Single-cell analysis of early antiviral gene expression reveals a determinant of stochastic IFNB1 expression

RIG-I-like receptors (RLRs) are cytoplasmic sensors of viral RNA that trigger the signaling cascade that leads to type I interferon (IFN) production. Transcriptional induction of RLRs by IFN is believed to play the role of positive feedback to further amplify viral sensing. We found that RLRs and several other IFN-stimulated genes (ISGs) are induced early in viral infection independent of IFN. Expression of these early ISGs requires IRF3/IRF7 and is highly correlated amongst them. Simultaneous detection of mRNA of IFNB1, viral replicase, and ISGs revealed distinct populations of IFNB1 expressing and non-expressing cells which are highly correlated with the levels of early ISGs but are uncorrelated with IFN-dependent ISGs and viral gene expression. Individual expression of RLRs made IFNB1 expression more robust and earlier, suggesting a causal relation between levels of RLR and induction of IFN.112Ysciescopu

Investigation of sliced body volume (SBV) as respiratory surrogate.

The purpose of this study was to evaluate the sliced body volume (SBV) as a respiratory surrogate by comparing with the real-time position management (RPM) in phantom and patient cases. Using the SBV surrogate, breathing signals were extracted from unsorted 4D CT images of a motion phantom and 31 cancer patients (17 lung cancers, 14 abdominal cancers) and were compared to those clinically acquired using the RPM system. Correlation coefficient (R), phase difference (D), and absolute phase difference (D(A)) between the SBV-derived breathing signal and the RPM signal were calculated. 4D CT reconstructed based on the SBV surrogate (4D CT(SBV)) were compared to those clinically generated based on RPM (4D CT(RPM)). Image quality of the 4D CT were scored (S(SBV) and S(RPM), respectively) from 1 to 5 (1 is the best) by experienced evaluators. The comparisons were performed for all patients, and for the lung cancer patients and the abdominal cancer patients separately. RPM box position (P), breathing period (T), amplitude (A), period variability (V(T)), amplitude variability (V(A)), and space-dependent phase shift (F) were determined and correlated to S(SBV). The phantom study showed excellent match between the SBV-derived breathing signal and the RPM signal (R = 0.99, D= -3.0%, D(A) = 4.5%). In the patient study, the mean (± standard deviation (SD)) R, D, D(A), T, V(T), A, V(A), and F were 0.92 (± 0.05), -3.3% (± 7.5%), 11.4% (± 4.6%), 3.6 (± 0.8) s, 0.19 (± 0.10), 6.6 (± 2.8) mm, 0.20 (± 0.08), and 0.40 (± 0.18) s, respectively. Significant differences in R and D(A) (p = 0.04 and 0.001, respectively) were found between the lung cancer patients and the abdominal cancer patients. 4D CT(RPM) slightly outperformed 4D CT(SBV): the mean (± SD) S(RPM) and S(SBV) were 2.6 (± 0.6) and 2.9 (± 0.8), respectively, for all patients, 2.5 (± 0.6) and 3.1 (± 0.8), respectively, for the lung cancer patients, and 2.6 (± 0.7) and 2.8 (± 0.9), respectively, for the abdominal cancer patients. The difference between S(RPM) and S(SBV) was insignificant for the abdominal patients (p = 0.59). F correlated moderately with S(SBV) (r = 0.72). The correlation between SBV-derived breathing signal and RPM signal varied between patients and was significantly better in the abdomen than in the thorax. Space-dependent phase shift is a limiting factor of the accuracy of the SBV surrogate

IFN-Independent Expression of RIG-I is a Determinant of Heterogeneous IFN-B Expression States in Antiviral Signaling

open11sciescopu

Assessment of the residual error in soft tissue setup in patients undergoing partial breast irradiation: results of a prospective study using cone-beam computed tomography.

PURPOSE: On-board cone-beam computed tomography (CBCT) provides soft tissue information that may improve setup accuracy in patients undergoing accelerated partial breast irradiation (APBI). We used CBCT to assess the residual error in soft tissue after two-dimensional kV/MV alignment based on bony anatomy. We also assessed the dosimetric impact of this error. METHODS AND MATERIALS: Ten patients undergoing APBI were studied as part of an institutional review board-approved prospective trial. Patients were aligned based on skin/cradle marks plus orthogonal kV/MV images registered based on bony landmarks to digitally reconstructed radiographs from the planning CT. A subsequent CBCT was registered to the planning CT using soft tissue information. This residual error and its dosimetric impact was measured. RESULTS: The root-mean-square of the residual error was 3, 4, and 4 mm, in the right-left, anterior-posterior, and superior-inferior directions, respectively. The average vector sum was 6+/-2 mm. Average reductions in mean dose to the lumpectomy cavity, clinical target volume (CTV), and planning target volume were 0.1%, 0.4%, and 1%, respectively. The mean difference in the clinical target and planning target volumes that received 95% of the prescribed dose (V95) were 1% and 4%. CONCLUSIONS: In this initial study with a modest number of patients, the residual error in soft tissue was typically \u3c5 \u3emm, and with the field margins used, the resultant dosimetric consequences were modest. In patients immobilized in a customized cradle, setup using orthogonal kV images thus appears accurate and reproducible. The CBCT technique may have particular utility in patients with larger breast volumes or breast deformations. Further studies involving larger numbers of patients are needed to further assess the utility of CBCT

