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BACKGROUND: An effective and safe treatment for nausea and vomiting of pregnancy (NVP) is lacking. OBJECTIVE: To assess the efficacy and safety of acupuncture, doxylamine-pyridoxine, and a combination of both in women with moderate to severe NVP. DESIGN: Multicenter, randomized, double-blind, placebo-controlled, 2 × 2 factorial trial. (ClinicalTrials.gov: NCT04401384). SETTING: 13 tertiary hospitals in mainland China from 21 June 2020 to 2 February 2022. PARTICIPANTS: 352 women in early pregnancy with moderate to severe NVP. INTERVENTION: Participants received daily active or sham acupuncture for 30 minutes and doxylamine-pyridoxine or placebo for 14 days. MEASUREMENTS: The primary outcome was the reduction in Pregnancy-Unique Quantification of Emesis (PUQE) score at the end of the intervention at day 15 relative to baseline. Secondary outcomes included quality of life, adverse events, and maternal and perinatal complications. RESULTS: No significant interaction was detected between the interventions (P = 0.69). Participants receiving acupuncture (mean difference [MD], -0.7 [95% CI, -1.3 to -0.1]), doxylamine-pyridoxine (MD, -1.0 [CI, -1.6 to -0.4]), and the combination of both (MD, -1.6 [CI, -2.2 to -0.9]) had a larger reduction in PUQE score over the treatment course than their respective control groups (sham acupuncture, placebo, and sham acupuncture plus placebo). Compared with placebo, a higher risk for births with children who were small for gestational age was observed with doxylamine-pyridoxine (odds ratio, 3.8 [CI, 1.0 to 14.1]). LIMITATION: The placebo effects of the interventions and natural regression of the disease were not evaluated. CONCLUSION: Both acupuncture and doxylamine-pyridoxine alone are efficacious for moderate and severe NVP. However, the clinical importance of this effect is uncertain because of its modest magnitude. The combination of acupuncture and doxylamine-pyridoxine may yield a potentially larger benefit than each treatment alone. PRIMARY FUNDING SOURCE: The National Key R&D Program of China and the Project of Heilongjiang Province "TouYan" Innovation Team.
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Terapia por Acupuntura , Antieméticos , Complicações na Gravidez , Gravidez , Criança , Feminino , Humanos , Doxilamina/efeitos adversos , Piridoxina/uso terapêutico , Piridoxina/efeitos adversos , Antieméticos/uso terapêutico , Qualidade de Vida , Vômito/tratamento farmacológico , Vômito/induzido quimicamente , Náusea/tratamento farmacológico , Complicações na Gravidez/tratamento farmacológico , Terapia por Acupuntura/efeitos adversosRESUMO
OBJECTIVE: The purpose of this study was to determine the clinical value of triple antibiotic therapy consisting of doxycycline, compound sulfamethoxazole and rifampicin in the treatment of brucellosis spondylitis. METHODS: A retrospective analysis was performed on 100 patients with brucellosis spondylitis admitted to the First Affiliated Hospital of Hebei North University from March 2016 to June 2019. Patients were divided into the following two groups: the control group (n = 50) treated with dual antibiotic therapy (rifampicin + compound sulfamethoxazole), and the observation group (n = 50) treated with triple antibiotic therapy (rifampicin + doxycycline + compound sulfamethoxazole). The treatment effect, low back pain relief, levels of erythrocyte sedimentation rate (ESR), procalcitonin (PCT) and C-reactive protein (CRP), as well as the adverse reactions were compared between the two groups. RESULTS: The response rate of the observation group was significantly higher than that of the control group (P < 0.05). Before treatment, there was no significant difference in the low back pain assessed by the visual analogue scale (VAS), or levels of ESR, PCT and CRP between the two groups (P > 0.05). But after treatment, the VAS score and the levels of ESR, PCT and CRP in observation group were lower than those in the control group (P < 0.05). No significant difference was found in the incidence of adverse reactions (P > 0.05). CONCLUSION: The triple antibiotic therapy of doxycycline, compound sulfamethoxazole and rifampicin is effective in the treatment of brucellosis spondylitis. It can significantly alleviate patients' back pain and inflammation with a high safety profile, which is worthy of clinical application.
