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Over 8% of women will be diagnosed with breast tumors (BT) in their lifetime. Tumors are formed by the uncontrollable development of tissues in a specific area of the body. They can be benign or malignant. The best survival rate can be expected with earlier screening and diagnosis of the tumor. To distinguish between benign and malignant tumors in x-ray images of the breast, segmentation of the tumor is a crucial first step. Screening mammography is an efficient method of detecting BT. As a result, the research presented two distinct deep learning models, termed SegNet and UNet architectures, to segment BT from mammograms. Datasets accessible to the public were utilized in the proposed system, specifically INbreast. Histogram equalization is used on datasets during preprocessing to improve the compressed areas and normalize the pixel dispersion. To avoid overfitting and boost the quantity of training data, augmentation techniques are employed. The metrics like the dice coefficient (DC) and the Intersection of Union (IoU) score are considered to evaluate the model. The metrics of the SegNets model are greater than the U-Net, as demonstrated by the experimental results. For the INbreast dataset, the SegNets achieve a maximum DC of 92.75% and an IoU score of 86.49%. [ABSTRACT FROM AUTHOR]

To investigate the conventional ultrasound (US), contrast-enhanced ultrasound (CEUS) manifestations and the corresponding histopathological characteristics of patients diagnosed with breast encapsulated papillary carcinoma (EPC) and to explore the value of CEUS in diagnosis of EPC.The clinical, pathological, US, and CEUS features of 16 patients (17 lesions) with EPC confirmed by postoperative histopathology were retrospectively analyzed.EPC was prevalent in the postmenopausal women. The majority of conventional US images of EPC showed complex cystic and solid masses with circumscribed margins (70.6%), enhanced posterior echo (94.1%), no sonographic calcification (88.2%), rich blood flow in the solid components within lesions (70.6%) on Color Doppler flow imaging, and high resistance index of blood flow (94.1%). Moreover, CEUS showed mainly centripetal hyperenhancement of the solid components within the lesions with irregular outline, and the enhancement area of the whole masses was essentially the same as the B-mode US area.EPC typically presents as a complex cystic and solid mass. CEUS is helpful to clarify the extent of the solid component and facilitate preoperative core-needle biopsy. A comprehensive evaluation by CEUS is valuable for diagnosing EPC and combining it with clinical features are helpful to further improve the diagnosis of this rare kind of breast cancer. [ABSTRACT FROM AUTHOR]

Breast cancer is a potentially life-threatening disease is one of the most common cancers specially for women. For fast and effective treatment early detection of the tumor is very important. But the frequent checkup is not possible for many people with the traditional way of detection due to their cost and availability. To detect the biomedical imaging terahertz (THz) frequency is a suitable range and using patch antenna in biomedical detection is cost effective compared to the traditional methods. So, to detect the early stage of breast tumor, this article has proposed a graphene based THz antenna. The primary goal of this antenna is to detect the breast tumor with the improvement of the performance and the secondary goal is to make the antenna very light weighted. The design of the antenna was done using computer simulation technology (CST) studio and the dimension of the antenna is kept 18×23 μm2 and a breast phantom model has been designed and the performance analysis of the antenna has been done for both free space and breast tissue. The return loss of the antenna in free space is -52.4422 dB at 6.96 THz. The details of the detection of tumor through the proposed patch antenna has been shown in this study. [ABSTRACT FROM AUTHOR]

Ultrawideband (UWB) time‐reversal techniques are widely used in microwave imaging systems to detect and localize breast tumors. Measuring the scattering electromagnetic fields from a breast phantom can be time‐reversed and back‐propagated to refocus on a tumor. In this study, a Debye model was applied to the breast phantom. Using the decomposition of the time‐reversal operator (TR‐DORT), images were obtained in the UWB frequency range of 3.1–10.6 GHz. The conventional TR imaging method employs the free‐space Green's function to refocus on the tumor, which degrades refocusing in a lossy and dispersive breast phantom. We propose the use of the cylindrical dyadic Green's function in a three‐layer medium for TR imaging. The excitation system consists of a circular array of spiral antennas. The imaging results of the proposed Green's function in TR‐DORT were subsequently calculated, indicating successful tumor detection in different application scenarios of the lossy and dispersive breast phantom. [ABSTRACT FROM AUTHOR]

Although, superkiller complex protein 8 (SKI8), previously known as WDR61 has been identified and mapped in breast tumor, little is currently known about its function. This study aims to elucidate the role of WDR61 in breast tumor development and its potential as a therapeutic target. Here, we show that tamoxifen‐induced knockout of Wdr61 reduces the risk of breast tumors, resulting in smaller tumor size and weight, and improved overall survival. Furthermore, we show that knockdown of WDR61 compromises the proliferation of breast tumor cells with reduced colony‐forming capacity. Further investigations demonstrate that the protective effect of WDR61 loss on breast tumor development is due to genomic instability. Mechanistic studies reveal that WDR61 interacts with the R‐loop, and loss of WDR61 leads to R‐loops accumulation in breast tumor cells, causing DNA damage and subsequent inhibition of cell proliferation. In summary, this study highlights the critical dependence of breast tumors on WDR61, which suppresses R‐loop and counteracts endogenous DNA damage in tumor cells. [ABSTRACT FROM AUTHOR]

Breast conserving treatment typically involves surgical excision of tumor and adjuvant radiotherapy targeting the breast area or tumor bed. Accurately defining the tumor bed is challenging and lead to irradiation of greater volume of healthy tissues. Preoperative stereotactic body radiotherapy (SBRT) which target tumor may solves that issues. We conducted a systematic literature review to evaluates the early toxicity and cosmetic outcomes of this promising treatment approach. Secondary we reviewed pathological complete response (pCR) rates, late toxicity, patient selection criteria and radiotherapy protocols. We retrieved literature from PubMed, Scopus, Web of Science, Cochrane, ScienceDirect, and ClinicalTrials.gov. The study adhered to the PRISMA 2020 guidelines. Ten prospective clinical trials (7 phase II, 3 phase I), encompassing 188 patients (aged 18–75 years, cT1-T3 cN0-N3 cM0, primarily with ER/PgR-positive, HER2-negative status,), were analyzed. Median follow-up was 15 months (range 3–30). Treatment involved single-fraction SBRT (15-21Gy) in five studies and fractionated (19.5–31.5Gy in 3 fractions) in the rest. Time interval from SBRT to surgery was 9.5 weeks (range 1–28). Acute and late G2 toxicity occurred in 0–17% and 0–19% of patients, respectively, G3 toxicity was rarely observed. The cosmetic outcome was excellent in 85–100%, fair in 0–10% and poor in only 1 patient. pCR varied, showing higher rates (up to 42%) with longer intervals between SBRT and surgery and when combined with neoadjuvant systemic therapy (up to 90%). Preoperative SBRT significantly reduce overall treatment time, enabling to minimalize volumes. Early results indicate excellent cosmetic effects and low toxicity. [ABSTRACT FROM AUTHOR]

It is necessary to verify whether nail fold capillaroscopy can be utilized for the early detection of breast cancer. To establish this technology, an animal model was developed, utilizing mice for nail fold observations. Nail fold capillaroscopy revealed a human-like anatomical pattern and facilitated the observation of cellular movement within blood vessels. Injection of MCF-7 or mammary fibroblasts in mice allowed the observation of cellular vibrations using motion microscopy from nail fold. We have named this technology 'capillary cell motion microscopy.' Intriguingly, we were able to identify distinct cellular vibrations in the MCF-7 group. Moreover, evaluating its effectiveness in mice with chemically induced cancer revealed higher sensitivity (81%-85%) compared to conventional methods (45%-68%). Capillary cell motion microscopy, operating at 0.5–1.5 Hz, provided clear distinction of tumor cells and demonstrated potential applicability in human subjects. While condition adjustments may be necessary, this method holds promise for noninvasive breast cancer detection through nail fold observations. [ABSTRACT FROM AUTHOR]

Background: Breast tumor is a fatal threat to the health of women. Ultrasound (US) is a common and economical method for the diagnosis of breast cancer. Breast imaging reporting and data system (BI‐RADS) category 4 has the highest false‐positive value of about 30% among five categories. The classification task in BI‐RADS category 4 is challenging and has not been fully studied. Purpose: This work aimed to use convolutional neural networks (CNNs) for breast tumor classification using B‐mode images in category 4 to overcome the dependence on operator and artifacts. Additionally, this work intends to take full advantage of morphological and textural features in breast tumor US images to improve classification accuracy. Methods: First, original US images coming directly from the hospital were cropped and resized. In 1385 B‐mode US BI‐RADS category 4 images, the biopsy eliminated 503 samples of benign tumor and left 882 of malignant. Then, K‐means clustering algorithm and entropy of sliding windows of US images were conducted. Considering the diversity of different characteristic information of malignant and benign represented by original B‐mode images, K‐means clustering images and entropy images, they are fused in a three‐channel form multi‐feature fusion images dataset. The training, validation, and test sets are 969, 277, and 139. With transfer learning, 11 CNN models including DenseNet and ResNet were investigated. Finally, by comparing accuracy, precision, recall, F1‐score, and area under curve (AUC) of the results, models which had better performance were selected. The normality of data was assessed by Shapiro‐Wilk test. DeLong test and independent t‐test were used to evaluate the significant difference of AUC and other values. False discovery rate was utilized to ultimately evaluate the advantages of CNN with highest evaluation metrics. In addition, the study of anti‐log compression was conducted but no improvement has shown in CNNs classification results. Results: With multi‐feature fusion images, DenseNet121 has highest accuracy of 80.22 ± 1.45% compared to other CNNs, precision of 77.97 ± 2.89% and AUC of 0.82 ± 0.01. Multi‐feature fusion improved accuracy of DenseNet121 by 1.87% from classification of original B‐mode images (p < 0.05). Conclusion: The CNNs with multi‐feature fusion show a good potential of reducing the false‐positive rate within category 4. The work illustrated that CNNs and fusion images have the potential to reduce false‐positive rate in breast tumor within US BI‐RADS category 4, and make the diagnosis of category 4 breast tumors to be more accurate and precise. [ABSTRACT FROM AUTHOR]

