Medical Molecular Biology Commons^™

Mbp-1 Upregulates Mir-29b That Represses Mcl-1, Collagens, And Matrix-Metalloproteinase-2 In Prostate Cancer Cells., Robert Steele, Justin L. Mott, Ratna B. Ray

Journal Articles: Biochemistry & Molecular Biology

c-myc promoter binding protein (MBP-1) is a multi-functional protein known to regulate expression of targets involved in the malignant phenotype. We have previously demonstrated that exogenous expression of MBP-1 inhibits prostate tumor growth, although the mechanism of growth inhibition is not well understood. We hypothesized that MBP-1 may modulate microRNA (miRNA) expression for regulation of prostate cancer cell growth. In this study, we demonstrated that exogenous MBP-1 upregulates miR-29b by 5-9 fold in prostate cancer cells as measured by real-time quantitative reverse transcription-PCR. Subsequent studies indicated that exogenous expression of miR-29b inhibited Mcl-1, COL1A1, and COL4A1. Further, a novel target …

Palmitoleate Attenuates Palmitate-Induced Bim And Puma Up-Regulation And Hepatocyte Lipoapoptosis., Yuko Akazawa, Sophie Cazanave, Justin L. Mott, Nafisa Elmi, Steven F. Bronk, Shigeru Kohno, Michael R. Charlton, Gregory J. Gores

Journal Articles: Biochemistry & Molecular Biology

BACKGROUND & AIMS: Saturated free fatty acids induce hepatocyte lipoapoptosis. This lipotoxicity involves an endoplasmic reticulum stress response, activation of JNK, and altered expression and function of Bcl-2 proteins. The mono-unsaturated free fatty acid palmitoleate is an adipose-derived lipokine which suppresses free fatty acid-mediated lipotoxicity by unclear mechanisms. Herein we examined the mechanisms responsible for cytoprotection.

METHODS: We employed isolated human and mouse primary hepatocytes, and the Huh-7 and Hep 3B cell lines for these studies. Cells were incubated in presence and absence of palmitate (16:0), stearate (18:0), and or palmitoleate (16:1, n-7).

RESULTS: Palmitoleate significantly reduced lipoapoptosis by palmitate …

Antimicrobial And Antioxidant Activities Of Essential Oil And Methanol Extract Of Jasminum Sambac From Djibouti, Fatou Abdoul-Latif, Prosper Edou, François Eba, Nabil Mohamed, Adwa Ali, Samatar Djama, Louis-Clément Obame, Mamoudou Hama Dicko

Pr. Mamoudou H. DICKO, PhD

The essential oil of jasminum sambac from Djibouti was subjected to screening for their possible antioxidant activity by two complementary test systems, namely DPPH free radical scavenging and beta-carotene-linoleic acid assays. Butylated hydroxytoluene (BHT) was used as positive control in both test systems. In the DPPH test system, the IC50 value of essential oil and methanol extract were respectively 7.43 and 2.30 μg/ml. In the beta-carotene-linoleic acid system, oxidation was effectively inhibited by Jasminum sambac, the RAA value of essential oil and methanol extract were respectively 96.6 and 93.9%. When compared to BHT, the essential oil and methanol extract had …

P66shc--A Longevity Redox Protein In Human Prostate Cancer Progression And Metastasis : P66shc In Cancer Progression And Metastasis., Mythilypriya Rajendran, Paul Thomes, Li Zhang, Suresh Veeramani, Ming-Fong Lin

Journal Articles: Biochemistry & Molecular Biology

p66Shc, a 66 kDa proto-oncogene Src homologous-collagen homologue (Shc) adaptor protein, is classically known in mediating receptor tyrosine kinase signaling and recently identified as a sensor to oxidative stress-induced apoptosis and as a longevity protein in mammals. The expression of p66Shc is decreased in mice and increased in human fibroblasts upon aging and in aging-related diseases, including prostate cancer. p66Shc protein level correlates with the proliferation of several carcinoma cells and can be regulated by steroid hormones. Recent advances point that p66Shc protein plays a role in mediating cross-talk between steroid hormones and redox signals by serving as a common …

