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Gesture recognition plays an important role in smart homes, such as human-computer interaction, identity authentication, etc. Most of the existing WiFi signal-based approaches exploit a large number of channel state information (CSI) datasets to train a gestures classification model; however, these models require a large number of human participants to train, and are not robust to the recognition environment. To address this problem, we propose a WiFi signal-based gesture recognition system with matched averaging federated learning (WiMA). Since there are differences in the distribution of WiFi signal changes caused by the same gesture in different environments, the traditional federated parameter average algorithm seriously affects the recognition accuracy of the model. In WiMA, we exploit the neuron arrangement invariance of neural networks in parameter aggregation, which can improve the robustness of the gesture recognition model with heterogeneous CSI data of different training environments. We carried out experiments with seven participant users in a distributed gesture recognition environment. Experimental results show that the average accuracy of our proposed system is up to 90.4%, which is very close to the accuracy of state-of-the-art approaches with centralized training models.
Assuntos
Gestos , Reconhecimento Automatizado de Padrão , Algoritmos , Humanos , Redes Neurais de Computação , Reconhecimento Automatizado de Padrão/métodos , Reconhecimento PsicológicoRESUMO
Renal fibrosis is a critical pathological process lead to a progressive loss of renal function. Jolkinolide B (JB) is a natural compound with anti-inflammatory activity from Euphorbia fischeriana Steud. The study evaluated the effect of JB on renal fibrosis in mice with unilateral ureteral obstruction (UUO). The results showed that JB could decrease renal fibrotic area, reduce phosphorylation of NF-κB p65 and the release of TNF-α, IL-6 and IL-1ß, restore the expression of vementin, α-SMA and E-cadherin, as well as TGF-ß1 and p-smad2/3. In conclusion, JB might reduce renal fibrosis by inhibiting inflammation induced by NF-κB pathway and EMT mediated by TGF-ß1/Smad pathway.
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Obstrução Ureteral , Animais , Anti-Inflamatórios/farmacologia , Diterpenos , Transição Epitelial-Mesenquimal , Fibrose , Rim/patologia , Camundongos , Estrutura Molecular , Transdução de Sinais , Fator de Crescimento Transformador beta1/farmacologia , Fator de Crescimento Transformador beta1/uso terapêutico , Obstrução Ureteral/tratamento farmacológico , Obstrução Ureteral/patologiaRESUMO
FAS and FAS ligand (FASL) play crucial roles in apoptotic signaling, and deregulation of this pathway may facilitate carcinogenesis. Studies on the association between the FAS/FASL polymorphisms (FAS-1377G/A rs2234767, FAS-670A/G rs1800682, and FASL-844C/T rs763110) and breast cancer risk have reported inconsistent results. Therefore, to characterize the relationship between those polymorphisms and breast cancer risk, we undertook a meta-analysis of those studies. Several electronic databases were searched for articles on the FAS/FASL polymorphisms and breast cancer risk. The genotype data were extracted; pooled odds ratios (OR) with 95% confidence intervals (CIs) were used to estimate the strength of the association. Five studies were eligible for our meta-analysis. Overall, we observed significant associations of the FAS-1377G/A polymorphism with breast cancer susceptibility (AG vs. GG: OR = 1.15, 95% CI 1.02-1.30; AA vs. GG: OR = 1.39, 95% CI 1.12-1.72; AG/AA vs. GG: OR = 1.18, 95% CI, 1.16-1.32; A vs. G: OR = 1.16, 95% CI 1.06-1.26), but we did not observe significant association of the Fas-670A/G and FasL-844C/T polymorphisms with breast cancer risk. In the subgroup analysis, we observed that the FAS-1377G/A and FASL-844C/T polymorphisms were associated with breast cancer risk in Chinese but not Whites; we still did not observed association of the FAS-670A/G polymorphism with breast cancer risk. Our meta-analysis revealed that FAS-1377G>A polymorphism was associated with an increased risk of breast cancer. FASL-844C>T polymorphism might be associated with a reduced breast cancer risk in Chinese. However, FAS-670A/G had no any effect on breast carcinogenesis.