Radiologists and clinicians must automatically examine breast and tumor locations and sizes accurately. In recent years, several neural network‐based feature fusion versions have been created to improve medical image segmentation. Multi‐modal image fusion photos may efficiently identify tumors. This work uses image fusion to identify computed tomography and magnetic resonance imaging alterations. A Gauss‐log ratio operator is recommended for difference image production. The Gauss‐log ratio and log ratio difference image complement the objective of improving the difference map through image fusion. The feature change matrix extracts edge, texture, and intensity from each picture pixel. The final change detection map classifies feature vectors as "changed" or "unchanged" which has been mapped for high‐resolution or low‐resolution pixels. This paper proposes a multi‐feature blocks (MFB) based neural network for multi‐feature fusion. This neural network modeling approach globalizes pixel spatial relationships. MFB‐based feature fusion also aims to capture channel interactions between feature maps. The proposed technique outperforms state‐of‐the‐art approaches which have been discussed in detail in experimental results section. [ABSTRACT FROM AUTHOR]

A flexible slotted metamaterial backed microstrip (SMBM) antenna operating at 2.45 GHz is proposed in this article for breast tumor detection. The substrate used is flexible optically transparent polydimethylsiloxane (PDMS) with 1-mm thickness, and copper is used for conducting layer. The SMBM antenna consists of partial ground and metasurface unit cells. It is noted that with the addition of metamaterial layers in the antenna the bandwidth, reflection co-efficient got improved and the specific absorption rate (SAR) value is reduced. Two different kinds of phantoms are arranged: one is a skin phantom and the other is a breast phantom; the antenna of the flat and flexible condition is placed on the phantoms and the analysis is observed. The detection of tumors can be observed by the variance in the value of E-Field, H-Field, and J-Surf between the phantom has a tumor and no tumor. A notable amount of difference is obtained which represents the existence of a tumor. The antenna has the SAR value, which is less than 1.6 W/kg as per the guidance of Federal Communications Commission (FCC) standard. Alongside SAR, by utilizing metamaterial, the gain of the SMBM antenna is likewise improved and the efficiency of the SMBM is expanded with 67% (to 92%) by the consideration of metamaterial construction. The results of the fabricated antenna are analyzed, and comparisons are made with the simulated antenna. [ABSTRACT FROM AUTHOR]

In preclinical studies, accurate monitoring of tumor dynamics is crucial for understanding cancer biology and evaluating therapeutic interventions. Traditional methods like caliper measurements and bioluminescence imaging (BLI) have limitations, prompting the need for improved imaging techniques. This study introduces a fast-scan high-frequency ultrasound (HFUS) protocol for the longitudinal assessment of syngeneic breast tumor grafts in mice, comparing its performance with caliper, BLI measurements and with histological analysis. The E0771 mammary gland tumor cell line, engineered to express luciferase, was orthotopically grafted into immunocompetent C57BL/6 mice. Tumor growth was monitored longitudinally at multiple timepoints using caliper measurement, HFUS, and BLI, with the latter two modalities assessed against histopathological standards post-euthanasia. The HFUS protocol was designed for rapid, anesthesia-free scanning, focusing on volume estimation, echogenicity, and necrosis visualization. All mice developed tumors, only 20.6% were palpable at day 4. HFUS detected tumors as small as 2.2 mm in average diameter from day 4 post-implantation, with an average scanning duration of 47 s per mouse. It provided a more accurate volume assessment than caliper, with a lower average bias relative to reference tumor volume. HFUS also revealed tumor necrosis, correlating strongly with BLI in terms of tumor volume and cellularity. Notable discrepancies between HFUS and BLI growth rates were attributed to immune cell infiltration. The fast HFUS protocol enables precise and efficient tumor assessment in preclinical studies, offering significant advantages over traditional methods in terms of speed, accuracy, and animal welfare, aligning with the 3R principle in animal research. [ABSTRACT FROM AUTHOR]

Objective To construct methoxy polyethylene glycol (mPEG) modified gold nanoparticles (AuNPs) loaded with doxorubicin (DOX) AuNPs-mPEG@DOX in order to reduce the toxicity and side effects of DOX. Methods AuNPsmPEG@DOX was prepared and characterized by Z-Average, Zeta potential and UV-Vis spectroscopy. The impact of thiol-linked DOX (HS-DOX) at various dosage concentrations on the drug adsorption rate and drug loading of AuNPs-mPEG@DOX was investigated. Furthermore, a HPLC method was developed to accurately determine the content of unadsorbed HS-DOX in AuNPsmPEG@DOX. The specificity, linearity, precision, stability and average recovery of this method were thoroughly investigated. The cytotoxic effect of AuNPs-mPEG@DOX on MCF-10A and MCF-7 cells was evaluated using a CCK-8 assay. Results AuNPsmPEG@DOX was successfully prepared with Z-Average of (46.12±0.49) nm, Zeta potential of (18.60±1.51) nm and the maximum absorption wavelength of 530 nm. An efficient HPLC method for the detection of unadsorbed HS-DOX in AuNPs-mPEG@DOX was devised. The optimal dosage concentration of HS-DOX for AuNPs-mPEG@DOX was determined to be 11.18 μg/ml, resulting in a drug adsorption rate of (9.21±2.88)% and a drug loading rate of (2.01±0.62)%. Cytotoxicity experiments demonstrated that AuNPs-mPEG@DOX significantly reduced the toxic and side effects of DOX on normal breast cells. Additionally, AuNPsmPEG@DOX and free DOX exhibited comparable cytotoxic effects on breast tumor cells when DOX concentration was equal to or greater than 4.75 μmol/L. Conclusion AuNPs-mPEG@DOX effectively reduce the toxicity of DOX, providing a reference for future research on reducing the toxicity of AuNPs-linked drugs. [ABSTRACT FROM AUTHOR]

Breast cancer is one of the most common cancers in the world, especially among women. Breast tumor segmentation is a key step in the identification and localization of the breast tumor region, which has important clinical significance. Inspired by the swin-transformer model with powerful global modeling ability, we propose a semantic segmentation framework named Swin-Net for breast ultrasound images, which combines Transformer and Convolutional Neural Networks (CNNs) to effectively improve the accuracy of breast ultrasound segmentation. Firstly, our model utilizes a swin-transformer encoder with stronger learning ability, which can extract features of images more precisely. In addition, two new modules are introduced in our method, including the feature refinement and enhancement module (RLM) and the hierarchical multi-scale feature fusion module (HFM), given that the influence of ultrasonic image acquisition methods and the characteristics of tumor lesions is difficult to capture. Among them, the RLM module is used to further refine and enhance the feature map learned by the transformer encoder. The HFM module is used to process multi-scale high-level semantic features and low-level details, so as to achieve effective cross-layer feature fusion, suppress noise, and improve model segmentation performance. Experimental results show that Swin-Net performs significantly better than the most advanced methods on the two public benchmark datasets. In particular, it achieves an absolute improvement of 1.4–1.8% on Dice. Additionally, we provide a new dataset of breast ultrasound images on which we test the effect of our model, further demonstrating the validity of our method. In summary, the proposed Swin-Net framework makes significant advancements in breast ultrasound image segmentation, providing valuable exploration for research and applications in this domain. [ABSTRACT FROM AUTHOR]

Key Clinical Message: Pseudoangiomatous stromal hyperplasia (PASH) is a rare lesion of the breast stromal tissue with unknown mechanism. Hormonal stimulation of mammary myofibroblasts is the most important theory due to stromal positivity of progesterone receptor (PR) or/and estrogen receptor (ER). We report a case of PASH with stromal PR/ER negativity. [ABSTRACT FROM AUTHOR]

