Search results for "chaperon"
showing 10 items of 358 documents
Functional characterisation of alpha-galactosidase a mutations as a basis for a new classification system in fabry disease.
2013
Fabry disease (FD) is an X-linked hereditary defect of glycosphingolipid storage caused by mutations in the gene encoding the lysosomal hydrolase α-galactosidase A (GLA, α-gal A). To date, over 400 mutations causing amino acid substitutions have been described. Most of these mutations are related to the classical Fabry phenotype. Generally in lysosomal storage disorders a reliable genotype/phenotype correlation is difficult to achieve, especially in FD with its X-linked mode of inheritance. In order to predict the metabolic consequence of a given mutation, we combined in vitro enzyme activity with in vivo biomarker data. Furthermore, we used the pharmacological chaperone (PC) 1-deoxygalacto…
Inhibition of HSP70: a challenging anti-cancer strategy.
2012
HSP70 is a chaperone that accumulates in the cells after many different stresses promoting cell survival in response to the adverse conditions. In contrast to normal cells, most cancer cells abundantly express HSP70 at the basal level to resist to various insults at different stages of tumorigenesis and during anti-cancer treatment. This cancer cells addiction for HSP70 is the rational for its targeting in cancer therapy. Much effort has been dedicated in the last years for the active search of HSP70 inhibitors. Additionally, the recent clinical trials on highly promising inhibitors of another stress protein, HSP90, showed compensatory increase in HSP70 levels and raised the question of nec…
Mitochondrial chaperones in cancer: From molecular biology to clinical diagnostics
2006
Mitochondria are cell organelles involved in processes of cell life and death, and therefore also in tumoral transformation. Indeed, mitochondria dysfunction is a prominent feature of cancer cells. Mitochondrial proteins and DNA have also been previously studied as markers of tumorigenesis. Heat shock proteins (HSPs) are ubiquitous evolutionary conserved proteins. HSPs enhance their expression in stressed cells and they are involved in gene expression regulation, DNA replication, signal transduction, differentiation, apoptosis, cellular senescence or immortalization. This review reflects recent views on the role of some mitochondrial molecular chaperones as prohibitin, mortalin and HSP60/HS…
Hsp60 and Hsp10 down-regulation predicts bronchial epithelial carcinogenesis in smokers with chronic obstructive pulmonary disease.
2006
BACKGROUND. The relation between smoking, chronic obstructive pulmonary disease (COPD), and lung cancer (LC) is an open field of investigation. A higher frequency of adenocarcinoma has been reported in patients with COPD. Heat shock proteins (Hsps) are implicated in tumoral cell growth and differentiation. The aim of the present study was to investigate the expression of Hsp60 and Hsp10 in bronchial biopsies from smokers with COPD and in 10 lung cancer patients and to evaluate the association between Hsps expression and carcinogenetic steps of LC. METHODS. An immunohistochemical study was performed for Hsp60 and Hsp10 in bronchial biopsies from 35 COPD (postbronchodilator forced expiratory …
The expression of HSP60 and HSP10 in large bowel carcinomas with lymph node metastase
2005
Abstract Background The involvement of Heat Shock Proteins (HSP) in cancer development and progression is a widely debated topic. The objective of the present study was to evaluate the presence and expression of HSP60 and HSP10 in a series of large bowel carcinomas and locoregional lymph nodes with and without metastases. Methods 82 Astler and Coller's stage C2 colorectal cancers, of which 48 well-differentiated and 34 poorly-differentiated, were selected along with 661 lymph nodes, including 372 with metastases and 289 with reactive hyperplasia only, from the same tumours. Primitive tumours and both metastatic and reactive lymph nodes were studied; specifically, three different compartment…
Oligodendroglioma cells shed microvesicles which contain TRAIL as well as molecular chaperones and induce cell death in astrocytes.
2011
Microvesicles (MVs) shed from G26/24 oligodendroglioma cells were previously reported to cause a reproducible, dose-dependent, inhibitory effect on neurite outgrowth, and eventually neuronal apoptosis, when added to primary cultures of rat cortical neurons. These effects were reduced but not abolished by functional monoclonal antibodies against Fas-L. In order to investigate whether MVs contain other factors able to induce cell death, we tested them for TRAIL and found clear evidence of its presence in the vesicles. This finding suggests the possibility that Fas-L and TRAIL cooperate in inducing brain cell death. Aimed at understanding the route through which the vesicles deliver their mess…
Generation of CD8+T cells expressing two additional T-cell receptors (TETARs) for personalised melanoma therapy
2015
Adoptive T-cell therapy of cancer often fails due to the tumor cells' immune escape mechanisms, like antigen loss or down-regulation. To anticipate immune escape by loss of a single antigen, it would be advantageous to equip T cells with multiple specificities. To study the possible interference of 2 T-cell receptors (TCRs) in one cell, and to examine how to counteract competing effects, we generated TETARs, CD8(+) T cells expressing two additional T-cell receptors by simultaneous transient transfection with 2 TCRs using RNA electroporation. The TETARs were equipped with one TCR specific for the common melanoma antigen gp100 and one TCR recognizing a patient-specific, individual mutation of…
Gp80 (clusterin; TRPM-2) mRNA level is enhanced in human renal clear cell carcinomas
1994
The gp80 glycoprotein complex (clusterin, apolipoprotein J, TRPM-2) is a widely expressed protein that has been attributed functions in tissue remodelling, immune defense and transport of lipids and biologically active peptides. The expression of the protein appears to be elevated in several neurodegenerative, apoptotic and malignant processes. We show here that in patients with renal clear cell carcinoma gp80 mRNA is 3-fold overexpressed in tissue of the tumors compared with adjacent non-tumor tissue.
Allogeneic effector/memory Th-1 cells impair FoxP3+ regulatory T lymphocytes and synergize with chaperone-rich cell lysate vaccine to treat leukemia
2011
AbstractTherapeutic strategies combining the induction of effective antitumor immunity with the inhibition of the mechanisms of tumor-induced immunosuppression represent a key objective in cancer immunotherapy. Herein we demonstrate that effector/memory CD4+ T helper-1 (Th-1) lymphocytes, in addition to polarizing type-1 antitumor immune responses, impair tumor-induced CD4+CD25+FoxP3+ regulatory T lymphocyte (Treg) immunosuppressive function in vitro and in vivo. Th-1 cells also inhibit the generation of FoxP3+ Tregs from naive CD4+CD25−FoxP3− T cells by an interferon-γ–dependent mechanism. In addition, in an aggressive mouse leukemia model (12B1), Th-1 lymphocytes act synergistically with …
The Odyssey of Hsp60 from Tumor Cells to Other Destinations Includes Plasma Membrane-Associated Stages and Golgi and Exosomal Protein-Trafficking Mod…
2012
BACKGROUND: In a previous work we showed for the first time that human tumor cells secrete Hsp60 via exosomes, which are considered immunologically active microvesicles involved in tumor progression. This finding raised questions concerning the route followed by Hsp60 to reach the exosomes, its location in them, and whether Hsp60 can be secreted also via other mechanisms, e.g., by the Golgi. We addressed these issues in the work presented here. PRINCIPAL FINDINGS: We found that Hsp60 localizes in the tumor cell plasma membrane, is associated with lipid rafts, and ends up in the exosomal membrane. We also found evidence that Hsp60 localizes in the Golgi apparatus and its secretion is prevent…