ABSTRACT
Mitochondrial oxidative phosphorylation (OXPHOS) has long been considered the primary energy source in breast cancer cells. Cytochrome c oxidase assembly factor 6 (COA6), which functions as a metal chaperone to transport copper to complex â £ during the OXPHOS process, plays a crucial role in the carcinogenesis of lung adenocarcinoma. Nevertheless, its specific function in breast cancer is undefined. The present investigation aimed to clarify COA6's expression profile and regulatory functions in breast cancer, as well as to unveil its underlying mechanisms. Initially, our findings revealed a significant upregulation of COA6 in breast cancer, as evidenced by an analysis of the TCGA database and tissue microarrays. This upregulation correlated with tumor size and histological grade. Additionally, survival analysis revealed that elevated COA6 amounts were correlated with decreased overall survival (OS) in breast cancer. To delve deeper into the functions of COA6, both COA6-overexpressing and COA6-knockdown breast cancer cell models were established. These experiments demonstrated COA6 is pivotal in regulating cell proliferation, apoptosis, migration, and invasion, thereby promoting cancer progression in vitro. Notably, functional enrichment analysis indicated COA6 might be involved in breast cancer progression by modulating oxidative phosphorylation (OXPHOS). Collectively, this study reveals an overt tumorigenic role for COA6 in breast cancer and sheds light on its potential mechanisms, offering valuable therapeutic targets for breast cancer therapy.
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Depth images and thermal images contain the spatial geometry information and surface temperature information, which can act as complementary information for the RGB modality. However, the quality of the depth and thermal images is often unreliable in some challenging scenarios, which will result in the performance degradation of the two-modal based salient object detection (SOD). Meanwhile, some researchers pay attention to the triple-modal SOD task, namely the visible-depth-thermal (VDT) SOD, where they attempt to explore the complementarity of the RGB image, the depth image, and the thermal image. However, existing triple-modal SOD methods fail to perceive the quality of depth maps and thermal images, which leads to performance degradation when dealing with scenes with low-quality depth and thermal images. Therefore, in this paper, we propose a quality-aware selective fusion network (QSF-Net) to conduct VDT salient object detection, which contains three subnets including the initial feature extraction subnet, the quality-aware region selection subnet, and the region-guided selective fusion subnet. Firstly, except for extracting features, the initial feature extraction subnet can generate a preliminary prediction map from each modality via a shrinkage pyramid architecture, which is equipped with the multi-scale fusion (MSF) module. Then, we design the weakly-supervised quality-aware region selection subnet to generate the quality-aware maps. Concretely, we first find the high-quality and low-quality regions by using the preliminary predictions, which further constitute the pseudo label that can be used to train this subnet. Finally, the region-guided selective fusion subnet purifies the initial features under the guidance of the quality-aware maps, and then fuses the triple-modal features and refines the edge details of prediction maps through the intra-modality and inter-modality attention (IIA) module and the edge refinement (ER) module, respectively. Extensive experiments are performed on VDT-2048 dataset, and the results show that our saliency model consistently outperforms 13 state-of-the-art methods with a large margin. Our code and results are available at https://github.com/Lx-Bao/QSFNet.
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OBJECTIVE: There are many factors that affect the survival of patients with gastric cancer, such as TNM stage, the patient's nutritional status, inflammation, and so on. In this study, the prognostic significance of preoperative fibrinogen-to-albumin ratio (FAR) and postoperative TNM staging in patients with gastric cancer was retrospectively studied. METHODS: A total of 265 patients (surgery dates from January 2007 to December 2013) were included in this retrospective study. All the patients were confirmed by pathology after operation. Categorical variables were compared using the χ2 test. Kaplan-Meier and log-rank tests were used for survival analysis. Cox proportional hazard models were used to assess prognostic factors. Nomogram was applied to predict the prognosis of overall survival (OS). RESULTS: The higher the FAR value, the more lymph node metastasis, the later the TNM stage, and the shorter the survival time. We established a new scoring system, the FAR-TNM score, which combined FAR and TNM stage. The FAR-TNM score was significantly related to tumor location, tumor size, Bormann types, differentiation, operative type, vascular invasion, nerve invasion, depth of invasion, lymphatic metastasis, and advanced TNM stage. Multivariate Cox regression analysis demonstrated that tumor location, TNM stage, adjuvant chemotherapy, and FAR-TNM score were independent prognostic elements for OS in patients with GC. CONCLUSIONS: The FAR-TNM score was a valuable independent prognostic indicator for GC patients after surgery, which can help clinicians to assist the treatment and long-term management of patients with gastric cancer.