Early detection of breast cancer can be a life‐saving measure for many patients. The inaccessibility of X‐rays, magnetic resonance imaging (MRI), and other medical facilities in many resource‐constrained areas hinders the early detection of breast cancer. In this paper, the use of a rectangular patch antenna for breast cancer detection is proposed by using multiwall carbon nanotubes (MWCNTs) as patch material. The proposed antenna is designed by CST software which is (30 × 40 × 1.66) mm in dimension. A breast model is designed including tumor and cancerous tumors by specific tissue properties for observing the antenna performance in different cases. In free space, the return loss of the designed antenna is observed at −33.414 dB. Moreover, the S11 is examined in a normal breast, a breast including a normal tumor, and a breast including a cancerous tumor is −32.641 dB, −34.94 dB, and −35.22 dB respectively. It can be utilized on a human body phantom model due to its adaptability and reduced radiation properties. The proposed antenna is miniature in size, cost‐effective, easily portable, and eco‐friendly. It can be used as a first screening tool for breast cancer patients, particularly in resource‐constrained regions. [ABSTRACT FROM AUTHOR]

Background: TGFβ induces several cell phenotypes including senescence, a stable cell cycle arrest accompanied by a secretory program, and epithelial-mesenchymal transition (EMT) in normal epithelial cells. During carcinogenesis cells lose the ability to undergo senescence in response to TGFβ but they maintain an EMT, which can contribute to tumor progression. Our aim was to identify mechanisms promoting TGFβ-induced senescence escape. Methods: In vitro experiments were performed with primary human mammary epithelial cells (HMEC) immortalized by hTert. For kinase library screen and modulation of gene expression retroviral transduction was used. To characterize gene expression, RNA microarray with GSEA analysis and RT-qPCR were used. For protein level and localization, Western blot and immunofluorescence were performed. For senescence characterization crystal violet assay, Senescence Associated-β-Galactosidase activity, EdU staining were conducted. To determine RSK3 partners FLAG-baited immunoprecipitation and mass spectrometry-based proteomic analyses were performed. Proteosome activity and proteasome enrichment assays were performed. To validate the role of RSK3 in human breast cancer, analysis of METABRIC database was performed. Murine intraductal xenografts using MCF10DCIS.com cells were carried out, with histological and immunofluorescence analysis of mouse tissue sections. Results: A screen with active kinases in HMECs upon TGFβ treatment identified that the serine threonine kinase RSK3, or RPS6KA2, a kinase mainly known to regulate cancer cell death including in breast cancer, reverted TGFβ-induced senescence. Interestingly, RSK3 expression decreased in response to TGFβ in a SMAD3-dependent manner, and its constitutive expression rescued SMAD3-induced senescence, indicating that a decrease in RSK3 itself contributes to TGFβ-induced senescence. Using transcriptomic analyses and affinity purification coupled to mass spectrometry-based proteomics, we unveiled that RSK3 regulates senescence by inhibiting the NF-κΒ pathway through the decrease in proteasome-mediated IκBα degradation. Strikingly, senescent TGFβ-treated HMECs display features of epithelial to mesenchymal transition (EMT) and during RSK3-induced senescence escaped HMECs conserve EMT features. Importantly, RSK3 expression is correlated with EMT and invasion, and inversely correlated with senescence and NF-κΒ in human claudin-low breast tumors and its expression enhances the formation of breast invasive tumors in the mouse mammary gland. Conclusions: We conclude that RSK3 switches cell fate from senescence to malignancy in response to TGFβ signaling. [ABSTRACT FROM AUTHOR]

This article proposes a low‐profile ultra‐wideband (UWB) antenna for breast tumor detection using the monostatic radar‐based microwave imaging (RBMI) technique. The proposed UWB antenna consists of a circular patch and ground plane along with a modified tapered feed line having a total size of 13 × 9 × 1.6 mm3. The designed antenna operates from 4 to 11 GHz based on a −10 dB reflection coefficient with a peak gain of 9.5 dBi at 4.8 GHz. Experimental validation is carried out after fabricating the prototype of the UWB antenna and the breast mimic. The measured backscattered signals are captured using the vector network analyzer (E‐5063A) by keeping the antenna at 10 mm from the breast phantom. After that, post‐processing of the measured data is done to detect the exact depth and location of the malignant tissue. The proposed antenna uses UWB band frequency of operation because it has some unique features, that is, it provides immunity to multipath fading, has a simple design, has a low cost of fabrication, and has biological friendliness. Moreover, due to the proposed antenna's resonance at a lower resonant frequency better depth of penetration is achieved in human body phantoms and the proposed antenna provides specific absorption rates (SAR) of 0.877 W/kg over 1 g of tissue at 4.8 GHz, which is an acceptable limit for SAR as per FCC guidelines. Therefore, the proposed antenna and monostatic RBMI technique are good candidates for breast tumor detection. [ABSTRACT FROM AUTHOR]

Objective：To discuss the effect of shear wave elastography (SWE) on the differential diagnosis of benign and malignant breast non-mass lesion (NML), and to clarify its clinical significance. Methods：A total of 158 patients with breast NML were selected and divided into benign lesion group (n=83) and malignant lesion group(n=75) according to the postoperative pathological type of the patients. The routine ultrasound and SWE examinations were conducted before operation, and the SWE parameters of the lesions, including the maximum (Emax), average (Emean), minimum (Emin), standard deviation (Esd) and whether the stiff rim sign presented or not at 1, 2 and 3 mm around the lesion were recorded. The SWE characteristics and differences in SWE parameters of the NML patients between two groups were analyzed, and the receiver operating characteristic curve(ROC) was plotted, and the area under curve (AUC), specificity and sensitivity were calculated. Results：There were statistically significant differences in age, lesion size, palpation, and whether menopause had crested of the NML patients between two groups (P<0. 01). All the lesions of the patients in two groups appeared as hyperechoic and irregular in shape. Compared with benign lesion group, the percentage of the patients with non-parallel, calcification and posterior echo attenuation in malignant lesion group was significantly increased (P<0. 01), and the percentage of the patients without blood supply was significantly decreased (P<0. 01). Compared with benign lesion group, the Emax, Emean, and Esd of the NML patients in malignant lesion group were significantly increased (P<0. 01), and the Emax, Emean, and Esd at 1, 2, and 3 mm around the lesion were all increased (P<0. 01). The stiff rim sign manifested as a circular or semi-circular red region around the lesions of the patients in malignant lesion group. Compared with benign lesion group, the percentage of hard rim sign of the NML patients in malignant lesion group was significantly increased (P<0. 01). Compared with inside the lesion, the Emin at 1, 2 and 3 mm around the lesion of the NML patients in benign lesion group and malignant lesion group were decreased(P<0. 01). The AUC of Emax at 1, 2 and 3 mm around the lesion were 0. 872, 0. 860, 0. 873 and 0. 866, respectively； the AUC of Emean were 0. 796, 0. 822, 0. 820 and 0. 815, respectively； the AUC of Esd were 0. 832, 0. 857, 0. 859, and 0. 842, respectively；the sensitivity and specificity of Emax inside the lesion were 85. 33% and 83. 13%, respectively； the sensitivity and specificity of Emax at 1 mm around the lesion were 82. 67% and 80. 72%, respectively； the sensitivity and specificity at 2 mm around the lesion were 78. 67% and 87. 95%, respectively； the sensitivity and specificity at 3 mm around the lesion were 80. 00% and 86. 75%, respectively； the specificity of Esd at 2 mm around the lesion was highest (93. 33%). Conclusion: The SWE parameters inside and around the lesion and the manifestation of stiff rim sign can provide the reference for the differential diagnosis of benign and malignant breast NML, and have good diagnostic performance. [ABSTRACT FROM AUTHOR]

Background: Breast cancer is a typically diagnosed and life‐threatening cancer in women. Thus, dynamic contrast‐enhanced magnetic resonance imaging (DCE‐MRI) is increasingly used for breast lesion detection and diagnosis because of the high resolution of soft tissues. Moreover, supervised detection methods have been implemented for breast lesion detection. However, these methods require substantial time and specialized staff to develop the labeled training samples. Purpose: To investigate the potential of weakly supervised deep learning models for breast lesion detection. Methods: A total of 1003 breast DCE‐MRI studies were collected, including 603 abnormal cases with 770 breast lesions and 400 normal subjects. The proposed model was trained using breast DCE‐MRI considering only the image‐level labels (normal and abnormal) and optimized for classification and detection sub‐tasks simultaneously. Ablation experiments were performed to evaluate different convolutional neural network (CNN) backbones (VGG19 and ResNet50) as shared convolutional layers, as well as to evaluate the effect of the preprocessing methods. Results: Our weakly supervised model performed better with VGG19 than with ResNet50 (p < 0.05). The average precision (AP) of the classification sub‐task was 91.7% for abnormal cases and 88.0% for normal samples. The area under the receiver operating characteristic (ROC) curve (AUC) was 0.939 (95% confidence interval [CI]: 0.920–0.941). The weakly supervised detection task AP was 85.7%, and the correct location (CorLoc) was 90.2%. A sensitivity of 84.0% at two‐false positives per image was assessed based on free‐response ROC (FROC) curve. Conclusions: The results confirm that a weakly supervised CNN based on self‐transfer learning is an effective and promising auxiliary tool for detecting breast lesions. [ABSTRACT FROM AUTHOR]

