Search results for "CELLULAR"

TBVAC2020: Advancing Tuberculosis Vaccines from Discovery to Clinical Development

2017

International audience; TBVAC2020 is a research project supported by the Horizon 2020 program of the European Commission (EC). It aims at the discovery and development of novel tuberculosis (TB) vaccines from preclinical research projects to early clinical assessment. The project builds on previous collaborations from 1998 onwards funded through the EC framework programs FP5, FP6, and FP7. It has succeeded in attracting new partners from outstanding laboratories from all over the world, now totaling 40 institutions. Next to the development of novel vaccines, TB biomarker development is also considered an important asset to facilitate rational vaccine selection and development. In addition, …

Mycobacterium tuberculosis secretory proteins downregulate T cell activation by interfering with proximal and downstream T cell signalling events

2015

Background Mycobacterium tuberculosis (M. tuberculosis) modulates host immune response, mainly T cell responses for its own survival leading to disease or latent infection. The molecules and mechanisms utilized to accomplish immune subversion by M. tuberculosis are not fully understood. Understanding the molecular mechanism of T cell response to M. tuberculosis is important for development of efficacious vaccine against TB. Methods Here, we investigated effect of M. tuberculosis antigens Ag85A and ESAT-6 on T cell signalling events in CD3/CD28 induced Peripheral blood mononuclear cells (PBMCs) of PPD+ve healthy individuals and pulmonary TB patients. We studied CD3 induced intracellular calc…

MMP-10/stromelysin-2 promotes invasion of head and neck cancer.

2011

BackgroundPeriostin, IFN-induced transmembrane protein 1 (IFITM1) and Wingless-type MMTV integration site family, member 5B (Wnt-5b) were previously identified as the invasion promoted genes of head and neck squamous cell carcinoma (HNSCC) by comparing the gene expression profiles between parent and a highly invasive clone. We have previously reported that Periostin and IFITM1 promoted the invasion of HNSCC cells. Here we demonstrated that Wnt-5b overexpression promoted the invasion of HNSCC cells. Moreover, stromelysin-2 (matrix metalloproteinase-10; MMP-10) was identified as a common up-regulated gene among Periostin, IFITM1 and Wnt-5b overexpressing HNSCC cells by using microarray data s…

Acidic Environment Leads to ROS-Induced MAPK Signaling in Cancer Cells

2011

Tumor micromilieu often shows pronounced acidosis forcing cells to adapt their phenotype towards enhanced tumorigenesis induced by altered cellular signalling and transcriptional regulation. In the presents study mechanisms and potential consequences of the crosstalk between extra- and intracellular pH (pH(e), pH(i)) and mitogen-activated-protein-kinases (ERK1/2, p38) was analyzed. Data were obtained mainly in AT1 R-3327 prostate carcinoma cells, but the principle importance was confirmed in 5 other cell types. Extracellular acidosis leads to a rapid and sustained decrease of pH(i) in parallel to p38 phosphorylation in all cell types and to ERK1/2 phosphorylation in 3 of 6 cell types. Furth…

Transmission of Information in Neoplasia by Extracellular Vesicles.

2015

Paracrine interactions among neoplastic and nonneoplastic cells in the immediate tumor microenvironment are important for tumor growth and metastatic spreading. Most of the studies in the past decade addressing these cellular interactions have focused on tumor cell-derived soluble molecules. Recently, these studies and interest have shifted to nanosized extracellular vesicles (EVs) and especially ectosome and exosome-associated molecules [1]. They contain not only proteins, but also lipids, mRNA, and microRNA [1], which can regulate gene expression in their target cells in a much more pleiotropic manner [1]. While exosomes originate by a sequential process of inward budding of late endosome…

Hematologic malignancies: The exosome contribution in tumor progression

2020

Abstract The bone marrow, composed of cells, extracellular matrix, and soluble factors, such as cytokines, chemokines and signaling molecules, provides a favorable microenvironment for hematologic tumor progression and for the development of drug resistance. Recently, extracellular vesicles (EVs), released by tumor and surrounding cells, have emerged as important players within the bone marrow niche. Here we will discuss the current knowledge on the EV- mediated crosstalk between tumor and normal cells, in order to better understand how vesicles can contribute to tumor progression. Advances in the knowledge of the role of cell-derived EVs in tumor microenvironment highlight the possibility …

Targeting cancer stem cells and the tumor microenvironment

2015

Compelling evidence indicates that the survival and behavior of cancer stem cells (CSCs) are positively regulated by specific stimuli received from the tumor microenvironment, which dictates the maintenance of stemness, invasiveness, and protection against drug-induced apoptotic signals. CSCs are per se endowed with multiple treatment resistance capabilities, thus the eradication of CSC pools offers a precious strategy in achieving a long-term cancer remission. Numerous therapies, aimed at eradicating CSCs, have been elaborated such as: (i) selective targeting of CSCs, (ii) modulating their stemness and (iii) influencing the microenvironment. In this context, markers commonly exploited to i…

Strikingly High Respiratory Quotients: A Further Characteristic of the Tumor Pathophysiome

2008

Conspicuously high respiratory quotients (RQs) are found in solid tumors in vivo. RQs in the range between 1.29 and 1.95 neither reflect the degree of substrate oxidation by tumor cells nor indicate the types of fuels involved in metabolic processes. Instead, such tumor RQs most probably are caused by (a) channeling of glycolytic end-products into lipogenesis, and by (b) CO2 release from the tumor following extracellular buffering of H+ -inos by bicarbonate. H+ -inos exported from the intracellular space into the interstitial compartment titrate extracellular bicarbonate to CO2 and H2O with the aid of the ectoenzyme carbonic anhydrase IX, which is activated at low pH. Strikingly high (RQs) …

Activation of tumor initiating cells during anti-angiogenic therapies promotes tumor progression and relapse formation in hepatocellular carcinoma

2016

Direct Activation of Bax by p53 Mediates Mitochondrial Membrane Permeabilization and Apoptosis

2004

The tumor suppressor p53 exerts its anti-neoplastic activity primarily through the induction of apoptosis. We found that cytosolic localization of endogenous wild-type or trans-activation–deficient p53 was necessary and sufficient for apoptosis. p53 directly activated the proapoptotic Bcl-2protein Bax in the absence of other proteins to permeabilize mitochondria and engage the apoptotic program. p53 also released both proapoptotic multidomain proteins and BH3-only proteins [Proapoptotic Bcl-2family proteins that share only the third Bcl-2homology domain (BH3)] that were sequestered by Bcl-xL. The transcription-independent activation of Bax by p53 occurred with similar kinetics and concentra…