During neurulation, cranial neural crest cells (CNCCs) migrate long distances from the neural tube to their terminal site of differentiation. The pathway traveled by the CNCCs defines the blueprint for craniofacial construction, abnormalities of which contribute to three-quarters of human birth defects. Biophysical cues like naturally occurring electric fields (EFs) have been proposed to be one of the guiding mechanisms for CNCC migration from the neural tube to identified position in the branchial arches. Such endogenous EFs can be mimicked by applied EFs of physiological strength that has been reported to guide the migration of amphibian and avian neural crest cells (NCCs), namely galvanotaxis or electrotaxis. However, the behavior of mammalian NCCs in external EFs has not been reported. We show here that mammalian CNCCs migrate towards the anode in direct current (dc) EFs. Reversal of the field polarity reverses the directedness.The response threshold was below 30mV/mm and the migration directedness and displacement speed increased with increase of field strength. Both CNCC line (O9-1) and primary mouse CNCCs show similar galvanotaxis behavior. Our results demonstrate for the first time that the mammalian CNCCs respond to physiological EFs by robust directional migration towards the anode in a voltage-dependent manner.
Background: Lung cancer metastases to the breast are less common and consequently have received much less attention in clinical practice. The purpose of this study was to provide a better understanding of clinical, ultrasonographic, and immunohistochemical features of breast metastases from primary lung cancer.Methods: This retrospective case series included patients with breast metastases from primary lung cancer between January 2012 and December 2020. Clinical features, ultrasonographic characteristics, and immunohistochemical findings were evaluated in this analysis.Results: In all, 7 cases (mean ± standard deviation age: 57.4±8.3 years; range, 49-70 years) were evaluated. The maximum size of breast lesions in 6 cases ranged from 1.2 to 4.5 cm, while 1 case showed a diffused pattern. Ultrasound features of breast metastases from lung cancer were irregular (5/7, 71.4%), indistinct (6/7, 85.7%), hypoechoic (7/7, 100.0%), and parallel (6/7, 85.7%) masses without calcification.Immunohistochemical staining test was positive for thyroid transcription factor 1 (TTF-1) in all patients (7/7, 100.0%), 3 cases (3/5, 60.0%) were negative for p63, 5 cases (5/5, 100.0%) were positive for cytokeratin 7 (CK7), 4 cases (4/5, 80.0%) were positive for napsin A. Conclusions:The ultrasonographic features of lung metastases to the breast are clinically important to understand. A known history of the primary lung cancer is of great importance when evaluating patients with a breast nodule. The presence of an ipsilateral lung cancer, breast nodule and axillary lymphadenopathy should be considered with pathological and immunohistochemical data to differentiate breast metastases from a primary breast malignancy in this setting.
Background: This study aimed to explore whether transforming growth factor β1 (TGF-β1) is correlated with the stiffness of breast lesions and if it can predict axillary lymph node (ALN) metastasis.Methods: A retrospective analysis was performed in our hospital. A total of 135 breast lesions in 130 patients who were to undergo vacuum-assisted excisional biopsy (VAEB) or surgery were enrolled between April 2018 and October 2018. Ultrasound (US) and shear wave elastography (SWE) examinations were performed for every lesion before VAEB or surgery. Pathology results obtained by VAEB or surgery were regarded as gold criteria. The elastic parameters and TGF-β1 expression level of malignant breast lesions were compared with those of benign lesions; the relationship between TGF-β1 expression level in breast lesions and the elastic parameters was analyzed; the TGF-β1 expression level in breast lesions with or without ALN metastasis were compared; and the efficacy of TGF-β1 expression level in predicting ALN metastasis was analyzed. Results:The malignant breast lesions were different from benign lesions in the maximum and mean elasticity (Emax, Emean), standard deviation of elasticity (ESD), elastic ratio of the lesions to the peripheral tissue (Eratio), and the occurrence rate of "stiff rim sign" (P<0.001). The expression level of TGF-β1 in benign breast lesions was significantly lower than that in malignant lesions (P<0.001), and the TGF-β1 expression level was positively correlated with Emax, Emean, ESD, and Eratio (r=0.869, 0.840, 0.834, and 0.734, respectively). The expression level of TGF-β1 in breast lesions with or without "stiff rim sign" was significantly different (P<0.001), and the TGF-β1 expression level in malignant breast lesions with ALN metastasis was significantly higher than that in malignant lesions without ALN metastasis (P=0.0009). When TGF-β1 expression level >0.3138 was taken as the cut-off value, its efficacy in predicting ALN metastasis was 0.853, with a sensitivity of 86.67%, and a specificity 83.33%. Conclusions:The expression level of TGF-β1 was positively correlated with the elastic parameters of breast lesions, and it could be useful for predicting ALN metastasis, especially for negative ALN diagnosis clinically.
