Medicine and Health Sciences Commons^™

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 …

Distance Saturation Product Predicts Health–Related Quality Of Life Among Sarcoidosis Patients, Julie M. Bourbonnais, Subramanian Malaisamy, Bhavinkumar D. Dalal, Priyan C. Samarakoon, Swapna R. Parikh, Lobelia Samavati

Wayne State University Associated BioMed Central Scholarship

Abstract

Background

Sarcoidosis is a chronic disease with different phenotypic manifestations. Health-related quality of life is an important aspect in sarcoidosis, yet difficult to measure. The objective of this study was to identify clinical markers predictive of poor quality of life in sarcoidosis patients that can be followed over time and targeted for intervention.

Methods

We assessed the quality of life of 162 patients with confirmed sarcoidosis in a prospective, cross-sectional study using the Sarcoidosis Health Questionnaire (SHQ) and Short Form-36 Health Survey (SF-36). We evaluated the validity of these questionnaires and sought to identify variables that would best explain …

Genetic Variation In Glutathione S-Transferase Omega-1, Arsenic Methyltransferase And Methylene-Tetrahydrofolate Reductase, Arsenic Exposure And Bladder Cancer: A Case–Control Study, Jennifer L. Beebe-Dimmer, Priyanka T. Iyer, Jerome O. Nriagu, Greg R. Keele, Shilpin Mehta, Jaymie R. Meliker, Ethan M. Lange, Ann G. Schwartz, Kimberly A. Zuhlke, David Schottenfeld, Kathleen A. Cooney

Wayne State University Associated BioMed Central Scholarship

Abstract

Background

Ingestion of groundwater with high concentrations of inorganic arsenic has been linked to adverse health outcomes, including bladder cancer, however studies have not consistently observed any elevation in risk at lower concentrations. Genetic variability in the metabolism and clearance of arsenic is an important consideration in any investigation of its potential health risks. Therefore, we examined the association between genes thought to play a role in the metabolism of arsenic and bladder cancer.

Methods

Single nucleotide polymorphisms (SNPs) in GSTO-1, As3MT and MTHFR were genotyped using DNA from 219 bladder cancer cases and 273 controls participating in a …

Empiric Guideline-Recommended Weight-Based Vancomycin Dosing And Mortality In Methicillin-Resistant Staphylococcus Aureus Bacteremia: A Retrospective Cohort Study, Ronald G. Hall Ii, Christopher A. Giuliano, Krystal K. Haase, Kathleen A. Hazlewood, Chistopher R. Frei, Nicolas A. Forcade, Sara D. Brouse, Todd Bell, Roger J. Bedimo, Carlos A. Alvarez

Wayne State University Associated BioMed Central Scholarship

Abstract

Background

No studies have evaluated the effect of guideline-recommended weight-based dosing on in-hospital mortality of patients with methicillin-resistant Staphylococcus aureus bacteremia.

Methods

This was a multicenter, retrospective, cohort study of patients with methicillin-resistant Staphylococcus aureus bacteremia receiving at least 48 hours of empiric vancomycin therapy between 01/07/2002 and 30/06/2008. We compared in-hospital mortality for patients treated empirically with weight-based, guideline-recommended vancomycin doses (at least 15 mg/kg/dose) to those treated with less than 15 mg/kg/dose. We used a general linear mixed multivariable model analysis with variables identified a priori through a conceptual framework based on the literature.

Results

A total …

Segmentation Of Corpus Callosum Using Diffusion Tensor Imaging: Validation In Patients With Glioblastoma, Mohammad-Reza Nazem-Zadeh, Sona Saksena, Abbas Babajani-Fermi, Quan Jiang, Hamid Soltanian-Zadeh, Mark Rosenblum, Tom Mikkelsen, Rajan Jain

Wayne State University Associated BioMed Central Scholarship

Abstract

Background

This paper presents a three-dimensional (3D) method for segmenting corpus callosum in normal subjects and brain cancer patients with glioblastoma.

Methods

Nineteen patients with histologically confirmed treatment naïve glioblastoma and eleven normal control subjects underwent DTI on a 3T scanner. Based on the information inherent in diffusion tensors, a similarity measure was proposed and used in the proposed algorithm. In this algorithm, diffusion pattern of corpus callosum was used as prior information. Subsequently, corpus callosum was automatically divided into Witelson subdivisions. We simulated the potential rotation of corpus callosum under tumor pressure and studied the reproducibility of the …

Healthcare Access And Mammography Screening In Michigan: A Multilevel Cross-Sectional Study, Tomi F. Akinyemiju, Amr S. Soliman, May Yassine, Mousumi Banerjee, Kendra Schwartz, Sofia Merajver

Wayne State University Associated BioMed Central Scholarship

Abstract

Background

Breast cancer screening rates have increased over time in the United States. However actual screening rates appear to be lower among black women compared with white women.

