Search results for " Cellular"

Vaccination with ENO1 DNA Prolongs Survival of Genetically Engineered Mice with Pancreatic Cancer

2013

Background & Aims Pancreatic ductal adenocarcinoma (PDA) is an aggressive tumor, and patients typically present with late-stage disease; rates of 5-year survival after pancreaticoduodenectomy are low. Antibodies against α-enolase (ENO1), a glycolytic enzyme, are detected in more than 60% of patients with PDA, and ENO1-specific T cells inhibit the growth of human pancreatic xenograft tumors in mice. We investigated whether an ENO1 DNA vaccine elicits antitumor immune responses and prolongs survival of mice that spontaneously develop autochthonous, lethal pancreatic carcinomas. Methods We injected and electroporated a plasmid encoding ENO1 (or a control plasmid) into Kras G12D /Cre (KC) mice …

Cytotoxicity of natural products and derivatives toward MCF-7 cell monolayers and cancer stem-like mammospheres

2015

Abstract Although cancer stem-like cells (CSCs) are rare, they can enter a non-proliferative or dormant state and resist therapy. Furthermore, quiescent CSCs are responsible for metastases that can appear after curative surgical treatment of a primary tumor. Because of drug resistance of CSCs, the development of novel therapies is urgently required that specifically target CSCs. Purpose The aim of the present study was to investigate the potential of a panel of natural products and derivatives to inhibit CSC-enriched mammospheres of MCF-7 breast cancer cells. Methods CD44high/CD24low cells were identified by flow cytometry and maintained as mammospheres. As a control, we used two clinically…

Cancer-Initiating Cells from Colorectal Cancer Patients Escape from T Cell-Mediated Immunosurveillance In Vitro through Membrane-Bound IL-4

2014

Abstract Cancer-initiating cells (CICs) that are responsible for tumor initiation, propagation, and resistance to standard therapies have been isolated from human solid tumors, including colorectal cancer (CRC). The aim of this study was to obtain an immunological profile of CRC-derived CICs and to identify CIC-associated target molecules for T cell immunotherapy. We have isolated cells with CIC properties along with their putative non-CIC autologous counterparts from human primary CRC tissues. These CICs have been shown to display “tumor-initiating/stemness” properties, including the expression of CIC-associated markers (e.g., CD44, CD24, ALDH-1, EpCAM, Lgr5), multipotency, and tumorigenic…

Characterization of the Adjuvant Effect of IL-12 and Efficacy of IL-12 Inhibitors in Type II Collagen-Induced Arthritis

1996

A destructive joint disease can be induced in susceptible DBA/1 mice by immunization with type II collagen emulsified with oil and either killed Mycobacterium tuberculosis or IL-12 as adjuvant. Cellular and humoral anti-collagen immune mechanisms appear to be involved in the pathogenesis of arthritis. We have characterized the adjuvant effect or IL-12 in more detail and addressed the question whether mycobacteria might act via the induction of endogenous IL-12. Injections of IL-12 into collagen-immunized DBA/1 mice promoted the development of IFN-gamma-producing CD4+ T cells and strongly upregulated the production of complement-fixing IgG2a and IgG2b antibodies resulting in severe arthritis…

Amplicon-based high-throughput pooled sequencing identifies mutations in CYP7B1 and SPG7 in sporadic spastic paraplegia patients

2011

Hereditary spastic paraplegia (HSP) is a neurodegenerative disorder defined clinically by progressive lower limb spasticity and weakness. HSP is a genetically highly heterogeneous condition with at least 46 gene loci identified so far, involving X-linked, autosomal recessive (AR) and autosomal dominant inheritance. For correct diagnosis, molecular testing is essential because clinical parameters by themselves are not reliable to differentiate HSP forms. The purpose of this study was to establish amplicon-based high-throughput genotyping for AR-HSP. A sample of 187 index cases with apparently sporadic or recessive spastic paraplegia were analyzed by applying an array-based amplification stra…

The Role of Fc Receptors on the Effectiveness of Therapeutic Monoclonal Antibodies.

2021

Since the approval of the first monoclonal antibody (mAb) in 1986, a huge effort has been made to guarantee safety and efficacy of therapeutic mAbs. As of July 2021, 118 mAbs are approved for the European market for a broad range of clinical indications. In order to ensure clinical efficacy and safety aspects, (pre-)clinical experimental approaches evaluate the respective modes of action (MoA). In addition to antigen-specificity including binding affinity and -avidity, MoA comprise Fc-mediated effector functions such as antibody dependent cellular cytotoxicity (ADCC) and the closely related antibody dependent cellular phagocytosis (ADCP). For this reason, a variety of cell-based assays have…

Light on the molecular and cellular mechanisms of bicuspid aortic valve to unveil phenotypic heterogeneity

2019

Research on bicuspid aortic valve disease (BAV) and related complications has grown in an exponential manner in the last decades. However, the current knowledge of the mechanisms underlying the development of this disease is still limited, since all clinical and surgical studies on BAV mainly focused their objects on its major vascular complications, such as ascending aortic aneurysms and dissection. It is now clear that a better understanding of the pivotal molecular and cellular pathophysiological aspects of bicuspid valve aortopathy, including natural history, phenotypic expression, histology, cellular mechanisms and pathways, is critical for improving its clinical management. This chang…

Water Dynamics in Biological Systems investigated using Neutron Scattering Techniques

Living systems can not survive in absence of the water environments which play a fundamental role in living functions. Thus in the scienti?c community many studies were and are addressed to characterize water and its dynamics properties in biological systems. However, a clear description of water in such systems has been not reached yet. In fact, the investigations performed with di?erent techniques - those based on Nuclear Magnetic Resonance or those based on Neutron Scattering - look at di?erent di?usive motions and interactions water-biomolecules, leading controversial results and hence generating many debates between scientists. In this thesis we support the idea that two water populati…

Low levels of both xanthine dehydrogenase and of cellular retinol binding protein are responsible for retinoic acid deficiency in malignant human mam…

2009

The seeming impairment of retinoid metabolism in human breast tumor cells has been attributed to the lower expression of cellular retinol binding proteins (CRBPs), of alcohol/retinol dehydrogenases, or aldehyde/retinaldehyde dehydrogenases. In a previous study we indicated that xanthine dehydrogenase (XDH) is able to oxidize actively both all-trans-retinol (t-ROL) bound to the CRBP (holo-CRBP) and all-trans-retinaldehyde (t-RAL) to all-trans-retinoic acid (t-RA) in human mammary epithelial cells (HMEC). Since both XDH and CRBP are required for the biosynthesis of t-RA, we have inspected their bioavailability in both estrogen-responsive and nonresponsive human mammary epithelial cancer cells…

Detection of natural killer T cells in mice infected with Rickettsia conorii.

2013

Little information is available regarding the role of natural killer T (NKT) cells during the early stage of Rickettsia conorii infection. Herein, C3H/HeN mice were infected with the Malish 7 strain of R. conorii. Splenocytes from these mice were analysed in the early stage of the infection by flow cytometry and compared with uninfected controls. Our results showed an increase in NKT cells in infected mice. Additionally, NKT interleukin (IL)-17(+) cells increased three days after infection, together with a concurrent decrease in the relative amount of NKT interferon (IFN)-γ(+) cells. We also confirmed a higher amount of NK IFN-γ(+) cells in infected mice. Taken together, our data showed tha…