Rab1A-Mediated Exosomal Sorting of miR-200c Enhances Breast Cancer Lung Metastasis.

Background: Recent therapeutic approaches have improved survival rate for women with breast cancer, but the survival rate for metastatic breast cancer is still low. Exosomes released by various cells are involved in all steps of breast cancer development. Methods: We established the multimodal imaging report expression in breast cancer cells with lentivirus vectors pGluc and pBirA to investigate the secreted exosomes. Comparative microRNA (miRNA) analysis was performed with miRNA qPCR array in mice with breast cancer lung metastasis. The co-immunoprecipitation and chromatin immunoprecipitation assays were used to identify the mechanism of miRNA sorting to exosomes. The potential therapeutic strategy using an anti-sorting antibody was used to investigate breast cancer lung metastasis. Results: We identified 26 high- and 32 low-expression level miRNAs in exosomes from metastasis compared to those from primary tumors and normal tissues. The tumor suppressors, including miR-200c and let-7a, were reduced in tumor tissues and metastasis but increased in the respective exosomes compared to normal tissues. Furthermore, the Ras-related protein (Rab1A) facilitated miR-200c sorting to exosomes circumventing the influence of tumor suppressor miR-200c on tumor cells, while the metastatic exosome cargo miR-200c inhibited F4/80+ macrophage immune response. Administration of anti-Rab1A antibody significantly repressed the trafficking of miR-200c to exosomes and breast cancer lung metastasis. Conclusion: Our study has identified a novel molecular mechanism for breast cancer lung metastasis mediated by exosome cargo miRNAs and provided a new therapeutic strategy for cancer immunotherapy.

Lactobacillus rhamnosus GG alleviates colitis caused by chemotherapy via biofilm formation.

BACKGROUND AND AIM: Severe colitis is a common side effect of chemotherapy in cancer patients. In this study, we attempted to enhance the viability of probiotics in a gastric acid environment and improve the colitis induced by dextran sulfate sodium (DSS) and docetaxel. METHODS: We purified Lactobacillus from yogurt and estimated their growth at pH 6.8 and pH 2.0. In the further investigation, the bacterial biofilm formation was used to define the mechanism by which administration of Lactobacillus rhamnosus (LGG) via oral gavage alleviates the colitis and intestine permeability of the mice induced by DSS and docetaxel. The potential benefit of probiotics on the treatment of breast cancer metastasis has been assessed as well. RESULTS: Lactobacillus from yogurt growth was unexpectedly faster in the pH 2.0 than in the neutral pH medium during the first hour. LGG administered in the fasting state via oral gavage significantly improved the preventive effect in the colitis caused by DSS and docetaxel. LGG reduced the permeability of the intestine and decreased the expression of proinflammatory cytokines, TNF-α, IL-1ß, and IL-6, in colitis by biofilm formation. Increasing the docetaxel dose may reduce breast tumor growth and metastasis in the lung but did not benefit survival due to severe colitis. However, the LGG supplement significantly improved the survival of tumor-bearing mice following a high dose of docetaxel treatment. CONCLUSIONS: Our findings provide new insights into the potential mechanism of probiotic protection of the intestine and provide a novel therapeutic strategy to augment the chemotherapeutic treatment of tumors.

Unsupervised Classification of Polarimetric SAR Image Based on Geodesic Distance and Non-Gaussian Distribution Feature.

Polarimetric synthetic aperture radar (PolSAR) image classification plays a significant role in PolSAR image interpretation. This letter presents a novel unsupervised classification method for PolSAR images based on the geodesic distance and K-Wishart distribution. The geodesic distance is obtained between the Kennaugh matrices of the observed target and canonical targets, and it is further utilized to define scattering similarity. According to the maximum scattering similarity, initial segmentation is produced, and the image is divided into three main categories: surface scattering, double-bounce scattering, and random volume scattering. Then, using the shape parameter α of K-distribution, each scattering category is further divided into three sub-categories with different degrees of heterogeneity. Finally, the K-Wishart maximum likelihood classifier is applied iteratively to update the results and improve the classification accuracy. Experiments are carried out on three real PolSAR images, including L-band AIRSAR, L-band ESAR, and C-band GaoFen-3 datasets, containing different resolutions and various terrain types. Compared with four other classic and recently developed methods, the final classification results demonstrate the effectiveness and superiority of the proposed method.

