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1.
Pain Pract ; 23(5): 511-522, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-36695542

RESUMO

OBJECTIVE: Our meta-analysis aimed to compare the analgesic effectiveness of ultrasound-guided preoperative erector spinae plane block (ESPB) versus paravertebral nerve block (PVB) in breast surgery. METHODS: PubMed, EMBASE, and the Cochrane Library were searched for randomized controlled trials (RCTs) between January 1, 1980 and April 31, 2021. The primary endpoints were perioperative pain score, analgesic consumption, and assessment of the block procedure. The secondary endpoints were intraoperative hemodynamic response, duration of surgery, postoperative antiemetic consumption, and adverse effects. RESULTS: Four RCTs comprised a total of 310 patients were included in our meta-analysis. No significant differences in the perioperative pain score and analgesic consumption were observed between ESPB and PVB in the operating room, post-anesthesia care unit (PACU), and ward (at 1, 16, 12, and 24 h), and the morning of postoperative day 1 (POD1) (all p > 0.05). Similarly, no significant differences in the duration of block, time to first analgesic, hemodynamic response, duration of surgery, postoperative antiemetic consumption, and adverse effects were observed (all p > 0.05). However, our meta-analysis revealed that ultrasound-guided preoperative ESPB significantly reduced the duration of procedure time and frequency of guidance interventions, as well as increased the block success rate among residents (all p < 0.05). CONCLUSIONS: Both ultrasound-guided preoperative ESPB and PVB showed comparable analgesic effects in patients undergoing breast surgery. However, with a significantly shorter procedure time and higher block success rate, our findings suggest that ESPB may be a simple alternative to PVB in breast surgery.


Assuntos
Antieméticos , Neoplasias da Mama , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Bloqueio Nervoso , Humanos , Feminino , Ensaios Clínicos Controlados Aleatórios como Assunto , Analgésicos , Ultrassonografia de Intervenção , Dor , Dor Pós-Operatória/tratamento farmacológico , Dor Pós-Operatória/prevenção & controle , Analgésicos Opioides
2.
Pain Med ; 21(10): 2412-2422, 2020 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-32488265

RESUMO

OBJECTIVE: To investigate whether perioperative ultrasound-guided serratus anterior plane block (SAPB) combined with general anesthesia is more effective and safer than current analgesic techniques for postoperative analgesia after video-assisted thoracoscopic surgery (VATS). METHODS: PubMed, the Cochrane Library, and EMBASE were searched for clinical trials published up to July 31, 2019. Outcomes, including operative duration, postoperative pain scores, postoperative analgesia use, patient satisfaction with analgesia, time to chest tube removal, length of stay, and adverse effects were analyzed. RESULTS: Four clinical trials, including 262 patients, met inclusion criteria. Ultrasound-guided SAPB reduced pain scores at zero, 15, 30, 45, and 60 minutes in the postoperative anesthesia care unit (all P < 0.05) and at one, two, six, 12, and 24 hours in the ward (all P < 0.001). Additionally, postoperatively, morphine consumption at 15 and 30 minutes, overall morphine consumption, and total consumption (morphine plus tramadol) were significantly lower in the SAPB cohort (P < 0.05). Similarly, postoperative tramadol consumption at one, two, six, 12, and 24 hours was also lower in this cohort (all P < 0.05). The postoperative consumption of fentanyl, tramadol, and total morphine in patient-controlled analgesia (PCA) at 24 hours was significantly reduced (P < 0.05). Moreover, SAPB provided better patient satisfaction with analgesia (P = 0.0038). However, no statistically significant difference was found in duration of operation, time to chest tube removal, length of stay, or side effects (all P > 0.05). CONCLUSIONS: Perioperative ultrasound-guided SAPB combined with general anesthesia provided more effective postoperative analgesia after VATS. However, no significant advantage was found regarding side effects.


Assuntos
Bloqueio Nervoso , Cirurgia Torácica Vídeoassistida , Analgésicos , Anestesia Geral , Humanos , Dor Pós-Operatória/tratamento farmacológico , Dor Pós-Operatória/prevenção & controle , Ultrassonografia de Intervenção
3.
BMC Cancer ; 19(1): 843, 2019 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-31455274

