Medical Specialties Commons^™

Analysis Of The Structure And Function Of A Timp-1/Cd63 Complex And Its Relationship To An Mt1-Mmp/Cd63 Complex, Richard B. Warner

Wayne State University Dissertations

The relationship of the extra-cellular matrix (ECM) and secreted proteins to intra-cellular functions has an important impact on disease progression. The tissue inhibitors of metalloproteinases (TIMPs), of which there are four, are known for their broad metalloprotease inhibitory abilities. TIMP-1 has been widely studied as an inhibitor of matrix metalloproteinases (MMPs) and therefore as a molecule that prevents ECM degradation and proteolytic cleavage of extra-cellular molecules, processes thought to be critical for tumor invasion and metastasis. However, TIMP-1 has shown in the clinic to have increased expression in cases of disease progression; especially, it is associated with poor prognosis in …

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 …

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 …

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 …

The Bca2 And Ampk Paradigm: Unraveling The Cancer Connection, Daniela (Buac) Ventro

Wayne State University Dissertations

THE BCA2 & AMPK PARADIGM: UNRAVELING THE CANCER CONNECTION

By

DANIELA (BUAC) VENTRO

December 2013

Advisor: Dr. Q Ping Dou and Angelika M. Burger (deceased)

Major: Cancer Biology

Degree: Doctor of Philosophy

Adenosine monophosphate-activated kinase (AMPK), a master regulator of cellular energy homeostasis, has emerged as a promising molecular target in the prevention of breast cancer, and phase II and III clinical trials using the FDA-approved, AMPK activating, anti-diabetic drug metformin are promising in this regard, but the question of why metformin is protective for some women but not others still remains. Breast Cancer Associated Gene 2 (BCA2/Rabring7/RNF115), a novel …

Prenatal Genetic Diagnosis Using Transcervically Derived And Immunomagnetically Isolated Trophoblast Cells, Swati Bajpayee

Honors College Theses

Trophoblast cells migrate from the placenta into the endocervical canal early in the first trimester and can be collected non-invasively by transcervical sampling (TCS), potentially providing fetal DNA for prenatal genetic diagnosis. Experiments were conducted to separate fetal cells from maternal cells within the TCS specimens and use the fetal cells to perform genetic analysis. Trophoblast cells were efficiently isolated from TCS specimens during weeks 5-18 of gestation using HLA-G antibody coupled to magnetic nanoparticles. Immunofluorescence microscopy revealed that 99% of isolated cells expressed the chorionic gonadotropin β subunit (β-CG), while the non-bound cell fraction expressed none. Immunomagnetically isolated cells …

Activation Of Amp-Activated Protein Kinase By 3,39-Diindolylmethane (Dim) Is Associated With Human Prostate Cancer Cell Death In Vitro And In Vivo, Di Chen, Sanjeev Banerjee, Qiuzhi C. Cui, Dejuan Kong, Fazlul H. Sarkar, Q. Ping Dou

Oncology Faculty Publications

There is a large body of scientific evidence suggesting that 3,39-Diindolylmethane (DIM), a compound derived from the digestion of indole-3-carbinol, which is abundant in cruciferous vegetables, harbors anti-tumor activity in vitro and in vivo. Accumulating evidence suggests that AMP-activated protein kinase (AMPK) plays an essential role in cellular energy homeostasis and tumor development and that targeting AMPK may be a promising therapeutic option for cancer treatment in the clinic. We previously reported that a formulated DIM (BR-DIM; hereafter referred as B-DIM) with higher bioavailability was able to induce apoptosis and inhibit cell growth, angiogenesis, and invasion of prostate cancer cells. …

Patients' And Caregivers' Inside Perspectives: Living With A Left-Ventricular Assist Device As Destination Therapy, Linda Marcuccilli

Wayne State University Dissertations

Left-ventricular assist devices (LVADs) have improved the quality of life for many patients with advanced heart failure. Past research focused on technology issues and survival rates, but patients' and caregivers' perspectives of living with an LVAD as a destination therapy (e.g., permanent alternative to transplant) was not explored. Roy's adaptation model provided a framework to guide an understanding of how participants adjusted and accepted living with destination therapy. A hermeneutic-phenomenology as described by van Manen was used to explore and describe the essence of destination therapy from patients' and caregivers' perspectives in order to understand the meaning of this experience. …

In Ovo Serial Skeletal Muscle Diffusion Tractography Of The Developing Chick Embryo Using Dti: Feasibility And Correlation With Histology, Zien Zhou, Zachary Delproposto, Lianming Wu, Jianrong Xu, Jia Hua, Yan Zhou, Yongquan Ye, Zishu Zhang, Jiani Hu, E Mark Haacke

Wayne State University Associated BioMed Central Scholarship

Abstract

Background

Magnetic resonance imaging is a noninvasive method of evaluating embryonic development. Diffusion tensor imaging (DTI), based on the directional diffusivity of water molecules, is an established method of evaluating tissue structure. Yet embryonic motion degrades the in vivo acquisition of long-duration DTI. We used a dual-cooling technique to avoid motion artifact and aimed to investigate whether DTI can be used to monitor chick embryonic skeletal muscle development in ovo, and to investigate the correlation between quantitative DTI parameters fractional anisotropy (FA) and fiber length and quantitative histologic parameters fiber area percentage (FiberArea%) and limb length.