Background This study aimed to explore whether collagen fiber features and collagen type I alpha 1 (COL1A1) are related to the stiffness of breast lesions and whether COL1A1 can predict axillary lymph node metastasis (LNM). Methods Ninety-four patients with breast lesions were consecutively enrolled in the study. Amongst the 94 lesions, 30 were benign, and 64 were malignant (25 were accompanied by axillary lymph node metastasis). Ultrasound (US) and shear wave elastography (SWE) were performed for each breast lesion before surgery. Sirius red and immunohistochemical staining were used to examine the shape and arrangement of collagen fibers and COL1A1 expression in the included tissue samples. We analyzed the correlation between the staining results and SWE parameters and investigated the effectiveness of COL1A1 expression levels in predicting axillary LNM. Results The optimal cut-off values for Emax, Emean, and Eratio for diagnosing the benign and malignant groups, were 58.70 kPa, 52.50 kPa, and 3.05, respectively. The optimal cutoff for predicting axillary LNM were 107.5 kPa, 85.15 kPa, and 3.90, respectively. Herein, the collagen fiber shape and arrangement features in breast lesions were classified into three categories. One-way analysis of variance (ANOVA) showed that Emax, Emean, and Eratio differed between categories 0, 1, and 2 (P < 0.05). Meanwhile, elasticity parameters were positively correlated with collagen categories and COL1A1 expression. The COL1A1 expression level > 0.145 was considered the cut-off value, and its efficacy in benign and malignant breast lesions was 0.808, with a sensitivity of 66% and a specificity of 90%. Furthermore, when the COL1A1 expression level > 0.150 was considered the cut-off, its efficacy in predicting axillary LNM was 0.796, with sensitivity and specificity of 96% and 59%, respectively. Conclusions The collagen fiber features and expression levels of COL1A1 positively correlated with the elastic parameters of breast lesions. The expression of COL1A1 may help diagnose benign and malignant breast lesions and predict axillary LNM.
Purpose: This study aimed to explore whether collagen fiber features and collagen type I alpha 1 (COL1A1) are related to the stiffness of breast lesions and whether COL1A1 can predict axillary lymph node metastasis (LNM).Methods: A prospective analysis was performed in our hospital. A total of 94 breast lesions in 94 patients were enrolled between May 2021 to December 2021. Ultrasound (US) and shear wave elastography (SWE) examinations were performed for every lesion before surgery. Pathology results obtained by surgery were regarded as gold criteria. Sirius red staining and Immunohistochemical were used to examine the collagen fibers shape and arrangement features and COL1A1 expression of included tissue samples, and analyze the correlation between SWE parameters and them. To analyze the effectiveness of COL1A1 expression level in predicting axillary LNM. Results: The optimal cutoff values for Emax, Emean, and Eratio for diagnosis of benign group and malignant group, were 58.70 kPa, 52.50 kPa, and 3.05. The optimal cutoff values for diagnosing axillary LNM were 107.5 kPa, 85.15 kPa, and 3.90, respectively. In the present study, collagen fiber shape and arrangement features in breast lesions were classified into three categories. For all 94 lesions, one-way ANOVA showed that Emax, Emean and Eratio were different between categories 0, 1, and 2 (all P< 0.05). The correlation coefficient between Emax and collagen category was 0.318 (P< 0.001), between Emean and collagen category was 0.261 (P= 0.001). And between Eratio and collagen category was 0.349 (P < 0.001). Emax, Emean and Eratio were all positively correlated with COL1A1 expression level (r=0.406, 0.362, 0.425, respectively). COL1A1 expression level >0.145 was taken as the cut-off value, its efficacy in benign and malignant breast lesions was 0.808, with a sensitivity of 66%, and a specificity 90%. COL1A1 expression level >0.150 was taken as the cut-off value, its efficacy in predicting axillary LNM was 0.796, with a sensitivity of 96%, and a specificity 59%. Conclusions: The expression level of the collagen fiber features and COL1A1 were positively correlated with the elastic parameters of breast lesions. The expression of COL1A1 might be helpful to diagnose benign and malignant breast lesions and predict axillary LNM.
