like Protein Spy1/Ringo Promotes Mammary Transformation And Is Elevated In Human Breast Cancer, Mohammad Al Sorkhy, Rosa-Maria Ferraiuolo, Espanta Jalili, Agnes Malysa, Andreea R. Fratiloiu, Bonnie F. Sloane, Lisa A. Porter

Wayne State University Associated BioMed Central Scholarship

Abstract

Background

Spy1 is a novel 'cyclin-like' activator of the G1/S transition capable of enhancing cell proliferation as well as inhibiting apoptosis. Spy1 protein levels are tightly regulated during normal mammary development and forced overexpression in mammary mouse models accelerates mammary tumorigenesis.

Methods

Using human tissue samples, cell culture models and in vivo analysis we study the implications of Spy1 as a mediator of mammary transformation and breast cancer proliferation.

Results

We demonstrate that this protein can facilitate transformation in a manner dependent upon the activation of the G2/M Cdk, Cdk1, and the subsequent inhibition of the anti-apoptotic regulator FOXO1. …

Erlin2 Promotes Breast Cancer Cell Survival By Modulating Endoplasmic Reticulum Stress Pathways, Guohui Wang, Gang Liu, Xiaogang Wang, Seema Sethi, Rouba Ali-Fehmi, Judith Abrams, Ze Zheng, Kezhong Zhang, Stephen Ethier, Zeng-Quan Yang

Wayne State University Associated BioMed Central Scholarship

Abstract

Background

Amplification of the 8p11-12 region has been found in approximately 15% of human breast cancer and is associated with poor prognosis. Previous genomic analysis has led us to identify the endoplasmic reticulum (ER) lipid raft-associated 2 (ERLIN2) gene as one of the candidate oncogenes within the 8p11-12 amplicon in human breast cancer, particularly in the luminal subtype. ERLIN2, an ER membrane protein, has recently been identified as a novel mediator of ER-associated degradation. Yet, the biological roles of ERLIN2 and molecular mechanisms by which ERLIN2 coordinates ER pathways in breast carcinogenesis remain unclear.

Methods

We established the MCF10A-ERLIN2 …

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 …

Spermine Oxidase (Smo) Activity In Breast Tumor Tissues And Biochemical Analysis Of The Anticancer Spermine Analogues Benspm And Cpenspm, Manuela Cervelli, Gabriella Bellavia, Emiliano Fratini, Roberto Amendola, Fabio Polticelli, Marco Barba, Rodolfo Federico, Fabrizio Signore, Giacomo Gucciardo, Rosalba Grillo, Patrick M. Woster, Robert A. Casero Jr, Paolo Mariottini

Wayne State University Associated BioMed Central Scholarship

Abstract

Background

Polyamine metabolism has a critical role in cell death and proliferation representing a potential target for intervention in breast cancer (BC). This study investigates the expression of spermine oxidase (SMO) and its prognostic significance in BC. Biochemical analysis of Spm analogues BENSpm and CPENSpm, utilized in anticancer therapy, was also carried out to test their property in silico and in vitro on the recombinant SMO enzyme.

Methods

BC tissue samples were analyzed for SMO transcript level and SMO activity. Student's t test was applied to evaluate the significance of the differences in value observed in T and NT …

Egfr/Met Association Regulates Egfr Tki Resistance In Breast Cancer, Kelly L. Mueller, Zeng-Quan Yang, Ramsi Haddad, Stephen P. Ethier, Julie L. Boerner

Wayne State University Associated BioMed Central Scholarship

Abstract

Breast cancers show a lack of response to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs), despite 30% of tumors expressing EGFR. The mechanism of this resistance is unknown; however, we have recently shown that Met kinase activity compensates for loss of EGFR kinase activity in cell culture models. Met has been implicated in the pathogenesis of breast tumors and therefore may cooperate with EGFR for tumor growth. Here we have found that EGFR phosphorylation and cell proliferation is in part regulated by Met expression. In addition, we found that Met constitutive phosphorylation occurred independent of the Met …

Vaccination With A Plasmid Dna Encoding Her-2/Neu Together With Low Doses Of Gm-Csf And Il-2 In Patients With Metastatic Breast Carcinoma: A Pilot Clinical Trial, Hã¥Kan Norell, Isabel Poschke, Jehad Charo, Wei Z. Wei, Courtney Erskine, Marie P. Piechocki, Keith L. Knutson, Jonas Bergh, Elisabet Lidbrink, Rolf Kiessling

Wayne State University Associated BioMed Central Scholarship

Abstract

Background

Adjuvant trastuzumab (Herceptin) treatment of breast cancer patients significantly improves their clinical outcome. Vaccination is an attractive alternative approach to provide HER-2/neu (Her2)-specific antibodies and may in addition concomitantly stimulate Her2-reactive T-cells. Here we report the first administration of a Her2-plasmid DNA (pDNA) vaccine in humans.

Patients and Methods

The vaccine, encoding a full-length signaling-deficient version of the oncogene Her2, was administered together with low doses of GM-CSF and IL-2 to patients with metastatic Her2-expressing breast carcinoma who were also treated with trastuzumab. Six of eight enrolled patients completed all three vaccine cycles. In the remaining two patients …

Sulforaphane Induces Cell Cycle Arrest By Protecting Rb-E2f-1 Complex In Epithelial Ovarian Cancer Cells, Christopher S. Bryant, Sanjeev Kumar, Sreedhar Chamala, Jay Shah, Jagannath Pal, Mahdi Haider, Shelly Seward, Aamer M. Qazi, Robert Morris, Assaad Semaan, Masood A. Shammas, Christopher Steffes, Ravindra B. Potti, Madhu Prasad, Donald W. Weaver, Ramesh B. Batchu

Wayne State University Associated BioMed Central Scholarship

Abstract

Background

Sulforaphane (SFN), an isothiocyanate phytochemical present predominantly in cruciferous vegetables such as brussels sprout and broccoli, is considered a promising chemo-preventive agent against cancer. In-vitro exposure to SFN appears to result in the induction of apoptosis and cell-cycle arrest in a variety of tumor types. However, the molecular mechanisms leading to the inhibition of cell cycle progression by SFN are poorly understood in epithelial ovarian cancer cells (EOC). The aim of this study is to understand the signaling mechanisms through which SFN influences the cell growth and proliferation in EOC.