High-fat diet-induced upregulation of exosomal phosphatidylcholine contributes to insulin resistance.

High-fat diet (HFD) decreases insulin sensitivity. How high-fat diet causes insulin resistance is largely unknown. Here, we show that lean mice become insulin resistant after being administered exosomes isolated from the feces of obese mice fed a HFD or from patients with type II diabetes. HFD altered the lipid composition of exosomes from predominantly phosphatidylethanolamine (PE) in exosomes from lean animals (L-Exo) to phosphatidylcholine (PC) in exosomes from obese animals (H-Exo). Mechanistically, we show that intestinal H-Exo is taken up by macrophages and hepatocytes, leading to inhibition of the insulin signaling pathway. Moreover, exosome-derived PC binds to and activates AhR, leading to inhibition of the expression of genes essential for activation of the insulin signaling pathway, including IRS-2, and its downstream genes PI3K and Akt. Together, our results reveal HFD-induced exosomes as potential contributors to the development of insulin resistance. Intestinal exosomes thus have potential as broad therapeutic targets.

Research on Turning Motion Targets and Velocity Estimation in High Resolution Spaceborne SAR.

The development of high resolution SAR makes the influence of moving target more prominent, which results in defocusing and other unexplained phenomena. This paper focuses on the research of imaging signatures and velocity estimation of turning motion targets. In this paper, the turning motion is regarded as the straight line motion of continuous change of moving direction. Through the analysis of the straight line motion with constant velocity and the geometric modeling of the turning motion in spaceborne SAR, the imaging signatures of the turning motion target are obtained, such as the broken line phenomenon at the curve. Furthermore, a method for estimating the turning velocity is proposed here. The radial velocity is calculated by the azimuth offset of the turning motion target and the azimuth velocity is calculated by the phase error compensated in the refocusing process. The amplitude and direction of the velocity can be obtained by using both of them. The results of simulation and GF-3 data prove the accuracy of the analysis of turning motion imaging signatures, and they also show the accuracy and validity of the velocity estimation method in this paper.

Analysis of the Azimuth Ambiguity and Imaging Area Restriction for Circular SAR Based on the Back-Projection Algorithm.

Circular synthetic aperture radar (CSAR) has a 360° observation capability on the central observation scenario. A typical way to process CSAR imaging is to cut data into small sub-apertures because most targets are only coherent at a very small observation angle. There are many sub-aperture imaging methods after development in recent years. The back-projection algorithm is widely used because it is simple and can be applied to an arbitrary trajectory. Because of the limitation of the Nyquist sampling frequency and influence of the antenna sidelobe, azimuth ambiguity is a phenomenon that may occur in the radar imaging process. The existing researches typically choose the back-projection (BP) imaging area according to the SAR platform flight path and the antenna beam width. The limitation of the CSAR imaging area and its azimuth ambiguity region are rarely analyzed theoretically. This paper focus on the sub-aperture imaging of CSAR, based on the BP algorithm, which derives the relationship of azimuth ambiguity with CSAR parameters such as the pause repeat frequency (PRF), slant range angle, velocity of radar platform, etc. This paper proposes an equation for the calculation of the azimuth ambiguity region and analyzes the limitations, which provides theoretical support for CSAR parameter design, imaging area selection, and azimuth ambiguity analysis.

Tumor-derived nanovesicles promote lung distribution of the therapeutic nanovector through repression of Kupffer cell-mediated phagocytosis.