Purpose

To assess determinants of breast cancer screening among women in Michigan USA, focusing on individual and neighborhood socio-economic status and healthcare access.

Methods

Data from 1163 women ages 50-74 years who participated in the 2008 Michigan Special Cancer Behavioral Risk Factor Survey were analyzed. County-level SES and healthcare access were obtained from the Area Resource File. Multilevel logistic regression models were fit using SAS Proc Glimmix to account for clustering …

Augmented Annotation And Orthologue Analysis For Oryctolagus Cuniculus: Better Bunny, Douglas B. Craig, Sujatha Kannan, Alan A. Dombkowski

Wayne State University Associated BioMed Central Scholarship

Abstract

Background

The rabbit is an important model organism used in a wide range of biomedical research. However, the rabbit genome is still sparsely annotated, thus prohibiting extensive functional analysis of gene sets derived from whole-genome experiments. We developed a web-based application that provides augmented annotation and orthologue analysis for rabbit genes. Importantly, the application allows comprehensive functional analysis through the use of orthologous relationships.

Results

Using data extracted from several public bioinformatics repositories we created Better Bunny, a database and query tool that extensively augments the available functional annotation for rabbit genes. Using the complete set of target genes …

Recent Updates On The Role Of Micrornas In Prostate Cancer, Oudai Hassan, Aamir Ahmad, Seema Sethi, Fazlul H. Sarkar

Wayne State University Associated BioMed Central Scholarship

Abstract

MicroRNAs (miRNAs) are short non-coding RNAs that are involved in several important biological processes through regulation of genes post-transcriptionally. Carcinogenesis is one of the key biological processes where miRNAs play important role in the regulation of genes. The miRNAs elicit their effects by binding to the 3' untranslated region (3'UTR) of their target mRNAs, leading to the inhibition of translation or the degradation of the mRNA, depending on the degree of complementary base pairing. To-date more than 1,000 miRNAs are postulated to exist, although the field is moving rapidly. Currently, miRNAs are becoming the center of interest in a …

Using Learned Under-Sampling Pattern For Increasing Speed Of Cardiac Cine Mri Based On Compressive Sensing Principles, Pooria Zamani, Mohammad Kayvanrad, Hamid Soltanian-Zadeh

Wayne State University Associated BioMed Central Scholarship

Abstract

This article presents a compressive sensing approach for reducing data acquisition time in cardiac cine magnetic resonance imaging (MRI). In cardiac cine MRI, several images are acquired throughout the cardiac cycle, each of which is reconstructed from the raw data acquired in the Fourier transform domain, traditionally called k-space. In the proposed approach, a majority, e.g., 62.5%, of the k-space lines (trajectories) are acquired at the odd time points and a minority, e.g., 37.5%, of the k-space lines are acquired at the even time points of the cardiac cycle. Optimal data acquisition at the even time points is learned …

Increased Prevalence Of Methicillin-Resistant Staphylococcus Aureus Nasal Colonization In Household Contacts Of Children With Community Acquired Disease, Yaseen Rafee, Nahed Abdel-Haq, Basim Asmar, Tanaz Salimnia, Celine Pharm, Michael J. Rybak Pharm, Muhammad Amjad

Wayne State University Associated BioMed Central Scholarship

Abstract

Background

To measure Methicillin-resistant Staphylococcus aureus (MRSA) nasal colonization prevalence in household contacts of children with current community associated (CA)-MRSA infections (study group) in comparison with a group of household contacts of children without suspected Staphylococcus aureus infection (a control group).

Methods

This is a cross sectional study. Cultures of the anterior nares were taken. Relatedness of isolated strains was tested using pulse field gel electrophoresis (PFGE).

Results

The prevalence of MRSA colonization in the study group was significantly higher than in the control group (18/77 (23%) vs 3/77 (3.9%); p ≤ 0.001). The prevalence of SA colonization was …

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. …

Does Cerclage Improve Neonatal Outcomes In A Molar Pregnancy And A Coexistent Fetus? A Case Report, Eduardo Aguin, Victor Aguin, Ligia Cisneros, Tina Aguin, Cosmas Van De Ven, Ray Bahado-Singh

Wayne State University Associated BioMed Central Scholarship

Abstract

Background

Complete hydatiform mole and coexistent viable fetus is very rare. The use of a cervical cerclage for cervical indications in the presence of this condition has never been reported. Although the diagnosis was made postnatal, the objective is to present a case with good neonatal outcome.

