Immune checkpoint blockades (ICBs) are promising, however they do not fit all types of tumor, such as those lack of tumor antigens. Induction of potent anti-tumor T cell immunity is critical for cancer therapy. In this study, we investigated the efficacy of immunotherapy via the immunogenic cell death (ICD) dying tumor cells in mouse models of lung metastasis and tumorigenesis. ICD was induced by short exposure to lethal dose of chemotherapeutic drug doxorubicin (Dox), which initiated an irreversible ICD program in tumor cells. We immunized mice with ICD dying tumor cells in prevention, therapy in lung metastasis models, and Gprc5a-knockout (ko) model of lung tumorigenesis. T cells and macrophages isolated from lymph nodes or tumor tissues were analyzed by flow cytometry. Cytokines were analyzed by ELISA or Q-PCR analysis. Immunization with these live but ICD dying tumor cells induced potent tumor-specific anti-tumor T cell immunity, which not only protected host from challenge by these tumor cells in prevention and therapy in mouse model of lung metastasis, but also prevented tumors development in Gprc5a-ko mouse model of lung tumorigenesis. The lymphocytes from lymph nodes and tumor tissues exhibited greatly enhanced activities of Th1 cells and M1 macrophages. Immunization with the ICD dying tumor cells evokes potent tumor-specific T cell immunity, which provides a novel approach for cancer immunotherapy.
Prospective observation of hemodynamic changes before and after the formation of atherosclerotic stenosis in the carotid artery is difficult. Thus, a vessel surface repairing method was used for retrospective hemodynamic study before and after atherosclerotic stenosis formation in carotid artery. The three-dimensional geometry of sixteen sinus atherosclerotic stenosis carotid arteries were repaired and restored as normal arteries. Computational fluid dynamics analysis was performed to estimate wall shear stress (WSS), velocity and vortex in atherosclerosis-free areas and sinus in stenosis-repaired carotid artery. The analysis was also performed in the stenotic segment and upstream and downstream of stenosis in stenotic carotid artery. Compared to the atherosclerosis-free areas in stenosis-repaired carotid artery, sinus presented significantly lower WSS (P < 0.05), lower velocity (P < 0.05) and apparent vortex. Compared to the sinus, the WSS in the upstream of stenosis was lower (P < 0.05), while in the downstream area was similar (P = 0.87), both upstream and downstream of stenosis demonstrated similar velocity to sinus (P = 0.76 and P = 0.36, respectively) and apparent vortex. Atherosclerosis-prone areas including normal carotid sinus and upstream and downstream of stenosis in stenotic carotid artery were subjected to lower WSS and velocity as well as apparent vortex, thereby might be associated with the formation and progress of atherosclerosis.
Purpose To noninvasively monitor carotid plaque vulnerability by exploring the relationship between pharmacokinetic parameters (PPs) of dynamic contrast‐enhanced magnetic resonance imaging (DCE‐MRI) and plaque types based on MRI‐modified American Heart Association (AHA) classification, as well as to assess the ability of PPs in discrimination between stable and vulnerable plaques suspected on MRI. Materials and Methods Of 70 consecutive patients with carotid plaques who volunteered for 3.0T MRI (3D time‐of‐flight [TOF], T 1 ‐weighted, T 2 ‐weighted, 3D magnetization‐prepared rapid acquisition gradient‐echo [MP‐RAGE] and DCE‐MRI), 66 participants were available for analysis. After plaque classification according to MRI‐modified AHA Lesion‐Type (LT), PPs ( K trans , k ep , v e , and v p ) of DCE‐MRI were measured. The Extended Tofts model was used for calculation of PPs. For participants with multiple carotid plaques, the plaque with the worst MRI‐modified AHA LT was chosen for analysis. Correlations between PPs and plaque types and the ability of these parameters to distinguish stable and vulnerable plaques suspected on MRI were assessed. Results Significant positive correlation between K trans and LT III to VI was found (ρ = 0.532, P < 0.001), as was the correlation between k ep and LT III to VI (ρ = 0.409, P < 0.001). Stable and vulnerable plaques suspected on MRI could potentially be distinguished by K trans (sensitivity 83%, specificity 100%) and k ep (sensitivity 77%, specificity 91%). Conclusion K trans and k ep from DCE‐MRI can provide quantitative information to monitor plaque vulnerability in vivo and differentiate vulnerable plaques suspected on MRI from stable ones. These two parameters could be adopted as imaging biomarkers for plaque characterization and risk stratification. Level of Evidence : 1 Technical Efficacy: Stage 2 J. MAGN. RESON. IMAGING 2017;46:870–876
Motivation: 4D-MR angiography techniques have been developed to visualize both luminal stenosis and collateral circulation. Goal(s): This study aimed to assess whether 4D-MRA (4D-PACK and 4D-S-PACK) can be used as a noninvasive alternative to intraarterial DSA in internal carotid artery occlusion (ICAO). Approach: We prospective enrolled patients diagnosed as internal carotid artery occlusion by ultrasound or CTA and scheduled for intra-arterial DSA for this study. All patients underwent carotid multi-contrast MR imaging and DSA. Results: 4D-PACK and 4D-S-PACK can be used to diagnose ICAO, type of Circle of Willis (CoW), collateral circulation via CoW and blood flow direction of cerebral arteries. Impact: We offered a noninvasive alternative to intraarterial DSA to diagnose ICAO, type of CoW, collateral circulation via CoW and blood flow direction. By using three durations, we could greatly reduce time cost while ensuring the accuracy of 4D-PACK and 4D-S-PACK.
We really appreciate your interest in our article published in the March 2012 issue of the Europace .1 We would like to thank you for your comments and opinions on right ventricular outflow tract (RVOT) pacing.2
The right ventricular apex (RVA) has been the elective pacing site in patients with potentially life-threatening bradycardias since 1959, because it is easily accessible, readily identified, and associated with a stable position and reliable chronic pacing parameters. Nevertheless, the conventional RVA pacing may have detrimental effects on atrial fibrillation, cardiac structure, and left …
Type 2 diabetes mellitus (T2DM) is a leading risk factor for the development and progression of chronic kidney disease (CKD). However, an accurate and convenient marker for early detection and appropriate management of CKD in individuals with T2DM is limited. Recent studies have demonstrated a strong correlation between the neutrophil-to-lymphocyte ratio (NLR) and CKD. Nonetheless, the predictive value of NLR for renal damage in type 2 diabetic patients remains understudied.
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