Background Shear wave elastography can evaluate tissue stiffness. Previous studies showed that the elasticity characteristics of breast lesions were related to the components of extracellular matrix which was regulated by transforming growth factor beta 1(TGF-β1) directly or indirectly. However, the correlation of the expression level of TGF-β1, its signal molecules and elasticity characteristics of breast lesions have rarely been reported. The purpose of this study was to investigate the correlation between the expression level of TGF-β1, its signal molecules, and the elasticity characteristics of breast lesions. Methods 135 breast lesions in 130 patients were included. Elasticity parameters, including elasticity modulus, the elasticity ratio, the “stiff rim sign”, were recorded before biopsy and surgical excision. The expression levels of TGF-β1 and its signal molecules, including Smad2/3, Erk1/2, p38 mitogen-activated protein kinase (MAPK), c-Jun N-terminal kinase 2 (JNK2), phosphoinositide 3-kinase (PI3K), and protein kinase B (PKB/AKT) were detected by immunohistochemistry. The diagnostic performance of the expression level of those molecules and their correlation with the elasticity characteristics were analyzed. Results Elasticity parameters and the expression levels of TGF- β1 and its signal molecules of benign lesions were lower than those of malignant lesions (P<0.0001). The expression levels of TGF- β1 and its signal molecules were correlated with elasticity parameters. The expression levels of TGF- β1 and its signal molecules in lesions with “stiff rim sign” were higher than those without “stiff rim sign” (P<0.05). And the expression levels of Smad2/3, Erk1/2, p38 MAPK, JNK2, PI3K and AKT were correlated with that of TGF- β1. The area under the curve for receiver operator characteristic curve of TGF-β1 and its signal molecules in the differentiation of malignant and benign breast lesions ranged from 0.920–0.960. Conclusions The expression levels of TGF-β1, its signal molecules of breast lesions showed good diagnostic performance and were correlated with the elasticity parameters. The expression levels of signal molecules were correlated with that of TGF- β1, which speculated that TGF- β1 might play an important role in the regulation of breast lesion elasticity parameters and multiple signal molecule expressions.
Background: Shear wave elastography (SWE) can evaluate the tissue stiffness. Previous studies showed that the elastic characteristics of breast lesions were related to the components of extracellular matrix (ECM) which was directly or indirectly regulated by transforming growth factor beta 1(TGF-β1). However, it is rarely reported whether there is a correlation between TGF-β1 and the elastic characteristics of breast lesions. The purpose of this study was to investigate the relationship between TGF-β1 with its signal transduction pathways and the elastic characteristics of breast lesions.Methods: 135 breast lesions in 130 patients were included. Before operation or biopsy, SWE was performed. Elastic characteristics such as the maximum, mean, minimum and standard deviation (SD) of elastic modulus (Emax, Emean, Emin, Esd), the elastic ratio of the lesions to the peripheral tissue (Eratio) and the "stiff rim sign" were recorded. The expression levels of TGF-β1, Smad2/3, Erk1/2, p38 MAPK, JNK2, PI3K and AKT were detected by immunohistochemistry. The elastic characteristics and the expression levels of the above-mentioned indexes of benign lesions were were analyzed.Results: Emax, Emean, Esd, Eratio, “stiff rim sign” detection rate and the expression levels of TGF- β 1, et al. of benign were lower than those of malignant lesions (P<0.0001). The expression levels of TGF- β 1, Smad2/3, Erk1/2, p38 MAPK, JNK2, PI3K and AKT were correlated with Emax, Emean, Esd, Eratio of breast lesions, the expression levels of TGF- β 1, et al. of lesions with “stiff rim sign” were higher than those of lesions without “stiff rim sign” (P<0.05). And the expression levels of Smad2/3, Erk1/2, p38 MAPK, JNK2, PI3K and AKT were corelated with that of TGF- β 1 (r=0.678, 0.633, 0.645, 0.611, 0.589, 0.663, P<0.0001).Conclusions: The expression levels of TGF-β1, et al. of breast lesions were corelated with the elastic characteristics, the expression levels of Smad2/3, Erk1/2, p38 MAPK, JNK2, PI3K and AKT were corelated with that of TGF- β 1, which speculated that TGF- β 1 might play an important role in the stiffness regulation of breast lesions through multiple signal transduction pathways.
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