Human colostrum and milk contain diverse cells and soluble components that have the potential to act against tumors. In breast cancer, macrophages play a significant role in immune infiltration and contribute to the progression and spread of tumors. However, studies suggest that these cells can be reprogrammed to act as an antitumor immune response. This study aimed to evaluate the levels of melatonin and its receptors, MT1 (melatonin receptor 1) and MT2 (melatonin receptor 2), in colostrum and assess the differentiation and polarization of the colostrum macrophages modulated by melatonin in the presence of breast tumor cells. Colostrum samples were collected from 116 mothers and tested for their melatonin and receptor levels. The colostrum cells were treated with or without melatonin and then cultured for 24 h in the presence or absence of breast tumor cells. The results showed that melatonin treatment increased the expression of MT1 and MT2 in the colostrum cells. Furthermore, melatonin treatment increased the percentage of M1 macrophages and decreased the percentage of M2 macrophages. When the colostrum macrophages were cocultured with breast tumor cells, melatonin reduced the percentage of both macrophage phenotypes and the cytokines tumor necrosis factor-alpha (TNF-α) and interleukin 8 (IL-8). These data suggest that melatonin can regulate the inflammatory process via M1 macrophages in the tumor microenvironment and, simultaneously, the progression of M2 macrophages that favor tumorigenesis. [ABSTRACT FROM AUTHOR]

Introduction Breast cancer is the most common cancer in women in India and accounts for 14% of all cancers in women. Rise in mortality is due to lack of awareness and proper screening. Mammography and presently available serum biomarkers have low sensitivity and specificity. In our quest to identify a better biomarker, we studied mammaglobin (MAM) in patients with breast cancer and benign breast tumors. Aim To evaluate serum mammaglobin in breast cancer patients and compare it with benign breast tumor patients and healthy controls. To compare it with existing biomarkers serum carcinoembryonic antigen (CEA) and cancer antigen 15–3 (CA 15–3). Materials and methods: This is a cross-sectional, case–control study of 77 subjects, of which 27 were breast cancer patients, 20 benign breast tumor patients, and 30 healthy controls. Serum CEA and CA15–3 were estimated by electrochemiluminescence immunoassay (ECLIA) and mammaglobin (MAM) by enzyme-linked immunosorbent assay (ELISA). Results Mammaglobin and CEA levels were elevated in breast cancer patients, followed by benign breast tumors when compared with controls (P < 0.000001). Mammaglobin showed 81.5% sensitivity, 100% specificity, 100% positive predictive value (PPV), and 88.9% negative predictive value (NPV). CEA showed 88.9% sensitivity, 82.5% specificity, 77.4% PPV, and 91.7% NPV. The area under the curve was the highest for MAM (0.892), followed by CEA (0.889) and CA 15–3 (0.555). CA15–3 showed poor diagnostic efficacy. Combined receiver operating characteristic (ROC) curve of the biomarkers MAM and CEA had an AUC of 0.913. Conclusion Mammaglobin proved to be an efficacious biomarker in diagnosing breast cancer. [ABSTRACT FROM AUTHOR]

BACKGROUND: Breast diseases are a significant health threat for women. With the fast-growing BSGI data, it is becoming increasingly critical for physicians to accurately diagnose benign as well as malignant breast tumors. OBJECTIVE: The purpose of this study is to diagnose benign and malignant breast tumors utilizing the deep learning model, with the input of breast-specific gamma imaging (BSGI). METHODS: A benchmark dataset including 144 patients with benign tumors and 87 patients with malignant tumors was collected and divided into a training dataset and a test dataset according to the ratio of 8:2. The convolutional neural network ResNet18 was employed to develop a new deep learning model. The model proposed was compared with neural network and autoencoder models. Accuracy, specificity, sensitivity and ROC were used to evaluate the performance of different models. RESULTS: The accuracy, specificity and sensitivity of the model proposed are 99.1%, 98.8% and 99.3% respectively, which achieves the best performance among all methods. Additionally, the Grad-CAM method is used to analyze the interpretability of the diagnostic results based on the deep learning model. CONCLUSION: This study demonstrates that the proposed deep learning method could help physicians diagnose benign and malignant breast tumors quickly as well as reliably. [ABSTRACT FROM AUTHOR]

In this paper, a wideband antenna is proposed for ultra-wideband microwave imaging applications. The antenna is comprised of a tapered slot ground, a rectangular slotted patch and four star-shaped parasitic components. The added slotted patch is shown to be effective in improving the bandwidth and gain. The proposed antenna system provides a realized gain of 6 dBi, an efficiency of around 80% on the radiation bandwidth, and a wide impedance bandwidth (S11 < −10 dB) of 6.3 GHz (from 3.8 to 10.1 GHz). This supports a true wideband operation. Furthermore, the fidelity factor for face-to-face (FtF) direction is 91.6%, and for side by side (SbS) is 91.2%. This proves the excellent directionality and less signal distortion of the designed antenna. These high figures establish the potential use of the proposed antenna for imaging. A heterogeneous breast phantom with dielectric characteristics identical to actual breast tissue with the presence of tumors was constructed for experimental validation. An antenna array of the proposed antenna element was situated over an artificial breast to collect reflected and transmitted waves for tumor characterization. Finally, an imaging algorithm was used to process the retrieved data to recreate the image in order to detect the undesirable tumor object inside the breast phantom. [ABSTRACT FROM AUTHOR]

Breast cancer is the most common type of cancer in women, and early detection is important to significantly reduce its mortality rate. This study introduces a detection and diagnosis system that automatically detects and classifies breast tumors in CT scan images. First, the contours of the chest wall are extracted from computed chest tomography images, and two-dimensional image characteristics and three-dimensional image features, together with the application of active contours without edge and geodesic active contours methods, are used to detect, locate, and circle the tumor. Then, the computer-assisted diagnostic system extracts features, quantifying and classifying benign and malignant breast tumors using a greedy algorithm and a support vector machine. The study used 174 breast tumors for experiment and training and performed cross-validation 10 times (k-fold cross-validation) to evaluate performance of the system. The accuracy, sensitivity, specificity, and positive and negative predictive values of the system were 99.43%, 98.82%, 100%, 100%, and 98.89% respectively. This system supports the rapid extraction and classification of breast tumors as either benign or malignant, helping physicians to improve clinical diagnosis. [ABSTRACT FROM AUTHOR]

To observe the characteristics of a new extracorporeal high intensity focused ultrasound transducer, titled Haifu system JCQ-B, and to compare its safety and efficacy for breast ablation with the standard Haifu system JC transducer. Ox liver with pig skin and pork ribs were prepared in a semi-sphere shape, served as in vitro acoustic model. The udders of female goats were used as in vivo acoustic model. Both in vitro and in vivo models were ablated by either JCQ-B or JC transducer. The morphology of biological focal region (BFR), the coagulative necrosis volume, and the temperature increase were observed and compared. The BFR morphology of JCQ-B transducer was circular both in vitro and in vivo, with a length-width ratio close to one. Under the same sonication parameters (sonication power, time and depth in tissue), coagulation necrosis volume caused by JCQ-B transducer was larger than that caused by JC transducer both in vitro and in vivo. The increase in temperature in the near and far acoustic pathways with JCQ-B transducer was significantly lower than that of JC transducer in vitro. After receiving high sonication energy during in vivo experimentation, there were no complications observed after the ablation of JCQ-B transducer, while small skin damage was observed after the ablation of JC transducer. The JCQ-B transducer improved the safety and efficacy of treatment by optimizing BFR morphology and ablation efficiency, which could be applied in the treatment of breast tumor. [ABSTRACT FROM AUTHOR]

BACKGROUND: Antennas for the microwave imaging system are large which results in higher radiation, manufacturing cost, poor radiation characteristics and it will be difficult to locate on breast tissues. OBJECTIVE: We propose a wearable ultra-wide band antenna for use in the diagnosis of breast cancer bio-medical applications. METHODS: The antenna has been fabricated on 1.6 mm FR4 substrate with a dimension of 28 × 14.4 mm 2 and can operate between 2 GHz–12 GHz with S 11 < - 10 dB with best radiation characteristics. The prototype of the proposed antenna was fabricated and practically tested and the results were found to be consistent with the simulated results. The proposed UWB antenna is intended to radiate and receive information covering the entire spectrum from 3 GHz to 13 GHz. For good impendence matching throughout the larger spectrum, the defected ground structure (diamond shape) was exploited. All the dimensions of the proposed design are confirmed by parametric study and optimization. RESULTS: The maximum simulated efficiency was ranging from 80 to 84% in the desired operating frequency. The maximum Specific Absorption Rate of the proposed antenna was 0.98 W/Kg. Therefore, the proposed UWB antenna could be the right structure for breast cancer diagnosis in terms of SAR. The antenna was found to have a substantial radiation efficiency of around 78%–84% in the desired operating bandwidth. The overall realized gain of the proposed UWB antenna was seen ranging from 1.8–4.2 dB which is sufficient for bio-medical applications. CONCLUSION: The breast phantom was modeled for the validation of the performance of the antenna and SAR was analyzed. The value of SAR of the designed antenna was observed at about 0.98 W/Kg, which is suitable for medical applications. [ABSTRACT FROM AUTHOR]