Tumor-derived nanovesicles have been widely used as a biomarker or therapeutic target in various tumor types. However, these nanovesicles have limited use in therapy due to the risk of advancing tumor development. Methods: Exosome-like nanovesicles (ENVs) were developed from metastatic breast cancer 4T1 cells-derived exosomes. The distribution of ENVs and their impact on macrophage-mediated phagocytosis were evaluated. The effect of ENVs pretreatment on anti-lung metastasis therapeutic effects of chemotherapeutic drugs delivered by DOTAP/DOPE liposomes in breast cancer-bearing mice was also examined. Results: We demonstrated that, following intravenous injection in mice, ENVs were preferentially uptaken by Kupffer cells and repressed phagocytosis. The decreased uptake appeared to be due to the translocation of membrane nucleolin from the inner face of the plasma membrane to the cell surface and intercellular Ca2+ fluxes, leading to altered expression of genes involved in phagocytosis by macrophages. Mice pretreated with 4T1-derived ENVs led to the decreased uptake of DOTAP: DOPE liposomes (DDL) in the liver. Consequently, doxorubicin-loaded DDL transported to the lungs instead of the liver, effectively inhibiting breast cancer lung metastasis. Importantly, 4T1 cells exosome-derived ENVs had no detectable toxicity in vivo and low-risk to promote tumor growth and metastasis compared to 4T1 cells exosomes. Conclusion: Our results suggested that pretreatment with 4T1 ENVs represents a strategy to escape Kupffer cell-mediated phagocytosis effectively targeting drug delivery vehicles to tumor metastasis, reducing the IC50 of the chemotherapeutic drugs, and avoiding adverse side effects.

An Improved Imaging Algorithm for High-Resolution Spotlight SAR with Continuous PRI Variation Based on Modified Sinc Interpolation.

This paper focuses on an improved imaging algorithm for spotlight synthetic aperture radar (SAR) with continuous Pulse Repetition Interval (PRI) variation in extremely high-resolution. Conventional SAR systems are limited in that a wide swath cannot be achieved with a high azimuth resolution in the meantime. This limitation can be overcome by Pulse Repetition Frequency (PRF) variation in a SAR system. However, there are problems such as the ambiguities of point targets or extended targets caused by nonuniform sampling. A reconstructive method, Nonuniform Discrete Fourier Transform (NUDFT) has been presented in the current literature, but it is rather computationally expensive. In this paper, a modified sinc interpolation based on NUDFT is proposed, which is used to reconstruct the uniformly sampled echo in time domain. Since the interpolation kernel length is relatively short, it is more computationally efficient. Then, the two-step processing approach combined with the modified sinc interpolation is further presented, which has much better accuracy than that combined with the conventional sinc interpolation. Both the simulated data and the extracted GF-3 data experiment demonstrate the validity and accuracy of the proposed approach.

An Improved BAQ Encoding and Decoding Method for Improving the Quantized SNR of SAR Raw Data.

When the original echo data of SAR are saturated for quantization, the performance of the commonly used block adaptive quantization (BAQ) algorithm will be degraded, which will degrade the imaging quality. This article proposes an improved Llody-Max codec method, which only needs to change the codec look-up table to get better quantization performance when the original echo is saturated. The simulation results show that the proposed method can reduce the quantization power loss, improve the echo signal-to-noise ratio (SNR), and reduce the influence of quantization saturation on the scattering mechanism of polarized SAR data, which have good practical application value.

Decimeter-Level Geolocation Accuracy Updated by a Parametric Tropospheric Model with GF-3.

GaoFen-3 (GF-3) is a multi-polarization C-band synthetic aperture radar (SAR) satellite in China with a resolution of up to 1 m. Up to now, the geolocation accuracy of GF-3 could be improved to 3 m. According to the current study, there still exist meter-level geolocation residuals caused by atmospheric path delay after compensating with a static tropospheric model. In this paper, we compensate the residuals with the sophisticated tropospheric model based on real meteorological data. The experimental results show that the tropospheric model has an accuracy on the millimeter level, which can increase GF-3’s geolocation accuracy to several decimeters compared with the static tropospheric model.

Geo-Positioning Accuracy Improvement of Multi-Mode GF-3 Satellite SAR Imagery Based on Error Sources Analysis.

The GaoFen-3 (GF-3) satellite is the only synthetic aperture radar (SAR) satellite in the High-Resolution Earth Observation System Project, which is the first C-band full-polarization SAR satellite in China. In this paper, we proposed some error sources-based weight strategies to improve the geometric performance of multi-mode GF-3 satellite SAR images without using ground control points (GCPs). To get enough tie points, a robust SAR image registration method and the SAR-features from accelerated segment test (SAR-FAST) method is used to achieve the image registration and tie point extraction. Then, the original position of these tie points in object-space is calculated with the help of the space intersection method. With the dataset clustered by the density-based spatial clustering of applications with noise (DBSCAN) algorithm, we undertake the block adjustment with a bias-compensated rational function model (RFM) aided to improve the geometric performance of these multi-mode GF-3 satellite SAR images. Different weight strategies are proposed to develop the normal equation matrix according to the error sources analysis of GF-3 satellite SAR images, and the preconditioned conjugate gradient (PCG) method is utilized to solve the normal equation. The experimental results indicate that our proposed method can improve the geometric positioning accuracy of GF-3 satellite SAR images within 2 pixels.

