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1.
Ann Surg Oncol ; 30(3): 1597-1613, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36380254

RESUMO

PURPOSE: This study aimed to summarize the efficacy and safety of neoadjuvant chemoimmunotherapy in resectable esophageal squamous cell carcinoma (ESCC). METHODS: Literature focusing on the efficacy and safety of neoadjuvant immunotherapy or chemoimmunotherapy in resectable ESCC published before June 2022 was retrieved from PubMed, Embase, Cochrane Library, and Web of Science. The risk of bias was assessed using the Cochrane risk-of-bias assessment tool. Subgroup and sensitivity analyses were further performed. RESULTS: A total of 452 patients from 15 studies were included in this meta-analysis. All of the studies explored the efficacy and safety of neoadjuvant chemoimmunotherapy. The pooled major pathological response (MPR) rate and pathological complete response (PCR) rate were 58.3% and 32.9%, respectively. The pooled incidence of treatment-related adverse events (TRAEs) and serious adverse events (SAEs) were 91.6% and 19.4%, respectively. The pooled R0 resection rate was 92.8%, and the resection rate was 81.1%. Incidence of anastomotic leakage, pulmonary infection, and postoperative hoarseness were 10.7%, 21.3%, and 13.0%, respectively. Compared with 2 cycles of neoadjuvant therapy, patients who received > 2 cycles of neoadjuvant therapy showed higher MPR rate (57.3% vs. 61.1%) and PCR rate (30.6% vs. 37.9%), and the incidence of TRAEs (89.2% vs. 98.9%) tended to be higher. However, no significant difference was found (P > 0.05). Two cycles of neoadjuvant therapy showed higher R0 resection rate and resection rate (R0 resection rate: 96.0% vs. 87.8%, P = 0.02; resection rate: 85.6% vs. 74.7%, P = 0.01). Pembrolizumab- and tislelizumab-based neoadjuvant therapy showed higher MPR rate (72.4% and 72.2%) and PCR rate (41.5 % and 50.0%). Compared with other ICIs, tislelizumab-based neoadjuvant therapy showed lower R0 resection rate (80.5%). The pooled incidence of SAEs for pembrolizumab-based neoadjuvant therapy (2.0%) was lower. Camrelizumab-based neoadjuvant therapy showed lower incidence of pulmonary infection (11.5%). CONCLUSIONS: Neoadjuvant chemoimmunotherapy is effective and safe for resectable ESCC.


Assuntos
Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Humanos , Carcinoma de Células Escamosas do Esôfago/terapia , Carcinoma de Células Escamosas do Esôfago/patologia , Terapia Neoadjuvante , Neoplasias Esofágicas/tratamento farmacológico , Neoplasias Esofágicas/patologia , Quimioterapia Adjuvante , Imunoterapia
2.
Mol Biol Rep ; 41(3): 1257-66, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24390317

RESUMO

Changes in the expression profiles of microRNAs (miRNAs) have been found in many cancers. The study was aimed to investigate the expression of miR-25, miR-223, and miR-375 in the serum of patients with esophageal squamous cell carcinoma (ESCC) and its effect on survival outcome. We examined the expression levels of miR-25, miR-223, and miR-375 in 20 pairs of ESCC cancer and matched paracancerous tissues, serum samples from 94 healthy volunteers and 194 patients with ESCC using quantitative reverse transcription polymerase chain reaction, and analyzed the relationship between expressions of serum miR-25, miR-223, and miR-375 and ESCC clinicopathological parameters as well as survival. Expressions of miR-25 and miR-223 were significantly increased in ESCC tissues compared with paracancerous tissues (P = 0.008 and 0.009, respectively), whereas the expression of miR-375 was significantly decreased in ESCC tissues compared with paracancerous tissues (P = 0.006). Expressions of serum miR-25 and miR-223 were significantly higher in ESCC patients than those in healthy controls, and, inversely, expression of serum miR-375 was significantly lower in ESCC patients than those in healthy controls (P = 0.007). High expression of serum miR-25 was significantly associated with lymph node metastasis (P = 0.01). Survival analysis showed that high expression of serum miR-223 and low expression of serum miR-375 were associated with poor survival in ESCC patients [hazard ratio (HR) = 1.717, 95% confidence intervals (CI) 1.139-2.588, P = 0.01; HR = 1.750, 95% CI 1.111-2.756, P = 0.016, respectively). Furthermore, Patients with high miR-223 and low miR-375 expression had higher risk of death than those with low miR-223 and high miR-375 expression (HR = 3.599, 95% CI 1.800-7.195, P = 2.92 × 10(-4)). In conclusion, miR-25, miR-223, and miR-375 were abnormally expressed in ESCC tissues and sera. Serum miR-223 and miR-375 are potential prognostic biomarkers for ESCC.