As an emerging cancer therapy with high selectivity, minimally invasive and low side effects, photodynamic therapy (PDT) has become the focus of current researches. The breast cancer is a malignant tumor with the highest incidence in women. Thus, it is valuable for improving its treatment efficiency to construct efficient photosensitizer. To this end, we engineered a high stable near-infrared photosensitizer NPA-NH 2 based on "step by step" strategy. By modifying the optically tunable amino group of NPA-NH 2 , a peroxynitrite (ONOO-) activated NPA-ONOO - theranostic agent with a new trifluoromethylsulfonamide recognization site was designed and synthesized. It possessed a good singlet oxygen-generating ability after ONOO- activation under 660 nm light, and a high sensitivity (limit of detection: 0.038 μM) and selectivity respond toward ONOO- in buffer solution. The theranostic agent was able to specially monitor ONOO- in tumor cells. Furthermore, we have succeeded in applying the NPA-ONOO - for efficient and precise photodynamic therapy of breast cancer cells and tumors in vivo. This work provides a new way for the design of highly stable photosensitizers and a reliable tool for effective treatment of breast tumors. [Display omitted] • Engineering a high stable theranostic agent with a new trifluoromethylsulfonamide recognization site. • The agent can response ONOO- with high sensitivity and selectivity in vitro and in vivo. • The agent showed a significant killing effect on breast cancer cells under 660 nm light. • Efficient photodynamic therapy of breast tumors in vivo was achieved by NPA-ONOO - . [ABSTRACT FROM AUTHOR]

Background: Micro RNA of Marsupenaeus japonicas has been known to promote apoptosis of tumor cells. However, the detailed mechanisms are not well understood. Results: Using tomographic microscope, which can detect the internal structure of cells, we observed breast tumor cells following treatment of the miRNA. Intriguingly, we found that mitochondria migrate to an adjacent tumor cells through a tunneling nanotube. To recapitulate this process, we engineered a microfluidic device through which mitochondria were transferred. We show that this mitochondrial transfer process released endonuclease G (Endo G) into tumor cells, which we referred to herein as unsealed mitochondria. Importantly, Endo G depleted mitochondria alone did not have tumoricidal effects. Moreover, unsealed mitochondria had synergistic apoptotic effects with subtoxic dose of doxorubicin thereby mitigating cardiotoxicity. Conclusions: Together, we show that the mitochondrial transfer through microfluidics can provide potential novel strategies towards tumor cell death. [ABSTRACT FROM AUTHOR]

Background: The cornerstone of management of phyllodes tumor is surgery. No standard of care exists regarding adjuvant therapy; however, local recurrence is a predominant pattern of failure. The aims of this study were to evaluate the clinical characteristics and treatment patterns of phyllodes tumor and to compare local recurrence and disease-free survival rates of patients with borderline and malignant phyllodes tumor treated with or without adjuvant radiotherapy. Materials and Methods: We analyzed the demographic data, treatment details, and recurrence patterns of all patients with nonmetastatic phyllodes tumors of the breast (n = 34) treated with a multimodality approach who presented to our institute from January 2015 to December 2020. Results: The median age at presentation was 41.2 years, and the median tumor size was 12.5 cm. All patients underwent definitive surgical procedures in the form of wide local excision or mastectomy. No recurrence was noted in the patients with a benign histology. After a median follow-up period of 38 months, the local recurrence rate was 27% for the patients with borderline and malignant histology treated with adjuvant radiotherapy (n = 11) versus 47% for those (n = 17) who did not receive adjuvant radiotherapy. The 3-year local recurrence-free survival rate was 72% in the adjuvant radiotherapy group, versus 51% in the surgery only group. Conclusion: The results of the current study confirm the excellent prognosis of patients with benign phyllodes tumor undergoing surgery alone. Local recurrence was the predominant mode of failure in the patients with borderline and malignant histology. Locoregional control was improved with the addition of postoperative radiotherapy in the patients with borderline and malignant histology irrespective of margin status. [ABSTRACT FROM AUTHOR]

Simple Summary: ROS and JAK/Stat3 cooperatively upregulate the expression of HIF-1α in bone marrow-derived mesenchymal stem cells under normoxic conditions in response to breast tumor cells. The upregulation of HIF-1α contributes in part to the increase in VEGF expression in the bone marrow-derived mesenchymal stem cells. Bone marrow-derived mesenchymal stem cells improve the angiogenic sprouting capacity of mature endothelial cells in a VEGF-dependent manner. Breast tumor cells recruit bone marrow-derived mesenchymal stem cells (BM-MSCs) and alter their cellular characteristics to establish a tumor microenvironment. BM-MSCs enhance tumor angiogenesis through various mechanisms. We investigated the mechanisms by which BM-MSCs promote angiogenesis in response to breast tumor. Conditioned media from MDA-MB-231 (MDA CM) and MCF7 (MCF7 CM) breast tumor cells were used to mimic breast tumor conditions. An in vitro spheroid sprouting assay using human umbilical vein endothelial cells (HUVECs) was conducted to assess the angiogenesis-stimulating potential of BM-MSCs in response to breast tumors. The ROS inhibitor N-acetylcysteine (NAC) and JAK inhibitor ruxolitinib attenuated increased HIF-1α in BM-MSCs in response to MDA CM and MCF7 CM. HIF-1α knockdown or HIF-1β only partially downregulated VEGF expression and, therefore, the sprouting capacity of HUVECs in response to conditioned media from BM-MSCs treated with MDA CM or MCF7 CM. Inactivation of the VEGF receptor using sorafenib completely inhibited the HUVECs' sprouting. Our results suggest that increased HIF-1α expression under normoxia in BM-MSCs in response to breast tumor cells is mediated by ROS and JAK/Stat3, and that both HIF-1α-dependent and -independent mechanisms increase VEGF expression in BM-MSCs to promote the angiogenic sprouting capacity of endothelial cells in a VEGF-dependent manner. [ABSTRACT FROM AUTHOR]

Breast cancer treatment failure is related to low response rates, high costs, and long-term toxicities. Thus, it is necessary to find less toxic, cheaper, and more effective treatments. In situ administration ensures drug delivery to tumor cells and decreases systemic toxic effects. The androstene-3β, 17α-diol (α-AED) reduces breast tumor cell proliferation and is an ideal candidate to treat mammary tumors. This study aims to identify the in vitro and in vivo effects of α-AED on a triple-negative mammary tumor model. An in vitro biphasic steroid effect was observed in mouse and human mammary tumor cells treated with α-AED. In this sense, cells treated with higher doses (100 and 200 μM) showed an antiproliferative effect. The α-AED administrated intratumorally reduced average tumor weight and increased the percentage of natural killer cells (NK), plasmatic, and plasmablast cells in mice tumors. Of note, VEGF levels in all α-AED-treated tumors was lower than in the control and vehicle groups. The tumor in situ increased response was reflected systemically by higher anti-4T1 IgG concentration in serum from α-AED-treated mice, but no other associated systemic changes were detected. The reduction in tumor size for the local injection of α-AED is associated with the anti-proliferative effect of this steroid, and the lower local levels of VEGF may be related to the imperceptible macroscopic metastasis in α-AED-treated mice. The above suggests that α-AED may be used in clinical studies to prove its efficacy as an alternative breast tumor treatment or in conjunction with already established therapies. [ABSTRACT FROM AUTHOR]

Automatic segmentation of breast cancer lesions in dynamic contrast-enhanced magnetic resonance imaging is challenged by low accuracy of delineation of the infiltration area, variable structure and shapes, large intensity heterogeneity changes, and low boundary contrast. This study constructed a two-stage breast cancer image segmentation framework and proposes a novel breast cancer lesion segmentation model (TR-IMUnet). The benchmark U-Net network model enables a rough delineation of the breast area in the acquired images and eliminates the influence of unrelated tissues (chest muscle, fat, and heart) on breast tumor segmentation. Based on the extracted results of the region of interest, the rectified linear unit (ReLU) function of the encoding–decoding structure in the model was replaced by an improved ReLU function to reserve and adjust the data dynamically according to input information. The segmentation accuracy of breast cancer lesions was improved by embedding a multi-scale fusion block and a transformer module in the coding path of the model, thereby obtaining multi-scale and global attention information. The experimental results showed that the breast tumor segmentation indexes Dice coefficient (Dice), Intersection over Union (IoU), Sensitivity (SEN), and Positive Predictive Value (PPV) increased by 4.27, 5.21, 3.37, and 3.68%, respectively, relative to the U-Net reference model. The proposed model improves the segmentation results of breast cancer lesions and reduces small area mis-segmentation and calcification segmentation. [ABSTRACT FROM AUTHOR]

