Co-delivery of proanthocyanidin and mitoxantrone induces synergistic immunogenic cell death to potentiate cancer immunotherapy.

Immunological checkpoint inhibitors provide a revolutionary method for cancer treatment. However, due to low tumor mutations and insufficient infiltration of immune cells into the tumor microenvironment, 85% of colorectal cancer patients cannot respond to checkpoint blockade immunotherapy. In this study, tumor microenvironment-responsive deformable nanoparticles (DMP@NPs) were rationally designed to improve immunotherapy by synergistically modulating the immune tumor microenvironment. DMP@NPs self-assemble from a newly synthesized tumor acidity responsive polypeptide checkpoint inhibitor polymer (PEG-DMA-DPPA-1) with immunogenic cell death (ICD) enhanced combination drugs containing a certain proportion of mitoxantrone (MITX) and proanthocyanidins (PC). Upon tumor acidity-triggered cleavage of PEG-DMA-DPPA-1, DMP@NPs undergo special "sphere-ring deformation" dissociation, gradually releasing polypeptide checkpoint inhibitor DPPA-1, MITX and PC. MITX/PC in vitro synergistically triggers higher ICD with the release of the high mobility group box-1 (HMGB-1) and calreticulin (CRT). After intravenous injection of DMP@NPs, the local tumor microenvironment of CT26 tumor-bearing mice was reprogrammed, and dendritic cell activation and T cell infiltration were significantly increased. Most importantly, the synergistic immune nanodrug DMP@NPs improved the efficacy of colorectal cancer immunotherapy and reduced toxicity and side effects for the immune organs.

Accuracy of 3-T MRI for Preoperative T Staging of Esophageal Cancer After Neoadjuvant Chemotherapy, With Histopathologic Correlation.

OBJECTIVE: The purpose of this study was to explore the value of 3-T MRI for evaluating the preoperative T staging of esophageal cancer (EC) treated with neoadjuvant chemotherapy (NAC), with histopathologic confirmation. SUBJECTS AND METHODS: This prospective study enrolled patients for whom endoscopic biopsy showed EC and pretreatment CT showed stage cT1N+M0 or cT2-T4aN0-N3M0. All patients received two cycles of NAC (paclitaxel and nedaplatin protocol) followed by 3-T MRI and surgical resection. Readers assigned a T category on MRI, and postoperative pathologic confirmation was considered the reference standard. Interreader agreement, the diagnostic accuracy of T staging on T2-weighted turbo spin-echo (TSE) BLADE (Siemens Healthcare), contrast-enhanced StarVIBE (Siemens Healthcare), high-resolution delayed phase StarVIBE, and the combination of the three sequences were analyzed and compared with postoperative pathologic T staging. RESULTS: The study included 79 patients. Mean time between NAC and MRI was 23 days. Interreader agreements of T category assignment were excellent for T2-weighted TSE BLADE (κ = 0.810, p < 0.0001), contrast-enhanced StarVIBE (κ = 0.845, p < 0.0001), high-resolution delayed phase StarVIBE (κ = 0.897, p < 0.0001), and the combination of the three sequences (κ = 0.880, p < 0.0001). The highest accuracy for T0, T1, T2, and T4a lesions was on high-resolution delayed phase StarVIBE (96.2%, 92.4%, 91.1%, and 91.1% for reader 1; 94.9%, 89.9%, 91.1%, and 94.9% for reader 2), and the highest accuracy for T3 lesions was on T2-weighted TSE BLADE (92.4% and 94.9% for reader 1 and reader 2, respectively). Diagnostic accuracy of the combination of the three sequences was not improved compared with individual sequences. CONCLUSION: High-resolution delayed phase StarVIBE had the highest diagnostic accuracy in staging EC after NAC for all T categories except T3, for which T2-weighted TSE BLADE had the highest accuracy. Combining all three sequences did not improve diagnostic accuracy.

Characteristics of wooden intraocular foreign body by magnetic resonance imaging in rabbits.