Assuntos
Carcinoma de Células Escamosas/sangue , Neoplasias Esofágicas/sangue , MicroRNAs/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patologia , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/patologia , Carcinoma de Células Escamosas do Esôfago , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Análise de Sobrevida
3.
Tohoku J Exp Med ; 232(2): 85-95, 2014 02.
Artigo em Inglês | MEDLINE | ID: mdl-24531034

RESUMO

MicroRNA (miRNA) is a type of small non-coding RNA molecule that has important roles in cancer initiation, promotion and progression by negatively regulating gene expression. In this study, we explored the role of miRNAs in the prognosis of patients with non-small cell lung cancer (NSCLC). The miRNA expression profiles were determined in 5 pairs of NSCLC and paracancerous tissues (3 adenocarcinomas and 2 squamous cell carcinomas). Aberrantly expressed miRNAs were validated by quantitative real-time PCR (qRT-PCR) in 61 pairs of NSCLC and paracancerous tissues. Differentially expressed miRNAs were further analyzed in sera from 94 healthy subjects and 94 advanced NSCLC patients receiving platinum-based chemotherapy. Three miRNAs (miR-19b, miR-146a, and miR-223) were significantly dysregulated in NSCLC tissues (P < 0.05). High miR-19b and low miR-146a expression in NSCLC tissues were associated with higher TNM stage, lymph node metastasis and poorer survival (P < 0.05). The serum levels of miR-19b in NSCLC patients were significantly higher (P < 0.001), whereas serum levels of miR-146a were significantly lower (P < 0.001), compared with those in controls. Serum levels of miR-19b and miR-146a were associated with overall survival of NSCLC patients (P < 0.05). Patients with low serum level of miR-19b and high serum level of miR-146a achieved a higher overall response rate and longer survival time (P < 0.05). These data suggest that miR-19b and miR-146a are potential biomarkers for the prediction of survival and response to chemotherapy in NSCLC.


Assuntos
Adenocarcinoma/diagnóstico , Biomarcadores Tumorais/sangue , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Carcinoma de Células Escamosas/diagnóstico , Metástase Linfática/diagnóstico , MicroRNAs , Adenocarcinoma/sangue , Carcinoma Pulmonar de Células não Pequenas/sangue , Carcinoma de Células Escamosas/sangue , China , Perfilação da Expressão Gênica , Humanos , MicroRNAs/sangue , Reação em Cadeia da Polimerase em Tempo Real , Análise de Regressão
4.
Int J Surg ; 110(1): 490-506, 2024 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-37800587

