RESUMO
Colorectal cancer (CRC) is the third leading malignancy worldwide in both new cases and deaths. Neoadjuvant radiotherapy is the standard preoperative regimens for locally advanced patients. However, approximately 50% of patients develop recurrence and metastasis after radiotherapy, which is largely due to the radiation resistance properties of the tumor, and the internal mechanism has not been elucidated. Here we found that CEMIP expression is up-regulated in a variety of tumor types, particularly in CRC. Public databases and clinical samples revealed that CEMIP expression is significantly higher in tumor tissues than in adjacent normal tissues in patients with locally advanced CRC who received neoadjuvant chemoradiotherapy, and it is closely related to the poor prognosis. Functional characterization uncovered that downregulation of CEMIP expression can enhance the radiosensitivity of CRC cells, which is confirmed to be achieved by promoting DNA damage and apoptosis. In vivo studies further verified that CEMIP knockdown can significantly improve the radiosensitivity of subcutaneously implanted colorectal tumors in mice, suggesting that CEMIP may be a radiation-resistant gene in CRC. Mechanistically, EGFR/PI3K/Akt signaling pathway is hypothesized to play a key role in CEMIP mediating radiation resistance. These results provide a potential new strategy targeting CEMIP gene for the comprehensive treatment of locally advanced CRC patients.
Assuntos
Neoplasias Colorretais , Animais , Camundongos , Apoptose/genética , Linhagem Celular Tumoral , Proliferação de Células/genética , Neoplasias Colorretais/genética , Neoplasias Colorretais/radioterapia , Neoplasias Colorretais/metabolismo , Regulação para Baixo , Fosfatidilinositol 3-Quinases/metabolismo , Tolerância a Radiação/genética , Hialuronoglucosaminidase/genéticaRESUMO
BACKGROUND: Colorectal cancer (CRC) is prevalent worldwide and is often challenged by treatment failure and recurrence due to resistance to radiotherapy. Here, we aimed to identify the elusive underlying molecular mechanisms of radioresistance in CRC. METHODS: Weighted gene co-expression network analysis was used to identify potential radiation-related genes. Colony formation and comet assays and multi-target single-hit survival and xenograft animal models were used to validate the results obtained from the bioinformatic analysis. Immunohistochemistry was performed to examine the clinical characteristics of ALDH1L2. Co-immunoprecipitation, immunofluorescence and flow cytometry were used to understand the molecular mechanisms underlying radioresistance. RESULTS: Bioinformatic analysis, in vitro, and in vivo experiments revealed that ALDH1L2 is a radiation-related gene, and a decrease in its expression induces radioresistance in CRC cells by inhibiting ROS-mediated apoptosis. Patients with low ALDH1L2 expression exhibit resistance to radiotherapy. Mechanistically, ALDH1L2 interacts with thioredoxin (TXN) and regulates the downstream NF-κB signaling pathway. PX-12, the TXN inhibitor, overcomes radioresistance due to decreased ALDH1L2. CONCLUSIONS: Our results provide valuable insights into the potential role of ALDH1L2 in CRC radiotherapy. We propose that the simultaneous application of TXN inhibitors and radiotherapy would significantly ameliorate the clinical outcomes of patients with CRC having low ALDH1L2.
Assuntos
Neoplasias Colorretais , NF-kappa B , Animais , Apoptose , Linhagem Celular Tumoral , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/genética , Neoplasias Colorretais/radioterapia , Regulação Neoplásica da Expressão Gênica , Humanos , NF-kappa B/genética , NF-kappa B/metabolismo , Tolerância a Radiação/genética , Transdução de Sinais , Tiorredoxinas/genética , Tiorredoxinas/metabolismo , Tiorredoxinas/uso terapêuticoRESUMO
In this paper a novel, to the best of our knowledge, deep neural network (DNN), VUR-Net, is proposed to realize direct and accurate phase unwrapping. The VUR-Net employs a relatively large number of filters in each layer and adopts alternately two types of residual blocks throughout the network, distinguishing it from the previously reported ones. The proposed method enables the wrapped phase map to be unwrapped precisely without any preprocessing or postprocessing operations, even though the map has been degraded by various adverse factors, such as noise, undersampling, deforming, and so on. We compared the VUR-Net with another two state-of-the-art phase unwrapping DNNs, and the corresponding results manifest that our proposal markedly outperforms its counterparts in both accuracy and robustness. In addition, we also developed two new indices to evaluate the phase unwrapping. These indices are proved to be effective and powerful as good candidates for estimating the quality of phase unwrapping.
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Differential measurement has strong anti-interference ability. We report the first, to the best of our knowledge, experimental demonstration of differential self-mixing interference signals using a randomly polarized laser for differential self-mixing interferometry (SMI). In the differential SMI system, the detection light can be divided into interference signals of $p$p-polarized and $s$s-polarized light with identical intensity and pi-shift phase difference. By exploiting such a new experimental phenomenon, we propose a noise-robust and low-cost self-mixing interferometer. Experiments show that the proposed approach can effectively suppress both periodic and aperiodic noise. Thus, the reported phenomenon and approach has a good application prospect in self-mixing interferometers.
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The existing lens correction methods deal with the distortion correction by one or more specific image distortion models. However, distortion determination may fail when an unsuitable model is used. So, methods based on the distortion model would have some drawbacks. A model-free lens distortion correction based on the phase analysis of fringe-patterns is proposed in this paper. Firstly, the mathematical relationship of the distortion displacement and the modulated phase of the sinusoidal fringe-pattern are established in theory. By the phase demodulation analysis of the fringe-pattern, the distortion displacement map can be determined point by point for the whole distorted image. So, the image correction is achieved according to the distortion displacement map by a model-free approach. Furthermore, the distortion center, which is important in obtaining an optimal result, is measured by the instantaneous frequency distribution according to the character of distortion automatically. Numerical simulation and experiments performed by a wide-angle lens are carried out to validate the method.