Subject(s)
Stomach Neoplasms , Humans , Neoplasm Staging , Retrospective Studies , Stomach Neoplasms/pathology , Prognosis , Gastrectomy , Lymphatic Metastasis , Fibrinogen , AlbuminsABSTRACT
Aberrant expression of DEPDC1B (DEP domain-containing protein 1B) has been shown to be associated with various types of malignant tumors. However, little is known about the role of DEPDC1B in epithelial ovarian cancer (EOC). The purpose of this study was to investigate the expression and role of DEPDC1B in EOC. Immunohistochemical staining of 60 high-grade serous ovarian cancer (HGSOC) showed that DEPDC1B expression was associated with response to first line chemotherapy, and DEPDC1B expression was higher in platinum-resistant patients than in platinum-sensitive patients. However, there was no association between DEPDC1B expression and age, preoperative CA125 level, ascites status, location, FIGO stage, and residual disease. Furthermore, our study demonstrated that increased DEPDC1B expression was correlated with reduced overall survival (OS) and progression-free survival (PFS) time in patients with HGSOC. Multivariate analysis showed that DEPDC1B independently predicted OS in patients with HGSOC. However, DEPDC1B expression was not an independent prognostic factor for PFS in patients with HGSOC. Moreover, our study demonstrated that DEPDC1B could promote the proliferation of OVCAR3 and SKOV3 cells by enhancing AKT phosphorylation at Ser473. Treatment with MK2206 and LY294002 significantly suppressed cell proliferation that is induced by DEPDC1B up-regulation in both OVCAR3 and SKOV3 cells. Together, these results revealed that DEPDC1B was an independent prognostic factor for OS in patients with HGSOC, and DEPDC1B may promote the proliferation of EOC cells via enhancing AKT phosphorylation at Ser473.
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Performance bottlenecks in the optimization of JND modeling based on low-level manual visual feature metrics have emerged. High-level semantics bear a considerable impact on perceptual attention and subjective video quality, yet most existing JND models do not adequately account for this impact. This indicates that there is still much room and potential for performance optimization in semantic feature-based JND models. To address this status quo, this paper investigates the response of visual attention induced by heterogeneous semantic features with an eye on three aspects, i.e., object, context, and cross-object, to further improve the efficiency of JND models. On the object side, this paper first focuses on the main semantic features that affect visual attention, including semantic sensitivity, objective area and shape, and central bias. Following that, the coupling role of heterogeneous visual features with HVS perceptual properties are analyzed and quantified. Second, based on the reciprocity of objects and contexts, the contextual complexity is measured to gauge the inhibitory effect of contexts on visual attention. Third, cross-object interactions are dissected using the principle of bias competition, and a semantic attention model is constructed in conjunction with a model of attentional competition. Finally, to build an improved transform domain JND model, a weighting factor is used by fusing the semantic attention model with the basic spatial attention model. Extensive simulation results validate that the proposed JND profile is highly consistent with HVS and highly competitive among state-of-the-art models.
ABSTRACT
With the rapidly emerging user-generated images, perception compression for color image is an inevitable mission. Whilst in existing just noticeable difference (JND) models, color-oriented features are not fully taken into account for coinciding with HVS perception characteristics, such as sensitivity, attention, and masking. To fully imitate the color perception process, we extract color-related feature parameters as local features, including color edge intensity and color complexity, as well as region-wise features, including color area proportion, color distribution position and color distribution dispersion, and inherent feature irrelevant to color content called color perception difference. Then, the potential interaction among them is analyzed and modeled as color contrast intensity. To utilize them, color uncertainty and color saliency are envisaged to emanate from feature integration in the information communication framework. Finally, color and uncertainty saliency models are applied to improve the conventional JND model, taking the masking and attention effect into consideration. Subjective and objective experiments validate the effectiveness of the proposed model, delivering superior noise concealment capacity compared with start-of-the-art works.
