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Full-Text Articles in Pathology

Hif Expression In Clear-Cell Renal Cell Carcinoma (Ccrcc) Tumors Of Adults With And Without Obstructive Sleep Apnea (Osa), Olivia Heppell, Carlos Guerra Londono, Nilesh Gupta Mar 2024

Hif Expression In Clear-Cell Renal Cell Carcinoma (Ccrcc) Tumors Of Adults With And Without Obstructive Sleep Apnea (Osa), Olivia Heppell, Carlos Guerra Londono, Nilesh Gupta

Medical Student Research Symposium

Introduction: Upregulation of hypoxia-inducible factors (HIF) is an important pathological feature shared by clear cell renal cell carcinoma (ccRCC) and obstructive sleep apnea (OSA). However, it is unclear whether OSA alters the pathogenesis of ccRCC via HIF expression.

Methods: A retrospective cohort of adults undergoing nephrectomy for ccRCC was identified electronically (IRB#16040-1). The diagnosis of OSA was established with preoperative STOP-BANG scores or polysomnography. A consecutive sample of 20 individuals with and 20 without OSA was selected. Clinical characteristics and pathology results were reviewed. Resected tumor sections were immunohistochemically stained for HIF-1& HIF-2 at antibody dilutions of 1:150. Intensity and …


Hormonal Regulation Of Glycine Decarboxylase And Its Metabolic Outcomes, Ruta Milind Jog Jan 2020

Hormonal Regulation Of Glycine Decarboxylase And Its Metabolic Outcomes, Ruta Milind Jog

Wayne State University Dissertations

The amino acid glycine is involved in generation of multiple critical metabolites including glutathione, heme, and creatinine. Interestingly, in both humans and rodents, circulating glycine levels are significantly reduced in obesity, glucose intolerance, type II diabetes and non-alcoholic fatty liver disease. The glycine cleavage system is the predominant glycine degradation pathway in humans. The rate-limiting enzyme of glycine cleavage system is glycine decarboxylase (GLDC), and loss-of-function mutations of GLDC cause hyperglycinemia. Here, we show that GLDC gene expression is upregulated in livers of mouse models of diabetes and diet-induced obesity as well as in the fasted state in normal animals. …


Molecular Docking And Inhibition Of Matrix Metalloproteinase-2 By Novel Difluorinatedbenzylidene Curcumin Analog, Aamir Ahmad, Afreen Sayed, Kevin R. Ginnebaugh, Vivek Sharma, Anita Suri, Arundhati Saraph, Subhash Padhye, Fazlul H. Sarkar Feb 2015

Molecular Docking And Inhibition Of Matrix Metalloproteinase-2 By Novel Difluorinatedbenzylidene Curcumin Analog, Aamir Ahmad, Afreen Sayed, Kevin R. Ginnebaugh, Vivek Sharma, Anita Suri, Arundhati Saraph, Subhash Padhye, Fazlul H. Sarkar

Department of Pathology

We recently described the synthesis and characterization of a novel difluorinatedbenzylidene analog of curcumin, commonly referred as CDF, which demonstrated significantly enhanced bioavailability and in vivo anticancer activity. CDF targets many factors similar to curcumin, albeit with more potency, as reported previously. To further highlight this differential behavior of CDF, we chose matrix metalloproteinase protein MMP-2 which is involved in the processes of invasion and metastasis of human tumors. Both curcumin and CDF were characterized for their binding characteristics using in silico docking studies; they were also evaluated via biological assays involving gelatin zymography, miRNA analysis, invasion assays and ELISA. …


Carp-1 Functional Mimetics Are A Novel Class Of Small Molecule Inhibitors Of Malignant Pleural Mesothelioma Cells, Shazia Jamal, Vino T. Cheriyan, Magesh Muthu, Sara Munie, Edi Levi, Abdelkader E. Ashour, Harvey I. Pass, Anil Wali, Mandip Singh, Arun K. Rishi Mar 2014

Carp-1 Functional Mimetics Are A Novel Class Of Small Molecule Inhibitors Of Malignant Pleural Mesothelioma Cells, Shazia Jamal, Vino T. Cheriyan, Magesh Muthu, Sara Munie, Edi Levi, Abdelkader E. Ashour, Harvey I. Pass, Anil Wali, Mandip Singh, Arun K. Rishi