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A technique called surface plasmon resonance digital holographic microscopy (SPRDHM) for optical imaging of cell membranes is proposed. The intensity and phase distributions of the reflected light that is modulated by the cell membrane in surface plasmon resonance can be simultaneously obtained. The imaging principle and capability are theoretically analyzed and demonstrated by experiments. In addition, the technique is compared with total internal reflection digital holographic microscopy (TIRDHM) in theory and experiment, respectively. The results show that the SPRDHM technique is better in spatial resolution and phase sensitivity than the TIRDHM technique for imaging of cell membranes.
Assuntos
Membrana Celular/ultraestrutura , Holografia/métodos , Microscopia/métodos , Ressonância de Plasmônio de Superfície/métodos , Holografia/instrumentação , Processamento de Imagem Assistida por Computador/estatística & dados numéricos , Microscopia/instrumentação , Cebolas/ultraestrutura , Fenômenos Ópticos , Ressonância de Plasmônio de Superfície/instrumentaçãoRESUMO
The main factor that limits the quality of an image reconstructed by the process of spatial filtering in digital holographic microscopy is discussed. A spatial filter determined by the distribution of the spectrum of the virtual image is designed automatically for real time dynamic analysis of a micro-object, and an optimal reconstructed phase image can be obtained. An experiment of a holographic image with an onion specimen is presented to prove the validity of this approach. Comparing the numerical reconstruction of the hologram by employing different spatial filters with the automatic spatial filtering shows the superiority of the automatic spatial filtering method, and it is suitable for dynamic and automatic analysis.
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A generalized Fourier analysis, by use of an adaptive multiscale windowed Fourier transform (AWFT), has been presented for the phase retrieval of fringe patterns. The Fourier transform method can be considered as a special case of AWFT method with a maximum window. The instantaneous frequency of the local signal is introduced to estimate whether the condition for separating the first spectrum component is satisfied for the phase retrieval of fringe patterns. The adaptive window width for this algorithm is determined by the length of the local stationary fringe pattern in order to balance the frequency and space resolution. The local stationary length of fringe pattern is defined as the signal satisfying the condition that whose first spectrum component is separated from all the other spectra within the local spatial area. In comparison with Fourier transform, fixed windowed Fourier transform and wavelet transform in numerical simulation and experiment, the adaptive multiscale windowed Fourier transform can present more accurate results of phase retrieval.
Assuntos
Algoritmos , Reconhecimento Automatizado de Padrão/métodos , Refratometria/métodos , Análise de FourierRESUMO
We describe a numerical reconstruction technique for digital holography by means of the two-dimensional Gabor wavelet transform (2D-GWT). Applying the 2D-GWT to digital holography, the object wave can be reconstructed by calculating the wavelet coefficients of the hologram at the peak of the 2D-GWT automatically. At the same time the effect of the zero-order diffraction image and the twin image are eliminated without spatial filtering. Comparing the numerical reconstruction of a holographic image by the analysis of the one-dimensional Gabor wavelet transform (1D-GWT) with the 2D-GWT, we show that the 2D-GWT method is superior to the 1D-GWT method, especially when the fringes of the hologram are not just along the y direction. The theory and the results of a simulation and experiments are shown.
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A numerical reconstruction technique of digital holography based on angular spectrum diffraction by means of the ridge of Gabor wavelet transform (GWT) is presented. Appling the GWT, the object wave can be reconstructed by calculating the wavelet coefficients of the hologram at the ridge of the GWT automatically even if the spectrum of the virtual image is disturbed by the other spectrum. It provides a way to eliminate the effect of the zero-order and the twin-image terms without the spatial filtering. In particular, based on the angular spectrum theory, GWT is applied to the digital holographic phase-contrast microscopy on biological specimens. The theory, the results of a simulation and an experiment of an onion specimen are shown.
Assuntos
Processamento de Imagem Assistida por Computador/instrumentação , Processamento de Imagem Assistida por Computador/métodos , Microscopia de Contraste de Fase/instrumentação , Microscopia de Contraste de Fase/métodos , Cebolas/metabolismo , Algoritmos , Compressão de Dados/métodos , Análise de Fourier , Holografia/métodos , Aumento da Imagem/métodos , Imageamento Tridimensional/métodos , Modelos Estatísticos , Reconhecimento Automatizado de Padrão/métodos , Processamento de Sinais Assistido por ComputadorRESUMO
A new method for phase retrieval of optical fringe patterns is presented. This method is based on a wavelet transform and is capable of extracting the full 2D phase distribution from a single fringe pattern. An important conclusion that the phase of the optical fringe pattern is equal to the phase of its wavelet transform on the ridge of the wavelet transform is theoretically clarified. The method is compared with the Fourier transform and the integration methods. A numerical simulation and an experimental example of phase retrieval are shown.
Assuntos
Algoritmos , Aumento da Imagem/métodos , Interpretação de Imagem Assistida por Computador/métodos , Microscopia de Contraste de Fase/métodos , Refratometria/métodos , Análise de Fourier , Reprodutibilidade dos Testes , Sensibilidade e EspecificidadeRESUMO
We present an analysis of a spatial carrier-fringe pattern in three-dimensional (3-D) shape measurement by using the wavelet transform, a tool excelling for its multiresolution in the time- and space-frequency domains. To overcome the limitation of the Fourier transform, we introduce the Gabor wavelet to analyze the phase distributions of the spatial carrier-fringe pattern. The theory of wavelet transform profilometry, an accuracy check by means of a simulation, and an example of 3-D shape measurement are shown.