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MOTIVATION: Light-field microscopy (LFM) is a compact solution to high-speed 3D fluorescence imaging. Usually, we need to do 3D deconvolution to the captured raw data. Although there are deep neural network methods that can accelerate the reconstruction process, the model is not universally applicable for all system parameters. Here, we develop AutoDeconJ, a GPU-accelerated ImageJ plugin for 4.4× faster and more accurate deconvolution of LFM data. We further propose an image quality metric for the deconvolution process, aiding in automatically determining the optimal number of iterations with higher reconstruction accuracy and fewer artifacts. RESULTS: Our proposed method outperforms state-of-the-art light-field deconvolution methods in reconstruction time and optimal iteration numbers prediction capability. It shows better universality of different light-field point spread function (PSF) parameters than the deep learning method. The fast, accurate and general reconstruction performance for different PSF parameters suggests its potential for mass 3D reconstruction of LFM data. AVAILABILITY AND IMPLEMENTATION: The codes, the documentation and example data are available on an open source at: https://github.com/Onetism/AutoDeconJ.git. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.
Subject(s)
Image Processing, Computer-Assisted , Imaging, Three-Dimensional , Image Processing, Computer-Assisted/methods , Imaging, Three-Dimensional/methods , Microscopy/methods , Neural Networks, ComputerABSTRACT
Currently, the target detection based on convolutional neural network plays an important role in image recognition, speech recognition and other fields. However, the current network model features a complex structure, a huge number of parameters and resources. These conditions make it difficult to apply in embedded devices with limited computational capabilities and extreme sensitivity to power consumption. In this regard, the application scenarios of deep learning are limited. This paper proposes a real-time detection scheme for cook assistant overalls based on the Hi3559A embedded processor. With YOLOv3 as the benchmark network, this scheme fully mobilizes the hardware acceleration resources through the network model optimization and the parallel processing technology of the processor, and improves the network reasoning speed, so that the embedded device can complete the task of real-time detection on the local device. The experimental results show that through the purposeful cropping, segmentation and in-depth optimization of the neural network according to the specific processor, the neural network can recognize the image accurately. In an application environment where the power consumption is only 5.5 W, the recognition speed of the neural network on the embedded end is increased to about 28 frames (the design requirement was to achieve a recognition speed of 25 frames or more), so that the optimized network can be effectively applied in the back kitchen overalls identification scene.
Subject(s)
Computers , Neural Networks, Computer , Problem Solving , Recognition, PsychologyABSTRACT
The human visual system (HVS) is a hierarchical system, in which visual signals are processed hierarchically. In this paper, the HVS is modeled as a three-level communication system and visual perception is divided into three stages according to the hierarchical predictive coding theory. Then, a novel just noticeable distortion (JND) estimation scheme is proposed. In visual perception, the input signals are predicted constantly and spontaneously in each hierarchy, and neural response is evoked by the central residue and inhibited by surrounding residues. These two types' residues are regarded as the positive and negative visual incentives which cause positive and negative perception effects, respectively. In neuroscience, the effect of incentive on observer is measured by the surprise of this incentive. Thus, we propose a surprise-based measurement method to measure both perception effects. Specifically, considering the biased competition of visual attention, we define the product of the residue self-information (i.e., surprise) and the competition biases as the perceptual surprise to measure the positive perception effect. As for the negative perception effect, it is measured by the average surprise (i.e., the local Shannon entropy). The JND threshold of each stage is estimated individually by considering both perception effects. The total JND threshold is finally obtained by non-linear superposition of three stage thresholds. Furthermore, the proposed JND estimation scheme is incorporated into the codec of Versatile Video Coding for image compression. Experimental results show that the proposed JND model outperforms the relevant existing ones, and over 16% of bit rate can be reduced without jeopardizing the perceptual quality.