RESUMO

BACKGROUND: Recent studies reported that blood-based microRNAs (miRNAs) could detect cancers and predict prognosis have opened a new field of utilizing circulating miRNAs as cancer biomarkers. In this pilot study, we conducted for the first time, to our knowledge, the evaluation of the applicability of salivary miRNAs as novel biomarkers for nasopharyngeal carcinoma (NPC) detection. METHODS: Microarray miRNA expression profiling was performed on saliva samples from 22 newly diagnosed NPC patients and 25 healthy controls, and 12 significantly down-regulated miRNAs were selected for quantitative real-time-PCR (qRT-PCR) validation and further analysis. Their target genes enriched by gene ontology and pathway analysis were used to construct regulatory and interaction networks. The receiver operating characteristic analyses (ROC) and logistic regression were calculated to assess discriminatory accuracy. RESULTS: Twelve dysregulated miRNAs screened by microarray that showed the same expression patterns with qRT-PCR analysis. Through bioinformatics analysis, the most prominent hub gene probably regulated by the 12 down-regulated miRNAs is found to be TP53. The ROC including the 12 miRNAs separated NPC patients from healthy controls with very high accuracy (areas under the receiver operating characteristic curve [AUC] = 0.999, sensitivity = 100.00%, specificity = 96.00%). Furthermore, if only six significantly dysregulated miRNAs were selected for the ROC analysis, the accuracy is still impressive (AUC = 0.941, sensitivity = 95.45%, specificity = 80.00%). CONCLUSIONS: This study highlights the potential for salivary miRNAs as biomarkers for the detection of NPC. Meanwhile, differentially expressed miRNAs in saliva might play critical roles in NPC by regulating their target genes, which associated with some significant pathways, such as p53 signaling pathway.


Assuntos
Biomarcadores Tumorais , MicroRNA Circulante , MicroRNAs/genética , Carcinoma Nasofaríngeo/diagnóstico , Carcinoma Nasofaríngeo/genética , Saliva/metabolismo , Adulto , Idoso , Estudos de Casos e Controles , Biologia Computacional/métodos , Feminino , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Redes Reguladoras de Genes , Estudo de Associação Genômica Ampla , Humanos , Biópsia Líquida , Masculino , Pessoa de Meia-Idade , Carcinoma Nasofaríngeo/metabolismo , Curva ROC
4.
Biochem Biophys Res Commun ; 486(4): 1143-1148, 2017 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-28391978

RESUMO

Bone cancer pain (BCP) is a serious chronic clinical condition and reactive oxygen species (ROS) were considered to be involved in its development and persistency. Normally, superoxide dismutase (SOD) converts superoxide anions to hydrogen peroxide (H2O2) and H2O2 is then naturalized to be water by peroxiredoxin 4. We reported previously that recombinant protein transduction domain (PTD)-Cu/Zn SOD effectively scavenged excessive ROS and prevented cardiomyocytes from hypoxia-reoxygenation damage. However, whether PTD-Cu/Zn SOD would prevent BCP development is unknown. In the current study, we found that an implanted carcinoma in the rat tibia induced remarkable hyperalgesia, increased H2O2 levels and decreased SOD and peroxiredoxin 4 levels. After administration of recombinant PTD-Cu/Zn SOD to these tumor-burden rats, their hyperalgesia was significantly attenuated and peroxiredoxin 4 expression was significantly increased. In addition, an increased expression of N-methyl-d-aspartic acid (NMDA) receptors and a decreased expression of γ-aminobutyric acid (GABA) receptors in this cancer pain were prevented by PTD-Cu/Zn SOD administration or peroxiredoxin 4 overexpression. Our data suggested that reactive oxygen species, at least in part, play a role in cancer metastatic pain development and persistency which can be attenuated by the adminstration of recombinant PTD-Cu/Zn SOD via the peroxiredoxin 4 modulation from oxidative stress.


Assuntos
Neoplasias Ósseas/metabolismo , Dor do Câncer/prevenção & controle , Peroxirredoxinas/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Proteínas Recombinantes de Fusão/administração & dosagem , Superóxido Dismutase-1/administração & dosagem , Animais , Antioxidantes/administração & dosagem , Neoplasias Ósseas/complicações , Neoplasias Ósseas/tratamento farmacológico , Dor do Câncer/diagnóstico , Dor do Câncer/etiologia , Linhagem Celular Tumoral , Relação Dose-Resposta a Droga , Feminino , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Proteínas Recombinantes de Fusão/genética , Superóxido Dismutase-1/genética , Resultado do Tratamento
6.
Kidney Int ; 85(1): 112-23, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24025645