A COMPARISON OF CLINICAL AND DOSIMETRIC OUTCOMES IN PATIENTS RECEIVING PARTIAL BREAST IRRADIATION WITH PHOTON-ONLY VERSUS MIXED PHOTON/ELECTRON TREATMENT PLANS

WOS: 000297487800015PubMed ID: 21440433Several series evaluating external-beam partial breast irradiation (PBI) have linked negative cosmetic outcomes to large normal tissue treatment volumes. We compared patients treated with PBI whose treatment plans included only photons to those whose plans incorporated electrons. Twenty-seven patients were identified: median age 67 years, pT1 82%, pN0 56%, margin negative 100%. All received 38.5 Gy using 3-5 noncoplanar photon beams (6-15X). Electrons (9-20 MeV) were included in 59%. Median follow-up was 22 months. Ninety percent experienced good/excellent cosmetic outcomes. Two patients had fair cosmesis, and both were treated with a mixed photon/electron approach. Median conformity index for photon-only treatment plans was 1.7 (range, 0.9-2.0) and for photon/electron plans, 1.0 (0.3-1.4). Median percent ipsilateral breast volume receiving 100% and 50% of prescription dose was 19 and 50 for photon-only plans vs. 10 and 38 for photon/electron plans (p < 0.05). Median percent target volume receiving 100% and 95% of prescription dose was 93 and 98 for photon-only plans vs. 75 and 94 for photon/electron plans (p < 0.05). A mixed photon/electron, noncoplanar technique decreases the volume of treated normal breast tissue at the cost of slightly decreased tumor bed coverage. Further study is needed to determine whether this results in a more favorable therapeutic ratio than photon-only approaches. (C) 2011 American Association of Medical Dosimetrists

Impact of glucose metabolism on PD-L1 expression in sorafenib-resistant hepatocellular carcinoma cells.

Hepatocellular carcinoma (HCC) is the fifth leading cause of cancer-related mortality worldwide. Programmed cell death ligand-1 (PD-L1) is an immune checkpoint protein that binds to programmed cell death-1 (PD-1), which is expressed in activated T cells and other immune cells and has been employed in cancer therapy, including HCC. Recently, PD-L1 overexpression has been documented in treatment-resistant cancer cells. Sorafenib is a multikinase inhibitor and the only FDA-approved treatment for advanced HCC. However, several patients exhibit resistance to sorafenib during treatment. This study aimed to assess the effect of glucose deprivation on PD-L1 expression in HCC cells. We used PD-L1-overexpressing HepG2 cells and IFN-γ-treated SK-Hep1 cells to explore the impact of glycolysis on PD-L1 expression. To validate the correlation between PD-L1 expression and glycolysis, we analyzed data from The Cancer Genome Atlas (TCGA) and used immunostaining for HCC tissue analysis. Furthermore, to modulate PD-L1 expression, we treated HepG2, SK-Hep1, and sorafenib-resistant SK-Hep1R cells with rapamycin. Here, we found that&nbsp;glucose deprivation reduced PD-L1 expression in HCC cells. Additionally,&nbsp;TCGA data and immunostaining analyses confirmed a positive correlation between the expression of hexokinase II (HK2), which plays a key role in glucose metabolism, and PD-L1. Notably, rapamycin treatment&nbsp; decreased the expression of PD-L1 and HK2 in both high PD-L1-expressing HCC cells and sorafenib-resistant cells. Our results suggest that the modulation of PD-L1 expression by glucose deprivation may represent a strategy to overcome PD-L1 upregulation in patients with sorafenib-resistant HCC

Nitrogen and sulfur codoped graphene : multifunctional electrode materials for high-performance Li-ion batteries and oxygen reduction reaction

N and S codoping of graphene is realized by a novel approach: covalent functionalization of graphene oxide using 2-aminothiophenol as a source of both N and S followed by thermal treatment. The resulting N- and S-codoped graphene has potential applications in high-performance lithium-ion batteries and as a metal-free catalyst for oxygen reduction reaction