Purpose: Breast cancer is the most commonly occurring cancer worldwide. The ultrasound reflectivity imaging technique can be used to obtain breast ultrasound (BUS) images, which can be used to classify benign and malignant tumors. However, the classification is subjective and dependent on the experience and skill of operators and doctors. The automatic classification method can assist doctors and improve the objectivity, but current convolution neural network (CNN) is not good at learning global features and vision transformer (ViT) is not good at extraction local features. In this study, we proposed a visual geometry group attention ViT (VGGA‐ViT) network to overcome their disadvantages. Methods: In the proposed method, we used a CNN module to extract the local features and employed a ViT module to learn the global relationship among different regions and enhance the relevant local features. The CNN module was named the VGGA module. It was composed of a VGG backbone, a feature extraction fully connected layer, and a squeeze‐and‐excitation block. Both the VGG backbone and the ViT module were pretrained on the ImageNet dataset and retrained using BUS samples in this study. Two BUS datasets were employed for validation. Results: Cross‐validation was conducted on two BUS datasets. For the Dataset A, the proposed VGGA‐ViT network achieved high accuracy (88.71±$\ \pm \ $1.55%), recall (90.73±$\ \pm \ $1.57%), specificity (85.58±$\ \pm \ $3.35%), precision (90.77±$\ \pm \ $1.98%), F1 score (90.73±$\ \pm \ $1.24%), and Matthews correlation coefficient (MCC) (76.34±7$\ \pm \ 7$3.29%), which were better than those of all compared previous networks in this study. The Dataset B was used as a separate test set, the test results showed that the VGGA‐ViT had highest accuracy (81.72±$\ \pm \ $2.99%), recall (64.45±$\ \pm \ $2.96%), specificity (90.28±$\ \pm \ $3.51%), precision (77.08±$\ \pm \ $7.21%), F1 score (70.11±$\ \pm \ $4.25%), and MCC (57.64±$\ \pm \ $6.88%). Conclusions: In this study, we proposed the VGGA‐ViT for the BUS classification, which was good at learning both local and global features. The proposed network achieved higher accuracy than the compared previous methods. [ABSTRACT FROM AUTHOR]

Objectives: To explore added value of diffusion-weighted imaging (DWI) as an adjunct to Kaiser score (KS) for differentiation of benign from malignant lesions on breast magnetic resonance imaging (MRI). Methods: Two hundred forty-six patients with 273 lesions (155 malignancies) were included in this retrospective study from January 2015 to December 2019. All lesions were proved by pathology. Two radiologists blind to pathological results evaluated lesions according to KS. Lesions with score > 4 were considered malignant. Four thresholds of ADC values −1.3 × 10−3mm2/s, 1.4 × 10−3mm2/s, 1.53 × 10−3mm2/s, and 1.6 × 10−3mm2/s were used to distinguish benign from malignant lesions. For combined diagnosis, a lesion with KS > 4 and ADC values below the preset cutoffs was considered as malignant; otherwise, it was benign. Sensitivity, specificity, and area under the curve (AUC) were compared between KS, DWI, and combined diagnosis. Results: The AUC of KS was significantly higher than that of DWI alone (0.941 vs 0.901, p = 0.04). The sensitivity of KS (96.8%) and DWI (97.4 – 99.4%) was comparable (p > 0.05) while the specificity of KS (83.9%) was significantly higher than that of DWI (19.5–56.8%) (p < 0.05). Adding DWI as an adjunct to KS resulted in a 0–2.5% increase of specificity and a 0.1–1.3% decrease of sensitivity; however, the difference did not reach statistical significance (p > 0.05). Conclusion: KS showed higher diagnostic performance than DWI alone for discrimination of breast benign and malignant lesions. DWI showed no additional value to KS for characterizing breast lesions. Key Points: • KS showed higher diagnostic performance than DWI alone for differentiation of benign from breast malignant lesions. • DWI alone showed a high sensitivity but a low specificity for characterizing breast lesions. • Diagnostic performance did not improve using DWI as an adjunct to KS. [ABSTRACT FROM AUTHOR]

Background: The use of archived formalin-fixed paraffin-embedded (FFPE) tumor tissues has become a common practice in clinical and epidemiologic genetic research. Simultaneous extraction of DNA and RNA from FFPE tissues is appealing but can be practically challenging. Here we report our results and lessons learned from processing FFPE breast tumor tissues for a large epidemiologic study. Methods: Qiagen AllPrep DNA/RNA FFPE kit was adapted for dual extraction using tissue punches or sections from breast tumor tissues. The yield was quantified using Qubit and fragmentation analysis by Agilent Bioanalyzer. A subset of the DNA samples were used for genome-wide DNA methylation assays and RNA samples for sequencing. The QC metrices and performance of the assays were analyzed with pre-analytical variables. Results: A total of 1859 FFPE breast tumor tissues were processed. We found it critical to adjust proteinase K digestion time based on tissue volume to achieve balanced yields of DNA and RNA. Tissue punches taken from tumor-enriched regions provided the most reliable output. A median of 1475 ng DNA and 1786 ng RNA per sample was generated. The median DNA integrity number (DIN) was 3.8 and median DV200 for RNA was 33.2. Of 1294 DNA samples used in DNA methylation assays, 97% passed quality check by qPCR and 92% generated data deemed high quality. Of the 130 RNA samples with DV200 ≥ 20% used in RNA-sequencing, all but 5 generated usable transcriptomic data with a mapping rate ≥ 60%. Conclusions: Dual DNA/RNA purification using Qiagen AllPrep FFPE extraction protocol is feasible for clinical and epidemiologic studies. We recommend tissue punches as a reliable source material and fine tuning of proteinase K digestion time based on tissue volume. Impact: Our protocol and recommendations may be adapted by future studies for successful extraction of archived tumor tissues. [ABSTRACT FROM AUTHOR]

Background: Selective activation of Delta-like 1 (DLL1)-Notch signaling is a new approach to activate CD8+ T cell and suppress tumor growth, while the efficacy remains modest. Lentinan (LNT) is a clinically used immunomodulation agent. Thus, we hypothesized that LNT could improve the efficacy of DLL1.Methods: The effects of LNT combined with DLL1 on tumor growth were evaluated by growth curve and tumor weight in EO771 breast and LAP0297 lung tumor models. The impacts on immune cells and gene expression in tumor tissues were determined by flow cytometry, qPCR. Neutrophil depletion was used to investigate the mechanism of the combination therapy on tumor growth. The data sets were compared using unpaired student's t-test or ordinary one-way ANOVA.Results:  LNT treatments additively improved the antitumor effects of DLL1 in EO771 breast tumor growth. Remarkably, LNT treatments synergistically enhanced the suppression of DLL1 on LAP0297 lung tumor growth, resulting in tumor regression. Mechanically, the combination of LNT and DLL1 interventions not only promoted the accumulation and activation of CD8+ T cells, but also increased intratumoral CD45+CD11b+Ly6G+ neutrophils. Reduced neutrophils by anti-Gr1 antibody administrations reversed the improved antitumor effects by LNT treatments in LAP0297 lung tumor. These results suggest that LNT treatments improve the inhibition of DLL1 on tumor growth via neutrophils.Conclusions: Our findings indicates that LNT and DLL1 may induce synergistical antitumor immunity via simultaneous modulating lymphoid and myeloid cell populations regardless of the type of tumor, providing a potential new strategy to potentiate cancer immunotherapy. [ABSTRACT FROM AUTHOR]

Retraction phenomenon is a unique sign on an automated breast volume scanner coronal plane image and has high specificity in differentiating benign lesions from malignant breast cancer. The purpose of this study was to quantify the retraction phenomenon by setting different rules to describe connected regions from different dimensions. In total, six quantitative indicators (FΩ1,FΓ,FS,FΩ2,FΩ3and FL) were obtained. FΩ1, FΩ2 and FΩ3 represent the relative areas of the connected region under different rules. FΓandFS represent the number ratio and absolute area of the connected region, respectively. FL represents the ratio of edge numbers. Two hundred fourteen patients with 214 lesions (90 benign and 124 malignant) were enrolled in this study. All quantitative indicators in the malignant group were significantly higher than those in the benign group (all p values <0.001). The indicator FΓ achieved the highest area under the receiver operating characteristic curve (AUC) (0.701, 95% confidence interval: 0.631-0.771). Both FΓ and FS had significant associations with axillary lymph node metastasis (p = 0.023 and 0.049). Compared with the classic texture feature gray-level co-occurrence matrix, retraction phenomenon quantization improved the AUC by 8.3%. The results indicate that retraction phenomenon quantitative indicators have certain value in distinguishing benign and malignant breast lesions and seem to be associated with axillary lymph node metastasis. [ABSTRACT FROM AUTHOR]

Breast cancer is increasing rapidly in women these days. It is diagnosed after the symptoms appear. The detection at an initial stage and the procedure of the treatment are the most significant strategies curing it effectively. For the determination of breast cancer, breast mammography is required. It can be one of the methods to recognize tumor in women's breasts because it lessens the risk of death by recognizing the tumor at an early level. This paper shows a combination of selection methods for step by step evaluation for Efficient Seeded Region Growing with enhanced performance to spot breast cancer. The suggested method has been divided into the following parts: First, preprocessing of breast image is performed to estimate the automatic extraction of Region of Interest. Second, an automatic threshold is calculated for the binarization process. Third, the numbers of seed points are determined automatically and their positions in the breast image are identified using the density of pixels value. Fourth, a method calculating the threshold value is proposed for the purpose of region creation in seed region growing. The given method is applied and tested on the two publicly available mammogram data sets; Mammographic Image Analysis Society (MIAS) and Digital Database for Screening Mammography (DDSM). It was observed that the proposed algorithm gives 94.6% and 95.3% True Positive Fraction (TPF) in case of MIAS and DDSM images, respectively. The parameters demonstrate that the given algorithm gives better results than the previously available methods. [ABSTRACT FROM AUTHOR]