Assuntos
Neoplasias da Mama/genética , Proteína Ligante Fas/genética , Predisposição Genética para Doença , Polimorfismo Genético , Receptor fas/genética , Feminino , Humanos , RiscoRESUMO
BACKGROUND: Regorafenib is a novel multikinase inhibitor approved for use in metastatic colorectal cancer (mCRC) and locally advanced gastrointestinal stromal tumors (GISTs). Hypertension is one of the major adverse events of this agent, but to date the incidence and risk of hypertension with regorafenib have not been systematically investigated. We have conducted a systematic review and meta-analysis of published clinical trials to determine its overall incidence and risk. METHODS: PubMed, Web of Science and abstracts presented at the American Society of Clinical Oncology annual meetings were searched to identify relevant studies published up to September 9, 2013. Eligible studies were prospective phase II or III clinical trials using regorafenib in cancer patients with data on hypertension available. The incidence and relative risk (RR) of hypertension were calculated using a random-effects model. RESULTS: Data from a total of 1,069 patients (regorafenib n = 750; controls n = 319) from five clinical trials were included for analysis. The overall incidence of all-grade and high-grade hypertension were 44.4 % [95 % confidence interval (CI) 30.8-59.0 %) and 12.5 % (95 % CI 5.2-27.1 %), respectively. The use of regorafenib in cancer patients was associated with a significantly increased risk of all-grade (RR 3.76, 95 % CI 2.35-5.99) and high-grade (RR, 8.39, 95 % CI 3.10-22.71) hypertension. The risk might vary with tumor types (P = 0.000). CONCLUSIONS: Patients with cancer receiving regorafenib have a significantly higher risk of developing hypertension. Close monitoring and appropriate management of this hypertension are strongly recommended.
Assuntos
Antineoplásicos/efeitos adversos , Hipertensão/induzido quimicamente , Neoplasias/tratamento farmacológico , Compostos de Fenilureia/efeitos adversos , Inibidores de Proteínas Quinases/efeitos adversos , Piridinas/efeitos adversos , Humanos , Hipertensão/epidemiologia , Incidência , Neoplasias/epidemiologia , RiscoRESUMO
PURPOSE: We undertook a meta-analysis of randomized trials to evaluate the efficacy of multitargeted antiangiogenic tyrosine kinase inhibitors (MATKIs) in addition to chemotherapy in metastatic breast cancer. METHODS: PubMed, Web of Knowledge databases and the ASCO meeting abstracts were searched for eligible literature published up to August 30, 2013. The endpoints included progression-free survival (PFS), overall survival (OS), overall response rate (ORR) and toxicities. Pooled hazard ratios (HRs) for survival outcomes and odds ratio (ORs) for dichotomous data with 95 % confidence intervals (CIs) were derived. RESULTS: Eight studies including 2,077 participants were analyzed. Compared to chemotherapy alone, adding MATKIs to chemotherapy resulted in a 14 % risk reduction of PFS events. However, the benefit did not reach statistical significance (HR 0.86; 95 % CI 0.70-1.04, P=0.126). Also, no OS benefit was observed (HR 1.03; 95 % CI 0.89-1.18, P=0.724). The addition of MATKIs significantly increased the ORR (OR 1.57; 95 % CI 1.30-1.91, P=0.000). Subgroup analysis revealed that sorafinib showed a significantly greater effect on PFS in patients with HER2 negative metastatic breast cancer (HR 0.67; 95 % CI 0.55-0.82, P=0.000) in comparison to chemotherapy alone. Additionally, sunitinib seemed to have no substantial efficacy for metastatic breast cancer. Toxicities were more frequent in patients receiving MATKIs. CONCLUSION: Overall, regimens consisting of MATKIs seemed not to be superior to chemotherapy alone in terms of PFS and OS, although significant improvement in ORR was observed. However, the addition of sorafenib significantly improved PFS. Further studies are needed to corroborate this finding.
