ABSTRACT
Medulloblastomas, the most common malignant pediatric brain tumors, can be classified into the wingless, sonic hedgehog (SHH), group 3, and group 4 subgroups. Among them, the SHH subgroup with the TP53 mutation and group 3 generally present with the worst patient outcomes due to their high rates of recurrence and metastasis. A novel and effective treatment for refractory medulloblastomas is urgently needed. To date, the tumor microenvironment (TME) has been shown to influence tumor growth, recurrence, and metastasis through immunosuppression, angiogenesis, and chronic inflammation. Treatments targeting TME components have emerged as promising approaches to the treatment of solid tumors. In this review, we summarize progress in research on medulloblastoma microenvironment components and their interactions. We also discuss challenges and future research directions for TME-targeting medulloblastoma therapy.
Subject(s)
Brain Neoplasms , Cerebellar Neoplasms , Medulloblastoma , Humans , Child , Hedgehog Proteins/genetics , Medulloblastoma/genetics , Tumor Microenvironment/genetics , Cerebellar Neoplasms/geneticsABSTRACT
BACKGROUND: Schwannomas are rare peripheral neural myelin sheath tumors that originate from Schwann cells. Of the different types of schwannomas, pelvic sciatic nerve schwannoma is extremely rare. Definite preoperative diagnosis of pelvic schwannomas is difficult, and surgical resection is the gold standard for its definite diagnosis and treatment. CASE SUMMARY: We present a case of pelvic schwannoma arising from the sciatic nerve that was detected in a 40-year-old man who underwent computed tomography for intermittent right lower back pain caused exclusively by a right ureteral calculus. Subsequently, successful transperitoneal laparoscopic surgery was performed for the intact removal of the stone and en bloc resection of the schwannoma. The total operative time was 125 min, and the estimated blood loss was inconspicuous. The surgical procedure was uneventful. The patient was discharged on postoperative day 5 with the simultaneous removal of the urinary catheter. However, the patient presented with motor and sensory disorders of the right lower limb, caused by partial damage to the right sciatic nerve. No tumor recurrence was observed at the postoperative appointment. CONCLUSION: Histopathological examination of the specimen confirmed the diagnosis of a schwannoma. Thus, laparoscopic surgery is safe and feasible for concomitant extirpation of pelvic schwannomas and other pelvic and abdominal diseases that require surgical treatment.
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BACKGROUND: Mycotoxin contaminated food poses a threat to human health. On-site detection of mycotoxin contamination is of significance to reduce the agricultural and food industries loss. Lateral flow immunochromatography (LFIC) as on-site detection method for mycotoxins has the advantages of low cost, easy to operate and short time-consuming. Of the various types of LFIC, photothermal LFIC possesses better sensitivity and stronger quantitative capability, but is unable to conduct synchronous multi-target analysis because that the laser can only activate one test area at a time. It was clear that a synchronous multi-target photothermal LFIC method was needed. RESULTS: In this study, a photothermal LFIC method for the simultaneous detection of three mycotoxins, deoxynivalenol (DON), aflatoxin B1 (AFB1) and zearalenone (ZEN), was developed. We broadened the laser source with a beam expander and realized the irradiation and activation of three test zones simultaneously. In addition, the competitive photothermal LFIC was constructed by using Cu2-xSe-Au nanocomposites with excellent photothermal properties (η = 87.47%) as photothermal signal probes and thermal imager as photothermal signal collector. Under optimized experimental conditions, the limits of detection (LOD) were 73 ng L-1, 45 ng L-1 and 43 ng L-1 for DON, AFB1 and ZEN, respectively. The method had good linearity in three orders of magnitude and good specificity. The recoveries of the three mycotoxins in oat, cornmeal and millet samples ranged from 78.6% to 112.4%. SIGNIFICANCE: Compared with previous studies, this method improved the sensitivity, broadened the linear range of detection without large equipment and realized synchronous multi-target analysis for DON, AFB1 and ZEN. We addressed a key limitation of photothermal LFIC by a simple way, facilitating the application of this technique in multi-target on-site detection in wider fields.