[Display omitted] • A one-pot method for the synthesis of new substituted pyrrolo[1,2- a ]thieno[3,2 e ]pyrimidine has been developed. • In vitro screening of the antitumor activity and molecular docking analysis of the synthesized compounds were performed. • The compounds demonstrated a selective toxicity against melanoma cancer, reducing tumor volume and weight without any toxicity. A new efficient and versatile one-pot three-component synthesis of substituted pyrrolo[1,2- a ]thieno[3,2-e]pyrimidine derivatives has been developed. It is based on a multistep cascade reaction from 2-aminothiophenes and 2-hydroxy-4-oxobut-2-enoic acids, and derivatives of cyanoacetic acid catalyzed by diisopropylethylamine. As a result, novel pyrrolo[1,2- a ]thieno[3,2- e ]pyrimidine derivatives (21 compounds) were synthesized in a mild reaction conditions with a high yield. The structures of the developed compounds were confirmed by NMR and elemental analysis. The influence of electron-withdrawing or electron-donor substituents on the antitumor activity of the developed compounds has been identified. In vitro screening analysis of 21 compounds revealed six lead candidates (12aa, 12dc, 12hc, 12ic, 12lb, and 12mb) that demonstrated the most significant antitumor activity against B16-F10, 4T1 and CT26 cells. Necrosis/apoptosis assay showed that apoptosis was the predominant mechanism of cell death. Molecular docking analysis revealed several potential targets for tested compounds, i.e. phosphatidylinositol 5-phosphate 4-kinase (PI5P4K2C), proto-oncogene serine/threonine-protein kinase (Pim-1), nicotinamide phosphoribosyltransferase (NAMPT) and dihydrofolate reductase (DHFR). The lead compound (12aa) can effectively induce cell apoptosis, possesses a high yield (98 %) and requires low-cost starting chemicals for its synthesis. In vivo experiments with melanoma-bearing mice confirmed that 12aa compound resulted in the significant tumor inhibition on 15 d after the therapy. In particular, tumor volume was ∼0.19 cm3 for 50 mg/kg versus ∼2.39 cm3 in case of untreated mice and tumor weight was ∼71.6 mg for 50 mg/kg versus ∼452.4 mg when considered untreated mice. Thus, our results demonstrated the high potential of the 12aa compound in the treatment of melanoma and can be recommended for further preclinical studies. [ABSTRACT FROM AUTHOR]

Simple Summary: Natural formulations and phytotherapies have shown promising antitumor activities. This review assesses the antitumor effects of curcumin on breast cancer. In particular, we discuss the effects of curcumin on the proliferation, viability, and apoptosis of breast cancer cell lineages and tumor volume. Studies have shown that curcumin administered at different concentrations inhibited proliferation, decreased viability, and induced apoptosis in human and animal breast cancer cells. Nanoparticle formulations of curcumin administered orally, via implant, or intraperitoneally reduced the tumor volume of human and murine mammary cells in vivo. Moreover, curcumin nanoformulations facilitate tumor growth inhibition in animal models of breast cancer. Randomized clinical trials are warranted to assess the efficacy and safety of curcumin formulations for clinical use. Breast cancer is one of the most common neoplasms among women. Anticancer strategies using natural formulations and phytotherapies are promising antitumor treatment alternatives. This review assesses the antitumor effects of curcumin on breast cancer reported in preclinical in vitro and in vivo animal models. We used five databases to search for preclinical studies published up to May 2021. The assessments included the effects of curcumin on the proliferation, viability, and apoptosis of breast cancer cell lineages and on tumor volume. In total, 60 articles met the inclusion criteria. Curcumin administered at different concentrations and via different routes of administration inhibited proliferation, decreased viability, and induced apoptosis in human and animal breast cancer cells. Nanoparticle formulations of curcumin administered orally, via implant, and intraperitoneally reduced the tumor volume of human and murine mammary cells in vivo. Moreover, curcumin nanoformulations exert positive effects on tumor growth inhibition in animal models of breast cancer. Further randomized clinical trials are warranted to assess the efficacy and safety of curcumin formulations for clinical use. [ABSTRACT FROM AUTHOR]

Simple Summary: The tumor microenvironment determines the prognosis and outcome for cancer patients. Herein, tumor-associated macrophages are not only highly abundant, but also play a crucial role in shaping a tumor-supporting microenvironment. Both their recruitment to the tumor as well as their functional polarization toward a pro-tumorigenic phenotype are mediated by tumor-derived factors including microRNAs. However, the impact of most microRNAs on the tumor cell-macrophage crosstalk remains to be elucidated. Thus, we reached out to investigate the role of hsa-miR-200c-3p (miR-200c) in tumor cell–macrophage interactions, as it was shown to be differentially expressed during cancer progression and metastasis. miR-200c was highly expressed in MCF7 breast tumor cells compared to macrophages. Furthermore, we identified a CD36-dependent uptake of miR-200c, derived from apoptotic tumor cells, into macrophages. In macrophages, elevated miR-200c levels reduced the expression of numerous migration-associated mRNAs, consequently reducing the capacity of macrophages to infiltrate into tumor spheroids. Finally, a distinct signature of miR-200c-repressed, predicted targets was identified, which strongly correlated with tumor infiltration. Targeting the miR-200c transfer from dying tumor cells to macrophages might therefore provide the opportunity to specifically modulate tumor-associated macrophage recruitment. Macrophages constitute a major part of the tumor-infiltrating immune cells. Within the tumor microenvironment, they acquire an alternatively activated, tumor-supporting phenotype. Factors released by tumor cells are crucial for the recruitment of tumor-associated macrophages. In the present project, we aimed to understand the role of hsa-miR-200c-3p (miR-200c) in the interplay between tumor cells and macrophages. To this end, we employed a coculture system of MCF7 breast tumor cells and primary human macrophages and observed the transfer of miR-200c from apoptotic tumor cells to macrophages, which required intact CD36 receptor in macrophages. We further comprehensively determined miR-200c targets in macrophages by mRNA-sequencing and identified numerous migration-associated mRNAs to be downregulated by miR-200c. Consequently, miR-200c attenuated macrophage infiltration into 3-dimensional tumor spheroids. miR-200c-mediated reduction in infiltration further correlated with a miR-200c migration signature comprised of the four miR-200c-repressed, predicted targets PPM1F, RAB11FIB2, RDX, and MSN. [ABSTRACT FROM AUTHOR]

Context: Targeting MUC1 antigens which are overexpressed in 80% of breast cancers can be widely used in the field of radioimmunoscintigraphy (RIS) of breast cancer.Aims: The aim of this study was to develop a new diagnostic labeled compound for breast cancer RIS.Settings and Design: In this study, an efficient indirect labeling method of PR81 with Indium-111 was developed and preliminary preclinical qualifications were reported.Subjects and Methods: 111In-DTPA-PR81 was prepared and its radiochemical purity and stabilities in human serum and in phosphate-buffered saline (PBS) buffer were surveyed. Furthermore, cellular studies including complex reactivity, binding specificity, cell toxicity, etc., were examined. Finally, biodistribution and scintigraphy of the complex were studied in normal and tumoral animals.Statistical Analysis Used: Statistical analyses were performed using SPSS 10.0.Results: 111In-DTPA-PR81 was prepared with a radiochemical purity of >99% at optimized conditions. Stability studies showed the radiochemical purity of >90% in PBS buffer after 96 h, while the stability in human serum showed decrement to 81% after 96 h. Reactivity of the complex with MUC1 was significantly (P < 0.005) higher than bovine serum albumin (BSA) (about 7-8 times), even though BSA concentration was about twice the MUC1. The binding specificity of the complex to the MUC1 antigen was confirmed by means of immunoreactivity assay. Cell toxicity examination showed no significant lethal effect of the radiolabeled compound on the cells. Biodistribution studies of the complex in normal rats were consistent with the biodistribution of antibodies and high accumulation was observed in the tissues expressing MUC1 antigen. The results of 111In-DTPA-PR81 scintigraphy in tumoral female BALB/c mice at 24 and 48 h after injection showed an increasement of the accumulation in the tumor site.Conclusions: 111In-DTPA-PR81 can be considered as a potential agent for imaging of the MUC1 +breast tumors. [ABSTRACT FROM AUTHOR]

The diagnosis of adenomyoepitheliomas is difficult and relies on the presence of a double component of epithelial and myoepithelial cells belonging to the breast lobules and ducts. The clinical and imaging characteristics are not specific; thus, the diagnosis is histological. In this article, we present a case of a young female who presented with a 2 cm lump in the breast without other clinical symptoms, which revealed a benign adenomyoepithelioma (AME). We performed a large excisional lumpectomy, and the patient recovered well with no complication or recurrence within two years follow-up. When it comes to adenomyoepitheliomas, the published literature is mainly composed of case reports, so much so that there are no evidence-based guidelines. Our case shows that an excisional lumpectomy is often enough when facing a small size tumor with no signs of malignancy, which contributes to the limited data on the subject. [ABSTRACT FROM AUTHOR]