Assuntos
Inibidores da Angiogênese/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Proteínas Tirosina Quinases/antagonistas & inibidores , Inibidores da Angiogênese/administração & dosagem , Inibidores da Angiogênese/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias da Mama/irrigação sanguínea , Neoplasias da Mama/enzimologia , Neoplasias da Mama/patologia , Intervalo Livre de Doença , Feminino , Humanos , Terapia de Alvo Molecular , Metástase Neoplásica , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
This study delves into the impact of digital inclusive finance on environmental pollution, with a specific focus on air pollution. Utilizing data from 265 Chinese cities, advanced econometric methods such as the bi-directional fixed effects model, threshold model, spatial Durbin model, and multi-period difference-in-differences model are employed, incorporating a variety of control variables. The empirical findings indicate that digital inclusive finance significantly reduces air pollution. This mechanism chiefly operates through enhancing public environmental consciousness and fostering green technological innovation. The study also uncovers the spatial spillover effect and non-linear characteristics of digital inclusive finance on air pollution, along with its interactive effects with specific policies (e.g., smart city pilot policies and the "major protection, no major development" initiative). Moreover, heterogeneity analysis reveals regional variations in the environmental effects of digital inclusive finance. These insights provide a novel perspective on the relationship between financial technology and environmental protection and offer crucial guidance for policymaking.
Assuntos
Poluição do Ar , Poluição do Ar/economia , Poluição do Ar/análise , Poluição do Ar/prevenção & controle , Humanos , China , Cidades , Poluição Ambiental/economia , Poluição Ambiental/prevenção & controleRESUMO
The current polyvinyl chloride (PVC) gel flexible actuators are facing challenges of high input voltage and an insufficient elastic modulus. In this study, we conducted a detailed study on the properties of PVC gel prepared by introducing the modifier polyvinyl chloride-vinyl acetate (P(VC-VA)). We compared a modified PVC gel with the traditional one in terms of the relative dielectric constant, mechanical modulus, and electromechanical actuation performance. Experimental results demonstrated that the introduction of P(VC-VA) enhanced the dielectric constant and reduced the driving electric field strength of PVC gels. The dielectric constant increased from 4.77 to 7.3. The electromechanical actuation performance increased by 150%. We employed the Gent model to fit the experimental results, and the actual experimental data aligned well with the expectations of the Gent model. The research results show that this type of plasticizing method effectively balanced the mechanical and electrical performance of PVC gels. This study summarizes the experimental results and performance analysis of PVC gels prepared using innovative plasticization methods, revealing the potential engineering applications of polymeric gels.
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Cornuside has been discovered to improve learning and memory in AD mice, however, its underlying mechanism was not fully understood. In the present study, we established an AD mice model by intracerebroventricular injection of Aß1-42, which were treated with cornuside (3, 10, 30 mg/kg) for 2 weeks. Cornuside significantly ameliorated cognitive function of AD mice in series of behavioral tests, including Morris water maze test, nest building test, novel object recognition test and step-down test. Additionally, cornuside could attenuate neuronal injury, and promote cholinergic synaptic transmission by restoring the level of acetylcholine (ACh) via inhibiting acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE), as well as facilitating choline acetyltransferase (ChAT). Furthermore, cornuside inhibited oxidative stress levels amplified as decreased malondialdehyde (MDA), by inhibiting TXNIP expression, improving total anti-oxidative capacity (TAOC), raising activities of superoxide dismutase (SOD) and catalase (CAT). Cornuside also reduced the activation of microglia and astrocytes, decreased the level of proinflammatory factors TNF-α, IL-6, IL-1ß, iNOS and COX2 via interfering RAGE-mediated IKK-IκB-NF-κB phosphorylation. Similar anti-oxidative and anti-inflammatory effects were also found in LPS-stimulated BV2 cells via hampering RAGE-mediated TXNIP activation and NF-κB nuclear translocation. Virtual docking revealed that cornuside could interact with the active pocket of RAGE V domain directly. In conclusion, cornuside could bind to the RAGE directly impeding the interaction of Aß and RAGE, and cut down the expression of TXNIP inhibiting ROS production and oxidative stress, as well as hamper NF-κB p65 mediated the inflammation.