Subject(s)
Mycotoxins , Zearalenone , Humans , Mycotoxins/analysis , Food Contamination/analysis , Zearalenone/analysis , Chromatography, Affinity , Aflatoxin B1/analysis , Limit of DetectionABSTRACT
Foodborne microbial contamination (FMC) is the leading cause of food poisoning and foodborne illness. The foodborne microbial detection methods based on isothermal amplification have high sensitivity and short detection time, and functional nucleic acids (FNAs) could extend the detectable object of isothermal amplification to mycotoxins. Therefore, the strategy of FNAs-mediated isothermal amplification has been emergingly applied in biosensors for foodborne microbial contaminants detection, making biosensors more sensitive with lower cost and less dependent on nanomaterials for signal output. Here, the mechanism of six isothermal amplification technologies and their application in detecting FMC is firstly introduced. Then the strategy of FNAs-mediated isothermal amplification is systematically discussed from perspectives of FNAs' versatility including recognition elements (Aptamer, DNAzyme), programming tools (DNA tweezer, DNA walker and CRISPR-Cas) and signal units (G-quadruplex, FNAs-based nanomaterials). Finally, challenges and prospects are presented in terms of addressing the issue of nonspecific amplification reaction, developing better FNAs-based sensing elements and eliminating food matrix effects.
Subject(s)
DNA, Catalytic , G-Quadruplexes , Nanostructures , Nucleic Acid Amplification Techniques/methods , DNA , DNA, Catalytic/geneticsABSTRACT
Electroconvulsive therapy (ECT) is an important treatment for depression. Although it is known as the most effective acute treatment for severe mood disorders, its therapeutic mechanism is still unclear. With the rapid development of neuroimaging technology, various neuroimaging techniques have been available to explore the alterations of the brain by ECT, such as structural magnetic resonance imaging, functional magnetic resonance imaging, magnetic resonance spectroscopy, positron emission tomography, single photon emission computed tomography, arterial spin labeling, etc. This article reviews studies in neuroimaging on ECT for depression. These findings suggest that the neurobiological mechanism of ECT may regulate the brain functional activity, and neural structural plasticity, as well as balance the brain's neurotransmitters, which finally achieves a therapeutic effect.
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Tungsten disulfide (WS2) is promising for potential applications in transistors and gas sensors due to its high mobility and high adsorption of gas molecules onto edge sites. This work comprehensively studied the deposition temperature, growth mechanism, annealing conditions, and Nb doping of WS2 to prepare high-quality wafer-scale N- and P-type WS2 films by atomic layer deposition (ALD). It shows that the deposition and annealing temperature greatly influence the electronic properties and crystallinity of WS2, and insufficient annealing will seriously reduce the switch ratio and on-state current of the field effect transistors (FETs). Besides, the morphologies and carrier types of WS2 films can be controlled by adjusting the processes of ALD. The obtained WS2 films and the films with vertical structures were used to fabricate FETs and gas sensors, respectively. Among them, the Ion/Ioff ratio of N- and P-type WS2 FETs is 105 and 102, respectively, and the response of N- and P-type gas sensors is 14% and 42% under 50 ppm NH3 at room temperature, respectively. We have successfully demonstrated a controllable ALD process to modify the morphology and doping behavior of WS2 films with various device functionalities based on acquisitive characteristics.
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AIM: Parkinson's disease (PD) is a pervasive neurodegenerative disease, and levodopa (L-dopa) is its preferred treatment. The pathophysiological mechanism of levodopa-induced dyskinesia (LID), the most common complication of long-term L-dopa administration, remains obscure. Accumulated evidence suggests that the dopaminergic as well as non-dopaminergic systems contribute to LID development. As a 5-hydroxytryptamine 1A/1B receptor agonist, eltoprazine ameliorates dyskinesia, although little is known about its electrophysiological mechanism. The aim of this study was to investigate the cumulative effects of chronic L-dopa administration and the potential mechanism of eltoprazine's amelioration of dyskinesia at the electrophysiological level in rats. METHODS: Neural electrophysiological analysis techniques were conducted on the acquired local field potential (LFP) data from primary motor cortex (M1) and dorsolateral striatum (DLS) during different pathological states to obtain the information of power spectrum density, theta-gamma phase-amplitude coupling (PAC), and functional connectivity. Behavior tests and AIMs scoring were performed to verify PD model establishment and evaluate LID severity. RESULTS: We detected exaggerated gamma activities in the dyskinetic state, with different features and impacts in distinct regions. Gamma oscillations in M1 were narrowband manner, whereas that in DLS had a broadband appearance. Striatal exaggerated theta-gamma PAC in the LID state contributed to broadband gamma oscillation, and aperiodic-corrected cortical beta power correlated robustly with aperiodic-corrected gamma power in M1. M1-DLS coherence and phase-locking values (PLVs) in the gamma band were enhanced following L-dopa administration. Eltoprazine intervention reduced gamma oscillations, theta-gamma PAC in the DLS, and coherence and PLVs in the gamma band to alleviate dyskinesia. CONCLUSION: Excessive cortical gamma oscillation is a compelling clinical indicator of dyskinesia. The detection of enhanced PAC and functional connectivity of gamma-band oscillation can be used to guide and optimize deep brain stimulation parameters. Eltoprazine has potential clinical application for dyskinesia.
