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Round ligament varicosities (RLV) are a very rare cause of an inguinal mass, which is very similar to an inguinal hernia, and should be taken seriously by women, especially in mid-pregnancy. Ultrasound can confirm the diagnosis of the RLV and can prevent unnecessary interventions. We report a case of a patient with bilateral RLV: the primigravida was 31 years old, G1P0, gestation 30+2w. The patient presented to the clinic 1 month ago due to the discovery of bilateral inguinal masses. After the diagnosis was confirmed by ultrasound, this patient received regular reviews during labor and delivery and is currently in good maternal condition. The patient came to the clinic 1 month after the discovery of bilateral inguinal area masses for 1 month.
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Objective: This study aims to explore the correlation between interleukin-6 (IL-6) levels and the condition of patients with psittacosis pneumonia, and extend these insights to the context of respiratory health in athletes.Methods: In a retrospective analysis, we included 14 patients diagnosed with psittacosis pneumonia (parrot fever) treated in our hospital from April 2018 to September 2021 as the study group (SG). As a control group (CG), we selected 20 patients with common pneumonia treated during the same period. We compared IL-6 levels between these groups and recorded changes in IL-6 levels in the SG before and after treatment. Additionally, we analyzed the correlation of IL-6 levels with procalcitonin (PCT) and C-reactive protein (CRP) levels.Results:The IL-2 levels in the SG were significantly lower than those in the CG, while IL-6 levels were significantly higher. No significant difference was observed in IL-10 and IL-6 levels between the groups (P>0.05). The average IL-6 level in the SG was 80.78±46.20 ng/L before treatment and 7.86±6.73 ng/L after treatment, showing a significant reduction (P<0.05). There was a significant positive correlation between IL-6 levels and PCT levels in the SG (r=0.2659, P<0.05), but the correlation with CRP levels was not significant (r=0.0033, P=0.8465). The Area Under Curve (AUC) of IL-6 for diagnosing psittacosis pneumonia was 0.7929 (P=0.0041). Conclusion: Patients with psittacosis pneumonia exhibit distinct interleukin level changes, particularly in IL-2 and IL-6, compared to those with ordinary pneumonia. The correlation of IL-6 with PCT levels suggests its potential as a marker in assessing respiratory health conditions, which could be relevant for monitoring respiratory health in athletes, given the heightened susceptibility to respiratory issues in this group (AU)
Subject(s)
Humans , Male , Female , Middle Aged , Aged , /blood , Psittacosis/diagnosis , Psittacosis/immunology , Pneumonia, Bacterial/diagnosis , Pneumonia, Bacterial/immunology , Retrospective Studies , Biomarkers/bloodABSTRACT
Microsystems are widely used in 5G, the Internet of Things, smart electronic devices and other fields, and signal integrity (SI) determines their performance. Establishing accurate and fast predictive models and intelligent optimization models for SI in microsystems is extremely essential. Recently, neural networks (NNs) and heuristic optimization algorithms have been widely used to predict the SI performance of microsystems. This paper systematically summarizes the neural network methods applied in the prediction of microsystem SI performance, including artificial neural network (ANN), deep neural network (DNN), recurrent neural network (RNN), convolutional neural network (CNN), etc., as well as intelligent algorithms applied in the optimization of microsystem SI, including genetic algorithm (GA), differential evolution (DE), deep partition tree Bayesian optimization (DPTBO), two stage Bayesian optimization (TSBO), etc., and compares and discusses the characteristics and application fields of the current applied methods. The future development prospects are also predicted. Finally, the article is summarized.
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With the rapid development of electronic information and computer science, the fast Fourier transform (FFT) has played an increasingly important role in digital signal processing (DSP). This paper presented a spectrum processing chiplet design method to solve slow speed, low precision, and low resource utilization in spectrum processing of general-purpose spectrum chips and field programmable gate array (FPGA). To realize signal processing, the Radix-2 4096-point FFT algorithm with pipeline structure is used to process spectral signals extracted from the time domain. To reduce the harm caused by spectrum leakage, a windowing module is added to optimize the input data, and the clock gating unit (CGU) is used to perform low-power management on the entire clock reset. The result shows the chiplet takes 0.368 ms to complete a 4096-point frequency sweep under a clock frequency of 61.44 MHz. The chiplet significantly improves speed and accuracy in spectrum processing, which has great application potential in wireless communication.