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Brucelose/tratamento farmacológico , Doxiciclina/uso terapêutico , Rifampina/uso terapêutico , Espondilite/tratamento farmacológico , Sulfametoxazol/uso terapêutico , Adulto , Brucelose/metabolismo , Doxiciclina/administração & dosagem , Quimioterapia Combinada , Feminino , Humanos , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Dor Lombar/tratamento farmacológico , Dor Lombar/metabolismo , Masculino , Estudos Retrospectivos , Rifampina/administração & dosagem , Espondilite/metabolismo , Sulfametoxazol/administração & dosagemRESUMO
Objective: This article aimed to investigate whether serum magnesium is associated with insulin resistance index and testosterone level in women with polycystic ovary syndrome (PCOS). Materials and Methods: Overall 1000 women with PCOS were enrolled in a randomized controlled trial and a cross-sectional analysis of the association of serum magnesium with glucose metabolism markers and testosterone was performed. Serum magnesium, glucose metabolism markers and testosterone were measured. Insulin resistance was evaluated by homeostatic model assessment of insulin resistance (HOMA-IR) and quantitative insulin-sensitivity check index (QUICKI). Multivariable linear regression and logistic regression models were used to estimate the association between serum magnesium, insulin resistance and testosterone. Results: In comparative analyses, women with higher quartile of serum magnesium had significantly lower fasting glucose, HOMA-IR and testosterone. Multiple linear regression showed serum magnesium was independently negatively associated with insulin, glucose, HOMA-IR, testosterone and positively associated with QUICKI (P for trend <0.05) after adjusting confounding covariates. Logistic regression showed serum magnesium in quartile 1 and 2 were independently associated with insulin resistance status (Quartile 1: OR: 2.15, 95%CI: 1.35-3.40, P = 0.001; Quartile 2: OR: 1.90, 95%CI: 1.20-3.02, P = 0.006), while quartile 1 was marginally associated with hyperandrogenemia status (Quartile 1: OR: 1.45, 95%CI: 0.99-2.11, P = 0.055) after adjusting confounding covariates. Conclusion: The current findings suggest that lower serum magnesium was associated with aggravated insulin resistance and higher testosterone levels among women with PCOS.
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Glucose/metabolismo , Resistência à Insulina , Magnésio/sangue , Síndrome do Ovário Policístico/sangue , Testosterona/sangue , Adulto , Glicemia/análise , Feminino , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Adulto JovemRESUMO
Low-cost and efficient bifunctional catalysts are urgently needed for overall water splitting used in large-scale energy storage. In this study, we develop a nickel and iron (di)sulfide (Ni-Fe-S) composite catalyst that is inâ situ synthesized and fixed within the intergranular nanopores inside high pure polycrystalline graphite. Two precursor solutions (reactants) may permeate the graphite intergranular pores to a depth of more than 3.5â mm. The nanoscale pores serve as an array of nanoreactors for the synthesis of the Ni-Fe-S nanoparticles under conditions much milder than usual. The prepared catalyst efficiently catalyzes both the hydrogen and oxygen evolution reactions (HER and OER) in 1.0 M KOH. It delivers a current density of 400â mA cm-2 at a full cell voltage of around 2.3â V without considerable activity decay over 24â h electrolysis. The active species of the catalyst are different for the HER and OER and discussed accordingly. The synthesis strategy based on the nanopores in a monolithic conductive substrate proves to be a simple, efficient, and promising way to prepare electrocatalysts that are cheap, abundant, and industrially attractive.
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OBJECTIVE: To investigate the relationships between sex hormone-binding globulin (SHBG) and comprehensive metabolic parameters including biometric, glycemic, lipid, liver, and renal functions of women with polycystic ovary syndrome (PCOS). Study Design and Methods. A total of 1000 women diagnosed as PCOS by modified Rotterdam criteria were enrolled in a randomized controlled trial. SHBG and comprehensive metabolic parameters were measured at the baseline visit. Metabolic parameters included biometric parameters, glucose and lipid panels, and liver and renal function parameters. An independent t-test and linear regression were performed to investigate the associations between SHBG and metabolic parameters. Logistic regression was used to detect the relationship between SHBG and the presence of metabolic syndrome. RESULTS: In comparative analyses, PCOS women with lower SHBG levels had higher body mass index, waist circumference, insulin, homeostatic model assessment-insulin resistance (HOMA-IR) index, systolic and diastolic blood pressure, triglycerides, apolipoprotein B (APOB), low-density lipoprotein (LDL), aspartate transferase (AST), alanine transferase (ALT), and blood urea nitrogen (BUN), but lower high-density lipoprotein (HDL) and apolipoprotein A1 (APOA1). In linear regression, SHBG was inversely associated with waist circumference, systolic blood pressure, triglyceride, LDL, APOB, ALT, AST, and BUN but positively associated with HDL and APOA1 after adjusting the BMI. In logistic regression, SHBG is a protective predictor for metabolic syndrome (odds ratio = 0.96; 95% confidence interval: 0.95-0.97). The area under the receiver-operator characteristic curve is 0.732 with a 95% confidence interval of 0.695-0.770. SHBG <26.75 mmol/L is the cutoff point with the best Youden index, which has a sensitivity of 0.656 and specificity of 0.698. CONCLUSIONS: Lower SHBG was associated with worsening biometric, lipid, liver, and renal functions but not glycemic parameters among women with PCOS. SHBG can be used as a tool to screen metabolic syndrome. This trial is registered with NCT01573858 and ChiCTR-TRC-12002081.