Subject(s)
Antiparkinson Agents , Dyskinesia, Drug-Induced , Gamma Rhythm , Levodopa , Piperazines , Serotonin Receptor Agonists , Serotonin Receptor Agonists/pharmacology , Serotonin Receptor Agonists/therapeutic use , Piperazines/pharmacology , Piperazines/therapeutic use , Gamma Rhythm/drug effects , Levodopa/adverse effects , Dyskinesia, Drug-Induced/drug therapy , Antiparkinson Agents/adverse effects , Animals , Rats , Disease Models, Animal , Motor Cortex/drug effects , Motor Cortex/physiopathologyABSTRACT
Hormone residues in food and drinking water endanger human health, therefore, on-site analysis techniques of superior performance are important for monitoring this risk. In this study, an ultra-sensitive photothermal lateral flow immunoassay (LFIA) for quantification of 17ß-estradiol (E2) has been developed. Anti-E2 antibody modified black phosphorus-Au (BP-Au) nanocomposite was developed as a photothermal contrast signal probe and the temperature at test-zone was recorded with an infrared camera. Under the irradiation of 808 nm laser at test-zone, it gave temperatures negatively related to the concentrations of E2 in samples. Under optimal detecting conditions, the developed photothermal LFIA exhibited a limit of detection of 50 pg mL-1, over 100-fold more sensitive than visual LFIA, and a linear range of 3 orders of magnitude. This method has been successfully applied to water, milk, and milk powder samples.
Subject(s)
Estradiol , Milk , Humans , Animals , Limit of Detection , Immunoassay/methods , Estradiol/analysis , Milk/chemistry , Phosphorus/analysis , Antibodies , Gold/chemistryABSTRACT
Objective: To evaluate whether depression is the contraindication of anterior cervical decompression and fusion (ACDF) for cervical spondylosis. Material and methods: Patients with single-segment cervical spondylosis who underwent ACDF from January 2015 to December 2018 in our department were retrospectively included in this study and divided into two groups. Patients who were diagnosed of depression and prescribed with antidepressant drugs for at least 6 months before surgery were included in the intervention group. Patients without depression were included in the control group. The Beck Depression Inventory (BDI) score was used to evaluate the severity of depression. Visual Analogue Scale (VAS) score, Japanese Orthopeadic Association (JOA) score, Neck Disability Index (NDI), and the 36-Item Short-Form Health Survey (SF-36) were recorded as indexes to assess the pain, cervical spine function, degree of cervical spine injury, and life quality, respectively. The operative time, operative blood loss, hospital stay and complications were also recorded and compared. Results: A total of 117 patients were included in this study, involving 32 patients in the intervention group and 85 patients in the control group. No significant differences were found in operative time, operative blood loss, hospital stay and complications between the two groups (P>0.05). The BDI score, VAS score, JOA score, NDI, SF-36 physical component score (SF-36 PCS) and SF-36 mental component score (SF-36 MCS) were all significantly improved at last follow-up in both the two groups. The intervention group showed higher BDI score and SF-36 MCS than the control group at both preoperative and the last follow-up (P<0.05), and the improvements of BDI score and SF-36 MCS were also higher in the intervention group (P<0.05). Although the intervention group showed higher VAS score, NDI, SF-36 PCS and lower JOA score at preoperative and last follow-up, respectively (P<0.05), there were no significant differences in the improvements of these indexes between the two group (P>0.05). Conclusions: Depression is not the contraindication of ACDF for cervical spondylosis. Depression patients who received preoperative antidepressants can achieve similar improvement of clinical symptoms from ACDF with non-depression patients.