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Transmembrane-4 L Six Family member 1 (TM4SF1) belongs to a family of integral membrane proteins implicated in cell growth and tumor progression. Glioma is the most common and aggressive malignant brain tumor in adults. In this study, we showed that TM4SF1 was highly expressed in glioma tumor tissues and cell lines. The expression levels of TM4SF1 were negatively correlated with patients' survival rates. Silencing TM4SF1 by RNA interference inhibited the proliferation, migration, and invasion of glioma cells. Moreover, TM4SF1 silencing induced glioma cell cycle arrest and early apoptosis. In contrast, overexpression of TM4SF1 in glioma cells exhibited the opposite effects. Mechanistically, we found that loss of TM4SF1 reduced phospho-ATK, Cyclin D1, Bcl-2, and MMP-9 levels in glioma cells. Taken together, these findings provide novel insights into glioma pathogenesis and suggest that TM4SF1 may represent a novel target for glioma intervention.
Subject(s)
Antigens, Surface/metabolism , Glioma , Neoplasm Proteins , Adult , Antigens, Surface/genetics , Apoptosis/genetics , Cell Line, Tumor , Cell Movement , Cell Proliferation , Gene Expression Regulation, Neoplastic , Glioma/genetics , Humans , Neoplasm Proteins/genetics , Neoplasm Proteins/metabolismABSTRACT
Background: Accurate interpretation of lung function tests requires appropriate spirometry reference values derived from large-scale population-specific epidemiological surveys. The aim of this cross-sectional study was to establish normal spirometric values for the population of healthy, nonsmoking Han Chinese adults residing in Zhejiang province, China. Methods: We measured lung function parameters such as forced expiratory volume in 1 s, forced vital capacity, peak expiratory flow, maximal midexpiratory flow, and diffusion capacity for carbon monoxide and considered age, height, and weight as independent factors that may modify these parameters. The clinical data were divided into the study arm and validation group. The study arms were used to construct predictive equations using stepwise multiple linear regression, and data from the validation group were used to assess the robustness of the equations. Results: The 3866 participants were randomized into a study arm (n = 1,949) and a validation arm (n = 1,917). Lung function parameters had a negative association with age and a positive association with height. Data from the two groups were similar. Predictive equations were constructed from the study arm, and the validation group was used to test the feasibility of the reference equations. Conclusions: The reference values we derived can be used to evaluate lung function in this cohort in both epidemiological studies and clinical practice.
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Computing systems are widely used in medical diagnosis, climate prediction, autonomous vehicles, etc. As the key part of electronics, the performance of computing systems is crucial in the intellectualization of the equipment. The conflict between performance, efficiency, and cost can be solved by choosing an appropriate computing system architecture. In order to provide useful advice and instructions for the designers to fabricate high-performance computing systems, this paper reviews the Chiplet-based computing system architectures, including computing architecture and memory architecture. Firstly, the computing architecture used for high-performance computing, mobile, and PC is presented and summarized. Secondly, the memory architecture based on mainstream memory and emerging non-volatile memory used for data storing and processing are introduced, and the key parameters of memory are compared and discussed. Finally, this paper is concluded, and the future perspectives of computing system architecture based on Chiplet are presented.