OBJECTIVE: Intraocular foreign body (IOFB), a frequent cause of ocular trauma, causes serious damage to the eyes. This study was designed to elaborate and compare the characteristics of different magnetic resonance imaging (MRI) sequences in detecting wooden IOFBs in rabbits. METHODS: The right vitreous of 24 healthy rabbits was randomly implanted with diverse wooden foreign bodies (diameter φ = 0.2 mm). The T1-weighted imaging (T1WI), T2-weighted imaging (T2WI), proton density-weighted imaging (PDWI), and susceptibility-weighted imaging (SWI) sequences were applied individually 2 weeks after the implantation. RESULTS: IOFBs were detected as linear low signals on T1WI, T2WI, PDWI, and SWI (SWI image). The detectable rates of poplar wood with a length of 0.5 mm were 0%, 50%, 0%, and 67% for T1WI, T2WI, PDWI, and SWI, respectively. SWI and T2WI sequences exhibited higher sensitivity than T1WI and PDWI. The detectable rates of the first three SWI sequences (magnitude, phase, and SWI) were all 67%, which was higher than that of the minimum intensity projection sequence (33%). CONCLUSION: MRI is practicable in the diagnosis of wooden IOFBs. SWI and T2WI are optimal for the integrated diagnosis of wooden IOFBs and could be used for diagnosis and immediate treatment.

Comparison between free-breathing radial VIBE on 3-T MRI and endoscopic ultrasound for preoperative T staging of resectable oesophageal cancer, with histopathological correlation.

OBJECTIVES: To compare the T staging of resectable oesophageal cancer (OC) using radial VIBE (r-VIBE) and endoscopic ultrasound (EUS) with pathological confirmation of the T stage. METHODS: Forty-three patients with endoscopically proven OC and indeterminate T1/T2/T3/T4a stage by computed tomography (CT) and EUS were imaged on a 3-T magnetic resonance imaging (MRI) scanner. T stage was scored on MRI and EUS by two independent radiologists and one endoscopist, respectively, and compared with postoperative pathological findings. T staging agreement between r-VIBE and EUS with postoperative pathological T staging was analysed by a kappa test. RESULTS: EUS and pathological T staging showed agreement of 69.8% (30/43). Radial VIBE and pathological T staging agreement was 86.0% (37/43) and 90.7% (39/43) for readers 1 and 2, respectively. High accuracy for T1/T2 stage was obtained for both r-VIBE readers (90.5% and 100% for reader 1 and reader 2, respectively) and EUS reader (100%). For T3/T4, r-VIBE showed accuracy of 81.8% and 90.9% for reader 1 and reader 2, respectively, while for EUS, accuracy was only 68.2% compared with pathological T staging. CONCLUSIONS: Contrast-enhanced r-VIBE is comparable to EUS in T staging of resectable OC with stage of T1/T2, and is superior to EUS in staging of T3/T4 lesions. KEY POINTS: • Radial VIBE may be useful in preoperative T staging of OC • Accuracy of staging on r-VIBE is higher in T1/2 than in T3/4 • Accuracy of EUS was 100% and 68.2% for T1/T2 and T3/T4 stage • Inter-reader agreement of T staging for r-VIBE was good.

Preoperative T Staging of Potentially Resectable Esophageal Cancer: A Comparison between Free-Breathing Radial VIBE and Breath-Hold Cartesian VIBE, with Histopathological Correlation.

PURPOSE: To compare the T staging of potentially resectable esophageal cancer using free-breathing radial VIBE (r-VIBE) and breath-hold Cartesian VIBE (C-VIBE), with pathologic confirmation of the T stage. MATERIALS AND METHODS: Fifty patients with endoscopically proven esophageal cancer and indeterminate T1/T2/T3 stage by CT scan were examined on a 3-T scanner. The MRI protocol included C-VIBE at 150 seconds post-IV contrast, immediately followed by a work-in-progress r-VIBE with identical spatial resolution (1.1 mm × 1.1 mm × 3.0 mm). Two independent readers assigned a T stage on MRI according to the 7th edition of UICC-AJCC TNM Classification, and postoperative pathologic confirmation was considered the gold standard. Interreader agreement was also calculated. RESULTS: The T staging agreement between both VIBE techniques and postoperative pathologic T staging was 52% (26/50) for C-VIBE, 80% (40/50) for r-VIBE for reader 1, and 50% (25/50), 82% (41/50) for reader 2, respectively. For the esophageal cancer with invading lamina propria, muscularis mucosae, or submucosa (T1 stage), r-VIBE achieved 86% (12/14) agreement for both readers 1 and 2. For invasion of muscularis propria (T2 stage), r-VIBE achieved 83% (25/30) for both readers 1 and 2, whereas for the invasion of adventitia (T3 stage), r-VIBE could only achieve agreement in 50% (3/6) and 67% (4/6) for readers 1 and 2, respectively. CONCLUSION: Contrast-enhanced free-breathing r-VIBE is superior to breath-hold CVIBE in T staging of potentially resectable esophageal cancer, especially for T1 and T2.