Search results for "Positive"
showing 10 items of 1875 documents
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…
Carboxyamidotriazole inhibits cell growth of imatinib-resistant chronic myeloid leukaemia cells including T315I Bcr-Abl mutant by a redox-mediated me…
2010
Mutation of the Bcr–Abl oncoprotein is one of most frequent mechanisms by which chronic myelogenous leukemia (CML) cells become resistant to imatinib. Here, we show that treat- ment of cell lines harbouring wild type or mutant BCR–ABL with carboxyamidotriazole (CAI), a calcium influx and signal transduction inhibitor, inhibits cell growth, the expres- sion of Bcr–Abl and its downstream signalling, and induces apoptosis. Moreover, we show that CAI acts by increasing intracellular ROS. Clinically significant, CAI has also inhibitory effects on T315I Bcr–Abl mutant, a mutation that causes CML cells to become insensitive to imatinib and second generation abl kinase inhibitors.
Exome Sequencing to Predict Neoantigens in Melanoma
2015
Abstract The ability to use circulating peripheral blood cells and matched tumor sequencing data as a basis for neoantigen prediction has exciting possibilities for application in the personalized treatment of cancer patients. We have used a high-throughput screening approach, combining whole-exome sequence data, mRNA microarrays, and publicly available epitope prediction algorithm output to identify mutated proteins processed and displayed by patient tumors and recognized by circulating immune cells. Matched autologous melanoma cell lines and peripheral blood mononuclear cells were used to create mixed lymphocyte tumor cell cultures, resulting in an expansion of tumor-reactive T cells to u…
Prognostic significance of spatial and density analysis of T lymphocytes in colorectal cancer.
2022
Abstract Background Although high T cell density is a strong favourable prognostic factor in colorectal cancer, the significance of the spatial distribution of T cells is incompletely understood. We aimed to evaluate the prognostic significance of tumour cell-T cell co-localisation and T cell densities. Methods We analysed CD3 and CD8 immunohistochemistry in a study cohort of 983 colorectal cancer patients and a validation cohort (N = 246). Individual immune and tumour cells were identified to calculate T cell densities (to derive T cell density score) and G-cross function values, estimating the likelihood of tumour cells being co-located with T cells within 20 µm radius (to derive T cell p…
Efficacy and safety of bosutinib (BOS) for Philadelphia chromosome–positive (Ph+) leukemia in older versus younger patients (pts).
2012
6511 Background: BOS is an oral dual Src/Abl kinase inhibitor with potent activity in Ph+ leukemia. Methods: Efficacy and safety of BOS 500 mg/d was evaluated in older (≥65 y; n = 119) and younger (<65 y; n = 451) pts in 3 cohorts: chronic phase chronic myeloid leukemia (CP CML) after imatinib (IM; CP2L cohort; n = 287); CP CML after IM + dasatinib (DAS) and/or nilotinib (NIL; CP3L cohort; n = 119); and accelerated/blast phase (AP/BP) CML or acute lymphoblastic leukemia after IM ± DAS and/or NIL (ADV cohort; n = 164). Results: Baseline events (≥65 y vs <65 y) included respiratory disorders (35% vs 13%), cardiac disorders (29% vs 9%), and diabetes (4% vs 4%). Median baseline medicatio…
mTOR Inhibition Improves Antitumor Effects of Vaccination with Antigen-Encoding RNA
2013
Abstract Vaccination with in vitro transcribed RNA encoding tumor antigens is an emerging approach in cancer immunotherapy. Attempting to further improve RNA vaccine efficacy, we have explored combining RNA with immunomodulators such as rapamycin. Rapamycin, the inhibitor of mTOR, was used originally for immunosuppression. Recent reports in mouse systems, however, suggest that mTOR inhibition may enhance the formation and differentiation of the memory CD8+ T-cell pool. Because memory T-cell formation is critical to the outcome of vaccination aproaches, we studied the impact of rapamycin on the in vivo primed RNA vaccine-induced immune response using the chicken ovalbumin-expressing B16 mela…
Assessment for the mean value total dressing method: Comparison with coupled cluster including triples methods for BF, NO+, CN+, C2, BeO, NH3, CH2, H…
1997
Limited previous experience with the mean value total dressing (MVTD) method had shown that MVTD energies for closed shell systems are generally better than CCSD(T) ones compared to FCI. The method, previously published as total dressing 2′(td-2′), is based on the single reference intermediate Hamiltonian theory. It is not a CC method but deals in a great part with the same physical effects that CC methods that incorporate amplitudes of triples such as CCSDT or its CCSDT-1n approaches. A number of test calculations comparing to diverse CC methods, as well as FCI and experiment when available, have been performed. The tests concern equilibrium energies in NH3 and CH2, equilibrium energies an…
State of the Art on Sustainability Assessment of Positive Energy Districts: Methodologies, Indicators and Future Perspectives
2021
The concept of Positive Energy District is one of the main areas of research and extensive applications of the principles of the clean energy transition within the building sector. In the past years, the most widely accepted definitions have focused specifically on carbon neutrality, while several other aspects regarding all sustainability approaches (including environmental, social and economic perspective) were included qualitatively or to a lesser degree. This paper proposes a discussion on the state of the art of the sustainability assessment of Positive Energy Districts, by investigating environmental, social and economic sustainability applications. The three sustainability dimensions…
Bispectral index changes in carotid surgery.
2010
Intraoperative monitoring of cerebral ischemia with shunting during carotid endarterectomy (CEA) remains controversial. Our objective was to evaluate the sensitivity and specificity of BIS changes during carotid clamping in relation to shunted patients in awake CEA.Eighty CEAs under cervical block were included. There were two patient groups: with clinical signs of cerebral ischemia (shunted patients) and without signs of cerebral ischemia (nonshunted patients). Data were based on bispectral index (BIS) values and neurological monitoring at different surgery time points, with special attention paid during carotid clamping. BIS values were compared between shunted and nonshunted patients. Se…
El capital psíquico. Aportes de la Psicología Positiva.
2006
The article presents a brief analysis of the central proposals of contemporary Positive Psychology. The notion of Psychologiocal Capital is presented and a proposal for categorization of its principal components in terms of cognitive, affective and psychosocial processes is explained.