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Cholangiocarcinoma (CCA), which is highly malignant, shows a relatively poor prognosis, due to the insensitivity of the tumour to chemotherapy and radiotherapy. Photodynamic therapy (PDT) has become a promising palliative therapeutic option for patients with unresectable cholangiocarcinoma (CCA), while the functional amount of ROS is limited by intracellular redox systemen. Sulfasalazine (SASP), a well-known anti-inflammatory agent, which also acts as an inhibitor of the amino acid transport system xc (xCT), decreases the intracellular glutathione (GSH) level, thus weakening the antioxidant defence of the cell by inhibition of the antiporter. However, the combination of SASP and PDT remains unexplored. We have reported that polyhematoporphyrin (PHP)-mediated PDT inhibits the cell viability of CCA cells and organoids. Furthermore, in PHP-enriched HCCC-9810 and TFK-1CCA cells, SASP enhances the sensitivity to PHP-mediated PDT through a GSH-dependent mechanism. We found that PHP-PDT can up-regulate xCT expression to promote cells against overloaded ROS, while SASP reduces GSH levels. After the combination of SASP and PHP-PDT, cell viability and GSH levels were significantly inhibited. xCT was also observed to be inhibited by SASP in human organoid samples. Our findings suggest that, in combination with PDT, SASP has potential as a promising approach against CCA.
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BACKGROUND AND AIM: Pancreatic cancer is one of the most malignant tumors worldwide. Zuojin pills (ZJP), a traditional Chinese medicine (TCM) formula, which can treat a variety of cancers. However, the active compounds present in ZJP and the potential mechanisms through which ZJP acts against pancreatic cancer have not been thoroughly investigated. METHODS: Data on pancreatic cancer-related genes, bioactive compounds, and potential targets of ZJP were downloaded from public databases. Bioinformatics analysis, including protein-protein interaction (PPI), Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses, was conducted to identify important components, potential targets, and signaling pathways through which ZJP affects pancreatic cancer. The results of this analysis were verified by in vitro experiments. RESULTS: The network pharmacology analysis results showed that 41 compounds and 130 putative target genes of ZJP were associated with anti-pancreatic cancer effects. ZJP may exert its inhibitory effects against pancreatic cancer by acting on key targets such as JUN, TP53, and MAPK1. Moreover, KEGG analysis indicated that the anti-pancreatic cancer effect of ZJP was mediated by multiple pathways, such as the PI3K-AKT, IL-17, TNF, HIF-1, and P53 signaling pathways. Among these, the PI3K-AKT signaling pathway, which included the highest number of enriched genes, may play a more important role in treating pancreatic cancer. The in vitro results showed that ZJP significantly inhibits the cell cycle and cell proliferation through the PI3K/AKT/caspase pathway and that it can induce apoptosis of pancreatic cancer cells, consistent with the results predicted by network pharmacological methods. CONCLUSION: This study preliminarily investigated the pharmacological effects of ZJP, which appear to be mediated by multiple compounds, targets and pathways, and its potential therapeutic effect on pancreatic cancer. Importantly, our work provides a promising approach for the identification of compounds in TCM and the characterization of therapeutic mechanisms.
Subject(s)
Antineoplastic Agents, Phytogenic/pharmacology , Drugs, Chinese Herbal/pharmacology , Pancreatic Neoplasms/drug therapy , Apoptosis/drug effects , Cell Cycle/drug effects , Cell Line, Tumor , Cell Proliferation/drug effects , Humans , Network Pharmacology , Pancreatic Neoplasms/genetics , Pancreatic Neoplasms/pathology , Phosphatidylinositol 3-Kinase/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Signal Transduction/drug effectsABSTRACT
Triptolide (TPL) is a diterpenoid triepoxide with broad antitumor efficacy, while lack of mechanism of action, severe systemic toxicity, and poor water solubility of TPL limited its usage. To unveil the mechanism of action and improve the pharmaceutical properties of TPL, here we explored the molecular mechanism of TPL and then fabricated TPL-loaded membrane protein-chimeric liposomes (TPL@MP-LP) and tested its anticancer efficacy against hepatocellular carcinoma (HCC). CCK8 assay, colony formation assay, EdU assay, and flow cytometry were used to examine the activity of TPL. RNA sequence and gain-and-loss of function assays were used to explore the molecular mechanisms. TPL@MP-LP was characterized by size, zeta potential, polydispersity index, and transmission electron microscopy. Cellular uptake and cell viability assay were performed to evaluate the internalization and anticancer efficacy of TPL@MP-LP in vitro. Biodistribution and in vivo antitumor efficacy of TPL@MP-LP were evaluated on orthotopic HCC mice models. TPL robustly inhibited HCC cells by inducing cell proliferation arrest, apoptosis via the mitochondrial pathway, and necroptosis via RIPK1/RIPK3/MLKL signaling. TPL was successfully loaded into MP-LP, with a drug-loading capacity of 5.62 ± 0.80%. MP-LP facilitated TPL internalization and TPL@MP-LP exerted enhanced anticancer efficacy against Huh7 cells. TPL@MP-LP showed targeting ability to the tumor site. More importantly, TPL@MP-LP treatment suppressed tumor growth but showed minimal damage to liver and renal functions. TPL exerted anticancer effects on HCC via inducing cell proliferation arrest, apoptosis, and necroptosis, and the MP-LP might be a promising delivery strategy to improve the antitumor efficacy while mitigating toxicity of TPL for HCC therapy.