RESUMO

Chronic allograft nephropathy (CAN) is a common finding in kidney grafts with functional impairment. Prolonged hypothermic storage-induced ischemia-reperfusion injury is associated with the early onset of CAN. As the noble gas xenon is clinically used as an anesthetic and has renoprotective properties in a rodent model of ischemia-reperfusion injury, we studied whether early treatment with xenon could attenuate CAN associated with prolonged hypothermic storage. Exposure to xenon enhanced the expression of insulin growth factor-1 (IGF-1) and its receptor in human proximal tubular (HK-2) cells, which, in turn, increased cell proliferation. Xenon treatment before or after hypothermia-hypoxia decreased cell apoptosis and cell inflammation after reoxygenation. The xenon-induced HK-2 cell proliferation was abolished by blocking the IGF-1 receptor, mTOR, and HIF-1α individually. In the Fischer-to-Lewis rat allogeneic renal transplantation model, xenon exposure of donors before graft retrieval or recipients after engraftment enhanced tubular cell proliferation and decreased tubular cell death and cell inflammation associated with ischemia-reperfusion injury. Compared with control allografts, xenon treatment significantly suppressed T-cell infiltration and fibrosis, prevented the development of CAN, and improved renal function. Thus, xenon treatment promoted recovery from ischemia-reperfusion injury and reduced susceptibility to the subsequent development of CAN in allografts.


Assuntos
Anestésicos Inalatórios/uso terapêutico , Nefropatias/prevenção & controle , Transplante de Rim/efeitos adversos , Traumatismo por Reperfusão/prevenção & controle , Xenônio/uso terapêutico , Animais , Linhagem Celular , Isquemia Fria/efeitos adversos , Avaliação Pré-Clínica de Medicamentos , Humanos , Fator de Crescimento Insulin-Like I/metabolismo , Nefropatias/imunologia , Nefropatias/patologia , Masculino , Ratos , Ratos Endogâmicos F344 , Ratos Endogâmicos Lew , Receptor IGF Tipo 1/metabolismo , Traumatismo por Reperfusão/etiologia
7.
J Clin Anesth ; 97: 111524, 2024 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-38941870

RESUMO

STUDY OBJECTIVE: HR18034, composed of the ropivacaine encapsulated in multi-lamellar, concentric circular structure liposomes as the major component and a small amount of free ropivacaine, has performed well in animal experiments and phase I clinical trials. This trial was to investigate the efficacy, safety, pharmacokinetic profile and the minimum effective dose of HR18034 for postoperative analgesia after hemorrhoidectomy compared with ropivacaine. DESIGN: A multicenter, randomized, double-blind trial. SETTING: 19 medical centers in China. PATIENTS: 85 patients undergoing hemorrhoidectomy between October 2022 to November 2022. INTERVENTIONS: Patients were randomly divided into HR 18034 190 mg group, 285 mg group, 380 mg group and ropivacaine 75 mg group, receiving single local anesthetic perianal injection for postoperative analgesia. MEASUREMENTS: The primary outcome was the area under the resting state NRS score -time curve within 72 h after injection. The second outcomes included the proportion of patients without pain, the proportion of patients not requiring rescue analgesia, cumulative morphine consumption for rescue analgesia, etc. Safety was evaluated by adverse events incidence and plasma ropivacaine concentrations were measured to explore the pharmacokinetic characteristics of HR18034. MAIN RESULTS: The areas under the NRS score (at rest and moving states)-time curve were significantly lower in HR 18034 380 mg group than ropivacaine 75 mg at 24 h, 48 h, and 72 h after administration. However, this superiority was not observed in HR18034 190 mg group and 285 mg group. There was no difference in cumulative morphine consumption for rescue analgesia between HR 18034 groups and ropivacaine group. CONCLUSIONS: HR 18034 380 mg showed superior analgesic efficacy and equivalent safety compared to ropivacaine 75 mg after hemorrhoidectomy, thus preliminarily determined as minimum effective dose.