Oncology Faculty Publications

Malignant pleural mesothelioma (MPM) is an asbestos-related thoracic malignancy that is characterized by late metastases, and resistance to therapeutic modalities. The toxic side-effects of MPM therapies often limit their clinical effectiveness, thus necessitating development of new agents to effectively treat and manage this disease in clinic. CARP-1 functional mimetics (CFMs) are a novel class of compounds that inhibit growth of diverse cancer cell types. Here we investigated MPM cell growth suppression by the CFMs and the molecular mechanisms involved. CFM-1, -4, and -5 inhibited MPM cell growth, in vitro, in part by stimulating apoptosis. Apoptosis by CFM-4 involved activation of …


Metabotropic Glutamate Receptor-1 Contributes To Progression In Triple Negative Breast Cancer, Malathi Banda, Cecilia L. Speyer, Sara N. Semma, Kingsley O. Osuala, Nicole Kounalakis, Keila E. Torres Torres, Nicola J. Barnard, Hyunjin J. Kim, Bonnie F. Sloane, Fred R. Miller, James S. Goydos, David H. Gorski Jan 2014

Metabotropic Glutamate Receptor-1 Contributes To Progression In Triple Negative Breast Cancer, Malathi Banda, Cecilia L. Speyer, Sara N. Semma, Kingsley O. Osuala, Nicole Kounalakis, Keila E. Torres Torres, Nicola J. Barnard, Hyunjin J. Kim, Bonnie F. Sloane, Fred R. Miller, James S. Goydos, David H. Gorski

Department of Surgery

TNBC is an aggressive breast cancer subtype that does not express hormone receptors (estrogen and progesterone receptors, ER and PR) or amplified human epidermal growth factor receptor type 2 (HER2), and there currently exist no targeted therapies effective against it. Consequently, finding new molecular targets in triple negative breast cancer (TNBC) is critical to improving patient outcomes. Previously, we have detected the expression of metabotropic glutamate receptor-1 (gene: GRM1; protein: mGluR1) in TNBC and observed that targeting glutamatergic signaling inhibits TNBC growth both in vitro and in vivo. In this study, we explored how mGluR1 contributes to TNBC …


Gold(Iii)-Dithiocarbamato Peptidomimetics In The Forefront Of The Targeted Anticancer Therapy: Preclinical Studies Against Human Breast Neoplasia, Chiara Nardon, Sara M. Schmitt, Huanjie Yang, Jian Zuo, Delores Fregona, Q. Ping Dou Jan 2014

Gold(Iii)-Dithiocarbamato Peptidomimetics In The Forefront Of The Targeted Anticancer Therapy: Preclinical Studies Against Human Breast Neoplasia, Chiara Nardon, Sara M. Schmitt, Huanjie Yang, Jian Zuo, Delores Fregona, Q. Ping Dou

Oncology Faculty Publications

Since the serendipitous discovery of cisplatin, platinum-based drugs have become well-established antitumor agents, despite the fact that their clinical use is limited by many severe side-effects. In order to both improve the chemotherapeutic index and broaden the therapeutic spectrum of current drugs, our most recent anti-neoplastic agents, Au(III) complexes, were designed as carrier-mediated delivery systems exploiting peptide transporters, which are up-regulated in some cancers. Among all, we focused on two compounds and tested them on human MDA-MB-231 (resistant to cisplatin) breast cancer cell cultures and xenografts, discovering the proteasome as a major target both in vitro and in vivo. …


The Role Of Pdgf C And Its Splice Variant In Breast Cancer, Alyssa Bottrell Jan 2014

The Role Of Pdgf C And Its Splice Variant In Breast Cancer, Alyssa Bottrell

Wayne State University Dissertations

The PDGF family consists of four members; while PDGF A and B are secreted as active dimers, PDGF C and D are secreted as latent dimers that undergo serine protease-mediated extracellular proteolytic activation. Gene expression analysis of breast cancer cell lines showed that PDGF C expression is associated with Basal B subtype breast cancer cells which have cancer stem cell-like characteristics. Furthermore, PDGF C expression is associated with triple-negative (estrogen receptor-, progesterone receptor- and HER2/neu-negative) breast cancer cells, a challenging type of breast cancer to treat. During the course of our study, we discovered a splice variant of PDGF C …


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 Jan 2013

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] …


Protein Tyrosine Phosphatase-1b Regulates The Tyrosine Phosphorylation Of The Adapter Grb2-Associated Binder 1 (Gab1) In The Retina, Ammaji Rajala, Ashok K. Dilly, Raju Vs Rajala Jan 2013