Subject(s)
Carcinoma, Hepatocellular/pathology , Diterpenes/pharmacology , Liposomes/chemistry , Liver Neoplasms/pathology , Membrane Proteins/chemistry , Phenanthrenes/pharmacology , Animals , Apoptosis/drug effects , Cell Line, Tumor , Cell Proliferation/drug effects , Cell Survival/drug effects , Chemistry, Pharmaceutical , Diterpenes/administration & dosage , Drug Carriers , Epoxy Compounds/administration & dosage , Epoxy Compounds/pharmacology , Humans , Male , Mice , Mice, Inbred BALB C , Particle Size , Phenanthrenes/administration & dosage , Random Allocation , Signal Transduction/drug effects , Surface PropertiesABSTRACT
Guanylate binding proteins (GBPs), a family of interferon-inducible large GTPase, play a pivotal role in cell-autonomous immunity and tumor malignant transformation. Glioblastoma (GBM) is the most prevalent and lethal primary brain tumor in adults. Here we show that GBP5 was highly expressed in GBM cell lines and in clinical samples, especially in the mesenchymal subtype. The expression levels of GBP5 were negatively correlated with the prognosis of GBM patients. Overexpression of GBP5 promoted the proliferation, migration, and invasion of GBM cells in vitro and in vivo. In contrast, silencing GBP5 by RNA interference exhibited the opposite effects. Consequently, targeting GBP5 in GBM cells resulted in impaired tumor growth and prolonged survival time of mice with GBM tumors. We further identified that the Src/ERK1/2/MMP3 axis was essential for GBP5-promoted GBM aggressiveness. These findings suggest that GBP5 may represent a novel target for GBM intervention.
Subject(s)
Brain Neoplasms/enzymology , GTP-Binding Proteins/metabolism , Glioblastoma/enzymology , Matrix Metalloproteinase 3/metabolism , Mitogen-Activated Protein Kinase 1/metabolism , Mitogen-Activated Protein Kinase 3/metabolism , src-Family Kinases/metabolism , Animals , Brain Neoplasms/genetics , Brain Neoplasms/pathology , Cell Line, Tumor , Cell Movement , Cell Proliferation , Female , GTP-Binding Proteins/genetics , Gene Expression Regulation, Neoplastic , Glioblastoma/genetics , Glioblastoma/pathology , Humans , Matrix Metalloproteinase 3/genetics , Mice, Nude , Neoplasm Invasiveness , Phosphorylation , Signal Transduction , Tumor BurdenABSTRACT
The aim of the study is to explore the expression profile variation of circular RNAs (circRNAs) in the peripheral blood of subjects with nonarteritic anterior ischemic optic neuropathy (NAION) and without NAION, to analyze the differential expression results, and to predict the role of circRNAs in disease development, providing novel ideas and methods for treatment and diagnosis. High-throughput sequencing to explore the expression profiles of RNAs in the peripheral blood of 6 NAION patients and 5 healthy controls was applied. Quality control obtained the advanced data from the original data by ticking out the unqualified data. Then, cluster analysis, volcano plot, coexpression network, and protein-protein interaction network (PPI) were performed. Gene ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway were used to analyze the whole expressed genes. Lastly, the quantitative real-time Polymerase Chain Reaction (qRT-PCR) was used to verify those significantly differentially expressed circRNAs and do some bioinformatics analysis and prediction in 12 NAION patients and 12 controls. There were significant differences in the expression of 49 circRNAs in the peripheral blood of NAION patients, in which there were 24 upregulations and 25 downregulations (variation folds > 2 and P < 0.05), and it was confirmed that hsa_circ_0005583, hsa_circ_0003922, hsa_circ_0002021, and hsa_circ_0000462 were significantly downregulated (variation folds > 2 and P < 0.05), especially hsa_circ_0005583 which was the most significantly changed one (P < 0.001), and are related to processes such as neurodegeneration, oxidative stress, immunity, and metabolism. The expression profile of circRNAs in the peripheral blood of NAION patients is significantly changed, enriching our understanding of the disease.