8.
Cancer Biol Ther ; 24(1): 2223375, 2023 12 31.
Artigo em Inglês | MEDLINE | ID: mdl-37337460

RESUMO

Molecular mechanisms behind potentially inferior prognosis of old cholangiocarcinoma (CCA) patients are unclear. Prevalence of interventional targets and the difference between young and old CCA patients are valuable for promising precision medicine. A total of 188 CCA patients with baseline tumor tissue samples were subgrouped into the young (≤45 years) and old (>45 years) sub-cohorts. Somatic and germline mutation profiles, differentially enriched genetic alterations, and actionable genetic alterations were compared. An external dataset was used for the validation of molecular features and the comparison of overall survival (OS). Compared to young patients, KRAS alterations were more common in old patients (P = .04), while FGFR2 fusions were less frequent (P = .05). TERT promoter mutations were exclusively detected in old patients. The external dataset (N = 392) revealed no significant difference in OS between young and old patients; however, old patient-enriched KRAS (hazard ratio [HR]: 1.96, 95% confidence interval [CI]: 1.37-2.80) and TERT alterations (HR: 2.03, 95% CI: 1.22-3.38) were associated with inferior OS. Approximately 38.3% of patients were identified of actionable oncogenic mutations indicative of a potential response to targeted therapy or immunotherapy. Actionable FGFR2 fusions (P = .01) and BRAFV600E (P = .04) mutations were more frequent in young females than old patients. The enrichment of KRAS/TERT alterations in CCA patients over 45 years resulted in inferior OS. Approximately one-third of CCA patients were eligible for targeted therapy or immunotherapy given the actionable mutations carried, especially young females.


Assuntos
Neoplasias dos Ductos Biliares , Colangiocarcinoma , Feminino , Humanos , Proteínas Proto-Oncogênicas p21(ras)/genética , Colangiocarcinoma/genética , Colangiocarcinoma/terapia , Prognóstico , Ductos Biliares Intra-Hepáticos/patologia , Neoplasias dos Ductos Biliares/genética , Neoplasias dos Ductos Biliares/terapia , Genômica , Mutação
9.
Lancet Reg Health West Pac ; 37: 100787, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37693877

RESUMO

Background: The mortality risk related to anaesthesia in China remains poorly characterized. The objective of this study was to evaluate the anaesthesia-related mortality in terms of its incidence, changes, causes and preventability in Hubei, China, between 2017 and 2021 using a series of annual surveys. Methods: We prospectively collected information on patient, surgical, anaesthesia, and hospital characteristics for 9,391,669 anaesthesia procedures performed between 2017 and 2021 in 10 cities within Hubei Province, China. Anaesthesia-related death was defined as death that deemed to be entirely or partially attributable to anaesthesia, occurring within 24 h following anaesthesia administration. All fatalities were scrutinized consecutively to determine their root causes and preventability. The incidence and patterns of anaesthesia-related deaths were analysed from 2017 to 2021. A mixed-effects model with a Poisson link function was fitted to evaluate the city-level annual changes in risk-adjusted incidence of anaesthesia-related deaths. Findings: 600 cases of anaesthetic deaths occurred from 2017 to 2021, yielding an incidence of 6.4 per 100,000 anaesthesia procedures [95% confidence interval (95% CI): 5.9, 6.9], and most were preventable (71.3%). There was a significant decrease from 2017 to 2021, in the incidences of anaesthesia-related death across all patients, those with American Society of Anaesthesiologists physical status (ASAPS) ≥III, and those who had general anaesthesia, with a percentage reduction of 57.6%, 59.1%, and 55.9%, respectively. The risk-adjusted annual changes indicated significant downward trends for the incidence of anaesthetic mortality from 2017 to 2018, 2019, 2020, and 2021. For instance, the risk-adjusted annual changes for the anaesthetic mortality incidence from 2017 to 2021 was -2.5 (95% CI: -1.4, -4.7). Interpretation: In this large, comprehensive database study conducted in Central China, the anaesthesia-related death incidence was 6.4 per 100,000. Notably, the incidence of anaesthesia-related deaths decreased between 2017 and 2021. However, further in-depth analysis is needed to understand the extent to which these trends represent a change in patient safety. Funding: Innovation and optimization of perioperative respiratory system management strategy (Hubei Technological Innovation Special Fund, 2019ACA167).

10.
Neurosci Res ; 166: 34-41, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-32454040

RESUMO

Neuropathic pain is a very complex chronic pain state, the detailed molecular mechanisms of which remain unclear. In the present study, Shank3 was found to play an important role in neuropathic pain in rats following spared nerve injury (SNI). Shank3 was upregulated in the spinal dorsal horn of rats subjected to SNI, and mechanical hypersensitivity to noxious stimuli in these rats could be alleviated by knock down of Shank3. Shank3 also interacted with hyperpolarization-activated cyclic nucleotide-gated channel 2 (HCN2) and promoted the expression of HCN2 in central neurons of the spinal dorsal. Together with the SNI-dependent increase of HCN2, we also found that the postsynaptic protein of excitatory synapse (PSD95) was increased in rats following SNI. Taken together, our results showed that Shank3 modulated neuropathic pain by facilitating the SNI-dependent increase of HCN2 and the expression of PSD95 in spinal dorsal horn neurons. Our findings revealed new synaptic remodeling mechanisms linking Shank3 with neuropathic pain.


