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Automated Quantification of Extranuclear ERα using Phosphor-integrated Dots for Predicting Endocrine Therapy Resistance in HR+/HER2? Breast Cancer
摘要： In addition to genomic signaling, Estrogen receptor alpha (ERα) is associated with cell proliferation and survival through extranuclear signaling contributing to endocrine therapy (ET) resistance. However, the relationship between extranuclear ERα and ET resistance has not been extensively studied. We sought to measure extranuclear ERα expression by immunohistochemistry using phosphor-integrated dots (IHC-PIDs) and to assess its predictive value for ET resistance. After quantitative detection of ERα by IHC-PIDs in vitro, we developed “the nearest-neighbor method” to calculate the extranuclear ERα. Furthermore, tissue sections from 65 patients with HR+/HER2- BC were examined by IHC-PIDs, and the total ERα, nuclear ERα, extranuclear ERα PIDs score, and ratio of extranuclear-to-nuclear ERα (ENR) were measured using the novel method. We demonstrate that quanti?cation of ERα using IHC-PIDs exhibited strong correlations to real-time qRT-PCR (r2 = 0.94) and ?ow cytometry (r2 = 0.98). High ERα ENR was signi?cantly associated with poor overall survival (p = 0.048) and disease-free survival (DFS) (p = 0.007). Multivariate analysis revealed that the ERα ENR was an independent prognostic factor for DFS [hazard ratio, 3.8; 95% CI, 1.4–11.8; p = 0.006]. Our automated measurement has high accuracy to localize and assess extranuclear ERα. A high ERα ENR in HR+/HER2- BC indicates decreased likelihood of bene?ting from ET.
关键词： estrogen receptor α,endocrine therapy resistance,breast cancer,prognostic,IHC-PIDs
更新于2025-11-21 11:08:12
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Green Synthesis of Carrier-Free Curcumin Nanodrugs for Light-activated Breast Cancer Photodynamic Therapy
摘要： Photodynamic therapy (PDT) is a promising procedure for breast cancer therapy. Curcumin (Cur), a hydrophobic polyphenol derived from the spice turmeric, has been considered as a potential photosensitizer for PDT with evoked immune response, excellent safety, and low cost. However, the translation of curcumin in clinical cancer therapy suffers from an insufficient therapeutic dose in tumor tissues due to its poor solubility and low bioavailability. In this study, carrier-free curcumin nanodrugs (Cur NDs) were prepared without using any toxic solvents through a facile and green reprecipitation method. Cur NDs exhibited distinct optical properties, light-sensitive drug release behavior, resulting in increased reactive oxygen species (ROS) generation and PDT efficacy on breast cancer cells compared with free Cur. Furthermore, cell apoptosis during Cur-based PDT was concomitant with the activation of the ROS-mediated JNK/caspase-3 signaling pathway. Overall, our carrier-free Cur nanodrugs may be promising candidates for facilitating the efficacy and safety of PDT against breast cancer.
关键词： Carrier-free,Curcumin,Light-responsive drug release,Breast cancer,Photodynamic therapy
更新于2025-11-14 15:26:12
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Characterization of Breast Lesions: Comparison of Digital Breast Tomosynthesis and Ultrasonography
摘要： Objective: To compare the diagnostic performance of digital breast tomosynthesis (DBT) and conventional breast ultrasound (US) to characterize breast lesions as benign or malignant. Materials and Methods: A total of 332 women, presenting for screening examinations or for breast biopsy between March and June 2012 were recruited to undergo digital mammography (DM), DBT, and breast US examination. Among them, 113 patients with 119 breast lesions depicted on DM were finally included. Three blinded radiologists performed an enriched reader study and reviewed the DBT and US images. Each reader analyzed the lesions in random order, assigned Breast Imaging Reporting and Data System (BI-RADS) descriptors, rated the images for the likelihood of malignancy (%) and made a BI-RADS final assessment. Diagnostic accuracy, as assessed by the area under the receiver operating characteristic curve, sensitivity, and specificity of DBT and US were compared. Results: Among the 119 breast lesions depicted on DM, 75 were malignant and the remaining 44 were benign. The average diagnostic performance for characterizing breast lesions as benign or malignant in terms of area under the curve was 0.899 for DBT and 0.914 for US (p = 0.394). Mean sensitivity (97.3% vs. 98.7%, p = 0.508) and specificity (44.7% vs. 39.4%, p = 0.360) were also not significantly different. Conclusion: Digital breast tomosynthesis may provide similar reader lesion characterization performance to that of US for breast lesions depicted on DM.