Subject(s)
Spinal Fusion , Spondylosis , Antidepressive Agents , Blood Loss, Surgical , Cervical Vertebrae/surgery , Contraindications , Decompression , Disability Evaluation , Diskectomy , Humans , Pain Measurement , Retrospective Studies , Spondylosis/complications , Spondylosis/surgery , Treatment OutcomeABSTRACT
Medulloblastoma (MB) is the most frequent malignant brain tumor in pediatrics. Since the current standard of care for MB consisting of surgery, craniospinal irradiation and chemotherapy often leads to a high morbidity rate, a number of patients suffer from longterm sequelae following treatment. Targeted therapies hold the promise of being more effective and less toxic. Therefore, the present study aimed to identify hub genes with an upregulated expression in MB and to search for potential therapeutic targets from these genes. For this purpose, gene expression profile datasets were obtained from the Gene Expression Omnibus database and processed using R 3.6.0 software to screen differentially expressed genes (DEGs) between MB samples and normal brain tissues. A total of 282 upregulated and 436 downregulated DEGs were identified. Functional enrichment analysis revealed that the upregulated DEGs were predominantly enriched in the cell cycle, DNA replication and cell division. The top 10 hub genes were identified from the proteinprotein interaction network of upregulated genes, and one identified hub gene [PDZ binding kinase (PBK)] was selected for further investigation due to its possible role in the pathogenesis of MB. The aberrant expression of PBK in MB was verified in additional independent gene expression datasets. Survival analysis demonstrated that a higher expression level of PBK was significantly associated with poorer clinical outcomes in nonWingless MBs. Furthermore, targeting PBK with its inhibitor, HITOPK032, impaired the proliferation and induced the apoptosis of two MB cell lines, with the diminished phosphorylation of downstream effectors of PBK, including ERK1/2 and Akt, and the activation of caspase3. Hence, these results suggest that PBK may be a potential prognostic biomarker and a novel candidate of targeted therapy for MB.
Subject(s)
Cerebellar Neoplasms , Medulloblastoma , Cerebellar Neoplasms/genetics , Child , Computational Biology/methods , Extracellular Signal-Regulated MAP Kinases , Gene Expression Profiling/methods , Gene Expression Regulation, Neoplastic , Humans , Medulloblastoma/genetics , Protein Interaction MapsABSTRACT
Accumulating evidence has highlighted the important roles of long intergenic non-coding RNAs (lincRNAs) during cancer progression. However, the involvement of LINC00478 in bladder cancer remains largely unclear. Accordingly, the current study sought to investigate the function of LINC00478 on malignant phenotypes of bladder cancer cells as well as the underlying mechanism. By integrating data from in silico analysis, we uncovered that LINC00478 was differentially expressed in bladder cancer. We further analyzed the expression of LINC00478 and matrix metalloprotein 9 (MMP9) in bladder cancer tissues and cell lines and observed a significant decline in LINC00478 expression and an elevation in MMP9 expression. In addition, chromatin immunoprecipitation, RNA-binding protein immunoprecipitation, and RNA pull-down assays predicted and validated that LINC00478 targeted lysine-specific demethylase-1 (KDM1A) and down-regulated the expression of MMP9 by decreasing the monomethylation on lysine 4 of histone H3 (H3K4me1) of MMP9 promoter. Treatment with KDM1A inhibitor tranylcypromine (TCP) also led to an increase in the enrichment of H3K4me1 in the MMP9 promoter region. Through gain- and loss-of-function approaches, we found that LINC00478 up-regulation diminished the malignant phenotype of bladder cancer cells in vitro, and further inhibited xenograft tumor growth and metastasis in vivo by repressing MMP9. Collectively, our findings unraveled a LINC00478-mediated inhibitory mechanism in bladder cancer via the recruitment of histone demethylation transferase KDM1A to the MMP9 promoter region, which can provide potential implications for novel therapeutic targets against bladder cancer.