A Range Ambiguity Suppression Processing Method for Spaceborne SAR with Up and Down Chirp Modulation.

Range ambiguity is one of the factors which affect the SAR image quality. Alternately transmitting up and down chirp modulation pulses is one of the methods used to suppress the range ambiguity. However, the defocusing range ambiguous signal can still hold the stronger backscattering intensity than the mainlobe imaging area in some case, which has a severe impact on visual effects and subsequent applications. In this paper, a novel hybrid range ambiguity suppression method for up and down chirp modulation is proposed. The method can obtain the ambiguity area image and reduce the ambiguity signal power appropriately, by applying pulse compression using a contrary modulation rate and CFAR detecting method. The effectiveness and correctness of the approach is demonstrated by processing the archive images acquired by Chinese Gaofen-3 SAR sensor in full-polarization mode.

The GF-3 SAR Data Processor.

The Gaofen-3 (GF-3) data processor was developed as a workstation-based GF-3 synthetic aperture radar (SAR) data processing system. The processor consists of two vital subsystems of the GF-3 ground segment, which are referred to as data ingesting subsystem (DIS) and product generation subsystem (PGS). The primary purpose of DIS is to record and catalogue GF-3 raw data with a transferring format, and PGS is to produce slant range or geocoded imagery from the signal data. This paper presents a brief introduction of the GF-3 data processor, including descriptions of the system architecture, the processing algorithms and its output format.

A Quality Assessment Method Based on Common Distributed Targets for GF-3 Polarimetric SAR Data.

The GaoFen-3 (GF-3) satellite, launched on 10 August 2016, is the first C-band polarimetric synthetic aperture radar (PolSAR) satellite in China. The PolSAR system of GF-3 can collect a significant wealth of information for geophysical research and applications. Being used for related applications, GF-3 PolSAR images must be of good quality. It is necessary to evaluate the quality of polarimetric data and achieve the normalized quality monitoring during 8-year designed life of GF-3. In this study, a new quality assessment method of PolSAR data based on common distributed targets is proposed, and the performance of the method is analyzed by simulations and GF-3 experiments. We evaluate the quality of GF-3 PolSAR data by this method. Results suggest that GF-3 antenna is highly isolated, and the quality of calibrated data satisfies the requests of quantitative applications.

MiR-30e inhibits tumor growth and chemoresistance via targeting IRS1 in Breast Cancer.

MicroRNA-30e (miR-30e) is downregulated in various tumor types. However, its mechanism in inhibiting tumor growth of breast cancer remains to be elucidated. In this study, we found that miR-30e was significantly downregulated in tumor tissues of breast cancer (BC) patients and cell lines, and overexpression of miR-30e inhibited cell proliferation, migration and invasion. To understand the potential mechanism of miR-30e in inhibiting tumor growth, we showed that miR-30e blocked the activation of AKT and ERK1/2 pathways, and the expression of HIF-1α and VEGF via directly targeting IRS1. Moreover, miR-30e regulates cell proliferation, migration, invasion and increases chemosensitivity of MDA-MB-231 cells to paclitaxel by inhibiting its target IRS1. MiR-30e also inhibited tumor growth and suppressed expression of IRS1, AKT, ERK1/2 and HIF-1α in mouse xenograft tumors. To test the clinical relevance of these results, we used 40 pairs of BC tissues and adjacent normal tissues, analyzed the levels of miR-30e and IRS1 expression in these tissues, and found that miR-30e levels were significantly inversely correlated with IRS1 levels in these BC tissues, suggesting the important implication of our findings in translational application for BC diagnostics and treatment in the future.

Unambiguous Imaging of Static Scenes and Moving Targets with the First Chinese Dual-Channel Spaceborne SAR Sensor.