Assuntos
Neuralgia , Animais , Proteína 4 Homóloga a Disks-Large , Hiperalgesia , Canais Disparados por Nucleotídeos Cíclicos Ativados por Hiperpolarização , Proteínas do Tecido Nervoso , Células do Corno Posterior , Canais de Potássio , Ratos , Corno Dorsal da Medula Espinal
11.
Cancer Med ; 9(17): 6166-6172, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32657029

RESUMO

BACKGROUND: This study aimed to compare the efficacy and toxicity of raltitrexed (Saiweijian® ) plus cisplatin (SP regimen) and 5-fluorouracil plus cisplatin (FP regimen) as concurrent chemoradiotherapy (CCRT) in patients with locally advanced nasopharyngeal carcinoma (LA-NPC). METHODS: Eligible patients (N = 135) were allocated randomly in a ratio of 1:1 to receive CCRT with either SP or FP. At least 2 cycles of chemotherapy was administrated during radiotherapy. Progression free survival (PFS) was primary endpoint. Secondary endpoints included overall survival (OS), loco-regional relapse free survival (LRRFS), distant metastasis free survival (DMFS) and toxicity. RESULTS: In this study, 68 patients received SP as CCRT, and 67 received FP. Objective responses were noted in 97.1% of the patients in the SP group and in 97.0% of the patients in the FP group (P = 1.00). At the end of a median 36 months follow-up period, the estimated 3-year PFS rates were 70.1% for SP and 66.6% for FP, respectively. The 3-year LRRFS, DMFS and OS rates were 88.9%, 74.7% and 84.0%, respectively, for the SP group, and 92.3%, 71.0% and 73.7%, respectively, for the FP group. Overall, there was no difference between treatment groups with regard to response or survival. The most frequent acute toxicities monitored in both groups were bone marrow suppression, gastrointestinal side effects and oral mucositis (OM). The overall incidence of grade 3-4 OM in the FP group (47.8%) was higher than in the SP group (11.8%). However, the incidence of other adverse effects observed in both groups was similar (P > .05). CONCLUSIONS: These data indicate that SP and FP therapies have similar efficacy in treating LA-NPC. The SP regimen showed a tolerable safety profile along with a lower frequency of severe OM and therefore, an improved life quality. In conclusion, SP was a well tolerated, effective, regimen for LA-NPC treatment.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Quimiorradioterapia/métodos , Carcinoma Nasofaríngeo/terapia , Neoplasias Nasofaríngeas/terapia , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Medula Óssea/efeitos dos fármacos , Quimiorradioterapia/efeitos adversos , Distribuição de Qui-Quadrado , Cisplatino/administração & dosagem , Cisplatino/efeitos adversos , Feminino , Fluoruracila/administração & dosagem , Fluoruracila/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Carcinoma Nasofaríngeo/mortalidade , Carcinoma Nasofaríngeo/patologia , Neoplasias Nasofaríngeas/mortalidade , Neoplasias Nasofaríngeas/patologia , Intervalo Livre de Progressão , Quinazolinas/administração & dosagem , Quinazolinas/efeitos adversos , Estomatite/induzido quimicamente , Tiofenos/administração & dosagem , Tiofenos/efeitos adversos , Adulto Jovem
13.
Scand J Gastroenterol ; 43(4): 456-64, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-18365911

RESUMO

OBJECTIVE: Although beta-catenin cytoplasmic stabilization and nuclear translocation play a key role in initiation of colorectal cancer (CRC), the mechanisms are far from clear. The aim of this study was to investigate the relation of expressions of cyclooxygenase (COX)-2 and E-cadherin, and the beta-catenin gene exon 3 mutation to the altered distribution of beta-catenin, and their roles in CRC progression and prognosis. MATERIAL AND METHODS: Expressions of beta-catenin, COX-2 and E-cadherin in 96 tissue specimens were detected by immunohistochemistry, and mutation of beta-catenin gene exon 3 was screened by polymerase chain reaction (PCR) and denaturing high-performance liquid chromatography (DHPLC). RESULTS: Cytoplasmic/nuclear expression of beta-catenin and reduced membranous expression of E-cadherin were associated, respectively, with the earlier and later stages of sequential colorectal carcinogenesis (p<0.05). The altered distribution of beta-catenin was significantly associated with both high Dukes' stages and poor differentiation of CRC (p<0.05). It also had a parallel relationship with COX-2 overexpression (p<0.05, Spearman's rank analysis), but not with reduced E-cadherin expression. Kaplan-Meier analysis showed a significantly worse survival rate for CRC patients with altered expression of beta-catenin (p<0.05, log-rank test). Nevertheless, we failed to find any exon 3 mutation of beta-catenin gene in all 60 cases of CRC. CONCLUSIONS: Altered distribution of beta-catenin occurs in the early stage of colorectal carcinogenesis and has a parallel relationship with COX-2 overexpression. It may serve as a potential marker for the progression and prognosis of CRC. The exon 3 mutation did not appear contributive to the abnormal expression of beta-catenin in CRCs in a Chinese population.