Assuntos
Doença de Alzheimer , Peptídeos beta-Amiloides , Disfunção Cognitiva , NF-kappa B , Fragmentos de Peptídeos , Receptor para Produtos Finais de Glicação Avançada , Transdução de Sinais , Animais , Camundongos , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/metabolismo , Doença de Alzheimer/induzido quimicamente , Peptídeos beta-Amiloides/toxicidade , Peptídeos beta-Amiloides/metabolismo , Fragmentos de Peptídeos/toxicidade , Disfunção Cognitiva/tratamento farmacológico , Disfunção Cognitiva/metabolismo , Disfunção Cognitiva/induzido quimicamente , Transdução de Sinais/efeitos dos fármacos , Receptor para Produtos Finais de Glicação Avançada/metabolismo , NF-kappa B/metabolismo , Masculino , Estresse Oxidativo/efeitos dos fármacosRESUMO
Studies on the association between the TCF7L2 rs12255372 polymorphism and breast cancer risk have reported conflicting results. To characterize the relationship between this polymorphism and breast cancer risk, we conducted a comprehensive literature search for relevant studies and performed a meta-analysis. A total of four studies including 5280 cases and 6026 controls were eligible for our analysis. Overall, we did find that this polymorphism correlates with breast cancer risk [TT versus GG: odds ratio (OR)=1.19, 95% confidence interval (CI)=1.02-1.40; GT versus GG: OR=1.10, 95% CI=1.01-1.19; T versus G: OR=1.12, 95% CI=1.05-1.19]. Furthermore, in the subgroup analysis by ethnicity, we did also find that this polymorphism associated with an increased breast cancer risk in white individuals (T versus G: OR=1.11, 95% CI=1.04-1.18). In summary, this meta-analysis suggests that the rs12255372 T allele is a low-penetrant risk factor for breast carcinogenesis. In the future, larger-scale and more well-designed studies based on homogeneous breast cancer patients are needed to validate our findings, especially in Asians.
Assuntos
Neoplasias da Mama/genética , Carcinogênese/genética , Polimorfismo de Nucleotídeo Único , Proteína 2 Semelhante ao Fator 7 de Transcrição/genética , Feminino , Predisposição Genética para Doença , HumanosRESUMO
PTGS2 genetic 3' untranslated region (3'UTR) miRNA binding sites variants are significantly associated with cancer risk; however, the roles of genetic variants in PTGS2 gene 3'UTR and post-transcriptional regulation have not been elucidated. We report that rs689470 and rs5275 in the PTGS2 3'UTR have potential miRNA-binding sites by using bioinformatics analysis. However, only the rs689470 was significantly associated with PTGS2 mRNA expression in lymphoblastoid cell lines (P = 0.026), but not for rs5275 (P = 0.626). rs689470 might be putative variants mediating the post-transcriptional regulation of target PTGS2 gene. Better understanding of how 3'UTR variants regulate PTGS2 activity will pave the way to targeting the PTGS2 pathway in cancer therapy.
Assuntos
Ciclo-Oxigenase 2/genética , RNA Mensageiro/metabolismo , Regiões 3' não Traduzidas , Sítios de Ligação , Linhagem Celular Tumoral , Biologia Computacional , Ciclo-Oxigenase 2/metabolismo , Bases de Dados Factuais , Feminino , Genótipo , Humanos , Desequilíbrio de Ligação , Masculino , MicroRNAs/metabolismo , Fenótipo , Polimorfismo de Nucleotídeo Único , Leucemia-Linfoma Linfoblástico de Células Precursoras/metabolismo , Leucemia-Linfoma Linfoblástico de Células Precursoras/patologiaRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Cornus officinalis Sieb. et Zucc., is a valuable herb commonly used in Chinese medicine clinics. Loganin is a major iridoid glycoside obtained from the traditional Chinese herb Corni Fructus. Loganin, which has been shown to improve depression-like behavior in mice exposed to acute stress, is probably a potential antidepressant candidate. AIM OF THE STUDY: Loganin was evaluated for its effect on chronic unpredictable mild stress (CUMS) induced depressive-like mice, and its action mechanisms were explored. MATERIALS AND METHODS: ICR mice were subjected to the CUMS stimulation method to induce depression. The therapeutic effect of loganin on depressive-like behavior was evaluated by a series of behavioral tests such as sucrose preference test (SPT), forced swim test (FST), tail suspension test (TST) and open-field test (OFT). In addition, the serum levels of adrenocorticotropic hormone (ACTH) and corticosterone (CORT) were measured using ELISA. The levels of monoamine neurotransmitters were detected by high performance liquid chromatography-electrochemical detection (HPLC-ECD). The levels of brain-derived neurotrophic factor (BDNF) in the hippocampus were measured using western blot analysis. RESULTS: The results showed that CUMS induced depressive-like behaviors in mice, as indicated by behavioral tests. Administration of loganin increased the sucrose preference in SPT, as well as decreased the immobility time in FST and TST. Loganin could also improve food intake, and increased crossing times in the OFT. In mechanism, loganin restored the secretion of monoamine neurotransmitters, ACTH and CORT to normal levels. In addition, loganin elevated the expression of BDNF in the hippocampus. In conclusion, loganin exerts antidepressant-like effects in CUMS model mice through modulating monoamine neurotransmitters, ACTH, CORT and BDNF. CONCLUSION: Loganin effectively ameliorated depressive-like symptoms in CUMS-exposed mice by increasing 5-hydroxytryptamine (5-HT) and dopamine (DA) levels, alleviating hypothalamic-pituitary-adrenal (HPA) axis dysfunction, and increasing BDNF expression. In conclusion, the findings of the current study extensive evidence for the application of loganin in stress-associated disorders, specifically targeting depression.