Subject(s)
Data Compression/methods , Image Processing, Computer-Assisted/methods , Models, Neurological , Sensory Thresholds/physiology , Visual Perception/physiology , Algorithms , Deep Learning , HumansABSTRACT
OBJECTIVE: ADAM12 is a member of a disintegrin and metalloproteinase family and has been reported to participate in the development of variety of tumors. However, the role of ADAM12 in Non-Hodgkin Lymphoma (NHL) has not been investigated. The present study was undertaken to determine the expression and biologic function of ADAM12 in human NHL. METHODS: First, we constructed a model of cell adhesion in NHL, the mRNA, and protein level of ADAM12 in suspension and the adhesion model was analyzed by RT-PCR and western blot. Then, flow cytometry assay and western blot were used to investigate the mechanism of ADAM12 in the proliferation of NHL cells. In vitro, after using siRNA interfering ADAM12 expression, we performed adhesion assay and cell viability assay to determine the effect of ADAM12 on adhesive rate and drug sensitivity. RESULTS: ADAM12 was lowly expressed in suspended cells and highly expressed in adherent NHL cells. In addition, ADAM12 was positively correlated with the proliferation and apoptosis of NHL cells by regulating the expression of p-AKT and p-GSK-3ß. Furthermore, ADAM12 promoted cell adhesion-mediated drug resistance (CAM-DR) in DLBCL via AKT signaling pathway. CONCLUSION AND DISCUSSION: Our data support a role for ADAM12 in NHL cell proliferation, adhesion, and drug resistance, and it may pave the way for a novel therapeutic approach for CAM-DR in NHL.
Subject(s)
ADAM12 Protein/genetics , Cell Adhesion/genetics , Drug Resistance, Neoplasm/genetics , Gene Expression Regulation, Neoplastic , Lymphoma, Non-Hodgkin/genetics , Animals , Antineoplastic Agents/pharmacology , Antineoplastic Agents/therapeutic use , Apoptosis/drug effects , Apoptosis/genetics , Biomarkers, Tumor , Cell Cycle/drug effects , Cell Cycle/genetics , Cell Line, Tumor , Cell Proliferation , Glycogen Synthase Kinase 3 beta/genetics , Glycogen Synthase Kinase 3 beta/metabolism , Humans , Lymphoma, Non-Hodgkin/drug therapy , Lymphoma, Non-Hodgkin/metabolism , Mice , Proto-Oncogene Proteins c-akt/genetics , Proto-Oncogene Proteins c-akt/metabolism , RNA Interference , RNA, Small Interfering/genetics , Signal TransductionABSTRACT
Dysregulation of TRIM44 has been reported to be involved in tumorigenesis, but its role in hepatocellular carcinoma (HCC) remains unclear. In the present study, we investigated the clinicopathological and biological significance of TRIM44 in HCC. We found that TRIM44 mRNA and protein expression was upregulated in HCC compared with matched normal tissues. Intriguingly, we also found that TRIM44 expression was significantly correlated with tumor size (P < 0.001), vascular invasion (P < 0.001), intrahepatic metastasis (P < 0.001), distant metastasis (P < 0.001), and Ki-67 expression (P < 0.001). Kaplan-Meier analysis showed that high TRIM44 staining was significantly correlated with shorter overall survival (P < 0.001). TRIM44 was an independent predictor of overall survival in patients with HCC. Furthermore, we found that ectopic expression of TRIM44 could promote cell proliferation via accelerating the G1/S-phase transition in HCC. Moreover, overexpression of TRIM44 could enhance the invasive and migratory capacity of HCC cells. Meanwhile, we found that high expression of TRIM44 could enhance resistance of HCC cells to doxorubicin via accelerating NF-κB activation. In conclusion, our results suggest that TRIM44 may be a novel prognostic indicator and potential therapeutic target of HCC.