RESUMO

BACKGROUND: The application of neoadjuvant immune checkpoint inhibitors combined with chemotherapy (NICT) in treating locally advanced oesophageal squamous cell carcinoma (ESCC) is a subject of considerable research interest. In light of this, we undertook a comprehensive meta-analysis aiming to compare the efficacy and safety of this novel approach with conventional neoadjuvant chemotherapy (NCT) in the management of ESCC. METHODS: A systematic search was conducted in PubMed, Embase, Cochrane Library, and Web of Science to gather relevant literature on the efficacy and safety of NICT compared to conventional NCT in locally advanced ESCC published before June 2023. Effect indicators, including odds ratios (ORs) with associated 95% CIs, were employed to evaluate the safety and efficacy outcomes. The risk of bias was assessed using the Cochrane bias risk assessment tool, and s ubgroup analysis and sensitivity analysis were conducted to investigate the findings further. RESULTS: A total of nine studies qualified for the meta-analysis, all of which investigated the efficacy and safety of NICT compared to conventional NCT. The pooled rates of pathologic complete response and major pathologic response in the NICT group were significantly higher compared to the NCT group, with values of 26.9% versus 8.3% ( P <0.00001) and 48.1% versus 24.6% ( P <0.00001), respectively. The ORs for achieving pathologic complete response and major pathologic response were 4.24 (95% CI, 2.84-6.32, I 2 =14%) and 3.30 (95% CI, 2.31-4.71, I 2 =0%), respectively, indicating a significant advantage for the NICT group. Regarding safety outcomes, the pooled incidences of treatment-related adverse events and serious adverse events in the NICT group were 64.4% and 11.5%, respectively, compared to 73.8% and 9.3% in the NCT group. However, there were no significant differences observed between the two groups in terms of treatment-related adverse events (OR=0.67, 95% CI, 0.29-1.54, P =0.35, I 2 =58%) or serious adverse events (OR=1.28, 95% CI, 0.69-2.36, P =0.43, I 2 =0%). Furthermore, no significant differences were found between the NICT and NCT groups regarding R0 resection rates, anastomotic leakage, pulmonary infection, and postoperative hoarseness. CONCLUSIONS: Neoadjuvant immune checkpoint inhibitors combined with chemotherapy demonstrate efficacy and safety in treating resectable oesophageal squamous cell carcinoma. Nevertheless, additional randomized trials are required to confirm the optimal treatment regimen.


Assuntos
Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Humanos , Terapia Neoadjuvante , Carcinoma de Células Escamosas do Esôfago/tratamento farmacológico , Carcinoma de Células Escamosas do Esôfago/cirurgia , Inibidores de Checkpoint Imunológico/efeitos adversos , Neoplasias Esofágicas/tratamento farmacológico , Neoplasias Esofágicas/cirurgia , Fístula Anastomótica , Resposta Patológica Completa
5.
JTO Clin Res Rep ; 5(2): 100621, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38371194

RESUMO

Introduction: In Chinese patients with NSCLC, prevalence of EGFR-mutated (EGFRm) disease is high. In the global phase 3 ADAURA study (NCT02511106), adjuvant osimertinib was found to have a statistically significant and clinically meaningful improvement in disease-free survival (DFS) versus placebo in resected stage IB to IIIA EGFRm NSCLC. We present efficacy and safety data from a subgroup analysis of 159 Chinese patients enrolled in the People's Republic of China from ADAURA. Methods: In ADAURA, patients with completely resected stage IB to IIIA EGFRm (exon 19 deletion/exon 21 L858R) NSCLC were randomized 1:1 to receive osimertinib (80 mg once daily) or placebo for 3 years or until disease recurrence/discontinuation. Adjuvant chemotherapy was permitted before randomization, per physician/patient choice. Primary end point was investigator-assessed DFS in stage II to IIIA disease; secondary end points included DFS in stage IB to IIIA (overall population), overall survival, health-related quality of life (HRQoL), and safety. Results: Of 682 patients enrolled globally, 159 patients in the People's Republic of China were included in this subgroup analysis (osimertinib n = 77; placebo n = 82). Baseline characteristics were balanced across the treatment arms. At data cutoff, stage II to IIIA DFS hazard ratio (HR) was 0.23 (95% confidence interval [CI]: 0.13-0.42; maturity 59%); stage IB to IIIA DFS HR was 0.29 (95% CI: 0.17-0.48; maturity 42%). At 13% maturity (21 deaths), HR for overall survival in the stage IB to IIIA population was 0.51 (95% CI: 0.21-1.20). HRQoL was maintained from baseline, and safety was consistent with the global population. Conclusions: In this population of Chinese patients from ADAURA, adjuvant osimertinib was found to have a clinically meaningful improvement in DFS versus placebo, with maintained HRQoL and a safety profile consistent with the global study population.