Assuntos
Fator Neurotrófico Derivado do Encéfalo , Depressão , Camundongos , Animais , Depressão/tratamento farmacológico , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Camundongos Endogâmicos ICR , Antidepressivos/farmacologia , Hipocampo , Hormônio Adrenocorticotrópico , Sacarose/metabolismo , Estresse Psicológico/tratamento farmacológico , Modelos Animais de Doenças , Comportamento AnimalRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Cornus officinalis Sieb. et Zucc., traditional Chinese medicine, has been widely used in the treatment of dementia. Cornel iridoid glycosides of Cornus officinalis is therapeutic to Alzheimer's disease (AD), while its pharmacodynamic material basis is not clear. Cornuside, an iridoid glycoside extracted from of Cornus officinalis Sieb. et Zucc, might be a potential anti-AD candidate. AIM OF THE STUDY: Cornuside was evaluated for its effect on scopolamine induced AD mice, and its action mechanisms were explored. MATERIALS AND METHODS: ICR mice were administered with 1 mg/kg scopolamine intraperitoneally to induce amnesia. The therapeutic effect of cornuside of cognitive function was evaluated via series of behavioral tests, including Morris water maze test, step-through test and step-down test. In addition, specific enzyme reaction tests were used to detect the content of acetylcholine (ACh) and malondialdehyde (MDA), as well as the activities of acetylcholinesterase (AChE), butyrylcholinesterase (BuChE), choline acetyltransferase (ChAT), superoxide dismutase (SOD), catalase (CAT), monoamine oxidase (MAO) in the brain. The levels of monoamine neurotransmitters were detected by high performance liquid chromatography-electrochemical detection (HPLC-ECD). RESULTS: Cornuside ameliorated the spatial memory impairment in Morris water maze test and cognitive disruption in step-through and step-down test. Furthermore, cornuside improved the level of ACh by reducing the activities of AChE and BuChE, and increasing the activity of ChAT in hippocampus. Cornuside also increased the levels of monoamine neurotransmitters by inhibiting MAO activity in hippocampus and cortex. In addition, cornuside attenuated MDA by enhancing the activities of SOD and CAT in hippocampus and cortex. CONCLUSION: Cornuside improved cognitive dysfunction induced by scopolamine in behavioral tests. The mechanisms of cornuside were further investigated from the aspects of neurotransmitters and oxidative stress. Cornuside could inhibit oxidative stress and neurotransmitter hydrolases, increase ACh and monoamine neurotransmitters, which finally contributed to its therapeutic effect on scopolamine induced amnesia.