Protein Tyrosine Phosphatase-1b Regulates The Tyrosine Phosphorylation Of The Adapter Grb2-Associated Binder 1 (Gab1) In The Retina, Ammaji Rajala, Ashok K. Dilly, Raju Vs Rajala

Wayne State University Associated BioMed Central Scholarship

Abstract

Background

Gab1 (Grb2-associated binder 1) is a key coordinator that belongs to the insulin receptor substrate-1 like family of adaptor molecules and is tyrosine phosphorylated in response to various growth factors, cytokines, and numerous other molecules. Tyrosine phosphorylated Gab1 is able to recruit a number of signaling effectors including PI3K, SHP2 and PLC-γ. In this study, we characterized the localization and regulation of tyrosine phosphorylation of Gab1 in the retina.

Results

Our immuno localization studies suggest that Gab1 is expressed in rod photoreceptor inner segments. We found that hydrogen peroxide activates the tyrosine phosphorylation of Gab1 ex vivo and …


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 Jan 2013

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 …


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 Jan 2013

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 …


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 Jan 2013

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 …


Linking Environmental Toxicant Exposure To Diabetes Susceptibility, Jannifer Beth Tyrrell Jan 2013

Linking Environmental Toxicant Exposure To Diabetes Susceptibility, Jannifer Beth Tyrrell

Wayne State University Dissertations

An important and unresolved question in the environmental health field is whether exposure to common environmental toxicants, such as dioxin and heavy metals like Pb, increase the risk of developing diabetes, especially in combination with other common metabolic stressors such as obesity.

Previous studies suggested that dioxin exposure increased peripheral insulin resistance but did not appear to cause fasting hyperglycemia or elevated hepatic glucose output. In concordance with those findings we observed that dioxin treatment caused a strong suppression of the expression of the key hepatic gluconeogenic genes PEPCK and G6Pase. However, this suppression was not solely mediated by the …


Network Insights On Oxaliplatin Anti-Cancer Mechanisms, Osama M. Alian, Asfar S. Azmi, Ramzi M. Mohammad Jan 2012

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 …


Recent Updates On The Role Of Micrornas In Prostate Cancer, Oudai Hassan, Aamir Ahmad, Seema Sethi, Fazlul H. Sarkar Jan 2012

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 …


A Novel Interaction Between 12-Lipoxygenase And Β4 Integrin Plays A Role In Cancer Progression, Sangeeta Joshi Jan 2012

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

Wayne State University Dissertations

No abstract provided.


Substance P And The Host Immune Response, Megan Elizabeth Foldenauer Jan 2012

Substance P And The Host Immune Response, Megan Elizabeth Foldenauer

Wayne State University Dissertations

This body of work examined the mechanism by which SP regulates host immunity, specifically, its control of growth factors and TLR expression in the P. aeruginosa-infected cornea. The role of mTOR and VIP in corneal infection and inflammation also was tested.

SP has a dual role in bacterial infection, unexpectedly upregulating growth factor production. This was accompanied by macrophage-specific upregulation of pro-inflammatory cytokines, downregulation of anti-inflammatory cytokines, and upregulation of anti-apoptotic genes, as well as a decrease in arginase-producing macrophages (M2 cells), important in stromal healing in these mice. All of these lead to worsened disease, despite the stimulatory effects …


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 Jan 2012

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 …


Identifying Sm22 As A Key Player In Arterial Diseases, Jianbin Shen Jan 2012

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 …


Estrogen Sulfotransferase (Sult1e1) Expression And Function In Mcf10a-Series Breast Epithelial Cells: Role As A Modifier Of Breast Carcinogenesis And Regulation By Proliferation State, Jiaqi Fu Jan 2011

Estrogen Sulfotransferase (Sult1e1) Expression And Function In Mcf10a-Series Breast Epithelial Cells: Role As A Modifier Of Breast Carcinogenesis And Regulation By Proliferation State, Jiaqi Fu