Subject(s)
Gene Expression Profiling , Optic Neuropathy, Ischemic/blood , Optic Neuropathy, Ischemic/genetics , RNA, Circular/genetics , Aged , Female , Gene Expression Regulation , Gene Ontology , Gene Regulatory Networks , Humans , Male , Middle Aged , Molecular Sequence Annotation , Protein Interaction Maps/genetics , RNA, Circular/metabolism , RNA, Messenger/genetics , RNA, Messenger/metabolism , Transcriptome/geneticsABSTRACT
Guanylate-binding protein 2 (GBP2) is an interferon-inducible large GTPase which is crucial to the protective immunity against microorganisms. However, its biological function in cancer remains largely unknown. Glioblastoma multiforme (GBM) is the most common and deadly brain tumor in adults. Here we show that GBP2 expression is highly elevated in GBM tumor and cell lines, particularly in those of the mesenchymal subtype. High GBP2 expression is associated with poor prognosis. GBP2 overexpression significantly promotes GBM cell migration and invasion in vitro, and GBP2 silencing by RNA interference exhibits opposite effects. We further show that fibronectin (FN1) is dramatically induced by GBP2 expression at both mRNA and protein levels, and FN1 is essential for GBP2-promoted GBM invasiveness. Inhibition of Stat3 pathway prevents GBP2-promoted FN1 induction and cell invasion. Consistently, GBP2 dramatically promotes GBM tumor growth and invasion in mice and significantly reduces the survival time of the mice with tumor. Taken together, these findings establish the role of GBP2/Stat3/FN1 signaling cascade in GBM invasion and suggest GBP2 may serve as a potential therapeutic target for inhibiting GBM invasion.
Subject(s)
Brain Neoplasms/pathology , Fibronectins/metabolism , GTP-Binding Proteins/metabolism , Glioblastoma/pathology , STAT3 Transcription Factor/metabolism , Animals , Brain Neoplasms/genetics , Cell Line, Tumor , Cell Movement/genetics , GTP-Binding Proteins/genetics , Glioblastoma/genetics , Humans , Mice , Mice, Nude , Neoplasm Invasiveness/genetics , Neoplasm Transplantation , RNA Interference , RNA, Small Interfering/genetics , STAT3 Transcription Factor/antagonists & inhibitors , Signal Transduction , Transplantation, HeterologousABSTRACT
Liver malignancies include primary and metastatic tumors. Limited progress has been achieved in improving the survival rate of patients with advanced stage liver cancer and who are unsuitable for surgery. Apart from surgery, chemoradiotherapy, trans-arterial chemoembolization and radiofrequency ablation, a novel therapeutic modality is needed for the clinical treatment of liver cancer. Photodynamic therapy (PDT) is a novel strategy for treating patients with advanced cancers; it uses a light-triggered cytotoxic photosensitizer and a laser light. PDT provides patients with a potential treatment approach with minimal invasion and low toxicity, that is, the whole course of treatment is painless, harmless, and repeatable. Therefore, PDT has been considered an effective palliative treatment for advanced liver cancers. To date, PDT has been used to treat hepatocellular carcinoma, cholangiocarcinoma, hepatoblastoma and liver metastases. Clinical outcomes reveal that PDT can be considered a promising treatment modality for all liver cancers to improve the quality and quantity of life of patients. Despite the advances achieved with this approach, several challenges still impede the application of PDT to liver malignancies. In this review, we focus on the recent advancements and discuss the future prospects of PDT in treating liver malignancies.