Assuntos
Caderinas/metabolismo , Neoplasias Colorretais/metabolismo , beta Catenina/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/análise , Membrana Celular/metabolismo , Núcleo Celular/metabolismo , Neoplasias Colorretais/genética , Neoplasias Colorretais/mortalidade , Ciclo-Oxigenase 2/metabolismo , Citoplasma/metabolismo , Feminino , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Mutação , Prognóstico , Taxa de Sobrevida , beta Catenina/genética
14.
J Cancer ; 9(9): 1642-1651, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29760803

RESUMO

Background: This study aimed to compare concurrent chemoradiotherapy (CCRT) plus cetuximab (C) with CCRT alone in locoregionally advanced nasopharyngeal carcinoma(NPC). Methods: A total of 682 locoregionally advanced NPC patients who had undergone chemoradiotherapy with or without cetuximab were included. Propensity score-matching method was used to match patients. Progression-free survival (PFS), overall survival (OS), locoregional relapse-free survival (LRFS), and distant metastasis-free survival (DMFS) were compared between the two treatment arms. Results: After matching, 225 patients were identified for the analysis. Compared to CCRT, CCRT plus C was associated with significantly improved 3-year PFS (83.7% vs 71.9%, P = 0.036), LRFS (98.6% vs 90.2%, P = 0.034) but not OS (91.4% vs 85.4%, P = 0.117). Among patients with T4 and/or N3 category, CCRT plus C significantly prolonged 3-year PFS (81.0% vs 61.4%, P = 0.022) and increased 3-year OS (88.0% vs 77.9%, P = 0.086). No significant differences were observed between CCRT plus C and CCRT alone groups with regard to 3-year PFS, OS, LRFS and DMFS rates in stage III patients. Acute oral and oropharyngeal mucositis during radiotherapy were more common in the CCRT plus C than that in CCRT, but late toxicities were comparable. Conclusions: This study reveals that patients with locoregionally advanced NPC could benefit from the addition of cetuximab to CCRT, and this therapeutic gain mainly originated from T4 and/or N3 subgroup although suffering more acute moderate to severe toxicities.

15.
DNA Cell Biol ; 36(9): 787-793, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28731781

RESUMO

Lung cancer is the most common solid tumor around the world. It has been reported that upregulation of long noncoding RNA (lncRNA) plasmacytoma variant translocation 1 (lncRNA-PVT1) is closely associated with tumor metastasis. However, the function and underlying molecular mechanism of lncRNA-PVT1 in nonsmall cell lung cancer (NSCLC) invasion remain unknown. In this study, we found that overexpression of lncRNA-PVT1 promoted the invasive ability of NSCLC cells, whereas silence of lncRNA-PVT1 suppressed cell invasion. Furthermore, we found that lncRNA-PVT1 upregulated MMP9 expression in a post-transcriptional manner. Specifically, lncRNA-PVT1 directly interacted with miR-200a and miR-200b, which suppressed MMP9 expression. Taken together, lncRNA-PVT1 functions as a competitive endogenous RNA to regulate MMP9 expression through competitively binding the common microRNAs, miR-200a and miR-200b. These findings suggest that lncRNA-PVT1 could predispose NSCLC patients to metastases and may serve as a promising target for antimetastatic therapies.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/genética , Neoplasias Pulmonares/genética , Metaloproteinase 9 da Matriz/genética , RNA Longo não Codificante/genética , Regiões 3' não Traduzidas , Carcinoma Pulmonar de Células não Pequenas/patologia , Linhagem Celular Tumoral , Movimento Celular/genética , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Pulmonares/patologia , Metaloproteinase 9 da Matriz/metabolismo , MicroRNAs/genética
16.
Biomed Pharmacother ; 93: 869-878, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28724212