Results

SFN at concentrations of 5 - 20 …

Ritonavir Blocks Akt Signaling, Activates Apoptosis And Inhibits Migration And Invasion In Ovarian Cancer Cells, Sanjeev Kumar, Christopher S. Bryant, Sreedhar Chamala, Aamer Qazi, Shelly Seward, Jagannath Pal, Christopher P. Steffes, Donald W. Weaver, Robert Morris, John M. Malone, Masood A. Shammas, Madhu Prasad, Ramesh B. Batchu

Wayne State University Associated BioMed Central Scholarship

Abstract

Background

Ovarian cancer is the leading cause of mortality from gynecological malignancies, often undetectable in early stages. The difficulty of detecting the disease in its early stages and the propensity of ovarian cancer cells to develop resistance to known chemotherapeutic treatments dramatically decreases the 5-year survival rate. Chemotherapy with paclitaxel after surgery increases median survival only by 2 to 3 years in stage IV disease highlights the need for more effective drugs. The human immunodeficiency virus (HIV) infection is characterized by increased risk of several solid tumors due to its inherent nature of weakening of immune system. Recent observations …

Sensitization Of Ovarian Cancer Cells To Cisplatin By Genistein: The Role Of Nf-Kappab, Leigh A. Solomon, Shadan Ali, Sanjeev Banerjee, Adnan R. Munkarah, Robert T. Morris, Fazlul H. Sarkar

Wayne State University Associated BioMed Central Scholarship

Abstract

Background

Platinum-resistance (PR) continues to be a major problem in the management of epithelial ovarian cancer (EOC). Response to various chemotherapeutic agents is poor in patients deemed PR. Genistein, a soy isoflavone has been shown to enhance the effect of chemotherapy in prostate and pancreatic cancer cells in vitro and in vivo by reversing chemo-resistance phenotype. The goal of this study was to investigate the effects of combination therapy with genistein and cisplatin as well as other cytotoxic conventional chemotherapeutic agents in platinum-sensitive (PS) and resistant EOC cells.

Methods

The PS human ovarian cancer cell line A2780 and its …

Inhibition Of Proteasome Activity By The Dietary Flavonoid Apigenin Is Associated With Growth Inhibition In Cultured Breast Cancer Cells And Xenografts, Di Chen, Kristin R. Landis-Piwowar, Marina S. Chen, Q Ping Dou

Wayne State University Associated BioMed Central Scholarship

Abstract

Introduction

Proteasome inhibition is an attractive approach to anticancer therapy and may have relevancy in breast cancer treatment. Natural products, such as dietary flavonoids, have been suggested as natural proteasome inhibitors with potential use for cancer prevention and therapeutics. We previously reported that apigenin, a flavonoid widely distributed in many fruits and vegetables, can inhibit proteasome activity and can induce apoptosis in cultured leukemia Jurkat T cells. Whether apigenin has proteasome-inhibitory activity in the highly metastatic human breast MDA-MB-231 cells and xenografts, however, is unknown.

Methods

MDA-MB-231 breast cancer cell cultures and xenografts were treated with apigenin, followed by …

Paradoxical Antiproliferative Effect By A Murine Mammary Tumor-Derived Epithelial Cell Line, Esteban N. Gurzov, Sanaa M. Nabha, Hamilto Yamamoto, Hong Meng, O Graciela Scharovsky, R Daniel Bonfil

Wayne State University Associated BioMed Central Scholarship

Abstract

Background

Despite significant advancement in breast cancer therapy, there is a great need for a better understanding of the mechanisms involved in breast carcinogenesis and progression, as well as of the role of epigenetic contributions from stromal cells in mammary tumorigenesis. In this study, we isolated and characterized murine mammary tumor-derived epithelial and myofibroblast cell lines, and investigated the in vitro and in vivo effect of cellular soluble factors produced by the epithelial cell line on tumor cells.

Methods

Morphology, immunophenotype, cytogenetics, invasiveness, and tumorigenicity of epithelial (LM-234ep) and myofibroblast (LM-234mf) cell lines isolated from two murine mammary adenocarcinomas …

Clioquinol And Pyrrolidine Dithiocarbamate Complex With Copper To Form Proteasome Inhibitors And Apoptosis Inducers In Human Breast Cancer Cells, Kenyon G. Daniel, Di Chen, Shirley Orlu, Qiuzhi Cui, Fred R. Miller, Q Ping Dou

Wayne State University Associated BioMed Central Scholarship

Abstract

Introduction

A physiological feature of many tumor tissues and cells is the tendency to accumulate high concentrations of copper. While the precise role of copper in tumors is cryptic, copper, but not other trace metals, is required for angiogenesis. We have recently reported that organic copper-containing compounds, including 8-hydroxyquinoline-copper(II) and 5,7-dichloro-8-hydroxyquinoline-copper(II), comprise a novel class of proteasome inhibitors and tumor cell apoptosis inducers. In the current study, we investigate whether clioquinol (CQ), an analog of 8-hydroxyquinoline and an Alzheimer's disease drug, and pyrrolidine dithiocarbamate (PDTC), a known copper-binding compound and antioxidant, can interact with copper to form cancer-specific proteasome …