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BACKGROUND: Colorectal cancer (CRC) is the third most common malignant tumor worldwide. Photodynamic therapy (PDT) is an emerging modality for the treatment of solid tumors. Sinoporphyrin sodium (DVDMS) is a new photosensitizer with good therapeutic killing effects on cancer cells. Recent findings have shown that microRNAs play important roles in many biological processes. However, the functions of microRNAs in DVDMS-induced PDT remain largely unclear. MATERIALS AND METHODS: Proteins involved in endoplasmic reticulum (ER) stress and apoptosis of CX-1 cells treated with DVDMS-PDT were examined by Western blotting and cell viability assays. 15 candidate miRNAs targeting RNA-dependent protein kinase-like ER kinase (PERK) were screened and verified using the TargetScan, miRWalk and miRDB databases. The downstream pathways of candidate miRNAs with high scores were studied by cell transfection, qRT-PCR, Western blotting and dual-luciferase reporter assays. The subcellular location of DVDMS was confirmed by laser confocal microscopy. RESULTS: DVDMS-PDT induced apoptosis via elevated ER stress and activation of the PERK/ATF4/CHOP/caspase cascade pathway in CX-1 cells. The endoplasmic reticulum was involved in the subcellular accumulation of DVDMS in CX-1 cells. Dual-luciferase reporting experiment confirmed that a direct crosslinking between miR-7112-3p and PERK. In addition, miR-7112-3p was highly expressed in CRC tissues compared with peripheral tissues. CONCLUSION: Our work showed that miR-7112-3p directly targeted PERK and further regulated PERK/ATF4/CHOP/caspase cascade pathway, resulting in enhanced apoptosis in CX-1 cells treated with DVDMS-PDT.
Subject(s)
Apoptosis/drug effects , Colorectal Neoplasms/drug therapy , Endoplasmic Reticulum Stress/drug effects , MicroRNAs/physiology , Photochemotherapy/methods , eIF-2 Kinase/metabolism , Cell Line, Tumor , Cell Survival/drug effects , Humans , Photosensitizing Agents/chemistry , Photosensitizing Agents/pharmacology , Porphyrins/chemistry , Porphyrins/pharmacology , Signal Transduction/drug effectsABSTRACT
BACKGROUND: Emerging data suggest the crucial regulatory roles of circular RNAs (circRNAs) in hepatocellular carcinoma (HCC). However, the pathophysiology role of circZFR in HCC remains largely unknown. AIMS: This study aims to disclose the functions of circZFR in HCC progression and its potential molecular mechanism. METHODS: circZFR and miR-511 were identified by qRT-PCR. Colony formation assay, wound-healing assay, transwell assay, and flow cytometry assay were performed to determine the cell proliferation, migration, invasion and apoptosis. Western blotting and immunohistochemistry (IHC) were utilized to evaluate the expression level of AKT1, GSK3ß, ß-catenin and cascades of proliferation-related proteins both in vitro and in vivo. Dual luciferase reporter assay was conducted to evaluate the interactions among circZFR, miR-511 and AKT1. RESULTS: The expression of circZFR was enhanced and the expression of miR-511 was down-regulated in HCC tissues and cells. Functionally, circZFR silencing or miR-511 overexpression suppressed cell proliferation, migration and invasion, and induced apoptosis of HCC cells. Mechanistically, circZFR acted as a miR-511 sponge to up-regulate its target gene AKT1, which activated cascades of proliferation-related proteins (c-Myc, cyclin D1, Survivin and Bcl-2). Furthermore, depletion of circZFR inhibited tumorigenesis and decreased the expression level of AKT1 in xenograft models. CONCLUSION: circZFR promotes HCC progression by directly down-regulating miR-511 to activate AKT1 signaling, suggesting that circZFR is a potential target in HCC treatment. Targeting circZFR may provide therapeutic benefits for HCC.