Subject(s)
Carcinoma, Hepatocellular/secondary , Carrier Proteins/metabolism , Cell Movement , Cell Proliferation , Drug Resistance, Neoplasm , Liver Neoplasms/pathology , Apoptosis , Biomarkers, Tumor/genetics , Biomarkers, Tumor/metabolism , Blotting, Western , Carcinoma, Hepatocellular/drug therapy , Carcinoma, Hepatocellular/metabolism , Carrier Proteins/antagonists & inhibitors , Carrier Proteins/genetics , Cell Cycle , Doxorubicin , Female , Gene Expression Regulation, Neoplastic , Humans , Immunoenzyme Techniques , Immunoprecipitation , Intracellular Signaling Peptides and Proteins , Liver Neoplasms/drug therapy , Liver Neoplasms/metabolism , Male , Middle Aged , Neoplasm Invasiveness , Neoplasm Staging , Prognosis , RNA, Messenger/genetics , RNA, Small Interfering/genetics , Real-Time Polymerase Chain Reaction , Reverse Transcriptase Polymerase Chain Reaction , Signal Transduction , Tripartite Motif Proteins , Tumor Cells, CulturedABSTRACT
YB-1 is a multifunctional protein, which has been shown to correlate with resistance to treatment of various tumor types. This study investigated the expression and biologic function of YB-1 in diffuse large B-cell lymphoma (DLBCL). Immunohistochemical analysis showed that the expression statuses of YB-1 and pYB-1(S102) were reversely correlated with the clinical outcomes of DLBCL patients. In addition, we found that YB-1 could promote the proliferation of DLBCL cells by accelerating the G1/S transition. Ectopic expression of YB-1 could markedly increase the expression of cell cycle regulators cyclin D1 and cyclin E. Furthermore, we found that adhesion of DLBCL cells to fibronectin (FN) could increase YB-1 phosphorylation at Ser102 and pYB-1(S102) nuclear translocation. In addition, overexpression of YB-1 could increase the adhesion of DLBCL cells to FN. Intriguingly, we found that YB-1 overexpression could confer drug resistance through cell-adhesion dependent and independent mechanisms in DLBCL. Silencing of YB-1 could sensitize DLBCL cells to mitoxantrone and overcome cell adhesion-mediated drug resistance (CAM-DR) phenotype in an AKT-dependent manner.
Subject(s)
Drug Resistance, Neoplasm/drug effects , Lymphoma, Large B-Cell, Diffuse/pathology , Y-Box-Binding Protein 1/metabolism , Cell Adhesion/drug effects , Cell Cycle/drug effects , Cell Line, Tumor , Cell Proliferation/drug effects , Female , Humans , Male , Middle Aged , Mitoxantrone/pharmacology , Multivariate Analysis , Phosphorylation/drug effects , Phosphoserine/metabolism , Prognosis , Proto-Oncogene Proteins c-akt/metabolismABSTRACT
The chaperonin containing t-complex polypeptide 1 (CCT) is known to mediate folding of proteins. CCT, subunit 8 (CCT8), is the θ subunit of CCT complex chaperonin. CCT8 has been reported to be dysregulated in several tumor tissues. In this study, we investigated the role of CCT8 in B-cell non-Hodgkin's lymphoma (NHL). Clinically, the expression levels of CCT8 in reactive lymphoid hyperplasia (RLH) and B-cell NHL specimens were investigated using immunohistochemical analysis. We found that CCT8 was highly expressed in proliferating germinal center cells compared with the quiescent cells of the follicular mantle zone. Furthermore, CCT8 was highly expressed in progressive lymphomas than in indolent lymphomas. Kaplan-Meier curve showed that high expression of CCT8 was significantly associated with shorter overall survival in patients with diffuse large B-cell lymphoma. Moreover, we demonstrated that CCT8 could promote the proliferation of B-cell NHL cells. In addition, we found that CCT8 could accelerate the G1/S transition in B-cell NHL. Finally, we demonstrated that overexpression of CCT8 could reverse cell adhesion-mediated drug resistance (CAM-DR) phenotype. Our study may shed new insights into the important role of CCT8 in cancer development.
Subject(s)
Chaperonin Containing TCP-1/physiology , Lymphoma, B-Cell/chemistry , Aged , Cell Adhesion , Cell Cycle , Cell Line, Tumor , Cell Proliferation , Chaperonin Containing TCP-1/analysis , Disease Progression , Drug Resistance, Neoplasm , Female , Germinal Center/chemistry , Germinal Center/pathology , Humans , Immunohistochemistry/methods , Lymphoma, B-Cell/pathology , Male , Middle Aged , Survival RateABSTRACT
BACKGROUND: The Karyopherin proteins are involved in the shuttling of cargo proteins, and certain RNAs, across the nuclear pore complex into and out of the cell nucleus. Karyopherin ß1 (Kpnß1) is a member of the Karyopherin ß superfamily of nuclear transport proteins. In addition to the nuclear import function, Kpnß1 is associated with the occurrence of tumors. This study investigated the expression and biologic function of Kpnß1 in diffuse large B-cell lymphoma (DLBCL). METHODS: The prognostic value of Kpnß1 expression was evaluated using immunohistochemical staining. The role of Kpnß1 on cell proliferation- and cell adhesion-mediated drug resistance (CAM-DR) was also determined. RESULTS: We demonstrated that Kpnß1 mRNA and protein expression levels were significantly higher in DLBCL B-cells and DLBCL cell lines than in normal CD19 purified B-cells. Immunohistochemical analysis suggested that the expression of Kpnß1 was correlated with Ki-67 (P < 0.001). Kaplan-Meier curve showed that high expression of Kpnß1 was significantly associated with shorter overall survival. In addition, Kpnß1 was associated with the proliferation of DLBCL cells. Importantly, we found that Kpnß1 could interact with p65 and promote CAM-DR via accelerating NF-κB activation in DLBCL. CONCLUSIONS: Patients with tumors highly expressing Kpnß1 have poorer overall survivals. Kpnß1 interacts with p65 and enhances CAM-DR.