Multichannel synthetic aperture radar (SAR) is a breakthrough given the inherent limitation between high-resolution and wide-swath (HRWS) faced with conventional SAR. This paper aims to obtain unambiguous imaging of static scenes and moving targets with the first Chinese dual-channel spaceborne SAR sensor. We propose an integrated imaging scheme with the dual-channel echoes. In the imaging scheme, the subspace-based error estimation algorithm is first applied to the spaceborne multichannel SAR system, followed by the reconstruction algorithm prior to imaging. The motion-adapted reconstruction algorithm for moving target imaging is initially achieved with the spaceborne multichannel SAR system. The results exhibit an effective suppression of azimuth ambiguities and false targets with the proposed process. This paper verifies the accuracy of the subspace-based channel error estimator and the feasibility of the motion-adapted reconstruction algorithm. The proposed imaging process has prospects for future HRWS SAR systems with more channels.

Fast Vessel Detection in Gaofen-3 SAR Images with Ultrafine Strip-Map Mode.

This study aims to detect vessels with lengths ranging from about 70 to 300 m, in Gaofen-3 (GF-3) SAR images with ultrafine strip-map (UFS) mode as fast as possible. Based on the analysis of the characteristics of vessels in GF-3 SAR imagery, an effective vessel detection method is proposed in this paper. Firstly, the iterative constant false alarm rate (CFAR) method is employed to detect the potential ship pixels. Secondly, the mean-shift operation is applied on each potential ship pixel to identify the candidate target region. During the mean-shift process, we maintain a selection matrix recording which pixels can be taken, and these pixels are called as the valid points of the candidate target. The l 1 norm regression is used to extract the principal axis and detect the valid points. Finally, two kinds of false alarms, the bright line and the azimuth ambiguity, are removed by comparing the valid area of the candidate target with a pre-defined value and computing the displacement between the true target and the corresponding replicas respectively. Experimental results on three GF-3 SAR images with UFS mode demonstrate the effectiveness and efficiency of the proposed method.

Exosomes from breast cancer cells stimulate proliferation and inhibit apoptosis of CD133+ cancer cells in vitro.

Exosomes are a family of bioactive vesicles that are secreted from various types of cell, including tumor cells. Exosomes derived from breast cancer cells have been demonstrated to perform important functions in tumor progression in vitro and in vivo. However, few studies exist regarding the function of exosomes in CD133+ breast cancer cells. In the present study, exosomes from 4T1 mouse breast cancer cells and mouse mammary gland epithelial cells were purified. The exosome-associated markers CD63, CD9 and CD81 were detected, and the size distribution and ζ potential of the exosomes were determined. Exosome uptake by CD133+ and CD133-4T1 cells was confirmed by confocal microscopy. An ATPlite assay indicated that the proliferation of CD133+ cells was increased and the apoptosis was suppressed by exosomes from 4T1 cells. Collectively, the findings of the present study demonstrate a novel mechanism by which the action of exosomes on CD133+ 4T1 cells may contribute to breast cancer progression.

[Mucoepidermoid carcinoma of nasopharynx: a report of twelve cases].

BACKGROUND & OBJECTIVE: Mucoepidermoid carcinoma of nasopharynx, a kind of primary adenocarcinoma of nasopharynx, is rare, and has seldom been reported. This article was to summarize the pathogenesis, clinical features, and treatment outcomes of this disease according to our experiences. METHODS: From Jan. 1975 to Dec. 2003, 12 patients with pathologically confirmed primary mucoepidermoid carcinoma of nasopharynx were treated in our hospital. We analyzed retrospectively their clinical data with literature review. RESULTS: The 12 patients with mucoepidermoid carcinoma of nasopharynx accounted for only 0.026% of all nasopharyngeal cancer patients diagnosed simultaneously in our hospital. Age of getting disease was 20 to 60 years old with male to female ratio of 2:1. Positive rates of Epstein-Barr virus serological tests (VCA-IgA, EA-IgA, and DNA enzyme ratio) were very low [50.0% (6/12), 11.1% (1/9), and 20.0% (1/5)]. Of the 11 patients with follow-up data, 4 received chemotherapy, 4 received surgery plus radiotherapy, and 3 received radiochemotherapy. The 5-, and 10-year survival rates of the 12 patients were 27.3%, and 9.0%. CONCLUSIONS: Mucoepidermoid carcinoma of nasopharynx is a special type of nasopharyngeal carcinoma with specific pathogenesis features. Surgery-predominant of complete lumpectomy combined treatment strategy is possibly accommodating.