6.
Int J Surg ; 109(8): 2168-2178, 2023 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-37318861

RESUMO

PURPOSE: Neoadjuvant chemoimmunotherapy (nICT) is a novel and promising therapy model for locally advanced esophageal squamous cell carcinoma.The objective of this study aimed to assessed the impact of additional neoadjuvant immunotherapy on patients' short-term outcomes, particularly the incidence of anastomotic leakage (AL) and pathological response. METHODS: Patients with locally advanced esophageal squamous cell carcinoma who received neoadjuvant chemotherapy (nCT)/ nICT combination with radical esophagectomy were enrolled from three medical centers in China. The authors used propensity score matching (PSM, ration:1:1, caliper=0.01) and inverse probability processing weighting (IPTW) to balance the baseline characteristics and compare the outcomes. Conditional logistic regression and weighted logistic regression analysis were used to further evaluate whether additional neoadjuvant immunotherapy would increase the risk of postoperative AL. RESULTS: A total of 331 patients getting partially advanced ESCC receiving nCT or nICT were enrolled from three medical centers in China. After PSM/IPTW, the baseline characteristics reached an equilibrium between the two groups. After matching, there were no significant difference in the AL incidence between the two groups ( P =0.68, after PSM; P =0.97 after IPTW), and the incidence of AL in the two groups was 15.85 versus 18.29%, and 14.79 versus 15.01%, respectively. After PSM/IPTW, both groups were similar in pleural effusion and pneumonia. After IPTW, the nICT group had a higher incidence of bleeding (3.36 vs. 0.30%, P =0.01), chylothorax (5.79 0.30%, P =0.001), and cardiac events (19.53 vs. 9.20%, P =0.04). recurrent laryngeal nerve palsy (7.85 vs. 0.54%, P =0.003). After PSM, both groups were similar in palsy of the recurrent laryngeal nerve (1.22 vs. 3.66%, P =0.31) and cardiac events (19.51 vs. 14.63%, P =0.41). Weighted logistic regression analysis showed that additional neoadjuvant immunotherapy was not responsible for AL (OR=0.56, 95% CI: [0.17, 1.71], after PSM; 0.74, 95% CI: [0.34,1.56], after IPTW). The nICT group had dramatically higher pCR in primary tumor than the nCT group ( P =0.003, PSM; P =0.005, IPTW), 9.76 versus 28.05% and 7.72 versus 21.17%, respectively. CONCLUSIONS: Additional neoadjuvant immunotherapy could benefit pathological reactions without increasing the risk of AL and pulmonary complications. The authors require further randomized controlled research to validate whether additional neoadjuvant immunotherapy would make a difference in other complications, and determine whether pathologic benefits could translate into prognostic benefits, which would require longer follow-up.


Assuntos
Doenças Cardiovasculares , Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Humanos , Carcinoma de Células Escamosas do Esôfago/cirurgia , Fístula Anastomótica/epidemiologia , Fístula Anastomótica/etiologia , Fístula Anastomótica/cirurgia , Neoplasias Esofágicas/cirurgia , Neoplasias Esofágicas/patologia , Terapia Neoadjuvante/efeitos adversos , Esofagectomia/efeitos adversos , Estudos Retrospectivos
7.
J Thorac Dis ; 15(11): 6228-6237, 2023 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-38090323

