This study investigated time-dependent group-level changes in chemical exchange saturation transfer (CEST) signals in a mouse model and explored utility in identifying stroke onset time. Multiparametric magnetic resonance imaging (diffusion weighted imaging, arterial spin labeling, and CEST) was conducted on 12 normal and 26 ischemic mice. Imaging findings were validated by immunohistochemical analysis. CEST parameters in infarct and penumbra were compared between strokes within 4.5 h and over 4.5 h. Correlations, regression, and receiver operating characteristic curves evaluated performance. Infarct guanidine, magnetization transfer (MT), nuclear Overhauser enhancement (NOE) (-3.5 ppm), and NOE (-1.6 ppm) significantly differed between groups and associated with onset time (P < .01). MT, NOE (-3.5 ppm), NOE (-1.6 ppm) showed significant associations with onset time in univariate logistic regression (P < .05). The NOE (-3.5 ppm) achieved an area under the curve of 0.848 (95% CI: 0.655-1.000), outperforming apparent diffusion coefficient (z = -2.397, P = .017) and cerebral blood flow (z = -2.271, P = .0271). NOE (-3.5 ppm) signals and lipid peroxidation both declined progressively with ischemic duration. These findings indicate that NOE (-3.5 ppm) signal attenuation parallels lipid peroxidation and may indicate progressive membrane lipid loss in ischemia.
Despite the increased water content in fibrotic livers, numerous studies reported a decrease in apparent diffusion coefficient (ADC) in liver fibrosis. We argue that the ADC decrease in fibrotic livers is due to the “T2 shine-through” of ADC, as the longer T2 in liver fibrosis leads to less signal decay between the low and high b -value images. The metric slow diffusion coefficient (SDC), predominantly measuring Brownian motion of water molecules, was proposed to mitigate the difficulties associated with this “T2 shine-through” of ADC. This study calculated ADC and SDC of 1 rat study with liver fibrosis induced by biliary duct ligation (BDL), and 3 sets of human liver fibrosis data. To tease out the menopausal effect on liver SDC, only the results of men's livers were analyzed for the human datasets. The rat study showed that liver ADC decreased stepwise (in weeks after BDL procedure) following fibrosis induction, and SDC increased stepwise. In human studies, all 3 datasets consistently showed that advanced fibrosis had a liver ADC lower than that of earlier stage fibrosis; advanced fibrosis had a liver SDC higher than that of earlier stage fibrosis.
Potent STING agonists are among the most promising strategies for reversing immunosuppression in “cold” tumors, but in vivo antitumor efficacy is frequently limited by dose-limiting systemic toxicity and inadequate tumor selectivity. To achieve localized STING activation and robust systemic immunity, we combined STING agonism with photodynamic therapy (PDT), creating a carrier-free nanoplatform (Ce6&SR717 NPs) through self-assembly of SR717 (STING agonist) and Ce6 (chlorin e6, photosensitizer). This excipient-free design achieves maximum drug loading, alleviates carrier-related safety issues, and realizes the spatiotemporally synchronized activation of PDT-induced immunogenic cell death and STING signaling through irradiation, which establishes an auto-amplifying cycle of on-site antigen release and systemic immune priming. In the murine breast cancer model, Ce6&SR717 NPs plus laser irradiation dramatically increased CD8 + T-cell infiltration within the tumor, triggered strong systemic antitumor immunity, and suppressed both primary and distant tumors. Collectively, these results identify Ce6&SR717 NPs as a safe and efficient modality for synergistic photo-immunotherapy of immunologically cold tumors.
Background This study aimed to evaluate the diagnostic performance of magnetic resonance imaging (MRI)-based radiomics for predicting pathological complete response (pCR) after neoadjuvant chemoradiotherapy in patients with locally advanced rectal adenocarcinoma. Methods Eligible studies developed MRI-based radiomics or deep learning models to predict pCR and reported sufficient data to reconstruct 2 × 2 contingency tables. Only validation cohorts were included in the quantitative synthesis. Study quality was assessed using Quality Assessment of Diagnostic Accuracy Studies-2 and the Radiomics Quality Score. Pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), and diagnostic odds ratio were estimated using a bivariate random-effects model. Hierarchical summary receiver operating characteristic (HSROC) analysis was performed. Results Thirty-eight studies were included. The pooled sensitivity and specificity were 0.82 (95% CI, 0.71-0.90) and 0.86 (95% CI, 0.80-0.91), respectively. The pooled PLR and NLR were 6.0 (95% CI, 4.0-8.9) and 0.21 (95% CI, 0.12-0.35), corresponding to a diagnostic odds ratio of 29 (95% CI, 14-61). HSROC analysis showed an area under the curve of 0.846. Subgroup analyses suggested improved performance for deep learning and combined clinical–radiomic models. Conclusion MRI-based radiomics demonstrates good diagnostic accuracy for predicting pCR after neoadjuvant chemoradiotherapy in rectal cancer, although methodological heterogeneity and limited prospective validation remain challenges.
The efficacy of chimeric antigen receptor (CAR)-T therapy in solid tumors is limited by the immunosuppressive microenvironment and poor T-cell infiltration. Radiotherapy offers immunomodulatory potential, yet its synergy with CAR-T via targeted internal radionuclides remains unexplored. Here, we identified protein regulator of cytokinesis 1 (PRC1) as a novel immunotherapeutic target. Through bioinformatic analysis, we engineered PRC1-specific CAR-T cells coexpressing the sodium iodide symporter (NIS) and an shRNA targeting SLC26A4, enabling enhanced iodide uptake and retention. These NIS-CAR-T cells demonstrated potent, antigen-restricted cytotoxicity and cytokine secretion upon co-culture with breast cancer cells. Low-dose 125 I selectively induced cytolysis in tumor cells without impairing CAR-T function. At low effector-to-target ratios mimicking poorly infiltrated “cold” tumors, internal irradiation via 125 I significantly boosted CAR-T killing, even against low-antigen tumors. This study introduces a multifunctional CAR-T platform that integrates internal radiotherapy to overcome key barriers in solid tumors, thereby offering a radiosensitized cellular therapy designed for the hostile tumor microenvironment.