Results

From 84 …

Expression Of Mir-34 Is Lost In Colon Cancer Which Can Be Re-Expressed By A Novel Agent Cdf, Sanchita Roy, Edi Levi, Adhip Pn Majumdar, Fazlul H. Sarkar

Wayne State University Associated BioMed Central Scholarship

Abstract

Background

Colorectal Cancer (CRC) is one of the leading causes of death worldwide. Numerous cellular events, including deregulated expression of microRNAs (miRNAs), specifically the family of miR-34 consisting of miR-34a, b and c, is known to regulate the processes of growth and metastasis.

Methods

We evaluated the expression of miR-34 in formalin-fixed paraffin-embedded (FFPE) human colon cancer tissue specimens compared to normal colonic mucosa. Moreover, we also assessed the expression of miR-34 in colon cancer cell lines treated with our newly developed synthetic analogue of curcumin referred as difluorinated curcumin (CDF) compared to well known inhibitor of methyl transferase. …

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 …

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 …

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. …

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 …

Network Insights On Oxaliplatin Anti-Cancer Mechanisms, Osama M. Alian, Asfar S. Azmi, Ramzi M. Mohammad

Wayne State University Associated BioMed Central Scholarship

Abstract

Oxaliplatin has been a crucial component of combination therapies since admission into the clinic causing modest gains in survival across multiple malignancies. However, oxaliplatin functions in a non-targeted manner, posing a difficulty in ascertaining precise efficacy mechanisms. While previously thought to only affect DNA repair mechanisms, Platinum-protein adducts (Pt-Protein) far outnumber Pt-DNA adducts leaving a big part of oxaliplatin function unknown. Through preliminary network modeling of high throughput data, this article critically reviews the efficacy of oxaliplatin as well as proposes a better model for enhanced efficacy based on a network approach. In our study, not only oxaliplatin’s function …

Acr Appropriateness Criteria®  Resectable Rectal Cancer, William E. Jones Iii, Charles R. Thomas Jr, Joseph M. Herman, May Abdel-Wahab, Nilofer Azad, William Blackstock, Prajnan Das, Karyn A. Goodman, Theodore S. Hong, Salma K. Jabbour, Andre A. Konski, Albert C. Koong, Miguel Rodriguez-Bigas, William Small Jr, Jennifer Zook, W Suh

Wayne State University Associated BioMed Central Scholarship

Abstract

The management of resectable rectal cancer continues to be guided by clinical trials and advances in technique. Although surgical advances including total mesorectal excision continue to decrease rates of local recurrence, the management of locally advanced disease (T3-T4 or N+) benefits from a multimodality approach including neoadjuvant concomitant chemotherapy and radiation. Circumferential resection margin, which can be determined preoperatively via MRI, is prognostic. Toxicity associated with radiation therapy is decreased by placing the patient in the prone position on a belly board, however for patients who cannot tolerate prone positioning, IMRT decreases the volume of normal tissue irradiated. The …

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 …

Type 2 Diabetes And Insomnia: Impact On Metabolic Control, Cheryl Lee Tannas

Wayne State University Dissertations

Diabetes is one of the most serious health challenges in the United States, affecting nearly 21 million Americans. The goal of diabetes management is to maintain the blood glucose close to normal to prevent diabetic complications and therefore extending life expectancy and improving quality of life. Research now indicates a relationship of the quantity and quality of sleep to glycemic control in type 2 diabetics. No research on the impact of insomnia on diabetes prevention and/or management was found in the literature. The purpose of this 11 week intervention study was to examine the effects of participation in Cognitive Behavioral …

Preterm Birth And The Perception Of Risk Among African Americans, Gwendolyn Simpson Norman

Wayne State University Dissertations

Background: African American women deliver preterm at a rate that is two to three times that of their white counterparts, and after decades of research, this disparity in birth outcomes still remains unexplained. While factors including income, education, neighborhood conditions, infection and stress have all been associated with prematurity, no combination of these factors has explained why the disparity persists. Recently, however, racism-specific stress has emerged as a possible factor contributing to this disparity. This study was designed to learn how preterm birth was explained by African Americans directly impacted by prematurity. Methods: Interviews were conducted with African American women …

A Novel Interaction Between 12-Lipoxygenase And Β4 Integrin Plays A Role In Cancer Progression, Sangeeta Joshi

Wayne State University Dissertations

No abstract provided.