ABSTRACT
Wafer-scale synthesis of p-type TMD films is critical for its commercialization in next-generation electro/optoelectronics. In this work, wafer-scale intrinsic n-type WS2 films and in situ Nb-doped p-type WS2 films were synthesized through atomic layer deposition (ALD) on 8-inch α-Al2O3/Si wafers, 2-inch sapphire, and 1 cm2 GaN substrate pieces. The Nb doping concentration was precisely controlled by altering cycle number of Nb precursor and activated by postannealing. WS2 n-FETs and Nb-doped p-FETs with different Nb concentrations have been fabricated using CMOS-compatible processes. X-ray photoelectron spectroscopy, Raman spectroscopy, and Hall measurements confirmed the effective substitutional doping with Nb. The on/off ratio and electron mobility of WS2 n-FET are as high as 105 and 6.85 cm2 V-1 s-1, respectively. In WS2 p-FET with 15-cycle Nb doping, the on/off ratio and hole mobility are 10 and 0.016 cm2 V-1 s-1, respectively. The p-n structure based on n- and p- type WS2 films was proved with a 104 rectifying ratio. The realization of controllable in situ Nb-doped WS2 films paved a way for fabricating wafer-scale complementary WS2 FETs.
ABSTRACT
Transition-metal dichalcogenides (TMDs) have attracted intense research interest for a broad range of device applications. Atomic layer deposition (ALD), a CMOS compatible technique, can enable the preparation of high-quality TMD films on 8 to 12 in. wafers for large-scale circuit integration. However, the ALD growth mechanisms are still not fully understood. In this work, we systematically investigated the growth mechanisms for WS2 and found them to be strongly affected by nucleation density and film thickness. Transmission electron microscope imaging reveals the coexistence and competition of lateral and vertical growth mechanisms at different growth stages, and the critical thicknesses for each mechanism are obtained. The in-plane lateral growth mode dominates when the film thickness remains less than 5.6 nm (8 layers), while the vertical growth mode dominates when the thickness is greater than 20 nm. From the resulting understanding of these growth mechanisms, the conditions for film deposition were optimized and a maximum grain size of 108 nm was achieved. WS2-based field-effect transistors were fabricated with electron mobility and on/off current ratio up to 3.21 cm2 V-1 s-1 and 105, respectively. Particularly, this work proves the capability of synthesis of TMD films in a wafer scale with excellent controllability of thickness and morphology, enabling many potential applications other than transistors, such as nanowire- or nanosheet-based supercapacitors, batteries, sensors, and catalysis.
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Antibiotics are widely used for treatment of bacterial infections, and their overuse has contributed to microbial resistance. Currently, an alternative antibiotic-free therapy for inactivating bacteria is of great interest. Black phosphorus (BP), a biocompatible and nontoxic rising-star two-dimensional layered material, has gained remarkable interest in many bioapplications including biosensing, cancer therapy, drug delivery, and also antibacterial treatment. However, BP nanosheets suffer from instability in ambient environments due to rapid oxidation and degradation. To address this issue, BP nanosheets were modified with quaternized chitosan (QCS) by electrostatic adsorption to prepare a BP-QCS composite for photothermal/pharmaco treatment of bacterial infection. The BP-QCS has obviously enhanced solubility and chemical stability in aqueous suspensions. We have demonstrated that under near-infrared (NIR) irradiation, the BP-QCS can synergistically inactivate more than 95% methicillin-resistant Staphylococcus aureus (S. aureus) (MRSA) and Escherichia coli within 10 min with a dose of only 75 µg/mL in vitro. Meanwhile, the BP-QCS composite under NIR can synergistically inactivate 98% S. aureus in vivo. Furthermore, the BP-QCS suspensions at effective antibacterial concentrations have negligible cytotoxicity and in vivo toxicity.