Subject(s)
Carcinoma, Hepatocellular/pathology , Liver Neoplasms/pathology , MicroRNAs/genetics , Proto-Oncogene Proteins c-akt/genetics , RNA, Circular/genetics , Animals , Apoptosis , Carcinoma, Hepatocellular/genetics , Cell Line, Tumor , Cell Proliferation/genetics , Down-Regulation , Female , Gene Expression Regulation, Neoplastic , Gene Knockdown Techniques , Humans , Liver Neoplasms/genetics , Male , Mice , Mice, Inbred BALB C , Up-Regulation , Xenograft Model Antitumor AssaysABSTRACT
BACKGROUND AND AIMS: The impact of portal hypertension (PH) on postoperative short-term outcomes and long-term survival in hepatocellular carcinoma (HCC) patients has lately been discussed controversially. This study aimed to explore the influence of PH on postoperative outcomes in HCC patients undergoing surgical resection. METHODS: Patients undergoing hepatectomy for HCC from 2010 to 2014 were enrolled. The impact of PH on postoperative complications, posthepatectomy liver failure (PHLF) and overall survival (OS) was evaluated. RESULTS: A total of 355 HCC patients were enrolled; 129 (36.3%) experienced postoperative complications and 21 (5.9%) developed PHLF. PH was identified as an independent predictor of PHLF. Patients with PH experienced a higher incidence of complications and PHLF than patients without PH. On the Cox proportional hazards regression model, PH was verified as a risk factor of OS for BCLC stage 0/A and B patients. Patients without PH had significantly better long-term survival compared to patients with PH both in the total cohort and in cirrhosis subgroup. CONCLUSION: Liver resection in HCC patients with PH showed a significantly increased postoperative complications and PHLF, and revealed a decreasing long-term survival than non-PH patients. Besides, tumor burden also played an important role in determining the OS. However, due to the improvement in surgical technique and perioperative management, surgery was feasible in carefully selected HCC patients with PH.
Subject(s)
Carcinoma, Hepatocellular/surgery , Hypertension, Portal/complications , Liver Failure/epidemiology , Liver Neoplasms/surgery , Postoperative Complications/epidemiology , Adult , Carcinoma, Hepatocellular/mortality , China/epidemiology , Female , Hepatectomy , Hospital Mortality , Humans , Incidence , Liver Cirrhosis/complications , Liver Neoplasms/mortality , Male , Middle Aged , ROC Curve , Retrospective Studies , Risk Factors , Survival AnalysisABSTRACT
AIM: To determine the therapeutic effect of photodynamic therapy (PDT) for middle-advanced stage upper gastrointestinal carcinomas. METHODS: We searched PubMed, EMBASE, the Cochrane Library, China National Knowledge Infrastructure, China Science and Technology Journal Database, and Wanfang Database from inception to April 2018 for randomized controlled studies. These studies compared PDT with other palliative therapies (radiotherapy, chemotherapy, or Nd:YAG laser) and compared PDT, radiotherapy, or chemotherapy alone with PDT combined with chemotherapy/radiotherapy. In our meta-analysis, both fixed and random effects models were used to estimate the risk ratio (RR) for dichotomous outcomes (the response rate and one-year survival rate). RESULTS: Ten random controlled clinical studies with 953 patients were included in the analysis. The effective rate for PDT was better than that of radiotherapy or Nd:YAG laser for the treatment of middle-advanced upper gastrointestinal carcinomas [RR = 1.36; 95% confidence interval (CI): 1.13-1.65; P = 0.001]. In addition, PDT combined with chemotherapy had significantly better efficacy and a higher one-year survival rate than PDT or chemotherapy alone (significant remission rate, RR = 1.62; 95%CI: 1.34-1.97; P < 0.00001; one-year survival rate, RR = 1.81; 95%CI: 1.13-2.89; P = 0.01). CONCLUSION: PDT is a useful method for the treatment of middle-advanced stage upper gastrointestinal carcinomas. PDT combined with chemotherapy or radiotherapy can enhance its efficacy and prolong survival time.