关键词： Breast US,Digital breast tomosynthesis,Diagnostic performance
更新于2025-09-23 15:23:52
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Synthesizing mammogram from digital breast tomosynthesis
摘要： The purpose of this study is to develop a new method for generating synthesized mammogram (SM) from digital breast tomosynthesis (DBT) and to assess its potential as an adjunct to DBT. We first applied multiscale bilateral filtering to the reconstructed DBT slices to enhance the high-frequency features and reduce noise. A maximum intensity projection (MIP) image was then obtained from the high-frequency components of the DBT slices. A multiscale image fusion method was designed to combine the MIP image and the central DBT projection view into an SM and further enhance the high-frequency features. We conducted a pilot reader study to visually assess the image quality of SM in comparison to full field digital mammograms (FFDM). For each DBT craniocaudal or mediolateral view, a clinical FFDM of the corresponding view was retrospectively collected. Three MQSA radiologists, blinded to the pathological and other clinical information, independently interpreted the SM and the corresponding FFDM side by side marked with the lesion locations. The differences in the BI-RADS assessments of both MCs and masses between SM and FFDM did not achieve statistical significance for all 3 readers. The conspicuity of MCs on SM was superior to that on FFDM and the BI-RADS assessments of MCs were comparable while the conspicuity of masses on SM was degraded and interpretation on SM was less accurate than that on FFDM. The SM may be useful for efficient prescreening of MCs in DBT but the DBT should be used for detection and characterization of masses.
关键词： synthesized mammography (SM),digital breast tomosynthesis (DBT),breast cancer
更新于2025-09-23 15:23:52
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Mapping Forest Structure Using UAS inside Flight Capabilities
摘要： We evaluated two unmanned aerial systems (UASs), namely the DJI Phantom 4 Pro and DJI Mavic Pro, for 3D forest structure mapping of the forest stand interior with the use of close-range photogrammetry techniques. Assisted flights were performed within two research plots established in mature pure Norway spruce (Picea abies (L.) H. Karst.) and European beech (Fagus sylvatica L.) forest stands. Geotagged images were used to produce georeferenced 3D point clouds representing tree stem surfaces. With a flight height of 8 m above the ground, the stems were precisely modeled up to a height of 10 m, which represents a considerably larger portion of the stem when compared with terrestrial close-range photogrammetry. Accuracy of the point clouds was evaluated by comparing field-measured tree diameters at breast height (DBH) with diameter estimates derived from the point cloud using four different fitting methods, including the bounding circle, convex hull, least squares circle, and least squares ellipse methods. The accuracy of DBH estimation varied with the UAS model and the diameter fitting method utilized. With the Phantom 4 Pro and the least squares ellipse method to estimate diameter, the mean error of diameter estimates was ?1.17 cm (?3.14%) and 0.27 cm (0.69%) for spruce and beech stands, respectively.
关键词： point cloud,diameter at breast height (DBH),photogrammetry,obstacle sensing,forestry,unmanned aerial system (UAS),vision positioning system
更新于2025-09-23 15:23:52
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Radiomic analysis of imaging heterogeneity in tumours and the surrounding parenchyma based on unsupervised decomposition of DCE-MRI for predicting molecular subtypes of breast cancer
摘要： Objectives This study aimed to predict the molecular subtypes of breast cancer via intratumoural and peritumoural radiomic analysis with subregion identification based on the decomposition of contrast-enhanced magnetic resonance imaging (DCE-MRI). Methods The study included 211 women with histopathologically confirmed breast cancer. We utilised a completely unsupervised convex analysis of mixtures (CAM) method by unmixing dynamic imaging series from heterogeneous tissues. Each tumour and the surrounding parenchyma were thus decomposed into multiple subregions, representing different vascular characterisations, from which radiomic features were extracted. A random forest model was trained and tested using a leave-one-out cross-validation (LOOCV) method to predict breast cancer subtypes. The predictive models from tumoural and peritumoural subregions were fused for classification. Results Tumour and peritumour DCE-MR images were decomposed into three compartments, representing plasma input, fast-flow kinetics, and slow-flow kinetics. The tumour subregion related to fast-flow kinetics showed the best performance among the subregions for differentiating between patients with four molecular subtypes (area under the receiver operating characteristic curve (AUC) = 0.832), exhibiting an AUC value significantly (p < 0.0001) higher than that obtained with the entire tumour (AUC = 0.719). When the tumour- and parenchyma-based predictive models were fused, the performance, measured as the AUC, increased to 0.897; this value was significantly higher than that obtained with other tumour partition methods. Conclusions Radiomic analysis of intratumoural and peritumoural heterogeneity based on the decomposition of image time-series signals has the potential to more accurately identify tumour kinetic features and serve as a valuable clinical marker to enhance the prediction of breast cancer subtypes.
