Novel Fatty Acid in Cordyceps Suppresses Influenza A (H1N1) Virus-Induced Proinflammatory Response Through Regulating Innate Signaling Pathways.

Influenza virus (IV) infections usually cause acute lung injury characterized by exaggerated proinflammatory responses. The paucity of therapeutic strategies that target host immune response to attenuate lung injury poses a substantial challenge in management of IV infections. In this study, we chemically synthesized a novel fatty acid (2Z,4E)-deca-2,4-dienoic acid (DDEA) identified from Chinese Cordyceps by using UHPLC-Q-TOF-MS techniques. The DDEA did not inhibit H1N1 virus replication but attenuated proinflammatory responses by reducing mRNA and protein levels of TNF-α, IFN-α, IFN-ß, IL-6, CXCL-8/IL-8, CCL-2/MCP-1, CXCL-10/IP-10, CCL-3/MIP-1α, and CCL-4/MIP-1ß in A549 cells and U937-derived macrophages. The anti-inflammatory effect occurred through downregulations of TLR-3-, RIG-I-, and type I IFN-activated innate immune signaling pathways. Altogether, our results indicate that DDEA may potentially be used as an anti-inflammatory therapy for the treatment of IV infections.

Machine Learning Based on a Multiparametric and Multiregional Radiomics Signature Predicts Radiotherapeutic Response in Patients with Glioblastoma.

METHODS: The MRI images, genetic data, and clinical data of 152 patients with GBM were analyzed. 122 patients from the TCIA dataset (training set: n = 82; validation set: n = 40) and 30 patients from local hospitals were used as an independent test dataset. Radiomics features were extracted from multiple regions of multiparameter MRI. Kaplan-Meier survival analysis was used to verify the ability of the imaging signature to predict the response of GBM patients to radiotherapy before an operation. Multivariate Cox regression including radiomics signature and preoperative clinical risk factors was used to further improve the ability to predict the overall survival (OS) of individual GBM patients, which was presented in the form of a nomogram. RESULTS: The radiomics signature was built by eight selected features. The C-index of the radiomics signature in the TCIA and independent test cohorts was 0.703 (P < 0.001) and 0.757 (P = 0.001), respectively. Multivariate Cox regression analysis confirmed that the radiomics signature (HR: 0.290, P < 0.001), age (HR: 1.023, P = 0.01), and KPS (HR: 0.968, P < 0.001) were independent risk factors for OS in GBM patients before surgery. When the radiomics signature and preoperative clinical risk factors were combined, the radiomics nomogram further improved the performance of OS prediction in individual patients (C-index = 0.764 and 0.758 in the TCIA and test cohorts, respectively). CONCLUSION: This study developed a radiomics signature that can predict the response of individual GBM patients to radiotherapy and may be a new supplement for precise GBM radiotherapy.

Application of active breathing control in 3-dimensional conformal radiation therapy for hepatocellular carcinoma: the feasibility and benefit.

BACKGROUND AND PURPOSE: To investigate the feasibility and effectiveness of utilizing active breathing coordinator (ABC) in 3DCRT for HCC. MATERIALS AND METHODS: A dosimetric comparison between the free-breathing (FB) plan and ABC plan in HCC 3DCRT was performed. Set-up errors and reproducibility of diaphragm position using ABC were measured, and patients' acceptance was also recorded. RESULTS: From April 2005 to February 2007, 28 HCC were irradiated with ABC and they tolerated ABC well. The mean dose to normal liver was reduced from 16.9Gy in FB plan to 14.3Gy in ABC plan. PTV for ABC and FB plans were 529cm(3) and 781cm(3), respectively, and V(23) were reduced from 45% to 30%. The predicted incidences of radiation-induced liver disease by Lyman model were 1% and 2.5%, respectively, in favor of ABC plan. The systematic and random errors for the ABC and FB plans were 1.2mm vs. 4.7mm, 1.6mm vs. 3.5mm, and 1.8mm vs. 2.7mm, respectively, in cranio-caudal, anterior-posterior, and left-right directions. The average intrafraction reproducibility of diaphragm position in cranio-caudal direction was 1.6mm, and the interfraction, 6.7mm. CONCLUSIONS: The utilization of ABC in HCC 3DCRT is feasible, and can reduce liver irradiation.

The Feasibility and Efficiency of Volumetric Modulated Arc Therapy-Based Breath Control Stereotactic Body Radiotherapy for Liver Tumors.