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Protein regulator of cytokinesis 1 (PRC1) has been reported in correlation with various malignancies. Functionality of PRC1 in nasopharyngeal carcinoma (NPC) was investigated, in perspective of long noncoding RNA (lncRNA) regulatory circuitry. Aberrant expressed messenger RNA and lncRNA were screened out from the Gene Expression Omnibus microarray database. NPC cell line CNE-2 was adopted for in vitro study and transfected with mimic or short hairpin RNA of miR-194-3p and PTPRG-AS1. The radioactive sensitivity, cell viability, migration, invasion, and apoptosis were detected. PTPRG-AS1 and PRC1 were upregulated in NPC, whereas miR-194-3p was downregulated. PTPRG-AS1 was found to specifically bind to miR-194-3p as a competing endogenous RNA and miR-194-3p targets and negatively regulates PRC1. Overexpressed miR-194-3p or silenced PTPRG-AS1 resulted in enhanced sensitivity to radiotherapy and cell apoptosis along with suppressed cell migration, invasion and proliferation in NPC. Furthermore, impaired tumor formation was also caused by miR-194-3p overexpression or PTPRG-AS1 suppression through xenograft tumor in nude mice. In our study, PTPRG-AS1/miR-194-3p/PRC1 regulatory circuitry was revealed in NPC, the mechanism of which can be of clinical significance for treatment of NPC.
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Proteínas de Ciclo Celular/metabolismo , MicroRNAs/genética , Carcinoma Nasofaríngeo/patologia , Neoplasias Nasofaríngeas/patologia , RNA Longo não Codificante/genética , Tolerância a Radiação/genética , Animais , Apoptose/genética , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Sobrevivência Celular/genética , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Técnicas de Silenciamento de Genes , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Pessoa de Meia-Idade , Carcinoma Nasofaríngeo/genética , Carcinoma Nasofaríngeo/radioterapia , Neoplasias Nasofaríngeas/genética , Neoplasias Nasofaríngeas/radioterapia , Transplante de Neoplasias , Transplante HeterólogoRESUMO
Background: Little knowledge about long non-coding RNAs(lncRNAs) in nasopharyngeal carcinoma (NPC) has been acquired. Methods: Next-generation sequencing was applied in 7 cases of NPC tissues and 7 cases of normal tissues in nasopharynx. PLEX, CNCI and CPAT soft-wares were used to predict novel lncRNAs. Real-time Quantitative PCR (qPCR) further validated the data in 20 cases of NPC tissues and 14 cases of normal tissues. Then the cis-regulators and trans-regulators and potential biological functions together with pathways were predicted by Bioinformatics. Results: Totally, 4248 novel lncRNAs were found to be expressed in our samples. And 2192 lncRNAs and 23342 mRNAs were considered to be differentially expressed in NPC. Among the results, 306 lncRNAs and 4599 mRNAs were significantly up-regulated, whereas 204 lncRNAs and 2059 mRNAs were significantly down-regulated, respectively. Moreover, 62 lncRNAs trans-regulated genes were involved in Epstein-Barr virus (EBV) infection pathway in our study. Jun proto-oncogene (JUN), which was related to a cis-regulator lncRNA RP4-794H19.1, was enriched in cancers and involved in Tumor Necrosis Factor (TNF) signaling pathway, might play a key role in NPC. Conclusion: These findings broadened the lncRNAs landscape of NPC tissues and shed light on the roles of these lncRNAs, which might be conducive to the comprehensive management of NPC.