Assuntos
Doença de Alzheimer , Disfunção Cognitiva , Acetilcolina/farmacologia , Acetilcolinesterase/metabolismo , Amnésia/induzido quimicamente , Amnésia/tratamento farmacológico , Animais , Butirilcolinesterase , Colina O-Acetiltransferase/metabolismo , Disfunção Cognitiva/induzido quimicamente , Disfunção Cognitiva/tratamento farmacológico , Glucosídeos , Hipocampo , Aprendizagem em Labirinto , Camundongos , Camundongos Endogâmicos ICR , Monoaminoxidase , Neurotransmissores , Estresse Oxidativo , Piranos , Escopolamina/farmacologia , Superóxido Dismutase/metabolismoRESUMO
RATIONALE: Depression is a serious neuropsychiatric disorder, which is characterized by sustaining mood disorders. Loganin, a major iridoid glycoside from Corni fructus, has a variety of pharmacological activities, including neuroprotective effect and hypnotic effect. However, little is known about the effects of loganin on stress-induced depression. OBJECTIVE: To investigate the effects of loganin on behavioral despair of mice, and whether serotonin (5-HT) and/or noradrenaline (NE) are involved in this process. METHODS: We tested the effectiveness of loganin using tail suspension test (TST). The possible mechanism was explored using reserpine-induced ptosis and hypothermia, and 5-HTP-induced head-twitch response in mice. The changes of 5-HT and NE in the prefrontal cortex, hippocampus, and striatum were measured through high-performance liquid chromatography (HPLC) analysis. Then, we identified the effects of depleting 5-HT and NE by PCPA (p-chlorophenylalanine) and DSP-4 (N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine hydrochloride) pretreatment, respectively. RESULTS: Loganin (12.5/50 mg/kg) induced antidepressant-like effects in mice submitted to TST. Loganin (12.5/50 mg/kg) ameliorated the reserpine-induced hypothermia and ptosis, as well as increased 5-HTP-induced head-twitch responses in mice. Loganin (50 mg/kg) significantly increased the levels of 5-HT in the prefrontal cortex, hippocampus, and striatum. Furthermore, only PCPA treatment could eliminate loganin-induced antidepressant-like effects in TST. CONCLUSION: Loganin exerts antidepressant-like effect in the TST depending on 5-HT levels in the central nervous system, which provide a potential agent for depression therapy.
Assuntos
Depressão , Atividade Motora , Animais , Antidepressivos/farmacologia , Comportamento Animal , Depressão/tratamento farmacológico , Iridoides , Camundongos , Serotonina/farmacologiaRESUMO
PURPOSE: Although existing evidence from clinical trials has demonstrated manifestation of gastrointestinal perforation with the use of ramucirumab, overall risks have yet to be reported. Therefore, we performed a meta-analysis of published randomized controlled trials (RCTs) to get a better understanding of the overall incidence and risk of gastrointestinal perforation associated with ramucirumab. METHODS: The PubMed and Web of Science databases as well as abstracts presented at American Society of Clinical Oncology conferences were searched to identify relevant studies published up to 01 May 2015. Eligible studies included randomized trials of ramucirumab either alone or in combination with another agent compared with the control arm without ramucirumab and that reported gastrointestinal perforation event. Overall incidence, relative risk (RR) and 95% confidence intervals (CI) were computed using fixed- or random-effects models depending on the heterogeneity of the included studies. RESULTS: A total of 4579 patients with a variety of solid malignancies from six RCTs were included in our meta-analysis. The incidence of gastrointestinal perforation related to ramucirumab was 1.5% (95% CI 1.1-2.1%) with a mortality of 29.8% (95% CI 14.9-50.7%). The RR of gastrointestinal perforation associated with ramucirumab was 2.56 (95% CI 1.29-5.09; P = 0.007). CONCLUSIONS: Treatment with the ramucirumab is associated with a significant increase in risk of gastrointestinal perforation in cancer patients.
Assuntos
Anticorpos Monoclonais/efeitos adversos , Antineoplásicos/efeitos adversos , Gastroenteropatias/induzido quimicamente , Perfuração Intestinal/induzido quimicamente , Anticorpos Monoclonais Humanizados , Gastroenteropatias/epidemiologia , Humanos , Incidência , Perfuração Intestinal/epidemiologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Risco , RamucirumabRESUMO
BACKGROUND AND OBJECTIVE: Ramucirumab is a novel antiangiogenic agent approved as second-line therapy for patients with advanced stomach cancer and gastroesophageal junction adenocarcinoma. Although existing evidence from clinical trials has demonstrated hypertension is one of the major adverse events of this agent, overall risks have yet to be reported. METHODS: We carried out a meta-analysis of published studies to determine the overall incidence and relative risk (RR) of hypertension associated with ramucirumab. Statistical analyses were conducted to calculate the summary incidence, RRs, and 95 % confidence intervals (CIs) by using a random effects model. RESULTS: Eleven studies with a total of 3,851 patients with multiple cancers were included. The overall incidence of all-grade hypertension was 20.0 % (95 % CI 15.0-26.0) with 8.6 % (95 % CI 6.3-11.7) being high-grade hypertension. The risk of developing hypertension was greater in ramucirumab-treated patients (RR for all grades 2.77, 95 % CI 1.94-3.94, p < 0.001, RR for high-grade 3.58, 95 % CI 2.45-5.23, p < 0.001). CONCLUSIONS: Administration of ramucirumab to patients with cancer is associated with increased risk of hypertension.