Burkitt lymphoma is one of the most aggressive non- Hodgkin lymphomas. The disease can be associated with extranodal involvement, especially in the structures of the neck and head, abdomen, kidneys and bone marrow. Breast involvement is rare. This type of lymphoma has an intrinsic propensity for central nervous system involvement. We report the case of an elderly patient diagnosed with Burkitt lymphoma with breast tumor and central nervous system infiltrates. [ABSTRACT FROM AUTHOR]

Chemokine receptor belongs to G-protein-coupled cell-surface receptors. CXCR4 as a chemokine receptor is over-expressed in many type of solid tumors and metastasis in which breast tumor is one of them. A CXCR4 targeted peptide was prepared and labeled with 99mTc. Subsequently, receptor binding internalization, in vivo tumor uptake and biodistribution were assessed. The receptor binding internalization rate was evaluated using 4T1 breast tumor cells. BALB/c female mice bearing 4T1 tumors were employed for investigation of radioconjugate biodistribution. Radioconjugate was obtained with labeling yield of > 95%. The highest achieved specific activity was 123 MBq/nmol. The in vitro cell uptake test resulted specific internalization into 4T1 cells (average of 1.90 ± 0.12% of total add at 2 h). Animal biodistribution data showed tumor uptake of 1.18 ± 0.11% ID/g after 30 min post injection. Our findings demonstrated that the labeled peptide can be a suitable candidate for breast tumors imaging. [ABSTRACT FROM AUTHOR]

Introduction: Paraneoplastic neurological syndromes (PNS) are rare neurological conditions and they are mostly triggered by autoimmune mechanisms. Cancer-related retinopathies (CAR) are even rarer and commonly related with breast tumor in woman. This limits our knowledge about pathophysiology of CAR. In this study, we question the association between histopathological findings and onconeural antibodies in breast cancer. Method: Thirty-two patients with newly diagnosed breast cancer admitted to the oncology outpatient clinic were included in the study. None of the participants have visual complaints. After the neurological examination of the patients, two tubes of 5 cc venous blood were obtained by screening onconeuronal antibodies. Samples were investigated in ASDETAE (İstanbul University Experimental Medicine Research Institute). Results: Patients included in the study included one patinet (3.1%) with grade 1, 14 patients (43.8%) with grade 2 and 17 patients (53.1%) with grade 3 invasive breast cancer. Perineural invasion was detected in 5 (15.6%) patients. Progesterone receptor positivity was found in 26 (81.2%) patients and estrogen receptor positivity was found in 27 (84.4%) patients. In 7 (21.9%) patients, CERBB2 was positive and in 25 (78.1%) patients, Ki 67 was positive. A total of 12 (37.5%) patients had onconeuroneal antibody positivity. Antibody positivity was significantly higher in patients with high grade tumor (p=0.008). Conclusion: There may be a relationship between tumor grade and the presence of onconeuronal antibodies in breast cancer patients. By the detection of new biochemical markers, significant contribution can be made to the early diagnosis and treatment of underlying cancer. [ABSTRACT FROM AUTHOR]

• Co-encapsulation of CpG ODN and p(IC) within tumor-derived exosome boosted type II interferon from T cells and tumor antigen specific antibody from B cells. • Dual adjuvant loaded exosomes regressed tumors by promoting Th1 biased immunity. • Exosomal formulations induced memory T-cell phenotype development that contribute to mammary tumor clearance and improved survival. Tumor-derived exosomes (TEXs) could be harnessed as an immunotherapeutic cancer vaccine. These nanovesicles are inherently possesses rich tumor antigen reservoirs. Due to their undesirable features such as poor or limited immunogenicity as well as facilitation of cancer development via mediating communication between tumor cells TEXs could be transformed into an effective immune adjuvant delivery system that initiates a strong humoral and cell-mediated tumor-specific immune response. Engineering TEXs to harbor immunostimulatory molecules still remains a challenge. Previously, we demonstrated that nucleic acid ligand encapsulated liposomes could trigger synergistic strong humoral, and cell mediated immune responses and provokes tumor regression to that of their standalone counterparts. In this study, we evaluated to immunogenicity of 4T1/Her2 cell-derived exosomes upon loading them with two potent immuno adjuvant, a TLR9 ligand, K-type CpG ODN and a TLR3 ligand, p(I:C). Engineered TEXs co-encapsulating both ligands displayed boosted immunostimulatory properties by activating antigen-specific primary and memory T cell responses. Furthermore, our exosome-based vaccine candidate elicited robust Th1-biased immunity as evidenced by elevated secretion of IgG2a and IFNγ. In a therapeutic cancer model, administration of4T1 tumor derived exosomes loaded with CpG ODN and p(I:C) to animals regress tumor growth in 4T1 tumor-bearing mice. Taken together this work implicated that an exosome-based therapeutic vaccine promoted strong cellular and humoral anti-tumor immunity that is sufficient to reverse established tumors. This approach offers a personalized tumor therapy strategy that could be implemented in the clinic. [ABSTRACT FROM AUTHOR]

Objective: To explore the express levels and diagnostic values of microRNA-6886 miR-6886 and microRNA-6819 miR-6819 in plasma exosomes of patients with the benign and malignant breast masses. Methods: The study enrolled 41 patients and 18 ones respectively with pathological diagnosis of breast malignant tumor and benign breast diseases patients. Separating the plasma exosomes of the two-group patients and detecting the relative expression level of the miR-6886, miR-6819 and miR-7110 with real-time fluorescent quantitative PCR. The value of a single miRNA or joint miRNAs in differential diagnosis of the benign and malignant breast masses was analyzed by the receiver-operating characteristic curve (ROC). Groups were compared by nonparametric rank and inspection. Methods: The express levels of miR-6886 and miR-6819 of plasma exosomes in the malignant breast tumor group were, significantly lower than those in the benign breast tumor group, which showed statistical difference miR-6886 Z=-2.321, P=0.020; miR-6819, Z=-2.321, P=0.020 . The expression levels of miR-7110 showed no statistical difference between the two groups. When miR-6886 and miR-6819 was tested separately, the AUCROC of miR-6886 was 0.691, and the sensitivity and specificity were 65.8% and 72.2%; the AUCROC of miR-6819 was 0.691, the sensitivity and specificity were 73.1% and 66.6%. While combining miR-6886and miR-6819, the AUCROC=0. 806, the sensitivity and specificity were 80.5% and 77.8%. Comparing with the separated testing, the AUC differences of combining tests were statistically significant (miR-6886, Z=4.082, P<0.001; miR-6819, Z=2.182, P=0.029). Conclusion: The combined detection of plasma exosome, miR-6886 and miR-6819, is expected to be a good serological marker for the differentiation of benign and malignant breast tumors. [ABSTRACT FROM AUTHOR]

Breast cancer is the most common cause of death in women. Early detection of this disease and diagnosis can cut the passing of women. Segmentation is an imperative technique in digital image analysis science. The aim of this work is focused on image analysis of breast tumors using image processing. The infected area of breast tumor identified by applying edge detection, filling gaps, dilating gaps, removing the border, smoothing objects have been used. This method appears more familiar to radiologists to check the abnormality of benign and malignant breast tumors. The analysis shows that both benign and malignant tumors have well-detected to find the tumors at the first stages. [ABSTRACT FROM AUTHOR]

Objective: To retrospectively analyze the safety and long-term clinical efficacy of gelatin sponge microparticles combined with the chemotherapy drug pirarubicin for hepatic transcatheter arterial chemoembolization (GSMs-TACE) in order to treat breast cancer liver metastasis (BCLM). Methods: Twenty-seven BCLM patients who underwent GSMs-TACE from July 2010 to July 2016 were enrolled. Tumor target blood vessels were slowly and regionally embolized with absorbable gelatin sponge particles and pirarubicin injections. Plain computed tomography (CT) scans and biochemical indexes were re-examined at 4 days after treatment, and enhanced CT scans or magnetic resonance images and biochemical indexes, 1 month later. For patients with stable tumors, the follow-up period was 2 to 3 months, and the tumor response was evaluated using Modified Response Evaluation Criteria in Solid Tumors. Adverse reactions, survival time, and prognostic factors were assessed. Results: By October 2019, 27 patients with BCLM had undergone GSMs-TACE, with an average of 2.44 ± 1.58 treatments. The 1-, 3-, and 5-year survival rates were 62.96%, 22.22%, and 14.81%, respectively, and the mOS was 22.0 months. No serious complications, such as acute liver failure and liver abscess, had occurred. There were two cases of acute cholecystitis that recovered after symptomatic treatment. Multivariate analysis of the prognosis showed that the primary tumor size, number of metastatic lymph nodes, estrogen receptor/progesterone receptor (ER/PR) status, and time to postoperative liver metastasis and combination therapy were statistically significant. Conclusions: The overall prognosis of BCLM was poor. GSMs-TACE was safe and effective for BCLM treatment and could prolong the median survival time of patients. Therefore, it is worthy of widespread clinical application. [ABSTRACT FROM AUTHOR]