关键词： Magnetic resonance imaging,Diagnostic imaging,Breast neoplasms
更新于2025-09-23 15:23:52
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Optical Imaging of Triple-Negative Breast Cancer Cells in Xenograft Athymic Mice Using an ICAM-1-Targeting Small-Molecule Probe
摘要： Purpose: The development of early, accurate diagnostic strategies for triple-negative breast cancer (TNBC) remains a significant challenge. Intercellular adhesion molecule-1 (ICAM-1) overexpressed in human TNBC cells is a potential molecular target and biomarker for diagnosis. In this study, small-molecule probe (denoted as γ3-Cy5.5) constructed with a short 17-mer linear peptide (γ3) and near-infrared fluorescence (NIRF) dye cyanine 5.5 (Cy5.5) was used to detect the expression of ICAM-1 in vitro and in vivo, and to diagnose TNBC via NIRF imaging. Procedures: Western blotting and flow cytometric analysis were used for the detection of ICAM-1 expression in MDA-MB-231 and MCF-7 cells. The cytotoxicity of the small-molecule probe γ3-Cy5.5 was detected using the CCK8 assay. The in vitro targeting of the small-molecule probe γ3-Cy5.5 was verified via flow cytometry and a laser scanning confocal microscope. Finally, the targeting of small-molecule probe in vivo and ex vivo was observed by NIRF imaging. Results: Western blotting and flow cytometry demonstrate that ICAM-1 was highly expressed in the MDA-MB-231 TNBC cell line. Laser confocal microscopy and flow cytometry results show that TNBC cells have an increased cellular uptake of γ3-Cy5.5 compared to the control probe γ3S-Cy5.5. With in vivo NIRF, a significantly higher Cy5.5 signal appeared in the tumors of mice administered γ3-Cy5.5 than those treated with γ3S-Cy5.5. The target-to-background ratio observed on the NIRF images was significantly higher in the γ3-Cy5.5 group (10.2, 13.6) compared with the γ3S-Cy5.5 group (4.4, 4.0) at 1 and 2 h, respectively. Conclusions: This is the first report of the use of ICAM-1-specific small-molecule probe for in vivo NIRF optical imaging of TNBC. This method provides a noninvasive and specific strategy for the early diagnosis of TNBC.
关键词： Triple-negative breast cancer,Near-infrared fluorescence imaging,Small-molecule probe,ICAM-1
更新于2025-09-23 15:23:52
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Breast tumor classification using different features of quantitative ultrasound parametric images
摘要： Rationale and objectives The ultrasound B-mode-based morphological and texture analysis and Nakagami parametric imaging have been proposed to characterize breast tumors. Since these three feature categories of ultrasonic tissue characterization supply information on different physical characteristics of breast tumors, by combining the above methods is expected to provide more clues for classifying breast tumors. Materials and methods To verify the validity of the concept, raw data were obtained from 160 clinical cases. Six different types of morphological-feature parameters, four texture features, and the Nakagami parameter of benignancy and malignancy were extracted for evaluation. The Pearson’s correlation matrix was used to calculate the correlation between different feature parameters. The fuzzy c-means clustering and stepwise regression techniques were utilized to determine the optimal feature set, respectively. The logistic regression, receiver operating characteristic curve, and support vector machine were used to estimate the diagnostic ability. Results The best performance was obtained by combining morphological-feature parameter (e.g., standard deviation of the shortest distance), texture feature (e.g., variance), and the Nakagami parameter, with an accuracy of 89.4%, a specificity of 86.3%, a sensitivity of 92.5%, and an area under receiver operating characteristic curve of 0.96. There was no significant difference between using fuzzy c-means clustering, logistic regression, and support vector machine based on the optimal feature set for breast tumors classification. Conclusion Therefore, we verified that different physical ultrasonic features are functionally complementary and thus improve the performance in diagnosing breast tumors. Moreover, the optimal feature set had the maximum discriminating performance should be irrelative to the power of classifiers.