RESUMO

Background: Camrelizumab has been demonstrated to be a feasible treatment option for locally advanced esophageal squamous cell carcinoma (ESCC) when combined with neoadjuvant chemotherapy. This trial was conducted to investigate the effectiveness and safety of camrelizumab-containing neoadjuvant therapy in patients with ESCC in daily practice. Methods: This prospective multicenter observational cohort study was conducted at 13 tertiary hospitals in Southeast China. Patients with histologically or cytologically confirmed ESCC [clinical tumor-node-metastasis (cTNM) stage I-IVA] who had received at least one dose of camrelizumab-containing neoadjuvant therapy were eligible for inclusion. Results: Between June 1, 2020 and July 13, 2022, 255 patients were enrolled and included. The median age was 64 (range, 27 to 82) years. Most participants were male (82.0%) and had clinical stage III-IVA diseases (82.4%). A total of 169 (66.3%) participants underwent surgical resection; 146 (86.4%) achieved R0 resection, and 36 (21.3%) achieved pathological complete response (pCR). Grades 3-5 adverse events (AEs) were experienced by 14.5% of participants. Reactive cutaneous capillary endothelial proliferation occurred in 100 (39.2%) of participants and all were grade 1 or 2. Conclusions: Camrelizumab-containing neoadjuvant therapy has acceptable effectiveness and safety profiles in real-life ESCC patients.

8.
Front Surg ; 9: 1079821, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36776472

RESUMO

Purpose: The present study aims to identify factors related to anastomotic leakage before esophagectomy and to construct a prediction model. Methods: A retrospective analysis of 285 patients who underwent minimally invasive esophagectomy (MIE). An absolute shrinkage and selection operator was applied to screen the variables, and predictive models were developed using binary logistic regression. Results: A total of 28 variables were collected in this study. LASSO regression analysis, combined with previous literature and clinical experience, finally screened out four variables, including aortic calcification, heart disease, BMI, and FEV1. A binary logistic regression was conducted on the four predictors, and a prediction model was established. The prediction model showed good discrimination and calibration, with a C-statistic of 0.67 (95% CI, 0.593-0.743), a calibration curve fitting a 45° slope, and a Brier score of 0.179. The DCA demonstrated that the prediction nomogram was clinically useful. In the internal validation, the C-statistic still reaches 0.66, and the calibration curve has a good effect. Conclusions: When patients have aortic calcification, heart disease, obesity, and a low FEV1, the risk of anastomotic leakage is higher, and relevant surgical techniques can be used to prevent it. Therefore, the clinical prediction model is a practical tool to guide surgeons in the primary prevention of anastomotic leakage.

9.
Zhonghua Yi Xue Za Zhi ; 91(44): 3131-3, 2011 Nov 29.
Artigo em Zh | MEDLINE | ID: mdl-22340656

RESUMO

OBJECTIVE: To evaluate the cosmetic effects and safety profiles of trans-areola single port endoscopic thoracic sympathectomy. METHODS: A retrospective study was conducted for 45 males and 7 females with palmar hyperhidrosis undergoing trans-areola single port endoscopic thoracic bilateral sympathectomy during April and June 2011. RESULTS: All operations were successfully performed without severe morbidity and mortality. No conversion to open technique was necessary. The mean unilateral operative duration was 6 minutes (range: 5 - 8). The time was calculated from the time of skin incision to that of dressing application over wound. The mean hospitalization duration was 2.2 days (range: 2 - 3). The mean follow-up period was 2.8 months (range: 1 - 7). All patients achieved excellent cosmetic effects. No incision scar was found. CONCLUSION: Trans-areola single port endoscopic thoracic sympathectomy is a safe and effective therapeutic procedure for primary palmar hyperhidrosis. The incision is undetectable with excellent cosmetic effects. The trans-areola route is a new ideal and promising approach for endoscopic thoracic sympathectomy.