Subject(s)
Anti-Bacterial Agents/administration & dosage , Chitosan/administration & dosage , Escherichia coli/drug effects , Methicillin-Resistant Staphylococcus aureus/drug effects , Nanocomposites/administration & dosage , Phosphorus/administration & dosage , Staphylococcal Infections/drug therapy , 3T3 Cells , Animals , Anti-Bacterial Agents/chemistry , Cell Survival/drug effects , Chitosan/chemistry , Disinfection/methods , Drug Delivery Systems , Drug Resistance, Bacterial , Drug Synergism , Escherichia coli/growth & development , Methicillin-Resistant Staphylococcus aureus/growth & development , Mice , Mice, Inbred BALB C , Nanocomposites/chemistry , Phosphorus/chemistry , Quaternary Ammonium Compounds/chemistryABSTRACT
Lateral flow assay (LFA) is one of the most prevalent commercially available techniques for point-of-care tests due to its simplicity, celerity, low cost and robust operation. However, conventional colorimetric LFAs have inferior limits of detection (LODs) compared to sophisticated laboratory-based assays. Here, we report a simple strategy of test-zone pre-enrichment to improve the LOD of LFA by loading samples before the conjugate pad assembly. The developed method enables visual LODs of miR-210 mimic and human chorionic gonadotropin protein, to be improved by 10-100 fold compared with a conventional LFA setup without introducing any additional instrument and reagent except for phosphate running buffer, while no obvious difference occurred for Aflatoxin B1 (AFB1). It takes about 6-8 min to enrich every 50 µL of sample diluted with phosphate running buffer, therefore we can get visual results within 20 min. We identified a parameter by modeling the entire process, the concentration of probe-analyte conjugate at test zone when signaling unit being loaded, to be important for the improvement of visual limit of detection. In addition, the test-zone pre-enrichment did not impair the selectivity when miR-210 mimic was adopted as target. Integrated with other optimization, amplification and modification of LFAs, the developed test-zone pre-enrichment method can be applied to further improve LOD of LFAs.
Subject(s)
Immunoassay/methods , Macromolecular Substances/analysis , Aflatoxin B1/analysis , Buffers , Chorionic Gonadotropin/analysis , Limit of DetectionABSTRACT
This study investigated the effects of Golgi membrane protein 73 (GP73) on the epithelial-mesenchymal transition (EMT) and on bladder cancer cell invasion and metastasis through the TGF-ß1/Smad2 signalling pathway. Paired bladder cancer and adjacent tissue samples (102) and normal bladder tissue samples (106) were obtained. Bladder cancer cell lines (T24, 5637, RT4, 253J and J82) were selected and assigned to blank, negative control (NC), TGF-ß, thrombospondin-1 (TSP-1), TGF-ß1+ TSP-1, GP73-siRNA-1, GP73-siRNA-2, GP73-siRNA-1+ TSP-1, GP73-siRNA-1+ pcDNA-GP73, WT1-siRNA and WT1-siRNA + GP73-siRNA-1 groups. Expressions of GP73, TGF-ß1, Smad2, p-Smad2, E-cadherin and vimentin were detected using RT-qPCR and Western blotting. Cell proliferation, migration and invasion were determined using MTT assay, scratch testing and Transwell assay, respectively. Compared with the blank and NC groups, levels of GP73, TGF-ß1, Smad2, p-Smad2, N-cadherin and vimentin decreased, and levels of WT1 and E-cadherin increased in the GP73-siRNA-1 and GP73-siRNA-2 groups, while the opposite results were observed in the WT1 siRNA, TGF-ß, TSP-1 and TGF-ß + TSP-1 groups. Cell proliferation, migration and invasion notably decreased in the GP73-siRNA-1 and GP73-siRNA-2 groups in comparison with the blank and NC groups, while in the WT1 siRNA, TGF-ß, TSP-1 and TGF-ß + TSP-1 groups, cell migration, invasion and proliferation showed the reduction after the EMT. These results suggest that GP73 promotes bladder cancer invasion and metastasis by inducing the EMT through down-regulating WT1 levels and activating the TGF-ß1/Smad2 signalling pathway.