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Anticorpos Monoclonais/efeitos adversos , Hipertensão/induzido quimicamente , Hipertensão/epidemiologia , Neoplasias/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Inibidores da Angiogênese/efeitos adversos , Inibidores da Angiogênese/uso terapêutico , Anticorpos Monoclonais/uso terapêutico , Anticorpos Monoclonais Humanizados , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Neoplasias/complicações , Fatores de Risco , Adulto Jovem , RamucirumabRESUMO
MicroRNAs (miRNAs) are short regulatory RNAs that negatively modulate protein expression at the post-transcriptional level. Additionally, they have been associated with the pathogenesis of a number of types of cancer. In the current study, two target sites for miR-150 were determined within the 3'-untranslated region of p27Kip1 (hereafter referred to as p27) mRNA, and it was determined that ectopic overexpression of miR-150 led directly to p27 downregulation in cancer cells. These findings indicate that miR-150 may be a novel regulator of p27 expression. In the databases of the University of California, Santa Cruz (UCSC) and Match online, two common transcription factors were identified for miR-150 and p27: Cooperates with myogenic proteins 1 (COMP1) and hepatocyte nuclear factor-4 (HNF-4). Using the Database for Annotation, Visualization, and Integrated Discovery (DAVID), it was determined that p27 is involved in pathways regulated by the target genes of miR-150. Therefore, these results suggest that there may be a regulatory loop between COMP1 and HNF-4-miR-150-p27. Additional functional studies are required to understand the molecular basis for the formation of this circuit loop, and provide an insight into the development of innovative therapies targeting specific tumor markers.
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Lin28B is a RNA-binding protein that inhibits the let-7 microRNA family and acts as an oncogene in various human malignant diseases. Conversely, the members of let-7 family function as tumor suppressers and are often inactivated in cancers. The interaction of Lin28B/let-7 plays a crucial part of tumorigenesis. In this study, the authors examined the Lin28B expression using immunohistochemistry in 190 breast cancers and analyzed the correlation of Lin28B immunostaining and clinicopathological characteristics. Breast cancer patients previously diagnosed with invasive ductal carcinomas were enrolled in this study. All cases went through surgical procedures as the initial treatment. The characteristics of every case were collected, including tumor size, pathologic grade, metastatic lymphoid nodes, and estrogen receptor α (ERα), progesterone receptor (PR), and HER2 status. The immunostaining was scored by two independent investigators. Eighty-three (43.7%) of 190 cases showed positive expression of Lin28B. Lin28B immunostaining was increased in tumors compared with the adjacent tissues. Overexpression of Lin28B was linked to poor differentiation, advanced-stage disease, and Ki67-positive status (all p<0.05). Besides, Lin28B expression was significantly different among breast cancer subtypes. This study addresses the role of Lin28B in breast cancers and provides insight of its predictive effects in disease development.
Assuntos
Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/metabolismo , Carcinoma Ductal de Mama/patologia , Proteínas de Ligação a RNA/biossíntese , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/genética , Carcinoma Ductal de Mama/genética , Feminino , Humanos , Pessoa de Meia-Idade , Proteínas de Ligação a RNA/genéticaRESUMO
OBJECTIVE: To identify the signatures of miRNAs differentially expressed in HER2(+) versus HER2(-) breast cancers that accurately predict the HER2 status of breast cancer, and to provide further insight into breast cancer therapy. METHODS: By the methods of literature search, aberrant expressed miRNAs were collected. By target prediction algorithm of TargetScan and PicTar and the data enrichment analysis, target gene sets of miRNAs differentially expressed in HER2(+) versus HER2(-) breast cancers were built. Then, using the Database for Annotation, Visualization, and Integrated Discovery (DAVID) database, the function modules of Gene Ontology categories and Kyoto Encyclopedia of Genes and Genomes (KEGG) and BIOCARTA pathway, biological functions and signaling pathways that are probably regulated by miRNAs, were analyzed. RESULTS: We got five sets of miRNAs expressed in different HER2 status of breast cancers finally. The five sets of data contain 22; 32; 3; 38; and 62 miRNAs, respectively. After miRNAs target prediction and data enrichment, 5,734; 22,409; 1,142; 22,293; and 43,460 target genes of five miRNA sets were collected. Gene ontology analysis found these genes may be involved in transcription, protein transport, angiogenesis, and apoptosis. Moreover, certain KEGG and BIOCARTA signaling pathways related toHER2 status were found. CONCLUSION: Using TargetScan and PicTar for data enrichment, and DAVID database, Gene Ontology categories, KEGG and BIOCARTA pathway for analysis of miRNAs different expression, we conducted a new method for biological interpretation of miRNA profiling data in HER2(+) versus HER2(-) breast cancers. It may improve understanding the regulatory roles of miRNAs in different molecular subtypes of breast cancers. Therefore, it is beneficial to improve the accuracy of experimental efforts to breast cancer and potential therapeutic targets.