Wayne State University Dissertations

Estrogen sulfotransferase (SULT1E1) catalyzes the sulfonation of estrogens, which limits estrogen mitogenicity. TaqMan Gene Expression assays were used to profile the mRNA expression of estrogen receptor (ERα and ERβ) and estrogen metabolism enzymes including cytosolic sulfotransferases (SULT1E1, SULT1A1, SULT2A1, and SULT2B1), steroid sulfatase (STS), aromatase (CYP19), 17β-hydroxysteroid dehydrogenases (17βHSD1 and 2), CYP1B1, and catechol-O-methyltransferase (COMT) in an MCF10A-derived lineage cell culture model for basal-like human breast cancer progression and in ERα-positive luminal MCF7 breast cancer cells. Low levels of ERα and ERβ mRNA were present in MCF10A-derived cell lines. SULT1E1 mRNA was more abundant in confluent relative to subconfluent MCF10A …


Utility Of Immunohistochemical Markers In Differentiating Benign From Malignant Follicular-Derived Thyroid Nodules, Husain A. Saleh, Bo Jin, John Barnwell, Opada Alzohaili Jan 2010

Utility Of Immunohistochemical Markers In Differentiating Benign From Malignant Follicular-Derived Thyroid Nodules, Husain A. Saleh, Bo Jin, John Barnwell, Opada Alzohaili

Wayne State University Associated BioMed Central Scholarship

Abstract

Background

Thyroid nodules are common among adults though only a small percentage is malignant, which can histologically mimic benign nodules. Accurate diagnosis of these thyroid nodules is critical for the proper clinical management.

Methods

We investigated immunoexpression in 98 surgically removed benign thyroid nodules including 52 hyperplastic nodules (HN) and 46 follicular/Hurthle cell adenomas (FA), and 54 malignant tumors including 22 follicular carcinoma (FC), 20 classic papillary carcinoma (PTC), and 12 follicular variant papillary carcinoma (FVPC).

Results

The staining results showed that malignant tumors express galectin-3, HBME-1, CK19 and Ret oncoprotein significantly more than benign nodules. The sensitivity of …


I-Kappa-Kinase-2 (Ikk-2) Inhibition Potentiates Vincristine Cytotoxicity In Non-Hodgkin's Lymphoma, Ayad Al-Katib, Alan A. Arnold, Amro Aboukameel, Angela Sosin, Peter Smith, Anwar N. Mohamed, Frances W. Beck, Ramzi M. Mohammad Jan 2010

I-Kappa-Kinase-2 (Ikk-2) Inhibition Potentiates Vincristine Cytotoxicity In Non-Hodgkin's Lymphoma, Ayad Al-Katib, Alan A. Arnold, Amro Aboukameel, Angela Sosin, Peter Smith, Anwar N. Mohamed, Frances W. Beck, Ramzi M. Mohammad

Wayne State University Associated BioMed Central Scholarship

Abstract

Background

IKK-2 is an important regulator of the nuclear factor-κB (NF-κB) which has been implicated in survival, proliferation and apoptosis resistance of lymphoma cells. In this study, we investigated whether inhibition of IKK-2 impacts cell growth or cytotoxicity of selected conventional chemotherapeutic agents in non-Hodgkin's lymphoma.

Two established model systems were used; Follicular (WSU-FSCCL) and Diffuse Large Cell (WSU-DLCL2) Lymphoma, both of which constitutively express p-IκB. A novel, selective small molecule inhibitor of IKK-2, ML120B (N-[6-chloro-7-methoxy-9H-β-carbolin-8-yl]-2-methylnicotinamide) was used to perturb NF-κB in lymphoma cells. The growth inhibitory effect of ML120B (M) alone and in combination with cyclophosphamide monohydrate (C), …


Pulmonary Carcinosarcoma Initially Presenting As Invasive Aspergillosis: A Case Report Of Previously Unreported Combination, Ariyo O. Olobatoke, Doina David, Wasif Hafeez, Thien Van, Husain A. Saleh Jan 2010

Pulmonary Carcinosarcoma Initially Presenting As Invasive Aspergillosis: A Case Report Of Previously Unreported Combination, Ariyo O. Olobatoke, Doina David, Wasif Hafeez, Thien Van, Husain A. Saleh

Wayne State University Associated BioMed Central Scholarship

Abstract

Carcinosarcoma of the lung is a malignant tumor composed of a mixture of carcinoma and sarcoma elements. The carcinomatous component is most commonly squamous followed by adenocarcinoma. The sarcomatous component commonly comprises the bulk of the tumor and shows poorly differentiated spindle cell features. Foci of differentiated sarcomatous elements such as chondrosarcoma and osteosarcoma may be seen. Aspergillus pneumonia is the most common form of invasive aspergillosis and occurs mainly in patients with malignancy, immunocompromizing or debilitating diseases. Patients with Aspergillus pneumonia present with fever, cough, chest pain and occasionally hemoptysis. Tissue examination is the most reliable method for …


