Search results for "tolerance"

Analysis of the prognostic impact of Treg-related genes in tumor and stroma in resectable NSCLC

2013

11073 Background: Immunosuppressive regulatory T lymphocytes (Tregs) have been proved to play a critical role in immune tolerance to tumor. In this study we have analyzed the expression of 11 genes related to Tregs in both tumor and stroma samples of resectable NSCLC patients. Methods: Primary tumor tissues of FFPE samples from 125 early-stage NSCLC patients were used in this retrospective study. The most representative areas of tumor cells and tumor stroma of each sample were carefully micro-dissected. RTqPCR using hydrolysis probes (TaqMan, Applied Biosystems) was performed to assess the expression of Treg markers such as: CD127, CD25, FOXP3, CTLA-4, IL-10, TGFB-1, LAG-3, GITR and TNF-a …

Evaluation of genetic melanoma vaccines in cdk4-mutant mice provides evidence for immunological tolerance against authochthonous melanomas in the skin

2005

We evaluated the efficacy of a candidate melanoma vaccine approach in mice genetically prone to develop melanoma due to the introduction of an oncogenic mutation (R24C) in the germline sequence of the cyclin-dependent kinase 4 (cdk4), a protein critically involved in cell cycle regulation. Melanomas were induced in cdk4-mutant mice by chemical carcinogenesis and UVB irradiation. A genetic prime-boost strategy targeting the clinically relevant differentiation antigen tyrosinase-related protein 2 (TRP2) was performed which was able to stimulate a melanocyte-specific cellular immune response associated with localized autoimmune vitiligo-like depigmentation. However, significant destruction of …

Partial tyrosinase-specific self tolerance by HLA-A*0201-restricted cytotoxic T lymphocytes in mice and man

2003

The human tyrosinase (hTyr) (369-377) cytotoxic T lymphocyte (CTL) epitope is presented by malignant melanoma and various nontransformed cells in association with human leukocyte antigen (HLA)-A*0201 (A2.1) and used for vaccination-based immunotherapy of melanoma patients. Its mouse homologue, mTyr (369-377), is naturally processed and bound by A2.1 with equivalent efficacy and thus enabled us to explore the effect of self tolerance on Tyr-specific T cells in different lines of A2.1 transgenic (Tg) mice and man. We found that self Tyr-reactive CTL in Tg mice and, importantly, in man were affected by partial tolerance resulting in only residual T lymphocytes of higher avidity for self Tyr al…

Dendritic cells as mediators of tumor-induced tolerance in metastatic melanoma.

1997

Escape from immune surveillance is critical for tumor progression in metastatic melanoma. We assessed the function of melanoma-derived dendritic cells (DCs) in patients presenting simultaneously with responding (rM) or progressing (pM) melanoma metastases. These rare coincidences allowed us to compare syngeneically the function of tumor DCs. CD83+ DCs were purified freshly from large responding (rDCs) or progressing (pDCs) metastases following chemo-immunotherapy. rDCs were 5 times more potent inducers of allogeneic T-cell proliferation than the pDCs that were used as control. Phenotypic analysis showed a marked depression of CD86 expression on pDCs. Culture supernatants from pM showed prod…

Lactate: A Metabolic Key Player in Cancer

2011

Abstract Increased glucose uptake and accumulation of lactate, even under normoxic conditions (i.e., aerobic glycolysis or the Warburg Effect), is a common feature of cancer cells. This phenomenon clearly indicates that lactate is not a surrogate of tumor hypoxia. Tumor lactate can predict for metastases and overall survival of patients, as shown by several studies of different entities. Metastasis of tumors is promoted by lactate-induced secretion of hyaluronan by tumor-associated fibroblasts that create a milieu favorable for migration. Lactate itself has been found to induce the migration of cells and cell clusters. Furthermore, radioresistance has been positively correlated with lactate…

Growth rates or radiobiological hypoxia are not correlated with local metabolite content in human melanoma xenografts with similar vascular network.

1995

Investigations were carried out on two lines of human melanomas (MF; n = 12 and EE; n = 13) xenografted in nude mice. The tumours were characterised by a similar vascular supply but showed a pronounced difference in the rate of volume growth and in the radiobiologically hypoxic fraction. The distribution of ATP, glucose and lactate in the tumours was investigated using quantitative bioluminescence and single photon imaging. Concentrations of the metabolites were obtained as global values for the entire tumour mass, in regions with densely packed, structurally intact tumour cells ('viable zones'), in areas with necrosis, stromal cells and fibrous material ('necrotic zones') and in adjacent n…

FAS(CD95) ligand expression by tumor cell variants can be unrelated to their capacity to induce tolerance or immune rejection.

1999

According to the results of in vitro experiments, Fas(CD95) ligand expression by cancer cells might induce apoptosis of activated T cells and contribute to immune tolerance. However, Fas ligand expression had never been explored in vivo in tumor cell models yielding either immune response or tolerance. In the present study, we analyzed the expression and function of Fas ligand in 2 clones of tumor cells originating from the same rat colon carcinoma. REGb cells were immunogenic and yielded tumors that regressed in immune-competent syngeneic hosts, whereas PROb cells induced active tolerance and yielded progressive tumors. Fas ligand was expressed on the plasma membrane of both REGb and PROb …

Latent heat flux variability and response to drought stress of black poplar: A multi-platform multi-sensor remote and proximal sensing approach to re…

2022

Abstract High-throughput mapping of latent heat flux (λET) is critical to efforts to optimize water resources management and to accelerate forest tree breeding for improved drought tolerance. Ideally, investigation of the energy response at the tree level may promote tailored irrigation strategies and, thus, maximize crop biomass productivity. However, data availability is limited and planning experimental campaigns in the field can be highly operationally complex. To this end, a multi-platform multi-sensor observational approach is herein developed to dissect the λET signature of a black poplar (Populus nigra) breeding population (“POP6”) at the canopy level. POP6 comprised more than 4600 …

ANALISI E SVILUPPO DI UN SETUP SPERIMENTALE PER LA DETERMINAZIONE DELLA TENACITÀ A FRATTURA A MODO II NEI MATERIALI COMPOSITI E IBRIDI

Il presente lavoro di Tesi si propone a compimento del percorso previsto dal Ciclo XXVI del corso di Dottorato di Ricerca in Ingegneria Civile e Ambientale – Indirizzo Materiali – seguito durante il triennio Gennaio 2013- Dicembre 2015 presso l’Università degli Studi di Palermo. L’elaborato si sviluppa in due principali sezioni. Dopo un’introduzione all’argomento affrontato, nella prima parte del lavoro, viene analizzato, sia sperimentalmente che numericamente, un setup tipicamente utilizzato nell’industria aeronautica per la caratterizzazione delle delaminazione a MODO II nei materiali compositi (Transverse Crack Tensile test – TCT-test). A partire dai risultati ottenuti dalle analisi prel…

Recombinant growth hormone therapy in patients with ischemic cardiomyopathy : effects on hemodynamics, left ventricular function, and cardiopulmonary…

1999

Background —We studied the effects of recombinant growth hormone (rhGH) on exercise capacity and cardiac function in patients with ischemic cardiomyopathy. Methods and Results —Seven patients (aged 55±9 years) with mild to moderate congestive heart failure (ejection fraction 31±4%) who were on standard therapy were included. The patients were studied at baseline, after 3 months of rhGH treatment, and 3 months after rhGH discontinuation. Cardiac function was assessed by exercise capacity, right heart catheterization at rest and after submaximal exercise, MRI, echocardiography, and Holter monitoring. When administered at a dose of 2 IU/d, rhGH doubled the serum concentration of insulin-like …