Subject(s)
Cell Proliferation/genetics , Drug Resistance, Neoplasm/genetics , Gene Expression Regulation, Neoplastic , Lymphoma, Large B-Cell, Diffuse/genetics , beta Karyopherins/genetics , Adult , Aged , Aged, 80 and over , Cell Adhesion/genetics , Cell Line, Tumor , Female , Humans , Lymphoma, Large B-Cell, Diffuse/metabolism , Lymphoma, Large B-Cell, Diffuse/mortality , Lymphoma, Large B-Cell, Diffuse/pathology , Male , Middle Aged , Up-Regulation , beta Karyopherins/metabolismABSTRACT
OBJECTIVES: Sam68 (Src-associated in mitosis 68 kDa), a substrate for tyrosine kinase c-Src during mitosis, is up-regulated in a variety of human cancers and acts oncogenically promoting tumour progression. This study has explored biological function and clinical significance of Sam68 in non-Hodgkin's lymphoma (NHL). MATERIALS AND METHODS: To examine Sam68 expression in NHL, clinically, eight diffuse large B-cell lymphomas and four reactive lymphoid hyperplasia fresh-frozen tissues were obtained for western blot and quantitative real-time PCR analyses. Using immunohistochemical staining, paraffin wax embedded sections from 164 cases of NHL patients were used to evaluate prognostic value of Sam68. Cell Counting Kit-8 (CCK-8) and soft agar colony assays were conducted to investigate the role of Sam68 in cell viability and cell proliferation respectively. Furthermore, effects of Sam68 on cell adhesion-mediated drug resistance (CAM-DR) was determined by CCK-8 assay and flow cytometric analysis. RESULTS: Expression status of Sam68 inversely correlated with clinical outcomes of patients with NHL, and it was also an independent prognostic factor for the outcomes. In addition, Sam68 was associated with proliferation of NHL cells. Knock-down of its gene inhibited cell proliferation and colony formation by delaying cell cycle progression. Furthermore, OCI-Ly8 and Jeko-1 cells adhering to FN and HS-5 expressed higher Sam68 protein, compared to their suspension counterparts. Sam68 promoted cell adhesion-mediated drug resistance (CAM-DR) via the AKT pathway. CONCLUSIONS: Increased Sam68 expression in NHL resulted in poor prognosis, and it promoted CAM-DR in NHL via AKT.