Nuclear Factor-Kappa B Localization And Function Within Intrauterine Tissues From Term And Preterm Labor And Cultured Fetal Membranes, Sonali Vora, Asad Abbas, Chong J. Kim, Taryn Ls Summerfield, Juan P. Kusanovic, Jay D. Iams, Roberto Romero, Douglas A. Kniss, William E. Ackerman Iv Jan 2010

Nuclear Factor-Kappa B Localization And Function Within Intrauterine Tissues From Term And Preterm Labor And Cultured Fetal Membranes, Sonali Vora, Asad Abbas, Chong J. Kim, Taryn Ls Summerfield, Juan P. Kusanovic, Jay D. Iams, Roberto Romero, Douglas A. Kniss, William E. Ackerman Iv

Wayne State University Associated BioMed Central Scholarship

Abstract

Background

The objective of this study was to quantify the nuclear localization and DNA binding activity of p65, the major transactivating nuclear factor-kappa B (NF-kappaB) subunit, in full-thickness fetal membranes (FM) and myometrium in the absence or presence of term or preterm labor.

Methods

Paired full-thickness FM and myometrial samples were collected from women in the following cohorts: preterm no labor (PNL, N = 22), spontaneous preterm labor (PTL, N = 21), term no labor (TNL, N = 23), and spontaneous term labor (STL, N = 21). NF-kappaB p65 localization was assessed by immunohistochemistry, and DNA binding activity was …


Application Of Magnetic Resonance Imaging To Understanding The Pathogenesis Of The X-Linked Leukodystrophy Pelizaeus-Merzbacher Disease, Jeremy Jerome Laukka Jan 2010

Application Of Magnetic Resonance Imaging To Understanding The Pathogenesis Of The X-Linked Leukodystrophy Pelizaeus-Merzbacher Disease, Jeremy Jerome Laukka

Wayne State University Dissertations

Myelin is a multilamellar membrane structure surrounding axons in both the CNS and PNS that facilitates nerve conduction. In the CNS, myelin is synthesized by oligodendrocytes, while in the PNS, myelin is synthesized by Schwann cells. In the CNS, Proteolipid protein 1 (PLP1), an integral membrane protein, is the major protein component of myelin, constituting ~50% of myelin protein. Mutations of the PLP1 gene in man cause a spectrum of neurological disease, ranging from the severe Pelizaeus-Merzbacher disease (PMD), that typically begins during infancy with nystagmus, seizures and hypotonia and evolves into spastic quadriparesis, cognitive impairment and ataxia, to ¡¥pure¡¦ …


A Unique Case Of Urinary Bladder Simple Melanosis: A Case Report And Review Of The Literature, Bo Jin, Syed Y. Zaidi, Melvin Hollowell, Christopher Hollowell, Husain Saleh Jan 2009

A Unique Case Of Urinary Bladder Simple Melanosis: A Case Report And Review Of The Literature, Bo Jin, Syed Y. Zaidi, Melvin Hollowell, Christopher Hollowell, Husain Saleh

Wayne State University Associated BioMed Central Scholarship

Abstract

Melanosis refers to abnormal or excessive deposition of melanin pigment in the cells and/or tissue, which can be seen in any organ but commonly in skin and oral mucosa. Melanosis of the urinary bladder is an extremely rare benign condition and only a handful of cases been reported in the English literature before. In this article, we report a new case of urinary melanosis, describe the differential diagnostic features from pseudomelanosis and offer clues for correct diagnosis. We also provide comprehensive review of the literature on the subject.