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Objective To investigate the role of methylprednisolone (MP) in treatment of spinal cord injured (SCI) with bone marrow mesenchymal stem cells (BMSCs) transplantation in rats and its effect on the expressions of tumor necrosis factor-α(TNF-α) and interleukin-1ß(IL-1ß) at the local tissues.Methods Forty male Sprague-Dawley(SD) rats were used to establish the models of SCI according to the modified Allen's contusion method and then divided into four groups (n=10 in each group) by using random numbers table:MP group,BMSCs group,BMSCs+MP group,and control group.MP was intravenously administrated immediately after SCI.BMSCs labeled by 5-bromo-2-deoxyuridine(BrdU)were transplanted into the injured sites of spinal cord after two hours of SCI.On the 1 st,7 th,and 14th days after SCI,when functional outcome measurements were evaluated by the Basso-Beattie-Bresnahan (BBB) score.On the 14th day after treatment,the spine cord tissues were harvested for the TNF-α/IL-1ß immunohistochemistry,and Tunel staining method was used to detect cell apoptosis rate.BrdU-positive BMSCs were examined in BMSCs group and BMSCs+MP group.Results Functional recovery of hind limb in MP+BMSCs group was the best among the four group.On the 1 st day after injury,the BBB scores showed no significant difference among four group(χ2=1.0756,P=0.7829).On the 7th and 14th day,the BBB score of MP+BMSCs group was significantly higher than MP group (χ2=17.7186,P=0.0002;χ2= 24.7259,P<0.0001) and BMSCs group (χ2=15.8110,P=0.0024;χ2=25.6014,P<0.0001),respectively.The BBB score of the control group was significantly lower than MP group (χ2=8.3265,P=0.0325;χ2=13.5060,P=0.0062) and BMSCs group (χ2=14.1166,P=0.0036;χ2=8.9613,P=0.0299),respectively.On the 14th day,immunohistochemical staining presented that the TNF-α and IL-1ß-positive cells in MP+BMSCs group were significantly lower than MP group (q=5.573,P=0.0004;q=4.596,P=0.0025) and BMSCs group (q=13.780,P<0.0001;q=8.456,P<0.0001),and control group was significantly higher than MP group (q=14.710,P<0.0001;q=6.710,P<0.0001) and BMSCs group (q=6.502,P=0.0001;q=2.849,P=0.0514).Tunel staining showed the apoptotic rate of spinal cord cells in four group were (48.47±5.70)%,(31.95±3.58)%,(41.39±2.33)%,and (23.48±2.69)%.The number of apoptotic cells in MP+BMSCs group was least in four groups;compared with the control group,the apoptotic rate significantly decreased in MP group (q=14.840,P<0.0001) and BMSCs group (q=6.716,P=0.0002);compared with the MP+BMSCs group,the apoptotic rate was significantly increased in the MP group (q=7.332,P=0.0001) and BMSCs group (q=15.460,P<0.0001). BrdU staining revealed BrdU-positive rate in MP+BMSCs group [(9.3000±0.5175)%] was significantly higher than that in BMSCs group [(6.6000±0.3399)%](t=4.361,P=0.0004).Conclusion MP can improve the function of the hind limbs of SCI rats treated with BMSCs transplantation and lower the expressions of TNF-α and IL-1ß in injured tissue.
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Interleucina-1beta/metabolismo , Transplante de Células-Tronco Mesenquimais , Metilprednisolona/farmacologia , Traumatismos da Medula Espinal/terapia , Fator de Necrose Tumoral alfa/metabolismo , Animais , Apoptose , Imuno-Histoquímica , Masculino , Células-Tronco Mesenquimais , Ratos , Ratos Sprague-Dawley , Medula Espinal/patologiaRESUMO
OBJECTIVE: To investigate the expression of integrin-linked kinase (ILK) and its relationship with clinicopathological parameters in laryngeal squamous cell carcinoma (LSCC). METHODS: 116 patients who had previously undergone complete resection of tumor for LSCC were studied retrospectively. The level of ILK expression in tumor tissues and adjacent nontumor tissues were determined by immunohistochemistry. RESULTS: Increased expression of ILK was found in 65.5% of cases. The expression of ILK protein was significantly associated with tumor grade (p=0.046), lymph node metastasis (p=0.020), and pTNM stage (p=0.019). Kaplan-Meier survival estimates showed a significant correlation between ILK expression and patient survival rate (log-rank p<0.05). The multivariate survival analysis revealed that N status was statistically significant prognostic factor (p<0.001). Other parameters, such as ILK expression, cannot predict disease prognosis separately. CONCLUSION: Increased expression of integrin-linked kinase is associated with lymph node metastases and patient survival rate in laryngeal squamous cell carcinoma. However, it does not appear to be an independent prognostic predictor in LSCC.