Subject(s)
Epithelial-Mesenchymal Transition/genetics , Membrane Proteins/genetics , Signal Transduction/genetics , Smad2 Protein/genetics , Transforming Growth Factor beta1/genetics , Urinary Bladder Neoplasms/genetics , Aged , Aged, 80 and over , Cell Line, Tumor , Cell Movement/genetics , Female , Humans , Male , Membrane Proteins/metabolism , Middle Aged , Neoplasm Invasiveness , Neoplasm Metastasis , RNA Interference , Smad2 Protein/metabolism , Transforming Growth Factor beta1/metabolism , Urinary Bladder Neoplasms/metabolism , Urinary Bladder Neoplasms/pathology , WT1 Proteins/genetics , WT1 Proteins/metabolismABSTRACT
Wilms' tumor (WT) is a most common renal cancer that occurs among children, and microRNA-19b (miR-19b) usually participates in various human cancers. Importantly, the PTEN/PI3K/Akt signaling pathway plays a key role in cell apoptosis, growth and proliferation. Thus, our present study aims to investigate the effect of miR-19b on the PTEN/PI3K/Akt signaling pathway during WT cell proliferation, migration, and apoptosis. WT tissues and adjacent normal tissues from WT patients were collected. qRT-PCR was applied to detect miR-19b expression in both the WT tissues and the adjacent normal tissues, immunohistochemistry was applied to detect the protein expressions of PTEN, P13K, and p-Akt, SK-NEP-1 cells were divided into the blank, negative control (NC), miR-19b mimics and miR-19b inhibitors groups. MTT assay, propidium iodide (PI) staining, Annexin-V/PI double-staining, Transwell assay and Western blotting were performed to examine cell proliferation, cycle, apoptosis, migration, and invasion, and the protein expressions of PTEN, P13K, Akt, and p-Akt. Increased miR-19b expression, positive expression rates of P13K and Akt, decreased PTEN expression rate, a negative correlation between PTEN expression and tumor lymph node metastasis, and a positive correlation between the expression of P13K and Akt and the clinical stages were observed in the WT tissues. The miR-19b inhibitors group exhibited decreased cell proliferation, cell cycle progression, migration and invasion, and protein expressions of PI3K and p-Akt but increased PTEN protein expression compared with the blank and NC groups. Thus, inhibition of miR-19b suppresses the progression of WT by modulating the PTEN/PI3K/AKT signaling pathway. J. Cell. Biochem. 118: 3424-3434, 2017. © 2017 Wiley Periodicals, Inc.
Subject(s)
Apoptosis , Cell Movement , Cell Proliferation , Kidney Neoplasms/metabolism , MicroRNAs/metabolism , PTEN Phosphohydrolase/metabolism , Phosphatidylinositol 3-Kinases/metabolism , Proto-Oncogene Proteins c-akt/metabolism , RNA, Neoplasm/metabolism , Signal Transduction , Wilms Tumor/metabolism , Cell Line, Tumor , Child , Child, Preschool , Female , Humans , Infant , Infant, Newborn , Kidney Neoplasms/genetics , Kidney Neoplasms/pathology , Male , MicroRNAs/genetics , PTEN Phosphohydrolase/genetics , Phosphatidylinositol 3-Kinases/genetics , Proto-Oncogene Proteins c-akt/genetics , RNA, Neoplasm/genetics , Wilms Tumor/genetics , Wilms Tumor/pathologyABSTRACT
OBJECTIVE: To study the expression of E-cadherin, N-cadherin, TGF-ß1 and Twist protein and investigate its significance in the occurrence and development of prostate cancer. METHODS: The expression of E-cadherin, N-cadherin, TGF-ß1 and Twist protein in 59 prostate cancer tissues and 21 adjacent tissues were detected by immunohistochemical SABC staining, and the correlation with clinicopathological features was analyzed. RESULTS: Positive rates of E-cadherin, N-cadherin, TGF-ß1 and Twist were 32.2%, 54.2%, 71.2% and 74.6%, respectively, in prostate cancer tissues and 85.7%, 9.52%, 19.0% and 9.52%, respectively, in cancer-adjacent tissues, with significant differences between the two groups (P<0.05). The reduced expression of E-cadherin was related to the differentiation of prostate cancer tissues and PSA level, but was not associated with clinical stage, lymph node metastasis, bony metastasis and age. The increased expression of N-cadherin, TGF-ß1 and Twist was related to the differentiation of prostate cancer tissues, clinical stage, lymph node metastasis, bony metastasis, but not to age. The difference in positive expression of N-cadherin and TGF-ß1 was significant between PSA≤20 µg/L group and PSA>20µg/L group, but the positive expression of Twist was not significant between groups. The expression of E-cadherin was highly negatively correlated with that of N-cadherin and also highly negatively correlated with that of Twist. The expression of TGF-ß1 was correlated with those of E-cadherin, N-cadherin and Twist. CONCLUSIONS: The reduced expression of E-cadherin, abnormal expression of N-cadherin, transformation form E-cadherin to N-cadherin and the increased expression of TGF-ß1 and Twist play an important role in the occurrence and development of prostate cancer.