Assuntos
Hiperidrose/cirurgia , Simpatectomia/métodos , Toracoscopia , Adolescente , Adulto , Feminino , Humanos , Masculino , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
10.
Arch Med Sci ; 17(1): 135-141, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33488866

RESUMO

INTRODUCTION: The DEK gene encodes a nuclear phosphoprotein which is involved in multiple cell metabolic processes, such as DNA damage repair, mRNA splicing, modifying chromatin structure and transcription regulation. DEK has been shown to be overexpressed in various solid human tumors and associated with patient prognosis. In this study, our aim was to investigate DEK protein expression and its relationship with clinicopathological parameters and prognosis in esophageal squamous cell carcinoma (ESCC). MATERIAL AND METHODS: Tissue samples were collected from 120 routinely diagnosed ESCC patients who underwent surgical resection at the Zhongshan Hospital, Xiamen University in the period from June 2011 to May 2013. The expression of DEK was determined by immunohistochemistry. RESULTS: DEK protein was ubiquitously distributed in the nucleus of ESCC cells, and its positive rate (71.7%) was significantly higher in cancer samples than those of para-carcinoma (21.4%) or normal esophageal (13.9%) tissues (p < 0.001). Similarly, significantly more cells overexpressing DEK were found in ESCC tissues (57.5%) in comparison with para-carcinoma samples (11.4%) and normal esophageal mucosa (0%, p < 0.001). The DEK overexpression rate was significantly different between patients with different tumor-node-metastasis (TNM) stages and differentiation degrees (p < 0.001). ESCC cases with elevated DEK amounts showed reduced disease-free and 5-year survival rates compared with those expressing low DEK amounts (p < 0.001). DEK overexpression was also confirmed to independently predict prognosis in ESCC (HR = 4.121, 95% CI: 1.803-9.42, p = 0.001). CONCLUSIONS: DEK expression is positively correlated with reduced survival in ESCC patients. DEK has potential to be an independent biomarker in predicting prognosis of ESCC patients.

11.
Biomark Med ; 11(5): 431-441, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28621611

RESUMO

AIM: To investigate whether plasma miR-19a can serve as a biomarker for esophageal squamous cell carcinoma (ESCC) diagnosis and prognosis. MATERIALS & METHODS: Plasma samples from 89 ESCC, 45 benign lesion patients and 80 healthy controls were subjected to RT-qPCR analyses for miR-19a. In addition, plasma samples from 30 patients were collected before and after surgery for the same analyses. RESULTS: Plasma miR-19a was significantly increased in ESCC patients compared with healthy controls. The sensitivity of miR-19a for early stages of ESCC was 68.09%. Combination of miR-19a and cytokeratin 19 fragment 21-1 (Cyfra21-1) further improved the sensitivity to 78.70%. Moreover, plasma miR-19a level was decreased in patients after surgery. CONCLUSION: Plasma miR-19a may serve as a potential biomarker that complements Cyfra21-1 in detecting early stages of ESCC.


Assuntos
Biomarcadores Tumorais/sangue , Carcinoma de Células Escamosas/sangue , Carcinoma de Células Escamosas/diagnóstico , Neoplasias Esofágicas/sangue , Neoplasias Esofágicas/diagnóstico , MicroRNAs/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/cirurgia , Regulação para Baixo , Neoplasias Esofágicas/patologia , Neoplasias Esofágicas/cirurgia , Carcinoma de Células Escamosas do Esôfago , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Estadiamento de Neoplasias , Prognóstico , Recidiva
12.
Talanta ; 154: 341-5, 2016 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-27154684

