67 research outputs found
Activated CD4+ T cells enhance radiation effect through the cooperation of interferon-γ and TNF-α
<p>Abstract</p> <p>Background</p> <p>Approaches that enhance radiation effect may lead to improved clinical outcome and decrease toxicity. Here we investigated whether activated CD4+ T cells (aCD4) can serve as an effective radiosensitizer.</p> <p>Methods</p> <p>CD4+ T cells were activated with anti-CD3 and anti-CD28 mAbs. Hela cells were presensitized with aCD4 or conditioned supernatant (aCD4S) or recombinant cytokines for 2 days, followed γ-irradiation. The treated cells were cultured for an additional 2 to 5 days for cell proliferation, cell cycle, and western blot assays. For confirmation, other cancer cell lines were also used.</p> <p>Results</p> <p>Presensitization of tumor cells with aCD4 greatly increased tumor cell growth inhibition. Soluble factors secreted from activated CD4<sup>+ </sup>T cells were primarily responsible for the observed effect. IFN-γ seemed to play a major role. TNF-α, though inactive by itself, significantly augmented the radiosensitizing activity of IFN-γ. aCD4S, but not IFN-γ or IFN-γ/TNF-α combination, was found to enhance the γ-irradiation-induced G2/M phase arrest. Bax expression was highly upregulated in Hela cells presensitized with aCD4S followed by γ-irradiation. The radio-sensitizing activity of aCD4 is not uniquely observed with Hela cell line, but also seen with other cancer cell lines of various histology.</p> <p>Conclusions</p> <p>Our findings suggest possible molecular and cellular mechanisms that may help explain the radio-sensitization effect of activated lymphocytes, and may provide an improved strategy in the treatment of cancer with radiotherapy.</p
Essential versus accessory aspects of cell death: recommendations of the NCCD 2015
Cells exposed to extreme physicochemical or mechanical stimuli die in an uncontrollable manner, as a result of their immediate structural breakdown. Such an unavoidable variant of cellular demise is generally referred to as âaccidental cell deathâ (ACD). In most settings, however, cell death is initiated by a genetically encoded apparatus, correlating with the fact that its course can be altered by pharmacologic or genetic interventions. âRegulated cell deathâ (RCD) can occur as part of physiologic programs or can be activated once adaptive responses to perturbations of the extracellular or intracellular microenvironment fail. The biochemical phenomena that accompany RCD may be harnessed to classify it into a few subtypes, which often (but not always) exhibit stereotyped morphologic features. Nonetheless, efficiently inhibiting the processes that are commonly thought to cause RCD, such as the activation of executioner caspases in the course of apoptosis, does not exert true cytoprotective effects in the mammalian system, but simply alters the kinetics of cellular demise as it shifts its morphologic and biochemical correlates. Conversely, bona fide cytoprotection can be achieved by inhibiting the transduction of lethal signals in the early phases of the process, when adaptive responses are still operational. Thus, the mechanisms that truly execute RCD may be less understood, less inhibitable and perhaps more homogeneous than previously thought. Here, the Nomenclature Committee on Cell Death formulates a set of recommendations to help scientists and researchers to discriminate between essential and accessory aspects of cell death
The effect of extended post-mortem ageing on the WarnerâBrazler shear force of longissimus thoracis from beef heifers from two sire breeds, slaughtered at 20 or 25 mo of age
peer-reviewedwere examined. Spring-born Angus Ă Holstein-Friesian heifers (n = 48) and Belgian Blue Ă
Holstein-Friesian heifers (n = 48) were slaughtered, within sire breed, at 20 or 25 mo of age. Approximately 48 h
post-mortem, LT steaks (2.5 cm) were removed, and either stored at â20°C for chemical analysis or vacuum-packed,
stored at 2°C for 7, 14 or 28 d post-mortem and then at â20°C pending WarnerâBratzler shear force (WBSF) analysis.
Muscle from Angus-sired heifers had higher (P < 0.001) intramuscular fat (IMF) concentration, lower (P < 0.001)
proportion of type IIX muscle fibres and higher (P < 0.001) proportion of type IIA and type I muscle fibres compared to
muscle from Belgian Blue-sired heifers. Collagen characteristics did not differ between sire breeds. Later slaughter
increased (P < 0.001) IMF concentration and decreased (P < 0.001) total and insoluble concentrations and collagen
solubility. There were no interactions between the main effects for WBSF and no difference between sire breeds.
Later slaughter and increasing the duration of ageing decreased (P < 0.05) WBSF. Based on threshold WBSF values
in the literature, all samples would be considered tender (<39 N) after 7 d ageing. Untrained consumers are likely
to detect the decrease in WBSF from 7 to 14 d ageing but not due to further ageing. Within the production system
examined and based on WBSF data, extending LT ageing to 28 d is not necessary to ensure consumer satisfaction
Visualization of the spatial positioning of the SNRPN, UBE3A, and GABRB3 genes in the normal human nucleus by three-color 3D fluorescence in situ hybridization
Intrathecal picrotoxin minimally alters electro-encephalographic responses to noxious stimulation during halothane and isoflurane anesthesia
Magnetic Resonance Imaging as a Sensitive and Specific Predictor of Neoplasms Removed for Intractable Epilepsy
Photon activation therapy: a Monte Carlo study on dose enhancement by various sources and activation media
Tissue solubility of four volatile anesthetics in fresh and frozen tissue specimens from swine
Magnetic Resonance Imaging of Intractable Complex Partial Seizures: Pathologic and Electroencephalographic Correlation
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