Electrospun Nanofibers For Neural Tissue Engineering, Jingwei Xie, Matthew R. Macewan, Andrea G. Schwartz, Younan Xia

MIIR Faculty Research

Biodegradable nanofibers produced by electrospinning represent a new class of promising scaffolds to support nerve regeneration. We begin with a brief discussion on electrospinning of nanofibers and methods for controlling the structure, porosity, and alignment of the electrospun nanofibers. The methods include control of the nanoscale morphology and microscale alignment for the nanofibers, as well as the fabrication of macroscale, three-dimensional tubular structures. We then highlight recent studies that utilize electrospun nanofibers to manipulate biological processes relevant to nervous tissue regeneration, including stem cell differentiation, guidance of neurite extension, and peripheral nerve injury treatments. The main objective of this feature …

An Epitope From Acanthamoeba Castellanii That Cross-React With Proteolipid Protein 139-151-Reactive T Cells Induces Autoimmune Encephalomyelitis In Sjl Mice, Chandirasegaran Massilamany, David Steffan, Jay Reddy

Jay Reddy Publications

We report here that an epitope (aa, 83-95) derived from Acanthamoeba castellanii (ACA) induces clinical signs of experimental autoimmune encephalomyelitis (EAE) in SJL/J mice reminiscent of the disease induced with myelin proteolipid protein (PLP) 139-151. By using IA^s/tetramers, we demonstrate that both ACA 83-95 and PLP 139-151 generate antigen-specific cross-reactive CD4 T cells and the T cells secrete identical patterns of cytokines and induce EAE with a similar severity. These results may provide insights into the pathogenesis of multiple sclerosis and ACA-induced granulomatous encephalitis.

Effect Of Dietary Folate Restriction On Colon Carcinogenesis In Dna Polymerase Β Haploinsufficient Mice, Lisa F. Ventrella Lucente

Wayne State University Dissertations

The data presented in this research is central to establishing the role that the base excision repair pathway (BER) plays in the development and progression of colon cancer when dietary folate is deficient. Both cellular folate restriction and BER deficiencies have been shown to result in the accumulation of endogenous damage and lesions that could eventually develop into carcinogenesis. In this study, a dietary folate deficiency (FD) resulted in a significant increase in aberrant crypt foci (ACF) formation and triggered liver tumorogenesis in wildtype (WT) animals, as did a BER deficiency in DNA polymerase Β haploinsufficient (Β-pol+/-) mice exposed to …

Imaging Spontaneous Mmtvneu Transgenic Murine Mammary Tumors: Targeting Metabolic Activity Versus Genetic Products., Mathew L Thakur, Devakumar Devadhas, Kaijun Zhang, Richard G Pestell, Chenguang Wang, Peter Mccue, Eric Wickstrom

Department of Radiology Faculty Papers

INTRODUCTION: Despite the great strides made in imaging breast cancer (BC) in humans, the current imaging modalities miss up to 30% of BC, do not distinguish malignant lesions from benign ones, and require histologic examinations for which invasive biopsy must be performed. Annually in the United States, approximately 5.6 million biopsies find benign lesions. More than 50% of human BCs overexpress cyclin D1, and all BCs exhibit VPAC1 oncogene products. Together, these gene products may provide an excellent biomarker for the early and accurate detection of BC. We have evaluated 4 biologically active peptide analogs that have high affinity for …

Immunomodulatory Effect Of Host And Fungal Eicosanoids During Host-Pathogen Interactions With Candida Albicans, Gitanjali Kundu

Wayne State University Dissertations

Candida albicans, an opportunistic fungal pathogen, poses a significant clinical threat to immunocompromised patients. Diseases associated with this fungus ranges from superficial mucosal infection to life-threatening systemic candidiasis. The mechanisms by which Candida persists at mucosal surfaces in the face of an adaptive response are unclear. Candida produces immunomodulatory oxylipins that cross-react functionally with host eicosanoids, which are considered to play important role in regulating innate and adaptive immune responses. Our objective was to characterize the role of prostaglandins produced by the host and this fungus during host pathogen interactions, both in vitro with dendritic cells (DCs) and macrophages, and …

