Radiomic features based on pyradiomics predict CD276 expression associated with breast cancer prognosis.

Background: CD276 is a promising immune checkpoint molecule with significant therapeutic potential. Several clinical trials are currently investigating CD276-targeted therapies. Purpose: This study aims to assess the prognostic significance of CD276 expression levels and to predict its expression using a radiomic approach in breast cancer (BC). Methods: A cohort of 840 patients diagnosed with BC from The Cancer Genome Atlas was included in this study. The Cancer Imaging Archive provided 98 magnetic resonance imaging (MRI) scans, which were randomly allocated to training and validation datasets in a 7:3 ratio. The association between CD276 expression and patient survival was assessed using Cox regression analysis. Feature selection was performed using the maximum relevance minimum redundancy algorithm and recursive feature elimination. Subsequently, support vector machine (SVM) and logistic regression (LR) models were constructed to predict CD276 expression. Results: The expression of CD276 was found to be elevated in BC. It was an independent risk factor for overall survival (hazard ratio = 1.579, 95 % CI: 1.054-2.366). There were eight radiomic features selected in total. In both the training and validation subsets, the SVM and LR models demonstrated favorable predictive abilities with AUC values of 0.744 and 0.740 for the SVM model and 0.742 and 0.735 for the LR model. These results indicate that the radiomic models efficiently differentiate the CD276 expression status. Conclusions: CD276 expression levels can have an impact on cancer prognosis. The MRI-based radiomic signature described in this study can discriminate the CD276 expression status.

Unraveling the pharmacodynamic substances and possible mechanism of Trichosanthis Pericarpium in the treatment of coronary heart disease based on plasma pharmacochemistry, network pharmacology and experimental validation.

ETHNOPHARMACOLOGICAL RELEVANCE: Coronary heart disease (CHD) is a chronic disease that seriously threatens people's health and even their lives. Currently, there is no ideal drug without side effects for the treatment of CHD. Trichosanthis Pericarpium (TP) has been used for several years in the treatment of diseases associated with CHD. However, there is still a need for systematic research to unravel the pharmacodynamic substances and possible mechanism of TP in the treatment of coronary heart. AIM OF THE STUDY: The purpose of current study was to explore the pharmacodynamic substances and potential mechanisms of TP in the treatment of CHD via integrating network pharmacology with plasma pharmacochemistry and experimental validation. MATERIALS AND METHODS: The effect of TP intervention in CHD was firstly assessed on high-fat diet combined with isoprenaline-induced CHD rats and H2O2-induced H9c2 cells, respectively. Then, the LC-MS was utilized to identify the absorbed components of TP in the plasma of CHD rats, and this was used to develop a network pharmacology prediction to obtain the possible active components and mechanisms of action. Molecular docking and immunohistochemistry were used to explore the interaction between TP and key targets. Subsequently, the efficacy of the active ingredients was investigated by in vitro cellular experiments, and their metabolic pathways in CHD rats were further analyzed. RESULTS: The effects of TP on amelioration of CHD were verified by in vivo and in vitro experiments. Plasma pharmacochemistry and network pharmacology screened six active components in plasma including apigenin, phenylalanine, quercetin, linoleic acid, luteolin, and tangeretin. The interaction of these compounds with potential key targets AKT1, IL-1ß, IL-6, TNF-α and VEGFA were preliminarily verified by molecular docking. And immunohistochemical results showed that TP reduced the expression of AKT1, IL-1ß, IL-6, TNF-α and VEGFA in CHD rat hearts. Then cellular experiments confirmed that apigenin, phenylalanine, quercetin, linoleic acid, luteolin, and tangeretin were able to reduce the ROS level in H2O2-induced HUVEC cells and promote the migration and tubule formation of HUVEC cells, indicating the pharmacodynamic effects of the active components. Meanwhile, the metabolites of TP in CHD rats suggested that the pharmacological effects of TP might be the result of the combined effects of the active ingredients and their metabolites. CONCLUSION: Our study found that TP intervention in CHD is characterized by multi-component and multi-target regulation. Apigenin, phenylalanine, linoleic acid, quercetin, luteolin, and tangeretin are the main active components of TP. TP could reduce inflammatory response and endothelial damage by regulating AKT1, IL-1ß, IL-6, TNF-α and VEGFA, reduce ROS level to alleviate the oxidative stress situation and improve heart disease by promoting angiogenesis to regulate endothelial function. This study also provides an experimental and scientific basis for the clinical application and rational development of TP.

Is repeat breast conservation possible for small ipsilateral breast cancer recurrence?

BACKGROUND: Most cases of ipsilateral breast tumor recurrence (IBTR) after breast-conserving surgery (BCS) involve small tumors. Although a few guidelines recommend mastectomy, several patients prefer repeat BCS (re-BCS). This study aimed to compare re-BCS and mastectomy in terms of prognosis in patients with IBTR and to identify candidates for re-BCS. METHODS: The data of patients with small IBTR between 1999 and 2015 were obtained from the Surveillance, Epidemiology, and End Results database. The outcomes of interest were overall survival (OS) and breast cancer-specific survival (BCSS). Multivariable Cox proportional hazards regression models and propensity score matching were applied. RESULTS: Of the 3648 patients with IBTR, 2831 (77.6%) underwent mastectomy and 817 (22.4%) underwent re-BCS. The multivariate Cox model showed that re-BCS was associated with a worse OS (hazard ratio [HR], 1.342; 95% confidence interval [CI], 1.084-1.663) and BCSS (HR, 1.454; 95% CI, 1.004-2.105) compared with mastectomy. The omission of radiation after re-BCS was associated with worse survival overall and especially in patients with estrogen receptor (ER)-negative IBTR (HR, 1.384; 95% CI, 1.110-1.724; and HR, 1.577; 95% CI, 1.075-2.314, respectively). No statistically significant differences were observed in the OS and BCSS between re-BCS with radiation and mastectomy. Subgroup analysis indicated that the surgical approach was not an independent factor for survival in the ER-positive patients with IBTR. CONCLUSIONS: Re-BCS should be considered with caution in patients with small IBTR. However, a positive ER status can be an important factor for choosing re-BCS, and radiation therapy may improve oncological safety after re-BCS. LAY SUMMARY: Repeat breast-conserving surgery (re-BCS) was investigated to determine if it is safe for patients with small ipsilateral breast tumor recurrence (IBTR) after breast-conserving surgery (BCS). This population-based cohort study included 2831 patients with small IBTR. Re-BCS was associated with a worse overall survival and breast cancer-specific survival compared with mastectomy. Further analysis found that the IBTR estrogen receptor status was an important basis for choosing re-BCS, and radiation may improve oncological safety after re-BCS.