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Four-and-a-half LIM protein2 (FHL2) is a member of the LIM-only protein family, which plays a critical role in tumorigenesis. We previously reported that FHL2 is upregulated and plays an oncogenic role in glioblastoma (GBM), the most common and aggressive brain tumor. GBM is also marked by amplification of the epidermal growth factor receptor (EGFR) gene and its mutations, of which EGFRvIII is the most common and functionally significant. Here we report that FHL2 physically interacts with the wild-type EGFR and its mutated EGFRvIII form in GBM cells. Expression of FHL2 caused increased EGFR and EGFRvIII protein levels and this was due to an increase in protein stability rather than an increase in EGFR mRNA expression. In contrast, FHL2 knockdown using RNA interference reduced EGFR and EGFRvIII protein expression and the phosphorylation levels of EGFR and AKT. Consistent with these features, EGFR expression was significantly lower in mouse FHL2-null astrocytes, where reintroduction of FHL2 was able to restore EGFR levels. Using established GBM cell lines and patient-derived neurosphere lines, FHL2 silencing markedly induced cell apoptosis in EGFRvIII-positive cells. Targeting FHL2 significantly prevented EGFRvIII-positive GBM tumor growth in vivo. FHL2 expression also positively correlated with EGFR expression in GBM samples from patients. Taken together, our results demonstrate that FHL2 interacts with EGFR and EGFRvIII to increase their levels and this promotes glioma growth, representing a novel mechanism that may be therapeutically targetable.
Subject(s)
Brain Neoplasms/pathology , Cell Proliferation , Glioblastoma/pathology , LIM-Homeodomain Proteins/metabolism , Muscle Proteins/metabolism , Transcription Factors/metabolism , Animals , Brain Neoplasms/genetics , Brain Neoplasms/metabolism , Cell Proliferation/genetics , Cells, Cultured , ErbB Receptors/genetics , ErbB Receptors/metabolism , Glioblastoma/genetics , Glioblastoma/metabolism , Humans , LIM-Homeodomain Proteins/genetics , Mice , Mice, Inbred C57BL , Mice, Knockout , Mice, Nude , Muscle Proteins/genetics , Proteasome Endopeptidase Complex/metabolism , Protein Binding , Protein Isoforms/genetics , Protein Isoforms/metabolism , Proteolysis , Transcription Factors/geneticsABSTRACT
Guanylate binding proteins (GBPs) are interferon-inducible large GTPases and play a crucial role in cell-autonomous immunity. However, the biology function of GBPs in cancer remains elusive. GBP3 is specifically expressed in adult brain. Here we show that GBP3 is highly elevated in human glioma tumors and glioma cell lines. Overexpression of GBP3 dramatically increased glioma cell proliferation whereas silencing GBP3 by RNA interference produced opposite effects. We further showed that GBP3 expression was able to induce sequestosome-1(SQSTM1, also named p62) expression and activate extracellular signal-regulated kinase (ERK1/2). The SQSTM1-ERK1/2 signaling cascade was essential for GBP3-promoted cell growth because depletion of SQSTM1 markedly reduced the phosphorylated ERK1/2 levels and GBP3-mediated cell growth, and inhibition of mitogen-activated protein kinase/ERK kinase abolished GBP3-induced glioma cell proliferation. Consistently, GBP3 overexpression significantly promoted glioma tumor growth in vivo and its expression was inversely correlated with the survival rate of glioma patients. Taken together, these results for the first time suggest that GBP3 contributes to the proliferation of glioma cells via regulating SQSTM1-ERK1/2 pathway, and GBP3 might represent as a new potential therapeutic target against glioma.