Assuntos
Biomarcadores Tumorais/genética , Neoplasias da Mama/genética , Biologia Computacional , Perfilação da Expressão Gênica , MicroRNAs/genética , Receptor ErbB-2/metabolismo , Neoplasias da Mama/metabolismo , Feminino , Redes Reguladoras de Genes , Humanos , Análise de Sequência com Séries de Oligonucleotídeos , Transdução de SinaisRESUMO
The transcription factor E2F1 is a key regulator of cell proliferation and apoptosis, and deregulated expression of E2F1 has been frequently found in a number of malignancies. Previous studies have indentified that E2F1 genetic 3' untranslated region (3'UTR) microRNA (miRNA) binding site variants are significantly associated with cancer risk; however, the roles of genetic variants in the E2F1 3'UTR in its post-transcriptional regulation have not been elucidated. Hence, using mRNA expression data from the HapMap online database, we analyzed the association between the variants at the miRNA binding sites of E2F1 and its mRNA expression. In the present study, we report the identification of 5 variants of putative miRNA binding sites in the E2F1 3'UTR by bioinformatic analysis. Among them, rs3213180 was found to be significantly associated with E2F1 expression in lymphoblastoid cell lines from the HapMap database (P=0.045); however, no significant association was demonstrated in this study for rs3213182 (P=0.345) and rs3213183 (P=0.402). This study demonstrated that rs3213180 may be a putative variant mediating the post-transcriptional regulation of the E2F1 target gene. In conclusion, 3'UTR polymorphism is significantly associated with E2F1 expression in lymphoblastoid cell lines. However, this finding requires validation in further functional analysis of the underlying mechanism involving E2F1 transcriptional activity associated with variants in the 3'UTR.
RESUMO
Published data on the association between the rs895819 (A>G) polymorphism in the terminal loop of pre-miR-27a and cancer risk is inconclusive. Therefore, we conducted a meta-analysis to estimate the association between this polymorphism and cancer. The PubMed, Web of science, and Embase databases were searched for articles on the hsa-miR-27a rs895819 polymorphism and cancer risk published up to November 24, 2012. The genotype data obtained in the searches were pooled in our meta-analysis, and pooled odds ratio (OR) with 95% confidence interval (CI) was used to assess the association. Seven studies with a total of 3849 cases and 4781 controls were eligible for analysis. Overall, we found no significant associations between the hsa-miR-27a rs895819 (A>G) polymorphism and cancer susceptibility (homozygote model: OR=0.88, 95% CI: 0.68-1.14; heterozygote model: OR=0.96, 95% CI: 0.79-1.17; dominant model: OR=0.94, 95% CI: 0.79-1.12; recessive model: OR=0.88, 95% CI: 0.69-1.12). In the subgroup analysis by ethnicity, we found that the rs895819 AG genotype was associated with a decreased risk of cancer in white individuals (dominant model: OR=0.85, 95% CI: 0.76-0.94; heterozygote model: OR=0.84, 95% CI: 0.75-0.94). This meta-analysis indicated that the hsa-miR-27a rs895819 polymorphism did not correlate with overall cancer risk in the general population. However, the rs895819 AG genotype may protect against the development of cancer in white individuals. Larger, better studies of homogeneous cancer patients are needed to further assess the correlation between this polymorphism and cancer risk.