An Mdm2 Antagonist (Mi-319) Restores P53 Functions And Increases The Life Span Of Orally Treated Follicular Lymphoma Bearing Animals, Ramzi M. Mohammad, Jack Wu, Asfar S. Azmi, Amro Aboukameel, Angela Sosin, Sherwin Wu, Dajun Yang, Shaomeng Wang, Ayad M. Al-Katib Jan 2009

An Mdm2 Antagonist (Mi-319) Restores P53 Functions And Increases The Life Span Of Orally Treated Follicular Lymphoma Bearing Animals, Ramzi M. Mohammad, Jack Wu, Asfar S. Azmi, Amro Aboukameel, Angela Sosin, Sherwin Wu, Dajun Yang, Shaomeng Wang, Ayad M. Al-Katib

Wayne State University Associated BioMed Central Scholarship

Abstract

Background

MI-319 is a synthetic small molecule designed to target the MDM2-P53 interaction. It is closely related to MDM2 antagonists MI-219 and Nutlin-3 in terms of the expected working mechanisms. The purpose of this study was to evaluate anti-lymphoma activity of MI-319 in WSU-FSCCL, a B-cell follicular lymphoma line. For comparison purpose, MI-319, MI-219 and Nutlin-3 were assessed side by side against FSCCL and three other B-cell hematological tumor cell lines in growth inhibition and gene expression profiling experiments.

Results

MI-319 was shown to bind to MDM2 protein with an affinity slightly higher than that of MI-219 and Nutlin-3. …


Emerging Role Of Garcinol, The Antioxidant Chalcone From Garcinia Indica Choisy And Its Synthetic Analogs, Subhash Padhye, Aamir Ahmad, Nikhil Oswal, Fazlul H. Sarkar Jan 2009

Emerging Role Of Garcinol, The Antioxidant Chalcone From Garcinia Indica Choisy And Its Synthetic Analogs, Subhash Padhye, Aamir Ahmad, Nikhil Oswal, Fazlul H. Sarkar

Wayne State University Associated BioMed Central Scholarship

Abstract

Garcinol, harvested from Garcinia indica, has traditionally been used in tropical regions and appreciated for centuries; however its biological properties are only beginning to be elucidated. There is ample data to suggest potent antioxidant properties of this compound which have been used to explain most of its observed biological activities. However, emerging evidence suggests that garcinol could be useful as an anti-cancer agent, and it is increasingly being realized that garcinol is a pleiotropic agent capable of modulating key regulatory cell signaling pathways. Here we have summarized the progress of our current research knowledge on garcinol and its observed …


Gene Expression Profiles In Primary Pancreatic Tumors And Metastatic Lesions Of Ela-C-Myc Transgenic Mice, Archana Thakur, Aliccia Bollig, Jiusheng Wu, Dezhong J. Liao Jan 2008

Gene Expression Profiles In Primary Pancreatic Tumors And Metastatic Lesions Of Ela-C-Myc Transgenic Mice, Archana Thakur, Aliccia Bollig, Jiusheng Wu, Dezhong J. Liao

Wayne State University Associated BioMed Central Scholarship

Abstract

Background

Pancreatic carcinoma usually is a fatal disease with no cure, mainly due to its invasion and metastasis prior to diagnosis. We analyzed the gene expression profiles of paired primary pancreatic tumors and metastatic lesions from Ela-c-myc transgenic mice in order to identify genes that may be involved in the pancreatic cancer progression. Differentially expressed selected genes were verified by semi-quantitative and quantitative RT-PCR. To further evaluate the relevance of some of the selected differentially expressed genes, we investigated their expression pattern in human pancreatic cancer cell lines with high and low metastatic potentials.

Results

Data indicate that genes …


Comparison Of Thin-Prep And Cell Block Preparation For The Evaluation Of Thyroid Epithelial Lesions On Fine Needle Aspiration Biopsy, Husain A. Saleh, Jamal Hammoud, Richard Zakaria, Aurang Khan Jan 2008

Comparison Of Thin-Prep And Cell Block Preparation For The Evaluation Of Thyroid Epithelial Lesions On Fine Needle Aspiration Biopsy, Husain A. Saleh, Jamal Hammoud, Richard Zakaria, Aurang Khan

Wayne State University Associated BioMed Central Scholarship

Abstract

Background

The objective of this study was to compare the utility of Thin-Prep (TP) cytologic preparation with that of Cell Block (CB) preparation in the diagnosis of thyroid lesions, mainly follicular epithelial lesions, by fine needle aspiration biopsy (FNAB). Feasibility of using the TP slides for immunocytochemical stains is also discussed.

Methods

A total of 126 consecutive cases of thyroid FNAB with TP slides and 128 consecutive cases of thyroid FNAB with CB slides were reviewed blindly by two cytopathologists. The presence of colloid, follicular cells, macrophages and lymphocytes/plasma cells were recorded and scored 0–4 on each case based …