RESUMO

A new method of capillary electrophoresis (CE) coupled with tris(2, 2'-bipyridyl) ruthenium(II) electrochemiluminescence (ECL) detection has been developed to detect four local anesthetics procainamide (PAH), tetracaine (TCH), proparacaine (PCH) and cinchocaine (CIN) simultaneously. An europium (III)-doped prussian blue analogue film (Eu-PB) modified platinum electrode was prepared and applied to improve the detection sensitivity. The parameters including additives, concentration and pH of the running buffer, separation voltage and detection potential that affect CE separation and ECL detection were optimized in detail. The four local anesthetics were baseline separated and detected within 10min under the optimized conditions. The detection limits (LOD) of PAH, TCH, PCH and CIN are 5.5×10(-8), 9.6×10(-8), 2.5×10(-8) and 3.5×10(-8)molL(-1) (S/N=3), respectively. RSDs of the migration time for four analytes range from 1.2% to 2.5% within intraday and from 2.4% to 4.9% in interday, RSDs of the peak area for four analytes are from 1.7% to 3.3% within intraday and from 2.2% to 5.6% in interday, respectively. The limits of quantitation (LOQ) (S/N=10) for PAH, TCH, PCH and CIN in human urine sample are 5.9×10(-7), 9.2×10(-7), 8.3×10(-7) and 5.0×10(-7)molL(-1), separately. The recoveries (n=3) of four analytes in human urine are from 87.6% to 107.7% with less than 5.9% in RSDs. The developed method was used to determine four local anesthetics in human urine samples and investigate the interaction between PAH and human serum albumin (HSA). The number of binding sites and the binding constant of PAH with HSA were calculated to be 1.03 and 2.4×10(4)Lmol(-1), respectively.


Assuntos
Procainamida/análise , Albumina Sérica Humana/análise , Anestésicos Locais , Eletroforese Capilar , Humanos , Medições Luminescentes
13.
Respir Physiol Neurobiol ; 219: 43-50, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26282788

RESUMO

OBJECTIVES: Transient receptor potential vanilloid 4 (TRPV4) calcium channels are known to promote endothelium-dependent relaxation of mouse mesenteric arteries but TRPV4's role in the pulmonary vasculature is uncertain. Thus, we characterized TRPV4 channel vascular tone regulation in mouse main pulmonary artery rings and in the isolated perfused pulmonary circulation and studied possible mechanisms behind these characterizations. METHODS AND RESULTS: Using myography and a TRPV4 specific agonist GSK1016790A in a C57BL/6 WT mouse model of isolated constant-flow lung perfusion, we studied vascular tone regulation in arterial rings from the main left and right pulmonary arteries and vascular resistance of the intra-pulmonary circulation beyond the second branches of the pulmonary arteries. Removal of the endothelium confirmed endothelial dependence. GSK1016790A relaxed the main pulmonary artery (EC50 4 × 10(-8)mol/L), which was inhibited by removal of the endothelium from main pulmonary artery rings. GSK1016790A significantly increased vascular resistance of the pulmonary circulation in isolated perfused lungs, but these effects were inhibited by a TRPV4 antagonist AB159908. A nitric oxide inhibitor NG-nitro-L-arginine methyl ester (L-NAME) and K(+) channel blockers apamin plus charybdotoxin (ChTx) significantly inhibited GSK1016790A in the main pulmonary artery and in an isolated perfused lung in vitro. CONCLUSIONS: Activated TRPV4 channels increase pulmonary vascular resistance and vasodilate the main pulmonary artery.


Assuntos
Pulmão/irrigação sanguínea , Pulmão/fisiologia , Artéria Pulmonar/fisiologia , Canais de Cátion TRPV/metabolismo , Animais , Apamina/farmacologia , Fármacos Cardiovasculares/farmacologia , Charibdotoxina/farmacologia , Inibidores Enzimáticos/farmacologia , Leucina/análogos & derivados , Leucina/farmacologia , Pulmão/efeitos dos fármacos , Masculino , Camundongos Endogâmicos C57BL , Modelos Cardiovasculares , NG-Nitroarginina Metil Éster/farmacologia , Óxido Nítrico/metabolismo , Bloqueadores dos Canais de Potássio/farmacologia , Canais de Potássio/metabolismo , Artéria Pulmonar/efeitos dos fármacos , Circulação Pulmonar/efeitos dos fármacos , Circulação Pulmonar/fisiologia , Sulfonamidas/farmacologia , Canais de Cátion TRPV/agonistas , Canais de Cátion TRPV/antagonistas & inibidores , Técnicas de Cultura de Tecidos , Resistência Vascular/efeitos dos fármacos , Resistência Vascular/fisiologia , Vasoconstrição/efeitos dos fármacos , Vasoconstrição/fisiologia , Vasodilatação/efeitos dos fármacos , Vasodilatação/fisiologia
14.
Cancer Chemother Pharmacol ; 73(2): 335-41, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24288122