Modulation Of Anti-Tumor Immune Response By Tgf-Β-Inducible Early Gene 1 (Tieg1), Andi Cani

Wayne State University Theses

Cancer immunotherapy has had limited clinical efficacy partly because regulatory T cells (Treg) suppress the immune response to tumor-associated antigens. Inducible regulatory T cells (iTreg), which are converted from naïve CD4 T cells by TGF-β, an abundant cytokine in the tumor microenvironment, may contribute to this immune suppression. Induction of Foxp3 by TGF-β is mediated by the transcription factor TIEG1 and abrogation of this protein prevents Foxp3 expression. We are testing the hypothesis that blockade of TIEG1 to prevent iTreg conversion will enhance immune response in DNA vaccination to the tumor associated antigen Her-2. Wild type and TIEG1 knockout mice …

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 …

Bickerstaff’S Brainstem Encephalitis, Miller Fisher Syndrome And Guillain-Barré Syndrome Overlap In An Asthma Patient With Negative Anti-Ganglioside Antibodies, Chongyu Han, Yuan Wang, Jianping Jia, Xunming Ji, Vance Fredrickson, Yuchuan Ding, Wei Sun, Jia Xu, Yong-Xin Sun

Wayne State University Associated BioMed Central Scholarship

Abstract

Background

Bickerstaff’s brainstem encephalitis (BBE), together with Miller Fisher syndrome (MFS) and Guillain-Barré syndrome (GBS) were considered to form a continuous clinical spectrum. An anti-GQ1b antibody syndrome has been proposed to underlie the common pathophysiology for the three disorders; however, other studies have found a positive anti-GM1 instead of anti-GQ1b antibody.

Case presentation

Here we report a 20-year-old male patient with overlapping BBE, MFS and GBS. The patient had a positive family history of bronchial asthma and had suffered from the condition for over 15 years. He developed BBE symptoms nine days after an asthma exacerbation. During the course …

Vitamin D Mitigates Age-Related Cognitive Decline Through The Modulation Of Pro-Inflammatory State And Decrease In Amyloid Burden, Teresita L. Briones, Hala Darwish

Wayne State University Associated BioMed Central Scholarship

Abstract

Background

Increasing evidence shows an association between the use of vitamin D and improvement in age-related cognitive decline. In this study, we investigated the possible mechanisms involved in the neuroprotective effects of vitamin D on age-related brain changes and cognitive function.

Methods

Male F344 rats aged 20 months (old) and 6 months (young) were used and randomly assigned to either vitamin D supplementation or no supplementation (control). A total of n = 39 rats were used in the study. Rats were individually housed and the supplementation group received a subcutaneous injection of vitamin D (1, α25-dihydroxyvitamin D3) 42 I.U./Kg …

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 …

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 …

Vip And Host Immunity, Xiaoyu Jiang

Wayne State University Dissertations

The purpose of the current dissertation was to examine how VIP regulates host immunity and corneal healing, specifically, its control of growth factors and TLR expression in the P. aeruginosa infected cornea. Firstly, VIP treatment increased growth factor expression (EGF, GHF, FGF and VEGF) in infected cornea. Notably, treatment with a mixture of EGF, FGF and HGF prevented corneal perforation, reduced pro-inflammatory cytokines and bacterial plate count, while increasing anti-inflammatory cytokines and antimicrobials such as murine beta-defensin2 and 3.

We also investigated the expression of TLR-signaling pathways in P. aeruginosa infected corneas with or without VIP treatment. PCR array and …

Identifying Sm22 As A Key Player In Arterial Diseases, Jianbin Shen

Wayne State University Dissertations

Background : Expression of vascular smooth muscle cell (VSMC) cytoskeleton markers including SM22 is down-regulated in arterial diseases including atherosclerosis where inflammation and osteochondrogenesis are present. However, the role of this downregulation in arterial pathogenesis is unknown. Hypothesis : Downregulation of SM22 may actively contribute to arterial pathogenesis. Methods : Five Sm22 knockout (Sm22^-/-) mice and their wild type littermates were subjected to carotid artery denudation, an artery injury model. Analyses were conducted on carotid arteries 2 weeks after injury. Primary VSMCs were isolated from mouse aortas and investigated individually at passage 2 to 4. Sm22 knockdown was …

Role Of Thromboxane Receptor-Alpha In Prostate Cancer Progression, Prasanna Ekambaram

Wayne State University Dissertations

Thromboxane A2 (TXA2) is a major arachidonic acid metabolite that signals through TXA2 receptors (TP) to induce platelet aggregation and smooth muscle contraction. TXA2 receptors are expressed as two different isoforms in humans, namely TP-alpha (TPα) and TP-beta (TPβ), which have common and distinct signaling pathways. Of the two TP receptor isoforms, studies have shown that TPα impacts tumor growth and progression of lung cancer. Previously our studies demonstrated that activation of Thromboxane receptor by TXA2 agonists could regulate prostate cancer (PCa) cell motility and cytoskeletal reorganization through activation of Rho-A. The primary objective of this study is to investigate …