关键词： Morphological features,Breast ultrasound,Nakagami parameter,Texture features,Classification
更新于2025-09-23 15:23:52
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Development of an Aptamer-Conjugated Polyrotaxane-Based Biodegradable Magnetic Resonance Contrast Agent for Tumor-Targeted Imaging
摘要： Gadolinium-based magnetic resonance imaging (MRI) contrast agents with biodegradability, biosafety, and high efficiency are highly desirable for tumor diagnosis. Herein, a biodegradable, AS1411-conjugated, α-cyclodextrin polyrotaxane-based MRI contrast agent (AS1411-G2(DTPA-Gd)-SS-PR) was developed for targeted imaging of cancer. The polyrotaxane-based contrast agent was achieved by the complexation of α-cyclodextrin (α-CD) and a linear poly(ethylene glycol) (PEG) chain containing disulfide linkages at two terminals. The disulfides enable the de-threading of the polyrotaxane into excretable small units due to cleavage of the disulfide linkages by reducing agents such as intracellular glutathione (GSH). Furthermore, the second-generation lysine dendron conjugated with gadolinium chelates and AS1411, a G-quadruplex oligonucleotide that has high binding affinity to nucleolin generally presenting a high level on the surface of tumor cells, coupled to the α-CD via click chemistry. The longitudinal relaxivity of AS1411-G2(DTPA-Gd)-SS-PR (11.7 mM?1 s?1) was two times higher than the clinically used Gd-DTPA (4.16 mM?1 s?1) at 0.5 T. The in vitro degradability was confirmed by incubating with 10 mM 1,4-Dithiothreitol (DTT). Additionally, the cytotoxicity, histological assessment and gadolinium retention studies showed that the prepared polyrotaxane-based contrast agent had a superior biocompatibility and was predominantly cleared renally without long-term accumulation toxicity. Importantly, AS1411-G2(DTPA-Gd)-SS-PR displayed the enhanced performance in MRI of breast cancer cells in vitro as well as a subcutaneous breast tumor in vivo due to the targeting ability of AS1411 aptamer. The enhanced performance was due to efficient multivalent interactions with tumor cells, producing faster accumulation and longer contrast imaging time at the tumor site. This work clearly confirms that the specially designed and fabricated α-CD-based polyrotaxane is a promising contrast agent with excellent contrast imaging performance and biosafety for tumor MR imaging.
关键词： AS1411 aptamer,biodegradability,polyrotaxanes,magnetic resonance imaging,breast cancer targeting
更新于2025-09-23 15:23:52
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Intratumorally Injected Photothermal Agent-Loaded Photodynamic Nanocarriers for Ablation of Orthotopic Melanoma and Breast Cancer
摘要： Traditional chemotherapy of cancers may lead to serious adverse reactions due to little drug distribution in tumors. Here, a combination of photothermal therapy (PTT) and photodynamic therapy (PDT) was used for local treatment of orthotopic melanoma and breast cancer via intratumoral (i.t.) injection of photothermal agent-loaded photodynamic nanocarriers. A hydrophobic derivative of indocyanine green, DCC, was synthesized and entrapped into a pH-sensitive photosensitizer-core copolymer, PDCZP, to form DCC@PDCZP. The nanocarriers showed remarkable fluorescence, high singlet oxygen quantum yields, and strong photothermal effect. Flow cytometry suggested that the nanocarriers were efficiently internalized by cancer cells. Near infrared thermal imaging and fluorescence self-imaging showed that the i.t. injected DCC@PDCZP mainly remained in the tumors but the intravenous (i.v.) nanocarriers were distributed a little. One i.t. injection of DCC@PDCZP was enough to ablate the orthotopic B16-F10 and 4T1 mouse tumors under 830 nm and 660 nm irradiation at 4 hours post-injection. More importantly, no local recurrences were found though scabs were formed at 9 days post-treatment. The major anticancer mechanisms included improvement of cancer cell necrosis due to hyperthermia, inhibition of neovascularization, and enhancement of cell apoptosis. The i.t. injection of PTT/PDT nanoformulations is thus a promising local treatment of superficial tumors.
关键词： zinc phthalocyanine,intratumoral injection,melanoma,indocyanine green,breast cancer,photodynamic therapy,photothermal therapy
更新于2025-09-23 15:23:52