RESUMO

PURPOSE: MicroRNA (miRNA) polymorphisms contribute to cancer susceptibility and prognosis. The aim of this study was to evaluate the effects of miRNA polymorphisms on clinical outcomes in patients with advanced esophageal squamous cell carcinoma (ESCC) treated with platinum-based chemotherapy. METHODS: Five polymorphisms (miR-146a rs2910164, miR-196a2 rs11614913, miR-100 rs1834306, miR-125a rs12976445 and miR-26a1 rs7372209) were genotyped in 378 patients with advanced ESCC recruited at Zhongshan Hospital. The associations between genotypes and drug response, toxicity, and overall survival were analyzed. RESULTS: miR-146a rs2910164 was significantly associated with an increased risk of severe hematological toxicity [odds ratio = 0.374, 95 % confidence interval (CI) 0.171-0.819, P = 0.014]. The TT genotypes of both miR-196a2 rs11614913 and miR-125a rs12976445 were associated with worse survival [hazard ratio (HR) = 1.552, 95 % CI 1.112-2.165, P = 0.010; HR = 2.171, 95 % CI 1.173-4.017, P = 0.014, respectively]. Combined analysis revealed a 4.073-fold increased risk of death in patients carrying two unfavorable genotypes (P = 0.002). CONCLUSIONS: Taken together, these findings indicate that miRNA polymorphisms may predict prognosis in advanced ESCC patients receiving platinum-based chemotherapy.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/genética , Neoplasias Esofágicas/tratamento farmacológico , Neoplasias Esofágicas/genética , MicroRNAs/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/metabolismo , Neoplasias Esofágicas/metabolismo , Carcinoma de Células Escamosas do Esôfago , Feminino , Predisposição Genética para Doença , Genótipo , Humanos , Estimativa de Kaplan-Meier , Masculino , MicroRNAs/metabolismo , Pessoa de Meia-Idade , Compostos Organoplatínicos/administração & dosagem , Polimorfismo de Nucleotídeo Único , Prognóstico
15.
Ann Thorac Surg ; 97(6): 2179-82, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24882301

RESUMO

Flail chest is caused by complex fractures of multiple ribs as a result of severe chest injuries, which results in paradoxical chest movements that severely compromise respiratory function. We report our experience of thoracoscopically assisted, minimally invasive surgical stabilization of massive anterolateral flail chest using a Nuss bar in three patients. This technique offers effective stabilization while having the advantages of short surgical time, minimal blood loss, less trauma, quicker recovery, and small and inconspicuous incisions.


Assuntos
Tórax Fundido/cirurgia , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Procedimentos Ortopédicos , Toracoscopia/métodos , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
16.
Ann Thorac Surg ; 98(5): e123-5, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25441832

RESUMO

The study presented a case of esophageal cancer presenting as intermittent fever with markedly elevated serum leukocyte and C-reactive protein. The patient's symptoms had not improved with antibiotic treatment. However, after thoracic esophagectomy, the fever faded and leukocyte serum levels rapidly normalized.


Assuntos
Carcinossarcoma/sangue , Neoplasias Esofágicas/sangue , Febre/etiologia , Biópsia , Carcinossarcoma/complicações , Carcinossarcoma/diagnóstico , Diagnóstico Diferencial , Neoplasias Esofágicas/complicações , Neoplasias Esofágicas/diagnóstico , Esofagoscopia , Febre/sangue , Febre/diagnóstico , Humanos , Masculino , Pessoa de Meia-Idade , Tomografia Computadorizada por Raios X
17.
Respir Physiol Neurobiol ; 227: 70, 2016 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-26773207
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