RESUMO

MicroRNA-98 (miR-98) is downregulated in many tumors, and is closely related to tumor progression. In addition, it shows anticarcinogenic functions in various tumor. However, few study show that the biological function and regulatory mechanisms of miR-98 in nasopharyngeal carcinoma (NPC) progression. The identification and its target genes which regulate by dysregulated miRNAs may strengthen our understanding of the molecular mechanisms of NPC. In this study, we observe that miR-98 is not only significantly reduced in NPC tissues, but also decreased markedly in NPC cell lines. Moreover, silencing miR-98 expression studies not only show miR-98 induced cell proliferation, migration and invasion in vitro, but also it promoted xenograft tumor growth in vivo in NPC. Furthermore, western blot assay was used to detected the level of STAT3 protein and we demonstrate that miR-98 regulate cells poliferation, migration and invasion through directly modulating functional target STAT3 by directly binding its 3'-UTR. These findings illustrate miR-98 as a anticarcinogenic functions through targeting STAT3, the miR-98/STAT3 pathway gives new clues for understanding NPC carcinogenesis and provides novel therapeutic targetsfor NPC.


Assuntos
Carcinoma/genética , Proliferação de Células/genética , MicroRNAs/genética , Neoplasias Nasofaríngeas/genética , Invasividade Neoplásica/genética , Fator de Transcrição STAT3/genética , Regiões 3' não Traduzidas/genética , Animais , Apoptose/genética , Carcinogênese/genética , Carcinoma/patologia , Linhagem Celular Tumoral , Movimento Celular/genética , Regulação para Baixo/genética , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas/patologia , Invasividade Neoplásica/patologia
17.
Neuroreport ; 28(2): 75-81, 2017 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-27893610

RESUMO

Neuronal network reconstruction is a pivotal determinant for functional recovery after spinal cord injury (SCI), the process of which includes synaptogenesis. Slit2 protein has been identified as a key regulator of axon regeneration and synapse formation in the vertebrate. Meanwhile, RhoA is the converging cascade of inhibitory molecules that interrupt synaptic plasticity in SCI. In the present study, we investigated the interaction among Slit2, Robo1, and RhoA and the potential roles of Slit2 in the pathological process of SCI. We showed that Slit2 was decreased, whereas Robo1 and RhoA were increased in the same surviving neurons in the spinal cord following SCI. We also found that inhibition of Slit2 led to upregulation of the expression of Robo1 and RhoA. However, the severe dysfunctions of the locomotor performance induced by SCI were reversed by treatments of Slit2-N, the active portion of Slit2, knockdown of Robo1 by the RNAi lentivirus, or inhibition of RhoA by the C3 exoenzyme, respectively. Further results suggested that downregulation of Slit2 and therefore upregulation of Robo1 and RhoA inhibited the activity of growth cone and hindered the formation of new synapses of surviving neurons near the injury sites of the spinal cord following SCI. Our study indicated a new mechanism of deficiency of synaptogenesis during the development of SCI and provided a potential strategy for the treatment of SCI.


Assuntos
Regulação da Expressão Gênica/fisiologia , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Receptores Imunológicos/metabolismo , Recuperação de Função Fisiológica/fisiologia , Traumatismos da Medula Espinal/terapia , Sinapses/metabolismo , Animais , Modelos Animais de Doenças , Feminino , Regulação da Expressão Gênica/genética , Peptídeos e Proteínas de Sinalização Intercelular/genética , Locomoção/genética , Microscopia Eletrônica de Transmissão , Proteínas do Tecido Nervoso/genética , Neurogênese/genética , RNA Mensageiro/metabolismo , Ratos , Ratos Sprague-Dawley , Receptores Imunológicos/genética , Traumatismos da Medula Espinal/metabolismo , Estatísticas não Paramétricas , Sinapses/ultraestrutura , Transdução Genética , Proteína rhoA de Ligação ao GTP/metabolismo , Proteínas Roundabout
18.
Oncotarget ; 8(45): 79953-79963, 2017 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-29108377