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Carcinoma de Células Escamosas/metabolismo , Neoplasias de Cabeça e Pescoço/metabolismo , Neoplasias Laríngeas/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Idoso , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/patologia , Feminino , Neoplasias de Cabeça e Pescoço/mortalidade , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Estimativa de Kaplan-Meier , Neoplasias Laríngeas/mortalidade , Neoplasias Laríngeas/patologia , Linfonodos/patologia , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Gradação de Tumores , Estadiamento de Neoplasias , Prognóstico , Carcinoma de Células Escamosas de Cabeça e Pescoço , Análise de SobrevidaRESUMO
The tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) selectively induces apoptosis in the majority of tumor cells, whilst sparing normal cells. However, the potential use of TRAIL in the treatment of cancer is limited by the inevitable emergence of drug resistance. The present study reports the upregulation of latent membrane protein 1 (LMP1)-induced TRAIL resistance via the enhanced expression of X-linked inhibitor of apoptosis protein (XIAP) in nasopharyngeal carcinoma (NPC) cells. LMP1-positive NPC cells were indicated to be more sensitive to TRAIL compared with LMP1-negative NPC cells in three NPC cell lines. CNE-1 is a LMP1-negative NPC cell line that was transfected with pGL6-LMP1; following which, sensitivity to TRAIL decreased. LMP1-induced TRAIL resistance was associated with the decreased cleavage of caspase-8,-3 and -9, BH3 interacting domain death agonist (Bid) and mitochondrial depolarization, without any effects on the expression of the death receptors, B-cell lymphoma (Bcl)-2 and Bcl-extra long. Knockdown of XIAP with small interfering RNA increased caspase-3 and -9 and Bid cleavage, and prevented LMP1-induced TRAIL resistance. Furthermore, embelin, the inhibitor of XIAP, prevented LMP1-induced TRAIL resistance in the Epstein-Barr virus (EBV)-positive CNE-1-LMP1 and C666-1 NPC cell lines. However, embelin did not enhance TRAIL-induced apoptosis in NP-69, which was used as a benign nasopharyngeal epithelial cell line. These data show that LMP1 inhibits TRAIL-mediated apoptosis by upregulation of XIAP. Embelin may be used in an efficacious and safe manner to prevent LMP1-induced TRAIL resistance. The present study may have implications for the development and validation of novel strategies to prevent TRAIL resistance in EBV-positive NPC.
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This study identifies promoter methylation status of RUNX3 in 77 LSCC patient tissues and their paired adjacent healthy tissues. Hypermethylation percentage RUNX3 occurred in LSCC samples was significantly higher than that in normal tissues, as well as associated with suppression of RUNX3 expression, TNM classification of malignant tumors stage, lymph node metastasis and poor overall survival rate. Reduced methylation and increased expression of RUNX3 genes in vitro was observed and decreased cell migration was further confirmed following 5-azacytidine treatment. RUNX 3 promoter hypermethylation can lead to down-regulation of RUNX3 in LSCC cancerous tissue.
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Carcinoma de Células Escamosas/genética , Movimento Celular , Subunidade alfa 3 de Fator de Ligação ao Core/genética , Metilação de DNA , Neoplasias de Cabeça e Pescoço/genética , Neoplasias Laríngeas/genética , Idoso , Azacitidina/farmacologia , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patologia , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Subunidade alfa 3 de Fator de Ligação ao Core/metabolismo , Metilação de DNA/efeitos dos fármacos , Metilases de Modificação do DNA/antagonistas & inibidores , Metilases de Modificação do DNA/metabolismo , Regulação para Baixo , Inibidores Enzimáticos/farmacologia , Feminino , Regulação Neoplásica da Expressão Gênica , Neoplasias de Cabeça e Pescoço/metabolismo , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Neoplasias Laríngeas/metabolismo , Neoplasias Laríngeas/patologia , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Regiões Promotoras Genéticas , RNA Mensageiro/metabolismo , Carcinoma de Células Escamosas de Cabeça e Pescoço , Fatores de TempoRESUMO
Pharyngoesophageal perforation after anterior cervical spine surgery is rare and the delayed cases were more rarely reported but potentially life-threatening. We report a case of pharyngoesophageal perforation 3 years after anterior cervical spine surgery. The patient presented with dysphagia, fever, left cervical mass and developing dyspnea 3 years after cervical spine surgery for trauma. After careful examinations, he underwent an emergency tracheostomy, neck exploration, hardware removal, abscess drainage and infected tissue debridement. 14 days after surgery, CT of the neck with oral contrast demonstrated no contrast extravasation from the esophagus. Upon review of literature, only 14 cases of pharyngoesophageal perforation more than 1 year after anterior cervical spine surgery were found. We discussed possible etiology, diagnosis and management and concluded that in cases of dysphagia, dyspnea, cervical pain, swelling and edema of the cervical area even long time after anterior cervical spine surgery, potential pharyngoesophageal damage should be considered.