Subject(s)
Adaptor Proteins, Signal Transducing/genetics , Cell Adhesion/genetics , Cell Proliferation/genetics , DNA-Binding Proteins/genetics , Drug Resistance/genetics , Lymphoma, Non-Hodgkin/genetics , RNA-Binding Proteins/genetics , Adaptor Proteins, Signal Transducing/metabolism , Apoptosis/genetics , Biomarkers, Tumor/genetics , Cell Line, Tumor , Coculture Techniques , DNA-Binding Proteins/metabolism , Female , Humans , Lymphoma, Non-Hodgkin/mortality , Lymphoma, Non-Hodgkin/pathology , Male , Middle Aged , Prognosis , Proto-Oncogene Proteins c-akt/metabolism , RNA, Messenger/biosynthesis , RNA-Binding Proteins/metabolismABSTRACT
OBJECTIVE: Fibulin-1 is a member of the fibulin gene family, characterized by tandem arrays of epidermal growth factor-like domains and a C-terminal fibulin-type module. Fibulin-1 plays important roles in a range of cellular functions including morphology, growth, adhesion and mobility. It acts as a tumor suppressor gene in cutaneous melanoma, prostate cancer and gastric cancer. However, whether fibulin-1 also acts as a tumor suppressor gene in lung adenocarcinoma remains unknown. We also determined the association of fibulin-1 expression with various clinical and pathological parameters, which would show its potential role in clinical prognosis. METHODS: We investigated and followed up 140 lung adenocarcinoma patients who underwent lung resection without pre- and post-operative systemic chemotherapy at the Affiliated Hospital of Nantong University from 2009 to 2013. Western blot assay and immunohistochemistry were used to evaluate the expression of fibulin-1 in lung adenocarcinoma tissues. We then analyzed the correlations between fibulin-1 expression and clinicopathological variables as well as the patients' overall survival rate. RESULTS: Both western blot assay and immunohistochemistry demonstrated that the level of fibulin-1 was downregulated in human lung adenocarcinoma tissues compared with that of normal lung tissues. Fibulin-1 expression significantly correlated with histological differentiation (P = 0.046), clinical stage (P< 0.01), lymph node status (P = 0.038) and expression of Ki-67 (P = 0.013). More importantly, multivariate analysis revealed that fibulin-1 was an independent prognostic marker for lung adenocarcinoma, and high expression of fibulin-1 was significantly associated with better prognosis of lung adenocarcinoma patients. CONCLUSIONS: The results supported our hypothesis that fibulin-1 can act as a prognostic factor in lung adenocarcinoma progression.
Subject(s)
Adenocarcinoma/pathology , Calcium-Binding Proteins/metabolism , Lung Neoplasms/pathology , Adenocarcinoma/mortality , Adenocarcinoma/surgery , Adenocarcinoma of Lung , Adult , Aged , Biomarkers, Tumor/metabolism , Blotting, Western , Disease Progression , Female , Follow-Up Studies , Humans , Immunohistochemistry , Kaplan-Meier Estimate , Ki-67 Antigen/metabolism , Lung Neoplasms/mortality , Lung Neoplasms/surgery , Lymphatic Metastasis , Male , Middle Aged , Multivariate Analysis , Neoplasm Staging , Prognosis , Stomach Neoplasms/mortalityABSTRACT
The expression and biologic function of the gene encoding vacuolar protein sorting 4B (VPS4B) in human multiple myeloma (MM) were investigated in this study. We determined that VPS4B expression is decreased in adherent MM cells and that knockdown of VPS4B expression induces cell adhesion-mediated drug resistance (CAM-DR) in MM. This induced CAM-DR phenotype manifested through down-regulation of cell apoptosis and requires phosphorylation of AKT and Erk. Finally, VPS4B expression was positively correlated with cell proliferation. Our findings support a role for VPS4B in MM cell proliferation, adhesion, and drug resistance, and pave the way for a novel therapeutic approach targeting this molecule.
Subject(s)
Adenosine Triphosphatases/genetics , Drug Resistance, Neoplasm/genetics , Endosomal Sorting Complexes Required for Transport/genetics , Gene Expression Regulation, Neoplastic , Multiple Myeloma/genetics , ATPases Associated with Diverse Cellular Activities , Adenosine Triphosphatases/metabolism , Apoptosis/genetics , Cell Adhesion/genetics , Cell Line, Tumor , Down-Regulation , Endosomal Sorting Complexes Required for Transport/metabolism , Gene Knockdown Techniques , Humans , Mitogen-Activated Protein Kinase 1/metabolism , Mitogen-Activated Protein Kinase 3/metabolism , Multiple Myeloma/drug therapy , Multiple Myeloma/metabolism , Phenotype , Phosphorylation , Proto-Oncogene Proteins c-aktABSTRACT
Mounting evidence has proved that cellular adhesion confers resistance to chemotherapy in multiple lymphomas. The molecular mechanism underlying cell adhesion-mediated drug resistance (CAM-DR) is, however, poorly understood. In this study, we investigated the expression and biologic function of histamine-releasing factor (HRF) in non-Hodgkin lymphomas (NHLs). Clinically, by immunohistochemistry analysis we observed obvious up-regulation of HRF in NHLs including diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL) and natural killer (NK)/T-cell lymphoma. Functionally, overexpression and knockdown of HRF demonstrated the antiapoptotic effect of HRF in NHL cells, which may be associated with activation of the p-CREB/BCL-2 signaling pathway. Moreover, cell adhesion assay demonstrated that adhesion to fibronectin (FN) or HS-5 up-regulated HRF expression, while knockdown of HRF resulted in decreased cell adhesion, which led to reversed CAM-DR. Our finding supports the role of HRF in NHL cell apoptosis, adhesion and drug resistance, and may provide a clinical therapeutic target for CAM-DR in NHL.