High-Density Screening Reveals A Different Spectrum Of Genomic Aberrations In Chronic Lymphocytic Leukemia Patients With ‘Stereotyped’ Ighv3-21 And Ighv4-34 B-Cell Receptors, Millaray Marincevic, Nicola Cahill, Rebeqa Gunnarsson, Anders Isaksson, Mahmoud Mansouri, Hanna Göransson, Markus Rasmussen, Mattias Jansson, Fergus Ryan, Karin Karlsson, Hans-Olov Adami, Fred Davi, Jesper Jurlander, Gunnar Juliusson, Kostas Stamatopoulos, Richard Rosenquist

Articles

Background The existence of multiple subsets of chronic lymphocytic leukemia expressing ‘stereotyped’ Bcell receptors implies the involvement of antigen(s) in leukemogenesis. Studies also indicate that ‘stereotypy’ may influence the clinical course of patients with chronic lymphocytic leukemia, for example, in subsets with stereotyped IGHV3-21 and IGHV4-34 B-cell receptors; however, little is known regarding the genomic profile of patients in these subsets. Design and Methods We applied 250K single nucleotide polymorphism-arrays to study copy-number aberrations and copy-number neutral loss-of-heterozygosity in patients with stereotyped IGHV3-21 (subset #2, n=29), stereotyped IGHV4-34 (subset #4, n=17; subset #16, n=8) and non-subset #2 IGHV3-21 (n=13) and …

Activation Of Tumor Cell Death Program By Targeting The Ubiquitin-Proteasome Pathway: Significance In Cancer Treatment And Prevention, Michael Joseph Frezza

Wayne State University Dissertations

ACTIVATION OF TUMOR CELL DEATH PROGRAM BY TARGETING THE UBIQUITIN-PROTEASOME PATHWAY: SIGNIFICANCE IN CANCER TREATMENT AND PREVENTION

by

MICHAEL FREZZA

August 2010

Advisor: Dr. Q. Ping Dou

Major: Cancer Biology

Degree: Doctor of Philosophy

The ubiquitin-proteasome pathway serves as a quality control mechanism to regulate the degradation of intracellular proteins involved in a wide array of cellular processes including tumorigeneis. Thus targeting key features of protein turnover responsible for the growth and proliferation of cancer have emerged as a favorable approach in cancer therapy. Both in vitro and in vivo experimental and clinical results have demonstrated the potential use of …

Molecular And Therapeutic Implications Of Notch1 Signaling In Pediatric T-Cell Acute Lymphoblastic Leukemia, Amanda Larson Gedman

Wayne State University Dissertations

T-cell acute lymphoblastic leukemia (T-ALL) accounts for 15% of pediatric ALL cases and is associated with early relapse and inferior outcome. The poorer prognosis of T-ALL compared to B-precursor ALL may in part reflect the lack of unique features on which to base therapy. NOTCH1 mutations are of particular interest since these were reported in 37-71% of T-ALLs. The prognostic value of NOTCH1 mutations remains controversial as both favorable and unfavorable associations were reported, whereas in other studies, there were no associations between NOTCH1 mutations and treatment outcome. We explored the impact of mutations in NOTCH1, FBW7 and PTEN on …

Recent Advances On Skin-Resident Stem/Progenitor Cell Functions In Skin Regeneration, Aging And Cancers And Novel Anti-Aging And Cancer Therapies., Murielle Mimeault, Surinder K. Batra

Journal Articles: Biochemistry & Molecular Biology

Recent advances in skin-resident adult stem/progenitor cell research have revealed that these immature and regenerative cells with a high longevity provide critical functions in maintaining skin homeostasis and repair after severe injuries along the lifespan of individuals. The establishment of the functional properties of distinct adult stem/progenitor cells found in skin epidermis and hair follicles and extrinsic signals from their niches, which are deregulated during their aging and malignant transformation, has significantly improved our understanding on the etiopathogenesis of diverse human skin disorders and cancers. Particularly, enhanced ultraviolet radiation exposure, inflammation and oxidative stress and telomere attrition during chronological aging …