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Abscesso , Vértebras Cervicais/cirurgia , Perfuração Esofágica , Esôfago , Faringe , Complicações Pós-Operatórias , Fusão Vertebral/efeitos adversos , Abscesso/diagnóstico , Abscesso/etiologia , Abscesso/cirurgia , Adulto , Parafusos Ósseos/efeitos adversos , Desbridamento/métodos , Descompressão Cirúrgica/métodos , Drenagem/métodos , Perfuração Esofágica/diagnóstico , Perfuração Esofágica/etiologia , Perfuração Esofágica/fisiopatologia , Perfuração Esofágica/cirurgia , Esôfago/lesões , Esôfago/patologia , Esôfago/fisiopatologia , Esôfago/cirurgia , Humanos , Masculino , Pescoço/diagnóstico por imagem , Pescoço/cirurgia , Faringe/lesões , Faringe/patologia , Faringe/fisiopatologia , Faringe/cirurgia , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/fisiopatologia , Complicações Pós-Operatórias/cirurgia , Fusão Vertebral/métodos , Tomografia Computadorizada por Raios X , Resultado do TratamentoRESUMO
Recent research has demonstrated that tropomyosinrelated kinase B (TrkB) plays an important role in neuronal survival, differentiation and migration; yet, its specific role in human nasopharyngeal carcinoma (NPC) is unclear. To elucidate its role in NPC, we examined TrkB expression in NPC tissues and cell lines, and investigated the correlation between TrkB expression and prognosis in patients with NPC. Immunohistochemical analysis was performed on NPC specimens from 108 patients with follow-up information. Additionally, reverse transcriptase-polymerase chain reaction (RT-PCR) and western blot analyses were used to determine TrkB expression levels in NPC and noncancerous nasopharyngeal tissues. RT-PCR and western blot analyses were also used to determine TrkB expression levels in 7 NPC cell lines and a nasopharyngeal epithelium cell line. High TrkB expression was significantly correlated with T classification, lymph node metastasis and clinical stage, respectively. Patients with NPC who had high TrkB expression had reduced disease-free survival and overall survival when compared with patients who had low TrkB expression. Multivariate Cox regression analysis revealed that TrkB overexpression was an independent prognostic factor for patients with NPC. Furthermore, TrkB was overexpressed in NPC specimens and cell lines. TrkB expression levels were significantly increased in NPC specimens, and enhanced levels were correlated with a poor prognosis in patients with NPC. These findings suggest that TrkB may contribute to NPC progression and represent a novel prognostic indicator for patients with NPC.
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Metástase Linfática/genética , Neoplasias Nasofaríngeas/genética , Proteínas Quinases/biossíntese , Biomarcadores Tumorais/genética , Carcinoma , Linhagem Celular Tumoral , Progressão da Doença , Intervalo Livre de Doença , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Glicoproteínas de Membrana , Pessoa de Meia-Idade , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas/mortalidade , Proteínas Quinases/genética , Proteínas Tirosina Quinases , RNA Mensageiro/biossíntese , Receptor trkB , Tropomiosina/biossíntese , Tropomiosina/genéticaRESUMO
Spike development in wheat is a complicated development process and determines the wheat propagation and survival. We report herein a proteomic study on the bread wheat mutant strain 5660M underlying spike development inhibition. A total of 121 differentially expressed proteins, which were involved in cold stress response, protein folding and assembly, cell-cycle regulation, scavenging of ROS, and the autonomous pathway were identified using MS/MS and database searching. We found that cold responsive proteins were highly expressed in the mutant in contrast to those expressed in the wild-type line. Particularly, the autonomous pathway protein FVE, which modulates flowering, was dramatically downregulated and closely related to the spike development inhibition phenotype of 5660M. A quantitative RT-PCR study demonstrated that the transcription of the FVE and other six genes in the autonomous pathway and downstream flowering regulators were all markedly downregulated. The results indicate that spike development of 5660M cannot complete the floral transition. FVE might play an important role in the spikes development of the wheat. Our results provide the theory basis for studying floral development and transition in the reproductive growth period, and further analysis of wheat yield formation.