RESUMO

PURPOSE: This study aimed to compare the efficacy of induction-concurrent (IC-CCRT) with concurrent-adjuvant (CCRT-AC) chemotherapy in patients with locoregionally advanced nasopharyngeal carcinoma (LA-NPC) treated by intensity-modulated radiotherapy (IMRT). MATERIALS AND METHODS: Data on 834 patients with newly diagnosed, non-metastatic stage III-IVA (except T3N0) NPC receiving either IC-CCRT or CCRT-AC between July, 2004 and December, 2014 were retrospectively reviewed. Propensity score matching (PSM) method was adopted to balance prognostic factors and match patients. Survival outcomes of matched patients between IC-CCRT and CCRT-AC were compared. RESULTS: The median follow-up duration is 45.2 months (range, 1.07-145.4 months). Overall, 309 pairs were selected by PSM. Univariate analysis revealed the CCRT-AC group achieved significantly higher 3-year DFS (83.9% vs. 78.7 %; P = 0.014) and OS (87.6% vs. 87.0%; P = 0.031). Multivariate analysis also identified treatment group (IC-CCRT vs. CCRT-AC) as an independent prognostic factor for 3-year DFS (HR, 1.546; 95% CI, 1.113-2.149; P = 0.009) and OS (HR, 1.487; 95% CI, 1.035-2.136; P = 0.032). Subgroup analysis revealed IC-CCRT was a protective factor for DMFS (HR, 0.145; 95% CI, 0.043-0.488; P = 0.002) in stage III disease; however, it could adversely affected DFS (HR, 2.009; 95% CI, 1.316-3.065; P = 0.001), OS (HR, 1.671; 95% CI, 1.060-2.636; P = 0.027) and DMFS (HR, 1.986; 95% CI, 1.155-3.416; P = 0.013) in stage IVA disease. CONCLUSIONS: CCRT-AC may be a more effective treatment modality in patients with stage IVA NPC disease, while IC-CCRT was superior in stage III disease.

19.
Oral Oncol ; 69: 26-32, 2017 06.
Artigo em Inglês | MEDLINE | ID: mdl-28559017

RESUMO

OBJECTIVES: Intensity-modulated radiotherapy (IMRT) has been applied in nasopharyngeal carcinoma (NPC) for nearly twenty years, while little is known about the ten-year survival outcomes. This study aimed at evaluating the 10-year survival outcomes for patients with NPC receiving IMRT. MATERIALS AND METHODS: Data on 614 patients with newly diagnosed, non-disseminated NPC treated by IMRT between 2004 and 2008 were retrospectively reviewed. Survival outcomes stratified by tumor stage were compared. RESULTS: The median follow-up duration was 112.7months (range, 7.6-156.8months) for the entire cohort. The 10-year local relapse-free survival rates for T1, T2 and T3 were 94.2%, 92.5% and 91.4% (P>0.05), respectively, and significantly higher than that of T4 disease (79.3%, P<0.05 for all rates). As N category increased from N0 to N3, the 10-year distant metastasis-free survival rates significantly decreased accordingly (P<0.01 for all rates). Furthermore, the 10-year overall survival rates were 100%, 87.1%, 75.5% and 55.6% for stage I, II, III and IV, respectively (P<0.05 except stage I and II). Multivariate analysis established tumor stage and age as independent prognostic factors. Late toxicities were assessable for 495 (80.6%) patients and most were Grade I/II damages. Xerostomia (387 of 489, 79.1%) and hearing impairment (212 of 495, 42.8%) remained the most troublesome. CONCLUSION: IMRT could achieve satisfactory survival outcomes for NPC patients with acceptable late toxicities. However, distant control still remains poor, especially for patients with N3 disease.


Assuntos
Neoplasias Nasofaríngeas/radioterapia , Radioterapia de Intensidade Modulada , Taxa de Sobrevida , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/uso terapêutico , Criança , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Nasofaríngeas/tratamento farmacológico , Prognóstico , Adulto Jovem
20.
Acta Otolaryngol ; 136(11): 1164-1167, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27387761

RESUMO

CONCLUSION: The results implied that CTCs were common even in early TNM stages and might become a potential parameter in evaluating therapeutic effects of radio and chemotherapies. BACKGROUND: Nasopharyngeal carcinoma (NPC) is a head and neck malignancy with an extraordinary high incidence in Southern China and a high metastasis rate. Analysis of circulating tumor cells (CTCs) in peripheral blood is a relatively new prognostic marker for cancer patients. PATIENTS AND METHODS: This retrospective study included data from 38 nasopharyngeal patients with poorly differentiated squamous cell carcinoma in TNM stage I (n = 2), TNM stage II (n = 12), TNM stage III (n = 8), and TNM stage IV (n = 16). CTCs in peripheral blood of all patients were counted before and 1 week as well as 1 months after radiotherapy. RESULTS: The data showed that in 52.6% of the patients CTCs could be detected in peripheral blood and the numbers were significantly decreased 1 month after radiotherapy treatment (p < 0.001). There was no correlation between CTC number or positivity and TNM stages or other clinical parameters.


Assuntos
Carcinoma de Células Escamosas/sangue , Neoplasias Nasofaríngeas/sangue , Células Neoplásicas Circulantes , Carcinoma , Carcinoma de Células Escamosas/radioterapia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas/radioterapia , Estudos Retrospectivos , Fatores de Risco
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