There are strong evidences showing the promising oncologic results of stereotactic body radiotherapy for liver tumors. This study aims to investigate the feasibility, plan quality, and delivery efficiency of image-guided volumetric modulated arc therapy-based voluntary deep exhale breath-holding technique in the stereotactic body radiotherapy for liver tumors. Treatment was planned using volumetric modulated arc therapy with 2 modified partial arc and replanned using intensity modulated radiation therapy technique for comparison. Dosimetric parameters were calculated for plan quality assessment. Quality assurance studies included both point and multiple planar dose verifications. Daily cone beam computed tomography imaging was used to measure and correct positional errors for target volumes and critical structures immediately prior to and during treatment delivery. Total monitor units and delivery times were also evaluated. No significant dosimetric difference was found between volumetric-modulated arc therapy and conventional intensity modulated radiation therapy plans. Both techniques were able to minimize doses to organs at risk including normal liver, kidneys, spinal cord, and stomach. However, the average monitor units with volumetric-modulated arc therapy were significantly lower (29.2%) than those with intensity modulated radiation therapy (P = .012). The average beam-on time in volumetric-modulated arc therapy plans was 22.2% shorter than that in intensity modulated radiation therapy plans. In conclusion, it is feasible to utilize volumetric modulated arc therapy in the treatment planning of stereotactic body radiotherapy for liver tumors under breath control mode. In comparison to conventional intensity modulated radiation therapy plans, volumetric modulated arc therapy plans are of high efficiency with less monitor units, shorter beam-on time, tolerable intrafractional errors as well as better dosimetrics, meriting further investigations, and clinical evaluations.

Dosimetric comparison of 3D conformal, IMRT, and V-MAT techniques for accelerated partial-breast irradiation (APBI).

The purpose is to dosimetrically compare the following 3 delivery techniques: 3-dimensional conformal radiation therapy (3D-CRT), intensity-modulated arc therapy (IMRT), and volumetric-modulated arc therapy (V-MAT) in the treatment of accelerated partial-breast irradiation (APBI). Overall, 16 patients with T1/2N0 breast cancer were treated with 3D-CRT (multiple, noncoplanar photon fields) on the RTOG 0413 partial-breast trial. These cases were subsequently replanned using static gantry IMRT and V-MAT technology to understand dosimetric differences among these 3 techniques. Several dosimetric parameters were used in plan quality evaluation, including dose conformity index (CI) and dose-volume histogram analysis of normal tissue coverage. Quality assurance studies including gamma analysis were performed to compare the measured and calculated dose distributions. The IMRT and V-MAT plans gave more conformal target dose distributions than the 3D-CRT plans (p < 0.05 in CI). The volume of ipsilateral breast receiving 5 and 10Gy was significantly less using the V-MAT technique than with either 3D-CRT or IMRT (p < 0.05). The maximum lung dose and the ipsilateral lung volume receiving 10 (V10) or 20Gy (V20) were significantly less with both V-MAT and IMRT (p < 0.05). The IMRT technique was superior to 3D-CRT and V-MAT of low dose distributions in ipsilateral lung (p < 0.05 in V5 and D5). The total mean monitor units (MUs) for V-MAT (621.0 ± 111.9) were 12.2% less than those for 3D-CRT (707.3 ± 130.9) and 46.5% less than those for IMRT (1161.4 ± 315.6) (p < 0.05). The average machine delivery time was 1.5 ± 0.2 minutes for the V-MAT plans, 7.0 ± 1.6 minutes for the 3D-CRT plans, and 11.5 ± 1.9 minutes for the IMRT plans, demonstrating much less delivery time for V-MAT. Based on this preliminary study, V-MAT and IMRT techniques offer improved dose conformity as compared with 3D-CRT techniques without increasing dose to the ipsilateral lung. In terms of MU and delivery time, V-MAT is significantly more efficient for APBI than for conventional 3D-CRT and static-beam IMRT.

Impact of volumetric modulated arc therapy technique on treatment with partial breast irradiation.

PURPOSE: To investigate the technical feasibility of volumetric modulated arc therapy (V-MAT) in the delivery of partial breast irradiation (PBI). METHODS AND MATERIALS: V-MAT and the standard, three-dimensional conformal radiotherapy (3D-CRT), were compared retrospectively in 8 patients previously treated with PBI. These patients' plans were replanned with a single partial arc using V-MAT that included partial blocking to minimize normal tissue dose. Dosimetric parameters were calculated to evaluate plan quality. Quality assurance studies included verifying both the point and the multiple planar doses. Total monitor units and delivery time were also evaluated, and collision clearance was analyzed. RESULTS: Volumes of ipsilateral lung irradiated to 10 Gy (V10) and 20 Gy (V20) by V-MAT were significantly less than those of 3D-CRT (p = 0.03 for V10 and p = 0.025 for V20). The volume of ipsilateral breast irradiated to 5 Gy was significantly less by using V-MAT than with 3D-CRT (p = 0.02), with a ratio of integrated dose of <1.00. The total mean monitor units (489 +/- 38) for V-MAT were significantly less than those for 3D-CRT (634 +/- 123) (p = 0.017), with a 23% reduction. The average machine delivery time was 1.21 +/- 0.10 min for the V-MAT plans and 6.28 +/- 1.40 min for the 3D-CRT plans, resulting in a reduction factor of 80.1%. The conformity indexes were 1.3 in the V-MAT plans and 1.5 in the 3D-CRT plans (p = 0.102). CONCLUSIONS: V-MAT technology is feasible for PBI patients. Compared to a conventional 3D-CRT technique, it is more efficient, offers equivalent or better dose conformity, delivers lower doses to the ipsilateral lung and breast, and may potentially reduce intrafractional motion.