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Proteínas de Transporte/análise , Flores/embriologia , Proteínas de Plantas/análise , Proteômica/métodos , Triticum/embriologia , Proteínas de Transporte/biossíntese , Resposta ao Choque Frio , Bases de Dados de Proteínas , Regulação para Baixo , Flores/crescimento & desenvolvimento , Regulação da Expressão Gênica de Plantas , Dobramento de Proteína , Espécies Reativas de Oxigênio , Reação em Cadeia da Polimerase em Tempo Real , Análise de Sequência de Proteína , Espectrometria de Massas em Tandem , Triticum/genética , Triticum/crescimento & desenvolvimentoRESUMO
Beclin-1 plays a critical role in the regulation of autophagy, apoptosis, differentiation and the development and progression of cancer. The aim of the present investigation was to analyze the Beclin-1 protein expression and to assess its prognostic significance in tissue of laryngeal squamous cell carcinoma (LSCC). Beclin-1 protein expression in 82 primary laryngeal squamous cell carcinoma and 40 paracarcinoma non-tumor tissue samples was analyzed by immunohistochemistry and correlated with clinicopathological parameters and patients' outcome. The expression of Beclin-1 in tumor tissues was significantly lower than that in non-tumor tissues (P = 0.035). Reduced Beclin-1 expression was significantly correlated with lymph node metastases (P = 0.021). Kaplan-Meier survival estimates showed a significant correlation between Beclin-1 expression and patient's survival rate (log-rank P < 0.05). Multivariate Cox proportional hazards model analysis confirmed that lymph node metastases (P = 0.048) and Beclin-1 expression (P = 0.029) were statistically significant, independent prognostic factors for LSCC. Our findings suggested that decreased Beclin-1 expression and lymph node metastases, as examined by immunohistochemistry, are both independent biomarker for poor prognosis of patients with LSCC.
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Proteínas Reguladoras de Apoptose/biossíntese , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patologia , Neoplasias de Cabeça e Pescoço/metabolismo , Neoplasias de Cabeça e Pescoço/patologia , Neoplasias Laríngeas/metabolismo , Neoplasias Laríngeas/patologia , Proteínas de Membrana/biossíntese , Adulto , Idoso , Proteínas Reguladoras de Apoptose/metabolismo , Proteína Beclina-1 , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Proteínas de Membrana/metabolismo , Pessoa de Meia-Idade , Prognóstico , Modelos de Riscos Proporcionais , Carcinoma de Células Escamosas de Cabeça e PescoçoRESUMO
OBJECTIVE: Identification of the primary tumour can prolong the life expectancy of patients with primary unknown cervical lymph node metastasis (PUCLNM) through targeted therapy. This study investigated the value of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET-CT) at identifying primaries in patients with PUCLNM. METHODS: Twenty-seven patients (21 males and 6 females, median age 48.2 ± 16.3, age range 30-73) with PUCLNM underwent FDG PET-CT to search for the primary tumour, which could not be detected by conventional diagnostic modalities. The results were analysed and correlated with either pathological findings or clinical follow up. RESULTS: Pathological FDG uptake suspicious for the primary was detected in 13 cases, while the primary tumour remained occult in 14 cases. Eleven of 13 patients with suspected primaries were confirmed by histological findings. One with a coexisting second tumour and three with unexpected distant metastases were found in patients with confirmed primaries. The most common primary location in patients with PUCLNM found in our study was nasopharynx. In those 14 patients with negative FDG PET-CT results, only one patient had a primary malignancy that was proven histologically after endoscopy with biopsy during a period of clinical follow up. The sensitivity, specificity, accuracy and positive predictive values of FDG PET-CT were 91.7, 86.7, 88.9 and 84.6%, respectively. CONCLUSION: FDG PET-CT is a useful tool to help search for unknown primaries in patients with cervical lymph node metastasis and has an acceptable diagnostic yield for the detection of distant malignancies.
Assuntos
Linfocintigrafia , Imagem Multimodal , Neoplasias Primárias Desconhecidas/diagnóstico por imagem , Tomografia por Emissão de Pósitrons , Tomografia Computadorizada por Raios X , Adulto , Idoso , Biomarcadores Tumorais/análise , Biópsia , Endoscopia , Feminino , Fluordesoxiglucose F18 , Humanos , Masculino , Pessoa de Meia-Idade , Radiografia Abdominal , Radiografia Torácica , Compostos RadiofarmacêuticosRESUMO
OBJECTIVE: To investigate the expression of E-cadherin and its relationship with clinicopathological parameters in laryngeal squamous cell carcinoma (LSCC). METHODS: Sixty-four patients who had previously undergone complete resection of tumor for LSCC were studied retrospectively. The level of E-cadherin expression in tumor tissues and paired nontumor tissues were determined by immunohistochemistry. RESULTS: The expression of E-cadherin in tumor tissues was significantly lower than nontumor tissues (P<0.001). Reduced E-cadherin expression was significantly correlated with lymph node metastases (P<0.001). Kaplan-Meier survival estimates showed a significant correlation between E-cadherin expression and patient survival rate (log-rank P<0.05). Multivariate Cox proportional hazards model analysis confirmed that lymph node metastases (P=0.001) and tumor stage (P=0.013) were statistically significant, independent predictor of prognosis. CONCLUSION: Expression of E-cadherin is an independent predictor of lymph node metastases in LSCC. However, it does not appear to be a better prognostic predictor than other established markers in LSCC.