Case presentation

A patient presented with vaginal spotting around 23 weeks. She has a history of four preterm deliveries. Her cervix was dilated and a cerclage was placed. She presented again with PPROM around 25 weeks. She went into spontaneous preterm labor and delivered a viable fetus that is a healthy girl …

Evaluation Of Age-Related Changes In Translocator Protein (Tspo) In Human Brain Using 11C-[R]-Pk11195 Pet, Ajay Kumar, Otto Muzik, Varun Shandal, Diane Chugani, Pulak Chakraborty, Harry T. Chugani

Wayne State University Associated BioMed Central Scholarship

Abstract

Background

We studied the distribution and expression of translocator protein in the human brain using ¹¹C-[R]-PK-11195 positron emission tomography (PK11195 PET) and evaluated age-related changes.

Methods

A dynamic PK11195 PET scan was performed in 15 normal healthy adults (mean age: 29 ±8.5 years (range: 20 to 49); 7 males) and 10 children (mean age: 8.8 ±5.2 years (range: 1.2 to 17); 5 males), who were studied for potential neuroinflammation but showed no focally increased PK11195 binding. The PET images were evaluated by calculating standard uptake values and regional binding potential, based on a simplified reference region model, as …

Hdm2 Antagonist Mi-219 (Spiro-Oxindole), But Not Nutlin-3 (Cis-Imidazoline), Regulates P53 Through Enhanced Hdm2 Autoubiquitination And Degradation In Human Malignant B-Cell Lymphomas, Angela M. Sosin, Angelika M. Burger, Aisha Siddiqi, Judith Abrams, Ramzi M. Mohammad, Ayad M. Al-Katib

Wayne State University Associated BioMed Central Scholarship

Abstract

Background

Lymphomas frequently retain wild-type (wt) p53 function but overexpress HDM2, thereby compromising p53 activity. Therefore, lymphoma is a suitable model for studying the therapeutic value of disrupting the HDM2-p53 interaction by small-molecule inhibitors (SMIs). HDM2 have been developed and are under various stages of preclinical and clinical investigation. Previously, we examined the anti-lymphoma activity of MI-319, the laboratory grade of a new class of HDM2 SMI, the spiro-oxindole, in follicular lymphoma. Since then, MI-219, the clinical grade has become readily available. This study further examines the preclinical effects and mechanisms of MI-219 in a panel of human lymphoma …

A Case–Control Study Of Occupation/Industry And Renal Cell Carcinoma Risk, Sara Karami, Joanne S. Colt, Kendra Schwartz, Faith G. Davis, Julie J. Ruterbusch, Stella S. Munuo, Sholom Wacholder, Patricia A. Stewart, Barry I. Graubard, Nathanial Rothman, Wong-Ho Chow, Mark P. Purdue

Wayne State University Associated BioMed Central Scholarship

Abstract

Background

The role of occupation in the etiology of renal cell carcinoma (RCC) is unclear. Here, we investigated associations between employment in specific occupations and industries and RCC, and its most common histologic subtype, clear cell RCC (ccRCC).

Methods

Between 2002 and 2007, a population-based case–control study of Caucasians and African Americans (1,217 cases; 1,235 controls) was conducted within the Detroit and Chicago metropolitan areas to investigate risk factors for RCC. As part of this study, occupational histories were ascertained through in-person interviews. We computed odds ratios (ORs) and 95% confidence intervals (CIs) relating occupation and industry to RCC …

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 …

Norepinephrine: The Next Therapeutics Frontier For Parkinson's Disease, Peter A. Lewitt

Wayne State University Associated BioMed Central Scholarship

Abstract

Tissue concentrations of norepinephrine (NE) are markedly decreased in various regions of the Parkinson's disease (PD) brain. As in the substantia nigra pars compacta, neuronal dropout and Lewy bodies are prominent changes affecting the locus coeruleus, which is the source of ascending NErgic projections. Despite the major roles of NE throughout the brain, there has been only minimal exploration of pharmacological intervention with NErgic neurotransmission. Cognitive operations, "freezing" of gait, tremor, dyskinesia, REM sleep regulation, and other aspects of brain function are tied into signaling by NE, and there is also evidence that it may have a role in …