Medicine and Health Sciences Commons^™

Distinct Signatures Of The Immune Responses In Low Risk Versus High Risk Neuroblastoma, Madhu Gowda, Kamar Godder, Maciej Kmieciak, Andrea Worschech, Maria-Libera Ascierto, Ena Wang, Francesco M. Marincola, Masoud H. Manjili

Microbiology and Immunology Publications

Background

Over 90% of low risk (LR) neuroblastoma patients survive whereas less than 30% of high risk (HR) patients are long term survivors. Age (children younger than 18 months old) is associated with LR disease. Considering that adaptive immune system is well developed in older children, and that T cells were shown to be involved in tumor escape and progression of cancers, we sought to determine whether HR patients may tend to show a signature of adaptive immune responses compared to LR patients who tend to have diminished T-cell responses but an intact innate immune response.

Methods

We performed microarray …

Tumor Escape And Progression Of Her-2/Neu Negative Breast Cancer Under Immune Pressure, Maciej Kmieciak, Kyle K. Payne, Michael O. Idowu, Margaret M. Grimes, Laura Graham, Maria-Libera Ascierto, Ena Wang, Xiang-Yang Wang, Harry D. Bear, Masoud H. Manjili

Microbiology and Immunology Publications

Background Emerging data from pre-clinical and clinical studies suggest that HER-2/neu-specific T cell responses could induce HER-2/neu antigen loss in the tumor cells. These data suggest that patients with HER-2/neu negative breast cancer might have had HER-2/neu positive premalignant lesions in the past that progressed to HER-2/neu negative breast cancer under HER-2/neu-specific immune pressure.

Methods We conducted a pilot study in patients with HER-2/neu positive and HER-2/neu negative breast cancers as well as a patient with ductal carcinoma in situ (DCIS). HER-2/neu expression was determined by FISH. HER-2/neu-specific T cell responses were determined by using IFN-γ ELISA. Expression of IFN-γ …

Er Stress And Lipid Metabolism In Adipocytes, Beth S. Zha, Huiping Zhou

Microbiology and Immunology Publications

The role of endoplasmic reticulum (ER) stress is a rapidly emerging field of interest in the pathogenesis of metabolic diseases. Recent studies have shown that chronic activation of ER stress is closely linked to dysregulation of lipid metabolism in several metabolically important cells including hepatocytes, macrophages, β-cells, and adipocytes. Adipocytes are one of the major cell types involved in the pathogenesis of the metabolic syndrome. Recent advances in dissecting the cellular and molecular mechanisms involved in the regulation of adipogenesis and lipid metabolism indicate that activation of ER stress plays a central role in regulating adipocyte function. In this paper, …

An Immunologic Portrait Of Cancer, Maria-Libera Ascierto, Valeria De Giorgi, Qiuzhen Liu, Davide Bedognetti, Tara L. Spivey, Daniela Murtas, Lorenzo Uccellini, Ben D. Ayotte, David F. Stroncek, Lofti Chouchane, Masoud H. Manjili, Ena Wang, Francesco M. Marincola

Microbiology and Immunology Publications

The advent of high-throughput technology challenges the traditional histopathological classification of cancer, and proposes new taxonomies derived from global transcriptional patterns. Although most of these molecular re-classifications did not endure the test of time, they provided bulk of new information that can reframe our understanding of human cancer biology. Here, we focus on an immunologic interpretation of cancer that segregates oncogenic processes independent from their tissue derivation into at least two categories of which one bears the footprints of immune activation. Several observations describe a cancer phenotype where the expression of interferon stimulated genes and immune effector mechanisms reflect patterns …

Pseudomonas Aeruginosa Elastase Provides An Escape From Phagocytosis By Degrading The Pulmonary Surfactant Protein-A, Zhizhou Kuang, Yonghua Hao, Brent E. Walling, Jayme L. Jeffries, Dennis E. Ohman, Gee W. Lau

Microbiology and Immunology Publications

Pseudomonas aeruginosa is an opportunistic pathogen that causes both acute pneumonitis in immunocompromised patients and chronic lung infections in individuals with cystic fibrosis and other bronchiectasis. Over 75% of clinical isolates of P. aeruginosa secrete elastase B (LasB), an elastolytic metalloproteinase that is encoded by the lasB gene. Previously, in vitro studies have demonstrated that LasB degrades a number of components in both the innate and adaptive immune systems. These include surfactant proteins, antibacterial peptides, cytokines, chemokines and immunoglobulins. However, the contribution of LasB to lung infection by P. aeruginosa and to inactivation of pulmonary innate immunity in vivo needs …

Identification And Phylogenetic Analysis Of Heme Synthesis Genes In Trypanosomatids And Their Bacterial Endosymbionts, João M. P. Alves, Logan Voegtly, Andrey V. Matveyev, Ana M. Lara, Flávia Maia Da Silva, Myrna G. Serrano, Gregory A. Buck, Marta M. G. Teixeira, Erney P. Camargo

Microbiology and Immunology Publications

It has been known for decades that some insect-infecting trypanosomatids can survive in culture without heme supplementation while others cannot, and that this capability is associated with the presence of a betaproteobacterial endosymbiont in the flagellate's cytoplasm. However, the specific mechanisms involved in this process remained obscure. In this work, we sequence and phylogenetically analyze the heme pathway genes from the symbionts and from their hosts, as well as from a number of heme synthesis-deficient Kinetoplastida. Our results show that the enzymes responsible for synthesis of heme are encoded on the symbiont genomes and produced in close cooperation with the …