Assuntos
Caderinas/análise , Carcinoma de Células Escamosas/patologia , Neoplasias Laríngeas/patologia , Metástase Linfática/patologia , Idoso , Carcinoma de Células Escamosas/cirurgia , Seguimentos , Humanos , Técnicas Imunoenzimáticas , Neoplasias Laríngeas/cirurgia , Laringectomia , Laringe/patologia , Linfonodos/patologia , Masculino , Pessoa de Meia-Idade , Esvaziamento Cervical , Estadiamento de Neoplasias , Valores de Referência , Estudos RetrospectivosRESUMO
The 5-year survival rate of nasopharyngeal carcinoma (NPC) is disappointing despite the much improved technologies in its treatment. Thus, finding more effective treatment for NPC has become an urgent priority. The tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) can selectively induce apoptosis in most tumor cells while sparing normal cells. However, its potential in the treatment of NPC has been limited by the eventual emergence of drug resistance. Bcl-2 and Akt contribute to TRAIL resistance in some cancer cells. In this study, CNE-2 was found to be the most resistant NPC cell line to TRAIL, and whether Bcl-2 small-interfering RNA (siRNA) and phosphatidylinositol 3-kinase (PI3-K) inhibitors (LY294002 and Wortmannin) could prevent TRAIL resistance in CNE-2 was also investigated. Results showed that both Bcl-2 siRNA and PI3-K inhibitors could prevent TRAIL resistance in CNE-2. Bcl-2 siRNA sensitized CNE-2 by activating the intrinsic apoptotic pathway and PI3-K inhibitors sensitized CNE-2 by activating both intrinsic and extrinsic pathways. Further, simultaneously targeting Bcl-2 and Akt was found to be a more efficient approach to prevent TRAIL resistance in CNE-2 and this synergistic effect happened at the level of Bid downstream. At last, the combinative treatments did not enhance toxicity of TRAIL in MRC5, a human benign fibroblast cell line. This study suggests that simultaneously targeting Bcl-2 and Akt pathway might be effective in preventing TRAIL resistance of NPC cells.
Assuntos
Proteínas Reguladoras de Apoptose/metabolismo , Neoplasias Nasofaríngeas/tratamento farmacológico , Proteínas Proto-Oncogênicas c-akt/antagonistas & inibidores , Proteínas Proto-Oncogênicas c-bcl-2/antagonistas & inibidores , Ligante Indutor de Apoptose Relacionado a TNF/farmacologia , Apoptose/efeitos dos fármacos , Proteínas Reguladoras de Apoptose/genética , Carcinoma , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/metabolismo , Linhagem Celular Tumoral , Resistencia a Medicamentos Antineoplásicos , Sinergismo Farmacológico , Humanos , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas/metabolismo , Proteínas Proto-Oncogênicas c-akt/biossíntese , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/biossíntese , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Transdução de Sinais/efeitos dos fármacosRESUMO
The 5-year survival rate of nasopharyngeal carcinoma (NPC) is still disappointing despite the much improved technologies in its treatment. Tumor necrosis factor-related apoptosis inducing ligand (TRAIL) can selectively induce apoptosis in most tumor cells while sparing normal cells. However, its potential in the treatment of NPC has been limited by the eventual emergence of drug resistance. Latent membrane protein 1 (LMP1) is a major oncogene of the human DNA tumor virus Epstein-Barr virus (EBV) and is associated with the development of NPC and the emergence of chemo-resistance in NPC. In this study, we investigated the potential role of LMP1 in TRAIL resistance in CNE-1 NPC cells. Results show that overexpression of LMP1 could induce TRAIL resistance in NPC cells without influencing death receptors. The LMP1-induced TRAIL resistance is associated with increased expression of FLIP and elevated cleavage of caspase-8 without altering the TRAIL-mediated mitochondrial events and Bid cleavage. Knockdown of the FLIP gene with siRNA prevented the LMP1-induced TRAIL resistance. Furthermore, we found that overexpression of LMP1 activated Akt. Inhibition of Akt with LY294002 completely prevented the LMP1-induced FLIP expression and TRAIL resistance. Together, these results show that LMP1 can inhibit the TRAIL-mediated apoptosis through activation of PI3K/Akt and expression of FLIP in CNE-1 NPC cells, and may provide new methods to prevent and reverse drug resistance in NPC.