Subject(s)
Apoptosis , Biomarkers, Tumor/metabolism , Cell Adhesion , Drug Resistance, Neoplasm , Lymphoma, Non-Hodgkin/drug therapy , Lymphoma, Non-Hodgkin/pathology , Biomarkers, Tumor/antagonists & inhibitors , Biomarkers, Tumor/genetics , Blotting, Western , Cell Proliferation , Flow Cytometry , Humans , Immunoenzyme Techniques , Lymphoma, Non-Hodgkin/metabolism , RNA, Small Interfering/genetics , Signal Transduction , Tumor Cells, Cultured , Tumor Protein, Translationally-Controlled 1ABSTRACT
In this study, the expression of neural precursor cell expressed developmentally downregulated 9 (NEDD9) in benign and malignant gastric tissues was investigated, and the significance of NEDD9 in gastric cancer prognosis was explored. Immunohistochemistry was used to detect NEDD9 expression in gastric cancer, nontumor gastric, and normal gastric tissues. The relationship between NEDD9 expression in gastric cancer tissues and the clinicopathologic factors was examined using the Mann-Whitney U test. The two factors between NEDD9 expression and tumor node metastasis (TNM) stage in gastric cancer patients were analyzed by Spearman rank correlation analysis. The Kaplan-Meier method and log-rank test were used to compare the overall survival of NEDD9 negative, weak positive expression, and strong positive expression group. NEDD9 expression rates were significantly higher (P < 0.001) in gastric cancer tissues (162 out of 187, 86.6 %) compared with normal (2 out of 11, 18.2 %) and nontumor (11 out of 58, 19.0 %) gastric tissues. The upregulated NEDD9 expression in gastric cancer tissue was significantly correlated with high preoperative CEA level (P = 0.044), poor differentiation (P = 0.007), tissue invasion (P = 0.015), present lymph node metastasis (P < 0.001), and high TNM stage (P < 0.001). NEDD9 expression was positively correlated with clinical TNM stage. Advancing clinical TNM stage corresponded with higher NEDD9 expression (r s = 0.289, P < 0.001). The overall 5-year survival of gastric cancer patients with strong positive NEDD9 expression was significantly shorter compared with the survival of NEDD9 negative and weakly positive expression group. NEDD9 may be used as a biomarker in the clinical setting to predict the prognosis of gastric cancer patients.
Subject(s)
Adaptor Proteins, Signal Transducing/biosynthesis , Biomarkers, Tumor/biosynthesis , Phosphoproteins/biosynthesis , Stomach Neoplasms/genetics , Adaptor Proteins, Signal Transducing/genetics , Aged , Biomarkers, Tumor/genetics , Gene Expression Regulation, Neoplastic , Humans , Kaplan-Meier Estimate , Lymphatic Metastasis/genetics , Male , Middle Aged , Neoplasm Staging , Phosphoproteins/genetics , Prognosis , Stomach Neoplasms/pathologyABSTRACT
Functional brain research has shown that the cerebral response to an external stimulus contains positive and negative signals. The positive signals are well studied, whereas explanations for the negative signals remain controversial. In this study, negative response was investigated using intrinsic optical imaging (OI) and a multi-electrode array (MEA) in rat with a hindlimb stimulus. The negative hemodynamic response (NHR) signals were measured by OI in contralateral and ipsilateral primary somatosensory forelimb, primary and secondary motor, and primary and secondary visual cortex areas. The spatial presentation of NHR signals showed diversity across subjects under an identical experimental paradigm. The NHR signals in different cortical areas had similar time courses but were in the opposite direction of the positive hemodynamic response (PHR) signals, and the amplitude of NHR signals was significantly smaller than that of PHR signals. Electrophysiological recording using an MEA in an NHR cortex area showed that spike activities decreased significantly during external stimulation, suggesting that the neuronal activity reduction has a strong relationship with the NHR signals. Our results highlight the importance of a negative response in a hemodynamics-based interpretation of neuroimaging signals.